SARS-COVID-19 TRIGGERED WERNICKE'S ENCEPHALOPATHY (CLINICAL CASE).

Patient P., born in 1956, was found by relatives in a state of confused consciousness, an act of involuntary urination and defecation, numbness and weakening of the strength of both lower limbs were recorded. He was taken by ambulance to the reception room of the Regional Clinical Center of Neurosurgery and Neurology. The following concomitant diseases are known from the life anamnesis: Atrial fibrillation, gout, hypertension and type II non-insulin-dependent diabetes mellitus. Objective status: general condition of medium severity, tophuses of small joints of hands and feet, knee and elbow joints. Pronounced deformity of hands and feet due to gouty lesions. Heart tones are weakened. Breath sounds are weakened. The abdomen is soft, not painful on palpation. Glasgow coma scale 14-15 points. Consciousness is confused, disoriented in time, space and own person. To clarify the diagnosis, clinical and laboratory and instrumental diagnostic methods were used. Neurological complications, in particular, acute encephalopathy, on the background of coronavirus infection, may develop in patients with the presence of such risk factors as advanced age, cardiovascular diseases, hypertension, diabetes, gout. Most of the neurological complications in COVID-19 are probably not related to the direct penetration of the virus into the CNS, but are a trigger for the development of the pathology. Neuroimaging in such cases does not reveal pathological changes or reflects non-specific disorders.

Neurological complications associated with influenza in hospitalized children.

BACKGROUND: Influenza is a known respiratory and potential neurotropic virus. This study aimed to determine the prevalence and outcomes of influenza-related neurological complications among hospitalized children. METHODS: All medical records of hospitalized children aged <18 years old diagnosed with influenza at a tertiary care hospital in Bangkok were retrospectively reviewed. Influenza infection was confirmed by rapid antigen or reverse transcription polymerase chain reaction tests. Neurological characteristics and clinical outcomes were analyzed using the Pediatric Cerebral Performance Category Scale. RESULTS: From 2013 to 2018, 397 hospitalized children with a median age of 3.7 years (interquartile range [IQR]: 1.6-6.9) were included. The prevalence of neurological complications, including seizure or acute encephalopathy, was 16.9% (95% confidence interval [CI]: 13.3-20.9). Influenza A and B were identified in 73.1% and 26.9% of the patients, respectively. Among 39 (58.2%) acute symptomatic seizure cases, 25 (37.3%) children had simple febrile seizures, 7 (10.4%) had repetitive seizures, and 7 (10.4%) had provoked seizures with pre-existing epilepsy. For 28 (41.8%) encephalopathy cases, the clinical courses were benign in 20 (29.9%) cases and severe in 8 (11.9%) cases. Ten (14.9%) children needed intensive care monitoring, and 62 (93.5%) fully recovered to their baselines at hospital discharge. Predisposing factors to the neurological complications included a history of febrile seizure (adjusted odds ratio [aOR]: 20.3; 95% CI: 6.6-63.0), pre-existing epilepsy (aOR: 3.6; 95% CI: 1.3-10.2), and a history of other neurological disorders (aOR: 3.5; 95% CI: 1.2-10.2). CONCLUSIONS: One fifth of hospitalized children with influenza had neurological complications with a favorable outcome. Children with pre-existing neurological conditions were at higher risk for developing neurological complications.

Co-Occurring Catatonia and COVID-19 Diagnoses Among Hospitalized Individuals in 2020: A National Inpatient Sample Analysis.

