Cases reported "Dyskinesia, Drug-Induced"

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1/9. From off-period dystonia to peak-dose chorea. The clinical spectrum of varying subthalamic nucleus activity.

    The effect of chronic bilateral high-frequency stimulation of the subthalamic nucleus (STN) on levodopa-induced dyskinaesias was investigated in eight patients with fluctuating Parkinson's disease complicated by functionally disabling off-period dystonia. All of the patients also had severe diphasic and peak-dose chorea, so that it was possible to study the effect of high-frequency stimulation on the different types of levodopa-induced dyskinaesias. Off-period fixed dystonia was reduced by 90% and off-period pain by 66%. After acute levodopa challenge, high-frequency stimulation of the STN reduced diphasic mobile dystonia by 50% and peak-dose choreic dyskinaesias by 30%. The effect of bilateral high-frequency stimulation of the STN on the Unified Parkinson's Disease Rating Scale motor score had the same magnitude as the preoperative effect of levodopa. This allowed the levodopa dose to be reduced by 47%. The combination of reduced medication and continuous high-frequency stimulation of the STN reduced the duration of on-period diphasic and peak-dose dyskinaesias by 52% and the intensity by 68%. Acute high-frequency stimulation of the STN mimics an acute levodopa challenge, concerning both parkinsonism and dyskinaesias, and suppresses off-period dystonia. Increasing the voltage can induce repetitive dystonic dyskinaesias, mimicking diphasic levodopa-induced dyskinaesias. A further increase in voltage leads to a shift from a diphasic-pattern dystonia to a peak-dose pattern choreodystonia. Chronic high-frequency stimulation of the STN also mimics the benefit of levodopa on parkinsonism and improves all kinds of levodopa-induced dyskinaesias to varying degrees. Off-period dystonia, associated with neuronal hyperactivity in the STN is directly affected by stimulation and disappears immediately. The effect of chronic high-frequency stimulation of the STN on diphasic and peak-dose dyskinaesias is more complex and is related directly to the functional inhibition of the STN and indirectly to the replacement of the pulsatile dopaminergic stimulation by continuous functional inhibition of the STN. Chronic high-frequency stimulation of the STN allows a very gradual increase in stimulation parameters with increasing beneficial effect on parkinsonism while reducing the threshold for the elicitation of stimulation-induced dyskinaesias. In parallel with improvement of parkinsonism, the levodopa dose can be gradually decreased. As diphasic dystonic dyskinaesias are improved to a greater degree than peak-dose dyskinaesias, both direct and indirect mechanisms may be involved. Peak-dose choreatic dyskinaesias, associated with little evidence of parkinsonism and thus with low neuronal activity in the STN, are improved, mostly indirectly. Fixed off-period dystonia, mobile diphasic dystonia and peak-dose choreodystonia seem to represent a continuous clinical spectrum reflecting a continuous spectrum of underlying activity patterns of STN neurons.
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2/9. Lesioning the thalamus for dyskinesia.

    Recent advances on understanding the pallidothalamic relation lead us to perform Vim-Vo thalamotomy (combined thalamic lesion in ventralis intermedius nucleus and ventralis oralis nucleus) for cases with dyskinesia. In our recent series of thalamotomies, there are 12 cases of dyskinesia caused by various etiologies. Therefore the clinical manifestation of the involuntary movement was different in each case, including, more or less, some elements of irregular involuntary hyperkinetic movement. Stereotactic operation was performed using Leksell's apparatus aided by Surgiplan and MRI. The Vim nucleus was identified by physiological study using microelectrodes. High background activity and kinesthetic neurons are reliable indicators of Vim nucleus (but only for the lateral part). Then, selective coagulation was made by dual coagulation needles. Since the Vo nucleus is located just rostral to the Vim nucleus, the coagulation needle was turned toward the anterior part to partly cover the Vo nucleus. Thus, selective Vim-Vo thalamotomy was shown to be quite successful for the treatment of dyskinesia.
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3/9. Parkinson's disease, subthalamic stimulation, and selection of candidates: a pathological study.

