626 LETTERS TO THE EDITOR Department of Neurology, Asan Medical Center University of Ulsan College of Medicine, Seoul, Korea *E-mail: sjchung@amc.seoul.kr Chang-Seok Ki, MD Department of Laboratory Medicine and Genetics Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea Mi J. Kim, MD Myoung C. Lee, MD Center for Parkinsonism and Other Movement Disorders Department of Neurology, Asan Medical Center University of Ulsan College of Medicine, Seoul, Korea References 1. Kitada T, Asakawa S, Hattori N, et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 1998; 392:605-608. 2. Periquet M, Latouche M, Lohmann E, et al. Parkin mutations are frequent in patients with isolated early-onset Parkinsonism. Brain 2003;126:1271-1278. 3. Khan NL, Graham E, Critchley P, et al. Parkin disease: a phenotypic study of a large case series. Brain 2003;126:1279-1292. 4. Hjermind LE, Johannsen LG, Blau N, et al. Dopa-responsive dystonia and early-onset Parkinson’s disease in a patient with GTP cyclohydrolase I deficiency? Mov Disord 2006;21:679682. 5. Tassin J, Durr A, Bonnet AM, et al. Levodopa-responsive dystonia. GTP cyclohydrolase I or parkin mutations? Brain 2000;123: 1112-1121. 6. Bandmann O, Marsden CD, Wood NW. Atypical presentations of dopa-responsive dystonia. Adv Neurol 1998;78:283-290. 7. Nomura Y, Uetake K, Yukishita S, et al. Dystonias responding to levodopa and failure in biopterin metabolism. Adv Neurol 1998; 78:253-266. 8. McGeer EG, McGeer PL. Some characteristics of brain tyrosine hydroxylase. In: Mandel J, editor. New concepts in neurotransmitter regulation. New York: Plenum; 1973. p 53-68. Dystonia as a First Presentation of Cryptogenic Stroke in a Young Patient with Right-to-Left Shunt Cryptogenic strokes account for as many as 63% of cerebrovascular events in young adults.1 Cardiac right-to-left shunt (RLS) is a known cause of thromboembolic stroke by paradoxical embolism (PE). PE is associated in conditions such as patent foramen ovale (PFO), pulmonary arteriovenous fistula, and atrial septal defects. The potential role of PFO and atrial septal aneurysm (ASA) in those cases has been investigated over several years. Movement disorders are relatively common after stroke. There is already some clinical evidence that damage to the Published online 7 January 2008 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.21921 Movement Disorders, Vol. 23, No. 4, 2008 brain early in life tends to lead to dystonia rather than other movement disorders.2 We report a case of a patient with distonia, thalamic, and deep white matter vascular lesions. Investigation revealed PFO. A 26-year-old right-handed female was referred to our service complaining of “stiffness and pain in her left arm.” Twenty months earlier she started having pain in her wrist. About five months later her hand became stiff and she started to lose coordination. Six months later, she detected the same signs in her left arm, and difficulty with her voice. In the following months she also felt that her left leg was awkward, hindering normal ambulation. Her medical history was unremarkable and she had no family history of movement disorders. On neurological examination, the patient’s mental status and cranial nerves were normal. Muscle strength was 5/5 with slightly brisk tendon reflexes. Her muscle tone was increased in her left arm but without cogwheel rigidity or tremor. Sensation to all modalities, coordination and gait were intact. She had mild dysarthria and a dystonic posture in her left arm, predominantly distally, giving a “claw hand appearance” (Fig. 1). Occasional athetotic movements were noticed in her left hand. The patient underwent a brain magnetic resonance imaging (MRI) scan, which revealed a subacute/chronic lesion in the left thalamus, with discrete impregnation by gadolinium. There were also some minor lesions in right thalamus and deep white matter interpreted as probable old ischemic lacunar infarctions (Fig. 2). Angiography by MRI was normal. Laboratory results, including complete blood cell count, PTTk, PT/INR, serum chemistry profile, VDRL, HIV, and viral hepatitis serology, hemoglobin electrophoresis, serum ceruloplasmin, and urinary copper levels and rheumatologic evaluation were normal. Cerebrospinal fluid (CSF) did not show any abnormality. Transesophageal echocardiography pointed to a RLS with passage of microbubbles from the right to the left atrium. Transcranial doppler also detected the presence of microbubbles in the middle cerebral artery after their injection in the antecubital vein. The patient was put on anticoagulation therapy with warfarin for three months. She underwent percutaneous closure of the RLS. Six months after the procedure