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A Benazzouz

Publications and source records attributed to A Benazzouz.

At least 37 records · Page 2Linked to original sources
PubMed2000

Changes in the firing pattern of globus pallidus neurons after the degeneration of nigrostriatal pathway are mediated by the subthalamic nucleus in the rat.

Changes in the neuronal activity of globus pallidus (GP) have been shown in animal models of parkinsonism. In order to study the implication of the subthalamic nucleus (STN) in these changes, the effects of STN lesions alone or in combination with 6-hydroxydopamine (6-OHDA) -induced damage to the substantia nigra compacta (SNc) were examined in rats using electrophysiological recordings of GP cells. In normal rats, the firing rate was 22.1+/-1.4 spikes/s. The pattern was regular in 45%, irregular in 49% and bursty in 6% of the cases. In rats with STN lesions, the firing rate of GP units (20.15+/-1.25 spikes/s) did not differ from that of normal rats and only regular (46%) and irregular (54%) cells were found; a bursty pattern was not observed. 6-OHDA lesions of the SNc induced no change in the firing rate of GP neurons (21.5+/-1.4 spikes/s, P>0.05) but a significant decrease in the percentage of regular cells (27%, P<0.001), a significant increase in burst cells (21%, P<0.001) with no change in the percentage of irregular units (52%) were observed. In rats with combined SNc and STN lesions, the firing pattern did not change from that of normal rats. The present results show that STN lesions induced the disappearance of bursts in normal rats and normalization of firing pattern in the GP units of rats with 6-OHDA lesions suggesting that the STN plays an important role in the modulation of the pattern of activity of GP neurons which may account for the therapeutic effect of STN lesions in Parkinson's disease.

Animals↗
PubMed2000

Mechanism of action of deep brain stimulation.

Initial observations in patients with tremor treated with deep brain stimulation (DBS) of the thalamus suggested that application of high-frequency stimulation (HFS) had a lesion-like effect. New clinical information from patients treated with DBS of the subthalamic nucleus (STN) and globus pallidus internus (GPi) suggested a more complex mechanism of action. Recent experiments in the rat have shown that HFS of the STN was accompanied by increased release of glutamate and dopamine in the substantia nigra and striatum, respectively. Observations made in the GPi of parkinsonian patients during surgery suggest that stimulation may excite GABA release in axons from afferent connections. Therefore, although depolarization block may remain a major mechanism of action, generation of action potentials and release of neurotransmitters may also be involved in the therapeutic effects of DBS in Parkinson's disease.

Animals↗
PubMed2000

Deep brain stimulation of the subthalamic nucleus for Parkinson's disease: methodologic aspects and clinical criteria.

The technique of deep brain stimulation (DBS) for the treatment of Parkinson's disease (PD) is evolving very rapidly. The subthalamic nucleus (STN) has become the preferred target in the past few years since our group demonstrated that high-frequency stimulation in this nucleus improves all cardinal features of PD, including resting tremor. This benefit in the parkinsonian symptoms allows a drastic reduction in daily levodopa requirements. Dyskinesias become drastically attenuated, possibly as a consequence of reduced dopaminergic medication but also because STN DBS may stabilize basal ganglia output activity, thus avoiding the problems associated with standard levodopa replacement therapy. DBS of the STN is associated with a marked improvement of motor function even in patients with advanced PD. Such a large degree of benefit in parkinsonian features relies on two crucial points that must be taken into consideration for achieving the best possible results with this technique: proper selection of patients and accuracy in targeting the STN. From a neurosurgical point of view, we believe that the most precise localization of the STN is obtained by using ventriculography to determine the stereotactic coordinates of the STN. This is complemented with intraoperative neuronal microrecording to define physiologically the sensorimotor region of the nucleus. Future advances in neuroimaging techniques may well lead to modifications of our current methodology.

Adult↗
PubMed1999

Neuroprotective effect of chronic inactivation of the subthalamic nucleus in a rat model of Parkinson's disease.

