Biomedical subjects

Sylvie Raoul

Publications and source records attributed to Sylvie Raoul.

9 recordsLinked to original sources

PubMed2006

Gene therapy of the brain in the dog model of Hurler's syndrome.

OBJECTIVE: A defect of the lysosomal enzyme alpha-L-iduronidase (IDUA) interrupts the degradation of glycosaminoglycans in mucopolysaccharidosis type I, causing severe neurological manifestations in children with Hurler's syndrome. Delivery of the missing enzyme through stereotactic injection of adeno-associated virus vectors coding for IDUA prevents neuropathology in affected mice. We examined the efficacy and the safety of this approach in enzyme-deficient dogs. METHODS: Because deficient dogs raise antibodies against IDUA in response to infusion, intracerebral vector injections were combined with an immunosuppressive regimen. RESULTS: Treatment was tolerated well. We observed broad dispersion of vector genomes in the brain of efficiently immunosuppressed dogs. The delivery of IDUA to large areas, which could encompass the entire brain, prevented glycosaminoglycan and secondary ganglioside accumulations. This condition was associated with drastic reduction of neuropathology throughout the encephalon. In contrast, vector injection combined with partial immunosuppression was associated with subacute encephalitis, production of antibodies against IDUA in brain tissues, and elimination of genetically modified cells. INTERPRETATION: Gene therapy directed to the entire brain is feasible and may be beneficial to children with Hurler's syndrome. The possibility of subacute encephalitis emphasizes the importance of preventing immune response against IDUA, a problem that needs to be considered in similar therapies for other genetic defects.

Adenoviridae↗

PubMed2005

Only physical aspects of quality of life are significantly improved by bilateral subthalamic stimulation in Parkinson's disease.

BACKGROUND: The well known global improvement of quality of life (QoL) after bilateral high frequency chronic deep brain stimulation of the subthalamic nucleus (STN DBS) in Parkinson's disease (PD) is in contrast to behavioral disturbances as observed after surgery. Indeed the impact of DBS on physical versus mental aspects of QoL in PD remains unknown. OBJECTIVE: To assess the influence of bilateral STN DBS on physical versus mental aspects of QoL in Parkinson's disease. METHODS: The results of 27 patients for the Unified Parkinson's disease Rating Scale (UPDRS), Parkinson's Disease Questionnaire 39 (PDQ39) and Short Form 36 health survey questionnaire (SF36) were compared before surgery and after 12 months of bilateral STN DBS. RESULTS: Comparing off-dopa conditions before versus 12 months after surgery, both UPDRS part II and part III significantly improved: 32.6% and 52%, respectively. UPDRS part I scores did not change significantly at 12 months. As for PDQ39, the global score significantly improved after surgery (21.1 %) as did four subscores: mobility (25.6 %), activity of daily living (34.5 %), stigma (40.1 %) and bodily discomfort (30 %). Three PDQ39 subscores, however, showed no significant changes: emotional well-being (10.7 %), social support (3.2%) and cognition (8.5 %) and one item even worsened: communication (-7.7 %). In SF36, only physical items significantly improved. CONCLUSION: Using clinician's based rating scale, bilateral STN DBS showed significant improvement in PD patients at 12 month follow up. However, using patient's self-assessment scales, the clinical benefit of STN DBS was more subtle: physical items of QoL significantly improved, whereas mental items such as emotional well-being, social support, cognition and communication showed no improvement. Our results are suggestive of a dissociation of motor and non-motor symptoms control after bilateral STN DBS in PD patients.

Adult↗

PubMed2005

Motor and non motor effects during intraoperative subthalamic stimulation for Parkinson's disease.

