Surgical outcome and prognostic factors of pediatric epilepsy caused by cortical dysplasia

Objects We analyzed 30 patients with cortical dysplasia (CD) and epilepsy to evaluate the clinical characteristics and surgical outcome of both epilepsy control and neurocognition.Materials and methods The mean ages at seizure onset and at the time of the operation were 3.6 years (range, 1 month–12.6 years) and 10.3 years (range, 1.5–18.3 years), respectively. The mean follow-up period was 3.2 years (range, 1–5.3 years). ¹⁸FDG-positron emission tomography was the most sensitive and magnetic resonance imaging was the most specific in localizing the lesion. Developmental/intellectual delay was predominant in the early-onset group (n=18, seizure onset <3 years), with intelligence tending to be normal in the late-onset group (n=12, seizure onset ≥3 years). Mild CD predominated in the late-onset epilepsy group and moderate or severe CD in the early-onset group (p=0.005). The surgical success rate of epilepsy control was 87%. A better outcome was obtained if the lesion was confined to the temporal lobe. School performance was favorable in 43%. The age at seizure onset and preoperative developmental/intellectual delay were the important prognostic factors in school performance as well as the epilepsy control. A total of 77% of patients had relatively good social adaptation. Successful epilepsy control and good school performance were affirmative conditions precedent to social adaptation.Conclusions Due to the favorable control of epilepsy and its effect on school performance and social adaptation, surgical treatment is strongly recommended for cortical dysplasia and intractable epilepsy.     

Abdominal Epilepsy in an Adolescent with Bilateral Perisylvian Polymicrogyria

Summary: Purpose : We report a patient with recurrent episodes of severe periumbilical pain accompanied by headache, pallor, dizziness, and visual hallucinations who was subsequently diagnosed as having abdominal epilepsy and a bilateral sylvian cortical malformation.
Methods and Results: During an EEG examination, the patient had a simple partial seizure, manifested as intense abdominal pain. The ictal EEG showed a focal electrographic seizure arising from the left frontotemporal region. Computed tomography scan was normal; however, magnetic resonance imaging (MRI) revealed asymmetric lesions involving both sylvian fissures compatible with polymicrogyria. Onset of treatment with sodium valproate was followed by a significant reduction of seizures.
Conclusions: Abdominal epilepsy should be suspected in adolescents or adults with paroxysmal episodes of abdominal pain associated with migraine-like symptoms. EEG and MRI investigations are indicated. A developmental brain disorder should be considered as a possible etiology.     

Interrelationship of genetics and prenatal injury in the genesis of malformations of cortical development

CONTEXT: Although the causes of some malformations of cortical development (MCD) have been established, others remain unclear. There are several lines of evidence supporting the theory of a complex mechanism that involves genetic and environmental factors. OBJECTIVE: To investigate the interrelationship of genetics and prenatal injury in the genesis of MCD. PATIENTS AND DESIGN: A series of 76 consecutive patients with MCD and their families were systematically questioned about their family histories of epilepsy or other neurological impairment and the occurrence of prenatal events. Whenever possible, magnetic resonance imaging was performed in other family members if MCD was suspected or in the presence of any neurological impairment. Patients were divided into 3 groups according to the type of MCD. Patients in group 1 had focal cortical dysplasia, group 2 had heterotopias (periventricular or subcortical) or agyria-pachygyria, and group 3 had polymicrogyria or schizencephaly. These findings were also compared with a disease-control group of 40 consecutive patients with epilepsy but without MCD. SETTING: Neurology clinic of a university hospital. RESULTS: Of the 76 patients with MCD, 21 (28%) had focal cortical dysplasia, 19 (25%) had heterotopias or agyria-pachygyria, and 36 (47%) had polymicrogyria or schizencephaly. There were 39 men and 37 women, aged 2 to 52 years (mean age, 13 years). In group 2, 6 patients (32%) had a family history of MCD, mental retardation, or miscarriages, suggesting a genetic predisposition. In group 3, family history of MCD was present in 5 patients (14%). Prenatal events occurred in 28 patients with MCD (37%) and 2 controls (5%) and were more frequent in patients with heterotopia or agyria-pachygyria and polymicrogyria (P<.001). Conversely, epilepsy occurred in all patients in group 1, in 17 patients (89%) in group 2, and in 17 patients (47%) in group 3. In group 3, epilepsy was less frequent (P<.001) and also more easily controlled (P =.005) than in other forms of MCD. CONCLUSIONS: Our findings support the idea of a spectrum among the different types of MCD. Focal cortical dysplasia (group 1) is associated with more frequent and severe epilepsy and less important genetic and prenatal events, heterotopias and agyria-pachygyria (group 2) are frequently associated with genetic predisposition, and polymicrogyria and schizencephaly (group 3) are less frequently associated with epilepsy but have a stronger association with genetic and detectable prenatal events.     

