Biomedical subjects
Publications and source records attributed to L Defebvre.
We report the clinical and MRI findings of a 31-year-old healthy immuno-competent patient who presented following 48 hours of diffuse headache with progressive and severe rhombencephalomyelitis signs. Cerebral and medullar MRI confirmed the central nervous system improvement. Serology showed relation with cytomegalovirus infection. Spontaneous improvement was observed and favoured by ganciclovir administration.
The averaging of the ongoing activity of the electroencephalogram (EEG) allows extracting the potentials that are time-locked and phase-locked to an event. These potentials are described as evoked potentials. There is another type of change in the ongoing EEG, which is time-locked but not phase-locked to an event: the EEG rhythm reactivity, also called "Event-Related Desynchronization and Synchronization" (ERD/ERS) by Pfurtscheller. These changes are often visible to the naked eye but they cannot be extracted by the averaging technique. Their quantification requires another method, which was suggested by Pfurtscheller and Aranibar in 1977. This method consists in measuring the temporal evolution of the power of EEG signal within a given frequency band before, during, and after an event. ERD corresponds to the decrease in power of an EEG rhythm related to an event. Conversely, ERS corresponds to an increase in amplitude of an EEG rhythm related to the event. ERD represents the activation of the subjacent cortical areas. ERS would partly traduce the setting at rest of the cortex; it would also be related to the somesthetics afferents inputs. This method can be applied to the study of cortical activation in many situations: memory tasks, auditory processing, attention, anticipatory behavior, and voluntary movement. Thus, a voluntary self-paced movement of the dominant hand is preceded by an ERD of mu and beta rhythms occurring respectively 2 000 and 1 500 ms before the movement onset. This ERD is recorded over the contralateral central region. It becomes bilateral at the movement onset and reaches its maximum at the movement offset. It is then followed by an ERS of the beta rhythms. We show that ERD/ERS phenomena vary with the type of movement, and that their study allows exploring the modifications of cortical excitability that are observed in Parkinson's disease and in epilepsy with focal motor seizures.
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PATHOPHYSIOLOGY: In Parkinson's disease, the neurodegenerative process of the nigrostriatal dopaminergic pathways induces an increase in activity of the subthalamic nucleus and the medial globus pallidus, which cause inhibition of thalamo-cortical outputs explaining parkinsonism. HIGH-FREQUENCY DEEP BRAIN STIMULATION: The adverse effects induced by lesions of subcortical structures (thalamotomy, pallidotomy) have increased interest in chronic electrical stimulation proposed as a new therapy in Parkinson's disease. This technique is reversible and can be modulated with less adverse effects. TWO TARGETS: Two targets may be proposed in case of severe motor fluctuations: the medial globus pallidus and the subthalamic nucleus. Pallidial stimulation improves dramatically levodopa-induced dyskinesia and, with a variable degree, the parkinsonian triad. Subthalamic stimulation rapidly reverses akinesia, rigidity and tremor and also dyskinesias which progressively tend to diminish after decreasing L-dopa dosage. LONG-TERM EFFICACY: A follow-up period of a few years has confirmed that the beneficial effect is maintained. However, stimulation dose not prevent the development of certain symptoms (postural impairment, cognitive decline). LIMITED INDICATIONS: Chronic electrical stimulation of medial globus pallidus and subthalamic nucleus may be proposed for parkinsonian patients with severe motor fluctuations associated with abnormal involuntary movements which are not controlled by different medical therapies. Parkinsonian symptoms must still be levodopa responsive and cause severe clinical disability severely limiting daily living activities. Cognitive impairment and other severe pathologies are contraindications.
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Tremor associated with a single focal thalamic lesion has rarely been reported. Furthermore, the exact localization of the lesions is difficult to determine because of the imprecision of "conventional" radiology (computed tomography scan and/or "standard" magnetic resonance imaging). The aim of this study was to identify which thalamic structures are involved in tremor associated with a single focal thalamic lesion. We selected two patients who presented with unilateral postural and kinetic tremor of the upper limb related to a localized thalamic infarction. Three-dimensional T1-weighted magnetic resonance imaging sequence (MP-RAGE sequence) was used to determine the precise topography of the lesions by stereotactic analysis using the atlas of Hassler. The lesions were located within the pulvinar, the sensory nuclei, the mediodorsal nucleus, and the ventral lateral posterior nucleus (according to the classification of Hirai and Jones), the latter including the ventral intermediate nucleus (Vim according to the classification of Hassler). However, the Vim was spared. The subthalamic area, which can induce tremor, was not involved. After having compared the topography of the lesions with the clinical findings, we suggest that thalamic tremors may result from the interruption of the cerebellar outflow tract to the Vim within the thalamus.
