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PubMed1990

[MRI study of hemiballism].

MRI findings of four hemiballism cases are described, and pathophysiology, pathogenesis and treatment of hemiballism are discussed. All cases had no family history. The lesions revealed by MRI and the pathogenesis were different each other. Case 1, a 17 years aged girl with a history of hyperthyroidism and repeated tonsillitis, showed right sided hemiballism which was recovered by prednisolone and haloperidol. Although her involuntary movement was ameliorated by administration of sodium valproate and phenytoin, phenytoin caused allergic agranulocytosis which required prednisolone treatment. T2 weighted MRI at the 31st disease day demonstrated hyperintensities in the left caudate nucleus, putamen, lateral pallidum, perirubral area and substantia nigra. Hyperintensity in the prerubral area suggested involvement of the subthalamic nucleus or its connecting pathway. Fourteen months later, she suffered from convulsion and mental confusion. There were theta wave bursts and delta waves in EEG. No abnormal findings in MRI and positive antinuclear antibody (ANA: X320, speckled type) were observed. Case 2, a 78 year aged woman, suffered from right sided hemiballism. MRI findings at the 58th disease day were the left putaminal infarction and lacunar state in the bilateral caudate nuclei and the deep white matter of the centrum semiovale. There were no abnormal findings in the subthalamic nucleus. Case 3, a 51 year aged man with diabetes mellitus, had right sided hemiballism. X-ray CT at the 8th disease day showed hyperdensity in the left subthalamic nucleus region which could not be observed at the 12th day. Hypointensity in the left subthalamic nucleus region was observed in both T2 weighted and proton density MRI at the 52nd day. Case 4, an 82 year aged woman, had right sided hemiballism which remarkably diminished at the third disease day and disappeared by the fifth day. Any pathogenic lesion concerning to hemiballism was detected by X-ray CT or MRI.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed2000

Subthalamic stimulation in Parkinson disease: a multidisciplinary approach.

BACKGROUND: High-frequency stimulation of the subthalamic nucleus constitutes a therapeutic advance for severely disabled patients with Parkinson disease. OBJECTIVE: To evaluate the efficacy and safety of continuous bilateral high-frequency stimulation of the subthalamic nucleus in patients with Parkinson disease. DESIGN: A prospective study of patients with Parkinson disease treated at a university hospital. PATIENTS AND METHODS: Electrodes were implanted bilaterally in the subthalamic nucleus of 23 consecutive patients with Parkinson disease who responded well to levodopa but had severe motor complications. There were 16 men and 7 women (mean +/- SEM age, 53 +/- 2 years) who had a mean +/- SEM disease duration of 14.7 +/- 1.0 years. Targets were determined by 3-dimensional magnetic resonance imaging, combined with intraoperative electrophysiologic recordings and stimulation. RESULTS: Six months after surgery, motor disability, levodopa-induced motor fluctuations, dyskinesias, and the daily dose of levodopa equivalent decreased significantly by 67%, 78%, 77%, and 61%, respectively, compared with the preoperative state. No significant morbidity was observed, except transient depression in 4 patients. CONCLUSIONS: The beneficial effects of subthalamic stimulation depend on (1) the criteria used for patient selection, (2) the precision with which the subthalamic nucleus is targeted (dependent on the 3-dimensional magnetic resonance imaging and the intraoperative electrophysiologic and clinical assessments), and (3) the long-term postoperative adjustment of stimulation variables.

