[Use of apomorphine in the treatment of Parkinson's disease].
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Biomedical subjects
Publications and source records attributed to P Pollak.
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The usefulness of high-frequency stimulation of the ventral intermediate nucleus (Vim) as the first neurosurgical procedure in disabling tremor was assessed in 26 patients with Parkinson's disease and 6 with essential tremor. 7 of these patients had already undergone thalamotomy contralateral to the stimulated side, and 11 others had bilateral Vim stimulation at the same time. Chronic stimulating electrodes connected to a pulse generator were implanted in the Vim. Tremor amplitude at rest, during posture holding, and during action and intention manoeuvres was assessed by means of accelerometry. Of the 43 thalami stimulated, 27 showed complete relief from tremor and 11 major improvement (88%). The improvement was maintained for up to 29 months (mean follow-up 13 [SD 9] months). Adverse effects were mild and could be eradicated by reduction or cessation of stimulation. This reversibility and adaptability, allowing control of side-effects, make thalamic stimulation preferable to thalamotomy, especially when treatment of both sides of the brain is needed.
The characteristics of nociceptive responses from presumed dopaminergic (DAergic) neurons in the SN were investigated in the anesthetized rat with extracellular recordings. 194 presumed DAergic neurons were recorded. A majority of these neurons (78%) were inhibited by intensive electrical stimulation performed at the tail (PNS) and 15% were excited. Both inhibitory and excitatory responses were intensity-dependent. Single shock stimulation of the lateral habenula (LHb) inhibited 89% of the tested DAergic neurons, most of which (83.8%) were also inhibited by PNS. LHb stimulation increased PNS-induced inhibition of DAergic neurons and electrical destruction of ipsilateral LHb depressed their nociceptive responses. Our results strongly suggest that DAergic neurons encode the nociceptive stimulation intensity and that the LHb shares a step in nociceptive projection to the SN.
Patients with left-sided visual neglect fail to copy the left part of drawings or the drawings on the left side of a sheet of paper. Our aim was to study the variations in copying drawings induced by passive stimulation in patients with left-sided visual neglect. No stimulation at all, tactile unilateral and bilateral, binaural auditory verbal, and nonverbal stimuli were randomly applied to 14 patients with right-hemisphere strokes. Only nonverbal stimuli decreased the neglect. As nonverbal stimuli mainly activate the right hemisphere, the decrease in neglect suggests right-hemispheric hypoactivity at rest in these patients. The absence of modification of neglect during verbal stimulation suggests a bilateral hemispheric activation and the persistence of interhemispheric imbalance. Our results showed that auditory pathways take part in the network involved with neglect. Passive nonverbal auditory stimuli may be of interest in the rehabilitation of patients with left visual neglect.
Using computed tomography and magnetic resonance imaging, we prospectively studied 100 patients hospitalized with a lacunar infarct. Our aim was to evaluate the capabilities of magnetic resonance imaging in the detection and delineation of lacunes in a project of clinicotopographic correlations. Seventy-nine patients had a classic lacunar syndrome; 35 had pure motor stroke, 26 had ataxic hemiparesis, seven had sensorimotor stroke, and 11 had pure sensory stroke. A miscellaneous group of 21 patients had less typical lacunar syndromes, primarily with brainstem signs and symptoms. Among a total of 153 lacunes, magnetic resonance imaging detected at least one lacune appropriate to the symptoms in 89 patients. In 16 patients at least two lesions correlated with the clinical features, and precise clinicotopographic correlations were possible in 68 patients. Magnetic resonance imaging was more effective when it was performed a few days after the stroke. Lesions causing different types of lacunar syndromes had significantly different volumes, suggesting that the size of the lesion may influence clinical features. Magnetic resonance imaging may be the imaging technique of choice in the study of lacunar syndromes.
We report 4 patients with hemiplegia due to a posterior cerebral artery occlusion. Associated clinical signs were aphasia, alexia or a neglect syndrome, hemianopia, and hemisensory loss. Hemiplegia was due to infarction in the lateral midbrain. The level of the occlusion in the posterior cerebral artery may be located distal to the junction with the posterior communicating artery.
