Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0233565 (bradykinesia)
 2,352 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present the case of a 51-year-old female who had a four-year history of Parkinson's disease with severe "on-off' and disabling progression of symptoms on chronic levodopa therapy. After obtaining FDA approval, we implanted a Medtronic deep brain stimulation lead stereotactically into the right anterior pallidum contralateral to her most symptomatologic side. Intra-operative stimulation trials at 100 Hz caused reproducible reversal of akinetic symptoms and simultaneous microelectrode recording of the posteroventral pallidum revealed decreased neural activity during anterior pallidal stimulation. The patient was evaluated pre-operatively and postoperatively using the Hoehn and Yahr Staging Scale, the Unified Parkinson's Disease Rating Scale (UPDRS), videotape, and a computerized data glove. Six months after implantation, the total UPDRS score was decreased from 68 to 8 and Hoehn and Yahr Staging improved from 3.0 to 1.5 during periods of chronic high frequency stimulation. Dramatic improvements in tremor, dystonia, bradykinesia, and akinesia were noted within seconds of stimulator activation and were also objectively measured using a computerized data glove. This case reveals the potential for therapeutic pallidal stimulation for Parkinson's akinetic symptomatology.
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PMID:Chronic anterior pallidal stimulation for Parkinson's disease. 874 80

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder that is generally considered to be nonfamilial. We report a brother and sister with clinical and pathologic findings characteristic of PSP. Both developed parkinsonism in the eighth decade of life and within 5 years exhibited severe postural instability, bradykinesia, rigidity, dystonia, dysarthria, dysphagia, urinary incontinence, pseudobulbar palsy, and supranuclear oculomotor dysfunction but no tremor. Neither responded to levodopa and/or carbidopa. Their mother and, possibly, maternal grandfather reportedly suffered from a parkinsonian syndrome. Essential tremor occurred in the siblings' father and in two of the brother's three children. Autopsy in the brother at age 81 years and sister at age 79 years revealed changes typical of PSP with atrophy and neurofibrillary tangles in the globus pallidus, subthalamic nucleus, and rostral tegmental brainstem. No Lewy bodies were present. These cases are the first pair of relatives reported with autopsy confirmation of PSP in both and raise the question of genetic predisposition to PSP.
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PMID:Autopsy-proven progressive supranuclear palsy in two siblings. 878 66

SCA1 is a dominant spinocerebellar ataxia (SCA) and a multi-systemic syndrome caused by abnormal expansion of unstable CAG repeat in a novel gene located on chromosome 6p22-p23. We clinically studied 35 Japanese SCA1 patients who were assumed to have come from a common origin. The age at onset ranged from 15-63 years, and significantly correlated with CAG repeat units of mutant alleles. Ataxia was the initial symptom, and the majority of patients had a similar history of signs and symptoms. Nystagmus was at first minimal, later attenuated, and a slow saccade followed. Limb tendon reflexes were mostly hyperactive and depressed with the development of diffuse amyotrophy. The cardinal feature was ataxia-hyperreflexia-late slow saccade syndrome with terminal amyotrophy. Although the phenotype of SCA1 overlaps with those of other dominant SCAs, some facets of the neurological events differ from either SCA2 with ataxia-hyporeflexia-slow saccade syndrome, or early-onset Machado-Joseph disease with dystonia-bradykinesia-spasticity syndrome.
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PMID:Clinical features and natural history of spinocerebellar ataxia type 1. 882 76

Twenty-eight centers completed a survey about their current practice of pallidotomy. This sample represents a non-exhaustive survey of the current practice of pallidotomy in North America and is not a study of outcomes. 1015 patients underwent 1219 pallidotomies: 811 (80%) unilateral, 72 (7%) staged bilateral, and 132 (13%) simultaneous bilateral. Pallidotomy has long been an accepted procedure and the indications for this surgery, in the opinion of the responding centers, were rated on a scale of 1 (poor) to 4 (excellent) and demonstrated dyskinesia as the best indication (median = 4); on-off fluctuations, dystonia, rigidity, and bradykinesia as good indications (median = 3); and freezing, tremor and gait disturbance as fair indications (median = 2). Most centers used MRI alone (50%) or in combination with CT scan (n = 6) or ventriculopathy (n = 5) to localize the target. The median values of pallidal coordinates were: 2 mm anterior to the midcommissural point 21 mm lateral to the midsagittal plane and 5 mm below the intercommissural line. Microrecording was performed by half of the centers (n = 14) and half of the remaining centers were considering starting it (n = 7). Main criteria used to define the target included the firing pattern of spontaneous neuronal discharges (n = 13) and the response to joint movement (n = 10). Most centers performed motor (n = 26) and visual (n = 23) macrostimulation. Twenty four centers performed test lesions using median values of 55 degrees C temperatures for 30 s. Final lesions consisted of 3 permanent lesions placed 2 mm apart, each lesion created with median values of 75 degrees C temperatures for 1 minute. Median hospital stay was 2 days.
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PMID:Pallidotomy: a survey of current practice in North America. 888 Jul 89

Rapid-onset dystonia-parkinsonism (RDP), first described in a large Midwestern family, is now reported in a second, apparently unrelated, family in which four individuals have this same syndrome. All four developed sudden onset of dysarthria, dysphagia, severe dystonic spasms, bradykinesia, and postural instability over less than 1 hour to a few days. Three of the four had stable limb dystonia for several years preceding the onset of combined dystonia-parkinsonism. Treatment with levodopa/carbidopa provided little benefit. We propose diagnostic criteria for RDP and further define the spectrum of this unusual disease.
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PMID:Rapid-onset dystonia-parkinsonism in a second family. 910 1

