Rolandic Epilepsy Research Articles

Factors Predicting Poor Response to Initial Therapy in Benign Childhood Epilepsy with Centrotemporal Spikes (BCECTS).

Background and Purpose:Benign childhood epilepsy with centrotemporal spikes (BCECTS) is the most common pediatric focal epilepsy syndrome and typically has positive clinical outcomes. However, a few patients experience recurrent seizures, and therefore, require treatment with antiepileptic drugs (AEDs). This study aimed to identify risk factors associated with poor response to initial AED therapy in BCECTS patients.Methods:We retrospectively reviewed the files of 57 patients who were diagnosed with BCECTS between January 2008 and September 2013. Patients not being treated with AEDs have been excluded. We placed the patients into two groups: (1) patients using 1 AED, and (2) patients using 2 AEDs. Clinical characteristics were then collected from the medical records.Results:Of the 57 patients, 41 (72%) were successfully treated with 1 AED, and 16 (28%) required 2 AEDs to control seizures. Multiple logistic regression analysis indicated that seizure onset prior to age 5 (odds ratio [OR]: 5.65, 95% confidence interval [CI]: 1.41–22.68) and history of febrile seizures (OR: 4.97, 95% CI: 1.06–23.36) were independent risk factors for poor response to initial therapy (p<0.05). Response to AEDs was not associated with the presence of focal slowing or generalized epileptiform discharges on EEG, abnormalities on MRI of the brain, frequency of afebrile seizures before drug therapy, or family history of febrile seizures or epilepsy.Conclusions:This study revealed that 28% of patients with BCECTS experienced poor responses to initial AED therapy. Factors predicting poor response to the initial AED included onset of seizures prior to age 5 and history of febrile seizures.

A Novel KCNQ2 Mutation in a Child with Benign Familial Neonatal Seizures and Rolandic Epilepsy

Voltage-gated potassium channel gene mutations in KCNQ2 and KCNQ3 α subunits may result in benign familial neonatal seizure (BFNS). Previous reports have implicated KCNQ2 mutations in patients with BFNS who later developed rolandic epilepsy (RE). We describe an 8-year-old boy with BFNS who developed RE. A three-generation pedigree showed multiple individuals presenting with seizures within the first days of life. Whole exome sequencing in this patient revealed a novel mutation in the KCNQ2 pore region. To our knowledge, this is the first report of BFNS with RE described with a KCNQ2 mutation localizing to the pore domain.

Risk factors for reading disability in families with rolandic epilepsy.

The high prevalence and impact of neurodevelopmental comorbidities in childhood epilepsy are now well known, as are the increased risks and familial aggregation of reading disability (RD) and speech sound disorder (SSD) in rolandic epilepsy (RE). The risk factors for RD in the general population include male sex, SSD, and ADHD, but it is not known if these are the same in RE or whether there is a contributory role of seizure and treatment-related variables. An observational study of 108 probands with RE (age range: 3.6-22 years) and their 159 siblings (age range: 1-29 years; 83 with EEG data) were singly ascertained in the US or UK through a proband affected by RE. We used a nested case-control design, multiple logistic regression, and generalized estimating equations to test the hypothesis of an association between RD and seizure variables or antiepileptic drug treatment in RE; we also assessed an association between EEG focal sharp waves and RD in siblings. Reading disability was reported in 42% of probands and 22% of siblings. Among probands, RD was strongly associated with a history of SSD (OR: 9.64, 95% CI: 2.45-37.21), ADHD symptoms (OR: 10.31, 95% CI: 2.15-49.44), and male sex (OR: 3.62, 95% CI: 1.11-11.75) but not with seizure or treatment variables. Among siblings, RD was independently associated only with SSD (OR: 4.30, 95% CI: 1.42-13.0) and not with the presence of interictal EEG focal sharp waves. The principal risk factors for RD in RE are SSD, ADHD, and male sex, the same risk factors as for RD without epilepsy. Seizure or treatment variables do not appear to be important risk factors for RD in probands with RE, and there was no evidence to support interictal EEG focal sharp waves as a risk factor for RD in siblings. Future studies should focus on the precise neuropsychological characterization of RD in families with RE and on the effectiveness of standard oral-language and reading interventions.

