Global uncertainty in the diagnosis of neurological complications of SARS-CoV-2 infection by both neurologists and non-neurologists: An international inter-observer variability study.

INTRODUCTION: Uniform case definitions are required to ensure harmonised reporting of neurological syndromes associated with SARS-CoV-2. Moreover, it is unclear how clinicians perceive the relative importance of SARS-CoV-2 in neurological syndromes, which risks under- or over-reporting. METHODS: We invited clinicians through global networks, including the World Federation of Neurology, to assess ten anonymised vignettes of SARS-CoV-2 neurological syndromes. Using standardised case definitions, clinicians assigned a diagnosis and ranked association with SARS-CoV-2. We compared diagnostic accuracy and assigned association ranks between different settings and specialties and calculated inter-rater agreement for case definitions as "poor" (κ ≤ 0.4), "moderate" or "good" (κ > 0.6). RESULTS: 1265 diagnoses were assigned by 146 participants from 45 countries on six continents. The highest correct proportion were cerebral venous sinus thrombosis (CVST, 95.8%), Guillain-Barré syndrome (GBS, 92.4%) and headache (91.6%) and the lowest encephalitis (72.8%), psychosis (53.8%) and encephalopathy (43.2%). Diagnostic accuracy was similar between neurologists and non-neurologists (median score 8 vs. 7/10, p = 0.1). Good inter-rater agreement was observed for five diagnoses: cranial neuropathy, headache, myelitis, CVST, and GBS and poor agreement for encephalopathy. In 13% of vignettes, clinicians incorrectly assigned lowest association ranks, regardless of setting and specialty. CONCLUSION: The case definitions can help with reporting of neurological complications of SARS-CoV-2, also in settings with few neurologists. However, encephalopathy, encephalitis, and psychosis were often misdiagnosed, and clinicians underestimated the association with SARS-CoV-2. Future work should refine the case definitions and provide training if global reporting of neurological syndromes associated with SARS-CoV-2 is to be robust.

Concurrence of Guillain-Barré syndrome and primary biliary cholangitis not related to SARS-CoV-2: Case report. / Concurrencia de síndrome de Guillain-Barré y colangitis biliar primaria no vinculado a SARS-CoV-2: reporte de caso.

Introduction: Guillain-Barré syndrome is a polyradiculoneuropathy of autoimmune origin, considered the most frequent cause of acute flaccid paralysis. Various associations of Guillain-Barré syndrome with other non-neurological autoimmune diseases have been reported, some of them extremely rare, such as that which occurs with primary biliary cholangitis, a chronic disease of autoimmune etiology whose diagnosis is also supported by the clinical picture. , in the alteration of liver enzymes and the presence of anti-mitochondrial antibodies. Clinical case: A 38-year-old male patient, with no history of previous comorbidities, who, after presenting with diarrheal disease two weeks prior, developed subacute onset ascending weakness associated with paresthesias in four extremities that progressed to quadriplegia and respiratory distress. Cerebrospinal fluid cytochemistry was performed, which showed albuminocytological dissociation and electromyography, which showed findings compatible with acute motor axonal neuropathy, for which he received treatment with intravenous immunoglobulin at 0.4g/kg/day, achieving improvement in the neurological condition. Since admission and during hospitalization, he presented persistent changes in liver enzymes which followed a cholestatic pattern, in addition to mild abdominal pain and generalized itching, for which he was evaluated by gastroenterology, who requested anti-mitochondrial antibodies that were positive. Concluding in the diagnosis of primary biliary cholangitis. Conclusion: The present case shows an extremely rare association of two autoimmune diseases Guillain-Barré syndrome and primary biliary cholangitis, so much so that it represents the first case reported, not linked to SARS-CoV-2.

