Gabapentin
Treatment in a Child
With Delayed-Onset
Hemichorea/
Hemiballismus
Sanjeev V. Kothare, MD*,
Phyllis Pollack, MD†,
Alan G. Kulberg, MD‡, and
Paula D. Ravin, MD§
A 13-year, 6-month-old female was evaluated for subacute onset of left-sided hemichorea/hemiballismus,
with an old, right parietal, cortical, and subcortical
stroke as the presumed cause. Treatment with gabapentin was initiated, with good results at 6-month
follow-up. Discussion of the differential diagnosis and
evaluation of delayed-onset movement disorders in
children and the mechanism of action of gabapentin is
included. © 2000 by Elsevier Science Inc. All rights
reserved.
Kothare SV, Pollack P, Kulberg AG, Ravin PD. Gabapentin treatment in a child with delayed-onset hemichorea/
hemiballismus. Pediatr Neurol 2000;22:68-71.

Introduction
Hemichorea/hemiballismus is an uncommon presentation in children compared with adults and is rarely
reported as a late complication of static lesions in the
brain. A 13-year, 6-month-old female is reported with
delayed-onset hemichorea/hemiballism and a discrete contralateral parietal and subcortical stroke attributable to a
cardiac embolism 8 years before resulting from infective
endocarditis involving the mitral valve. The mechanisms
of production of hemichorea/hemiballismus and the favor-

From the *Division of Pediatric Neurology and †Division of Pediatric
Cardiology; Department of Pediatrics; and Departments of ‡Pediatrics
and §Neurology; University of Massachusetts Memorial Health Care,
Worcester, Massachusetts.

68

PEDIATRIC NEUROLOGY

Vol. 22 No. 1

able response to gabapentin are discussed. Differences
between this case and others caused by antiphospholipid
antibody syndrome [1] or Sydenham’s chorea [2] are also
discussed with regard to their treatment and prognosis.
Case Report
A 13-year, 6-month-old, right-handed female presented to the emergency room because of worsening of left upper and lower extremity jerky
movements, dysarthria, and drooling from the left angle of the mouth
during the previous 2 months. Her past medical history was significant
for a mitral valve prolapse diagnosed at 4 years of age. At age 5, she
developed episodic left upper extremity tingling and numbness and
weakness of the left hand. Streptococcus viridans infective endocarditis
was diagnosed at 5 years, 6 months and was adequately treated with
intravenous antibiotics. During the next 8 years, she continued to have
episodic dysesthesias of the left upper extremity and intermittently
dropped objects from her left hand. During the past 3-4 years, she also
began to develop exertional dyspnea because of worsening mitral
regurgitation. Two months before the current presentation with involuntary movements, she underwent an uncomplicated mitral valvuloplasty.
Her past medical history was also significant for a few years of migraines
with visual auras at a frequency of 2-3 monthly before the onset of her
current symptoms. They were readily relieved using simple analgesics.
She had begun menstruating 8 months before the onset of the movement
disorder. Her birth history and early developmental milestones were
unremarkable. She had been an honor student in seventh grade but in the
eighth grade had not been doing well because of poor concentration. Her
family history was significant for migraines in the mother. Her cardiac
medications had been withdrawn after her surgery.
On examination, she weighed 67 kg and was afebrile. She had no skin
rashes or joint inflammation. The systemic examination was significant
for a systolic murmur at the apex of the precordium. The neurologic
examination revealed a labile affect, dysarthric speech, normal cognitive
skills, hippus in both pupils, and normal vision and extraocular movements. Her motor examination revealed choreiform movements of her
tongue, choreiform movements of her left upper extremity with associated athetosis of her left hand, occasional hemiballistic movements of her
left upper and lower extremities, normal sensation and strength, and no
cerebellar signs. Her gait was jerky in character, her tendon reflexes were
normal, and she had normal plantar responses on the right and equivocal
responses on the left.
The results of the laboratory studies were as follows: leukocyte count
was 7,900/mm3, erythrocyte sedimentation rate was 3 mm/hour, hemoglobin was 12.3 gm/dL, platelet count was 193,000/mm3, antistreptolysin-O titer was less than 1:128 (normal less than 1:256), serum copper
was 969 ␮g/L (normal 700-1,750 ␮g/L), serum ceruloplasmin was 35.9
mg/dL (normal 20-52 mg/dL), and 24-hour urine copper was 11 ␮g. The
serum electrolytes and protein electrophoresis, prothrombin and partial
thromboplastin times, and thyroid functions were normal, and the throat
culture, antinuclear antibodies, rheumatoid factor, and antiphospholipid
antibody profile were negative. Magnetic resonance imaging of the brain
revealed a small, old ischemic infarct involving the right posterior
parietal cortex and extending into the underlying subcortical white

