A long-term follow-up of weight changes in subthalamic nucleus stimulated Parkinson's disease patients.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) constitutes the mainstay treatment in advanced Parkinson's disease (PD) with motor fluctuations. Despite its efficacy on motor signs and quality of life, emergent adverse events have been recently reported. Among them, weight gain (WG) is a recognized adverse event of subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD). Also, WG is poorly known at the long-term and predisposing factors have not yet been identified. We conducted a cross-sectional study of WG in 47 STN-DBS PD patients between 1999-2006. Data on disease history, motor status and dopaminergic drug treatment were retrospectively collected at surgery and 1 year post-surgery. Weight at disease diagnosis and at surgery, as well as the current weight and height were gathered by an autoquestionnaire. Moreover, the weight before surgery was obtained and verified in medical files in more than 90% of our patients. Sixty-six patients who underwent surgery between 1999-2006 were included, but six were deceased, four refused to participate and nine were lost for follow-up. So, 47 (71%) were retained in our analysis. A total of 78.7% of patients gained weight. On average 4.7 years follow up after surgery, the mean weight gain was +7.2±8.1kg compared to the preoperative assessment (p<0.001) and the mean BMI gain was +2.7±3.0kg/m(2) compared to pre-surgery values (p<0.001). The patients gained more weight after surgery than they had lost during disease evolution before surgery. Women and patients with a more severe UPDRS-III "off" drug score before surgery significantly gained more weight. Our study provides further evidence that the WG is a problem after STN-DBS and concerns a majority of patients at the long term. It may expose them to complications that should be considered for prevention and the patient's information before surgery.

[Deep-brain stimulation of the internal pallidum in multiple system atrophy]. / Stimulation cérébrale profonde du pallidum interne dans l'atrophie multisystématisée.

INTRODUCTION: The experience with deep-brain stimulation (DBS) in multiple-system atrophy (MSA) is sparse and generally disappointing. DBS is currently not recommended in MSA and its use is often related to a misdiagnosis. OBSERVATION: We describe the outcome of bilateral DBS of the internal pallidum in a 46-year-old woman suffering from MSA that initially resembled Parkinson's disease with prominent levodopa-induced dyskinesias. DBS of the left internal pallidum was performed in 1998 after a ten-year clinical course and improved dyskinesias. Six months later, the right side was implanted. A few months after the second surgery, the patient progressively developed signs of cerebellar and dysautonomic impairment and MSA was diagnosed. CONCLUSION: Our observation confirms the ineffectiveness of DBS of the internal pallidum in MSA and even suggests a harmful effect. DBS remains contra-indicated in atypical parkinsonism.

Side-effects of subthalamic stimulation in Parkinson's disease: clinical evolution and predictive factors.

Chronic bilateral high-frequency stimulation of the subthalamic nucleus (STN) is an alternative treatment for disabling forms of Parkinson's disease when on-off fluctuations and levodopa-induced dyskinesias compromise patients' quality of life. The aim of this study was to assess the evolution of side-effects during the first year of follow-up and search for clinical predictive factors accounting for their occurrence. We compared the frequency of side-effects at 3 and 12 months after surgery in a cohort of 44 patients. The off-medication scores of Unified Parkinson's Disease Rating Scale (UPDRS) II, III, axial symptoms, disease duration and age at surgery were retained for correlation analysis. Dysarthria/hypophonia, weight gain and postural instability were the most frequent chronic side-effects. Whereas dysarthria/hypophonia remained stable over time, weight gain and postural instability increased during the first year post-op. High axial and UPDRS II scores at surgery were predictive of dysarthria/hypophonia. Age and axial score at surgery were positively correlated with postural instability. Despite the occurrence of side-effects, the benefit/side-effects ratio of STN stimulation was largely positive during the first year of follow-up. Age, intensity of axial symptoms and UDPRS II off-medication score before surgery are predictive factors of dysarthria/hypophonia and postural instability after surgery.

Evolution of postural stability after subthalamic nucleus stimulation in Parkinson's disease: a combined clinical and posturometric study.

OBJECTIVES: The occurrence of postural and balance disorders is a frequent feature in advanced forms of Parkinson's disease (PD). However, the pathological substrate of these disturbances is poorly understood. METHODS: In the present work, we investigated the evolution of posturometric parameters [center of pressure (CoP) displacement and CoP area] and axial scores between the pre-operative period and 3 months post-operative in seven PD patients who underwent bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN). RESULTS: After surgery, the patients leaned backwards much more regardless of the STN stimulation, suggesting that surgery could have a deleterious effect on postural adaptation. During the post-operative period, the improvement in axial and postural scores was similar under levodopatherapy and DBS. On the other hand, DBS of the STN significantly reduced the CoP displacement and the CoP area, whereas levodopatherapy tended only to reduce the CoP displacement and to increase the CoP area significantly. CONCLUSIONS: These data suggest that DBS of the STN and levodopa do not act on the same neurological systems involved in posture regulation. DBS of the STN could improve posture via a direct effect on the pedunculopontine nucleus, which is known to be involved in posture regulation.

