Major neurological syndromes with COVID-19: lessons to learn

Objective: Covid-19 is a highly infectious viral disease, and our understanding of the impact of this virus on the nervous system is limited. Therefore, we aimed to do a systematic analysis of the neurological manifestations. Methods: We retrospectively studied the clinical, laboratory, and radiological findings of patients with major neurological syndromes (MNS) in Covid-19 over 6 months. Results: We had 39 patients with major neurological syndromes (MNS). The most common MNS was cerebrovascular disease (CVD) (61.53%), in which ischemic stroke (83.33%), cortical sinus thrombosis (12.50%), and haemorrhagic stroke (4.16%) were seen. Among ischemic stroke patients, 50% had a large vessel occlusion, and 66.66% of patients with CVD had a significant residual disability. Cranial neuropathy (15.38%), GBS (10.26%), encephalitis (7.26%), and myelitis (5.12%) were the other MNS. Among the three encephalitis cases, two had CSF-Covid-19 PCR positivity and had severe manifestations and a poor outcome. Associated comorbidities included hypertension (30.76%), diabetes mellitus (12.82%), chronic kidney diseases (7.69%), and polycythaemia vera (2.56%). Lung involvement was seen in 64.1% of patients. Mortality was 17.94% in MNS with Covid-19. Conclusions: The most common major neurological syndrome associated with Covid-19 is CVD with increased frequency of large vessel occlusion causing significant morbidity and mortality. Simultaneous lung and other systemic involvement in MNS results in a deleterious outcome.

Tract specific CNS involvement post COVID-19 vaccine: A case report

We hereby report an interesting case of tractopathy following COVID-19 vaccine. Acute transverse myelitis following COVID-19 infection or vaccination is well documented. However, to the best of our knowledge, no case of selective tract involvement following COVID-19 vaccine has been reported so far. One case of tract-specific central nervous system involvement following COVID-19 infection has been reported from India. We report the case of a 46-year-old male who developed clinical and radiological evidence of tractopathy involving the corticospinal tracts and posterior columns following the first dose of the Covishield vaccine.

Acute Flaccid Myelitis in a Pediatric Patient With Coronavirus Disease 2019.

The etiology of acute flaccid myelitis (AFM) has yet to be determined. Viral link has been suggested, but severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated AFM has not been reported in children. We describe a three-year-old boy, with AFM associated with coronavirus disease 2019 (COVID-19) infection. In the era of COVID-19 pandemic, patients with AFM should be tested for SARS-CoV-2.

Long-segment myelitis after traumatic paraplegia in COVID-19 positive patient: An unusual case report

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has devastated the mankind globally, and countless lives have been lost all around the world. This disease has been linked to various extrapulmonary symptoms and consequences in addition to typical respiratory illness. This case highlights a probable neurological complication of SARS-CoV-2 infection. A 28-year-old healthy man, sustained wedge compression of D12 vertebra following road traffic accident, presented with paraplegia. One week following admission, the patient had a progressive neurological deterioration and developed high grade fever with weakness in both upper limbs. The patient developed quadriplegia 10 days after admission. Magnetic resonance imaging (MRI) brain and spine were done. MRI brain was normal, whereas MRI spine showed D11-D12 anterolisthesis with cord compression with T2 hyperintensity of cervical cord. His SARS-CoV-2 reverse transcriptase polymerase chain reaction turned out to be positive. We hereby report a case of posttraumatic long-segment myelitis with coronavirus disease 2019 as a probable etiology.

Acute encephalomyelitis in a 52-year-old male post messenger ribonucleic acid severe acute respiratory syndrome coronavirus 2 vaccination: a case report.

BACKGROUND: Acute disseminated encephalomyelitis is a well-known, but rare, side effect of some vaccines, or symptom following a febrile illness. CASE: A 69-year-old, otherwise healthy Hispanic male presented with acute fever, confusion, and later progressive weakness after receiving the first dose of the mRNA-1273 (Moderna) severe acute respiratory syndrome coronavirus 2 vaccine. Considering the progressive deterioration of the patient, despite being on multiple immunosuppressive agents, a brain biopsy was obtained, which revealed nonspecific meningoencephalitis. CONCLUSION: In this case, we highlight the need for a regulatory framework to assist clinicians and patients with coverage of treatment for acute disseminated encephalomyelitis. The use of intravenous immunoglobulin in conjunction with glucocorticoids seems to be an effective treatment option.

