REVIEW
Myoclonus: a pragmatic approach
Correspondence to
Dora Lozsadi, Department of
Neurosciences, St George’s
Hospital, Blackshaw Rd, London
SW17 0QT, UK;
lozsadi@doctors.org.uk
Dora Lozsadi
Abstract
Myoclonus is a brief (less than half a sec-
ond) contraction involving agonist and
antagonist muscles, leading to a sudden
jerk. It may be a normal phenomenon,
as in the so-called ‘sleep starts’. When
pathological, myoclonus is a symptom
of a broad range of neurological and
systemic diseases. Alternatively, it may
signal non-organic illness (8% of myo-
clonus is psychogenic). This review
provides pragmatic and systematic
guidance to the assessment and differ-
ential diagnosis of adult patients pre-
senting with myoclonus.
Introduction
We have all experienced physiologi-
cal myoclonus in the form of hiccups,
sneezes or sleep starts (hypnic jerks).
Myoclonus may sometimes be gener-
ated by a normal brain under toxic or
metabolic stress.1 Pathological myo-
clonus may occur in many neurologi-
cal diseases, such as epilepsy, dementia
or movement disorder. Subtle jerks
may pass unrecognised, for example,
teenagers with juvenile myoclonic
epilepsy may describe themselves as
‘clumsy’ due to jerks in the morning.
Myoclonus in the older people may
be misdiagnosed as unexplained falls
or a ‘bouncing gait’ (figure 1).
Myoclonus is transient in a quarter
of cases, responding to treatment of
the underlying cause. However, its
successful management depends on
correctly diagnosing the aetiology.
With such a wide range of causes,
the clinical assessment of pathological
myoclonus in adults requires a sys-
tematic approach. This review aims
to facilitate its management through
describing an approach to the clini-
cal review, differential diagnosis and
optimal treatment of patients with
myoclonus.
Practical Neurology 2012;12:215–224. doi:10.1136/practneurol-2011-000107
Definition
Myoclonus (or electric chorea) is a
sudden, brief (most often <100 ms),
jerky, shock-like involuntary move-
ment. It may be positive or negative.
When positive, the cause is the con-
traction of a single (or a group) ago-
nist and antagonist muscles. When
negative, there is transient (<500 ms)
interruption of tonic muscle tone,
with momentary weakness or loss of
postural tone, for example, asterixis
(‘liver flap’). Movements are always
simple (unlike chorea) and are not
suppressible voluntarily (unlike tics).
The numbers: incidence/prevalence
Myoclonus is not common. Its lifetime
prevalence compares with that of dys-
tonia or of cauda equina lesions. The
lifetime prevalence of myoclonus in
Minnesota, USA, excluding transient
myoclonus, was 8.6 per 100 000 popu-
lation. The prevalence increases after the
age of 50. For example, among 85-year-
olds, it may be as high as 40 per 100 000.
Perhaps 0.5% of nursing home residents
have myoclonus, and 1.2% of people
with Alzheimer’s dementia have myo-
clonus (an up to 50% in the advanced
stages). Over 27% of myoclonus is tran-
sient, mostly from drug adverse effects
or metabolic abnormalities. About 8%
of myoclonus is psychogenic.
Is it myoclonus?
Positive myoclonus is usually easy to
recognise as a rapid, simple, brief move-
ment of a limb or limbs, often with an
identifiable trigger. This must be distin-
guished from other involuntary move-
ments such as tics, tremor (figure 2),
dystonia and psychogenic movement
disorders (table 1). In complex cases,
the bedside classification of abnor-
mal movements may not be possible.
Neurophysiology should then help,
215
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Figure 1 Proximal lower limb myoclonus (presumed subcortical) leading
to loss of balance and falls (image downloaded from internet).
Figure 2 Multi-channel EMG of (A) cortical myoclonus affecting the arm from a contralateral frontal glioma. Note the synchronised activity in agonist
and antagonist muscles. (B) Lower limb tremor leading to rhythmic, alternating activation of agonist and antagonist muscles. Note these features do not
distinguish myoclonus from tremor (Meinck 2007).2
216 Practical Neurology 2012;12:215–224. doi:10.1136/practneurol-2011-000107
for example, EEG, multi-channel EMG (with or
without time-locked EEG and back-averaging;
figure 2) and magnetoencephalography.2
Negative myoclonus – a sudden brief loss of tone –
is harder to recognise and must be actively sought,
watching the patients holding out their arms.