the patient had not developed any new neurological impairment but her original neurological deficits persisted. The dystonia symptoms were treated with botulinum toxin type A (Dysport®) injections in affected muscles. Cerebral brain ischemia may occur in young patients and the spectrum of etiologies in young adults is different from that in older patients. Parodoxical embolism is an uncommonly diagnosed cause of unexplained ischemic cerebral events. Most of them have been associated with PFO.3,4 The role of parodoxical embolism through a PFO and stroke remains controversial. The presumed pathophysiology of PE seems to be fibrin-rich thrombus direct embolization from thrombi formed within the PFO, and associated ASA or atrial arrythmias.5 Coagulation defects associated with right-left shunts have also been described.6 We detected a different origin of like emboli because of atrial septal defect with RLS. Cerebrovascular accidents can be responsible for several types of abnormal involuntary movements. Thalamic strokes have been associated with chorea, dystonia, tremor, myoclonus, and other complex movements. A previous study divided dystonia related to LETTERS TO THE EDITOR 627 FIG. 1. Left hand dystonia. (A) Both hands are outstretched showing a clear left hand dystonia, characterized as a forced flexion of the wrist and hyperextension of the metacarpophalangeal joints, slight adduction of her thumb and marked flexion of her fifth finger. (B) Larger view of left hand distonia. FIG. 2. Brain MRI scan showed: (A–C) Axial FLAIR images demonstrate hyperintense lesions within bilateral thalamus and deep white matter. (D, E) Axial T2-weighted images show hyperintense lesions on bilateral thalamus and deep white matter. (F) An axial T1-weighted with gadolinium reveals a discrete lesion enhancement on left thalamus. thalamic lesions into two subgroups: dystonic spasms and myoclonic dystonia.7 The former consisted of sustained contractions causing twisting and repetitive movements or abnormal posture as seen in our patient. The pathogenesis of these movements seems to be related to disruption of the pallidothalamic projections as well as a proprioceptive or cerebellar dysfunction.8 Thalamogeniculate, tuberothalamic, and paramedian territories are the most common involved areas, but posterior choroidal territory is also described as a common site. The abnormal movements usually start gradually and progressively worsened over weeks or months.7 We could not establish a sudden onset in our case but the history suggested a progressive course over at least one year. According to the literature, there may be a long latency between the insult and symptom onset7. We conclude that isolated dystonia can be an uncommon initial manifestation of cryptogenic stroke in young patients. Further, RLS should be regarded as a possible cause in sudden onset but also showing progressive focal or hemidystonia. Pedro Braga-Neto, MD* Denizart Santos-Neto, MD Gustavo Wruck Kuster, MD Gisele Sampaio Silva, MD, PhD Department of Neurology and Neurosurgery Universidade Federal de São Paulo São Paulo, Brazil *E-mail: pbraganeto@hotmail.com Vera Lúcia Ferreira Vieira, MD Department of Clinical Medicine Universidade Federal do Espı́rito Santo Brazil Vanderci Borges, MD, PhD Orlando Graziani Povoas Barsottini, MD, PhD Department of Neurology and Neurosurgery Universidade Federal de São Paulo São Paulo, Brazil Movement Disorders, Vol. 23, No. 4, 2008 628 LETTERS TO THE EDITOR References 1. Leys D, Bandu L, Henon H, et al. Clinical Outcome in 287 consecutive young adults (15 to 45 years) with ischemic stroke. Neurology 2002;59:26 –23. 2. Alarcóm F, Zijlmans JCM, Dueñas G, Cevallos N. Post-stroke movement disorder: report of 56 patients. J Neurol Neurosurg Psychiatry 2004;75:1568 –1574. 3. Lechat P, Mas JL, Lascault G, Loron P, et al. Prevalence of patent foramen ovale in patients with stroke. N Engl J Med 1988;318: 1148 –1152. 4. Webster MWI, Chancellor AM, Smith HJ, Swift DL, Sharpe DN, Bass NM. Patent foramen ovale in young stroke patients. Lancet 1988;2:11–12. 5. Kizer JR, Devereux RB. Patent foramen ovale in young adults with unexplained stroke. N Engl J Med 2005;353:2361–2372. 6. Chaturvedi S. Coagulation abnormalities in adults with cryptogenic stroke and patent formen ovale. J Noeurol Sci 1998;160:158 –160. 7. Lehéricy S, Grand S, Pollak P, et al. Clinical characteristics and topography of lesions in movement disordes due to thalamic lesions. Neurology 2001;57:1055–1066. 