Changes in quality of life, burden and mood among spouses of Parkinson's disease patients receiving neurostimulation.

BACKGROUND: Deep brain stimulation improves motor function and quality of life in patients with Parkinson's disease. The impact of these changes on patients' spouses is largely unknown. METHODS: Twenty-six spouses of patients undergoing surgery were evaluated before and 12 months after surgery, using the 36-Item Short Form Health Survey for quality of life, the Beck Depression Inventory, and the Zarit Burden Inventory. RESULTS: The spouses' mean mood and quality of life scores changed little, while burden improved in younger spouses. There was no significant change in the spouses' overall status. However, at the individual level the effect of surgery was more frequently negative than positive. Changes in psychological status and quality of life in the spouses did not correlate with changes in the patients' motor status or quality of life. CONCLUSIONS: Spouses' experience of neurostimulation for Parkinson's disease is variable and complex. The improvement in burden experienced by younger spouses may reflect a greater capacity to cope with new situations.

Development of a positron probe for localization and excision of brain tumours during surgery.

The survival outcome of patients suffering from gliomas is directly linked to the complete surgical resection of the tumour. To help the surgeons to delineate precisely the boundaries of the tumour, we developed an intraoperative positron probe with background noise rejection capability. The probe was designed to be directly coupled to the excision tool such that detection and removal of the radiolabelled tumours could be simultaneous. The device consists of two exchangeable detection heads composed of clear and plastic scintillating fibres. Each head is coupled to an optic fibre bundle that exports the scintillating light to a photodetection and processing electronic module placed outside the operative wound. The background rejection method is based on a real-time subtraction technique. The measured probe sensitivity for (18)F was 1.1 cps kBq(-1) ml(-1) for the small head and 3.4 cps kBq(-1) ml(-1) for the large head. The mean spatial resolution was 1.6 mm FWHM on the detector surface. The gamma-ray rejection efficiency measured by realistic brain phantom modelling of the surgical cavity was 99.4%. This phantom also demonstrated the ability of the probe to detect tumour discs as small as 5 mm in diameter (20 mg) for tumour-to-background ratios higher than 3:1 and with an acquisition time around 4 s at each scanning step. These results indicate that our detector could be a useful complement to existing techniques for the accurate excision of brain tumour tissue and more generally to improve the efficiency of radio-guided cancer surgery.

Neuroprotective gene therapy for Huntington's disease, using polymer-encapsulated cells engineered to secrete human ciliary neurotrophic factor: results of a phase I study.

Huntington's disease (HD) is a monogenic neurodegenerative disease that affects the efferent neurons of the striatum. The protracted evolution of the pathology over 15 to 20 years, after clinical onset in adulthood, underscores the potential of therapeutic tools that would aim at protecting striatal neurons. Proteins with neuroprotective effects in the adult brain have been identified, among them ciliary neurotrophic factor (CNTF), which protected striatal neurons in animal models of HD. Accordingly, we have carried out a phase I study evaluating the safety of intracerebral administration of this protein in subjects with HD, using a device formed by a semipermeable membrane encapsulating a BHK cell line engineered to synthesize CNTF. Six subjects with stage 1 or 2 HD had one capsule implanted into the right lateral ventricle; the capsule was retrieved and exchanged for a new one every 6 months, over a total period of 2 years. No sign of CNTF-induced toxicity was observed; however, depression occurred in three subjects after removal of the last capsule, which may have correlated with the lack of any future therapeutic option. All retrieved capsules were intact but contained variable numbers of surviving cells, and CNTF release was low in 13 of 24 cases. Improvements in electrophysiological results were observed, and were correlated with capsules releasing the largest amount of CNTF. This phase I study shows the safety, feasibility, and tolerability of this gene therapy procedure. Heterogeneous cell survival, however, stresses the need for improving the technique.

Correlation of in vitro infiltration with glioma histological type in organotypic brain slices.