Riluzole improves motor deficits and attenuates loss of striatal neurons in a sequential double lesion rat model of striatonigral degeneration (parkinson variant of multiple system atrophy).

We investigated neuroprotective effects of riluzole, an anti-glutamatergic agent that is FDA approved for disease-modifying therapy in amyotrophic lateral sclerosis (ALS), in an established double lesion rat model of striatonigral degeneration (SND), the neuropathological substrate of parkinsonism associated with MSA (MSA-P). Riluzole was administered prior to and consecutively for ten days following double lesion placement in the left-sided medial forebrain bundle and ipsilateral striatum. Assessment of motor behaviour using a flex field system showed a significant reduction of motor disturbance in animals with striatonigral lesions treated with riluzole compared to lesioned but untreated animals (P<0.001). DARPP-32 immunohistochemistry revealed a significant reduction of absolute striatal lesion volume in riluzole treated animals compared to lesioned but untreated animals (P<0.01). No significant difference in counts of nigral dopaminergic neurons was found in treated versus untreated double-lesioned animals. The results of our study indicate that riluzole mediates neuroprotective effects in the double lesion rat model of MSA-P. Whether riluzole also protects autonomic and cerebellar pathways that are frequently affected in MSA remains to be determined. Nonetheless, our study is the first to provide an experimental rationale for exploring possible neuroprotective effects of riluzole in MSA.

Epidemiology of multiple system atrophy: a prevalence and pilot risk factor study in Aquitaine, France.

We investigated the prevalence of multiple system atrophy (MSA) in Gironde, France, through a network of 120 public and private specialists and assessed the relationship between some environmental factors and MSA in a case-control study involving 50 MSA patients, 50 Parkinson's disease (PD) patients and 50 healthy controls. The occupational exposure to pesticides was evaluated through a job-exposure matrix. On prevalence day (November 1, 1998), the crude prevalence of MSA in Gironde was 1.94/100,000 inhabitants. We found no significant relationship between occupational exposure to pesticides and MSA. PD patients were significantly less frequently ever-smokers than controls and the same tendency was observed for MSA patients. We also described the clinical features that heralded the disease among this nonselected population.

The value of external anal sphincter electromyography for the diagnosis of multiple system atrophy.

OBJECTIVE: To assess the value of external anal sphincter electromyography (ASEMG) for the diagnosis of multiple system atrophy (MSA) among various causes of parkinsonism. ASEMG denervation profiles have previously been proposed as a diagnosis test for MSA, but their specificity is disputed. METHODS: ASEMG variables of 52 parkinsonian patients were analyzed according to the clinical diagnosis: MSA (n = 31) or no MSA (n = 21). Mean motor unit potential duration, percentage of polyphasicity, and the electromyographer's interpretation were analyzed according to clinical diagnosis, disease duration, genitourinary symptoms, gender, parity, and history of pelvic surgery. RESULTS: All patients with MSA showed ASEMG denervation. Mean motor unit potential duration was the most discriminant variable. No patient with MSA had a mean duration less than 12 ms and no patient without MSA had one greater than 16 ms. ASEMG discriminates between patients with MSA and Parkinson's disease. Using a threshold of 13 ms, the sensitivity was 80% and specificity was almost 70% (positive predictive value, 80%) for the diagnosis of MSA. Age, history of pelvic surgery, and to a lesser extent, female gender, parity, disease duration, and presence of urinary symptoms increased the likelihood of abnormal ASEMG. CONCLUSION: ASEMG was highly sensitive and rather specific for the diagnosis of MSA.

Brain stem infiltration by mixed Langerhans cell histiocytosis and Chester-Erdheim disease: more than just an isolated case?

Langerhans cell histiocytosis is classically considered as totally different from Chester-Erdheim's disease which consists in the infiltration of various parenchymas by macrophagic CD68-positive histiocytes. We report the case of a 46-year-old woman with a long history of diabetes insipidus who presented typical lesions of Langerhans cell histiocytosis on vulvar and skin biopsies as well as bony cellular infiltrates characteristic of Chester-Erdheim's disease. A few months later she presented cerebellar disorders and died after an 18-month course. At autopsy the pons was enlarged, due to numerous cellular infiltrates which were also scattered in the middle cerebellar pedoncles, dentate nuclei, midbrain and hypothalamus. There were S100-protein positive Langerhans cells intermingled with numerous ovoid CD68-positive histiocytes. There are a few reported cases of Chester-Erdheim's disease presenting foci of Langerhans cells histiocytosis in other parenchymas. In addition, there are 10 reported cases with diabetes insipidus and bilateral infiltration of the brain stem and cerebellum, considered as presenting either one type of histiocytosis or the other. Our case demonstrates that both histiocytoses may coexist in the brain and thus correspond in fact to the same pathology in certain particular cases.

[Fulminant orthochromatic leukodystrophy in an adult]. / Leucodystrophie orthochromatique d'évolution rapide chez l'adulte.

