Prevalence Of Drug-resistant Epilepsy Research Articles

Real-world evidence of epidemiology, patient characteristics, and mortality in people with drug-resistant epilepsy in the United Kingdom, 2011-2021.

A third of people with epilepsy are drug resistant. People with drug-resistant epilepsy (DRE) have a higher risk of mortality and physical injuries than those who respond to anti-seizure medication (ASM). This study describes patient characteristics, comorbidities, and mortality in people with DRE in the UK. The Clinical Practice Research Datalink was utilised to select people with DRE prescribed a third ASM between 1 January 2011 and 31 March 2021. Annual incidence and prevalence of DRE, patient characteristics, comorbidities, and mortality rates were analysed. Subgroup analysis was performed by age, sex, presence of intellectual disabilities and time from epilepsy diagnosis to DRE. A total of 34,647 people with DRE were included (mean ± SD age 42.68 ± 23.59years, 52.6% females). During the study period, annual DRE incidence ranged from 1.99% to 3.12%. As of 31 March 2021, DRE prevalence was 26.6% (95% confidence interval [CI] 26.3%-26.8%). A greater proportion of people with DRE resided in the most deprived regions, with 21.1% and 16.7% in the top two quintiles of the Index of Multiple Deprivation respectively, compared to < 15% in the three less deprived regions. All-cause mortality ranged from 3,687 to 4,802 per 100,000 persons with DRE, four times higher than that in the general population in the UK. Variations existed across subgroups. Considerable disease burden was observed in people with DRE in the UK. The findings emphasise the importance of early DRE diagnosis and appropriate disease management in people who develop DRE.

Early Treatment with Vigabatrin Does Not Decrease Focal Seizures or Improve Cognition in Tuberous Sclerosis Complex: The PREVeNT Trial.

This study was undertaken to test the hypothesis that early vigabatrin treatment in tuberous sclerosis complex (TSC) infants improves neurocognitive outcome at 24 months of age. A phase IIb multicenter randomized double-blind placebo-controlled trial was conducted of vigabatrin at first epileptiform electroencephalogram (EEG) versus vigabatrin at seizure onset in infants with TSC. Primary outcome was Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) cognitive assessment score at 24 months. Secondary outcomes were prevalence of drug-resistant epilepsy, additional developmental outcomes, and safety of vigabatrin. Of 84 infants enrolled, 12 were screen failures, 4 went straight to open label vigabatrin, and 12 were not randomized (normal EEG throughout). Fifty-six were randomized to early vigabatrin (n = 29) or placebo (n = 27). Nineteen of 27 in the placebo arm transitioned to open label vigabatrin, with a median delay of 44 days after randomization. Bayley-III cognitive composite scores at 24 months were similar for participants randomized to vigabatrin or placebo. Additionally, no significant differences were found between groups in overall epilepsy incidence and drug-resistant epilepsy at 24 months, time to first seizure after randomization, and secondary developmental outcomes. Incidence of infantile spasms was lower and time to spasms after randomization was later in the vigabatrin group. Adverse events were similar across groups. Preventative treatment with vigabatrin based on EEG epileptiform activity prior to seizure onset does not improve neurocognitive outcome at 24 months in TSC children, nor does it delay onset or lower the incidence of focal seizures and drug-resistant epilepsy at 24 months. Preventative vigabatrin was associated with later time to onset and lower incidence of infantile spasms. ANN NEUROL 2023.

Characteristics associated with drug resistant epilepsy in children up to 36 months old with Congenital Zika Syndrome

ObjectivesTo verify characteristics associated with drug resistant epilepsy in children up to 36 months of age with Congenital Zika Syndrome (CZS). MethodsThis is a prospective cohort study with children aged up to 36 months diagnosed with CZS. Obstetric, demographic, phenotype and other clinical signs, cranial tomography, growth and motor development of the children were collected. ResultsOf a total of 109 children diagnosed with CZS, 100 (91.7%) had epilepsy and 68 (68%) with drug resistant seizures. The types of seizures associated with drug resistant epilepsy were focal seizures from the occipital lobe, generalized tonic and generalized tonic-clonic seizures. There was an association between drug resistant epilepsy and microcephaly at birth, severe microcephaly at birth, excess nuchal skin, ventriculomegaly, reduced brain parenchyma volume, and hypoplasia or malformation of the cerebellum. Difficulty sleeping, irritability, continuous crying, dysphagia and gross motor function were clinical signs associated with drug resistant epilepsy, as were the presence of ocular abnormalities, low head circumference in the first year of life and low weight in the first six months. ConclusionsThe prevalence of drug resistant epilepsy in children up to 36 months with CZS was 62.4% and was associated with the severity of the child's neurological damage, with emphasis on the reduction of brain parenchyma volume and damage to the cerebellum.

