Onset of progressive motor impairment in patients with critical central nervous system demyelinating lesions.

OBJECTIVE: To compare progressive motor impairment onset attributable to a "critical" central nervous system (CNS) demyelinating lesion in patients with highly restricted versus unlimited magnetic resonance imaging (MRI) lesion burden. METHODS: We identified 135 patients with progressive motor impairment for ⩾1 year attributable to a "critical" demyelinating lesion with: MRI burden of 1 lesion ("progressive solitary sclerosis"), 2-5 lesions ("progressive paucisclerosis"), or unrestricted (>5) lesions and "progressive unilateral hemiparesis." Neuroradiology review of brain and spinal cord MRI documented unequivocally demyelinating lesions. RESULTS: A total of 33 (24.4%) patients had progressive solitary sclerosis; 56 (41.5%) patients had progressive paucisclerosis; and 46 (34.1%) patients had progressive unilateral hemiparesis. Median age at onset of progressive motor impairment was younger in progressive solitary sclerosis (49 years; range 24-73) and progressive paucisclerosis (50 years; range 30-64) than in progressive unilateral hemiparesis (54 years; range 39-77; p = 0.02 and p = 0.003, respectively). Within progressive unilateral hemiparesis, motor-progression onset was similar between those with 4-10, 11-20, or >20 brain lesions (55, 54, 53 years of age, respectively; p = 0.44). CONCLUSION: Motor-progression age is similar, but paradoxically earlier, in cohorts with highly restricted CNS lesion burden than in those with unrestricted lesion burden with progressive unilateral hemiparetic MS. The "critical" demyelinating lesion rather than total brain MRI lesion burden is the major contributor to motor-progression onset in these cohorts.

Demographics and clinical characteristics of episodic hypothermia in multiple sclerosis.

BACKGROUND: Episodic hypothermia (EH) can occur in multiple sclerosis (MS). The putative mechanism is impairment of thermoregulation due to a presumed demyelinating hypothalamic lesion. OBJECTIVE: To describe a cohort of patients with MS, who developed EH. METHODS: Patients were identified through review of the Mayo Clinic electronic medical record (1996 to July 2015). Search terms were [multiple sclerosis] or [MS] within the diagnoses field and [hypothermia] within any field. We reviewed records for accuracy of diagnoses and abstracted relevant data. Magnetic resonance imaging (MRI) was reviewed for presence of hypothalamic lesions. RESULTS: Of 156 patients, 34 had concurrent MS and hypothermia. Thirty-two (94%) had progressive disease at EH onset. Median MS duration was 19.9 years, and median expanded disability status scale (EDSS) was 8.0. Most patients presented with alterations in consciousness. Infection was suspected as the precipitating factor in 19 (56%), but clinically/laboratory supported in only 9 (28%). MRI lesions were evident within the hypothalamus in only 4 (14%). CONCLUSION: EH occurs predominantly in patients with advanced secondary progressive MS. The major manifestation is altered consciousness. Infection is often suspected as causal, but infrequently confirmed. Although commonly implicated, hypothalamic lesions were rarely evident on MRI and were absent in two post-mortem evaluations.

Progressive motor impairment from a critically located lesion in highly restricted CNS-demyelinating disease.