Introducción: El síndrome de Guillain-Barré es una polirradiculoneuropatia de origen autoinmune, considerada la causa más frecuente de parálisis flácida aguda. Se han reportado diversas asociaciones del síndrome de Guillain-Barré con otras enfermedades autoinmunes no neurológicas, algunas de ellas extremadamente raras, como la que ocurre con la colangitis biliar primaria, una enfermedad crónica de etiología autoinmune cuyo diagnóstico se sustenta, además del cuadro clínico, en la alteración de las enzimas hepáticas y la presencia de anticuerpos anti-mitocondriales. Caso clínico: Paciente varón de 38 años, sin antecedente de comorbilidades previas, quien luego de presentar enfermedad diarreica dos semanas antes, desarrolló debilidad ascendente de inicio subagudo asociado a parestesias en cuatro extremidades que progresó hasta generar cuadriplejia y dificultad respiratoria. Se le realizó examen citoquímico de líquido cefalorraquídeo que evidenció disociación albumino-citológica y electromiografía que mostró hallazgos compatibles con neuropatía axonal motora aguda. Recibió tratamiento con inmunoglobulina intravenosa a dosis de 0,4 gramos por kilogramo al día, logrando mejoría del cuadro neurológico. Desde su ingreso y durante la hospitalización, presentó alteración persistente de las enzimas hepáticas que seguía un patrón colestásico. Además, se agregó dolor abdominal de leve intensidad y prurito generalizado, por lo cual fue evaluado por gastroenterología, quienes solicitaron anticuerpos anti-mitocondriales que resultaron positivos. Con esta prueba, se comprobó el diagnóstico de colangitis biliar primaria. Conclusión: El presente caso muestra una asociación extremadamente rara de dos enfermedades autoinmunes; síndrome de Guillain-Barré y colangitis biliar primaria, tanto así que representa el primer caso reportado, no vinculado a SARS-CoV-2.

Historical Perspectives on the Neurologic Manifestations of Viral Pandemics.

Neurologic symptoms have been reported in over 30% of hospitalized patients with coronavirus disease 2019 (COVID-19), but the pathogenesis of these symptoms remains under investigation. Here, we place the neurologic complications of COVID-19 within the context of three historical viral pandemics that have been associated with neurologic diseases: (1) the 1918 influenza pandemic, subsequent spread of encephalitis lethargica, and lessons for the study of COVID-19-related neuroinflammation; (2) the controversial link between the 1976 influenza vaccination campaign and Guillain-Barré Syndrome and its implications for the post- and parainfectious complications of COVID-19 and COVID-19 vaccination; and (3) potential applications of scientific techniques developed in the wake of the human immunodeficiency virus pandemic to the study of postacute sequelae of COVID-19.

Is there a causal nexus between COVID-19 infection, COVID-19 vaccination, and Guillain-Barré syndrome?

Guillain-Barré syndrome (GBS) is an immune-mediated inflammatory polyradiculoneuropathy, which commonly leads to a very high level of neurological disability. Especially, after the global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the causation between GBS and SARS-CoV-2 infection and the coronavirus disease 2019 (COVID-19) vaccination have aroused widespread concern. In the review, we analyzed the impacts of SARS-CoV-2 infection and COVID-19 vaccination on GBS globally, aiming to further understand the characteristics of GBS associated with COVID-19. Based on the electrophysiological data, patients suffering from GBS related to COVID-19 manifested as an acute inflammatory demyelinating polyneuropathy (AIDP). Moreover, we summarized the current findings, which may evidence GBS linking to SARS-CoV-2 infection and COVID-19 vaccination, and discussed the underlying mechanisms whether and how the SARS-CoV-2 virus and COVID-19 vaccination can induce GBS and its variants.

Post COVID-19 Guillain-Barre syndrome presents as sensory dominant neuropathy with reversible conduction failure.