Impairment in energy metabolism is thought to be involved in the aetiology of Huntington's disease. In line with this hypothesis, chronic systemic administration of the mitochondrial toxin 3-nitropropionic acid to rats and monkeys produces selective striatal lesions similar to Huntington's disease. The present study examined whether rats treated with varying regimen of 3-nitropropionic acid could present motor abnormalities reminiscent of Huntington's disease symptomatology, correlated with Huntington's disease specific striatal symptomatology. Subacute 3-nitropropionic acid treatment (15 mg/kg per day intraperitoneally for 10 days) produced dramatic motor symptoms associated with extensive neuronal loss and gliosis in the lateral striatum as well as severe hippocampal degeneration in 50% of the cases. In contrast, chronic 3-nitropropionic acid treatment (10 mg/kg per day subcutaneously for one month) led to more subtle excitotoxic-like lesions, selective for the dorsolateral striatum and more closely resembling Huntington's disease striatal pathology. Animals with these Huntington's disease-like lesions showed spontaneous motor symptoms including mild dystonia, bradykinesia and gait abnormalities, which were barely detectable on visual inspection but could be readily identified and quantified by computerized video analysis. In these chronic animals, the degree of striatal neuronal loss was significantly correlated with the severity of spontaneous motor abnormalities, as is the case in Huntington's disease. The present study demonstrates that chronic low-dose 3-nitropropionic acid treatment in rats results in a valuable model of both the histological features and motor deficits which occur in Huntington's disease. Despite the interanimal variability in terms of response to 3-nitropropionic acid treatment, this rat model may be particularly useful for evaluating the functional benefits of new therapeutic strategies for Huntington's disease, particularly those aiming to reduce the severity of motor symptoms.
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PMID:Quantifiable bradykinesia, gait abnormalities and Huntington's disease-like striatal lesions in rats chronically treated with 3-nitropropionic acid. 917 64

Stereotactic surgery for movement disorders is currently undergoing a re-evaluation. A new understanding of the pathophysiology makes the surgical lesion a logical step for the aleviation of both hyperkinetic symptoms such as tremor and hypokinetic symptoms like bradykinesia. Advances in imaging and electrophysiological control render these procedures more accurate and safer. Indications are medically refractory, Parkinsonean tremor, essential tremor, cerebellar tremor, bradykinesia and L-Dopa induced dyskinesis. The standard procedure is ablative surgery, i.e. thalamotomy for tremors and pallidotomy for bradykinesia, dystonia and L-Dopa induced dyskinesias. Deep brain stimulation is a novel alternative for selected patients which is currently evaluated. Neural transplantation of autologus, fetal or genetically manipulated cell suspensions into the striatum for the time being is experimental.
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PMID:[Stereotactic treatment of movement disorders]. 931 81

The pathophysiology of dystonia is unclear, but several clues implicate striatal dopamine dysfunction. In contrast, the causal relationship between striatal dopamine deficiency and parkinsonism is well defined. We now suggest that parkinsonism or dystonia may occur following striatal dopamine deficiency. Baboons treated with intracarotid 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) developed transient hemidystonia prior to hemiparkinsonism. The day after MPTP treatment, most animals had spontaneous ipsilateral turning. Within a few days, all developed contralateral hemidystonia, with the arm and leg extended and externally rotated. This transient dystonia preceded hemiparkinsonism with flexed posture, bradykinesia, and postural tremor that persisted for up to 1.5 years. Dystonia corresponded temporally with a decreased striatal dopamine content and a transient decrease in D2-like receptor number. The time course of dystonia and parkinsonism is analogous to lower limb dystonia as the first, frequently transient, symptom of Parkinson's disease in humans. The association of striatal dopamine deficiency with dystonia and parkinsonism implies that other factors influence clinical manifestations.
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PMID:MPTP induces dystonia and parkinsonism. Clues to the pathophysiology of dystonia. 937 34

To evaluate the clinical characteristics of Machado-Joseph disease (MJD) with reference to CAG repeat length and disease duration, we analyzed neurologic findings in 108 patients from 84 families. The majority of MJD patients presented with an ataxic gait as the initial symptom. Dysarthria and nystagmus were observed from an early stage. Bulging eyes, muscle atrophy and bradykinesia developed later. Patients with a shorter CAG repeat length or later onset had more frequent involvement of proprioceptive sensory deficit. Incidence of abnormal reflexes, tones, and proprioceptive sensation was not associated with disease duration, but with CAG repeat length. Based on these results, we propose a new clinical classification: type A (juvenile type), with hyperreflexia and dystonia, but without a proprioceptive sensory deficit; type C (adult type), with hyporeflexia and a proprioceptive sensory deficit, but without dystonia; and type B (intermediate type), the remaining patients with a mixed presentation.
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PMID:CAG repeat length and disease duration in Machado-Joseph disease: a new clinical classification. 941 38

Wilson's disease is an autosomal-recessive inherited disorder that results in predominantly hepatic and neurologic manifestations. Neurologic abnormalities include tremor, ataxia, bradykinesia, rigidity, chorea, and dystonia. We report the clinical, radiologic, and serial FDG PET findings in a 20-year-old woman who presented with an asymmetric upper limb tremor caused by Wilson's disease. Reduced striatal and cerebral cortical glucose metabolism was demonstrated on a FDG PET study performed before the commencement of D-penicillamine therapy. After 6 months of treatment, the patient had shown only minimal clinical improvement, despite an increase in striatal and cerebral cortical glucose metabolism on a repeat FDG PET study. After 14 months of treatment, however, a moderate clinical improvement was noted and there was further increase in glucose metabolism on FDG PET.
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PMID:Pretreatment and posttreatment positron emission tomographic scan imaging in a 20-year-old patient with Wilson's disease. 945 44


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