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A 57-year-old woman presented with a 20-year history of progressive lower extremity weakness, spasticity, and proprioception deficits. She was given a diagnosis of primary progressive multiple sclerosis at age 38. Her Achilles tendons were enlarged (figure 1). Brain MRI was normal. Spine MRI demonstrated T2-hyperintense signal involving the posterior and lateral columns (figure 2). Serum cholestanol level was elevated. CYP27A1 gene sequencing revealed 2 pathogenic variants, c.1183C>T(p.Arg395Cys) and c.410G>A(p.Arg137Gln), confirming the diagnosis of cerebrotendinous xanthomatosis (CTX). Spinal xanthomatosis is a rare variant of CTX presenting with progressive corticospinal and posterior column signs.1 Early treatment with chenodeoxycholic acid may improve outcomes.2

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune, inflammatory disorder of the central nervous system that typically presents with recurrent episodes of optic neuritis, longitudinally extensive myelitis, brainstem, diencephalic, and cerebral syndromes. Up to 80% of NMOSD patients have a circulating pathogenic autoantibody that targets the water channel aquaporin-4 (AQP4-IgG). The discovery of AQP4-IgG transformed our understanding of the pathogenesis of the disease and its possible treatment targets. Monoclonal antibodies targeting terminal complement (eculizumab), CD19 (inebilizumab), and the interleukin-6 receptor (satralizumab) have demonstrated efficacy in NMOSD attack prevention in recent phase 3 trials and have gained subsequent regulatory approval in the USA and other countries. We aim to review the evidence supporting the efficacy of these new drugs.

A 60-year-old woman with a history of multiple sclerosis was evaluated for cognitive concerns. At age 30 years she had an episode of optic neuritis, followed by an episode of bilateral lower extremity numbness at age 35 years. In the following years, she had at least 6 further multiple sclerosis relapses, the last one approximately 3 years before the current presentation. She was initially treated with interferon, but she did not tolerate it. She had been taking glatiramer acetate for the past 3 years. She had noticed progressive deterioration of her gait for the past 3 years, having to use a cane on occasions. Magnetic resonance imaging of the brain showed multiple demyelinating lesions), and magnetic resonance imaging of the cervical spine showed 1 small demyelinating lesion at C6. Vitamin B12 level and thyroid function were normal. Comprehensive neuropsychological testing showed multidomain cognitive impairment, mainly impairment of speed of information processing, spatial discrimination skills, and attention/concentration. The patient’s multiple sclerosis phenotype was consistent with secondary progressive multiple sclerosis. Her cognitive impairment profile, mainly affecting information processing speed and disinhibition suggestive of frontal dysfunction, was consistent with multiple sclerosis. The patient began a cognitive rehabilitation program, and learning and memory aids were recommended. Lifestyle changes were also recommended, including weight loss and physical exercise. She was given recommendations for sleep hygiene and began taking gabapentin for neuropathic pain and restless legs. Cognitive impairment is common in patients with multiple sclerosis. Slowed cognitive processing speed and episodic memory decline are the most common cognitive deficits in MS, with additional difficulties in executive function, verbal fluency, and visuospatial analysis.

Usually used in emergency settings, bedside sonographic measurement of optic nerve sheath diameter can aid in diagnosing elevated intracranial pressure. We report a case of a 26-year-old male hospitalized for CAR T-cell therapy with Axicabtagene Ciloleucel for treatment of relapsed diffuse large B-cell lymphoma, who developed progressive symptoms of immune effector cell-associated neurotoxicity syndrome. Fundoscopic examination suggested the presence of blurred optic disc margins. Bedside ocular ultrasound revealed wide optic nerve sheath diameters and bulging optic discs bilaterally. The patient had a ventriculostomy placed for monitoring and received treatment with steroids and mannitol, as well as tocilizumab. After 7 days in the ICU, the patient recovered with no evidence of long-term neurological deficits.