Guillain-Barré syndrome (GBS) has several clinical variants. The sensory presentations of GBS are atypical but well-recognized. We report a patient who presented with predominantly sensory symptoms associated with reversible conduction failure (RCF). RCF is a well-defined neurophysiological abnormality noted mainly in axonal GBS and may be misinterpreted as evidence of demyelination. A 25-year-old woman presented 2 weeks after a coronavirus 2019 infection with acute sensory symptoms, distal allodynia, mild weakness, and mild hyporeflexia in her upper limbs. A nerve conduction study (NCS) showed delayed motor distal latencies, and lumbar puncture confirmed cytoalbuminologic dissociation. After excluding other etiologies, she was diagnosed with GBS, treated with an IV immunoglobulin course, and showed remarkable recovery. Results of a repeat NCS were consistent with RCF and confirmed the presence of axonal GBS. Increased awareness of sensory GBS and RCF is expected to improve the diagnosis and management of atypical GBS presentations.

Concomitant Guillain-Barré Syndrome and COVID-19: A Meta-Analysis of Cases.

Background and Objectives: Recent findings demonstrate that the transmigration of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) to the nervous system implicates severe neurotropic pathologies, including the onset of the rare disease called Guillain-Barré syndrome (GBS) which is characterized by immune-mediated polyneuropathy. This study aimed to identify the predisposing factors and the clinical features of coronavirus disease 2019 (COVID-19)-induced GBS. Materials and Methods: We have performed an analysis of 147 cases. A systematic review of the published research work was performed per the PRISMA statement to obtain individual participant data (IPD) for the meta-analysis. The search was conducted through PubMed, using the combined search terms "Guillain-Barré syndrome" and "COVID-19". All case reports and series in the English language with accessed full text were included in the search. Results: A systematic database search led to the retrieval of 112 peer-reviewed articles published between 1 April 2020, and 8 February 2022. The articles comprised 16 case series and 96 case reports containing IPD for 147 patients. Our findings showed that 77.6% of all cases were 40 years or older. Males comprised most of the cases (65.3%; n = 96). The intensive care unit (ICU) admission was 44.9%, and the need for mechanical ventilation (MV) was 38.1%. The patients presented with hyporeflexia or areflexia (84.4%; n = 124), lower limb strength and sensation impairment (93.2%; n = 138), upper limb strength and sensation impairment (85.7; n = 126), and somatic sensation impairment (72.8%; n = 107). The patients presented with increased cerebral spinal fluid (CSF) protein levels (92%; n = 92) and the presence of CSF albuminocytological dissociation (83.5%; n = 71). The most common variant of GBS observed was acute inflammatory demyelinating polyneuropathy (AIDP). We found that predisposing factors concomitant with COVID-19 and GBS were male gender and older age. Among the cases, patient mortality was 10.9%. Conclusions: A gap of knowledge exists regarding the complete spectrum of clinical characteristics of COVID-19-related GBS. Recent findings suggest that SARS-CoV-2 triggers GBS, as it follows a similar para-infectious pattern as the other viral agents contributing to the onset of GBS.

[COVID-19-associated damage of the peripheral nervous system]. / COVID-19-assotsiirovannye porazheniya perifericheskoi nervnoi sistemy.

Based on the available literature data, the article discusses the prevalence of various forms of damage of the peripheral nervous system in COVID-19 and in the post-COVID period. Information about the clinical features and the course of individual cranial neuropathies, chronic dysimmune neuropathies, Guillain-Barré syndrome, drug-induced neuropathies, fine fiber neuropathy, myasthenia gravis and polyneuropathy of critical conditions was systemized in the context of coronavirus infection. SARS-CoV-2 can trigger various stages of pathogenesis, including neuroimmune ones, which cause long-term consequences of COVID-19, including those associated with the damage of the peripheral nervous system. Awareness of COVID-19-associated pathological conditions will allow assessment of the possible risks of damage of the peripheral nervous system, recognize them at early stages and develop more effective approaches for treatment.

Long-term neurologic outcomes of COVID-19.

