LETTERS TO THE EDITORS 2. Peter R, Mishra V, Fraser WD. Severe hypocalcaemia after being given intravenous biphosphonate. Lesson of the week. Br Med J 2004;328:335–336. 3. Breen TL, Shane E. Prolonged hypocalcaemia after treatment with zoledronic acid in a patient with prostate cancer and vitamin D deficiency. J Clin Oncol 2004;22:1531–1532. 4. Hung VH, Monson JP. Endocrine emergencies. In: Harris PE, Bouloux PM, editors. Endocrinology in Clinical Practice. London: Martin Dunitz; 2003. p 471– 486. 5. Murray RML, Grill V, Crinis N, Ho PWM, Davison J, Pitt P. Hypocalcaemic and normocalcaemic hyperparathyroidism in patients with advanced prostatic cancer. J Clin Endocrinol Metab 2001;86:4133– 4138. Donepezil Also Effective in the Treatment of Tourette’s Syndrome? 2027 controlled trials, considering those effects especially in case of long-term treatment. Helmut Niederhofer, MD, PhD* Department of Pediatrics Regional Hospital of Bolzano Bolzano, Italy *E-mail: helmutniederhofer@yahoo.de Reference 1. Havslett RL, Tizaby Y. Effects of donepezil, nicotine and haloperidol on the central serotonergic system in mice: implications for Tourette’s syndrome. Pharmacol Biochem Behav 2005;81:879 – 886. Symptomatic Restless Leg Syndrome after Lacunar Stroke: A Lesion Study Sudden, involuntary, repetitive muscle movements (motor tics) and vocalizations (vocal tics) characterize Tourette’s syndrome (TS), which is also known as Gilles de la Tourette syndrome for the neurologist who first described the syndrome in 1885. The disorder is highly associated with behavioral problems, such as obsessions and compulsions, inattention, hyperactivity, and impulsivity. Symptom onset typically occurs during childhood or early adolescence. Although genetic hypotheses have been discussed, the etiopathogenesis of Tourette’s syndrome has not been ascertained, but 5-HT2A receptors seem to be involved. We hypothesized that donepezil, which has been shown to reduce the 5-HT2A receptor density,1 may have some benefit with respect to narcolepsy and cataplexy. For that reason, we investigated its efficacy for a patient suffering from TS. We describe an 18-year-old woman 2 years after the onset of the syndrome. Disease onset occurred with involuntary repetitive muscle movements and vocalizations. Family history was negative for sleep or other neurological disorders. No triggering factors or accompanying symptoms could be identified. Comorbidities, especially obsessive– compulsive disorders, have been excluded by clinical interview, and attention-deficit hyperactivity disorder has been excluded by clinical interview and Conner’s scales. A routine EEG was normal. After obtaining informed consent, we initiated donepezil 10 mg tid for 2 consecutive weeks. Four days after start of treatment, the patient reported a “significant improvement” of the symptoms, and improvement of both the involuntary muscle movements and the vocalizations has been noticed (Yale Global Tic Severity Scale: total motor score decreased from 18 to 11; total phonic score decreased from 17 to 12). After cessation of donepezil therapy, i.e., after the third week, total motor and phonic scores increased again both to 16. We administered tiaprid, which led to a decrease of the scores to 10 and 11, respectively, and which did not change significantly also 3 months after the trial. To our knowledge, this is the first report illustrating the clinical efficacy of donepezil for Tourette’s syndrome. Its possible efficacy seems to be comparable to that of tiaprid. In regards to adverse side effects of acetylcholinesterase inhibitors such as hepatotoxicity, this observation should be confirmed in We present an otherwise healthy male patient who suffered a microangiopathic lacunar ischemic stroke within the left-hemispheric thalamus at the age of 62, causing a right-sided hemihypesthesia and hemihypalgesia that recovered almost completely afterward. After initiation of thrombocyte aggregation inhibitor therapy, no further strokes have occurred to date. Six years later, the patient noticed for the first time a symptom complex consisting of unpleasant sensations (paresthesias/dysesthesias) “deep inside” the right leg localized distal of the knee, which were strictly unilateral and occurred only in the evening or night during periods of rest, i.e., lying in bed. The sensations were accompanied by an urge to move the leg, and the leg discomfort could be completely relieved by movement such as walking, resulting in insomnia. Cumulative sleep time was reduced to approximately 5 hours per night, and the patient reported prolonged sleep latency and frequent awakenings from sleep due to restless legs syndrome (RLS) symptoms. Due to fulfillment of the essential clinical criteria,1 RLS was diagnosed. Dopaminergic treatment with levodopa was initiated, followed by complete relief, thus constituting an additional supportive criterion for RLS. After some years, dopaminergic medication was switched to pramipexole due to augmentation, again resulting in stable improvement since then. Augmentation in this case meant shifting of symptoms to approximately 2 hours earlier than was the typical daily onset of symptoms before pharmacologic intervention,1 but the symptoms never extended to previously unaffected limbs and always remained restricted to the right leg only. Magnetic resonance imaging (MRI) of the brain, performed 9 years after the insult, showed the lacunar lesion in the left thalamus, mainly localized