Abstracts

Neuronal ceroid lipofuscinosis type 2 (NCL2), characterized by deficiency of the enzyme tripeptidyl peptidase 1, is a rare but important cause of neurologic morbidity in pediatric patients, characterized by seizures, language and motor delays, movement disorders, and vision loss around the age of 3. With the approval of cerliponase alfa, an enzyme replacement therapy given intraventricularly, children with NCL2 have had slower decline of motor and language function as well as lengthened life expectancy. However, due to the treatment’s recent approval in 2017, the clinical course of patients on cerliponase alfa is not well documented, thus we hope to explore long-term outcomes in 5 patients with NCL2 on cerliponase alfa in this single-center case series.

A retrospective case series was done on 5 patients with NCL2 on cerliponase alfa at a single pediatric hospital. Data was collected to study each patient’s initial presentation and clinical course both before and after starting cerliponase alfa in terms of seizure burden, anti-seizure medication (ASM) regimen, and electroencephalogram (EEG) changes.

All patients presented with seizures of varying semiology around the age of 3 years with a mean onset age of 35 months. Throughout their disease course, the patients exhibited seizure semiologies including generalized tonic-clonic (GTC), focal, atypical absence, myoclonic, and atonic seizures. All patients progressed to refractory epilepsy, defined as epilepsy persisting after two failed ASMs, with failure of the second ASM occurring at a mean age of 49 months. Two patients required vagal nerve stimulator (VNS) placement at ages 68 and 67 months due to refractory seizures. In terms of EEG findings, mild to moderate diffuse generalized slowing, loss of well formed posterior dominant rhythm, and both multifocal and generalized epileptiform discharges were seen at the time of starting ERT. EEG showed evidence of progression to Lennox Gastaut Syndrome in 4 patients at a mean age of 110 months. Patients were started on cerliponase alfa at a mean age of 56 months. Upon initiating cerliponase alfa, patients exhibited subjective improvement in convulsive seizure burden initially, with seizure free period of 5-12 months. During the treatment course, most patients have progressed to weekly seizures despite continuing ERT. Alongside cerliponase alfa, all patients required a regimen of at least two ASMs for optimal seizure control, with 3 patients requiring ≥3 ASMs.

Patients with NCL2 present with seizures of varying semiology which progresses to refractory epilepsy. Based on this case series, cerliponase alfa infusions improve the seizure burden of patients with NCL2 initially; however, patients show evidence of disease progression after several years on the therapy.