Factors not considered in the study of drug-resistant epilepsy: Psychiatric comorbidities, age, and gender.

In basic research and clinical practice, the control of seizures has been the most important goal, but it should not be the only one. There are factors that remain poorly understood in the study of refractory epilepsy such as the age and gender of patients and the presence of psychiatric comorbidities. It is known that in patients with drug‐resistant epilepsy (DRE), the comorbidities contribute to the deterioration of the quality of life, increase the severity, and worsen the prognosis of epilepsy. Some studies have demonstrated that patients diagnosed with a co‐occurrence of epilepsy and psychiatric disorders are more likely to present refractory seizures and the probability of seizure remission after pharmacotherapy is reduced. The evidence of this association suggests the presence of shared pathogenic mechanisms that may include endocrine disorders, neuroinflammatory processes, disturbances of neurotransmitters, and mechanisms triggered by stress. Additionally, significant demographic, clinical, and electrographic differences have been observed between women and men with epilepsy. Epilepsy affects the female gender in a greater proportion, although there are no studies that report whether refractoriness affects more females. The reasons behind these sex differences are unclear; however, it is likely that sex hormones and sex brain differences related to chromosomal genes play an important role. On the other hand, it has been shown in industrialized countries that prevalence of DRE is higher in the elderly when compared to youngsters. Conversely, this phenomenon is not observed in developing regions, where more cases are found in children and young adults. The correct identification and management of these factors is crucial in order to improve the quality of life of the patients.

Spotlight on the April 27 Issue

#### Notable in Neurology This Week This issue features an article that examines the link between lateropulsion and spatial neglect in patients with acute stroke; another investigates the association between cholinesterase inhibitors and cognitive decline in patients with Alzheimer dementia. A featured Views & Reviews examines the incidence and prevalence of drug-resistant epilepsy. ### Association of White Matter Hyperintensity Markers on MRI and Long-term Risk of Mortality and Ischemic Stroke: The SMART-MR Study In a prospective cohort of patients with symptomatic cerebral, coronary, or peripheral arterial disease or an abdominal aortic aneurysm, the volume, type, and shape of white matter changes seen on brain MRI were associated …

Celiac Disease in Children: An Association With Drug-Resistant Epilepsy

BackgroundNeurological manifestations are commonly reported in patients with celiac disease (CD). We aimed to characterize epilepsy features in a pediatric population with CD and the effect of a gluten-free diet (GFD) on seizure burden. MethodsA retrospective chart review was performed on pediatric patients treated at the University of Utah and Primary Children's Hospital in Salt Lake City, Utah, with both epilepsy and CD and compared with a control group with epilepsy only. ResultsWe identified 56 patients with epilepsy and biopsy-confirmed CD (n = 36, 64%) or elevated tissue transglutaminase antibodies (tTG-Ab) without biopsy-confirmed CD (n = 20, 36%). Age- and gender-matched controls were selected from patients with epilepsy only (n = 168). Patients with biopsy-proven CD or positive tTG-Ab had high percentage of drug-resistant epilepsy (DRE) compared with the control group (P < 0.05). Age at seizure onset preceded the diagnosis of CD on average by 5.9 years for patients with DRE (P < 0.01) compared with 2.2 years for those with drug-responsive epilepsy. Adhering to a GFD reduced seizure frequency or resulted in weaning dosage or weaning off of one or more antiseizure medications in a majority of patients with DRE. ConclusionsDRE was more prevalent in pediatric patients with biopsy-confirmed CD and positive tTG-Ab compared with the control group (which included childhood epilepsy syndromes), but comparable with the prevalence of DRE in the general population. Adherence to a GFD in combination with antiseizure medications appears to reduce seizure burden for those with CD and DRE.

Incidence and Prevalence of Drug-Resistant Epilepsy: A Systematic Review and Meta-analysis.

