1. Sharrief A. Diagnosis and Management of Cerebral Small Vessel Disease. Continuum (Minneap Minn). 2023;29(2):501-518. doi:10.1212/CON.0000000000001232

Cerebral small vessel disease (CSVD) is one of the most common clinical conditions that a neuroimager will encounter. CSVD is associated with an increased risk of clinical ischemic and hemorrhagic stroke, silent infarcts, and cognitive decline and dementia. It has well-defined radiographic features and various clinical presentations. Despite its increasing prevalence with the aging population, few specific therapies exist to decrease its progression.

CSVD contributes to significant morbidity and mortality through its impact on stroke risk, cognitive decline, and dementia. Small vessel disease accounts for approximately 22% of ischemic stroke, and small vessel disease burden increases the risk of recurrent stroke following ischemic or hemorrhagic stroke. CSVD manifests as “silent” brain infarcts as well as clinically recognized small vessel ischemic strokes. Silent brain infarcts, which are also included in the classification of “covert cerebral small vessel disease,” are more common than acute ischemic stroke, with an estimated prevalence of 10% to 20% in adults. These lesions are often found incidentally but are associated with an increased risk of stroke and death, as well as other neurologic, neuropsychiatric, and cognitive symptoms, which are poorly recognized in clinical practice. CSVD accounts for most of the intracerebral hemorrhage (ICH) through arteriosclerosis (sometimes referred to as hypertensive arteriosclerosis) and cerebral amyloid angiopathy (CAA).

Age is the most common nonmodifiable risk factor for CSVD, and the aging of the population has led to the increased global prevalence of CSVD. Almost 100% of adults aged 90 and older have evidence of CSVD, with 36% of adults aged 80 to 90 demonstrating evidence of cerebral microbleeds.

Several modifiable clinical risk factors are associated with the development of CSVD. These include hypertension, obstructive sleep apnea, diabetes mellitus, hyperlipidemia, and tobacco use. Chronic kidney disease is associated with increased presence of cerebral microbleeds, white matter hyperintensities, and silent brain infarctions.

In 2013, a multidisciplinary group from the Centers for Standards in Neurodegeneration published a position paper describing the need for consistent terminology and setting the standard for describing CSVD. They described six radiographic phenotypes of CSVD: (1) recent small subcortical infarct, (2) white matter hyperintensity, (3) lacune of presumed vascular origin, (4) widened perivascular spaces, (5) cerebral microbleed, and (6) brain atrophy.

4 tables and 5 figures with this, including MR

2. Perneczky R, Jessen F, Grimmer T, et al. Anti-amyloid antibody therapies in Alzheimer’s disease. Brain. 2023;146(3):842-849. doi:10.1093/brain/awad005

New disease-modifying therapies (DMT) promise a step change in dementia care and prevention. At present, monoclonal antibodies (mAbs) targeting amyloid-β (Aβ) are the most prevalent drugs in phase III trials, with robust evidence on their engagement of the biological target in humans. However, clinical efficacy is less consistent across different agents, and the overall trial evidence so far indicated that successful Aβ clearance in early Alzheimer’s disease has at best very small effects on cognitive decline. The authors present this update which aims to elucidate the key reasons for those inconsistencies. To showcase the challenges with developing DMTs for Alzheimer’s disease, they start with an analysis of the three most recent anti-Aβ mAbs with completed phase III trials. They provide reasons why results of meta-analyses of the previous trials are less relevant in the appreciation of the new lecanemab data, including differences in drug dose, cohort characteristics, mAb specificity and adverse events.

Aducanumab, a human IgG1 mAb targeting amino acids of the Aβ peptide, is specific for Aβ plaques and on 7 June 2021, the US Food and Drug Administration (FDA) approved aducanumab for the treatment of Alzheimer’s disease.  Significant side effects also occurred during treatment with aducanumab in the phase III trials. Of particular importance were amyloid-related imaging abnormalities with edema (ARIA-E) and/or microhemorrhages (ARIA-H) on brain MRI scans, with an incidence of 35% and 36% in the two phase III studies, and 25% of affected participants experiencing symptoms, particularly in carriers of the APOE ϵ4 allele.

While the primary aim of the phase III studies was to provide evidence for the clinical efficacy of aducanumab, the approval now granted is based on proof of meeting the surrogate biomarker end point of reducing Aβ plaques on PET. This accelerated approval route chosen by the FDA for aducanumab is intended for drugs targeting serious diseases, expected to have a significant added value over the available therapy, even if there is residual uncertainty about the ultimate clinical benefit. There must be substantial evidence for efficacy on a surrogate end point reflecting the underlying disease pathology, with no requirement for demonstration of any clinical benefit. While biomarker evidence was sufficient for approval by FDA, the European Medicines Agency was unlikely to follow the US decision, and the developer therefore withdrew the marketing authorization application; approval for the marketing of aducanumab will not be granted in the EU.

On September 27 2022, results were announced from CLARITY AD, a large worldwide clinical trial with 1795 participants with early Alzheimer’s disease, showing that lecanemab had achieved its primary end point, a statistically significant slowdown of clinical disease progression on the CDR-SB. In this phase III trial the treatment group received 10 mg/kg lecanemab intravenously every 2 weeks, with participants receiving either placebo or lecanemab in a 1:1 ratio.

Over the 18-month study period, both groups deteriorated on the Clinical Dementia Rating Scale-sum of the boxes (CDR-SB) and on other secondary clinical end points, as expected in Alzheimer’s disease. However, clinical deterioration in the lecanemab group was 27% slower compared to placebo after 18 months, resulting in a statistically highly significant difference.

1 table, 3 figures, no imaging

3. Haug CJ, Drazen JM. Artificial Intelligence and Machine Learning in Clinical Medicine, 2023. Drazen JM, Kohane IS, Leong TY, eds. New England Journal of Medicine. 2023;388(13):1201-1208. doi:10.1056/NEJMra2302038

What are the standards to which AI and machine learning–based interventional research should be held, if an app is going to be accepted as the standard that will shape, reform, and improve clinical practice? That research has three components. First, the research must be structured to answer a clinically meaningful question in a way that can influence the behavior of the health professional and lead to an improvement in outcomes for a patient. Second, the intervention must be definable, scalable, and applicable to the problem at hand. It must not be influenced by factors outside the domain of the problem and must yield outcomes that can be applied to similar clinical problems across a wide range of populations and disease prevalence. Can AI and machine learning–driven care meet these standards — ones that we demand from a novel therapeutic intervention or laboratory-based diagnostic test — or do we need to have a unique set of standards for this type of intervention? Third, when the results of the research are applied in such a way as to influence practice, the outcome must be beneficial for all patients under consideration, not just those who are like the ones with characteristics and findings on which the algorithm was trained. This raises the question of whether such algorithms should include consideration of public health (i.e., the use of scarce resources) when diagnostic or treatment recommendations are being made and the extent to which such considerations are part of the decision-making process of the algorithm. Such ethical considerations have engaged health professionals and the public for centuries.

3 figures

4. Sarraj A, Hassan AE, Abraham MG, et al. Trial of Endovascular Thrombectomy for Large Ischemic Strokes. New England Journal of Medicine. 2023;388(14):1259-1271. doi:10.1056/NEJMoa2214403

The authors performed a prospective, randomized, open-label, adaptive, international trial involving patients with stroke due to occlusion of the internal carotid artery or the first segment of the middle cerebral artery to assess endovascular thrombectomy within 24 hours after onset. Patients had a large ischemic-core volume, defined as an ASPECT score of 3 to 5 (range, 0 to 10, with lower scores indicating larger infarction) or a core volume of at least 50 ml on computed tomography perfusion or diffusion-weighted magnetic resonance imaging. Patients were assigned in a 1:1 ratio to endovascular thrombectomy plus medical care or to medical care alone. The primary outcome was the modified Rankin scale score at 90 days (range, 0 to 6, with higher scores indicating greater disability). Functional independence was a secondary outcome.

The trial was stopped early for efficacy; 178 patients had been assigned to the thrombectomy group and 174 to the medical-care group. The generalized odds ratio for a shift in the distribution of modified Rankin scale scores toward better outcomes in favor of thrombectomy was 1.51.  A total of 20% of the patients in the thrombectomy group and 7% in the medical-care group had functional independence. Mortality was similar in the two groups. In the thrombectomy group, arterial access-site complications occurred in 5 patients, dissection in 10, cerebral-vessel perforation in 7, and transient vasospasm in 11. Symptomatic intracranial hemorrhage occurred in 1 patient in the thrombectomy group and in 2 in the medical-care group.

The results of the SELECT2 trial, which involved patients from broad geographic regions, showed that endovascular thrombectomy plus medical care resulted in better clinical outcomes than medical care alone in patients with a large ischemic core who presented within 24 hours after the time they were last known to be well.

2 figures, 3 tables

5. Schnurman Z, Benjamin CG, Miceli M, Sen C. Clival Chordomas in the Endoscopic Endonasal Era: Comparison With Management With Open Skull Base Approaches. Neurosurgery. 2023;92(4):756-761. doi:10.1227/neu.0000000000002286

The most significant surgical advancement for treating clival chordomas has been the increasing application of the endoscopic endonasal approach over the past 2 decades. Using a ventral, midline approach endoscopically, through the nasal passages, has been argued to be a more logical trajectory to reach clival chordomas, with the possibility of reducing extensive bone removal, brain retraction, and manipulation of cranial nerves that is inherent to larger open approaches.

The objective of this study was to compare a large series of patients treated by a single surgeon using primarily endoscopic endonasal approaches with previously published outcomes by the same surgeon using open skull base approaches. Between 2006 and 2020, 68 patients with skull base chordoma underwent resection using primarily endoscopic endonasal approaches. Outcomes and complications were compared with previously published results of resection of chordomas from 1991 to 2005 using open skull base approaches.

Compared with the prior cohort, the current principally endoscopic cohort demonstrated similar rates of OS and progression-free survival, but patients undergoing first-time resection had significantly higher rates of radical resection (82.9% compared with 64.3%) and required fewer staged surgeries.

There was no difference in survival rates for patients treated in the current era, primarily using endoscopic endonasal techniques, compared with previously published results using open skull-base approaches by the same surgeon. Although use of endoscopic endonasal approach resulted in higher rates of radical resection, patients undergoing first-time resection and fewer staged surgeries were required. The reason for the discrepancy in improvements in rates of radical resections between first-time resections and repeat resections is that repeat resections more frequently required open skull base approaches, with only 33% using the endoscopic endonasal approach alone, and 41% requiring open lateral approaches.

3 tables, 1 figure, no images

6. Lee BC, Tsai HH, Liu CJ, et al. Cerebral Venous Reflux and Cerebral Amyloid Angiopathy: An Magnetic Resonance Imaging/Positron Emission Tomography Study. Stroke. 2023;54(4):1046-1055. doi:10.1161/STROKEAHA.122.040503

Cerebral venous outflow alterations contribute to central nervous system pathology in aging and neurodegenerative disorders and are potentially linked to underlying cerebral microangiopathy. The authors investigated whether cerebral venous reflux (CVR) is more closely associated with cerebral amyloid angiopathy (CAA) than hypertensive microangiopathy in intracerebral hemorrhage (ICH) survivors. This cross-sectional study included 122 patients of spontaneous ICH with magnetic resonance and positron emission tomography imaging studies (2014–2022) in Taiwan. The presence of CVR was defined as abnormal signal intensity in the dural venous sinus or internal jugular vein on magnetic resonance angiography. Cerebral amyloid load was measured using the Pittsburgh compound B standardized uptake value ratio. Clinical and imaging characteristics associated with CVR were evaluated in univariable and multivariable analyses. In the subset of patients with CAA, they applied univariable and multivariable linear regression analyses to evaluate the association between CVR and cerebral amyloid retention.

Compared with patients without CVR (n=84), patients with CVR (n=38) were significantly more likely to have CAA-ICH (53.7% versus 19.8%) and had a higher cerebral amyloid load, 1.28 versus 1.06. In a multivariable model, CVR was independently associated with CAA-ICH (odds ratio, 4.81 after adjustment for age, sex and conventional small vessel disease markers. In CAA-ICH, higher PiB retention was observed in patients with CVR than patients without CVR. In multivariable analysis after adjustment for potential confounders, the presence of CVR was independently associated with a higher amyloid load.

They conclude that in spontaneous ICH, CVR is associated with CAA and a higher amyloid burden. The authors results suggest venous drainage dysfunction potentially plays a role in CAA and cerebral amyloid deposition.

3 tables, 3 figures, with MR imaging

7. Ioannidis JPA, Pezzullo AM, Boccia S. The Rapid Growth of Mega-Journals. JAMA. 2023;2015(5). doi:10.1001/jama.2023.3212

Mega-journals, those that publish large numbers of articles per year, are growing rapidly across science and especially in biomedicine. Although 11 Scopus-indexed journals published more than 2000 biomedical full papers (articles or reviews) in 2015 and accounted for 6% of that year’s literature, in 2022 there were 55 journals publishing more than 2000 full articles, totaling more than 300,000 articles (almost a quarter of the biomedical literature that year). In 2015, 2 biomedical research journals (PLoS One and Scientific Reports) published more than 3500 full articles. In 2022, there were 26 such prolific journals. The accelerating growth of mega-journals creates both threats and opportunities for biomedical science.

No figures or tables

8. Sabben C, Charbonneau F, Delvoye F, et al. Endovascular Therapy or Medical Management Alone for Isolated Posterior Cerebral Artery Occlusion: A Multicenter Study. Stroke. 2023;54(4):928-937. doi:10.1161/STROKEAHA.122.042283

The authors conducted a multicenter international observational study of consecutive stroke patients admitted within 6 hours from symptoms onset in 26 stroke centers with isolated occlusion of the first (P1) or second (P2) segment of the posterior cerebral artery and treated either with BMM+EVT or BMM alone. Propensity score with inverse probability of treatment weighting was used to account for baseline between-groups differences. The primary outcome was 3-month good functional outcome (modified Rankin Scale [mRS] score 0–2 or return to baseline modified Rankin Scale). Secondary outcomes were 3-month excellent recovery (modified Rankin Scale score 0–1), symptomatic intracranial hemorrhage, and early neurological deterioration.

Overall, 752 patients were included (167 and 585 patients in the BMM+EVT and BMM alone groups, respectively). Median age was 74 years, 329 (44%) patients were female, median National Institutes of Health Stroke Scale was 6, and occlusion site was P1 in 188 (25%) and P2 in 564 (75%) patients. Baseline clinical and radiological data were similar between the 2 groups following propensity score weighting. EVT was associated with a trend towards lower odds of good functional outcome and was not associated with excellent functional outcome. EVT was associated with a higher risk of symptomatic intracranial hemorrhage and early neurological deterioration.

More than one-third of this cohort was unable to live independently at 3 months (mRS above 2), and 57% of patients had some degree of disability (mRS above 1), in line with previous reports. This indicates that despite relatively low NIHSS scores on admission (median value of 6), proximal PCA occlusion stroke is a disabling condition.

In this observational study of patients with proximal posterior cerebral artery occlusion, EVT was not associated with good or excellent functional outcome as compared to BMM alone. However, EVT was associated with higher rates of symptomatic intracranial hemorrhage and early neurological deterioration. EVT should not be routinely recommended in this population, but randomization into a clinical trial is highly warranted.

3 figures, 3 tables, no imaging

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1. Dittrich TD, Sporns PB, Kriemler LF, et al. Mechanical Thrombectomy Versus Best Medical Treatment in the Late Time Window in Non-DEFUSE-Non-DAWN Patients: A Multicenter Cohort Study. Stroke. 2023;54(3):722-730. doi:10.1161/STROKEAHA.122.039793

The authors assessed the efficacy and safety of mechanical thrombectomy (MT) in adult stroke patients with anterior circulation large vessel occlusion presenting in the late time window not fulfilling the DEFUSE-3 (Thrombectomy for Stroke at 6 to 16 Hours With Selection by Perfusion Imaging trial) and DAWN (Thrombectomy 6 to 24 Hours After Stroke With a Mismatch Between Deficit and Infarct trial) inclusion criteria. This was a cohort study of adults with anterior circulation large vessel occlusion admitted between 6 and 24 hours after last-seen-well at 5 participating Swiss stroke centers between 2014 and 2021. Mismatch was assessed by CT or MR perfusion with automated software (RAPID or OLEA). They excluded patients meeting DEFUSE-3 and DAWN inclusion criteria and compared those who underwent MT with those receiving best medical treatment alone by inverse probability of treatment weighting using the propensity score. The primary efficacy end point was a favorable functional outcome at 90 days, defined as a modified Rankin Scale score shift toward lower categories. The primary safety end point was symptomatic intracranial hemorrhage within 7 days of stroke onset; the secondary was all-cause mortality within 90 days.

Among 278 patients with anterior circulation large vessel occlusion presenting in the late time window, 190 (68%) did not meet the DEFUSE-3 and DAWN inclusion criteria and thus were included in the analyses. Of those, 102 (54%) received MT. In the inverse probability of treatment weighting analysis, patients in the MT group had higher odds of favorable outcomes compared with the best medical treatment alone group (modified Rankin Scale shift: acOR, 1.46) and lower odds of all-cause mortality within 90 days (aOR, 0.59). There were no significant differences in symptomatic intracranial hemorrhage (MT versus best medical treatment alone: 5% versus 2%, P=0.63).