BACKGROUND: COVID-19 is associated with a range of neuropsychiatric manifestations. While case reports and case series have reported catatonia in the setting of COVID-19 infection, its rate has been poorly characterized. OBJECTIVE: This study reports the co-occurrence of catatonia and COVID-19 diagnoses among acute care hospital discharges in the United States in 2020. METHODS: The National Inpatient Sample, an all-payors database of acute care hospital discharges, was queried for patients of any age discharged with a diagnosis of catatonia and COVID-19 in 2020. RESULTS: Among 32,355,827 hospitalizations in the 2020 National Inpatient Sample, an estimated 15,965 (95% confidence interval: 14,992-16,938) involved a diagnosis of catatonia without COVID-19 infection, 1,678,385 (95% confidence interval: 1,644,738-1,712,022) involved a diagnosis of COVID-19 without a co-occurring catatonia diagnosis, and 610 (95% confidence interval: 578-642) involved both catatonia and COVID-19 infection. In an adjusted model, a diagnosis of COVID-19, but not a diagnosis of catatonia or the combination of catatonia and COVID-19, was associated with increased mortality. Patients with catatonia and COVID-19 were frequently diagnosed with encephalopathy and delirium codes. CONCLUSIONS: Catatonia and COVID-19 were rarely co-diagnosed in 2020, and catatonia diagnosis was not associated with increased mortality in patients with COVID-19. Further research is needed to better characterize the phenomenology of catatonia in the setting of COVID-19 infection and its optimal treatment.

COVID-19 and Acute Neurologic Complications in Children.

BACKGROUND: Little is known about the epidemiology and outcomes of neurologic complications associated with coronavirus disease 2019 (COVID-19) in children. METHODS: We performed a cross-sectional study of children 2 months to <18 years of age with COVID-19 discharged from 52 children's hospitals from March 2020 to March 2022. Neurologic complications were defined as encephalopathy, encephalitis, aseptic meningitis, febrile seizure, nonfebrile seizure, brain abscess and bacterial meningitis, Reye's syndrome, and cerebral infarction. We assessed length of stay (LOS), ICU admission, 30 day readmissions, deaths, and hospital costs. We used multivariable logistic regression to identify factors associated with neurologic complications. RESULTS: Of 15 137 children hospitalized with COVID-19, 1060 (7.0%) had a concurrent diagnosis of a neurologic complication. The most frequent neurologic complications were febrile seizures (3.9%), nonfebrile seizures (2.3%), and encephalopathy (2.2%). Hospital LOS, ICU admission, ICU LOS, 30 day readmissions, deaths, and hospital costs were higher in children with neurologic complications compared with those without complications. Factors associated with lower odds of neurologic complications included: younger age (adjusted odds ratio [aOR]: 0.97; 95% confidence interval [CI]: 0.96-0.98), occurrence during delta variant predominant time period (aOR: 0.71; 95% CI: 0.57-0.87), presence of a nonneurologic complex chronic condition (aOR: 0.80; 95% CI: 0.69-0.94). The presence of a neurologic complex chronic condition was associated with higher odds of neurologic complication (aOR 4.14, 95% CI 3.48-4.92). CONCLUSIONS: Neurologic complications are common in children hospitalized with COVID-19 and are associated with worse hospital outcomes. Our findings emphasize the importance of COVID-19 immunization in children, especially in high-risk populations, such as those with neurologic comorbidity.

COVID-19 related acute necrotizing encephalopathy with extremely high interleukin-6 and RANBP2 mutation in a patient with recently immunized inactivated virus vaccine and no pulmonary involvement.

BACKGROUND: We report the first case of COVID-19 associated acute necrotizing encephalopathy (ANE) without pulmonary disease in a patient with an extremely high interleukin-6 (IL-6) level and Ran Binding Protein 2 (RANBP2) mutation. CASE PRESENTATION: A 29-year-old woman recently immunized with inactivated viral vaccine-BBIBP32-CorV (Sinopharm) presented with alteration of consciousness. Her body temperature was 37° Celsius, blood pressure 42/31 mmHg, heart rate 130 bpm, respiratory rate 20 per minute, and oxygen saturation 98%. Respiratory examination was unremarkable. Neurological examination revealed stupor but preserved brainstem reflexes. Non-contrast computerized tomography of the brain showed symmetrical hypodense lesions involving bilateral thalami and cerebellar hemispheres characteristic of ANE. No pulmonary infiltration was found on chest radiograph. SARS-CoV-2 was detected by PCR; whole genome sequencing later confirmed the Delta variant. RANBP2 gene analysis revealed heterozygous Thr585Met mutation. Serum IL-6 was 7390 pg/mL. Urine examination showed pyelonephritis. Her clinical course was complicated by seizure, septic shock, acute kidney injury, and acute hepatic failure. She later developed coma and passed away in 6 days. CONCLUSIONS: ANE is caused by cytokine storm leading to necrosis and hemorrhage of the brain. IL-6 was deemed as a prognostic factor and a potential treatment target of ANE in previous studies. RANBP2 missense mutation strongly predisposes this condition by affecting mitochondrial function, viral entry, cytokine signaling, immune response, and blood-brain barrier maintenance. Also, inactivated vaccine has been reported to precipitate massive production of cytokines by antibody dependent enhancement (ADE). The true incidence of COVID-19 associated ANE is not known as were the predictors of its development. We proposed these potential two factors (RANBP2 mutation and ADE) that could participate in the pathogenesis of ANE in COVID-19 apart from SARS-CoV2 infection by itself. Further study is needed to confirm this hypothesis, specifically in the post-vaccination period. Role of RANBP2 mutation and its application in COVID-19 and ANE should be further elaborated.

