Movement Disorders
Vol. 17, No. 4, 2002, pp. 831–845
© 2002 Movement Disorder Society

Clinical/Scientific Notes
fulfilling the criteria for PD described elsewhere,7 were recruited from the central area of Japan between 1996 and 2000.
The patients were divided into the early-onset group (EOPD;
onset at or before 50 years; n ⳱ 64; mean age, 53.8 ± 5.8 years)
and the late onset group (LOPD; onset after 50 years; n ⳱ 172;
mean age, 69.0 ± 7.5 years). Two hundred twenty healthy individuals were selected from the annual health examination at
a city clinic. The control group was matched for age (mean,
63.2 ± 9.1 years; age range, 40–82 years), sex ratio (132
women and 88 men), and birth place (Kyoto and Osaka prefectures) with the PD group. The study protocol was approved
by the institutional ethical committees and informed consent
was obtained from each participant.
Leukocyte DNA was isolated by using standard protocols.
Genotyping for 1215A/G polymorphism in the DAT1 gene was
performed by the polymerase chain reaction-restriction fragment length polymorphism method by using a restriction enzyme DdeI and the following primers: 5⬘-TGTGGCAGGCCATGCTTCTCG-3⬘ and 5⬘-CCCCCTCGGGTGGAAGGAACC-3⬘.
The data were evaluated by ␹2 or Fisher’s exact test, by using
the standard statistical software (Stat View v. 5.0; Abacus Concepts, CA). The corrected P values (Pc) were obtained by multiplying the uncorrected P values (Pu) with the number of
comparisons. A P <0.05 was taken as the level of significance.

Association Between Dopamine Transporter
Gene Polymorphism and Susceptibility to
Parkinson’s Disease in Japan
Masataka Nishimura, MD,1* Ryuji Kaji, MD,1
Mitsuhiro Ohta, PhD,2 Ikuko Mizuta, PhD,3
and Sadako Kuno, MD,3
1

Department of Clinical Neuroscience, Tokushima University
Hospital, Tokushima, Japan
2
Department of Clinical Chemistry, Kobe Pharmaceutical
University, Kobe, Japan
3
Department of Clinical Research Center, Utano National
Hospital, Ukyo-ku, Kyoto, Japan

Abstract: We studied a polymorphism in the dopamine transporter (DAT) gene in 236 Japanese patients with Parkinson’s
disease (PD) and compared the results with 220 controls. The
1215A/G genotype of the DAT gene was significantly different
between PD patients and controls, suggesting a possible involvement of DAT in genetic susceptibility to PD. © 2002
Movement Disorder Society
Key words: Parkinson’s disease; dopamine transporter;
polymorphism; case-control study; early-onset Parkinson’s disease
Parkinson’s disease (PD) is characterized by the progressive
loss of dopamine neurons in the substantia nigra. Although the
pathogenesis of sporadic PD is unknown, a combination of
environmental and inherited factors as well as aging is thought
to contribute to the development of the disease.
Dopamine transporters (DAT) uptake neurotoxic substances
such as 1-methyl-4-phenylpyridinium (MPP+),1 in the dopaminergic nerve terminals and may confer susceptibility to cytotoxic effects of neurotoxic substance. The gene encoding DAT1
contains a variable number of tandem repeat (VNTR) polymorphism in the 3⬘-flanking region and a diallelic A/G polymorphism at position 1215 of the gene, which are in almost complete linkage disequilibrium.2 Although several studies have
been performed on a possible association between the DAT1
gene polymorphisms and PD, the findings have not been
consistent.2–6 We investigated whether 1215A/G polymorphism in the DAT1 gene may be responsible in part for genetic
susceptibility to PD in Japanese patients.

Results
The distribution of 1215A/G genotype in the DAT1 gene is
shown in Table 1. Both the patient and control populations
were in Hardy-Weinberg equilibrium. The A/G genotype
showed a marginally significant difference between total PD
patients and controls (␹2 ⳱ 7.77; P ⳱ 0.021). The difference
was more obvious in the genotype between EOPD patients and
the total control group (Pu ⳱ 0.0051; Pc ⳱ 0.01). Comparison
of the EOPD patients with age-matched controls (n ⳱ 136; age
range, 40–65 years; mean age, 52.8 ± 7.1 years) also showed a
significant association (Pu ⳱ 0.0074; Pc ⳱ 0.015). The frequency of the 1215G allele also decreased significantly in
EOPD patients compared to both the total control group (Pu ⳱
0.0076; Pc ⳱ 0.015) and the age-matched control group (Pu ⳱
0.011; Pc ⳱ 0.022). There was no 1215G frequency variation
with age in the control group (data not shown).

Patients and Methods

Discussion

A total of 236 Japanese PD patients (141 women and 95
men; age range, 35–86 years; mean age, 65.5 ± 9.7 years)

The association between DAT1 1215A/G polymorphism and
Parkinson’s disease is a matter of debate.2,3 Morino and colleagues3 reported a significant decrease in the frequency of the
1215G allele in Japanese PD patients compared to controls. The
association was, however, not replicated in another set of Japanese PD patients and controls.2 Our results supported the association proposed by Morino and associates,3 and we also
detected the more obvious difference between the EOPD group
and controls.

*Correspondence to: Masataka Nishimura, MD, Department of
Clinical Neuroscience, Tokushima University Hospital, Tokushima
770-8503, Japan. E-mail: m_nishim@clin.med.tokushima-u.ac.jp
Received 12 July 2001; Revised 28 December 2001; Accepted 11
January 2002
Published online 4 April 2002 in Wiley InterScience (www.
interscience.wiley.com). DOI 10.1002/mds.10187

831

832

CLINICAL/SCIENTIFIC NOTES
TABLE 1. Distribution of DAT1 1215 A/G alleles in patients with Parkinson’s disease and controls
Allele
Genotype
n

A/A (%)

A/G (%)

G/G (%)

Controls
Total PD
Early-onset controls
EOPD

220
236
136
64

174 (79.1)
200 (84.7)
107 (78.7)
60 (93.8)

46 (20.9)
32 (13.6)
29 (21.3)
4 (6.3)

0 (0.0)
4 (1.7)
0 (0.0)
0 (0.0)

Controls (Morino et al.3)
Controls (Kimura et al.2)

132
300

100 (86.6)
249 (83.0)

32 (24.2)
50 (16.7)

0 (0.0)
1 (0.3)

P
0.021
Pu ⳱ 0.0051a
Pc ⳱ 0.010b
Pu ⳱ 0.0074c
Pc ⳱ 0.015b

Allele A
(%)

Allele G
(%)

89.5
91.5
89.3
96.9

10.5
8.5
10.7
3.1

87.9
91.3

12.1
8.7

P
0.31
Pu ⳱ 0.0076a
Pc ⳱ 0.015b
Pu ⳱ 0.011c
Pc ⳱ 0.022b

DAT, dopamine transporter; PD, Parkinson’s disease; EOPD, early-onset PD. P value was calculated by ␹2 test or Fisher’s exact test with a 2 ×
3 or a 2 × 2 contingency table. Pu, uncorrected P value; Pc corrected P value.
a
P value was calculated between EOPD and controls (n ⳱ 220).
b
Since PD patients were divided into two groups (EOPD and late-onset PD); Pc was obtained by multiplying Pu by 2.
c
P value was calculated between EOPD and age-matched, early onset controls (n ⳱ 136).

There are several explanations for the discrepancy in a casecontrol study. It may be due to sample differences or population
stratification. Geographic and environmental differences must
be taken into account. Because the false-positive rate can be
significantly reduced by achieving very low P value (10−6 to
10−8), we cannot rule out a type 1 error, despite our independent replication.
Although the pathogenesis involved in the progressive degeneration of nigral dopamine neurons in PD is still unknown,
certain people with a particular genotype and an exposure to
appropriate environmental toxins or stimuli may develop PD.
Neurotoxins, including 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) and 6-hydroxydopamine, enter
dopamine neurons by means of the DAT1, leading to selective
degeneration of dopamine neurons.
Because the A/G polymorphism does not cause an amino
acid substitution, the polymorphism may be part of a haplotype
that also includes functionally relevant polymorphisms in the
DAT1 gene. Further research will be necessary to detect combined effects of the DAT gene polymorphism with other genes
related with dopamine metabolism8 and environmental exposures.9,10

of a polymorphism in the dopamine-transporter gene with Parkinson’s disease. Mov Disord 1997;12:760–763.
7. Calne DB, Snow BJ, Lee C. Criteria for diagnosing Parkinson’s
disease. Ann Neurol 1992;32:S125–S127.
8. Wu RM, Cheng CW, Chen KH, Lu SL, Shan DE, Ho YF, Chern
HD. The COMT L allele modifies the association between MAOB
polymorphism and PD in Taiwanese. Neurology 2001;56:375–
382.
9. Menegon A, Board PG, Blackburn AC, Mellick GD, Le Couteur
DG. Parkinson’s disease, pesticides, and glutathione transferase
polymorphisms. Lancet 1998;352:1344–1346.
10. De Palma G, Mozzoni P, Mutti A, Calzetti S, Negrotti A. Casecontrol study of interactions between genetic and environmental
factors in Parkinson’s disease. Lancet 1998;352:1986–1987.

