Case 309: Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy.

HISTORY: A 64-year-old man presented with a 6-month history of lightheadedness and intermittent balance and coordination difficulties. Two months before admission, symptoms became more substantial and persistent, with a worsening sense of disequilibrium and unsteady gait. He reported difficulties pronouncing words and mild word-finding difficulties. His wife noted a change in his cognition and memory over the same time. His medical history included well-controlled chronic obstructive pulmonary disease (COPD) secondary to a long history of smoking with associated unintentional 30-lb (13.6-kg) weight loss over the previous 3 years, for which chest CT scanning was performed, revealing no abnormality. On clinical examination, the patient was alert and oriented but had slurred speech. A positive Romberg sign was noted, finger-to-nose and hand rapid alternating movement tests revealed impairment on the right side, and his gait was ataxic. The motor examination revealed normal muscle tone, bulk, and power in the upper and lower extremities. Sensory testing results were normal. Initial MRI of the brain at admission revealed abnormal findings in the left supratentorial brain. Of note, this patient's presentation predated the COVID-19 pandemic. Cerebrospinal fluid (CSF) analysis revealed predominant pleocytosis (23 × 106/L; normal range, [0-5] × 106/L) (78% lymphocytes, 22% monocytes), elevated protein level (1.23 g/L; normal range, 0.19-0.64 g/L), oligoclonal bands (faint one or two), and a high immunoglobulin G (IgG) index (0.130 g/L; normal reference, ≤0.059 g/L). Despite extensive initial work-up for inflammatory, infectious, autoimmune, or neoplastic causes, a definitive diagnosis was not reached. Thus, repeat MRI of the brain was performed 2 weeks after admission.

Myoclonus and cerebellar ataxia associated with COVID-19: a case report and systematic review.

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic in December 2019, neurological manifestations have been recognized as potential complications. Relatively rare movement disorders associated with COVID-19 are increasingly reported in case reports or case series. Here, we present a case and systematic review of myoclonus and cerebellar ataxia associated with COVID-19. METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline using the PubMed and Ovid MEDLINE databases, from November 1, 2019 to December 6, 2020. RESULTS: 51 cases of myoclonus or ataxia associated with COVID-19, including our case, were identified from 32 publications. The mean age was 59.6 years, ranging from 26 to 88 years, and 21.6% were female. Myoclonus was multifocal or generalized and had an acute onset, usually within 1 month of COVID-19 symptoms. Myoclonus occurred in isolation (46.7%), or with ataxia (40.0%) or cognitive changes (30.0%). Most cases improved within 2 months, and treatment included anti-epileptic medications or immunotherapy. Ataxia had an acute onset, usually within 1 month of COVID-19 symptoms, but could be an initial symptom. Concurrent neurological symptoms included cognitive changes (45.5%), myoclonus (36.4%), or a Miller Fisher syndrome variant (21.2%). Most cases improved within 2 months, either spontaneously or with immunotherapy. CONCLUSIONS: This systematic review highlights myoclonus and ataxia as rare and treatable post-infectious or para-infectious, immune-mediated phenomena associated with COVID-19. The natural history is unknown and future investigation is needed to further characterize these movement disorders and COVID-19.

Paraneoplastic cerebellar degeneration as a presenting manifestation of non-Hodgkin's lymphoma.

BACKGROUND: Paraneoplastic Cerebellar degeneration (PCD) is one of the classical paraneoplastic syndromes (PNS) which is characterised by subacute onset, progressive cerebellar ataxia and is usually associated with small cell lung carcinoma, adeno carcinoma of breast and ovary followed by Hodgkin's lymphoma. OBJECTIVE: We herein report a case of subacute onset, progressive cerebellar ataxia in a 37-year-old female, who on evaluation was found to have non-Hodgkin's lymphoma and experienced good clinical response to treatment. DISCUSSION: As compared to solid tumours, chances of association of PNS with Lymphomas is quite low and there are only few case reports in the literature showing association of PCD with non-Hodgkin's lymphoma. As PCD is one of the classical PNS, it is very important to identify subtle cerebellar manifestations in an otherwise apparently normal individual, as early diagnosis and aggressive treatment can immensely improve the mortality and morbidity associated with this syndrome. CONCLUSION: This case signifies the importance of suspecting PNS as an important differential diagnosis in a young patient presenting with subacute onset progressive cerebellar ataxia and evaluating her extensively for malignancy in spite of no paraneoplastic antibody been detected as early diagnosis and treatment can lead to gratifying response. We do agree that 2 weeks follow up is a short time interval to determine whether the response was sustained or not, for which a long term follow up is required.

Acute Cerebellar Ataxia in COVID-19 Infection: A Case Report.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has been widely reported to cause symptoms such as fever, cough, sore throat, fatigue, and shortness of breath. Neurologic complications have not been widely reported without associated respiratory symptoms. These neurologic manifestations have been found mostly in the elderly. There has been no report of ataxia or COVID-19 cerebellitis in the young adult population without associated respiratory symptoms. CASE REPORT: Here we report the case of a 30-year-old patient who presented with isolated cerebellar symptoms and was diagnosed with COVID-19 cerebellitis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: It is important for emergency physicians to know that COVID-19 can have many clinical manifestations and to have a high level of suspicion with acute neurologic symptoms.

