NEUROLOGICAL SIGN
Asterixis
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1 potential causes, both in neurology and general
Department of Neurology, The
Walton Centre NHS Foundation
Trust, Liverpool, UK
2
Institute of Infection and Global
Health, University of Liverpool,
Liverpool, UK
3
Department of Hepatology,
Royal Liverpool University
Hospital, Liverpool, UK
4
Cognitive Function Clinic, The
Walton Centre NHS Foundation
Trust, Liverpool, UK
Correspondence to
Dr Mark A Ellul, Department of
Neurology, The Walton Centre
NHS Foundation Trust, Lower
Lane, Liverpool L9 7LJ, UK;
ellulm@liverpool.ac.uk
Accepted 12 September 2016
To cite: Ellul MA, Cross TJ,
Larner AJ. Pract Neurol
Published Online First: [ please
include Day Month Year]
doi:10.1136/practneurol-
2016-001393
Mark A Ellul,1,2 Timothy J Cross,3 Andrew J Larner4
ABSTRACT
Adams and Foley described asterixis in the 1940s
in patients with hepatic encephalopathy, but it
has since been associated with a wide range of
medicine. Here, we review the history,
characteristics and clinical significance of this
important clinical sign.
INTRODUCTION
Asterixis describes sudden, brief, arrhyth-
mic lapses of sustained posture owing to
involuntary interruption in muscle con-
traction. The term was coined by
Raymond Adams and Joseph Foley
(apparently with the help of a classics
scholar from Boston College to advise
them on Greek) to describe a movement
disorder that they saw in the context of
liver disease.1 Most general physicians
are familiar with the sign through asses-
sing patients with hepatic encephalop-
athy, renal insufficiency or respiratory
failure. However, it has many other
causes, both structural and systemic, and
its manifestations can be extremely
varied.
PHENOMENOLOGY AND
PHYSIOLOGY
Asterixis can be either unilateral or bilat-
eral. It is typically asynchronous, irregular
and variable in frequency and amplitude.
It may affect either the upper limbs,
lower limbs or both. In severe cases it can
affect the face or tongue. The degree of
asterixis can be assessed based on the
joints that are affected: ranging from
flickers of the small finger joints to lapses
of posture in the proximal limbs. ‘Truncal
asterixis’ has also been described, with
loss of tone in postural muscles causing
falls2 (see figure 1 and the online
supplementary video for an example of a
patient with typical asterixis).
The sign was originally described as a
‘flapping tremor’,1 although being a nega-
tive phenomenon it cannot be a tremor in
the strict sense and is often regarded as a
Ellul MA, et al. Pract Neurol 2016;0:1–3. doi:10.1136/practneurol-2016-001393
form of negative myoclonus. The average
frequency of movements is said to be in
the region of 3–5 Hz, although in our
experience it is often significantly less,
for example, 0.5–2 Hz. ‘Mini-asterixis’
describes very fine asterixis affecting the
fingers, which may be mistaken for
tremor.
On electromyography (EMG) of the
involved muscles, each loss of tone is
associated with a silent period of 50–
200 ms.3 Its pathophysiology is unclear,
although there are several theories. There
seems to be a role for the ascending acti-
vating systems, connected with arousal,
which are disturbed in encephalopathies
and in lesions of the thalamus and mid-
brain. Indeed, the experience of ‘nodding
off ’ during a night shift (or a lecture!)
could be considered as an intermittent
loss of neck extension associated with
low arousal. Studying asterixis using mag-
netoencephalography coupled with
surface EMG reveals involvement of the
contralateral primary motor cortex
(M1),3 although the cortical mechanisms
are yet to be determined.
CLINICAL EXAMINATION AND
IMPLICATIONS
Since asterixis is a disorder of posture, it
makes sense that in eliciting the sign the
clinician should ask the patient to adopt
a constant posture that is then held
against gravity. Classically, this involves
extending the arms, pronated, at 90° to
the body and extending the wrists with
the fingers spread. Often the patient is
asked to close their eyes, although there
is no evidence that this improves detec-
tion of the sign. As well as looking for
intermittent loss of posture in fingers,
wrists or arms, the examiner can feel for
subtle loss of tone using gentle pressure
on the hands. To this can be added
straight leg raising with dorsiflexion at
the ankle, looking for asterixis in the
lower extremity.
1
 NEUROLOGICAL SIGN

Numerous reports in the literature describe asterixis

associated with structural brain pathology. Typically,
these are discrete lesions ( particularly thalamic)
causing contralateral asterixis. Occasionally, unilateral
pathology is associated with bilateral asterixis, for
example, subdural haematoma causing mass effect.
There are some reports of ipsilateral asterixis asso-
ciated with a single lesion, although none clearly
causative.2 Many patients with structural lesions have
comorbid metabolic disturbances that cloud the clin-
ical picture.

