A comparative study of cognitive and behavioral profiles between sporadic and type 8 amyotrophic lateral sclerosis.

INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) type 8 (ALS8) is caused by VAPB gene mutations. The differences between neuropsychological and behavioral profiles of patients with sporadic ALS (sALS) and those with ALS8 are unclear. We aimed to compare cognitive performance and behavioral aspects between sALS and ALS8 patients. METHODS: Our study included 29 symptomatic ALS8 patients (17 men; median age 49 years), 20 sALS patients (12 men; median age 55 years), and 30 healthy controls (16 men; median age 50 years), matched for sex, age, and education. Participants underwent neuropsychological assessments focused on executive functions, visual memory, and facial emotion recognition. Behavioral and psychiatric symptoms were evaluated using the Hospital Anxiety and Depression Scale and the Cambridge Behavioral Inventory. RESULTS: Clinical groups (sALS and ALS8) exhibited lower global cognitive efficiency and impaired cognitive flexibility, processing speed, and inhibitory control compared with controls. ALS8 and sALS showed similar performance in most executive tests, except for poorer verbal (lexical) fluency in those with sALS. Apathy, anxiety, and stereotypical behaviors were frequent in both clinical groups. DISCUSSION: sALS and ALS8 patients demonstrated similar deficits in most cognitive domains and had comparable behavioral profiles. These findings should be considered in the care of patients.

Memory for emotional information in sporadic and Type 8 amyotrophic lateral sclerosis.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is often shown to cause episodic memory deficits. Here, we investigated whether such memory deficits are differentially expressed according to the emotional valence of stimuli and whether they are similarly reproduced in both individuals with sporadic ALS (sALS) and familial Type 8 ALS (ALS8). METHOD: Twenty individuals with sALS, 18 individuals with ALS8, and 19 healthy controls were recruited for the study. After a neuropsychological and psychopathological assessment, all participants responded to a recognition memory test wherein images varying in terms of valence were initially shown. After a short interval, the images were shown again intermixed with new images, and the participants' task was to indicate whether each image was "old" or "new" and to estimate the confidence in their responses. RESULTS: Both the sALS and the ALS8 groups showed significantly lower recognition of positive relative to negative valence images (d = 0.92 and d = 0.74, respectively), an effect that was completely absent for healthy controls (d = 0.17). These effects were qualified by a significant interaction involving the factors of valence and group (ηp² = 0.12). CONCLUSIONS: The current findings demonstrate that sALS and ALS8 are associated with decreased recognition of emotional information, an effect that is nonetheless restricted to positive valence stimuli. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Structural brain and spinal cord damage in symptomatic and pre-symptomatic VAPB-related ALS.

INTRODUCTION: The VAPB gene is associated with fALS (fALS 8). This disease presents a variable phenotype and no study sought to characterize its neuroanatomical abnormalities until now. This study aims to evaluate structural brain and spinal cord abnormalities in symptomatic and pre-symptomatic VAPB-related ALS. METHODS: This cohort included 10 presymptomatic and 20 symptomatic carriers of the Pro56Ser VAPB variant as well as 30 matched controls and 20 individuals with sporadic ALS. They underwent detailed clinical evaluation and MRI in a 3 T scanner. Using volumetric T1 sequence, we computed cerebral cortical thickness (FreeSurfer), basal ganglia volumetry (T1 Multi-atlas) and SC morphometry (SpineSeg). DTI was used to assess white matter integrity (DTI Multi-atlas). Groups were compared using a generalized linear model with Bonferroni-corrected p values<0.05. We also plotted VAPB brain expression map using Allen Human Brain Atlas to compare with imaging findings. RESULTS: Mean age of presymptomatic and symptomatic subjects were 43.2 and 51.9 years, respectively. Most patients had a predominant lower motor neuron phenotype (16/20). Sleep complaints and tremor were the most frequent additional manifestations. Compared to controls, symptomatic subjects had pallidal, brainstem and SC atrophy, whereas presymptomatic only had SC atrophy. This pattern also contrasted with the sALS group that presented motor cortex and corticospinal abnormalities. Brain structural damage and VAPB expression maps were highly overlapping. CONCLUSION: VAPB-related ALS has a distinctive structural signature that targets the basal ganglia, brainstem and SC, which are regions with high VAPB expression. Neuroanatomical SC changes are evident before clinical onset of the disease.

