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BACKGROUND Progressive multifocal leukoencephalopathy, (PML) a demyelinating disease of the brain, caused by the John Cunningham (JC Virus) is usually seen in patients who are immunocompromised. Here, we describe a case of an immunocompetent patient diagnosed with PML and a comprehensive literature review. CASE DESCRIPTION A 64-year-old Caucasian male presented with acute worsening of progressive neurological decline with difficulty in vision and reading. Based on history, examination, CSF markers, histopathology, and MRI Brain at the time of presentation diagnosed the patient with PML in a setting of no immunosuppression disorder. Patient was started on Pelfilgrastim with significant systematic improvement. RESULT In our literature review, it was seen that the average age of symptom presentation was 57.5 with predominance in males. Most of the patients presented with progressive neurological deficits with symptomology ranging from mild confusion, aphasia, anxiety to sensory disturbances with numbness, hemiparesis and hemianopsia. Out of the 21 cases, patients responded to mirtazapine and intravenous pulse methylprednisolone (IVMP). The mortality rate was close to 50% with 11 fatal cases and 10 non-fatal cases. CONCLUSION Our case and literature review demonstrate the possibility that PML may very rarely occur in patients that our immunocompetent. Furthermore, our review showed that patients responded well to mirtazapine and IVMP. We also want to highlight that mortality rate was lower in this review and was only compared to morality in PML associated with immunocompromised status. This article is protected by copyright. All rights reserved.

OBJECTIVE Progressive multifocal leukoencephalopathy (PML) is a serious viral infection associated with disease-modifying therapies (DMT) for multiple sclerosis (MS) including sphingosine 1-phosphate receptor (S1PR) modulators. The objective of this review was to investigate the characteristics of PML in MS patients associated with drugs of the S1PR modulator. METHODS We conducted a literature review and analysis of 24 patients from 12 publications in PubMed, SCOPUS and EMBASE. This is a descriptive analysis and study of characteristics of PML associated fingolimod and related S1PR modulator group of DMT. RESULTS A total of 24 cases of PML in MS patients treated with fingolimod were identified. Of these, 21 cases contained data regarding changes in the expanded disability status scale (EDSS). One case of PML in association with ozanimod treatment in a clinical trial was also identified. In PML cases associated with fingolimod, the mean age at the time of PML diagnosis was 50.91 ± 11.5 years. All patients were treated with fingolimod for more than 24 months. Compared to patients who improved or were stable, in terms of EDSS, after symptomatic management of PML, the non-improved groups were significantly older. There were no fatalities in either group during the reported follow-up period. CONCLUSION The incidence of PML appears to be extremely low in MS patients treated with S1PR modulators. Risk of PML increases with increase in duration of treatment with S1PR modulators like fingolimod, and increased age at the time of PML diagnosis is associated with worse prognosis.

Gliomatosis cerebri (GC) is a diffuse infiltrative neoplastic glial process with a devastating prognosis. Considering its rarity, unpredictable clinical manifestations, and lack of characteristic radiographic features, GC is a difficult diagnosis that is quite often delayed. In this report, we present a case of a 61-year-old man with a history of chronic alcohol abuse and atrial fibrillation who presented with right arm weakness initially presumed to be from an acute ischemic stroke. GC was not diagnosed until six months after initial symptoms and diagnosis was indicated when considering the neurocognitive findings in conjunction with suggestive radiographic findings. The presence of a rapid, expansile lesion in the cortex, corpus callosum, and infratentorial structures with mild parenchymal enlargement, as shown in our case, is more revealing of an invasive entity typical of GC rather than an ischemic process and other pathologies. This case demonstrates the fatal challenges of its prompt recognition and the therapeutic limitations for those patients presenting with advanced symptoms at the time of diagnosis. Recognizing GC in cases with such rapid multilobe clinical features with similar diffusely invasive patterns of growth on imaging can avoid a delay in diagnosis and improve patient quality of life.

Objective To report a unique case and literature review of post COVID-19 vaccination associated transverse myelitis and with abnormal MRI findings. Background Coronavirus disease have been reported to be associated with several neurological manifestations such as stroke, Guillain-Barré syndrome, meningoencephalitis amongst others. There are only a few reported cases of transverse myelitis with the novel coronavirus (n-CoV-2). Here, we identify a post COVID-19 vaccination patient diagnosed with acute transverse myelitis. Method A retrospective chart review of a patient diagnosed with post SARS-CoV-2 vaccination acute transverse myelitis, and a review of literature of all the reported cases of other post vaccination and transverse myelitis, from December 1st, 2010 till July 15th, 2021, was performed. Conclusion To our knowledge, this is the one of early reported case of transverse myelitis and with post SARS-CoV-2 vaccination, who responded well to plasmapheresis. Further studies would be recommended to identify the underlying correlation between COVID-19 vaccination and transverse myelitis.

