Myoclonus is a clinical term meaning a quick involuntary jerk, seen in normal subjects under certain circumstances, including sleep, and in certain disease states. It is important as a symptom that may impair function and as an
indicator of neurological dysfunction. Not until patients with
myoclonus and major functional disability were reported in the 1960s was attention given to understanding its basis and
pharmacotherapy. Reports of
myoclonus developing after anoxic
brain injury, and its response to treatment with the
serotonin precursor
5-hydroxytryptophan (5-HTP), drew special attention. Further experience showed that only a few patients with
myoclonus benefit from
5-HTP therapy.
Benzodiazepines (BDZs) are often helpful in the treatment of
myoclonus. Their beneficial effects decline with chronic administration because of drug tolerance, and the theoretical basis for BDZ responses remains unclear. The relationships between
myoclonus, clonus, and
epilepsy are discussed, as is the possible contribution of slow signaling transmembrane receptors to synchronization of motoneuron firing, which is suggested as a hallmark of
myoclonus.
Myoclonus may originate in many CNS sites, but the brain-stem reticular formation is especially relevant to
myoclonus. Brain-stem
serotonin neurons have special influence on spinal motoneurons, on startle responses, and on
myoclonus. Among
5-HT receptors, 5-HT1A receptors are related to some forms of
myoclonus, although 5-HT2 receptors are also implicated. GABAA receptors are related to some forms of
myoclonus. Blockade of GABAA receptors or
GABA synthesis regularly evokes convulsive
seizures, but administration of many
GABA agonists and some
GABA uptake blockers paradoxically may evoke
myoclonus. Injection of
GABA receptor blockers into some brain areas has
anticonvulsant effects. Stimulation of GABAA receptors may therefore promote or antagonize
myoclonus depending on which
GABA receptors are involved, the state of the system, etc. The role of
glycine receptors is well established in some animal models, but has yet to be clearly established for human
myoclonus.
Opiates may produce
myoclonus when given intrathecally or in high dosage. The concept of excitant
anesthetics and special function of certain
GABA receptors is discussed.