Microsoft word - tardive.v07

STATUS DYSTONICUS IN TARDIVE DYSTONIA SUCCESSFULLY
TREATED BY BILATERAL DEEP BRAIN STIMULATION
Norbert Kovacs1, MD, PhD; Istvan Balas2, MD, PhD; Jozsef Janszky1, MD, PhD; Maria Simon3, MD, PhD, Sandor Fekete3, MD, PhD; Samuel Komoly1, MD, D.Sc 1Department of Neurology, University of Pecs, Pecs, Hungary 2Department of Neurosurgery, University of Pecs, Pecs, Hungary 2Department of Psychiatry, University of Pecs, Pecs, Hungary Correspondence to:
Word count for text: 705, Word count for abstract: none, character count for title: 94
Running title: Status dystonicus in tardive dystonia

Keywords: Psychosis, tardive dystonia , dystonic storm, status dystonicus, deep brain
stimulation
Financial disclosure: NK and JJ are supported by a government based Bolyai Scholarship of
the Hungarian Scientific Academy. NK, JJ, MS, SK, SF received a grant from Norwegian
Financial Mechanism (HU00114) of European Union. NK also received a support from the
Hungarian Neuroimaging Foundation. JJ was supported by Abbreviations: Hungarian
Research Fund (OTKA-NKTH F68720).
BFMDRS = Burke-Fahn-Marsden Dystonia Rating Scale; DBS = deep brain stimulation; EPS =
Extrapyramidal symptoms; GPi = internal part of globus pallidus; SD = status dystonicus
This is a preprint of an article published in Clinical Neurology and Neurosurgery http://www.sciencedirect.com/science/article/pii/S0303846711002356 We present the case of an 18-year-old boy, who was treated by risperidon (up to 8mg/day) and clonazepam (up to 4mg/day) combination because of schizophrenia since the age of 16. Due to an acute psychotic episode up to 5 mg/day haloperidol was introduced as an add- on therapy to risperidon resulting in acute oculogyric symptoms in July, 2009. After a usage of 16 days, the haloperidol medication was completely stopped, whereas biperiden (2mg tid) was introduced. Subsequently, risperidon was also replaced by olanzapine (10mg/day). However, severe segmental dystonia developed with the combination of retrocollis, toricollis and oculofacial dyskinesia in September, 2009. Because brain MRI was negative and Wilson’s disease, DYT-1 positive dystonia or acoruloplasminemia could not be diagnosed in the background, we proposed a tardive etiology. Meanwhile his tardive dystonia showed slow progression under the combination of olanzapine (10mg/day) and biperiden (10mg/day), therefore, this combination was replaced by clozapine (225mg/day) in October, 2009. In December 2009, the patient was admitted to our neurological ward in the condition of status dystonicus (SD). The dystonic symptoms differed completely from the previously observed ones. More pronounced and long-lasting fixed dystonic postures were accompanied by continuous, disabling dyskinetic movements of the face and all extremities resulting in extreme pain and several self-injuries (e.g. extremities bumped into furniture). Despite of elevated level of cretine-kinase (CK, 871U/l), no other clinical signs of neuroleptic malignant syndrome could be identified. Therefore, the elevated CK level was thought to be the consequence of extreme muscle activity and injuries. No obvious provoking factor (e.g. infection, metabolic alterations) could be identified in the background of acute worsening. Because the disabling hyperkinetic symptoms interfered with sleeping and resulted in increased cardiovascular demand (e.g. tachycardia) and extreme pain to the patient, first bolus clonazepam and later continuous intravenous midazolam was applied for achieving an immediate relief (up to 500mg/day). However, whenever we tried to lower this light sedation, the dystonic symptoms reappeared in a more aggravated manner. Because clonazepam and midazolam were associated with a worsening in the dystonic symptoms after their temporary effects vanished, we switched to continuous propofol sedation (up to 6000mg/day). Because neither light-, nor deep sedation improve the life-threatening symptoms of SD, we decided to implant Medtronic 3389 electrodes into the internal part of globus pallidus (GPi) bilaterally. Few days after initiating GPi deep brain stimulation (DBS), dystonic symptoms began to dramatically improve. Postoperatively the patient received clozapine (225 mg/day) whereas the improvement in dystonic symptoms remained persistent. (Table 1).