Occipital encephalocele and epilepsy]

We report the incidence of epilepsy in 7 patients with occipital encephalocele (meningocele: 6 cases, meningoencephalocystocele: 1 case). Two cases had epilepsy and a case without the history of epileptic seizure had an epileptic pattern on the EEG. All these 3 cases had cortical dysplasia(CD) such as schizencephaly and subcortical gray matter, and two of them were associated with mental retardation. The location of the prominent CD was correlated with the EEG abnormalities and clinical epileptic pattern in each case. Associated hydrocephalus and placement of VP shunt had no significant influence on the occurrence of the epilepsy. Thus, complicated CD is thought to be epileptogenic in patients with occipital encephalocele.     

Changing ictal-onset EEG patterns in children with cortical dysplasia

Purpose

Cortical dysplasia (CD) is intrinsically epileptogenic. We hypothesize that CDs clinically emerging in the early developing brain tend to extend into multifocal or larger epileptic networks to pronounce intractability in contrast to CDs which clinically emerge at a later age.

Methods

We evaluated the spatial and temporal profiles of ictal-onset EEG patterns in children with histopathologically confirmed CD. We designated Group A as children with changing ictal-onset EEG patterns over time, and Group B without change. We compared seizure profiles, consecutive scalp video-EEGs (VEEGs), MRI, MEG, and surgical outcomes.

Results

We found 14 children consisting of 10 Group A patients (7 girls) and 4 Group B patients (all boys). Eight (80%) Group A patients had their seizure onset < 5 years while all Group B patients had seizure onset ? 5 years (p < .05). Changes of ictal onset EEG pattern in Group A consisted of bilateral (4 patients), extending (2); extending and bilateral (2); and generalized (2). We saw MRI lesions (6) and single clustered MEG spike sources (MEGSSs) in (5). Six patients underwent surgery before 15 years of age, and 4 of them attained seizure freedom. All 4 Group B patients had MRI lesions and single clustered MEGSSs. Three patients underwent surgery after 15 years of age. All 4 patients attained seizure freedom.

Conclusion

Ictal-onset EEG patterns change over time in children with early seizure onset and intractable epilepsy caused by CD. Younger epileptic children with CD more frequently have multifocal epileptogenic foci or larger epileptogenic foci. Early resection of CD, guided by MRI, MEG, and intracranial video EEG, resulted in seizure freedom despite changes in ictal-onset EEG patterns.     

Voxel-based morphometry and intellectual assessment in patients with congenital bilateral perisylvian syndrome

Congenital bilateral perisylvian syndrome (CBPS) presents with heterogeneous clinical manifestations such as pseudobulbar palsy, language disorder, variable cognitive deficits, epilepsy, and perisylvian abnormalities (most frequently polymicrogyria) on imaging studies. We investigated the relationship between seizures and extent of gray matter (GM) and white matter (WM) abnormalities using voxel-based morphometry (VBM) of brain magnetic resonance imaging (MRI) as well the association between seizures, structural abnormalities and cognitive ability. In this cross-sectional study, we evaluated 51 healthy volunteers and 18 patients with CBPS with epilepsy (seizure group, n = 7) and without (non-seizure group, n = 11). We used VBM (SPM8/DARTEL) to investigate areas with excess and atrophy of both gray and white matter, comparing groups of patients with controls. Intellectual ability of patients was assessed by the WISC-III or WAIS-III. Both groups with CBPS and the control group were homogeneous with respect to gender (p = 0.07) and age (p = 0.065). Besides perisylvian polymicrogyria, the seizure group exhibited areas with GM and WM reduction including temporal, frontal, parietal and occipital lobes. In contrast, we identified fewer areas with GM and WM reduction in the non-seizure group. The seizure group presented worse intellectual performance (performance IQ and global IQ) than the non-seizure group. The seizure group presented with a more widespread pattern of cortical and sub-cortical abnormalities, as well as worse cognition. Our results suggest that patients with CBPS and epilepsy appear to have widespread neuronal damage that goes beyond the areas with MRI-visible perisylvian polymicrogyria.     

