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Marc Peschanski

Publications and source records attributed to Marc Peschanski.

25 records · Page 2Linked to original sources

Fetal neural grafts for Huntington's disease: a prospective view.

Intrastriatal transplantation of striatal neuroblasts from human fetuses is a promising approach for treatment of Huntington's disease, on the basis of many experimental animal studies and, most recently, pilot clinical trials. Technically, several issues remain to be resolved (e.g., the precise site of dissection of the fetal tissue; the number and location of the fetal striatal implants; or the use of immunosuppressive therapy), and await larger-scale trials and purposely designed protocols. Further clinical data must also be obtained, and preliminary promising results must be replicated in a patient group large enough to provide conclusive results. It is important to establish (1) the amount of clinical benefit provided to the patient by the grafted cells; (2) the anticipated duration of clinical benefits; and (3) the secondary rate of decline after the benefit of the graft has been overbalanced. Evaluation of these parameters will require very long-term follow-up of the patients involved, over several years after grafting, before the technique can eventually be proposed widely to patients.

Animals↗

Clinical relevance of electrophysiological tests in the assessment of patients with Huntington's disease.

Assessment programs recently designed to follow-up patients with Huntington's disease (HD) in therapeutic trials have not included electrophysiological testing in the list of mandatory examinations. This omission is likely due to the current lack of data establishing a clear correlation between the electrophysiological results and those of clinical assessment. We address this issue in a cohort of 36 patients at relatively early stages of the disease (I and II). Electrophysiological studies comprised the recording of palmar sympathetic skin responses (SSRs), blink reflexes (BRs), thenar long latency reflexes (LLRs), cortical somatosensory evoked potentials (SEPs), and electromyographic silent periods evoked by transcranial magnetic stimulation (SPs). Results were analyzed with reference to disease duration and staging and to specific cognitive, psychiatric, and motor alteration. SEPs were the most and very sensitive markers, because they were abnormal in 94% of patients. Except for LLRs, alteration of electrophysiological results increased in parallel to the evolution of the disease. Except for LLRs and SSR latency, electrophysiological results correlated with those of specific clinical examinations. In particular, an increased BR latency or a reduced amplitude of the N20 component of SEPs correlated with the extent of bradykinesia, whereas a reduced amplitude of SSRs or of the N30 component of SEPs correlated with hyperkinesia. Overall, electrophysiological tests, in particular SEPs and BRs, appeared sensitive and interesting in the follow-up of HD patients and correlated with various clinical parameters, suggesting that these easy to perform and noninvasive repeatable examinations could be added fruitfully to the assessment programs for HD.

Adult↗

The antalgic efficacy of chronic motor cortex stimulation is related to sensory changes in the painful zone.

Epidural motor cortex stimulation (MCS) could achieve good pain control in patients with drug-resistant chronic neurogenic pain. In the search for parameters associated with the favourable outcome of this surgical procedure, quantitative sensory testing was performed in a series of 31 patients treated by MCS for chronic pain. Non-nociceptive and nociceptive sensory thresholds were measured in the painful area and its contralateral homologous zone with the stimulator in 'off' and in 'on' position. All 13 patients who exhibited normal or quite normal non-nociceptive thermal thresholds within the painful area benefited from MCS. Of the remaining 18 patients with altered thermal sensory thresholds, eight patients nevertheless experienced good pain control by MCS. In these eight 'good responders', sensory thresholds were improved by switching 'on' MCS. In contrast, the last 10 patients showed abnormal thermal thresholds that were not modified by switching 'on' MCS, and did not respond clinically to MCS. Therefore, 'good responders' to MCS could be identified by the absence of alteration of non-nociceptive sensory modalities within the painful area, or by abnormal sensory thresholds that could be improved by MCS. These results additionally suggest that MCS acts on neural pathways involved in sensory discrimination that, in turn, are able to modulate the transmission of pain signals.

Adult↗

Invasion of human glioma biopsy specimens in cultures of rodent brain slices: a quantitative analysis.

