Standardized assessment of seizures in patients with juvenile neuronal ceroid lipofuscinosis

Abstract

AIM To evaluate seizure phenomenology, treatment, and course in individuals with juvenile neuronal ceroid lipofuscinosis (JNCL). METHOD Data from an ongoing natural history study of JNCL were analyzed using cross-sectional and longitudinal methods. Seizures were evaluated with the Unified Batten Disease Rating Scale, a disease-specific quantitative assessment tool. RESULTS Eighty-six children (44 males, 42 females) with JNCL were assessed at an average of three annual visits (range 1–11y). Eighty-six percent (n=74) experienced at least one seizure, most commonly generalized tonic-clonic, with mean age at onset of 9 years 7 months (SD 2y 10mo). Seizures were infrequent, typically occurring less often than once every 3 months, and were managed with one to two medications for most participants. Valproate (49%, n=36) and levetiracetam (41%, n=30) were the most commonly used seizure medications. Myoclonic seizures occurred infrequently (16%, n=14). Seizure severity did not vary by sex or genotype. Seizures showed mild worsening with increasing age. INTERPRETATION The neuronal ceroid lipofuscinoses (NCLs) represent a group of disorders unified by neurodegeneration and symptoms of blindness, seizures, motor impairment, and dementia. While NCLs are considered in the differential diagnosis of progressive myoclonus epilepsy, we show that myoclonic seizures are infrequent in JNCL. This highlights the NCLs as consisting of genetically distinct disorders with differing natural history.

Guidelines for incorporating scientific knowledge and practice on rare diseases into higher education: neuronal ceroid lipofuscinoses as a model disorder

“…Not all NCLs are created equal. For example, children with CLN1 and CLN2 diseases often develop intractable seizures, whereas seizures are less common and more easily managed in CLN3 disease [32]. Thus, seizure management will be different and may be specific to the genetic type.…”

Future perspectives: Moving towards NCL treatments

“…As candidate treatments for other forms of NCL make their way into clinical trials, the successful efforts for CLN2 will serve as an important model. The first CLN3 human clinical trial is also under way (Phase 2 trial of CellCept, ClinicalTrials.gov NCT01399047) and is aiding in the optimization of an across-site CLN3 rating scale for future analysis of efficacy (15–17). …”

Hidden gems: validity and reproducibility of measures of oropharyngeal dysphagia – secondary conclusions and contributions

“…At least 14 different genes 1,2 are now known to be involved in the pathogenesis of these conditions which show recessive inheritance and are linked by common symptoms together with the presence of abnormal lysosomal storage in neurons and other cells. Juvenile NCL, caused by mutations in the gene CLN3, and sometimes referred to as Batten disease (especially in North America), is the subject of the paper by Augustine et al 3 Over 80% of affected young people are homozygous or heterozygous for a common disease allele, a deletion of approximately 1kb in exon 6. Although there is some phenotypic variation even between affected siblings, many individuals follow a typical course with progressive vision loss over 6 to 24 months in the early school years, followed by some slowing of academic progress and then seizures towards the end of primary school or in the early adolescent years.…”