Communications should be addressed to:
Dr. Ravin; Department of Neurology; University of Massachusetts
Memorial Health Care; 55 Lake Avenue North;
Worcester, MA 01655-0318.
Received May 3, 1999; accepted August 10, 1999.

© 2000 by Elsevier Science Inc. All rights reserved.
PII S0887-8994(99)00104-6 ● 0887-8994/00/$20.00

matter up to the lateral ventricle. Technetium-99 hexamethylpropylene amineoxime single-photon emission computed tomography of
the brain was normal. Electroencephalography revealed mild slowing
of the background activity in the right posterior quadrant without any
epileptiform activity on a sleep-deprived study.
Gabapentin 300 mg three times daily was initiated and gradually
increased during the next 4 weeks to 1,600 mg three times daily (4,800
mg daily; 75 mg/kg/day). There was near complete disappearance of the
choreiform movements in her extremities, minimal persistent disarticulation, and improved attention and performance in school. No dizziness,
nausea, or sedation at the time of the peak dose was observed. She did
complain of an occasional increase in the choreiform movements at the
end of the dose intervals, with resolution of these symptoms within 30
minutes of taking the gabapentin.
Two months after a 6-month course of gabapentin was discontinued,
she observed a slight increase in the involuntary movements of her left
face and tongue, with dysarthric speech, which worsened after lack of
sleep and at the end of the day. Repeated erythrocyte sedimentation rate,
antinuclear antibodies, C3 complement levels, antiphospholipid antibody
titers, and antistreptolysin-O titers were normal.

Discussion
This patient qualifies under the rubric of the delayedonset movement disorder after childhood central nervous
system injury, namely a right parietal, cortical, and subcortical embolic infarct associated with S. viridans infective endocarditis. She described episodes of paresthesia on
her left side and clumsiness of her left hand since the time
of the infective endocarditis, which was indicative of her
original central nervous system insult, but she did not
manifest hemichorea/hemiballismus until at least 8 years
later. A number of triggers for the delayed onset can be
postulated. It is possible that hypoperfusion of an old
penumbra during mitral valvuloplasty contributed to the
emergence of the new signs. In addition, estrogenic effects
on the D2 receptors with the advent of puberty or the stress
of heart surgery under hypothermia could have been
precipitating factors. A review by Jankovic and Scott [3]
describes the typical delayed-onset movement disorder
after a childhood injury as having a latency of 4.9 ⫾ 7.8
years and a predominance of segmental or unilateral
movements, as was observed with the authors’ patient.
However, these have been predominantly dystonic in
character. None had chorea/ballismus as a manifestation of
their movement disorder, as observed in this patient.
The evaluation for pediatric movement disorders of this
type was pursued, as illustrated in Table 1. Other causes of
the hemichorea/hemiballismus (Table 2) were excluded.
The family history was not suggestive of Huntington’s
disease, and there was no history of drug intake. Her
cardiac surgery and postoperative period were also unremarkable. No earlier signs of chorea, such as akathisia,
dysarthria, or personality changes, were evident on careful
chart review. That her initial endocarditis was documented
as S. viridans and not the group A beta-hemolytic strain
also argues against a latent Sydenham’s chorea being
reactivated. Furthermore, pathologic examination of her
mitral valve did not demonstrate Aschoff bodies, such as
are observed in rheumatic heart valve disease, or changes

Table 1.