Negative myoclonus is an important cause of unex-
plained falls in the older subjects (bouncing gait).
Clinical approach
After deciding the patient has myoclonus:
■ explore the clinical context
■ determine the features of the myoclonus
■ consider where within the nervous system the
myoclonus arises
■ look for associated features.
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Table 1 Myoclonus mimics

Myoclonus Positive myoclonus
• Active contraction of group of agonist and antagonist muscles followed by an inhibitory phase (figure 2)
• Rarely vocal (causing hiccup)
• Mostly <100 ms
• Involuntary, non-suppressible
• Often stimulus-sensitive
Negative myoclonus • Brief loss of muscle tone
• Less common
Tics Often vocal; non-stereotyped; voluntarily suppressible
Tremor Rhythmic, involuntary oscillatory movement of a body part; alternating contraction of agonist then antagonist muscles
(figure 2); agonist and antagonist contractions may follow distinct rhythmicity
Dystonia Complex movements; duration >100 ms
Psychogenic Contraction always >50 ms; preceded by prefrontal Bereitschaft potential on EEG back-averaging; movements abate and stop
with distraction; movements do not occur in sleep; often with other non-organic features
Clonic (and other) seizures Rapid, rhythmic events; difficult to differentiate from myoclonic jerks (which are stand alone or arrhythmic); note that myoclonic
jerks may comprise a part of other seizures, for example, generalised tonic-clonic seizures
Cataplexy Brief (<2 min) atonia, triggered by laughter or other emotion; brainstem inhibition of muscle tone; muscle tone loss is gradual,
rarely causing injury; associated with other narcolepsy features

Generalised cortical myoclonus

History taking should focus on age of onset, family
history, precipitating events (hypoxia, toxins, medi-
cations), triggers (sensory stimulus, movement),
the body parts involved and the rhythmicity of the
myoclonus. Looking for associated neurological
symptoms and signs (dystonia, cerebellar signs, sei-
zures, etc) or neurological syndromes (eg, dementia)
helps to select appropriate investigations, to identify
underlying pathology and to optimise treatment.
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, trig-
gered by active or passive movement, muscle stretch
or photic stimulation. Jerks are generated in the
contralateral (pre)frontal cortex, and affect the dis-
tal 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 angio-
pathy (a multi-focal disease), Angelman syndrome
and coeliac disease (interhemispheric facilitation).
Table 2 outlines other associated conditions.
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 µV). 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 spe-
cific 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 (remem-
bering potential teratogenicity in women) and
for clonazepam. There is only anecdotal evidence
for other medications such as topiramate, zonisa-
mide, 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 typi-
cally more prolonged than cortical myoclonus
(up to 500 ms). The movement may be provoked by

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Table 2 Causes of cortical, subcortical and mixed myoclonus

Cortical myoclonus Mixed Subcortical myoclonus

Cortical lesions causing epileptic myoclonus Alzheimer’s disease Subcortical brainstem lesions
Myoclonic epilepsy with ragged-red fibres Lance–Adams syndrome Metabolic, for example, renal failure
Coeliac disease Myoclonus-dystonia syndrome
Spinocerebellar ataxia type 6 Palatal myoclonus
Autosomal recessive storage diseases, for example, sialidosis, ceroid lipofuscinosis, Hyperekplexia (familial or sporadic)
Lafora body disease, Gaucher’s disease
Unverricht–Lundborg disease (autosomal recessive) Opsoclonus-myoclonus syndrome
Limbic encephalitis Myoclonus-dystonia
Huntington’s disease (young-onset akinetic-rigid variant) Creutzfeldt–Jakob disease
Parkinsonism: multiple system atrophy (olivopontocerebellar atrophy form),
corticobasal degeneration, dementia with Lewy bodies
Idiopathic Parkinson’s disease
Rasmussen’s encephalitis
Angelman syndrome
Amyloid angiopathy
Note that in many other diseases the myoclonus source has not been electrophysiologically identified.

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

a stimulus (eg, noise, giving an exaggerated startle
reflex = hyperekplexia) or by an action or inten-
tion (Lance–Adams syndrome). Jerks may origi-
nate 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 recom-
mended treatment for subcortical myoclonus.