Severe encephalopathy associated with SARS-CoV-2 Omicron BA.1 variant infection in a neonate.

INTRODUCTION: The coronavirus disease 2019 (COVID-19), including the Omicron variant, is less severe in children than in adults. To date, there has been no detailed description of COVID-19-associated severe encephalopathy due to the Omicron variant during the neonatal and early infantile periods. CASE PRESENTATION: During the outbreak of the Omicron variant, a 29-day-old male presented with a pale and ill appearance. The patient was intubated for mechanical ventilation owing to recurrent apnea, which subsequently turned out to be a breath-holding that may have been caused by seizure. In addition, nonconvulsive status epilepticus was observed. Total duration of repetitive seizure activities was approximately 30 min per hour when seizures were most severe. Brain magnetic resonance imaging (MRI) on day 14 revealed extensive hyperintensity in the T2 sequence, hypointensity in the fluid-attenuated inversion recovery (FLAIR) sequence in the deep and subcortical white matter, and diffusion restriction in the corpus callosum. The Omicron BA.1 variant of the severe acute respiratory syndrome coronavirus 2 was detected in his respiratory sample. Follow-up MRI on day 45 revealed multiple cystic cavitations. CONCLUSION: Although COVID-19 is not severe in most children, life-threatening conditions such as COVID-19-associated severe encephalopathy can occur during the neonatal and early infantile periods.

Can plasma exchange therapy be an option for the treatment of SARS-CoV-2 Related Splenial Lesion Syndrome: Two cases from the pediatric intensive care unit.

BACKGROUND: Reversible splenial lesion syndrome (RESLES) is characterized by a temporary lesion in the splenium of the corpus callosum. RESLES is one of the most common causes of Mild encephalitis/encephalopathy reversible splenial lesion (MERS) and a rare clinical syndrome for the pediatric population. In a limited number of pediatric case reports, association with SARS-COV-2 in was reported. We aimed to increase the awareness of neurological involvement and treatment options of RESLES in children diagnosed with MIS-C. CASE PRESENTATION: We report two cases with a diagnosis of multisystem inflammatory syndrome-children who developed RESLES during the disease course. Fever, blurred vision, ataxia and encephalopathy were the main central nervous system symptoms. In our first case, we observed a rapid recovery in clinical symptoms and complete resolution of the splenial lesion in with intravenous immunoglobulin (IVIG) and methylprednisolone treatment. However, our second case did not respond to IVIG and methylprednisolone treatment. We performed therapeutic plasma exchange therapy and observed a successful recovery both in brain magnetic resonance imaging and echocardiographic findings. CONCLUSION: Although IVIG and methylprednisolone are the first choice treatment methods in MIS-C cases progressing with RESLES, therapeutic plasma exchange may be an option for the treatment of unresponsive cases.

COVID-19 encephalopathy: an unusual presentation with new-onset seizure causing convulsive status epilepticus.

Although neurological manifestations such as headache and myalgias have been observed with COVID-19, presentation with more serious neurological illness is uncommon and rare. We report a case of a middle-aged woman who presented to the emergency department of a tertiary care hospital. Her clinical presentation was primarily neurological rather than the more common presentation with respiratory manifestations. She presented with generalised tonic-clonic seizures, along with history of undocumented low-grade fever and generalised body aches. The positive SARS-CoV-2 RT-PCR nasal swab, the cerebrospinal fluid analysis (lymphocytic pleocytosis) and electroencephalogram were consistent with viral encephalitis; brain imaging was unremarkable. This case highlights the variable presenting features of COVID-19 infection as patients can primarily present with neurological manifestations in the absence of significant respiratory symptoms. We believe it is important to recognise neurological disease associated with SARS-CoV-2 in patients with asymptomatic respiratory infection.