OBJECTIVE: To report progressive motor impairment from a critically located central nervous system (CNS) demyelinating lesion in patients with restricted magnetic resonance imaging (MRI)-lesion burden. METHODS: We identified 38 patients with progressive upper motor-neuron impairment for >1 year, 2-5 MRI CNS-demyelinating lesions, with one seemingly anatomically responsible for progressive motor impairment. Patients with any alternative etiology for progressive motor impairment were excluded. A neuroradiologist blinded to clinical evaluation reviewed multiple brain and spinal-cord MRI, selecting a candidate critically located demyelinating lesion. Lesion characteristics were determined and subsequently compared with clinical course. RESULTS: Median onset age was 47.5 years (24-64); 23 (61%) women. Median follow-up was 94 months (18-442); median Expanded Disability Status Scale Score (EDSS) at last follow-up was 4.5 (2-10). Clinical presentations were progressive: hemiparesis/monoparesis 31; quadriparesis 5; and paraparesis 2; 27 patients had progression from onset; 11 progression post-relapse. Total MRI lesions were 2 ( n = 8), 3 ( n = 12), 4 ( n = 12), and 5 ( n = 6). Critical lesions were located on corticospinal tracts, chronically atrophic in 26/38 (68%) and involved cervical spinal cord in 27, cervicomedullary/brainstem region in 6, thoracic spinal cord in 4, and subcortical white matter in 1. CONCLUSION: Progressive motor impairment may ascribe to a critically located CNS-demyelinating lesion in patients with highly restricted MRI burden. Motor progression from a specific demyelinating lesion has implications for understanding multiple sclerosis (MS) progression.

Pneumatic dilation versus laparoscopic Heller myotomy for the treatment of achalasia: variables related to a good response.

Achalasia is a motor disorder characterized by esophageal aperistalsis and failure of lower esophageal sphincter relaxation. The cardinal symptoms are dysphagia, food regurgitation and weight loss. The most effective treatments are pneumatic dilation (PD) of the cardia and Heller esophageal myotomy with partial fundoplication. There is still controversy regarding which treatments should be initially done. The aims of this study were to evaluate clinical response and the variables related to good results in both treatments. Ninety-two patients with achalasia diagnosed by esophageal manometry were randomized to receive either PD or laparoscopic Heller myotomy with partial fundoplication. After the procedure, patients were followed up clinically and submitted to esophageal manometry and pH monitoring. Three months after treatment, 73% of the patients from PD group and 84% of the surgery group had good results (P = 0.19). After 2 years of follow-up, 54% of the PD group and 60% of the surgery group (P = not significant) were symptom free. Variables related to a good response to PD were a 50% drop in lower esophageal sphincter pressure (LESP) or a LESP <10 mmHg after treatment. Patients over 40 years old with LESP ≤32 mmHg before treatment and a drop in LESP >50% after treatment significantly achieved better responses after surgical treatment when compared with PD. The reflux rate was significantly higher in the PD group (27.7%) compared with the surgery group (4.7%), P = 0.003. We concluded that surgical treatment and PD for achalasia are equally effective even after 2 years of follow-up. The choice of treatment for achalasia should be based on the following parameters: treatment availability, rate of good results, complication rates, variables related to good responses and also the patient's wish.

Laboratory evaluation for the differential diagnosis of possible multiple sclerosis in the United States: A physician survey.

BACKGROUND: There is limited evidence and lack of guidelines for diagnostic laboratory evaluation of patients with possible multiple sclerosis (MS). OBJECTIVE: To survey neurologists on their practice of laboratory testing in patients with possible MS. METHODS: An online survey was developed to query the frequency of serum and cerebrospinal fluid (CSF) studies ordered in the routine evaluation of patients with possible MS, and in three hypothetical clinical cases. Non-MS specialist neurologists who evaluate patients for MS in their practice were invited to participate by MedSurvey (a medical market research company). RESULTS: The survey was completed by 190 neurologists. A mean of 17.2 (SD: 17.0) tests in serum and CSF were reported "always" ordered in the evaluation of patients with possible MS. CSF oligoclonal bands was the most frequently selected ("always" among 73.7% of participants). Antinuclear antibody (43.2%), erythrocyte sedimentation rate (34.2%), and thyroid stimulating hormone (31.6%) were also among the most frequently ordered. DISCUSSION: Extensive laboratory evaluations are often completed in the evaluation of possible MS. However, many of these tests have poor specificity and false positive results could yield unnecessary increased costs, diagnostic delay, and potentially misdiagnosis. Further research is needed to identify optimal laboratory approaches for possible MS.

Processing speed and memory test performance are associated with different brain region volumes in Veterans and others with progressive multiple sclerosis.

