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Biomedical subjects

Stephan Chabardes

Publications and source records attributed to Stephan Chabardes.

7 recordsLinked to original sources
PubMed2007

Viral clostridial light chain gene-based control of penicillin-induced neocortical seizures.

Restraining excitatory neurotransmission within a seizure focus provides a nondestructive treatment strategy for intractable neocortical epilepsy. Clostridial toxin light chain (LC) inhibits synaptic transmission by digesting a critical vesicle-docking protein, synaptobrevin, without directly altering neuronal health. This study tests the treatment efficacy of adenoviral vector delivered LC (AdLC) on a model of seizures in rats induced by motor cortex penicillin (PCN) injection. LC expression significantly reduced electroencephalogram (EEG) frequency, amplitude, duration, and latency compared to control groups injected with either an adenoviral vector bearing green fluorescent protein (AdGFP) or phosphate buffered solution (PBS). Correspondingly, LC gene expression improved behavioral manifestations including seizure severity and latency. There was no statistical difference in motor function before and after vector administration between treatment and control groups. Histological analysis revealed spatially discrete LC expression with corresponding synaptobrevin depletion in the cortex surrounding the injection site. Thus, vector-mediated LC gene delivery is capable of improving both the EEG and behavioral manifestations of PCN-induced focal neocortical seizures through synaptobrevin depletion.

Animals↗
PubMed2005

A putative generalized model of the effects and mechanism of action of high frequency electrical stimulation of the central nervous system.

High-frequency stimulation (HFS) of neural structures has been used since 1997 as an alternative to lesions in functional neurosurgery of movement disorders, and more recently, it has been applied to the treatment of epilepsies, obsessive-compulsive disorders, cluster headaches, and has other applications in experimental models, particularly for obesity. Although their clinical efficacy is not questioned, and that the effects most of the time parallel those of ablative techniques, leading to the concept of functional inhibition, the intimate mechanisms by which HFS induces excitation within fiber bundles and seems to inhibit cellular nuclei is still strongly debated. Principally due to the observation of long-term clinical effects over a period up to 15 years, it is clear that the mechanism is not due to a progressive lesion, as at every moment the interruption of stimulation reverses totally the effects. There is no current proof that long-term HFS is able to reset neural networks, or to induce profound modifications of the functional organization or of the synaptic connectivity. To understand what is responsible for the immediate, reversible and adaptable effects of HFS, several mechanisms must be considered, which might be involved simultaneously or in sequence: i) Jamming of neural transmission through stimulated nuclei is one possibility, based on the principle that the regular imposed activity might drive the neurons to fire in a regular pattern, making it impossible to transmit more subtle messages, either normal or abnormal. Although it is difficult to prove this type of mechanism, it might account for the reports of increased activity following HFS in various structures. ii) Direct inhibition of spike initiation at the level of the membrane could be due to activation of inhibitory terminals, particularly gaba-ergic, or by a blockade of the voltage gated ion channels. iii) Recent data show that HFS decreases the production and release of low molecular weight proteic neurotransmitters, which could account for the functional inhibition while the efferent axon is still excited by the electrical stimulus. iv) Retrograde activation of upstream neuronal structures, as reported in the external pallidum during stimulation of STN, might be responsible of additional jamming-like effects due to collisions with descending spikes.

Animals↗
PubMed2003

Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson's disease.