They conclude that two out of 3 patients with anterior circulation large vessel occlusion presenting in the late time window did not meet the DEFUSE-3 and DAWN inclusion criteria. In these patients, MT was associated with higher odds of favorable functional outcomes without increased rates of symptomatic intracranial hemorrhage. These findings support the enrollment of patients into ongoing randomized trials on MT in the late window with more permissive inclusion criteria.

Both DEFUSE-3 and DAWN trials had very restrictive inclusion criteria. In this MT group, the main reasons for DEFUSE-3 ineligibility were distal occlusion site (ie, isolated occlusion of the M2 segment), low baseline NIHSS score (ie, <6 points), premorbid functional disability (ie, mRS score >2 points), and treatment with intravenous tissue-type plasminogen activator >4.5 hours after last known-well. Main reasons for DAWN ineligibility were the absence of clinical-imaging-mismatch, low baseline NIHSS score (ie, <10 points), and premorbid functional disability (ie, mRS score >1 point).

2 figures, 4 tables

2. Puetz V, Lutsep HL, Nguyen TN. Endovascular Therapy for Basilar Artery Occlusion: Among the First to Conceptualize, Last to Prove. Stroke. 2023;(March):905-908. doi:10.1161/strokeaha.122.041645

Nice summary of the current state of endovascular therapy for BAO.

The BASICS (Basilar Artery International Cooperation Study) and BEST (Basilar Artery Occlusion: Endovascular Interventions vs Standard Medical Treatment) trials were 2 seminal randomized trials comparing EVT to best medical management (BMM) in patients with BAO presenting up to the 6 and 8 hour window of estimated time of BAO. Both trials were neutral in demonstrating superiority of EVT for BAO despite a direction of treatment effect in favor of EVT.  Several concepts emerged from the BASICS trial in the selection of BAO patients that now define the care and benchmark for future study. In contrast to the traditional concept of time since last known well in the acLVO trials, the BASICS registry and BASICS trial defined the notion of estimated time of onset. Patients who had transient or minor neurological symptoms prior to the estimated time of acute BAO could be candidate for intravenous thrombolysis (IVT) and enrollment in the BASICS trial, hence broadening inclusion of patients who may have otherwise been excluded. We also learned from BASICS that patients with minor deficits, defined as a NIHSS score below 10, had equivocal outcomes of EVT compared to BMM.

ATTENTION (Endovascular Treatment for Acute Basilar-Artery Occlusion) was a randomized trial comparing endovascular versus best medical management in patients with BAO presenting within 12 hours of estimated time of BAO, with moderate to severe symptoms as defined by NIHSS score ≥10, and posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) ≥6. (pc-ASPECTS reference -https://doi.org/10.1161/STROKEAHA.107.511162). The primary end point of good functional outcome defined as modified Rankin Scale score 0 to 3 was 2-fold greater in the EVT compared to MM group.

BAOCHE (Basilar Artery Occlusion Chinese Endovascular) was a randomized trial also comparing EVT versus best medical management in patients with BAO presenting from 6 to 24 hours since symptom onset, NIHSS score ≥6, and pc-ASPECTS ≥6. As the enrollment window was extended, approximately 18% of patients received IVT. The trial was halted after interim analysis demonstrated a nearly 2-fold greater proportion of patients achieving the primary outcome (modified Rankin Scale score 0 to 3) in the EVT compared to MM group.

The “good-scan-occlusion” paradigm, which has been applied in the acLVO EVT trials by selection of patients based on the detection of an acLVO and an ASPECTS score of 5 to 6 or above, has now been shown to work for identifying patients with BAO who benefit from EVT. ATTENTION and BAOCHE were the first BAO trials which applied imaging scores, including pc-ASPECTS ≥6 and the pons-midbrain index. The good news is that in patients with BAO, this principle works for late-window patients until 24 hours without requiring advanced imaging.

3. Chandra R, Saini HS, Palmer KN, Cerejo R. The link between reversible cerebral vasoconstriction syndrome and transient global amnesia. Headache: The Journal of Head and Face Pain. 2023;63(1):168-172. doi:10.1111/head.14432

RCVS is a cerebrovascular phenomenon that presents clinically as recurrent TCHs predominantly affecting females. Although RCVS is a self-limited entity, significant complications of subarachnoid hemorrhage, cerebral infarction and seizures have been reported leading to disability and poor functional outcomes. According to recent literature, the frequency of TCH is the most predictive diagnostic factor for RCVS with a sensitivity and specificity of 74% and 98%, respectively. Definite TGA is characterized by a sudden onset of anterograde amnesia without clouding or loss of consciousness, lack of epileptic features, head trauma and focal neurologic deficits witnessed by a reliable observer during the attack, furthermore the amnestic event must resolve within 24 h. RCVS and TGA are rare disorders with an annual incidence of three and 3–10 cases per million, respectively, in the general population. The patient described in this case was given an RCVS2 score of 8 (recurrent TCH, vasoconstrictive trigger present) indicating sensitivity and specificity of 90% and 99%, respectively for diagnosis of RCVS. He also met the criteria for definite TGA as he had witnessed clear anterograde amnesia during the attack without head trauma, epileptic features, and focal neurologic deficits with resolution of amnesia within 12 h from onset. Interestingly, the MRI findings in this patient correlated with symptom onset in that it suggested an acute/subacute timeframe. Given the chronology of events that led to the patient’s hospital admission, it is likely that RCVS led to his presentation of TGA. RCVS and TGA are two acute and reversible intra-cerebral conditions whose coexistence has been reported in a total of six cases worldwide (see table). The authors report the seventh case, linking RCVS to TGA and propose a common pathophysiologic link.

1 table, 1 figure

4. Gilligan M, McGuigan C, McKeon A. Paraneoplastic Neurologic Disorders. Curr Neurol Neurosci Rep. 2023;(January). doi:10.1007/s11910-023-01250-w

Paraneoplastic neurologic disorders are heterogeneous autoimmune diseases occurring in the context of a non-nervous system cancer (solid organ or hematologic). They can arise as the clinical presentation for a previously undiagnosed cancer (e.g., a woman who presents with ataxia in whom ovarian adenocarcinoma is subsequently detected). Paraneoplastic neurological disorders can also arise during treatment for a recently diagnosed cancer, or can be the clinical presentation alerting the treating providers to a cancer relapse. These disorders can target any part of the neuraxis, rostrocaudally, from cerebral cortex to neuromuscular junction, though certain classical syndromes, now known as “high risk phenotypes,” have the highest risk for accompanying cancer (Limbic encephalitis, Encephalomyelitis, Rapidly progressive cerebellar syndrome, Subacute sensory neuronopathy, Gastro-intestinal pseudo-obstruction, Lambert Eaton myasthenic syndrome, Opsoclonus myoclonus, Dermatomyositis).

In paraneoplastic limbic encephalitis, T2 hyperintensity of the mesial temporal lobes is typical, occasionally with contrast enhancement. In extra-limbic paraneoplastic encephalitides, MRI may demonstrate extratemporal lobar abnormalities that can resemble infectious or neoplastic processes. Linear, radial enhancement extending from the lateral ventricles is a characteristic MRI imaging finding in GFAP astrocytopathy. Distinctive radiological features also arise in GABAA-R encephalitis characterized by multi-lobar deep white matter and juxtacortical lesions on FLAIR imaging (without enhancement). In many instances, MRI of the brain can be entirely normal, including most patients with anti-NMDA receptor encephalitis.

3 tables, 1 figure

5. Tochigi S, Isoshima A, Ohashi H, et al. Preoperative assessment of dominant occipital sinus in patients with Chiari malformation type I: anatomical variations and implications for preventing potentially life-threatening surgical complications. J Neurosurg. 2023;138(2):540-549. doi:10.3171/2022.5.JNS212973

The surgical treatment of Chiari malformation type I (CM-I) frequently involves dural incision at the posterior cranial fossa. In cases of persistent patent occipital sinus (OS), the sinus is usually obliterated and divided. However, there are some patients whose OS is prominent and requires crucial modification of the operative planning to avoid potentially life-threatening massive hemorrhage and disturbance of cerebral venous circulation. In the present study, the anatomical variations of the dominant OS in patients with CM-I were analyzed and the authors attempted to develop treatment recommendations for patients with CM-I with dominant OS. The study included 213 patients with CM-I who underwent MR venography (MRV) prior to surgical treatment. OS dominance was assessed using 2D time-of-flight MRV or 3D phase-contrast MRV. Particular attention was paid to the pattern of venous outflow channels. The characteristics of the patients with dominant OS and the surgical outcomes were retrospectively reviewed. Dominant OS was identified in 7 patients (3.3%). The age in those with dominant OS was significantly younger than in those without. The incidence of concurrent scoliosis in the patients with dominant OS was significantly higher than in those without. All the dominant OSs were found to be of the oblique type. Multiple variations of venous drainage are described, with a helpful graphic. Bilateral OOSs with bilateral hypoplastic TSs were found in 2 patients (0.9%). Instead of performing Y-shaped dural incision and duraplasty, surgical procedures were modified depending on the types of the OOSs to preserve their venous drainage routes. Although massive bleeding from the dominant OS during dural incision occurred in 1 patient, none suffered neurological deterioration. The syrinx volume decreased in all but 1 of the patients postoperatively.

Considering the potentially devastating outcomes after obliterating a dominant OS resulting from Y-shaped duraplasty for CM-I, evaluating the venous drainage pattern prior to surgery is indispensable for safe surgical treatment. Even though the additional evaluation is costly and time-consuming, obtaining MRV prior to surgery is recommended, especially for the young and for patients with concurrent scoliosis.

4 figures, 2 tables, with MRI and MRV

6. Cools MJ, Wellons JC, Iskandar BJ. The Nomenclature of Chiari Malformations. Neurosurg Clin N Am. 2023;34(1):1-7. doi:10.1016/j.nec.2022.08.003

Nice review, particularly of the less commonly described Chiari 0, 0.5, and 1.5.

Regarding Chiari 0, in 1998, Iskandar and colleagues described five patients who presented with syringomyelia without tonsillar herniation who responded to posterior fossa decompression, which came to be known as a Chiari 0 malformation. Their patients all had improvement in clinical symptoms and a decrease in syrinx size. In a subsequent article with 10 additional patients, the authors showed similar findings, showing postoperative syrinx improvement in 9 patients, and stabilization in 1. Kyoshima and colleagues similarly described their experience with four patients with syringomyelia without tonsillar descent that improved after posterior fossa decompression, which they termed “tight cisterna magna.” It later became evident that patients with a Chiari type 0 malformation, whereas they lack tonsillar herniation, seem to have MRI evidence of other more subtle posterior fossa structural abnormalities, including the location of the obex below the level of the foramen magnum, indicating caudal descent of the brainstem, an enlarged anterior-posterior brainstem diameter at the level of the foramen magnum on sagittal imaging, an increase in the basion to opisthion distance compared with normal controls.

The challenge with the Chiari 0 diagnosis, which keeps it controversial, is the inability to distinguish Chiari 0 from true idiopathic syringomyelia. Although a lower position of the obex and other structural variations noted above, along with crowding of the subarachnoid spaces at the foramen, may be suggestive of Chiari 0 –the only reliable distinguishing feature is the response to posterior fossa decompression (postoperative resolution of the syrinx indicates Chiari 0 pathophysiology). This means that at least for now, Chiari 0 is a postoperative diagnosis, and remains a diagnosis of exclusion, in that all other causes of syringomyelia and symptoms need to be carefully ruled out, including tumor, arachnoiditis, tethered cord, and trauma.

1 table, 3 figures, with MRI

7. Chalif EJ, Morshed RA, Oh T, Dalle Ore C, Aghi MK, Gupta N. Neurosurgical Outcomes for Pediatric Central Nervous System Tumors in the United States. Neurosurgery. 2023;92(2):407-420. doi:10.1227/neu.0000000000002215

Limited data exist on pediatric central nervous system (CNS) tumors, and the results from the National Cancer Database, the largest multicenter national cancer registry, have not previously been comprehensively reported. The authors aimed to capture pediatric neurosurgical outcomes and investigate possible disparities of care. The National Cancer Database was queried for pediatric patients who were diagnosed with CNS tumors from 2004 to 2018. Primary outcomes included 30/90 days postoperative mortality (30M/90M), readmission within 30 days of discharge (30R), and length of inpatient stay (LOS). Twenty four thousand nine hundred thirty cases met the inclusion criteria, of which were 4753 (19.1%) juvenile pilocytic astrocytomas, 3262 (13.1%) medulloblastomas, 2200 (8.8%) neuronal/mixed neuronal-glial tumors, and 2135 (8.6%) ependymal tumors.

Patients aged 0 to 4 years had significantly poorer outcomes than patients in older age groups (90M: 3.5% vs 0.7%-0.9%). Tumor size was a strong predictor of poor outcomes with each additional cm in diameter conferring a 26%, 7%, and 23% increased risk of 90M, 30R, and prolonged LOS, respectively. Data over the study period demonstrated year over year improvements of 4%, 3%, and 2%, respectively, for 90M, readmission within 30 days of discharge, and prolonged LOS. Facilities with a high volume of pediatric tumor cases had improved 90M and LOS. Patients with private health insurance had better outcomes than patients with government insurance.

The authors demonstrate that treatments and outcomes differ by patient race, income, and insurance status. In addition, patients of lower socioeconomic status were more often treated at a low volume facility (LVF), and these were both risk factors for poorer outcomes. Although one might hypothesize that aggressive surgical intervention at LVFs was not as often pursued, thereby leading to worse outcomes, they found no statistically significant differences in extent of resection (EOR) between high volume facility and LVF or among socioeconomic groups. They also investigated these outcome differences by examining which patients were more likely to receive adjuvant treatment. Hispanic patients had reduced rates of radiation treatment compared with White patients, government-insured patients had reduced rates of chemoradiation than privately insured patients, and receipt of chemoradiation correlated negatively with lower income. Of note, many of the same socioeconomic groups that had less adjuvant treatment also had poorer outcomes.

They conclude that there is substantial variability in surgical morbidity and mortality of pediatric CNS tumors. Additional investigation is warranted to reduce outcome differences that may be based on socioeconomic factors.

3 tables, 5 figures, no imaging

8. Kashkoush AI, Whiting BB, Desai A, et al. Clinical Outcomes After Nonoperative Management of Large Acute Traumatic Subdural Hematomas in Older Patients: A Propensity-Scored Retrospective Analysis. Neurosurgery. 2023;92(2):293-299. doi:10.1227/neu.0000000000002192

The authors investigated inpatient mortality after conservative management of large aSDHs. Single-center retrospective review of adult patients with traumatic brain injury from 2018 to 2021 revealed 45 large aSDHs that met inclusion criteria. Inpatient outcomes included mortality, length of stay, and discharge disposition. Follow-up data included rate of surgery for chronic SDH progression. Patients with large aSDHs were 2:1 propensity score–matched to patients with small (<1 cm) aSDHs based on age, Injury Severity Scale, Glasgow Coma Scale, and Rotterdam computed tomography scale. Median age was (78 years), sex (male 52%), and race (Caucasian 91%) which were similar between both groups. Inpatient outcomes including length of stay (P = .32), mortality (P = .37), and discharge home (P = .28) were similar between those with small and large aSDHs. On multivariate logistic regression (odds ratio [95% CI]), increased in-hospital mortality was predicted by Injury Severity Scale , Rotterdam computed tomography scale 3 to 4, parafalcine, tentorial location, or presence of an intracranial contusion. Patients with large aSDHs trended toward higher progression on follow-up computed tomography of the head (36% vs 16%) and higher rates of chronic SDH surgery (25% vs 7%). They conclude that in conservatively managed patients with minimal symptoms and mass effect on computed tomography of the head, increasing SDH size did not contribute to worsened in-hospital mortality or length of stay. Patients with large aSDHs may undergo an initial course of nonoperative management if symptoms and the degree of mass effect are mild.

6 tables, 1 figure

The American Society of Neuroradiology is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Visit the ASNR Education Connection website to claim CME credit for this podcast.

1. Kato S, Maesawa S, Bagarinao E, et al. Magnetic resonance–guided focused ultrasound thalamotomy restored distinctive resting-state networks in patients with essential tremor. J Neurosurg. 2023;138(2):306-317. doi:10.3171/2022.5.JNS22411

Magnetic resonance–guided focused ultrasound (MRgFUS) thalamotomy ameliorates symptoms in patients with essential tremor (ET). How this treatment affects canonical brain networks has not been elucidated. The purpose of this study was to clarify changes of brain networks after MRgFUS thalamotomy in essential tremor patients by analyzing resting-state networks (RSNs). Fifteen patients with ET were included in this study. Left MRgFUS thalamotomy was performed in all cases, and MR images, including resting-state functional MRI (rsfMRI), were taken before and after surgery. MR images of 15 age- and sex-matched healthy controls (HCs) were also used for analysis. Using rsfMRI data, canonical RSNs were extracted by performing dual regression analysis, and the functional connectivity (FC) within respective networks was compared among pre-MRgFUS patients, post-MRgFUS patients, and healthy controls. The severity of tremor was evaluated using the Clinical Rating Scale for Tremor (CRST) score pre- and postoperatively, and its correlation with RSNs was examined. Preoperatively, essential tremor patients showed a significant decrease in functional connectivity in the sensorimotor network (SMN), primary visual network (VN), and visuospatial network (VSN) compared with HCs. The decrease in functional connectivity in the sensorimotor network correlated with the severity of tremor. After MRgFUS thalamotomy, essential tremor patients still exhibited a significant decrease in functional connectivity in a small area of the sensorimotor network, but they exhibited an increase in the cerebellar network (CN). In comparison between pre- and post- MRgFUS patients, the functional connectivity in the sensorimotor network and the visuospatial network significantly increased after treatment.