Acute cerebellar ataxia and myoclonus with or without opsoclonus: a para-infectious syndrome associated with COVID-19.

BACKGROUND AND PURPOSE: Patients with COVID-19 can have central or peripheral neurological manifestations. METHODS: The cases of two patients with acute cerebellar ataxia and myoclonus associated with COVID-19 are reported (with Video S1) and five previously reported patients are discussed. RESULTS: Acute cerebellar ataxia and myoclonus started between 10 days and 6 weeks after the first manifestations of COVID-19. Opsoclonus or ocular flutter was present in four patients. Patients were treated with intravenous immunoglobulins and/or steroids except for one patient, resulting in a striking improvement within a week. CONCLUSION: Acute cerebellar ataxia and myoclonus with or without opsoclonus belongs to the wide spectrum of neurological manifestations associated with COVID-19. It is important to recognize this possible manifestation since early treatment allows for rapid recovery.

Neurological and Neuropsychiatric Impacts of COVID-19 Pandemic.

BACKGROUND: Albeit primarily a disease of respiratory tract, the 2019 coronavirus infectious disease (COVID-19) has been found to have causal association with a plethora of neurological, neuropsychiatric and psychological effects. This review aims to analyze them with a discussion of evolving therapeutic recommendations. METHODS: PubMed and Google Scholar were searched from 1 January 2020 to 30 May 2020 with the following key terms: "COVID-19", "SARS-CoV-2", "pandemic", "neuro-COVID", "stroke-COVID", "epilepsy-COVID", "COVID-encephalopathy", "SARS-CoV-2-encephalitis", "SARS-CoV-2-rhabdomyolysis", "COVID-demyelinating disease", "neurological manifestations", "psychosocial manifestations", "treatment recommendations", "COVID-19 and therapeutic changes", "psychiatry", "marginalised", "telemedicine", "mental health", "quarantine", "infodemic" and "social media". A few newspaper reports related to COVID-19 and psychosocial impacts have also been added as per context. RESULTS: Neurological and neuropsychiatric manifestations of COVID-19 are abundant. Clinical features of both central and peripheral nervous system involvement are evident. These have been categorically analyzed briefly with literature support. Most of the psychological effects are secondary to pandemic-associated regulatory, socioeconomic and psychosocial changes. CONCLUSION: Neurological and neuropsychiatric manifestations of this disease are only beginning to unravel. This demands a wide index of suspicion for prompt diagnosis of SARS-CoV-2 to prevent further complications and mortality.

Les impacts neurologiques et neuropsychiatriques d'une infection à la COVID-19. CONTEXTE: Bien qu'il s'agisse principalement d'une maladie des voies respiratoires, la maladie infectieuse à coronavirus apparue en 2019 (COVID-19) s'est avérée avoir un lien de causalité avec une pléthore d'impacts d'ordre neurologique, neuropsychiatrique et psychologique. Cette étude entend donc analyser ces impacts tout en discutant l'évolution des recommandations thérapeutiques se rapportant à cette maladie. MÉTHODES: Les bases de données PubMed et Google Scholar ont été interrogées entre les 1er janvier et 30 mai 2020. Les termes clés suivants ont été utilisés : « COVID-19 ¼, « SRAS ­ CoV-2 ¼, « Pandémie ¼, « Neuro ­ COVID ¼, « AVC ­ COVID ¼, « Épilepsie ­ COVID ¼, « COVID ­ encéphalopathie ¼, « SRAS ­ CoV-2 ­ encéphalite ¼, « SRAS ­ CoV-2 ­ rhabdomyolyse ¼, « COVID ­ maladie démyélinisante ¼, « Manifestations neurologiques ¼, « Manifestations psychosociales ¼, « Recommandations thérapeutiques ¼, « COVID-19 et changement thérapeutiques ¼, « Psychiatrie ¼, « Marginalisés ¼, « Télémédecine ¼, « Santé mentale ¼, « Quarantaine ¼, « Infodémique ¼ et « Médias sociaux ¼. De plus, quelques articles de journaux relatifs à la pandémie de COVID-19 et à ses impacts psychosociaux ont également été ajoutés en fonction du contexte. RÉSULTATS: Il appert que les manifestations neurologiques et neuropsychiatriques des infections à la COVID-19 sont nombreuses. Les caractéristiques cliniques d'une implication des systèmes nerveux central et périphérique sautent désormais aux yeux. Ces caractéristiques ont fait l'objet d'une brève analyse systématique à l'aide de publications scientifiques. En outre, la plupart des impacts d'ordre psychologique de cette pandémie se sont révélés moins apparents que les changements réglementaires, socioéconomiques et psychosociaux. CONCLUSION: Les manifestations neurologiques et neuropsychiatriques de cette maladie ne font que commencer à être élucidées. Cela exige donc une capacité accrue de vigilance en vue d'un diagnostic rapide, et ce, afin de prévenir des complications additionnelles et une mortalité accrue.