Background: Cognitive dysfunction and brain atrophy are both common in progressive multiple sclerosis (MS) but are seldom examined comprehensively in clinical trials. Antioxidant treatment may affect the neurodegeneration characteristic of progressive MS and slow its symptomatic and radiographic correlates. Objectives: This study aims to evaluate cross-sectional associations between cognitive battery components of the Brief International Cognitive Assessment for Multiple Sclerosis with whole and segmented brain volumes and to determine if associations differ between secondary progressive (SPMS) and primary progressive (PPMS) MS subtypes. Design: The study was based on a baseline analysis from a multi-site randomized controlled trial of the antioxidant lipoic acid in veterans and other people with progressive MS (NCT03161028). Methods: Cognitive batteries were conducted by trained research personnel. MRIs were processed at a central processing site for maximum harmonization. Semi-partial Pearson's adjustments evaluated associations between cognitive tests and MRI volumes. Regression analyses evaluated differences in association patterns between SPMS and PPMS cohorts. Results: Of the 114 participants, 70% had SPMS. Veterans with MS made up 26% (n = 30) of the total sample and 73% had SPMS. Participants had a mean age of 59.2 and sd 8.5 years, and 54% of them were women, had a disease duration of 22.4 (sd 11.3) years, and had a median Expanded Disability Status Scale of 6.0 (with an interquartile range of 4.0-6.0, moderate disability). The Symbol Digit Modalities Test (processing speed) correlated with whole brain volume (R = 0.29, p = 0.01) and total white matter volume (R = 0.33, p < 0.01). Both the California Verbal Learning Test (verbal memory) and Brief Visuospatial Memory Test-Revised (visual memory) correlated with mean cortical thickness (R = 0.27, p = 0.02 and R = 0.35, p < 0.01, respectively). Correlation patterns were similar in subgroup analyses. Conclusion: Brain volumes showed differing patterns of correlation across cognitive tasks in progressive MS. Similar results between SPMS and PPMS cohorts suggest combining progressive MS subtypes in studies involving cognition and brain atrophy in these populations. Longitudinal assessment will determine the therapeutic effects of lipoic acid on cognitive tasks, brain atrophy, and their associations.

Neurologic Manifestations of Common Variable Immunodeficiency: Impact on Quality of Life.

BACKGROUND AND OBJECTIVES: Common variable immunodeficiency is a systemic disease and not solely a disease of humoral immunity. Neurologic symptoms associated with common variable immunodeficiency are underrecognized and warrant further study. This work aimed to characterize the neurologic symptoms reported by people living with common variable immunodeficiency. METHODS: We conducted a single academic medical center study of neurologic symptoms reported by adults previously diagnosed with common variable immunodeficiency. We used a survey of common neurologic symptoms to determine the prevalence of these symptoms in a population with common variable immunodeficiency and further assessed these patient-reported symptoms with validated questionnaires and compared symptom burden with other neurologic conditions. RESULTS: A volunteer sample of adults (aged 18 years or older) previously diagnosed with common variable immunodeficiency at the University of Utah Clinical Immunology/Immune Deficiency Clinic who were able to read and comprehend English and willing and able to answer survey-based questions were recruited. Of 148 eligible participants identified, 80 responded and 78 completed the surveys. The mean age of respondents was 51.3 years (range 20-78 years); 73.1% female and 94.8% White. Patients with common variable immunodeficiency reported many common neurologic symptoms (mean 14.6, SD 5.9, range 1-25), with sleep issues, fatigue, and headache reported by more than 85%. Validated questionnaires addressing specific neurologic symptoms supported these results. T-scores on Neuro QoL questionnaires for sleep (mean 56.4, SD 10.4) and fatigue (mean 54.1, SD 11) were higher, indicating more dysfunction, than in the reference clinical population (p < 0.005). The Neuro QoL questionnaire for cognitive function showed a lower T-score (mean 44.8, SD 11.1) than that in the reference general population (p < 0.005), indicating worse function in this domain. DISCUSSION: Among survey respondents, there is a marked burden of neurologic symptoms. Given the impact of neurologic symptoms on health-related quality-of-life measures, clinicians should screen patients with common variable immunodeficiency for the presence of these symptoms and offer referral to neurologists and/or symptomatic treatment when indicated. Frequently prescribed neurologic medications may also affect the immune system, and neurologists should consider screening patients for immune deficiency before prescribing them.

