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G L Defer

Publications and source records attributed to G L Defer.

At least 19 recordsLinked to original sources
PubMed2006

[Study of episodic memory in multiple sclerosis using the California Verbal Learning Test: the data favour altered encoding].

INTRODUCTION: Alteration of episodic memory is one of the main cognitive deficits observed in MS patients. PATIENTS AND METHODS: We studied episodic memory in a group of 71 MS patients (37 RR, 34 SP) with the California Verbal Learning test (CVLT). Direct scores and calculated indices from CVLT performances were analyzed in comparison with controls. RESULTS: We observed a deficit of episodic memory in 69 p.cent of patients. This deficit was related to an alteration of encoding and retrieval processes. Despite SP-MS patients performances were constantly lower than those of RR-MS patients no significant difference was observed between the two groups. Significant correlation between the disease duration and CVLT performances were observed for the whole group but not for RR- or SP-MS groups separately, indicating that duration is more important than the phase of the disease in the worsening of memory deficit.

Adult↗
PubMed2003

[Familial idiopathic striato-pallido-dentate calcifications: clinical and brain imaging study in a family].

Familial idiopathic basal ganglia calcification (FIBGC) is a rare condition and its pathophysiology has not so far been elucidated. We report the results of a clinical study in two patients of a family affected with FIBGC. Brain imaging with 18-FDG-PET was performed in one. Psychiatric and cognitive troubles were the main clinical symptoms. Basal ganglia calcifications were associated with white matter lesions. The PET study performed in one patient revealed a striatal and a posterior cingulate hypometabolism. Posterior cingulate gyrus is involved in episodic memory processing, and could be involved in episodic memory deficit observed in this patient. These results suggest that a cortical dysfunction could be associated to the disease. The underlying mechanism, that could be a neuronal loss, a cortical deafferentation or an alteration of synaptic transmission, remains to be elucidated.

Adult↗
PubMed2001

Migration pathways of human glioblastoma cells xenografted into the immunosuppressed rat brain.

Diffuse invasion of the brain by tumor cells is a hallmark of human glioblastomas and a major cause for the poor prognosis of these tumors. This phenomenon is only partially reproduced by rodent models of gliomas that display a very high rate of proliferation and limited cell migration. We have analyzed the development of human glioblastoma cells (GL15) xenografted into the brain of immunosuppressed rats, in order to define the characteristics of tumor cell invasion. As identified by the specific immunolabeling of the tumor cells for the human HLA-ABC antigen, GL15 tumors reproduced the three types of intraparenchymal invasion observed in patients. First, a majority of multipolar tumor cells intermingled rapidly and profusely with host neural cells in the margin of the injection site. This progressively enlarging area was principally responsible for the tumor growth over time. Second, in the gray matter, columns of thin bipolar tumor cells aligned along capillary walls. Third, in the white matter, elongated bipolar isolated tumor cells were observed scattered between axonal fibers. The maximum migration distances along white matter fibers remained significantly higher than the maximum migration distances along blood vessels, up to two months after injection. Development of the tumor was associated with a significant increase of vascularization in the area of tumor spread. Xenografting of human GL15 glioblastoma cells into the immunosuppressed rat brain allowed to differentiate between the three classical types of invasion identified in the clinic, to quantify precisely the distances of migration, and to evaluate cell morphology for each of these routes. The present results support the existence of host/tumor cells interactions with specific characteristics for each type of invasion.

Animals↗
PubMed2001

Brainstem gliomas in adults: prognostic factors and classification.

