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Acute Dystonic Reaction to Ecstasy
To the Editor:
Ecstasy (3,4-methylenedioxymethamphetamine)is a
recreational drug widely used in Europe and the United
States. Intake of ecstasy frequently causes trismus or
bruxism, muscle stiffness, and ataxia, and may also cause
psychiatric side effects such as paranoia, depression, or
psychosis (1). Occasional reports describe more severe
ecstasy-related adverse effects, including convulsions,
collapse, hyperthermia, disseminated intravascular coagulation, hypotension, and hepatotoxicity (1). In the patient, described here consumption of ecstasy led to an
unusual neurological complication.
A 22-year-old man, who had no personal or family history of neurological or systemic disease, but who admitted being an occasional cocaine user, took two tablets of
ecstasy. Several months had elapsed since his last intake
of cocaine, and he had never taken ecstasy before. Approximately 11 h after ingesting ecstasy, he awoke from a
normal night’s sleep with a feeling of restlessness, accompanied by difficulty in turning his head and mild dysphagia. Neurological examination on the same day showed
spasmodic torticollis to the right with laterocollis and a
coarse action tremor of the right upper limb. These manifestations responded promptly to intramuscular anticholinergic treatment (biperidene lactate, 10 mg). The
tremor and dysphagia disappeared gradually within 4
days, the torticollis within 11 days. When treatment was
interrupted 19 days after the onset of symptoms, the patient complained only of discomfort on turning his head to
the left, a symptom that disappeared completely within 2
weeks. Eight months after taking ecstasy, he remained
symptom-free.
Our patient’s clinical picture resembles an acute dystonic reaction to antidopaminergic neuroleptic drugs. The
effectiveness of the symptomatic anticholinergic treatment also suggests a basal ganglia dysfunction. Interestingly, his disorder had a longer recovery course than that
usually seen in patients with neuroleptic-induced dystonic reactions. The long time course might depend not
upon pharmacokinetic mechanisms but on underlying
changes in receptor sensitivity. Ecstasy stimulates serotonin release (2), and serotonergic pathways innervate the
substantia nigra and globus pallidus (3), the two major
output structures of the basal ganglia. Although ecstasy,
like other amphetamine derivatives, exerts major effects
on serotonin release, it also influences dopaminergic systems. In the case reported here, the fact that the patient
had consumed c o c a i n e a well-known dopamine stimulant (4hwithout complaining of adverse effects makes it
unlikely that stimulation of the dopaminergic system precipitated his acute ecstasy-related dystonic reaction. Unusual dystonic reactions of this kind, presumably occur,
as do neuroleptic-induced reactions, only in predisposed
individuals (5). Alternatively, ecstasy-related acute dystonia might go unreported because drug users tend to
underestimate self-limiting complications. Whatever the
explanation, acute dystonia induced by ecstasy hardly
surprises, considering that another psychostimulant, co-

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caine, can precipitate or even induce hyperkinetic movement disorders (6). This case report suggests that young
adults with acute-onset dystonia should be questioned
about possible ecstasy intake.
Albert0 Priori
Istituto Mediterraneo di Neuroscienze
Pozzilli, Italy
Laura Bertolasi
Clinica Neurologica Universita degli Studi di Verona
Verona, Italy
Alfred0 Berardelli
Dipartimento di Scienze Neurologiche
Universita di Roma “La Sapienza”
Roma, Italy

Mario Manfredi
Istituto Mediterraneo di Neuroscienze
Pozzilli, and
Dipartimento di Scienze Neurologiche
Universita di Roma “La Sapienza”
Roma, Italy

References
1 . Henry JA. Ecstasy and the dance of death. Br Med J 1992;
30554.
2. Rudnick G, Wall SC. The molecular mechanisms of “ecstasy”: serotonin transporters are targets for MDMAinduced serotonin release. Proc Nut1 Acud Sci USA 1992;
89: 18 17-182 1.
3. Jacobs BL, Fornal CA. 5-HT and motor control: a hypothesis. Trends Neurosci 1993;16:346-352.
4. Jaffe J. Drug addiction and drug abuse. In: Goodman Gilman
A, Goodman LS, Rall TW, Murad F, eds. The pharmucological busis of rherupeutics. New York: Macmillan, 1985:
532-581.
5 . Tarsy D. Neuroleptic induced movement disorders. In:
Quinn NP, Jenner PG, eds. Disorders of movement. London: Academic Press, 1989:361-394.
6. Cardoso FE, Jankovic J. Cocaine-related movement disorders. Mov Disord 1993;8:175-178.

