Movement Disorders
Vol. 23, No. 4, 2008, pp. 620-628
© 2008 Movement Disorder Society

Letters to the Editor Related to New Topics

in some cases, chorea ceased when hyperthyroidism was corrected, and eventually reappeared as hyperthyroidism developed again.3 Although most cases involve Grave’s disease, a
few reports of chorea due to iatrogenic thyrotoxicosis have
been published.7 The pathophysiology of hyperthyroidism-related chorea is poorly understood, which is not surprising in
view of the wide range of metabolic pathways affected by
thyroid hormones. Chorea is associated with complex dysfunction within the basal ganglia system. Hyperthyroidism could
modify basal ganglia function through neurotransmitter alteration and (or) gene dysregulation. It has been suggested that
thyroid hormones could functionally affect the dopaminergic
system within the basal ganglia, possibly through an increased
sensitivity of the dopaminergic receptors.3 However, thyroid
hormones also play an important role in regulating central
noradrenergic, serotoninergic, and cholinergic systems, and
complex interactions may occur.8,9 Furthermore, thyroid hormones also control gene expression in the nervous central
system. Among thyroid hormones target genes, the Rhes
(Ras homolog enriched in striatum) gene, which encodes a
small GTP-binding protein, is of particular interest, as it is
predominantly expressed in the striatum.10 Thyroid hormones
also modify the expression of the transcriptional coactivator
PGC-1, a protein which regulates metabolic pathways and
biological processes in brain (and other tissues), especially in
the striatum.11 However, whether modified gene expression is
involved in hyperthyroidism induced chorea remains
speculative.
In the observation we report, the patient had two other
potential causes of chorea, i.e., ischemic focal lesions of the
basal ganglia and MMS. Focal lesions involving the caudate
nucleus and (or) the putamen may be associated with chorea.12 However, in this case, chorea is contralateral to the
lesion and is not likely to have a relapsing-remitting course,
as what was observed in our patient. MMS has also been
associated with chorea.13 In this condition, related basal
ganglia hypoperfusion could play a part in the genesis of
choreic movement.14,15 Interestingly, the association of
MMS and Grave’s disease is probably not fortuitous, as
several patients with this association have been previously
reported. It has been hypothesized that both conditions may
share a common autoimmune mechanism.15 In most of these
cases, cerebrovascular accidents occurred when patients
were thyrotoxic, suggesting that thyroid hormones could
have facilitate these accidents, possibly through hemodynamic changes and (or) sympathetic nervous system-mediated vasculopathy.15
In the present case, the rapid improvement of the chorea
after correction of the hyperthyroidism demonstrates that
high levels of thyroid hormones were the main causative
factor. However, we cannot rule out the possibility that
MMS was a predisposing factor, although not sufficient by
itself to trigger the chorea.

