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.

Development of Acute Transverse Myelitis following COVID-19 Infection: A Review on the Potential Pathways.

BACKGROUND: Acute transverse myelitis (ATM) is a rare neurological disorder in adults characterized by localized inflammation of gray and white matter in one or more contiguous spinal cord segments in the absence of a compressive injury. Several reports have connected the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the pathophysiology of ATM. SUMMARY: Direct invasion of the spinal cord, cytokine storm, or an autoimmune response are the possible pathways by which the SARS-CoV-2 virus can affect the spinal cord and lead to ATM. Direct invasion is facilitated by the presence of angiotensin-converting enzyme 2 (ACE2) receptors on the membranes of the spinal cord neurons. Cytokine storm syndrome could be derived from elevated levels of several immunological factors following severe involvement with coronavirus disease 2019 (COVID-19). Finally, autoimmune responses can cause post-infectious ATM through several hypothesized processes, including molecular mimicry, epitope spreading, bystander activation, and polyclonal B-cell activation. KEY MESSAGES: COVID-19-induced ATM is mostly a longitudinally-extensive ATM (LEATM), in which more spinal cord segments are damaged, which results in a worse sequel compared to short-segment ATM. Therefore, it is suggested that COVID-19 patients, particularly severe cases, be followed up for a probable incidence of ATM, even long after recovery from the disease and elimination of the virus from the host, because an early diagnosis and effective therapy may stop the spread of inflammation to adjacent segments.

Anti-myelin Oligodendrocyte Glycoprotein Antibody-positive Myelitis after Coronavirus Disease 2019.

We herein report a case of anti-myelin oligodendrocyte glycoprotein (MOG) antibody-related myelitis caused by coronavirus disease (COVID-19) infection in 2021. A 22-year-old man with no history of any related illness contracted COVID-19. Eight days later, he developed bladder problems, paraplegia and sensory disturbances. Cervical spinal cord magnetic resonance imaging revealed extensive hyperintensity at T2 and spinal cord lesions extending from C4 to Th1. The patient was diagnosed with transverse myelitis and started on intravenous methylprednisolone, plasma exchange and intravenous immunoglobulin therapy. The symptoms improved only after intravenous methylprednisolone therapy. Anti-MOG antibodies were found in his serum and cerebrospinal fluid during routine screening. As this observation is unusual and could cause serious health problems, we wonder if COVID-19 triggered this autoimmune response.

Acute Inflammatory Diseases of the Central Nervous System After SARS-CoV-2 Vaccination.

BACKGROUND AND OBJECTIVES: Acute inflammatory CNS diseases include neuromyelitis optica spectrum disorders (NMOSDs) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Both MOGAD and acute disseminated encephalomyelitis (ADEM) have been reported after vaccination. Consequently, the mass SARS-CoV-2 vaccination program could result in increased rates of these conditions. We described the features of patients presenting with new acute CNS demyelination resembling NMOSDs or MOGAD within 8 weeks of SARS-CoV-2 vaccination. METHODS: The study included a prospective case series of patients referred to highly specialized NMOSD services in the UK from the introduction of SARS-CoV-2 vaccination program up to May 2022. Twenty-five patients presented with new optic neuritis (ON) and/or transverse myelitis (TM) ± other CNS inflammation within 8 weeks of vaccination with either AstraZeneca (ChAdOx1S) or Pfizer (BNT162b2) vaccines. Their clinical records and paraclinical investigations including MRI scans were reviewed. Serologic testing for antibodies to myelin oligodendrocyte glycoprotein (MOG) and aquaporin 4 (AQP4) was performed using live cell-based assays. Patients' outcomes were graded good, moderate, or poor based on the last clinical assessment. RESULTS: Of 25 patients identified (median age 38 years, 14 female), 12 (48%) had MOG antibodies (MOGIgG+), 2 (8%) had aquaporin 4 antibodies (AQP4IgG+), and 11 (44%) had neither. Twelve of 14 (86%) antibody-positive patients received the ChAdOx1S vaccine. MOGIgG+ patients presented most commonly with TM (10/12, 83%), frequently in combination with ADEM-like brain/brainstem lesions (6/12, 50%). Transverse myelitis was longitudinally extensive in 7 of the 10 patients. A peak in new MOGAD cases in Spring 2021 was attributable to postvaccine cases. Both AQP4IgG+ patients presented with brain lesions and TM. Four of 6 (67%) seronegative ChAdOx1S recipients experienced longitudinally extensive TM (LETM) compared with 1 of 5 (20%) of the BNT162b2 group, and facial nerve inflammation was reported only in ChAdOx1S recipients (2/5, 40%). Guillain-Barre syndrome was confirmed in 1 seronegative ChAdOx1S recipient and suspected in another. DISCUSSION: ChAdOx1S was associated with 12/14 antibody-positive cases, the majority MOGAD. MOGAD patients presented atypically, only 2 with isolated ON (1 after BNT162b2 vaccine) but with frequent ADEM-like brain lesions and LETM. Within the seronegative group, phenotypic differences were observed between ChAdOx1S and BNT162b2 recipients. These observations might support a causative role of the ChAdOx1S vaccine in inflammatory CNS disease and particularly MOGAD. Further study of this cohort could provide insights into vaccine-associated immunopathology.