Exaggerated startle (hyperekplexia) is where
unexpected stimuli provoke proximal tonic
stiffening, often with falls and associated vocalisa-
tion.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 spi-
nal cord, and is generated by pacemaker circuits

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involved in locomotion. Jerks affect muscles
innervated by one or two neighbouring spinal
segments (myotomes). The myoclonus is often
stimulus-sensitive and rhythmic (1–3 Hz) and
may occur during sleep as well as wakefulness.
Propriospinal myoclonus
Propriospinal myoclonus involves several con-
secutive spinal segments. The source of activa-
tion 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 incom-
pletely understood, EMG studies may show a mus-
cle recruitment pattern suggesting propriospinal
myoclonus. Occasionally patients may have truncal
jerks when awake or drowsy, in keeping with prop-
riospinal 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 dura-
tion 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 den-
ervated 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.
Clinical assessment
Non-epileptic myoclonus (11% of all patients
with myoclonus); Epileptic myoclonus
(17% of all patients with myoclonus)
Non-epileptic (‘essential’ or ‘cryptogenic’) myo-
clonus classically has no other neurological
REVIEW
symptoms and ‘no underlying brain abnormality’.
Recently discovered genetic mutations account
for some clinically distinct syndromes of non-
epileptic myoclonus.
Myoclonus-dystonia
Myoclonus-dystonia is an autosomal dominant
form usually associated with ε-sarcoglycan,
DYT11 mutation on chromosome 7q21. Fifty per
cent of gene carriers have dystonia. The symptom
onset is in childhood or early adolescence, before
the age of 20. The myoclonus is subcortical,
spontaneous or stimulus-sensitive, and typically
spares the lower limbs. Dystonia, when present,
affects the body part affected by myoclonus.
Dystonia and myoclonus improve strikingly with
alcohol.
Other familial conditions
Other familial conditions include hereditary
geniospasm (chin myoclonus) manifesting as
childhood-onset autosomal dominant chin myo-
clonus. The myoclonus is rhythmic (5–10 Hz)
and is aggravated by stress, emotion and concen-
tration. The symptoms often improve with age.
In familial essential myoclonus, the phenotype
varies, with the clinical features forming a con-
tinuum between essential myoclonus and benign
essential tremor; some probands show features of
both. The movements respond to clonazepam or
anticholinergics.
Epileptic myoclonus (17%)
Epileptic myoclonus comprises cortical myoclonic
jerks, associated with ictal (poly)spike-and-wave
EEG discharges, time-locked with and preced-
ing EMG-recorded muscle contraction. There is
photosensitivity, ‘giant’ somatosensory evoked
potentials and lack of the prefrontal Bereitschaft
potential. Epileptic myoclonus is often associ-
ated with other primary generalised seizures
and patients may have additional neurological
problems.
Fragments of epilepsy
A young person with isolated myoclonus, and no
associated features, deserves special attention. The
jerk characteristics may provide localising features.
Cortical myoclonus (see above) is usually epileptic;
EEG may help to confirm this. When the jerks are
generalised and isolated or irregular, the diagno-
sis is essentially epileptic myoclonus. The patient
may have an autosomal dominant family history.
This condition overlaps with juvenile myoclonic
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epilepsy without absences and generalised tonic-
clonic seizures. Rhythmic myoclonus suggests cor-
tical tremor (benign autosomal dominant familial
myoclonic epilepsy or familial adult myoclonic
epilepsy type 1). The symptoms typically present
after the age of 18 with tremulous finger move-
ments (9–10 Hz), myoclonus and rare convulsive
seizures.
In an adolescent with generalised cortical myo-
clonus, it is important to ask whether this is the
first sign of a progressive pathology, such as the
rare Unverricht–Lundborg disease (onset of
action, intention myoclonus typically before the
age of 16), myoclonic epilepsy with ragged-red
fibres (MERRF) (where myoclonus does not fol-
low a diurnal pattern), myoclonic epilepsy with
mitochondrial myopathy and sensory ataxia
(MEMSA; see below), or the common, more
benign juvenile myoclonic epilepsy (myoclonus
typically occurs early morning, provoked by alco-
hol or by sleep deprivation). Substance abuse is
among the differential diagnosis, and renal func-
tion should be assessed to exclude autosomal
dominant myoclonus-renal failure syndrome.
