Neurologic Manifestations and Complications of COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a global pandemic. Beyond the well-described respiratory manifestations, SARS-CoV-2 may cause a variety of neurologic complications, including headaches, alteration in taste and smell, encephalopathy, cerebrovascular disease, myopathy, psychiatric diseases, and ocular disorders. Herein we describe SARS-CoV-2's mechanism of neuroinvasion and the epidemiology, outcomes, and treatments for neurologic manifestations of COVID-19.

Comparison of cutaneous silent period parameters in patients with primary Sjögren's syndrome with the healthy population and determination of its relationship with clinical parameters.

Small fiber neuropathy (SFN) is one of the main neurological manifestations in primary Sjögren's Syndrome (pSS). For the detection of SFN, cutaneous silent period (CSP) measurement is gaining popularity recently due to its non-invasiveness and practical application. Evaluating SFN involvement in patients with pSS using CSP and evaluating its relationship with clinical parameters. Patients with a diagnosis of pSS and healthy volunteers demographically homogeneous with the patient group were included in the study. The CSP responses were recorded over the abductor pollicis brevis muscle. The latency and duration values of the responses were obtained. In patient group, EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), Hospital Anxiety and Depression Scale (HADS), Short Form-36 (SF-36) questionnaire, Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) and Central Sensitization Inventory (CSI) were applied for the evaluation of symptom severity, mood, quality of life, presence of neuropathic pain and central sensitization, respectively. The mean CSP latency was significantly longer in patient group compared to control group (p < 0.001). Mean CSP duration was also significantly shorter in patient group (p < 0.001). There were no significant differences in CSP parameters according to patients' neuropathic pain or central sensitization profile. There were significant correlations of CSP parameters (latency and duration, respectively) with ESSPRI dryness (ρ = 0.469, p = 0.004; ρ = -0.553, p < 0.001), fatigue (ρ = 0.42, p = 0.011; ρ = -0.505, p = 0.002), pain (ρ = 0.428, p = 0.009; ρ = -0.57, p < 0.001) subscores and mean ESSPRI score (ρ = 0.631, p < 0.001; ρ = -0.749, p < 0.001). When SF-36 subscores and CSP parameters were investigated, a significant correlation was found only between "bodily pain" subscore and CSP duration (ρ = -0.395, p = 0.017). In HADS, LANSS and CSI evaluations, a significant correlation was found only between HADS anxiety score and the CSP duration (ρ = 0.364, p = 0.02). As indicated by CSP measurement, SFN is more prominent in patients with pSS than in the healthy population. It is important to investigate the presence of SFN because of its correlation with the leading symptoms in the clinical spectrum of pSS.

Central nervous system manifestations of dengue infection: data from a tertiary care Centre in South India.

BACKGROUND: Dengue fever is the second most common mosquito-borne disease affecting human beings and neurological manifestations (NMs) of this arboviral infection are increasingly being reported. METHODS: In this retrospective study, conducted in a tertiary care centre in south India, we sought to describe the spectrum of NMs of dengue fever. The records of all patients admitted in the Department of Internal Medicine over 8 years, with a diagnosis of dengue-based on clinical symptoms and the detection of dengue IgM antibodies or detection of NS1 antigen or nucleic acid by reverse transcriptase-polymerase chain reaction (RT-PCR); with Glasgow coma score (GCS) ≤14, neck stiffness, focal neurological signs, seizures, or visual disturbances-were explored. RESULTS: Of 1121 patients admitted with dengue fever, 341 (30%) had severe dengue and 23 (2%) had NMs. Encephalopathy was seen in 9 patients (39%), encephalitis in 6 (27%), cerebellitis in 4 (17%), acute disseminated encephalomyelitis (ADEM) in 2 (9%), ischaemic stroke in 1 (4%) patient, and neuro-ophthalmological manifestations in 1 (4%) patient. The median duration of hospital stay was 7 days. Nine (39% of) patients required intensive care unit (ICU) admission and 5 (22%) had fatal outcomes. There was no association between thrombocytopenia, metabolic acidosis, transaminitis, hyponatremia, the type of dengue infection, and the various NMs described. CONCLUSIONS: The NMs of dengue infection are varied, and a high index of suspicion is needed to identify them in patients who present with lethargy or altered sensorium on the background of an acute febrile illness suggestive of dengue.