Statin therapy and multiple sclerosis disability in a population-based cohort.

BACKGROUND: Axonal damage and inflammatory demyelination both occur in multiple sclerosis (MS). Some studies suggest that statins, through pleiotropic effects, reduce inflammatory episodes and protect neurons. However, other studies suggest statins have disparate impacts on these pathologic processes. OBJECTIVE: The objective of this study was to assess disability progression in MS patients receiving statin therapy. METHODS: We performed a retrospective medical record review of an established population-based MS prevalence cohort in Olmsted County, Minnesota, comparing disability progression between patients receiving statins and controls. RESULTS: Duration of statin use ranged from 1.9 to 20.3 years with a mean and standard deviation of 6.8 ± 4 years. Years between assessments ranged from 0.6 to 8.2 (75% of patients having intervals >6.4 years). The median (interquartile range) absolute change of disability among the statin group was 0 (0 to +1), compared with +0.5 (0, +1) in the no-statin group. Distributions were not significantly different (p = 0.39). The mean (standard deviation) absolute change of disability scores among the statin group was +0.69 (+1.49), not significantly different from +0.61 (+1.31) in the no-statin group. Likewise, annualized disability scores did not differ significantly (p = 0.23). Eighteen (40%) patients worsened by 1.0 or more on Expanded Disability Status Scale (EDSS) in the statin group and 36 (40%) in the no-statin group (p = 0.85, chi-squared test). CONCLUSIONS: In this cohort, disability progression did not differ between those receiving statin therapy and controls. These findings support the hypothesis that statins, in doses currently prescribed for hyperlipidemia, do not affect the long-term course of MS.

Biogenesis and significance of central nervous system myelin.

The central nervous system is composed of neurons and glia cells. Although neurons have long been considered the functionally important cells, an ever-expanding body of research has revealed many critical functions of neuroglia. Among these, the myelin sheath elaborated by oligodendrocytes acts as a dynamic partner to the axons it enwraps and can no longer be considered as an inert membrane. In addition to its best known roles of providing insulation and optimizing conduction velocity, myelination modulates the maturation, survival, and regenerative capacity of axons through trophic support and signaling molecules. Myelin is produced through a complex process involving cell differentiation, biosynthesis of specialized lipids and proteins, interaction with environmental signals, and coordinated changes in cell morphology. Understanding the pathophysiology of primary myelin disorders, and the challenges faced in treating them, is facilitated through understanding of the structure, function, and generation/regeneration of myelin.

Adrenal Crisis Presenting as Recurrent Encephalopathy Mimicking Autoimmune, Infectious Encephalitis, and Common Variable Immune Deficiency: A Case Report.

INTRODUCTION: Adrenal crisis can present with life-threatening complications and mimic autoimmune or infectious encephalitis, and common variable immune deficiency (CVID). The literature regarding the neurological complications of adrenal crisis is limited and focuses on patients who present with hypotension and electrolyte abnormalities. CASE REPORT: A 30-year-old man presented 3 times to our hospital with encephalopathy, fever, and left sided weakness with a history of multiple autoimmune diseases and prior hospitalizations for encephalopathy. During his first 2 admissions, he was normotensive and without electrolyte abnormalities. Extensive workup for infectious, paraneoplastic, seizure, metabolic, toxic, and vascular etiologies, and autoimmune encephalitis was negative. His exam returned to baseline with empiric steroid treatment, and he was discharged. He re-presented 2 months later with encephalopathy for a third admission. During this subsequent presentation, he had hyponatremia, low serum osmolality, elevated urine sodium, undetectable morning cortisol, and 21-α hydroxylase autoantibodies. A diagnosis of autoimmune adrenal insufficiency was established, he was treated with physiological doses of hydrocortisone and fludrocortisone, and improved rapidly to near baseline function. He has remained relapse-free at 4-year follow up. During all admissions, he was also found to have low immunoglobulin G levels and met criteria for CVID; however, his immunoglobin levels recovered with steroid replacement. CONCLUSION: The reported patient demonstrated some of the neurological complications of adrenal crisis which can mimic other autoimmune conditions such as CVID. The neurologist should be aware that recurrent encephalopathy from adrenal insufficiency can occur regardless of hemodynamic or electrolyte changes on typical hospital metabolic panels.