BACKGROUND: Although the short-term benefits of bilateral stimulation of the subthalamic nucleus in patients with advanced Parkinson's disease have been well documented, the long-term outcomes of the procedure are unknown. METHODS: We conducted a five-year prospective study of the first 49 consecutive patients whom we treated with bilateral stimulation of the subthalamic nucleus. Patients were assessed at one, three, and five years with levodopa (on medication) and without levodopa (off medication), with use of the Unified Parkinson's Disease Rating Scale. Seven patients did not complete the study: three died, and four were lost to follow-up. RESULTS: As compared with base line, the patients' scores at five years for motor function while off medication improved by 54 percent (P<0.001) and those for activities of daily living improved by 49 percent (P<0.001). Speech was the only motor function for which off-medication scores did not improve. The scores for motor function on medication did not improve one year after surgery, except for the dyskinesia scores. On-medication akinesia, speech, postural stability, and freezing of gait worsened between year 1 and year 5 (P<0.001 for all comparisons). At five years, the dose of dopaminergic treatment and the duration and severity of levodopa-induced dyskinesia were reduced, as compared with base line (P<0.001 for each comparison). The average scores for cognitive performance remained unchanged, but dementia developed in three patients after three years. Mean depression scores remained unchanged. Severe adverse events included a large intracerebral hemorrhage in one patient. One patient committed suicide. CONCLUSIONS: Patients with advanced Parkinson's disease who were treated with bilateral stimulation of the subthalamic nucleus had marked improvements over five years in motor function while off medication and in dyskinesia while on medication. There was no control group, but worsening of akinesia, speech, postural stability, freezing of gait, and cognitive function between the first and the fifth year is consistent with the natural history of Parkinson's disease.

Activities of Daily Living↗
PubMed2002

Treatment results: Parkinson's disease.

Deep brain stimulation (DBS) is a neurosurgical treatment of Parkinson's disease that is applied to three targets: the ventral intermediate nucleus of the thalamus (Vim), the globus pallidus internas (GPi) and the subthalamic nucleus (STN). Vim DBS mainly improves contralateral tremor and, therefore, is being supplanted by DBS of the two other targets, even in patients with tremor dominant disease. STN and GPi DBS improve off-motor phases and dyskinesias. There is little comparative data between these procedures. The magnitude of the motor improvement seems more constant with STN than GPi DBS. STN DBS allows a decrease in antiparkinsonian drug doses and consumes moderate current. These advantages of STN over GPi DBS are offset by the need for more intensive postoperative management. The DBS procedure has the unique advantage of reversibility and adjustability over time. Patients with young-onset Parkinson's disease suffering from levodopa-induced motor complications but still responding well to levodopa and who exhibit no behavioral, mood, or cognitive impairment benefit the most from STN DBS. Adverse effects more specific of the DBS procedure are infection, cutaneous erosion, and lead breaking or disconnection. Intracranial electrode implantation can induce a hematoma or contusion. Most authors agree that the benefit to risk ratio of DBS is favorable.

Electric Stimulation Therapy↗
PubMed2002

Intraoperative micro- and macrostimulation of the subthalamic nucleus in Parkinson's disease.

Studying the clinical effects induced by electrical stimulation of the subthalamic nucleus (STN) area in a parkinsonian patient under local anesthesia is a mandatory step to determine the precise location of the final chronic electrode. Using multiple microelectrodes, preferably in a concentric parallel array allows a precise mapping of the STN region. The most reliable features to determine the suitable target are stimulation-induced dyskinesias and rigidity decrease at a low intensity without adverse effects or only at far higher intensities. New skills are needed to assess all stimulation-induced effects and interpret them in anatomo-functional terms.

Brain Mapping↗
PubMedDate not supplied

Unsupervised Spike Sorting of extracellular electrophysiological recording in subthalamic nucleus of Parkinsonian patients.

The present study demonstrates the application of the Unsupervised Spike Sorting algorithm (USS) to separation of multi-unit recordings and investigation of neuronal activity patterns in the subthalamic nucleus (STN). This nucleus is the main target for deep brain stimulation (DBS) in Parkinsonian patients. The USS comprises a fast unsupervised learning procedure and allows sorting of multiple single units, if any, out of a bioelectric signal. The algorithm was tested on a simulated signal with different levels of noise and with application of Time and Spatial Adaptation (TSA) algorithm for denoising. The results of the test showed a good quality of spike separation and allow its application to investigation of neuronal activity patterns in a medical application. One hundred twenty-four single channel multi-unit records from STN of 6 Parkinsonian patients were separated with USS into 492 single unit trains. Auto- and crosscorrellograms for each unit were analyzed in order to reveal oscillatory, bursting and synchronized activity patterns. We analyzed separately two brain hemispheres. For each hemisphere the percentage of units of each activity pattern were calculated. The results were compared for the first and the second operated hemispheres of each patient and in total.

Action Potentials↗