Focal myoclonus occurs in epilepsia partialis
continua. Jerks most often affect arms, are typi-
cally <6 Hz, and altered by sensory or motor limb
stimulation. The EEG shows focal slow waves and
giant somatosensory evoked potentials. The dis-
ease process may be benign with fixed deficit (eg,
in ischaemic lesion), but may be associated with
a progressive clinical picture (eg, Rasmussen’s
encephalitis or glioma).
Childhood myoclonic epilepsy
Two-thirds of patients with epileptic myoclonus
present to paediatricians before the age of 5. Most
do not survive to adulthood and therefore do not
attend adult neurologists. This section focuses on
syndromes encountered in patients after the age
of 16.
Epileptic encephalopathies are determined by –
and thus reflect – the developmental maturation
of brain at time of onset. Early myoclonic enceph-
alopathy at age of 4–8 months may develop into
infantile spasms. Between ages 3 and 6, the condi-
tion may evolve into Lennox–Gastaut syndrome,
the most common epileptic encephalopathy.
These children have developmental delay and pri-
marily generalised seizures. Tonic seizures are the
most characteristic seizure type. Tonic seizures
are most characteristic with ictal EEG showing
10Hz fast rhythm on interictal background of dif-
fuse, slow spike-wave complexes. The aetiology is
220 Practical Neurology 2012;12:215–224. doi:10.1136/practneurol-2011-000107
variable, and includes focal lesions, trauma, peri-
natal hypoxia, metabolic causes and so on. Most
cases survive into adulthood but have intellectual
disability and treatment-resistant seizures.
Severe myoclonic epilepsy in infancy (or Dravet’s
syndrome; 80% are due to SCN1A mutation) is
rare. It manifests with febrile seizures, with onset
before the age of 1. Treatment-resistant afebrile
seizures follow, and by the age of 4, there is evident
developmental delay. As patients reach adulthood,
secondarily generalised seizures dominate the
clinical picture, often provoked by rises in body
temperature. Patients rarely survive beyond third
decade. Myoclonus occurs in only about one in 24
of patients. There is often ataxia, dysarthria, inten-
tion tremor, abnormal eye movements and fea-
tures of autism or psychosis. Poor mobility due to
kyphosis and flat/claw feet is common. Myoclonic
astatic epilepsy (Doose syndrome) presents at the
age of 3–4. The seizure types include subcortical
myoclonus (leading to falls and vocalisation), and
astatic, atonic attacks that may appear as ‘head
nodding’. Early convulsions and status epilepticus
indicate poor cognitive outcome. Seizures typi-
cally arise from sleep in the early morning. Up to
90% have only mild or no learning difficulty. The
epilepsy may remit by adolescence. Generalised
epilepsy with febrile seizures plus is a recently
described familial, often autosomal dominant epi-
lepsy syndrome with a broad clinical phenotype.
At one extreme, patients may suffer severe myo-
clonic epilepsy in infancy (see above), while at the
other they may have only uncomplicated febrile
convulsions between the ages of 3 months and 6
years. A proportion of this milder group develop
myoclonic epilepsy later in life. The commonest
underlying cause is a sodium-channel mutation
(SCN1A or 1B).
Idiopathic generalised myoclonic epilepsy
Epilepsy with myoclonic absences is the earliest
onset of these syndromes, presenting in childhood
(<12 years). Absence seizures are associated with
rhythmic bilateral jerks of the limbs and/or head,
with ictal EEG showing 2.5–3.0 Hz spike-and-
wave. Generalised tonic-clonic seizures may also
occur, with developmental delay and a typically
poor prognosis. In familial adult myoclonic epi-
lepsy type 2 (autosomal dominant), the median
age of onset is 20 years. The condition manifests
as cortical myoclonus, tremor and seizures. The
clinical course is variable, but often benign.