GABA-A Receptor Encephalitis After Autologous Hematopoietic Stem Cell Transplant forMultiple Myeloma: Three Cases and Literature Review.

BACKGROUND AND OBJECTIVES: The relationship between autologous hematopoietic stem cell transplant (aHSCT) for multiple myeloma (MM) and anti-GABAA receptor (GABAAR) encephalitis is unknown. We aimed to describe the clinical features, diagnostic process, and outcome of 3 cases of anti-GABAAR encephalitis in patients with a history of prior aHSCT for MM. METHODS: A case series of 3 patients. Anti-GABAAR antibody was tested at the University of Pennsylvania Laboratory. RESULTS: The patients were all male, aged 52 (case 1), 61 (case 2), and 62 (case 3) years at encephalitis symptom onset. The duration between completion of aHSCT and the onset of encephalitis was 43, 18, and 9 months, respectively. All 3 patients presented with new seizures and altered cognitive function. Other symptoms included headache and visual obscurations in cases 1 and 2 and intractable vertigo and mania in case 3. Brain MRI demonstrated nonenhancing multifocal T2-weighted/fluid-attenuated inversion recovery cortical and subcortical hyperintensities in all 3 patients. Cases 2 and 3 underwent brain biopsy before initiating immunomodulatory therapy, which demonstrated nonspecific encephalitis with astrogliosis in the white matter; these 2 patients were started on immunotherapy for the treatment of anti-GABAAR encephalitis after 22 days and 3 months, respectively, from the first presentation. Case 1 was started on empiric immunotherapy within 8 days of presentation without requiring brain biopsy, given characteristic MRI imaging. CSF analysis demonstrated the presence of anti-GABAAR antibodies in all 3 cases. Cases 1 and 3 also tested positive for anti-GABAAR antibodies in the serum (serum test was not performed in case 2). Cases 1 and 2 recovered to work full-time within 1 year. Case 3 reported occasional myoclonic-like movement. DISCUSSION: We highlight the importance of considering anti-GABAAR encephalitis in patients with seizures, multifocal nonenhancing brain lesions, and a history of aHSCT for MM. Awareness in recovered post-aHSCT patients with MM may be crucial because prompt recognition can avoid brain biopsy and delays in treatment. The rapid initiation of immunotherapy while awaiting autoantibody results will likely improve functional outcomes.

Biopsy-proven PML in an HIV-negative patient with discoid lupus: Failure to detect JC virus in CSF.

We present a case of a 58-year-old man with a history of severe discoid lupus erythematosus and acute encephalopathy and incoordination. Antinuclear antibody testing was weakly positive but all other laboratory tests for systemic lupus erythematosus were negative and serum quantitative immunoglobulins and lymphocytes were normal. MRI brain showed T2/FLAIR hyperintensities within the bilateral parietal and temporal lobes with involvement of subcortical U fibers. CSF PCR was negative for varicella-zoster virus, herpes simplex, JCV and BK virus. However, JCV antibody index was elevated (3.88; reference: < 0.2). Right parietal brain biopsy was consistent with JCV infection and diagnostic of progressive multifocal leukoencephalopathy (PML). To the best of our knowledge, this is the first reported case of PML in a patient with discoid lupus without other traditional risk factors for the disease and highlights the need for clinical vigilance in this patient population.

Aquaporin-4 Autoantibody Detection by ELISA: A Retrospective Characterization of a Commonly Used Assay.