Transverse myelitis following COVID-19: Insights from a multi-center study and systematic literature review.

INTRODUCTION: We aimed to provide insights into transverse myelitis (TM) following COVID-19 by analyzing cases treated at tertiary care neurology centers and a systemic review of the literature. METHODS: The retrospective observational multi-center study was conducted at the four university neurology departments in Croatia, Slovenia, Serbia, and Austria. We searched for acute myelitis cases that occurred during or after COVID-19. A systemic review of the literature on COVID-19 and transverse myelitis was performed. RESULTS: We identified 76 persons with TM associated with COVID-19, 13 from the multi-center study and 63 from the literature review. Most of the participants (55.6%) had an intermediate latency, 25.4% had short and 19% long latency from COVID-19 symptoms to TM. The clinical presentation consisted of the typical TM signs. More than half of the participants had inflammatory changes in the CSF, with rare patients having intrathecal OCB synthesis and positive serology for anti-MOG or anti-AQP4 antibodies. Persons with autonomic symptoms and CSF pleocytosis were significantly more common to have an intermediate latency of 8 to 21 days from COVID-19 to TM (p = 0.005 and p = 0.003; respectively). According to logistic regression analysis, only participants with lesions evident on spinal cord MRI compared to normal spinal cord MRI had reduced risks for poor recovery. >80% of participants were treated with a combination of corticosteroids and intravenous immunoglobulins or plasma exchange with 73% having incomplete recovery. CONCLUSION: Our study further characterizes clinical, laboratory, and MRI features, as well as treatment of TM associated with COVID-19.

Acute cerebellitis, transverse myelitis and polyradiculoneuritis related to post-COVID-19 infection.

CONTEXT: Guillain-Barré syndrome (GBS), acute cerebellitis and transverse myelitis are rare complications of COVID-19 infection separately. The combination of these three, however, has not yet been reported. FINDINGS: We present an atypical case (42-year-old man) that developed acute ascending flaccid paraparesis, ataxia and urinary retention two weeks after COVID-19 infection. Neurological examination revealed distal and proximal weakness (4/5) on lower extremities, decreased tendon reflexes, sixth cranial nerve palsy and dysmetria without sensory disturbance. His cranial MRI showed cerebellitis whereas the spinal MRI showed transverse myelitis at the T11/12 level. Albuminocytologic dissociation was present in the cerebrospinal fluid. The nerve conduction study was concordant with early findings of GBS. He recovered well after corticosteroid treatment without needing any immunotherapy. On day seven of hospitalization, the modified Rankin Scale score was 0. CONCLUSION: COVID-19 infection may present with a combination of neurological manifestations such as cerebellitis, transverse myelitis and GBS. This patient presented significant functional recovery after treatment with corticosteroid without immunotherapy.

Transverse Myelitis Following SARS-CoV-2 Vaccination: A Pharmacoepidemiological Study in the World Health Organization's Database.

BACKGROUND: Transverse myelitis (TM) has recently been associated by health authorities with Ad26.COV2.S (Janssen/Johnson & Johnson), one of the 5 US Food and Drug Administration (FDA) or European Medicines Agency (EMA) labeled severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. It is unknown whether a similar association exists for the other FDA or EMA labeled SARS-CoV-2 vaccines (BNT162b2 [Pfizer/BioNTech], mRNA-1273 [Moderna], ChAdOx1nCov-19 [Oxford-AstraZeneca], and NVX-CoV2373 [Novavax]). This study aimed to evaluate the association between SARS-CoV-2 vaccine class and TM. METHODS: This observational, cross-sectional, pharmacovigilance cohort study examined individual case safety reports from VigiBase, the World Health Organization's pharmacovigilance database. We first conducted a disproportionality analysis with the information component (IC) using the reports of TM that occurred within 28 days following exposure to the FDA or EMA labeled SARS-CoV-2 vaccines, from December 1, 2020 (first adverse event related to a SARS-CoV-2 vaccine) to March 27, 2022. Second, we analyzed the clinical features of SARS-CoV-2 vaccine-associated TM cases reported in VigiBase. RESULTS: TM was significantly associated both with the messenger ribonucleic acid (mRNA)-based (n = 364; IC025  = 0.62) and vector-based (n = 136; IC025  = 0.52) SARS-CoV-2 vaccines that are authorized by the FDA or the EMA. CONCLUSIONS: Findings from this observational, cross-sectional pharmacovigilance study showed that mRNA-based and vector-based FDA/EMA labeled SARS-CoV-2 vaccines can be associated with TM. However, because TM remains a rare event, with a previously reported rate of 0.28 cases per 1 million vaccine doses, the risk-benefit ratio in favor of vaccination against SARS-CoV-2 virus remains unchallenged. Rather, this study suggests that clinicians should consider the diagnosis of TM in patients presenting with early signs of spinal cord dysfunction after SARS-CoV-2 vaccination. ANN NEUROL 2022;92:1080-1089.