Characteristics of diabetic and non-diabetic carpal tunnel syndrome in terms of clinical, electrophysiological, and Sonographic features: a cross-sectional study.

BACKGROUND: Although diabetes is considered a major risk factor for carpal tunnel syndrome (CTS), the characteristics of diabetic CTS have not been fully understood. OBJECTIVE: This study is aimed at evaluation of the clinical, electrophysiological, and ultrasonographic findings of non-diabetic and diabetic CTS. METHODS: This retrospective, cross-sectional study included patients diagnosed with CTS. Patient age, sex, involved side, body mass index, clinical and electrophysiological findings, and median nerve cross-sectional area (CSA) were identified. Diabetes was identified through patient or guardian interviews, medical records, and medication history. Linear and binary logistic regression models were established to confirm the associations between the electrophysiological findings, median nerve CSA, and clinical outcomes. Covariates, such as age, sex, body mass index, diabetes, symptom duration, and thenar muscle weakness were adjusted. RESULTS: Out of the 920 hands, 126 and 794 belonged to the diabetic and non-diabetic CTS groups, respectively. The patients were significantly older in the diabetic CTS group (P < 0.001). The rate of thenar weakness in the diabetic CTS group was also significantly higher than that in the non-diabetic CTS group (P = 0.009). The diabetic CTS group had a more severe electrodiagnostic grade (P = 0.001). The prolonged onset latency of the compound motor nerve action potential (CMAP) and median nerve CSA were well associated with the degree of clinical symptoms. Increased median nerve CSA was significantly associated with prolonged CMAP onset latency (ß = 0.64; P = 0.012), prolonged transcarpal latency (ß = 0.95; P = 0.044), and decreased CMAP amplitude (ß = -0.17; P = 0.002) in the non-diabetic CTS group. CONCLUSION: Diabetic CTS had more profound electrophysiological abnormalities. Distal motor latency and median nerve CSA were not only associated with each other, but also with clinical symptoms. Further studies are needed to investigate the pathophysiological mechanisms underlying diabetic CTS.

Chronic Ciguatera Poisoning: A Case Report.

Ciguatera is a common marine, toxin-borne illness caused by the consumption of fish that contain toxins that activate voltage-sensitive sodium channels. The clinical manifestations of ciguatera are typically self-limited, but chronic symptoms may occur in a minority of patients. This report describes a case of ciguatera poisoning with chronic symptoms, including pruritus and paresthesias. A 40-y-old man was diagnosed with ciguatera poisoning after consuming amberjack while vacationing in the US Virgin Islands. His initial symptoms, including diarrhea, cold allodynia, and extremity paresthesias, evolved into chronic, fluctuating paresthesias and pruritus that became worse after the consumption of alcohol, fish, nuts, and chocolate. After a comprehensive neurologic evaluation failed to reveal another cause for his symptoms, he was diagnosed with chronic ciguatera poisoning. His neuropathic symptoms were treated with duloxetine and pregabalin, and he was counseled to avoid foods that triggered his symptoms. Chronic ciguatera is a clinical diagnosis. Signs and symptoms of chronic ciguatera can include fatigue, myalgias, headache, and pruritus. The pathophysiology of chronic ciguatera is incompletely understood but may involve genetic factors or immune dysregulation. Treatment involves supportive care and avoidance of foods and environmental conditions that may exacerbate symptoms.

[Neurological forms of long COVID in adults: Critical approach]. / Formes neurologiques du COVID long de l'adulte : approche critique.

Now recognized by health authorities, long COVID is identified as a frequent condition complicating the evolution of SARS-CoV-2 infection. Its polymorphic and sometimes disconcerting clinical expression raises questions about its mechanism. Patterns of clinical expression suggest extensive involvement of the nervous system through an almost ubiquitous cognitive complaint. This article reviews the neurological symptoms and forms of these patients, and the neuropsychological explorations aimed at objectifying a cognitive deficit. The studies published until now confronted with the clinical mode of expression, did not make it possible to define a deficit neuropsychological profile at the level of the groups, and evoked more a functional impairment than a lesion. However, each series mentions a small number of patients in whom a cognitive deficit is objectified. The uncertainties about the causes of the prolonged forms of COVID, the heterogeneity of the published studies, and the virtual absence of temporal evolution data should make one cautious about the interpretation of these data but should in no way delay or prevent taking into account care of these patients.