We report the first French family with dentatorubral-pallidoluysian atrophy (DRPLA) in which three members, a 36-year-old woman (proband), her 34-year-old sister, and 14-year-old brother were affected. There was no family history of DRPLA and their father presented at age 66 with pes cavus but without any other neurologic symptoms. Molecular analysis of the DRPLA gene from blood leukocytes showed CAG repeat sizes to be 68/16 in the proband, 62/15 in her father, and 16/16 in her mother. This study provides support for the variable clinical presentation of this disease with incomplete penetrance in the father and demonstrates that DRPLA can be observed in the French Caucasian population.
We analyzed the segregation of genetic markers spanning chromosomal regions 2p13, 4p14-15, 4q21-23, 6q25-27, and 17q21 in nine French families affected by autosomal-dominant probable Parkinson's disease. These regions have been linked or associated with familial Parkinson's disease. Multipoint linkage and haplotype analyses excluded 2p13 and 4p14-15 loci in five of nine families. For three families, which were equivocal for two-point linkage at D4S405, the ubiquitin carboxy-terminal hydrolase gene (UCH-L1) was sequenced. In one family, a novel UCH-L1 M124L mutation that did not segregate with early-onset disease was identified. This suggests that rare variants in this gene may not be pathogenic. In seven of nine families, it could be inferred that affected individuals did not share 4q21-23 (alpha-synuclein) haplotypes. All families were unequivocally excluded by haplotype analysis from the parkin locus on 6q25-27. Finally, the 17q21 region was excluded in four of nine families, and no mutation in the tau gene was identified in the five remaining families. Findings from this study confirm genetic heterogeneity within familial parkinsonism.
In treatment for severe Parkinson's disease (PD), a recent procedure was developed which consists of implanting electrodes in the internal Globus Pallidus (GPi) for chronic electrical stimulation. The consequences on cognitive function of such an intervention are quite variable. Although most group studies observed no significant post-operative change, individual cases of post-operative cognitive impairment were reported. The present study reports the case of a PD patient who underwent bilateral implantation of deep brain stimulation electrodes in the GPi and who, after surgery, suffered from a severe dysexecutive syndrome. An extensive neuropsychological examination showed a selective negative effect of pallidal stimulation on tests assessing executive function. When the stimulation was turned off, the impairment was partly reversible. This observation emphasizes the role of the GPi in executive function.
OBJECTIVE: (1) To determine if there are changes in event-related desynchronization/event-related synchronization (ERD/ERS) patterns when the movement is sustained? (2) To determine, from a technical point of view for ERD calculation, if it is possible to take the reference period during muscular activation? METHODS: Eight healthy subjects performed two series of brief and sustained self-paced extensions with their dominant wrist. The end of the sustained movement was externally triggered by the examinator. ERD/ERS was calculated in mu and beta bands from 13 source derivations covering motor areas, computed from 29 scalp electrodes. Movement onset and offset were determined by electromyographic activity (EMG) of wrist extensors. RESULTS: When the movement was sustained, power in the mu and beta bands returned to baseline values within 4-5 s. Movement duration had little effect, if at all, on both pre and post-movement periods. Compared to brief movement, after the onset of the prolonged movement, mu ERD just returned to baseline, without synchronization. In contrast, beta ERS was still present though earlier and much lower. CONCLUSIONS: The reference period for ERD calculation may be taken during muscular activation if its duration is long enough. Beta synchronization may occur despite a non-deactivated motor cortex, suggesting a contribution from afferent somesthetic inputs.