Diabetes Mellitus Presenting as Paroxysmal
Kinesigenic Dystonic Choreoathetosis
Paroxysmal kinesigenic dystonic choreoathetosis
(PKC) is a disorder that is characterized by attacks of
chorea, dystonia, or tonic posturing lasting <5 min and
triggered by sudden movements or startle (1). These episodes can occur up to 100 times a day and can be preceded by paresthesias or vague sensory phenomenon.
Some patients have pain associated with the dystonia.
Both familial and sporadic cases can occur. Sensorium is
not altered during the episodes. Patients are asymptomatic between attacks (2). PKC has been reported in patients with thalamic infarcts (3), multiple sclerosis (4),
basal ganglia calcifiprogressive supranuclear palsy (3,
cations (6), thyrotoxicosis (7), and hypoglycemia (8).
Nonketotic hyperglycemia can cause seizures, visual hallucinations, focal neurologic signs, disturbance of con-

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sciousness, choreoathetosis, and myoclonic twitches
(9,lO). We describe a patient with PKC affecting the right
arm secondary to new onset diabetes mellitus.
A 68-year-old right-handed man presented with right
arm intermittent paresthesias that started in the fingers
and moved up to involve the entire arm. Several hours
later, numbness was followed by severe pain and then
involuntary right arm movements. The episodes of involuntary movements occurred eight to 10 times a day and
lasted 3-5 min. They were precipitated by movement of
that arm as when grasping for a glass of water and when
stressed or excited. There was a history of essential hypertension for which he was taking nifedipine extended
release tablet 120 mg/day. He had polyuria and polydypsia for 2-3 weeks. He had no history of seizures or myocardial infarction. He denied fever, chills, sweats, cold
intolerance, muscle cramps, or extremity weakness. He
quit smoking 30 years ago. On examination, blood pressure was 132/86 mm/Hg, pulse 82 beats/min and regular,
and respirations were 18/min. He was afebrile. On neurological examination, he was alert and oriented without
cognitive deficits. Muscle strength was normal, except in
the right hand, where it was 4/5. Abnormal movements
were characterized by internal rotation of the right arm,
extension at the elbow, and pronation of the hand 360” so
that the ventral aspect of the hand faced upward. The
dystonic posture of the right arm persisted throughout the
3-5-min period. The patient reported no paresthesias or
dysesthesias between attacks, and his neurologic exam
was normal, except for mild right hand weakness, which
had been present for many years. There was no rigidity,
bradykinesia, or tremor. Deep tendon reflexes were symmetric and decreased. Plantar reflexes were flexor. Laboratory was significant for a serum glucose = 688 mgldl,
BUN = 30 mg/dl, and creatine = 1.6. Serum osmolality
was calculated to be 310 mOsm/kg H,O. Serum acetone
was negative. MRI of the head revealed a circular lesion
in the left posterior parietal white matter and prominence
of the left sylvian fissure consistent with left hemispheric
atrophy (Fig. 1). Note was made of small lesions in the
basal ganglia thought to be consistent with VirchowRobin spaces. Electroencephalogram, recorded during an
episode of dystonia, was normal. The patient was hydrated and treated with insulin. His abnormal movements
decreased in frequency and severity over the next 7 days.

At the time of discharge, his serum glucose was 198 mg/dl
and his PKC had resolved. His diabetes was managed
with glipizide 10 mg bid and diet. There was no recurrence on follow-up at 6 months.