Several evidences showed that glutamate can be implicated in the degenerative process of dopaminergic neurons in Parkinson's disease. The treatment with NMDA antagonists have been shown to induce a neuroprotective effect in animal models of this disease. As subthalamic nucleus neurons send direct glutamatergic projections to the substantia nigra, we studied the effects of kainic acid lesion of this nucleus on the degeneration of dopaminergic neurons induced by microinjection of 6-hydroxydopamine in the striatum of rat done one week after the first lesion. Animals were killed 15 days after the injection of 6-hydroxydopamine. Immunohistochemical study showed that lesion of the subthalamic nucleus can prevent the degeneration of substantia nigra dopaminergic somata when carried out one week prior to 6-hydroxydopamine injection in the striatum. Nevertheless neurochemical results showed that this lesion did not antagonize the striatal 6-hydroxydopamine-induced dopamine depletion in the striatum 15 days after 6-hydroxydopamine injection.

Animals↗
PubMed1999

Thalamic, subthalamic nucleus and internal pallidum stimulation in Parkinson's disease.

The limits of drug therapy in severe forms of Parkinson's disease have lead to a renewal of functional neurosurgery of the basal ganglia and the thalamus. Deep brain stimulation (DBS) of these structures was developed with the aims of reducing the morbidity of surgery and of offering an adaptative treatment. DBS was first applied to the thalamus in patients with severe tremor. Tremor of the hemibody is greatly reduced by stimulation of the contralateral electrode in 85% of the cases. There is little change in other symptoms. However, motor fluctuations and dyskinesias are a more frequent problem than severe tremor; in attempt to treat these symptoms, DBS has recently been applied to the subthalamic nucleus (STN) and the internal pallidum (GPi). STN stimulation greatly decreases off motor symptoms and motor fluctuations, which allows a reduction of drug dosage and consequently of dyskinesias. GPi stimulation decreases dyskinesias in most patients, but the effect on off motor symptoms is more variable from one series to another, from very good to nil. The severe morbidity of DBS applied to these 3 targets is low. Comparative studies of the cost and the efficacy of DBS and lesions applied to these different targets are now required.

Electric Stimulation↗
PubMed1999

High-frequency stimulation of the subthalamic nucleus suppresses experimental resting tremor in the monkey.

The effect of high-frequency stimulation of the subthalamic nucleus on parkinsonian-like resting tremor was investigated in two monkeys (Macaca fascicularis). Unilateral tremor of the arm and leg was induced by electrical coagulation of the brainstem area including the substantia nigra and the red nucleus. The tremor was only seen at rest condition with a very stable frequency of 4.46+/-0.59 Hz (mean+/-S.D.). Apomorphine (0.10-0.4 mg/kg, s.c.) completely blocked the tremor, suggesting that it was a dopaminergic-dependent symptom just like the parkinsonian tremor. When the stimulating frequency varied from 20 to 1000 Hz, both mono- and bipolar stimulation (square pulses, 0-5 mA, 0.06 ms) of the subthalamic nucleus suppressed resting tremor in a frequency-dependent manner but monopolar stimulation was more effective. These effects remained stable for more than two years. The present results suggest that the subthalamic nucleus is involved in the control and mechanism of resting tremor and that the high-frequency stimulation of the subthalamic nucleus can be used as an alternative therapy in parkinsonian patients with akinesia, rigidity and resting tremor.

Animals↗
PubMed1999

The vimentin promoter as a tool to analyze the early events of retinoic acid-induced differentiation of cultured embryonal carcinoma cells.

The vimentin gene encodes an intermediate filament protein expressed in the parietal endoderm, mesodermal, and early neural cells in vivo but by most in vitro-cultured cells regardless of their embryonic origin. Here we show that the vimentin gene promoter is very active in F9 embryonal carcinoma cells and increases in activity during differentiation. Using a series of 5'-deletion mutants, we provide evidence that the regions of the promoter involved in F9 cell activity are different from those previously demonstrated to be active in differentiated cell lines. Furthermore, we show that in differentiating F9 cells the activities of two different regions of the promoter are significantly enhanced. A distal region (-1710/-957) appears to contain functional binding sites for the murine Hox-A5 homeoprotein as demonstrated by band shift and footprinting experiments. A proximal region (-140/-78) contains a 30-bp repetitive sequence found in other genes activated during differentiation of F9 cells. Using band shift assays and methylation interference, we present evidence that a sequence-specific single-stranded DNA-binding protein(s) specifically interacts with the minus strand of the 30-bp sequence.

Animals↗
PubMed1999

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.

Adult↗
PubMed1998

Electrical stimulation of the subthalamic nucleus in advanced Parkinson's disease.