Guillain-Barré syndrome (GBS) is an immune-mediated demyelinating disorder which attacks the peripheral nervous system. Antecedent infection or vaccine administration are known to precipitate the onset of this disorder. Its typical presentation leads to a symmetric, rapidly progressive, ascending paresis with associated sensory deficits and impaired reflexes. We present a rare case of a bi-facial diplegia variant of GBS, within four weeks of the COVID-19 vaccination. Due to its chronology, clinical manifestations, and cerebrospinal fluid (CSF) findings, we propose this case to be a rare complication of the COVID-19 vaccination.

A 47-year-old man with a history of isolated, severe, recurrent episcleritis of the left eye, on adalimumab and methotrexate for the past 2 years, presented with acute vertigo. Two days later, in addition to ongoing vertigo, he developed a mild headache behind his right eye, which intensified over 5 days and worsened with Valsalva maneuver and when lying down. He denied nausea, vomiting, light or sound sensitivity, or a history of headaches. On the fifth day of symptoms, he developed double vision, which persisted regardless of the severity of the headache and was worse when looking to the right. On examination, vital signs were normal without evidence of fever. Extraocular movements were notable for mildly restricted gaze of the right eye when looking toward the right side. Pupils were reactive, ophthalmoscopic examination did not show papilledema, and finger to nose test was normal. Mental status, strength, sensation, and reflexes were normal.

The involvement of the central nervous system in sarcoidosis can manifest with a variety of neurological symptoms, and most of them can be nonspecific. The diagnosis of neurosarcoidosis (NS) can therefore be very challenging without a tissue biopsy. Both computed tomography (CT) and magnetic resonance imaging (MRI) are important imaging modalities in the diagnosis of NS, and MRI is the modality of choice due to its superior soft-tissue contrast resolution. We present a case series of NS with interesting neuroimaging features, complex neurological presentations, and clinical courses. We identify five cases presenting with clinically isolated neurosarcoidosis (CINS) without any other signs or symptoms of systemic disease which were diagnosed as NS on biopsy. In the first case, we describe a patient with an intramedullary cervical spinal cord lesion. In the second case we describe a patient presenting with inflammatory changes and enhancement in the orbit. The third case demonstrates a lesion with calcification around the region of the foramen of Monro. The fourth case shows multiple ring-enhancing lesions. Lastly, the fifth case exhibits unusual findings with both optic neuritis and a cerebellar nodule. We aim to describe the complicated clinical course with neurological workup, neuro-imaging, and eventual diagnosis and treatment of these challenging cases to highlight the variable presentations of NS. This case series will remind clinicians that NS should always be in the differential diagnosis when a patient presents with nonspecific neurological symptoms with unusual neuroimaging findings.

Background Limited literature exists on Cerebrospinal fluid (CSF) findings in COVID-19 patients with neurological symptoms. In this review, we conducted a descriptive analysis of CSF findings in patients with COVID-19 to understand prognosis and explore therapeutic options. Methods We searched PubMed, Google Scholar, and Scopus databases using the keywords “SARS-CoV-2 in cerebrospinal fluid” and “SARS-CoV-2 and CNS Complications”" for reports of CSF findings in COVID-19 related neurological manifestations. Descriptive analyses were conducted to observe the CSF protein and cell counts based on age, gender, severity, fatality of COVID-19, and whether central (CNS) or peripheral nervous system (PNS) was associated. Results A total of 113 patients were identified from 67 studies. Of these, 7 patients (6.2%) were fatal COVID-19 cases and 35 patients (31%) were considered severe COVID-19 cases. CSF protein was elevated in 100% (7/7) of the fatal cases with an average of 61.28 mg/dl and in 65.0% (52/80) in non-fatal cases with an average 56.73 mg/dl. CSF protein levels were elevated in 74.5% (38/51) patients with non-severe COVID-19 and 68.6% (24/35) in those with a severe COVID-19 infection. CSF cell count was increased in 43% of fatal cases, 25.7% severe cases, and 29.4% of non-severe cases. Conclusion Our analysis showed that the most common CSF findings situation in COVID-19 infection is elevated protein with, very occasionally, mild lymphocyte predominant pleocytosis. Further studies to elucidate the pathophysiology of neurological complications in COVID-19 are recommended.

