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It is well known the potential of severe acute respiratory coronavirus type 2 (SARS-CoV-2) infection to induce post-acute sequelae, a condition called Long COVID. This syndrome includes several symptoms, but the central nervous system (CNS) main one is neurocognitive dysfunction. Recently it has been demonstrated the relevance of plasma levels of neurofilament light chain (pNfL), as a biomarker of early involvement of the CNS in COVID-19. The aim of this study was to investigate the relationship between pNfL in patients with post-acute neurocognitive symptoms and the potential of NfL as a prognostic biomarker in these cases. A group of 63 long COVID patients ranging from 18 to 59 years-old were evaluated, submitted to a neurocognitive battery assessment, and subdivided in different groups, according to results. Plasma samples were collected during the long COVID assessment and used for measurement of pNfL with the Single molecule array (SIMOA) assays. Levels of pNfL were significantly higher in long COVID patients with neurocognitive symptoms when compared to HC (p = 0.0031). Long COVID patients with cognitive impairment and fatigue symptoms presented higher pNfL levels when compared to long COVID patients without these symptoms, individually and combined (p = 0.0263, p = 0.0480, and 0.0142, respectively). Correlation analysis showed that levels of cognitive lost and exacerbation of fatigue in the neurocognitive evaluation had a significative correlation with higher pNfL levels (p = 0.0219 and 0.0255, respectively). Previous reports suggested that pNfL levels are related with higher risk of severity and predict lethality of COVID-19. Our findings demonstrate that SARS-CoV-2 infection seems to have a long-term impact on the brain, even in patients who presented mild acute disease. NfL measurements might be useful to identify CNS involvement in long COVID associated with neurocognitive symptoms and to identify who will need continuous monitoring and treatment support.

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Leukoaraiosis is a neuroimaging marker of small-vessel disease that is characterized by high signal intensity on fluid-attenuated inversion recovery MRI. There is increasing evidence from pathology and neuroimaging suggesting that the structural abnormalities that characterize leukoaraiosis are actually present within regions of normal-appearing white matter, and that the underlying pathophysiology of white matter damage related to small-vessel disease involves blood-brain barrier damage. In this study, we aim to verify whether leukoaraiosis is associated with elevated signal intensity on fluid-attenuated inversion recovery imaging, a marker of brain tissue free-water accumulation, in normal-appearing white matter. We performed a cross-sectional study of adult patients admitted to our hospital with a diagnosis of acute ischaemic stroke or transient ischaemic attack. Leukoaraiosis was segmented using a semi-automated method involving manual outlining and signal thresholding. White matter regions were segmented based on the probabilistic tissue maps from the International Consortium for Brain Mapping 152 atlas. Also, normal-appearing white matter was further segmented based on voxel distance from leukoaraiosis borders, resulting in five normal-appearing white matter strata at increasing voxel distances from leukoaraiosis. The relationship between mean normalized fluid-attenuated inversion recovery signal intensity on normal-appearing white matter and leukoaraiosis volume was studied in a multivariable statistical analysis using linear mixed modelling, having normal-appearing white matter strata as a clustering variable. One hundred consecutive patients meeting inclusion and exclusion criteria were selected for analysis (53% female, mean age 68 years). Mean normalized fluid-attenuated inversion recovery signal intensity on normal-appearing white matter was higher in the vicinity of leukoaraiosis and progressively lower at increasing distances from leukoaraiosis. In a multivariable analysis, the mean normalized fluid-attenuated inversion recovery signal intensity on normal-appearing white matter was positively associated with leukoaraiosis volume and age (B = 0.025 for each leukoaraiosis quartile increase; 95% confidence interval 0.019-0.030). This association was found similarly across normal-appearing white matter strata. Voxel maps of the mean normalized fluid-attenuated inversion recovery signal intensity on normal-appearing white matter showed an increase in signal intensity that was not adjacent to leukoaraiosis regions. Our results show that normal-appearing white matter exhibits subtle signal intensity changes on fluid-attenuated inversion recovery imaging that are related to leukoaraiosis burden. These results suggest that diffuse free-water accumulation is likely related to the aetiopathogenic processes underlying the development of white matter damage related to small-vessel disease.