Activities of Daily Living↗

PubMed1989

Neural mechanisms underlying parkinsonian symptoms based upon regional uptake of 2-deoxyglucose in monkeys exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

The 2-deoxyglucose metabolic mapping technique has been used to investigate the neural mechanisms which underlie the symptoms of Parkinsonism in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine primate model of Parkinson's disease. In six cynomolgus monkeys, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine was either (a) administered intravenously to induce generalized Parkinsonism, or (b) infused into one carotid artery to induce unilateral Parkinsonism. Post-mortem examination revealed profound cell loss from the substantia nigra, pars compacta either bilaterally or unilaterally in the two groups, respectively. In addition, there was pathological involvement of the ventral tegmental area and locus coeruleus in animals receiving intravenous 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. 2-Deoxyglucose autoradiography revealed widespread changes in 2-deoxyglucose uptake in the brains of parkinsonian animals when compared to controls. Most of these changes were in basal ganglia and related structures and were qualitatively similar in the two groups of experimental animals. Prominent increases in 2-deoxyglucose uptake were observed in the lateral segment of the globus pallidus (24-27%), the ventral anterior and ventral lateral nuclei of the thalamus (14-22%) and the nucleus tegmenti pedunculopontinus of the caudal midbrain (17-69%). A profound decrease (17-26%) in 2-deoxyglucose uptake was observed in the subthalamic nucleus. We propose these data to indicate that in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism there is the following pattern of abnormal neuronal activity in basal ganglia circuitry: (i) increased activity in the projection from the putamen to the lateral segment of the globus pallidus; (ii) decreased activity in the projection from the putamen to the medial segment of the globus pallidus; (iii) decreased activity in the projection from the lateral segment of the globus pallidus to the subthalamic nucleus; (iv) increased activity in the projection from the subthalamic nucleus to the globus pallidus; and (v) increased activity in neurons of the medial segment of the globus pallidus projecting to the ventral anterior/ventral lateral thalamus and the pedunculopontine nucleus. These results are compared to the 2-deoxyglucose uptake findings in previous studies from this laboratory in hemiballism and hemichorea in the monkey. The central importance of the subthalamic nucleus in all three conditions is proposed, and supportive evidence for the excitatory nature of subthalamic efferent fibres is adduced.

Animals↗

PubMed1999

Systemic administration of NMDA and AMPA receptor antagonists reverses the neurochemical changes induced by nigrostriatal denervation in basal ganglia.

In Parkinson's disease, nigrostriatal denervation leads to an overactivity of the subthalamic nucleus and its target areas, which is responsible of the clinical manifestations of the disease. Because the subthalamic nucleus uses glutamate as neurotransmitter and is innervated by glutamatergic fibers, pharmacological blockade of glutamate transmission might be expected to restore the cascade of neurochemical changes induced by a dopaminergic denervation within the basal ganglia. To test this hypothesis, two types of glutamate antagonists, the NMDA receptor antagonist MK-801 and the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist LY293558, were administered systemically, either alone or in combination with L-DOPA, in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal dopamine pathway. The effect of treatment was assessed neurochemically by analyzing at the cellular level the functional activity of basal ganglia output structures and the subthalamic nucleus using the expression levels of the mRNAs coding for glutamic acid decarboxylase and cytochrome oxidase, respectively, as molecular markers of neuronal activity. The present study shows that treatment with glutamate antagonists, and particularly with AMPA antagonists, alone or in combination with L-DOPA, reverses the overactivity of the subthalamic nucleus and its target areas induced by nigrostriatal denervation. These results furnish the neurochemical basis for the potential use of glutamate antagonists as therapeutic agents in Parkinson's disease.

Animals↗

PubMed1994

[Adult-onset dementia with abundant neurofibrillary tangles resembling progressive supranuclear palsy].

We described an autopsy case of 79-year-old woman with clinically unclassified senile dementia. The patient developed forgetfulness at the age of 73, and later, persecution mania, apathy and episodic stupor, but no extrapyramidal symptoms. Neuropathological examination revealed severe neuronal loss and gliosis of substantia nigra, moderate neuronal loss and marked grumose degeneration of dentate nucleus, and mild astrocytosis of subthalamic nucleus. Abundant neurofibrillary tangles (NFT) were observed in subthalamic nucleus, globus pallidus, substantia nigra, locus ceruleus, tegmentum of brain stem, pontine nucleus, inferior olive, and dentate nucleus. Gallyas silver impregnation method showed a wide distribution of argyrophilic grains and threads in cerebrum, brain stem and cerebellum. Although absence of clinical and neuropathological hallmarks excluded the diagnosis of progressive supranuclear palsy (PSP), the distribution of NFT and argyrophilic grains in this patient resembled PSP.

