Authors:
Marina Babiy, MD
Michael D. Stubblefield, MD
Maryann Herklotz, PT
Michael Hand, PT

Falls

Affiliations:
From the New York-Presbyterian
Hospital; Weill Medical College of
Cornell University, New York, New
York (MB, MDS); and the Memorial
Sloan-Kettering Center, New York,
New York (MDS, M. Herklotz, M.
Hand).

Correspondence:
All correspondence should be
addressed to Marina Babiy, MD, 436
East 69th Street, 6-C, New York, NY
10021. All requests for reprints
should be addressed to Michael D.
Stubblefield, MD, Rehabilitation
Service, Memorial Sloan-Kettering
Center, 1275 York Avenue, New York,
NY 10021.
0894-9115/05/8402-0136/0
American Journal of Physical
Medicine & Rehabilitation
Copyright © 2005 by Lippincott
Williams & Wilkins
DOI: 10.1097/01.PHM.0000151943.06257.64

CASE REPORTS

Asterixis Related to Gabapentin as
a Cause of Falls
ABSTRACT
Babiy M, Stubblefield MD, Herklotz M, Hand M: Asterixis related to gabapentin
as a cause of falls. Am J Phys Med Rehabil 2005;84:136 –140.
Negative myoclonus, commonly known as asterixis, is often observed in patients
with toxic-metabolic encephalopathies or focal brain lesions. It is a movement
disorder characterized by postural lapses resulting from brief cessation of tonic
muscular contraction. Negative myoclonus has a characteristic appearance on
needle electromyography. Lapses in continuous postural muscle activity can
lead to falls. This increased risk of falls makes it particularly important to
recognize and treat negative myoclonus, especially in patients with multiple
medical problems, deconditioning, and gait disturbances. To our knowledge,
there have been no published reports implicating negative myoclonus as a cause
of falls in adults. We present a case of asterixis as a cause of falls and near falls
in a patient with metastatic breast cancer and normal mental status who was
receiving gabapentin.
Key Words: Falls, Asterixis, Negative Myoclonus, Gabapentin

F

alls and near falls occur in about one third of the elderly, and they can lead
to major debilities in a large proportion of patients.1 Falling is associated with
injury, immobility, weakness, and isolation. One of the most disabling consequences of falling is the fear of another fall. Falls may occur as the result of a
number of disorders, including muscle weakness (stroke, spinal cord injury,
and myopathy), syncopal episodes (orthostatic hypotension, aortic stenosis,
and cardiac arrhythmias), Parkinsonism, ataxia (vitamin deficiency, cervical
spondylosis, cerebellar dysfunction, and spinal cord dysfunction), apraxia (normal pressure hydrocephalus), gait disturbances (Trendelenburg gait from L5
radiculopathy), vertigo, and movement disorders (myoclonus and tremor).1,2
Myoclonus can be classified as either positive or negative myoclonus.
Positive myoclonus, also known as myoclonus, is a type of movement disorder
characterized by involuntary bursts of muscle activity. These bursts of muscle
activity cause brief, jerky, shock-like movements. Negative myoclonus is also a
motor phenomenon that is characterized clinically by involuntary movements.
These movements are superficially similar to those seen with positive myoclonus. Pathophysiologically, however, negative myoclonus differs from positive
myoclonus in that the defect is a brief and sudden interruption, as opposed to
increase, in muscular activity. Negative myoclonus is synonymous with the

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term “asterixis,” a word that was coined by Adams
and Foley to describe transient postural lapses resulting from brief cessation of postural tonic electromyographic (EMG) activity.3 Asterixis is often
used to describe the negative myoclonus seen in
patients with toxic-metabolic encephalopathies or
focal brain lesions.
The combination of positive and negative myoclonus has been known to cause a severe disturbance of balance and gait in patients with myoclonic encephalopathies.4 Negative myoclonus, in
particular, interferes with balance and gait by disrupting control of postural adjustments. This loss
of postural control can allow or provoke adverse
changes in the position of the body’s center of
mass.2 As a result, patients frequently report feeling unsteady and having a fear of falling. Postural
lapses during stance generally occur when a substantial number of muscles are involved or when
antigravity muscles are affected.
It stands to reason that the periodic loss of
postural control induced by negative myoclonus
could lead to falls. Despite the fact that both negative myoclonus and falls are reasonably common,
our review of the literature did not reveal previous
reports of falls attributable to negative myoclonus
in adults. We present a case of negative myoclonus
as contributing to falls in a patient with breast
cancer who was receiving gabapentin.