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Cognitive dysfunction is often reported in patients with post-coronavirus disease 2019 (COVID-19) syndrome, but its underlying mechanisms are not completely understood. Evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein or its fragments are released from cells during infection, reaching different tissues, including the CNS, irrespective of the presence of the viral RNA. Here, we demonstrate that brain infusion of Spike protein in mice has a late impact on cognitive function, recapitulating post-COVID-19 syndrome. We also show that neuroinflammation and hippocampal microgliosis mediate Spike-induced memory dysfunction via complement-dependent engulfment of synapses. Genetic or pharmacological blockage of Toll-like receptor 4 (TLR4) signaling protects animals against synapse elimination and memory dysfunction induced by Spike brain infusion. Accordingly, in a cohort of 86 patients who recovered from mild COVID-19, the genotype GG TLR4-2604G>A (rs10759931) is associated with poor cognitive outcome. These results identify TLR4 as a key target to investigate the long-term cognitive dysfunction after COVID-19 infection in humans and rodents.

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OBJECTIVES: This study aimed to analyze cognitive impairment associated with long-term coronavirus disease 2019 (COVID-19) syndrome and its correlation with anxiety, depression, and fatigue in patients infected with severe acute respiratory syndrome coronavirus. METHODS: This was a cross-sectional study of 127 patients with COVID-19. Tests to screen for neuropsychiatric symptoms included the Fatigue Severity Scale, Mini-Mental State Exam 2 (MMSE-2), Symbol Digit Modalities Test (SDMT), and Hospital Anxiety and Depression Scale. RESULTS: In cognitive tests, SDMT was abnormal in 22%, being more sensitive than MMSE-2 to detect cognitive changes. Furthermore, although manifestations such as fatigue, depression, and anxiety were frequent in the post-COVID-19 phase, these 3 conditions, known to contribute to cognitive impairment, were slightly correlated with worse performance on the rapid screening tests. CONCLUSIONS: In patients with mild COVID-19 and cognitive complaints, SDMT helped to confirm disturbances in the attention domain and processing speed.

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Olfactory dysfunction is reported frequently in patients with coronavirus disease 2019. However, an effective treatment for this dysfunction is unknown. The present study evaluated carbamazepine as a treatment option for olfactory dysfunction based on its use in cases of neuralgia, especially of the V cranial nerve. The study included 10 patients with coronavirus disease with olfactory complaints who were part of a cohort of 172 coronavirus disease patients monitored for late neurological manifestations. Carbamazepine was administered for 11 weeks. The adverse effects reported were drowsiness (9/10) and dizziness (2/10); 9 of the 10 patients reported improved olfactory function after carbamazepine treatment. While the role of carbamazepine in the control of post-coronavirus disease olfactory dysfunction could not be confirmed in this study, the satisfactory response observed in most patients in this series suggests that further studies are warranted.

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Xantomatose cerebrotendínea (XCT) é uma doença congênita autossômica recessiva rara multissistêmica do me-tabolismo do ácido biliar que leva ao acúmulo de intermediários do colesterol em diversos tecidos. A principal ma-nifestação da doença é o acometimento neurológico progressivo e irreversível, que inicia na infância e evolui com disfunção neurológica grave na fase adulta. Sintomas não neurológicos característicos como xantomas tendíneos, cataratas de início na infância e diarreia crônica infantil também podem estar presentes. No Brasil, não existe te-rapia medicamentosa para a doença. A principal abordagem terapêutica para retardar a progressão do quadro é o acompanhamento multidisciplinar com o objetivo de melhorar a qualidade de vida. Apesar dos sintomas iniciarem na infância, a maioria dos pacientes demora em média 16 anos para receber o diagnóstico, fase na qual o dano neurológico já é extenso e as abordagens terapêuticas não são mais eficazes. Neste estudo é relatado o caso de paciente de 47 anos com XCT que iniciou os sintomas na infância, com piora neurológica aos 38 anos e diagnóstico aos 44 anos, fase na qual a neurodegeneração já era grave e irreversível. Os testes laboratoriais e Imagem de Res-sonância Magnética indicaram alterações características da doença. Ressalta-se a importância de ter a XTC como diagnóstico diferencial na presença de um quadro neurológico progressivo, amplo e variado, associado com xanto-mas tendíneos e outros sinais e sintomas específicos. Por tratar-se de doença crônica e degenerativa, o diagnóstico precoce é essencial para que se possa instituir medidas que melhorem a qualidade de vida (AU)

