We report the case of a 15-year-old boy who experienced frequent myoclonic seizures and ataxia for 3 years. He had normal neuropsychiatric development before the initial onset of seizures at the age of 12 years. He presented with generalized and focal myoclonic seizures. Progressive ataxia and psychomotor and speech regression developed 6 months later. The myoclonic seizures were refractory to multiple antiepileptic drugs (AEDs) including clobazam, sodium valproate, levetiracetam, and phenobarbital in full dosage. Furthermore, he had dysarthria and poor feeding, which necessitated nasogastric tube feeding. He was completely bedridden for several months. When he was admitted to our hospital at the age of 15 years and 9 months, he had nearly continuous focal facial myoclonus, which subsequently spread to the extremities. The facial myoclonus lasted for 15-20 s and occurred more than 100 times per day. His electroencephalogram (EEG) (Fig. 1) revealed focal spikes arising from bilateral centrotemporal regions, followed by ictal myoclonic seizures with generalized muscle contraction activities lasting 15-20 s observed on the EEG. Because progressive myoclonic epilepsy was suspected, extensive workups were performed. The plasma amino acid test, tandem mass spectrometry, and muscle biopsy revealed nonspecific changes. Magnetic resonance images (Fig. 2) of the patient's brain showed mild brain atrophy. Apocrine skin biopsy did not show the presence of Lafora bodies. Genetic testing for EPM2A, EPM2B, and CSTB revealed negative results. However, abnormal somatosensory-evoked potentials with giant cortical waves were found. Cherry-red spots on bilateral maculae on the eye grounds were observed. Therefore, we performed genetic testing under the suspicion of sialidosis. Direct sequence analysis of PCR-amplified DNA of this patient had identified the presence of compound heterozygous mutations in NEU1. One of the mutations was a common missense mutation c.544A > G, causing the amino acid substitution Ser182Gly. The other one was a nonsense mutation c.619C > T, which yielded a termination codon, thus producing a truncated protein (Fig. 3). The diagnosis of PMEs with sialidosis type I was thus made.
After admission, the patient had a partial myoclonic status, which was resistant to many antiseizure medications and also did not respond to a ketogenic diet. The patient's condition was complicated by aspiration pneumonia and generalized tonic-clonic (GTC) seizures. Eventually, he was started on perampanel therapy at 4 mg/day, with rapid titration to 8 mg/day. He showed a positive response. The number of seizure episodes significantly reduced after 3 days' of treatment with 8 mg/day of perampanel. Complete remission of the myoclonus and GTCs was achieved after titration to 10 mg/day for 3 days. The patient's clinical condition also improved. He could speak a few sentences, and feed himself with assistance. After 2 months, he could walk several steps with device. During 20-month follow-up, complete remissions of the myoclonic seizures and GTCs sustained under combination therapy with topiramate, sodium valproate, levetiracetam, clobazam, and perampanel, with total weaning of phenobarbital. He is currently receiving a perampanel dose of 10 mg/day. His neurological and cognitive functions remained stable. He has returned to school and moves with a wheelchair. His recent intelligence quotient (IQ) was 52. No previous IQ data were available for this patient before the disease onset.