Language and central temporal auditory processing in childhood epilepsies.

Because of the relationship between rolandic, temporoparietal, and centrotemporal areas and language and auditory processing, the aim of this study was to investigate language and central temporal auditory processing of children with epilepsy (rolandic epilepsy and temporal lobe epilepsy) and compare these with those of children without epilepsy. Thirty-five children aged between eight and 14 years old were studied. Two groups of children participated in this study: a group with childhood epilepsy (n=19), and a control group without epilepsy or linguistic changes (n=16). There was a significant difference between the two groups, with the worst performance in children with epilepsy for the gaps-in-noise test, right ear (p<0.001) and left ear (p<0.001) tests, and duration pattern test--naming (p=0.002) and humming (p=0.002). In auditory P300, there was no significant difference in latency (p=0.343) and amplitude (p=0.194) between the groups. There was a significant difference between the groups, with the worst performance in children with epilepsy, for the auditory-receptive vocabulary (PPVT) (p<0.001) and phonological working memory (nonwords repetition task) tasks (p=0.001). We conclude that the impairment of central temporal auditory processing and language skills may be comorbidities in children with rolandic epilepsy and temporal lobe epilepsy.

CLINICAL AND ELECTROENCEPHALOGRAPHIC CHARACTERISTICS OF IDIOPATHIC CHILDHOOD FOCAL EPILEPSY WITH CENTROTEMPORAL SPIKES

Idiopathic childhood focal epilepsy with centrotemporal spikes, which is more known as rolandic epilepsy (RE), is age- and localization-related epilepsy with childhood onset, which is characterized mainly by short-lasting hemifacial and oropharyngeal seizures generally occurring when awakening or falling asleep, by the normal neurological status of patients, by specific electroencephalographic changes and complete arrest of seizures during therapy or when achieving puberty. RE is the most common epilepsy in childhood. Its prevalence is 21 per 100,000 healthy children. It is characterized by an onset that is clearly related to age. In 85 % of cases, RE occurs at 4–10 years of age with its peak at about 9 years. The clinical manifestations of this form of epilepsy are several types of seizures, such as oropharyngolaryngeal, hemifacial, faciobrachial, secondarily generalized convulsive, unilateral seizures with the possible development of short duration Todd’s paresis. Other types of seizures (absence, atonic, and myoclonic ones) are uncharacteristic of RE. They may occur occasionally on aggravation resulting from the use of carbamazepine or oxcarbazepine or permanently on transformation into pseudo-Lennox syndrome. According to the definition, focal neurological symptoms and behavioral and intellectual disorders are absent in patients with RE. However, there have been recent observations suggesting that speech, cognitive, and behavioral disorders may occur (at the same time rarely) in children with RE. Magnetic resonance imaging (MRI) fails to reveal the abnormality in the vast majority of cases. The described MRI changes in nearly 10 % of the patients with RE are an incidental finding and irrelevant to the course of the disease. Valproate in small doses is a first-choice drug; if it is inefficient, levetiracetam, topiramate, or a combination of valproate and ethosuximide are administered. Sulthiame (ospolot) as monotherapy is used in Germany. Based on their findings and the data available in the literature, the authors consider the etiology, pathogenesis, clinical manifestations of RE and its diagnosis, treatment principles, and prognosis. The specific features of the electroencephalographic pattern in this disease are detailed.

