No abstract

ObjectiveTo evaluate MRI-based parameters as biomarkers of Amyotrophic Lateral Sclerosis (ALS) progression.MethodsTwenty-seven patients and 27 controls performed two clinical and MRI acquisitions 8 months apart. ALSFRS-R scale was used to quantify disease severity at both time points. Multimodal analyses of MRI included cortical thickness measurements (FreeSurfer software), analysis of white matter integrity using diffusion-tensor imaging (tract-based spatial statistics-TBSS) and measurement of cervical spinal cord cross-sectional area (SpineSeg software). All analyses were corrected for multiple comparisons. The standardized response mean (SRM = mean score change / standard deviation of score change) was calculated for all methods herein employed and used for comparison purposes.ResultsThere were 18 men and mean age at first examination was 51.9 years. Mean ALSFRS-R scores at baseline and follow-up were 34.0 and 29.0, respectively. There was no region with progressive cortical thinning, but there was significant brainstem volumetric reduction (p = 0.001). TBSS analyses revealed progressive increase of AD (axial diffusivity) and MD (mean diffusivity) at the corpus callosum (p < 0.05), whereas SpineSeg showed progressive cord area reduction (p = 0.002). Cervical spinal cord cross-sectional area reduction was the only MRI parameter that correlated with ALSFRS-R change (r = 0.309, p = 0.038). SRM for ALSFRS-R was 0.95, for cord area 0.95, for corpus callosum AD 0.62 and MD 0.65, and for brainstem volume 0.002.ConclusionsStructural MRI is able to detect short term longitudinal changes in ALS. Cervical spinal cord morphometry is a promising neuroimaging marker to assess ALS course.

Background: Functional evaluation instruments for patients with neuromuscular disorders are rare. The Motor Function Measure (MFM)

Factors associated with increased mortality and prolonged length of stay in an adult intensive care unit Fatores associados à maior mortalidade e tempo de internação prolongado em uma unidade de terapia intensiva de adultos

Objective ANO5‐related myopathy is an important cause of limb‐girdle muscular dystrophy (LGMD) and hyperCKemia. The main descriptions have emerged from European cohorts, and the burden of the disease worldwide is unclear. We provide a detailed characterization of a large Brazilian cohort of ANO5 patients. Methods A national cross‐sectional study was conducted to describe clinical, histopathological, radiological, and molecular features of patients carrying recessive variants in ANO5. Correlation of clinical and genetic characteristics with different phenotypes was studied. Results Thirty‐seven patients from 34 nonrelated families with recessive mutations of ANO5 were identified. The most common phenotype was LGMD, observed in 25 (67.5%) patients, followed by pseudometabolic presentation in 7 (18.9%) patients, isolated asymptomatic hyperCKemia in 4 (10.8%) patients, and distal myopathy in a single patient. Nine patients presented axial involvement, including one patient with isolated axial weakness. The most affected muscles according to MRI were the semimembranosus and gastrocnemius, but paraspinal and abdominal muscles, when studied, were involved in most patients. Fourteen variants in ANO5 were identified, and the c.191dupA was present in 19 (56%) families. Sex, years of disease, and the presence of loss‐of‐function variants were not associated with specific phenotypes. Interpretation We present the largest series of anoctaminopathy outside Europe. The most common European founder mutation c.191dupA was very frequent in our population. Gender, disease duration, and genotype did not determine the phenotype.

Sensory neuronopathies (SNs) are a specific subgroup of peripheral nervous system diseases characterized by primary degeneration of dorsal root ganglia and their projections. Multifocal sensory symptoms often associated to ataxia are the classical features of SN. Several different etiologies have been described for SNs, but immune-mediated damage plays a key role in most cases. SN may herald the onset of some systemic autoimmune diseases, which further emphasizes how important the recognition of SN is in clinical practice. We have thus reviewed available clinical, neurophysiological, and therapeutic data on autoimmune disease-related SN, namely, in patients with Sjögren's syndrome, autoimmune hepatitis, and celiac disease.

Friedreich's ataxia (FA) is the most frequent autosomal recessive ataxia and essentially considered a disease of the dorsal root ganglia and spinal cord. It is caused by homozygous GAA expansions in the Frataxin gene in most cases. Although only a few studies have addressed cerebral involvement in FA, cognitive symptoms have lately been emphasized. To evaluate brain damage in vivo, we employed whole-brain VBM and analysis of pre-defined regions of interest (ROIs) over the cerebellum to compare 24 patients with 24 age-and-sex-matched normal controls. (1)H-MRS of deep cerebral white matter (WM) was subsequently performed. Mean age of patients was 28 years (range 14-45), mean duration of disease was 14 years (range 5-28) and 11 were men. Mean length of shorter (GAA1) and longer (GAA2) alleles were 735 and 863, respectively. VBM analysis identified WM atrophy in the posterior cyngulate gyrus, paracentral lobule and middle frontal gyrus. ROIs over the infero-medial cerebellar hemispheres and dorsal brainstem presented gray matter atrophy, which correlated with duration of disease (r = -0.4). NAA/Cr ratios were smaller among patients (P = 0.006), but not Cho/Cr (P = 0.08). Our results provide evidence of axonal damage in the cerebellum, brainstem and subcortical WM in FA. This suggests that neuronal dysfunction is more widespread than previously thought in FA.

To estimate the frequency of and to characterize muscle excitability abnormalities in Machado-Joseph disease (MJD).Design: Machado-Joseph disease is a common autosomal dominant cerebellar ataxia caused by an unstable CAG trinucleotide repeat expansion. Muscle cramps and fasciculations are frequent and sometimes disabling manifestations. However, their frequency and pathophysiological mechanisms remain largely unknown. Symptomatic patients with MJD (hereinafter MJD patients) with molecular confirmation were assessed prospectively. A standard questionnaire addressing clinical features of muscle cramps and fasciculations was used. The Cramps Disability Scale was used to quantify crampsrelated disability. Patients underwent neurophysiological testing with routine techniques. F waves of the right median nerves were obtained, and persistence indexes were calculated. Four muscles (deltoid, first dorsal interossei, tibialis anterior, and vastus lateralis) were examined by needle electromyography. A semiquantitative scale (from 0 [no activity] to 4 [continuous activity]) was used to determine the frequency of rest fasciculations in each muscle.Results: Fifty MJD patients (29 men) were included in the study. Their mean age at examination was 46.3 years, their mean age at onset of the disease was 35 years, and the mean duration of disease was 11.2 years. Abnormal CAG n varied from 59 to 75 repeats. Forty-one patients presented with muscle cramps; in 10, this was their first symptom. The frequency of cramps varied between 1 and 90 episodes a week. For 15 patients, cramps were the chief complaint, frequently disturbing sleep or work (Cramps Disability Scale score, 2 or 3). Lower limbs were affected in 37 individuals, but unusual regions, such as the face and abdominal muscles, were also involved. Fasciculations were found in 25 individuals; in 8 patients, they included facial muscles. However, fasciculations were not a significant complaint for any of these patients. The clinical and neurophysiological profile of MJD patients with and without cramps was not significantly different. However, MJD patients with fasciculations had more severe damage to their peripheral nerves.Conclusions: Muscle excitability abnormalities were found in 41 MJD patients (82%), and they were the presenting complaint in 10 (20%). They are related to altered excitability of peripheral motor axons, but mechanisms underlying cramps and fasciculations are possibly distinct in MJD patients.