Early juvenile reading epilepsy and later frontotemporal dementia (FTD): expanding the clinical phenotype of C9ORF72 mutation?

C9orf72 mutation (C9+) is a common genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis. C9+ clinical phenotype is heterogeneous and epilepsy has been recently described in few cases. We report a 47-year-old patient who developed reflex reading epilepsy (RRE) at the age of 19. After the first years with exclusive reflex seizures, afterwards the patients developed drug-resistant, unprovoked seizures and progressive cognitive deterioration. In the last years, a progressive motor impairment with spastic tetraparesis also occurred. During the hospitalization, the patient underwent an extensive workup identifying C9+ expansion and a family history suggestive for an autosomal dominant inheritance. This report, together with the few cases already described, raises the possibility that epileptic manifestations are part of the clinical phenotype of C9ORF72 mutation and reflect hyperexcitability of cortical networks involved in neurodegeneration.

Incidence and spatial distribution of adult-onset primary malignant and other central nervous system tumors in Southern Sardinia, Italy.

PURPOSE: To study for the first time the incidence of adult-onset CNS tumors in Southern Sardinia, Italy. METHODS: Clinical records of patients > 18 years old who were diagnosed with primary CNS tumors during 2016-2019 in the study area were reviewed. Meningiomas, cranial/paraspinal nerve tumors, lymphomas, and pituitary tumors were excluded. Cases were classified according to the 2016 WHO classification of CNS tumors and to the morphology codes from the International Classification of Diseases-Oncology, third edition. Age-adjusted incidence rates were calculated by the direct method to the 2011-2020 European standard population. Kulldorff's spatial scan statistic was used to identify geographic clusters of patients who shared increased/decreased tendency to develop CNS tumors. RESULTS: CNS tumors were diagnosed in 234 incident patients, but histological diagnosis was available in 222/234 patients (95%) aged 64.3 ± 13.5 years at diagnosis. Crude incidence rate was 7.1 per 100,000 persons-year (95% CI, 6.2-8.1), 6.2 per 100,000 persons-year (95% CI, 5.4-7.0) when age-adjusted. CNS tumors were more frequent in men and after age 40. Glioblastoma accounted for 76% of the total (adjusted rate, 4.7 per 100,000 persons-year; 95% CI, 4.0-5.4). Spatial analysis revealed geographic variations of glioblastoma incidence within the study area. CONCLUSION: Although the distribution of tumor diagnoses in Sardinia reflects expected age and gender-related patterns in western populations, our findings would indicate a slightly higher incidence of glial tumors, glioblastoma in particular, in Sardinia than in other European countries. The identification of spatial clusters of high/low risk will serve as a resource for etiological research.