Background Guidelines to provide recommendations about driving restrictions for patients with brain metastases are lacking. We aim to determine whether clinical neurologic examination is sufficient to predict suitability to drive in these patients by comparison with an occupational therapy driving assessment (OTDA). Methods We prospectively evaluated the concordance between neurology assessment of suitability to drive (pass/fail) and OTDA in 41 individuals with brain metastases. Neuro-oncology evaluation included an interview and neurological examination. Participants subsequently underwent OTDA during which a battery of objective measures of visual, cognitive, and motor skills related to driving was administered. Results The mean age of patients who failed OTDA was age 68.9 years vs 59.3 years in the group members who passed (P = .0046). The sensitivity of the neurology assessment to predict driving fitness compared with OTDA was 16.1% and the specificity 90%. The 31 patients who failed OTDA were more likely to fail Vision Coach, Montreal Cognitive Assessment, and Trail Making B tests. Conclusions There was poor association between the assessment of suitability to drive by neurologists and the outcome of the OTDA in patients with brain metastases. Subtle deficits that may impair the ability to drive safely may not be evident on neurologic examination. The positive predictive value was high to predict OTDA failure. Age could be a factor affecting OTDA performance. The results raise questions about the choice of assessments in making recommendations about driving fitness in people with brain metastases. OTDA should be strongly considered in patients with brain metastases who wish to continue driving.

Post-transplantation lymphoproliferative disorder (PTLD) is a complication of solid organ and hematopoietic stem cell transplantation. Cases with isolated central nervous system (CNS) disease are rare. Epstein-Barr virus (EBV) plays a causative role. We present a patient with EBV cerebellitis documented 5 months prior to development of primary CNS PTLD (PCNS-PTLD). This case report demonstrates progression from EBV CNS infection to lymphoproliferative disorder, highlighting the importance of serial clinical and imaging monitoring in transplant patients post-EBV CNS infection. PCNS-PTLD should always be considered in the differential diagnosis for transplant patients presenting with CNS symptoms, even in cases with no evidence of EBV viremia. Earlier diagnosis and appropriate treatment could result in improved outcomes.

Paraneoplastic neurological syndromes are more commonly seen with malignancies such as small cell lung cancer, thymoma, gynecological malignancies, and breast cancer as well as seminoma. With the introduction of immune checkpoint inhibitor (ICI) cancer immunotherapy we see an increase of autoimmune neurological complications in patients with malignancies not traditionally associated with paraneoplastic neurological syndromes, such as melanoma and renal cell carcinoma. Immune checkpoint inhibitors enhance antitumor immune responses resulting often in immune-related adverse effects that can affect any organ, including the central and peripheral nervous system, neuromuscular junction and muscle. Neurological complications are rare; neuromuscular complications are more common than central nervous system ones but multifocal neurological presentations are often encountered. The vast majority of neurological complications appear within 3 months of ICI initiation, but have been described even after ICI cessation. Neural autoantibody testing reveals autoantibodies in approximately half of the patients with CNS complications. Early suspicion and diagnosis is critical to avoid worsening and improve outcomes. Therapeutic strategies depend on the severity of the symptoms and initially typically involve discontinuation of ICI and high dose steroids. Further immunosuppression might be necessary. Outcomes are dependent on patient's characteristics and clinical presentations.

Background and ObjectiveSevere attacks of myelin oligodendrocyte glycoprotein (MOG) antibody–associated disorder (MOGAD) and aquaporin-4 (AQP4) antibody–positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) may require ventilatory support, but data on episodes are limited, particularly for MOGAD. We sought to compare the frequency, characteristics, and outcomes of MOGAD and AQP4-NMOSD attacks requiring ventilatory support.MethodsThis retrospective descriptive study identified Mayo Clinic patients (January 1, 1996–December 1, 2020) with MOGAD or AQP4-NMOSD and an attack requiring noninvasive or invasive ventilation at Mayo Clinic or an outside facility by searching for relevant terms in their electronic medical record. Inclusion criteria were (1) attack-related requirement for noninvasive (bilevel positive airway pressure or continuous positive airway pressure) or invasive respiratory support (mechanical ventilation); (2) MOG or AQP4 antibody positivity with fulfillment of MOGAD and AQP4-NMOSD clinical diagnostic criteria, respectively; and (3) sufficient clinical details. We collected data on demographics, comorbid conditions, indication for and duration of respiratory support, MRI findings, treatments, and outcomes. The races of those with attacks requiring respiratory support were compared to those without such attacks in MOGAD and AQP4-NMOSD.ResultsAttacks requiring ventilatory support were similarly rare in patients with MOGAD (8 of 279, 2.9%) and AQP4-NMOSD (11 of 503 [2.2%]) (p= 0.63). The age at attack (median years [range]) (MOGAD 31.5 [5–47] vs AQP4-NMOSD 43 [14–65];p= 0.01) and percentage of female sex (MOGAD 3 of 8 [38%] vs AQP4-NMOSD 10 of 11 [91%];p= 0.04) differed. The reasons for ventilation differed between MOGAD (inability to protect airway from seizure, encephalitis or encephalomyelitis with attacks of acute disseminated encephalomyelitis 5 [62.5%] or unilateral cortical encephalitis 3 [37.5%]) and AQP4-NMOSD (inability to protect airway from cervical myelitis 9 [82%], rhombencephalitis 1 [9%], or combinations of both 1 [9%]). Median ventilation duration for MOGAD was 2 days (range 1–7 days) vs 19 days (range 6–330 days) for AQP4-NMOSD (p= 0.01). All patients with MOGAD recovered, but 2 of 11 (18%) patients with AQP4-NMOSD died of the attack. For AQP4-NMOSD, Black race was overrepresented for attacks requiring ventilatory support vs those without these episodes (5 of 11 [45%] vs 88 of 457 [19%];p= 0.045).DiscussionVentilatory support is rarely required for MOGAD and AQP4-NMOSD attacks, and the indications differ. Compared to MOGAD, these attacks in AQP4-NMOSD may have higher morbidity and mortality, and those of Black race were more predisposed, which we suspect may relate to socially mediated health inequality.