Age of Onset↗

PubMed1989

Dyskinesia in the primate following injection of an excitatory amino acid antagonist into the medial segment of the globus pallidus.

Injection of an excitatory amino acid antagonist, kynurenic acid, into the medial segment of the globus pallidus of the conscious monkey elicited dyskinesia of the contralateral limbs. In most respects the dyskinesia was indistinguishable from the disorder that is produced by ablation of the subthalamic nucleus, or injection of a GABA antagonist into the subthalamic nucleus. Injections of kynurenic acid into the lateral segment of the globus pallidus, by contrast, did not provoke dyskinesia. The effect of kynurenic acid is attributed to the blockade of neurotransmission from the subthalamic nucleus to the medial pallidal segment, and the results suggest that the neurotransmitter utilised by this pathway is an excitatory amino acid.

Animals↗

PubMed2005

Activation of the subthalamic region during emotional processing in Parkinson disease.

OBJECTIVE: To elucidate the involvement of the human subthalamic nucleus (STN) region in the processing or transmission of emotional information. METHODS: Local field potentials (LFPs) were recorded from this region in 10 patients with Parkinson disease (PD) undergoing bilateral implantation of the STN for high-frequency stimulation. LFP recordings were made while patients viewed pleasant and unpleasant emotionally arousing and neutral pictures. RESULTS: A significant decrease (event-related desynchronization [ERD]) in the local alpha power (8 to 12 Hz) was found for all stimulus categories starting at about 0.5 seconds after stimulus presentation. However, 1 to 2 seconds poststimulus, the ERD was larger in trials of pleasant (mean ERD: 21.6 +/- 2.8%; p < 0.009) and unpleasant (mean ERD: 15.0 +/- 4.2%; p = 0.018) stimuli compared with neutral stimuli (mean ERD: 4.4 +/- 4.2%). CONCLUSION: The delayed modulation of alpha activity recorded from the area of the subthalamic nucleus in PD may reflect the processing or transmission of information related to emotional stimuli. "Limbic" activation in the region of the subthalamic nucleus may explain why high-frequency stimulation of the subthalamic nucleus alters affect in some patients with PD.

Affect↗

PubMed1993

[Ballism, hemiballism].

Ballism, which is seen relatively infrequently among movement disorders, is characterized by the abrupt onset of vigorous, rapidly executed, poorly patterned in voluntary movement of the limbs. Hemiballism is mostly associated with the lesion in the subthalamic nucleus. However, it occasionally occurs as a result of lesions outside the subthalamic nucleus. The natural history of hemiballism caused by vascular subthalamic lesion usually shows gradual disappearance within days or weeks. Death from exhaustion has however been reported in some patients within four to six weeks after the onset. Hemiballism caused by lesions outside the subthalamic nucleus tends to persist for a longer period. Intensive treatment is therefore required. Successful treatments of hemiballism with haloperidol or chlorpromazine are wellknown, but, in older patients, sulpiride can be the first choice of medications because of its lesser side effect.

Cerebrovascular Disorders↗

PubMed2000

[A 77-year-old man with gait and gaze disturbance].

