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Biomedical subjects

Anne-Marie Bonnet

Publications and source records attributed to Anne-Marie Bonnet.

13 recordsLinked to original sources
PubMed2006

Motor score of the Unified Parkinson Disease Rating Scale as a good predictor of Lewy body-associated neuronal loss in the substantia nigra.

BACKGROUND: How well the motor symptoms assessed by the motor section of the Unified Parkinson Disease Rating Scale (UPDRS3) reflect the neuronal loss observed in the substantia nigra is not known. OBJECTIVE: To study the relationships among the motor symptoms assessed by the UPDRS3, Lewy body-associated neuronal loss in the substantia nigra, and duration of disease. DESIGN: Longitudinal, prospective, clinicopathological study. SETTING: Long-term care facility of a university hospital. PATIENTS: Eighteen elderly patients with a parkinsonian syndrome, studied prospectively but selected post mortem on the basis of the presence of Lewy bodies, and 5 age-matched control subjects. METHODS: One map of a section of the substantia nigra, indicating the location of all the nucleolated neuronal profiles, was drawn for each case. Neuronal density was estimated using a tessellation method. The relationship between time and neuronal loss and between neuronal loss and motor symptoms (assessed by the UPDRS3) was studied by means of regression analysis, using linear and exponential models. RESULTS: The neuronal density was linearly linked with the UPDRS3 score (r = -0.83 [P<.001]). Each point added to the UPDRS3 score corresponded to an estimated loss of 25 neurons/mm(3). The density of neuronal profiles in the substantia nigra decreased exponentially with time (r = -0.73 [P<.001]). Extrapolation of the curve suggested a presymptomatic phase of 5 years. CONCLUSION: The UPDRS3 score is linearly linked to neuronal density, which, in Lewy body diseases, decreases exponentially with time at a similar pace in this series of elderly patients and in the younger patients described in the literature.

Aged↗
PubMed2005

Back problems in Parkinson's disease: an underestimated problem.

STUDY DESIGN: Cross-sectional survey. OBJECTIVES: To estimate the extent of back pain in Parkinson's disease (PD). SUMMARY OF BACKGROUND DATA: PD is a common and disabling condition during the course of which back pain may develop. In contrast, the literature on the epidemiology of back pain in PD is poor. METHODS: Patients with PD, seen consecutively in a neurology clinic over a period of 4 months, were inquired about back pain through a self-questionnaire and compared to an age- and sex-matched control group of chronically ill patients. RESULTS: The study involved 104 parkinsonians (mean age: 67.3 years) who had had PD for an average of 11.6 years, and 100 controls (mean age: 65.8 years) who had chronic heart disease or diabetes for an average of 14.2 years. Sixty-two parkinsonians and 23 controls reported back pain. The prevalence was 59.6% in the parkinsonian group and 23.0% in the control group (P < 0.0001). Pain severity was evaluated with a visual analogic scale and averaged 54 +/- 23 mm in parkinsonians and 41 +/- 19 mm in control (P < 0.0001). CONCLUSIONS: Chronic back pain is quite common in PD. It is responsible for a substantial functional impact and needs more attention to reduce disability of such patients.

Adult↗
PubMed2005

G2019S LRRK2 mutation in French and North African families with Parkinson's disease.

Mutations in LRRK2 were recently identified in autosomal dominant Parkinson's disease (PD), including the G2019S mutation. To evaluate its frequency, we analyzed 198 probands with autosomal dominant PD, mostly from France and North Africa. Surprisingly, the frequency in North African families (7/17, 41%) was greater than those from Europe (5/174, 2.9%). The clinical features in 21 patients, including 1 with a homozygous mutation, were those of typical PD, with lower Mini-Mental State Examination scores. There were also 15 unaffected mutation carriers, aged 32 to 74 years. LRRK2 mutations appear to be a common cause of autosomal dominant PD, particularly in North Africa.

Adult↗
PubMed2004

Effects of high-frequency stimulation on subthalamic neuronal activity in parkinsonian patients.