Highlights • The role of pre-existing immunosuppression on COVID-19 risk and outcomes is unclear • Immunotherapy is being evaluated for COVID-19-related cytokine release syndrome • We report a fingolimod-treated MS patient who developed severe COVID-19 • COVID-19 recovery occurred after stopping fingolimod and treating with tocilizumab, Background : Treatment decisions in patients with multiple sclerosis (MS) during the coronavirus disease 2019 (COVID-19) pandemic are challenging. It is not known whether and how various disease modifying therapies, especially immunosuppressive drugs, affect COVID-19 risk and disease course. Methods : Case report Results : We report a fingolimod-treated MS patient who developed severe COVID-19 but recovered after treatment with tocilizumab. Conclusion : This report suggests that a brief course of tocilizumab for the treatment of severe COVID-19 may be effective while not aggravating pre-existing MS.

In recent years there has been a dramatic rise in available disease-modifying therapies for the treatment of relapsing multiple sclerosis (MS). Dimethyl fumarate (DMF) is an oral drug approved by the FDA for relapsing MS with unique immunomodulatory and cytoprotective effects.Herein, the authors provide the reader with a review of the literature obtained via a PubMed database search and provide their expert opinion on the use of DMF in clinical practice. The article details DMF's mechanism of action, long-term data on efficacy, tolerability and safety.Since approval, growing experience with DMF in clinical practice demonstrates a combination of efficacy, ease of administration along with an acceptable safety profile. The authors believe that DMF is a valuable long-term treatment option in patients with relapsing MS. However, long-term follow up studies are needed to provide further data on progressive multifocal leukoencephalopathy (PML) risk stratification for MS patients on treatment with DMF. Indeed, despite the strong association with lymphopenia, not all patients with DMF associated PML experienced prolonged overall lymphopenia, suggesting that additional predictive metrics are still needed.

The authors report the case of a 39-year-old woman with leukemic meningitis. A right frontal Ommaya reservoir was placed for intrathecal chemotherapy. During and immediately following the first injection of chemotherapy, the patient developed an episode of nausea, emesis, frontal headache and diarrhea. These same symptoms were later elicited during a second and third administration of chemotherapy. Post-placement head computed tomography showed the tip of the catheter projecting approximately 1.5 cm inferior to the floor of the left frontal ventricle. After a revision of the Ommaya catheter due to suboptimal positioning, subsequent intrathecal chemotherapy administration was tolerated without any of the adverse symptoms previously encountered. The case documents an unusual complication arising from catheter migration in the setting of intrathecal chemotherapy and also demonstrates the value in troubleshooting Ommaya reservoir complications rather than prematurely abandoning its use in favor of lumbar puncture.