To evaluate the incidence and prevalence of drug-resistant epilepsy (DRE) as well as its predictors and correlates, we conducted a systematic review and meta-analysis of observational studies. Our protocol was registered with PROSPERO, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology reporting standards were followed. We searched MEDLINE, Embase, and Web of Science. We used a double arcsine transformation and random-effects models to perform our meta-analyses. We performed random-effects meta-regressions using study-level data. Our search strategy identified 10,794 abstracts. Of these, 103 articles met our eligibility criteria. There was high interstudy heterogeneity and risk of bias. The cumulative incidence of DRE was 25.0% (95% confidence interval [CI]: 16.8-34.3) in child studies but 14.6% (95% CI: 8.8-21.6) in adult/mixed age studies. The prevalence of DRE was 13.7% (95% CI: 9.2-19.0) in population/community-based populations but 36.3% (95% CI: 30.4-42.4) in clinic-based cohorts. Meta-regression confirmed that the prevalence of DRE was higher in clinic-based populations and in focal epilepsy. Multiple predictors and correlates of DRE were identified. The most reported of these were having a neurologic deficit, an abnormal EEG, and symptomatic epilepsy. The most reported genetic predictors of DRE were polymorphisms of the ABCB1 gene. Our observations provide a basis for estimating the incidence and prevalence of DRE, which vary between populations. We identified numerous putative DRE predictors and correlates. These findings are important to plan epilepsy services, including epilepsy surgery, a crucial treatment option for people with disabling seizures and DRE.

Short-term treatment outcome of childhood epilepsy in Jos, Nigeria

Background: Childhood epilepsy causes tremendous burden for the child, the family, the society and the healthcare system. While the majority of patients with epilepsy respond well to one antiepileptic drug (AED), many respond poorly to antiepileptic therapy with two or more AEDs, or develop drug-resistant epilepsy (DRE). We evaluated the short-term treatment outcomes of childhood epilepsy at a tertiary hospital in Nigeria. Methods: We reviewed the clinical records of newly diagnosed children with epilepsy that were commenced on AEDs from January 2011 to December 2015 and completed follow-up for at least 2 years. We evaluated their treatment outcomes and studied the association between the treatment outcomes and patients’ characteristics. Results: Three hundred and twenty-six patients met the eligibility criteria. The remission rate was 64.1%, the relapse rate at 2 years was 5.3% while the prevalence of drug-resistant epilepsy was 19.9%. Children with focal seizures were 1.5 times more likely to achieve remission compared to those with generalized seizures (adjusted odds ratio = 1.52; P = 0.008). Similarly children with normal neurologic examination were about 6 times more likely to achieve remission compared to those with abnormal neurologic examination (adjusted odds ratio = 5.79; P

Unsatisfactory results of a drug resistant epilepsy surgical treatment: reasons analysis and treatment optimization way

The relevance of the studied problem was caused by high prevalence of drug resistant epilepsy, an increased structural epilepsy detection and extension indications for a surgical treatment.The purpose of article consisted in a research of the reasons of low efficiency of epilepsy surgical treatment in adult population with a cross-disciplinary approach position.Material and methods.The leading approach was the retrospective open research of the failure factors at 14 patiens.Results.It was revealed unsatisfactory result of epilepsy surgical treatment was caused by a complex of the reasons. The disease features have been the main reason for a failure in 100% of cases, additional reasons: irrational pharmacotherapy -in 86%, the surgical reasons — in 36% of cases.Conclusions.The unsatisfactory result of epilepsy surgical treatment was caused by a complex of the reasons. Cross-disciplinary approach to a problem, improvement of the epilepsy managment, further researches are required. Materials of article can be useful for the personified approach at surgical treatment of epilepsy.