Reversible Chorea in Association with Graves’
Disease and Moyamoya Syndrome
Hyperthyroidism and moyamoya syndrome (MMS) are rare
causes of chorea.1 Here, we report a patient who had chorea
associated with both conditions.
A 19-year-old woman from Ivory Coast was admitted
because of movement disorder. There was no family history
of neurological diseases. The patient had been diagnosed
with Graves’ disease at age 18 and had since showed poor
compliance with carbimazole therapy. Upon admission, free
thyroxine level was more than 100 pmol/L (range 12–23),
thyroid stimulating hormone was undetectable (less than
0.001 mUI/L, range 0.3– 4.4), and thyroid stimulating antibodies were positive: 21.1 UI/L. About 2 weeks before
admission, she had progressively developed movement disorder, balance impairment, and dysarthria. On examination,
the patient had a diffuse goiter and typical signs of thyrotoxicosis, including warm, moist skin, and tachycardia. She
had mild and diffuse choreic movements, predominating in
the facial area. Movements involved symmetrically both
upper limbs, mainly in sustained posture. The patient had
mild dysarthria and tandem walk was impaired. Mild slowing of alternating movements of both hands was present.
Neurological examination was otherwise normal. Routine
blood count, electrolytes, urea, creatinine, liver function
panel, were all normal. Autoantibody screen was negative
for anticardiolipids, lupus anticoagulant, Antibeta2GP1, antinuclear antibody, and anti dsDNA antibody. Brain magnetic resonance imaging (MRI) showed high signal intensity
lesions on FLAIR and T2 sequences in the left anterior
putamen and the head of the left caudate nucleus (Fig. 1).
MR angiography showed severe stenosis of the extremity of
the internal carotid arteries, at the origin of both middle
cerebral arteries, as well as of the left anterior cerebral
artery. Four-vessel cerebral angiography showed bilateral
severe stenosis of the supraclinoid portion of the internal
carotid arteries with MMS (Fig 2.). Treatment with carbimazole (20 mg/day) and levothyroxine (synthetic T4) 50 ␮g/
day was resumed, in association with propanolol. Clinical
signs of thyrotoxicosis and neurological symptoms subsided
within a few weeks. Three months later, the patient had
normal neurological examination and her thyroid tests results were normal. Because of poor observance, two relapses
occurred in the following year, consisting of the reappearance of clinical signs of hyperthyroidism and chorea. Thyroidectomy was finally performed and the patient has since
remained free of symptoms.
The association of hyperthyroidism and chorea has been
reported in several patients.2-6 A causal relationship is likely, as
Published online 9 January 2008 in Wiley InterScience (www.
interscience.wiley.com). DOI: 10.1002/mds.21941

620

LETTERS TO THE EDITOR

621

FIG. 1. Cerebral Axial T2 weighted MRI. Hyperintense lesion in the left caudate and lenticular nucleus.

FIG. 2. Conventional right (A) and left (B) internal carotid artery angiogram. Frontal view. Extremely severe bilateral stenoses of the internal carotid
bifurcation and M1 segments. Development of an important collateral circulation from the lenticulostriate arteries.

Movement Disorders, Vol. 23, No. 4, 2008

622

LETTERS TO THE EDITOR

Acknowledgments: We thank Drs Z. Kahal and B.
Mouchet for referring the patient, and Dr L. Freeman for
writing assistance.
Béatrice Garcin, MD
Department of Neurology
AP-HP, Henri Mondor Hospital
Créteil, France
Taina Louissaint, MD
Department of Internal Medicine
AP-HP, Henri Mondor Hospital
Créteil, France
Hassan Hosseini, MD, PhD
Department of Neurology
AP-HP, Henri Mondor Hospital
Créteil, France
Raphaël Blanc, MD
Department of Neuroradiology
AP-HP, Henri Mondor Hospital
Créteil, France
Gilles Fénelon, MD, PhD*
Department of Neurology
AP-HP, Henri Mondor Hospital
Créteil, France
*E-mail: gilles.fenelon@hmn.aphp.fr