BACKGROUND: High-frequency stimulation of the subthalamic nucleus (STN) is a neurosurgical alternative to medical treatment in levodopa-responsive forms of Parkinson disease. The mechanism of action of STN stimulation remains controversial, although an inhibition of overactive STN neurons has been postulated. OBJECTIVE: To determine the effects of high-frequency STN stimulation on the neuronal activity of STN neurons in Parkinson disease patients. PATIENTS: Single-unit recordings of the neuronal activity of the STN were obtained before, during, and after the application of intra-STN electrical stimulation in 15 Parkinson disease patients. Changes in firing frequency and pattern were analyzed using various combinations of stimulus frequency (range, 14-140 Hz). RESULTS: Stimulation at a frequency greater than 40 Hz applied within the STN significantly decreased the firing frequency and increased the burst-like activity in the firing pattern of STN neurons. An aftereffect was observed in cells that had been totally inhibited during high-frequency stimulation. CONCLUSION: The beneficial effects of high-frequency stimulation result from a change in the firing pattern of cellular discharge and a blockade of the spontaneous overactivity of STN neurons.

Aged↗
PubMed2004

Subthalamic stimulation in Parkinson disease: with or without anesthesia?

OBJECTIVE: To study the effects of general anesthesia on the postoperative outcome of patients with Parkinson disease (PD) who underwent surgery using bilateral placement of stimulating electrodes within the subthalamic nucleus (STN). DESIGN: Retrospective analysis. SETTING: Hôpital de la Salpêtrière, Paris, France. PATIENTS: Fifteen PD patients who underwent bilateral implantation of electrodes within the STN received general anesthesia because of severe anxiety, poorly tolerated off-period dystonia, or respiratory difficulties. These patients were compared with 15 patients matched for age, disease duration, and parkinsonian motor disability who underwent the same neurosurgical procedure under local anesthesia. MAIN OUTCOME MEASURE: Motor disability scores. RESULTS: After surgery, the severity of parkinsonian motor disability was markedly improved in both groups of patients. Compared with patients who were under local anesthesia during the operation, the residual parkinsonian motor score under stimulation (with ["on"] or without ["off"] levodopa) and the intensity of stimulation were higher in patients who were under general anesthesia during the operation. CONCLUSIONS: Although the improvement of parkinsonian motor disability is greater in PD patients who receive local anesthesia during surgery, general anesthesia can be performed in patients unable to tolerate prolonged states without levodopa.

Aged↗
PubMed2003

Subthalamic stimulation in Parkinson disease: intraoperative predictive factors.

BACKGROUND: High-frequency stimulation of the subthalamic nucleus (STN) is an effective treatment for advanced forms of Parkinson disease. Postoperative improvement of motor parkinsonian disability is known to depend on patient selection and surgical targeting. OBJECTIVE: To determine which clinical and electrophysiological variables evaluated during the operation predict the postoperative clinical outcome of patients with Parkinson disease treated by bilateral high-frequency stimulation of the STN. METHODS: Intraoperative clinical and electrophysiological data obtained in 41 patients with Parkinson disease who underwent bilateral implantation of electrodes for STN stimulation were correlated with the improvement in parkinsonian disability assessed 6 months after the operation. RESULTS: The extent of STN neuronal activity recorded along the trajectory of the therapeutic electrode had no effect on the postoperative clinical outcome. The intraoperative improvement in segmental akinesia, but not rigidity, was predictive of the postoperative improvement in parkinsonian motor disability and reduction in daily levodopa-equivalent dosage. Parkinsonian motor disability scores assessed after surgery were lower in patients with intraoperative stimulation-induced dyskinesias than in those without stimulation-induced dyskinesias. CONCLUSION: The improvement of segmental akinesia and the observation of dyskinesias provoked by stimulation during the operation predict the best postoperative effects of bilateral STN stimulation on parkinsonian motor disability.

Disability Evaluation↗
PubMed2003

Coding polymorphisms in the parkin gene and susceptibility to Parkinson disease.

BACKGROUND: Mutations in the parkin gene, an E3 protein-ubiquitin ligase, cause autosomal recessive early-onset Parkinson disease (PD). The role of polymorphisms in the parkin gene as risk factors for PD is still unclear, as the results in the literature are contradictory. PATIENTS: We compared the allele and genotype frequencies of the Ser167Asn, Arg366Trp, Val380Leu, and Asp394Asn polymorphisms in 194 patients with PD (92 familial and 102 sporadic) and 125 control subjects. RESULTS: Homozygous Val380 was significantly associated with sporadic PD (P =.008). There was also a trend toward an association of homozygous Asp394 with familial PD (P =.07). CONCLUSIONS: Some parkin polymorphisms appear to be risk factors for sporadic or familial PD. The functional effects of these coding polymorphisms need to be established, and further studies on parkin polymorphisms in PD should be undertaken.