The sensorimotor network and cerebellar network, which are considered to be associated with the cerebello-thalamo-cortical loop, exhibited increased connectivity after MRgFUS thalamotomy. In addition, the FC of the visual network, which declined in essential tremor patients compared with HCs, tended to normalize postoperatively. This demonstrates the possibility of using RSN changes as biomarkers for successful treatment.

5 figures, 4 tables

2. Jamshidi AM, Soldozy S, Levi AD. Percutaneous Direct Pars Repair in Young Athletes. Neurosurgery. 2023;92(2):263-270. doi:10.1227/neu.0000000000002210

Lumbar pars defects are common in adolescent athletes and are often due to recurrent axial loading and traumatic stressors. The objective of the study was to present an updated case series of young athletes who underwent percutaneous direct pars repair after failure of conservative management.

The literature suggests that conservative management should be used for at least 6 months before surgical intervention. In this series of 21 patients, all patients failed conservative management after a mean nonoperative treatment duration of 20.5 ± 9.3 months. These cases were specifically referred from outside institutions for a minimally invasive surgical option after failure of conservative treatment.

A single-center, nonrandomized, retrospective observation study of athletes who were referred for minimally invasive direct pars repair after failure of at least 6 months of conservative management was performed. A total of 21 patients were included (mean age 17.47 years, range 14-25 years), 6 of whom were female (29%). All patients presented with bilateral pars fractures, with L5 being the most frequent level involved (n = 13). The average follow-up time was 31.52 months.

The visual analog scale score for back pain was significantly reduced from 7.62 preoperatively to 0.28 at the final postoperative examination (P < .01). Fusion was noted in 20 of the 21 patients on final follow-up (95%).

They conclude that percutaneous direct pars repair is a safe and effective means in treating young adolescents who have failed conservative management. The advantages included minimized muscle and soft tissue dissection, reduced blood loss, and early mobilization and recovery. In young athletes who desire return to high-level physical activity, this surgical technique is of particular benefit and should be considered in this patient population.

Despite conservative measures, some patients continue to experience pain. Surgical repair of the pars defect can be offered for this small minority of patients who qualify. In this cohort, despite the broad referral area and adherence to minimum conservative treatment periods combined with the 12-year recruitment period, only 21 surgical cases were selected. These facts highlight that the indication for surgery is relatively rare and that most patients respond well to conservative treatment. For those who underwent surgery, a similar return-to-play rate was seen when compared with those patients who were managed conservatively (90.3%vs 92.2%, respectively).

4 figures, 2 tables, with MR, CT, intraop fluoro

3. Schaff LR, Mellinghoff IK. Glioblastoma and Other Primary Brain Malignancies in Adults. (a review) JAMA. 2023;329(7):574. doi:10.1001/jama.2023.0023

Approximately 50% of malignant brain tumors are glioblastomas, and 30% are diffusely infiltrating lower-grade gliomas. Other malignant brain tumors include primary central nervous system (CNS) lymphoma (7%) and malignant forms of ependymomas (3%) and meningiomas (2%). Symptoms of malignant brain tumors include headache (50%), seizures (20%-50%), neurocognitive impairment (30%-40%), and focal neurologic deficits (10%-40%). MRI before and after a gadolinium-based contrast agent is the preferred imaging modality for evaluating brain tumors. Diagnosis requires tumor biopsy with consideration of histopathological and molecular characteristics. Treatment varies by tumor type and often includes a combination of surgery, chemotherapy, and radiation.

For patients with glioblastoma, the combination of temozolomide with radiotherapy improved survival when compared with radiotherapy alone (2-year survival, 27.2% vs 10.9%; 5-year survival, 9.8% vs 1.9%). In patients with anaplastic oligodendroglial tumors with 1p/19q codeletion, probable 20-year overall survival following radiotherapy without vs with the combination of procarbazine, lomustine, and vincristine was 13.6% vs 37.1% (80 patients) in the EORTC 26951 trial and 14.9% vs 37% in the RTOG 9402 trial (125 patients). Treatment of primary CNS lymphoma includes high-dose methotrexate-containing regimens, followed by consolidation therapy with myeloablative chemotherapy and autologous stem cell rescue, nonmyeloablative chemotherapy regimens, or whole brain radiation.

3 figures and 2 tables, including a schematic of Integration of Histological Features and Molecular Alterations in the Revised WHO Classification of Tumors of the Central Nervous System

4. Mantovani A, Garlanda C. Humoral Innate Immunity and Acute-Phase Proteins. N Engl J Med. 2023;388(5):439-452. doi:10.1056/NEJMra2206346

Systemic manifestations of inflammation include fever, alterations in leukocyte counts, cardiovascular reactions, endocrine responses, and reorientation of metabolism in association with increased production of a diverse set of molecules referred to as acute-phase proteins. The prototypic acute-phase protein, C-reactive protein, was originally described as a molecule that was present in the circulation of patients with infections and that was capable of recognizing the C-type polysaccharides of Streptococcus pneumoniae. The appearance of increased levels of acute phase proteins in blood and other body fluids is part of a more complex response to local inflammation or to systemic inflammation (e.g., sepsis) that has been referred to as the acute-phase response, which is characterized by decreased production of albumin by hepatocytes, reorientation of iron metabolism, and hormonal changes.

Innate immunity is a first line of resistance against microbial pathogens and is involved in the activation of adaptive immune responses, as well as in tissue repair. Innate immunity is made up of a cellular arm and a humoral arm. The molecular strategies used by the cellular arm to sense microbial moieties and tissue damage involve cell-associated pattern-recognition molecules located in different cellular compartments (plasma membrane, endosomes, and cytoplasm) and belonging to different molecular families, including toll-like receptors (TLRs), nucleotide- binding oligomerization domain (NOD)–like and retinoic acid–inducible gene I (RIG-I)– like receptors.

The activation of these receptors leads to the expression of cytokines (including interferons and chemokines), adhesion molecules, and antimicrobial effectors or to the scavenging of microbes through phagocytosis. The humoral arm of the innate immune system is made up of different classes of molecules, such as pentraxins, collectins, and ficolins, which functionally act as ancestors of antibodies (anteantibodies) by initiating complement activation, opsonizing microbes and damaged cells, agglutinating or neutralizing microbes, and regulating inflammation.

4 figures, 1 table

5. Hornung AL, Barajas JN, Rudisill SS, et al. Prediction of lumbar disc herniation resorption in symptomatic patients: a prospective, multi-imaging and clinical phenotype study. Spine Journal. 2023;23(2):247-260. doi:10.1016/j.spinee.2022.10.003

Prospective study with patients recruited at a single center study which aimed to identify determinants that may predict early versus late LDH resorption. Ninety-three consecutive patients diagnosed with acute symptomatic LDH were included in this study with a mean age of 48.7 years. LDH resorption was classified as early (<3 months) or late (>3 months) (n=23 early resorption and n=67 late resorption groups). Lumbar MRIs were performed approximately every 3 months for 1 year from time of enrollment to assess disc integrity. A prediction model of pretreatment factors was constructed.

Using four pretreatment clinical factors, a prognostic model was developed to predict the likelihood of disc resorption within 3 months of conservative management consisting of gabapentin, acupuncture, and avoidance of anti-inflammatory medication. The model, which demonstrated good discrimination and excellent overall performance, identified greater L4 posterior vertebral height, greater sacral slope, and greater herniated volume at baseline to be most predictive of early resorption. In contrast, the presence of multiple herniations was associated with a low probability of early resorption. No association with disc degeneration grade, endplate changes including Modic changes, HIZ presence, or osteophytes.

3 figures, 7 tables

6. Fadda G, Flanagan EP, Cacciaguerra L, et al. Myelitis features and outcomes in CNS demyelinating disorders: Comparison between multiple sclerosis, MOGAD, and AQP4-IgG-positive NMOSD. Front Neurol. 2022;13. doi:10.3389/fneur.2022.1011579

Inflammatory myelopathies can manifest with a combination of motor, sensory and autonomic dysfunction of variable severity. Depending on the underlying etiology, the episodes of myelitis can recur, often leading to irreversible spinal cord damage and major long-term disability. Three main demyelinating disorders of the central nervous system, namely multiple sclerosis (MS), aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders (AQP4+NMOSD) and myelin oligodendrocyte glycoprotein-IgG associated disease (MOGAD), can induce spinal cord inflammation through different pathogenic mechanisms, resulting in a more or less profound disruption of spinal cord integrity. This ultimately translates into distinctive clinical-MRI features, as well as distinct patterns of disability accrual, with a step-wise worsening of neurological function in MOGAD and AQP4+NMOSD, and progressive disability accrual in MS. Early recognition of the specific etiologies of demyelinating myelitis and initiation of the appropriate treatment is crucial to improve outcome.

In this review article the authors summarize and compare the clinical and imaging features of spinal cord involvement in these three demyelinating disorders, both during the acute phase and over time, and outline the current knowledge on the expected patterns of disability accrual and outcomes.

Several elements differentiate the typical imaging features of AQP4+NMOSD from MS. A single, longitudinally extensive lesion (i.e., spanning over three or more vertebral segments) is observed in over 80% of cases, but lesions may appear short in 14% of cases, particularly when imaged during the phase of development or resolution. During myelitis attacks, T1-hypointensity can be observed even with conventional sequences, in contrast to the typical T1 isointensity observed in MS or MOGAD spinal cord lesions. Lesions in AQP4+NMOSD predominantly appear centrally located on axial views. Cervical lesions may sometimes extend rostrally to involve the medulla. Gadolinium enhancement is present in almost all myelitis lesions acutely, with variable patterns but typically localizing at lesion margin, with ring or elongated ring enhancement pattern observed in about 30% of cases. A characteristic imaging finding is the presence of bright spotty lesions, defined as areas of higher T2-hyperintensity within the spinal cord lesion that are comparable to the signal intensity of CSF. This finding has shown specificity for AQP4+NMOSD of 94% vs. a range of inflammatory and non-inflammatory myelopathies, and a sensitivity of 40%.

2 tables, 4 figures with MRI

7. Flanagan EP, Geschwind MD, Lopez-Chiriboga AS, et al. Autoimmune Encephalitis Misdiagnosis in Adults. JAMA Neurol. 2023;80(1):30. doi:10.1001/jamaneurol.2022.4251

This retrospective multicenter study took place from January 1, 2014, to December 31, 2020, at autoimmune encephalitis subspecialty outpatient clinics including Mayo Clinic (n = 44), University of Oxford (n = 18), University of Texas Southwestern (n = 18), University of California, San Francisco (n = 17), Washington University in St Louis (n = 6), and University of Utah (n = 4). Inclusion criteria were adults (age 18 years) with a prior autoimmune encephalitis diagnosis at a participating center or other medical facility and a subsequent alternative diagnosis at a participating center. A total of 393 patients were referred with an autoimmune encephalitis diagnosis, and of those, 286 patients with true autoimmune encephalitis were excluded.

A total of 107 patients were misdiagnosed with autoimmune encephalitis, and 77 (72%) did not fulfill diagnostic criteria for autoimmune encephalitis. The median (IQR) age was 48 (35.5-60.5) years and 65 (61%) were female. Correct diagnoses included functional neurologic disorder (27 [25%]), neurodegenerative disease (22 [20.5%]), primary psychiatric disease (19 [18%]), cognitive deficits from comorbidities (11 [10%]), cerebral neoplasm (10 [9.5%]), and other (18 [17%]). Onset was acute/subacute in 56 (52%) or insidious (>3 months) in 51 (48%). MRI of the brain was suggestive of encephalitis in 19 of 104 patients (18%) and cerebrospinal fluid (CSF) pleocytosis occurred in 16 of 84 patients (19%). Thyroid peroxidase antibodies were elevated in 24 of 62 patients (39%). Positive neural autoantibodies were more frequent in serum than CSF (48 of 105 [46%] vs 7 of 91 [8%]) and included 1 or more of GAD65 (n = 14), voltage-gated potassium channel complex (LGI1 and CASPR2 negative) (n = 10), N-methyl-D-aspartate receptor by cell-based assay only (n = 10; 6 negative in CSF), and other (n = 18). Adverse reactions from immunotherapies occurred in 17 of 84 patients (20%). Potential contributors to misdiagnosis included overinterpretation of positive serum antibodies (53 [50%]), misinterpretation of functional/psychiatric, or nonspecific cognitive dysfunction as encephalopathy (41 [38%]).

When evaluating for autoimmune encephalitis, a broad differential diagnosis should be considered, and misdiagnosis occurs in many settings including at specialized centers. In this study, red flags suggesting alternative diagnoses included an insidious onset, positive nonspecific serum antibody, and failure to fulfill autoimmune encephalitis diagnostic criteria.

1 figure, 3 tables

8. Xu Y, Cheng L, Yuan L, Yi Q, Xiao L, Chen H. Progress on Brain and Ocular Lymphatic System. Surguchov A, ed. Biomed Res Int. 2022;2022:1-8. doi:10.1155/2022/6413553

Glymphatic system is mainly composed of three parts: para-arterial CSF influx channel, paravenous ISF efflux channel, and the water channel aquaporin-4 (AQP4) in astrocytes connecting the 2 channels. In 2012, Iliff et al., (J. J. Iliff,M. Wang, Y. Liao et al., Science Translational Medicine, vol. 4, no. 147, p. 147ra111, 2012) used in vivo imaging technology to discover for the first time the way in which CSF and ISF exchange substances and named it the glymphatic system. In brief, CSF flows into the brain through the paraarterial space and exchanges with ISF via AQP4; this type of exchange can drive metabolites and ISF into the paravenous space and then into the CSF circulation or directly through the lymphatic capillaries into the cervical lymphatics.

In 2015, Louveau et al. (Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, et al. Structural and functional features of central nervous system lymphatic vessels. Nature [Internet]. 2015; Available from: http://www.nature.com/doifinder/10.1038/nature14432 ) confirmed the existence of MLV. The team stained the entire meninges and found lymphatic vessels that drained CSF into the deep cervical lymph nodes. These vessels clear the brain of metabolites and are responsible for the migration of T cells. In the same year, Aspelund et al. not only found lymphatic vessels in mouse meninges but also studied the distribution of lymphatic vessels in detail and found that the MLV extends down to the base of the skull along the transverse sinus, sigmoid sinus, and nasal vein, as well as branches of the middle and anterior dural arteries. Since then, researchers have confirmed the existence of MLV in fish, rats, and nonprimates. Further study found that although the structure of MLV was similar to peripheral lymphatic vessels to a certain extent, the structure of MLV had a certain uniqueness, which was shown as follows: (1) lack of smooth muscle cells and valve structure, (2) diameter less than the peripheral lymphatic vessels, and (3) responsible for the migration of T-lymphoid immune cells.

4 figures (graphics)

ChatGPT recommended references!

“There have been numerous research papers published on the glymphatic system in recent years. Here are a few key references that are important for understanding the current state of knowledge:

Iliff, J. J., Wang, M., Liao, Y., Plogg, B. A., Peng, W., Gundersen, G. A., … & Nedergaard, M. (2012). A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Science translational medicine, 4(147), 147ra111. doi: 10.1126/scitranslmed.3003748

Xie, L., Kang, H., Xu, Q., Chen, M. J., Liao, Y., Thiyagarajan, M., … & Nedergaard, M. (2013). Sleep drives metabolite clearance from the adult brain. Science, 342(6156), 373-377. doi: 10.1126/science.1241224

Jessen, N. A., Munk, A. S., Lundgaard, I., & Nedergaard, M. (2015). The glymphatic system: a beginner’s guide. Neurochemical research, 40(12), 2583-2599. doi: 10.1007/s11064-015-1581-6

Kiviniemi, V., Wang, X., Korhonen, V., Keinänen, T., Tuovinen, T., Autio, J., … & LeVan, P. (2016). Ultra-fast magnetic resonance encephalography of physiological brain activity—glymphatic pulsation mechanisms? Journal of cerebral blood flow and metabolism, 36(6), 1033-1045. doi: 10.1177/0271678X15613986

Lukić, I. K., Glunčić, M., Boban, M., & Heffer, M. (2019). Glymphatic system: current concepts and relevance to neurosurgery. World neurosurgery, 126, 605-614. doi: 10.1016/j.wneu.2019.03.215

These papers cover various aspects of the glymphatic system, including its function, regulation, and potential clinical applications.”

The American Society of Neuroradiology is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Visit the ASNR Education Connection website to claim CME credit for this podcast.

1. Wu KY, Spinner RJ, Shin AY. Traumatic brachial plexus injury: diagnosis and treatment. Curr Opin Neurol. 2022;35(6):708-717. doi:10.1097/WCO.0000000000001124

A comprehensive physical examination aids in localizing (preganglionic or postganglionic) and characterizing the severity of injury (partial or complete). This is crucial to prognostication and determining the optimal reconstructive strategy. A preganglionic injury indicates an avulsion of the rootlets from the spinal cord, precludes the use of that spinal nerve as a donor for nerve grafting, and limits the reconstructive options available. In contrast, a postganglionic injury indicates a lesion distal to the dorsal root ganglion and still affords the possibility of reconstruction with nerve grafts.

