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Deep brain stimulation in the treatment of tardive dystonia

2006; Lippincott Williams & Wilkins; Volume: 119; Issue: 9 Linguagem: Inglês

10.1097/00029330-200605010-00017

2542-5641

Jianguo Zhang, Kai Zhang, Zhongcheng Wang,

Genetic Neurodegenerative Diseases

Dystonia refers to a clinical syndrome in which sustained involuntary muscle contractions result in twisting and repetitive movements, or abnormal postures. Secondary dystonia is associated with acquired or exogenous causes, hereditary neurologic syndromes or neurodegenerative disorders. Tardive dystonia is a special type of secondary dystonia due to exposure to certain medicines such as neuroleptics, with a chronic and persistent extrapyramidal symptoms. Dystonia is a severely disabling and painful disease. Tardive dystonia is not rare, whereas its treatment is still very challenging. Most previous reports with both medications and surgeries proved to be disappointing. Enlightened with early reports in treating dystonia with lesions or neurostimulations, one case of tardive dystonia was treated with deep brain stimulation (DBS) in our hospital in July 2003, the target being bilateral subthalamic nucleus (STN). The outcome was perfect during a follow-up of 3 months. CASE REPORT Patient A 28-year-old Albanian girl was in perfect health before February 1999 when she started to have confusion and mild paranoia. After an episode of dystonic attack, she could not take care of herself any more. After taking haloperidol, first orally and then intramuscularly, she recovered well of the disease. From May 2000, she developed deformation of the right hand with involuntary movements. Medicines could not control the symptoms, and the patient's condition deteriorated gradually. The Involuntary movements spread from her trunk to the head, neck, limbs, and mouth. The muscular tension increased. Tremors of her hands were so frequent that she could not take a bath, nor feed herself. Before admission, she had been prescribed tetrabenazine 75 mg/d, tioridazina cloridrato 75 mg/d and stilnox 20 mg/d. Her past history was not contributable and she had no family history of dystonia. On admission, physical examination showed muscle tension increased in all the extremities. The tendon reflexes were hyperactive. Her facial expression was asymmetrical with frequent blink and forced mouth opening. Her speech was blurring. When she was in supine position, her head rotated to left, the neck twisted to right, shoulder lifted, trunk flexed forward and backward incessantly, and the limbs distorted. The patient showed postural tremor of the hands and slightly unsteady gait. Her body was retroflexed, and the right arm was stiff. The symptoms were aggravated in resting state and alleviated when dancing or walking backwards. Previous laboratory test showed normal ceruloplasmina and acanthosis-missing. And DYT-1 gene was negative. She was diagnosed with tardive dystonia. Treatment The operation was performed on July 15, 2003. In brief, the patient's head was fixed with a leksell stereotactic frame and received MRI (3.0 Tesla) examination before the surgery. MRI showed no obvious pathological change in the bilateral basal ganglia. The image was then transferred to the Surgiplan Workstation (Elekta, Sweden) in the operation room. The STN was then chosen as the target for stimulation, which was 2 mm posterior to the midcommissural point, 13 mm lateral to the midplane of the third ventricle and 4 mm below the intercommissural line. The anatomical boundary of STN was clearly visible on FLAIR and T2-weighted images and the coordinates were calculated automatically by surgiplan system. The patient was operated under local anesthesia. Intraoperative microelectrode recording was used to verify the firing pattern of the STN. The length of the STN was 7 mm on the left and 4 mm on the right side. The signals demonstrated a high frequency and high amplitude firing pattern with a high background noise. The electrical activity was rhythmic and “tremor cells” could be detected. Quadripolor electrodes (Medtronic Inc., electrode 3389, USA) were implanted bilaterally in the STN. During the operation, the patient had a feeling of muscular relaxation with tentative stimulation in the bilateral STN. Physical examination showed that muscle tension decreased significantly, and the patient could open and close her mouth normally. Her postural tremor was alleviated. There was no obvious side effect such as extremities numbness and eye movement disturbances. No complication occurred after the surgery. Six days after the operation, the patient was given general anesthesia. A pulse generator (IPG, Medtronic Inc., kinetra, USA) was implanted subcutaneously in the right