CASE REPORT
A 74-yr-old woman with a medical history of
diabetes, hypertension, and stage IV breast cancer
with metastasis to bone and liver was admitted to
the Memorial Sloan-Kettering Cancer Center for
frequent falls and near falls. Her falls had occurred
as an outpatient and did not result in injury. When
she was seen by the physical therapist as an inpatient, she subjectively reported a fear of falling. Her
bilateral lower limbs would buckle transiently and
recover spontaneously during transfers and ambulation. She was provided with a rolling walker and
began to receive transfer training, gait training,
and safety education from the physical therapist. A
rehabilitation medicine consult was requested for
further evaluation.
The patient had been diagnosed with breast
cancer in 1981 and underwent a right-sided modified radical mastectomy followed by chemotherapy
with cyclophosphamide, methotrexate, and 5-florouracile (CMF). A recurrence of her cancer with
bony metastases to the thoracic spine was discovered in 1998. She was treated with tamoxifen,
Arimidex, and pamidronate and with radiation
therapy to the thoracic spine at the T7 through T9
levels. Radiation was followed by cyclophosphamide, methotrexate, and 5-florouracile chemotherFebruary 2005

apy. Her disease continued to progress, and by
early 2002, she had developed new metastasis to
the liver and bone, including the base of the skull
and spine. She was treated with doxorubicin, oral
dexamethasone, and pamidronate. In mid-2002,
she developed T8 epidural spinal cord compression
and underwent a posterolateral decompression and
fixation without residual neurologic sequelae. Subsequent imaging of her brain and spinal cord did
not reveal any additional areas of spinal cord compression, brain metastasis, or leptomeningeal disease. No abnormalities of hepatic or renal function,
anoxia, or drug intoxication had been reported in
her medical history.
Her medications included gabapentin (300 mg
orally twice a day) for neuropathic pain presumed
to be secondary to chemotherapy-induced neuropathy, glyburide, metoprolol XL, hydrochlorothiazide/losartan, 100-␮g fentanyl patch every 3 days,
omeprazole, docusate sodium, bisacodyl, epoetin
alfa, and sucralfate. Her gabapentin dose had been
stable for several months.
On physical examination, her vital signs, including temperature, respiration rate, blood pressure, and pulse were normal. The cardiac, lung,
and abdominal examination revealed no abnormalities. Neurologic examination revealed an alert and
oriented elderly woman. Her gait was slightly
broad based and unsteady, with occasional bilateral
knee buckling. The patient demonstrated mild bilateral dysmetria on finger-to-nose-finger and heelto-shin examination. Negative myoclonus was
noted in the bilateral upper limbs by noting a
characteristic “flap” while the patient actively extended both hands at the wrists. Negative myoclonus was also noted in the bilateral lower limbs by
having the patient actively extend the leg at the
knee while the examiner supported the knee. No
positive myoclonus was observed and there were no
abnormal movements in the face or trunk. Cranial
nerves and tone were normal. Sensory examination, including light touch, pinprick, and position
sense were normal. Muscle strength was grade 4/5
and symmetric in all muscle groups tested in the
bilateral upper and lower limbs. Deep tendon reflexes were absent throughout.
Laboratory values, including sodium, potassium, calcium, glucose, creatinine, prothrombin
time, activated partial thromboplastin, and urinalysis, were normal. A limited needle EMG examination of the extensor carpi radialis (Fig. 1) and right
vastus lateralis (Fig. 2) was performed and demonstrated intermittent pauses of 40 –100 msecs on
submaximal sustained contraction.
The clinical diagnosis of gait disorder secondary to negative myoclonus and mild ataxia was
made. Gabapentin was discontinued because no
Asterixis as a Cause of Falls

137

FIGURE 1 Needle electromyographic (EMG) recording from the right extensor carpi radialis
(ExtCarRad).

other of the patient’s medications had a known
association with negative myoclonus. The EMG
was not repeated after discontinuation of the gabapentin. The patient was prescribed bilateral soft
knee supports for ambulation. Physical therapy
continued for lower limb strengthening, gait training, balance training, and safety education for fall
prevention. The soft knee supports minimized the
buckling of the patient’s knees as she ambulated
with the rolling walker. Before discharge to a subacute rehabilitation facility, the patient’s gait had
improved somewhat, and she was able to ambulate
safely with supervision and a rolling walker. There
were no reported instances of falls during the hospital course. She was lost to follow-up once discharged to the subacute rehabilitation facility, and
later died of her metastatic breast cancer.