Juvenile myoclonic epilepsy (historic names:
Rabot’s benign familial myoclonic epilepsy; Janz

syndrome awakening myoclonus epilepsy) is the
most common primary generalised epilepsy syn-
drome, comprising >5% of all epilepsies. The
onset is in teenage years (average age 15 years)
with bilateral cortical myoclonus, most com-
monly of the upper limbs and occurring within
2 h of awakening. If subtle, these may be dis-
missed as ‘morning clumsiness’, and patients may
only present after the first convulsion, typically
provoked by sleep deprivation and alcohol.7
It is important to secure the diagnosis, as, even
after prolonged remission, there is a high risk
of relapse following withdrawal of antiepileptic
medication.
Progressive myoclonus epilepsy
This group of familial diseases often presents in
adolescence and follows a progressive course.
Unverricht–Lundborg disease (Baltic myo-
clonus; also encountered in the Mediterranean;
autosomal recessive inheritance) has an onset
around the age of 11 (up to 18). The symptoms
include action and stimulus-sensitive cortical
myoclonus in half of the patients and early morn-
ing convulsive seizures in the remainder. Ataxia,
tremor, dysarthria and emotional lability may fol-
low years later, and progressive cognitive decline
develops over decades. MERRF is rare and mater-
nally inherited (mitochondrial). The symptoms
typically start in childhood with ataxia, myopa-
thy and cortical myoclonus. Patients may develop
generalised tonic-clonic seizures after the second
decade (or even earlier). Other features include
hearing loss, dementia and cardiac defects. The
clinical features overlap with the syndrome of
mitochondrial encephalopathy with lactic acido-
sis and stroke-like episodes (MELAS). POLG1
mutations are the recently recognised cause of
a previously phenotypically defined spectrum of
diseases. Myoclonus features in several of these,
myoclonic epilepsy, mitochondrial myopathy and
sensory ataxia, present in adolescents with ataxia
(MEMSA), followed by myoclonus and other sei-
zures, with myopathy and encephalopathy.
Sensory ataxic neuropathy with dysarthria and
ophthalmoparesis (SANDO) is autosomal reces-
sively inherited and more commonly features
myoclonus. The symptoms have an adult-onset,
rarely even presenting first in the elderly subjects.
Patients may have psychiatric abnormalities, head-
ache, muscle weakness, visual impairment and
hepatopathy. Sodium valproate may precipitate
fulminant hepatic failure in patients with POLG
mutations, and is best avoided.
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Familial adult-onset myoclonic epilepsy type 3 is
a rare member of this group. These patients show
cortical tremor, myoclonus, frequent seizures,
progressive dementia and cerebellar ataxia. The
inheritance is autosomal dominant.
Symptomatic myoclonus (72%)
Acute/subacute myoclonus often associated
with systemic disease
Neurologists will most likely encounter such cases
when reviewing inpatient admissions or ward
consults. Most often the underlying illness will
dominate the clinical picture and allow a secure
diagnosis.8 It is important to review any pre-
scribed medications and to exclude factors that
may aggravate myoclonus, for example, through
checking thyroid function and serum calcium
and considering potential pH disturbances (see
below). It is important to remember the possibil-
ity of a focal central nervous system lesion, often
vascular in the acute setting. It must be remem-
bered that jerks resembling myoclonus are some-
times psychogenic.
Postanoxic encephalopathy (leading to Lance–
Adams syndrome): Early (<24 h postinsult)
myoclonus often presents as a ‘subtle generalised
convulsive state’ (previously referred to as ‘myo-
clonic status’) in a comatose patient. This indicates
extensive cortical neuronal loss and an extremely
poor outcome, an agonal state. Intention, action,
mixed subcortical and cortical myoclonus >48
h after a hypoxic insult suggest Lance–Adams
syndrome. There may be an exaggerated startle,
cognitive impairment, cerebellar, extrapyramidal
and pyramidal features. Chronic myoclonus may
lead to fragmentation of movement and signifi-
cantly hinder rehabilitation. Negative myoclonus
may affect mobility (bouncing gait). Clonazepam,
sodium valproate, levetiracetam or selective sero-
tonin reuptake inhibitors (SSRIs) may improve
myoclonus.
Recognising the disease pattern (eg, in a patient
with a cortical stroke and contralateral myoclonus,
or postanoxic brain injury) is often sufficient to
secure a diagnosis. When the cause of myoclonus
is not obvious, it is important to do a systemic
screen for potential infective, toxic, metabolic or
autoimmune disease. Meningo-encephalitis with
myoclonus is most commonly caused by herpes
simplex virus in the UK, and rarely arbovirus. The
presentation may be similar in autoimmune limbic
encephalitis, with headache, short-term memory
impairment and seizures, including myoclonus.