BACKGROUND: In many patients with idiopathic Parkinson's disease, treatment with levodopa is complicated by fluctuations between an "off" period, when the medication is not working and the motor symptoms of parkinsonism are present, and an "on" period, when the medication is causing improved mobility, often accompanied by debilitating dyskinesias. In animal models of Parkinson's disease, there is overactivity in the subthalamic nucleus, and electrical stimulation of the subthalamic nucleus improves parkinsonism. We therefore sought to determine the efficacy and safety of electrical stimulation of the subthalamic nucleus in patients with Parkinson's disease. METHODS: We studied 24 patients with idiopathic Parkinson's disease in whom electrodes were implanted bilaterally in the subthalamic nucleus under stereotactic guidance with imaging and electrophysiologic testing of the location. Twenty were followed for at least 12 months. Clinical evaluations included the Unified Parkinson's Disease Rating Scale, a dyskinesia scale, and timed tests conducted before and after surgery, when patients were off and on medications. RESULTS: After one year of electrical stimulation of the subthalamic nucleus, the patients' scores for activities of daily living and motor examination scores (Unified Parkinson's Disease Rating Scale parts II and III, respectively) off medication improved by 60 percent (P<0.001). The subscores improved for limb akinesia, rigidity, tremor, and gait. In the testing done on medication, the scores on part III improved by 10 percent (P<0.005). The mean dose of dopaminergic drugs was reduced by half. The cognitive-performance scores remained unchanged, but one patient had paralysis and aphasia after an intracerebral hematoma during the implantation procedure. CONCLUSIONS: Electrical stimulation of the subthalamic nucleus is an effective treatment for advanced Parkinson's disease. The severity of symptoms off medication decreases, and the dose of levodopa can be reduced with consequent reduction in dyskinesias.

Activities of Daily Living↗
PubMed1998

Opposite motor effects of pallidal stimulation in Parkinson's disease.

We studied the effects--on parkinsonian signs, on levodopa-induced dyskinesias, and on levodopa response--of acute experimental high-frequency stimulation of the internal pallidum (GPi) during off-drug and on-drug phases. Thirteen quadripolar electrodes were evaluated in 8 patients with Parkinson's disease (PD). Stimulation of the most ventral contacts, lying at the ventral margin of or just below the GPi, led to pronounced improvement in rigidity and a complete arrest of levodopa-induced dyskinesias. The antiakinetic effect of levodopa was also blocked and the patients became severely akinetic. Stimulation of the most dorsal contacts, lying at the dorsal border of the GPi or inside the external pallidum, usually led to moderate improvement of off-drug akinesia and could also induce dyskinesias in some patients. When using an intermediate contact for chronic stimulation, a good compromise between these opposite effects was usually obtained, mimicking the effect of pallidotomy. We conclude that there are at least two different functional zones within the globus pallidus, at the basis of a different pathophysiology of the cardinal symptoms of PD. The opposite effects may explain the variable results of pallidal surgery reported in the literature and may also largely explain the paradox of PD surgery. A possible anatomical basis for these differential functional effects could be a functional somatotopy within the GPi, with the segregation of the pallidofugal fibers from the outer portion of the GPi, on one hand, forming the ventral ansa lenticularis and from the inner portion of the GPi, on the other hand, forming the dorsal lenticular fasciculus.

Apomorphine↗
PubMed1998

Inhibition of levodopa effects by internal pallidal stimulation.

We report three patients with bilateral GPi stimulation for stage 4 Parkinson's disease (PD) with severe levodopa-induced dyskinesias (LID). In all three it was possible to completely inhibit LID using high-stimulation parameters. Parallel to complete inhibition of LID, an inhibition of the anti-akinetic effect of levodopa was observed, whereas, at the same time, rigidity was markedly improved. GPi stimulation is adaptable over time, and stimulation parameters have to be programmed according to off- and on-period motor symptoms. The main interest of stimulation is the possibility of finding a compromise between LID alleviation in on-phase without loss of the beneficial motor effects and improvement in parkinsonism in off-phase. In some patients, residual dyskinesias have to be accepted so as not to aggravate on-period motor symptoms by a presumed overinhibition of basal ganglia outflow.

Antiparkinson Agents↗
PubMed1998

Treatment of tremor in Parkinson's disease by subthalamic nucleus stimulation.

