Fasciculation in amyotrophic lateral sclerosis: origin and pathophysiological relevance

Abstract

This review considers the origin and significance of fasciculations in neurological practice, with an emphasis on fasciculations in amyotrophic lateral sclerosis (ALS), and in benign fasciculation syndromes. Fasciculation represents a brief spontaneous contraction that affects a small number of muscle fibres, causing a flicker of movement under the skin. While an understanding of the role of fasciculation in ALS remains incomplete, fasciculations derive from ectopic activity generated in the motor system. A proximal origin seems likely to contribute to the generation of fasciculation in the early stages of ALS, while distal sites of origin become more prominent later in the disease, associated with distal motor axonal sprouting as part of the reinnervation response that develops secondary to loss of motor neurons. Fasciculations are distinct from the recurrent trains of axonal firing described in neuromyotonia. Fasciculation without weakness, muscle atrophy or increased tendon reflexes suggests a benign fasciculation syndrome, even when of sudden onset. Regardless of origin, fasciculations often present as the initial abnormality in ALS, an early harbinger of dysfunction and aberrant firing of motor neurons.

Muscular cramp: causes and management

“…Fasciculations arising from motoneuron cell bodies originate from the most excitable motoneurons, i.e. those most likely to fire during minimal voluntary activity . Increased motoneuronal excitability implies instability of the motoneuronal cell membrane, due to leakiness to potassium or sodium currents or from calcium influx from open NMDA or AMPA channels associated, in ALS, with glutamate toxicity .…”

“…those most likely to fire during minimal voluntary activity . Increased motoneuronal excitability implies instability of the motoneuronal cell membrane, due to leakiness to potassium or sodium currents or from calcium influx from open NMDA or AMPA channels associated, in ALS, with glutamate toxicity . It might also result, in part, from centrally mediated descending excitatory activity in the context of motoneuronal membrane instability .…”

Comparison of cross‐sectional areas and distal‐proximal nerve ratios in amyotrophic lateral sclerosis

“…In recent years, neuromuscular ultrasound has gained recognition as a noninvasive and complementary tool for the diagnosis of neuromuscular disorders . In ALS, ultrasound has proven useful in detecting fasciculations, a clinical hallmark of ALS . However, fasciculations may also be present in patients with multifocal motor neuropathy (MMN) and peripheral nerve hyperexcitability syndromes (PNHS), both of which may be mistaken for ALS, particularly in the early disease stages .…”

Sensory modulation of fasciculation discharge frequency

“…Fasciculations, a major and very early clinical feature of amyotrophic lateral sclerosis (ALS), represent spontaneous discharges of motor units or portions of motor units . There is only sparse scientific evidence that fasciculation discharges can be modulated.…”