Teaching NeuroImage: Nevus Flammeus, Ocular Melanosis, and Seizures in Young Adult With Sturge-Weber and Klippel-Trenaunay Overlap Syndrome
http://n.neurology.org/cgi/content/short/100/20/984?rss=1

An 18-year-old man with delayed gross motor and language development and congenital glaucoma presented with recurrent seizures since 3 months of age. The seizures were characterized by left focal onset with secondary generalization and complicated by frequent drug noncompliance. Examination revealed a port-wine stain over the face and extremities (Figure, A), bluish-grey discoloration of the eyes and periocular region (Figure, B and E), and limb-length discrepancy with right upper-limb hyperplasia (Figure, C). These examination findings along with frontal atrophy and gyral calcifications seen on CT (Figure, D) prompted a diagnosis of Sturge-Weber (SW) and Klippel-Trenaunay (KT) overlap syndrome with ocular melanosis. Both SW and KT syndromes are mesodermal phacomatoses which share port-wine stain as a common clinical feature.1 The presence of glaucoma, epilepsy, and cerebral gyral calcification are unique to SW, while the limb hyperplasia is exclusive to KT,1 with ocular melanosis being additional.2

266

5

What Are the Roles of Pericytes in the Neurovascular Unit and Its Disorders?
http://n.neurology.org/cgi/content/short/100/20/970?rss=1

Pericytes are fundamental components of the neurovascular unit (NVU). They interact with endothelial cells, basal lamina (basement membrane), and glial cells and have a critical role in maintenance of blood-brain barrier (BBB) stability, local control of capillary blood flow, angiogenesis, and immune responses. Pericytes may also function as stem cells with potential to differentiate to into smooth muscle, glial cells, or neurons. A wide range on neurologic disorders, including vascular disorders, neurodegenerative disorders such as Alzheimer disease (AD), traumatic injury, and multiple sclerosis (MS) are associated with changes in pericyte structure and function affecting the NVU. Dysfunctional pericyte signaling may be a potential biomarker of NVU pathology and provides therapeutic targets for neuroprotection. The functions of pericytes and their role in neurologic disorders have been the subject of several comprehensive reviews.1-13

96

0

Neurologic Care of Forcibly Displaced Persons: Emerging Issues in Neurology
http://n.neurology.org/cgi/content/short/100/20/962?rss=1

There is a growing number of forcibly displaced persons (FDPs) worldwide. With more than 100 million people forcibly displaced today, there is an urgent mandate to understand the neurologic care needs of this population and how neurologists and other health care workers can most effectively provide that care. In this Emerging Issues in Neurology article, we attempt to (1) define the scope of the problem of providing neurologic care to FDPs, (2) highlight commonly encountered clinical challenges related to neurologic care of FDPs, and (3) provide useful clinical information for neurologists and other clinicians who deliver care to FDPs with neurologic needs. We address the terminology of forcible displacement and how terms may differ across a person's migration journey. Common challenges encountered by FDPs with neurologic needs across settings include loss of support systems, loss of personal health information, language barriers and differing expression of symptoms, differing belief systems, epidemiologic patterns of disease unfamiliar to the clinician, and patients' fear and perceived risks of engaging with health systems. Practical approaches are shared for clinicians who encounter an FDP with a neurologic presentation. Finally, the article discusses many unmet neurologic needs of FDPs, which require significant investment. These include addressing lapses in neurologic care during displacement and understanding the effects of forcible displacement on people with chronic neurologic conditions. Future research and educational resources should focus on improving epidemiologic intelligence for neurologic conditions across geographies, developing curricula for optimizing the neurologic care of FDPs, and evaluating the most appropriate and effective uses of health technologies in humanitarian settings.