We report a 77-year-old Japanese man with progressive gait disturbance. He was well until his 71 years of the age (1992), when he noted an onset of disturbance in his speech, which was followed by difficulty in using his left hand. He did not attempt to use his left hand afterwards. He started to fall down in the spring of 1994. He was admitted to our service on October 6, 1994. Neurologic examination revealed an alert and oriented man. He showed limb-kinetic apraxia in his left hand with anosognosia for his apraxia. Vertical gaze was impaired. He walked in small steps. He had moderate axial and limb rigidity. He had no weakness, ataxia, or tremor. Deep tendon reflexes were normal. Plantar response was flexor. Sensation was intact. His gait had progressively become worse and he was admitted to another hospital in April of 1996. At that time he was disoriented to time. He was only able to walk a few steps with support. He continued to show limb-kinetic apraxia in his left hand. He developed dementia and dysphagia and he expired on October 27, 1998. He was discussed in a neurological CPC, and the chief discussant arrived at the conclusion that the patient had corticobasal degeneration. Most of the participants agreed with this diagnosis, but a few of them thought that progressive supranuclear palsy would be more likely. Post-mortem examination revealed no gross cortical atrophy. The right hemisphere was kept frozen for future biochemical analysis. The left precentral gyrus showed spongy changes, neuronal loss and gliosis. The pallidum, putamen, and the subthalamic nucleus were unremarkable, however, neurofibrillary tangles were seen in the subthalamic nucleus. The substantia nigra showed only slight neuronal loss; neuronal pigments were well retained. A few neurofibrillary tangles were seen in the remaining neurons. The cerebellar dentate nucleus showed grumose degeneration. Gallyas-Braak staining revealed many tuft-shaped astrocytes in the precentral gyrus. Pathologic diagnosis was progressive supranuclear palsy. Some participants thought that this diagnosis was unacceptable, because the pathologic changes in the substantia nigra, globus pallidus, and the subthalamic nucleus, which were usually severely involved in PSP, did not show typical changes of PSP. In addition, the predominant clinical feature was limb-kinetic apraxia, although he showed vertical gaze paresis and parkinsonian gait, which could also be seen in corticobasal degeneration. There was a big discussion among participants with regard to the diagnosis.

Aged↗

PubMed2005

Physiological recordings from electrodes implanted in the basal ganglia for deep brain stimulation in Parkinson's disease. the relevance of fast subthalamic rhythms.

Deep brain stimulation electrodes implanted in the subthalamic nucleus of patients with Parkinson's disease allow electrophysiological recordings from the human basal ganglia. Subthalamic local field potential recordings revealed the presence of multiple rhythms, from the classical EEG frequency range (<50 Hz), to surprisingly high frequencies (70 Hz and 300 Hz). Fast rhythms are particularly attractive because of their likely interaction with the excitatory mechanisms of action of deep brain stimulation. Here we investigated whether the two rhythms at 70 Hz and at 300 Hz represent distinct modes of operation, and therefore different targets, within the subthalamic nucleus. We retrospectively analyzed the dataset we used to describe the 300 Hz rhythm (Foffani, Priori et al., Brain 126: 2153-2163, 2003) searching for significant 70 Hz oscillations after levodopa administration. Whereas (as previously reported) 300 Hz activity was a consistent feature in the dataset, significant 70 Hz activity was observed in only 2 of 11 nuclei. Therefore, 70 Hz oscillations are not a necessary condition for the presence of 300 Hz oscillations. The two rhythms probably arise from different mechanisms, reflecting different functional and/or spatial aspects of subthalamic pathophysiology. Fast subthalamic oscillations could be exploited for intra-operative electrophysiological monitoring of the subthalamic nucleus, post-operative confirmation of electrode placement and patient-specific 'reglage' of the electrical parameters for chronic deep brain stimulation.

Basal Ganglia↗

PubMed2004

Autonomic and emotional responses to open and hidden stimulations of the human subthalamic region.