[COVID-19: Neurological manifestations and complications during the acute phase of the disease]. / Covid-19 : manifestations et complications neurologiques à la phase aiguë de la maladie.

The neurological manifestations and complications of the acute phase of COVID-19 are numerous. They mainly concern the central nervous system in the frequent forms of encephalopathy, encephalitis and neurovascular pathologies. Peripheral neurological manifestations mainly include acute polyneuropathies such as Guillain-Barré syndrome and intensive care neuromyopathies. Most of these manifestations were described during the first wave of the pandemic. The epidemiological, clinical, paraclinical, pathophysiological and therapeutic aspects are addressed in this general review of the literature published from 2020 to early 2023.

Clinical outcomes of HIV-syphilis coinfection among patients with no neurological symptoms: a retrospective cohort study.

OBJECTIVE: Our objective was to describe and compare the occurrence of neurological outcomes and neurosyphilis in people living with HIV with incident syphilis and no neurological symptoms who underwent early screening for asymptomatic neurosyphilis (ANS) or regular clinical management without a lumbar puncture. METHODS: This was a retrospective cohort study in a single referral centre of Sao Paulo, Brazil. Patients with incident syphilis diagnosed between January 2000 and August 2016 and meeting the adapted criteria for ANS investigation suggested by Marra et al. (CD4+ T-cell counts ≤350 cells/mm³ and/or venereal disease research laboratory test results ≥1:16) were identified. Those with no neurological symptoms and immediately referred for lumbar puncture were categorized as group 1, and those not referred for cerebrospinal fluid collection were categorized as group 2. We compared the occurrence of neurological symptoms and neurosyphilis diagnoses between the groups using incidence rates and Kaplan-Meier curves. RESULTS: We included 425 participants with a median follow-up of 6 years. The incidence rate of neurological symptoms was 36.5/1000 person-years in group 1 and 40.6/1000 person-years in group 2 (incidence rate ratio [IRR] 0.90; 95% confidence interval [CI] 0.57-1.39; p = 0.62). The incidence rate of neurosyphilis was 15.0 cases/1000 person-years in group 1 and 6.7 cases/1000 person-years in group 2 (IRR 2.26; 95% CI 0.93-5.68; p = 0.05). CONCLUSIONS: We found no statistically significant differences between groups in the incidence rates of neurological symptoms and neurosyphilis. Our findings support the current guidelines, which suggest a less invasive approach regarding ANS investigation among people living with HIV with incident syphilis.

Unusual neurologic manifestations of Vogt-Koyanagi-Harada disease: a systematic literature review.

BACKGROUND AND PURPOSE: The usual neurologic manifestations of Vogt-Koyanagi-Harada (VKH) disease include aseptic meningitis and headaches. We performed the present study to review all unusual neurologic manifestations reported in VKH disease to summarize them. METHODS: A literature search was performed in the English language on Scopus and Medline via PubMed from 1946 to July 31, 2021, by using the following terms: "Vogt Koyanagi Harada disease" OR "VKH disease" AND "Brain" OR "Spinal cord" OR "CNS" OR "Central nervous system" OR "Neurologic" OR "Peripheral nervous system" OR "Polyneuropathies. Our inclusion criteria were unusual neurologic manifestations of VKH disease. RESULTS: Our literature search yielded 417 total articles (PubMed = 334, Scopus = 83) from which 32 studies comprising 43 patients (22 men and 21 women, of which 62.8% were younger than 50 years) were included in this systematic literature review. Regarding the study design, all studies were case reports and published between 1981 and 2021. CNS involvement was the most reported (93%) in VKH disease. Peripheral nervous system involvement represents 7% of cases. The cerebral lesions were parenchymal inflammatory lesions in the white matter or posterior fossa with or no contrast enhancement (16.3%), leptomeningitis (9.3%), pachymeningitis (7%), meningoencephalitis (2.3%), ischemic stroke (4.6%), hemorrhagic stroke (2.3%), transient ischemic attack (2.3%), and hydrocephalus (2.3%). The optic nerve lesions were anterior ischemic optic neuropathy (20.9%) and optic neuritis (9.3%). Concerning spinal cord lesion, it was mainly myelitis (14%). CONCLUSION: This systematic literature review provides a summary of the different unusual neurologic manifestations reported in VKH disease.

