Fasciculations are caused by spontaneous depolarization of lower motor neurons, which results in contraction of the muscle fibers in the associated motor unit. Clinically this manifests as a visible twitch of the muscle beneath the skin. In most instances this twitching is not sufficient to cause joint movement, though this can be seen in late-stage motor neuron diseases in which a single motor unit may innervate a large territory within the muscle. Patients often become quite concerned by fasciculations due to their association with amyotrophic lateral sclerosis (ALS); however, unless weakness and/or hyperreflexia are present, more benign causes of fasciculations are substantially more likely.
Evaluation of fasciculations should include a careful examination of all body regions including the limbs, trunk, and bulbar regions. Patients should be examined with limited clothing to avoid obstructing the view of proximal fasciculations. Many patients describe muscle twitching that is not visible to the examiner despite a careful search of all body regions. In these instances, provided the remainder of the neurologic examination is unremarkable, reassure patients that a dangerous neurologic condition is unlikely and reexamine in 6 months to be sure there is no clinical change. It is quite unusual for these patients to progress to manifest a clinically discernable neurologic condition.
Fasciculations that occur repetitively in a single muscle are typically less concerning for ALS than more diffuse fasciculations. Electromyography and nerve conduction studies (EMG/NCS) are helpful for identifying nerve or nerve root injury which may explain the presence of focal fasciculations.
Diffuse fasciculations are substantially more concerning, as they are more likely to be related to a systemic or diffuse motor neuron/nerve root process.
Myokymia is due to the repetitive involuntary firing of multiple motor units in concert (grouped fasciculations). Limb myokymia is most commonly associated with a delayed radiation therapy effect, though it can occur rarely secondary to a radiculopathy or mononeuropathy in the absence of radiation exposure. Facial myokymia can be seen in multiple sclerosis or mass lesions; in such cases, a magnetic resonance image (MRI) of the brain should be performed.
Isaac syndrome is a disorder of motor neuron hyperactivity characterized by fasciculations, cramps, and impaired muscle relaxation. Issac syndrome is caused by autoantibodies usually directed against CASPR2 and less frequently LGI1. If the patient also has dysautonomia and a limbic encephalitis, then it is referred to as Morvan syndrome. During the needle EMG study of a patient with motor neuron hyperactivity, neuromyotonia may be seen. Neuromyotonia is characterized by very-high-frequency (> 100 Hz) spontaneous motor unit discharges that tend to rapidly dissipate. Issac syndrome can occur as an isolated autoimmune syndrome, in the setting of other disorders of autoimmunity (e.g., myasthenia gravis), or as a paraneoplastic process. Cancers most commonly associated with Isaac syndrome are thymoma, lung cancer, and lymphoma. Symptomatic treatment of fasciculations, cramps, and impaired muscle relaxation can be achieved with sodium channel antagonists, such as phenytoin or carbamazepine. Definitive treatment is immunosuppression with intravenous immunoglobulin (IVIG) or plasmapheresis. In paraneoplastic cases, treatment must also be directed at the underlying malignancy.
Rarely, hypocalcemia or hypomagnesemia may cause benign fasciculations; measurement of serum electrolytes can be considered in patients with risk factors for such abnormalities.
Diffuse fasciculations combined with diffuse weakness in the absence of numbness is highly concerning for a motor neuron disorder, such as ALS. Look for evidence of upper motor neuron dysfunction (i.e., brisk reflexes) to support this diagnosis. A thorough evaluation should be performed to exclude ALS mimics (see Chapter 96).