In contrast to childhood brainstem gliomas, adult brainstem gliomas are rare and poorly understood. The charts of 48 adults suffering from brainstem glioma were reviewed in order to determine prognostic factors, evaluate the effect of treatment and propose a classification of these tumours. Mean age at onset was 34 years (range 16-70 years). The main presenting symptoms were gait disturbance (61%), headache (44%), weakness of the limbs (42%) and diplopia (40%). Four patterns were identified on MRI, representing non-enhancing, diffusely infiltrative tumours (50%), contrast-enhancing localized masses (31%), isolated tectal tumours (8%) and other patterns (11%). Treatment consisted of partial resection (8%), radiotherapy (94%) and chemotherapy (56%). Overall median survival was 5.4 years. On univariate analysis, the following favourable prognostic factors were identified (P< 0.01): age of onset <40 years, duration of symptoms before diagnosis >3 months, Karnofski performance status >70, low-grade histology, absence of contrast enhancement and 'necrosis' on MRI. On multivariate analysis, the duration of symptoms, the appearance of 'necrosis' on MRI and the histological grade of the tumour remained significant and independent prognostic factors (P< 0.05). Eighty-five percent of the tumours could be classified into one of the following three groups on the basis of clinical, radiological and histological features. (i) Diffuse intrinsic low-grade gliomas (46%) usually occurred in young adults with a long clinical history before diagnosis and a diffusely enlarged brainstem on MRI that did not show contrast enhancement. These patients were improved by radiotherapy in 62% of cases and had a long survival time (median 7.3 years). Anaplastic transformation (appearance of contrast enhancement, 27%) and relentless growth without other changes (23%) were the main causes of death. (ii) Malignant gliomas (31%) occurred in elderly patients with a short clinical history. Contrast enhancement and necrosis were the rule on MRI. These tumours were highly resistant to treatment and the patients had a median survival time of 11.2 months. (iii) Focal tectal gliomas (8%) occurred in young patients and were often revealed by isolated hydrocephalus. The course was indolent and the projected median survival period exceeded 10 years. In conclusion, adult brainstem gliomas are different from the childhood forms and resemble supratentorial gliomas in adults. Low-grade tumours have a clinicoradiological pattern that is so characteristic that the need for a potentially harmful biopsy is debatable. The optimum timing of treatment for supratentorial low-grade tumours remains unclear. In high-grade gliomas, the prognosis remains extremely poor despite aggressive treatment with radiotherapy and chemotherapy.

Adult↗
PubMed2001

[Memory and executive functions in multiple sclerosis: preliminary findings with a cognitive battery].

Twenty one MS patients suffering from a relapsing-remitting (four patients), a secondary progressive (12 patients) or a primary progressive form of the disease (five patients) were assessed using a cognitive battery specifically devoted to executive and memory processes. Results showed that, patients without significant depressive state evaluated by the MADR scale, exhibited significant impairments in executive processes, working, episodic and procedural memories whereas short term memory, language and global intellectual efficiency were normal. The preliminary data suggest an impairment of encoding, a process previously underestimated in this disease. In addition, the battery was easily administered to the patients and relevant for the cognitive assessment of MS.

Adult↗
PubMed2000

[Frequency and nature of neurologic emergencies].

In the last decade, it has been shown that neurological problems account for approximately 15% of medical emergencies treated in metropolitan France, in all types of medical establishments. Four major diagnostic groups are concerned: stroke, epilepsy and loss of consciousness, headache, confusional syndromes and behavioural disorders. Among patients seen in emergency units for neurological problems, 80% require hospital admission. These figures underline the need for medical and administrative directors of public hospitals to take greater account of the neurological emergency in providing adequate means to meet this demand.

Emergencies↗
PubMed2000

Safety and tolerability assessment of intrastriatal neural allografts in five patients with Huntington's disease.