References

Abstract: A character from one of Charles Dickens’s lesser
known works is presented, whose attributes suggest a possible
diagnosis of progressive supranuclear palsy. © 2002 Movement
Disorder Society
Key words: progressive supranuclear palsy; historical

1. Tipton KF, Singer TP. Advances in our understanding of the
mechanisms of the neurotoxicity of MPTP and related compounds.
J Neurochem 1993;61:1191–1206.
2. Kimura M, Matsushita S, Arai H, Takeda A, Higuchi S. No evidence of association between a dopamine transporter gene polymorphism (1215A/G) and Parkinson’s disease. Ann Neurol 2001;
49:276–277.
3. Morino H, Kawarai T, Izumi Y, Kazuta T, Oda M, Komure O,
Udaka F, Kameyama M, Nakamura S, Kawakami H. A single
nucleotide polymorphism of dopamine transporter gene is associated with Parkinson’s disease. Ann Neurol 2000;47:528–531.
4. Kim JW, Kim DH, Kim SH, Cha JK. Association of the dopamine
transporter gene with Parkinson’s disease in Korean patients. J
Korean Med Sci 2000;15:449–451.
5. Leighton PW, Le Couteur DG, Pang CC, McCann SJ, Chan D,
Law LK, Kay R, Pond SM, Woo J. The dopamine transporter gene
and Parkinson’s disease in a Chinese population. Neurology 1997;
49:1577–1579.
6. Le Couteur DG, Leighton PW, McCann SJ, Pond SM. Association

Movement Disorders, Vol. 17, No. 4, 2002

Did Charles Dickens Describe Progressive
Supranuclear Palsy in 1857?
A.J. Larner, MD*
Walton Centre for Neurology and Neurosurgery,
Liverpool, United Kingdom

The novels of Charles Dickens have fascinated readers ever
since their first publication, not least because of the numerous
engaging characters that are described therein.1 These often
minutely-observed figures have prompted later readers to ad*Correspondence to: Dr. A.J. Larner, Walton Centre for Neurology
and Neurosurgery, Lower Lane, Fazakerley, Liverpool, L9 7LJ, United
Kingdom. E-mail: larner-a@wcnn-tr.nwest.nhs.uk
Received 10 September 2001; Revised 30 November 2001; Accepted 11 December 2001
Published online 29 March 2002 in Wiley InterScience (www.
interscience.wiley.com). DOI 10.1002/mds.10170

CLINICAL/SCIENTIFIC NOTES
duce descriptions of specific diseases: the Pickwickian syndrome, based on the obese and hypersomnolent “Joe the fat
boy” in the Pickwick Papers (1837) is a case in point.
Neurologists have been able to detect in Dickens’s descriptions various neurological disorders,2–4 including movement
disorders.5,6 In David Copperfield (1850), it has been suggested
that Uriah Heep suffers from generalized dystonia and Mr.
Creakle from spasmodic dysphonia6; and in Little Dorrit
(1857) Jeremiah Flintwinch has torticollis and Pancks manifests features of Gilles de la Tourette syndrome,5 this last account appearing some years before that of the eponymous author (1885). The accuracy of the descriptions, as judged retrospectively, prompts the belief that they are based on the
observation of actual patients.6 Although there are dangers in
this type of extrapolation, nonetheless I venture to suggest another possible Dickensian first.

Case Report
In The Lazy Tour of Two Idle Apprentices, Dickens and his
friend Wilkie Collins, thinly disguised as Francis Goodchild
and Thomas Idle, respectively, describe a journey through the
north of England from Carlisle to Doncaster undertaken in
September 1857. Their account was originally published in
installments, beginning in October 1857, in Dickens’s magazine Household Words.7
At an inn in Lancaster, “Mr Goodchild [Dickens] writes the
present account of his experience” (p. 195), relating an encounter with:
“A chilled, slow, earthy, fixed old man. A cadaverous man
of measured speech. An old man who seemed as unable to
wink, as if his eyelids had been nailed to his forehead. An
old man whose eyes—two spots of fire—had no more
motion that [sic] if they had been connected with the back
of his skull by screws driven through it, and rivetted and
bolted outside, among his grey hair.”
“He had come in and shut the door, and he now sat
down. He did not bend himself to sit, as other people do,
but seemed to sink bolt upright, as if in water, until the
chair stopped him.” (p. 194).

Discussion
Read from a neurologist’s perspective, these passages suggest the presence of the following clinical features:

833

Ankylosing spondylitis might account for the fixed posture that
necessitates sinking into a chair bolt upright, but the other
neurological features are out with this diagnosis.
In their study, Steele and associates expressed surprise that
such a distinctive disorder as PSP had not been previously
reported8 but a number of earlier cases have subsequently been
identified,10 dating back to that of the American ophthalmologist Campbell Posey in 1904. If Dickens’s account is that of a
case of PSP, occurring in the mid-nineteenth century, it predates the eponymous clinical description by more than 100
years.

References
1. Greaves J. Who’s who in Dickens. London: Hamish Hamilton Elm
Tree Books; 1972.
2. Brain R. Dickensian diagnoses. BMJ 1955;ii:1553–1556.
3. Perkin GD. Disorders of gait. J Neurol Neurosurg Psychiatry 1996;
61:199.
4. Cosnett JE. Charles Dickens and sleep disorders. Dickensian 1997;
93:200–204.
5. Cosnett JE. Dickens, dystonia and dyskinesia. J Neurol Neurosurg
Psychiatry 1991;54:184.
6. Garcia-Ruiz PJ, Gulliksen LL. Movement disorders in David Copperfield [in Spanish]. Neurologia 1999;14:359–360.
7. Dickens C, Collins W. The lazy tour of two idle apprentices. In: No
thoroughfare and other stories. Stroud: Alan Sutton; 1990. p 128–
227.
8. Steele JC, Richardson JC, Olszewski J. Progressive supranuclear
palsy: a heterogeneous degeneration involving the brainstem, basal ganglia and cerebellum with vertical gaze and pseudobulbar
palsy, nuchal dystonia, and dementia. Arch Neurol 1964;10:
333–358.
9. Litvan I, Agid Y, Calne D, Campbell G, Dubois B, Duvoisin RC,
Goetz CG, Golbe LI, Grafman J, Growdon JH, Hallett M, Jankovic
J, Quinn NP, Tolosa E, Zee DS. Clinical research criteria for the
diagnosis of progressive supranuclear palsy (Steele-RichardsonOlszewski syndrome): report of the NINDS-SPSP International
Workshop. Neurology 1996;47:1–9.
10. Lees AJ. The Steele-Richardson-Olszewski syndrome (progressive
supranuclear palsy). In: Marsden CD, Fahn S, editors. Movement
disorders 2. London: Butterworth; 1987. p 272–287.

Parkinsonian Syndrome Induced by
Amlodipine: Case Report
Hélio A.G. Teive, MD,* Francisco M.B. Germiniani, MD,
and Lineu César Werneck, MD, PhD

1. Ophthalmoplegia: “eyes … had no motion”;
2. Lid retraction: “eyelids … nailed to his forehead”; combined with the inability to wink, this hints at the man’s
staring expression, sometimes known as Stellwag’s sign;
3. Axial dystonia with rigidity: “fixed”, “he did not …bend to
sit”; the fact that he sinks bolt upright and is stopped by the
chair (en bloc sitting) suggests postural instability. This has
sometimes been termed the “rocket man sign”.

Abstract: An elderly patient who developed marked symptoms
of parkinsonism in response to amlodipine for the treatment of
arterial systemic hypertension is described. She had a complete

In addition there are hints of bradykinesia (“slow”) and possibly pseudobulbar palsy (“measured speech”).
These features are suggestive of the syndrome of progressive
supranuclear palsy (PSP) described by Steele and colleagues8
The information in Dickens’s account, however, is insufficient
to fulfil currently accepted clinical diagnostic criteria for
PSP9,10: significantly the unsteady gait of PSP is not mentioned, even though the individual is described entering a room.

A videotape accompanies this article.
*Correspondence to: Hélio A.G. Teive, Rua General Carneiro 1103/
102, CEP: 80.060-150, Curitiba, Paraná, Brazil.
E-mail: hagteive@mps.com.br
Received 12 March 2001; Revised 16 November 2001; Accepted 14
January 2002
Published online 2 April 2002 in Wiley InterScience (www.
interscience.wiley.com). DOI 10.1002/mds.10185

Movement Disorders Unit, Neurology Service, Hospital de
Clı́nicas, Federal University of Paraná, Curitiba, PR, Brazil

Movement Disorders, Vol. 17, No. 4, 2002

834

CLINICAL/SCIENTIFIC NOTES

reversal of her motor symptoms after discontinuation of the
drug. © 2002 Movement Disorder Society
Key words: parkinsonian syndrome; amlodipine; druginduced parkinsonism
Drug-induced parkinsonism represents the second leading
cause of parkinsonism1 in some countries, such as Brazil. The
antidopaminergic drugs most often related to parkinsonian syndrome (PK) are calcium channel blockers, neuroleptics, and
anti-emetic drugs.1–5 We describe the case of an elderly patient
who developed marked symptoms of parkinsonism in response
to amlodipine for the treatment of arterial systemic hypertension. She had a complete reversal of her motor symptoms after
discontinuation of the drug.

