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,
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Welter ML, Grabli D, Vidailhet M. Deep brain stimulation for hyperkinetics disorders:
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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,
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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
In Kooperation mit: Dr. Matthias Bohnsack Invasive Kardiologie am Klinikum Elmshorn Praxis: Friedenstr. 4, 25335 Elmshorn, Tel: 04121-485757 Patienteninformation Herzkatheteruntersuchung Sehr geehrte Patientin, sehr geehrter Patient, dieses Merkblatt soll Ihnen in Ergänzung zu dem Ihnen ebenfalls vorliegenden Aufklärungsbogen die Herzkatheteruntersuchung näherbringen,
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