OBJECTIVE. The purpose of this article is to present a brief review of literature evaluating different imaging modalities with special focus on 18F-FDG PET/CT in differentiating cerebral toxoplasmosis and primary CNS lymphoma. CONCLUSION. Differentiating cerebral toxoplasmosis and primary CNS lymphoma is crucial in the care of patients with HIV infection. Delayed diagnosis can lead to considerable morbidity and mortality. The reference standard for diagnosis is biopsy and histopathologic examination. Biopsy has disadvantages due to its invasive nature and associated complications. Noninvasive imaging can be an alternative to biopsy for differentiation of toxoplasmosis and primary CNS lymphoma. Despite advances in MRI techniques, prophylaxis of opportunistic infection, and treatment of HIV infection, clinical situations continue to arise in which the diagnosis is not clear. In these instances, molecular imaging can be helpful.

West Nile virus (WNV) is a single-stranded RNA arbovirus of Flavivirus genus that is endemic to the United States and known to cause neuroinvasive disease. Diagnosis is confirmed by the presence of WNV-specific IgM antibodies within serum or cerebrospinal fluid (CSF). Radiologically, it presents as hyperintense T2 signal within deep brain structures (ie, thalami and mid-brain) with or without cerebral peduncle and substantia nigra involvement. On diffusion-weighted imaging, restricted diffusion is reported in basal ganglia and disseminated throughout the white matter. In this report, we describe the imaging findings for 2 cases of WNV from our institution; a 56-year-old female and a 34-year-old female. Increased vigilance for WNV is warranted, particularly in immunosuppressed patients presenting with a clinical picture of viral meningoencephalitis despite initial negative magnetic resonance imaging or CSF analysis. A high suspicion for WNV disease should prompt repeat imaging or laboratory workup.

Intracranial hemorrhagic metastases are a relatively common finding in patients with thyroid carcinoma. Consequently, more unusual vascular lesions may be overlooked in contemplating a differential diagnosis in this patient group. A 50-year-old female with previously treated papillary thyroid carcinoma presented to the emergency department following new onset seizures. Her work up revealed multiple intraparenchymal brain lesions, hyperdense on computed tomography and demonstrating susceptibility effect, T1 shortening and contrast enhancement on magnetic resonance imaging, suggestive of metastases. Subsequent studies revealed lesional architecture consistent with multiple cavernous malformations, made evident by resolution of edema and evolution of blood products. Clinicians should be aware of the possibility of unusual intracranial hemorrhagic lesions in oncology patients which may only become evident on serial imaging evaluation. Cavernous hemangioma has typical MRI characteristic features which includes “mulberry” appearance on T2-weighted and fluid attenuation inversion recovery images with varying internal signal intensity which indicates multiple stages of blood products within the cavernous hemangioma. The lesions commonly have a typical T2-weighted dark hemosiderin rim. Blood sensitive demonstrates prominent surrounding hypointensity representing blooming secondary to internal blood products and/or calcification, if present. Cavernous hemangioma may rarely demonstrate some degree of contrast enhancement. Perfusion imaging may show alteration in capillary permeability involving cavernous malformations which has been previously described in the literature.

As the news of approval of COVID-19 vaccination emerge, neurologists across the globe ponder upon whether to use immunotherapies in patients with Multiple Sclerosis (MS). This paper highlights the mechanism of various disease modifying therapies (DMTs) as well as the recently approved Pfizer and Moderna vaccines for COVID-19 as well as guidelines as introduced by National Multiple Sclerosis Society. As their mechanisms counteract each other at the molecular level, we believe further evidence and data might lay the foundation to formulate much needed recommendations for the usage of these medications while vaccinating MS patients on DMTs.

Background: The data on neurological manifestations in COVID-19 patients has been rapidly increasing throughout the pandemic. However, data on CNS and PNS inflammatory disorders in COVID-19 with respect to CSF, serum and neuroimaging markers is still lacking. Methods: We screened all articles resulting from a search of PubMed, Google Scholar and Scopus, using the keywords “SARS-CoV-2 and neurological complication”, “SARS-CoV-2 and CNS Complication” and “SARS-CoV-2 and PNS Complication” looking for transverse myelitis, vasculitis, acute disseminated encephalomyelitis, acute hemorrhagic necrotizing encephalitis (AHNE), cytotoxic lesion of the corpus callosum (CLOCC) and Guillain-Barré syndrome (GBS), published between 1 December 2019 to 15 July 2021. Results: Of the included 106 CNS manifestations in our study, CNS inflammatory disorders included transverse myelitis (17, 14.7%), AHNE (12, 10.4%), ADEM (11, 9.5%), CLOCC/MERS (10, 8.6%) and vasculitis (4, 3.4%). Others were nonspecific encephalopathy, encephalitis, seizures and stroke. Most patients were >50 years old (75, 70.8%) and male (64, 65.3%). Most (59, 63.4%) were severe cases of COVID-19 and 18 (18%) patients died. Of the included 94 PNS manifestations in our study, GBS (89, 92.7%) was the most common. Most of these patients were >50 years old (73, 77.7%) and male (59, 64.1%). Most (62, 67.4%) were non-severe cases of COVID-19, and ten patients died. Conclusion: Our comprehensive review of the clinical and paraclinical findings in CNS and PNS manifestations of COVID-19 provide insights on the pathophysiology of SARS-CoV-2 and its neurotropism. The higher frequency and severity of CNS manifestations should be noted by physicians for increased vigilance in particular COVID-19 cases.