Spatial distribution of the clinical effects induced by deep brain stimulation during the intraoperative investigation of the subthalamic nucleus (STN) for Parkinson's disease (PD) was analysed in 17 patients under local anesthesia. The stimulation parameters were 130 hertz, 100 micros, and voltage ranged from 0.05 to 5 volts. Optimal motor response was assessed as the total and lasting disappearance of wrist rigidity on the side opposite to stimulation. Among the adverse effects induced by stimulation, special attention was given to frequently observed autonomic effects (AE). Full motor response was achieved in 49.2% of the 301 points evaluated,with a mean voltage (MV) of 0.94 volts; paresthesiae occurred in 6.6% (MV: 2 volts), dystonia in 10.6% (MV: 3.4 volts), autonomic effects in 19.6% (MV: 3.1 volts) and oculomotor effects in 31.6% (MV: 3 volts). The motor target was located in the posterodorsal part of the nucleus and the optimal point for motor response was close to the superior limit of the nucleus. Whereas other adverse effects occurred relatively far from the motor target, AE occurred with statistic significance near this point. Their neural substrates, such as limbic system and their relationship with postoperative behavioral disorders, are discussed.

Adult↗

PubMed2005

Decompression and transposition of the pudendal nerve in pudendal neuralgia: a randomized controlled trial and long-term evaluation.

BACKGROUND: We assess that pudendal neuralgia is a tunnel syndrome due to a ligamentous entrapment of the pudendal nerve and have treated 400 patients surgically since 1987. We have had no major complication. We conducted a randomized controlled trial to evaluate our procedure. METHODS: A sequential, randomized controlled trial to compare decompression of the pudendal nerve with non-surgical treatment. Patients aged 18-70, had chronic, uni/bilateral perineal pain, positive temporary response to blocks at the ischial spine and in Alcock's canal. They were randomly assigned to surgery (n=16) and control (n=16) groups. Primary end point was improvement at 3 months following surgery or assignment to the non-surgery group. Secondary end points were improvement at 12 months and at 4 years following surgical intervention. RESULTS: A significantly higher proportion of the surgery group was improved at 3 months. On intention-to-treat analysis 50% of the surgery group reported improvement in pain at 3 months versus 6.2% of the non-surgery group (p=.0155); in the analysis by treatment protocol the figures were 57.1% versus 6.7% (p=.0052). At 12 months, 71.4% of the surgery group compared with 13.3% of the non-surgery group were improved, analyzing by treatment protocol (p=.0025). Only those randomized to surgery were evaluated at 4 years: 8 remained improved at 4 years. No complications were encountered. CONCLUSIONS: In this study we demonstrate that decompression of the pudendal nerve is an effective and safe treatment for cases of chronic pudendal neuralgia that have been unresponsive to analgesia and nerve blocks. Following surgery, other medical interventions may be necessary.

Adolescent↗

PubMed2004

Fear recognition is impaired by subthalamic nucleus stimulation in Parkinson's disease.

Behavioural disturbances such as disorders of mood, apathy or indifference are often observed in Parkinson's disease (PD) patients with chronic high frequency deep brain stimulation of subthalamic nucleus (STN DBS). Neuropsychological modifications causing these adverse events induced by STN DBS remain unknown, even if limbic disturbances are hypothesised. The limbic system supports neural circuits processing emotional information. The aim of this work is to evaluate changes of emotional recognition in PD patients induced by STN DBS. Thirty PD patients were assessed using a computerised paradigm of recognition of emotional facial expressions [Ekman, P., & Friesen, W. V. (1976). Pictures of facial affect. Palo Alto, CA: Consulting Psychologists Press], 15 before STN DBS and 15 after. The two patients groups were compared to a group of 15 healthy control subjects. One series of 55 pictures of emotional facial expressions was presented to each patient. Patients had to classify the pictures according to seven basic emotions (happiness, sadness, fear, surprise, disgust, anger and no emotion). The intact ability to percept faces was firstly assured using the Benton Recognition Test. Recognition of fear expressions was significantly and selectively reduced in the post-operative group in comparison to both pre-operative and control groups. Our results demonstrate for the first time a selective reduction of recognition of facial expressions of fear by STN DBS. This impairment could be the first neuropsychological marker of a more general limbic dysfunction, thought to be responsible for the behavioural disorders reported after STN DBS.