A COVID Constellation: A Case of Transverse Myelitis and Acquired von Willebrand Syndrome.

The coronavirus disease 2019 (COVID-19) pandemic revealed a myriad of postinfectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequelae, many of which remain poorly understood. We describe a rare presentation of a patient developing 2 simultaneous COVID-19 sequelae: transverse myelitis and acquired von Willebrand syndrome (AVWS). There have been numerous published case reports of patients developing transverse myelitis after a diagnosis of COVID-19. However, none have described AVWS as an observed complication from SARS-CoV-2 infection. To our knowledge, this case report is the first to describe AVWS as a result of COVID-19 infection, suggesting that patients with a prior diagnosis of COVID-19 are susceptible to developing this rare bleeding disorder.

Severe disease exacerbation after mRNA COVID-19 vaccination unmasks suspected multiple sclerosis as neuromyelitis optica spectrum disorder: a case report.

BACKGROUND: Since the beginning of the COVID-19 pandemic and development of new vaccines, the issue of post-vaccination exacerbation or manifestation of demyelinating central nervous system (CNS) disorders has gained increasing attention. CASE PRESENTATION: We present a case of a 68-year-old woman previously diagnosed with multiple sclerosis (MS) since the 1980s who suffered a rapidly progressive severe sensorimotor paraparesis with loss of bladder and bowel control due to an acute longitudinal extensive transverse myelitis (LETM) after immunization with the mRNA Pfizer-BioNTech COVID-19 vaccine. Detection of Aquaporin-4-antibodies (AQP4) in both serum and CSF led to diagnosis of AQP4-antibody positive neuromyelitis optica spectrum disorder (NMOSD). Treatment with intravenous corticosteroids and plasmapheresis led to a slight improvement of the patient's symptoms. CONCLUSIONS: Pathogenic mechanisms of post-vaccination occurrence of NMOSD are still unknown. However, cases like this should make aware of rare neurological disorders manifesting after vaccination and potentially contribute to improvement of management of vaccinating patients with inflammatory CNS disorders in the future. So far two cases of AQP4-antibody positive NMOSD have been reported in association with viral vector COVID-19 vaccines. To our knowledge, we report the first case of AQP4-antibody positive NMOSD after immunization with an mRNA COVID-19-vaccine.

Early SARS-CoV-2-associated acute transverse myelitis: A case for neurotropism?

There are increasing reports of immune-mediated and para-infectious syndromes beyond the well-known respiratory manifestations of severe-acute-respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the spectrum of severe neurological sequelae of SARS-CoV-2 remains undefined. We present the case of a 66-year-old female with rapidly progressive lower limb neurology 3 days post SARS-CoV-2 infection. Clinical and radiological findings were in keeping with transverse myelitis and treatment success was achieved with methylprednisolone and remdesivir. This report will discuss the associations between SARS-CoV-2 and acute transverse myelitis. We believe this is one of few described cases of early SARS-CoV-2-associated transverse myelitis secondary to neurotropism and the first successfully treated with the inclusion of remdesivir in the therapeutic regimen.

COVID-19 vaccine associated transverse myelitis-Evusheld as an option when vaccination is not recommended due to severe adverse events.

Individuals who experience severe COVID-19-vaccine-related adverse reactions such as transverse myelitis may be precluded from receiving further vaccination to protect from SARS-CoV-2 infection. Although the mechanism of autoimmune spinal cord inflammation resulting in transverse myelitis is unclear, it may be safe to administer antibody therapy for preventing COVID-19. Recently, Evusheld, tixagevimab with cilgavimab, two spike-protein directed monoclonal antibodies were authorized by the U.S. FDA and U.K. MHRA for administration to individuals when vaccination is not recommended. We report the safe administration of Evusheld to a patient who experienced transverse myelitis 11 months previously as a result of receiving the Moderna mRNA vaccine. This patient has experienced no adverse events to Evusheld. Additional experience and data collection are warranted to determine the safety of this prophylactic therapy.

Acute demyelinating encephalomyelitis and transverse myelitis in a child with COVID-19.