This study describes issues related to the safety and tolerability of fetal striatal neural allografts as assessed in five patients with Huntington's disease. Huntington's disease (HD) is characterized by motor, cognitive, and behavioral disturbances. The latter include psychological disturbances and, as a consequence, we took particular care to analyze behavioral changes, in addition to the usual "safety" follow-up. We conducted multidisciplinary follow-up at least 2 years before and 1 year after grafting. Psychological care extended to close relatives. The grafting procedure itself was altogether safe and uneventful, and there were no apparent clinical deleterious effects for 1 year. The immunosuppressive treatment, however, was complicated by various problems (irregular compliance, errors of handling, side effects). Direct psychological consequences of the transplantation procedure were rare and not worrisome, although mood alteration requiring treatment was observed in one patient. Indirectly, however, the procedure required patients and relatives to accept constraints that tended to complicate familial situations already marred by aggressivity and depression. All patients and close relatives expressed major expectations, in spite of our strong and repeated cautioning. It is clearly important to be aware of these particular conditions since they may eventually translate into psychological difficulties in coping with the long-term clinical outcome of the procedure, if not beneficial. Despite an overall good tolerance, therefore, this follow-up calls for caution regarding the involvement of HD patients in experimental surgical protocols.

Adult↗
PubMed2000

Pharmacokinetics of all-trans retinoic acid, 13-cis retinoic acid, and fenretinide in plasma and brain of Rat.

We have measured the pharmacokinetics of three retinoids, all-trans retinoic acid, 13-cis retinoic acid, and fenretinide in rat blood and rat brain [especially white matter (WM) and gray matter (GM)] to help select retinoids for treating human malignant glioma. All-trans retinoic acid permeated well into the WM, giving peak concentration in WM of 25.7 microg/g, 6 to 7 times higher than the peak serum concentration. There was less 13-cis retinoic acid in WM: area under the curve (AUC)(0-->infinity) WM/AUC(0-->infinity) serum = 18.00 microg ml(-1) h/32.67 microg ml(-1) h. The ratio WM/GM was over 1 for these two compounds, but the half-lives were short in the serum and cerebral tissue (0.57-1.02 h). Fenretinide had different pharmacokinetics: the peak concentrations were in serum (1.7 microg/ml) and WM (1.2 microg/ml)-low, but the AUC(0-->infinity) was large (25.55 microg ml(-1) in serum and 57.53 microg ml(-1) in WM) due to its long elimination half-life (13.78 h in serum and 17.77 h in WM). These findings provide information that may be used to select a retinoid and establish therapeutic regimens that provide optimal efficacy with minimal toxicity.

Animals↗
PubMed2000

[Surgical treatment: inclusion criteria].

Different surgical strategies have been suggested to treat PD patients. Cerebral grafting remains experimental and pallidotomy is not performed among the French neurosurgery departments. Therefore selection criteria for surgical interventional therapies will be only discussed for deep brain stimulation (DBS) even if these criteria are not really different between grafting, pallidotomy and DBS. Choice of selection criteria is very important in order to separate PD patients with a high probability of clinical benefit after surgery from those in whom the surgical procedure includes a high risk of morbidity. A selection procedure is proposed according to data of the literature and to the results of a questionnaire filled by 7 french expert centers involved in surgical therapies of PD. The selection procedure in a patient with a parkinsonian syndrome lasting for more 5 years has to include:

Humans↗
PubMed1999

Core assessment program for surgical interventional therapies in Parkinson's disease (CAPSIT-PD).

In 1992 the Core Assessment Program for Intracerebral Transplantations (CAPIT) was published providing the minimal requirements for a common patient evaluation protocol. Despite the intent, the program was thought to be too laborious to carry out in large scale trials, and it also lacked evaluations of cognitive functions and quality of life. Moreover, the CAPIT was designed for neural transplantation only and has not been revised since. Since then, pallidotomy and deep brain stimulation have emerged as additional treatment modalities but there exists no common tool for evaluation of, and between, the techniques. In 1996, within the framework of NECTAR (Network for European CNS Transplantation and Restoration), a dedicated program entitled "Neurosurgical Interventions in Parkinson's Disease" (NIPD) was funded by the European Union Biomed 2 program to develop a new Core Assessment Program for Surgical Interventional Therapies in PD (CAPSIT-PD) and to establish an European registry for patients with PD subjected to functional neurosurgery. This article presents the recommendations of this new program.

Clinical Protocols↗