88

0

Brain Shrinkage in Anti-{beta}-Amyloid Alzheimer Trials: Neurodegeneration or Pseudoatrophy?
http://n.neurology.org/cgi/content/short/100/20/941?rss=1

One of the puzzling observations from anti–amyloid-β therapeutic trials for Alzheimer disease (AD) has been that treated arms fail to show preservation of brain volume. In this issue of Neurology®, Alves et al.1 presented a meta-analysis of anti–amyloid-β therapies and show that the agents do not slow the rate of brain volume loss. Depending on the class of drug, these new agents can even accelerate loss of whole-brain and hippocampal volume and increase ventricular volume. This association has been seen with some of the beta-secretase inhibitors and with several of the antiamyloid monoclonal antibodies.

83

0

Clinical Reasoning: A Teenager With Chronic Meningitis--Does Occam's Razor Apply?
http://n.neurology.org/cgi/content/short/100/17/828?rss=1

A 14-year-old girl presented with subacute onset headache, fever, and vomiting and was managed initially with antibiotics for suspected bacterial meningitis. Her symptoms further evolved over the next few weeks with systemic signs and symptoms favoring chronic meningitis with raised intracranial pressure. After the etiologic workup was unrevealing, she was started on empirical antituberculous therapy. After a period of partial improvement, symptoms recurred with a new-onset focal seizure. Her imaging findings evolved from features suggestive of focal leptomeningitis to multifocal heterogeneous enhancing cortical and subcortical lesions with hemorrhagic foci, leading to brain biopsy that confirmed diagnosis. Our case highlights the utility of diagnostic biopsy in patients with "chronic meningitis" in uncertain cases rather than confining the approach to the law of parsimony. The decision to initiate empirical therapy in chronic meningitis should be considered on a case-by-case basis and take into account factors, such as clinical examination findings, immune status, recent exposures, and potential risks of treatment. Atypical MRI features should lower the threshold for meningocortical biopsy when indicated.

464

3

Author Response: Hyperacute Perfusion Imaging Before Pediatric Thrombectomy: Analysis of the Save ChildS Study
http://n.neurology.org/cgi/content/short/100/17/843?rss=1

We thank Drs. Siegler and Nguyen for their insightful comments on our article.1 We found no significant difference in median admission to recanalization times in the perfusion imaging group (1.5 hours, interquartile range [IQR] 1.0–2.5) compared with the nonperfusion group (1.5 hours, IQR 1.0–1.9, p = 0.455). Time of skin puncture was not collected in the Save ChildS study, but will be an important data point for future studies.

444

1

NEXMIF Epilepsy: An Alternative Cause of Progressive Myoclonus
http://n.neurology.org/cgi/content/short/100/14/672?rss=1

An 8-year-old boy with generalized myoclonic epilepsy followed by progressive cognitive decline presented with worsening myoclonus despite being compliant with prescribed clobazam. The movements (Video 1) in conjunction with a worsening cognitive status over time were concerning for a progressive myoclonic epilepsy. Initial EEG captured frequent myoclonic seizures time-locked with spike-wave activity (Figure). Overnight EEG revealed normal sleep architecture. His seizures stopped with valproic acid load. Genetic testing revealed a heterozygous pathogenic variant in NEXMIF (c.2478_2479dup), which is associated with NEXMIF encephalopathy. NEXMIF encephalopathy is characterized by mild to severe intellectual disability and includes myoclonic seizures, absence seizures, and atonic seizures.1

106

0

Natural Course and Prognosis of Primary Spinal Glioblastoma: A Nationwide Study
http://n.neurology.org/cgi/content/short/100/14/e1497?rss=1

Background and Objectives
Primary spinal glioblastoma (PsGBM) is extremely rare. The dramatic neurologic deterioration and unresectability of PsGBM makes it a particularly disabling malignant neoplasm. Because it is a rare and heterogeneous disease, the assessment of prognostic factors remains limited.

Methods
PsGBMs were identified from the French Brain Tumor Database and the Club de Neuro-Oncologie of the Société Francaise de Neurochirurgie retrospectively. Inclusion criteria were age 18 years or older at diagnosis, spinal location, histopathologic diagnosis of newly glioblastoma according to the 2016 World Health Organization classification, and surgical management between 2004 and 2016. Diagnosis was confirmed by a centralized neuropathologic review. The primary outcome was overall survival (OS). Therapeutic interventions and neurologic outcomes were also collected.

