Sub-acute delayed failure of subthalamic DBS in Parkinson's disease: the role of micro-lesion effect.

OBJECTIVE: To study delayed failure after subthalamic nucleus (STN) deep brain stimulation in Parkinson's disease (PD) patients. METHODS: Out of 56 consecutive bilaterally STN-implanted PD patients, we selected subjects who, after initial clinical improvement (1 month after surgery), lost benefit (delayed failure, DF). RESULTS: Five patients developed sub-acutely severe gait disorders (DF). In 4/5 DF patients, a micro-lesion effect, defined as improvement without stimulation, was observed; immediate post-operative MRI demonstrated electrode located above or behind to the STN. CONCLUSIONS: Patients presenting micro-lesion effect should be carefully monitored, as this phenomenon can mask electrodes misplacement and evolution in DF.

Long-term outcome of 50 consecutive Parkinson's disease patients treated with subthalamic deep brain stimulation.

OBJECTIVE: To describe the long-term outcome in 50 consecutive advanced Parkinson's disease (PD) patients treated with subthalamic nucleus deep brain stimulation (STN-DBS). METHOD: Assessments were carried out at baseline, 6 months, 2 years, and 5 years postoperatively. RESULTS: Compared to baseline scores without medication, we found a highly significant improvement of UPDRS III with stimulation, maintained at 5 years (p<0.001). This improvement, however, tended to diminish over time. Dyskinesia and off periods were also improved (p<0.0001 for both). Seventeen patients died during follow-up, who tended to be older at surgery (p<0.01). CONCLUSIONS: STN-DBS is an effective treatment for advanced PD patients, and the beneficial effect is maintained at 5 years. However, worsening occurs over time due to disease progression.

Changes of the cortex proteome and Apolipoprotein E in transgenic mouse models of Alzheimer's Disease.

Transgenic mice carrying human Amyloid Precursor Protein mutations present amyloid plaque deposition in the brain upon aging. In this study, we characterized the changes of cortex proteome and endogenous Apolipoprotein E in these mice. Differential analysis of two-dimensional electrophoresis images revealed spots altered upon aging, transgene addition and plaque deposition. Alpha-synuclein and cytochrome oxidase polypeptide Va were up-regulated in transgenic mice. Upon aging, expression of ATP synthase alpha, alpha enolase, UMP-CMP kinase, and dihydropyrimidinase like-2 protein was modified. These proteins and their modification probably play a role in the amyloid aggregate formation in these mice.

[Neuronal death and growth factors: new therapeutic approaches in Parkinson's disease]. / Dégénérescence, régénérescence: un espoir thérapeu- tique pour la maladie de Parkinson.

Neurodegenerative disorders represent a major and growing cause of morbidity and mortality in our populations, and a therapeutic challenge for the years to come. This paper reviews the mechanisms implicated in neuronal death, focusing on the model of Parkinson's disease. Available data are critically presented, and oriented in a therapeutic perspective. Neuroprotective strategies are mentioned, along with stem cell transplantation, growth factor production and gene therapy.

[Wilson's disease: Clinical presentations]. / Maladie de Wilson: les présentations cliniques.

Wilson's disease is a rare genetic condition, transmitted on a recessive autosomal mode, which involves a disturbance of copper metabolism. Its prevalence is 1: 30000. It is treatable but may be lethal if not managed early and treated adequately. It is caused by the loss of function of an adenosine triphosphatase (ATP 7B), which is due to a mutation in the ATP 7B gene on chromosome 13. This leads to a decrease or absence of copper transport to the bile and its accumulation within certain organs, particularly the liver and the brain. In this article we present two cases of Wilson's disease in two young male patients. We also briefly review the pathophysiology of the illness, discuss the latest guidelines for diagnosis and treatment and outline the recent genetic discoveries.

[Current treatment of Parkinson's disease: problems and controversies]. / Traitement actuel de la maladie de Parkinson: difficultés et controverses.