Contributions of Magnetoencephalography to Characterizing Brain Function in Pediatric Epilepsy: Evidences of Validity and Added Value

Magnetoencephalography (MEG) and magnetic source imaging are considered among the few available noninvasive modalities that can address, in pediatric populations, clinically relevant questions at the individual level. The contribution of MEG to the localization of the irritative zone (based on interictal epileptiform discharges), and the characterization of function-specific cortex (i.e., functional mapping), has proven to be as accurate as those derived from invasive “gold standard” procedures like the intracarotid amobarbital procedure and cortical stimulation mapping. Here, we will review some of the evidences supporting the added value of MEG in the study of pediatric epilepsy with special interest in the seminal studies where the clinical validity of MEG has been established after comparing MEG-derived estimates with those derived from the well-established invasive “gold standard” procedures. In the first section, we revisit a study where MEG is applied to characterize distinct patterns of propagation of interictal epileptiform discharges in relation with the clinical evolution of children with typical and atypical variants of benign rolandic epilepsy. This study serves to illustrate the additional value of MEG's high spatiotemporal resolution. Intralobar, interlobar, and interhemispheric patterns of propagation were demonstrated using MEG and associated to the clinical features exhibited by children with rolandic epilepsy. The second section of this article reviews part of the experience accumulated, in more than 800 clinical cases, by the MEG Laboratory at the University of Texas-Houston. In different studies, MEG-derived estimates for language and sensorimotor functions were compared with those derived from the gold standard invasive procedures (i.e., intracarotid amobarbital procedure and direct cortical stimulation) and tested against surgical outcome measurements. In these studies, authors benefit from some of the strengths of MEG as a valid, and noninvasive, tool to characterize brain function in pediatric population, demonstrating the utility of MEG in studying the issue of epilepsy in the developing brain.

Interhemispheric Connectivity in Drug-Naive Benign Childhood Epilepsy With Centrotemporal Spikes

Decreased intelligence quotients (IQ) have been consistently reported in drug-naive benign childhood epilepsy with centrotemporal spikes (BECTS). We aimed to identify the neurophysiological basis of IQ deficits by studying interhemispheric and anatomical functional connectivity in BECTS patients. Resting-state functional and structural magnetic resonance images were acquired in 32 children with BECTS and 25 healthy controls. The IQ was estimated using Wechsler Intelligence Scale for Children China-Revised. The functional connectivity between bilateral homotopic voxels was calculated and compared between groups. Homotopic regions showing abnormal functional connectivity in patients were adopted as regions of interest for analysis by diffusion-tensor imaging tractography. The fractional anisotropy, fiber length, and fiber number were compared between groups. Abnormal homotopic connectivities were correlated with IQ in BECTS patients. Compared with control subjects, patients showed decreased IQ, and decreased voxel-mirrored homotopic connectivity (VMHC) in the bilateral frontal lobule and cerebellum. The performance and full scale IQ significantly increased with the VMHC strength of the middle frontal gyrus (MFG) in controls but not in BECTS patients. A significant negative correlation was observed between VMHC in the premotor cortex and disease duration. Microstructural features within white matter tracts connecting functionally abnormal regions did not reveal any differences between groups. This study provides preliminary evidence for the disrupted functional cooperation between hemispheres in children with BECTS. The findings suggest that the hyposynchrony between the bilateral MFG may be involved in the decreased IQ of BECTS patients.

Todd Paralysis in Rolandic Epilepsy.

Investigators from University of Gaziantep, Turkey described the clinical and EEG findings of patients with benign epilepsy of childhood with centrotemporal spikes (BECTS) experiencing postictal Todd paralysis.

Local Activity and Causal Connectivity in Children with Benign Epilepsy with Centrotemporal Spikes