Normal pressure hydrocephalus associated with COVID-19 infection: a case report.

BACKGROUND: COVID-19 is a pandemic disease responsible for many deaths worldwide. Many neurological manifestations have been described. We report a case of normal pressure hydrocephalus (NPH) 2 months after acute COVID19 infection, in a patient without other risk factors. CASE PRESENTATION: A 45-year-old male patient presented an 8-month history of progressive gait disorder and cognitive impairment after being hospitalized for SARS-CoV-2 infection. Magnetic resonance imaging (MRI) was compatible with NPH. A spinal tap test was positive and there was progressive improvement after shunting, with complete resolution of symptoms. CONCLUSION: Other infections such as syphilis, cryptococcosis and Lyme disease have been associated with NPH. Possible mechanisms for NPH after COVID include disruption of choroid plexus cells by direct viral invasion or as a result of neuroinflammation and cytokine release and hypercoagulability leading to venous congestion and abnormalities of CSF flow. Given the significance of NPH as a cause of reversible dementia, it is important to consider the possibility of a causal association with COVID19 and understand the mechanisms behind this association.

Neurologic manifestations of COVID-19 in critically ill patients: results of the prospective multicenter registry PANDEMIC.

BACKGROUND: Neurologic manifestations are increasingly reported in patients with coronavirus disease 2019 (COVID-19). Yet, data on prevalence, predictors and relevance for outcome of neurological manifestations in patients requiring intensive care are scarce. We aimed to characterize prevalence, risk factors and impact on outcome of neurologic manifestations in critically ill COVID-19 patients. METHODS: In the prospective, multicenter, observational registry study PANDEMIC (Pooled Analysis of Neurologic DisordErs Manifesting in Intensive care of COVID-19), we enrolled COVID-19 patients with neurologic manifestations admitted to 19 German intensive care units (ICU) between April 2020 and September 2021. We performed descriptive and explorative statistical analyses. Multivariable models were used to investigate factors associated with disorder categories and their underlying diagnoses as well as to identify predictors of outcome. RESULTS: Of the 392 patients included in the analysis, 70.7% (277/392) were male and the mean age was 65.3 (SD ± 3.1) years. During the study period, a total of 2681 patients with COVID-19 were treated at the ICUs of 15 participating centers. New neurologic disorders were identified in 350 patients, reported by these centers, suggesting a prevalence of COVID-19-associated neurologic disorders of 12.7% among COVID-19 ICU patients. Encephalopathy (46.2%; 181/392), cerebrovascular (41.0%; 161/392) and neuromuscular disorders (20.4%; 80/392) were the most frequent categories identified. Out of 35 cerebrospinal fluid analyses with reverse transcriptase PCR for SARS-COV-2, only 3 were positive. In-hospital mortality was 36.0% (140/389), and functional outcome (mRS 3 to 5) of surviving patients was poor at hospital discharge in 70.9% (161/227). Intracerebral hemorrhage (OR 6.2, 95% CI 2.5-14.9, p < 0.001) and acute ischemic stroke (OR 3.9, 95% CI 1.9-8.2, p < 0.001) were the strongest predictors of poor outcome among the included patients. CONCLUSIONS: Based on this well-characterized COVID-19 ICU cohort, that comprised 12.7% of all severe ill COVID-19 patients, neurologic manifestations increase mortality and morbidity. Since no reliable evidence of direct viral affection of the nervous system by COVID-19 could be found, these neurologic manifestations may for a great part be indirect para- or postinfectious sequelae of the infection or severe critical illness. Neurologic ICU complications should be actively searched for and treated.

Comparing LASSO and random forest models for predicting neurological dysfunction among fluoroquinolone users.