OBJECTIVE: Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the most frequent neurodegenerative cognitive disorders. However, FTD remains poorly recognised clinically. The use of (99m)HmPAO-single photon emission computed tomography (SPECT) has been demonstrated in the differentiation of AD and FTD. Nethertheless, there are very few comparative studies designed to assess its precise value in this differential diagnosis. The aim was to determine a simple decision rule, deduced from statistical analysis, which, if applied to regions of interest (ROIs) and mini mental state examination (MMSE), could improve the predictive value of SPECT in differential diagnosis between AD and FTD. METHODS: Forty patients, 20 with probable AD and 20 with probable FTD were included. All patients underwent brain SPECT imaging, after an intravenous injection of (99m)Tc HmPAO-(555mBq). For each patient, 20 ROIs were determined on the Fleishig's slice and their activity was normalised to the mean cerebellar activity. Bivariate analysis (Wilcoxon rank tests) and multivariate analysis (stepwise discriminant analysis) were performed to determine the subgroup of variables able to give the highest predictive value for this differential diagnosis. A simple decision rule was built from a predictive score derived by factorial discriminant analysis. RESULTS: As previously described, the fixation defect was found in frontal regions of interest (ROIs) in FTD and in the left temporoparietal-occipital ROIs in AD. Among the 21 variables, five were finally selected: right median frontal, left lateral frontal, left tempoparietal, left temporoparietal-occipital areas, and MMSE. One hundred per cent of patients with FTD were correctly classified by the decision rule (20/20 patients) and 90% of patients with AD (18/20). CONCLUSION: AD and FTD are differentiated by SPECT. Automatic classification based on a decision rule deduced from factorial discriminant analysis could enhance its performance.
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The aim of this study was to specify the frontal type dysfunction widely reported in Parkinson's disease (PD) early in the course of the disease and before dopaminergic therapy. Seventeen "de novo" PD patients and 17 healthy control subjects performed modified versions of the Stroop word-color test and the Brown Peterson paradigm. A dissociation between results on the two tasks was observed in PD patients. They had difficulties in inhibiting a strong habitual response and establishing a new, better adapted pattern of response; but they performed as well as controls in a dual-task paradigm requiring correct allocation of the processing resources of working memory. Early in the course of the disease, untreated PD patients suffer from dysfunction of the supervisory attentional system. However, the present findings suggest that this system is not a single unit but rather could be composed of multiple subsystems whose sensitivity depends on the origin of frontal dysfunction. Indeed, only a few of these subsystems seemed to be impaired in de novo PD patients. It can be hypothesized that those involved in the phenomena of adaptation and consolidation of currently appropriate responses depend on the dorsolateral prefrontal loop, which is affected by the dopaminergic innervation of the caudate nucleus.
Cortical electroencephalographic rhythms reactivity may be quantified using event-related desynchronization (ERD) and synchronization (ERS) methods. We therefore studied cortical activation occurring during programming and performance of voluntary movement in healthy subjects. EEG power evolution within the reactive frequency bands (mu and beta central rhythms) was averaged before, during and after a minimum of 50 self-paced flexions of the thumb. Recordings in 18 normal adults showed that ERD (decrease in power) of mu rhythm started 2,000 ms before movement onset, while ERD of beta rhythm started 1,500 ms before movement onset. Early ERD of mu and beta rhythms were located over the contralateral central region covering primary motor cortex. They were followed by bilateral ERD occurring over ipsilateral and contralateral central regions during performance of the movement. At the end of the movement, an ERS (increase in power) of beta rhythm occurred. These results suggest that programming of voluntary movement induces early activation in contralateral sensorimotor areas, while performance of the movement induces bilateral activation in sensorimotor areas. ERS of beta rhythm occurring at the end of the movement could correspond to inactivation of motor areas activated by movement. Based on EEG activity, ERD and ERS prove to be useful methods to analyze cortical activation during programming and performance of voluntary movements with good spatial and temporal resolution.
