Optical coherence tomography does not support optic nerve involvement in amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: In recent years a possible non-motor involvement of the nervous system in amyotrophic lateral sclerosis (ALS) has come into the focus of research and has been investigated by numerous techniques. Optical coherence tomography (OCT) - with its potential to reveal neuroaxonal retinal damage - may be an appropriate tool to investigate whether the anterior visual pathway is involved. Our aim was to determine whether OCT-based measures of retinal nerve fiber layer, ganglion cell layer, inner nuclear layer and outer nuclear layer thickness are abnormal in ALS, or correlated with disease severity. METHODS: Seventy-six ALS patients (144 eyes) and 54 healthy controls (108 eyes; HCs) were examined with OCT, including automated intraretinal macular segmentation. ALS disease severity was determined with the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised. RESULTS: There was no significant difference between ALS patients and HCs in any of the examined OCT measures. Moreover, OCT parameters showed no correlation with clinical measures of disease severity. CONCLUSIONS: These findings indicate that involvement of the anterior visual pathway is not one of the non-motor manifestations of ALS.

Multipoint incremental motor unit number estimation as an outcome measure in ALS.

BACKGROUND: Improved outcome measures are necessary to reduce sample size and increase power in amyotrophic lateral sclerosis (ALS) clinical trials. Motor unit number estimation (MUNE) is a potentially attractive tool. MUNE methods previously employed in multicenter trials exhibited excessive variability and were prone to artifact. OBJECTIVE: To evaluate a modification of standard incremental MUNE in a multicenter natural history study of subjects with ALS. METHODS: Fifty healthy subjects were evaluated twice and 71 subjects with ALS were studied repeatedly for up to 500 days. Side and nerve studied was based on clinical examination findings. Nerves were stimulated at 3 specified locations and 3 increments were obtained at each location. Average single motor unit action potential (SMUP) amplitude was calculated by adding the amplitude of the third increment at each location and dividing by 9; SMUP was divided into maximum CMAP amplitude to determine the MUNE. RESULTS: Test-retest variability was 9% in normal subjects. Average MUNE for normal subjects was 225 (±87), and was 41.9 (±39) among subjects with ALS at baseline. Subjects with ALS showed clear decrements over time, with an overage rate of decline of approximately 9% per month. SMUP amplitude increased with time in a fashion consistent with the known pathophysiology of ALS. CONCLUSION: Multipoint incremental MUNE has a number of attributes that make it attractive as an outcome measure in ALS and other diseases characterized by motor unit loss. It can be rapidly performed on any EMG machine and has repeatability and rates of decline that favorably compare to other previously described methods.

Targeted stem cell transplantation strategies in ALS.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder that results in paralysis and ultimately death due to respiratory failure. Transplantation of neural precursor cells (NPCs) derived from the central nervous system is a promising therapeutic strategy for treatment of brain and spinal cord disorders such as ALS. ALS is a particularly challenging disease for designing relevant therapies, and presently no effective treatment exists. Despite such daunting challenges, a number of the potential benefits of NPC transplantation coincide with the neuropathological obstacles associated with ALS, including neuronal and glial replacement and non-replacement functions such as delivery of trophic support. Knowledge of the underlying disease-specific pathways involved in neurodegeneration and the contributions of different cellular subtypes to the disease go hand-in-hand with advances in NPC transplantation biology, and will aid in targeting cell-specific therapies to neurodegenerative disorders such as ALS. It is with these multiple cell targets that NPC transplantation may lend itself well to understanding and possibly slowing disease processes. A number of studies have already demonstrated the potential benefits of cell transplantation in ALS models. Lastly, practical issues such as timing and method of cell delivery, immune suppression, and the need for combinatorial approaches with non-cell based strategies must all be considered for eventual translation to the clinic.

Pregnenolone sulfate augments NMDA receptor mediated increases in intracellular Ca2+ in cultured rat hippocampal neurons.

The ability of the neuroactive steroid pregnenolone sulfate to alter N-methyl-D-aspartate (NMDA) receptor-mediated elevations in intracellular Ca2+ ([Ca2+]i) was studied in cultured fetal rat hippocampal neurons using microspectrofluorimetry and the Ca2+ sensitive indicator fura-2. Pregnenolone sulfate (5-250 microM) caused a concentration-dependent and reversible potentiation of the rise (up to approximately 800%) in [Ca2+]i induced by NMDA. In contrast, the steroid failed to alter basal (unstimulated) [Ca2+]i or to modify the rise in [Ca2+]i that occurs when hippocampal neurons are depolarized by high K+ in the presence of the NMDA receptor antagonist CPP. These data suggest that the previously reported excitatory properties of pregnenolone sulfate may be due, in part, to an augmentation of the action of glutamic acid at the NMDA receptor.