Myoclonus is an extremely common expression of underlying cerebral dysfunction. In this sense, in many cases the presence of myoclonus is a relatively trivial observation, in that it is typically the underlying cause of the myoclonus which is the medical problem which requires attention and treatment.

It is likely that many forms of myoclonus lie on a spectrum between myoclonus and tremor, and the two phenomena have clinical and neurophysiological overlap. Some forms of myoclonus have clear-cut evidence for being of cortical origin, whereas others are cortical–subcortical or purely subcortical. From a clinical viewpoint, myoclonus is basically a jerk, and the usual differential diagnosis includes tics, dystonic jerks, chorea and exaggerated startle responses.

Typical definitions of myoclonus note that it is:

From a phenomenological perspective, differential can include:

Spasms, as seen in multiple sclerosis (tonic spasms), auto-immune encephalitis, stiff person syndrome and tetanus may also merit consideration.

Polyminimyoclonus was originally described in the setting of spinal muscular atrophy, and that movements associated with a clinical impression of polyminimyoclonus may have a number of causes, of which myoclonus is only one.

As noted elsewhere in this section, cortical tremor is a manifestation of underlying myoclonus.

The classification of myoclonus is variable and difficult, predominantly because of the very large number of disease processes that affect cerebral hemispheric function and that can bring about myoclonus.  A physiological approach has the benefit of being more manageable, as compared to a list of aetiologies, which tends to be lengthy. However, it should be pointed out that the utility of classifications is quite limited, and frequently does not contribute significantly to diagnosis or meaningful therapy.

 “Physiological classification of myoclonus is of both pathophysiological and practical importance given that myoclonus is managed differently according to its presumed generators”1. To some extent this statement is correct, and medical conditions do require classification for a number of valid reasons; however, by and large, treatment of myoclonus rests on a fairly restricted numbers of drugs, and there is no specific benefit from treating one form of myoclonus with a particular agent, or another type of myoclonus with a different agent.

The understanding of myoclonus is bedevilled by the inclusion of rare entities, some of which have marked geographical restriction, since are rate mutations found only in certain ethnic groups. For example, although Unverricht-Lundborg disease and sialidoses may be classical forms of myoclonus, they appear to be extremely uncommon in Africa.

It should also be pointed out that the neurophysiological investigation of myoclonus, which is largely aimed at indicating the presence of some degree of cortical excitability, is quite problematic. One physiological approach to myoclonus is to divide it into two groups, cortical and subcortical.  In this classification, cortical forms of myoclonus are defined by the presence of enlarged somatosensory evoked potentials (SEP), jerk-locked back-averaged (JLBA) potentials, and enhanced long latency reflexes (C reflexes), whereas subcortical forms are largely delineated by the absence of these features. In addition to cortical and subcortical types, the presence of generalized spike and wave discharges on EEG indicates the presence of cortical–subcortical interactions, analogous to absence seizures of idiopathic generalized epilepsy.  With respect to establishing whether cortical myoclonus is present, although myoclonic jerks are commonly understood to be less than 50 ms in duration, this is unlikely to be of sufficient specificity to exclude myoclonus if the duration is longer than 50 ms, as may be seen in epilepsia partialis continua, EPC. Similarly, although cortical myoclonus is defined by features of purported cortical excitability (enlarged SEP, C-reflex and JLBA potentials), many cases have only one or none of these physiological features. It is likely, given the wide range of pathological conditions that can lead to some form of cortical myoclonus, that the neurophysiological findings are broad and not pathognomonic. A well-established example is corticobasal degeneration, where no spike is detected on JLBA, but abnormal C-reflexes may be present. In a recent report, half of a group of patients with myoclonus had only one feature suggestive of cortical myoclonus: giant SEPs were found in less than half and JLBA seen in about one in five cases2.

The term cortical reflex myoclonus is not uncommonly used synonymously with cortical myoclonus. The descriptor reflex refers to the observation made that a peripheral stimulus applied to an extremity might result in a myoclonic jerk. It was hypothesized that the stimulus travelled from the periphery up to cortex and then elicited a cortical discharge, resulting in myoclonus. From these cases, the hypothesis was generalized to account for the presence of myoclonus in many forms of progressive myoclonic epilepsy and other brain disorders associated with myoclonus, the underlying concept being that cortex is diffusely hyperexcitable and that minimal peripheral cortical stimuli could travel up to cortex and thereby bring about reflex myoclonic jerks.

Stimulus sensitive myoclonus is a somewhat artificial concept usually commented on when the patient has myoclonus that results on application of a painful stimulus to an extremity, or when the distal interphalangeal joint is rapidly flexed. However, the overwhelming majority of patients with myoclonus display stimulus sensitivity, in that their myoclonus is exacerbated by posture-holding, in which case the stimulus consists of activation of spindle afferents by muscle stretch.

Myoclonus may be either positive or negative, and both forms are commonly found in the same affected patients. Positive and negative myoclonus is linked to an increase and decrease in tone respectively immediately prior to the jerk. Negative myoclonus is well established to have a preceding period of relatively diminished EEG activity immediately prior to the jerk.

In general, it is uncommon to see EEG discharges associated with myoclonic jerks, although they are a feature of juvenile myoclonic epilepsy and may be seen with progressive myoclonic epilepsies and paediatric conditions (Doose and Dravet syndromes).

 

  1. Kojovic M, Cordivari C, Bhatia K. Myoclonic disorders: a practical approach for diagnosis and treatment. Ther Adv Neurol Disord. 2011;4(1):47-62.
  2. Latorre A, Rocchi L, Cordivari C, Berardelli A, Bhatia KP, Rothwell JC. Reply: "Reappraisal of cortical myoclonus: Electrophysiology is the gold standard". Mov Disord. 2018;33(7):1191.