Background To determine the predictive value of retinal microvascular abnormalities for cerebrovascular ischemic diseases (CVDs), we aimed to investigate the quantitative association between retinal microvascular changes and CVD subcategories: white matter hyperintensities (WMHIs), lacunar infarcts (LIs), and cerebral infarctions (CIs). Methods Using Meta-analyses Of Observational Studies in Epidemiology guidelines, we searched 6 databases through September 2016 for studies evaluating the linkage between retinal microvascular abnormalities and WMHI, and LI and CI. Studies were included if they reported odds ratios (ORs) and 95% confidence intervals or raw patient level data (that were computed into ORs). Unadjusted and vascular risk-factor adjusted ORs were pooled into meta-analysis using DerSimonian Laird random effects model. Study quality and dissemination biases were assessed and integrated. Results From 24,444 search-identified records, 28 prospective studies encompassing 56,379 patients were eligible for the meta-analysis. After vascular risk-factor adjustment, focal arteriolar narrowing was associated with WMHI (OR, 1.24 [1.01-1.79]), LI (OR, 1.77 [1.14-2.74]), and CI (OR, 1.75 [1.14-2.69]). Venular dilation was associated with LI (OR, 1.46 [1.10-1.93]), and retinal hemorrhages with WMHI (OR, 2.23 [1.34-3.70]). Any retinopathy exhibited significant association with CI (OR, 1.96 [1.65-2.50]). Heterogeneity was significant (I2>50%) for all syntheses except retinal hemorrhages and WMHI, and retinopathy and CI (I2=0 ⋅ 0%). Associations remained significant after adjustments for quality and publication bias. Conclusions We found the most significant association between retinal hemorrhages and WMHI. Focal arteriolar narrowing and retinopathy predicted CVD subtypes after risk-factor adjustment, suggesting that features different than traditional vascular risk factors, are involved in CVD pathophysiology.

The differential diagnosis for immune-mediated myelopathies is broad. Although clinical manifestations overlap, certain presentations are suggestive of a particular myelopathy etiology. Spine MRI lesion characteristics including the length and location, and the pattern of gadolinium enhancement, help narrow the differential diagnosis and exclude an extrinsic compressive cause. The discovery of specific antibodies that serve as biomarkers of myelitis such as aquaporin-4-IgG and myelin-oligodendrocyte -glycoprotein-IgG (MOG-IgG), has improved our understanding of myelitis pathophysiology and facilitated diagnosis. In this review we will focus on the pathophysiology, clinical presentation, imaging findings and treatment and outcomes of uncommon immune-mediated myelopathies.

The clinical benefit of patent foramen ovale (PFO) closure in patients with cryptogenic stroke (CS) for recurrent stroke prevention has been a subject of extensive debate. Prior clinical trials failed to show superiority of PFO closure versus medical therapy. Meta-analyses suggested a possible benefit of PFO closure in select patients.The objective of this study was to critically assess current evidence regarding the efficacy of PFO closure compared with medical therapy for recurrent stroke prevention in patients with CS.The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario with a clinical question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, medical librarian, and vascular neurology and interventional cardiology content experts.A randomized, controlled trial was selected for critical appraisal. This trial compared the efficacy of PFO closure and medical therapy in recurrent stroke prevention. A total of 663 patients who had a recent CS attributed to PFO, with a large interatrial shunt or with an associated atrial septal aneurysm were included. No stroke occurred among the 238 patients in the PFO closure group, whereas 14 of the 235 patients in the antiplatelet therapy group had recurrent strokes.Among patients who had a recent CS attributed to PFO with a large interatrial shunt or with an associated atrial septal aneurysm, the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone.

Background Catamenial epilepsy refers to cyclic seizure exacerbation in relation to the menstrual cycle. Three distinct patterns have been described: C1-perimenstrual, C2-periovulatory, and C3-inadequate luteal. There is experimental and clinical evidence that gonadal steroid hormones affect neuronal excitability with estrogens being mainly proconvulsant and progesterone anticonvulsant. If reproductive steroids have a role in seizure occurrence, they may also have a role in treatment. Objective The objective of this study was to critically assess current evidence regarding the efficacy of progesterone as adjunctive therapy in women with intractable catamenial epilepsy. Methods The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario with a clinical question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, medical librarian, and content experts in the fields of epilepsy and gynecology. Results A randomized, placebo-controlled clinical trial was selected for critical appraisal. This trial compared the efficacy of adjunctive cyclic natural progesterone therapy versus placebo for seizures in women with intractable partial epilepsy, stratified by catamenial and noncatamenial status. There was no significant difference in proportions of responders between progesterone and placebo in the catamenial and noncatamenial strata. Prespecified secondary analysis showed that the level of perimenstrual seizure exacerbation is a significant predictor of the responder rate for progesterone therapy. Conclusions Cyclic natural progesterone is not superior to placebo in reducing seizure frequency in women with intractable partial epilepsy. Posthoc findings suggest that progesterone may benefit a subset of women with perimenstrually exacerbated seizures.