An autoimmune/paraneoplastic pathology should
Practical Neurology 2012;12:215–224. doi:10.1136/practneurol-2011-000107 221
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be sought if encephalitis is atypical for herpes Table 3 Substances that cause or aggravate myoclonus
simplex virus, cerebrospinal fluid PCR is nega- Anaesthetic agents Enflurane, ethomidate
tive or acyclovir is ineffective. Other rare infec-
tive causes include HIV, West Nile and JC virus, Antibiotics Penicillin, cephalosporins, imipenem,
quinolones
Whipple’s disease (myoclonus, dementia, ocu-
Antihelminthics and antivirals Piperazine, acyclovir
lomotor paresis and gastrointestinal symptoms)
Antidepressants Lithium, monoamine oxidase inhibitors,
and tetanus may also cause stimulus-sensitive SSRIs (serotonin syndrome), tricyclic
myoclonus and spasms. The clinical presentation antidepressants
of stiff person syndrome may resemble tetanus. Antiepileptic drugs Carbamazepine, gabapentin,
lamotrigine, phenobarbital, phenytoin,
Creutzfeldt–Jakob disease, characterised by the pregabalin, primidone, valproate (!),
triad of rapidly progressive dementia, myoclonus vigabatrin
and focal (mostly upper motor neurone) signs, Antihypertensives Ca-channel antagonists, caverdilol
shows a rhythmic myoclonus which is <2 Hz, Antipsychotics Buspirone, dopamine receptor blockers
cortical, subcortical or negative, present at rest, Cytotoxics Chlorambucil
action-induced or reflex. Late in the disease when Dopamine agonists Bromocriptine, L-dopa
myoclonus is prominent, dystonia and apraxia Heavy metals Aluminium, bizmuth, mercury
may resemble corticobasal degeneration. Others Baking soda, carbon monoxide,
cannabinoids, cimetidine, cocaine,
Exposure to drugs or toxins (table 3) may cause opiates, strychnine, tetanus toxin,
asterixis or asymmetric, non-rhythmic, general- toluene
ised or multi-focal jerks. Many patients also have Withdrawal syndromes Benzodiazepine
headache, encephalopathy, seizures and ataxia.
Note that water-soluble contrast agents, including
25 years). Other causes include coeliac disease
metrizamide (for myelography) and diclofenac,
(stimulus-sensitive, action myoclonus often with
can cause segmental myoclonus.
other seizure types; gastrointestinal symptoms may
Metabolic and toxic encephalopathies are often
not be prominent), some mitochondrial cytopa-
accompanied by myoclonus. These include renal
thies (see under Progressive myoclonus epilepsy),
failure (uraemic cortical reflex myoclonus), liver
spinocerebellar ataxias (myoclonus reported in
failure (asterixis = liver flap, a form of negative
SCA2, 6, 8, 14 and 19), dentato-rubro-pallido-
myoclonus, see above) and endocrinopathies
Luysian atrophy and postanoxic encephalopathy
(dysthyroid state, diabetes mellitus with hypogly-
(see under Acute/subacute myoclonus often asso-
caemia as well as hyperglycaemia). Other sys-
ciated with systemic disease).
temic abnormalities include electrolyte (sodium
Some late-onset metabolic encephalopathies
or calcium), pH disturbances (alkalosis), hyper-
may also lead to myoclonus. The autosomal reces-
capnia and hypoxaemia. Mechanical insults, such
sively inherited type 3 GM2 gangliosidosis may
as heat, electric shock and decompression injury,
present to the adult neurologist. Features include
may also result in myoclonus.
startle myoclonus, lower motor neurone lesions
Chronic, often progressive myoclonus (sometimes resembling motor neurone disease),
in neurology patients prominent cherry red macula (figure 4) and pre-
Myoclonus, although often not the presenting or served intellect.