COVID-19-associated rhino-orbital-cerebral mucormycosis: A systematic review, meta-analysis, and meta-regression analysis.

BACKGROUND: Till now, no meta-analysis is available to address the clinical profile, risk factors, different interventions, and outcomes among COVID-19-associated rhino-orbito-cerebral mucormycosis (C-ROCM) cases. MATERIALS AND METHODS: Eight literature databases were screened using appropriate keywords from November 1, 2019, to June 30, 2021. The objectives were to analyze the clinical and microbiological profile, risk factor/comorbidity, intervention, and outcome. "R-metafor package" was used for analysis. RESULTS: A total of 23 studies were included. The mean age of presentation of C-ROCM was 54.6 years. The most common presentation was ptosis (72.7%), lid edema (60.6%), proptosis (60.6%), ophthalmoplegia (57.3%), loss of vision (53.7%), facial edema (34.7%), and nasal-blockage (11.8%). Evidence of intracranial spread was seen in 42.8% of cases. Rhizopus was the most common fungus (57.1%) isolated in fungal culture. Among C-ROCM patients, diabetes was the commonest comorbid condition, and the use of corticosteroids related to COVID-19 treatment was the most common risk factor (85.75%). Compared to controlled diabetics, C-ROCM was significantly higher among uncontrolled diabetics (odds ratio [OR] 0.15, 95% confidence interval [C.I.] 0.041-0.544, P = 0.0010). However, no significant association was seen between C-ROCM and COVID-19 severity (OR 0.930, 95% C.I. 0.212-4.087, P = 0.923). For treatment, amphotericin-B was the most common antifungal drug used which was followed by surgical options. However, mortality was high (prevalence 0.344, 95% C.I. 0.205-0.403) despite treatment. CONCLUSION: Although local rhino-orbito symptoms were the first to appear, rapid intracranial extension was seen in a significant number of C-ROCM cases. Uncontrolled diabetes and excessive use of corticosteroid were the most common risk factors present among the C-ROCM cases. High index clinical suspicion is imperative (specifically among COVID-19 patients with diabetes), and routine screening may be helpful.

Multiple demyelinating sensory and motor mononeuropathy associated with COVID-19: a case report.

The involvement of the nervous system may occur in 36.4% of patients with COVID-19. Cases have been described of cerebrovascular diseases, encephalitis, encephalopathies, and changes in smell and taste. Two months after being discharged from hospital with COVID-19, a 63-year-old male patient presented with a predominantly demyelinating multiple sensory and motor mononeuropathy. A diagnostic possibility of multiple sensory and motor demyelinating mononeuropathy (Lewis-Sumner syndrome) was made. Treatment with human immunoglobulin was initiated. COVID-19 may be associated with multiple demyelinating sensory and motor mononeuropathy.

COVID-19 triggered encephalopathic crisis in a patient with glutaric aciduria type 1.

OBJECTIVES: The impact of coronavirus disease-19 (COVID-19) on metabolic outcome in patients with inborn errors of metabolism has rarely been discussed. Herein, we report a case with an acute encephalopathic crisis at the course of COVID-19 disease as the first sign of glutaric aciduria type 1 (GA-1). CASE PRESENTATION: A 9-month-old patient was admitted with encephalopathy and acute loss of acquired motor skills during the course of COVID-19 disease. She had lethargy, hypotonia, and choreoathetoid movements. In terms of COVID-19 encephalopathy, the reverse transcription-polymerase chain reaction assay test for COVID-19 was negative in cerebral spinal fluid. Brain imaging showed frontotemporal atrophy, bilateral subcortical and periventricular white matter, basal ganglia, and thalamic involvement. Elevated glutarylcarnitine in plasma and urinary excretion of glutaric and 3-OH-glutaric acids was noted. A homozygote mutation in the glutaryl-CoA dehydrogenase gene led to the diagnosis of GA-1. CONCLUSIONS: With this report, neurological damage associated with COVID-19 has been reported in GA-1 patients for the first time in literature.