either the resting state or from tonic contraction.
The pathophysiology of myoclonus is not well understood and may be a manifestation of a wide
variety of pathologic conditions affecting the brain,
spinal cord, or even the peripheral nerves. Many
types of drugs and toxins have been reported to
induce myoclonus, including bismuth salts, valproic acid, lithium, antipsychotic agents, and
monoamine oxidase inhibitors.5 Myoclonus can be
seen in epilepsy or in other neurologic conditions.
In contrast to positive myoclonus, the brief,
jerky, involuntary movements of negative myoclonus are due to an interruption of muscular activity
that causes a sudden postural pause. It usually
involves tonically recruited muscles, and the interruption of antigravitational muscle activity results
in downward displacement of the joint. Negative
myoclonus can be demonstrated in the hands by
asking the patient to gently squeeze the examiner’s
fingers; this results in brief and subtle lapses of
tonic muscle activity.4 Like positive myoclonus,
negative myoclonus can be classified as cortical or
subcortical, in terms of its origin, and as rhythmic
or irregular.2 It becomes more prominent after
sustained activity and is exacerbated by fatigue.
Negative myoclonus interferes with balance and
gait by disrupting the control of postural adjustments
and thereby provoking abnormal changes in the
position of the center of mass.4 Patients frequently
report feeling unsteady, having a fear of falling
during walking, and the sensation that knees will
“give way.” Postural lapses may occur during
stance only when significant numbers of muscles
involved in antigravity posture are affected
simultaneously.3

DISCUSSION
Myoclonus (or positive myoclonus) is a term
used to describe involuntary movements that are
“brief and shock like.”4 As in clonus, myoclonus is
a monophasic phenomenon caused by the involuntary contraction of a muscle, muscle group, or
body segment. These contractions are caused by a
transient increase in muscle activity. Myoclonic
contractions are usually irregular in rhythm and
amplitude and involve a muscle group or body
segment (segmental myoclonus). These brief bursts
of muscle activity (with or without tonic muscular
contraction) lead to the abnormal movements that
are seen clinically.
Myoclonus can be demonstrated on needle
EMG as a burst of electrical muscle activity from

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Babiy et al.

FIGURE 2 Needle electromyographic (EMG) recording
from the right vastus lateralis (VastusLat).

Am. J. Phys. Med. Rehabil. ● Vol. 84, No. 2

Negative myoclonus can be observed in a variety of clinical conditions ranging from the physiologic form, seen occasionally with the onset of
sleep or after prolonged exercise, to the pathologic
form observed in patients with toxic-metabolic encephalopathies or with focal brain lesions (asterixis). There is also a paroxysmal form of negative
myoclonus known as epileptic negative myoclonus
that is seen in epileptic patients.6 A case report on
two children with idiopathic partial epilepsy of
childhood has been described. These reports demonstrate epileptic negative myoclonus manifesting
as intermittent falls and fecal incontinence.7
Asterixis is most easily demonstrated by asking
patients to actively extend their wrist with their
arms in the extended position.2 If asterixis is
present, the examiner will observe brief and repetitive loss of wrist extension so that the hand seems
to flap (liver flap). Asterixis was first described in
patients with hepatic encephalopathy, but it is now
known to represent a nonspecific neurologic finding associated with multiple forms of toxic and
metabolic encephalopathies (hepatic, uremic) and
occurs in patients with focal lesions of the central
nervous system, including subcortical and brainstem structural lesions.6 A number of drugs have
been shown to be associated with asterixis, and
they include gabapentin, carbamazepine, valproic
acid, phenytoin, lithium, clozapine, L-dopa, ifosfamide, and ceftazidime.5,8,9 A case demonstrating
asterixis as a clinical sign of phenytoin toxicity has
been described.9 Asterixis has also been shown to
be a primary manifestation of ifosfamide encephalopathy in a patient who had been treated for plasmacytoma.8 Neurotoxic substances are also associated with asterixis, in particular, ammonia and
manganese.10
Electrodiagnostically, negative myoclonus is
characterized by an interruption of EMG activity
for 50 –200 msecs.2,4 The duration of the silent
period can last up to 400 msecs. The longer the
duration of postural lapses, the more pronounced
and potentially disabling is the movement disorder.3 Asterixis can be focal or multifocal (involvement of several adjacent muscles simultaneously),
but it is usually multifocal in distribution and is
very rarely generalized. It often has an arrhythmical presentation and is present only during a tonic,
postural muscle contraction. Accordingly, it is
never present when a person is at rest.4
Involvement of serotonergic, GABA-ergic, benzodiazepine, cholinergic, and dopamine systems
could play a role in myoclonic disorders. A number
of drugs have been used in the treatment of myoclonus, including 5-hydroxytryptophan, carbidopa,
L-dopa, clonazepam, sodium valproate, primidone,
apomorphine, ethosuximide, and piracetam.5,7,10
February 2005