Case Report
An 83-year-old female patient had a geriatric follow-up for
arterial systemic hypertension, osteoporosis, depression, and
vestibular syndrome (light-headedness). Her treatment consisted of enalapril–hydrochlorothiazide, vitamin E, vitamin D,
calcium, bromazepam, paroxetine, omeprazole, and selegiline
(for possible neuroprotective purposes). On follow-up, vestibular symptoms disappeared without specific treatment.
After a cardiological evaluation, she discontinued the use of
enalapril–hydrochlorothiazide and began amlodipine 10 mg a
day. Two months later, the patient complained of progressive
gait disorder, bradykinesia, tremor, disequilibrium, and frequent falls. Neurological examination disclosed a rigid-akinetic
syndrome, with severe bradykinesia, postural instability, cogwheel rigidity, and a predominantly postural tremor that also
had a rest component (Videotape, Segment 1).
Whole blood count, VDRL, TSH, vitamin B12, and folic
acid were all normal. A magnetic resonance imaging (MRI)
study of the brain was also normal. Amlodipine was withdrawn, and after 30 days, her motor function reverted back to
normal (Videotape, Segment 2). Paroxetine dose remained unchanged (20 mg once a day). She was followed up at 3, 6, and
12 months and on her last neurological examination she demonstrated only mild bradykinesia.

Discussion
PK is characterized by the combination of at least two of the
following signs: tremor, rigidity, bradykinesia, and postural
instability. Its most common cause is Parkinson’s disease
(PD).1–4 In a large number of studies, drug-induced parkinsonism represents the second most common cause of PK.1–4 In
Brazil, the studies of Cardoso and colleagues1 and Herdoiza
(personal communication) have found that the second leading
cause of PK was drug-induced parkinsonism (predominantly
due to the calcium-channel blockers flunarizine and cinnarizine). Similar results were reported by Errea-Abad and associates, and by Kuzuhara and Lau.2–4
Commonly recognized drugs that can induce PK are neuroleptics, dopamine depletors and anti-emetic drugs.1–5 Other
smaller series and case reports have suggested that a constantly
increasing number of drugs are responsible for the development
of PK or for a worsening of the motor function in a parkinsonian patient. Drugs in the latter group include frequently used

Movement Disorders, Vol. 17, No. 4, 2002

drugs such as methyldopa, nifedipine, captopril, amiodarone,
cimetidine, meperidine, diltiazem, verapamil, lithium, phenytoin, valproic acid, and veralipride, among others.2–4,6–11
Conflicting data have been reported discussing whether selective serotonin reuptake inhibitors, such as paroxetine, may
worsen parkinsonian motor symptoms. Jimenez-Jimenez and
coworkers reported in 1994 on the case of a patient with earlyonset parkinsonism and depression. The addition of paroxetine
aggravated the parkinsonism, which improved after withdrawal
of this drug.12 Tesei and colleagues studied 65 outpatients with
PD and depression, evaluating the paroxetine (10–20 mg once
a day). Two patients had exacerbation of parkinsonian motor
symptoms, and the conclusion drawn was that paroxetine is
safe and effective to treat depression in PD.13 Similar results
were observed by Ceravollo and associates, who studied 29
patients with PD and depression with paroxetine use for 6
months. Parkinsonian motor function did not change and one
patient had worsening of the tremor.14 In the present case report, there was no clinical relation between the use of paroxetine and the development of parkinsonian motor symptoms.
Amlodipine is a long-action calcium entry blocker of the
dihydropyridine class that is used for treatment of arterial hypertension and angina pectoris. It inhibits the calcium influx
through slow channels in peripheral vascular and coronary
smooth muscle cells, thus producing marked vasodilation in
peripheral and coronary vascular beds.15
The effects of amlodipine on the dopaminergic system have
not been thoroughly studied but there is some information
about nifedipine, a drug structurally related to amlodipine.
Mena and coworkers described the effects of calcium antagonists, such as flunarizine, cinnarizine, diltiazem, verapamil, nifedipine and nicardipine on the dopamine system. All calcium
antagonists tested reduced dopamine neurotransmission both in
vitro and in vivo.16
The pathogenic mechanism responsible for flunarizine–
cinnarizine PK is not completely understood but some authors
believe that this is due to presynaptic factors (loss of tyrosine
hydroxylase in monoaminergic and serotoninergic neurons
leading to dopamine depletion), as well as postsynaptic ones
(block of striatal dopaminergic receptors).17,18
Negrotti and Calzetti evaluated the natural course of
calcium-entry blocker-induced PK in 13 elderly patients who
had been previously exposed to cinnarizine, flunarizine, or
both. None of the patients showed a full recovery of extrapyramidal signs.19 Based on this experience, one should always
question whether a patient previously diagnosed with persistent
or recurrent flunarizine–cinnarizine PK might actually have a
latent form of idiopathic Parkinson’s disease that worsened as
a result of chronic use of calcium channel blockers.
Sempere and colleagues reported in 1995 on a 68-year-old
female patient who used amlodipine (10 mg/day) for the treatment of arterial hypertension. She developed a parkinsonian
syndrome 3 months after she started using amlodipine. Amlodipine was withdrawn, and 4 months later the patient was
normal.20
We have briefly described an elderly patient who developed
a marked PK induced by the use of amlodipine with resolution
of symptoms after discontinuation of the drug. We emphasize
that calcium antagonist drugs, such as amlodipine, which are
frequently used for treatment of arterial hypertension and angina pectoris in the elderly, may induce or worsen previously
diagnosed PK, particularly in women.

CLINICAL/SCIENTIFIC NOTES

835

Legends to the Videotape
Segment 1. The patient with severe parkinsonism: bradykinesia, postural instability, gait disorder, postural hand tremor,
and rigidity.
Segment 2. The patient 30 days after withdrawal of amlodipine, without any remaining signs of parkinsonism.

References
1. Cardoso F, Camargos ST, Silva GA Jr. Etiology of parkinsonism in
a Brazilian movement disorders clinic. Arq Neuropsiquiatr 1998;
56:171–175.
2. Errea-Abad JM, Ara-Callizo JR, Aibar-Remon C. Drug-induced
parkinsonism. Clinical aspects compared with Parkinson disease.
Rev Neurol 1998;27:35–39.
3. Kuzuhara S. Drug-induced parkinsonism. Nippon Rinsho 1997;55:
112–117.
4. Llau ME, Nguyen L, Senard JM, Rascol O, Montastruc JL. Druginduced parkinsonian syndromes: a 10-year experience at a regional center of pharmaco-vigilance. Rev Neurol 1994;50:757–
762.
5. Friedman JH. Drug-induced parkinsonism. In: Lang AE, Weiner
WJ, editors. Drug-induced movement disorders. Mt. Kisco, NY:
Futura Publishing; 1992. p 41–83.
6. Riley DE. Secondary parkinsonism. In: Jankovic J, Tolosa E, editors. Parkinson’s disease and movement disorders. 3rd ed. Baltimore: Williams and Wilkins; 1998. p 319–320.
7. Dick RS, Barold SS. Diltiazem-induced parkinsonism. Am J Med
1989;87:95–96.
8. Padrell MD, Navarro M, Faura CC, Horga JF. Verapamil-induced
parkinsonism. Am J Med 1995;99:436.
9. Holroyd S, Smith D. Disabling parkinsonism due to lithium: a case
report. J Geriatr Psychiatry Neurol 1995;8:118–119.
10. Onofrj M, Thomas A, Paci C. Reversible parkinsonism induced by
prolonged treatment with valproate. J Neurol 1998;245:794–796.
11. Goni M, Jimenez M, Feijoo M. Parkinsonism induced by phenytoin. Clin Neuropharmacol 1985;8:383–384.
12. Jiménez-Jiménez FJ, Tegeiro J, Martínez-Junquera G, CabreraValdivia F, Alarcón J, García-Albea E. Parkinsonism exacerbated
by paroxetine. Neurology 1994;44:2406.
13. Tesei S, Antonini A, Canesi M, Zecchinelli A, Mariani CB, Pezzoli
G. Tolerability of paroxetine in Parkinson’s disease: a prospective
study. Mov Disord 2000;15:986–989.
14. Ceravolo R, Nuti A, Piccini A, Dell’Agnello G, Belli G, Gambaccini G, Dell’Osso L, Murri L, Bonuccelli U. Paroxetine in Parkinson’s disease: effects on motor and depressive symptoms. Neurology 2000;55:1216–1218.
15. Murdoch D Heel RC. Amlodipine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in cardiovascular disease. Drugs 1991;41:478–505.
16. Mena MA, Garcia de Yebenes MJ, Tabernero C, Casajeros MJ,
Pardo B, Gacia de Yebenes J. Effects of calcium antagonists on the
dopamine system. Clin Neurpharmacol 1995;18:410–426.
17. Martı́-Massó J, Poza JJ. Cinnarizine-induced parkinsonism: Ten
years later. Mov Disord 1998;13:453–456.
18. Gimenéz-Roldán S, Mateo D. Cinnarizine-induced-parkinsonism:
susceptibility related to aging and essential tremor. Clin Neuropharmacol 1991;14:156–164.
19. Negrotti A, Calzetti S. A Long-term follow-up study of
cinnarizine- and flunarizine-induced parkinsonism. Mov Disord
1997;12:107–110.
20. Sempere AP, Duarte J, Cabezas C, Coria F, Claveria LE. Parkinsonism induced by amlodipine. Mov Disord 1995;10:115–116.