The recent resurgent interest in functional surgery for the treatment of Parkinson's disease (PD) has focused on the effects on akinesia and levodopa-induced dyskinesia. Stimulation of the subthalamic nucleus (STN) improves akinesia and rigidity but its effects on tremor have not been studied. The objective of this study was to assess the efficacy of STN stimulation on tremor in patients with the complete parkinsonian triad with motor fluctuations. Of 27 consecutive patients with STN stimulation (26 bilateral), 15 exhibited tremor rated at least 2/4 according to item 20 (rest tremor) of the Unified Parkinson's Disease Rating Scale (UPDRS) in at least one limb. The mean preoperative tremor score was 11.3+/-5.6 in off-drug and 1.2+/-2.4 in on-drug conditions. The postoperative tremor scores at the last follow up (from 1-12 months) were 2.2+/-2.2 off-drug/on-stimulation and 0.2+/-0.4 on-drug/on-stimulation. Both rest and action tremors were improved in all patients. The UPDRS tremor score was reduced by 80%, rigidity score by 65%, and akinesia score by 51% on average. For the three symptoms, the stimulation effect was close to that induced before surgery by a suprathreshold dose of levodopa given in the morning. STN stimulation can be considered an interesting alternative to thalamic or internal pallidal surgery even in PD patients with severe high-amplitude tremor. In keeping with electrophysiological data in monkeys rendered parkinsonian by MPTP injections, our results emphasize the importance of the oscillation of a neuronal loop involving the STN in the pathophysiology of parkinsonian tremor.

Adult↗
PubMed1998

Long-term electrical inhibition of deep brain targets in movement disorders.

Stimulation of the thalamic nucleus ventralis intermedius (Vim) at high (130-Hz) frequency has been used over the last 8 years as a treatment in 134 patients with movement disorders (91 Parkinson's disease [PD], 23 essential tremor [ET], 21 various dyskinesias and dystonias, including four multiple sclerosis [MS]), implanted with long-term electrodes connected to a programmable stimulator. In PD patients, tremor was selectively suppressed for < or = 11 years. In ET patients, results were satisfactory, but in 35% of the cases deteriorated with time, when tremor had an action component. Other types of dyskinesias were much less influenced. Sixty-eight patients were bilaterally implanted, and 14 were implanted contralateral to a previous thalamotomy. Side effects were often minor, well tolerated, and immediately reversible. Three secondary scalp infections led to temporary removal of implanted material. There was no permanent morbidity. Long-term Vim stimulation, which is reversible, adaptable, and well tolerated, even by bilaterally operated-on (68 of 134) and by elderly patients, should replace thalamotomy in the regular surgical treatment of parkinsonian and essential tremors. More recently, we stimulated the subthalamic nucleus (STN) in 51 patients (44 bilateral) and the globus pallidus internus (GPi) in 12 patients (seven bilateral). STN stimulation has a spectacular effect on akinesia and rigidity and may improve the patients so as to maintain them all day at a level similar to their best "on" periods. A 30-50% reduction in drug dosage was possible in most of the patients. GPi stimulation has indications and effects similar to those of pallidectomy: abnormal involuntary movements are totally suppressed, whereas effects on akinesia and rigidity are not so important as they are with STN stimulation. For all three targets, morbidity is low and reversible, even when bilateral implantations are performed. The deep-brain stimulation method has now proved its safety as compared with ablative surgery and is able to provide a significant improvement to these severely disabled patients. Long-term follow up is establishing the security of the method, which should be considered in earlier stages of the disease actively to participate to rehabilitation.

Electric Stimulation↗
PubMed1998

High-frequency stimulation of the subthalamic nucleus suppresses absence seizures in the rat: comparison with neurotoxic lesions.

High-frequency electrical stimulation of deep brain structures has recently been developed for the surgical approach of neurologic disorders. Applied to the thalamus in tremors or to the subthalamic nucleus in Parkinson's disease, high-frequency stimulation has been demonstrated to exert a local inhibiting influence, leading to symptoms alleviation. In the present study, bilateral high-frequency stimulations (130 Hz) of the subthalamic nuclei suppressed ongoing spontaneous absence seizures in rats. This effect was dissociated from motor side-effects and appears specific to the subthalamic nucleus. Bilateral excitotoxic lesions of the subthalamic nuclei only partially suppressed absence-seizures. These results confirm the involvement of the basal ganglia system in the control of generalized seizures and suggest that high-frequency stimulations could be used in the treatment of some forms of seizures.