Spectrum of Serious Neurological and Psychiatric Adverse Events in Indian COVID-19 Vaccine Recipients: A Systematic Review of Case Reports and Case Series.

Indian data regarding serious neurological and psychiatric adverse events, following coronavirus disease 2019 (COVID-19) vaccination, are lacking. We, therefore, systematically evaluated cases of post-vaccinal serious neurological and psychiatric adverse reactions published from India. A systematic review of cases published from India, which were archived in PubMed, Scopus, and Google Scholar databases, was performed; pre-print databases along with ahead-of-print contents were searched in addition. Retrieved articles, as on June 27, 2022, were evaluated following PRISMA guidelines. EndNote 20 web tool was used to make a PRISMA flow chart. Individual patients' data were compiled in a tabular form. The protocol of the systematic review was registered with PROSPERO (CRD42022324183). A total of 64 records describing 136 instances of serious neurological and psychiatric adverse events were identified. More than 50% (36/64) reports were from the following four states, namely, Kerala, Uttar Pradesh, New Delhi, and West Bengal. The mean age of persons developing these complications was 44.89 ± 15.77 years. In the majority, adverse events occurred within 2 weeks of administration of the first dose of COVISHIELD vaccine. Immune-mediated central nervous system (CNS) disorders were identified in 54 instances. Guillain-Barre syndrome and other immune-mediated peripheral neuropathies were reported in 21 cases. Post-vaccinal herpes zoster was recorded in 31 vaccine recipients. Psychiatric adverse events were recorded in six patients. In Indian recipients of COVID-19 vaccine, a variety of serious neurological complications were reported. The overall risk appears minuscule. Immune-mediated central and peripheral neuronal demyelinations were the most frequently reported post-vaccinal adverse events. A large number of cases of herpes zoster have also been reported. Immune-mediated disorders responded well to immunotherapy.

Clinical presentation and rehabilitation outcomes in post-coronavirus disease-2019 vaccination longitudinal extensive transverse myelitis: Report of three cases with follow-up at 8 months

Longitudinally extensive transverse myelitis (LETM) is an infrequent subtype of acute transverse myelitis, which presents with sensory, motor and autonomic dysfunction after a focal or widespread inflammation of the spinal cord due to either direct infection or an autoimmune response. We present case reports of three females who developed LETM following COVID-19 vaccination. Their clinical presentation, deficits and rehabilitation outcome at discharge and at 8 months follow-up have been briefly described.

Transverse myelitis as neurologic sequelae in a COVID-19 recovered patient

Background: Months after the initial report of an unknown cause of pneumonia outbreak in Wuhan, China, the SARS-COV-2 continues its rampant spread globally. This novel corona virus has been known to cause severe respiratory illness. It is important to be wary of the complications that would soon present at the Out-patient centers after being cured from the infection. Case: This is a case of a 59-year-old, female who came in at the Out-Patient Clinic with progressive bilateral pins and needles sensation of the feet after recovering from COVID-19 infection followed by a sensory level on T7-T10. Case Report: Here we present a case of transverse myelitis as a complication of COVID-19 infection, the first to have occurred after recovery from the virus. With the success of treatments and recoveries, possible post infectious sequelae could be the next wave that could come into the present picture of the pandemic. Conclusion(s): Post infectious transverse myelitis after recovering from COVID-19 is a possibility and that documentation of such cases and other complications must be reported.Copyright © 2022

The Longitudinal Study of Neuromyelitis Optica Spectrum Patients Epidemiological Characteristics, a Six Years Follow Up Survey from Isfahan, Iran