Apomorphine, a dopaminergic agonist was given over a period of 12 months to 14 parkinsonian patients suffering from severe L-dopa induced on-off effects. Nine patients (mean age: 52 years; mean age at onset of the disease: 37 years), were treated by continuous infusion with a portable minipump, and 5 others by multiple injections with a penject. The mean duration of daily off periods was reduced by two thirds in all patients. The motor fluctuation intensity was only diminished in the 9 patients treated by continuous infusion. These patients received a mean apomorphine daily dose of 93 mg and L-dopa dosage was reduced by 53 p. 100. Red fibrous subcutaneous nodules occurred at the injection sites in all patients treated by infusion. This study confirms the effectiveness of subcutaneous apomorphine administration in the treatment of severe motor fluctuations.
The striatal dopaminergic innervation was investigated postmortem in 49 control and 57 parkinsonian brains by assessing the binding of tritiated alpha-dihydrotetrabenazine ([3H]TBZOH), a specific ligand of the vesicular monoamine transporter. The density of [3H]TBZOH binding sites in the caudate nucleus of control subjects decreased significantly with age, suggesting an age-dependent reduction in striatal dopamine innervation. In contrast, an increase with the age at time of death was observed in patients with Parkinson's disease, although the density of [3H]TBZOH binding sites was subnormal. Mean values represented 26.5% and 12.7% of control values in the caudate nucleus and in the putamen, respectively. The binding of [3H]TBZOH in the caudate nucleus decreased exponentially with the duration of Parkinson's disease. The rate of [3H]TBZOH binding decrease, an index of the rate of striatal dopaminergic denervation, was about twice as high in parkinsonian patients as in controls and was not related to the age at onset of the disease. The data suggest that (1) parkinsonian symptoms appear above a threshold degeneration state corresponding to 50% of the normal innervation at the age of 60, and (2) aging does not play a major role in the process of nigrostriatal neuron degeneration in Parkinson's disease.
Three young women (aged 18 years, 19 years and 19 years) who developed progressive neuropsychic and neurologic disturbances with hearing loss and multifocal retinal artery branch occlusions are reported. This retinocochleocerebral syndrome has been reported previously only in 12 young North American women. Its pathogenesis is unknown, but an atypical viral infection of the vessel walls has been suggested. Abnormalities of T lymphocytes subsets in blood in one of the patients suggested an immunological dysfunction, but all other tests, including immunological reactions on brain and skin biopsies, were negative or non-specific. Steroids and immunosuppressive agents have been advocated on an empirical basis, but the second patient showed a substantial recovery without any therapy and the third gradually deteriorated despite azathioprine, cyclophosphamide, prednisone and plasma exchanges. This retinocochleocerebral syndrome probably corresponds to an arteriolopathy of unknown nature.
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A 53-year-old hypertensive man presented with the sudden onset of an isolated lemniscal sensory syndrome of the entire left side of his body. Magnetic resonance images showed a small lacune in the right paramedian pons corresponding to the location of the medial lemniscus.
54 patients with idiopathic Parkinson's disease (PD), 26 patients with Alzheimer's disease (AD) and 18 control subjects, all over 55, have performed neuropsychological tests, evaluating global intellectual function (Rosen's cognitive scale, WAIS digit symbol, WAIS similitude and WMS logical memory tests) and visuospatial functions (Rey lacunar pictures, Poppelreuter and Benton line orientation tests). AD group results were distinctly different from those of the PD and the control groups (p less than 0.001). In the PD group, only the Rosen's scale total score and the visuospatial tests were slightly altered (p less than 0.05). In a PD subgroup with a normal Rosen's scale result, the Benton line orientation test was different from controls (p less than 0.05). In another PD subgroup with Rosen's scale score comparable to a midly impaired AD subgroup, all the neuropsychological tests were abnormal. Only the WAIS digit symbol test, altered in this PD subgroup, was different comparing these 2 subgroups (p less than 0.05). With regard to the PD total group, the neuropsychological perturbed PD subgroup was older, had a longer duration of disease, a higher depression's score, less tremor and a worse equilibrium. These results might reflect a neuropsychological defect heterogeneity among PD patients, related to various pathophysiological hypothesis which are discussed in this paper.