Diffuse invasion of the brain, an intrinsic property of gliomas, renders these tumours incurable, and is a principal determinant of their spatial and temporal growth. Knowledge of the invasive potential of gliomas is highly desired in order to understand their behaviour in vivo. Comprehensive ex vivo invasion studies including tumours of different histological types and grades are however lacking, mostly because reliable physiological invasion assays have been difficult to establish. Using an organotypic rodent brain slice assay, we evaluated the invasiveness of 42 grade II-IV glioma biopsy specimens, and correlated it with the histological phenotype, the absence or presence of deletions on chromosomes 1p and 19q assessed by fluorescent in situ hybridisation, and proliferation and apoptosis indices assessed by immunocytochemistry. Oligodendroglial tumours with 1p/19q loss were less invasive than astrocytic tumours of similar tumour grade. Correlation analysis of invasiveness cell proliferation and apoptosis further suggested that grade II-III oligodendroglial tumours with 1p/19q loss grow in situ as relatively circumscribed compact masses in contrast to the more infiltrative and more diffuse astrocytomas. Lower invasiveness may be an important characteristic of oligodendroglial tumours, adding to our understanding of their more indolent clinical evolution and responsiveness to therapy.

[Early diagnosis of bacterial brain abscesses: interest of diffusion-weighted MRI]. / Diagnostic précoce des abcès cérébraux bactériens: intérêt de l'IRM en séquences de diffusion.

Three cases of bacterial brain abscesses, in immunocompetent patients, are reported. In all these cases, the diffusion-weighted magnetic resonance (MRI) with apparent diffusion coefficient (ADC) map has permitted an early diagnosis and a rapid treatment. This emergency MRI showed in the three cases a low signal on TI-weighted images, a high signal on T2-weighted and echo-planar images, and a decrease of ADC (0.36- 0.49 x 10(-3) mm2/s). So, this new MRI technique provides an available and rapid element in the brain abscess diagnosis which often remains a complex clinical and radiological diagnosis.

Cyclosporin A protects striatal neurons in vitro and in vivo from 3-nitropropionic acid toxicity.

The neuroprotective properties of cyclosporin A (CsA) are mediated by its ability to prevent mitochondrial permeability transition during exposure to high levels of calcium or oxidative stress. By using the mitochondrial toxin 3-nitropropionic acid (3NP), the present study assessed whether CsA could protect striatal neurons in vitro and in vivo. In vitro, 3NP produced a 20-30% reduction of striatal glutamic acid decarboxylase-immunoreactive (GAD-ir) neurons. A single treatment with CsA protected GAD-ir neurons from 3NP toxicity at lower (0.2 or 1.0 microM), but not at higher (5.0 microM) doses. Similar findings were seen when the cultures were treated twice with cyclosporin. In vivo experiments used the Lewis rat model of Huntington's disease (HD) in which a low 3NP dose was delivered subcutaneously through an osmotic minipump. Rats received unilateral or bilateral intrastriatal saline injections to disrupt the blood-brain barrier (BBB) and facilitate CsA reaching vulnerable neurons. In the first experiment, CsA treated 3NP-lesioned rats displayed significantly more dopamine-and adenosine-3;, 5;-monophosphate-regulated phosphoprotein (DARPP32-ir) neurons ipsilateral to BBB disruption compared to the contralateral intact striatum, indicating that disruption of the BBB maybe necessary for CsA's neuroprotective effects. In the second experiment, stereological counts of DARPP32-ir neurons revealed that CsA protected striatal neurons in a dose-dependent manner following bilateral disruption of the striatal BBB. Rats treated with the higher (15 or 20 mg/kg) but not lower (5 mg/kg) doses of CsA displayed greater numbers of DARRP32-ir striatal neurons relative to vehicle-treated 3NP-lesioned rats. Thus, under conditions in which CsA can gain access to striatal neurons, significant protection from 3NP toxicity is observed. Therefore, CsA or more lipophilic analogues of this compound, may be of potential therapeutic benefit by protecting vulnerable neurons from the primary pathological event observed in HD.

[Endoscopic surgery of third ventricle lesions]. / Approche endoscopique des lésions du troisième ventricule.