Causes of choreoathetosis/ballismus in children

Benign: hereditary chorea
Immunologic: systemic lupus erythematosus, antiphospholipid antibody
syndrome, Henoch-Schönlein purpura, multiple sclerosis, Behçet’s
disease, polyarteritis nodosa
Infectious/postinfecitous: Sydenham’s chorea, subacute sclerosing
panencephalitis, encephalitis, toxoplasmosis, syphilis, diptheria,
typhoid
Vascular: postpump (cardiac surgery) chorea, poststroke chorea,
moyamoya disease, cerebral palsy
Neurometabolic/degenerative: juvenile Huntington’s disease,
neuroacanthocytosis, propionic acidemia, Wilson’s disease,
Hallervorden-Spatz syndrome, Lesch-Nyhan disease, glutaric
acidemia, pyruvate decarboxylase deficiency, GM2 gangliosidosis,
phenylketonuria, Leigh’s disease
Metabolic: hyperthyroidism, chorea gravidarum, Addison’s disease,
hypo/hypernatremia, hypo/hypercalcemia, hypo/hyperglycemia, liver
failure, renal failure, porphyria, vitamins B1 and B12 deficiency
Drugs: metoclopramide, dopaminergics, cocaine, amphetamines,
phenytoin, carbamazepine, valproic acid, ethosuximide, lithium, oral
contraceptives, isoniazid, tricyclic antidepressants, antihistamines,
anticholinergics, methylphenidate
Paroxysmal: paroxysmal dystonic (nonkinesigenic) choreoathetosis,
paroxysmal kinesigenic choreoathetosis
Toxins: alcohol intoxication and withdrawal, anoxia, carbon monoxide,
manganese, mercury, thallium, toluene
Tumors
Psychogenic
Data from Tuite and Lange [11].

typical of Libman-Sacks disease. The magnetic resonance
imaging scan dated her stroke as old and localized it
appropriately for the production of left-sided paresthesia.
Treatment of hemichorea secondary to stroke in adults
is usually aggressive because of concomitant hemiballismus. The most effective drugs in large clinical trials have
been phenobarbital, haloperidol, and reserpine, all of
which have significant adverse effects [4]. Alternatively,
gamma-aminobutyric acid (GABA)-ergic medications,
such as sodium valproate, clonazepam, and baclofen [5],
have been demonstrated to be effective for childhood
Table 2. Investigations in a case of choreoathetosis/ballismus in
children
Complete blood count, peripheral smear, platelet count, erythrocyte
sedimentation rate
Magnetic resonance imaging of the brain
Prothrombin time, partial thromboplastin time
Antinuclear antibody titer, lupus anticoagulant, antiphospholipid
antibody syndrome
Antistreptolysin-O titer, throat culture, pregnancy test
Serum copper, ceruloplasmin, and 24-hour urinary copper, slit lamp
eye examination for Kayser-Fleischer rings
Serum electrolytes, glucose, calcium, magnesium, uric acid, lactate,
ammonia, liver function tests
Urinary organic acids, genetic testing for Huntington’s disease
Thyroid function tests (triiodothyronine, thyroxine, thyrotropin)
Fluorodeoxyglucose positron emission tomography of the brain
Single-photon emission computed tomography of the brain
Data from Tuite and Lange [11].

Kothare et al: Gabapentin in Choreoathetosis 69

Figure 1. Basal ganglia movement modulation circuitry: (A) normal and (B) in chorea. Gpe: globus pallidus externa; Gpi: globus pallidus interna;
PPN/MEA: pedunculopontine nucleus/midbrain extrapyramidal area; SNc: substantia nigra pars compacta; SNr: substantia nigra pars reticulata; STN:
subthalamic nucleus; Striatum: caudate and putamen; ⫹: excitatory input; ⫺: inhibitory input; Ø: neutral input.