The authors institutional preference is to use CT myelography with a multidetector row CT scanner. This allows for submillimeter resolution of the cervical rootlets, which typically measure 1mm in thickness. The classic pathognomic findings of preganglionic BPI are signs of root avulsion and pseudomeningocele formation. Traumatic pseudomeningocele formation results from bulging of the cerebrospinal fluid (CSF)-containing arachnoid membrane through a dural tear. Pseudomeningoceles can also occur in the absence of root avulsions, and therefore, must be correlated with the patient’s clinical examination. Pseudomeningocele formation occurs between 1- and 3-weeks following injury and delaying CT myelography or MRI will provide a higher diagnostic yield. MR neurography allows for greater soft tissue resolution and the ability to image the spinal cord and postganglionic brachial plexus.  Diffusion-weighted MR neurography heavily suppresses background body signals to selectively visualize and highlight tissues, such as nerves, with a long T2 relaxation time. High resolution FIESTA neurography had a 93% accuracy, 84% sensitivity, and 96% specificity in predicting a healthy C5 spinal root amenable for grafting. Additionally, MR provides information on the surrounding soft tissues including cervical spinal cord injury and muscle denervation.

4 figures, 1 table. 48 references with recommended readings.

2. Broekema AEH, Simões de Souza NF, Soer R, et al. Noninferiority of Posterior Cervical Foraminotomy vs Anterior Cervical Discectomy With Fusion for Procedural Success and Reduction in Arm Pain Among Patients With Cervical Radiculopathy at 1 Year. JAMA Neurol. 2023;80(1):40. doi:10.1001/jamaneurol.2022.4208

The Foraminotomy ACDF Cost-Effectiveness Trial (FACET) was designed to compare the clinical- and cost-effectiveness of posterior vs anterior surgery in patients with cervical radiculopathy due to foraminal nerve root compression. Posterior surgery was hypothesized to be noninferior to anterior surgery. The trial includes a follow-up of 2 years. The current study presents the clinical effectiveness results at 1 year of follow-up.

This multicenter investigator-blinded noninferiority randomized clinical trial was conducted from January 2016 to May 2020 with a total follow-up of 2 years. Patients were included from 9 hospitals in the Netherlands. Of 389 adult patients with 1-sided single-level cervical foraminal radiculopathy screened for eligibility, 124 declined to participate or did not meet eligibility criteria. Patients with pure axial neck pain without radicular pain were not eligible. Of 265 patients randomized (132 to posterior and 133 to anterior), 15 were lost to follow-up and 228 were included in the 1-year analysis.

Primary outcomes were proportion of success using Odom criteria and decrease in arm pain using a visual analogue scale from 0 to 100 with a noninferiority margin of 10%. Secondary outcomes were neck pain, disability, quality of life, work status, treatment satisfaction, reoperations, and complications.

Among 265 included patients, the mean (SD) age was 51.2 (8.3) years; 133 patients (50%) were female and 132 (50%) were male. Patients were randomly assigned to posterior (132) or anterior (133) surgery. The proportion of success was 0.88 (86 of 98) in the posterior surgery group and 0.76 (81 of 106) in the anterior surgery group and the between-group difference in arm pain was −2.8 at 1-year follow-up, indicating noninferiority of posterior surgery. Decrease in arm pain had a between-group difference of 3.4, crossing the noninferiority margin with 1.8 points.

These findings suggest noninferiority of posterior surgery compared to anterior surgery and may be used to inform patient counseling and shared decision-making between physicians and patients with 1-sided foraminal radiculopathy.

3 tables, 2 figures, no imaging

3. Mitchell P, Lee SCM, Yoo PE, et al. Assessment of Safety of a Fully Implanted Endovascular Brain-Computer Interface for Severe Paralysis in 4 Patients. JAMA Neurol. Published online January 9, 2023:1-9. doi:10.1001/jamaneurol.2022.4847

Case reports of investigational BCI devices have described control of exoskeletons, prosthetic limbs, and communication technologies and demonstrated the ability to directly decode speech and handwriting from cortical motor activity. Application to wider patient populations is limited, in part by the invasiveness of craniotomy or partial skull removal to implant electrodes in or on the brain. The blood vessels of the brain offer a less invasive route for obtaining access to the motor cortex. Venous stenting has routinely been performed for treating idiopathic intracranial hypertension in the transverse sinus, with a major complication rate of less than 2%. An endovascular device incorporating recording electrodes and implantable in the superior sagittal sinus has recently been developed (Stentrode; Synchron).

The Stentrode With Thought-Controlled Digital Switch (SWITCH) study, a single-center, prospective, first in-human study, evaluated 5 patients with severe bilateral upper-limb paralysis, with a follow-up of 12 months. From a referred sample, 4 patients with amyotrophic lateral sclerosis and 1 with primary lateral sclerosis met inclusion criteria and were enrolled in the study. Surgical procedures and follow-up visits were performed at the Royal Melbourne Hospital, Parkville, Australia. Training sessions were performed at patients’ homes and at a university clinic. The study start date was May 27, 2019, and final follow-up was completed January 9, 2022.

In this prospective, open-label, first in-human study conducted in Australia, an endovascular motor neuroprosthesis BCI implanted in the SSS of 4 patients with severe paralysis was associated with no serious adverse events and no occlusion of target vessels or device migration during the 12-month follow-up period. The BCI maintained a stable signal through- out the study, and all participants successfully controlled a computer with the BCI. Endovascular access to the sensorimotor cortex offers an alternative to BCI technologies, where electrodes are placed in or on the dura by open-brain surgery.

3 figures

4. Hara T, Matsushige T, Yoshiyama M, Hashimoto Y, Kobayashi S, Sakamoto S. Association of circumferential aneurysm wall enhancement with recurrence after coiling of unruptured intracranial aneurysms: a preliminary vessel wall imaging study. J Neurosurg. 2022;138(January):1-7. doi:10.3171/2022.4.jns22421

Recent histopathological studies of unruptured intracranial aneurysms (UIAs) have confirmed that aneurysm wall enhancement (AWE) on MR vessel wall imaging (VWI) is related to wall degeneration with in vivo inflammatory cell infiltration. Therefore, pretreatment aneurysm wall status on VWI may be associated with recurrence after endovascular treatment.

VWI with gadolinium was performed on 67 consecutive saccular unruptured intracranial aneurysms before endovascular treatment between April 2017 and June 2021. The mean (range) follow-up period after treatment was 24.4 months. AWE patterns were classified as circumferential AWE (CAWE), focal AWE (FAWE), and negative AWE (NAWE).

AWE patterns were as follows: 10 CAWE (14.9%), 20 FAWE (29.9%), and 37 NAWE (55.2%). Follow-up MRA detected aneurysm recurrence in 18 of 69 cases (26.1%). Univariate analysis identified maximum diameter (5.8 mm in patients with stable aneurysms vs 7.7 mm in those with unstable aneurysms), aspect ratio, aneurysm location in posterior circulation (4.1% vs 27.8%), volume embolization ratio, and AWE pattern as significant predictive factors of recurrence. Among the 3 AWE patterns, CAWE was significantly more frequent in the unstable group, but no significant differences in stability of the treated aneurysms were observed with the FAWE and NAWE patterns. In multivariate logistic regression analysis, CAWE pattern and volume embolization ratio ≥ 25% remained as significant factors associated with aneurysm stability after coiling.

They conclude that the CAWE pattern, which suggests a specific feature of aneurysm wall degeneration, may negatively affect the durability of coiled aneurysms. Although the long-term stability of coiled aneurysms and the requirement for retreatment currently remain unclear, VWI before coiling provides novel insights into the stability of coiled aneurysms.

3 tables, 3 figures with angio and MR

5. Hasegawa H, Inoue A, Helal A, Kashiwabara K, Meyer FB. Pineal cyst: results of long-term MRI surveillance and analysis of growth and shrinkage rates. J Neurosurg. 2022;138(January):1-7. doi:10.3171/2022.4.jns22276

Pineal cyst (PC) is a common abnormality located adjacent to or within the pineal gland. Several previous studies reported the prevalence to be 1%–4%; however, it appears that these studies were based on a somewhat biased population that had neurosurgical/ neurological concerns. In fact, the real prevalence of PC among asymptomatic healthy volunteers has been reported to be as low as 0.2%. Radiologically, PC is usually delineated as a simple cyst with a thin, smooth, contrasted wall measuring up to 2 mm. Atypical findings including internal septations, thicker wall with nodularity, multilobulated shape, and multicystic appearance are possible. Signal intensity (SI) on MRI is variable depending on the cyst components, although usually it is similar but slightly hyperintense to CSF on T1-weighted and FLAIR images.

The goals of this study were to evaluate the long-term natural history of PC and elucidate risk factors for cyst growth and shrinkage, using our electronic database with long-term follow-up.

The records and MRI of 409 consecutive patients with PC were retrospectively examined (nonsurgical cohort). Cyst growth and shrinkage were defined as a ≥ 2-mm increase and decrease in cyst diameter in any direction, respectively.

The median radiological follow-up period was 10.7 years. The median change in maximal diameter was −0.6 mm. During the observation period, cyst growth was confirmed in 21 patients (5.1%). Multivariate logistic regression analysis revealed that only age was significantly associated with cyst growth. No patient required resection during the observation period. Cyst shrinkage was confirmed in 57 patients (13.9%). Multivariate analysis revealed that maximal diameter and cyst CSF T2 signal intensity ratio were significantly associated with cyst shrinkage.

They conclude that only 5% of PCs, mainly in patients younger than 50 years of age, have the potential to grow, while cyst shrinkage is more likely to occur across all age groups. Younger age is associated with cyst growth, while larger diameter and higher signal intensity on T2-weighted imaging are associated with shrinkage. Surgery is rarely needed.

3 tables, 3 figures, with MR

6. Xiong GX, Collins JE, Ferrone ML, Schoenfeld AJ. Prospective comparison of 1-year survival in patients treated operatively and non-operatively for spinal metastatic disease: results of the prospective observational study of spinal metastasis treatment (POST). Spine Journal. 2022;23(1):14-17. doi:10.1016/j.spinee.2022.02.004

A major change occurred in the field of spine surgery in 2005 following the landmark publication of Patchell et al. regarding the efficacy of spine surgery for restoration of ambulatory function in patients with spinal metastatic disease. In the succeeding 15 years, enthusiasm grew for surgical interventions as a standard treatment option for patients with spinal metastases. Several investigations touted that surgery not only preserved ambulatory ability but also improved survival. There was a concern that many of these investigations were confounded by selection bias and controversy remains regarding the utility of spine surgery in subsets of patients with spinal metastases based on baseline neurologic status. To address this, the authors planned an analysis that accounted for confounding by indication and compared patients treated operatively and nonoperatively for spinal metastases within the Prospective Observational study of Spinal metastasis Treatment (POST). The authors hypothesized that patients treated surgically would have superior one-year survival to those managed nonoperatively.

87 instances of surgical intervention and 122 cases of nonoperative treatment were included. The average age of both cohorts approximated 60.5 years. Lung cancer was the most common primary tumor (20%), followed by breast (16%) and prostate (14%). The thoracic spine was the most common site of surgical intervention (70%). Most surgeries consisted of fusion-based procedures (79%), including 26 corpectomies. Combined chemotherapy and radiation was the most common nonoperative modality (80%).

Overall, 50% of the cohort died by 1-year following presentation (105/209). In the operative group, the mortality rate was 46% at 1-year, as compared to 54% in the nonoperative cohort. This represented a 25% reduction in the odds of mortality but was not significantly different. Following propensity score adjustment, accounting for confounding by indication in the decision for surgery, surgical intervention offered a 28% reduction in the odds of mortality but still did not demonstrate statistical significance.

They conclude that their findings add to a growing body of evidence that indicates surgical intervention is not uniformly beneficial across all individuals with spinal metastases. Although the benefits of surgery for patients with neurologic deficits, acute loss of ambulatory function, and spinal instability are incontrovertible, robust evidence is lacking for those without neurologic compromise or impaired ambulatory function.

1 figure, 1 table

7. Alhammoud A, Korytkowski PD, Lavelle WF, Metkar US. Proximal junctional kyphosis in adult spinal deformity: An up-to-date review. Semin Spine Surg. 2022;34(4):100992. doi:10.1016/j.semss.2022.100992

The formal definition of proximal junctional kyphosis is the criteria of 1) a proximal junctional angle (PJA) of greater than or equal to 10° and 2) a proximal junctional angle greater than 10°compared to preoperative measurements. Typically, the PJA is defined as the angle between the lower endplate of the upper instrumented vertebra (UIV) and the upper endplate of two vertebrae above the UIV (UIV + 2). Other studies have used different values to define PJA such as 15° and 20°. Additionally, some papers have used upper instrumented vertebra +2 or UIV + 1 to measure the PJA. Both methods for measuring the PJA have demonstrated adequate reproducibility.

Many risk factors for proximal junctional kyphosis have been identified. Patient-specific risk factors include higher body mass index (BMI), older age, presence of a comorbidity, male sex, low bone mineral density (BMD), and osteoporosis. There is evidence for sarcopenia as a risk factor by observing decreased muscle volume at the T10 to L2 level in proximal junctional kyphosis patients. Measuring the psoas cross-sectional area is another method that can indicate sarcopenia as a risk factor for PJK.

2 figures, 1 table.  Really one figure, since the lone figure is duplicated in the paper….a rather unusual copyediting failure in my experience.

8. Fuentes AM, Khalid SI, Mehta AI. Predictors of Subsequent Intervention After Middle Meningeal Artery Embolization for Treatment of Subdural Hematoma: A Nationwide Analysis. Neurosurgery. 2023;92(1):144-149. doi:10.1227/neu.0000000000002151

Middle meningeal artery (MMA) embolization has recently emerged as an effective technique to treat subdural hematomas (SDHs). Studies to date have been limited, largely, to single-center studies with limited follow-up and have not assessed subsequent surgical interventions and factors associated with these interventions.

Using an all-payer claims database patients who underwent MMA embolization between January 2010 and October 2020 after the diagnosis of SDH were identified. Rates of post-MMA embolization surgical interventions, including craniotomy and burr hole drainage, were accessed within 5 years following.

A total of 322 patients were included. Of this cohort, 55 (17.1%) required subsequent intervention within 5 years, with 36 (11.2%) receiving burr hole evacuation and 19 (5.9%) receiving craniotomy. Factor Xa inhibitor use was independently associated with subsequent interventions after MMA embolization procedures. Of the other patient factors evaluated, including age, sex, comorbidity status, and use of vitamin K antagonists, antiplatelets, and factor Xa inhibitors, none were found to be significantly associated with future interventions.

Patients taking factor Xa inhibitors are at especially high risk of subsequent intervention after MMA embolization. In this cohort, factor Xa inhibitor use, but not vitamin K antagonist or antiplatelet use, was significantly associated with increased odds of subsequent intervention within 5 years. Xa inhibitors include Xarelto, Eliquis.

1 table, 1 figure, no imaging

The American Society of Neuroradiology is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Visit the ASNR Education Connection website to claim CME credit for this podcast.

1. Kamagata K, Andica C, Takabayashi K, et al. Association of MRI Indices of Glymphatic System With Amyloid Deposition and Cognition in Mild Cognitive Impairment and Alzheimer Disease. Neurology. 2022;99(24):e2648-60. doi:10.1212/WNL.0000000000201300

According to the glymphatic hypothesis, subarachnoid CSF enters the brain’s interstitial space from the periarterial space through the AQP4 channel expressed in the astrocyte end-feet and then mixes with the interstitial fluid (ISF) and waste solutes in the brain. The resulting CSF/ISF exchange and waste products, such as Aβ, are then drained out of the brain by the perivenous efflux pathway. Recent studies have demonstrated the possibility of measuring glymphatic functions using MRI, with most of them being MRI tracer–based studies using a gadolinium-based contrast agent (GBCA). Both intrathecal and intravenous GBCA administration are relatively invasive. Promising MRI-based noninvasive methods that do not require MRI tracers, namely, perivascular space (PVS) volumetry, calculation of the fractional volume of free water (FW) in brain parenchyma (i.e., brain ISF) from a bitensor diffusion tensor imaging (DTI) model, and calculation of the diffusivity along the PVS (ALPS) index, were recently introduced for the indirect evaluation of perivascular network activity.

Elevated WM FW has been reported in patients with Alzheimer disease, suggesting the stagnation of fluid drainage caused by glymphatic dysfunction. Using DTI, Taoka et al. proposed the ALPS index, which is calculated from the diffusivity along the deep medullary vein at the level of the lateral ventricle body, as a measure of perivascular clearance activity in the human brain.

In this study, MRI measures including perivascular space (PVS) volume fraction (PVSVF), fractional volume of free water in white matter (FW-WM), and index of diffusivity along the perivascular space (ALPS index) of patients with MCI, those with AD, and healthy controls from the Alzheimer’s Disease Neuroimaging Initiative database were compared. MRI measures were also correlated with the levels of CSF biomarkers, PET SUVR, and cognitive score in the combined subcohort of patients with MCI and AD.

36 patients with AD, 44 patients with MCI, and 31 healthy controls were analyzed. Patients with AD had significantly higher total, WM, and basal ganglia perivascular space volume fraction and fractional volume of free water in white matter and a lower ALPS index than healthy controls. Meanwhile, the MCI group only showed significantly higher total and WM PVSVF.

