Predictors of genetic diagnosis in individuals with developmental and epileptic encephalopathies.

OBJECTIVE: To evaluate the clinical predictors of positive genetic investigation in developmental and epileptic encephalopathies, beyond the influence of Dravet Syndrome. METHODS: The study included 98 patients diagnosed with developmental and epileptic encephalopathies. The patients underwent Sanger sequencing of SCN1A, Chromosomal Microarray Analysis, and Whole Exome Sequencing. The association of clinical variables with a positive genetic test was investigated using univariate and multivariate analysis. RESULTS: Genetic diagnosis was identified in 47 (48 %) patients with developmental and epileptic encephalopathies. Beyond Dravet Syndrome influence, first seizure in the context of fever (p < 0.01), seizures precipitated by temperature (p = 0.04), cognitive regression (p = 0.04), hypotonia (p < 0.01), and focal seizures (p = 0.03) increased the chances of a positive genetic investigation. In contrast, atonic seizures (p = 0.01) and generalized discharges on electroencephalogram (p = 0.02) decreased the chances. Dravet Syndrome was positively associated with a genetic developmental and epileptic encephalopathies etiology (p < 0.01), whereas epilepsy with myoclonic-atonic seizures (p = 0.01), developmental and epileptic encephalopathies with spike-wave activation in sleep (p = 0.04), and Lennox-Gastaut syndrome (p = 0.03) were negatively associated. In multivariate analysis, the first seizure in the context of fever (p < 0.01) and hypotonia (p = 0.02) were positively, and atonic seizures (p = 0.01) were negatively and independently associated with a genetic etiology. CONCLUSION: The predictive variables of genetic investigation in developmental and epileptic encephalopathies are first seizure in the context of fever and hypotonia, whereas atonic seizures decrease the chances of finding a genetic cause for developmental and epileptic encephalopathies. Regarding epileptic syndromes, Dravet Syndrome is highly associated with a positive genetic test, whereas epilepsy with myoclonic-atonic seizures, developmental and epileptic encephalopathies with spike-wave activation in sleep, and Lennox-Gastaut syndrome are rarely associated with a positive genetic investigation.

Dysregulation of NEUROG2 plays a key role in focal cortical dysplasia.

OBJECTIVE: Focal cortical dysplasias (FCDs) are an important cause of drug-resistant epilepsy. In this work, we aimed to investigate whether abnormal gene regulation, mediated by microRNA, could be involved in FCD type II. METHODS: We used total RNA from the brain tissue of 16 patients with FCD type II and 28 controls. MicroRNA expression was initially assessed by microarray. Quantitative polymerase chain reaction, in situ hybridization, luciferase reporter assays, and deep sequencing for genes in the mTOR pathway were performed to validate and further explore our initial study. RESULTS: hsa-let-7f (p = 0.039), hsa-miR-31 (p = 0.0078), and hsa-miR34a (p = 0.021) were downregulated in FCD type II, whereas a transcription factor involved in neuronal and glial fate specification, NEUROG2 (p < 0.05), was upregulated. We also found that the RND2 gene, a NEUROG2-target, is upregulated (p < 0.001). In vitro experiments showed that hsa-miR-34a downregulates NEUROG2 by binding to its 5'-untranslated region. Moreover, we observed strong nuclear expression of NEUROG2 in balloon cells and dysmorphic neurons and found that 28.5% of our patients presented brain somatic mutations in genes of the mTOR pathway. INTERPRETATION: Our findings suggest a new molecular mechanism, in which NEUROG2 has a pivotal and central role in the pathogenesis of FCD type II. In this way, we found that the downregulation of hsa-miR-34a leads to upregulation of NEUROG2, and consequently to overexpression of the RND2 gene. These findings indicate that a faulty coupling in neuronal differentiation and migration mechanisms may explain the presence of aberrant cells and complete dyslamination in FCD type II. Ann Neurol 2018;83:623-635.

Systematic review of the screening, diagnosis, and management of ADHD in children with epilepsy. Consensus paper of the Task Force on Comorbidities of the ILAE Pediatric Commission.

