Asterixis.

Asterixis is a type of negative myoclonus characterized by irregular lapses of posture of various body parts. It is an uncommon but important sign in clinical neurology. Initially described as a "liver flap," its utility encompasses a galaxy of neurological and nonneurological situations. Asterixis has a rich history. Despite being described over 70 years ago, its exact pathogenesis remains unknown. Its significance as a tool for the evaluation and prognosis of encephalopathies has been suggested. This review presents its history, clinical implications and its significance.

Introduction

Asterixis is a disorder of motor control characterized by an inability to actively maintain a position and consequent irregular myoclonic lapses of posture affecting various parts of the body independently.[1] It is a type of negative myoclonus characterized by a brief loss of muscle tone in agonist muscles followed by a compensatory jerk of the antagonistic muscles.[2] First described as early as 1949 by James Foley and Raymond Adams,[3] asterixis is considered as a hard sign in neurology associated with a number of conditions, most commonly metabolic encephalopathies. Unilateral asterixis has been more commonly associated with structural brain lesions.[4] We review the history, clinical significance, and impact of this interesting clinical sign.

History

Specialists at Thorndike Laboratory at Boston City Hospital noted abnormal movements in their patients and referred to these as “liver flap.” James Foley explained the asynchronous flapping to a Jesuit classics scholar, Father Cardigan while they drank metaxa at the Athens Olympia Cafι. In the conversation, the name “anisosterixis” was coined: An (negative)-iso (equal)-sterixis (solidity). Considering it to be too polysyllabic, Foley and Raymond Adams shortened it to “asterixis.” The term came into common parlance, more so because of the influence of Harrison's Textbook of Medicine, which had Adams in its editorial board.[5]

Pathophysiology

The exact mechanism of generation of asterixis remains elusive several decades since its first description. Abnormal function of diencephalic motor centers that regulate the agonist and antagonist tones has been considered to be important.[6] Electrophysiological evaluation has revealed negative sharp waves in the contralateral central area, suggesting abnormal motor field activity in the cortex.[7] Miniasterixis has been proposed to be due to motor cortex involvement leading to pathologically slowed and synchronized motor cortical wave.[8]

It has been postulated that fluid shifts cause swelling of Alzheimer type II astrocytes and metabolic derangements. This compromises the blood–brain barrier with upregulation of peripheral benzodiazepine receptor and production of neurosteroids. But how exactly these lead to asterixis and why this circuitry is particularly vulnerable are unclear.[9]

Eliciting The Sign

Asterixis is tested by extending the arms, dorsiflexing the wrists, and spreading the fingers to observe for the “flap” at the wrist. The flap is due to irregular myoclonic lapses of posture caused by involuntary 50-200-ms silent periods appearing in tonically active muscles.[19] Testing asterixis at the hip joint involves keeping the patient in a supine position with knees bent and feet flat on the table, leaving the legs to fall to the sides. Negative myoclonus of the lower limbs at the hip joints repetitively occurs and is appreciated by looking at the knees.

Clinical Significance

Asterixis is an uncommon but significant sign in central nervous system (CNS) disorders [Table 1]. Bilateral asterixis is usually due to metabolic encephalopathies. The classic description has been in hepatic diseases but other causes can commonly cause asterixis including azotemia and respiratory disease. Electrolyte abnormalities such as hypokalemia and hypomagnesemia have been implicated. Importantly, several drugs can cause bilateral asterixis and include phenytoin, valproate, carbamazepine, metoclopramide, and barbiturates. Phenytoin can also unmask latent asterixis due to unilateral lesions and asterixis due to phenytoin has also been referred to as “phenytoin flap.” Some antipsychotics such as lithium and clozapine and antibiotics such as ceftazidime have been rarely implicated.[2] Lithium can cause asterixis at both the therapeutic and toxic plasma levels.[9]

Table 1

Causes of asterixis

Bilateral asterixis	Unilateral asterixis
Metabolic: Liver failure, azotemia, respiratory failure	Focal brain lesions at:
Drugs:	Thalamus
Sedatives: Benzodiazepines, barbiturates	Corona radiate
Anticonvulsants: Phenytoin (phenytoinflap), carbamazepine, valproic acid,gabapentin	Anterior cerebral artery territory
Antipsychotics: Lithium	Primary motor cortex
Antibiotics: Ceftazidime	Parietal lobe
Others: Metoclopramide	Cerebellum
Dyselectrolytemia: Hypomagnesemia,hypokalemia	Midbrain
	Pons
Bilateral structural brain lesions

Unilateral asterixis is usually due to focal brain lesions in the genu and anterior portions of the internal capsule or ventrolateral thalamus.[10] A study of 45 cases with asterixis revealed ischemic or hemorrhagic disorders of the CNS to be the most frequent causes of asterixis (95.5%) and the thalamus the most frequent localization for unilateral asterixis to result (54%).[4] A good correlation was found between the presence of unilateral asterixis and structural intracranial disease.[4] Unilateral asterixis has been reported in cases of cerebrovascular insult at multiple locations including the cerebellum,[11] posterior thalamic-subthalamic paramedian region,[12] midbrain,[13] and pons.[14]

Asterixis has also been said to have a prognostic value. It is rarely seen in early or advanced hepatic encephalopathy. It disappears with the onset of coma. Appearance of asterixis may thus, signify worsening of encephalopathy. At the same time, a disappearance of asterixis with worsening of consciousness may also be worrisome.[15] The portal-systemic encephalopathy index (PSE index) has been used in many studies to measure the efficacy of therapy for hepatic encephalopathy and combines the degree of asterixis with other variables to arrive at a score.[15] Similarly, asterixis has been included as a measure of severity in various scoring models for respiratory disease.[16]

Conclusion

Asterixis is an interesting yet poorly understood sign in clinical neurology. Despite years of research, its exact pathogenesis has not been established. The evaluation and management of asterixis are dependent on the underlying pathology and a thorough search for varied causes at varied locations must be made. The old dictum that asterixis is almost always associated with hepatic encephalopathy no longer holds and terms such as “liver flap” should be discarded. Asterixis has also been used as a prognostic marker and as an index of recovery from the underlying condition. However, its clinical utility in such situations is yet to be tested.

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Conflicts of interest

There are no conflicts of interest.