Background High efficacy disease modifying therapies (DMT) in the management of Multiple Sclerosis (MS) have a favorable effect on relapse rate and disability progression; however, they can expose patients to significant risks, such as progressive multifocal leukoencephalopathy (PML). Objective The study aims to investigate prognostic factors that can determine outcome in MS-related PML patients. Methods We conducted a literature review and meta-analysis of 194 patients from 62 articles in PubMed, SCOPUS and EMBASE. Results Out of 194 patients (66.5% women, 33.5% men), 81% had progression in their EDSS score by at least 1 point from the time of PML diagnosis (EDSS-P group). The remaining patients had either stable or improved EDSS (EDSS-S group). In univariate analysis, older age at the time of PML diagnosis was associated with higher probability of disability accumulation and worsening of EDSS by at least 1 point (mean age = 44.8, p = 0.046). After adjusting for other variables, age at time of PML diagnosis remained a significant predictive variable in the multivariable logistic model (OR = 0.93, 95% CI: 0.88–0.99, p = 0.037). Natalizumab is the most commonly associated DMT linked to PML, followed by fingolimod and others including dimethyl fumarate, ocrelizumab, alemtuzumab. Among the different treatments used, no therapeutic agent was found to be superior in improving post-PML EDSS. Conclusions Younger age and lower JCV viral load at the time of PML diagnosis were associated with better outcome in MS-associate PML, while none of the PML therapies was superior over the others or associated with favorable outcome.

Since early December 2019, the Coronavirus Disease 19 (COVID-19), the disease caused by the virus Sars-Cov-2, has devastated communities on a global scale, infected over 200 million people, and caused over 4.3 million deaths worldwide [1]. In December 2020, the FDA approved two mRNA vaccines for Sars-Cov-2. After tiresome effort by healthcare workers around the world, over 4.7 billion doses of the vaccine have been administered as of August 2021 [1]. Multiple Sclerosis (MS) is a chronic inflammatory disease characterized by demyelinating and neurodegenerative changes of the Central Nervous System. Viral infections have been shown to trigger severe relapse and increase progression of the disease. Initial recommendations for patients with MS were to receive the COVID-19 vaccine if possible. There was some concern over vaccination itself inducing relapse of disease, but the risks of severe disease due to COVID-19 greatly outweigh the potential risks of the vaccine [2]. Current guidelines for MS therapy indicate the use of Disease Modifying Therapies (DMTs). The question remains as to whether patients on these therapies, especially newer DMTs such as ofatumumab, ozanimod, cladribine, siponimod, ocrelizumab, and fingolimod, will mount adequate responses from the COVID-19 vaccine, given that immunocompromised patients were excluded from early trials. It has been well documented that immunosuppressive therapies significantly diminish the normal immune response to vaccinations [3]. Furthermore, with lack of longitudinal studies surrounding the COVID-19 vaccine and the pandemic in general, we are severely lacking in data that could provide a threshold antibody level to determine whether a patient is sufficiently immunized. It has been suggested that any patient with MS requiring DMT will likely require booster vaccinations [4]. On August 12, 2021, the FDA announced the authorization of a third dose of the COVID-19 vaccine to ‘certain immunocompromised individuals.’ In this literature review, we aim to make a recommendation on whether patients with MS taking DMTs should receive the third dose of the COVID-19 vaccination, and establish goals for future studies on immune responses to vaccination in these patients.

Novel coronavirus disease (COVID‐19) first described in Wuhan, China in December 2019, has rapidly spread across the world and become a global public health emergency. Literature on the neurological manifestations of COVID‐19 is limited. We report a 24‐year‐old male, who presented with vertigo, dysarthria, and bradyphrenia 3 weeks after being diagnosed with COVID‐19 on nasopharyngeal reverse transcription polymerase chain reaction. The patient was diagnosed with acute cerebellitis based on magnetic resonance imaging features and showed improvement posttreatment with intravenous methylprednisone for 5 days. The scope of this article is to highlight the importance of early identification of neurological symptoms and timely management as the outcomes may be catastrophic.