BACKGROUND: Corona virus disease 2019 (COVID-19) includes a wide range of diseases with varying pathophysiology in children and adults. Although the disease mainly affects the respiratory tract, neurological involvement is also reported in the literature. The most common neurological complaints due to COVID-19 are headache, dizziness and anosmia. Acute necrotizing myelitis, acute demyelinating encephalomyelitis (ADEM), acute axonal neuropathy, acute transverse myelitis, and Guillian-Barre syndrome have been reported as neurological dysfunctions associated with COVID-19. CASE: A ten-year-old male patient presented with complaints of fever, headache and generalized muscle pain. The patient developed inability to walk and significant muscle weakness during the disease course, and he was diagnosed with ADEM and transverse myelitis on magnetic resonance imaging (MRI). As the etiological agent, COVID-19 was detected in both the respiratory panel sample and the cerebrospinal fluid (CSF) sample by the polymerase chain reaction (PCR) technique. Pulse steroid, IVIG, and plasmapheresis treatment were administered. He started to stand with support during follow-up. CONCLUSION: We presented a case of COVID-19 related ADEM and transverse myelitis who responded to pulse steroid, IVIG, and plasmapheresis.

Longitudinally extensive transverse myelitis after Covid-19 vaccination: case report and review of literature.

Mass vaccination has been the main policy to overcome the Covid-19 pandemic. Several vaccines have been approved by the World Health Organization. With growing vaccination, safety concerns and adverse events that need prompt evaluation are also emerging. Herein, we report a case of a healthy woman with longitudinally extensive transverse myelitis after vaccination with the AstraZeneca vaccine. The patient was successfully treated after ruling out all the possible causes.

Acute transverse myelitis progressing to permanent quadriplegia following COVID-19 infection.

As of January 2022, there have been over 350 million confirmed cases of COVID-19 in the world. The most common symptoms in those infected are fever, cough, malaise, and myalgia, however pulmonary, hematologic, gastrointestinal, renal, and neurologic complications have also been reported. Acute transverse myelitis (ATM) is an uncommon neurological syndrome characterized by acute or subacute spinal cord dysfunction that can lead to paresthesias, sensory and autonomic impairment, and even paralysis. Etiologies are often unclear; however, potential causes include infection, neoplastic, drug or toxin induced, autoimmune, and acquired. Treatment for ATM primarily consists of steroids and plasmapheresis, which often reverses any neurologic symptoms. ATM has rarely been reported as a complication of COVID-19 infections. A 43-year-old female presented to the emergency department for evaluation of progressive numbness and tingling in her legs ten days after developing upper respiratory symptoms from a COVID-19 infection. Physical examination and magnetic resonance imaging confirmed a diagnosis of ATM. During her hospital course, she experienced rapid progression of her paresthesias and developed complete loss of motor function in her upper and lower extremities. Within 48 hours after emergency department arrival, she required intubation due to worsening diaphragmatic and chest wall paralysis. Her treatment included a long-term steroid regimen and plasmapheresis, and unfortunately, she did not have any neurologic recovery. We present a very rare case of ATM progressing to complete quadriplegia following COVID-19 infection.

[Acute disseminated encephalomyelitis and myelitis associated with new coronavirus infection COVID-19. Case report].

Acute disseminated encephalomyelitis (AEM) and acute transverse myelitis (OPM) are autoimmune demyelinating diseases of the central nervous system. Two clinical observations of AEM and OPM developed after suffering acute coronavirus infection (SARS-CoV-2) are presented. Differential diagnosis was carried out with multiple sclerosis, encephalitis of an infectious nature, compressive myelopathy, and opticomyelitis. Both observations show an almost complete recovery of lost functions. The pathogenetic mechanisms of the development of AEM and OPM in patients with coronavirus infection are discussed. The onset of central nervous system dysimmune lesion in the context of coronavirus infection makes it necessary to monitor the clinical situation with the involvement of a neurologist for timely diagnosis and determination of therapeutic tactics that can reduce the degree of disability of patients.

A possible Guillain-Barré syndrome/transverse myelitis overlap syndrome after recent COVID-19.

Neurological manifestations are common in SARS-CoV-2 infection, including life-threatening acute muscle weakness, due to neuromuscular disorders such as acute transverse myelitis (TM) and Guillain-Barré syndrome (GBS). These syndromes can rarely coexist and present as an overlap syndrome. Here, we report a patient who developed acute symmetrical proximal lower limb weakness 5 days after diagnosis of COVID-19. GBS was diagnosed due to the presence of motor signs, albumin-cytological dissociation in cerebrospinal fluid examination and axonal damage according to nerve condition tests. However, abnormal areas on MRI of the thoracic spine and lack of improvement with intravenous immunoglobulin supported a diagnosis of TM. Therefore, a possible overlap between GBS and TM was established. To our knowledge, this is the third case report of GBS/TM overlap syndrome after COVID-19. The patient's full and rapid recovery with intravenous corticosteroids and plasmapheresis supports our diagnosis.