The patient and his caregiver gave informed consent to present his case and videos in scientific journals according to the Declaration of Helsinki. Dopamine-receptor-blocking antipsychotic drugs may cause various acute and delayed- onset movement disorders including acute dystonia, parkinsonism, akathisia, tardive dyskinesia and tardive dystonia. Despite tardive movement disorders were described 50 years ago, their medical treatment is still disappointing in some cases. However, a growing number of evidence suggests that tardive dystonia and/or dyskinesia might be an excellent indication for bilateral GPi-DBS with an improvement of 65-100% measured by Burke-Fahn-Marsden Dystonia Rating Dystonic storm or status dystonicus is an extremely rare form dystonia representing an emergency situation. Severe, disabling and long-lasting muscle contractions characterize SD resulting in increased cardiopulmonary demand, unbearable pain, elevated creatine-kinase levels, and sometimes spontaneous femur fracture[4]. Despite immediate and adequate treatment including sedation, intrathecal baclofen pump or DBS, the mortality of SD is still approximately 10%[5]. SD is usually triggered by metabolic disturbances, surgery, infections or changes in medication. In our case, however, no provoking factor could be identified. The present paper might have some interesting observations: To our knowledge, this is the first published case where tardive dystonia resulted in status dystonicus. As mentioned by Mariotti et al[5]., benzodiazepine drugs seemed to have a worsening effect on the dystonic symptoms. Whenever the temporary effect of clonazepam or midazolam vanished or were suspended, the dystonic symptoms reappeared in an aggravated manner compared to the severity before these drugs were administrated, which could be interpreted as a possible rebound phenomenon. Our case further supports the impression that drug-refractory tardive symptoms might be good indication for GPi-DBS, even in cases where these symptoms evolve Sako W, Goto S, Shimazu H, Murase N, Matsuzaki K, Tamura T, Mure H, Tomogane Y, Arita N, Yoshikawa H, Nagahiro S, Kaji R. Bilateral deep brain stimulation of the globus pallidus internus in tardive dystonia. Mov Disord 2008;23:1929-1931. Gruber D, Trottenberg T, Kivi A, Schoenecker T, Kopp UA, Hoffmann KT, Schneider GH, Kuhn AA, Kupsch A. Long-term effects of pallidal deep brain stimulation in tardive dystonia. Neurology 2009;73:53-58. Welter ML, Grabli D, Vidailhet M. Deep brain stimulation for hyperkinetics disorders: dystonia, tardive dyskinesia, and tics. Curr Opin Neurol 2010;23:420-425. Balas I, Kovacs N, Hollody K. Staged bilateral stereotactic pallidothalamotomy for life- threatening dystonia in a child with Hallervorden-Spatz disease. Mov Disord 2006;21:82- Mariotti P, Fasano A, Contarino MF, Della Marca G, Piastra M, Genovese O, Pulitano S, Chiaretti A, Bentivoglio AR. Management of status dystonicus: our experience and review of the literature. Mov Disord 2007;22:963-968. Dr. Kovacs is supported by the government-based Bolyai Scholarship of the Hungarian Scientific Academy, and a grant from Norwegian Financial Mechanism (HU00114) of European Union, and he also received a grant from the Hungarian Neuroimaging Foundation. Dr. Balas reported no financial disclosure Dr. Janszky is supported by the government-based Bolyai Scholarship of the Hungarian Scientific Academy, Hungarian Research Fund (OTKA-NKTH F68720) and a grant from Norwegian Financial Mechanism (HU00114) of European Union. He reports no other financial Dr. Simon is supported by a grant from Norwegian Financial Mechanism (HU00114) of European Union; he reported no other financial disclosure Dr. Fekete is supported by a grant from Norwegian Financial Mechanism (HU00114) of European Union; he reported no other financial disclosure Dr. Komoly is supported by a grant from Norwegian Financial Mechanism (HU00114) of European Union; he reported no other financial disclosure

Source: http://neurology.hu/wp31/download/2011_CNN_tardivestatus.pdf