in the ventrolateral nucleus. No additional lesions of vascular or other origin were found. An additional MRI-based analysis of cerebral white matter fibers using the technique of diffusion tensor imaging demonstrated a partial discontinuation of the white matter connections between brainstem, thalamus, and cortex within the area of the lesion (Fig. 1). The analysis of periodic limb movements in sleep (PLMS) according to standardized criteria was performed dur- Published online 19 September 2006 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.21053 Published online 21 September 2006 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.21107 Movement Disorders, Vol. 21, No. 11, 2006 2028 LETTERS TO THE EDITORS system.2 The lesion localization in our patient is one element of this widespread functional loop system; in particular, the thalamic ventrolateral nuclear group is known to be closely connected to the basal ganglia. The localization in the case study is closely adjacent to the results of a morphometric MRI study,4 which demonstrated structural changes within the bilateral thalamus in idiopathic RLS; however, it has to be noted that the authors reported an increase of gray matter. Moreover, a functional MRI study in RLS patients showed brain activation in the thalamus and in the cerebellum during periodic limb movement and sensory leg discomfort and, thus, supported the role of the thalamus in the generation of RLS symptoms.5 In summary, this case provides the first lesion-based human model for the diagnosis RLS with the identification of one well-defined brain area. Alexander Unrath, MD Jan Kassubek, MD Department of Neurology University of Ulm Ulm, Germany *E-mail: jan.kassubek@uni-ulm.de FIG. 1. A–C: T1-weighted magnetic resonance imaging (MRI) of the patient in coronal, sagittal, and axial view showing the localization of the thalamic lesion. D: Color-coded visualization of white matter tracts derived from diffusion tensor MRI data, demonstrating partial discontinuation of the projection tracts. ing a polysomnographic recording under pausing of pramipexole approximately 9.5 years after the insult. The polysomnography showed marked, highly pathological PLMS of the right leg, whereas PLMS on the left side were only very infrequent, thus constituting a further supportive criterion for the diagnosis of unilateral RLS. This is the first description in the literature of a clinically typical symptomatic RLS, fulfilling all essential diagnostic criteria of the International RLS Study Group,1 which occurred secondary to one well-defined cerebral lesion. The long latency between the stroke and the development of RLS suggests an additional factor to have changed at the time when RLS symptoms started. However, this factor can only be speculated on. The case provides deeper insights into the still undetermined pathoanatomy of RLS due to the following constellation: (1) one single lesion in an eloquent area, precisely delineated in MRI; (2) strictly unilateral RLS, contralateral to the lesion; (3) no pre-existing RLS and negative family history for RLS; (4) no relevant comorbidities, including normal nerve conduction velocity measurements and normal iron status. Other disorders associated with secondary RLS, including uremia, polyneuropathy, or neurodegenerative diseases,2 allow a much less precise assessment of one single structure being involved. Also, one previous case report of RLS in association with stroke described a pre-existing familiar RLS, which worsened after a basal ganglia infarct3 and did not add substantially to the pathophysiological concepts. From what is known about RLS pathophysiology, the most intriguing approach is a functional disturbance of the sensorimotor network loops, including the spinal cord, the thalamus, the basal ganglia, the sensorimotor cortex, and the limbic Movement Disorders, Vol. 21, No. 11, 2006 References 1. Allen RP, Picchietti D, Hening WA, et al. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003;4: 101–119. 2. Trenkwalder C, Paulus W, Walters AS. The restless legs syndrome. Lancet Neurol 2005;4:465– 475. 3. Anderson KN, Bhatia KP, Losseff NA. A case of restless legs syndrome in association with stroke. Sleep 2005;28:147–148. 4. Etgen T, Draganski B, Ilg C, et al. Bilateral thalamic gray matter changes in patients with restless legs syndrome. Neuroimage 2005; 24:1242–1247. 5. Bucher SF, Seelos KC, Oertel WH, Reiser M, Trenkwalder C. Cerebral generators involved in the pathogenesis of the restless legs syndrome. Ann Neurol 1997;41:639 – 645. Metodopramide-Induced Palatopharyngeal Myoclonus Patient 1 is a 66-year-old woman with type II diabetes and peripheral vascular disease who presented to us after a left below-the-knee amputation. She was started on metoclopramide 5 mg p.o. tid for diabetic gastroparesis. On admission to our hospital, her neurological examination revealed no bradykinesia, masked facies, cogwheel rigidity, or tremor. Three weeks later, the patient complained of an unpleasant sensation associated with breathing. Her voice became softer and different in tone. While lying supine, she had a low-amplitude tremor of her anterior neck. The tremor was accompanied by a clicking sound emanating from her throat and by an alteration in the sound of her voice. When the patient sat forward, the tremor and clicking subsided, and her voice returned to normal. She Published online 7 September 2006 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.21074