Results
Thirty-three patients with a histopathologically confirmed PsGBM (median age 50.9 years) were included (27 centers). The median OS was 13.1 months (range 2.5–23.7), and the median progression-free survival was 5.9 months (range 1.6–10.2). In multivariable analyses using Cox model, Eastern Cooperative Oncology Group (ECOG) performance status at 0–1 was the only independent predictor of longer OS (hazard ratio [HR] 0.13, 95% CI 0.02–0.801; p = 0.02), whereas a Karnofsky performance status (KPS) score p = 0.03) and a cervical anatomical location (HR 4.14, 95% CI 1.32–12.98; p = 0.01) were independent predictors of shorter OS. The ambulatory status (Frankel D–E) (HR 0.38, 95% CI 0.07–1.985; p = 0.250) was not an independent prognostic factor, while the concomitant standard radiochemotherapy with temozolomide (Stupp protocol) (HR 0.35, 95% CI 0.118–1.05; p = 0.06) was at the limit of significance.

Discussion
Preoperative ECOG performance status, KPS score, and the location are independent predictors of OS of PsGBMs in adults. Further analyses are required to capture the survival benefit of concomitant standard radiochemotherapy with temozolomide.

107

0

Reader Response: Endovascular vs Medical Management for Late Anterior Large Vessel Occlusion With Prestroke Disability: Analysis of CLEAR and RESCUE-Japan
http://n.neurology.org/cgi/content/short/100/13/641-a?rss=1

We were intrigued with the study conducted by Siegler et al.1 who analyzed the potential benefits of mechanical thrombectomy among patients with acute stroke with preexisting disabilities. We would like to outline important limitations in comparing baseline (prestroke) and poststroke modified Rankin scale (mRS) scores.

14197

2

Disentangling the Association Between Neurologic Deficits, Patient-Reported Impairments, and Quality of Life After Ischemic Stroke
http://n.neurology.org/cgi/content/short/100/13/e1321?rss=1

Background and Objectives
The EuroQol Group 5-Dimension Self-Reported Questionnaire (EQ-5D) is a well-established instrument to assess quality of life and generates generic utility values for health states reported by patients, derived from assessments by the general public. We hypothesized that language problems and other nonmotor deficits are not captured as well as motor deficits by this system. We aimed to quantify the association between disabling neurologic deficits and the EQ-5D dimension scores and the utility score in patients with ischemic stroke.

Methods
We used data of the Interventional Management of Stroke III trial. Missing data were imputed by multiple imputation. The association between neurologic deficits (individual NIH Stroke Scale [NIHSS] item scores) and the EQ-5D-3L (5 three-level dimension scores and utility score) at 90 days was assessed with ordinal logistic regression and Tobit regression, respectively. The explained variance of each model was estimated with Nagelkerke pseudo-R2 or R2.

Results
In total, 525 surviving patients were included. Complete data on both the NIHSS and EQ-5D were available for 481/525 (91.6%) patients. At 90 days, 161/491 (32.8%) patients had aphasia and 226/491 (46.0%) patients had paresis of at least 1 limb. Limb paresis, facial palsy, sensory loss, and dysarthria explained most of the variance in all EQ-5D dimension scores and the utility score. In the utility score, 8.9% of the variance was explained by neglect, 10.0% by aphasia, 10.8% by hemianopia, and 17.5%–24.1% by limb paresis.

Discussion
The impact of neurologic deficits on the EQ-5D in patients with ischemic stroke is mostly due to limb paresis, while the EQ-5D is less sensitive to other nonmotor deficits such as hemianopia, aphasia, and neglect. This may lead to overestimation of quality of life and, consequently, underestimation of the (cost-)effectiveness of treatments and interventions.

Trial Registration Information
ClinicalTrials.gov (http://www.clinicaltrials.gov/). Unique identifier: NCT00359424.

52309

0