Optical coherence tomography in neurodegenerative disorders.

BACKGROUND: Structural imaging of the brain is the most widely used diagnostic tool for investigating neurodegenerative diseases. More advanced structural imaging techniques have been applied to early or prodromic phases, but they are expensive and not widely available. Therefore, it is highly desirable to search for noninvasive, easily accessible, low-cost clinical biomarkers suitable for large-scale population screening, in order to focus on making diagnoses at the earliest stages of the disease. In this scenario, imaging studies focusing on the structures of the retina have increasingly been used for evaluating neurodegenerative diseases. The retina shares embryological, histological, biochemical, microvascular and neurotransmitter similarities with the cerebral cortex, thus making it a uniquely promising biomarker for neurodegenerative diseases. Optical coherence tomography is a modern noninvasive imaging technique that provides high-resolution two-dimensional cross-sectional images and quantitative reproducible three-dimensional volumetric measurements of the optic nerve head and retina. This technology is widely used in ophthalmology practice for diagnosing and following up several eye diseases, such as glaucoma, diabetic retinopathy and age-related macular degeneration. Its clinical impact on neurodegenerative diseases has raised enormous interest over recent years, as several clinical studies have demonstrated that these diseases give rise to reduced thickness of the inner retinal nerve fiber layer, mainly composed of retinal ganglion cells and their axons. In this review, we aimed to address the clinical utility of optical coherence tomography for diagnosing and evaluating different neurodegenerative diseases, to show the potential of this noninvasive and easily accessible method.

Amyotrophic lateral sclerosis type 8 is not a pure motor disease: evidence from a neuropsychological and behavioural study.

OBJECTIVE: Amyotrophic lateral sclerosis type 8 (ALS8) is a familial form of motor neuron disease, with predominance of lower motor neuron degeneration, and is caused by mutation of the vesicle-associated membrane protein-associated protein B (VAPB). We aimed to compare the cognitive profile of patients with ALS8 and healthy controls (HC), and to screen for behavioural features in ALS8 patients. METHODS: The sample was composed of ALS8 patients (n = 22; 14 men; median age 48 years old; median disease duration 6.5 years) and HC (n = 33; 19 men; median age 48 years old). Patients and HC were matched for sex, age and educational level. Participants underwent behavioural, psychiatric (Hospital Anxiety and Depression Scale and Cambridge Behavioural Inventory-Revised) and neuropsychological assessments, focused on executive functions, visual memory, and facial emotion recognition. RESULTS: ALS8 patients exhibited subtle deficits in executive functions. Compared to controls, ALS8 patients were significantly impaired in measures of flexibility and inhibitory control. ALS8 patients and HC did not differ in scores of facial emotion recognition. There was clinically relevant anxiety and depression in 36% and 27% of ALS8 patients, respectively. Behavioural disorders such as stereotypic and motor behaviours were present in more than 30% of patients. CONCLUSIONS: ALS8 patients present mild executive dysfunction and behavioural changes such as mood disorders, apathy and stereotypic behaviour. Our findings suggest that ALS8 is not a pure motor disorder and it is associated with subtle cognitive and behavioural impairments.

Atypical subacute sclerosing panencephalitis: case report.

Subacute sclerosing panencephalitis (SSPE) is a progressive inflammatory disorder of the central nervous system with both poor prognosis and high mortality. The disease has been related to a persistent and aberrant measles virus infection and no effective treatment has been available. We report a case of SSPE with atypical features including seizures at onset and a fulminant course in a 8 years-old boy who had been previously immunized against measles.

Tetraparesis secondary to cervical ossification of the posterior longitudinal ligament: case report.

