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.

Behavioral manifestations in a Brazilian non-demented C9orf72-negative ALS population.

Cognitive decline and behavioral changes are common features in amyotrophic lateral sclerosis (ALS) and imply worse prognosis as well as increased disease burden for patients and caregivers. Currently, there is a lack of studies regarding behavioral profile in Brazilian ALS cohorts. We assessed the prevalence and profile of behavioral impairment (ALSbi) in a Brazilian non-demented C9orf72-negative ALS cohort according to broad behavioral assessment and the latest consensus. Among 76 initially recruited consecutive ALS patients, 70 were included, including seven ALS type 8 (VAPB-related ALS) individuals. Patients with Frontotemporal Dementia (FTD) diagnosis were excluded. Sixteen ALS patients (23%) were diagnosed as ALSbi. Among ALS type 8 individuals, 2 (28.6%) were diagnosed as ALSbi. Neuropsychiatric Inventory Questionnaire (NPI) total scores did positively correlate with age, but not with other demographic or clinical data. Apathy was the most prevalent finding in the ALSbi subgroup, although the prevalence (20%) was smaller than reported in previous literature. Dysphoria and anxiety were also prevalent findings in the whole ALS cohort. Future studies with larger cohorts and validated ALS-specific tools are needed in order to expand our knowledge.

Análise comparativa do volume hipocampal e talâmico em pacientes com epilepsia de lobo temporal mesial com e sem resposta adequada ao tratamento farmacológico / Comparative analysis of thalamic and hippocampal volume in patients with mesial temporal lobe epilepsy responsive or not to drug therapy

OBJETIVO: Verificar variação no volume hipocampal e talâmico entre pacientes com epilepsia de lobo temporal mesial (ELTM) refratários ou responsivos ao tratamento medicamentoso. MÉTODOS: Foram analisados 26 pacientes com ELTM com boa resposta ao tratamento medicamentoso (grupo "benigno"), 25 refratários e 23 controles por meio do delineamento manual dos limites anatômicos do hipocampo e tálamo, em cortes sequenciais das imagens de RM. O Software DISPLAY foi utilizado. Análise estatística foi realizada com o programa Systat 9. RESULTADOS: Houve diferença estatística entre os controles e os grupos benigno e refratário para os volumes do tálamo ipsilateral ao foco epileptogênico (p=0,00004). Não houve diferença estatística entre os três grupos para os volumes de tálamo contralateral ao foco epileptogênico. Houve correlação significativa entre hipocampo ipsilateral e tálamo ipsilateral ao foco epileptogênico (r=0,35 e p=0,004). Quanto maior a idade, menor o volume talâmico ipsilateral (p=0,002 e r=-0,37). CONCLUSÃO: Os dados demonstraram que atrofia hipocampal está presente também em pacientes com ELTM e bom controle medicamentoso, sem diferença significativa com a atrofia de pacientes refratários. A atrofia do tálamo foi correlacionada com a idade dos pacientes, o que também pode indicar que outros fatores além da frequência de crises influenciam o grau de lesão nesta estrutura.

OBJECTIVE: To investigate the variation of thalamic and hippocampal volume in patients with mesial temporal lobe epilepsy (MTLE) refractory or responsive to drug therapy. METHODS: We analyzed 26 patients with MTLE responsive to drug therapy, 25 refractory and 23 controls through the manual delineation of anatomic limits of the hippocampus and thalamus, in sequential sections of MR images. The DISPLAY software was used. Statistical analysis was performed using the program Systat 9. RESULTS: There were statistically significant differences between controls and patients groups for thalamic volumes ipsilateral to epileptogenic focus (p=0.00004). There was no statistical difference between the 3 groups for the volumes of the thalamus contralateral to the epileptogenic focus. There was significant correlation between ipsilateral hippocampus and thalamus ipsilateral to epileptogenic focus (r=0.35, p=0.004). The older the age, the lower the ipsilateral thalamic volume (p=0.002 and r=-0.37). CONCLUSION: The data showed that hippocampal atrophy is also present in patients with TLE and good seizure control. The atrophy of thalamus was correlated with the age of patients, which may also indicate that other factors besides the seizure frequency influences the degree of damage of this structure.