ABSTRACT
SYNGAP1 haploinsufficiency results in a developmental and epileptic encephalopathy (DEE) causing generalized epilepsies accompanied by a spectrum of neurodevelopmental symptoms. Concerning interictal epileptiform discharges (IEDs) in electroencephalograms (EEG), potential biomarkers have been postulated, including changes in background activity, fixation-off sensitivity (FOS) or eye closure sensitivity (ECS). In this study we clinically evaluate a new cohort of 36 SYNGAP1-DEE individuals. Standardized questionnaires were employed to collect clinical, electroencephalographic and genetic data. We investigated electroencephalographic findings, focusing on the cortical distribution of interictal abnormalities and their changes with age. Among the 36 SYNGAP1-DEE cases 18 presented variants in the SYNGAP1 gene that had never been previously reported. The mean age of diagnosis was 8 years and 8 months, ranging from 2 to 17 years, with 55.9% being male. All subjects had global neurodevelopmental/language delay and behavioral abnormalities; 83.3% had moderate to profound intellectual disability (ID), 91.7% displayed autistic traits, 73% experienced sleep disorders and 86.1% suffered from epileptic seizures, mainly eyelid myoclonia with absences (55.3%). A total of 63 VEEGs were revised, observing a worsening of certain EEG findings with increasing age. A disorganized background was observed in all age ranges, yet this was more common among older cases. The main IEDs were bilateral synchronous and asynchronous posterior discharges, accounting for ≥50% in all age ranges. Generalized alterations with maximum amplitude in the anterior region showed as the second most frequent IED (≥15% in all age ranges) and were also more common with increasing age. Finally, diffuse fast activity was much more prevalent in cases with 6 years or older. To the best of our knowledge, this is the first study to analyze EEG features across different age groups, revealing an increase in interictal abnormalities over infancy and adolescence. Our findings suggest that SYNGAP1 haploinsufficiency has complex effects in human brain development, some of which might unravel at different developmental stages. Furthermore, they highlight the potential of baseline EEG to identify candidate biomarkers and the importance of natural history studies to develop specialized therapies and clinical trials.
ABSTRACT
La cefalea es una patología frecuente en las consultas pediátricas de Atención Primaria, correspondiendo la mayoría de ellas a cefaleas primarias que no requieren exámenes complementarios. Cuando la cefalea es sugestiva de patología intracraneal hay que realizar pruebas de imagen, siendo los tumores una causa frecuente de cefalea secundaria. No obstante, otras patologías benignas pueden dar clínica de hipertensión intracraneal (HTIC) como es el caso de la hemicerebelitis. Presentamos un caso de una niña de 10 años de edad, con cefalea y evolución a HTIC de inicio agudo. La resonancia magnética reveló una inflamación unilateral del cerebelo, diagnosticándose de hemicerebelitis. Nuestra paciente mantuvo síntomas hasta la realización de la punción lumbar que la dejó asintomática. El pronóstico de esta patología es excelente y la remisión clínica completa. En la mayoría de los casos, queda una atrofia cerebelosa del hemisferio afecto residual, generalmente sin repercusión clínica. La evolución clínica y hallazgos de la resonancia magnética ayudan a descartar malignidad y adoptar un enfoque conservador tanto diagnóstico como terapéutico (AU)
Headache is a frequent pathology in pediatric Primary Care, most of which correspond to primary headaches that do not require additional examination. When headache is suggestive of intracranial pathology, imaging tests are needed, since tumors are a frequent cause of secondary headache. However, intracranial hypertension (IH) may be a symptom of other benign pathologies, such as hemicerebellitis. We present the case of a 10-year-old girl, with headache that progresses into IH of acute onset. Magnetic resonance imaging revealed unilateral inflammation of the cerebellum, diagnosed as hemicerebellitis. Symptoms continued until a lumbar puncture was performed, after which the patient became asymptomatic. This pathology has an excellent prognosis, and clinical remission is complete. In most cases, a residual cerebellar atrophy of the affected hemisphere remains, generally without clinical impact. The clinical course and the findings of magnetic resonance imaging help to discard malignancy and to take a diagnostic and therapeutic conservative approach (AU)
