Shirley Triche

Neuronal activity in the basal ganglia in patients with generalized dystonia and hemiballismus

Microelectrode recording was performed in the basal ganglia of 3 patients with generalized dystonia and 1 patient with hemiballismus secondary to a brainstem hemorrhage. Neuronal activity was recorded from the internal and external segments of the globus pallidus and assessed for mean discharge rate and pattern of spontaneous activity. The responses of neurons in the internal segment of the globus pallidus to passive and active movements were also evaluated. Mean discharge rates of neurons in both segments of the pallidum in patients with dystonia and the patient with hemiballismus were considerably lower than those reported for patients with idiopathic Parkinsons disease. In addition, the pattern of spontaneous neuronal activity was highly irregular, occurring in intermittent grouped discharges separated by periods of pauses. Although receptive fields in the dystonia patients were widened and less specific than those reported in normal monkeys, neuronal responses to movement were uncommon in the hemiballismus patient. Before surgery, patients with dystonia experienced abnormal posturing and involuntary movements. Coactivation of agonist–antagonist muscle groups was observed both at rest and during the performance of simple movements. After pallidotomy there was a significant reduction in the involuntary movement associated with these disorders and a more normal pattern of electromyographic activity during rest and movement. Given the improvement in dystonic and hemiballistic movements in these patients after ablation of the sensorimotor portion of the internal segment of the globus pallidus, we suggest that pallidotomy can be an effective treatment for patients with dystonia and also for patients with medically intractable hemiballismus. Based on the finding of decreased neuronal discharge rates in pallidal neurons, we propose that physiologically dystonia most closely resembles a hyperkinetic movement disorder. A model for dystonia is proposed that incorporates the observed changes in the rate and pattern of neuronal activity in the pallidum with data from neuroimaging with positron emission tomography and 2‐deoxyglucose studies. Ann Neurol 1999;46:22–35

Prevalence of vitamin d insufficiency in patients with Parkinson disease and Alzheimer disease.

BACKGROUND A role for vitamin D deficiency in Parkinson disease (PD) has recently been proposed. OBJECTIVE To compare the prevalence of vitamin D deficiency in a research database cohort of patients with PD with the prevalence in age-matched healthy controls and patients with Alzheimer disease (AD). DESIGN Survey study and blinded comparison of plasma 25-hydroxyvitamin D (25[OH]D) concentrations of stored samples in a clinical research database at Emory University School of Medicine. SETTING Referral center (PD and AD patients), primary care clinics, and community setting (controls). PARTICIPANTS Participants were recruited into the study between May 1992 and March 2007. Every fifth consecutively enrolled PD patient was selected from the clinical research database. Unrelated AD (n = 97) and control (n = 99) participants were randomly selected from the database after matching for age, sex, race, APOE genotype, and geographic location. MAIN OUTCOME MEASURES Prevalence of suboptimal vitamin D and mean 25(OH)D concentrations. RESULTS Significantly more patients with PD (55%) had insufficient vitamin D than did controls (36%) or patients with AD (41%; P = .02, chi(2)test). The mean (SD) 25(OH)D concentration in the PD cohort was significantly lower than in the AD and control cohorts (31.9 [13.6] ng/mL vs 34.8 [15.4] ng/mL and 37.0 [14.5] ng/mL, respectively; P = .03). CONCLUSIONS This report of 25(OH)D concentrations in a predominantly white PD cohort demonstrates a significantly higher prevalence of hypovitaminosis in PD vs both healthy controls and patients with AD. These data support a possible role of vitamin D insufficiency in PD. Further studies are needed to determine the factors contributing to these differences and elucidate the potential role of vitamin D in pathogenesis and clinical course of PD.

Cognitive impairments in advanced PD without dementia

Objective: To determine the nature and frequency of cognitive impairments in nondemented patients with advanced PD and their relationship to other variables potentially predictive of neuropsychological performance. Methods: The neuropsychological performance of nondemented, nondepressed patients with idiopathic PD (n = 61) was quantified with respect to clinically available normative data. The relationship of neuropsychological measures to motor symptoms, age, years of education, disease duration, age at disease onset, disease deterioration rate, and dopaminergic therapy was assessed. Results: Impairment was most frequent on measures sensitive to frontal lobe function (67% on Wisconsin Card Sorting Test number of categories, 30% on letter fluency, 30% on verbal learning). Poorer performance on multiple neuropsychological measures was related to greater overall motor abnormality (total Unified Parkinson’s Disease Rating Scale score), increased bradykinesia on medication, older age, longer disease duration, and reduced education. Conclusions: Even in the absence of dementia or depression, patients with advanced PD are likely to show clinically significant impairments on neuropsychological measures sensitive to changes in dorsolateral prefrontal regions participating in cognitive basal ganglia-thalamocortical circuits.

Neuropsychological and psychiatric sequelae of pallidotomy for PD: Clinical trial findings

ObjectiveTo evaluate the neuropsychological and psychiatric sequelae of unilateral posterior pallidotomy for treatment of PD. MethodsPatients with idiopathic PD completed baseline and 3- and 6-month assessments after random assignment to an immediate surgery (n = 17) or medical management (n = 16) group. ResultsCompared with the medical management group, the immediate surgery group with single lesions centered on the posterior internal pallidum showed superior naming and response inhibition, better verbal recall at 6 months, but greater distractibility, a tendency toward lower phonemic fluency, and a transient (3 months’ only) semantic fluency deficit. The group with left lesions had more neuropsychological deficits than the group with right lesions or the medical management group, although these occurred mainly at 3 (but not 6) months. At 6 months, the patients with left lesions showed better verbal memory retention than the patients with right lesions. On most measures, the pattern of individual clinical change did not differ as a function of surgery or lesion laterality, with the exception of a higher frequency of decline in phonemic fluency in the patients with left lesions at 6 months. Although psychiatric status did not change overall, a history of depression tended to increase the risk of a depressive episode following surgery. ConclusionsWell-targeted, uncomplicated, unilateral pallidotomy does not produce overall neuropsychological or psychiatric change, although there are subtle changes on specific measures sensitive to frontal lobe function.

Temporal profile of improvement of tardive dystonia after globus pallidus deep brain stimulation.

BACKGROUND Several case reports and small series have indicated that tardive dystonia is responsive to globus pallidus deep brain stimulation. Whether different subtypes or distributions of tardive dystonia are associated with different outcomes remains unknown. METHODS We assessed the outcomes and temporal profile of improvement of eight tardive dystonia patients who underwent globus pallidus deep brain stimulation over the past six years through record review. Due to the retrospective nature of this study, it was not blinded or placebo controlled. RESULTS Consistent with previous studies, deep brain stimulation improved the overall the Burke-Fahn-Marsden motor scores by 85.1 ± 13.5%. The distributions with best responses in descending order were upper face, lower face, larynx/pharynx, limbs, trunk, and neck. Patients with prominent cervical dystonia demonstrated improvement in the Toronto Western Spasmodic Torticollis Rating Scale but improvements took several months. In four patients the effects of deep brain stimulation on improvement in Burke Fahn Marsden score was rapid, while in four cases there was partial rapid response of neck and trunk dystonia followed by was gradual resolution of residual symptoms over 48 months. CONCLUSION Our retrospective analysis shows excellent resolution of tardive dystonia after globus pallidus deep brain stimulation. We found instantaneous response, except with neck and trunk dystonia where partial recovery was followed by further resolution at slower rate. Such outcome is encouraging for using deep brain stimulation in treatment of tardive dystonia.