They conclude that changes in PVS-related MRI parameters occur in MCI and AD, possibly due to impairment of the glymphatic system. They report the associations between MRI parameters and Aβ deposition, neuronal change, and cognitive impairment in AD.

Lots of caveats with this paper, including that the ALPS index cannot evaluate whole brain glymphatic function. It is based on the orthogonal geometric relationship between projection and association fibers and medullary arteries and veins in the lateral ventricle body. Therefore, the ALPS can only be evaluated at the level of the lateral ventricle body. The ALPS index does not exclusively measure the diffusivity of the perivenous space around the deep medullary vein—that is, it is also influenced by the surrounding white matter microstructure included in the ROI.

5 figures and 1 table

2. Zhang JK, Jayasekera D, Song C, et al. Diffusion Basis Spectrum Imaging Provides Insights Into Cervical Spondylotic Myelopathy Pathology. Neurosurgery. 2023;92(1):102-109. doi:10.1227/neu.0000000000002183

Diffusion basis spectrum imaging (DBSI) is a noninvasive quantitative imaging modality that may improve understanding of cervical spondylotic myelopathy (CSM) pathology through detailed evaluations of spinal cord microstructural compartments.

A single-center prospective cohort study enrolled 50 patients with CSM and 20 controls from 2018 to 2020. All patients underwent clinical evaluation and diffusion weighted MRI, followed by diffusion tensor imaging and DBSI analyses. Diffusion weighted MRI metrics assessed white matter integrity by fractional anisotropy, axial diffusivity, radial diffusivity, and fiber fraction. In addition, DBSI further evaluates extra axonal changes by isotropic restricted and nonrestricted fraction. Including an intra axonal diffusion compartment, DBSI improves estimations of axonal injury through intra-axonal axial diffusivity. Patients were categorized into mild, moderate, and severe CSM using modified Japanese Orthopedic Association classifications. Imaging parameters were compared among patient groups using independent samples t tests and ANOVA.

Diffusion tensor imaging and DBSI fractional anisotropy, axial diffusivity, and radial diffusivity were significantly different between control and patients with CSM. DBSI fiber fraction, restricted fraction, and nonrestricted fraction were significantly different between groups. DBSI intra-axonal axial diffusivity was lower in mild compared with moderate and severe CSM.

The authors state that the results highlight the ability of DBSI to provide more granular assessments of white matter tract integrity and support its application as a noninvasive imaging biomarker of CSM disease severity and a potential predictor of postoperative improvement.

4 figures and 1 table.  Interesting, but very early data. I would have liked to see some routine MR imaging correlations with the diffusion metrics.

3. Andersen BM, Reardon DA. Immunotherapy approaches for adult glioma: knowledge gained from recent clinical trials. Curr Opin Neurol. 2022;35(6):803-813. doi:10.1097/wco.0000000000001118

Despite the widespread success of therapies targeting the T-cell checkpoints programmed-death 1 and cytotoxic T lymphocyte antigen 4 in other malignancies, recent phase III trials in glioblastoma confirm the lack of efficacy of anti-programmed-death 1 monotherapy in more than 90% of patients. Vaccination approaches remain under investigation for high-grade glioma and have shown activity in some low-grade glioma patients. Chimeric antigen receptor T cells now feature a new generation of products engineered to potentially withstand glucocorticoid therapy. Oncolytic viral therapies have similarly advanced in sophistication, with drug-sensitive gene expression and tumor-selective modifications. Combinations of therapies hold promise for overcoming the numerous mechanisms of immune suppression in glioma.

As the complex interplay of glioma-associated immune cells comes into focus, clinical trials will likely also increase in complexity. Although many approaches hold promise in our ability to eradicate glioma through activation of an immune response, success in further combination clinical trials will require careful selection of drug combinations, the timing of drug administration, treatment and dose combinations, tumor tissue-based immune analysis, cooperation with various drug developers, and additional safety evaluation.

1 table

4. el Naamani K, Saad H, Chen CJ, et al. Comparison of Flow-Redirection Endoluminal Device and Pipeline Embolization Device in the Treatment of Intracerebral Aneurysms. Neurosurgery. 2023;92(1):118-124. doi:10.1227/neu.0000000000002148

The use of flow diverters for treating intracranial aneurysms has been widely used in the past decade; however, data comparing pipeline embolization device (PED; Medtronic Inc) and flow-redirection endoluminal device (FRED; MicroVention) in the treatment of intracranial aneurysms remain scarce.

This is a single-center retrospective review of aneurysms treated with PED and FRED devices. Patients treated with PED or FRED were included. Cases requiring multiple or adjunctive devices were excluded. Primary outcome was complete aneurysm occlusion at 6 months. Secondary outcomes included good functional outcome, need for retreatment, and any complication.

The study cohort comprised 150 patients, including 35 aneurysms treated with FRED and 115 treated with PED. Aneurysm characteristics including location and size were comparable between the 2 cohorts. 6-month complete occlusion rate was significantly higher in the PED cohort (74.7% vs 51.5%) but lost significance after inverse probability weights. Patients in the PED cohort were associated with higher rates of periprocedural complications (3.5% vs 0%), and the rate of in-stent stenosis was approximately double in the FRED cohort.

Compared with PED, FRED offers modest 6 months occlusion rates, which may be due to aneurysmal and baseline patient characteristics differences between both cohorts. Although not significant, FRED was associated with a higher complication rate mostly because of in-stent stenosis. Additional studies with longer follow-up durations should be conducted to further evaluate FRED thrombogenicity and efficacy.

2 tables and 4 figures, with catheter angios

5. Salem MM, Srinivasan VM, Tonetti DA, et al. Microsurgical Obliteration of Craniocervical Junction Dural Arteriovenous Fistulas: Multicenter Experience. Neurosurgery. 2023;92(1):205-212. doi:10.1227/neu.0000000000002196

Dural arteriovenous fistulas (dAVFs) located at craniocervical junction are extremely rare (1%-2% of intracranial/spinal dAVFs). Their angio-architectural complexity renders endovascular embolization to be challenging given multiple small feeders with risk of embolysate reflux into vertebral artery and limited transvenous access. The available literature discussing microsurgery for these lesions is limited to few case reports.

Prospectively maintained registries at 13 North American centers were queried to identify craniocervical junction dAVFs treated with microsurgery (2006-2021). Thirty-eight patients (median age 59.5 years, 44.7% female patients) were included. The most common presentation was subarachnoid/intracranial hemorrhage (47.4%) and myelopathy (36.8%) (92.1% of lesions Cognard type III-V). Direct meningeal branches from V3/4 vertebral artery segments supplied 84.2% of lesions. All lesions failed (n = 5, 13.2%) or were deemed inaccessible/unsafe to endovascular treatment. Far lateral craniotomy was the most used approach (94.7%). Intraoperative angiogram was performed in 39.5% of the cases, with angiographic cure in 94.7% of cases (median imaging follow-up of 9.2 months) and retreatment rate of 5.3%.

They conclude that craniocervical dAVFs represent rare entity of lesions presenting most commonly with hemorrhage or myelopathy because of venous congestion. Microsurgery using a far lateral approach provides robust exposure and visualization for these lesions and allows obliteration of the arterialized draining vein intradurally as close as possible to the fistula point.

5 figures, 4 tables including catheter angio, intraop photos and intraoperative indocyanine green images.

6. Fusini F, Girardo M, Aprato A, et al. Percutaneous Cement Discoplasty in Degenerative Spinal Disease: Systematic Review of Indications, Clinical Outcomes, and Complications. World Neurosurg. 2022;168:219-226. doi:10.1016/j.wneu.2022.10.008

Percutaneous cement discoplasty (PCD) is a minimally invasive surgical technique that hopes to improve stability by injecting bone cement into a severely degenerated disc. This procedure is intended to decrease spinal instability in advanced disc degeneration and seems to show promising results in the short and middle term. The procedure was developed as an alternative interbody spacer option in patients unsuitable for conventional surgery. The principle of PCD is based on vertebral segment instability, where disc degeneration causes spondylolisthesis with a reduced neuroforamen area.

Despite the spread of this technique, the real benefit of this technique is unclear, with little evidence regarding postoperative outcomes at longer follow-up, actual hospital stay, complications, and reoperation after PCD.

In this systematic review, a total of 7639 documents was retrieved from the databases search. After duplication removal and title/abstract screening, a total of 15 articles was selected. According to inclusion and exclusion criteria, 5 full text articles were included in the review.

All included studies were case series with a retrospective study design. The level of evidence for included articles was IV. A total of 25 major complications (requiring surgical intervention or long-term intravenous therapy) were collected: 9 cases of radiculopathy due to cement leakage or disc extrusion or persistent radiculopathy, 3 cases of deep infection, 5 cases of pain recurrence at a different level, 5 persistent pain after procedure needing fusion surgery, 2 adjacent vertebral fractures requiring vertebroplasty, and 1 case of deep vein thrombosis.

The methodologic quality of the articles included showed a poor Methodological index for nonrandomized studies score (median 9, range 6   11). The prospective collection of data and calculation of sample size, appropriate follow-up, and unbiased endpoint assessment were the parameters with lower scores.

Safe to say we don’t really know if this is effective given the quality of evidence and limited literature.

2 tables, no images.

7. Koch G, Casula EP, Bonnì S, et al. Precuneus magnetic stimulation for Alzheimer’s disease: a randomized, sham-controlled trial. Brain. 2022;145(11):3776-3786. doi:10.1093/brain/awac285

Repetitive transcranial magnetic stimulation (rTMS) is emerging as a non-invasive therapeutic strategy in the battle against Alzheimer’s disease. Alzheimer’s disease patients primarily show alterations of the default mode network for which the precuneus is a key node. Here, the authors hypothesized that targeting the precuneus with TMS represents a promising strategy to slow down cognitive and functional decline in Alzheimer’s disease patients.

They performed a randomized, double-blind, sham-controlled, phase 2, 24-week trial to determine the safety and efficacy of precuneus stimulation in patients with mild-to-moderate Alzheimer’s disease. Fifty Alzheimer’s disease patients were randomly assigned in a 1:1 ratio to either receive precuneus or sham rTMS (mean age 73.7 years; 52% female). The trial included a 24-week treatment, with a 2-week intensive course in which rTMS (or sham) was applied daily five times per week, followed by a 22-week maintenance phase in which stimulation was applied once weekly. The Clinical Dementia Rating Scale–Sum of Boxes was selected as the primary outcome measure, in which post-treatment scores were compared to baseline. Secondary outcomes included score changes in the Alzheimer’s Disease Assessment Scale–Cognitive Subscale, Mini-Mental State Examination and Alzheimer’s Disease Cooperative Study–Activities of Daily Living scale. Moreover, single-pulse TMS in combination with EEG was used to assess neurophysiological changes in precuneus cortical excitability and oscillatory activity.

The findings show that patients that received precuneus repetitive magnetic stimulation presented a stable performance of the Clinical Dementia Rating Scale–Sum of Boxes score, whereas patients treated with sham showed a worsening of their score. Compared with the sham stimulation, patients in the precuneus stimulation group also showed also significantly better performances for the secondary outcome measures, including the Alzheimer’s Disease Assessment Scale–Cognitive Subscale, Mini-Mental State Examination and Alzheimer’s Disease Cooperative Study–Activities of Daily Living scale. Neurophysiological results showed that precuneus cortical excitability remained unchanged after 24 weeks in the precuneus stimulation group, whereas it was significantly reduced in the sham group. Finally, they found an enhancement of local gamma oscillations in the group treated with precuneus stimulation but not in patients treated with sham. They conclude that 24 weeks of precuneus rTMS may slow down cognitive and functional decline in Alzheimer’s disease. Repetitive TMS targeting the default mode network could represent a novel therapeutic approach in Alzheimer’s disease patients.

5 figures, 2 tables

8. Mair G, White P, Bath PM, et al. External Validation of e-ASPECTS Software for Interpreting Brain CT in Stroke. Ann Neurol. 2022;92(6):943-957. doi:10.1002/ana.26495

The purpose of this study was to test e-ASPECTS software in patients with stroke. Marketed as a decision support tool, e-ASPECTS may detect features of ischemia or hemorrhage on computed tomography (CT) imaging and quantify ischemic extent using Alberta Stroke Program Early CT Score (ASPECTS).

Using CT from 9 stroke studies, the authors compared software with masked experts. As per indications for software use, they assessed e-ASPECTS results for patients with/without middle cerebral artery (MCA) ischemia but no other cause of stroke. In an analysis outside the intended use of the software, they enriched their dataset with non-MCA ischemia, hemorrhage, and mimics to simulate a representative “front door” hospital population. With final diagnosis as the reference standard, they tested the diagnostic accuracy of e-ASPECTS for identifying stroke features (ischemia, hyperattenuated arteries, and hemorrhage) in the representative population.  The authors included 4,100 patients. Final diagnosis was ischemia (78%), hemorrhage (14%), or mimic (8%). From 3,035 CTs with expert-rated ASPECTS, most (2084/3035, 69%) e-ASPECTS results were within one point of experts. In the representative population, the diagnostic accuracy of e-ASPECTS was 71% for detecting ischemic features, 85% (83–86%) for hemorrhage. Software identified more false positive ischemia (12% vs 2%) and hemorrhage (14% vs <1%) than experts.

In conclusion, on independent testing, e-ASPECTS provided moderate agreement with experts and overcalled stroke features. Therefore, future prospective trials testing impacts of artificial intelligence (AI) software on patient care and outcome are required before widespread implementation of stroke decision-support software.

4 figures, 4 tables…no imaging.

The American Society of Neuroradiology is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Visit the ASNR Education Connection website to claim CME credit for this podcast.

1. Boulenoir N, Turc G, ter Schiphorst A, et al. Should Patients With Acute Minor Ischemic Stroke With Isolated Internal Carotid Artery Occlusion Be Thrombolysed? Stroke. 2022;(November):3304-3312. doi:10.1161/strokeaha.122.039228

Isolated cervical or intracranial internal carotid artery occlusion (iICAo), without associated occlusion of the circle of Willis (ie, without T-shaped, L-shaped, or tandem occlusions), is observed in ≈5% of acute stroke patients admitted in an early time window, with atherosclerosis as the leading cause followed by dissection and cardioembolism. Clinical severity is highly variable, in part as a function of collateral circulation, and patients with iICAo frequently present with minor neurological deficits. Given the lack of evidence derived from randomized controlled trials, the management of acute iICAo remains unclear. The early clinical course of acute iICAo treated or not with reperfusion therapies has been reported in few observational studies, all with small samples, and remains little known. In the 4.5-hour window, international guidelines recommend intravenous thrombolysis (IVT) in the context of disabling ischemic minor stroke in general, whereas an expert consensus from the European Stroke Organization suggests using IVT in nondisabling minor stroke with large vessel occlusion. Regarding iICAo, the authors recently reported a worrying 30% rate of early neurological deterioration (END) occurring within 24 hours following IVT in a multicentric cohort of patients with minor stroke iICAo, which occurred mostly within the first 2 hours from IVT start and was ascribed to artery-to-artery embolism in 3/4th of the cases. These observations led the authors to propose that IVT may foster carotid thrombus fragmentation and subsequent distal embolism and could therefore be deleterious in this situation. However, this study lacked a control group (ie, nonthrombolysed acute minor stroke with iICAo), which limited interpretation. In this paper, the authors tested the above hypothesis by comparing the incidence and mechanisms of early neurological deterioration within 24 hours (END24h), END within 7 days, and 3-month outcome of patients with acute minor stroke iICAo treated with IVT or antithrombotics only.

189 patients were included (IVT=95; antithrombotics=94 [antiplatelets, n=58, anticoagulants, n=36]) from 34 centers.

Four key findings emerged: (1) END was a frequent event in this population— occurring in 1 of 3 patients within the first week, predominantly in case of nonatheromatous cause—and was strongly associated with poor 3-month outcome; (2) END was of thromboembolic origin in two-thirds of the cases; (3) the rate of END within the first 24 hours was 2-fold higher following IVT, driven by higher odds of thromboembolic END; and (4) however, the rate of END occurring within 7 days did not significantly differ between the 2 treatment groups, and 3-month outcome was similar.

The higher END24h incidence following IVT, together with the lack of better 3-month functional outcome as found here, may suggest that the benefit/risk ratio may not favor IVT at least in case of nondisabling symptoms, a situation where the benefit of IVT is unproven. Apart from IVT alone, 3 other therapeutic options may be considered in this population. First, adding early post-IVT antiplatelet administration may be an attractive approach to prevent thromboembolic ENDs. A post hoc analysis of ARTIS, a randomized trial comparing early (within 90 minutes of IVT start) addition of aspirin after IVT versus IVT alone in an unselected acute stroke population, found that aspirin increased the risk of END24h due to intracranial hemorrhage, and had no effect on incidence of nonhemorrhagic END24h. However, this approach could still be of interest in populations at high risk of post-IVT thromboembolic END and low risk of intracranial hemorrhage, such as nonatheromatous iICAo with minor symptoms, and should be further tested, perhaps with later antiplatelet agent administration. Second, in patients with non-IVT–treated iICAo, more intensive antithrombotic strategies than aspirin alone may be of interest. An observational study focusing on patients with non-IVT–treated iICAo admitted within 24 hours from symptom onset suggested that, as compared to standard antiplatelet therapy, anticoagulation was associated with lower END7d rate. More intensive antiplatelet therapies such as dual antiplatelet therapy plus argatroban may reduce END risk, as reported in branch atherosclerosis disease. Last, direct—as opposed to rescue—endovascular therapy may be considered to prevent END. Two case series in acute iICAo suggested that immediate endovascular therapy including angioplasty and stenting may afford high rates of successful recanalization, although appeared to be associated with a substantial rate of intracranial embolism.

