MYOCLONUS ( MEDSACPE)

Where is the Myoclonus Generated?

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.