The endoscopic approach of the tumors of the third ventricle interests mainly the colloid cysts but also offers the possibilities of biopsies. Twenty two patients (16 men and 6 women, average age 41 years) presenting with hydrocephalus related to a tumor of the pineal area were treated by a ventriculostomy with attempt at biopsy : they are outside of the limits of this report. Twenty two other patients (15 men, 7 women, average age 39 years) were operated on from 1994 to 1999 for a colloid cyst, and 2 of them were admitted in emergency in sudden coma. The CT scan showed a colloid cyst (hyperdense in 16 patients) associated with an hydrocephalus, except for a patient previously shunted. The diameter of the cyst varied from 4 to 50 mm (average of 20 mm). All the patients were operated on using a rigid endoscope. Among the 20 patients presenting a tumor of the pineal area, a biopsy was possible only in 4 cases (20%). There were no hemorrhage nor neurological disorders. In all the cases, the size and the number of the specimens were sufficient to allow the histological diagnosis. For the patients presenting with colloid cyst, the average follow-up is 2 years. All the preoperative symptoms disappeared except for the memory disorders which were improved. The post-operative Evans index decreased significantly. No residual cyst was observed on the post-operative MRI in 14 patients (63%). Among these patients, an asymptomatic recurrence was observed and remained stable after 44 months of follow-up. A residual cyst was observed in 8 patients (36%), with a diameter from 5 to 25 mm (average 9 mm). No patient required a shunt procedure, and no patient presented hemorrhagic complication. Endoscopy is especially useful in the first line treatment of the colloid cysts of the third ventricle.

Chronic recurrent transverse myelitis or multiple sclerosis.

The simultaneous occurrence of multiple sclerosis and transverse myelitis is known in the literature. Apart from the spinal symptoms, other neurological signs of brain involvement are usually found and magnetic resonance imaging (MRI) reveals disseminated foci in the brain. The positive evoked responses, the immunological abnormalities of the cerebrospinal fluid (CSF), and the oligoclonality together prove the presence of multiple sclerosis. In these cases the symptoms of transverse myelitis can separately precede other signs of multiple sclerosis, or appear as a relapse. Recurrent transverse myelitis as an independent entity, with negative MRI and CSF immunology, is an exciting topic in terms of the etiological factors and therapeutic considerations. The view in the literature is that the occurrence of transverse myelitis as an independent entity is rather rare. The present article reports the case of a female patient with recurrent spinal cord signs, and negative MRI and CSF immunology. During a ten-year follow-up observation period, symptoms of multiple sclerosis did not develop. Further studies of such cases are needed in order to clarify the etiological factors, the pathomechanism and the therapeutic considerations relating to this relatively new and probably independent clinical entity.

[Microsurgical vascular decompression in the treatment of facial hemispasm. A retrospective study of a series of 65 cases and review of the literature]. / La décompression vasculaire microchirurgicale dans le traitement du spasme hémifacial. Etude rétrospective d'une série de 65 cas et revue de la littérature.

The results of a series of 65 consecutive patients operated on to relieve hemifacial spasm (HFS) at Pierre Wertheimer Hospital in Lyon and at Henri Mondor Hospital in Creteil, using the same microvascular decompression (MVD) method, are reported. MDV was performed through a retromastoid keyhole approach. A neurovascular conflict (NVC) was found in 62 cases (i.e., 95.5%). The conflicting vessel was the posterior inferior cerebellar artery (PICA) in 23 cases (35.4%), the anterior inferior cerebellar artery (AICA) in 22 cases (33.8%), the vertebro-basilar artery (VBA) with PICA and/or AICA in 13 cases (20%), and VBA alone in 4 cases (3.1%). The conflicting artery was maintained apart from the REZ of VII nerve by interposing a ball made of Teflon fibers and/or a plaque of Dacron. Forty-five patients (69.2%) were totally cured, 16 patients (24.6%) had only a partial (more than 50%) improvement, and in 4 patients (6.2%) surgery failed. Follow-up ranged from 1 month to 13 years (mean: 4 years and 8 months). Important was that in 9 patients, total relief of spasm occurred only secondarily with a delay sometimes as long as one year. Post-operative complications were dominated by: 1) facial nerve deficits in 16 cases (24.6%), of which 14 were transient and 2 were permanent; 2) hearing decrease in 10 cases (15.4%), of which 5 were transient and 5 were permanent. These complications were encountered at the start of the experience and at a time when monitoring of intraoperative brainstem auditory evoked potentials (BAEP) was not routinely done. Our data proved to be consistent with those published in the literature.