Micrographia Secondary to Lenticular Lesions
Pascal Derkinderen, MD, PhD,1 Sophie Dupont, MD, PhD,2
Jean-Sébastien Vidal, MD,1 François Chedru, MD,3
and Marie Vidailhet, MD1*
1

Department of Neurology, Hôpital Saint Antoine,
Paris, France
2
Service de Neurologie 1, Groupe Hospitalier
Pitié-Salpêtrière, Paris, France
3
Department of Neurology, Centre Hospitalier de Meaux,
Meaux, France
Abstract: Four patients with a stroke developed micrographia.
In 2 patients, the condition was pure and in the 2 other patients
it was associated with signs of writer’s cramp. We conclude
that infarct of the left lenticular nucleus could either mimic
pure micrographia similar to that of Parkinson’s disease or
micrographia associated with dystonia. © 2002 Movement Disorder Society
Key words: micrographia; stroke; lenticular nucleus; focal
dystonia; writer’s cramp
Micrographia is a prominent sign of Parkinson’s disease but it
has also been reported as a symptom of focal cerebral lesions.
The first description of micrographia as a focal sign of neurological disease was by Pick1 in the beginning of the twentieth
century. We report on four new cases of micrographia secondary to strokes involving the lenticular nucleus. Two patients
had associated features of writer’s cramp, whereas the two
other patients had pure micrographia.

Case Reports
Patient 1 was a 59-year-old, right-handed woman who presented in 1988 describing an episode of aphasia and alexia that
lasted 30 minutes. Computed tomography (CT) scan of the
brain performed 2 days after the episode was reported as normal. Six months after the stroke, she noticed that her handwriting became progressively smaller. Examination in 1999 disclosed a calligraphy that was smaller than premorbid samples
and became even smaller as she continued writing (Fig. 1).
There was a slight postural tremor of the right arm but no rest
tremor, bradykinesia, or rigidity and no focal dystonia. There
was no weakness of the right hand, and repetitive right finger
movements were normal. MRI of the brain showed an infarct of
the whole left lenticular nucleus and to a lesser extent the head
of the left caudate nucleus. A treatment with 300 mg per day of
levodopa (L-dopa) was not effective.
Patient 2 was a 29-year-old right-handed woman who suddenly developed a right hemiplegia and aphasia. Magnetic resonance imaging (MRI) showed an infarct involving the left len*Correspondance to: Marie Vidailhet, Service de Neurologie, Hôpital Saint Antoine, 184 rue du faubourg Saint Antoine, 75012 Paris,
France.E-mail: marie.vidailhet@sat.ap-hop-paris.fr
Received 19 October 2001; Revised 18 December 2001; Accepted
11 January 2002
Published online 10 April 2002 in Wiley InterScience (www.
interscience.wiley.com). DOI 10.1002/mds.10189

Movement Disorders, Vol. 17, No. 4, 2002

836

CLINICAL/SCIENTIFIC NOTES
third right finger. During writing, there was an excessive pen
pressure of all fingers and a tendency to loose the pen. Calligraphy was smaller than before the stroke but no decrease in size
was noticed as the patient continued writing.

Discussion

FIG. 1. Examples of handwriting from Patients 1 and 2. They showed
typical micrographic handwriting with a decrease in size as they continued writing, similar to that observed in Parkinson’s disease.

ticular nucleus, the left internal capsule, and the anterior thalamus secondary to a left carotid dissection. Motor condition and
aphasia improved within 3 months but the patient developed
increasing difficulties in writing. She held the pen correctly and
wrote with normal speed but her handwriting was small with a
slight decrease in size as she continued to write, until it was
barely legible (Fig. 1). Except for a slight impairment of rapid
alternating movement without decrease of amplitude of the
right hand and fingers, neurological examination was otherwise
unremarkable; no tone change, focal dystonia, or muscle
cramping was observed. As slowness in finger movements was
not associated with rigidity or decrease in amplitude of rapid
alternative movements, L-dopa treatment was not proposed.
Patient 3 was a 42-year-old, right-handed man who presented
with an acute right hemiplegia without aphasia. MRI of the
brain showed an infarct of the left lenticular nucleus and of the
left internal capsule, consecutive to a dissection of the left
carotid. Hemiplegia resolved over the next 2 weeks but he
developed progressively difficulties in writing. Six months after the stroke, examination disclosed a micrographia that was
constant as he continued writing. It was associated with an
excessive contraction of the thumb, index finger, and muscles
of the forearm and with an excessive wrist supination. There
was no tremor or weakness of the right hand.
Patient 4 was a 50-year-old, right-handed man who presented
with a sudden right hemiplegia associated with alexia evident 3
days after surgery for epilepsy. Both hemiplegia and alexia
resolved within 5 days. CT scan and MRI of the brain showed
an infarct of the left lenticular nucleus and the adjacent internal
capsule. Seven months after the stroke, examination disclosed
a slight weakness of the right hand and a postural tremor of the

Movement Disorders, Vol. 17, No. 4, 2002

Micrographia is a prominent symptom of Parkinson’s disease but it has also been described as a consequence of focal
cerebral lesions. Our four patients developed micrographia secondary to an infarct of the lenticular nucleus with mild (Patients
2, 3, and 4) or no (Patient 1) involvement of the spinal tract.
The first case of micrographia due to focal lesions of the brain
was first reported by Pick in 1903 in a young patient who
suffered from syphilitic infarct that involved the left thalamus
and the genu of internal capsule.1 Although experimental lesions of corticospinal tracts may lead to impairment of fine
motor skills, the involvement of the internal capsule was minor
compared to the striatal lesions and could not account for the
isolated modification in handwriting. Consistent with our findings, most of the recent reports of micrographia secondary to
focal lesions involved the lenticular nucleus (see Pullicino et
al.,2 references) or the internal capsule3 contralateral to the
dominant hand. Some reports also described micrographia due
to a demyelinating lesion of the left parietal lobe4 after infarct
of the left thalamus5 and as a consequence of cerebral deep
venous thrombosis.6
Our four cases were notable for the occurrence of micrographia with a focal dystonia during writing in two patients,
whereas the two other patients had a pure micrographia (i.e.,
not associated with focal signs of dystonia or parkinsonism). It
has been suggested that lenticular dysfunction in these cases are
sufficient to induce dysfunction of complex, repetitive and sequential motor actions such as handwriting, leading to micrographia.7 In addition, delayed-onset8 focal dystonia of the hand
was related to lesions of the sensorimotor part of the putamen.9
In our patients, there is a combination of akinesia (with micrographia) and dystonia, similar to writer’s cramp. The striatal
lesions could be associated with secondary dysfunction of the
striato-pallido-cortical pathways and impaired activation of the
motor and premotor areas. Indeed, akinesia in Parkinson’s disease is related to a failure to activate basal ganglia to supplementary motor area (SMA) projections.10 Underactivation of
SMA was also observed in writer’s cramp,11 whereas overactivity of the SMA was associated with more severe and widespread dystonia secondary to basal ganglia lesions. We suggest
that the occurrence of both akinesia and writer’s cramp as a
consequence of lenticular lesion could lead to disturbances of
activation and loss of selectivity in recruiting parallel motor
circuits in the motor and premotor cortex.

References
1. Pick A. Über eine eigenthümliche Schreibstörung, Mikrographie,
in folge cerebraler Erkrankung. Prag Med Wochenschr 1903;28:
1–4.
2. Pullicino P, Lichter D, Benedict R. Micrographia with cognitive
dysfunction: minimal sequelae of putaminal infarct. Mov Disord
1994;9:371–373.
3. Noda S, Itoh H, Goda S. Micrographia due to focal cerebral lesions
as seen in the dysarthria-clumsy hand syndrome. Neurology 1994;
44:150–151.
4. Scolding NJ, Lees AJ. Micrographia associated with a parietal lobe

CLINICAL/SCIENTIFIC NOTES
lesion in multiple sclerosis. J Neurol Neurosurg Psychiatry 1994;
57:739–741.
5. Kim JS, Im JH, Kwon SU, Kang JH, Lee MC. Micrographia after
thalamo-mesencephalic infarction: evidence of striatal dopaminergic hypofunction. Neurology 1998;51:625–627.
6. Murray BJ, Llinas R, Caplan LR, Scammell T, Pascual-Leone A.
Cerebral deep venous thrombosis presenting as micrographia and
hypophonia. Neurology 2000;54:751–753.
7. Marsden CD. The mysterious motor function of the basal ganglia:
the Robert Wartenberg lecture. Neurology 1982;32:514–539.
8. Scott BL, Jankovic J. Delayed-onset progressive movement disorders after static brain lesions. Neurology. 1996;46:68–74.
9. Lehéricy S, Vidailhet M, Dormont D, Chiras J, Mazetti P, Marsault
C, Agid Y. Striatal and thalamic dystonia: an MR anatomo-clinical
study. Arch Neurol 1996;53:241–250.
10. Jenkins IH, Fernandez W, Playford ED, Lees AJ, Frackowiak RS,
Passingham RE, Brooks DJ. Impaired activation of the supplementary motor area in Parkinson’s disease is reversed when akinesia is
treated with apomorphine. Ann Neurol 1992;32:749–757.
11. Ibanez V, Sadato N, Karp B, Deiber MP, Hallett M. Deficient
activation of the motor cortical network in patients with writer’s
cramp. Neurology 1999;53:96–105.