Epilepsy in an elderly population: Classification, etiology and drug resistance

PurposeTo characterize epilepsy in an elderly population and describe the prevalence of drug resistant epilepsy (DRE) using recently validated International League Against Epilepsy (ILAE) criteria. MethodsUsing a case-control design, 72 patients aged 60 years and older (cases) and 223 patients under age 60 (controls) were identified from the Saskatchewan Epilepsy Program database. Patients’ charts were retrospectively reviewed. Bivariate and multiple logistic regression analyses were performed to identify variables that were associated with epilepsy in elderly patients. ResultsForty-seven elderly patients (65%) had focal epilepsy, while 9 (13%) had generalized epilepsy. The most common etiology in elderly patients with epilepsy was unknown in 30 (48%) patients. Other identified etiologies included brain tumors in 14 (19.4%), genetic in 6 (8%), degenerative disease in 4 (5%), stroke in 6 (8%) and head injury in 3 (4%). Significantly fewer elderly patients met criteria for DRE compared to non-elderly patients (26% vs. 51%, p = 0.001). In the multiple logistic regression analysis, elderly patients with epilepsy were more likely to have the presence of stroke, psychiatric comorbidity and to be on monotherapy. ConclusionIn our sample, elderly patients with epilepsy were more likely to have seizures resulting from brain tumors and stroke, and less likely to have DRE than non-elderly patients. These unique features of elderly patients strongly suggest that clinical practice guidelines are needed to facilitate the highest quality of care in elderly patients with epilepsy.

Anxiety and depressive disorders in people with epilepsy: A meta-analysis.

Comorbid anxiety and depressive disorders in people with epilepsy (PWE) are highly prevalent and associated with various adverse outcomes. However, the prevalence of anxiety disorders in PWE across studies is highly variable. Our aim was to estimate the prevalence and moderating factors of anxiety and depressive disorders in PWE. Following prospective registration (PROSPERO; CRD42015027101), electronic databases were searched for studies that reported the prevalence of both anxiety and depressive disorders in samples of PWE up until July 2016. Data extracted included the prevalence of anxiety and depressive disorders, and moderators of interest (e.g., method of diagnosis, prevalence of drug-resistant epilepsy). Meta-analysis of the overall pooled prevalence of anxiety and depressive disorders was conducted. The search yielded 8,636 unique articles, with 27 studies meeting final inclusion criteria (3,221 PWE). The pooled prevalence of anxiety and depressive disorders was 20.2% (95% confidence interval [CI] 15.3-26.0%) and 22.9% (95% CI 18.2-28.4%), respectively. Method of diagnosis significantly moderated anxiety disorder prevalence (Q statistic with one degree of freedom [Q1 ] = 36.29, p < 0.0001); the prevalence of anxiety disorders based on unstructured clinician assessment was 8.1% (95% CI 5.7-11.4%), compared to a prevalence of 27.3% (95% CI 22.1-33.3%) based on a structured clinical interview. There were no significant moderators of depressive disorder diagnosis. Findings suggest the prevalence of anxiety and depressive disorders in PWE are equivalent, and variability in prevalence of anxiety disorders across studies can be attributed partly to the method of diagnosis. These findings also challenge widely held assumptions that psychiatric comorbidity is more common in people with drug-resistant epilepsy. Future research should aim to improve the detection and management of these comorbidities in PWE, particularly anxiety disorders, which have remained relatively neglected.

Antiepileptic drugs--a review.

Epilepsy is a common neurological condition that affects approximately 1% of the general population. In addition, about 10% of the population experiences a seizure sometime during life. The treatment options for epilepsy have come a long way from the bromides to the current era in which we now have multiple treatment modalities, including medications, implantable devices, and surgery. Antiepileptic drugs (AEDs) are the mainstay for treatment of epilepsy with about 70% of children achieving good control with medications alone. The past decade has witnessed the emergence of multiple AEDs-with more than 24 AEDs to choose from presently. The newer drugs provide us with novel mechanisms of action and improved safety profile. This expanded choice of AEDs has made it possible to offer tailored-treatment plans based on unique patient profiles. However, such an ever-increasing choice of medications also poses a challenge for the treating physician as far as choosing the initial drug is concerned-especially because there is limited data comparing the efficacy of one drug to the other. An additional humbling fact remains that, despite an increase in the choice of medications, we are still only able to treat the symptoms of seizures without making any significant progress in reversing or stopping the underlying mechanism of epileptogenesis or in offering neuroprotection from epileptogenesis. Therefore, it is not surprising that, despite the wide array of AED choices, the prevalence of drug-resistant epilepsy has not improved. This article aims at giving a short overview of currently available AEDs.

Long-term outcome of epilepsy in patients with Prader-Willi syndrome.