The neurologic manifestations of acute COVID-19 are well characterized, but a comprehensive evaluation of postacute neurologic sequelae at 1 year has not been undertaken. Here we use the national healthcare databases of the US Department of Veterans Affairs to build a cohort of 154,068 individuals with COVID-19, 5,638,795 contemporary controls and 5,859,621 historical controls; we use inverse probability weighting to balance the cohorts, and estimate risks and burdens of incident neurologic disorders at 12 months following acute SARS-CoV-2 infection. Our results show that in the postacute phase of COVID-19, there was increased risk of an array of incident neurologic sequelae including ischemic and hemorrhagic stroke, cognition and memory disorders, peripheral nervous system disorders, episodic disorders (for example, migraine and seizures), extrapyramidal and movement disorders, mental health disorders, musculoskeletal disorders, sensory disorders, Guillain-Barré syndrome, and encephalitis or encephalopathy. We estimated that the hazard ratio of any neurologic sequela was 1.42 (95% confidence intervals 1.38, 1.47) and burden 70.69 (95% confidence intervals 63.54, 78.01) per 1,000 persons at 12 months. The risks and burdens were elevated even in people who did not require hospitalization during acute COVID-19. Limitations include a cohort comprising mostly White males. Taken together, our results provide evidence of increased risk of long-term neurologic disorders in people who had COVID-19.

Concomitant Guillain-Barré syndrome and cerebral venous thrombosis complicating a SARS-CoV-2 infection: a case report.

Cerebral venous thrombosis associated to acute inflammatory axonal polyneuropathy during infection with SARS-CoV-2 (coronavirus-2) is unusual. We describe the case of a 66-year-old patient with typical clinical and electrophysiological criteria of acute axonal motor neuropathy, who was positive for SARS-CoV-2. The symptoms started with fever associated with respiratory symptoms, and complicated one week later by headaches, and general weakness. The examination showed bilateral peripheral facial palsy, predominantly proximal tetraparesis, and areflexia with tingling of limbs were found. The whole was concomitant with the diagnosis of an acute polyradiculoneuropathy. Electrophysiologic evaluation confirmed the diagnosis. Cerebrospinal fluid examination showed albuminocytologic dissociation, and brain imaging revealed sigmoid sinus thrombophlebitis. Neurological manifestations improved during treatment with plasma exchange and anticoagulants. Our case draws attention to the occurrence of cerebral venous thrombosis and Guillain-Barré syndrome (GBS) in patients with COVID-19. The neuro-inflammation induced by the systemic immune response to infection, can lead to neurological manifestations. Further studies should be conducted on the full clinical spectrum of patients with COVID-19 with neurological symptoms.

COVID-19 Associated Guillain-Barré Syndrome: A Report of Nine New Cases and a Review of the Literature.

BACKGROUND: Guillain-Barré syndrome (GBS)-a rare condition characterized by acute-onset immune-mediated polyneuropathy-has been registered as a neurological manifestation of COVID-19, suggesting a possible link between these two conditions. METHODS: We report a case series of patients with COVID-19-related GBS hospitalized in the Neurology Department of Colentina Clinical Hospital, Bucharest, Romania, between March 2020 and March 2021. Several variables were analyzed, such as the mean interval between the onset of COVID-19 symptoms and neurological ones, clinical features, treatment course, and outcome. Further on, we conducted a thorough literature review based on the PubMed and ScienceDirect scientific databases. RESULTS: A total of 9 COVID-19 patients developed symptoms of GBS, out of which in 7, it manifested as an acute inflammatory demyelinating polyneuropathy (AIDP). Five patients presented respiratory failure, 2 requiring mechanical ventilation. All patients received a course of intravenous immunoglobulins, 2 additionally requiring plasma exchange. Upon discharge, all but 1 patient (who had not regained the ability to walk) had a positive outcome, and 1 died during admission. In the literature review, we analyzed the published sources at the time of writing. CONCLUSIONS: A link between COVID-19 and GBS might be possible; therefore, increased vigilance is required in the early identification of these cases for prompt diagnosis and treatment. Some notable differences such as an earlier onset of GBS symptoms, higher respiratory dysfunction, and higher mortality rates in COVID-19 patients have been observed between the presentation of GBS in the context of COVID-19 and GBS of other causes.

Falls in people post-Guillain-Barré syndrome in the United Kingdom: A national cross-sectional survey of community based adults.