This study was aimed at determining the spatiotemporal distribution of event-related desynchronization (ERD) during self-paced voluntary movement in order to establish the interest of this method for the analysis of movement programming in Parkinson's disease. Desynchronization of mu rhythm was recorded 2 s before to 0.5 s after right then left self-paced voluntary wrist flexions from 11 leads covering the primary sensorimotor cortex (central), supplementary motor area (frontocentral) and parietal cortex (parietocentral). Recordings were obtained from ten control subjects, ten patients treated for Parkinson's disease (bilateral symptoms) and 20 patients presenting with right or left hemiparkinsonism before and after chronic administration of L-dopa. In the control group, ERD started over the contralateral primary sensorimotor cortex 1,750 ms before movement and was bilateral just before performance of the movement. In both treated and de novo Parkinson's disease groups, decrease in ERD latency (1,000 to 1,250 ms before movement) was only observed when movements were performed with the akinetic hand and corresponded to a decrease in motor cortical activity. This confirmed that programming of movement is affected in Parkinson's disease. Earlier ERD with central ipsilateral distribution were also observed, suggesting that other cortical areas might be activated to compensate for dysfunction of movement programming and to increase the level of cortical activity required for performance of the movement. The administration of L-dopa to de novo hemiparkinsonians patients resulted in increased ERD latency over contralateral and ipsilateral central areas. As in the treated Parkinson's disease group, frontocentral ERD could also be recorded. L-dopa would thus partially restore the affected motor programmation and modulate cortical activation in both supplementary motor area and primary motor cortex, the later receiving more afferences from basal ganglia.
In five generations of the French M-E kindred, 11 members are now known to be or have been affected by a form of spongiform encephalopathy previously recorded as Gerstmann-Sträussler-Scheinker disease. Mean age at onset was 28 years (range 21-34 years). In six instances, these patients were hospitalized in psychiatric institutions with various diagnoses, the most frequent being mania or mania-like symptoms. Dementia occurred progressively after a lengthy course. Histological studies showed atrophy of the cerebellar molecular layer, which contained kuru and multicentric plaques labelled with anti-prion protein antibodies. Spongiosis was not prominent and remained largely limited to the periphery of plaques; it was more marked in the thalamus, where plaques were scarce. A 192 base pair (bp) insert (eight extra repeats of 24 bp) in the octapeptide coding region of the prion protein gene (PRNP) within a codon-129 methionine allele was found in four symptomatic subjects. Early age at onset, the prominence of psychiatric symptoms and the long course of the disease are noticeable clinical features in this family with an inherited prion disease due to a new insertional mutation in PRNP.
OBJECTIVE: To investigate the cognitive profile of first degree relatives of patients with familial Parkinson's disease to determine whether these subjects presented signs of neuropsychological dysfunction compared with healthy controls. Results of recent genetic and neuroimaging studies suggest a genetic contribution to the aetiology of Parkinson's disease and underline the interest in identifying preclinical signs of the disease. METHODS: A battery of tests evaluating executive function was administered to 41 first degree relatives of patients with well documented familial Parkinson's disease and 39 healthy controls. A factorial discriminant analysis allowed isolation of a subgroup of 15 first degree relatives who could be considered as impaired compared with the healthy controls. Among these 15 "deviant" relatives, nine performed globally worse than the control subjects on all tasks. The six other subjects had mean or even high scores on all task variables, except on those highly correlated with the discriminant score of the factorial discriminant analysis. RESULTS AND CONCLUSION: Among the first degree relatives of patients with familial Parkinson's disease, some manifested executive dysfunction comparable with that typically associated with the disease. Such impairment could represent a preclinical form of Parkinson's disease.
The spatiotemporal pattern of event-related desynchronization (ERD) during the motor preparation period preceding a self-paced voluntary wrist-flexion was compared in two groups of 10 right and 10 left hemiparkinsonian patients, before and after chronic administration of L-DOPA. ERD was computed in the 9-11 Hz frequency band from 11 source derivations covering the medial frontocentral, central and parietocentral areas, during two successive left and right experimental conditions (100 self-paced wrist flexions). In the two groups ERD appeared with a shorter latency over the contralateral primary sensorimotor area, when the movements were performed with the akinetic hand. After L-DOPA administration, earlier ERD onset before the movement was observed in both groups over the contralateral and ipsilateral central and parietocentral areas. A medial frontocentral ERD distribution was also observed before the onset of movement, especially in the right hemiparkinsonian group. Delayed ERD onset, which shows that programming of movement is affected in Parkinson's disease, may be partially corrected by L-DOPA therapy.