Hully M.,AP HP |
Vuillaumier-Barrot S.,Biochemistry and Genetic Laboratory |
Le Bizec C.,Biochemistry and Genetic Laboratory |
Boddaert N.,AP HP |
And 26 more authors.
European Journal of Medical Genetics | Year: 2015
Introduction: Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a rare genetic disorder due to mutations or deletions in SLC2A1, resulting in impaired glucose uptake through the blood brain barrier. The classic phenotype includes pharmacoresistant epilepsy, intellectual deficiency, microcephaly and complex movement disorders, with hypoglycorrhachia, but milder phenotypes have been described (carbohydrate-responsive phenotype, dystonia and ataxia without epilepsy, paroxysmal exertion-induced dystonia).The aim of our study was to provide a comprehensive overview of GLUT1DS in a French cohort. Methods: 265 patients were referred to the French national laboratory for molecular screening between July 2006 and January 2012. Mutations in SLC2A1 were detected in 58 patients, with detailed clinical data available in 24, including clinical features with a focus on their epileptic pattern and electroencephalographic findings, biochemical findings and neuroimaging findings. Results: 53 point mutations and 5 deletions in SLC2A1 were identified. Most patients (87.5%) exhibited classic phenotype with intellectual deficiency (41.7%), epilepsy (75%) or movement disorder (29%) as initial symptoms at a medium age of 7.5 months, but diagnostic was delayed in most cases (median age at diagnostic 8 years 5 months). Sensitivity to fasting or exertion in combination with those 3 main symptoms were the main differences between mutated and negative patients (p < 0.001). Patients with myoclonic seizures (52%) evolved with more severe intellectual deficiency and movement disorders compared with those with Early Onset Absence Epilepsy (38%). Three patients evolved from a classic phenotype during early childhood to a movement disorder predominant phenotype at a late childhood/adulthood. Conclusions: Our data confirm that the classic phenotype is the most frequent in GLUT1DS. Myoclonic seizures are a distinctive feature of severe forms. However a great variability among patients and overlapping through life from milder classic phenotype to paroxysmal-prominent- movement-disorder phenotype are possible, thus making it difficult to identify definite genotype-phenotype correlations. © 2015 Elsevier Masson SAS.
Ory-Magne F.,Clinical Investigation Center 9302 |
Ory-Magne F.,University Hospital of Toulouse |
Corvol J.-C.,French Institute of Health and Medical Research |
Corvol J.-C.,University Pierre and Marie Curie |
And 25 more authors.
Neurology | Year: 2014
Objective: The AMANDYSK trial was designed to assess long-term efficacy of chronic treatment with amantadine in patients with Parkinson disease (PD) and levodopa-induced dyskinesia (LID). Methods: This was a 3-month, multicenter, randomized, double-blind, placebo-controlled, parallelgroup, wash-out study conducted in 57 amantadine-treated ($200 mg/d for $6 months) dyskinetic patients with PD. The primary outcome measure was the change from baseline in a Unified Parkinson's Disease Rating Scale (UPDRS) dyskinesia subscore (items 32 [duration] 1 33 [severity]). Secondary outcomes included other LID measurements ("responders" analysis, premature dropout for LID, Abnormal Involuntary Movement Scale). Exploratory outcomes included time with troublesome dyskinesia as measured by diaries, UPDRSMotor Examination (part III) for motor symptoms of PD, and fatigue and apathy scores for nonmotor symptoms. Results: UPDRS items 32 1 33 deteriorated more in patients switched to placebo ("discontinuing" group) (11.7 6 2.0 units; 95% confidence interval 0.9, 2.4) as compared with those maintained on amantadine ("continuing" group) (10.2 6 1.5 units; 95%confidence interval 20.4, 0.8; p 5 0.003). Secondary outcomes confirmed this difference because there were significantly more responders, more dropouts for LID, greater increase in "ON" time with troublesome dyskinesia, and greater worsening of Abnormal Involuntary Movement Scale score in the discontinuing group. There were no between-group differences in the UPDRS Motor Examination, whereas apathy (as measured by caregivers) and fatigue scores tended to worsen more in patients randomized to placebo. Conclusion: Wash-out of amantadine in dyskinetic patients with PD significantly worsened LID. No significant effect was observed on motor parkinsonian symptoms, while exploratory outcomes suggested that amantadine might improve apathy and fatigue in such patients. Classification of evidence: This article providesClass II evidence that in patientswith PD,withdrawing amantadine significantly aggravates LID in a median time of 7 days. © 2014 American Academy of Neurology.