BACKGROUND: Fluoroquinolones are associated with central (CNS) and peripheral (PNS) nervous system symptoms, and predicting the risk of these outcomes may have important clinical implications. Both LASSO and random forest are appealing modeling methods, yet it is not clear which method performs better for clinical risk prediction. PURPOSE: To compare models developed using LASSO versus random forest for predicting neurological dysfunction among fluoroquinolone users. METHODS: We developed and validated risk prediction models using claims data from a commercially insured population. The study cohort included adults dispensed an oral fluoroquinolone, and outcomes were CNS and PNS dysfunction. Model predictors included demographic variables, comorbidities and medications known to be associated with neurological symptoms, and several healthcare utilization predictors. We assessed the accuracy and calibration of these models using measures including AUC, calibration curves, and Brier scores. RESULTS: The underlying cohort contained 16 533 (1.18%) individuals with CNS dysfunction and 46 995 (3.34%) individuals with PNS dysfunction during 120 days of follow-up. For CNS dysfunction, LASSO had an AUC of 0.81 (95% CI: 0.80, 0.82), while random forest had an AUC of 0.80 (95% CI: 0.80, 0.81). For PNS dysfunction, LASSO had an AUC of 0.75 (95% CI: 0.74, 0.76) versus an AUC of 0.73 (95% CI: 0.73, 0.74) for random forest. Both LASSO models had better calibration, with Brier scores 0.17 (LASSO) versus 0.20 (random forest) for CNS dysfunction and 0.20 (LASSO) versus 0.25 (random forest) for PNS dysfunction. CONCLUSIONS: LASSO outperformed random forest in predicting CNS and PNS dysfunction among fluoroquinolone users, and should be considered for modeling when the cohort is modest in size, when the number of model predictors is modest, and when predictors are primarily binary.

Development and validation of an instrument for measuring parkinsonian motor impairment: TRAPS-D.

BACKGROUND: Parkinson's disease is incurable, idiopathic, degenerative, and progressive, and affects about 1% of the elderly population. Multidisciplinary clinical treatment is the best and most adopted therapeutic option, while surgical treatment is used in less than 15% of those affected. In practice, there is a lack of reliable and validated scales for measuring motor impairment, and monitoring and screening for surgical indications. OBJECTIVE: To develop and validate an instrument for measuring parkinsonian motor impairment in candidates for neurosurgical treatment. METHOD: The development and validation methods followed published guidelines. The first part was the choice of domains that would make up the construct: cardinal signs of disease (tremor, rigidity (stiffness), posture/balance/gait, hypokinesia/akinesia, and speech), along with pain and dyskinesia. A multi-professional working group prepared an initial pilot instrument. Ten renowned specialists evaluated, judged, and suggested modifications to the instrument. The second phase was the evaluation of the content of each domain and the respective ability to classify commitment intensity. The third phase was the correction of the main flaws detected and new submission to the board. The instrument was applied to 41 candidates for neurosurgical treatment in two situations: with and without medication RESULTS: The final form received 100% agreement from the judges. Its average time for application was 8 min. It was very responsive (p = 0.001, Wilcoxon) in different situations (On-Off). CONCLUSION: TRASP-D is a valid instrument for measuring motor impairment in patients with Parkinson's disease who are candidates for neurosurgical treatment. It allows measurement in multiple domains with reliability and sensitivity.

[Neurocovid-19: effects of COVID-19 on the brainNeurocovid-19: efeitos da COVID-19 no cérebro]. / Neurocovid-19: efectos del COVID-19 en el cerebro.

In the COVID-19 pandemic, direct and indirect effects on mental health have been reported, including neurological, neuropsychiatric, and neuropsychological symptoms with possible long-term effects. Also, it is suspected that in the coming years there could be a worldwide increase in the incidence of neurodegenerative disorders.The objective of this article is to review the most up-to-date information on brain damage associated with COVID-19, as well as the neuropsychiatric symptoms of the disease. The exact mechanisms of brain damage have not yet been clarified, and further longitudinal and international research-including studies that incorporate epidemiological, clinical, and diagnostic variables-is required to define these mechanisms and establish their impact on mental health, as well as their long-term consequences.

Durante a pandemia de COVID-19 foram relatados efeitos diretos e indiretos na saúde mental, incluindo sintomas neurológicos, neuropsiquiátricos e neuropsicológicos com possíveis efeitos no longo prazo, e suspeita-se que nos próximos anos poderá haver um aumento nas taxas de incidência de doenças neurodegenerativas em todo o mundo.O objetivo deste artigo é revisar as informações mais atualizadas sobre os danos cerebrais associados à COVID-19 e seus sintomas neuropsiquiátricos. Os mecanismos exatos desses danos ainda não foram esclarecidos, sendo necessário continuar com pesquisas longitudinais e internacionais ­ incluindo estudos que contenham variáveis ­ epidemiológicas, clínicas e diagnósticas ­ para defini-los e estabelecer sua repercussão na saúde mental, bem como suas consequências no longo prazo.