OBJECTIVE: Aquaporin-4 (AQP4) serum autoantibodies are detected by a variety of methods. The highest sensitivity is achieved with cell-based assays, but the enzyme-linked immunosorbent assay (ELISA) is still commonly utilized by clinicians worldwide. METHODS: We performed a retrospective review to identify all patients at the University of Utah who had AQP4 ELISA testing at ARUP Laboratories from 2010 to 2017. We then reviewed their diagnostic evaluation and final diagnosis based on the ELISA titer result. RESULTS: A total of 750 tests for the AQP4 ELISA were analyzed, and 47 unique patients with positive titers were identified. Less than half of these patients (49%) met the clinical criteria for neuromyelitis optica spectrum disorder (NMOSD). In cases of low positive titers (3.0-7.9 U/mL, n = 19), the most common final diagnosis was multiple sclerosis (52.6%). In the moderate positive cohort (8.0-79.9 U/mL, n = 14), only a little more than half the cohort (64.3%) had NMOSD. In cases with high positives (80-160 U/mL, n = 14), 100% of patients met clinical criteria for NMOSD. CONCLUSIONS: Our data illustrates diagnostic uncertainty associated with the AQP4 ELISA, an assay that is still commonly ordered by clinicians despite the availability of more sensitive and specific tests to detect AQP4 autoantibodies in patients suspected of having NMOSD. In particular, low positive titer AQP4 ELISA results are particularly nonspecific for the diagnosis of NMOSD. The importance of accessibility to both sensitive and specific AQP4 testing cannot be overemphasized in clinical practice.

Modern Look at Transverse Myelitis and Inflammatory Myelopathy: Epidemiology of the National Veterans Health Administration Population.

BACKGROUND AND OBJECTIVES: To characterize population-level data associated with transverse myelitis (TM) within the US Veterans Health Administration (VHA). METHODS: This retrospective review used VHA electronic medical record from 1999 to 2015. We analyzed prevalence, disease characteristics, modified Rankin Scale (mRS) scores, and mortality data in patients with TM based on the 2002 Diagnostic Criteria. RESULTS: We identified 4,084 patients with an International Classification of Diseases (ICD) code consistent with TM and confirmed the diagnosis in 1,001 individuals (90.7% males, median age 64.2, 67.7% Caucasian, and 31.4% smokers). The point prevalence was 7.86 cases per 100,000 people. Less than half of the cohort underwent a lumbar puncture, whereas only 31.8% had a final, disease-associated TM diagnosis. The median mRS score at symptom onset was 3 (interquartile range 2-4), which remained unchanged at follow-up, although less than half (43.2%) of the patients received corticosteroids, IVIg, or plasma exchange. Approximately one-quarter of patients (24.3%) had longitudinal extensive TM, which was associated with poorer outcomes (p = 0.002). A total of 108 patients (10.8%) died during our review (94.4% males, median age 66.5%, and 70.4% Caucasian). Mortality was associated with a higher mRS score at follow-up (OR 1.94, 95% CI, 1.57-2.40) and tobacco use (OR 1.87, 95% CI, 1.17-2.99). DISCUSSION: This national TM review highlights the relatively high prevalence of TM in a modern cohort. It also underscores the importance of a precise and thorough workup in this disabling disorder to ensure diagnostic precision and ensure optimal management for patients with TM in the future.

The Future of Progressive Multiple Sclerosis Therapies.

INTRODUCTION: Multiple sclerosis (MS) affects more than a million people in the US. A considerable portion of these patients either begin with primary progressive disease or eventually transition to secondary progressive MS. A progressive disease course is the most critical factor affecting disability accumulation. The relatively recent development of treatments for relapsing multiple sclerosis has had a profound impact on the disease course for many with MS. Unfortunately, therapies for progressive MS have not had the same degree of advancement in general. New insights into the pathophysiology of progressive MS may lead to new treatments. OBSERVATIONS: In this review, we identify some of the significant challenges encountered in the development of therapies for progressive MS, assess the evidence for use of currently approved therapies for patients with progressive MS, identify some of the current therapies in development from progressive MS, and consider the role for discontinuing therapy in certain patients. CONCLUSIONS: Developing effective disease modifying therapies that slow or stop the gradual accumulation of neurologic disability in progressive MS represents a critical unmet need. As the understanding of the inflammatory and neurodegenerative aspects of MS are better elucidated there may be opportunity for advancement in the treatment of progressive MS.

