Epilepsy in individuals with neurofibromatosis type 1

Abstract

SUMMARYPurpose: To describe the clinical characteristics and outcomes of individuals with neurofibromatosis type 1 (NF1) and seizures in the largest cohort reported to date. Methods: A retrospective cross-sectional review of 536 individuals with NF1 was performed, and clinical data from 51 individuals with a history of at least one seizure were analyzed. Key Findings: In individuals with NF1, 9.5% had a history of at least one unprovoked seizure, and 6.5% had documented epilepsy. Individuals with seizures were more likely to have inherited NF1 from their mother (p = 0.001). Focal seizures were the most common type, occurring in 57% of individuals, although generalized seizures, specific electroclinical syndromes, and the presence of multiple seizure types were also noted. Moreover, in 21% of individuals with a previously unremarkable magnetic resonance imaging (MRI) study, neuroimaging at seizure onset revealed a new structural abnormality. In this population, 77% of individuals required multiple antiepileptic drugs (AEDs), and some required epilepsy surgery, with the best results following temporal lobe glioma resection. Significance: Compared to the general population, seizures are more common in individuals with NF1, where they are often focal and related to an intracranial neoplasm. These observations suggest that all individuals with NF1 and a new seizure should undergo MRI despite previous normal neuroimaging. Individuals with seizures and NF1 typically require more aggressive therapy than those without NF1 and should be considered for epilepsy surgery when appropriate.

Racial/Ethnic Differences in Pediatric Brain Tumor Diagnoses in Patients with Neurofibromatosis Type 1

“…Select demographic information, including birth date, sex, and race/ethnicity, and clinical history information (including NF1 and brain tumor diagnoses), was abstracted from records for all subjects in the CIDER database with an NF1-related International Classification of Diseases Ninth Revision (ICD-9) code (237.70, or 237.71). NF1 diagnoses for patients identified using ICD-9 codes were validated through review of their medical records for NF1 clinical signs as previously described (29). …”

Modulation of GABAergic transmission in development and neurodevelopmental disorders: investigating physiology and pathology to gain therapeutic perspectives

“…The phenotype is not homogeneous, and it includes presence of neurofibromas, cognitive impairment and increased epilepsy (Costa and Silva, 2002; Diggs-Andrews and Gutmann, 2013; Ostendorf et al, 2013). Increased hyperactivity, sleep disturbance, and emotional issues are also present (Johnson et al, 2005; Leschziner et al, 2013).…”

“…Accordingly, GABAergic signaling has been implicated in a number of neurodevelopmental disorders, such as autism (Tabuchi et al, 2007; Coghlan et al, 2012), Fragile X (Curia et al, 2009; Coghlan et al, 2012), Rett Syndrome (Medrihan et al, 2008; Coghlan et al, 2012), Down Syndrome (Chakrabarti et al, 2010; Costa and Scott-McKean, 2013), Schizophrenia (Lewis et al, 2012), Tourette Syndrome (Kalanithi et al, 2005; Di Cristo, 2007), and Neurofibromatosis type I (Costa et al, 2002; Diggs-Andrews and Gutmann, 2013). Unfortunately, in most cases GABAergic drugs are dangerous because either they silence the neuronal network activity in a developing brain or, more often, they trigger epilepsy in patients with neurodevelopmental disorders, who -similarly to infants- (Connell et al, 1989; Sankar and Painter, 2005; Briggs and Galanopoulou, 2011; Loscher et al, 2013) are at higher risk of seizures per se (Rissman and Mobley, 2011; Coghlan et al, 2012; Ostendorf et al, 2013; Williams et al, 2013). Finding viable therapeutic treatments targeting GABAergic transmission in neurodevelopmental disorders is thus both of great importance and a big challenge.…”

Associations between allergic conditions and pediatric brain tumors in Neurofibromatosis type 1

“…We queried CIDER for International Classification of Diseases Ninth Revision (ICD-9) codes 237.70 or 237.71 for Neurofibromatosis to identify an initial set of 820 individuals with NF ICD-9 codes documented in their medical records from 7/1/1997 to 6/1/2014. Of these, 634 unique cases were verified through medical record review for the NF1 NIH diagnostic criteria [24] as described previously [25]. Patient records that included physician notes (history and physical), patient questionnaires, anesthesia records, outpatient surgery and pre-hospitalization forms, imaging records, administrative notes, and allergy status notes from inpatient records were examined for reported brain tumor and allergy/asthma diagnoses along with age of diagnoses.…”