subclavicular region. The patient was discharged one week later. Outcomes The stimulator was turned on 1 month later. The parameters was programmed for several times and the current parameter was as follows: voltage, left side 3.0 V, right side 1.5 V; pulse width, 90 μs; and frequency, 185 Hz (monopolar stimulation). Clinical manifestations of the patient, UDRS and BFMS scale were assessed before, and in one and three months after the surgery to evaluate the efficacy of the bilateral STN-DBS. After the stimulator was turned on, the symptoms of the patient improved gradually. After 3 months of follow-up, she recovered incredibly well. Her facial expression was natural without blink and torsion. Her speech was clear and fluent, she could close her mouth easily. Her neck did not twist any more. There was neither abnormal posture nor repetitive movement of the extremities. She could totally attend to herself. The remaining symptoms included slight elevation of her right shoulder and slight postural tremor. Physical examination showed a slight increase of muscle tension. Tendon reflexes were hyperactive. The medicine taken were tetrabenazine 75 mg/d and tioridazina cloridrato 75 mg/d. The UDRS score was 94, 38 and 7.5; and BFMS score was 98.5, 42.5 and 8, respectively, before, and in one and three months after the surgery. The improvement was more than 90% after 3 months of follow-up. The improvement was kept stable for at least 2.5 years. The patient was in perfect health according to the telephone visit in January, 2006. She could take care of herself without attendance. There was neither involuntary movement of the limbs nor abnormal posture. Her speech was clear. The only symptom was slight stiffness in her right arm. The parameter of the stimulator has not been reprogrammed. DISCUSSION Dystonia may occur as a primary condition (idiopathic or primary dystonia) that is familial or occurs without a family history, which may results from certain environmental factors or “insults” that affect the brain (secondary or symptomatic dystonia). In addition, spinal cord or peripheral injuries may also be responsible for secondary dystonia. It may be associated with certain nondegenerative, neurochemical disorders (known as “dystonia-plus syndromes”) that are characterized by neurologic features, such as parkinsonism or myoclonus. It is also a primary feature of certain, usually hereditary, neurodegenerative disorders (so-called “heredodegenerative dystonias”). Unlike trauma, inflammation and toxicity induced secondary dystonia, tardive dystonia is a special type of secondary dystonia due to exposure to certain medications, most commonly neuroleptics. At first, the disease was regarded as a subtype of tardive dyskinesia. In 1982, it was first recognized and described by Burke1 as a specific clinical syndrome distinguishable from tardive dyskinesia. The diagnostic criteria include: (1) Chronic dystonia must be present. (2) If other involuntary movements are present, dystonia is the primary affecting syndrome. (3) Dystonia develops during or within 2 months of neuroleptic drug withdrawal. (4) Other causes of secondary dystonia have been ruled out. (5) There is no family history of dystonia. In our case, the patient had taken haloperidol before she got the symptoms of abnormal movement and postures in her right upper limbs. The symptoms extended to the face, neck, trunk and extremities and deteriorated progressively. Combined with past history, family history and laboratory tests, her disease conformed to the above criteria and could be diagnosed as tardive dystonia easily. It is now believed that tardive dyskinesia as a consequence of exposure to neuleptics has an average prevalence of 15%-20% and may coexist with persistent tardive dystonia in 1%-4%.2 Because nearly 1% of the world's population is known to suffer from schizophrenia and neuroleptics are widely used to treat the disorder, the incidence of tardive dystonia may be expected to be substantial. As to the pathogenesis of tardive dystonia, most believe that it is related to the hypersensitivity of dopamine receptor in striatum. Trugman proposed that repetitive stimulation of the D1 receptor by endogenous dopamine resulting in sensitization of the D1 mediated striatal output in the presence of D2 receptor blockage is a fundamental mechanism that mediates tardive dyskinesia and dystonia.3 The hypothesis that sensitization of the D1-mediated striatal output is involved in the pathogenesis is consistent with both the delayed onset of dyskinesia after neuroleptic initiation and the persistence of symptoms after neuroleptic withdrawal. The model predicts that D1 antagonist combined with stimulation of the D2 receptor will be beneficial in the treatment of tardive dystonia, which