This study examines the clinical characteristics, outcomes and types of management in SARS-CoV-2 infected patients, in the hospitals affiliated with West Virginia University. We included patients from West Virginia with SARS-CoV-2 infection between 15 April to 30 December 2020. Descriptive analysis was performed to summarize the characteristics of patients. Regression analyses were performed to assess the association between baseline characteristics and outcomes. Of 1742 patients, the mean age was 47.5 years (±22.7) and 54% of patients were female. Only 459 patients (26.3%) reported at least one baseline symptom, of which shortness of breath was most common. More than half had at least one comorbidity, with hypertension being the most common. There were 131 severe cases (7.5%), and 84 patients (4.8%) died despite treatment. The mean overall length of hospital stay was 2.6 days (±6.9). Age, male sex, and comorbidities were independent predictors of outcomes. In this study of patients with SARS-CoV-2 infection from West Virginia, older patients with underlying co-morbidities had poor outcomes, and the in-hospital mortality was similar to the national average.

Background The literature on neurological manifestations in COVID-19 patients has been rapidly increasing with the pandemic. However, data on CNS inflammatory disorders in COVID-19 are still evolving. We performed a literature review of CNS inflammatory disorders associated with coronavirus disease-2019 (COVID-19). Methods We screened all articles resulting from a search of PubMed, Google Scholar and Scopus, using the keywords; “SARS-CoV-2 and neurological complication”, “SARS-CoV-2 and CNS Complication” looking for reports of transverse myelitis, longitudinally extensive transverse myelitis, neuromyelitis optica, myelitis, Myelin Oligodendrocyte Glycoprotein Antibody Disorder (MOGAD), Acute Disseminated Encephalomyelitis (ADEM), Acute Hemorrhagic Necrotizing Encephalitis/Acute Hemorrhagic Leukoencephalitis (AHNE/AHLE), Cytotoxic lesion of the Corpus Callosum/Mild Encephalopathy Reversible Splenium Lesion(CLOCC/MERS) and Optic neuritis published between December 01, 2019 and March 15, 2021. Results Our literature search revealed 43 patients meeting the diagnosis of myelitis, including Transverse Myelitis, ADEM, AHNE/AHLE or CLOCC/MERS and Optic neuritis. Acute myelitis was most commonly associated with non-severe COVID-19 and all reported cases of AHNE/AHLE had severe COVID-19 infection. Based on IDSA/ATS criteria of either requiring vasopressor for septic shock or mechanical ventilation, 49% (n = 18) patients were considered to have a severe COVID infection. There were 7 (n = 19%) fatalities. Conclusion To our knowledge, this is among the first reviews that includes the clinical features, neuroimaging, CSF findings and outcomes in COVID-19-associated CNS inflammatory disorders. Our observational review study reveals that although rare, myelitis, ADEM, AHNE and CLOCC can be associated with COVID-19 infection. Further studies using MRI imaging and CSF analysis in early diagnosis and intervention of these disorders are warranted.

Objective To report a unique case and literature review of post COVID-19 associated transverse myelitis and dysautonomia with abnormal MRI and CSF findings. Background Coronavirus disease have been reported to be associated with several neurological manifestations such as stroke, Guillain-Barre syndrome, meningoencephalitis amongst others. There are only few reported cases of transverse myelitis with the novel coronavirus (n-CoV-2) and only one reported case identifying dysautonomia in COVID-19 patient. Here, we identify a COVID-19 patient diagnosed with acute transverse myelitis in addition to dysautonomia following with complete resolution of symptoms. Method A retrospective chart review of a patient diagnosed with post SARS-CoV-2 infection acute transverse myelitis and dysautonomia, and a review of literature of all the reported cases of transverse myelitis and COVID-19, from December 1st, 2019 till December 25th, 2020, was performed. Conclusion To our knowledge, this is the first reported case of transverse myelitis and dysautonomia in a patient with SARS-CoV-2 infection, who responded to intravenous methyl prednisone and bromocriptine. Follow-up imaging of the spine showed complete resolution of the lesion. Further studies would be recommended to identify the underlying correlation between COVID-19 and transverse myelitis.

