Paroxysmal choreoathetosis associated with thyrotoxicosis.

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Paroxysmal
Choreoathetosis Associated
with Thyrotoxicosis
Kenneth H . Fischbeck, MD, and Robert B. Layzer, M D
Acquired paroxysmal choreoathetosis can be associated with a variety of structural and metabolic disorders. A patient is presented who had paroxysmal
choreoathetosis associated with thyrotoxicosis and
who responded to treatment o f the underlying thyroid
disease.
Fischbeck K H , Layzer RB: Paroxysmal
choreoathetosis associated with thyrotoxicosis.
Ann Neurol 6:453-454, 1979
The syndrome of paroxysmal choreoathetosis can be
either familial o r acquired [ I , 101. Patients with the
familial form may be further classified according to
whether or not the movement disorder is induced by
sudden voluntary movement (kinesigenic o r nonkinesigenic). The acquired form of paroxysmal
choreoathetosis generally arises in older patients and
is thought to be a manifestation of underlying structural or metabolic brain disease. Diseases which have
been found to be associated with paroxysmal choreoathetosis are neuromyelitis optica [ 4 ] , multiple sclerosis [6, 9, 111, birth asphyxia [9, 141, and
hypoparathyroidism with hypocalcemia [ 161. We describe here a case of acquired paroxysmal choreoathetosis associated with thyrotoxicosis.
From the Department of Neurology, University of California
School of Medicine, San Francisco, CA.
Accepted for publication May 18, 1979.
Address reprint requests to Dr Layzer, Department of Neurology,
University of California School of Medicine, San Francisco, CA
94143.
A 35-year-old woman was admitted with complaints of
weakness and muscle spasms. Grand ma1 seizures had
begun at age I 3 years and responded well to treatment with
phenobarbital and phenytoin. At age 26 she had had an
episode of status epilepticus, which left her with memory
impairment that recovered after several months. Eighteen
months prior to admission, dysphagia, diplopia, dysarthria,
and generalized weakness developed. Myasthenia gravis
was diagnosed o n the basis of response to anticholinesterase treatment. Around the same time she began to have
episodes of generalized tonic spasm involving the face,
arms, and legs. H e r workup at another hospital was unremarkable except for right temporal slowing on one electroencephalogram and a small area of low density in the high
right parietal area o n a C T brain scan. She tolerated anticholinesterase treatment poorly, and her myasthenic
symptoms gradually progressed. The episodes of muscle
spasm became more severe and more frequent, occurring
an average of once per week in the month before admission. Raising her arms over her head seemed to precipitate
the attacks, which were more common when she was tired
or excited. She did not drink alcohol and had n o family
history of a similar disorder. She had taken no medication
for several months before admission.
General examination at admission was remarkable for
proptosis, greater o n the right than the left, and a precordial systolic ejection murmur. She was diaphoretic, though
vital signs were normal. Neurological examination showed
decreased eye movements with contracture of the right
lateral rectus muscle, nasal speech, facial weakness, and
reduced vital capacity. There was weakness of the neck and
proximal arm muscles. Deep tendon reflexes were increased in the legs, but plantar reflexes were flexor. She
had a fine tremor of the fingers and slight continual
choreiform movements, particularly in the left hand and
foot .
Treatment with pyridostigmine, atropine, and phenytoin
was started. While in the hospital the patient was noted to
have episodes of paroxysmal choreoathetosis, which she
called “muscle spasms,” one to four times per day. The
episodes usually lasted one or two minutes and began in the
left arm, with tonic flexion of the fingers, wrist, and elbow
and occasional coarse, rhythmic shaking of the hand. The
tonic spasm would spread to involve the face, which would
be contorted, with the mouth drawn open and a fixed stare.