Adult↗
PubMed2003

How much phenotypic variation can be attributed to parkin genotype?

To establish phenotype-genotype correlations in early-onset parkinsonism, we have compared the phenotype of a large series of 146 patients with and 250 patients without parkin mutations. Although no single sign distinguished the groups, patients with mutations had significantly earlier and more symmetrical onset, dystonia more often at onset and hyperreflexia, slower progression of the disease, and a tendency toward a greater response to levodopa despite lower doses. After forward stepwise multiple logistic regression analysis, dystonia at onset and brisk reflexes were not longer significantly different but were correlated with age at onset rather than the presence of the parkin mutation. Age at onset in carriers of parkin mutations varied as did the rate of progression of the disease: the younger the age at onset the slower the evolution. The genotype influenced the phenotype: carriers of at least one missense mutation had a higher United Parkinson's Disease Rating Scale motor score than those carrying two truncating mutations. The localization of the mutations was also important because missense mutations in functional domains of parkin resulted in earlier onset. Patients with a single heterozygous mutation had significantly later and more asymmetrical onset and more frequent levodopa-induced fluctuations and dystonia than patients with two mutations.

Adolescent↗
PubMed2003

Parkinson's disease, subthalamic stimulation, and selection of candidates: a pathological study.

We report on a patient with Parkinson's disease (PD) who was moderately improved by stimulation of the subthalamic nucleus (STN) and died 2 years after electrode implantation. After neurosurgery, symptoms that had responded to levodopa treatment preoperatively continued to improve. Postural instability, dysarthria, and cognitive impairment continued to worsen, despite STN stimulation and levodopa treatment. Postmortem examination of the brain confirmed the diagnosis of PD and showed that the electrodes had been correctly positioned within the STN. The failure of STN stimulation in this patient confirms the importance of screening and excluding patients from surgery with evolving parkinsonian axial symptoms or cognitive impairment.

Aged↗
PubMed2002

Compulsions, Parkinson's disease, and stimulation.

Pathophysiological models suggest that obsessive compulsive disorder (OCD) might be associated with dysfunctions in cortico-striato-pallido-thalamo-cortical neuronal circuits. We implanted subthalamic electrodes to alleviate parkinsonian symptoms in two patients who had Parkinson's disease and a history of severe OCD. Parkinsonian disability improved postoperatively in both patients, and 2 weeks after the procedure, their compulsions had disappeared and obsessive symptoms improved (58% improvement for patient 1 on the Yale-Brown obsessive compulsive scale, 64% for patient 2). The improvements in these two patients suggest that high-frequency stimulation could improve function in the subcortical-limbic circuitry in patients with severe OCD.

Electric Stimulation Therapy↗
PubMed2002

Association study between iron-related genes polymorphisms and Parkinson's disease.

We have conducted a case-control study in order to test for an association between 8 intragenic polymorphisms of 5 iron-related genes (transferrin, transferrin receptor1, HFE, frataxin and lactoferrin) and Parkinson disease. Comparison of genotypes and allele frequencies did not differ significantly between cases and controls for all studied polymorphisms except the G258S transferrin polymorphism, for which a higher frequency of the G allele was found among cases (p=0.033), particularly among cases with onset older than 60 (p=0.0017) and with negative family history (p=0.022). This finding suggests that genetic variations in the control of iron metabolism may contribute to the pathogenesis of the disease.

Age of Onset↗
PubMed2002

Tactile hallucinations in Parkinson's disease.

Hallucinations occur in up to 40% of patients with Parkinson's disease (PD) and are mainly of a visual nature. We prospectively studied 8 patients with PD and tactile hallucinations (TH). TH occurred with a clear sensorium, and were long-lasting. In most cases they involved animals, were combined with other types of hallucinations occurring simultaneously (mainly formed visual hallucinations), and predominated in the evening and/or at night. Pharmacological and disease-related factors, including a disorder in rapid-eye-movement sleep mechanisms, could play a part in the pathophysiology of these hallucinations.

Aged↗