The aim of the current study was to localize the epileptic focus and characterize its causal relation with other brain regions, to understand the cognitive deficits in children with benign childhood epilepsy with centrotemporal spikes (BECTS). Resting-state functional magnetic resonance imaging (fMRI) was performed in 37 children with BECTS and 25 children matched for age, sex and educational achievement. We identified the potential epileptogenic zone (EZ) by comparing the amplitude of low frequency fluctuation (ALFF) of spontaneous blood oxygenation level dependent fMRI signals between the groups. Granger causality analysis was applied to explore the causal effect between EZ and the whole brain. Compared with controls, children with BECTS had significantly increased ALFF in the right postcentral gyrus and bilateral calcarine, and decreased ALFF in the left anterior cingulate cortex, bilateral putaman/caudate, and left cerebellum. ALFF values in the putaman/caudate were positively correlated with verbal IQ scores in patients. The ALFF values in cerebellum and performance IQ scores were negatively correlated in patients. These results suggest that ALFF disturbances in the putaman/caudate and cerebellum play an important role in BECTS cognitive dysfunction. Compared with controls, the patients showed increased driving effect from the EZ to the right medial frontal cortex and posterior cingulate cortex and decreased causal effects from the EZ to left inferior frontal gyrus. The causal effect of the left inferior frontal gyrus negatively correlated with disease duration, which suggests a relation between the epileptiform activity and language impairment. All together, these findings provide additional insight into the neurophysiological mechanisms of epilepitogenisis and cognitive dysfunction associated with BECTS.

Potential risk for neuropsychological deficits from subclinical epileptiform discharges in children with benign rolandic epilepsy

Benign rolandic epilepsy (BRE) is a benign condition, but may display different degrees of neuropsychological deficits, such as cognitive disturbances, attention deficit hyperactivity disorder, and other behavioral deficits. The aim of this study was to assess the neuropsychological functions and their relationship to the characteristics of interictal epileptiform discharges in children with BRE. A total of 33 children with newly diagnosed BRE (19 males/14 females, 8.2 ± 2.4 yr) were involved in the study. All children underwent a sleep electroencephalography and a comprehensive neuropsychological evaluation, which included Korean versions of the Wechsler intelligence scale for children III, frontal executive neuropsychological test, Rey complex figure test, Wisconsin card sorting test, attention deficit diagnostic scale, and child behavior checklist. The average monthly seizure frequency of the subjects was 0.8 ± 0.8, and the spike index was 14.1 ± 18.4/min (right) and 18.8 ± 22.1/min (left). On the whole, subjects exhibited normal cognitive function, frontal executive function, memory and other neuropsychological sub-domain scores. The group with a higher spike index on the left hemisphere scored lower on attention deficit diagnostic scale, auditory verbal learning test, and stroop test (P min) scored lower on full scale and performance intelligence quotient (110.7 ± 18.0 vs. 96.8 ± 11.2; 107.4 ± 16.4 vs. 94.3 ± 12.8) (P

Study of etiological profile of infantile and childhood focal seizures at a tertiary care centre in South India

Objective is to evaluate the etiology of focal seizures at a tertiary care center in Indian children. Design is a cross sectional study. Setting is outpatient and inpatient of a tertiary care teaching children hospital in South India. A total of 150 consecutive children aged 1 mo to 18 yr presenting with focal seizures defined as per international league against epilepsy classification, participated in this study. A detailed history was taken and clinical examination was done was along with the investigation for the etiology of focal seizures with routine and specific tests, computerized tomography (CT) scan and/or magnetic resonance imaging (MRI) and electroencephalography (EEG). All of the findings were recorded in a pre-designed pro forma and results were analyzed. The mean age presentation was 6.5 yr. Male preponderance was noticed with a ratio of 1.2 : 1. Complex partial seizures were the most common (68%) type of focal seizures. Neurologic deficits were noticed in 36 (24%) patients; most common form was hemiparesis. CT scan abnormalities were noted in 76% of the patients, most common CT finding was inflammatory granuloma. In four cases, where CT scan was inconclusive of neurocysticercosis (NCC) versus tu- berculoma, MRI showed features of tuberculoma. The most common etiology of focal seizures was inflammatory granulomas; NCC (69%) and tuberculoma (15%), followed by perinatal insult (8%) and stroke (7.3%). EEG was diagnostic in cases of Rolandic epilepsy in seven (4.6%) cases. CT brain is a valuable tool in identifying the underlying etiology of focal seizures. MRI is helpful in cases of diagnostic dilemma between NCC and tuberculoma by CT scan. EEG is diagnostic of benign Rolandic epilepsy.