A Particular Type of Epilepsy in Children with Congenital Hemiparesis Associated with Unilateral Polymicrogyria

PURPOSE: Polymicrogyria (PMG) is often associated with symptomatic focal epilepsy and neurologic dysfunction. We investigated the clinical and laboratory features of a group of children with congenital hemiparesis, unilateral polymicrogyria on magnetic resonance imaging (MRI), and a peculiar epileptic syndrome. METHODS: Twelve patients (seven girls and five boys) with a mean age of 7.8 years (range, 5-13 years) were studied. All patients underwent clinical evaluation, computed tomography (CT) and MRI scanning, and neuropsychological assessment at initial examination. Patients were followed up from 1 to 7 years (mean, 4.5 years). RESULTS: Partial motor seizures with secondary generalization with onset between age 1 and 6 years (mean age, 2 years) were recorded in all patients. The course of epilepsy was similar in all patients with development of atypical absences, negative myoclonus, and gait difficulties. EEG recording demonstrated continuous spike-wave or bilateral abnormality throughout. Frequent relapses of the atonic and myoclonic seizures were seen in seven patients. However, during follow-up, seven patients were seizure free, and the others have not developed this particular seizure pattern. A single case underwent cortical resection 23 months ago and has had no seizures since then. Mental retardation was mild in nine and moderate in three patients. CONCLUSIONS: Children with unilateral polymicrogyria may develop a syndrome of negative myoclonus seizures that appears to be age specific and responsive to antiepileptic drug (AED) treatment. Despite limited follow-up time, a good outcome was observed in most cases.     

Metabolic Changes in Neuronal Migration Disorders: Evaluation by Combined MRI and Proton MR Spectroscopy

PURPOSE: To assess the role of 1H-magnetic resonance spectroscopy (MRS) in detecting biochemical abnormalities in neuronal migration disorders (NMDs). METHODS: We performed 1H-MRS studies on 17 brain NMD areas [five polymicrogyria, eight subcortical heterotopia, and four cortical dysplasia on magnetic resonance imaging (MRI)]. The study group consisted of 15 patients, all but one affected by partial epileptic seizures. Spectra were acquired from volumes of interest localized on NMDs and contralateral sides and compared with those obtained on gray and white matter of 18 neurologic controls. RESULTS: NMD lesions were characterized by lower N-acetylaspartate to creatine (NAA/Cr) and choline to Cr (Cho/Cr) ratios than those of the white (p = 0.002 and p = 0.004) and gray matter (p = 0.03 and p = 0.06) of neurologic controls. In addition, the normal-appearing contralateral sides to the NMD lesions showed a significant decrease of Cho/Cr ratio when compared with those of white (p = 0.003) and gray matter (p = 0.05) of neurologic controls. No relation was found between NAA/Cr decrease, EEG abnormalities, and NMD sides, or between NAA/Cr ratios, duration of epilepsy, and frequency of seizures. Lactate signal was detected in the spectra of four patients who had an epileptic seizure a short time before MR examination. CONCLUSIONS: NAA/Cr decrease may be related more to structural and functional alteration of the NMD sides than to epileptic activity in these lesions. Low Cho/Cr may be related to a more extensive diffuse hypomyelination than suggested by the MRI findings. An activation of anerobic glycolysis during and after seizures could account for the presence of lactate. These data confirm that H-MRS is an advanced technique that may provide useful biochemical information in vivo on neurobiologic processes underlying NMDs.     

Bilateral focal polymicrogyria in Ehlers-Danlos syndrome

BACKGROUND: Ehlers-Danlos syndrome (EDS) is a heterogeneous group of generalized connective tissue disorders that has been described in association with epilepsy and cerebral cortical dysplasia, mostly gray matter heterotopias, in 3 reports. However, to our knowledge, association of EDS with another type of cortical cerebral dysplasia, bilateral focal polymicrogyria, has never previously been described. SETTING: Two research-oriented hospitals. PATIENTS: We describe 2 patients with EDS and bilateral polymicrogyria. The first, a 29-year-old black man, presented with EDS of unspecified type, seizures, and bilateral frontocentral and frontoposterior polymicrogyria with hypoplasia of the inferior part of the cerebellar vermis. The second, a 20-year-old woman, had type III EDS, seizures and congenital bilateral perisylvian syndrome with polymicrogyria. CONCLUSIONS: The association of bilateral focal polymicrogyria and EDS in these 2 patients suggests that extracellular matrix proteins implicated in the pathogenesis of EDS, such as collagen and tenascin, may play an important role in cerebral cortical formation and organization. In a clinical setting, the association of EDS with these cortical structural lesions has implications for diagnosis and management.     