4 tables, 2 figures, no imaging

2. Siegler JE, Shu L, Yaghi S, et al. Endovascular Therapy for Cerebral Vein Thrombosis: A Propensity-Matched Analysis of Anticoagulation in the Treatment of Cerebral Venous Thrombosis. Neurosurgery. 2022;91(5):749-755. doi:10.1227/neu.0000000000002098

Definitive treatment of CVT includes recanalization of occluded cerebral vein or dural sinus with anticoagulation for 3 to 6 months. Endovascular treatment (EVT) in the form of thrombectomy is considered in patients for whom anticoagulation may be contraindicated, or symptoms progress despite anticoagulation, and is recommended with a low level of evidence by the American Heart Association (Class IIb, Level of Evidence C). Systematic review and meta-analyses indicate that EVT is reasonable and safe as a salvage treatment for CVT, with similar patient outcomes compared with medically managed patients. However, these data are limited by small patient populations, with the largest cohort comprising 63 patients. Furthermore, the adjunctive benefit of endovascular treatment in CVT was not proven in the TO-ACT multicenter randomized clinical trial. In Thrombolysis or Anticoagulation for Cerebral Venous Thrombosis (TO-ACT), the likelihood of achieving a good functional outcome (modified Rankin Scale [mRS] 0-1) was no different between the endovascular and medically managed arms.

Of the 1025 patients from the original ACTION-CVT cohort, 987 (96%) had complete demographic and treatment data for this analysis and were included.

This analysis of the ACTION-CVT multicenter cohort study represents the largest observational cohort study of patients with CVT who underwent medical or EVT management.

The authors found no difference in excellent functional outcome (mRS 0-1) at 90 days and no difference in secondary clinical or radiographic outcomes with EVT over medical treatment of CVT. In a sensitivity analysis limiting inclusion of patients based on eligibility for the TO-ACT randomized clinical trial, there was no significant difference in the prespecified primary outcome based on treatment. Altogether, their findings provide real-world data supporting the TO-ACT trial results. It is possible that only a subgroup (or subgroups) of patients with CVT may benefit from EVT (eg, refractory intracranial hypertension, progressive venous infarction, or hemorrhage expansion), and this needs to be determined by future randomized clinical trials. Furthermore, among the few patients who underwent successful recanalization with EVT and had available recanalization and long-term follow-up data (n = 11), there was a suggestion of improved outcomes when compared with patients treated using medical management.

2 figures, 2 tables, no imaging

3. Jack MM, Smith BW, Capek S, et al. The spectrum of brachial plexopathy from perineural spread of breast cancer. J Neurosurg. 2022;137(November):1-10. doi:10.3171/2021.12.JNS211882

The differential diagnosis for breast cancer–related upper- extremity neurological issues is vast. The nerves can be damaged directly during surgery (especially with axillary lymph node dissections), compressed by local disease progression/recurrence, chemically damaged in a length dependent fashion from chemotherapy regimens, or injured – typically in a delayed fashion—as a complication of radiation treatments. One less common and thus less often recognized insult to the brachial plexus in patients with breast cancer is perineural spread.

The aim of this study was to describe the clinical, pathological, and radiological findings in the largest series of patients with pathologically verified perineural spread of breast cancer to the brachial plexus. A total of 19 female patients who all presented with evidence of brachial plexopathy, who had pathological evidence of perineural spread of breast cancer on fascicular nerve biopsy, and who were treated at the authors institution between 1999 and 2021 were included in the study.

The patients in this series developed symptoms of brachial plexopathy on average 12 years after their initial diagnosis. This length of time makes a chemotherapy induced neuropathy much less likely. In this time frame, radiation plexopathy and perineural spread are two leading differential diagnoses. However, radiation-induced neuropathy and perineural spread can be difficult to distinguish clinically. Additionally, a long-term complication of breast cancer treatment such as lymphedema could be at play, given that there are many reports of compressive neuropathies in patients with cancer-related lymphedema. To this point, 42% of patients in this series received a carpal tunnel decompression, 11% received a cubital tunnel decompression, and 5% had a cervical decompression. One patient underwent all three types of procedures prior to the diagnosis of perineural spread. However, the true diagnosis remained elusive in all cases. Given its rarity and alternative diagnoses with similar presentations, perineural spread can be difficult to diagnose. This difficulty explains why patients had a mean time course of more than 2 years from the onset of brachial plexus symptoms until the diagnosis of perineural infiltration of the brachial plexus.

Patients with a history of breast cancer presenting with pain, weakness, or numbness should be evaluated for the possibility of perineural spread. In contrast to radiation injury, which is more severe regarding distal function, perineural spread can affect both the proximal and distal musculature in isolation. Imaging characteristics including a sugar-coating pattern on brachial plexus MRI and increased FDG uptake on PET imaging can be used to strengthen a diagnosis. Selective biopsy will help to make a clear diagnosis. Unfortunately, breast cancer with perineural spread is associated with high mortality, with nearly every patient in this cohort dying within 6 years.

5 tables, 3 figures, including MR, PET

4. Whiteley WN, MacRaild A, Wang Y, et al. Clinical Diagnosis and Magnetic Resonance Imaging in Patients With Transient and Minor Neurological Symptoms: A Prospective Cohort Study. Stroke. 2022;(November):3419-3428. doi:10.1161/strokeaha.122.039082

One strategy is to use magnetic resonance imaging (MRI) of the head for every patient with transient or minor neurological symptoms. MRI of the brain may detect diffusion- weighted imaging (DWI) lesions that are typical of acute brain ischemia or (rarely) may make a positive diagnosis of an alternative cause for symptoms such as multiple sclerosis or brain tumor. Where the diagnosis of TIA or stroke is secure, the pattern of ischemia seen on MRI may help to identify the underlying cause, such as multivascular-territory ischemia in cardioembolism.

To measure the benefits of an MRI strategy that scans all patients rather than a clinically targeted strategy, we need an estimate of the proportion of patients with positive DWI at different levels of clinical probability of a diagnosis of a TIA or minor stroke. For example, if the great majority of patients with a high clinical probability of TIA or stroke had DWI changes, or the great majority of patients with a low clinical probability had a negative MRI, then MRI could be targeted at those with intermediate clinical suspicion. However, if clinical probability did not identify a very high or low probability of DWI lesions, then a policy to scan all patients might be preferred.

Of the 272 participants, most had an MRI brain ≤2 days of symptom onset (157, 58%). Participants were mostly male (145, 53%); had a mean age of 60 (SD, 14); had only one episode of neurological symptoms (205, 75%); and had mild or no neurological signs (NIH Stroke Scale, 0: 247, 91%), which had either not resolved at presentation (118, 43%) or had resolved but lasted for ≥1 hour (94, 35%). In most participants, symptoms were monosymptomatic or all began simultaneously (156, 57%). Common non-focal symptoms were tiredness or fatigue (54%), headache (43%), and nausea or sickness. MRI evidence of acute brain ischemia was present in 61 (22%) participants. Of these 61 participants, 16 (26%) had one cortical infarct, 16 (26%) had one subcortical lacunar infarct, 11 (18%) had one cerebellar or brain stem infarct, and 18 (30%) had >1 infarct. The acute infarcts were all thought to be relevant to the participant’s symptoms.

MRI scanning in all patients presenting with transient or minor neurological symptoms is likely to identify some patients who would otherwise not receive a diagnosis of stroke or TIA because they were otherwise thought to be at low risk. However, whether this strategy is cost-effective, or how MRI scanning could best be targeted, is unclear.

4 tables, 2 figures, no imaging

5. Ayrignac X, Carra-Dallière C, Marelli C, Taïeb G, Labauge P. Adult-Onset Genetic Central Nervous System Disorders Masquerading as Acquired Neuroinflammatory Disorders: A Review. JAMA Neurol. 2022;79(10). doi:10.1001/jamaneurol.2022.2141

In this review, the authors provide a comprehensive description of the main genetic neuroinflammatory disorders that may be mistaken as acquired neuroinflammatory diseases and propose a diagnostic strategy to identify patients who may be proposed for targeted gene or next-generation sequencing (panel gene analysis or whole-exome/ whole-genome sequencing) and who may benefit from potential new therapies.

– Genetic leukodystrophies (X-ALD, MLD)

– Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a late-onset autosomal dominant inflammatory microangiopathy caused by TREX1 gene mutations

– Cytotoxic T lymphocyte antigen 4 (CTLA-4) is an inhibitory receptor that is constitutively expressed on regulatory T cells. Its upregulation on effector T cells after activation inhibits their proliferation. Heterozygous germline CTLA4 mutations have been recently described in patients with immune dysregulation and immunodeficiency

-Alexander disease is a very rare leukodystrophy caused by dominantly inherited mutations in the GFAP gene, resulting in astrocyte dysfunction leading to abnormal cytoplasmic inclusions within astrocytes (Rosenthal fibers). Depending on the age at symptom onset, 3 main clinical forms have been identified: neonatal/infantile (birth to 2 years), juvenile (2-14 years), and adult.

CLIPPERS is a recently described neuroinflammatory syndrome of unknown origin. It is typically characterized by symptomatic pontine T2/FLAIR hyperintense lesions with punctate (diameter <3mm) and curvilinear gadolinium-enhancing lesions that are responsive to and require maintenance treatment with steroids to avoid symptom relapse. In addition to pontine and cerebellar gadolinium-enhancing lesions, involvement of juxtacortical areas and spinal cord has been described. The biopsy of these gadolinium-enhancing lesions reveals perivascular and parenchymal CNS infiltrates composed of T cells and macrophages. In the absence of a specific biomarker, according to the diagnostic criteria published in 2017, the definite diagnosis of CLIPPERS can be made when the clinical, radiological, and histological criteria are met, and probable CLIPPERS made in the absence of histological confirmation. Nevertheless, CLIPPERS diagnosis is difficult, and its mimics, including autoimmune gliopathies (ie,myelin oligodendrocyte glycoprotein–associated disorders and autoimmune GFAP astrocytopathy), primary angiitis of the CNS, histiocytosis (Erdheim- Chester disease), and CNS lymphoma, must be excluded by appropriate ancillary tests.

Importantly, one-third of the tested patients with probable or definite CLIPPERS carry mutations in genes implicated in familial HLH (hemophagocytic lymphohistiocytosis).

2 figures, 2 tables, with many MR images

6. Catapano JS, Rumalla K, Srinivasan VM, Lawrence PM, Larson Keil K, Lawton MT. A taxonomy for brainstem cavernous malformations: subtypes of pontine lesions. Part 1: basilar, peritrigeminal, and middle peduncular. J Neurosurg. 2022;136(6):1-15. doi:10.3171/2022.1.JNS212690

The 323 pontine BSCMs were classified into 6 distinct subtypes: basilar (6 [1.9%]), peritrigeminal (53 [16.4%]), middle peduncular (MP) (100 [31.0%]), inferior peduncular (47 [14.6%]), rhomboid (80 [24.8%]), and supraolivary (37 [11.5%]). Part 1 of this 2-part series describes the taxonomic basis for the first 3 of these 6 subtypes of pontine CM. Basilar lesions are in the anteromedial pons and associated with contralateral hemiparesis. Peritrigeminal lesions are in the anterolateral pons and are associated with hemiparesis and sensory changes. Patients with MP lesions presented with mild anterior inferior cerebellar artery syndrome with contralateral hemisensory loss, ipsilateral ataxia, and ipsilateral facial numbness without cranial neuropathies. A single surgical approach and strategy were preferred for each subtype: for basilar lesions, the pterional craniotomy and anterior transpetrous approach was preferred; for peritrigeminal lesions, extended retrosigmoid craniotomy and transcerebellopontine angle approach; and for MP lesions, extended retrosigmoid craniotomy and trans–middle cerebellar peduncle approach. Favorable outcomes were observed in 123 of 143 (86%) patients with follow-up data. There were no significant differences in outcomes between the 3 subtypes or any other subtypes.

9 figures and 1 table with multiple graphics

7. Dmytriw AA, Dibas M, Adeeb N, et al. The Pipeline Embolization Device: a decade of lessons learned in the treatment of posterior circulation aneurysms in a multicenter cohort. J Neurosurg. 2022;137(November):1-8. doi:10.3171/2021.12.JNS212201

This study is a retrospective review of consecutive posterior circulation aneurysms managed with the PED at four academic institutions in the US between January 1, 2011, and January 1, 2021. Factors related to case selection, rates of aneurysm occlusion, or complications were identified and evaluated. Angiographic outcomes as well as thromboembolic and hemorrhagic complications were investigated.

This study included 117 patients (median age 60 years). At a median follow-up of 12 months, adequate occlusion (> 90%) was attained in 73.2% of aneurysms. Aneurysm occlusion rates were similar over the study interval. Thromboembolic and hemorrhagic complications were reported in 12.0% and 6.0% of the procedures, respectively.

The authors observed a trend toward a decline in the rate of thromboembolic and hemorrhagic complications with improved operator experience in using the PED for posterior circulation aneurysms. The use of single-device PED flow diversion significantly increased, as did the tendency to treat smaller aneurysms and observe large unruptured fusiform/dolichoectatic lesions. These findings reflect changes attributable to evolving judgment with maturing experience in PED use.

4 tables, 2 figures with angiograms

8. Rezai Jahromi B, Niemelä M. “Dolichoectatic Vertebrobasilar Artery Aneurysms.” Neurosurg Clin N Am [Internet]. 2022 Oct;33(4):419–29. Available from: https://doi.org/10.1016/j.nec.2022.06.003

Intracranial artery dolichoectasia (IADE) is a heterogenous arterial disease that is underdiagnosed and identified mainly in stroke patients. The abnormal lengthening (dolicho) and enlargement (ectasia) of intracranial arteries are poorly defined, especially in anterior circulation arteries. IADE of the vertebrobasilar artery was defined by Smoker and colleagues as follows: (1) basilar artery diameter larger than 4.5 mm, (2) tortuous of basilar artery more lies laterally from margin of clivus or dorsum sellae, and (3) basilar artery is above the suprasellar cistern. No definitions or criteria currently exist for anterior circulation dolichoectasia. Accurate natural history and epidemiologic studies are lacking due to an undefined population and cohorts, and also because IADEs are seen as normal anatomic variations.

The lack of classification related to the outcome and progression of IADE, as well as its underdiagnosis by physicians, has resulted in inconsistent studies on its epidemiology, disease progression, definition, and pathophysiology. Most patients are diagnosed after stroke by a neurologist and referred for neurosurgical evaluation when disease progression has reached a level with cranial nerve palsies or other treatments requiring decompression. Most IADE occurs in posterior circulation, making such cases vertebrobasilar dolichoectasia; some develop separate aneurysms, or the whole arterial segment expands aneurysmatically.

Despite the apparently poor prognosis of VBADAs, there have been no randomized clinical trials on this aspect. VBADA patients also have concomitant= diseases that force clinicians to treat lesions conservatively. Individual vascular plasticity and collateral formation have brought hope that VBADAs can be treated conservatively: If the patient is lucky, the VBADA may stabilize, and the aneurysm will stop growing while the brain stem perforators are kept intact. After the BA has enlarged by 10 mm or more, the probability of rupture increases whereas enlargement also brings the possibility of the cranial nerve stretching and the brainstem compressing. There are contradictory reports on whether thrombosis formation stabilizes or promotes VBADA’s malignant activity. The risk of stroke increases much earlier at 4.5 mm BA diameter, which forces patients to be treated prophylactically with antithrombotic medication (ASA), statins, and hypertension medication. Clinicians should closely follow-up on patients when VBADA shows any signs of activity.

4 figures with CT, CTA, MR and catheter angiography

The American Society of Neuroradiology is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Visit the ASNR Education Connection website to claim CME credit for this podcast.

1. Benjamini D, Priemer DS, Perl DP, Brody DL, Basser PJ. Mapping astrogliosis in the individual human brain using multidimensional MRI. Brain. Published online August 12, 2022:5-6. doi:10.1093/brain/awac298

There are currently no noninvasive imaging methods available for astrogliosis assessment or mapping in the central nervous system despite its essential role in the response to many disease states, such as infarcts, neurodegenerative conditions, traumatic brain injury, and infection. Multidimensional MRI is an increasingly employed imaging modality that maximizes the amount of encoded chemical and microstructural information by probing relaxation (T1 and T2) and diffusion mechanisms simultaneously. The authors use the exquisite sensitivity of this modality to derive a signature of astrogliosis and disentangle it from normative brain at the individual level using machine learning. They investigated ex vivo cerebral cortical tissue specimens derived from seven subjects who sustained blast induced injuries, which resulted in scar-border forming astrogliosis without being accompanied by other types of neuropathologic abnormality, and from seven control brain donors. By performing a combined postmortem radiology and histopathology correlation study they found that astrogliosis induces microstructural and chemical changes that are detected with multidimensional MRI, and which can be attributed to astrogliosis because no axonal damage, demyelination, or tauopathy were histologically observed in any of the cases in the study. Importantly, they showed that no one-dimensional T1, T2, or diffusion MRI measurement can disentangle the microscopic alterations caused by this neuropathology. Based on these finding, they developed a within-subject anomaly detection procedure that generates MRI-based astrogliosis biomarker maps ex vivo, which were significantly and strongly correlated with co-registered histological images of increased glial fibrillary acidic protein deposition. The findings elucidate the underpinning of MRI signal response from astrogliosis, and the demonstrated high spatial sensitivity and specificity in detecting reactive astrocytes at the individual level, and if reproduced in vivo, will significantly impact neuroimaging studies of injury, disease, repair, and aging.