Neurological manifestations associated with COVID-19: a nationwide registry (preprint)

Background: The clinical description of the neurological manifestations in COVID-19 patients is still underway. This study aims to provide an overview of the spectrum, characteristics and outcomes of neurological manifestations associated with SARS-CoV-2 infection. Methods: We conducted a nationwide, multicentric, retrospective study during the French COVID-19 epidemic in March-April 2020. All COVID-19 patients with de novo neurological manifestations were eligible. Results: We included 222 COVID-19 patients with neurological manifestations from 46 centers throughout the country. Median age was 65 years (IQR 53-72), and 136 patients (61.3%) were male. COVID-19 was severe or critical in almost half of the patients (102, 45.2%). The most common neurological diseases were COVID-19 associated encephalopathy (67/222, 30.2%), acute ischemic cerebrovascular syndrome (57/222, 25.7%), encephalitis (21/222, 9.5%), and Guillain-Barre Syndrome (15/222, 6.8%). Neurological manifestations appeared after first COVID-19 symptoms with a median (IQR) delay of 6 (3-8) days in COVID-19 associated encephalopathy, 7 (5-10) days in encephalitis, 12 (7-18) days in acute ischemic cerebrovascular syndrome and 18 (15-28) days in Guillain-Barre Syndrome. Brain imaging was performed in 192 patients (86.5%), including 157 MRI (70.7%). Brain MRI of encephalitis patients showed heterogeneous acute non vascular lesion in 14/21 patients (66.7%) with associated small ischemic lesion or microhemorrhages in 4 patients. Among patients with acute ischemic cerebrovascular syndrome, 13/57 (22.8%) had multi territory ischemic strokes, with large vessel thrombosis in 16/57 (28.1%). Cerebrospinal fluid was analyzed in 97 patients (43.7%), with pleocytosis in 18 patients (18.6%). A SARS-CoV-2 PCR was performed in 75 patients and was positive only in 2 encephalitis patients. Among patients with encephalitis, ten out of 21 (47.6%) fully recovered, 3 of whom received corticosteroids (CS). Less common neurological manifestations included isolated seizure (8/222, 3.6%), critical illness neuropathy (8/222, 3.6%), transient alteration of consciousness (5/222, 2.3%), intracranial hemorrhage (5/222, 2.3%), acute benign lymphocytic meningitis (3/222, 1.4%), cranial neuropathy (3/222, 1.4%), single acute demyelinating lesion (2/222, 0.9%), Tapia syndrome (2/222, 0.9%), cerebral venous thrombosis (1/222, 0.5%), sudden paraparesis (1/222, 0.5%), generalized myoclonus and cerebellar ataxia (1/222, 0.5%), bilateral fibular palsy (1/222, 0.5%) and isolated neurological symptoms (headache, anosmia, dizziness, sensitive or auditive symptoms, hiccups, 15/222, 6.8%). The median (IQR) follow-up of the 222 patients was 24 (17-34) days with a high short-term mortality rate (28/222, 12.6%). Conclusion: Neurological manifestations associated with COVID-19 mainly included CAE, AICS, encephalitis and GBS. Clinical spectrum and outcomes were broad and heterogeneous, suggesting different underlying pathogenic processes.

Cytokine Release Syndrome-Associated Encephalopathy in Patients with COVID-19 (preprint)

Severe disease and uremia are risk factors for neurological complications of coronavirus disease-2019 (COVID-19). An in-depth analysis of a case series was conducted to describe the neurological manifestations of patients with COVID-19 and gain pathophysiological insights that may guide clinical decision-making – especially with respect to the cytokine release syndrome (CRS). Extensive clinical, laboratory, and imaging phenotyping was performed in five patients. Neurological presentation included confusion, tremor, cerebellar ataxia, behavioral alterations, aphasia, pyramidal syndrome, coma, cranial nerve palsy, dysautonomia, and central hypothyroidism. Neurological disturbances were remarkably accompanied by laboratory evidence of CRS. SARS-CoV-2 was undetectable in the cerebrospinal fluid. Hyperalbuminorachy and increased levels of the astroglial protein S100B were suggestive of blood-brain barrier (BBB) dysfunction. Brain MRI findings comprised evidence of acute leukoencephalitis (n = 3, of whom one with a hemorrhagic form), cytotoxic edema mimicking ischemic stroke (n = 1), or normal results (n = 2). Treatment with corticosteroids and/or intravenous immunoglobulins was attempted – resulting in rapid recovery from neurological disturbances in two cases. Patients with COVID-19 can develop neurological manifestations that share clinical, laboratory, and imaging similarities with those of chimeric antigen receptor-T cell-related encephalopathy. The pathophysiological underpinnings appear to involve CRS, endothelial activation, BBB dysfunction, and immune-mediated mechanisms.