Seizures in juvenile Huntington's disease: Frequency and characterization in a multicenter cohort

Abstract

Little is known about the epilepsy that often occurs in the juvenile form of Huntington's disease (HD), but is absent from the adult-onset form. The primary aim of this study was to characterize the seizures in juvenile HD (JHD) subjects with regard to frequency, semiology, defining EEG characteristics, and response to antiepileptic agents. A multicenter, retrospective cohort was identified by database query and/or chart review. Data on age of HD onset, primary HD manifestations, number of CAG repeats, the presence or absence of seizures, seizure type(s), antiepileptic drugs used, subjects' response to antiepileptic drugs (AEDs), and EEG results were assembled, where available. Ninety subjects with genetically confirmed JHD were included. Seizures were present in 38% of subjects and were more likely to occur with younger ages of HD onset. Generalized tonic-clonic seizures were the most common seizure type, followed by tonic, myoclonic, and staring spells. Multiple seizure types commonly occurred within the same individual. Data on EEG findings and AED usage are presented. Seizure risk in JHD increases with younger age of HD onset. Our ability to draw firm conclusions about defining EEG characteristics and response to AEDs was limited by the retrospective nature of the study. Future prospective studies are required.

ABHD6 Blockade Exerts Antiepileptic Activity in PTZ-Induced Seizures and in Spontaneous Seizures in R6/2 Mice

“…This subset of patients are afflicted by Juvenile HD (JHD), an early and more aggressive variant of the disease which uniquely features myoclonic seizures in 38% of patients (Cloud et al, 2012), which are refractory to standard anti-epileptic medications (Osborne et al, 1982; Landau and Cannard, 2003; Gonzalez-Alegre and Afifi, 2006). Therefore epilepsy is emerging as a major co-morbidity and unmet medical need of patients with JHD and yet little is known about the molecular mechanisms underlying seizure incidence in this patient population.…”

A two years longitudinal study of a transgenic Huntington disease monkey

“…Given the age of rHD1, the imaging findings and progressive development of cognitive behavioral decline, especially seizures, this particular animal may parallel human juvenile onset HD (JHD) even only with a small expansion of polyglutamine (29Q) compared to normal rhesus macaque (10-11Q) at the HTT gene. JHD patients have motor symptom onset younger than age 21, with a higher incidence of seizures in very young onset cases and stiffness, parkinsonism, and dystonia outweighing chorea especially in very young onset cases [49-54]. Seizures are unusual in adult onset HD [49].…”

“…JHD patients have motor symptom onset younger than age 21, with a higher incidence of seizures in very young onset cases and stiffness, parkinsonism, and dystonia outweighing chorea especially in very young onset cases [49-54]. Seizures are unusual in adult onset HD [49]. Imaging data in human JHD is very sparse, with caudate atrophy being the most consistent finding [55-58], which parallels with our findings that reduction in caudate volume was more profound compared to the putamen.…”

“…The progression of rHD1 is closer to juvenile onset HD than adult onset with the development of seizures, early impact on cognition and mild motor impairment [49-54]. We acknowledged that additional animals need to be prepared and studied using the same behavioral and cognitive tasks as well as neuroimaging procedures across development.…”

The unique co-occurrence of spinocerebellar ataxia type 10 (SCA10) and Huntington disease

“…It is interesting to note that the presence of epilepsy in this patient groups her with the Mexican/Venezuelan/Argentinian phenotype rather than the Brazilian phenotype. These symptoms would be unlikely to occur in adult HD patients, although seizures are relatively common in juvenile HD presenting before the age of 10 [11]. Similarly the presentation in the mid 30s with chorea, difficulty suppressing head movements during saccades and breakdown of alternating eye movements would be entirely consistent with the expected course of disease for 48 CAG repeat huntingtin [12].…”