Treating patients with Parkinson's disease is not an easy task for the physician who is facing a disease well responsive to symptomatic therapy, yet escaping any curative approaches. In spite of the large therapeutic armamentarium available, many issues remained unsolved, as indications of a particular therapeutic agent are only loosely defined and evolving according to various parameters such as disease progression and severity, the profile of potentially serious adverse effects, the physician's level of expertise and patient's expectations. The growing experience acquired with subthalamic nucleus deep brain stimulation has shown that indications for such a surgery have to be cautiously examined. After initial therapeutic enthusiasm, we are now at a time of problems and controversies.

Suicide after successful deep brain stimulation for movement disorders.

The authors observed a high rate of suicide (6/140 patients, 4.3%) in a large cohort of patients with movement disorders treated with deep brain stimulation (DBS). Apparent risk factors included a previous history of severe depression and multiple successive DBS surgeries, whereas there was no relationship with the underlying condition, DBS target, electrical parameters, or modifications of treatment. Paradoxically, all patients experienced an excellent motor outcome following the procedure. The authors propose that patients at high risk for suicide should be excluded from DBS surgery.

L-dopa-induced dyskinesia improvement after STN-DBS depends upon medication reduction.

The authors studied the long-term evolution of levodopa-induced dyskinesia (LID) after levodopa challenge in two groups of six STN-deep brain stimulation-treated Parkinson disease (PD) patients, one requiring medication after surgery and the other not. A dramatic (96%) reduction of LID severity was obtained in the six postoperatively untreated patients compared to a moderate improvement (47%) in the treated group (p < 0.03). These data support dopaminergic stimulation and striatal desensitization as major determinants of LID in PD.

[Recurrent encephalopathy after small bowel resection. Implication of D-lactate]. / Encéphalopathie complexe, transitoire et récidivante après résection étendue de l'intestin grêle. Responsabilité du D-Lactate.

Recurrent episodes of confusion are most commonly due to transient brain dysfunction related to vascular, epileptic or metabolic abnormalities. We report here a 54-year-old patient who, in the months following an extensive surgery of the small intestine, developed several acute confusional episodes characterized by encephalopathic signs (such as behavioral changes, desorientation and somnolence), ataxia, nystagmus and dysarthria. A number of metabolic changes were demonstrated during the episodes, including metabolic acidosis with increased anion gap and an elevated blood level of D-lactate. Symptoms disappeared after treatment with antibiotics. D-lactate encephalopathy is a rare cause of recurrent confusion which could be suspected based on a characteristic association of clinical signs. Diagnosis is confirmed by appropriate dosages. We discussed the possible mechanisms leading to confusional episodes.

CSF detection of the 14-3-3 protein in unselected patients with dementia.

OBJECTIVE: To determine the usefulness of the 14-3-3 test in patients with dementia of various causes. BACKGROUND: Recent reports have suggested that the detection of the 14-3-3 protein in the CSF of patients with Creutzfeldt--Jakob disease is a highly sensitive and specific marker of the disease that might be used as a diagnostic criterion. We examined the validity of this test when applied to a cohort of unselected patients prospectively examined for an ongoing dementing process. METHODS: One hundred patients underwent an extensive neurologic examination for dementia, including a CSF 14-3-3 protein immunoblotting assay. Final clinical diagnoses were compared with the qualitative results of the test, and statistical measures of test validity were carried out. RESULTS: We found a positive test in 14 of 100 patients, only two of whom had definite Creutzfeldt--Jakob disease. Positive results were found in patients with various degenerative dementias, including AD (4), frontotemporal dementia (2), and dementia with Lewy body (1), and in patients with vascular dementia (1), carcinomatous meningitis (1), and anoxic encephalopathy (1). In two other positive patients, the dementia could not be confidently classified. Sensitivity, specificity, and negative predictive value were fairly good, but positive predictive value was poor. Similar results were found independently of the disease duration. There was no correlation between intensity nor pattern of the 14-3-3 protein expression and diagnosis. CONCLUSIONS: The 14-3-3 test is not valid for discriminating between Creutzfeldt--Jakob disease and non-Creutzfeldt--Jakob disease in unselected patients with dementia. Positive results are found in various degenerative and secondary, prion-unrelated dementias.