Stereotactic ventral intermediate nucleus (Vim) thalamotomy may improve drug resistant severe parkinsonian tremor. However, tremor may recur and bilateral thalamotomy is known to induce unacceptable side effects in a proportion of patients. A high frequency (130 Hz) chronic Vim stimulation was performed in 4 parkinsonian patients, 2 of them having previously undergone a thalamotomy on the other side. Tremor was suppressed in all patients at the price of slight paresthesias. This improvement has been lasting from 2 to 14 months. Beneficial and adverse effects were suppressed at once each time the stimulation was stopped. These preliminary results are encouraging but a longer delay and more patients are obviously needed.
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A man underwent Magnetic Resonance Imaging (MRI) of the left carotid artery 11 days after a spontaneous dissection of this vessel. T1 weighed images were obtained in the frontal and axial planes. There was a hyperintense lesion expanding the arterial wall due to the hematoma. The image of the lumen was narrowed. These findings corresponded to the angiographic abnormalities. In this case MRI was able to diagnose specifically and non invasively carotid artery dissections. Its sensitivity remains to be evaluated.
Four patients with focal brainstem ischemic strokes and various types of horizontal oculomotor disturbances have been studied clinically and radiologically. One had a six nerve palsy, one a unilateral internuclear ophthalmoplegia, one a Fisher's one-and-a-half syndrome, and one a paramedian pontine reticular formation syndrome with a sixth nerve palsy. In all patients a C.T. Scan and a Magnetic Resonance Imaging (MRI) were obtained. The MRI study was performed on a CGR Magniscan 5000 with a superconducting magnet of 0.5 Tesla. In all patients a hypersignal in T2 weighted images was shown and corresponded to the brainstem infarct. MRI allowed accurate delineation of the lesion and clinico-radiologic correlations in three patients. But the low specificity of MRI does not permit to distinguish edema from necrosis, gliosis or demyelination in a region with a pathological MRI signal. In one patient this low specificity and perhaps partial volume effects decreased the accuracy of the clinico-topographic correlation.
Six patients with a clinical diagnosis of lateral medullary infarction have been studied by CT scan and Magnetic Resonance Imaging (MRI). The MRI study was performed on a CGR Magniscan 5000 with a superconducting magnet of 5 Tesla. In all patients T2 weighted images (TR = 2000, TE 60, 120) in joined section of 9 or 6 mm thickness were obtained in the axial plane. Three patients were also studied in T1 weighted sequences (TR = 500, TE = 28). A lateral medullary infarct was shown in 5 patients. MRI findings were consistent with a hemorrhagic infarct in one case. Occlusion of a vertebral artery was suggested in 2 cases and was confirmed by angiography. In 3 cases, an associated ipsilateral cerebellar infarct was demonstrated. The CT scan had only shown bleeding in the medulla oblongata in the hemorrhagic infarction case, and a cerebellar infarction in another case. Some clinical manifestations are discussed with regard to the results of MRI. MRI appears as the best current method to improve clinico-topographic correlations in medullary infarcts.
Clinical and biochemical effects of Gamma-vinyl-Gaba (GVG) have been evaluated in a blind video-controlled study in 10 psychiatric patients (mean age 71 yr) with tardive dyskinesia. CSF free and total Gaba and homocarnosine concentrations increased from three to five fold with GVG treatment. Despite the GVG-induced biological effects on Gaba metabolism, GVG did not consistently improve tardive dyskinesia. Psychomotor side-effects occurred in older patients, who only tolerated GVG dosages of 2-4 g/day.