Background: In view of the emerging coronavirus pandemic, the demand for knowledge about the impact of SARS-CoV-2 on people with Multiple Sclerosis (MS) continues to grow. Patients receiving disease modifying therapy (DMT) for MS have a higher background risk of infection-related health care utilization when compared to the general population. Therefore, there is a need of evidence-based recommendations to reduce the risk of infection and also managing MS patients with SARS-CoV-2. Case Description: We present three patients with history of Multiple Sclerosis (MS) on DMTs presenting with worsening MS symptoms likely pseudo exacerbation who were diagnosed with COVID-19. Discussion: An extensive review of 7 articles was performed, in addition to a brief review on DMTs use in MS patients with COVID-19. In our cases, all patients were on DMT and severe course of disease was noted in 2 cases. No fatality was observed. Conclusions: This review provides a base on the clinical characteristics, outcomes and the roles of DMTs in MS patients suffering from n-cov-2. Physicians need to be vigilant about considering COVID-19 infection related relapse in the MS patients, especially in this COVID-19 pandemic era and look for pseudo-exacerbation. As most cases are found to have mild course and full recovery on DMTs, further research is needed to formulate evidence-based guidelines. This review will particularly be helpful for the researchers and registries to collect future data on MS and COVID-19., Highlights • Our cases presented with MS pseudo-exacerbation, with confirmatory COVID-19 • In our review, most MS patients had mild course of COVID-19 • Most of them recovered and fatality was observed only in 9 patients • Use of DMTs in MS patients with moderate to severe COVID-19 is debatable • Studies are required to develop guidelines for managing MS with COVID-19

We performed a systematic literature review of neuroimaging, predominantly focusing on magnetic resonance imaging (MRI) findings associated with neurological manifestations of coronavirus disease-2019 (COVID-19). We screened articles from PubMed, Google Scholar and Scopus, looking for reports that would potentially have neuroimaging findings in patients with COVID-19. Data analysis was performed with patient-based data based on the availability of clinical characteristics and outcomes for each individual patient from the studies. Chi square and Wilcoxon rank-sum tests were used to report COVID-19 severity and outcomes based on neurological imaging indicators and pathophysiology. A total of 171 patients with COVID-19 having neurological complications, from 134 studies, were identified in our review. The most common neuroimaging finding was ischemic stroke (62, 36.2%) cases, followed by CNS inflammatory disorder (44, 25.7%), and hemorrhagic stroke (41, 24.0%). Around 51% of all the fatal COVID-19 cases had an ischemic stroke. Among patients with ischemic stroke, the mean age of those who suffered from COVID-19 infection was 57.5 years (SD = 15.4) whereas it was 50.7 years (SD = 15.1) among those without stroke/other diagnosis. Fatality was more common in patients with ischemic stroke compared to those with other diagnosis (40% vs. 22%, p = 0.011). The most frequently published neuroimaging findings in patients with COVID-19 were ischemic stroke, CNS inflammatory disorder, and hemorrhagic disorder. In those studies, ischemic stroke was associated with fatality, and was more frequently seen in older patients. Based on our findings, early usage of MRI in COVID-19 patients may be recommended.

The novel coronavirus outbreak of SARS-CoV-2 first began in Wuhan, China, in December 2019. The most striking manifestation of SARS-CoV-2 is atypical pneumonia and respiratory complications; however, various neurological manifestations are now well recognized. Currently, there have been very few case reports regarding COVID-19 in patients with a known history of myasthenia gravis. Myasthenia gravis (MG) causes muscle weakness, especially respiratory muscles, in high-risk COVID-19 patients, which can lead to severe respiratory compromise. There are few reported cases of severe myasthenia crisis following COVID-19, likely due to the involvement of the respiratory apparatus and the use of immunosuppressive medication. We report the first case of ocular MG developing secondary to COVID-19 infection in a 65-year-old woman. Two weeks prior to hospitalization, the patient suffered from cough, fever, and diarrhea and was found to be positive for COVID-19 via a nasopharyngeal RT-PCR swab test. The electrodiagnostic test showed decremental response over more than 10% on repetitive nerve stimulation test of orbicularis oculi. She tested positive for antibodies against acetylcholine receptor. COVID-19 is known to cause the release of inflammatory cytokines, leading to immune-mediated damage. MG is an immune-mediated disorder caused by molecular mimicry and autoantibodies against the neuromuscular junction.

Background: To study the nature and frequency of occurrence of “significant” neurological complications in coronavirus disease-2019 (COVID-19) via a systematic review of the literature.Methods: We screened all articles resulting from a search of PubMed, Cochrane, Google Scholar and Scopus, using the keywords "COVID-19 and CNS", "SARS-CoV-2 and CNS”, “COVID-19 and neurological manifestation”, “SARS2 and neurological manifestation” and “COVID-19 and Brain” looking for reports of significant neurological manifestations that would potentially have an impact on the outcome.Results: Twenty-six articles met the inclusion criteria. The significant neurological diagnoses reported were stroke, Guillain Barre Syndrome (GBS) and its variants, encephalitis, seizures, acute hemorrhagic necrotizing encephalopathy, acute disseminated encephalomyelitis (ADEM) and transverse myelitis. Although stroke, predominantly ischemic, was observed in ~ 6% of COVID-19 patients from Wuhan, China, mortality in this cohort was 38%. Of the 24 pooled patients with reports of etiology, 17 had large vessel occlusions. GBS occurred in 5/1200 (0.4%) of the COVID-19 cohort from Italy. One of the six reported encephalitis cases, the ADEM case and the report of transverse myelitis do not have data for conclusive diagnosis.Conclusion: The most frequent significant neurological association with COVID-19 is stroke, predominantly ischemic. In a cohort from Wuhan, China, this was as frequent as ~ 6%, with a 38% mortality. Most common reported etiology is large vessel occlusion. Other reported significant neurological complications are GBS/variants, encephalitis, seizures and acute hemorrhagic necrotizing encephalopathy. The reports of ADEM and transverse myelitis lacked diagnostically conclusive data.