A 27-year-old man from Marocco developed a progressive dementia leading within a year to a mutic akinetic state. The course of the disease was also marked by epileptic seizures. MRI revealed diffuse white matter involvement. A frontal white matter brain biopsy was consistent with the diagnosis of orthochromatic leucodystrophy, i.e: presence of sudanophilic lipids and pigmented cells associated with myelin loss. Adult forms of orthochromatic leucodystrophy are very rare. Our case was characterized by a fulminant course.

[Langerhans-cell histiocytosis and Erdheim-Chester disease: probably not a fortuitous association]. / Histiocytose langerhansienne et maladie d'Erdheim-Chester: une association probablement non fortuite.

BACKGROUND: Erdheim Chester disease (MEC) is a rare non-Langerhans cell histiocytosis characterized by multi-visceral involvement. We report a case of MEC associated with Langerhans cell histiocytosis (HCL). CASE REPORT: A 46-year-old women presented skin and vulvar localization of HCL associated with typical MEC bone involvement. Despite chemotherapy (vinblastine) and prednisone, the disease progressed to involve the central nervous system, leading to fatal outcome. Post-mortem examination showed HCL in skin, MEC in bones and central nervous system, and intermediate histiocytic proliferation in the encephalon. DISCUSSION: Usually, MEC and HCL are considered as distinct entities. MEC is characterized by a xanthogranulomatous proliferation of CD 68+ foamy histiocytes nested in fibrosis, and HCL by a proliferation of PS 100+ and CD1a+ Langerhans cells. However, our observation, as well as previous reports, suggests that MEC is part of the HCL spectrum.

[Cerebrovascular complications of non-bacterial thrombotic endocarditis: value of transesophageal echocardiography]. / Complications cérébrovasculaires de l'endocardite non bactérienne thrombosante: intérêt de l'échographie cardiaque transoesophagienne.

Non bacterial thrombotic endocarditis is a frequent cause of cerebrovascular complications in patients with cancer. Clinical features are often misleading and symptoms are hardly linked to valvular thrombosis in the absence of systemic embolism. We describe here a case mainly illustrating two aspects: clinical and neuroradiological manifestations of multiple distal brain infarcts and the value of transoesophageal echocardiography for the diagnosis.

Differential influence of haloperidol and sulpiride on dopamine receptors and peptide mRNA levels in the rat striatum and pituitary.

We examined the effect of chronic administration (14 days) of haloperidol (2 mg/kg/day) or sulpiride (100 mg/kg/day), on the mRNA levels of various genes in the rat striatum and pituitary by quantitative in situ and Northern blot hybridizations. In the pituitary, haloperidol and sulpiride induced similar increases of mRNAs of pro-opiomelanocortin (POMC) (+65% and +73%), prolactin (PRL) (+821% and +840%) and growth hormone (GH) (+32% and +47%), but sulpiride induced a greater increase of D2R mRNA (+125%) than haloperidol (+92%). In the striatum, sulpiride and haloperidol had different effects: sulpiride induced a higher increase than haloperidol of both preproenkephalin A (PPA) mRNA (+67% versus +47%) and D2 dopamine receptor (D2R) mRNAs (+72% versus +40%). Moreover, haloperidol and sulpiride had opposite effects on substance P (SP) mRNA. Haloperidol decreased the amount of SP mRNA by 20% while sulpiride increased it by 20%. The D1 dopamine receptor (D1R) mRNA level was not significantly modified after either treatment. Our results demonstrate that the effect of a chronic haloperidol treatment on striatal dopamine receptors and neuropeptide mRNA levels is different to that of sulpiride, whereas it is similar on pituitary hormones mRNA levels.

Merrf family with 8344 mutation in tRNA (lys). Evidence of a mitochondrial vasculopathy in muscle biopsies.

This article reports a new MERRF family. The mother, regarded as suffering from Ramsay-Hunt Syndrome, and her three daughters, had the same clinical pattern: myoclonic epilepsy and ataxia. Two daughters were studied on morphological, biochemical and molecular genetic levels. Muscle biopsies showed ragged-red fibres and mitochondrial vasculopathy. Arterioles were strongly SDH-reactive and COX-negative. By electron microscopy, abnormal mitochondria were observed in skeletal muscle fibres, in smooth muscle fibres of intramuscular vessels and in sweat gland epithelium. The study of the respiratory chain showed complex IV and I + IV deficiency, respectively. Mitochondrial tRNA (lys) mutation at position 8344 was pointed out as previously reported in the MERRF syndrome.

[Choreo-acanthocytosis]. / La chorée-acanthocytose.

We report a case of choreo-acanthocytosis in a 33 year-old man with mild chorea of the limbs but no involuntary movements of the face, areflexia, epilepsy and personality changes. Acanthocytosis was 10-20% and creatine-phosphokinase levels were raised. Electrophysiological data were consistent with lower motor neurone dysfunction. Muscle biopsy revealed changes typical of neurogenic atrophy. Nerve biopsy showed a severe loss of large myelinated axons. Electron microscopic examination was in favour of primary axonal damage affecting mainly myelinated fibers and only slightly unmyelinated fibers.