A meta-analysis of literacy and language in children with rolandic epilepsy.

Rolandic epilepsy is the most common childhood epilepsy, often presenting with neuropsychological impairments. The aim of the study was to formally assimilate the findings of existing studies varying widely in methodology, thereby confirming the nature and prevalence of impairments in literacy and language. Using meta-analytical techniques, we evaluated 22 studies of literacy and/or language skills in children with rolandic epilepsy, published after 2000, among participants with IQs>70 and in which effect sizes could be acquired. Diagnosis required the presence of classical centrotemporal spikes arising from a normal background on electroencephalograms; a clinical history including at least one seizure; and no additional neurological condition. Overall effect size and heterogeneity were measured for single-word reading, phonological processing, and expressive and receptive language. Mean effect sizes (Cohen's d) ranged from 0.50 (95% confidence interval [CI] 0.23-0.78) for phonological processing, through 0.71 (95% CI 0.52-0.90) for word reading and 0.72 (95% CI 0.34-1.1) for receptive language, to 0.75 (95% CI 0.45-1.05) for expressive language. While group differences for reading measures were consistent, those for language were heterogeneous and varied across studies explained by age and IQ of samples. The presence of reading and phonological processing deficits in children with rolandic epilepsy highlights the importance of early literacy and language assessment in this population.

Extending the phenotypic spectrum of RBFOX1 deletions: Sporadic focal epilepsy.

Partial deletions of the RBFOX1 gene encoding the neuronal splicing regulator have been reported in a range of neurodevelopmental diseases including idiopathic/genetic generalized epilepsy (IGE/GGE), childhood focal epilepsy, and self-limited childhood benign epilepsy with centrotemporal spikes (BECTS, rolandic epilepsy), and autism. The protein regulates alternative splicing of many neuronal transcripts involved in the homeostatic control of neuronal excitability. Herein, we examined whether structural deletions affecting RBFOX1 exons confer susceptibility to common forms of juvenile and adult focal epilepsy syndromes. We screened 807 unrelated patients with sporadic focal epilepsy, and we identified seven hemizygous exonic RBFOX1 deletions in patients with sporadic focal epilepsy (0.9%) in comparison to one deletion found in 1,502 controls. The phenotypes of the patients carrying RBFOX1 deletions comprise magnetic resonance imaging (MRI)-negative epilepsy of unknown etiology with frontal and temporal origin (n = 5) and two patients with temporal lobe epilepsy with hippocampal sclerosis. The epilepsies were largely pharmacoresistant but not associated with intellectual disability. Our study extends the phenotypic spectrum of RBFOX1 deletions as a risk factor for focal epilepsy and suggests that exonic RBFOX1 deletions are involved in the broad spectrum of focal and generalized epilepsies.

The Clinical Implications of Todd Paralysis in Children With Benign Rolandic Epilepsy.

The aim of this study was to describe the clinical and electroencephalographic (EEG) findings of postictal Todd paralysis in benign rolandic epilepsy of childhood and find out the possible correlation with migraine. Based on International Headache Society pediatric migraine criteria, patients were investigated for migraine, and 12 of the 108 patients with benign rolandic epilepsy (6 girls and 6 boys, 11.1%) were found to have postictal Todd paralysis. Ten of these 12 patients (83.3%) had pediatric migraine based on the diagnostic criteria. We showed comorbidity of migraine and benign rolandic epilepsy with postictal Todd paralysis in children. Increased incidence of migraine in the present study suggest that children who have benign rolandic epilepsy and postictal Todd paralysis are more likely to have migraines.