The Spectrum of Neuroimaging Findings on CT and MRI in Adults With COVID-19.

Neurologic involvement is well-recognized in COVID-19. This article reviews the neuroimaging manifestations of COVID-19 on CT and MRI, presenting cases from the New York City metropolitan region encountered by the authors during the first surge of the pandemic. The most common neuroimaging manifestations are acute infarcts with large clot burden and intracranial hemorrhage, including microhemorrhages. However, a wide range of additional imaging patterns occur, including leukoencephalopathy, global hypoxic injury, acute disseminated encephalomyelitis, cytotoxic lesions of the corpus callosum, olfactory bulb involvement, cranial nerve enhancement, and Guillain-Barré syndrome. The described CNS abnormalities largely represent secondary involvement from immune activation that leads to a prothrombotic state and cytokine storm; evidence for direct neuroinvasion is scant. Comorbidities such as hypertension, complications of prolonged illness and hospitalization, and associated supportive treatments also contribute to the CNS involvement in COVID-19. Routine long-term neurologic follow-up may be warranted, given emerging evidence of long-term microstructural and functional changes on brain imaging after COVID-19 recovery.

Special report of the RSNA COVID-19 task force: systematic review of outcomes associated with COVID-19 neuroimaging findings in hospitalized patients.

OBJECTIVE: We reviewed the literature to describe outcomes associated with abnormal neuroimaging findings among adult COVID-19 patients. METHODS: We performed a systematic literature review using PubMed and Embase databases. We included all studies reporting abnormal neuroimaging findings among hospitalized patients with confirmed COVID-19 and outcomes. Data elements including patient demographics, neuroimaging findings, acuity of neurological symptoms and/or imaging findings relative to COVID-19 onset (acute, subacute, chronic), and patient outcomes were recorded and summarized. RESULTS: After review of 775 unique articles, a total of 39 studies comprising 884 COVID-19 patients ≥ 18 years of age with abnormal neuroimaging findings and reported outcomes were included in our analysis. Ischemic stroke was the most common neuroimaging finding reported (49.3%, 436/884) among patients with mortality outcomes data. Patients with intracranial hemorrhage (ICH) had the highest all-cause mortality (49.7%, 71/143), followed by patients with imaging features consistent with leukoencephalopathy (38.5%, 5/13), and ischemic stroke (30%, 131/436). There was no mortality reported among COVID-19 patients with acute disseminated encephalomyelitis without necrosis (0%, 0/8) and leptomeningeal enhancement alone (0%, 0/12). Stroke was a common acute or subacute neuroimaging finding, while leukoencephalopathy was a common chronic finding. CONCLUSION: Among hospitalized COVID-19 patients with abnormal neuroimaging findings, those with ICH had the highest all-cause mortality; however, high mortality rates were also seen among COVID-19 patients with ischemic stroke in the acute/subacute period and leukoencephalopathy in the chronic period. ADVANCES IN KNOWLEDGE: Specific abnormal neuroimaging findings may portend differential mortality outcomes, providing a potential prognostic marker for hospitalized COVID-19 patients.

Encephalopathy in patients with COVID-19: A review.

Encephalopathy and encephalitis are major and devastating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus-associated central nervous system complications. Hypoxic/metabolic changes produced by intense inflammatory response against the virus triggers cytokine storm and subsequently acute respiratory distress syndrome and multiple organ failure. Hypoxic/metabolic changes result in encephalopathy. The presence of comorbidities predisposes to hypoxic/metabolic changes responsible for encephalopathy. Altered consciousness, ranging from mild confusion, delirium, to deep coma, is hallmark clinical features. Cortical and subcortical T2/FLAIR signal changes are common neuroimaging abnormalities. In a few isolated case reports of SARS-CoV-2 encephalitis, the virus has been demonstrated in cerebrospinal fluid. The presence of anosmia and ageusia can help in differentiation from other encephalopathies. We analyzed published reports on coronavirus disease 2019-associated encephalopathy. Encephalopathy is common in older patients, the majority are more than 50 years of age. The patients having encephalopathy/encephalitis are either severely or critically ill. Many patients were already on mechanical ventilation. Lung abnormalities are noted in almost all of the patients, presenting with encephalopathy. Encephalopathy is always preceded by commoner clinical features, like, fever, cough, dyspnoea, and headache. In majority, patients are already in the intensive care unit, when encephalopathy develops.