Ossification of the posterior longitudinal ligament (OPLL) is a rare cause of myelopathy in non-Oriental populations and relatively unrecognized by general practitioners. A case of an Afro-Brazilian 54-years-old woman presenting with tetraparesis due to cervical OPLL is presented. Emphasis is made for the inclusion of OPLL in the differential diagnosis of compressive cervical myelopathy.

Optical coherence tomography in neurodegenerative disorders / Tomografia de coerência óptica em doenças neurodegenerativas

ABSTRACT Structural imaging of the brain is the most widely used diagnostic tool for investigating neurodegenerative diseases. More advanced structural imaging techniques have been applied to early or prodromic phases, but they are expensive and not widely available. Therefore, it is highly desirable to search for noninvasive, easily accessible, low-cost clinical biomarkers suitable for large-scale population screening, in order to focus on making diagnoses at the earliest stages of the disease. In this scenario, imaging studies focusing on the structures of the retina have increasingly been used for evaluating neurodegenerative diseases. The retina shares embryological, histological, biochemical, microvascular and neurotransmitter similarities with the cerebral cortex, thus making it a uniquely promising biomarker for neurodegenerative diseases. Optical coherence tomography is a modern noninvasive imaging technique that provides high-resolution two-dimensional cross-sectional images and quantitative reproducible three-dimensional volumetric measurements of the optic nerve head and retina. This technology is widely used in ophthalmology practice for diagnosing and following up several eye diseases, such as glaucoma, diabetic retinopathy and age-related macular degeneration. Its clinical impact on neurodegenerative diseases has raised enormous interest over recent years, as several clinical studies have demonstrated that these diseases give rise to reduced thickness of the inner retinal nerve fiber layer, mainly composed of retinal ganglion cells and their axons. In this review, we aimed to address the clinical utility of optical coherence tomography for diagnosing and evaluating different neurodegenerative diseases, to show the potential of this noninvasive and easily accessible method.

RESUMO A avaliação estrutural do cérebro, feita por meio dos exames de neuroimagem, é a forma mais utilizada de ferramenta diagnóstica e de acompanhamento das doenças neurodegenerativas. Técnicas de imagem mais sofisticadas podem ser necessárias especialmente nas fases mais precoces, antes mesmo do surgimento de quaisquer sintomas, porém costumam ser caras e pouco acessíveis. Sendo assim, é de fundamental importância a busca de biomarcadores não invasivos, de fácil acesso e baixo custo, que possam ser utilizados para rastreio populacional e diagnóstico mais precoce. Nesse cenário, o número de estudos com ênfase em técnicas de imagem para avaliação estrutural da retina em pacientes com doenças neurodegenerativas tem aumentado nos últimos anos. A retina apresenta similaridade embriológica, histológica, bioquímica, microvascular e neurotransmissora com o córtex cerebral, tornando-se assim um biomarcador único e promissor nas doenças neurodegenerativas. A tomografia de coerência óptica é uma moderna técnica de imagem não invasiva que gera imagens seccionais bidimensionais de alta resolução e medidas volumétricas tridimensionais reprodutivas do disco óptico e da mácula. Essa tecnologia é amplamente utilizada na prática oftalmológica para o diagnóstico e o seguimento de diversas doenças oculares, como glaucoma, retinopatia diabética e degeneração macular relacionada à idade. A redução da espessura da camada de fibras nervosas da retina e das camadas de células ganglionares em pacientes com doenças neurodegenerativas foi demonstrada em diversos estudos clínicos nos últimos anos. Nesta revisão, abordamos as principais aplicações clínicas da tomografia de coerência óptica nas doenças neurodegenerativas e discutimos o seu papel como potencial biomarcador nessas afecções.

Ischemic stroke and patent foramen ovale: case report.

Approximately 40% of ischemic strokes have no clearly definable etiology and are termed cryptogenic strokes. Patent foramen ovale, a small communication between the left and right atria, is considered to be a risk factor for cerebral embolism. In this study, we report the case of a 29-year-old woman with diagnosis of ischemic stroke due to patent foramen ovale who has undergone percutaneous endovascular closure. The aim of this report is to discuss the relevant aspects of the patent foramen ovale and the cryptogenic stroke, its clinical presentation, diagnosis, management and recurrence.

