Safety and feasibility of transcranial direct current stimulation in amyotrophic lateral sclerosis - a pilot study with a single subject experimental design.

INTRODUCTION: Transcranial direct current stimulation (tDCS) has been explored as a neuromodulatory tool to prime motor function in several neurological disorders. Studies using tDCS in amyotrophic lateral sclerosis (ALS) are limited. We investigated the safety, feasibility and effects of long-term tDCS in an individual with ALS. METHODS: A 36-year-old male diagnosed with clinically definite ALS received 12 sessions each of anodal, sham, and cathodal tDCS. Outcome measures included disease progression (revised ALS functional rating scale (ALSFRS-R)), clinical measures of endurance and mobility, and corticomotor excitability. RESULTS: No adverse events or change in disease progression were noticed during the study. Small improvement in gait speed (15% increase) was noticed with anodal tDCS only. CONCLUSIONS: This case study demonstrates the safety and feasibility of long-term facilitatory and inhibitory tDCS on a single participant with ALS. This study serves as a guideline for implementing tDCS in future ALS trials.

Validation of Simplified Visual Acuity Testing Protocols in Amyotrophic Lateral Sclerosis.

High- and low-contrast visual acuity (HCVA, LCVA) are potential quantitative markers of neurological dysfunction in amyotrophic lateral sclerosis (ALS). The complex nature and duration of gold standard (GS) protocols precludes widespread use in neurology settings. This study compares simplified to GS visual acuity (VA) protocols. Monocular HCVA and LCVA were measured in ALS (n = 10) and control (n = 4) subjects using six protocols, varying by two chart and three refraction methods. Intraclass correlation coefficients between simplified and GS protocols ranged from 0.83 to 0.98 (HCVA, excellent agreement) and 0.56 to 0.75 (LCVA, moderate agreement). Differences between LCVA and GS protocols exceeded test-retest reliability. Simplified HCVA protocols using LCD (liquid crystal display) tablet charts and/or pinhole correction produced valid measurements. None of the modified LCVA testing protocols produced valid measurements.

Diffuse Colour Discrimination as Marker of Afferent Visual System Dysfunction in Amyotrophic Lateral Sclerosis.

Abnormalities of the inner and intermediate retinal structures in patients with amyotrophic lateral sclerosis (ALS) have been described using optical coherence tomography and histopathology. Colour vision is a potential marker of these structural changes. The purpose of this study is to test the hypothesis that colour vision impairment is associated with ALS. Monocular (right eye) colour vision was assessed in subjects with definite or probable ALS (n = 25, aged 50-80 years) and control (n = 21, aged 46-89 years) subjects with corrected near visual acuity of at least 20/40 using the L'Anthony D15 color test (desaturated), scored by c-index, a measure of diffuse colour discrimination. Of ALS subjects, 16/25 (64%) had impaired colour vision (c-index >1.8). Comparing with our normal subjects and accounting for age, 72% (n = 18) of ALS subjects had colour vision below the 50th percentile, 52% (n = 13) had colour vision below the 25th percentile, 24% (n = 6) had colour vision below the 10th percentile, and 8% (n = 2) had colour vision below the 2nd percentile. In multivariate models of ln(c-index) and age, the intercept was higher and the slope was flatter in ALS subjects, suggesting that colour vision deficits are more prominent in younger ALS patients. Diffuse colour discrimination deficits are detected in ALS subjects at younger ages than in control subjects. Further study is needed to confirm these findings and to determine if the ALS colour discrimination abnormalities correlate with structural markers of retinal involvement and ALS disease severity.

High and Low Contrast Visual Acuity Are Not Affected in Amyotrophic Lateral Sclerosis.

The afferent visual system may be affected by neuro-degeneration in amyotrophic lateral sclerosis (ALS) based on observations of visual function impairment and retinal inclusions on histopathology in ALS patients. To test the hypothesis that visual acuity is impaired in ALS, we compared three measures of visual acuity in ALS patients (n = 25) attending a multidisciplinary ALS clinic and age matched control subjects (n = 25). Bilateral monocular and binocular visual acuities were assessed using high contrast (black letters on white background) and low contrast (2.5%, 1.25% grey letters on white background) visual acuity charts under controlled lighting conditions following refraction. Binocular summation was calculated as the difference between binocular and best monocular acuity scores. There were no associations between binocular or monocular high contrast visual acuity or low contrast visual acuity and amyotrophic lateral sclerosis diagnosis (generalized estimating equation models accounting for age). Binocular summation was similar in both amyotrophic lateral sclerosis and control subjects. There was a small magnitude association between increased duration of ALS symptoms and reduced 1.25% low contrast visual acuity. This study does not confirm prior observations of impaired visual acuity in patients with amyotrophic lateral sclerosis and does not support this particular measure of visual function for use in broad scale assessment of visual pathway involvement in ALS patients.

Disseminated intravascular large-cell lymphoma with initial presentation mimicking Guillain-Barré syndrome.

We report a patient with intravascular large B-cell lymphoma who initially presented with acute ascending weakness and sensory changes. Electrodiagnostic testing and cerebral spinal fluid (CSF) studies were initially suggestive of a demyelinating polyneuropathy. Further clinical evaluation and testing were consistent with mononeuropathy multiplex. Autopsy revealed disseminated intravascular large-cell lymphoma. Intravascular large-cell lymphoma should be considered in the differential diagnosis of a rapidly evolving neuropathy associated with other organ involvement.

Organization of carboxysome genes in the thiobacilli.

The order of genes in the carboxysome gene clusters of four thiobacilli was examined and the possibility of the cluster forming an operon evaluated. Furthermore, carboxysome peptide homologs were compared with respect to similarities in primary sequence, and the unique structural features of the shell protein CsoS2 were described.