We performed a microstimulation study of the subthalamic region of Parkinsonian patients who underwent bilateral electrode implantation in the subthalamic nuclei and whose heart rate and heart rate variability were recorded. The stimulation of the dorsalmost region, which includes the zona incerta and the dorsal pole of the subthalamic nucleus, produced autonomic responses that were constant over time. In fact, hidden stimulations (the patient is not aware of being stimulated) and open stimulations (the patient is aware of being stimulated) always induced the same responses. By contrast, the stimulation of the ventralmost region, which includes the ventral pole of the subthalamic nucleus and the substantia nigra pars reticulata, produced autonomic and emotional responses that were inconstant over time and varied according to the condition. In fact, different responses were elicited with hidden and open stimulations. These data suggest that the dorsal subthalamic nucleus and/or the zona incerta are involved in autonomic control, whereas the ventral subthalamic nucleus and/or the substantia nigra reticulata are involved in associative/limbic-related autonomic activity. The difference between the open and hidden stimulations in the ventral subthalamic region can explain previous studies in which open and hidden stimulations produced different therapeutic outcomes.

Aged↗

PubMed2006

Involvement of human basal ganglia in offline feedback control of voluntary movement.

Practice makes perfect, but the neural substrates of trial-to-trial learning in motor tasks remain unclear. There is some evidence that the basal ganglia process feedback-related information to modify learning in essentially cognitive tasks , but the evidence that these key motor structures are involved in offline feedback-related improvement of performance in motor tasks is paradoxically limited. Lesion studies in adult zebra finches suggest that the avian basal ganglia are involved in the transmission or production of an error signal during song . However, patients with Huntington's disease, in which there is prominent basal ganglia dysfunction, are not impaired in error-dependent modulation of future trial performance . By directly recording from the subthalamic nucleus in patients with Parkinson's disease, we demonstrate that this nucleus processes error in trial performance at short latency. Local evoked activity is greatest in response to smallest errors and influences the programming of subsequent movements. Accordingly, motor parameters are least likely to change after the greatest evoked responses so that accurately performed trials tend to precede other accurate trials. This relationship is disrupted by electrical stimulation of the nucleus at high frequency. Thus, the human subthalamic nucleus is involved in feedback-based learning.

Aged↗

PubMed1988

Chorea and myoclonus in the monkey induced by gamma-aminobutyric acid antagonism in the lentiform complex. The site of drug action and a hypothesis for the neural mechanisms of chorea.

Experiments are described in which the gamma-aminobutyric acid (GABA) antagonist bicuculline was injected into the lentiform complex of conscious monkeys. Injections into either the lateral segment of the globus pallidus, or the medial part of the putamen, gave rise to chorea of the contralateral limbs and/or orofacial region. Control injections of vehicle alone were without effect. Injections of bicuculline into the lateral part of the putamen gave rise to contralateral myoclonus. The chorea produced by lateral pallidal or medial putaminal injections was virtually indistinguishable from the dyskinesia (chorea/ballism) which has been shown, in previous studies, to be induced by injection of GABA antagonists into the subthalamic nucleus. It is proposed that the primary site of action of the GABA antagonist in producing chorea, in the present studies, was the lateral segment of the globus pallidus. The mode of action is suggested to be interruption of GABAergic transmission from the striatum to the lateral pallidal segment. Since this also occurs in Huntington's disease, it is proposed that experimental chorea induced by this method in the monkey may be a useful model of the dyskinesia seen in Huntington's disease in man. Loss of influence of inhibitory striatopallidal fibres would lead to abnormally increased activity of lateral pallidal neurons. These in turn project to the subthalamic nucleus, upon which they have an inhibitory action. Dyskinesia is thus produced by physiological inhibition of the subthalamic nucleus, whose destruction, both in man and the monkey, is known to produce ballism. It is proposed that ballism and chorea share common neural mechanisms, both involving the loss of influence of the subthalamic nucleus on the medial segment of the globus pallidus.

Animals↗

PubMed1980

Projections of the feline globus pallidus.