References
1. Cardoso F, Seppi K, Mair KJ, et al. Seminar on choreas. Lancet
Neurol 2006;5:589-602.
2. Nagaoka T, Matsushita S, Nagai Y, Kobayashi K. A woman who
trembled, then had chorea. Lancet 1998;351:1326.
3. Ristić AJ, Svetel M, Dragaševic N, et al. Bilateral choreaballism associated with hyperthyroidism. Mov Disord 2004;19:
982-983.
4. Heoffron W, Eaton RP. Thyrotoxicosis presenting as choreoathetosis. Ann Intern Med 1970;73:425-428.
5. Fidler SM, O’Rourke RA, Buchsbaum HW. Choreoathetosis as a
manifestation of thyrotoxicosis. Neurology 1971;21:55-57.
6. Pozzan GB, Battistella PA, Rigon F, et al. Hyperthyroid-induced
chorea in an adolescent girl. Brain Dev 1992;14:126-127.
7. Isaacs JD, Rakshi J, Baker R,Brooks DJ, Warrens AN. Chorea
associated with thyroxine replacement therapy. Mov Disord 2005;
20:1656-1670.
8. Bauer M, Heinz A, Whybrow PC. Thyroid hormones, serotonin
and mood: of synergy and significance in the adult brain. Mol
Psychiatry 2002;7:140-156.
9. Smith JW, Evans AT, Costall B, Smythe JW. Thyroid hormones,
brain function and cognition: a brief review. Neurosci Biobehav
Rev 2002;26:45-60.
10. Spano D, Branchi I, Rosica A, et al. Rhes is involved in striatal
function. Mol Cell Biol 2004;24:5788-5796.
11. Lin J, Handschin C, Spiegelman BM. metabolic control through
the PGC-1 family of transcription coactivators. Cell Metab 2005;
1:361-370.
12. Bhatia KP, Marsden CD. The behavioral and motor consequences
of focal lesions of the basal ganglia in man. Brain 1994;117:859876.
13. Gonzalez-Alegre PG, Ammache Z, Davis PH, Rodnitzky RL.
Moyamoya-induced paroxysmal dyskinesia. Mov Disord 2003;18:
1051-1056.

Movement Disorders, Vol. 23, No. 4, 2008

14. Hong YH, Ahn TB, Oh CW, et al. Hemichorea as an initial
manifestation of moyamoya disease: reversible striatal hypoperfusion demonstrated on single photon emission computed tomography. Mov Disord 2002;17:1380-1383.
15. Nakamura K, Yanaka K, Ihara S, Nose T. Multiple intracranial
arterial stenoses around the circle of Willis in association with
Graves’ disease: report of two cases. Neurosurgery 2003;53:12101215.

Atypical Stereotypies and Vocal Tics in Rett
Syndrome: An Illustrative Case

Hand sterotypies are the signature sign of Rett syndrome (RTT)
and their presence plays a key role in diagnosis.1 We have
found that hand movements, which may involve the hands
together or apart, are very standardized in individual girls. We
also found additional stereotypies (including vocal ones) that
changed over time, not previously reported in RTT and we
hypothesized the existence of tics in this disorder.1
Most studies stress that stereotyped hand movements coincide with or follow the disappearance of purposeful prehension
in RTT; however, more recently, different studies reported
stereotypies as coinciding with or preceding the loss of purposeful hand movements in this disorder.1-3 Thus we believe
that the particularly compulsive stereotypies in patients with
RTT are likely to contribute to loss or reduction of hand use.
We present the case of a girl with RTT with a very atypical
presentation that illustrates the complexity of movement disorders and psychiatric symptoms that can be present in RTT and
their probable interference in function.
In a center for autistic children a child psychiatrist noticed
that one 6-year-old girl stood out from the majority of the other
children in that she had intense eye contact.
This girl was the second child of an unrelated and healthy
couple and her perinatal history was normal. Family history
was unremarkable for tics, obsessive-compulsive symptoms,
and neurologic or psychiatric problems. When she was born her
occipital frontal circumference (OFC) was below the 5th percentile but increased progressively to 50 percentile by 6 months
of age. She achieved head control at 3 months, grasped an
object at 4 months, and had intentional prehension at 5 months.
She walked unsupported and uttered her first words at 13
months. She never crawled.
She had a high pitched voice and echolalia. She spoke
complex frequently coprolalic phrases and her vocabulary was
notable for unusual words. She had some phobias and repetitive
compulsive behaviors such as switching lights on and off and
opening and closing drawers. She never acquired sphincter
control.
At 4 years old she met DSM-IV4 diagnostic criteria for
autistic disorder and developmental quotient (QD) evaluation

This article includes supplementary video clips, available online at
http://www.interscience.wiley.com/jpages/0885-3185/suppmat.
Published online 16 January 2008 in Wiley InterScience (www.
interscience.wiley.com). DOI: 10.1002/mds.21939