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune, rare demyelinating disease of the central nervous system characterized by recurrent attacks which usually involve optic nerves and spinal cord. Although the most common symotoms are myelitis and optic neuritis, it can be presented as cerebral syndromes mainly those related to the brain stem and diencephalon. Since NMOSD is a rare disease and the epidemiological data on this disorder is still insufficient, the establishment of registry and long-term follow up studies are needed to assess the disease course and behavior over a period of time. Material(s) and Method(s): We stablished an electronic registry system for NMOSD patients in the MS center of Kashani hospital, Isfahan, Iran, since spring 2016. Every patient suspected for NMOSD and documented in our database was included in a follow up study to monitor their disease course and progression. Anti AQP4 antibody and Anti MOG antibody were checked for all patients in a unique lab by cell based assay method. Demographic data and clinical characteristics such as family history, comorbidities,education, number of relapses, presentation signs and radiological findings were recorded. Moreove, relapses, treatment change, triggers, and COVID-19 infection were documented. We investigated the effect of the COVID19 pandemic and vaccination on NMOSD patients. Result(s): This study included 173 cases with definite diagnosis of NMOSD, and 56 ones were seropositive for AQP4 Ab. 142 were females of which 46 were in the seropositive group. Their mean age was 40.02+/-11.11 years (45.78+/-12.88 in AQP4Ab positive group). The mean of age at disease onset was about 30.16+/-11.90 years. The mean time of follow up was 55.84+/-18.94 months until today. In 76 patients, there were LETM in the first cervical MRI. 123 patients revealedbabnormality in the first brain MRI. 27 patients had hypothyroidism as the most common comorbidity. 36 cases reported positive family history of multiple sclerosis and also 4 had a family history of NMOSD. Conclusion(s): The mean age of onset did not differ between seropositive and seronegative group but it was higher than MS patients. Brain MRI showed abnormality in NMOSD patients. Female/male was 4.4/1 which is lower than other studies.Copyright © 2022

Transverse myelitis 48 hours after the administration of an mRNA COVID 19 vaccine

Background Vaccinations against SARS-CoV-2 have been a topic of political, social, and medical intrigue since the declaration of the COVID-19 pandemic in early 2020. The vaccine side effects have been relatively mild to date, with few observed systemic effects. Case presentation A 69-year-old previously healthy female presented with symptoms of asymmetric bilateral lower and upper extremity weakness 2 days after vaccination with the Pfizer-BioNTech mRNA vaccine. MRI of the cervical spine revealed a non-compressive myelitis extending from C3-4 to T2-3. Common known causes of transverse myelitis were ruled out by diagnostic techniques. Conclusions Transverse myelitis is a rare autoimmune disorder that has been shown to have a temporal association with vaccination in the past. With a progressively partisan societal view on vaccinations, it is important for clinicians to remain vigilant on documenting potential associations without encouraging fear of causation.Copyright © 2021 The Author(s)

clinical-laboratory interaction in the diagnosis of autoimmune neurological conditions: focus on the coVid-19 pandemic.

The interaction between clinic and laboratory is crucial for the diagnostic process of neurological disorders, in particular in patients with autoimmune/inflammatory conditions. In these conditions, different diagnostic assays with specific sensitivity and specificity are available. Many laboratories use commercial assays based on line-blot techniques (for the detection of antibodies to intracellular antigens, such as Hu and Yo) or fixed cell-based-assays (for the detection of antibodies to surface antigens such as NMDAR or LGI1 or to oligodendrocytes-MOG- or astrocytes-AQP4). However, assays with higher sensitivity, such as live CBA or immunohistochemistry on rat brain/cerebellum are available and allow the detection of additional antibodies, also to unknown antigens, by evaluating specific patterns of positivity. In this context, the continuous interaction between clinicians and laboratory physicians is necessary to guide antibody testing and select those cases which need additional advanced investigations. This concept was even more relevant during the COVID-19 pandemic, which led to an increase of samples referred to reference laboratories, in particular from patients with encephalitis or myelitis, for whom the differential diagnosis between an infectious vs. postinfectious vs. inflammatory vs. autoimmune process was challenging. The interaction between clinicians and laboratory physicians in this area focused on solving some important questions, and in particular: 1) to understand whether SARS-CoV-2 infection could cause autoimmune neurological diseases;2) to clarify the course of SARS-CoV-2 infection in patients with autoimmune neurological diseases;3) to understand if vaccines could induce autoimmune neurological diseases;and 4) to understand the effect of vaccination in patients with autoimmune neurological diseases. The constant scientific exchange between the various professional figures led to an improvement of the diagnostic process of these neurological disorders, with a significant impact on patients' prognosis and quality of life.Copyright © 2022 EDIZIONI MINERVA MEDICA.

Autoimmune spinal cord lesions associated with novel coronavirus infection.