Familial Essential Tremor Is Not Associated
with SCA-12 Mutation in Southern Italy
Giuseppe Nicoletti, MD,1 Grazia Annesi, PhD,1
Sara Carrideo, PhD,1 Carmine Tomaino, PhD,1
Alfonso Di Costanzo, MD,2 Mario Zappia, MD,1,3
and Aldo Quattrone, MD1,3*
1

Institute of Neurological Sciences, National Research
Council, Piano Lago di Mangone, Cosenza, Italy
2
Department of Neurology, 2nd University of Naples,
Naples, Italy
3
Institute of Neurology, University Magna Graecia,
Catanzaro, Italy

Abstract: We investigated 30 patients with familial essential
tremor (ET) for spinocerebellar ataxia type 12 (SCA-12) mutations. No patient presented a CAG repeat larger than 19,
suggesting that familial ET and SCA-12 are distinct diseases.
© 2002 Movement Disorder Society
Key words: essential tremor; SCA-12; point mutation studies
Autosomal dominant cerebellar ataxias (ADCA) are a heterogeneous group of hereditary neurodegenerative disorders characterized primarily by progressive cerebellar ataxia and classified clinically in various subgroups. Recently, Holmes and colleagues1 identified in a large American pedigree of German
descent, a novel form of ADCA termed spinocerebellar ataxia

*Correspondence to: Aldo Quattrone, Clinica Neurologica, Policlinico Universitario Mater Domini, Via T. Campanella, 88100 Catanzaro, Italy. E-mail: quattrone.unicz@interbusiness.it
Received 23 September 2001; Revised 10 December 2001; Accepted
11 January 2002
Published online 4 April 2002 in Wiley InterScience (www.
interscience.wiley.com). DOI 10.1002/mds.10191

837

type 12 (SCA-12). SCA-12 was mapped on chromosome 5q3133.1 Affected subjects had expansions containing 66 to 78 CAG
repeats in the 5⬘-untranslated region of the gene encoding
PPP2R2B, a brain-specific regulatory subunit of protein phosphatase PP2A,1 whereas controls had 7 to 28 repeats. SCA-12
is a slowly progressive ADCA that differs from other SCAs
because it typically begins with tremor of head and arms, often
diagnosed as essential tremor (ET).2 We conducted a study to
screen individuals who presented with familial ET for SCA-12
mutation.

Patients and Methods
Thirty index cases (12 men and 18 women, from 30 families)
with familial ET underwent DNA analysis for the SCA-12
mutation. All subjects fulfilled the diagnostic criteria of classic
hereditary ET as defined by the consensus statement of the
Movement Disorder Society.3 Patients with sporadic tremor
were excluded from the study. Fifty-eight healthy subjects (23
men and 35 women) served as controls. Patients and controls
were matched for sex but not for age. All cases and controls
were from the same ethnic and socioeconomic background
(southern Italy). Genomic DNA was prepared from leucocytes
harvested from whole blood by using standard methods. The
PCR for the CAG repeat in the 5⬘UTR of the gene PPP2R2B
was performed in 25 ␮l containing 100 ng of genomic DNA
template 20 pmol of each oligonucleotide primer, 200 ␮l of
dNTP, and 1 U of Taq DNA polymerase (Promega, MI). Primer
sequences 5⬘-TGCTGGGAAAGAGTCGTG-3⬘ (forward) and
5⬘-GCCAGCGCACTCACCCTC-3⬘ (reverse) were designed to
amplify the CAG repeat. The samples were run in a model
PTC-100 Thermal Cycler (MJ Research, Watertown, MA). To
determine the size of the CAG repeat, 1/10 of precipitated
samples mixed with loading buffer was run on a 10% nondenaturing polyacrylamide gel at 500 V overnight. After electrophoresis, the gels were stained with silver nitrate. The size of
the polymorphic SCA-12 alleles was detected after silver nitrate staining by comparison with previously sequenced alleles.

Results
The range of allele size was 9 to 21 in both patients and
controls; the most frequent allele was the 10-repeat allele
(44.8% of controls, 43.3% of patients). No patient with familial
ET presented a repeat larger than 19. No difference in allelic
distribution was found between patients and controls (Fig. 1).

Discussion
A recent study2 has shown that, in patients with SCA-12, the
most common neurological sign at onset of the disease, which
usually begins in young adulthood (mean age of onset, 34
years), is a tremor of the head and arms. The tremor observed
in SCA-12 patients resembled ET, and several members of the
original family were diagnosed as ET at an early stage in their
clinical courses.2 With progression of the disease, cerebellar
dysfunction and parkinsonian signs (bradykinesia, increased
muscular tone) developed in most patients with SCA-12,2 but
cerebellar signs were usually less prominent and disabling than
those observed in other SCAs, suggesting that subjects with

Movement Disorders, Vol. 17, No. 4, 2002

838

CLINICAL/SCIENTIFIC NOTES

Impact of Cervical Dystonia on Quality of Life
Laura Camfield, MA,1 Yoav Ben-Shlomo, MRCP,2
Thomas T. Warner, PhD, MRCP,1* and The Epidemiological
Study of Dystonia in Europe Collaborative Group
1

FIG. 1. Distribution of CAG repeats at the SCA-12 locus on 60 chromosomes from 30 patients with familial essential tremor and on 116
normal chromosomes. Open bars, patients; filled bars, controls.

SCA-12 may be erroneously diagnosed as having ET rather
than a hereditary ataxia.
No patient with familial ET harboured the SCA-12 mutation,
confirming that familial ET and SCA-12 are distinct diseases.
It should be noted, however, that we did not search for point
mutations in the PPP2R2B gene and, thus, we cannot exclude
that other mutations different from CAG expansion could cause
familial ET. Indeed, it has been reported that CAG repeat expansions or point mutations in a single gene may lead to different phenotypes, such as the case of mutations in the gene
encoding the ␣1A voltage-dependent calcium channel subunit
(CACNA1A) in which CAG expansion causes spinocerebellar
ataxia type 6 (SCA-6),4 whereas missense or truncating mutations lead to familial hemiplegic migraine or episodic ataxia
type 2.5 Therefore, further point mutational studies are needed
to definitively conclude that the PPP2R2B gene is not involved
in familial ET.

References
1. Holmes SE, O’Hearn EE, McInnis MG, Gorelick-Feldman DA,
Kleiderlein JJ, Callahan C, Kwak NG, Ingersoll-Ashworth RG,
Sherr M, Sumner AJ, Sharp AH, Ananth U, Seltzer WK, Boss MA,
Vieria-Saecker AM, Epplen JT, Riess O, Ross CA, Margolis RL.
Expansion of a novel CAG trinucleotide repeat in the 5’ region of
PPP2R2B is associated with SCA12. Nat Genet 1999;23:391–392.
2. O’Hearn E, Holmes SE, Calvert PC, Ross CA, Margolis RL. SCA12: tremor with cerebellar and cortical atrophy is associated with a
CAG repeat expansion. Neurology 2001;56:299–303.
3. Deuschl G, Bain P, Brin M. Consensus statement of the Movement
Disorder Society on tremor. Mov Disord 1998;13(Suppl. 3):2–23.
4. Zhuchenko O, Bailey J, Bonnen P, Ashizawa T, Stockton DW,
Amos C, Dobyns WB, Subramony SH, Zoghbi HY, Lee CC. Autosomal dominant cerebellar ataxia (SCA6) associated with small
polyglutamine expansions in the ␣1A-voltage-dependent calcium
channel. Nat Genet 1997;15:62–69.
5. Ophoff RA, Terwindt GM, Vergouwe MN, van Eijk R, Oefner PJ,
Hoffman SM, Lamerdin JE, Mohrenweiser HW, Bulman DE, Ferrari M, Haan J, Lindhout D, van Ommen GJ, Hofker MH, Ferrari
MD, Frants RR. Familial hemiplegic migraine and episodic ataxia
type-2 are caused by mutations in the Ca 2+ channel gene
CACNL1A4. Cell 1996;87:543–552.

Movement Disorders, Vol. 17, No. 4, 2002

University Department of Clinical Neurosciences, Royal
Free and University College Medical School,
London, United Kingdom
2
Department of Social Medicine, University of Bristol,
Bristol, United Kingdom

Abstract: We studied the effect of cervical dystonia on quality
of life in a cohort of 289 patients by using a generic health
status measurement scale (SF36). Cervical dystonia had a significant negative impact on quality of life compared with agematched general population data. This negative impact was
comparable to that seen in multiple sclerosis, Parkinson’s disease, and stroke. © 2002 Movement Disorder Society
Key words: cervical dystonia; quality of life; SF36
Cervical dystonia is the most common form of focal dystonia,
with a prevalence of between 50 and 200 per million persons.1
Most cases are primary or idiopathic. It is characterised by
involuntary muscle contractions within the neck, which lead to
rotation, extension, or displacement of the head, sometimes
associated with tremor and pain.2 Such movements are visible
and stigmatising. Little is known about the impact of cervical
dystonia on quality of life. This study compared quality of life
in cervical dystonia with that of the general population and
three other better-known neurological conditions, multiple sclerosis (MS), Parkinson’s disease (PD), and stroke. Quality of life
was assessed by using a generic questionnaire, the Medical
Outcomes Study Short-Form 36-Item Health Survey (SF36).3

Subjects and Methods
Patients with primary cervical dystonia were identified by
the Epidemiological Study of Dystonia in Europe (ESDE) Collaborative Group.1,4 All cases were diagnosed by movement
disorder specialists in seven European countries. Cases of paediatric and secondary dystonia were excluded. Patients received
a postal questionnaire containing the SF36 that had been translated and back-translated to ensure accuracy and comparability.
Completed questionnaires were returned, and data were collated on a central database for analysis.
The SF36 is a validated health status measure which contains
eight domains of health, four physical and four emotional, that
cover activities of daily living, emotional state, pain, fatigue,
social participation, and perceptions of health. A score ranging
from 0 (worst health) to 100 (best health) is generated for each
domain. SF36 population data were taken from a crosssectional sample of British adults aged 55 to 59 years.5 For the
comparison of cervical dystonia with other conditions, we ex*Correspondence to: T.T. Warner, University Department of Clinical
Neurosciences, Royal Free and University College Medical School,
Royal Free Campus, Rowland Hill Street, London NW3 2PF, United
Kingdom. E-mail: t.warner@rfc.ucl.ac.uk
Received 30 June 2001; Revised 7 November 2001; Accepted 28
November 2001
Published online 26 March 2002 in Wiley InterScience (www.
interscience.wiley.com). DOI 10.1002/mds.10127

