Myoclonus: Phenomenology, etiology, physiology, and treatment

Clinical features

The whole body or most of it may be affected in a single jerk (generalized myoclonus) and with prominent involvement of the trunk could be called “axial” myoclonus. Many different parts of the body may be affected, not necessarily at the same time (multifocal myoclonus); or myoclonus may be confined to one particular region of the body (focal or segmental myoclonus) ( Video 18.1 ). Myoclonic jerks may occur repetitively and rhythmically or irregularly. They may be evident at rest, on maintaining a posture, or on movement (action myoclonus). Jerks may be triggered by external stimuli (reflex myoclonus), which can be visual, auditory, or somesthetic (touch, pin-prick, muscle stretch) ( Video 18.2 ).

Video 18.1 Examples of different types of myoclonus. (A) This patient presented with just some focal twitching of the left hand; present at rest, it was increased with movement. Subsequently, dementia developed, and a brain biopsy proved Alzheimer disease. (B) The second segment from this same patient taken 2 years later shows worsening of the myoclonus and difficulty in moving the arm. (C) The next patient has a multifocal myoclonus from an unknown encephalopathy. She has myoclonus at rest, but it is brought out with kinetic movement. She also has sensory evoked myoclonus that is triggered by quick stretches to the finger flexors.

Video 18.2 Examples of negative myoclonus. (A) This patient has Lafora body disease and demonstrates negative myoclonus, also called asterixis. (B) The second patient has negative myoclonus triggered by sensory stimuli. (A, Courtesy Hiroshi Shibasaki, MD.)

Pathophysiology

The clinical features of myoclonus and the results of electrophysiologic investigation allow a relatively precise prediction as to its site of origin in the nervous system ( ; ; ). On this basis, myoclonus may be shown to arise in the cerebral cortex (cortical myoclonus), in the brainstem (brainstem myoclonus), or in the spinal cord (spinal myoclonus). Rarely, lesions of spinal roots, nerve plexi, or peripheral nerves can cause myoclonus (peripheral myoclonus) ( ), although purists might say that true myoclonus arises only from the central nervous system. Hemifacial spasm, the result most often of neurovascular compression of the seventh cranial nerve, might be considered a form of peripheral myoclonus. Disorders arising from peripheral injury are discussed in more detail in Chapter 26 .

Cortical myoclonus, in which the abnormal activity originates in the sensorimotor cortex and is transmitted down the spinal cord in pyramidal pathways, may manifest as focal jerks, sometimes repetitive (epilepsia partialis continua), that can propagate into focal motor seizures, with or without secondary generalization ( ). Rapid rhythmic myoclonus can present as “cortical tremor” ( ).

Myoclonus arising in the brainstem may take different forms ( ). One employs the pathways responsible for the startle reflex, causing exaggerated startle syndromes and the hyperekplexias. Another is independent of startle mechanisms, but causes generalized muscle jerks (brainstem reticular myoclonus). A third is the palatal myoclonus (tremor) syndrome.

In the spinal cord, two forms of myoclonus are recognized; spinal segmental myoclonus affects a restricted body part, involving a few spinal segments, and propriospinal myoclonus produces generalized axial jerks, usually beginning in the abdominal muscles.

Neurophysiologic assessment

Polymyography (recording the duration, distribution, and stimulus sensitivity of electromyographic [EMG] activity in affected muscles) is the first step in assessing a patient with myoclonus ( ; ; ; ). Most myoclonic jerks are due to brief EMG bursts of 10 to 50 ms. In this circumstance, the origin must be a brief discharge of a cluster of neurons controlling the motor system, such as in primary motor cortex. The underlying physiology is likely to be a paroxysmal depolarizing shift (PDS), and, thus, is a “fragment of epilepsy.” Therefore, this type of myoclonus can be called epileptic myoclonus. EMG bursts in the 100-ms range are observed in select situations such as spinal myoclonus. Longer jerks of more than 100 ms are likely to be dystonic or functional (psychogenic), though occasionally these have been shown to be organic. In myoclonus, agonists and antagonists usually fire synchronously ( Fig. 18.1 ).