Aged↗

PubMed2003

Staged lesions through implanted deep brain stimulating electrodes: a new surgical procedure for treating tremor or dyskinesias.

Thalamotomy and pallidotomy have been shown to have some efficacy for treating some movement disorders such as disabling tremor or parkinsonian levodopa-induced dyskinesias (LID). Compared to continuous deep brain stimulation (DBS), this surgical procedure has the disadvantage of irreversibility and a lack of adaptability. Making a lesion involves a risk of inducing permanent side effects, especially if the lesion is large, or of observing a resurgence of the symptoms if the lesion is too small. We performed unilateral pallidotomy in one patient suffering from LID and unilateral thalamotomy in two patients suffering from tremor through the lead classically used for DBS. The technique of lead implantation was similar to that used for DBS treatment but, instead of connecting the lead to a pulse generator, it was left in place and used to make a radiofrequency lesion. This technique allowed the lesion to be kept as small as possible, thereby minimizing the risk of permanent side effects and made possible to extend the lesion if the symptoms reappeared. One lesioning session was enough to relieve tremor in the two patients treated by thalamotomy; three lesioning sessions over a 7-month period were required to relieve drug-induced dyskinesias in the patient treated by pallidotomy. In all 3 patients, disabling symptoms were still relieved without any permanent side effects 6 months after the last lesion was performed.

Aged↗

PubMed2003

Removal of ethmoidal malignant tumors by the isolated paralateronasal approach with resection of the cribriform plate and the dura mater.

OBJECTIVE: A series of ethmoidal tumors was resected by an entirely extracranial approach through a lateral rhinotomy incision, with partial maxillectomy and removal of the cribriform plate and dura mater from below. METHODS: Thirty-four consecutive patients (32 male, 2 female; mean age 64 years, range 45-78) with malignant tumors of the ethmoid sinus were operated by this technique between July 1998 and February 2002. All had complete tumor resection, including the cribriform plate and the dura mater. Excision was performed en bloc 23 times (68%). Although cerebral involvement was encountered in four cases (T4 IC), this technique was adequate for tumor resection, together with corticectomy when necessary. The method used for tumor resection and rebuilding of the anterior skull base is described in detail. RESULTS: There were no immediate postoperative deaths. One patient developed pneumococcal meningitis with cerebrospinal fluid leakage as a result of a technical error and required further surgery. Four patients presented a confusion syndrome that regressed during the hospital stay, 2 complained of transient diplopia, and 4 had hematoma of the abdominal wall. Mean follow-up of 10.4 months (1-41 months) is still too short to reach definitive conclusions about oncologic results. CONCLUSIONS: This approach is particularly suitable for removal of tumors in contact with or invading the cribriform plate. Tumor resection is as extensive as with the traditional mixed approach, but does not require the frontal lobes to be drawn aside.

Adenocarcinoma↗

PubMed2002

Hajdu-Cheney syndrome and syringomyelia. Case report.

This 7-year-old boy with Hajdu-Cheney syndrome presented with cervical syringomyelia related to rapidly progressing platybasia. Decompressive craniectomy provided temporary improvement, and his clinical status was eventually stabilized after external immobilization, according to findings at 2.5 years of follow up. In a review of the literature the authors found 57 cases of the syndrome, only three of which were associated with syringomyelia. The youth of the patient, the severe form and rapid course of the disease, and the very specific anatomical conditions related to cranial and facial deformities raised various therapeutic problems.

Child↗

PubMed2002

Inverted-hook occipital clamp system in occipitocervical fixation. Technical note.

The authors describe an occipitocervical fixation procedure in which they use inverted occipital hooks inserted through a burr hole drilled in the squamous part of the occipital bone. Fifteen patients with unstable lesions of the occipitocervical junction underwent occipitocervical internal fixation. The mean follow-up period was 21 months (range 2-63 months). No implant failed, and postoperative immobilization was not required. The placement of a posterior occipitocervical graft (for which fusion is uncertain) can be avoided in certain conditions.

Adult↗