The organization of globus pallidus (GP) projections was studied in cats using autoradiographic and horseradish peroxidase (HRP) techniques. Both methods confirmed the existence of a topographically organized projection to subthalamic nucleus (STN). Although all but the most caudal GP projects to STN, the heaviest projection is to the lateral two-thirds. In addition, HRP studies showed that the GP projection to the medial part of substantia nigra, pars reticulata receives projections from the rostral lateral GP, while lateral substantia nigra receives input from caudal GP. There is in addition a small projection from caudal GP to the caudal lateral mesencephalon. This most caudal projection of GP arises from the portion of GP which projects the least to the subthalamic nucleus. Mesencephalic and pontine cells labeled after injection of horseradish peroxidase into STN were in areas receiving projections from GP and entopeduncular nucleus, suggesting there may be reciprocal relationships between these areas. Labeled cells were located in the lateral part of subthalamic nucleus after injection into the lateral portion of substantia nigra pars reticulata, but cells were not labeled after medial injection. Pontine injections of HRP also revealed that cells in fields of Forel and zona incerta project to pons but very few subthalamic nucleus cells project there.

Amygdala↗

PubMed1995

Does the blockade of excitatory amino acid transmission in the basal ganglia simply reverse reaction time deficits induced by dopamine inactivation?

It has recently been hypothesized that excessive excitatory amino acid (EAA) activity in the corticostriatal pathway and in the subthalamic nucleus could account for the expression of the motor deficits resulting from alteration in dopamine function in the basal ganglia. The present study investigated the potential benefit of blocking excitatory amino acid transmission in the basal ganglia, subsequent to the inactivation of dopaminergic function of rats performing a reaction time (RT) task. Disruption of dopamine activity by the neurotoxin 6-hydroxydopamine (6-OHDA) injected in the striatum or by systemic administration of the D2 dopamine receptor antagonist raclopride, impaired the performance of rats trained to release a lever quickly after a visual stimulus. RTs, measured by the time elapsing from the stimulus onset to the lever release, were lengthened after both treatments. The blockade of EAA transmission at the N-methyl-D-aspartate (NMDA) receptor, by systemic injections of the NMDA receptor antagonist dizocilpine or by excitotoxic lesions of the subthalamic nucleus, in animals with dopamine lesions, significantly reversed the increase of RTs. Performance of animals with subthalamic nucleus lesions did not return to pre-operative values, however. The blockade of NMDA receptors in the striatum, by a local injection of the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV), in animals treated with raclopride, was found to decrease RTs and improve performance. Analysis of RT distributions in the three groups of animals revealed that blocking EAA activity with NMDA receptor antagonists improved performance by shifting RTs back towards baseline values, preserving a normal distribution. In contrast, lesions of the subthalamic nucleus disrupted performance, as shown by the scattered distribution of RTs. The results indicate that treatment with NMDA receptor antagonists but not subthalamotomy provides a possible beneficial treatment in the present model of Parkinsonism.

Journal Article↗

PubMed1983

Microiontophoretic studies on the nature of the neurotransmitter in the subthalamo-entopeduncular pathway of the rat.

The aim of the present study was to determine the identity of the neurotransmitter released by the pathway from the subthalamic nucleus to the entopeduncular nucleus in the rat, using extracellular stimulating and recording techniques and microiontophoresis. In order to avoid stimulation of passing fibers at the level of the subthalamic nucleus, (collaterals to the entopeduncular nucleus of the caudato-nigral pathway, or direct projections to the entopeduncular nucleus from the substantia nigra or nucleus tegmenti pedunculopontinus), the experiments were performed in rats bearing chronic ipsilateral lesions in order to make these pathways degenerate. Under such conditions, subthalamic nucleus stimulation suppressed the spontaneous firing of all the entopeduncular nucleus cells studied (n = 40) for 15-25 ms (mean duration +/- S.E.M.:21.88 +/- 1.57 ms). Entopeduncular nucleus cells were identified by antidromic activation from the ventral anterior thalamic nucleus (40%) or lateral habenula nucleus (68%). Low doses of iontophoretically applied GABA (60 cells) or glycine (15 cells) were inhibitory upon entopeduncular cells, while acetylcholine or carbamylcholine were poorly excitatory (18 cells), or had no effect (28 cells). The subthalamic nucleus-evoked inhibition of entopeduncular neurons was reversed by microiontophoretically applied bicuculline or picrotoxin, at doses which blocked the GABA-induced response, but not that produced by glycine or acetylcholine. With similar experiments, strychnine and atropine were ineffective. This excludes a possible role of glycine or acetylcholine in the subthalamic-evoked inhibitory response of entopeduncular cells. The present study strongly suggest that GABA is a neurotransmitter in the inhibitory subthalamo-entopeduncular pathway.