OP13 – 2799: Landau-Kleffner syndrome (LKS), continuous spike and waves during slow-wave sleep syndrome (CSWSS), and Rolandic epilepsy (RE) – A genetic and immunological study

Objective LKS and CSWSS present with seizures, language and cognitive regression. Genetic studies have identified mutations in the GRIN2A gene, and copy-number-variants in genes encoding cell adhesion proteins (including CASPR2, contactin-2). Given that some affected patients respond to steroids we looked for autoantibodies to similar neuronal targets. Methods A previously genetically characterised cohort of patients with LKS (4 patients), CSWSS (23), RE (14), epilepsy with autism or neurodevelopmental disorder (2) and unaffected controls (10) was tested for neuronal surface antibodies (Abs) to GRIN1, GRIN2A and 2B, CASPR2 and contactin-2 proteins using cell-based-assays, and VGKC-complex-Abs by radioimmunoprecipitation. Results 8 samples were positive (8/53; 15%), 4 for CASPR2-Abs (low positive) and 4 for VGKC-complex-Abs (113–1102 pM). All samples were negative for contactin-2, GRIN1, 2A and 2B-Abs. Positive results were found in CSWSS patients (n=3; 2 VGKC-complex, 1 CASPR2), Rolandic epilepsy (n=3; 1 VGKC-complex, 2 CASPR2-Ab positive), and a neurodevelopmental disorder (dyspraxia, CASPR2-Ab); one control was VGKC-complex-Ab positive (unaffected father of an antibody positive patient). 3 positives were found in a single three-generation French family affected by LKS, CSWSS and RE, 2 also had GRIN2A mutations. Conclusion Overall, none of the 4 LKS patients in the cohort were antibody positive, 13% CSWSS (3/23) and 21% Rolandic epilepsies (3/14) had low positive CASPR2 or VGKC-complex-Abs. The three positive results in 3 different generations of the same GRIN2A family, which included an unaffected sibling with the disease associated GRIN2A mutation and an unaffected father with a positive antibody, suggests a possible dual aetiology in a small subset of epilepsy patients where autoantibodies might influence the presentation and severity of genetic cases. However, low level neuronal antibodies, and even genetic mutations, may not always be causal, but their coexistence in some patients suggests that these complex genetic diseases may also have a neuroinflammatory component.

PP01.7 – 2726: A novel description of a homozygous partial deletion of RBFOX1 gene causing epileptic encephalopathy, severe intellectual disability and progressive post-natal microcephaly

Objective Partial deletions of the gene encoding the neuronal splicing regulator RBFOX1 have been reported in a range of neurodevelopmental diseases, including idiopathic generalized epilepsy, Rolandic epilepsy (RE), Autosomal dominant lateral temporal epilepsy (ADLTE) or idiopathic generalized epilepsy (IGE). Patients often exhibit severe co-morbid neuro-developmental disorders such as intellectual disability (ID) and Autism spectrum disorders (ASD) or microcephaly. Heterozygous RBFOX1 knockout mouse models demonstrate deregulated splicing, disrupting genes involved in synaptic transmission and membrane excitability leading to increased susceptibility for seizure events. All patients reported so far have a hemizygous deletion/mutation and the transmitting parents in most cases were asymptomatic. We report a female toddler, that first presented with adversive seizures at four months of age, progressing to intractable epilepsy. EEG demonstrated generalized spike & wave activity. Currently at the age of thirty months she has profound ID and progressive post-natal microcephaly. Extensive diagnostic workup was uninformative – including whole exome sequencing (WES) for known epilepsy mutations. Brain MRI demonstrated non-specific findings. Her parents are first cousins of Arab origin. Ten family members are noted for epilepsy, intellectual disability of different severities and autism, however none has the same severe presentation as the patient. Methods and results Chromosomal micro-array analysis (CMA) revealed a 426 KB homozygous deletion in chromosome 16p13.3 at the 5' UTR end of the RBFOX1 gene. The asymptomatic parents are heterozygous for the deletion. Conclusion This is the first case of a homozygous partial deletion of the RBFOX1 gene in a toddler suffering from epileptic encephalopathy with profound ID and progressive postnatal microcephaly detected by CMA. Our case strengthens the association of partial RBFOX1 deletions in neurodevelopmental diseases and extends the RBFOX1-related phenotypic spectrum.