[Central nervous system adverse events potentially associated with drugs used for COVID-19: scoping reviewEventos adversos en el sistema nervioso central potencialmente relacionados con los medicamentos para tratar la COVID-19: revisión exploratoria]. / Eventos adversos no sistema nervoso central potencialmente relacionados aos medicamentos utilizados na COVID-19: revisão de escopo.

Objective: To identify central nervous system (CNS) adverse events potentially associated with prophylaxis or drug treatment for COVID-19, and to describe the characteristic of the individuals affected. Methods: A scoping review was performed using a search strategy to retrieve articles from PubMed, EMBASE, SciELO, Scopus, CINAHL and BVS databases. Studies reporting on individuals receiving prophylactic or curative drugs for COVID-19 with at least one CNS adverse event were included. Articles reporting on CNS adverse events associated with medication for other health conditions were excluded. Results: The search retrieved 1 547 articles, eight of which met the inclusion criteria. Seven studies had an observational design. A total of 3 035 individuals were assessed, of whom 1 701 were health care professionals and 1 978 were women. Curative treatment with hydroxychloroquine, chloroquine, lopinavir/ritonavir, and azithromycin was the most frequent (n = 5). The most common adverse events were headache, dizziness, mood disturbances, and drowsiness. Suicide was the most frequent severe event. Six adverse events were unexpected for hydroxychloroquine, chloroquine, and doxycycline. Conclusion: Potential CNS adverse events were unspecific and in general potentially associated with the use of hydroxychloroquine (monotherapy or associated with antibiotics). The data confirm the unfavorable risk/benefit profile of these drugs for the prevention and management of signs and symptoms of SARS-CoV-2 infection.

Objetivo: Identificar los eventos adversos en el sistema nervioso central (SNC) potencialmente relacionados con el uso de medicamentos empleados para profilaxis o tratamiento de la COVID-19, y caracterizar a las personas afectadas. Métodos: Se realizó una revisión exploratoria a partir de una estrategia de búsqueda en las bases de datos PubMed, EMBASE, SciELO, Scopus, Cummulative Index to Nursing and Allied Health Literature (CINAHL) y la Biblioteca Virtual de Salud (BVS). Se incluyeron estudios de personas que emplearon medicamentos con fines profilácticos o curativos para la COVID-19 y presentaron al menos un evento adverso en el SNC. Se excluyeron los artículos en los cuales se notificaron eventos adversos en el SNC potencialmente relacionados con medicamentos para tratar otros problemas de salud. Resultados: Se recuperaron 1 547 artículos, de los cuales ocho cumplieron con los criterios de admisibilidad. Siete estudios tuvieron un diseño observacional. Se analizaron 3 035 personas, de las cuales 1 701 eran profesionales de salud y 1 978, mujeres. El tratamiento más utilizado fue el curativo (n = 5), con hidroxicloroquina, cloroquina, lopinavir/ritonavir y azitromicina. Los eventos adversos comúnmente citados fueron dolor de cabeza, mareos, trastornos del estado de ánimo y somnolencia. El suicidio fue el evento grave más frecuente. Seis eventos inesperados (mioclonías, temblor, trastorno de la marcha, disgeusia, hiperhidrosis y desasosiego) guardaron relación con el empleo de hidroxicloroquina, cloroquina y doxiciclina. Conclusión: Los eventos adversos del SNC fueron inespecíficos y, en general, posiblemente estuvieron relacionados con el uso de hidroxicloroquina (sola o combinada) para el tratamiento curativo de la COVID-19. Los datos corroboran la relación desfavorable de riesgo/beneficio de esos medicamentos en la prevención y el manejo de los signos y síntomas de la infección por el SARS-CoV-2.

Headache, anosmia, ageusia and other neurological symptoms in COVID-19: a cross-sectional study.