Neurosarcoidosis: Longitudinal experience in a single-center, academic healthcare system.

OBJECTIVE: To characterize patients with neurosarcoidosis within the University of Utah healthcare system, including demographics, clinical characteristics, treatment, and long-term outcomes. METHODS: We describe the clinical features and outcomes of patients with neurosarcoidosis within the University of Utah healthcare system (a large referral center for 10% of the continental United States by land mass). Patients were selected who met the following criteria: (1) at least one International Classification of Diseases Clinical Modification, 9th revision code 135 or International Classification of Diseases Clinical Modification, 10th revision code D86* (sarcoidosis) and (2) at least one outpatient visit with a University of Utah clinician in the Neurology Department within the University of Utah electronic health record. RESULTS: We identified 56 patients meeting the study criteria. Thirty-five patients (63%) were women, and most patients (84%) were white. Twelve patients (22%) met the criteria for definite neurosarcoidosis, 36 patients (64%) were diagnosed with probable neurosarcoidosis, and 8 patients (14%) were diagnosed with possible neurosarcoidosis. A total of 8 medications were used for the treatment of neurosarcoidosis. Prednisone was the first-line treatment in 51 patients (91%). Infliximab was the most effective therapy, with 87% of patients remaining stable or improving on infliximab. Treatment response for methotrexate and azathioprine was mixed, and mycophenolate mofetil and rituximab were the least effective treatments in this cohort. CONCLUSIONS: This is a comprehensive characterization of neurosarcoidosis within a single healthcare system at the University of Utah that reports long-term response to treatment and outcomes of patients with neurosarcoidosis. Our results suggest the use of infliximab as a first-line therapy for neurosarcoidosis.

Novel clinical features of glycine receptor antibody syndrome: A series of 17 cases.

Objective: To describe novel clinical features of GlyRα1-IgG-positive patients. Methods: Patients with a positive serum GlyRα1-IgG were identified during a 2-year period from July 2016 to December 2018 at 2 academic centers and followed prospectively. All patients in this series were evaluated in the Neuroimmunology and Autoimmune Neurology clinics at the University of Utah or the University of Colorado. Results: Thirteen of 17 patients had phenotypes more typically associated with glutamic acid decarboxylase (GAD65) antibody syndromes, consisting of stiff-person syndrome (SPS) with parkinsonism or cerebellar signs. One patient with parkinsonism had a presentation similar to rapidly progressive multiple system atrophy with severe dysautonomia. Ten of 17 patients had various visual symptoms including visual snow, spider web-like images forming shapes and 3-dimensional images, palinopsia, photophobia, visual hallucinations, synesthesia, and intermittent diplopia. Three of 17 patients presented with primarily autoimmune epilepsy accompanied by psychiatric symptoms. Conclusions: Clinicians should consider testing for GlyR antibodies in GAD65 antibody-negative or low-positive GAD65 antibody patients with SPS-like presentations, especially in the setting of atypical features such as visual disturbances, parkinsonism, or epilepsy.

Antineuronal Nuclear Autoantibody Type 1/Anti-Hu-Associated Opsoclonus Myoclonus and Epilepsia Partialis Continua: Case Report and Literature Review.