OBJECT: The reliable assessment of the invasiveness of gliomas in vitro has proved elusive, because most invasion assays inadequately model in vivo invasion in its complexity. Recently, organotypical brain cultures were successfully used in short-term invasion studies on glioma cell lines. In this paper the authors report that the invasiveness of human glioma biopsy specimens directly implanted into rodent brain slices by using the intraslice implantation system (ISIS) can be quantified with precision. The model was first validated by the demonstration that, in long-term studies, established glioma cells survive in the ISIS and follow pathways of invasion similar to those in vivo. METHODS: Brain slices (400 microm thick) from newborn mice were maintained on millicell membranes for 15 days. Cells from two human and one rodent glioblastoma multiforme (GBM) cell lines injected into the ISIS were detected by immunohistochemistry or after transfection with green fluorescent protein-containing vectors. Preferential migration along blood vessels was identified using confocal and fluorescent microscopy. Freshly isolated (< or = 24 hours after removal) 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate-prelabeled human glioma biopsy specimens were successfully implanted in 19 (83%) of 23 cases, including 12 GBMs and seven lower grade gliomas (LGGs). Morphometric quantification of distance and density of tumor cell invasion showed that the GBMs were two to four times more invasive than the LGGs. Heterogeneity of invasion was also observed among GBMs and LGGs. Directly implanted glioma fragments were more invasive than spheroids derived from the same biopsy specimen. CONCLUSIONS: The ISIS combines a high success rate, technical simplicity, and detailed quantitative measurements and may, therefore, be used to study the invasiveness of biopsy specimens of gliomas of different grades.

Animals↗

The organization of spinal pathways to ventrobasal thalamus in an experimental model of pain (the arthritic rat). An electrophysiological study.

The spinal ascending pathways responsible for neuronal ventrobasal (VB) thalamic responses elicited by joint stimulation of the posterior paw were determined in arthritic rats used as a model of experimental pain. Responses of a same neurone to mechanical (movement--pressure--brushing) or thermal stimulation (50 degrees C) were analysed before and after discrete lesions in the white matter of the spinal cord. For 6 neurones responding exclusively to brushing applied on a small receptive field (RF) strictly contralateral to the recording site, responses were not altered as long as the contralateral dorsal column was intact. Twenty neurones exhibited bilateral symmetrical RF located on the posterior paws including the ankles and for some units the digits. They were driven by moderate pressure and/or mild sustained joint movement and by immersion in a hot water bath at 50 degrees C. Their responses were not significantly modified when the lesions destroyed most of the dorsal and the dorsolateral parts of the spinal cord. In 16/20 cases effect of one hemisection of the cord was studied: when the hemisection was contralateral to the recording site (n = 8) VB neuronal responses elicited from the paw ipsilateral to this side were eliminated in 6/8 cases; when the 1/2 section was ipsilateral to the recording site (n = 8) the lesion induced the elimination of the responses elicited from the paw opposite to the recorded VB for one unit only. The involvement of the spino-reticular pathways which have not only a crossed but also a non-crossed component is suggested. This hypothesis is discussed by comparison to data previously obtained, showing that by contrast in healthy rats the spino-thalamic tract is essential for VB neuronal responses to noxious stimuli.

Afferent Pathways↗

Functional changes in ventrobasal thalamic neurones responsive to noxious and non-noxious cutaneous stimuli after chloralose treatment: new evidence for the presence of pre-existing "silent connections" in the adult nervous system?

Twenty-five neurones of the thalamic VB complex of the rat, first characterized under moderate volatile anaesthesia (1/3 oxygen - 2/3 nitrous oxide, 0.5% halothane) were subsequently studied under deep chloralose anaesthesia. As described in a previous study, neurones were classified during the control period as "noxious" (N) "non-noxious" (Nn), or "convergent" (NnN) according to their responsiveness to cutaneous mechanical stimulations. For all the N (n = 15) and NnN (n = 4) neurones, the responses induced by noxious stimuli (mechanical electrical or thermal) progressively disappeared after chloralose administration. Simultaneous with disappearance of the responses elicited by noxious stimuli, responses to non-noxious stimuli appeared for 12 N neurones: 5 responded to a brisk tap applied to any part of the body, and 7 to brushing of light touch from a new receptive field (RF), at a variable distance from the initial RF, but always contralateral to the recording site. The Nn neurones (n = 6) continued to be activated by light touch or brushing but there was a consistent concentric enlargement of their RF. The NnN neurones also presented an enlarged RF to the non-noxious stimuli. The depressive an "unmasking" effects of chloralose are discussed and compared to the various indications of pre-existing connections in the CNS.

Animals↗