Introduction: Despite the recognized linkage between retinal microvascular abnormalities and cerebrovascular ischemic diseases (CVD), the retinal findings’ standardization and the degree of association remain unclear. We aimed to investigate the quantitative association between various retinal microvascular signs and CVD. Hypothesis: retinal microvascular abnormalities best predictive of CVD could be identified by synthesizing estimates of CVD risk from population-based studies. Methods: We followed MOOSE guidelines and systematically searched 6 databases through September 2016 for studies evaluating the association between retinal microvascular abnormalities and white matter hyperintense lesions (WMHI), lacunar infarcts (LI), and cerebral infarctions (CI). Adjusted and unadjusted odds ratios (ORs) and confidence intervals were pooled into the analyses using the DerSimonian and Laird random effects model. Study quality and dissemination biases were assessed and integrated. Results: Thirty-four prospective studies encompassing 84,144 patients were eligible for meta-analysis. After adjustment for vascular risk factors, focal arteriolar narrowing was associated with WMHI (OR, 1.24 [1.01-1.79]), LI (OR, 1.77 [1.14-2.74]), and CI (OR, 1.75 [1.14-2.69]). Venular dilation was significantly associated with LI (OR, 1.46 [1.10-1.93]), whereas retinal hemorrhage was associated with WMHI (OR, 2.23 [1.34-3.70]). Arteriovenous nicking was associated with WMHI (OR, 1.51 [1.22-1.88]) and LI (OR, 1.70 [1.05-2.76]). Any retinopathy exhibited significant association with WMHI, LI, and CI. Heterogeneity was significant ( I 2 >50%) for all syntheses except retinal hemorrhages and WMHI, retinopathy and CI ( I 2 =0.0%) and respectively LI ( I 2 =45.80%). Conclusions: Retinal hemorrhages were most highly associated with WMHI. Focal arteriolar narrowing and retinopathy were associated with WMHI, LI, and CI. Our findings may assist in the development of a noninvasive retinal microvascular tool for routine use in CVD research and clinical practice.

INTRODUCTION: Brain tumors can result in focal neurological and cognitive deficits which may impair the ability to drive. There are no evidence-based recommendations on driving restrictions for patients with brain metastases. Recommendations vary per practice, with extrapolation based on local driving and epilepsy laws. Occupational Therapy driving assessment (OTDA) may provide insight into limitations for this population. OBJECTIVE: To determine whether clinical neurologic examination is sufficient to predict suitability to drive in patients with brain metastases. METHODS: We assessed the concordance between Neurology assessment of suitability to drive (pass/fail) and OTDA in individuals with brain metastases. 40 subjects were prospectively enrolled. Neurooncology evaluation was performed as standard of care, including an interview and neurological examination. Subjects subsequently underwent OTDA during which a battery of objective measures of visual, cognitive and motor skills related to driving was administered. RESULTS: Preliminary results from the first 29 patients included are reported. Mean age was 68 years. Lung was the primary location of the tumor in 62% cases. More patients in the group that failed OTDA had bilateral brain metastasis (77.3% vs 42.9%,p=0.0478). The sensitivity of the Neurology assessment to predict driving fitness compared to OTDA was 22.7% and the specificity 71.4%. The 22 patients who failed OTDA were more likely to fail on Vision Coach (81.8%), MOCA (68.2%) and Trail Making (50%) tests. DISCUSSION: There was poor correlation between the assessment of suitability to drive by Neurology and the outcome of the OTDA in patients with brain metastases. Subtle deficits that may impair the ability to drive safely may not be evident on neurologic examination. The Vision Coach, MOCA and Trail Making tests were the most sensitive tests to predict driver safety. The results raise questions about the choice of assessments in making recommendations about fitness to drive in people with brain metastases.

Background Myxomas are rare cardiac tumors which often present with stroke caused by tumorous or thrombotic emboli. Treatment with intravenous recombinant tissue plasminogen activator (rtPA) and intra-arterial thrombolysis has been described previously but mechanical thrombectomy has not yet been reported, and treatment of myxoma-related ischemic stroke remains a clinical and technical challenge. Methods Two patients with ischemic stroke due to cardiac myxoma in which mechanical thrombectomy was performed are presented. Results Endovascular thrombectomy after intravenous rtPA (bridging therapy) was safely achieved in both cases, although with different clinical outcomes and degrees of recanalization. Conclusions In stroke secondary to cardiac myxoma, mechanical thrombectomy might represent a safe and effective treatment option. The authors suggest the use of histological examination of the clot for diagnosis as its composition may explain the differences in treatment outcome.