movement disorders caused by static encephalopathy,
stroke, and closed head injury [6]. Carbamazepine has also
been demonstrated to be effective in pediatric movement
disorders, including nonhereditary chorea [7]. The major
side effects from these drugs, hepatotoxicity and nausea, as
well as the requirements for frequent blood monitoring, make
their use less attractive. On the other hand, gabapentin has
putative GABA-ergic effects and transient side effects (sedation, dizziness), with no proven toxicity or drug interactions
to date [8]. It was recently demonstrated to be successful in
the treatment of a 4-year-old female with familial paroxysmal
choreoathetosis and to be well tolerated [9].
Figure 1A illustrates the normal basal ganglia circuitry,
with the presumed mechanism of production of chorea
illustrated in Figure 1B [10]. Thalamic stimulation of the
motor cortex is enhanced as the final common pathway.
Gabapentin has been demonstrated in animal models to
increase GABA turnover rates in selective areas of the brain,
specifically the thalamus. Its beneficial action in our patient
may be related to increased inhibition of thalamic activity,
thus dampening thalamic excitatory output to the cortex.
The introduction of gabapentin in this patient was slow,
with titration within 4 weeks to 4,800 mg/day, equivalent
to a dose of 75 mg/kg daily. No dose escalation was
required during the subsequent 6 months. A 2-month trial
discontinuation during the summer school break resulted

70

PEDIATRIC NEUROLOGY

Vol. 22 No. 1

in recurrence of the choreiform movements of the tongue
and left side of the face and dysarthric speech; autoimmune markers remained negative. One can infer that the
movement disorder was caused by a static lesion because
inflammatory and autoimmune chorea do not follow this
type of course [11]. In the case of Sydenham’s chorea the
natural history is 3-6 months of chorea, with spontaneous
resolution [12,13]. Antiphospholipid antibody syndrome
tends to be complicated by recurrent episodes of microvascular thrombosis when anticoagulation therapy is not
introduced [1]. The long-term efficacy and safety of
gabapentin remains to be determined.
The authors thank Mya Jewers for assistance with manuscript preparation.

References
[1] von Schevin E, Athreya BH, Rose CD, Goldsmith DP, Morton L.
Clinical characteristics of antiphospholipid antibody syndrome in children. Pediatrics 1996;129:339-45.
[2] Gordis L, Markowitz M. Rheumatic fever. In: Schaeffer AJ, ed:
Major problems in clinical pediatrics. Philadelphia: WB Saunders,
1972:147-55.
[3] Jankovic J, Scott BL. Delayed onset progressive movement
disorders after static brain lesions. Neurology 1996;46:68-74.
[4] Dewy RB, Jankovic J. Hemiballism-hemichorea, clinical and
pharmacologic findings in 21 patients. Arch Neurol 1989;46:862-7.

[5] James Rowan A. Valproate. In: Engel J, Pedley TA, eds.
Epilepsy: A comprehensive textbook, 1st ed. New York: LippincottRaven, 1998:1599-607.
[6] Pranzatelli MR. Antidyskinetic drug therapy for pediatric movement disorders. J Child Neurol 1996;11:355-69.
[7] Roig M, Montserrat L, Gallart A. Carbamazepine: An alternative
drug for the treatment of nonhereditary chorea. Pediatrics 1988;82:492-5.
[8] Taylor CP. Emerging perspectives on the mechanism of action
of gabapentin. Neurology 1994;44 (Suppl 5):S10-6.
[9] Chudnow RS, Mimbela RA, Owen DB, Roach S. Gabapentin for
familial paroxysmal dystonia choreoathetosis. Neurology 1997;49:
1441-2.

[10] Wichmann T, Delong MR. Physiology of the basal ganglia and
pathophysiology of movement disorders of basal ganglia origin. In:
Watts RL, Koller WC, eds. Movement disorders/neurological principles
and practice. New York: McGraw-Hill, 1997:87-97.
[11] Tuite PJ, Lang AE. Syndromes of disordered postures and
movement. In: Berg BO, ed. Principles of child neurology, 1st ed. New
York: McGraw-Hill, 1996:1513-41.
[12] Marques-Diaz MJ, Mercadante MT, Tucker D, Lombroso P.
Sydenham’s chorea. Psychiatry Clin North Am 1997;20:809-20.
[13] Cardoso F, Eduardo C, Silva AP, Mota CC. Chorea in 50
consecutive patients with rheumatic fever. Mov Disord 1997;12:
701-3.

Kothare et al: Gabapentin in Choreoathetosis 71