Myoclonus can arise from several levels in the nervous system, ranging from cerebral cortex to peripheral nerve. Cortical Myoclonus Cortical (or pyramidal) myoclonic jerks are mostly epileptic, brief (<50 ms), stimulus-sensitive, triggered by active or passive movement, muscle stretch or photic stimulation. Jerks are generated in the contralateral (pre)frontal cortex, and affect the distal limbs, arms more than legs. This is because of the more prominent motor cortical representation of distal as compared with proximal limb muscles. [3]
Focal Myoclonus Focal myoclonus results from a contralateral frontal lesion, such as epilepsia partialis continua in Rasmussen encephalitis or a Jacksonian march from a frontal tumour. Multi-focal Myoclonus Multi-focal myoclonus occurs in amyloid angiopathy (a multi-focal disease), Angelman syndrome and coeliac disease (interhemispheric facilitation). Table 2 outlines other associated conditions. Generalised Cortical Myoclonus Generalised cortical myoclonus (bilateral and synchronous) is a feature of a primary generalised epilepsy syndrome; other generalised seizures, for example, absences or generalised tonic-clonic seizures will accompany the myclonus. EEG may show generalised spike-and-wave activity between attacks, ictal polyspike and wave time- locked with the jerks, and absence of prefrontal Bereitschaft potential. (The Bereitschaft potential is the EEG potential that precedes volitional motor activity). Diffuse cortical hyperexcitability is confirmed by EEG photosensitivity (photoparoxysmal response) and giant somatosensory evoked potentials (P25 N33 complex >10 V). There may be a long-loop C-reflex at rest. The treatment of cortical myoclonus depends on its clinical context. Epileptic myoclonus is treated as part of the epileptic syndrome. Most patients with other seizure types need no specific treatment for the myoclonus. Where specific treatment is needed, there is class II evidence for piracetam (levetiracetam is an alternative) and class IV evidence for sodium valproate (remembering potential teratogenicity in women) and for clonazepam. There is only anecdotal evidence for other medications such as topiramate, zonisamide, primidone and phenobarbital. [4]
Subcortical Myoclonus Subcortical myoclonus manifests as a typically bilateral, non-epileptic, flexor jerk, affecting axial or proximal limb muscles. Contractions are typically more prolonged than cortical myoclonus (up to 500 ms). The movement may be provoked by a stimulus (eg, noise, giving an exaggerated startle reflex = hyperekplexia) or by an action or intention (LanceAdams syndrome). Jerks may originate in various regions: diencephalic (thalamic, basal ganglia; [5] see figure 3) or brainstem (reticular reflex myoclonus). Multi-channel electromyogram (EMG)recording may indicate rostro- caudal recruitment, for example, activation of facial nerve before trigeminal nerve innervated muscles. Other conditions associated with subcortical myoclonus are shown in Table 2. Clonazepam is the recommended treatment for subcortical myoclonus.
(Enlarge Image) Figure 3. MR scan (A) and perfusion CT scan (B) of a 73-year-old man with left-sided myoclonic jerks of <800 ms duration, showing abnormal signal in the right putamen. The jerks disappeared on the fifth antiepileptic drug, carbamazepine 400 mg daily. Clinical improvement accompanied resolution of MR (C) and CT (D) abnormalities (Civardi et al 2010). 5
Exaggerated startle (hyperekplexia) is where unexpected stimuli provoke proximal tonic stiffening, often with falls and associated vocalisation. [6] Infantile-onset dominantly inherited forms cause a startle-induced myoclonic jerk (startle reflex) followed by stiffness lasting several seconds. Sporadic cases typically present later and are not accompanied by tonic contraction. Hyperekplexia may be a prominent early feature of the recently described LGI1 antibody-associated autoimmune encephalitis. Clonazepam is the drug of choice. Spinal Myoclonus Spinal Segmental Myoclonus Spinal segmental myoclonus originates in the spinal cord, and is generated by pacemaker circuits involved in locomotion. Jerks affect muscles innervated by one or two neighbouring spinal segments (myotomes). The myoclonus is often stimulus-sensitive and rhythmic (13 Hz) and may occur during sleep as well as wakefulness. Propriospinal Myoclonus Propriospinal myoclonus involves several consecutive spinal segments. The source of activation is typically the mid-thoracic cord, causing initial abdominal spasm. From here, the stimulus spreads simultaneously rostrally and caudally via propriospinal pathways, causing a simultaneously ascending and descending rapid wave of jerks. Both these conditions are rare, typically caused by underlying spinal lesions, such as trauma, demyelination or arteriovenous malformation. Confirming the diagnosis and excluding non-organic jerks often requires multi-channel EMG with simultaneous, time-locked EEG recordings. The treatment is aimed at the underlying cause; some patients respond to clonazepam. Restless Legs Syndrome and Periodic Limb Movement in Sleep Although the underlying mechanism is incompletely understood, EMG studies may show a muscle recruitment pattern suggesting propriospinal myoclonus. Occasionally patients may have truncal jerks when awake or drowsy, in keeping with propriospinal myoclonus. However, this hypothesis does not account for coexisting subcortical pathology (eg, Parkinson's disease), the fact that movements are suppressible (resembling tics) and the variable duration of individual spasms (100 ms to 5 s). Peripheral Myoclonus This is caused by various root, plexus or nerve lesions. The onset is often delayed or follows a period of pain or paraesthesia affecting a denervated area (mimicking complex regional pain syndrome). The myoclonus is focal, involving denervated muscles, is often rhythmic and has low frequency. It may overlap or accompany fasciculation, myokymia and spasms. Hemifacial spasm is by far the commonest form of peripheral myoclonus. All other forms are rare.