Attention-deficit/hyperactivity disorder (ADHD) is a common and challenging comorbidity affecting many children with epilepsy. A working group under the International League Against Epilepsy (ILAE) Pediatric Commission identified key questions on the identification and management of ADHD in children with epilepsy. Systematic reviews of the evidence to support approaches to these questions were collated and graded using criteria from the American Academy of Neurology Practice Parameter. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) requirements were followed, with PROSPERO registration (CRD42018094617). No increased risk of ADHD in boys with epilepsy compared to girls with epilepsy was found (Level A). Valproate use in pregnancy is associated with inattentiveness and hyperactivity in offspring (1 class I study), and children with intellectual and developmental disabilities are at increased risk of ADHD (Level A). Impact of early seizure onset on development of ADHD was unclear (Level U), but more evident with poor seizure control (Level B). ADHD screening should be performed from 6 years of age, or at diagnosis, and repeated annually (Level U) and reevaluated after change of antiepileptic drug (AED) (Level U). Diagnosis should involve health practitioners with expert training in ADHD (Level U). Use of the Strength and Difficulties Questionnaire screening tool is supported (Level B). Formal cognitive testing is strongly recommended in children with epilepsy who are struggling at school (Level U). Behavioral problems are more likely with polytherapy than monotherapy (Level C). Valproate can exacerbate attentional issues in children with childhood absence epilepsy (Level A). Methylphenidate is tolerated and effective in children with epilepsy (Level B). Limited evidence supports that atomoxetine is tolerated (Level C). Multidisciplinary involvement in transition and adult ADHD clinics is essential (Level U). In conclusion, although recommendations could be proposed for some of the study questions, this systematic review highlighted the need for more comprehensive and targeted large-population prospective studies.

The relevance of attention deficit hyperactivity disorder in self-limited childhood epilepsy with centrotemporal spikes.

In this study, we aimed to evaluate the attentional and executive functions in patients with benign childhood epilepsy with centrotemporal spikes (BCECTS) with and without attention-deficit hyperactivity disorder (ADHD) compared with controls and compared with patients with ADHD without epilepsy. We evaluated 12 patients with BCECTS and ADHD (66.7% boys; mean age of 9.67years); 11 children with non-ADHD BCECTS (63.6% boys; mean age of 11.91years); 20 healthy children (75% boys; mean age of 10.15years); and 20 subjects with ADHD without epilepsy (60% boys; mean age of 10.9years). We used a comprehensive battery of neuropsychological tests to evaluate attentional and executive functions in their broad domains. Patients with BCECTS and ADHD had worse performance in Conners' Continuous Performance Test II (reaction time standard error [p=0.008], variability [p=0.033], perseverations [p=0.044] and in reaction time interstimuli interval [p=0.016]). Patients with ADHD showed worse performance in Trail Making Test B errors [p=0.012]. In conclusion, patients with BCECTS and ADHD had worse executive and attentional performance compared with controls than non-ADHD patients with BCECTS. Regardless of the presence of epilepsy, ADHD also negatively impacted executive and attentional functions but in different executive subdomains compared with patients with epilepsy.

The executive profile of children with Benign Epilepsy of Childhood with Centrotemporal Spikes and Temporal Lobe Epilepsy.

RATIONALE: Benign Epilepsy of Childhood with Centrotemporal Spikes (BECTS) and temporal lobe epilepsy (TLE) represent two distinct models of focal epilepsy of childhood. In both, there is evidence of executive dysfunction. The purpose of the present study was to identify particular deficits in the executive function that would distinguish children with BECTS from children with TLE. METHODS: We prospectively evaluated 19 consecutive children and adolescents with TLE with hippocampal sclerosis (HS) (57.9% male; mean 11.74years [SD 2.05]; mean IQ 95.21 [SD 15.09]), 19 with BECTS (36.8% male; mean 10.95years [SD 2.33]; mean IQ 107.40 [SD 16.01]), and 21 age and gender-matched controls (33.3% male; mean 11.86years [SD 2.25]; mean IQ 108.67 [15.05]). All participants underwent a neuropsychological assessment with a comprehensive battery for executive and attentional functions. We used ANOVA and chi-square to evaluate differences on demographic aspects among groups (BECTS, TLE-HS, and control groups). Group comparisons on continuous variables were complemented by MANOVA and Bonferroni posthoc comparisons. RESULTS: Patients with BECTS had worse performance than controls in: Matching Familiar Figures Test, time (p=0.001); Matching Familiar Figures Test, time×errors index (p<0.001); Verbal Fluency for foods (p=0.038); Trail Making Test, part B time (p=0.030); Trail Making Test, part B number of errors (p=0.030); and WCST, number of categories achieved (p=0.043). Patients with BECTS had worse performance than patients with TLE-HS on Matching Familiar Figures Test, time (p=0.004), and Matching Familiar Figures Test, time×errors index (p<0.001). Patients with TLE-HS had worse performance than controls on the following tests: Verbal Fluency for foods (p=0.004); Wisconsin Card Sorting Test, the number of categories achieved (p<0.001); and Wisconsin Card Sorting Test, the number of perseverative errors (p=0.028). Patients with TLE-HS had worse performance than patients with BECTS on Digit Backward (p=0.002); and the Wisconsin Card Sorting Test, the number of perseverative errors (p<0.001). CONCLUSIONS: Patients with TLE and BECTS present distinct cognitive profiles. Patients with TLE-HS had worse performance in mental flexibility, concept formation, and working memory compared to BECTS. Patients with BECTS had worse inhibitory control compared to children with TLE-HS. Both TLE-HS and BECTS had a higher number of errors on an inhibitory control test. However, patients with BECTS had a slower mental processing even when compared to patients with TLE-HS. Rehabilitation programs for children with epilepsy must include children with benign epilepsies and must take into account the epileptic syndrome and its particular neurocognitive phenotype.

