Early intervention for conversion disorder: neurologists and psychiatrists working together

Objective To evaluate the efficacy of an early multidisciplinary (neurology and psychiatry) intervention for conversion disorder (CD). Methods Consecutive patients newly diagnosed with CD from 2005 to 2007 were compared to a control group of newly diagnosed CD patients receiving usual care. At 3 years, a questionnaire evaluated self‐rated subjective outcome, symptom severity, SF‐36 scores, employment status and medical care use. Results Data from 12 cases (mean age 25.5 ± 8.2; 9 females) and 11 controls (mean age 34.7 ± 13.5; 10 females) showed that 83% of cases had a good subjective outcome (symptom improved or cured) when only 36% of controls had a good outcome (p < 0.05). Cases significantly improved their SF‐36 scores on subscales involving physical complaints compared to controls. A minority (20%) of cases reduced or ceased professional activity when 70% of controls did (p < 0.001). Only 16% of cases sought further medical advice for the initial symptom when 73% of controls did. Both groups accepted psychiatric referrals (83% of cases and 73% of controls) and found it beneficial. Conclusions Early intervention involving both neurologists and psychiatrists is effective for CD in alleviating physical complaints, reducing sick leave and health care us

Strong EBV-specific CD8+ T-cell response in patients with early multiple sclerosis

Epstein-Barr virus (EBV) has been associated with multiple sclerosis (MS), however, most studies examining the relationship between the virus and the disease have been based on serologies, and if EBV is linked to MS, CD8+ T cells are likely to be involved as they are important both in MS pathogenesis and in controlling viruses. We hypothesized that valuable information on the link between MS and EBV would be ascertained from the study of frequency and activation levels of EBV-specific CD8+ T cells in different categories of MS patients and control subjects. We investigated EBV-specific cellular immune responses using proliferation and enzyme linked immunospot assays, and humoral immune responses by analysis of anti-EBV antibodies, in a cohort of 164 subjects, including 108 patients with different stages of MS, 35 with other neurological diseases and 21 healthy control subjects. Additionally, the cohort were all tested against cytomegalovirus (CMV), another neurotropic herpes virus not convincingly associated with MS, nor thought to be deleterious to the disease. We corrected all data for age using linear regression analysis over the total cohorts of EBV- and CMV-infected subjects. In the whole cohort, the rate of EBV and CMV infections were 99% and 51%, respectively. The frequency of IFN-γ secreting EBV-specific CD8+ T cells in patients with clinically isolated syndrome (CIS) was significantly higher than that found in patients with relapsing-remitting MS (RR-MS), secondary-progressive MS, primary-progressive MS, patients with other neurological diseases and healthy controls. The shorter the interval between MS onset and our assays, the more intense was the EBV-specific CD8+ T-cell response. Confirming the above results, we found that EBV-specific CD8+ T-cell responses decreased in 12/13 patients with CIS followed prospectively for 1.0 ± 0.2 years. In contrast, there was no difference between categories for EBV-specific CD4+ T cell, or for CMV-specific CD4+ and CD8+ T-cell responses. Anti-EBV-encoded nuclear antigen-1 (EBNA-1)-specific antibodies correlated with EBV-specific CD8+ T cells in patients with CIS and RR-MS. However, whereas EBV-specific CD8+ T cells were increased the most in early MS, EBNA-1-specific antibodies were increased in early as well as in progressive forms of MS. Our data show high levels of CD8+ T-cell activation against EBV—but not CMV—early in the course of MS, which support the hypothesis that EBV might be associated with the onset of this diseas

Investigation of memory, executive functions, and anatomic correlates in asymptomatic FMR1 premutation carriers

AbstractFragile X–associated tremor/ataxia syndrome (FXTAS) is a late-onset movement disorder associated with FMR1 premutation alleles. Asymptomatic premutation (aPM) carriers have preserved cognitive functions, but they present subtle executive deficits. Current efforts are focusing on the identification of specific cognitive markers that can detect aPM carriers at higher risk of developing FXTAS. This study aims at evaluating verbal memory and executive functions as early markers of disease progression while exploring associated brain structure changes using diffusion tensor imaging. We assessed 30 aPM men and 38 intrafamilial controls. The groups perform similarly in the executive domain except for decreased performance in motor planning in aPM carriers. In the memory domain, aPM carriers present a significant decrease in verbal encoding and retrieval. Retrieval is associated with microstructural changes of the white matter (WM) of the left hippocampal fimbria. Encoding is associated with changes in the WM under the right dorsolateral prefrontal cortex, a region implicated in relational memory encoding. These associations were found in the aPM group only and did not show age-related decline. This may be interpreted as a neurodevelopmental effect of the premutation, and longitudinal studies are required to better understand these mechanisms

Stimulation cérébrale profonde dans la maladie de Parkinson: effets moteurs et comportementaux