Spinal cord affection, according to various sources, is a common complication of a new coronavirus infection. The article describes various variants of spinal cord pathology in COVID-19, their potential mechanisms of development, approaches to treatment and outcomes of the disease. Three patients who were observed at the Research Center of Neurology and represent the most interesting cases of classic transverse myelitis, myelitis with predominant involvement of the lateral and posterior cords, and longitudinal widespread myelitis associated with antibodies to myelin oligodendrocyte glycoprotein (MOG) are considered in detail. These clinical observations demonstrate the importance of early diagnosis and selection of adequate therapy for a favorable outcome of the disease.Copyright © 2022 Ima-Press Publishing House. All rights reserved.

Glial fibrillary acidic protein astrocytopathy in a patient with recent mRNA SARS-CoV-2 vaccination: COVERSHEET

Background: Literature describing triggers of GFAP astrocytopathy (GFAP-A) is limited. We report a case of GFAP-A in a patient with recent messenger ribonucleic acid (mRNA) severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) vaccination and discuss the possible pathogenesis. Case description: A 45-year-old gentleman presented with features of meningoencephalitis 31 days after the first dose and 4 days after the second dose of mRNA SARS-CoV-2 vaccination. He sequentially developed brainstem/cerebellar, autonomic and cord dysfunction. Cerebrospinal fluid was positive for GFAP autoantibody. Clinical improvement occurred after intravenous methylprednisolone and immunoglobulins. Conclusion(s): Although we are uncertain of a causal link of GFAP-A to mRNA vaccine, indirect activation of an underlying dysregulated immune milieu is plausible.Copyright © 2021 The Author(s)

Spinal cord involvement in COVID-19: A review.

CONTEXT: Recent literature points towards myelitis, like encephalitis, as a common central nervous system complication of COVID-19. This review elaborates on disorders of the spinal cord caused by the SARS-CoV-2 virus. OBJECTIVES: To review the published data about SARS-CoV-2-associated spinal cord disorders and assess their clinical, neuroimaging, treatment, and prognostic aspects. METHODS: The PubMed and Google Scholar databases were searched for published cases using the search items "COVID-19 OR SARS-CoV-2 AND myelitis", "COVID-19 OR SARS-CoV-2 AND myelopathy", and "COVID-19 OR SARS-CoV-2 AND spinal cord". RESULTS: Thirty-three isolated cases were included in the present review, of which 14 were aged 60 years and above (range: 3-70 years). Eighteen patients had lung abnormalities on chest imaging. Eight patients had developed either an areflexic paraparesis or quadriparesis. In 17 patients, neuroimaging demonstrated longitudinally extensive transverse myelitis, while 3 cases showed neuroimaging changes in the spinal cord as a part of acute disseminated encephalomyelitis syndrome. Cerebrospinal fluid (CSF) examinations revealed inflammatory changes in 18 patients. However, the SARS-CoV-2 virus in the CSF was discovered in 2 patients. In 2 patients, anti-SARS-CoV-2 antibodies were demonstrated in the CSF. Following treatment, 13 patients were able to walk. CONCLUSIONS: A variety of COVID-19-related spinal cord manifestations, such as acute transverse myelitis, acute necrotizing myelitis, SARS-CoV-2 myelitis, acute disseminated encephalomyelitis, neuromyelitis optica spectrum disorder, hypoxic myelopathy, MOG antibody-associated myelitis, spinal cord infarction, and spinal epidural abscess, have been reported. The possible mechanisms of this involvement being direct invasion, cytokine storm, coagulopathy, and an autoimmune response. However, response to treatment has been generally unsatisfactory, with many patients having residual weakness necessitating long-term rehabilitation.

Acute Inflammatory Cns Diseases Following Vaccination against Sars-Cov-2

Background Vaccination is a recognised trigger of ADEM and approximately 50% paediatric cases have antibodies to MOG. The SARS-CoV-2 mass vaccination programme could therefore trigger cases of MOGAD. Neuromyelitis optica (NMO) is an autoimmune inflammatory condition of the CNS associ- ated with antibodies to AQP4. Method Ten patients (ages 22 - 65 years) with antibodies to MOG or AQP4 were referred to the NHS England NMO service having developed acute onset CNS inflammation within 8 weeks of vaccination. Results Eight patients had MOGAD, seven of whom received the AstraZeneca vaccine (AZV) and one the Pfizer vaccine (PV). Only the post-PV MOGAD patient presented with typical adult-onset phenotype of isolated ON. All post-AZV MOGAD patients presented atypically;85.7% had LETM and 71.4% had intrac- erebral lesions, resembling ADEM more commonly seen in paediatric MOGAD. The atypical presentation supports a causative role of AZV, but the role of PV is less convincing. Two patients had AQP4-NMOSD with typical demographic features. Both received AZV. Less typically, one young adult presented with LETM rather than characteristic young adult ON, the other had a silent short segment myelitis, which is rarely seen in AQP4-NMOSD. Both patients achieved good outcomes. Conclusion We discuss the potential causation and pathophysiological mechanisms.

