Clinical and electroencephalogram features of neuronal ceroid lipofuscinosis

Abstract

Objective To summarize the clinical and electroencephalogram features of neuronal ceroid lipofuscinosis (NCL). Methods A retrospective analysis of the clinical phenotypes and electroencephalogram features of patients diagnosed with NCL in Department of Pediatrics, Peking University First Hospital from February 2000 to August 2015 were conducted. Results Among the 30 patients, 18 were male and 12 were female.The age of onset was between 9 months to 7 years old.The first symptoms included seizure in 22 patients, psychomotor developmental delay or regre-ssion in 7 cases, and visual loss in 1 case.Clinical manifestations included psychomotor regression in 29 cases, epilepsy in 28 cases, visual impairment in 19 cases, ataxia in 20 patients, and positive pyramidal tract sign in 13 cases.Twenty-one patients accepted fundus oculi examination.Seven patients were found with macular degeneration, 8 cases with optic nerve atrophy, 2 cases with retinal pigment degeneration, and 8 patients were normal.Brain atrophy were found in all 30 cases, including diffuse brain atrophy in 14 cases, only cerebellar atrophy in 6 cases, and cerebral atrophy with periventricular T2W high signal in 10 cases.Video electroencephalogram(EEG) examination was performed in 27 patients and their backgrounds were diffuse slow waves.Seven patients didn′t have physiological vertex sharp waves or sleep spindles.Generalized epileptiform discharges were captured in 6 cases, focal epileptiform discharges in 15 cases.Both of generalized and focal epileptiform discharges were captured in 6 cases.Generalized slow wave burst in 4 cases, and intermittent photic stimulation evoked epileptiform discharges in 3 cases.Ten patients were observed with clinical seizures, including 4 cases of myoclonic episodes, 3 cases of atypical absences, 3 cases of focal seizures, 1 case of atonic and one of tonic spasms.Peripheral blood enzyme examination was taken in 13 patients, among whom 8 patients were identified with tripeptidyl peptidase 1 (TPP1) deficiency and 1 patient with palmitoyl protein thioesterase 1 (PPT1) deficiency.Twenty-eight patients accepted skin and/or muscle electron microscope examination.Osmiophilic granular was found in 2 cases, curvilinear bodies in 15 cases, fingerprint profiles in 2 cases, curvilinear and linear bodies in 1 case, fingerprint profiles and osmiophilic granular in 1 case.NCL-related gene detection was conducted in 3 patients, with 1 patient identified with CLN6 compound heterozygous mutations and 2 patients with TPP1 homozygous mutations.Thirty patients were classified into 3 groups based on the onset age, enzymatic examination results and pathological examination of skin and muscle, including 5 cases of infantile NCL, 20 cases of late-infantile NCL, and 5 cases of juvenile NCL. Conclusions The clinical features of NCL included multiple types of epileptic seizures (among which myoclonus was the most common type), psychomotor developmental delay or regression, vision loss, ataxia, and positive pyramidal tract sign.Its MRI was characterized with brain atrophy.EEG showed diffuse slow wave activity, with focal and/or generalized epileptiform discharges.Specific enzyme examination, and skin or muscle pathology or gene test could help to make diagnosis. Key words: Neuronal ceroid lipofuscinosis; Epilepsy; Magnetic resonance imaging; Tripeptidyl peptidase 1; Palmitoyl protein thioesterase 1; Pathology; Gene