BACKGROUND: Opsoclonus-myoclonus syndrome is a rare clinical condition that has been associated with neuroblastoma. There are few reported examples of ANNA-1/anti-Hu antibodies in children with neuroblastoma and opsoclonus-myoclonus, all in children aged less than three years of age. METHODS: We describe the new onset of focal seizures without alteration of consciousness and opsoclonus-myoclonus in an 11-year-old girl with ANNA-1/anti-Hu positivity and a paraspinal ganglioneuroblastoma. A systematic review of the literature of children with ANNA-1/anti-Hu positivity and malignancy was also performed. RESULTS: Fourteen patients were identified, eight of whom had opsoclonus-myoclonus. Although epilepsia partialis continua has been described in association with several neuronal autoantibodies, association with ANNA-1/anti-Hu has not been reported. CONCLUSIONS: We describe epilepsia partialis continua in a child with ANNA-1/anti-Hu antibodies and neuroblastoma. Testing for antineuronal antibodies should be considered in children presenting with either opsoclonus-myoclonus or epilepsia partialis continua.

Adult-onset Opsoclonus-Myoclonus Syndrome Associated With Ganglionic Acetylcholine Receptor Autoantibody.

INTRODUCTION: Opsoclonus-myoclonus syndrome (OMS) may have a toxin induced, parainfectious, or paraneoplastic etiology. Several autoantibodies have been associated with adult-onset OMS, most commonly antineuronal nuclear antibody 2 (Ri), and it is most frequently associated with breast or small cell lung cancer. The nicotinic ganglionic acetylcholine receptor autoantibody (α3-AChR Ab) has not been described in association. CASE REPORT: A 46-year-old woman was evaluated for symptoms of oscillopsia, tremor, gait imbalance, and mild cognitive deficits that began 6 weeks prior. Neurological examination demonstrated opsoclonus, myoclonus, and mild gait ataxia. Laboratory evaluation revealed an elevated α3-AChR Ab at 0.27 nmol/L (normal ≤0.02 nmol/L) with no other autoantibodies or infectious etiology detected. Thorough screening revealed no evidence of associated malignancy. Immunotherapy with weekly methylprednisolone led to significant improvement. CONCLUSIONS: This first reported case of α3-AChR Ab positivity in the setting of adult-onset OMS expands the spectrum of associated autoantibodies. The mechanism of disease may be linked to cholinergic nuclei within the brainstem. This case suggests including α3-AChR Ab in the evaluation of adult-onset OMS, and highlights the importance of further understanding α3-AChR within the brain.

Progressive solitary sclerosis: Gradual motor impairment from a single CNS demyelinating lesion.

OBJECTIVE: To report patients with progressive motor impairment resulting from an isolated CNS demyelinating lesion in cerebral, brainstem, or spinal cord white matter that we call progressive solitary sclerosis. METHODS: Thirty patients were identified with (1) progressive motor impairment for over 1 year with a single radiologically identified CNS demyelinating lesion along corticospinal tracts, (2) absence of other demyelinating CNS lesions, and (3) no history of relapses affecting other CNS pathways. Twenty-five were followed prospectively in our multiple sclerosis (MS) clinic and 5 were identified retrospectively from our progressive MS database. Patients were excluded if an alternative etiology for progressive motor impairment was found. Multiple brain and spinal cord MRI were reviewed by a neuroradiologist blinded to the clinical details. RESULTS: The patients' median age was 48.5 years (range 23-71) and 15 (50%) were women. The median follow-up from symptom onset was 100 months (range 15-343 months). All had insidiously progressive upper motor neuron weakness attributable to the solitary demyelinating lesion found on MRI. Clinical presentations were hemiparesis/monoparesis (n = 24), quadriparesis (n = 5), and paraparesis (n = 1). Solitary MRI lesions involved cervical spinal cord (n = 18), cervico-medullary/brainstem region (n = 6), thoracic spinal cord (n = 4), and subcortical white matter (n = 2). CSF abnormalities consistent with MS were found in 13 of 26 (50%). Demyelinating disease was confirmed pathologically in 2 (biopsy, 1; autopsy, 1). CONCLUSIONS: Progressive solitary sclerosis results from an isolated CNS demyelinating lesion. Future revisions to MS diagnostic criteria could incorporate this presentation of demyelinating disease.