Brain and Central Nervous System Infections: Viruses

Several viruses are neurotropic, resulting in a multitude of clinical presentations, including acute or chronic meningitis, encephalitis, myelitis, polyradiculitis, and peripheral neuropathy. All segments of the nervous system, central or peripheral, can be involved in viral infections. Viruses can directly affect the nervous system, such as in meningitis and encephalitis, or indirectly (parainfectious or postinfectious) from inflammatory or immunologic reactions, such as in Guillain-Barré syndrome (GBS) or acute disseminated encephalomyelitis (ADEM). © 2022 Elsevier Inc. All rights reserved.

A Case of Transverse Myelitis After Moderna Severe Acute Respiratory Syndrome Coronavirus Vaccination.

Transverse myelitis (TM) is an inflammatory syndrome of the spinal cord that presents with acute-to-subacute neurological deficits. The differential for TM is broad and includes demyelinating, infectious, neoplastic and paraneoplastic, autoimmune, and metabolic/toxic etiologies. With the novel severe acute respiratory syndrome coronavirus pandemic, more commonly referred to as the coronavirus infectious disease of 2019 (COVID-19), there have been increasing reports of neurological complications. In this case report, we describe a novel case of longitudinally-extensive TM associated with the Moderna vaccination.

Neuro-Ophthalmic Complications of COVID-19 Infection and Vaccination.

The COVID-19 pandemic has led to the identification of new disease phenotypes associated with infection by the SARS-CoV-2 virus. This includes multiple neuro-ophthalmological sequelae, which have been associated with COVID-19 infection and administration of COVID-19 vaccines. Some of these associations have a plausible pathophysiological link to the infection or vaccination but true causation has yet to be established. We review the literature for associations reported between COVID-19 infection or vaccination and neuro-ophthalmic sequelae and review the potential pathophysiological processes that may underlie these associations.

An unusually fulminant case of encephalomyelitis in an 80 year old

Background: There have been reports of demyelinating syndromes in association with COVID-19 and to a much lesser extent COVID 19 vaccines. The association between demyelination and vaccines, in general, remains controversial. We review a presentation of fulminant demyelination, and discuss antecedent COVID-19 vaccination, the formulation of a broader differential diagnosis and ultimately the pathologic diagnosis. Case presentation: An 80-year-old woman presented with seizure, encephalopathy, quadriparesis and ultimately expired. She received a SARS-CoV-2 vaccine one day prior. Imaging revealed contrast enhancing cerebral lesions, longitudinally extensive transverse myelitis. CSF was markedly inflammatory. Pathologic examination of the CNS lesions revealed demyelination and inflammation beyond white matter, not restricted to a perivenular distribution. Conclusion(s): This case depicts a seemingly fulminant course of a diffuse demyelinating syndrome characterized clinicopathologically as Marburg's variant of multiple sclerosis. There are several unique aspects of this case including the extremely rapid course, the unusual evolution of CSF abnormalities, with hypoglycorrhachia and markedly elevated protein. The proximity to vaccination is a pertinent association to document, though we cannot unequivocally prove causation.Copyright © 2022 The Authors

Autoimmune spinal cord lesions associated with novel coronavirus infection.

Spinal cord affection, according to various sources, is a common complication of a new coronavirus infection. The article describes various variants of spinal cord pathology in COVID-19, their potential mechanisms of development, approaches to treatment and outcomes of the disease. Three patients who were observed at the Research Center of Neurology and represent the most interesting cases of classic transverse myelitis, myelitis with predominant involvement of the lateral and posterior cords, and longitudinal widespread myelitis associated with antibodies to myelin oligodendrocyte glycoprotein (MOG) are considered in detail. These clinical observations demonstrate the importance of early diagnosis and selection of adequate therapy for a favorable outcome of the disease.Copyright © 2022 Ima-Press Publishing House. All rights reserved.