Evolution of motor and sensory deficits in amyotrophic lateral sclerosis estimated by neurophysiological techniques

Abstract

Although amyotrophic lateral sclerosis is a degenerative disease of the upper and lower motor neurons, there is evidence that the disease can affect other systems, including the sensory system. On the other hand, within the motor neuron pool there is possibly a predilection of the degenerative process for the motor neurons fibers with the fastest conduction velocity (MNFCV). We studied these two aspects of the disease in a group of 50 patients by prospectively assessing several sensory indices and by studying the selectivity of the spinal motor neuron loss. At baseline, nerve conduction studies and somatosensory evoked potentials showed abnormal slowing in the peripheral and central sensory pathways. Thermal thresholds for heating were elevated but were normal for cooling. In more than 60% of the patients at least one of the sensory tests studied was abnormal. However, except for a significant decrease in the amplitude of the sensory nerve action potentials of the sural nerves, these afferent dysfunctions were not progressive over the follow-up period of 6 months, in contrast to the marked deterioration in motor functions. Three different statistical models were applied to evaluate the presence of demyelination, selective loss of MNFCV, or the purely random degeneration of fast- and slow-conducting motor neurons. These data indicate a selective loss of the MNFCV and suggest that subclinical abnormalities of the sensory system in ALS are often present but almost nonprogressive. Furthermore, the amyotrophic lateral sclerosis disease process seems preferentially to affect MNFCV.

Targeting functional subtypes of spinal motoneurons and skeletal muscle fibers in vivo by intramuscular injection of adenoviral and adeno-associated viral vectors

“…Axons of fast motoneurons sprout less readily than axons of slow motoneurons and form neuromuscular junctions, which, in animal models are more vulnerable to motoneuron disease (Frey et al 2000). In patients with amyotrophic lateral sclerosis, neuromuscular transmission appears weaker in fast than slow motor units (Theys et al 1999).…”

Motoneurons Derived from Embryonic Stem Cells Express Transcription Factors and Develop Phenotypes Characteristic of Medial Motor Column Neurons

“…Enkephalin-containing GABAergic neurons projecting from the striatum to the external segment of the globus pallidus are the first to degenerate in patients with Huntington's disease (Reiner et al, 1988;Sapp et al, 1995). The fastest conducting, and presumably largest, motor neurons preferentially die in patients with amyotrophic lateral sclerosis (Theys et al, 1999).…”

A Mouse Model of Pharyngeal Dysphagia in Amyotrophic Lateral Sclerosis

“…Although ALS is classically considered a motor neuron disease, subtle evidence of sensory pathology of the central and peripheral neurons involved in limb sensation has been well documented [25][26][27][28][29][30]. It is currently unknown whether pathology of the central and peripheral sensory components involved in swallowing may be contributing to dysphagia in ALS.…”