most prominent feature, may accompany other
neurological symptoms. Common associated Progressive dyskinesia/bradykinesia with myoclonus
problems include ataxia, dystonia, dementia and The Westphal variant (early-onset, bradykinetic
visual symptoms. presentation) of Huntington’s disease is the
most common condition where extrapyramidal
Progressive myoclonic ataxia (Ramsay Hunt syndrome) features and myoclonus occur together. Action
This group of patients show mostly cortical, spo- tremor and myoclonus may be prominent. Other
radic, action myoclonus with a slowly progressive features include Parkinsonism, early gait abnor-
ataxia. Dementia and epilepsy may also rarely be mality, chorea, psychiatric symptoms, personality
present. There are two important paediatric-onset change, oculomotor abnormalities, all followed
autosomal recessive syndromes that occasionally by dementia.
feature myoclonus. Ataxia telangiectasia develops Idiopathic Parkinson’s disease is rarely accom-
before the age of 5 and Friedreich’s ataxia typi- panied by myoclonus. In one case series, how-
cally develops before 15 years of age (rarely after ever, three of 11 patients with unexplained

222 Practical Neurology 2012;12:215–224. doi:10.1136/practneurol-2011-000107


Figure 4 Macular cherry red spot in Tay–Sachs disease (figure 2 from:
Suvarna and Hajela. Postgrad Med J 2008;54:54–7).
unsteadiness, declining mobility and unresponsive
to L-dopa or dopamine agonists showed orthos-
tatic myoclonus that responded to clonazepam.
This reversible myoclonus of Parkinson’s disease
is probably underdiagnosed.
Other extrapyramidal diseases not typically
accompanied by myoclonus include Wilson’s
disease (asterixis may accompany liver disease),
focal and segmental dystonias (eg, spasmodic tor-
ticollis), the rare pantothenate kinase-associated
neurodegeneration (PANK) and neuroaxonal dys-
trophy (Seitelberger’s disease).
Progressive cognitive decline (dementia)
withmyoclonus
Teenager-onset
In a teenager patient with myoclonus and cog-
nitive deficit, the differential diagnosis is mostly
that of epileptic myoclonus (EEG will help). This
includes childhood myoclonic epilepsy (most
commonly Lennox–Gastaut syndrome; see under
Childhood myoclonic epilepsy), progressive myo-
clonus epilepsy (mitochondrial cytopathies and
rarely Unverricht–Lundborg disease; see under
Progressive myoclonus epilepsy) and autosomal
recessive metabolic disorders (including Gaucher’s
disease type 3).
Gaucher’s disease type 3 mostly presents before
the age of 16 with the triad of strabismus, trismus
and opisthotonus, sometimes with slowly pro-
gressive spasticity, ataxia, dementia and promi-
nent bulbar dysfunction.
Lafora body disease may develop in teenagers
with disabling cortical, multi-focal, stimulus-sen-
sitive myoclonus, photosensitive occipital sei-
zures leading to generalised tonic-clonic seizures,
REVIEW
even status epilepticus, with cognitive decline
and deteriorating school performance. Cerebellar
ataxia, behavioural changes (delusions and psy-
chosis) and tetraparesis may follow, leading to
death within 10 years of onset.
Mid-life-onset
In the adult to middle-aged patient, myoclonus
may be the presenting symptom of early-onset
Alzheimer’s disease (associated with the prese-
nilin-1 mutation), dentato-rubro-pallido-Luysian
atrophy with prominent ataxia and mitochondrial
cytopathies (see above).
Older-onset
Most cases of progressive dementia with myo-
clonus present in the older subjects. The most
common cause is Alzheimer’s disease; in the
advanced stages, over 50% of patients may
be affected. The jerks are mixed cortical and
subcortical, and may be spontaneous, reflex or
generalised. When rhythmic, the myoclonus may
mimic a 5–10 Hz hand tremor (polymyoclonus).
Corticobasal degeneration is another, though
rare, neurodegenerative condition, which typi-
cally presents with asymmetric apraxia, dystonia
(alien hand), action and stimulus-sensitive myo-
clonus, cortical sensory loss followed by dementia
with prominent parietal function loss (eg, acalcu-
lia, visuospatial deficit).
Progressive supranuclear palsy, fronto-temporal
dementia and dementia with Lewy bodies may
rarely manifest myoclonus. The jerks are not dis-
abling, usually affect the upper limbs and when
repetitive may appear as a tremor of approxi-
mately 6 Hz. The bradykinetic form of multi-
ple system atrophy may show similar myoclonic
fine finger tremor (jerky hand; 5–7 Hz cortical
myoclonus).