There is no study analyzing the effect of antimyoclonic drugs on negative myoclonus. The value of
physical therapy has not been evaluated, but it
could be potentially beneficial.4 Our patient responded to physical therapy, safety training, use of
an assistive device, and soft knee supports, all of
which probably contributed to functional improvement in addition to discontinuation of gabapentin.
Treatment of negative myoclonus should involve identification and correction of metabolic
abnormalities and withdrawal of potentially causative or contributing agents, as was done in our
patient. Prevention and treatment of hepatic encephalopathy in cirrhotic patients with ammonialowering strategies, including lowering dietary
protein intake, use of lactulose, neomycin, sodium
benzoate, and L-ornithine-aspartate, is recommended. Central nervous system–acting drugs
such as benzodiazepine receptor antagonists
(flumazenil) and dopamine agonists (L-dopa and
bromocriptine) have been used, but with limited
success.5,10 If an offending causative agent has
been identified, such as phenytoin or ifosfamide, it
should be discontinued or titrated to a lower
dosage.

CONCLUSION
In the present case, multiple medical conditions likely contributed to her history of falls. Although the patient had some degree of what was
presumed to be neuropathic pain from chemotherapy, her physical examination did not demonstrate
any sensory deficits and the chemotherapeutic
agents she had been exposed to are not particularly
neurotoxic. She did have symmetrical weakness,
likely due to deconditioning, that would be expected to contribute to her falls; however, it was
only mild and was out of proportion to the marked
knee buckling exhibited on ambulation. It is most
likely that the patient’s negative myoclonus was a
major contributor to her knee buckling and frequent falls.
The cause of this patient’s negative myoclonus
is also elusive. Her laboratory values did not support a metabolic cause, and save for gabapentin,
none of her medications were thought likely to be
contributing. The patient did improve when the
gabapentin was discontinued, but her physical
therapy had been continued and soft knee supports
had been added. The relative contributions from
each of these modalities cannot be determined.
To the best of our knowledge negative myoclonus has not been described in the literature as a
potential cause of falls in adult patients. Because
the major clinical manifestation is interruption of
tonic postural muscle activity, negative myoclonus
may significantly interfere with balance and posAsterixis as a Cause of Falls

139

tural control during standing and ambulation. It
also could result in the subjective sensations of
unsteadiness and knee buckling and the fear of
falling. The presence of negative myoclonus may be
particularly worrisome in patients who are debilitated, deconditioned, or have other disturbances of
gait that increase their fall risk. Physicians taking
care of such patients need to be particularly vigilant in recognizing negative myoclonus on physical
exam. Moreover, negative myoclonus should be
considered in the differential diagnosis of patients
with multiple falls or near falls that do not have an
obvious cause. If necessary, a needle EMG can help
confirm the diagnosis of negative myoclonus. Once
identified, appropriate treatment of metabolic abnormalities should be instituted, and any offending
agents known or suspected to cause negative myoclonus should be discontinued or have their dosages decreased.

140

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3. Toro C, Hallett M, Rothwell JC, et al: Physiology of negative
myoclonus. Adv Neurol 1995;67:211–7
4. Obeso JA, Artieda J, Burleigh A: Clinical aspects of negative
myoclonus. Adv Neurol 1995;67:1–7
5. Duarte J, Sempere AP, Cabezas MC, et al: Postural myoclonus induced by phenytoin. Clin Neuropharmacol 1996;
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6. Guerrini R, Dravet C, Genton P, et al: Epileptic negative
myoclonus. Neurology 1993;43:1078 – 83
7. Capovilla G, Rubolli G, Beccaria F, et al: Intermittent falls
and fecal incontinence as a manifestation of epileptic negative myoclonus in idiopathic partial epilepsy of childhood.
Neuropediatrics 2000: 31:273–5
8. Meyer T, Ludolph AC, Munch C: Ifosfamide encephalopathy
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