Discussion
Nonketotic hyperglycemia can cause diffuse alterations
in many parts of the central nervous system. Coma and
seizures can be associated with nonketotic hyperglycemia
and occurs more commonly than in ketotic hyperglycemia. Aphasia, hemiparesis, hemisensory loss, hemianopsia, nystagmus, and tonic eye deviation have also been
reported (9). Focal neurologic changes in the absence of
seizure activity can often be seen as a presenting symptom of nonketotic coma (11). The mean age of patients
with nonketotic coma is 62 years (12). Most of these patients have old infarcts, cerebral arteriosclerosis, or lacunar states. These lesions expose certain neuronal groups
to the adverse biochemical conditions of nonketotic hyperglycemia. Our patient had left cortical atrophy secondary to a previous infarct. Thus, the left hemisphere most
likely was more susceptible to metabolic changes.
PKC has been described in patients with multiple sclerosis (4), head trauma (13), thyrotoxicosis (7), hypoparathyroidism (14), hypoglycemia (8), and basal ganglia calcifications (6). In addition, specific ischemic lesions have
been associated with PKC and include lesions of the putamen, right frontoparietal region, thalamus, and brainstem
(3). Morres et al. (15) described what they thought was
PKC as a manifestation of nonketotic hyperglycemia but
their patient experienced shaking and jerking of the right
arm and leg. Their patient had no dystonic posturing.
They later mention that the patient probably had “movement induced myoclonic jerking” (15). Rector et al. (10)
described three patients with choreoathetosis or ballism
secondary to nonketotic hyperglycemia. Their patients
symptoms were not paroxysmal and not precipitated by
movement (10). To our knowledge, this is the first report
of PKC as the presenting symptom of diabetes mellitus.
Two changes are proposed, one metabolic and the
other circulatory, that attempt to explain the focal right
arm dystonic choreoathetosis that occurred during nonketotic hyperglycemia. The biochemical alterations vary
depending on whether the hyperglycemia is associated

FIG. 1. Cranial MRI showing a
subcortical infarct in the left postenor parietal lobe. T1-weighted image on the left (TR = 683, TE = 16)
with decreased intensity and T2weighted image on the right (TR =
2.500, TE = 90) demonstrate highintensity characteristics of the lesion. There is prominence of the
left Sylvian fissure consistent with
left cortical atrophy. The small
rounded lesions in the basal ganglia
are most likely Virchow-Robin
spaces.

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with ketosis or nonketosis. In nonketotic states gamma
amino n-butyric acid (GABA) becomes depleted. GABA
and L-glutamic acid are both amino acids and are present
in high concentrations in nervous tissue. During the stress
of nonketotic hyperglycemia the energy requirements
change due to inhibition of the Krebs cycle thought to be
the result of a direct influence from a hyperosmolar environment. Brain tissue then resorts to using ketone bodies and amino acids for metabolism, GABA is metabolized to succinic acid via the succinic semialdehyde pathway (GABA shunt) (12). This shunt can be used as an
alternative pathway to the Krebs cycle and can generate
as much as 40% of the total energy requirements in brain
tissue. As a consequence to the greater utilization of the
GABA shunt, GABA is depleted.
In patients with Huntington’s disease with chorea type,
neuronal subpopulations that utilize GABA as a neurotransmitter are preferentially lost in striatal neurons projecting to the globus pallidus externa (GPe) via the indirect pathway of the motor circuit of the basal gangliathalamocortical circuit (16,17). In primates, forty-seven
percent of the GPe neurons are allocated to the active
movement of the arm. In comparison, ten per cent are
involved with active leg movements (18). Because of the
relatively large number of GPe neurons functionally arranged in parallel circuits for both the execution and preparation of limb movement, these neurons are most SUSceptible to GABA depletion. As to why the dystonia involved the right arm, the patient could have either had
lesions in the left basal ganglia not seen on MRI or the
infarct in the left subcortical white matter could have interfered with t he circuitry of the basal gangliathalamocortical pathway.
Hyperglycemia has been shown to decrease cerebral
regional blood flow independent of changes in serum osmolality. Statistically significant (p < 0.01) blood flow
decreases occurred in the globus pallidus and thalamus
(19). Therefore, hyperglycemia induced regional blood
flow pallidal and thalamic decreases could also contribute
to the dysfunction of susceptible neurons. Again, due to
the relatively high number of GPe neurons controlling
active arm movements, these neurons would be rendered
most susceptible to diminished regional blood flow.
We describe a unique case of paroxysmal kinesigenic
dystonic choreoathetosis as the presenting symptom of
diabetes mellitus first appearing as non-ketotic hyperglycemia.
John D. Clark
Rajesh Pahwa
William C. Koller
Department of Neurology
David Morales
Department of Internal Medicine
University of Kansas Medical Center
Kansas C i o , Kansas, U.S.A.