Prader-Willi syndrome is a multisystemic genetic disorder that can be associated with epilepsy. There is insufficient information concerning the clinical and electroencephalographic characteristics of epilepsy and the long-term outcome of these patients. The aim of this study is to describe seizure types, electroencephalographic patterns and long-term seizure outcome in Prader-Willi syndrome patients suffering from epilepsy. We retrospectively studied 38 patients with Prader-Willi syndrome and seizures. Results of neuroimaging studies were obtained for 35 individuals. We subdivided these patients into two groups: group A, 24 patients, without brain lesions; and group B, 11 patients, with brain abnormalities. All patients were re-evaluated after a period of at least 10 years. Twenty-one patients (55.2 %) were affected by generalized epilepsy and 17 patients (44.8 %) presented focal epilepsy. The most common seizure type was generalized tonic-clonic seizure. The mean age at seizure onset was 4.5 years (ranged from 1 month to 14 years). In the follow-up period, seizure freedom was achieved in 32 patients (84.2 %). Seizure freedom was associated with electroencephalographic normalization, while the six children presenting drug-resistant epilepsy showed persistence of electroencephalographic abnormalities. Group B patients showed a higher prevalence of drug-resistant epilepsy. Patients with Prader-Willi syndrome were frequently affected by generalized seizures. Most of the patients had a favorable evolution, although, patients with brain abnormalities presented a worse outcome, suggesting that the presence of these lesions can influence the response to antiepileptic therapy.

A validation of the new definition of drug-resistant epilepsy by the International League Against Epilepsy.

To establish applicability, the recently proposed International League Against Epilepsy (ILAE) consensus on drug-resistant epilepsy (DRE) requires testing in clinical and research settings. This study evaluates the reliability and validity of these criteria in a clinical population. In phase I, two independent evaluators reviewed 97 randomly selected medical records of patients with epilepsy at two separate intervals. Both ILEA consensus and standard diagnostic criteria were employed. Kappa, weighted kappa, and intraclass correlation coefficient (ICC) were used to determine interobserver and intraobserver variability. In phase II, ILAE consensus criteria were applied to 250 patients with epilepsy to determine risk factors associated with development of DRE and to calculate point prevalence. The interobserver agreement of the four definitions was as follows: Berg (0.56), Kwan and Brodie (0.58), Camfield and Camfield (0.69), and ILAE (0.77). The intraobserver agreement of the four definition was as follows: Berg (0.81), Kwan and Brodie (0.82), Camfield and Camfield (0.72), and ILAE (0.82). The prevalence of DRE was the following: with the Berg's definition was 28.4%, Kwan and Brodie 34%, Camfield and Camfield 37%, and with ILAE was 33%. This is first study to establish reliability and validity of ILAE criteria for the diagnosis of DRE. This new definition compares favorably with previously established constructs, which continue to retain clinical significance.

Prevalence of drug resistant epilepsy in adults with epilepsy attending a neurology clinic of a tertiary referral hospital in Singapore

To determine the proportion of population of adult people with epilepsy (PWE) in Singapore, who suffer from drug resistant epilepsy (DRE). All adult PWE who had attended the neurology specialist clinic of a tertiary referral hospital in Singapore were profiled for drug responses according to the definition for DRE as specified by the International League against Epilepsy (ILAE) 2010 consensus. This is a retrospective cohort study. Data collected included demographics, characteristics of seizure and epilepsy, blood biochemistry levels, electroencephalogram and brain imaging findings, and medication histories. The types and dosages of antiepileptic drugs (AEDs) used were retrieved from case notes and checked against pharmacy records. Each patient was counselled upon the diagnosis of epilepsy and taught to maintain a seizure diary. The dates and number of seizures were retrieved from these diaries at each visit. Treatment-related adverse effects were routinely assessed and hence, patients were assumed to not have treatment-related adverse effects when no relevant documentation was encountered. The prevalence rate of DRE in this clinic was 21.5%, while 40.9% of PWE were drug responsive/seizure free at the point prevalence day (n=557). From multivariate analysis, patients with structural-metabolic aetiology [odds ratio (OR) 1.78, 95% confidence interval (CI) 1.003-3.148], mental retardation [OR 2.51, 95% CI 1.073-5.863], psychiatric illnesses [OR 3.349, 95% CI 1.181-9.501] and pre-treatment seizure frequency of more than once monthly [OR 2.775, 95% CI 1.190-6.469] were found to be more likely to have DRE (p≤0.05). Although the influence of Indian ethnicity on the risk of DRE was only found in the univariate analysis, it warrants investigation in a larger cohort. The findings may aid policy makers in designing treatment guidelines and allocating resources around PWE, with careful considerations that at any given time, 1 in 5 PWE have DRE.