Cerebrotendinous xanthomatosis (CTX) is a rare, multisystemic autosomal-recessive disease of biliary acid me-tabolism that leads to accumulation of cholesterol intermediates in multiple tissues. Its primary presentation is progressive and irreversible neurological damage, beginning in childhood and progressing to neurological dys-function in adulthood. There also are characteristic non-neurological symptoms, including tendinous xanthomas, cataracts beginning in childhood, and chronic infantile diarrhea. In Brazil, there is no available treatment for CTX. The primary therapeutic approach to slow disease progression is a palliative one, with multidisciplinary team. While CTX symptoms begin in childhood, most patients are diagnosed at approximately age 16, when neurological damage is extensive and therapeutic approaches are no longer effective. Here, we report a case of a 47-year-old female patient with CTX with symptoms beginning in childhood, with neurological worsening at the age of 38 and diagnosis at 44, at which neurodegeneration was already severe and irreversible. Laboratory tests and magnetic resonance imaging indicated characteristic symptoms. It is important to consider CTX as a differential diagnosis in the presence of a progressive, wide, and varied neurological picture, with tendinous xanthomas and other specific symptoms. Because it is a chronic and degenerative disease, early diagnosis is essential to establish measures to improve the quality of life (AU)

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RESUMO: Modelo do Estudo: Relato de caso. Importância do problema: No mundo, mais de três milhões de pessoas estão vivendo com deficiência física devido à hanseníase. O Brasil é o segundo país com o maior número de casos novos registrados.A magnitude e o alto risco de incapacidade mantêm a doença como problema de saúde pública. O diagnóstico de hanseníase em geral é simples. Porém, quadros com ausência de lesões cutâneas características, somente com alterações neurais, representam um desafio para o diagnóstico diferencial com outras doenças neurológicas. Comentários: Relatamos o caso de um paciente encaminhado ao serviço de neurologia com história clínica e eletroneuromiografia compatíveis com polineuropatia desmielinizante, sem qualquer lesão cutânea ao exame de admissão. O raciocínio clínico inicial foi direcionado para o diagnóstico das polineuropatias desmielinizantes inflamatórias adquiridas como Polineuropatia Desmielinizante Inflamatória Crônica (CIDP) e suas variantes. No entanto, após anamnese e exame físico detalhados, chamou a atenção a ausência do componente atáxico e a presença predominante de alterações sensitivas de fibra fina, espessamento de nervo e importante fator epidemiológico para hanseníase, motivando a suspeita e a in-vestigação desta enfermidade por meio da biópsia de nervo que foi sugestiva de hanseníase. Após três meses, em novo exame do paciente para biopsiar áreas de anestesia para reforçar o diagnóstico, observou-se o surgimento de extensas lesões levemente hipocrômicas no tronco e membros inferiores, cuja biópsia definiu o diagnóstico de hanseníase. (AU)

ABSTRACT: Study: Case report. Importance: Worldwide over three million people are living with disabilities due to leprosy. Brazil is the second country with the highest number of new cases registered. The magnitude and high risk of disability make the disease a public health problem. The diagnosis of leprosy can be simple. However, in the absence of skin lesions and with many possibilities of neurological impairment, diagnosis can become a challenge. Comments: We report the case of a patient referred to the neurology service with a clinical history and electrophysiological tests compatible with demyelinating polyneuropathy, without any skin lesion at admission examination. The initial clinical research was directed to the diagnosis of acquired inflammatory demyelinating polyneuropathies such as Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)and its variants. However, after anamnesis and detailed physical examination, the absence of the ataxic component and the predominant presence of sensory alterations of fine fiber, nerve thickening and important epidemiological factor for leprosy,led to the suspicion and investigation of this disease by nerve biopsy that was suggestive of leprosy. After three months, in a new patient examination "to perform a biopsy in areas of anesthesia" to reinforce the diagnosis, there was the appearance of extensive slightly hypochromic lesions in the trunk and lower limbs, whose biopsy defined the diagnosis of leprosy.(AU)

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