Wenyu Liu1, Bo Yan2, Dongmei An3, Jiahe Xiao4, Fayun Hu5, Dong Zhou6. 1. Department of Neurology, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu 610041, China. Electronic address: wenyuliu9218@163.com. 2. Department of Neurology, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu 610041, China. Electronic address: yanbo96@163.com. 3. Department of Neurology, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu 610041, China. Electronic address: andongmei2010@gmail.com. 4. Department of Radiology, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu 610041, China. Electronic address: xiaojiahe@hotmail.com. 5. Department of Neurology, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu 610041, China. Electronic address: hufayun2006@163.com. 6. Department of Neurology, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu 610041, China. Electronic address: zhoudong66@yahoo.de.
Abstract
OBJECTIVE: The purpose of this study was to better delineate the clinical spectrum of periventricular nodular heterotopia (PNH) in a large patient population after long term follow up. Specifically, this study aimed to relate PNH subtypes to clinical or epileptic outcomes, epileptic discharges and underlying Filamin A (FLNA) mutations by analyzing anatomical features. METHODS: The study included 100 patients with radiologically confirmed nodular heterotopia. Patients' FLNA gene sequences and medical records were analyzed. Two-sided Chi-square test and Fisher's exact t-test were used to assess associations between the distribution of PNHs and specific clinical features. RESULTS: Based on imaging data, patients were subdivided into three groups: (a) classical (bilateral frontal and body, n=41 patients), (b) bilateral asymmetrical or posterior (n=16) and (c) unilateral heterotopia (n=43). Most patients with classical heterotopia were females (P=0.033) and were likely to have arachnoid cysts (P=0.025) and cardiac abnormalities (P=0.041), but were mostly seizure-free. Additionally, hippocampal abnormalities (P=0.022), neurological deficits (P=0.028) and cerebellar abnormalities (P=0.005) were more common in patients with bilateral asymmetrical heterotopia. Patients with unilateral heterotopia were prone to develop refractory epilepsy (P=0.041). FLNA mutations were identified in 8 patients. CONCLUSIONS: Each group's distinctive genetic mutations, epileptic discharge patterns and overall clinical outcomes confirm that the proposed classification system is reliable. These findings could not only be an indicator of a more severe morphological and clinical phenotype, but could also have clinical implications with respect to the epilepsy management and optimization of therapeutic options.
OBJECTIVE: The purpose of this study was to better delineate the clinical spectrum of periventricular nodular heterotopia (PNH) in a large patient population after long term follow up. Specifically, this study aimed to relate PNH subtypes to clinical or epileptic outcomes, epileptic discharges and underlying Filamin A (FLNA) mutations by analyzing anatomical features. METHODS: The study included 100 patients with radiologically confirmed nodular heterotopia. Patients' FLNA gene sequences and medical records were analyzed. Two-sided Chi-square test and Fisher's exact t-test were used to assess associations between the distribution of PNHs and specific clinical features. RESULTS: Based on imaging data, patients were subdivided into three groups: (a) classical (bilateral frontal and body, n=41 patients), (b) bilateral asymmetrical or posterior (n=16) and (c) unilateral heterotopia (n=43). Most patients with classical heterotopia were females (P=0.033) and were likely to have arachnoid cysts (P=0.025) and cardiac abnormalities (P=0.041), but were mostly seizure-free. Additionally, hippocampal abnormalities (P=0.022), neurological deficits (P=0.028) and cerebellar abnormalities (P=0.005) were more common in patients with bilateral asymmetrical heterotopia. Patients with unilateral heterotopia were prone to develop refractory epilepsy (P=0.041). FLNA mutations were identified in 8 patients. CONCLUSIONS: Each group's distinctive genetic mutations, epileptic discharge patterns and overall clinical outcomes confirm that the proposed classification system is reliable. These findings could not only be an indicator of a more severe morphological and clinical phenotype, but could also have clinical implications with respect to the epilepsy management and optimization of therapeutic options.
Authors: Laura Montier; Zulfi Haneef; Jay Gavvala; Daniel Yoshor; Robert North; Terence Verla; Paul C Van Ness; Janice Drabek; Alica M Goldman Journal: Epilepsia Date: 2019-09-06 Impact factor: 5.864
Authors: Sali M K Farhan; Kevin C J Nixon; Michelle Everest; Tara N Edwards; Shirley Long; Dmitri Segal; Maria J Knip; Heleen H Arts; Rana Chakrabarti; Jian Wang; John F Robinson; Donald Lee; Seyed M Mirsattari; C Anthony Rupar; Victoria M Siu; Michael O Poulter; Robert A Hegele; Jamie M Kramer Journal: Hum Mol Genet Date: 2017-11-01 Impact factor: 6.150