The pulmonary manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (COVID-19) are well known. The literature on neurological manifestations and complications in patients with COVID-19 has been increasing but is still sparse. At present, there are only a few reported case reports and clinical studies on neurological manifestations of COVID-19, of which ischemic stroke is one of the most common ones. Coagulopathy and vascular endothelial dysfunction have been proposed as the complications of COVID-19 which can ultimately lead to ischemic stroke. In this case report, we present a case of multifocal ischemic stroke in a patient with COVID-19. This patient had persistent encephalopathy and dysarthria after recovering from hypoxic respiratory failure and subsequently developed ischemic stroke in multiple vascular territories during hospital admission., Highlights • Hypercoagulopathy and vascular endothelial dysfunction have been proposed as complications of COVID 19 which can lead to stroke. • Diagnoses of stroke in critically ill patients hospitalized with COVID-19 using MRI brain can be challenging due to multiple factors. • Patient with COVID-19 with stroke in multiple vascular territories after he had persistent encephalopathy and dysarthria. • MRI brain is more sensitive and specific modality to detect brain tissue that has been damaged by an ischemic stroke than a CT head.

Background and purpose Previous cross-sectional studies have reported the involvement of thalamus, pallidum, superior cerebellar peduncle, temporal cortex, and fronto-parietal white matter in multiple sclerosis (MS)-related fatigue. However, the longitudinal imaging correlates of fatigue severity variation in MS remain unclear. Methods Structural and diffusion tensor imaging (DTI) data were collected from 43 relapsing remitting MS (RRMS) patients with fatigue (Fatigue Severity Scale [FSS] range: 1-7). Subcortical nuclei volume using FreeSurfer and cortical diffusion indices using a cross-modality technique were measured at baseline and year 1. Results The pallidal volume had significantly decreased (P = .002) by year 1, although the fatigue score variation was not significant. At year 1, the pallidal volume (P = .023) and fractional anisotropy (FA, P = .013) of right temporal cortex (RTC) correlated significantly with FSS. Conclusions The pallidal volume and the FA-RTC may be used to evaluate longitudinal fatigue severity variation. Our study proposes new biomarkers to monitor fatigue severity in MS patients.

Few cross-sectional studies have investigated the correlation between neurochemical changes and multiple sclerosis (MS) fatigue, but little is known on the fatigue-related white matter differences between time points. We aim to investigate the longitudinal neurometabolite profile of white matter in MS fatigue. Forty-eight relapsing remitting multiple sclerosis (RRMS) patients with an expanded disability status scale (EDSS) &le, 4 underwent high field 1H-multivoxel magnetic resonance spectroscopy (MRS) at baseline and year 1. Fatigue severity was evaluated by the fatigue severity scale (FSS). Patients were divided into low (LF, FSS &le, 3), moderate (MF, FSS = 3.1&ndash, 5), and high fatigue (HF, FSS &ge, 5.1) groups. In a two-way analysis of variance (ANOVA), we observed a decline in the ratio of the sum of N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) to the sum of creatine (Cr) and phosphocreatine (PCr) in the right anterior quadrant (RAQ) and left anterior quadrant (LAQ) of the MRS grid in the HF group at baseline and year 1. This decline was significant when compared with the LF group (p = 0.018 and 0.020). In a one-way ANOVA, the fatigue group effect was significant and the ratio difference in the right posterior quadrant (RPQ) and left posterior quadrant (LPQ) of the HF group was also significant (p = 0.012 and 0.04). Neurochemical changes in the bilateral frontal white matter and possibly parietooccipital areas were noted in the HF group at two different time points. Our findings may shed some light on the pathology of MS fatigue.