Guillain-Barré syndrome (GBS) has several enduring effects that can lead to further harm and/or lower quality of life. These effects include falling and body pain, neither of which have been fully explored. This study aims to examine the risk factors associated with falling and potential causes of body pain in a post-GBS population. A cross-sectional survey of 216 participants was conducted using an electronic questionnaire that included. Self-report measures for: overall health, balance, anxiety and depression levels, body pain and demographics related to GBS experience and falls. A large proportion of individuals post-GBS experience ongoing problems beyond those expected with ageing. Comparative tests indicated that people reporting falls in the previous 12 months had: poorer levels of mobility, poorer F-scores, higher levels of body pain, poorer balance, poorer anxiety and depression scores and higher levels of fatigue. Gender did not appear to contribute to falls. Injuries following falls were associated with a lack of physiotherapy postdischarge and time since GBS. In a regression analysis of the identified and expected key variables, age and body pain statistically predicted falls. In over a quarter of cases reported here, respondents did not receive community physiotherapy following hospital discharge. In the midst and aftermath of COVID-19, provision of rehabilitation needs to be recalibrated, not just for COVID patients, but the wider community with ongoing needs. Issues around well-being and quality of life in the post-GBS community also need further consideration.

Neurological Sequelae of COVID-19 in Rehabilitation Settings.

Neurological symptoms of post-acute sequelae of COVID-19 (PASC), also known as Long COVID, are recognized. Four neurological syndromes (transverse myelitis, ischemic stroke, headache, and Guillain-Barré syndrome) associated with PASC are reviewed here, with a particular focus on issues related to rehabilitation.

Guillain-Barré Syndrome in a Child With Multisystem Inflammatory Syndrome Related to COVID-19.

Guillain-Barré syndrome has been associated with acute severe acute respiratory syndrome coronavirus 2 infection in children. Here, we report a 4-year-old boy who developed Guillain-Barré syndrome in the course of multisystem inflammatory syndrome related to COVID-19.

Post SARS-CoV-2 Guillain-Barré syndrome in a child: case report and review of the literature.

Guillain-Barré syndrome has been defined as a post-infectious immune-mediated polyneuropathy. COVID-19 usually presents with respiratory symptoms but can less commonly present with extra-respiratory manifestations such as neurological symptoms. Few cases were published in the literature regarding post-COVID-19 infection Guillain-Barré in the pediatric age group. In this paper, we present a 13-year-old male with possible Guillain-Barré syndrome occurring 2 weeks after a presumed COVID-19 infection. We conducted a systematic review and searched for published pediatric cases until March 2022. We included 35 patients in 25 publications.

Guillain-Barré syndrome as a fatal complication of SARS-CoV-2 infection - An autopsy case.

We presented a case of a 57-year-old female, who was tested positive for SARS-CoV-2 infection and was admitted to a hospital seven days later with signs of early pneumonia. The second day after her admission to the hospital, and nine days after the first positive PCR test, examination showed progressive ascendant weakness of the arms and legs with persisting paresthesia, lab tests showed increased concentration of proteins in the cerebrospinal fluid with albumino-cytological dissociation. She was diagnosed with Guillain-Barré syndrome (GBS). She was on low-flow oxygen support of 3 L/min, with good oxygen saturation (97-99%), without clinical or radiological progression of pneumonia. After receiving a negative PCR test for COVID-19 (11 days after the initial, positive test), four days after admission, she was set to be transferred to a specialized neurology clinic, however, she died unexpectedly during admission. The autopsy showed light to moderate lung edema, signs of moderate to severe coronary atherosclerosis and early myocardial ischemia. Histochemical and immunohistochemical staining of the peripheral nerves sampled from the cervical and brachial plexuses, showed foci of demyelination as well as infiltration with inflammatory cells, predominantly macrophages, and lymphocytes to a lesser degree. It was concluded that the causes of death were a breathing disorder and the paralysis of the diaphragm due to inflammatory polyneuropathy caused by GBS, initiated by SARS-CoV-2 infection. With the lack of similar autopsy cases, we believe that the presented case could be a valuable addition to the understanding of GBS development in SARS-CoV-2 related cases.