CLINICAL/SCIENTIFIC NOTES
tracted relevant data from prior publications or personal communication. The comparison conditions were Parkinson’s disease,6 long-term stroke survivors,7 and multiple sclerosis.8 The
PD subjects were recruited from a cross-sectional survey of
patients attending neurology clinics with Hoehn and Yahr
scores of between 1 and 5. Stroke survivors were recruited from
hospitalised and nonhospitalised cases who had survived for 6
years. The multiple sclerosis study was a cross-sectional prevalence study and included patients with progressive, relapsingremitting, and benign disease. We compared mean values
across the eight domains by five age groups (20–39, 40–49,
50–59, 60–69, 70+ years), sex, and educational level (basic
education <16 years, further education 16 to 18 years, higher
education >18 years). Age and education were analysed both as
nominal and ordinal data, and P values are shown for both
heterogeneity and trend, respectively.
We used a heterogeneity test (Q statistic) to compare differences in mean scores across studies, excluding the normative
data, under a fixed effects model analogous to the methods used
for meta-analysis, to test whether any observed differences
across groups were statistically significant. Where significant
differences were observed, we repeated the analysis, excluding
first the study with the best or worst scores. If there was still
significant heterogeneity, we excluded both the best and worst
scores. In this way, we could determine whether heterogeneity
was due to any one specific disease group or was the result of
differences in scores across all disease groups.

Results
The response rate to the postal survey was 75%; a relatively
high figure for a postal study. Data was obtained from 101 men
and 188 women with cervical dystonia. The mean age was 52.8
(S.D., 14.3 years) and 56.7 (S.D., 12.5 years) years for men and
women, respectively. Patients on average waited 4.6 years
(S.D., 7.8 years) from disease onset to correct diagnosis. As one
might expect, there was a statistically significant age-related
deterioration of quality of life for both physical functioning and
general health (see Table 1), and both the pain and physical role

839

limitation domains were of borderline significance (P for trend
⳱ 0.06). None of the other domains showed significant differences by age group. Males had better scores than females in all
domains, and these differences reached statistical significance
for energy/vitality, pain, and physical function. Subjects of
lower education level had worse quality of life scores across all
domains, although there was no statistically significant trend
for the social function and emotional role limitation domains.
Patients with cervical dystonia scored much worse in all
eight domains (range, 14 to 35 points) than a cross-section of
the general population of similar age (Table 2). There was
marked heterogeneity for each domain across all four disease
groups (P < 0.001). Cervical dystonia patients scored best for
physical function score and worst for mental health and emotional role limitation compared with other neurological conditions. This finding remained statistically significant even after
excluding the MS patients (P < 0.001) for physical function and
stroke patients for the other domains. For emotional role limitation, cervical dystonia patients had values similar to those of
the MS group (P ⳱ 0.72). For general health (P ⳱ 0.80) and
pain (P ⳱ 0.20), there was no significant differences between
the cervical dystonia, PD, and MS groups after excluding the
stroke group. Cervical dystonia patients showed values similar
to those of stroke patients for energy and vitality (P ⳱ 0.18)
but were significantly better than MS (P < 0.001) and worse (P
< 0.001) than PD patients. Cervical dystonia patients scored
significantly worse than either stroke or PD for physical role
limitation (P < 0.001) but were significantly better than MS
patients (P < 0.001).

Discussion
Although cervical dystonia is usually nonprogressive and
limited to involuntary muscle spasm of the neck, its detrimental
effect on health status is comparable to progressive and generalised conditions clinically perceived to be of greater severity. We found clear age-related differences, particularly in the
physical domains, which are similar to those seen in the general
population,5 but even more marked amongst people with dys-

TABLE 1. Mean values of SF36 domains for patients with cervical dystonia by age group, sex and educational level

Energy/vitality

Age group (yr)
20–39
40–49
50–59
60–69
70+
P for heterogeneity
P for trend
Sex
M
F
P for heterogeneity
Education level (yr)
<16
16–18
>18
P for heterogeneity
P for trend

Pain

Physical
function

Role
limitation
physical

General
health

Mental
health

Social
function

Role
limitation
emotional

Mean

S.E.

Mean

S.E.

Mean

S.E.

Mean

S.E.

Mean

S.E.

Mean

S.E.

Mean

S.E.

Mean

S.E.

51.8
44.9
44.0
45.6
42.9

4.1
2.3
2.2
2.7
2.6
0.37
0.17

60.6
55.0
52.9
43.4
47.7

5.2
3.3
3.2
3.3
3.6
0.35
0.06

84.2
72.9
62.5
58.3
53.9

4.2
3.2
3.0
3.2
4.5
<0.0001
<0.0001

57.3
45.6
43.8
45.7
34.8

7.7
5.0
4.6
5.6
6.2
0.26
0.06

61.9
51.7
47.9
48.1
44.3

3.8
3.1
2.3
2.6
2.6
0.01
<0.001

59.1
56.8
57.4
57.4
59.6

3.7
2.5
2.6
2.8
2.6
0.96
0.82

61.4
59.3
62
60.6
66.3

5.2
3.4
3.2
3.3
3.5
0.77
0.38

64.5
45.5
50.9
47.6
47.2

6.9
5.3
4.9
5.7
7.0
0.33
0.25

49.9
42.8

1.9
1.5
0.005

59.7
50.3

2.5
2.0
0.005

71.1
61.9

2.6
2.1
0.007

49.7
42.2

4.2
3.1
0.150

52.9
48.3

2.1
1.6
0.100

60.6
56.2

2.0
1.6
0.100

63.5
60.6

2.5
2.1
0.400

55.3
46.9

4.4
3.2
0.120

42.1
48.7
47.5

1.8
2.0
2.7
0.03
0.03

49.6
54.6
61.7

2.4
2.6
3.3
0.02
0.004

39
67.9
75.6

2.3
2.8
3.6
0.004
<0.0001

39.5
44.4
58.8

3.7
4.0
5.6
0.01
0.01

45.4
52.8
55.8

1.9
2.3
2.7
0.003
0.001

53.7
63.6
57.9

2.0
1.9
2.6
0.003
0.040

58.4
67.4
60

2.6
2.4
3.5
0.04
0.32

44.5
56.6
51.9

3.9
4.4
5.5
0.12
0.14

Movement Disorders, Vol. 17, No. 4, 2002

840

CLINICAL/SCIENTIFIC NOTES
TABLE 2. Mean scores for SF-36 domains comparing cervical dystonia with general population and other
neurological conditions*

SF-36 domain
Physical
Energy/vitality
Pain
Physical function
Role limitation physical
Mental
General health
Mental health
Social function
Role limitation emotional

General
population2
(55–59 years)
(n ⳱ 712)

Cervical
dystonia
(n ⳱ 289)

Parkinson’s
disease3
(n ⳱ 193)

Stroke4
(n ⳱ 639)

Multiple
sclerosisa
(n ⳱ 311)

60.3 (20.5)
76.7 (25.0)
79.4 (22.9)
80.1 (34.9)

45.3 (19.7)
53.6 (26.4)
65.1 (42.9)
44.8 (41.5)

55.4 (29.2)
52.9 (20.8)
48.2 (22.2)
70.6 (41.7)

47.4 (27.0)
72.3 (30.6)
48.3 (35.4)
65.0 (45.9)

36.9 (21.8)
59.5 (29.3)
33.4 (32.6)
27.0 (37.3)

68.4 (21.6)
75.9 (17.4)
86.9 (21.9)
84.8 (31.3)

50.0 (20.9)
57.7 (20.9)
61.6 (26.8)
49.9 (43.0)

49.7 (43.1)
64.6 (29.2)
73.1 (16.7)
73.0 (26.4)

59.5 (28.6)
81.3 (15.8)
67.2 (39.6)
84.6 (34.0)

48.0 (22.8)
64.9 (20.1)
54.0 (31.1)
51.3 (42.8)

*All domains showed significant heterogeneity across mean values (P < 0.0001).
a
Somerset M., personal communication.

tonia. There was no age-related decline for mental health and
social function, again, as seen in the general population.
Women and patients of lower educational level consistently
reported worse quality of life. These patterns mirror the normative data, although gender differences are less clear and
relatively small in the general population.5 These results suggest the presence of a chronic disorder such as cervical dystonia
heighten the trends seen in the general population.
Two other studies have analysed the SF36 and other health
measures in cohorts of dystonia patients. Gudex and colleagues9 studied the effect of dystonia and its treatment with
botulinum toxin in two groups of patients: those with focal
dystonia (mainly cervical dystonia and blepharospasm; n ⳱
93) and nonfocal dystonia (n ⳱ 37).9 They found a significant
negative impact of dystonia on quality of life and a small positive effect of botulinum toxin treatment. A recent study examined health-related quality of life in 25 cervical dystonia patients and 25 with cranial dystonia by using the SF36 and
EuroQol (EQ-5D), and the effect of botulinum toxin on this.10
For CD, all domains were affected, although baseline scores for
all domains were higher than those seen in our study. This
finding may reflect patient selection: those in the recent study
were all receiving botulinum toxin therapy on a long-term basis, whereas our much larger cohort is a more representative
cross-section of cervical dystonia with both untreated patients
and botulinum toxin treated patients at different phases of the
treatment cycle.
Our comparison across different neurological disorders was
relatively crude, as it was not possible to adjust for age and sex
differences between studies because these data were not available. Confounding by sex is unlikely to have biased our results
to a great extent as the sex differences are not marked.5 Similarly, taking account of differences in the age structure of these
disorders would have increased the relative impact of cervical
dystonia. This effect is because, apart from multiple sclerosis,
the mean age for the other groups would have been much older.
Patients with cervical dystonia had relatively low mental
health and emotional role limitation scores, a finding also seen
in the study by Hilker and associates.10 This may result from
anxiety, depression, and isolation due to a lack of recognition,
understanding, and support for this disease. Jahanshahi and
Marsden11,12 in a study comparing cervical dystonia (torticol-