    We report on a patient with Parkinson's disease (PD) who was moderately improved by stimulation of the subthalamic nucleus (STN) and died 2 years after electrode implantation. After neurosurgery, symptoms that had responded to levodopa treatment preoperatively continued to improve. Postural instability, dysarthria, and cognitive impairment continued to worsen, despite STN stimulation and levodopa treatment. Postmortem examination of the brain confirmed the diagnosis of PD and showed that the electrodes had been correctly positioned within the STN. The failure of STN stimulation in this patient confirms the importance of screening and excluding patients from surgery with evolving parkinsonian axial symptoms or cognitive impairment.
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4/9. Immediate and sustained relief of levodopa-induced dyskinesias after dorsal relocation of a deep brain stimulation lead. Case report.

    The authors demonstrate that high-frequency electrical stimulation dorsal to the subthalamic nucleus (STN) can directly suppress levodopa-induced dyskinesias. This 63-year-old woman with idiopathic parkinson disease underwent surgery for placement of bilateral subthalamic deep brain stimulation (DBS) electrodes to control progressive rigidity, motor fluctuations, and levodopa-induced dyskinesias. The model 3389 DBS leads were implanted with microelectrode guidance. magnetic resonance imaging confirmed proper placement of the leads. Postoperatively the patient exhibited improvement in all of her parkinsonian symptoms; however, her right leg dyskinesias had not improved. Based on their previous experiences treating levodopa-induced dyskinesias with subthalamic stimulation through the more dorsally located contacts of the model 3387 lead, the authors withdrew the implanted 3389 lead 3 mm. Following relocation of the lead they were able to suppress the right leg dyskinesias by using the most dorsal contacts. The patient's dopaminergic medication intake increased slightly. These findings indicate that electrical stimulation dorsal to the STN can directly suppress levodopa-induced dyskinesias independent of dopaminergic medication changes. The 3389 lead may provide inadequate coverage of the subthalamic region for some patients.
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5/9. Chronic bilateral subthalamic deep brain stimulation in a patient with homozygous deletion in the parkin gene.

    Chronic subthalamic nucleus deep brain stimulation (STN-DBS) is an efficacious treatment for idiopathic Parkinson's disease (PD) that cannot be further improved by medical therapy. We present a case of an individual with juvenile parkinsonism caused by homozygous deletion of exon 3 in the parkin gene with disabling long-term side-effects from levodopa who underwent bilateral STN neuromodulation. Parkin-linked parkinsonism may show clinical features different from sporadic PD, yet it shares levodopa responsiveness. Because levodopa responsiveness is a predictor of STN-DBS efficacy, we argued that this kind of surgical approach might be efficacious in hereditary parkin-linked juvenile parkinsonism. We evaluated clinical and functional assessment before and 12 months after surgery. The results showed that the Unified parkinson disease Rating Scales Motor score improved by 84% in our patient, the levodopa equivalent daily dose medication (LEDD) was reduced by 66%, and, finally, disabling and severe dyskinesias disappeared.
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6/9. A blessing in disguise: resolution of tardive dyskinesia with development of cervical myelitis.

    Tardive dyskinesia (TD), which is frequently seen in patients treated with dopamine receptor blocking agents, is difficult to manage. We report on a young Chinese man with bipolar disorder who developed TD after haloperidol treatment, involving the trunk, limbs, and orofacial area. TD persisted despite switching to atypical antipsychotic agents and treatment with valproate, benzodiazepines, and tetrabenazine. Resolution only occurred years later when he developed quadriplegia arising from infective myelitis of the cervical cord (C4-5). He had concomitant vertebral osteomyelitis, which was successfully treated with intravenous antibiotics. With intensive rehabilitation, he recovered the use of his limbs, but had no recurrence of TD. We attribute the resolution of orofacial dyskinesias with a cervical lesion to the interconnections between the orofacial area and cervical spine via the trigeminal nucleus (which has fibers descending as far caudally as C6), as well as to resetting of cortical maps.
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7/9. Tardive dyskinesia with inflated neurons of the cerebellar dentate nucleus. Case reports and morphometric study.

