Neurologic manifestations associated with COVID-19: a multicentre registry.

OBJECTIVES: To provide an overview of the spectrum, characteristics and outcomes of neurologic manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We conducted a single-centre retrospective study during the French coronavirus disease 2019 (COVID-19) epidemic in March-April 2020. All COVID-19 patients with de novo neurologic manifestations were eligible. RESULTS: We included 222 COVID-19 patients with neurologic manifestations from 46 centres in France. Median (interquartile range, IQR) age was 65 (53-72) years and 136 patients (61.3%) were male. COVID-19 was severe or critical in 102 patients (45.2%). The most common neurologic diseases were COVID-19-associated encephalopathy (67/222, 30.2%), acute ischaemic cerebrovascular syndrome (57/222, 25.7%), encephalitis (21/222, 9.5%) and Guillain-Barré syndrome (15/222, 6.8%). Neurologic manifestations appeared after the 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 ischaemic cerebrovascular syndrome and 18 (15-28) days in Guillain-Barré syndrome. Brain imaging was performed in 192 patients (86.5%), including 157 magnetic resonance imaging (70.7%). Among patients with acute ischaemic cerebrovascular syndrome, 13 (22.8%) of 57 had multiterritory ischaemic strokes, with large vessel thrombosis in 16 (28.1%) of 57. Brain magnetic resonance imaging of encephalitis patients showed heterogeneous acute nonvascular lesions in 14 (66.7%) of 21. Cerebrospinal fluid of 97 patients (43.7%) was analysed, with pleocytosis found in 18 patients (18.6%) and a positive SARS-CoV-2 PCR result in two patients with encephalitis. The median (IQR) follow-up was 24 (17-34) days with a high short-term mortality rate (28/222, 12.6%). CONCLUSIONS: Clinical spectrum and outcomes of neurologic manifestations associated with SARS-CoV-2 infection were broad and heterogeneous, suggesting different underlying pathogenic processes.

Somatic symptom disorder in patients with post-COVID-19 neurological symptoms: A preliminary report from the somatic study (Somatic Symptom Disorder Triggered by COVID-19)

Objectives: To assess the diagnosis of somatic symptom disorder (SSD) in patients with unexplained neurological symptoms occurring after SARS-CoV-2 infection, also referred to as long COVID. Design: Single-centre observational study. Participants: Adult patients experiencing unexplained long-lasting neurological symptoms after mild COVID. Of the 58 consecutive patients referred in our centre, 50 were included. Intervention: Patients were contacted for a standardised psychometric evaluation by phone, followed by a self- survey. Main outcome: Positive diagnosis of SSD according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5). Results: Although the patients did not meet the DSM-5 criteria for a functional neurological symptom disorder specifically, SSD diagnosis based on DSM-5 criteria was positive in 32 (64%) patients. In the remaining 18 patients, SSD was considered possible given the high score on diagnostic scales. Physical examination were normal for all. Brain MRI showed unspecific minor white matter hyperintensities in 8/46 patients. Neuropsychological assessment showed exclusively mild impairment of attention in 14 out of 15 tested patients, in discrepancy with their major subjective complaint. Forty-five (90%) patients met criteria for Chronic Fatigue Syndrome. Seventeen (32%) patients were screened positive for mood-anxiety disorders, 19 (38%) had a history of prior SSD and 27 (54%) reported past trauma. Additional self- survey highlighted post-traumatic stress disorder in 12/43 (28%), high levels of alexithymia traits and perfectionism. Long-lasting symptoms had a major impact with a high rate of insomnia (29/43, 67%), psychiatric follow-up (28/50, 56%) and work or pay loss (25/50, 50%). Conclusion: A majority of patients with unexplained long-lasting neurological symptoms after mild COVID met diagnostic criteria for SSD and may require specific management. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Somatic symptom disorder in patients with post-COVID-19 neurological symptoms: a preliminary report from the somatic study (Somatic Symptom Disorder Triggered by COVID-19).

OBJECTIVES: To assess the diagnosis of somatic symptom disorder (SSD) in patients with unexplained neurological symptoms occurring after SARS-CoV-2 infection, also referred to as long COVID. DESIGN: Single-centre observational study. PARTICIPANTS: Adult patients experiencing unexplained long-lasting neurological symptoms after mild COVID. Of the 58 consecutive patients referred in our centre, 50 were included. INTERVENTION: Patients were contacted for a standardised psychometric evaluation by phone, followed by a self-survey. MAIN OUTCOME: Positive diagnosis of SSD according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5). RESULTS: Although the patients did not meet the DSM-5 criteria for a functional neurological symptom disorder specifically, SSD diagnosis based on DSM-5 criteria was positive in 32 (64%) patients. In the remaining 18 patients, SSD was considered possible given the high score on diagnostic scales. Physical examination were normal for all. Brain MRI showed unspecific minor white matter hyperintensities in 8/46 patients. Neuropsychological assessment showed exclusively mild impairment of attention in 14 out of 15 tested patients, in discrepancy with their major subjective complaint. Forty-five (90%) patients met criteria for Chronic Fatigue Syndrome. Seventeen (32%) patients were screened positive for mood-anxiety disorders, 19 (38%) had a history of prior SSD and 27 (54%) reported past trauma. Additional self-survey highlighted post-traumatic stress disorder in 12/43 (28%), high levels of alexithymia traits and perfectionism. Long-lasting symptoms had a major impact with a high rate of insomnia (29/43, 67%), psychiatric follow-up (28/50, 56%) and work or pay loss (25/50, 50%). CONCLUSION: A majority of patients with unexplained long-lasting neurological symptoms after mild COVID met diagnostic criteria for SSD and may require specific management. TRIAL REGISTRATION NUMBER: NCT04889313.