(from the journal abstract) The last 15 years have seen the progressive introduction of deep-brain stimulation (DBS) for the treatment of Parkinson's disease. This advance has been possible thanks to better understanding of the organisation of the basal ganglia with parallel segregated loops involved in the control of movement, behaviour, mood and cognition that interact through interneurons or collateral projections. Deep-brain stimulation, which allows by stimulation adjustments to optimise the benefit/side effect ratio, has made possible bilateral treatments needed for treating Parkinson's disease, while former available lesions were contraindicated because of the substantial side effects they produced. Thalamic ventral intermediate nucleus was the first target. It affects the cerebello-thalamocortical pathway and is mainly effective on tremor with little benefit on the other signs of Parkinson's disease. For Parkinson's disease it has progressively completely been replaced by the two other targets and is currently mainly used to treat medication-resistant essential tremor. Internal posterior part of globus pallidus acts on the common output nucleus of the basal ganglia loops. It has been proven very effective for treating motor fluctuations, mainly dyskinesia. Its effects on motor signs of Parkinson's disease are moderate and variably observed probably secondary to the organisation of this relatively large nucleus, with deep-brain stimulation effects depending upon precise localisation. Globus pallidus deep-brain stimulation does not allow antiparkinsonian medication reduction, in contrast to subthalamic deep-brain stimulation, but necessitates a progressive increase of drugs, with some decrease in efficacy with time. Globus pallidus being very effective on dyskinesia is currently rather used to treat other movement disorders, e.g. dystonia. Subthalamic deep-brain stimulation has become the main target for treating Parkinson's disease. It is acting on the indirect pathway, correcting the subthalamic hyperactivity secondary to disinhibition following dopamine depletion in Parkinson's disease. Subthalamic deep-brain stimulation improves the four major signs of Parkinson's disease, with effects mimicking levodopa: response to levodopa challenge being one of the best predictive parameters of the response to subthalamic deep-brain stimulation. This treatment allows substantial antiparkinsonian drug reduction. The latter is the main responsible for dyskinesia reduction observed after subthalamic deep-brain stimulation. Subthalamic deepbrain stimulation effects are maintained for at least 5 years although increase in axial signs and dementia is observed with Parkinson's disease progression. Beside the motor effects, deep-brain stimulation may induce acute or chronic neurobehavioural changes. The former is probably secondary to direct effect on structures adjacent to the targeted nuclei or involvement of parallel basal ganglia circuitry. The latter, which develops over months or years, is possibly also related to medication changes, neuronal plasticity following deep-brain stimulation, adaptation difficulties and dramatic socio-familial modification induced by the motor effects of deep-brain stimulation. Depression, apathy, anxiety, mania, pathological gambling, sexual behaviours and hallucinations have all been described following deep-brain stimulation. These changes, which underline the importance of basal ganglia circuitry in mood and behaviour, may have severe consequences including suicides. If the acute effects can usually easily be corrected by deep-brain stimulation tuning, the chronic modifications need to be detected and often necessitate a multidisciplinary approach. This careful multidisciplinary (neurologist, neuropsychologist, neurosurgeon, psychiatrist) collaboration is important not only for the selection but also for the follow-up of Parkinson's disease patients treated by deep-brain stimulation. (PsycINFO Database Record (c) 2005 APA, all rights reserved

Non-dopaminergic drugs for motor symptoms

A new optimism that Parkinson's disease can be defeated is energizing the research community. Halting the progression of the disease, restoring function, and even prevention are all realistic goals. This comprehensive volume provides state-of-the-art information on all aspects of Parkinson's disease, including epidemiology, genetics, diagnosis, treatment, and social issues. Novel and attractive models are included to simplify difficult-to-understand concepts, with emphasis on therapeutics. Written by leaders in the field, Parkinson's Disease emphasizes both the importance of early diagnosis and the search for more effective therapies

Résistances thérapeutiques dans les mouvements anormaux

Therapeutic strategies for essential tremor (ET) and Parkinson's disease (PD) can be divided into two successive steps, one based on oral medications and the other, more invasive, using pumps or functional neurosurgery. When ET becomes refractory to propranolol, primidone and other, second-choice compounds, deep brain stimulation of the VIM nucleus of the thalamus can be considered. When PD becomes resistant to dopamine replacement therapy using various combinations of dopaminergic agents, then three options can be discussed: first, a subcutaneous apomorphine mini-pump, second, a jejunal levodopa-delivery system by means of percutaneous gastrostomy, and third, bilateral deep brain stimulation of the subthalamic nucleus. The above interventions are successful in about 80% of cases

Stimulation cérébrale profonde : passé, présent et avenir

Recently awarded by the prestigious Lasker Foundation, high-frequency deep brain stimulation (DBS) has been used for the first time in 1987 in tremor and in 1993 in Parkinson's disease (PD) by the Grenoble group. So far, over 100 000 patients have been operated on worldwide. In PD, DBS induces an almost complete abatement of tremor, motor fluctuations and dyskinesias along with a reduction in levodopa dose. Although its mechanism of action is not fully understood, DBS would inhibit or modulate the expression of abnormal neuronal networks associated with given symptoms. It is therefore expected that DBS will extend to other severe neurological and psychiatric disorders. Furthermore, technological advances of the procedure are ongoing to optimize final outcomes

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