Surgical outcome in occipital lobe epilepsy: Implications for pathophysiology

Medically refractory occipital lobe epilepsies are increasingly treated with surgery, but outcome and its relationship to etiology, pathological substrate, occipital lobe location, surgical approach, and electroclinical features have not been systematically investigated in a substantial group of patients. Thirty-five patients who underwent surgery for intractable occipital lobe seizures were retrospectively evaluated. Outcome and occipital lobe location were analyzed with respect to surgical procedure, pathology, clinical seizure characteristics, seizure onset and termination locations, and localization of interictal spikes. Most patients had developmental abnormalities (14) or tumors (13, all gliomas). Developmental abnormalities consisted of focal cortical dysplasia (5), heterotopia (2), hamartoma (3), cortical duplication (1), polymicrogyria (1), Sturge-Weber syndrome (1), and tuberous sclerosis(1). There was 1 patient with a vascular abnormality, 1 with chronic inflammatory changes, 4 with gliosis, 1 with cerebral ossification, and 1 with normal pathology. Developmental abnormalities had significantly worse outcome (45% excellent/good) than tumors (85% excellent/good). In the developmental group, low-grade focal cortical dysplasias had better outcome than heterotopia and hamartoma regardless of type of surgical procedure. Pathological groups did not significantly differ with respect to location within the occipital lobe (overall medial [50%] or lateral [38%]); clinical seizure characteristics referable to specific lobe (occipital [14%], temporal [34%], frontal [23%], more than one type [29%]); electroencephalographic localization (to occipital [17%], temporal [27%], or other/multifocal locations [56%]); or intracranial ictal onset or termination location. Electroclinical variables were also unrelated to the occipital lobe location of abnormality. Surgical outcome was not predicted by surgical approach (lesion excision with margins or lobectomy). The main pathological substrates of uncontrolled occipital lobe epilepsy are gliomas and developmental abnormalities. Whereas resection of occipital lobe tumors associated with chronic epilepsy produces nearly uniform seizure control, outcome after resection of occipital lobe developmental abnormalities is less uniform.     

Clinical,EEG, and positron emission tomography features of childhood-onset epilepsy with localized cortical dysplasia detected by magnetic resonance imaging

We studied clinical, EEG, and positron emission tomography (PET) findings in 18 patients with childhood-onset epilepsy with localized cortical dysplasia detected by magnetic resonance imaging. The age at onset of epilepsy was prior to 6 months of age in about half of the patients; the oldest patient was 7 years. Unilateral dysplastic lesions were more frequently associated with partial epilepsy, whereas bilateral dysplasia was associated more with generalized epilepsy. Patients with partial epilepsy had secondarily generalized seizures more often at the onset. Two patients with partial epilepsy presented generalized seizures transiently: undetermined epilepsy with infantile spasms triggered by partial seizures in one and epilepsy with continuous spike waves during slow-wave sleep in the other. The size of the lesion was not correlated with seizure outcome but was significantly correlated with mental outcome. The PET abnormality of glucose metabolism usually corresponded to the areas of cortical dysplasia and EEG focus, but the correspondence was better in partial epilepsy than generalized epilepsy.     

Seizures in fetal alcohol spectrum disorders: Evaluation of clinical,electroencephalographic, and neuroradiologic features in a pediatric case series

Seizures are observed with a frequency of 3–21% in children with fetal alcohol spectrum disorders (FASD). However, clinical, neuroradiologic, and electroencephalography (EEG) features are poorly described. In this study, 13 patients with FASD and epilepsy or seizures were identified retrospectively from the databases of seven Italian pediatric neurology divisions. Eleven children were affected by epilepsy, and two had at least one documented seizure. Both generalized and focal seizures were observed. EEG showed diffuse or focal epileptic activity; two children developed electric status epilepticus during sleep (ESES). Structural brain anomalies, including polymicrogyria, nodular heterotopia, atrophy, and Arnold‐Chiari type 1 malformation, were discovered in almost 50% of patients. Control of seizures was not difficult to obtain in 11 cases; one patient showed pharmacoresistant epilepsy. EEG and clinical follow‐up are recommended in children with FASD and epilepsy, since severe conditions requiring aggressive treatment, such as in ESES, may develop. Neuroradiological evaluation is warranted because several types of brain anomalies could be associated with maternal alcohol consumption during pregnancy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here .     