Clinical Outcome of Acute Ischemic Strokes in Patients with COVID-19.

INTRODUCTION: Acute ischemic stroke (AIS) and thrombotic events (TEs) were reported in patients with COVID-19. Clinical outcome of AIS in the course of COVID-19 remains unknown. We compared early clinical outcome and mortality of COVID-positive (+) patients admitted for AIS with COVID-negative (-) ones. We hypothesized that COVID+ patients would have poorer clinical outcomes and present a higher rate of TEs and mortality compared with COVID- ones. METHODS: In this multicentric observational retrospective study, we enrolled patients over 18 years old admitted for AIS in 3 stroke units of the Parisian region during lockdown from March 17, 2020, to May 2, 2020. COVID-19 status as well as demographic, clinical, biological, and imaging data was collected retrospectively from medical records. Poor outcome was defined as modified Rankin score (mRS) 3-6 (3-6) at discharge. We also compared TE frequency and mortality rate through a composite criterion in both groups. RESULTS: Two hundred and sixteen patients were enrolled; mean age was 68 years old, and 63% were male. Forty patients were CO-VID+ (18.5%) and 176 were COVID-. Obesity was statistically more frequent in the COVID+ group (36 vs. 13% p < 0.01). The percentage of patients with mRS (3-6) at discharge was higher in the COVID+ group compared with the COVID- group (60 vs. 41%, p = 0.034). The main predictor of presenting a mRS (3-6) at discharge was high NIHSS score at admission (OR, CI 95%: 1.325, 1.22-1.43). Mortality rate was higher in the COVID+ group (12 vs. 3.4%, p = 0.033) as well as TE frequency (15 vs. 2.8%, p < 0.01). CONCLUSION: In this study, patients with AIS infected by SARS-CoV-2 showed a poorer early outcome than COVID- ones. However, when compared to other factors, COVID-19 was not a significant predictor of poor outcome. Vascular morbidity and mortality rates were significantly higher in the COVID+ group compared with the COVID- group.

Manifestations neurologiques associées au COVID-19

Résumé Les manifestations neurologiques associées au COVID-19 sont fréquentes et variées. Alors que des symptômes non spécifiques tels que des céphalées, des vertiges, des douleurs et des myalgies sont décrits dans 2 à 30% des cas, on retrouve des atteintes neurologiques plus sévères chez 8 à 13% des patients hospitalisés. Il s’agit d’atteintes neurologiques centrales ou périphériques, avec au premier plan des encéphalopathies, des accidents vasculaires cérébraux mais également des encéphalites et des syndromes de Guillain-Barré. Les troubles du goût et de l’odorat, assez caractéristiques du COVID-19, touchent quant à eux 34 à 86% des patients. A l’heure actuelle, les mécanismes en cause dans ces atteintes neurologiques sont imparfaitement compris. Les études autopsiques mettent en lumière le possible rôle du sepsis et de l’hypoxie, de l’infection/dysfonction endothéliale, de l’inflammation et d’atteintes immunomédiées. Le rôle pathogène direct du virus sur le parenchyme cérébral reste quant à lui incertain. Introduction: The COVID-19 pandemic highlighted the existence of neurological manifestations associated with SARS-CoV-2 infection. The aim of this review was to summarize the prevalence and the range of neurological manifestations associated with COVID-19, and to expose the main hypotheses about the pathogenic pathways based on available neuropathological studies. Methods: Articles have been identified by searches of PubMed and Google scholar up to November 15, 2020, using a combination of COVID-19 and neurology search terms and adding relevant references in the articles. Results: Nonspecific neurological symptoms such as headache, dizziness, pain and myalgia, have been reported in 2 to 30% of COVID-19 hospitalized patients. More severe neurological diseases affected 8 to 13% of COVID-19 hospitalized patients including various central or peripheral manifestations. Among central nervous system involvement, encephalopathy and cerebrovascular disease – especially ischemic stroke - were the most frequent, followed by encephalitis, myelitis, meningitis, and posterior reversible encephalopathy syndrome. Guillain-Barré syndrome and variants were the most common form of peripheral nervous system involvement, followed by critical illness neuromyopathy, plexopathy, polyneuropathy, oculomotor neuropathy, and Tapia syndrome. Encephalopathy, ischemic stroke and encephalitis occurred 6 to 12 days in median after the first signs of COVID-19, while Guillain-Barré syndrome occured later, at 15 to 23 days in median. Taste and smell disorders affected 34 to 86% of patients and occurred 3.5 days in median after the onset of infection. Pathogenic pathways of nervous system involvement in COVID-19 remain poorly understood. Neuropathological studies highlighted the possible role of sepsis and hypoxia, endothelial infection / dysfunction, inflammation and immune-mediated disease. While the presence of SARS-CoV-2 in the brain was confirmed in some COVID-19 patients, there were no definite evidence to support its direct pathogenicity on brain parenchyma. Conclusion: Neurological involvement in COVID-19 is frequent and include various manifestations. Most of them are encephalopathies and strokes, probably linked to viral sepsis, hypoxia and/or endotheliitis. A wide range of post infectious disorders were also reported, such as encephalitis and Guillain-Barré syndrome. To date no studies demonstrated definite evidence of a direct pathogenicity of SARS-CoV-2 on brain.