The right arm was involved in a similar manner, though less
severely, and the trunk and legs were usually held in tonic
extension. She remained conscious throughout, although
unable t o speak, and as soon as the episode ended she was
able to give a detailed account of the events that had transpired. An electroencephalogram showed only diffuse
slowing. The episodes continued despite treatment with
phenytoin at 300 mg per day (serum level, 10 pg/ml)
and did not respond to intravenous administration of
diphenhydramine or benztropine. She was started on
clonazepam. O n the fourth hospital day the patient developed a low-grade fever and supraventricular tachycardia. Thyroid function tests showed a thyroxine level of
22.0 p d d l (normal, 5.3 to 14.5 pgldl), radioactive
triiodothyronine uptake of 42% (normal, 26 to 359&),
thyroxine index of 7.5 (normal, 1.4 to 5 . 1 ) , and tri-
0364-5 1341791 10453-02$01.25 @ 1979 by Kenneth H. Fischbeck
453
odothyronine radioimmunoassay of 549 ngldl (normal,
100 to 200 ng/dl). She was started on therapy with propranolol, propylthiouracil, and potassium iodide.
With treatment her fever and tachycardia resolved, and
within two weeks the thyroid function tests returned to
normal. Her paroxysmal movement disorder gradually subsided thereafter. The myasthenia was treated with
thymectomy, prednisone, and plasmapheresis. By the time
of discharge five weeks after the start of treatment for
thyrotoxicosis, h e r strength had improved considerably and
she had only mild chorea in the left hand and arm. The
patient experienced n o further episodes of generalized
dystonia and choreoathetosis in the month after discharge;
she was then lost to follow-up.
Discussion
Thyrotoxicosis causes a variety of central nervous
system disturbances such as hyperreflexia, fine rapid
tremor, psychiatric disorders, and increased seizure
frequency. Chorea as a manifestation of hyperthyroidism has been reported since the late nineteenth
century [15]. Recent reports emphasize that the
movement disorder is associated with high levels of
serum thyroxine and that chorea subsides after the
thyroxine is brought into the normal range with appropriate treatment [1, 2, 5 , 12, 13, 171. Patients
with this disorder have also been shown to respond
to treatment with the beta-adrenergic blocking agent
propranolol and dopamine receptor blocker
haloperidol before the hyperthyroidism is brought
under control [ l , 5 , 81. Such observations prompted
Klawans and co-workers [ 7 , 8 ]to propose that hyperthyroidism produces chorea by increasing the sensitivity of striatal catecholamine receptors. Supporting that proposal are the findings that hyperthyroid
patients have decreased cerebrospinal fluid levels of
homovanillic acid (suggesting decreased catecholamine turnover secondary to increased receptor sensitivity) [8] and that guinea pigs made hyperthyroid
are more sensitive to stimulation by apomorphine,
a dopamine agonist [?I. Only a few patients with
thyrotoxicosis develop chorea, however, and perhaps
those who do have an underlying structural abnormality in the basal ganglia so that a subclinical catecholamine imbalance is aggravated by the addition of
thyrotoxicosis.
O u r patient differs from other reported cases of
thyrotoxic chorea in that her movement disorder was
paroxysmal, whereas the others had continuous
chorea. A similar mechanism may be involved, however. The patient’s episode of hypoxic encephalopathy at age 26 could well have done damage to striatal
neurons, thereby providing the underlying structural
substrate for adventitious movement. The episodes
of choreoathetosis may have been produced by
paroxysmal bursts of activity from damaged neurons
further made hyperexcitable by thyroxine-induced
hypersensitivity to dopamine. Treatment of the
thyrotoxicosis may have raised the firing threshold of
these cells and allowed the patient’s movement disorder to come under control.
It is also possible that the paroxysmal choreoathetosis was another autoimmune phenomenon in a
patient who has myasthenia and thyrotoxicosis, both
presumably autoimmune diseases. If this were the
case, her symptomatic improvement might have been
caused by treatment with prednisone and plasmapheresis rather than by the treatment for
thyrotoxicosis.
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454 Annals of Neurology Vol 6 No 5 November 1979