Atypical subacute sclerosing panencephalitis: case report

Subacute sclerosing panencephalitis (SSPE) is a progressive inflammatory disorder of the central nervous system with both poor prognosis and high mortality. The disease has been related to a persistent and aberrant measles virus infection and no effective treatment has been available. We report a case of SSPE with atypical features including seizures at onset and a fulminant course in a 8 years-old boy who had been previously immunized against measles.

Panencefalite esclerosante subaguda (PES) é uma doença inflamatória e progressiva do sistema nervoso central com prognóstico reservado e alta mortalidade. A doença tem sido relacionada com a infecção persistente e anormal pelo vírus do sarampo e não há tratamento específico disponível. Relatamos um caso de PES com características atípicas representadas por início do quadro com crises convulsivas e apresentação fulminante em menino de 8 anos previamente imunizado contra o vírus do sarampo.

Tetraparesis secondary to cervical ossification of the posterior longitudinal ligament: case report

Ossification of the posterior longitudinal ligament (OPLL) is a rare cause of myelopathy in non-Oriental populations and relatively unrecognized by general practitioners. A case of an Afro-Brazilian 54-years-old woman presenting with tetraparesis due to cervical OPLL is presented. Emphasis is made for the inclusion of OPLL in the differential diagnosis of compressive cervical myelopathy.

Ossificação do ligamento longitudinal posterior (OLLP) é causa rara de mielopatia na população não Oriental e relativamente subdiagnosticada por clínicos gerais. Relata-se um caso de mulher de 54 anos descendência Afro-Brasileira com tetraparesia associada a OLLP cervical. Enfatiza-se a inclusão da OLLP como diagnóstico diferencial de mielopatia cervical compressiva.

Ischemic stroke and patent foramen ovale: case report / Acidente vascular encefálico isquêmico e forame oval patente: relato de caso

Approximately 40 percent of ischemic strokes have no clearly definable etiology and are termed cryptogenic strokes. Patent foramen ovale, a small communication between the left and right atria, is considered to be a risk factor for cerebral embolism. In this study, we report the case of a 29-year-old woman with diagnosis of ischemic stroke due to patent foramen ovale who has undergone percutaneous endovascular closure. The aim of this report is to discuss the relevant aspects of the patent foramen ovale and the cryptogenic stroke, its clinical presentation, diagnosis, management and recurrence.

Aproximadamente 40 por cento dos acidentes vasculares encefálicos isquêmicos não apresentam etiologia definida e são classificados como criptogênicos. O forame oval patente, uma pequena comunicação entre os átrios direito e esquerdo, é considerado um fator de risco para embolismo cerebral. No presente artigo, relatamos o caso de uma jovem de 29 anos com o diagnóstico de acidente vascular encefálico isquêmico decorrente do forame oval patente que foi submetida ao fechamento endovascular percutâneo. O presente relato discute aspectos relevantes da apresentação clínica, diagnóstico, manejo clínico e recorrência desta condição.

Leucoencefalopatia multifocal progressiva em um paciente com leucemia linfoblástica aguda: relato de caso / Progressive multifocal leukoencephalopathy in a patient with acute lymphoblastic leukemia: case report

Leucoencefalopatia multifocal progressiva é uma patologia em que os oligodendrócitos são destruídos pelo Poliomavírus JC, um agente infeccioso comum na infância, que persiste na forma latente. O vírus pode ser ativado em indivíduos imunocomprometidos, particularmente em pacientes com síndrome de imunodeficiência adquirida, linfoma e doença mieloproliferativas crônicas. Relatamos um caso de um jovem portador de leucemia cujos pais queixaram-se de seu distúrbio comportamental há um mês. O diagnóstico foi estabelecido por critérios clínico-radiológicos. Não houve confirmação etiológica por meios anátomo-patológico. O presente estudo aborda aspectos relevantes da apresentação clínica e diagnóstico desta patologia rara, assim como sua associação com a leucemia.