Drug-resistant epilepsy and epileptic phenotype-EEG association in MECP2 mutated Rett syndrome

Objective To determine in MECP2-mutated Rett syndrome (RTT [MIM 312750]): (1) the prevalence of drug-resistant epilepsy (DRE); (2) whether the presence of DRE is related to the abnormal EEG patterns or to the particular MECP2 mutant genotype. Methods Retrospective survey of a large population of patients ( n = 154) evaluated between 1978 to 2007 (May) at the Child Psychiatry and Neurology Unit of Siena (Italy) with both clinical and genetic (i.e. MECP2 mutated) diagnoses of RTT. Some subjects were followed for up to 20 years. Among those, cases with epilepsy were first selected for study; within that group, cases with DRE were identified and studied. The association between clinical severity of their epilepsy and quantitative or qualitative scores of EEG severity was tested using rank coefficients (Spearman’s rho values). The relationship between DRE and RTT genotype category (i.e. gene deletion, gene duplication, early truncating mutation, late truncating mutation, and missense mutation) or a specific MECP2 genotype was tested using the chi-square test. A p-value <0.05 (two sided) was considered to indicate statistical significance. Results Prevalence of DRE was 16% (i.e. 16 DRE out of 100 MECP2-mutated RTT epileptic patients). No significant relationship was found between clinical severity of DRE and quantitative ( p = 0.9190) or qualitative EEG scores ( p = 0.1511). In addition, no significant relationship was found between the DRE and the RTT genotype category (chi-square = 1.147, DF = 4, p = 0.8867), or a specific MECP2 genotype (chi-square = 30.958, DF = 39, p = 0.8173). Conclusions Although RTT MECP2-mutated patients suffer from a serious and progressive encephalopathy, it is “epileptogenic” but not “DREgenic” as they have a decreased risk (16%) for DRE compared to the general epileptic population (DRE: 20-40%). The presence of DRE is not related to abnormal EEG findings or a particular MECP2 mutant genotype. Significance These observations could be of help in the practical management and family counseling.

Cardo AB, Sweden

To determine in MECP2-mutated Rett syndrome (RTT [MIM 312750]): (1) the prevalence of drug-resistant epilepsy (DRE); (2) whether the presence of DRE is related to the abnormal EEG patterns or to the particular MECP2 mutant genotype.Retrospective survey of a large population of patients (n = 154) evaluated between 1978 to 2007 (May) at the Child Psychiatry and Neurology Unit of Siena (Italy) with both clinical and genetic (i.e. MECP2 mutated) diagnoses of RTT. Some subjects were followed for up to 20 years. Among those, cases with epilepsy were first selected for study; within that group, cases with DRE were identified and studied. The association between clinical severity of their epilepsy and quantitative or qualitative scores of EEG severity was tested using rank coefficients (Spearman’s rho values). The relationship between DRE and RTT genotype category (i.e. gene deletion, gene duplication, early truncating mutation, late truncating mutation, and missense mutation) or a specific MECP2 genotype was tested using the chi-square test. A p-value <0.05 (two sided) was considered to indicate statistical significance.Prevalence of DRE was 16% (i.e. 16 DRE out of 100 MECP2-mutated RTT epileptic patients). No significant relationship was found between clinical severity of DRE and quantitative (p = 0.9190) or qualitative EEG scores (p = 0.1511). In addition, no significant relationship was found between the DRE and the RTT genotype category (chi-square = 1.147, DF = 4, p = 0.8867), or a specific MECP2 genotype (chi-square = 30.958, DF = 39, p = 0.8173).Although RTT MECP2-mutated patients suffer from a serious and progressive encephalopathy, it is “epileptogenic” but not “DREgenic” as they have a decreased risk (16%) for DRE compared to the general epileptic population (DRE: 20-40%). The presence of DRE is not related to abnormal EEG findings or a particular MECP2 mutant genotype.These observations could be of help in the practical management and family counseling.