Neurological manifestations and complications of coronavirus disease 2019 (COVID-19): a systematic review and meta-analysis.

BACKGROUND: The spectrum of neurological involvement in COVID-19 is not thoroughly understood. To the best of our knowledge, no systematic review with meta-analysis and a sub-group comparison between severe and non-severe cases has been published. The aim of this study is to assess the frequency of neurological manifestations and complications, identify the neurodiagnostic findings, and compare these aspects between severe and non-severe COVID-19 cases. METHODS: A systematic search of PubMed, Scopus, EBSCO, Web of Science, and Google Scholar databases was conducted for studies published between the 1st of January 2020 and 22nd of April 2020. In addition, we scanned the bibliography of included studies to identify other potentially eligible studies. The criteria for eligibility included studies published in English language (or translated to English), those involving patients with COVID-19 of all age groups, and reporting neurological findings. Data were extracted from eligible studies. Meta-analyses were conducted using comprehensive meta-analysis software. Random-effects model was used to calculate the pooled percentages and means with their 95% confidence intervals (CIs). Sensitivity analysis was performed to assess the effect of individual studies on the summary estimate. A subgroup analysis was conducted according to severity. The main outcomes of the study were to identify the frequency and nature of neurological manifestations and complications, and the neuro-diagnostic findings in COVID-19 patients. RESULTS: 44 articles were included with a pooled sample size of 13,480 patients. The mean age was 50.3 years and 53% were males. The most common neurological manifestations were: Myalgia (22.2, 95% CI, 17.2 to 28.1%), taste impairment (19.6, 95% CI, 3.8 to 60.1%), smell impairment (18.3, 95% CI, 15.4 to 76.2%), headache (12.1, 95% CI, 9.1 to 15.8%), dizziness (11.3, 95% CI, 8.5 to 15.0%), and encephalopathy (9.4, 95% CI, 2.8 to 26.6%). Nearly 2.5% (95% CI, 1 to 6.1%) of patients had acute cerebrovascular diseases (CVD). Myalgia, elevated CK and LDH, and acute CVD were significantly more common in severe cases. Moreover, 20 case reports were assessed qualitatively, and their data presented separately. CONCLUSIONS: Neurological involvement is common in COVID-19 patients. Early recognition and vigilance of such involvement might impact their overall outcomes.

Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology.

Scientists and health professionals are exhaustively trying to contain the coronavirus disease 2019 (COVID-19) pandemic by elucidating viral invasion mechanisms, possible drugs to prevent viral infection/replication, and health cares to minimize individual exposure. Although neurological symptoms are being reported worldwide, neural acute and long-term consequences of SARS-CoV-2 are still unknown. COVID-19 complications are associated with exacerbated immunoinflammatory responses to SARS-CoV-2 invasion. In this scenario, pro-inflammatory factors are intensely released into the bloodstream, causing the so-called "cytokine storm". Both pro-inflammatory factors and viruses may cross the blood-brain barrier and enter the central nervous system, activating neuroinflammatory responses accompanied by hemorrhagic lesions and neuronal impairment, which are largely described processes in psychiatric disorders and neurodegenerative diseases. Therefore, SARS-CoV-2 infection could trigger and/or worse brain diseases. Moreover, patients with central nervous system disorders associated to neuroimmune activation (e.g. depression, Parkinson's and Alzheimer's disease) may present increased susceptibility to SARS-CoV-2 infection and/or achieve severe conditions. Elevated levels of extracellular ATP induced by SARS-CoV-2 infection may trigger hyperactivation of P2X7 receptors leading to NLRP3 inflammasome stimulation as a key mediator of neuroinvasion and consequent neuroinflammatory processes, as observed in psychiatric disorders and neurodegenerative diseases. In this context, P2X7 receptor antagonism could be a promising strategy to prevent or treat neurological complications in COVID-19 patients.