BACKGROUND: Neurological symptoms are frequent among patients with COVID-19. Little is known regarding the repercussions of neurological symptoms for patients and how these symptoms are related to one another. OBJECTIVES: To determine whether there is an association between the neurological symptoms in patients with COVID-19, and to characterize the headache. METHOD: This was a cross-sectional study. All hospital inpatients and health workers at the Hospital Universitario Oswaldo Cruz with a PCR-confirmed COVID-19 infection between March and June 2020 were considered for the study and were interviewed by telephone at least 2-months after the acute phase of the disease. These patients were identified by the hospital epidemiological surveillance department. A semi-structured questionnaire was used containing sociodemographic and clinical data and the ID-Migraine. RESULTS: A total of 288 patients was interviewed; 53.1% were male; with a median age of 49.9 (41.5-60.5) years; 91.7% presented some neurological symptom; 22.2% reported some neurological symptom as the symptom that troubled them most during COVID-19. Neurological symptoms were: ageusia (69.8%), headache (69.1%), anosmia (67%), myalgia (44.4%), drowsiness (37.2%), agitation (20.8%); mental confusion (14.9%), syncope (4.9%) and epileptic seizures (2.8%). Females, those who presented with fever, sore throat, anosmia/ageusia and myalgia also presented significantly more with headache (logistic regression). The most frequent headache phenotype was a non-migraine phenotype, was of severe intensity and differed from previous headaches. This persisted for more than 30 days in 18% and for more than 90 days in 10% of patients. Thirteen percent of those with anosmia and 11% with ageusia continued with these complaints after more than 90 days of the acute phase of the disease. Aged over 50 years, agitation and epileptic seizures were significantly associated with mental confusion (logistic regression). CONCLUSION: Headache is frequent in COVID-19, is associated with other symptoms such as fever, sore throat, anosmia, ageusia, and myalgia, and may persist beyond the acute phase of the disease.

Inflammatory Disorders of the Central Nervous System Vessels: Narrative Review.

Inflammatory disorders of the central nervous system (CNS) vessels, also called CNS vasculitides, can cause substantial disability or even be fatal. Inflammation of the CNS vessels can be caused by primary angiitis of the CNS (PACNS), inflammatory cerebral amyloid angiopathy, or systemic inflammatory disorders. Clinical symptoms of these disorders are often non-specific, such as encephalopathy, cognitive and affective abnormalities, headache and focal neurological symptoms. Diagnostic workup includes a thorough neuropsychiatric examination, blood and cerebrospinal fluid analysis and magnetic resonance imaging (MRI) of the brain and its vessels. Biopsy of the brain remains the gold standard diagnostic test. Timely diagnosis and treatment initiation is of high importance, as it might prevent severe complications, such as ischemic and hemorrhagic stroke. In this review, we describe the specific characteristics of primary and secondary non-infectious CNS vasculitides which help to establish the diagnosis, discuss the peculiarities of the diagnostic workup and present current treatment recommendations.

What can the neurological manifestations of COVID-19 tell us: a meta-analysis.

BACKGROUND: Covid-19 became a global pandemic in 2019. Studies have shown that coronavirus can cause neurological symptoms, but clinical studies on its neurological symptoms are limited. In this meta-analysis, we aimed to summarize the various neurological manifestations that occurred in COVID-19 patients and calculate the incidence of various neurological manifestations. At the same time, we further explored the mechanism of nervous system injury and prognosis in COVID-19 patients in combination with their nervous system manifestations. This study provides a reference for early clinical identification of COVID-19 nervous system injury in the future, so as to achieve early treatment and reduce neurological sequelae. METHODS: We systematically searched all published English literature related to the neurological manifestations of COVID-19 from January 1, 2020, to April 30, 2021, in Pubmed, Embase, and Cochrane Library. The keywords used were COVID-19 and terminology related to the nervous system performance. All included studies were selected by two independent reviewers using EndNote and NoteExpress software, any disagreement was resolved by consensus or by a third reviewer, and the selected data were then collected for meta-analysis using a random-effects model. RESULTS: A total of 168 articles (n = 292,693) were included in the study, and the meta-analysis showed that the most common neurological manifestations of COVID-19 were myalgia(33%; 95%CI 0.30-0.37; I2 = 99.17%), smell impairment(33%; 95%CI 0.28-0.38; I2 = 99.40%), taste dysfunction(33%; 95%CI 0.27-0.39; I2 = 99.09%), altered mental status(32%; 95%CI 0.22-0.43; I2 = 99.06%), headache(29%; 95%CI 0.25-0.33; I2 = 99.42%), encephalopathy(26%; 95%CI 0.16-0.38; I2 = 99.31%), alteration of consciousness(13%; 95%CI 0.08-0.19; I2 = 98.10%), stroke(12%; 95%CI 0.08-0.16; I2 = 98.95%), dizziness(10%; 95%CI 0.08-0.13; I2 = 96.45%), vision impairment(6%; 95%CI 0.03-0.09; I2 = 86.82%), intracerebral haemorrhage(5%; 95%CI 0.03-0.09; I2 = 95.60%), seizure(4%; 95%CI 0.02 -0.05; I2 = 98.15%), encephalitis(2%; 95%CI 0.01-0.03; I2 = 90.36%), Guillan-Barré Syndrome (GBS) (1%; 95%CI 0.00-0.03; I2 = 89.48%). CONCLUSIONS: Neurological symptoms are common and varied in Covid-19 infections, and a growing number of reports suggest that the prevalence of neurological symptoms may be increasing. In the future, the role of COVID-19 neurological symptoms in the progression of COVID-19 should be further studied, and its pathogenesis and assessment methods should be explored, to detect and treat early neurological complications of COVID-19 and reduce mortality.