References
1. Kertesz A. Kinesigenic choreoathetosis. Neurology 1967;17:
680-6!90.

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2. Plant G. Focal paroxysmal kinesigenic choreoathetosis. J
Neurol Neurosurg Psychiatry 1983;46:345-348.
3. Camal A, Greene P, Khandj A. Paroxysmal kinesigenic dystonic choreoathetosis associated with a thalamic infarct.
Mov Disord 1990;5:235-238.
4. Shibasaki H, Kuriowa Y,Fukuoka J. Painful tonic seizures
in multiple sclerosis. Arch Neurol 1974;30:47-51.
5 . Adam A, Orinda D. Focal paroxysmal kinesigenic
choreoathetosis preceding the development of SteeleRichardson-Olszewski syndrome. 3 Neurol Neurosurg Psychiatry 1986;49:957-959.
6. Michell F, Pardal M, Parera I, Giannaula R. Sporadic paroxysmal dystonic choreoathetosis associated with basal ganglia calcifications. Ann Neurol 1986;20:750.
7. Fishbeck K, Layzer R. Paroxysmal choreoathetosis associated with thyrotoxicosis. Ann Neurol 1979;6:453-454.
8. Newman RP, Kinkle WR. Paroxysmal choreoathetosis due
to hypoglycemia. Arch Neurol 1984;41:341-342.
9. Maccario M. Neurologic dysfunction associated with nonketotic hyperglycemia. Arch Neurol 1968;19:525-534.
10. Rector WG, Jr., Herlong HF, Moses H, 111. Nonketotic hyperglycemia appearing as choreoathetosis or ballism. Arch
Intern Med 1982;142:154-155.
11. Arieff AI, Carroll HJ. Nonketotic hyperosmolar coma with
hyperglycemia: clinical features, pathophysiology, renal
function, acid-base balance, plasma-csf equilibria and the
effects of therapy in 37 cases. Medicine 1972;51:73-94.
12. Guisado R, Arieff AI. Neurologic manifestations of diabetic
coma: correlation with biochemical alterations in the brain.
Metabolism 1975;24:665-679.
13. Robin J . Paroxysmal choreoathetosis following head injury.
Ann Neurol 1977;2:447448.
14. Tabaee-Zadeh M, Frame B, Kapphahn K. Kinesiogenic
choreoathetosis and idiopathic hypoparathyroidism. N Engl
J Med 1972;286:762-763.
15. Morres CA, Dire DJ. Movement disorders as a manifestation
of nonketotic hyperglycemia. J Emerg Med 1989;7:359-364.
16. Albin RL, Reiner A, Anderson KD, Penney JB, Young AB.
Striatal and nigral neuron subpopulations in rigid Huntington’s Disease: implications for the functional anatomy of
chorea and rigidity-akinesia. Ann Neurol 1990;27:357-365.
17. Alexander GE, Crutcher MD, DeLong MR. Basal gangliathalamocortical circuits: parallel substrates for motor, oculomotor, “prefrontal” and ‘‘limbic’’ functions. Prog Brain
Res 1990;85:119-146.
18. DeLong MR, Crutcher MD, Georgepoulos AP. Primate globus pallidus and subthalamic nucleus: function organization.
3 Neurophysiol 1985;53:530-543.
19. Duckrow RB, Beard DC, Brennan RW. Regional cerebral
blood flow decreases during hyperglycemia. Ann Neurol
1985;17967-272.

Does Fluoxetine Aggravate Parkinson’s Disease? A
Pilot Prospective Study
To the Editor:
The number of drugs able to induce parkinsonism or
aggravate Parkinson’s disease is now rapidly growing.
Besides reserpine, tetrabenazine, and classical neurolep-

Movement Disorders, Val. 10, No. 3, 1995