Neuronal migration disorders, genetics, and epileptogenesis

Several malformation syndromes with abnormal cortical development have been recognized. Specific causative gene defects and characteristic electroclinical patterns have been identified for some. X-linked periventricular nodular heterotopia is mainly seen in female patients and is often associated with focal epilepsy. FLN1 mutations have been reported in all familial cases and in about 25% of sporadic patients. A rare recessive form of periventricular nodular heterotopia owing to ARGEF2 gene mutations has also been reported in children with microcephaly, severe delay, and early-onset seizures. Lissencephaly-pachygyria and subcortical band heterotopia represent a malformative spectrum resulting from mutations of either the LIS1 or the DCX (XLIS) gene. LIS1 mutations cause a more severe malformation posteriorly. Most children have severe developmental delay and infantile spasms, but milder phenotypes are on record, including posterior subcortical band heterotopia owing to mosaic mutations of LIS1. DCX mutations usually cause anteriorly predominant lissencephaly in male patients and subcortical band heterotopia in female patients. Mutations of the coding region of DCX were found in all reported pedigrees and in about 50% of sporadic female patients with subcortical band heterotopia. Mutations of XLIS have also been found in male patients with anterior subcortical band heterotopia and in female patients with normal brain magnetic resonance imaging. The thickness of the band and the severity of pachygyria correlate with the likelihood of developing severe epilepsy. Autosomal recessive lissencephaly with cerebellar hypoplasia, accompanied by severe delay, hypotonia, and seizures, has been associated with mutations of the reelin (RELN) gene. X-linked lissencephaly with corpus callosum agenesis and ambiguous genitalia in genotypic males is associated with mutations of the ARX gene. Affected boys have severe delay and infantile spasms with suppression-burst electroencephalograms. Early death is frequent. Carrier female patients can have isolated corpus callosum agenesis. Schizencephaly has a wide anatomoclinical spectrum, including focal epilepsy in most patients. Familial occurrence is rare. Initial reports of heterozygous mutations in the EMX2 gene have not been confirmed. Among several syndromes featuring polymicrogyria, bilateral perisylvian polymicrogyria shows genetic heterogeneity, including linkage to chromosome Xq28 in some pedigrees, autosomal dominant or recessive inheritance in others, and an association with chromosome 22q11.2 deletion in some patients. About 65% of patients have severe epilepsy. Recessive bilateral frontoparietal polymicrogyria has been associated with mutations of the GPR56 gene.     

Bilateral periventricular nodular heterotopia with amniotic band syndrome

The amniotic (constriction) band syndrome is characterized by distal ring constrictions, intrauterine amputations, and acrosyndactyly. External constriction by amniotic bands is the generally accepted mechanism: early amniotic rupture leads to formation of mesodermal fibrous strands that constrict, entangle, and amputate distal portions of limbs. Etiology is heterogeneous. Anecdotal cases involving central nervous system abnormalities (e.g., acrania, anencephaly, polymicrogyria, congenital bilateral perisylvian syndrome, neuronal heterotopia, septo-optic dysplasia, and spinal cord tethering) have been reported. We describe a 9-year-old girl with typical features of constriction band syndrome localized to the lower limbs who had also profound mental retardation and drug-resistant epilepsy associated with bilateral periventricular nodular heterotopia (a brain malformation of neuronal migration and proliferation caused by mutations in the X-linked filamin 1 gene [FLN1] on chromosome Xq28). The karyotype was normal, as was mutational screening for FLN1. The occurrence of bilateral periventricular nodular heterotopia in the context of amniotic band syndrome is novel (chance occurrence of both: 0.000004%).     

Bilateral frontal polymicrogyria: a newly recognized brain malformation syndrome

BACKGROUND AND OBJECTIVE: Polymicrogyria is a brain malformation characterized by abnormal cortical lamination, excessive cortical folding, and fusion of the cortical molecular layer. Two distinct bilateral localized forms have been described: bilateral perisylvian polymicrogyria, which has proved to be genetically heterogeneous, and bilateral parasagittal parieto-occipital polymicrogyria, which has been described only in sporadic patients. We describe 13 patients with symmetric polymicrogyria of both frontal lobes back to the precentral sulcus: bilateral frontal polymicrogyria (BFP). METHODS: Review of clinical records, brain MRI, and EEG results of 13 patients; correlation with other regional polymicrogyrias. RESULTS: The abnormal cortex extended from the frontal poles anteriorly to the precentral gyrus posteriorly and to the frontal operculum inferiorly and was relatively symmetric in all 13 patients. All patients presented with developmental delay and mild spastic quadriparesis, but variably impaired language development (12/13), mental retardation (11/13), and epilepsy (5/13) also occurred. BFP was sporadic in 13 of 13 patients, but 2 of 13 had consanguineous parents. CONCLUSIONS: BFP extends the spectrum of the recognized bilateral symmetric regional polymicrogyria syndromes.     

