Prevalence of dentatorubral-pallidoluysian atrophy in a large series of white patients with cerebellar ataxia.

BACKGROUND: Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare neurodegenerative disorder mainly diagnosed in Japan. Its prevalence is low in other countries. Three phenotypes are described: choreoathetoid movements, cerebellar ataxia, and progressive myoclonic epilepsy. OBJECTIVE: To evaluate the frequency of DRPLA in European patients with sporadic or autosomal dominant cerebellar ataxia. METHODS: We analyzed a series of 809 index patients with either autosomal dominant cerebellar ataxia (416 families) or progressive cerebellar ataxia without a family history of the disease (393 cases) for the DRPLA mutation. RESULTS: We identified a CAG repeat expansion in the DRPLA gene in one family and in one patient without a family history. The familial case illustrates the phenomenon of anticipation and the previously established correlation between the phenotype and size of the expansion. A censored-history family or expansion of large normal CAG repeats during paternal transmission could be implicated in the patient without a family history. CONCLUSIONS: This study enables us to estimate the frequency of the disease as 0.25% in both families with autosomal dominant cerebellar ataxia and sporadic cases of ataxia in our series, confirming the very low frequency of DRPLA in Europe. In both familial and sporadic cases, molecular testing for DRPLA could be restricted to patients with ataxia with one of the following features: chorea, dementia, or myoclonic epilepsy.

[Difficulties and obstacles during medical treatment of epilepsies]. / Difficultés et obstacles au cours du traitement médical des épilepsies.

MULTIPLE OBSTACLES: There are many and various difficulties and obstacles during the medical treatment of epilepsy. They may create major stumbling blocks and largely jeopardize the control of this type of disease. POOR COMPLIANCE: Particularly frequent (30 to 50% of epileptics), it is one of the principle causes of pseudo-pharmaco-resistance. THE SIDE EFFECTS OF DRUGS: These are also frequent (15 to 30% of cases). Whatever their severity, they may be an important obstacle to the success of the treatment. Some of these effects are idiosyncratic, dose-independent, whereas others, non-idiosyncratic, are dose and time-dependent. THE AGGRAVATION OF EPILEPSY WITH ANTIEPILEPTIC AGENTS: This is possible and is usually due to an error in diagnosis, either in the type of seizure or the type of epilepsy in cause and which leads the physician to select an inappropriate treatment. Pregnancy may aggravate the progression of epilepsy in around a quarter of cases. Strict monitoring of the treatment is required. Intercurrent diseases and/or their treatment may have an impact on the epilepsy and its treatment. The diseases may be common affections or bacterial infections, psychiatric problems, lupus erythematosus or HIV infection. Likewise, the possible impact of commonly prescribed drugs such as those for gastric ulcers, asthma, cardiovascular diseases or even immunosuppressor treatments should be known. Renal failure and hepatic diseases often have a negative impact on antiepileptic treatments.

Oxidative stress level in circulating neutrophils is linked to neurodegenerative diseases.

Alzheimer's and Parkinson's diseases are the most common neurodegenerative conditions. Oxidative lesions are a hallmark of both diseases, but the respective roles of systemic and cerebral dysfunction are not elucidated. As circulating neutrophils are the most powerful sources of reactive oxygen species, we measured oxidative stress levels in resting neutrophils from 44 Alzheimer's and Parkinson's disease patients and compared them to 40 healthy counterparts. Significantly increased oxidative stress levels were observed in patients' groups, while control groups had very similar levels irrespective of age. One-third of the neurodegenerative patients presented with oxidative stress levels higher than those of any healthy donor. This increase was not due to an elevated production of reactive oxygen species during the neutrophil oxidative burst. Mitochondrial mass and activity were altered in neutrophils of the Parkinsonian group compared to controls, but not in those from Alzheimer's disease group. To our knowledge, this is the first report linking oxidative stress and mitochondrial parameters in circulating neutrophils from neurodegenerative and normal donors. Our results indicate that oxidative stress levels in circulating neutrophils are of interest for further mechanistic studies of neurodegenerative diseases and might open the perspective of a diagnostic tool.

Value of (99m)Tc-ECD SPET for the diagnosis of dementia with Lewy bodies.

Despite improved diagnostic accuracy, differentiation of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) on the basis of clinical findings remains problematic. The purpose of this retrospective study was to evaluate the utility of technetium-99m ethyl cysteinate dimer (ECD) single-photon emission tomography (SPET) as a potential tool for the diagnosis of DLB and discrimination from AD. Cerebral perfusion patterns detected by (99m)Tc-ECD SPET were compared in patients presenting with a probable diagnosis of DLB ( n=34) or AD ( n=28). Tracer distribution was quantified using the region of interest technique in eight symmetrical paired zones and expressed as a perfusion index (ratio of mean uptake in a brain region to that in the cerebellum). Comparison of findings in the DLB and AD groups demonstrated significant differences in mean perfusion indexes in the right occipital region ( P=0.004), left occipital region ( P=0.005) and left medial temporal region ( P=0.013). Mean perfusion indexes in the right and left occipital regions were lower in DLB than in AD patients. Conversely, the mean perfusion index in the left medial temporal region was lower in AD than in DLB patients. DLB was correctly identified in 22 patients (sensitivity, 65%) while AD was correctly identified in 20 patients (specificity, 71%). In the DLB group, right and left occipital perfusion indexes were 0.95 or more in all eight non-hallucinating patients, and bilateral occipital hypoperfusion was observed in 15 of the 26 patients with visual hallucinations (57.7%). To our knowledge, this is the first study in which (99m)Tc-ECD SPET has been used exclusively for the diagnosis of DLB. The results suggest that brain perfusion scintigraphy could be helpful in distinguishing DLB from AD if diagnosis based on clinical criteria alone is difficult. The findings also support a link between visual hallucinations and structural/functional changes in the occipital region in DLB patients.