Box 1 Causes of asterixis

Metabolic
▸ Hepatic encephalopathy
▸ Renal failure
▸ Respiratory failure (hypoxia and/or hypercapnia)
Figure 1 Still image from online supplementary video. A man ▸ Hypoglycaemia
aged 72 years with a background of liver cirrhosis due to non- ▸ Electrolyte abnormalities (hypokalaemia,
alcoholic steatohepatitis was admitted to hospital with acute hypomagnesaemia)
decompensation due to an upper gastrointestinal bleed. He was
▸ Wilson’s disease
mildly confused but orientated to place and time. On prolonged
extension of the arms and wrists, there was bilateral, ▸ Urea cycle disorders
intermittent, asynchronous loss of posture at the wrists, with Drugs
superimposed fine movements of the fingers. There was no ▸ Antiepileptics (most commonly phenytoin, valproate,
asterixis at the ankles. carbamazepine, gabapentin)
▸ Levodopa
There is a significant latent period between adopt- ▸ Opiates
ing the posture and the beginning of asterixis, so it is ▸ Anticholinergics
important to wait at least 30 s before concluding that ▸ Benzodiazepines
the sign is absent. ▸ Lithium
Asterixis is normally asymptomatic and found ▸ Clozapine
during clinical examination for another presentation, ▸ Less commonly:
typically encephalopathy. However, occasionally it is a – Metrizamide (contrast medium for myelography,
presenting feature, causing troublesome jerky move- now rarely used)
ments of the dominant hand, irregular handwriting or – Chloral hydrate
even falls in the case of lower limb or truncal asterixis. Structural
The prevalence of asterixis in normal controls is ▸ Haemorrhage (subdural, subarachnoid or
unknown. intraparenchymal)
Adams and Foley first described asterixis in hepatic ▸ Infarction
encephalopathy, and the sign is part of the West ▸ Neoplasia ( primary or metastatic)
Haven Criteria,4 used to grade the severity of enceph- ▸ Cerebral toxoplasmosis
alopathy and its response to treatment. It appears to ▸ Viral encephalitis
be a relatively sensitive sign of hepatic encephalopathy,
but is very non-specific, and was subsequently found
in a variety of other metabolic abnormalities. It may Key points
be associated with either hypercapnia or hypoxia,2
and therefore is not a reliable sign of type 2 respira-
▸ Asterixis is a non-specific sign of cerebral pathology.
tory failure, as occasionally suggested.
▸ It may affect all four limbs, the trunk and the face.
A wide variety of medications are implicated in
▸ It can be associated with a range of metabolic and
causing asterixis (box 1), of which antiepileptics are
structural pathologies, or it can represent a drug side
probably the most frequent, particularly valproate and
effect.
phenytoin. The serum phenytoin concentration seems
▸ In hepatic encephalopathy, asterixis may help in
to correlate approximately with the severity of aster-
grading severity and in assessing response to
ixis, although it can occur even at concentrations
treatment.
normally considered subtherapeutic.2

2 Ellul MA, et al. Pract Neurol 2016;0:1–3. doi:10.1136/practneurol-2016-001393


Contributors MAE and AJL both contributed to literature
review, writing and editing of the manuscript. TJC
helped with the patient video and reviewed the
manuscript.
Competing interests None declared.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally
peer reviewed. This paper was reviewed by David Nicholl,
Birmingham, UK.
Ellul MA, et al. Pract Neurol 2016;0:1–3. doi:10.1136/practneurol-2016-001393
NEUROLOGICAL SIGN
REFERENCES
1 Laureno R. Raymond Adams: a life of mind and muscle, Vol.
177. Oxford University Press, 2009:235–7.
2 Pal G, Lin MM, Laureno R. Asterixis: a study of 103 patients.
Metab Brain Dis 2014;29:813–24.
3 Butz M, Timmermann L, Gross J, et al. Cortical activation
associated with asterixis in manifest hepatic encephalopathy.
Acta Neurol Scand 2014;130:260–7.
4 Ellul MA, Gholkar SA, Cross TJ. Hepatic encephalopathy due
to liver cirrhosis. BMJ 2015;351:h4187.
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