8. Kim JS. Delayed onset mixed involuntary movements after thalamic stroke clinical, radiological and pathophysiological findings. Brain 2001;124:299 –309. Dopaminergic Drug-Induced Tics in PARK2Positive Parkinson’s Disease Subjects with PARK2-positive Parkinson’s disease (PD) may develop levodopa-induced dyskinesias at early stages in the course of their disease.1 Thus far, however, the occurrence of tics has less frequently been reported.2 A 42-year-old man with a 4-year history of PARK2-positive early-onset PD (homozygotic deletion of the exons 4 and 5) under regular medication with 300 mg levodopa (started 2 years earlier), 2.1 mg pramipexole (started 1 year earlier), and 1 mg rasagiline (started 6 months earlier) presented with a 6-month history of paroxysmal involuntary screaming, which occurred primarily in the evening hours or in time of complete relaxation during day time. These episodes started with a delay of 5 days after the onset of rasagiline medication. He described an urge to produce brief sniffing, grunting, and screaming sounds in times when he was relaxing or ready to fall asleep. He was able to suppress the screaming sounds for several minutes with exacerbation of screaming thereafter. The screaming tics were so loud during the night that they disturbed the patient’s neighbors. His previous medical and family history was unremarkable regarding tic disorder, obsessive-compulsive disorder, or attention deficit hyperactivity disorder and he had a normal physical and mental development. Clinical examination under dopaminergic medication revealed a parkinsonism with left body preponderance, intermittent resting tremor of the upper limbs, and This article includes supplementary video clips, available online at http://www.interscience.wiley.com/jpages/0885-3185/suppmat. Published online 7 January 2008 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.21905 Movement Disorders, Vol. 23, No. 4, 2008 mild dyskinetic movements like choreo-athetotic movements of the neck and proximal limb muscles and intermittent mild signs of foot dystonia, i.e., striatal foot deformity. When asked to lie down and relax in a recumbent position, he started after a while to produce simple phonic tics, such as grunting, sniffing, and screaming, as well as simple motor tics such as blinking, yawing, and trunk flexions (Video). We interpret the tics to represent dopaminergic drug-induced side effects in this patient with early onset PARK2-positive PD. This hypothesis was strengthened when after pausing rasagiline, pramipexole, and all dopaminergic drugs on separate occasions the phonic tics disappeared (albeit at the price of a deterioration of motor functions). The time to disappearance of tics depended on the dopaminergic drug to be withdrawn. Tics were remarkably reduced after an overnight withdrawal of all dopaminergic drugs and disappeared within 2 and 5 days after pausing pramipexole and rasagiline, respectively. Relaxation of physical and mental activity when lying down reduces distractibility from the internal urge to generate tics, and may thus be responsible for the strong association between the relaxed position and the occurrence of dopaminergic tics in our patient. Intracortical inhibition in the motor system is reduced in tic disorders,3 and neuroimaging data suggest that in tic disorders paralimbic and sensory association areas are critically implicated in tic generation, similar to movements triggered internally by unpleasant sensations, as has been shown for pain or itching.4 However, we do not have a satisfactory explanation for why the tics in our patient occurred mainly during a recumbent position. Manuel Dafotakis, MD* Gereon R. Fink, MD Dennis A. Nowak, MD Department of Neurology University Hospital University of Cologne Cologne, Germany Institute of Medicine Research Centre Juelich Juelich, Germany *E-mail: m.dafotakis@fz-juelich.de LEGEND TO THE VIDEO The patient was asked to lay down during the course of the clinical examination. After 10 to 15 minutes of relaxation, he started to produce simple motor and phonic tics, such as grunting and screaming which were accompanied by sudden flexion movements of the trunk. References 1. Ishikawa A, Tsuji S. Clinical analysis of 17 patients in 12 Japanese families with autosomal-recessive type juvenile parkinsonism. Neurology 1996;47:160-166. 2. Jankovic JJ. Tics and Tourette’s syndrome. In: Jankovic JJ, Tolosa E, editors. Parkinson’s disease and movement disorders. Philadelphia: Lippincott Williams and Wilkins; 2002. p 311-330. 3. Ziemann U, Paulus W, Rothenberger A. Decreased motor inhibition in Tourette’s disorder: evidence from transcranial magnetic stimulation. Am J Psychiatry 1997;154:1277-1284. 4. Bohlhalter S, Goldfine A, Matteson S, et al. Neural correlates of tic generation in Tourette syndrome: an event-related functional MRI study. Brain 2006;129:2029-2037.