    Four autopsied cases of tardive dyskinesia manifesting oral hyperkinesia revealed markedly inflated neurons in the cerebellar dentate nucleus (DN), which had not been described previously. The inflation of the neurons was proved to be statistically significant (P less than 0.01) by morphometric study. The nuclei were usually situated in the central portion of the cytoplasm. This inflated change was different from both central chromatolysis and grumose degeneration of the DN, typically observed in progressive supranuclear palsy and dentatorubropallidolysian atrophy, and seemed to be easy to miss without careful observation, since neuronal loss and gliosis were very mild in the DN. Among a few autopsied cases of tardive dyskinesia reported previously, degeneration of the DN was described in only two. It is believed, however, that the inflated neurons of the DN may not be so rare and may be related to the occurrence of some involuntary hyperkinesia, especially oral hyperkinesia following some neurotoxic disorders and/or neuroleptic medications.
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8/9. Chronic thalamic stimulation improves tremor and levodopa induced dyskinesias in Parkinson's disease.

    Chronic thalamic stimulation was performed in 10 Parkinsonian patients with disabling tremor and poor response to drug therapy. During the stereotactic procedure, an electrode was introduced in the ventralis intermediate nucleus of the thalamus. Test stimulation was performed during the intra-operative procedure and a few days after surgery using an external stimulator. When tremor was obviously reduced by thalamic stimulation, an internal stimulator was implanted under the clavicle. tremor was initially suppressed in all cases and reappeared whenever stimulation was stopped. patients were followed for 22 to 34 months. tremor was controlled in eight cases but reappeared after three months in two cases. levodopa induced dyskinesias were observed before electrode implantation in 5 cases. They consisted of peak-dose choreic or ballistic dyskinesias in 4 cases and biphasic dystonic dyskinesias in 3 cases. Peak-dose dyskinesias were greatly improved or suppressed in all cases. Biphasic dyskinesias were improved in 2 cases. Thalamic stimulation was well tolerated. Mild dystonic hand posture related to the deep brain stimulation was observed in one case. No neuropsychological side-effects were noted. Thalamic stimulation could prove to be an adequate treatment for resistant tremor and levodopa induced dyskinesias.
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9/9. High-frequency stimulation of the globus pallidus internalis in Parkinson's disease: a study of seven cases.

    The effectiveness of ventroposterolateral pallidotomy in the treatment of akinesia and rigidity is not a new discovery and agrees with recent investigations into the pathogenesis of Parkinson's disease, which highlight the role played by the unbridled activity of the subthalamic nucleus (STN) and the consequent overactivity of the globus pallidus internalis (GPi). Because high-frequency stimulation can reversibly incapacitate a nerve structure, we applied stimulation to the same target. Seven patients suffering from severe Parkinson's disease (Stages III-V on the Hoehn and Yahr scale) and, particularly, bradykinesia, rigidity, and levodopa-induced dyskinesias underwent unilateral electrode implantation in the posteroventral GPi. Follow-up evaluation using the regular Unified Parkinson's Disease Rating Scale has been conducted for 1 year in all seven patients, 2 years in five of them, and 3 years in one. In all cases high-frequency stimulation has alleviated akinesia and rigidity and has generally improved gait and speech disturbances. In some cases tremor was attenuated. In a similar manner, the authors observed a marked diminution in levodopa-induced dyskinesias. This could be an excellent primary therapy for younger patients exhibiting severe bradykinesia, rigidity, and levodopa-induced dyskinesias, which would allow therapists to keep ventroposterolateral pallidotomy in reserve as a second weapon.
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