Acetylcholine↗

PubMed1999

Effect of a functional impairment of corticostriatal transmission on cortically evoked expression of c-Fos and zif 268 in the rat basal ganglia.

The activity-dependent induction of immediate-early genes is commonly used to map activated neuronal networks. In a previous analysis of the cortico-basal ganglia circuits, we have shown that a cortical stimulation produces Fos protein expression in the striatum and the subthalamic nucleus, with a pattern which conforms to the anatomical organization of cortical projections [Sgambato V. et al. (1996) Neuroscience 81, 93-112]. In the present study, we examined the effects of a unilateral blockade of the corticostriatal transmission on c-fos and zif 268 messenger RNA expression evoked in the substantia nigra pars reticulata and the subthalamic nucleus following stimulation of the ipsilateral motor cortex. The blockade of the corticostriatal pathway was performed either by an excitotoxic striatal lesion or by an application of the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione within the striatum. After application of the glutamate receptor antagonist, which prevented the cortical stimulation activating the GABAergic striatonigral pathway, the induction of both c-fos and zif 268 messenger RNAs was facilitated in the ipsilateral substantia nigra pars reticulata. In the subthalamic nucleus ipsilateral to the application of 6-cyano7-nitroquinoxaline-2,3-dione, the cellular discharges evoked by stimulation of the cortex were considerably shortened as a result of the blockade of the disinhibitory striato-pallido-subthalamic circuit. However, a strong expression of immediate-early genes was still induced by the cortical stimulation. By contrast, after unilateral kainate lesion of the striatum, the cortical stimulation was no longer able to induce c-fos and zif 268 messenger RNA expression in the ipsilateral subthalamic nucleus and in the substantia nigra pars reticulata bilaterally. The lack of immediate-early gene induction strongly contrasted with the neuronal discharges evoked in these nuclei by the cortical stimulation. Comparison between the cortically evoked neuronal activities and the pattern of immediate-early gene expression suggests that the induction of immediate-early genes in the basal ganglia mainly reflects the level of synaptic activity rather than the frequency of discharge of the postsynaptic neurons. Moreover, the results stress that modifications of immediate-early gene expression observed in the basal ganglia after an acute or a chronic interruption of the corticostriatal transmission are not superimposable.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMedDate not supplied

[Treatment of a case of generalised dystonia using subthalamic stimulation].

INTRODUCTION: Generalised dystonia is an entity that does not usually respond well to medical treatment. Different surgical targets have therefore been used in the treatment of dystonia, including several thalamic nuclei or the internal globus pallidus. The subthalamic nucleus plays a fundamental role in the physiology of the basal ganglia. It could therefore be considered to be a good potential target for stimulation. CASE REPORT: A patient who was confined to a wheelchair and who had not responded to a number of different medical treatment protocols or to a bilateral thalamotomy was treated with bilateral deep brain stimulation in the subthalamic nucleus. Tetrapolar electrodes were placed in both subthalamic nuclei in two stages. The patient showed a significant improvement from the very beginning of the post-operative period. After six months' progression, the patient was able to walk unaided and the dystonic seizures diminished significantly. Unfortunately, the patient died from choking. We used a bipolar stimulation protocol at 50 Hz with 210 micros pulses, which do not reach the levels of maximum charge density that are considered to be harmful. CONCLUSION: The subthalamic nucleus can be a good surgical target for deep brain stimulation in cases of generalised dystonia; it responds well to stimulation at intermediate frequencies with safe charge densities.

Dystonia↗