Epilepsy in patients with advanced Fukuyama congenital muscular dystrophy.

BACKGROUND: Recent advances in respiratory management have improved survival for patients with Fukuyama congenital muscular dystrophy (FCMD), characterized by congenital muscular dystrophy and brain malformation. Previous studies reported that more than half of patients exhibit seizures in childhood. However, little is known about epilepsy after childhood. METHODS: To elucidate the long-term clinical course of epilepsy, we retrospectively reviewed all medical records in nine patients (6 males, mean age 20.7 years) with FCMD diagnosed between 1981 and 2019. RESULTS: The follow-up periods ranged from 6 to 30 years (mean 18.4 years). A total of 75 EEG recordings were available from nine patients. In some patients, EEGs were normal during early childhood but tended to show paroxysmal discharges with age. Overall, epileptic seizures were observed in six patients. Except for one presenting with afebrile seizure at one year of age, the remaining five patients developed epilepsy between 13 and 22 years of age. The most common seizure type was focal impaired awareness seizure. After adolescence, four patients exhibited status epilepticus. Their convulsive movements of the seizures became less prominent with progression of the disease. At the last evaluation, most patients (5/6) had uncontrolled seizures. CONCLUSIONS: Despite presence of distinct brain malformation, epileptic seizures may develop after childhood in FCMD patients. Our experience suggests that clinicians should be careful not to overlook epileptic seizures, especially in advanced-stage patients who had profound muscle weakness.

Comprehensive analysis of coding variants highlights genetic complexity in developmental and epileptic encephalopathy.

Although there are many known Mendelian genes linked to epileptic or developmental and epileptic encephalopathy (EE/DEE), its genetic architecture is not fully explained. Here, we address this incompleteness by analyzing exomes of 743 EE/DEE cases and 2366 controls. We observe that damaging ultra-rare variants (dURVs) unique to an individual are significantly overrepresented in EE/DEE, both in known EE/DEE genes and the other non-EE/DEE genes. Importantly, enrichment of dURVs in non-EE/DEE genes is significant, even in the subset of cases with diagnostic dURVs (P = 0.000215), suggesting oligogenic contribution of non-EE/DEE gene dURVs. Gene-based analysis identifies exome-wide significant (P = 2.04 × 10-6) enrichment of damaging de novo mutations in NF1, a gene primarily linked to neurofibromatosis, in infantile spasm. Together with accumulating evidence for roles of oligogenic or modifier variants in severe neurodevelopmental disorders, our results highlight genetic complexity in EE/DEE, and indicate that EE/DEE is not an aggregate of simple Mendelian disorders.

Ictal 99mTc-Ethyl Cysteinate Dimer SPECT Findings of a Girl With Refractory Localization-Related Epilepsy Who Developed Transient Ictal Bradycardia.

Ictal bradycardia, which is considered to be one of the causes of sudden unexplained death in epilepsy, is rare. A 10-year-old girl with focal cortical dysplasia in her right centroparietal region developed transient ictal bradycardia during cluster seizures. Brain magnetic resonance imaging demonstrated a high signal intensity lesion adjacent to the focal cortical dysplasia lesion. Ictal 99mTc-ethyl cysteinate dimer single-photon emission computed tomography (SPECT) detected hyperperfusion in an area containing the high signal intensity lesion, which was located close to the insular cortex. Since the hyperperfusion zone observed on SPECT was considered to reflect seizure propagation, it is possible that the ictal bradycardia experienced in the present case was caused by the following mechanism: The repetitive seizure activity caused the high-intensity lesion seen on MRI to expand into the right insular cortex, which controls cardiac rhythm, resulting in ictal bradycardia.

[Evaluation of six cases with hypothalamic hamartoma: the relationship between MRI findings and clinical features].

OBJECTIVE: We evaluated the relationship between MRI findings and clinical features in patients with hypothalamic hamartoma (HH). METHODS: We retrospectively reviewed MRI and clinical data (mental retardation, precocious puberty, behavioral problems, and epilepsy) in six patients (3 males and 3 females, ages 12 to 26) with HH. Based on the MRI classification by Arita, HH was classified into two types: parahypothalamic (P) and intrahypothalamic (I). RESULTS: Only one patient was classified as having P-type HH and five were classified as having I-type HH. The patient with P-type HH (diameter 21 mm) showed precocious puberty and mild behavioral problems, but did not developed epilepsy. On the other hand, all patients with I-type HH (diameter 10-32 mm, median 17 mm) developed epilepsy and behavioral problems. Except for one patient, who had the smallest sized HH, I-type four patients developed mental retardation and precocious puberty. Among patients with I-type HH, the size of the tumor was inversely correlated with the age at epilepsy onset and with the degree of mental retardation (DQ/IQ). CONCLUSION: Our data suggested that the MRI classification by Arita, when combined with tumor size, might be helpful in predicting the clinical manifestations in patients with HH.