The distribution of muscles involved may suggest that it arises as a result of a lesion of a peripheral nerve, part of a plexus, a spinal root, or a restricted number of segments of the spinal cord (segmental myoclonus). Myoclonic muscle jerks affecting axial muscles (neck, shoulders, trunk, and hips) may arise in the brainstem as an exaggerated startle response or brainstem reticular myoclonus, or in the spinal cord. In brainstem myoclonus, there is no preceding cortical discharge. Cranial nerve muscles are usually activated from the XI nucleus up the brainstem; limb and axial muscles are activated in descending order. In propriospinal myoclonus, the first muscles activated are usually in the thoracic cord, with slow upward and downward spread. Cortical myoclonus is indicated when somatosensory evoked potentials produced by peripheral nerve stimulation are pathologically enlarged, and a cortical correlate can be back-averaged in the ongoing electroencephalogram (EEG) by triggering from the EMG of the muscle jerk ( ; ). Stimuli generating giant somatosensory evoked potentials often provoke a subsequent EMG burst of myoclonic activity (the C reflex) at a latency compatible with conduction through fast corticomotoneuron pathways from the motor cortex to muscle. The giant somatosensory evoked potentials usually consist of an enlarged P ₂₅ /N ₃₃ component; the first major cortical negative peak (N ₂₀ ), reflecting arrival of the sensory volley in the cortex, usually is of normal size. The motor volleys in cortical myoclonus activate the cranial and limb musculature in descending order via fast-conducting corticospinal pathways. Abnormal corticomuscular and intermuscular coupling also can be a sensitive physiologic feature in cortical myoclonus ( ). The increased cortical excitability in cortical myoclonus may well be due to loss of inhibitory interneurons ( ). Cortical reflex myoclonus usually consists of positive EMG discharges, but negative cortical reflex myoclonus also occurs ( ; ; ), where a giant somatosensory cortical potential is time-locked to EMG silence. Subcortical myoclonus is suggested when reflex myoclonus triggered by peripheral stimuli occurs after a latency that is too short to involve cortical pathways ( ; ).

Functional (psychogenic) myoclonus is suggested if stimulus-evoked jerks are of very variable latency and longer than a voluntary reaction time ( ; ; ), and when the Bereitschaftspotential is evident before EMG bursts on jerk-locked back-averaging of the EEG, as in voluntary movement ( ; ). Event-related desynchronization study, in addition to the Bereitschaftspotential, may increase the sensitivity ( ). Psychogenic myoclonus can affect any part of the body ( ). Findings that helped to establish the functional nature of the myoclonus are improvement with distraction or placebo, complexity of the movement rather than a simple jerk, prolonged latency to sensory induced jerks, and the presence of other psychogenic features such as incongruous sensory loss or false weakness. The general approach to functional disorders is reviewed in Chapter 27 .

carried out a large study to evaluate the utility of electrophysiologic testing in myoclonus. There were 72 patients with a variety of types of myoclonus and the physiologic assessment aided in establishing the diagnosis in about half the patients. Elsewhere the authors point out that, in their experience with referrals to the clinical neurophysiology laboratory, functional myoclonus is the most frequent followed next by cortical myoclonus ( ).

Cause

With regard to cause, many neurologic conditions may produce myoclonus and a classification has been published in a textbook of neurology ( Table 18.2 ) ( ; ; ; ). It is, however, useful to consider several broad categories.

Physiologic myoclonus refers to muscle jerks occurring in specific circumstances in normal subjects. These include sleep jerks (hypnic jerks) and hiccup. Essential myoclonus consists of multifocal myoclonus in which there is no other neurologic deficit or abnormality on investigation. Although this has traditionally been a category, even from the time of Lundborg, most cases of essential myoclonus are now recognized as dystonic myoclonus. Myoclonus of epilepsy refers to conditions in which the major clinical problem is one of epilepsy, but one of the manifestations of the epileptic attacks is myoclonic jerks. Symptomatic myoclonus refers to the many conditions in which generalized or multifocal muscle jerking is a manifestation of an underlying identifiable neurologic disease. Psychogenic (functional) myoclonus refers to myoclonus produced as a conversion symptom ( ; ; ).

In the survey by , symptomatic myoclonus was most common, followed by myoclonus of epilepsy and essential myoclonus. Dementing illnesses were the most common cause of symptomatic myoclonus. More modern epidemiology may offer different results because a retrospective study might miss myoclonus in patients with prominent epilepsy and because essential myoclonus is now only rarely considered. Finally, psychogenic myoclonus was not well recognized at the time of that study.