Progressive ocular signs/symptoms with myoclonus
Eye signs rarely accompany myoclonus, and so
when present, they help differential diagnosis
(table 4). In cases such as the autosomal recessive
ceroid lipofuscinosis (Batten’s, Kufs’ disease), the
eye signs are prominent, the patients often present
to an ophthalmologist. Retinal degeneration, retin-
itis pigmentosa and optic atrophy with early vis-
ual loss frequently dominates the clinical picture.
Myoclonus occurs in 83% of these patients, with
psychiatric symptoms, ataxia and Parkinsonism.
In juvenile-onset cases (around the age of 6),
there is additional learning difficulty, speech and
Practical Neurology 2012;12:215–224. doi:10.1136/practneurol-2011-000107 223
 REVIEW
Table 4 Eye signs with myoclonus: a diagnostic aid
Eye signs associated with
myoclonus Underlying disease
Retinitis pigmentosa/optic atrophy Neural ceroid lipofuscinosis
Cherry red macula GM2 gangliosidosis
Cherry red macula (+/− optic Sialidosis (cherry red myoclonus
atrophy) syndrome)
Optic atrophy Mitochondrial cytopathy
Krabbe’s disease (rare in adults)
Horizontal supranuclear gaze palsy Gaucher’s disease
Vertical supranuclear gaze palsy Progressive supranuclear palsy
Opsoclonus Opsoclonus-myoclonus syndrome
sleep disturbance. In adult forms (onset typically
in the third decade, but may be as late as fifth),
there is cognitive decline. Mitochondrial cytopa-
thies as well as Krabbe’s disease (a rare cause of
central and peripheral demyelination) may show
optic atrophy as an isolated ocular sign.
A cherry red macula (figure 4) is a rare sign
typically seen in sialidosis (cherry red myoclonus
syndrome). Cortical action myoclonus may be a
presenting feature and becomes a major cause
of disability with disease progression. In the
juvenile form, there may be additional optic
atrophy. GM2 gangliosidosis is another storage
disease with myoclonus and cherry red macula.
Abnormal eye movements associated with myo-
clonus may be detected in progressive supranu-
clear palsy (vertical supranuclear gaze palsy),
Gaucher’s disease (horizontal supranuclear
gaze palsy) and oscillopsia in the opsoclonus-
myoclonus syndrome. Opsoclonus-myoclonus
syndrome (descriptively referred to as ‘dancing
limbs-dancing eyes’) is easy to diagnose. The
signs include multi-directional saccades persisting
in sleep, brainstem myoclonus, ataxia and confu-
sion. Half of adult cases are paraneoplastic.
Closing remarks
Myoclonus is a clinically defined, brief, simple
involuntary movement. It may be generated at any
level of the neuraxis. Because movement is the
final common motor output pathway of the nerv-
ous system, there are various underlying neuro-
logical and systemic aetiologies. When myoclonus
is a feature of a common syndrome (eg, juvenile
myoclonic epilepsy) or one with easily recognis-
224 Practical Neurology 2012;12:215–224. doi:10.1136/practneurol-2011-000107
able characteristics (opsoclonus-myoclonus, or
hemifacial spasm), pattern recognition alone can
secure the diagnosis. In other cases, a ‘systematic
approach’ helps to avoid misdiagnosis.
I recommend initial clinical and, if necessary,
electrophysiological localisation of the source of
the myoclonus. For example, cortical myoclonus
is often epileptic or associated with a focal lesion.
Additional prominent neurological or systemic
symptoms, signs and associations (see above)
help to narrow the differential diagnosis further.
Metabolic and iatrogenic factors may cause or
aggravate jerks, and so all cases should have a
review of prescribed, over-the-counter and rec-
reational drugs and also a routine blood screen.
Investigations should then be tailored to refine
the differential diagnosis or to confirm suspected
diagnoses (eg, muscle biopsy in MERRF).
Myoclonus is slowly emerging from centuries of
confusing nomenclature to be a well-defined clinical
sign. The classification is likely to be further revised
with future clinical and experimental analysis of its
underlying mechanisms and better understanding of
the connectivity of the motor system.
Funding None.
Competing interests None.
Peer and provenance Commissioned; externally peer reviewed.
Reviewed by Peter Bain, London.
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