Cognitive Development in Children with Rolandic Epilepsy: Results of a Current PubMed Search

Aims: The study aims to review empirical findings concerning cognitive development in children with rolandic epilepsy (RE).

Rolandic Epilepsy: Retrospective Analysis of Neuropsychological and Clinical Data

Aims: Rolandic epilepsy (RE) is characterized by typical EEG discharges, absence of underlying diseases, normal cerebral morphology, and benign course with remission up to reaching puberty. The aim of this study was to assess-associated cognitive deficits and the effect of antiepileptic drugs (AED) on cognitive function in patients with RE.

Epilepsy, cognitive deficits and neuroanatomy in males with ZDHHC9 mutations.

ObjectiveSystematic investigation of individuals with intellectual disability after genetic diagnosis can illuminate specific phenotypes and mechanisms relevant to common neurodevelopmental disorders. We report the neurological, cognitive and neuroanatomical characteristics of nine males from three families with loss-of-function mutations in ZDHHC9 (OMIM #300799).MethodsAll known cases of X-linked intellectual disability (XLID) due to ZDHHC9 mutation in the United Kingdom were invited to participate in a study of neurocognitive and neuroimaging phenotypes.ResultsSeven out of nine males with ZDHHC9 mutations had been diagnosed with epilepsy, exceeding epilepsy risk in XLID comparison subjects (P = 0.01). Seizure histories and EEG features amongst ZDHHC9 mutation cases shared characteristics with rolandic epilepsy (RE). Specific cognitive deficits differentiated males with ZDHHC9 mutations from XLID comparison subjects and converged with reported linguistic and nonlinguistic deficits in idiopathic RE: impaired oromotor control, reduced verbal fluency, and impaired inhibitory control on visual attention tasks. Consistent neuroanatomical abnormalities included thalamic and striatal volume reductions and hypoplasia of the corpus callosum.InterpretationMutations in ZDHHC9 are associated with susceptibility to focal seizures and specific cognitive impairments intersecting with the RE spectrum. Neurocognitive deficits are accompanied by consistent abnormalities of subcortical structures and inter-hemispheric connectivity. The biochemical, cellular and network-level mechanisms responsible for the ZDHHC9-associated neurocognitive phenotype may be relevant to cognitive outcomes in RE.

Functional brain connectome and sensorimotor networks in rolandic epilepsy

Rolandic epilepsy (RE) is a form of well-characterized childhood epilepsy whose focal electroencephalographic abnormalities affect the same well-delineated local brain regions. Little is known about how the focal electroencephalographic discharges interfere with the topological organization of whole-brain networks in RE patients. Seventy-three patients RE patients and 73 healthy children underwent rsfMRI. The whole-brain functional networks were constructed by thresholding the partial correlation matrices of 90 brain regions, and their topological properties were analyzed using graph theory-based approaches. We used network-based statistics to evaluate functional connectivity. The correlations between the network properties and the clinical and cognitive characteristics were calculated. The global topologic organization of the functional brain network was disrupted in RE patients, as manifested by reduced clustering coefficient and local and global efficiency and increased characteristic path length. The RE patients exhibited less connectivity among the sensorimotor areas; this reduction in the mean functional connectivity in this network correlated to altered global small-world properties. The RE patients exhibited decreased nodal centralities, predominantly in the bilateral postcentral gyrus, in the frontal, parietal and temporal lobes around the rolandic fissure and in areas related to linguistics and attention control (p<0.05, FDR-corrected). The altered nodal centralities in the bilateral postcentral gyrus and the left posterior cingulate cortex were correlated with subscales in Child Behavior Checklist. These results support the hypothesis that RE is associated with systemic brain disorganization and that the functional defect in rolandic areas contribute to symptomatology and electrophysiology in RE. Nodal abnormalities appear to imply the disturbances in linguistics and attention observed in RE patients.