Concurrence between Guillain-Barré syndrome and immune thrombocytopenic purpura possibly induced by long COVID-19. / Concurrencia entre el síndrome de Guillain-Barré y púrpura trombocitopénica inmune posiblemente inducidos por COVID-19 prolongado.

During acute SARS-CoV-2 infection, there is persistent deregulation of the immune system that can last up to 8 months after the acute condition is controlled. This, added to other factors, is possibly associated with an increased risk of the appearance and concurrence of autoimmune diseases. The simultaneous occurrence of GBS and ITP has been rarely reported in the literature, and GBS is rarely associated with another autoimmune disease. We present the case of a man who, one month after his recovery from acute moderate COVID-19, presented concurrent GBS and ITP with an adequate response to treatment.

Durante la infección aguda por el SARVS-CoV-2 se produce una desregulación del sistema inmune que puede durar hasta ocho meses después de controlado el cuadro agudo. Esto, sumado a otros factores, posiblemente este asociado con un aumento del riesgo de aparición y concurrencia de enfermedades autoinmunes. La aparición simultanea del síndrome de Guillain-Barré (SGB) y púrpura trombocitopénica (PTI) se ha reportado poco en la literatura, y el SGB raramente se asocia con otra enfermedad autoinmune. Presentamos el caso de un varón que luego de un mes de tener un cuadro agudo de COVID-19 moderado, presentó concurrentemente SGB y PTI con respuesta adecuada al tratamiento.

Frequency of exposure to arboviruses and characterization of Guillain Barré syndrome in a clinical cohort of patients treated at a tertiary referral center in Brasília, Federal District.

BACKGROUND: Guillian Barré syndrome (GBS) is an acute autoimmune polyradiculoneuropathy often associated with previous exposure to infectious agents. METHODS: A clinical cohort of 41 patients with GBS admitted to the Base Hospital Institute of the Federal District between May 2017 and April 2019 was followed up for 1 year. Serological tests for arbovirus detection and amplification of nucleic acids using polymerase chain reaction for zika virus (ZIKV), dengue virus (DENV), and chikungunya virus (CHIKV) were performed. RESULTS: The cohort consisted of 61% men with a median age of 40 years, and 83% had GBS-triggering events. A total of 54% had Grade 4 disability, 17% had Grade 3, 12% had Grade 2, 10% had Grade 5, and 7% had Grade 1. The classic form occurred in 83% of patients. Nerve conduction evaluations revealed acute demyelinating inflammatory polyneuropathy (51%), acute motor axonal neuropathy (17%), acute sensory-motor neuropathy (15%), and indeterminate forms (17%). Four patients were seropositive for DENV. There was no laboratory detection of ZIKV or CHIKV infection. Ninety percent of patients received human immunoglobulin. Intensive care unit admission occurred in 17.1% of the patients, and mechanical ventilation was used in 14.6%. One patient died of Bickerstaff's encephalitis. Most patients showed an improvement in disability at 10 weeks of follow-up. CONCLUSIONS: GBS in the Federal District showed a variable clinical spectrum, and it was possible to detect recent exposure to DENV.

Finger Drop-Dominant Variant of Guillain-Barre Syndrome in a Patient With COVID-19: A Case Report.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 that may trigger Guillain-Barre syndrome (GBS) in selected patients. We describe a case of GBS presenting as marked finger extensor weakness in a 73-year-old woman with COVID-19. Her clinical and electrophysiological findings were consistent with a diagnosis of acute motor axonal neuropathy subtype of GBS with prominent finger dropping. Treatment with intravenous immunoglobulin for 5 days completely resolved her finger extension weakness after 19 months, although other involved extremities recovered earlier at 3 months. This study highlights that COVID-19-associated GBS can present in various forms aside from the classic variant, even in patients without any COVID-19 symptoms. Therefore, it is important to always consider the diagnosis of GBS in patients with COVID-19.