is in accordance with the observed moderate amelioration of these dyskinesias using bromocriptine, a partial D1 antagonist and D2 agonist. Nonetheless, there are still controversies about the hypothesis. The facts that some patients do not show an increase in the dopamine metabolic products and the uncertainty of dopamine antagonist indicate that the underlying mechanisms might be much more complicated. The persistence and irreversibility of tardive dystonia was ascertained by Kiriakakis.4 He followed up 107 patients with tardive dystonia and found that only 14% of the patients alleviated without further intervention. Medications included anticholinergics, dopamine antagonists, GABA agonists. Some of the patients received botulinum toxin injection, mainly in focal dystonia. But none of the above medicines were effective enough to control dystonia in all the patients satisfactorily. In the past, myectomy (myotomy), ramisectomy (rhizotomy) and peripheral denervation were the surgical methods to treat dystonia. These procedures are rarely performed today due to their side effects. During the past decade, stereotactic surgery, including ablation surgery and neurostimulation, has been resuscitating in the treatment of movement disorders such as Parkinson's disease, as well as dystonia. The results of ablative thalamic surgery were variable, with about 50% of patients demonstrating some postoperative improvement.5 Pallidotomy has been reported to be effective in various dystonic disorders, including generalized dystonia, segmental dystonia and hemidystonia, yielding about 50% to 80% improvement in several studies.5–7 Now DBS has replaced ablative surgery in some neurosurgical centers. Katayama8 performed bilateral globus pallidus internus (GPi) DBS in 5 primary dystonia patients, BFMS before and after surgery was between 18 to 62, and 4 to 23, respectively. The improvement was between 51% to 92%. Trottenberg9 performed bilateral stereotactic electrode placement in ventral intermediate nucleus of thalamus (VIM) and GPi. After bilateral stimulation of the GPi, the patient showed a clear and stable improvement of the painful dystonic syndrome within hours. Stimulation of VIM did not improve the hyperkinetic movements and simultaneous stimulation of both GPi and VIM did not show any additional benefit. Although there is not a unanimous conclusion that DBS is better than ablation surgery in the treatment of dystonia, more and more neurosurgeons prefer DBS to ablation, which is likely the case in Parkinson's disease. The efficacy, safety and reversibility are all advantages of DBS. Krause10 reported that the disadvantage of DBS is expense. Most patients with dystonia need much higher voltage than Parkinsonian patients, thus the exhaustion of battery would be much quicker. However, this conclusion was drawn when GPi was chosen as a target. As to the target selected, GPi seems to be a better one than VIM, while no comparison between GPi and STN was reported. In this patient with tardive dystonia, we performed bilateral STN-DBS and got perfect outcome after 3 months of follow-up. The amelioration of symptoms was more than 90%. BFMS and UDRS score improved significantly and this improvement was progressive and continuous. In most of other reports of DBS surgery in dystonia with GPi as the target, the results were variable, although most believed that tardive dystonia was a good candidate for GPi-DBS surgery.9,11–13 Though we need more cases to verify our conclusion, we now believe that STN might also be a good target for tardive dystonia. The mechanism of STN-DBS should be similar as that of GPi-DBS, in that STN is an upstream nucleus in the basal ganglia motor circuit. In the hypothesis of Trugman, D1-mediated striatal output is preferentially directed to the GPi and substantia nigra pars reticulata (SNr), and D2-mediated output is preferentially directed to the external segment of the globus pallidus.3 Stimulation of STN can both modulate activities of GPi and SNr, making it a more suitable target theoretically. In Parkinson's disease, GPi was firstly chosen before STN was taken as an alternative and believed to be the ideal target for the disease. Would this also happen in the surgical treatment of dystonia? More comparison is needed to evaluate the efficacy of the two targets. As to the parameters selected, since the symptoms in the right limbs of our patient were more severe than those in the left, the voltage on the right side was also higher. However, their voltages were not significantly higher than that of most Parkinsonian patients'. Unlike GPi, the battery exhaustion would be only slightly quicker. This might also be an advantage for STN-DBS in the treatment of tardive dystonia since STN is much smaller a nucleus than GPi.