7 figures, 1 table

2. Salih M, Enriquez-Marulanda A, Khorasanizadeh M, Moore J, Prabhu VC, Ogilvy CS. Cerebrospinal Fluid Shunting for Idiopathic Intracranial Hypertension: A Systematic Review, Meta-Analysis, and Implications for a Modern Management Protocol. Neurosurgery. 2022;91(4):529-540. doi:10.1227/neu.0000000000002086

This systematic review and meta-analysis assessed the outcome after CSF shunting for IIH by analyzing the published literature on the topic over a period of approximately 21 years. Although these are largely retrospective observational studies with some heterogeneity, a total of 372 patients from 15 studies were available for analysis. They selected the 3 cardinal and most disabling symptoms for this review; although other symptoms such as diplopia due to a sixth nerve palsy and pulsatile tinnitus may be noted, they are not consistently reported. They focused on headache, papilledema, and visual impairment for meta-analysis because most studies reported outcomes for these 3 symptoms and physical signs. The results of this study indicate that the most significant improvement was seen in papilledema; almost 96% of patients were noted to have an improvement in papilledema with CSF shunting. Headache also showed substantial improvement, with a 91% rate of improvement. Improvement of visual symptoms was noted in 85%.

Procedural complications and long-term durability of CSF shunting was also assessed. Intraprocedural complications and periprocedural infection or hemorrhage were not reported in any study. 12 studies reported periprocedural low-pressure headache due to CSF overdrainage. In most cases, original headache of patients improved for a short period of time after shunting, and they subsequently developed a headache that was related to body position. The overall occurrence rate of low-pressure headache was 20%. This may also be related to the relatively high rate of LP shunt placement that was observed in this analysis. There were no reports of malpositioned catheters or intracranial complications noted on cranial computed tomography (CT) in these patients. Overall, the most common reason for revision was catheter obstruction with recurrence of symptoms and signs of increased intracranial pressure. Other reasons for revision included abdominal catheter migration and infection.

Current management protocols were also discussed. Neuroimaging evaluation includes a high-quality MR and signs suggestive of IIH include flattening of the posterior scleral margins, widening of the peri-optic CSF space, tortuosity of the optic nerves, “empty-sella,” cerebellar tonsillar descent, and very small or slit-like ventricles. This is complemented by an MRV study to assess the status of the intracranial venous sinus pathways and look for any focal stenosis, atresia, or other venous abnormalities that may predispose an individual to developing IIH. If no contraindications exist, this is followed by a lumbar puncture (LP) to assess the opening CSF pressure and also allow removal of CSF from the lumbar subarachnoid cistern to ascertain any therapeutic benefit from CSF drainage. Routine CSF studies are also performed, and the patient is followed in clinic in 1 to 2 weeks to assess the response to CSF drainage. The diagnosis of IIH is confirmed by this collation of clinical symptomatology, neurological and ophthalmological evaluations, LP, and neuroimaging studies.

6 figures, 3 tables, no imaging

3. Lehrer EJ, Ahluwalia MS, Gurewitz J, et al. Imaging-defined necrosis after treatment with single-fraction stereotactic radiosurgery and immune checkpoint inhibitors and its potential association with improved outcomes in patients with brain metastases: an international multicenter study of 697 patients. J Neurosurg. Published online September 1, 2022:1-10. doi:10.3171/2022.7.JNS22752

Brain metastasis is the most common intracranial neoplasm. Conservative estimates indicate that a brain metastasis will be diagnosed in 10%–30% of cancer patients at some time during their disease course. Historically, these patients had a poor prognosis with a median overall survival (OS) of approximately 3.5 months. Treatment also consisted of a multimodal approach involving corticosteroids, resection, and whole-brain radiation therapy (WBRT). Treatment-related morbidity has markedly decreased in recent years because of the widespread adoption of stereotactic radiosurgery (SRS) and the incorporation of memantine and hippocampal avoidance in WBRT. Furthermore, improved systemic therapies, such as immune checkpoint inhibitors (ICIs), have demonstrated an improvement in OS across multiple advanced malignancies, such as non–small cell lung cancer (NSCLC), melanoma, and renal cell carcinoma (RCC), and they are now widely used in this setting.

Multiple retrospective single-institution studies have demonstrated that OS is improved when SRS is combined with ICIs, particularly when these therapies are administered within 4 weeks of one another. A complication of SRS is the development of radiation necrosis (RN), which can be associated with significant neurological morbidity with roughly 50% of patients being symptomatic. The incidence of RN following SRS ranges from 5% to 25%, with different studies using various diagnostic criteria ranging from pathological tissue diagnosis to imaging changes. Multiple factors have demonstrated an association with RN, such as dose-volume relationships, previous WBRT, use of systemic therapies, and choice of radiosurgery platform. Furthermore, the use of ICIs has demonstrated a strong association with the development of RN.

There were 697 patients with 4536 brain metastases with a median follow-up of 13.6 months who were included in the analysis. Treatment-related imaging changes (TRICs) were diagnosed in 9.8% of patients, and MRI was the diagnostic modality in 97.1% of the patients. The median number of brain metastases per patient was 3. The median age was 66 years, and 54.1% of patients were male. Primary tumor histology was NSCLC, melanoma, and RCC in 57.3%, 36.3%, and 6.4% of cases, respectively. TRICs were classified using MRI, PET, MR spectroscopy, or biopsy findings. MRI findings, such as contrast enhancement and perilesional edema, as well as specific enhancement patterns such as a “soap bubble” and “Swiss cheese” appearance, were noted. Although PET and MR spectroscopy were used in a minority of cases, the radiotracer standardized uptake value and choline/creatinine ratios were noted for PET and MR spectroscopy imaging, respectively. A multidisciplinary consensus by local clinical providers at each participating SRS site was mandated. TRICs following ICI and SRS were associated with a median OS benefit of approximately 6 months in this retrospective multicenter study.

2 figures, 3 tables, no imaging

4. Triplett JD, Kutlubaev MA, Kermode AG, Hardy T. Posterior reversible encephalopathy syndrome (PRES): diagnosis and management. Pract Neurol. 2022;22(3):183-189. doi:10.1136/practneurol-2021-003194

PRES often presents non-specifically with symptoms manifesting over several hours or days. Encephalopathy develops in 28%–94% of patients and ranges from mild confusion and cognitive deficits to stupor and sometimes coma. Seizures affecting up to 74%–87% of patients and typically occur within 24–48 hours of presentation; in a minority (3%–17%), seizures may evolve into status epilepticus, and rarely this is the presenting symptom. Headaches develop in up to half of patients with PRES and are usually dull, diffuse, and gradual in onset. A thunderclap headache can occur in the context of PRES but should raise the suspicion of reversible cerebral vasoconstriction syndrome (RCVS). This condition occurs in the context of similar risk factors to PRES but is distinguished mainly by thunderclap headache, cerebral vasculopathy, infarction, and subarachnoid or intracranial hemorrhage.

PRES is associated with numerous conditions and iatrogenic causes, though most frequently with hypertension, renal failure, eclampsia, transplant and immunosuppressive use, sepsis, autoimmune disorders and exposure to cytotoxic medications. Rarer iatrogenic causes include linezolid, intravenous immunoglobulin and intoxication with LSD, cocaine, and even scorpion poisoning.

The typical CT and MRI features of PRES include almost symmetrical hemispheric vasogenic oedema affecting subcortical white matter and often extending to the overlying cortex, best seen on MRI with FLAIR sequences. MRI diffusion-weighted imaging usually confirms vasogenic oedema with absence of restricted diffusion. Postcontrast enhancement occurs in 38%–50% of patients in one of three patterns: a leptomeningeal pattern, a cortical pattern within regions of altered FLAIR signal or a combined pattern.

Brain imaging shows bilateral cortical–subcortical vasogenic oedema that falls into three anatomical patterns seen in about 70% of patients: a dominant parieto-occipital pattern (22%), a holohemispheric watershed pattern (23%); and superior frontal sulcus pattern (27%). A central-variant (brainstem) pattern has also been identified, affecting the brainstem, basal ganglia, posterior limb of the internal capsule, cerebellum and periventricular regions, but has no cortical or subcortical involvement.

Intracranial hemorrhages are found on imaging in 10%–25% of cases, mostly intraparenchymal or subarachnoid. Up to 65% of patients who undergo follow-up MRI with susceptibility-weighted imaging have microhemorrhages.

PRES and RCVS are well known to overlap, and so cerebral CT or MR angiography is recommended to help to distinguish them. In RCVS, vessel wall MR angiography shows arterial wall thickening but without arterial wall enhancement, consistent with transient vasoconstriction. However, PRES occurs in 9%–38% of RCVS cases, and 87% of PRES cases have angiographic changes consistent with RCVS.

2 figures with imaging, 2 tables and an information box and keypoints

5. Baldassari LE, Wattjes MP, Cortese ICM, et al. The neuroradiology of progressive multifocal leukoencephalopathy: A clinical trial perspective. Brain. 2022;145(2):426-440. doi:10.1093/brain/awab419

Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection caused by JC virus (JCV), involving an infection of white matter (principally oligodendrocytes) and neurons in the brain, and leading to irreversible demyelination and neuroaxonal damage. Despite the persistent risk of PML among patients with immunosuppressive conditions and a growing risk of PML among patients treated with immunomodulatory agents, no therapeutics are approved for the treatment of PML.

Regarding imaging of PML in routine clinical care, there is substantial experience supporting the use of T2-weighted sequences (including T2-FLAIR) for identifying and monitoring individual lesions; gadolinium enhancement for identifying PML-IRIS (albeit not reliably); DWI for determining whether a lesion is actively expanding; and potentially SWI for assessing lesion chronicity. Perfusion, magnetization transfer, spectroscopy, and PET remain research applications at this time. Quantification of atrophy and lesion volumes are emerging areas of interest in the field of PML, but only limited data are available. Techniques for brain and lesion volume quantification are now available but require further research regarding performance and clinical application. In addition, there is no evidence supporting or refuting the application of ultra-high field MRI in PML. A limited number of case reports describe PML lesion characteristics and PML lesion evolution based 7 T MRI but do not report advances in lesion detectability and characterization relative to standard MRI field strengths. With respect to therapeutic trials, imaging outcome measures should ideally be objective, quantifiable using standardized methods, specific to the disease of interest, and correlated (both cross-sectionally and longitudinally) to clinically meaningful symptoms and disability. A surrogate end point should be predictive of the true clinical end point of interest and be in the causal pathway. Imaging measures show promise in this regard, potentially as surrogates of either a clinical measure or event (e.g. survival, degree of physical disability, quality of life) or disease activity (e.g. resolution of infection). Though extent of involvement on MRI (e.g. unilobar or widespread/ multilobar, as well as lesion burden) and the presence of supratentorial versus infratentorial lesions have been shown to be associated with survival and functional outcomes in some studies of PML, these data are generally limited, heterogeneous, and confounded by other clinical features (e.g. age, underlying disease, and baseline disability) known to be associated with survival.

1 table, 4 figures with imaging

6. Sekeres MA, Taylor J. Diagnosis and Treatment of Myelodysplastic Syndromes. JAMA. 2022;328(9):872. doi:10.1001/jama.2022.14578

Myelodysplastic neoplasms (MDS), formerly known as myelodysplastic syndromes, are clonal hematopoietic malignancies that cause morphologic bone marrow dysplasia along with anemia, neutropenia, or thrombocytopenia. MDS are associated with an increased risk of acute myeloid leukemia (AML). The yearly incidence of MDS is approximately 4 per 100 000 people in the United States. MDS are characterized by reduced numbers of peripheral blood cells, an increased risk of acute myeloid leukemia transformation, and reduced survival. The median age at diagnosis is approximately 70 years, and the yearly incidence rate increases to 25 per 100 000 in people aged 65 years and older. Risk factors associated with MDS include older age and prior exposures to toxins such as chemotherapy or radiation therapy. MDS are more common in men compared with women (with yearly incidence rates of approximately 5.4 vs 2.9 per 100 000). MDS typically has an insidious presentation, consisting of signs and symptoms associated with anemia, thrombocytopenia, and neutropenia. MDS can be categorized into subtypes that are associated with lower or higher risk for acute myeloid leukemia transformation and that help with therapy selection. Patients with lower-risk MDS have a median survival of approximately 3 to 10 years, whereas patients with higher-risk disease have a median survival of less than 3 years. Therapy for lower-risk MDS is selected based on whether the primary clinical characteristic is anemia, thrombocytopenia, or neutropenia. Management focuses on treating symptoms and reducing the number of required transfusions in patients with low-risk disease. For patients with lower-risk MDS, erythropoiesis stimulating agents, such as recombinant humanized erythropoietin or the longer-acting erythropoietin, darbepoetin alfa, can improve anemia in 15% to 40% of patients for a median of 8 to 23 months. For those with higher-risk MDS, hypomethylating agents such as azacytidine are first-line therapy. Hematopoietic cell transplantation is considered for higher-risk patients and represents the only potential cure.

3 tables, 1 graphic

7. Martín-Aguilar L, Lleixà C, Pascual-Goñi E. Autoimmune nodopathies, an emerging diagnostic category. Curr Opin Neurol. 2022; 579-585. doi:10.1097/wco.0000000000001107

The recent discovery of pathogenic antibodies against the nodes of Ranvier has led to the recognition of a new group of antibody-mediated neuropathies with well established clinical features and disease mechanisms that differ from classical inflammatory neuropathies. The nodes of Ranvier are small regions located at periodic interruptions of the myelin sheath in myelinated nerve fibers. Complex axoglial interactions configure their organization in a series of domains: the nodes, paranodes and juxtaparanodes. This organization is essential for the ability of myelinated fibers to conduct nerve impulses by saltatory conduction, a much faster and more energy-efficient mechanism of impulse propagation than that observed in unmyelinated fibers. Nodal/paranodal antibodies targeting cell adhesion molecules (CAMs) of the paranodal and nodal axo-glial junctions including contactin 1 (CNTN1), contactin-associated protein 1 (Caspr1), neurofascin 155 (NF115) and pan-neurofascin (panNF) were initially reported in 5–10% of patients that meet the clinical and electrodiagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP).

Clinical spectrum of autoimmune nodopathy includes acute, subacute or chronic onset sensory-motor neuropathies mimicking Guillain-Barre syndrome and chronic inflammatory demyelinating polyneuropathy but may differ in their response to IVIG. Neurophysiologically they overlap with acquired demyelinating neuropathies, but ultrastructural studies and animal models demonstrated antibody-mediated pathology restricted to the node.

1 table, no imaging

8. Shah VA, Thompson RE, Yenokyan G, et al. One-Year Outcome Trajectories and Factors Associated with Functional Recovery among Survivors of Intracerebral and Intraventricular Hemorrhage with Initial Severe Disability. JAMA Neurol. 2022;21287. doi:10.1001/jamaneurol.2022.1991

In this post hoc analysis (Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage phase 3 trial (CLEAR-III) and the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation (MISTIE-III) phase 3 trial) of patients with ICH and IVH and initial severe disability, more than 40% of patients recovered to good outcome by 1 year. Prediction of long-term functional recovery was significantly associated with improvement after inclusion of more granular baseline characteristics (ie, diabetes, leukoaraiosis, IVH volume, and pineal shift) and hospital events, including cerebral hypoperfusion, ischemic stroke, sepsis, persistent hydrocephalus, need for supportive interventions (mechanical ventilation and gastrostomy), and hematoma evolution. Significant reduction in hematoma and IVH volumes in the first month were strongly associated with long-term functional recovery, highlighting the importance of minimally invasive interventions to reduce blood volume. The combined cohort experienced higher rates of good 1-year outcome than previously reported, despite the inclusion of only patients with high-severity ICH and IVH. Outcomes from these clinical trials may be biased by rigid exclusion criteria, including baseline Glasgow Coma Scale score less than 4, fixed pupils, infratentorial extension, and baseline mRS greater than 1, limiting generalizability. However, outcomes were less impacted by early withdrawal of life-sustaining treatment, which occurred in only 88 of 999 patients (8.8%) in the first month, compared with 20% to 30%in prior studies. Patients with ICH who are maximally treated have favorable outcomes at a similar rate, highlighting the possible negative impact of early pessimistic prognostication on future recovery.

3 figures, 2 tables, no imaging

9. Selim MH. Time for a New Perspective on Intracerebral Hemorrhage. JAMA Neurol. 2022;79(9):844. doi:10.1001/jamaneurol.2022.1988

The recovery of patients with ICH takes a long time; many patients who have severe disability during hospitalization can achieve significant recovery over the following months to year. Accurate prognostication requires longer periods of evaluation after treatment. Most patients with ICH who die in the hospital do so after decisions are made to withdraw life-sustaining measures because of perceived high likelihood of poor long-term outcomes. These new findings give us an opportunity to pause and rethink how we approach ICH. The current American Heart Association/ American Stroke Association guidelines for the treatment of patients with spontaneous ICH recommend aggressive guideline-concordant care for all patients with ICH, unless they have previously documented their desire to limit these treatments before the onset of their ICH, including the postponement of new do-not-attempt-resuscitation and/or intubation orders or the withdrawal of medical support until at least the second full day of hospitalization. The author would argue that a much longer period is needed to promote maximal treatment for these patients. It is time for new evidence supported perspective on ICH.