Movement Disorders, Vol. 17, No. 4, 2002

lis) and cervical spondylosis patients, attributed the high scores
for depression from the people with cervical dystonia to negative body concept arising from the visible postural abnormality
of the head. More surprisingly, cervical dystonia appears to
have a disproportionate negative impact on physical role limitation, despite good physical function. One possible explanation is that pain limits such activities. This finding would be
consistent with the worse pain scores for cervical dystonia
compared with stroke, but fails to explain why cervical dystonia patients were more limited in their physical activities compared with Parkinson’s disease or MS patients, despite having
very similar pain scores. Another possibility is that cervical
dystonia patients consciously limit activities that make their
dystonia visible to others. Anecdotally, patients report that they
experience both mockery and avoidance behaviour from the
public who attribute their dystonic movements to inebriation,
mental illness, or cognitive impairment. Clinical recognition is
also poor as evidenced by the duration from disease onset to
correct diagnosis. Although new therapeutic advances may improve symptoms, improving quality of life will also depend on
helping both patients and the public accept and understand this
unusual disorder.
Acknowledgments: We thank European Dystonia Federation for funding the study, and Alistair Newton for helping
organise it; Dr. Maree Hackett, Prof. Ruth Bonita, and Maggie
Somerset for providing additional data, and all the participants
for taking part in the study. All the authors helped design the
study, interpreted the results, and wrote the manuscript. L.C.
and T.T.W. coordinated the data collection across all centres.
L.C. entered the data and analysed it with Y.B.S. The ESDE
participants were London, U.K.: L. Camfield, Dr. T.T. Warner,
Dr. M. Jahanshahi, Dr. Y. Ben-Shlomo; Innsbruck, Austria: Dr.
J. Wissel, Prof. W. Poewe; Turku, Finland: Dr. R.J. Marttila;
Bordeaux, France: Prof. P. Burbaud, Prof. A. Lagueny; Rome,
Italy: Dr. Antonio Curra, Prof. A. Beradelli and Dr. A. Bentivoglio, Dr. Enza-Maria Valente, Prof. A. Albanese; Munich,
Germany: Dr. F. Asmus, Dr. T. Gasser; Barcelona, Spain: Dr.
F. Marti, Prof. E. Tolosa.

CLINICAL/SCIENTIFIC NOTES
REFERENCES
1. Epidemiological Study of Dystonia in Europe Collaborative
Group. A prevalence study of primary dystonia in eight European
countries. J Neurol 2000;24:787–793.
2. Dauer WT, Burke RE, Greene P, Fahn S. Current concepts on the
clinical features, aetiology and management of idiopathic cervical
dystonia. Brain 1998;121:547–560.
3. Ware JE Jr. Sherbourne CD. The MOS 36-item short-form health
survey (SF-36). I. Conceptual framework and item selection. Med
Care 1992;30:473–483.
4. Epidemiological Study of Dystonia in Europe Collaborative
Group. Sex-related influences on the frequency and age of onset of
primary dystonia. Neurology 1999;53:1871–1873.
5. Jenkinson C, Coulter A, Wright L. SF36 health survey questionnaire: normative data for adults of working age. Br Med J 1993;
306:1437–1440.
6. Rubenstein LM, Voelker MD, Chrischilles EA, Glenn DC, Wallace RB, Rodnitzky RL. The usefulness of the functional status
questionnaire and MOS SF36 in PD research. Qual Life Res 1998;
7:279–290.
7. Hackett ML, Duncan JR, Anderson CS, Broad JB, Bonita R.
Health-related quality of life among long-term survivors of stroke.
Results from the Auckland Stroke Study, 1991–1992. Stroke 2000;
31:440–447.
8. Somerset M, Campbell R, Sharp D, Peters T. What do people with
multiple sclerosis want and expect from health care services?
Health Expect 2001;4:29–37.
9. Gudex C, Hawthorne MR, Butler AG, Duffey P. Effect of dystonia
and botulinum toxin treatment on health-related quality of life.
Mov Disord 1998;13:941–946.
10. Hilker R, Schischniaschvili M, Ghaemi M, Jacobs A, Rudolf J.
Health related quality of life is improved by botulinum neurotoxin
type A in long term treated patients with focal dystonia. J Neurol
Neurosurg Psychiatry 2001;71:193–199.
11. Jahanshahi M, Marsden CD. Body concept, disability and depression in patients with spasmodic torticollis. Behav Neurol 1990;3:
117–131.
12. Jahanshahi M. Psychosocial factors and depression in torticollis. J
Psychosom Res 1991;35:493–507.

Orthostatic Paroxysmal Dystonia
Kapil D. Sethi, MD, FRCP,1* Ki Hyeong Lee, MD,1
Vasanti Deuskar, MD,2 and David C. Hess, MD1
1

Department of Neurology, Medical College of Georgia,
Georgia, USA
2
Department of Radiology, VA Medical Center,
Augusta, Georgia, USA

Abstract: A 52-year-old man with a history of cerebrovascular
disease presented with a 3-year history of paroxysmal hemidystonia precipitated by assuming an upright position after sitting or lying down. MRA showed occlusion of the contralateral
A videotape accompanies this article.
*Correspondence to: Kapil D Sethi, Department of Neurology,
Medical College of Georgia, 1120 15th Street, Augusta, GA 30912.
E-mail: ksethi@neuro.mcg.edu
Received 6 July 2001; Revised 19 October 2001; Accepted 18 December 2001
Published online 10 April 2002 in Wiley InterScience (www.
interscience.wiley.com). DOI 10.1002/mds.10182

841

internal carotid artery (ICA) and near-total occlusion of the
ipsilateral ICA. Subtraction single proton emission computed
tomography demonstrated decreased perfusion in the contralateral frontoparietal cortex during the typical dystonic spell. We
have coined the term “orthostatic paroxysmal dystonia” for this
phenomenon. © 2002 Movement Disorder Society
Key words: paroxysmal dyskinesia; SPECT; carotid artery
disease
Paroxysmal dyskinesias are a heterogeneous group of disorders
manifesting as episodes of abnormal involuntary movements
arising out of a background of normal motor behavior.1 The
abnormal movements may be choreic, ballistic, dystonic, athetotic, tremulous, or a combination of these movements. Most
cases are idiopathic and familial, but sporadic cases and symptomatic cases with varied etiologies are well described. Orthostatic limb shaking from carotid hypoperfusion is a welldescribed phenomenon.2,3 However, recurrent stereotypic dystonic limb movements from carotid occlusive disease have not
been described previously. We describe herein a patient with
carotid artery disease who developed paroxysmal hemidystonia
precipitated by assuming an upright posture. We have coined
the term “orthostatic paroxysmal dystonia” for this phenomenon.

Methods and Results
A 52-year-old right-handed man complained of a 3-year history of episodes of right hand and leg stiffening and “spasming
up.” These episodes consisted of involuntary twisting of his
right hand and right foot without clonic movement. These episodes would occur only upon standing after prolonged sitting or
lying, with a frequency of approximately three times per day.
The patient also admitted to going blind in the left eye in bright
light and was very sensitive to sunlight.
There was a history of diabetes mellitus with multiple episodes of hypoglycemia. However, the dystonic spells were unrelated to the hypoglycemic episodes. He was diagnosed with a
pituitary adenoma approximately 22 years previously. The adenoma was treated with surgery and postoperative radiotherapy
that had resulted in hypopituitarism. He had sustained a stroke
4 years prior to study, resulting in mild right hemiparesis and
marked dysarthria. He made a gradual recovery but residual
deficits included slight clumsiness on the right arm and dysarthria. The spells began 1 year later.
Medications included aspirin, trazodone, sertraline, atorvastatin, depo-testosterone, ranitidine, and insulin. Examination
showed him to be alert and oriented but his speech was slow
without dysphasic errors. There was a mild pronator drift with
spasticity but no weakness in the right upper extremity. The
deep tendon reflexes were hyperactive on the right. Upon
standing quickly after lying supine, he developed abnormal
posture of his right hand and foot without clonic movements.
The wrist extended and the fingers spread out accompanied by
plantar flexion of the foot and curling of the toes. This condition lasted 1 to 2 minutes. The face was not involved. Auditory
startle or sudden movements while lying or sitting did not
provoke this dystonic posture. Hyperventilation while lying
down did not precipitate the dystonia. However, hyperventilation while sitting followed by an upright posture was the most
effective way to precipitate an attack. The patient also reported
that he would occasionally have a brief episode while yawning

Movement Disorders, Vol. 17, No. 4, 2002

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CLINICAL/SCIENTIFIC NOTES

repeatedly. No significant orthostatic hypotension was observed during the position changes (supine blood pressure [BP],
140/80; pulse rate [PR], 74 beats/minute; upright BP, 130/75;
PR, 80 beats/minute, 3 minutes after standing).
We performed a standard electroencephalogram (EEG) for
30 minutes, during which his typical episode was not recorded.
The EEG did not show any epileptiform discharges or focal

slow waves before, during, and after the position change. Magnetic resonance angiography demonstrated complete occlusion
of the left internal carotid artery and near total occlusion of the
supraclinoid portion of the right internal carotid artery (Fig. 1).
A single emission computed tomographic (SPECT) study
was performed at baseline and during the brief dystonic attack
provoked by standing up rapidly from a sitting position. Ra-

FIG. 1. Magnetic resonance angiography (MRA) and magnetic resonance imaging (MRI) of the brain. MRA demonstrated complete occlusion of the
left internal carotid artery (ICA) and near-complete occlusion of the right ICA at the supraclinoid portion. A: The right ICA supplied blood flow to
the left MCA/ACA through A-Com. MCA, middle cerebral artery; ACA, anterior cerebral artery; A-Com, anterior communicating artery. B: The
vertebrobasilar artery and posterior cerebral artery (PCA) were patent. Brain MRI showed small ischemic lesions in the both upper pons (C) and
sub-insular area (D).