Porphyria attacks in prepubertal children and adolescents.

CONTEXT: The clinical and laboratory features of dominant acute hepatic porphyrias (AHPs) in prepubertal children and adolescents have not been well established. OBJECTIVE: To evaluate clinical and laboratory features of AHPs in prepubertal children and adolescents compared to adults. DATA SOURCES: OVID (Embase Classic+Embase and MEDLINE), Scopus, and Google Scholar. STUDY SELECTION: Studies describing symptomatic children or adolescents (<18 years old) with increased urinary porphobilinogen were included. DATA EXTRACTION: Two reviewers independently extracted the data, with a third reviewer arbitrating discrepancies. RESULTS: 100 studies were included describing 112 patients (26 prepubertal children and 86 adolescents). Differences were found between prepubertal children and adolescents regarding sex distribution (female-to-male ratio: 1:2 vs. 4:1), clinical manifestations, and concomitant clinical manifestations. LIMITATIONS: There was variation in the methods used to diagnose porphyria attacks across studies, and some elements of the quality of individual studies were unclear. CONCLUSIONS: Prepubertal children with AHPs and porphyria attacks presented with distinct demographic and clinical characteristics from adolescents and adults. Nearly two-thirds of the affected children were males, and about half had a concomitant medical condition that can constitutively upregulate hepatic δ-aminolevulinic acid synthase-1. Adolescents were comparable to adults in almost all respects.

Respiratory Syncytial Virus-Associated Neurologic Complications in Children: A Systematic Review and Aggregated Case Series.

OBJECTIVES: To describe the features and frequency of respiratory syncytial virus (RSV)-associated severe acute neurologic disease in children. STUDY DESIGN: We performed a systematic review of the literature to identify reports of severe acute neurologic complications associated with acute RSV infection in children aged <15 years (PROSPERO Registration CRD42019125722). Main outcomes included neurologic, clinical, and demographic features of cases and the frequency of disease. We aggregated available case data from the published literature and from the Australian Acute Childhood Encephalitis (ACE) study. RESULTS: We identified 87 unique studies from 26 countries describing a spectrum of RSV-associated severe acute neurologic syndromes including proven encephalitis, acute encephalopathy, complex seizures, hyponatremic seizures, and immune-mediated disorders. The frequency of RSV infection in acute childhood encephalitis/encephalopathy was 1.2%-6.5%. We aggregated data from 155 individual cases with RSV-associated severe acute neurologic complications; median age was 11.0 months (IQR 2.0-21.5), most were previously healthy (71/104, 68%). Seizure was the most frequently reported neurologic feature (127/150, 85%). RSV was detected in the central nervous system of 12 cases. Most children recovered (81/122, 66%); however, some reports described partial recovery (33/122, 27%) and death (8/122, 7%). CONCLUSIONS: RSV-associated neurologic complications have been widely reported, but there is substantial heterogeneity in the design and quality of existing studies. The findings from our study have implications for the investigation, management, and prevention of RSV-associated neurologic complications. Further, this systematic review can inform the design of future studies aiming to quantify the burden of childhood RSV-associated neurologic disease.