Seizures occur 2–3 times more frequently in Multiple Sclerosis (MS) patients compared to the general population. The prevalence of seizures is reported to be 1.5–7.8% in MS population. However, it is unclear if seizure is an indirect symptom of neuroinflammation in MS. In our study, we explored the relevance of cerebrospinal fluid (CSF) findings in this unique patient cohort with MS and seizures. We retrospectively reviewed the charts of 32 MS patients with subsequent seizures (MSSS) and 12 patients with seizures followed by MS (SFMS). These two study groups were compared with two control groups - MS without seizures (MSNOS) and seizures without MS (SNOMS). Clinical characteristics and CSF findings between these groups were compared using boot strapped independent t-test. The CSF lymphocyte percentage of the SFMS group (95.6 ± 3) was significantly higher compared to MSNOS (66.0 ± 36.9, p = .04) and SNOMS (81.7 ± 10.0, p = .03). The CSF IgG index was significantly higher in SFMS group (1.9 ± 1.2, p = .02) as compared to MSSS group (0.99 ± 0.4). Patients with seizures as initial symptom of MS may have higher degree of CNS inflammation. Nonspecific clinical symptoms and atypical imaging findings in patients presenting with seizures may warrant close monitoring for development of MS.

Background The COVID-19 pandemic caused by SARS-COV-2 began in Wuhan, China in December 2019. Reports of COVID-19 with central (CNS) and peripheral nervous (PNS) system manifestations are emerging. In this systematic review, we compared and summarized the demographics, clinical features, Brighton criteria, immunological and laboratory findings with a focus on modified Erasmus GBS Outcome Score (mEGOS) in SARS-CoV-2 patients with GBS and its variants. Methods Based on PRISMA guidelines, we searched three databases (PubMed, Scopus, and Google Scholar) for studies on COVID-19 and GBS between December 1, 2019 to July 15, 2020. For descriptive analysis, we studied two groups with: 1) acute inflammatory demyelinating polyradiculoneuropathy (AIDP) variant, and 2) Non-AIDP/Other variants. We compared mEGOS scores for patients in both groups along with other key clinical features. Results Of the 50 GBS cases identified from 37 studies, 33 (66%) had acute inflammatory demyelinating polyradiculopolyneuropathy (AIDP) while 17 (34%) were of other (non-AIDP) variants. There mEGOS scores did not differ between AIDP patients and AMAN/AMSAN patients. Majority of the AIDP (66.7%) and AMAN/AMSAN (57.2%) patients belonged to Brighton level 1 indicating maximum diagnostic certainty. Conclusion To our knowledge, this is among the first reviews that includes GBS variants and the clinical prediction tool mEGOS for prognostication in COVID-19 patients. Further research is needed to assess whether IVIG is preferable over plasmapheresis in this population of GBS patients. It would also be crucial to follow these patients over time to identify the long-term disability as well as treatment outcomes., Highlights • Majority of GBS variants in COVID-19 patients were AIDP. • Most AIDP, AMAN/AMSAN patients exhibited Brighton level 1-maximum diagnostic certainty. • The mean latency between COVID-19 infection and GBS ranged between 11 and 13 days.

Ocrelizumab is a humanized CD20 monoclonal antibody which was approved for management of Relapsing Remitting Multiple Sclerosis (RRMS) and Primary Progressive Multiple Sclerosis (PPMS) in 2017. We present 2 patients, a 67-year-old woman with history of PPMS and a 42-year-old woman with RRMS, who were started on ocrelizumab and were diagnosed with invasive ductal cell breast carcinoma after 2 years of ocrelizumab infusion followed by discontinuation of the drug. Large trials conducted for ocrelizumab showed malignancies in a total of 4 cases with RRMS in OPERA 1 trial conducted over 2 years from 2011 to 2013 (breast cancer, renal cell carcinoma, and melanomas) and in 11 cases with PPMS seen in ORATORIO trial conducted in 2017. There are currently no other published case reports of breast cancer in setting of ocrelizumab use for MS outside of large trials on literature review.

Varicella zoster virus (VZV) has been increasingly linked with encephalitis and atypical presentations in immunosuppressed patients. We present a patient with history of immunosuppressant intake for polymyositis who initially presented with throbbing frontal headache that raised the suspicion of migraine. She did not respond to anti-migraine medication and later developed stimulus induced myoclonus. She then had significant neurological decline and eventually became encephalopathic. Her initial imaging of brain was unremarkable which warranted further investigations. She was then diagnosed to be VZV positive in the cerebrospinal fluid (CSF) sample that confirmed VZV encephalitis. She responded well to IV Acyclovir treatment and her neurological function improved significantly. In this case, there was delay in diagnosis of VZV in the setting of immunosuppression and non-specific clinical presentation. Therefore, we encourage to strongly consider early VZV diagnostic work up and treatment in immunocompromised patients who can present with non-specific symptoms without a typical cutaneous rash., Highlights • VZV encephalitis can be differential diagnoses of immunocompromised patients in absence of cutaneous lesions. If untreated it can be uniformly fatal. • Newly onset headache that mimics status migraine in immunocompromised status raises red flag for VZV encephalitis.