Movement Disorders, Vol. 17, No. 4, 2002

CLINICAL/SCIENTIFIC NOTES
dioisotope injection (99mTc-ECD) for initial baseline study was
performed while the patient was in a sitting position with eyes
open under ambient lighting. No involuntary movement or dystonic posturing was noted during and immediately after injection. A second SPECT study was done 2 weeks later. To elicit
the dystonic posturing of the right arm and leg, the patient was
asked to stand up rapidly after hyperventilation for 2 minutes in
the sitting position. The patient developed a brief dystonic attack, lasting approximately 2 minutes during which the radionuclide was injected. SPECT images were taken 1 hour after
the injection of radionuclide by using the same scanner and
protocol (dual-headed gamma camera system, ADAC Labs,
Milpitas, CA). Through the reconstruction process from original acquisition, a series of contiguous images oriented in the
transverse planes was created. To visualize the area that
showed most prominent changes in blood flow during orthostatic dystonia, the second or ictal SPECT scan was subtracted
from the first or baseline SPECT scan by using computerized
image anaylsis software (Analyze PC v. 2.5, Biomedical Imaging Resources, Mayo Foundation, Rochester, MN). Briefly, the
ictal SPECT scan was transformed into the baseline SPECT
scan by transformation matrix calculated from a coregistration
process of the two images using voxel matching algorithm.
Both baseline image and transformed ictal image were normalized to their average voxel intensity. Then, the transformed
ictal scan was subtracted from the baseline scan. The resulting
subtracted SPECT image was measured for the average intensity and standard deviation. Ideally the average intensity of the
subtracted SPECT should be within 0 ± 0.05. To exclude the
random noise, the subtracted image was thresholded to display
only pixels with intensity values greater than 2 standard devia-

843

tions above zero. The result showed significant decrease of
blood flow in the the left frontal and parietal cortex during the
dystonic episode (Fig. 2).

Discussion
Paroxysmal dyskinesia can be classified into four basic varieties: paroxysmal kinesigenic dyskinesia (PKD), paroxysmal
nonkinesigenic dyskinesia (PNKD), paroxysmal exertioninduced dyskinesia (PED), and paroxysmal hypnogenic dyskinesia (PHD).4 Orthostatic paroxysmal dystonia has not been
described previously but may be considered as a variant of
PKD.
Cerebrovascular disease is an uncommon cause of paroxysmal dyskinesia. Tonic spasms resembling those seen in demyelinating disease have been described in patients with putaminal5 and thalamic infarcts.6 An unusual case of focal PKD
involving the muscles supplied by the lower cranial nerves due
to an old medullary hemorrhage has been described.7 Moyamoya disease was reported to be responsible for paroxysmal
chorea.8 Paroxysmal dyskinesia was reported in association
with transient cerebral ischemia.9
Recurrent limb shaking and other involuntary movements
have been associated with carotid artery occlusive disease. This
clinical phenomenon is described as brief, involuntary, coarse,
irregular, wavering movement or tremble involving the arm–
hand alone, or arm–hand and leg together occurring when the
patient stands up or with walking.2,3 However, to our knowledge, hemidystonia has not been described in this clinical setting.
The patient we describe has severe large vessel disease due
to diabetes mellitus and superimposed accelerated arterioscle-

FIG. 2. Subtracted single photon emission computed tomography (SPECT). A significant decrease in blood flow during orthostatic dystonia of right
leg and arm induced by abrupt standing up from a sitting position is demonstrated in the left frontal and parietal cortex as well as in right cerebellar
hemisphere. Colored areas indicate the brain region where the cerebral perfusion decreased more than 2 S.D. above average compared with the other
areas during the dystonic episode, i.e., where the pixel intensity is >2 S.D. above zero in subtracted SPECT (SPECT during baseline minus SPECT
during dystonia). A,D: Baseline SPECT. B,E: Combined baseline + subtract SPECT. C,F: Subtract SPECT. (Color figure can be viewed in the online
issue, which is available at www.interscience.wiley.com.)

Movement Disorders, Vol. 17, No. 4, 2002

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CLINICAL/SCIENTIFIC NOTES

rosis due to radiation. This resulted in delayed visual recovery
after exposure to bright light as the decrease of ocular blood
supply delayed the recovery of pigment in the cones of the
retina. Also, upon standing, the slight orthostatic drop in systemic pressure seemed enough to cause distal territory ischemia. Even though the patient’s clinical manifestation is different from the “limb shaking transient ischemic attacks” described previously, it is most likely that intermittent cerebral
ischemia from a carotid territory low-perfusion state associated
with postural change may explain both phenomena.
Prolonged EEG/video monitoring was not performed on our
patient. The possibility of recurrent focal seizure secondary to
ischemia, however, does not seem to be responsible for the
hemidystonia. First, his symptoms always involved both arm
and leg at the same time without progression or generalization.
Second, ictal SPECT showed decreased perfusion instead of
hyperperfusion that is usually indicative of seizure focus. Also
the previous studies reported video/EEG, monitoring paroxysmal limb shaking in the patients with carotid occlusive disease,
showed no epileptiform discharges during the episodes.10 In a
recent report, Schindler and colleagues11 demonstrated hyperperfusion of anterior cingulate gyrus in a case of paroxysmal
nocturnal dystonia. The patient they reported clearly had a
history of complex partial seizures with secondary generalization and developed predominantly nocturnal dystonic episodes.
The patient’s interictal/ictal EEG showed epileptiform discharges, and the ictal SPECT showed hyperperfusion in the
bilateral cingulate gyrus. Our patient, in comparison, never had
a previous history of unprovoked seizures and interictal EEG
was normal. Also the ictal SPECT during the dystonic episode
showed a decreased perfusion. These differences may provide
enough evidence that our patient’s finding cannot be explained
by an epileptic phenomenon.
In addition to the ischemic phenomenon, one may consider
muscle activity during the upright posture as a possible trigger
for orthostatic dystonia. A tilt table test may have helped in this
aspect. As the patient developed his typical episodes during
repeated yawning occasionally, it is very unlikely that the
hemidystonia might be due to sudden increase of muscle activity. Moreover, simple positional change from the supine to
erect position was not enough to precipitate dystonia. Prolonged supine position followed by standing or supine position
with hyperventilation were necessary prerequisites for the paroxysmal hemidystonia. Both sudden positional change and repeated yawning decrease the cerebral perfusion in the left
hemisphere that had a marginal blood flow due to the ipsilateral
carotid occlusion. Even the slightest change in blood pressure,
which may not necessarily meet the criteria of orthostatic hypotension, may have compromised the cerebral perfusion on
the left hemisphere.
With regard to the pathophysiologic substrates for paroxysmal dystonia, contradictory findings have been published. In
some cases of focal dystonia such as writer’s cramp, decrease
of cerebral perfusion to premotor and sensory motor cortex
during the dystonia was implicated by using PET scan studies.12 In two patients with familial exercise-induced paroxysmal dystonia, ictal SPECT studies using Tc99m-ECD showed
decreased ictal perfusion in the frontal cortex and increased
perfusion in the cerebellar cortex.13 On the contrary, a SPECT
study in a case of idiopathic hemidystonia reported ictal hy-

Movement Disorders, Vol. 17, No. 4, 2002

perperfusion of the contralateral thalamus and basal ganglia but
no significant change of perfusion in cortical areas.14 In our
patient, the decrease of cerebral perfusion in contralateral frontal/parietal cortex was present during the dystonia.
Our case supports the concept that cortical areas are involved
in the pathogenesis of paroxysmal dystonia. The possible explanation is that either inhibition of premotor cortex or
sensory–motor cortex from hypoperfusion in these areas may
release a primary motor pathway that leads to random and
simultaneous activation of agonistic-antagonistic muscles. Hypoperfusion in the contralateral cerebellum may be explained
by crossed cerebro–cerebellar diaschisis.15
By using subtraction SPECT method, we could avoid the
problems with traditional SPECT study such as different radioisotope dose and different imaging angles. O’Brien and associates16 validated this method in their study. Further study in
PKD or PKND patients using this method may clarify the role
of this technique in the study of paroxysmal dyskinesias. The
finding of abnormal limb posturing on assuming an upright
posture should warrant a search for cerebrovascular disease.

Legend to the Videotape
The patient develops dystonic posturing of the right arm
when he is standing up from the supine position.

References
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