Animals↗
PubMed1998

Subthalamic nucleus or internal pallidal stimulation in young onset Parkinson's disease.

The aim of this study was to compare, retrospectively, the value of chronic bilateral stimulation of the internal globus pallidus (GPi) and the subthalamic nucleus (STN) in patients with young onset Parkinson's disease. We selected 13 consecutive patients with similar characteristics at the time of surgery: age at onset < 40 years, disabling motor fluctuations (Hoehn and Yahr stage 4 or 5 in off-drug phases) and levodopa-induced dyskinesias (LID). Eight patients were operated on in the STN and five in the GPi. The Unified Parkinson's Disease Rating Scale (UPDRS), timed motor tests and a LID scale were compared in on- and off-drug conditions before surgery and 6 months after surgery on stimulation using the chronic electrical parameters found to improve best the motor state of the individual patient, without adverse effects. In off-drug phases, the motor score of the UPDRS was improved by 71% with STN stimulation and by 39% with GPi stimulation on average. This difference was statistically significant (P < 0.05). Whereas rigidity and tremor showed good improvement in both groups, the decrease in the akinesia score was more pronounced in the STN group. In the STN group, the improvement of all motor symptoms was very close, or equal, to the best levodopa response. Thus the levodopa test was predictive of outcome. The improvement in off-drug period motor handicap allowed a decrease in the levodopa-equivalent dose only in the STN group (-56%). The voltage, frequency and pulse width used for chronic stimulation were lower in the STN group. In the on-drug phases there was a marked improvement in LID in the GPi group, as measured by the dyskinesias score during an acute levodopa test, whereas there was only a small decrease in the STN group (P < 0.05). However, in the long term, the reduction of levodopa dosage in the STN group led to an indirect reduction of LID similar to that in the GPi group during activities of everyday life. In conclusion, the overall results favour the neurosurgical treatment of Parkinson's disease by stimulating the STN rather than the GPi.

Adult↗
PubMed1998

Diagnostic value of two rapid and individual D-dimer assays in patients with clinically suspected pulmonary embolism: comparison with microplate enzyme-linked immunosorbent assay.

A semiquantitative enzyme-linked immunosorbent assay (ELISA) test (Instant IA D-dimer) and a new quantitative rapid and individual test (STA-Liatest DDi) were compared with the reference microplate ELISA (Asserachrom D-Di) for D-dimer testing in 142 patients clinically suspected of pulmonary embolism, on the basis of clinical symptoms and signs, electrocardiogram, blood gases and chest X-Ray abnormalities. The cut-off value for the quantitative tests was 500 ng/ml and Instant IA was interpreted by three readers. Pulmonary embolism was confirmed by lung scan or angiography in 60 patients (42%). The sensitivities of ELISA and STA-Liatest DDi were 92% [95% confidence interval (CI) 82-97%] and 93% (95% CI 84-98%), respectively. The three readings of Instant IA D-dimer disagreed in 27 (19%) of the patients and sensitivity varied from 83 to 93% according to the readers. In the 115 patients with concordant readings, sensitivity was 92% (95% CI 82-98%). These results suggest that STA Liatest DDi may be used instead of microplate ELISA for the exclusion of pulmonary embolism, whereas the use of Instant IA D-dimer for this purpose is limited by the number of discordant results.

Adult↗
PubMed1997

Roles of GABA, glutamate, acetylcholine and STN stimulation on thalamic VM in rats.

The effects of high frequency stimulation of the subthalamic nucleus (STN) and of iontophoretic application of different neurotransmitters on neuronal activities of the ventromedial thalamic nucleus (VM) were investigated in rats. GABA, when applied iontophoretically, inhibited VM neuronal activity while bicuculline, L-glutamic acid and acetylcholine enhanced the firing rates of the same VM neurons. High frequency stimulation of the STN increased VM neuronal activity in a frequency-dependent manner, which could be blocked by MK801. These results suggest that GABAergic, cholinergic and glutamatergic input information converge in the same VM neurons and that an increase in the delivery of glutamatergic neurotransmitter activities in the VM is involved in the process of high frequency stimulation of the STN.

Acetylcholine↗