Focal cortical malformations can show asymmetrically higher uptake on interictal fluorine-18 fluorodeoxyglucose positron emission tomography (PET)

Interictal fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) is a component of the presurgical evaluation of patients with medically intractable epilepsy, including patients with malformations of cortical development. The authors describe 3 cases of focal cortical malformations that displayed asymmetrically higher uptake on FDG-PET performed in the interictal state in patients undergoing evaluation for possible focal resection for refractory localization-related epilepsy. The evaluation included routine and prolonged video electroencephalography (EEG), magnetic resonance imaging (MRI), interictal FDG-PET with concurrent EEG, and single-photon emission computed tomography (SPECT). All 3 patients had focal cortical malformations on MRI corresponding to regions of asymmetrically higher uptake on FDG-PET. EEG confirmed that the FDG-PET studies were performed in the interictal state. The lesions included a large region of subcortical heterotopia in the right frontal lobe, a left temporal lobe dysplasia, and a region of subcortical heterotopia in the right occipital lobe. In both patients with subcortical heterotopia, there were other focal regions of cortical malformation that were not associated with abnormal or asymmetric uptake on FDG-PET. Previous reports describe decreased uptake on interictal PET in most cases of focal cortical malformations. Normal to increased uptake has been reported with band heterotopia. The authors demonstrate that other types of focal malformations of cortical development, including focal subcortical heterotopia and lobar dysplasia, can be associated with asymmetrically higher uptake on interictal FDG-PET.     

灰质异位所致癫痫的外科治疗

目的 探讨大脑灰质异位(HGM)与癫痫的关系,以及手术治疗的价值. 方法 回顾性分析解放军第四五八医院神经外科自2004年5月至2006年5月收治的6例HGM所致癫痫患者的临床特点、手术方式以及随访结果. 结果 6例患者中,4例行异位灰顶切除+皮层热灼,1例行异位灰顶切除+皮层热灼+前颞叶切除.1例行单纯皮层热灼.术后随访2～4年,5例至今未见发作,1例发作明显缓解. 结论 对于HGM所致的难治性癫痫,外科手术是一个有效的治疗方法.     

Phenotypic and imaging features of FLNA-negative patients with bilateral periventricular nodular heterotopia and epilepsy

PurposePeriventricular nodular heterotopia (PVNH) is a malformation of cortical development due to impaired neuronal migration resulting in the formation of nodular masses of neurons and glial cells in close proximity to the ventricular walls. We report the clinical characteristics of the largest case series of FLNA-negative patients with seizures and bilateral periventricular heterotopia.MethodsParticipants were recruited through the Epilepsy Phenome/Genome Project (EPGP), a multicenter collaborative effort to collect detailed phenotypic data and DNA on a large number of individuals with epilepsy, including a cohort with symptomatic epilepsy related to PVNH. Included subjects had epilepsy, and MRI confirmed bilateral PVNH. Magnetic resonance imaging studies were visually and quantitatively reviewed to investigate the topographic extent of PVNH, symmetry, and laterality.Key findingsWe analyzed data on 71 patients with bilateral PVNH. The incidence of febrile seizures was 16.6%. There was at least one other family member with epilepsy in 36.9% of this population. Developmental delay was present in 21.8%. Focal onset seizures were the most common type of seizure presentation (79.3%). High heterotopia burden was strongly associated with female gender and trigonal nodular localization. There was no evidence for differences in brain volume between PVNH subjects and controls. No relationship was observed between heterotopic volume and gender, developmental delay, location of PVNH, ventricular or cerebellar abnormalities, laterality of seizure onset, age at seizure onset, and duration of epilepsy.SignificanceA direct correlation was observed between high heterotopia burden, female gender, and trigonal location in this large cohort of FLNA-negative bilateral PVNH patients with epilepsy. Quantitative MRI measurements indicated that this correlation is based on the diffuse nature of the heterotopic nodules rather than on the total volume of abnormal heterotopic tissue.