The American Society of Neuroradiology is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Visit the ASNR Education Connection website to claim CME credit for this podcast.

1. Makarenko S, Alzahrani I, Karsy M, Deopujari C, Couldwell WT. Outcomes and surgical nuances in management of giant pituitary adenomas: a review of 108 cases in the endoscopic era. J Neurosurg. 2022;137(September):1-12. doi:10.3171/2021.10.jns21659

Pituitary adenomas are histologically benign lesions that are the third most common intracranial neoplasm. They account for 10%–25% of intracranial neoplasms, with a prevalence of 17%. A subgroup of these lesions that are ≥ 4 cm in maximum diameter are classified as giant pituitary adenomas. Estimated at 5%–10% of all pituitary lesions, these giant pituitary adenomas are particularly challenging to manage because surgery can be problematic in large lesions that grow beyond the sella turcica due to limited space and the proximity of key anatomical structures such as the optic nerves, chiasm, carotid arteries, and cranial nerves, as well as the normal pituitary gland. The lesions may present with symptoms of mass effect such as headaches, visual loss, and diplopia, but also symptoms resulting from inappropriate hormonal secretion.

The authors present a 108-patient, single-surgeon series of management of giant pituitary adenomas. They characterize the lesions and discuss surgical outcomes. They also outline how the surgical management paradigm has evolved with experience and illustrate surgical nuances utilized to treat these lesions with case examples.

Patients in this study underwent resection of a pituitary adenoma with stereotactic image guidance and use of microvascular Doppler probes when necessary to identify the carotid arteries and to guide the extent of bony resection. The approach was selected on a case-by-case basis: either transnasal microscopic transsphenoidal resection with or without assistance of an endoscope for visualization or a transcranial approach. In select cases, a combination of transsphenoidal and transcranial approaches was used to achieve GTR, which was defined as no visible tumor on follow-up imaging. Autologous fat or fascia lata graft was used in cases in which there was a high risk of postoperative CSF leak. Surgicel (Ethicon) was used to buttress the fat graft packing in a “sling technique” within the sphenoid sinus.

The mean preoperative tumor diameter in this cohort was 4.6, with a mean volume of 25.9 cm3. Ninety-seven patients underwent transsphenoidal approaches only, 3 underwent transcranial resection, and 8 patients underwent a combined approach. Gross-total resection was achieved in 42 patients. Tumor stability without a need for additional therapy was achieved in 77 patients, with 26 patients undergoing subsequent adjuvant radiotherapy. Among 100 patients with sufficient follow-up, 14 underwent adjuvant therapy—repeat operation and/or adjuvant radiation therapy—because of recurrence or tumor progression. Six patients with recurrence were observed without additional treatment. Overall, the morbidity associated with removal of these lesions was 11.1%; the most common morbidities were cerebrospinal fluid leak (5 patients, 4.6%) and hydrocephalus (4 patients, 3.7%).

They conclude that giant pituitary tumors still represent a surgical challenge, with significant morbidity. Gross-total resection occurs in a minority of patients. Surgical goals for removal of giant pituitary tumors should include attempts at removal of most tumor tissue to minimize the risk of residual tumor apoplexy by tailoring the approach along the major axis of the tumor.

7 figures with MR

2. Peng D, Yan M, Liu T, et al. Prognostic Factors and Treatments Efficacy in Spontaneous Spinal Epidural Hematoma. Neurology. 2022;99(8):e843-e850. doi:10.1212/WNL.0000000000200844

Spontaneous spinal epidural hematoma (SSEH) is a relatively uncommon but potentially devastating disorder. Patients generally present with sudden onset acute back or neck pain, followed by progressive motor, sensory symptoms, or sphincter dysfunction, which ultimately leads to complete/incomplete motor deficit caused by spinal cord/nerve root compression or cauda equina. Once the diagnosis is suspected, early surgical intervention should be considered. Although there is no consensus on the ideal timing for surgery, most authors consider that surgery performed within 12 hours after the onset of symptoms is associated with better outcomes. Owing to the relative rarity of SSEH, many of these reports were gleaned from single-center data with limited sample sizes. The clinical implication of these studies is therefore might be limited. A recent individual patient data meta-analysis from the published literature enrolled 617 patients and identified that severity of preoperative neurologic deficit and use of anticoagulants determine the postoperative outcomes, but not the time interval between symptom onset and surgery.

A total of 105 patients with SSEH were retrieved from medical records, with a mean age of 51.3 years. Eighty-three patients (79%) complained of acute onset of severe neck or back pain. Eighty-two patients (78%) suffered from moderate to severe neurologic deficits. Anticoagulation usage was found in 20% of cases. Lower thoracic spine, use of anticoagulants, sphincter function disfunction, severe neurologic deficits at admission, and rapid deterioration (<1 hour) were found to be associated with poor outcomes. Surgical decompression was performed in 74 (70%) cases.

They conclude that preoperative neurologic deficit and extended paraplegia time were strongly correlated with the prognosis in the subset of patients who underwent surgical decompression. Timely surgical decompression is recommended for patients with moderate/severe neurologic deficits or progressive neurologic deterioration.

3 tables, 1 figure, no imaging

3. Neth BJ, Carabenciov ID, Ruff MW, Johnson DR. Temporal Trends in Glioblastoma Survival. The Neurologist. 2022;27(3):119-124. doi:10.1097/NRL.0000000000000393

Glioblastoma is the most common primary CNS malignancy with a current median overall survival (OS) of ~15 months, ranking near the worst prognoses of all cancer. Historical management has focused on surgical resection and radiation therapy (RT) alone, with little additional progress until 2005 with the FDA approval of temozolomide (TMZ) as a first-line chemotherapy in combination with RT and maximal surgical resection, leading to a population-level survival benefit.

Multiple analyses have also documented a subsequent improvement in survival several years after TMZ was fully integrated into the standard of care. The reasons for this later improvement well after the FDA approval of TMZ are less clear, with hypotheses including use of bevacizumab (BEV), incremental improvements in RT and surgical techniques, and better quality of supportive care. In recent years, there have been further advances in GBM management such as the FDA approval of tumor-treating fields (TTF) (TT Fields represent a non-invasive anticancer modality consisting of low-intensity, intermediate-frequency, alternating electric fields delivered via cutaneous transducer arrays configured to provide optimal tumor-site coverage), continued advancements to RT, and surgical techniques with the tumor visualizing agent 5-ALA.

The authors evaluated population-based data (2000-2017) from the Survival, Epidemiology, and End Results (SEER) program of the National Cancer Institute (NCI) to identify recent trends in GBM survival.

A total of 38,352 patients diagnosed with GBM between 2000 and 2017 met inclusion criteria. Median survival and percent survival to 12 and 24 months all progressively increased between 2000 and 2011. There were no significant differences in survival comparing 2009-2011 with 2012-2014 or 2015-2017. During the 2015-2017 period, median survival was 11 months.

After a period of progressive improvement in GBM survival between 2000 and 2011, survival plateaued. Subsequent advances since 2011 have not yet been translated to improved survival on the population-level as of 2017. As the most common primary CNS malignancy, GBM continues to have dismal survival despite persistent efforts in management and therapeutic development. After modest gains in short-term survival after the introduction of TMZ and BEV, there has been negligible survival improvement since 2011.

2 figures, 3 tables, no imaging

4. Winegar BA. Imaging of Painful Ophthalmologic Disorders. Neurol Clin. 2022;40(3):641-660. doi:10.1016/j.ncl.2022.03.002

Nice pictorial review with 21 figures. Always disconcerting to see a diagnosis that you have never made in 35+ years of neuroradiology…meaning that I don’t know about this pathology. Hence, the following:  Inflammation of the optic nerve sheath is termed optic perineuritis. Most cases are a form of idiopathic orbital inflammation but may be secondary to a variety of systemic diseases such as sarcoidosis, IgG4-related disease, Behcet’s disease, granulomatosis with polyangiitis, and systemic lupus erythematosus or infections (eg, tuberculosis, syphilis, herpes simplex virus, herpes zoster virus). Symptoms of optic perineuritis may mimic optic neuritis, including pain, typically exacerbated by eye movement, and variable degree of vision loss. As opposed to optic neuritis, optic perineuritis is not self-limited and requires corticosteroids for treatment. On MRI, contrast enhancement and inflammation are centered on the optic nerve sheath, resulting in “tramtrack” appearance on axial images.

5. Tang LL, Guo R, Zhang N, et al. Effect of Radiotherapy Alone vs Radiotherapy With Concurrent Chemoradiotherapy on Survival Without Disease Relapse in Patients With Low-risk Nasopharyngeal Carcinoma. JAMA. 2022;328(8):728. doi:10.1001/jama.2022.13997

Concurrent chemoradiotherapy has been the standard treatment for stage II nasopharyngeal carcinoma (NPC) based on data using 2-dimensional conventional radiotherapy. There is limited evidence for the role of chemotherapy with use of intensity-modulated radiation therapy (IMRT). The purpose of this clinical trial was to determine if the omission of concurrent chemotherapy (ie, treatment with IMRT alone) was noninferior to treatment with concurrent chemoradiotherapy in patients with low-risk NPC. For this trial, low risk was defined as stage II or T3N0M0 disease without adverse features.

In this randomized clinical trial that included 341 participants with low-risk nasopharyngeal carcinoma who received IMRT alone vs concurrent chemoradiotherapy, the 3-year failure-free survival rate was 90.5%vs 91.9%, respectively. The difference met the noninferiority margin criterion of 10%.

3 figures, 2 tables

6. Wingerchuk DM, Lucchinetti CF. Neuromyelitis Optica Spectrum Disorder. Ropper AH, ed. New England Journal of Medicine. 2022;387(7):631-639. doi:10.1056/NEJMra1904655

NMOSD accounts for 1 to 2% of all cases of CNS inflammatory demyelinating disease in the United States and Europe, with multiple sclerosis being much more common, but NMOSD accounts for one third or more of cases of CNS inflammation in Asian and other non-White populations.

Six core clinical syndromes have been identified in NMOSD. They are classified by their location: optic nerve, spinal cord, area postrema of the dorsal medulla, other brain-stem regions, diencephalon, or cerebrum. These syndromes are manifested as acute attacks and relapses of neurologic dysfunction, with symptoms that typically evolve over a period of days. The most common syndromes are optic neuritis and transverse myelitis, as well as area postrema syndrome, which causes intractable or repetitive vomiting and hiccups. Multifocal lesions may result in a simultaneous or rapidly sequential combination of syndromes (e.g., optic neuritis and myelitis).

The sentinel attack involves the optic nerve or spinal cord in more than 85% of affected adults. Patients with optic neuritis present with unilateral or bilateral visual loss or scotoma, dyschromatopsia, and ocular pain exacerbated by eye movement that is not distinguishable from optic neuritis in multiple sclerosis or from an idiopathic form. Acute transverse myelitis causes limb weakness, numbness, sensory loss or pain below the lesion level, and bladder and bowel dysfunction.

Confirmation that an attack is due to NMOSD is greatly aided by the detection on MRI of characteristic lesions in the brain, optic nerve, optic chiasm, or spinal cord. In the acute phase, T2-weighted MRI sequences may show new or enlarging inflammatory lesions, and T1-weighted sequences obtained with gadolinium may show enhancement of actively inflamed lesions. Abnormalities on orbital MRI have a predilection for the optic chiasm or the adjacent posterior optic nerve but may occupy the full length of the nerve. MRI of the spinal cord typically shows longitudinally extensive transverse myelitis, defined as a lesion that is at least three contiguous vertebral segments in length.

1 figure, 2 tables, with MR imaging

7. Diener HC, Easton JD, Hart RG, Kasner S, Kamel H, Ntaios G. Review and update of the concept of embolic stroke of undetermined source. Nat Rev Neurol. 2022;18(August):455-465. doi:10.1038/s41582-022-00663-4

The definition of cryptogenic stroke in the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification (the most widely used classification system for ischemic stroke) and other classification schemes of stroke etiology includes three distinct groups of patients. The first is patients in whom diagnostic evaluation is incomplete, precluding identification of the causative pathology. Typical examples include patients who die soon after hospital admission, leaving no time for diagnostic investigation, and patients with other terminal illnesses that render diagnostic evaluation and therapeutic decisions less important. The second is patients who are diagnosed with two or more co-existing potential causes of stroke. A typical example is a patient with atrial fibrillation and an atherosclerotic plaque that is located ipsilateral to the infarct and is causing high-degree stenosis. Approximately 5% of patients with ischemic stroke have multiple obvious stroke aetiologies. The third is patients in whom the recommended diagnostic work-up is completed but no cause of stroke is identified.

In the TOAST classification, large-artery atherosclerotic strokes are defined as being associated with either substantial (>50%) stenosis or occlusion of a major brain artery or branch cortical artery. This arbitrary definition is now considered a limitation of the TOAST classification, as it does not include thromboembolic strokes provoked by an unstable plaque causing <50% stenosis, commonly described as a non-stenotic plaque. Subsequent etiological classifications have attempted to address this limitation; for example, the Causative Classification System and the Atherosclerosis, Small vessel disease, Cardioembolism, Other, Dissection (ASCOD) classification both allow stenosis of <50% to contribute to the final etiological determination. The prevalence of supracardiac atherosclerosis — that is, non-stenotic atherosclerotic plaques in the carotid, vertebrobasilar or intracranial arteries, or in the aortic arch — is remarkably high among patients with embolic stroke of undetermined source (ESUS). Among these patients, aortic arch atherosclerosis is prevalent in 29% (complex in 8%), carotid atherosclerosis in 40%, vertebrobasilar atherosclerosis in 4% and intracranial atherosclerosis in 13%. The risk of recurrent stroke with each of these pathologies could differ so that optimal treatment might also differ.

2 tables and 1 information box, but no imaging

8. Gao P, Wang T, Wang D, et al. Effect of Stenting Plus Medical Therapy vs Medical Therapy Alone on Risk of Stroke and Death in Patients With Symptomatic Intracranial Stenosis. JAMA. 2022;328(6):534. doi:10.1001/jama.2022.12000

Prior randomized trials have generally shown harm or no benefit of stenting added to medical therapy for patients with symptomatic severe intracranial atherosclerotic stenosis, but it remains uncertain as to whether refined patient selection and more experienced surgeons might result in improved outcomes.

Multicenter, open-label, randomized, outcome assessor–blinded trial conducted at 8 centers in China. A total of 380 patients with transient ischemic attack or nondisabling, nonperforator (defined as nonbrainstem or non–basal ganglia end artery) territory ischemic stroke attributed to severe intracranial stenosis (70%-99%) and beyond a duration of 3 weeks from the latest ischemic symptom onset were recruited between March 5, 2014, and November 10, 2016, and followed up for 3 years.

The risk of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year occurred in 8.0% in the percutaneous transluminal angioplasty and stenting group vs 7.2% in the medical therapy alone group, a difference that was not statistically significant.

They conclude that among patients with transient ischemic attack or ischemic stroke due to symptomatic severe intracranial atherosclerotic stenosis, the addition of percutaneous transluminal angioplasty and stenting to medical therapy, compared with medical therapy alone, resulted in no significant difference in the risk of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. The findings do not support the addition of percutaneous transluminal angioplasty and stenting to medical therapy for the treatment of patients with symptomatic severe intracranial atherosclerotic stenosis.

3 figures, 2 tables, no imaging

9. Anderson CS, Song L, Liu J. Therapeutic Strategies for Intracranial Atherosclerosis. JAMA. 2022;328(6):529-531

The China Angioplasty and Stenting for Symptomatic Intracranial Severe Stenosis (CASSISS) trial, was undertaken with special care to address perceived shortcomings of previous studies and allow an assessment of the effectiveness of the Wingspan stent combined with standard medical therapy vs standard medical therapy alone. The medical therapy included dual antiplatelet therapy, commenced 3 to 5 days prior to the procedure and continued for 90 days after, and guideline-recommended use of statins and antihypertensive therapy to manage stroke risk factors. Participating sites were carefully selected and narrow inclusion criteria were used to identify a potential “responder group” at low procedural risk: patients with TIA or nondisabling, non-perforator territory, ischemic stroke from severe isolated intracranial stenosis (70%-99%) that occurred between 3 weeks and 12 months prior to randomization. Rigorous performance, training, and quality control procedures were used, and efforts were made toward achieving a high level of patient follow-up, with blinded and objective outcome assessments over 3 years.

Despite the efforts to improve patient selection and operator experience, the CASSISS trial redemonstrated that any potential benefit of stenting for ICAS in terms of long-term stroke prevention appears to be at least counterbalanced by the short-term procedural risk, which includes both ischemic and hemorrhagic events. Although arguments can be made that the restrictive inclusion criteria inevitably led to a biased, stable, “lower-risk” patient group, the trial further highlights the importance of best medical management of cardiovascular risk factors, in particular, use of statins and blood pressure– lowering agents to achieve guideline recommended targets in this patient population.

No figures

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