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(Abst. 1.112), 2014

Authors: Alfonso Fasano, Felippe Borlot, Anthony Lang and Danielle Andrade
Content: Rationale: Given the poor knowledge of the clinical features of Dravet syndrome patients surviving until the adulthood, we prospectively investigated the motor abnormalities in a consecutive sample of adults with genetically proven Dravet syndrome. Dravet syndrome is a severe genetic epileptic encephalopathy, mainly caused by SCN1A mutations. Children usually develop frequent and pharmacoresistant seizures of several types. Besides cognitive delay, some patients later develop gait ataxia. "Crouch gait" has also been described in older patients. Methods: Adults with clinical and genetic diagnosis of Dravet syndrome were included. Previous exposure to antipsychotics was an exclusion criterion. A modified UPDRS was used. Patients who presented a severe bradykinesia, gait disorder or balance impairment underwent a trial of oral levodopa 300 mg/day plus carbidopa 75 mg/day and were videotaped after 3 and 16 weeks. Groups were compared by Mann-Whitney U test and Spearman test was used for correlation analysis. Results: Twelve patients entered the study. All but one patient presented severe cognitive delay; mild spasticity was seen in 12% of patients. All cases presented a mild to severe flexion of the head in the sagittal plane (42.9±19.7°) and eight (66%) fulfilled the diagnostic criteria for antecollis. Severity significantly correlated with age (ρ=0.59, p=0.04). The three oldest patients presented camptocormia and one of them also had Pisa syndrome. Eleven out of the 12 (91%) patients presented with parkinsonism; UPDRS significantly correlated with age (ρ=0.61, p=0.03), but not with seizure frequency; UPDRS was not different in patients receiving valproate (n=8, 10.8±7.9) or not (n=4, 14.5±7.9), nor correlated with the daily dose (ρ=0.11, p=0.73). Nine patients had gait impairment with small steps, en bloc turns, "crouch" gait, and wide base. Postural reflexes varied from normal to inability to stand unassisted. Parental consent for levodopa treatment was obtained in two of the four most affected patients. These patients obtained sustained improvement in slowness and rigidity; remarkably, one of them was no longer wheelchair-bound for long-distance walks. Conclusions: We describe for the first time that the majority of adult Dravet syndrome patients have features of parkinsonism and antecollis. Meaningful improvement after levodopa trial was seen. These findings expand the phenotype of a disease mainly known by its severe epilepsy and cognitive delay to include drug-responsive movement abnormalities. Knowledge of levodopa responsiveness may greatly diminish the burden of care of such complex patients.