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 features of childhood-onset paroxysmal kinesigenic dyskinesia with PRRT2 gene mutations.

AIM: To define better the phenotype and genotype of familial and sporadic cases of paroxysmal kinesigenic dyskinesia (PKD) caused by mutations in the PRRT2 gene presenting in the paediatric age group. METHOD: We report the detailed clinical and molecular genetic features of 11 patients (six females, five males) with childhood-onset PRRT2-mutation-positive PKD. RESULTS: Mean age at disease onset was 8 years 7.5 months (range 5-11y), and clinical presentation was characterized by daily short paroxysmal episodes of dystonia/dyskinesia. Most patients also had non-kinesigenic attacks in addition to the classical movement-induced paroxysmal episodes. One family demonstrated great phenotypic variability with PKD, infantile convulsions, and/or hemiplegic migraine affecting different family members with the same mutation. All patients in whom antiepileptics (carbamazepine/phenytoin) were tried showed a dramatic improvement with complete abolition of dyskinetic episodes. INTERPRETATION: Our case series provides a detailed clinical description of patients with PRRT2-PKD, and reports a spectrum of disease-causing mutations, thereby expanding both the clinical phenotype and mutation spectrum of disease.

Memory in children with temporal lobe epilepsy is at least partially explained by executive dysfunction.

An association between memory and executive dysfunction (ED) has been demonstrated in patients with mixed neurological disorders. We aimed to investigate the impact of ED in memory tasks of children with temporal lobe epilepsy (TLE). We evaluated 36 children with TLE and 28 controls with tests for memory, learning, attention, mental flexibility, and mental tracking. Data analysis was composed of comparison between patients and controls in memory and executive function; correlation between memory and executive function tests; and comparison between patients with mild and severe ED in memory tests. Children with TLE had worse performance in focused attention, immediate and delayed recall, phonological memory, mental tracking, planning, and abstraction. Planning, abstraction, and mental tracking were correlated with visual and verbal memory. Children with severe ED had worse performance in verbal and visual memory and learning tests. This study showed that ED was related to memory performance in children with TLE.

Neuropsychological assessment of children with rolandic epilepsy: executive functions.

Rolandic epilepsy (RE) is the most common type of childhood focal epilepsy. Although there is no intellectual deficit, children with RE may have specific cognitive impairments. The aims of this study were to identify changes in executive functions in children with RE and to verify the influence of epilepsy and seizure variables. We evaluated 25 children with RE and 28 healthy controls. A comprehensive neuropsychological battery was utilized. The results showed that the RE children had worse performance than the control group in some categories of the Wisconsin Card Sorting Test, the Trail Making Test part B, and the Verbal Fluency Test (FAS). Children with earlier onset of epilepsy had worse performance when compared with children with later onset of epilepsy. We conclude that children with RE may show a deficit in executive function despite their normal IQ. The set of tests was more extensive than what was previously used in other studies. Our study suggests that early seizures can interfere with brain development. Regarding cognition, the term benign should be used cautiously in RE.

Comparison of motor and cognitive performance in infants during the first year of life.

PURPOSE: To compare motor and cognitive performance in infants with typical development in the 1st, 2nd, 3rd, 6th, 9th, and 12th months after birth. METHODS: This was a repeated-measures study with unequal sample sizes in the follow-up periods, comprising 94 infants born at term. Infants with genetic syndromes, malformations, congenital infections, or hospitalized in intensive care units were excluded. The Bayley Scales of Infant Development II were used for evaluation of cognitive and motor performance. RESULTS: There were significant differences between motor and cognitive performance at 1, 2, and 3 months. However, at 6, 9, and 12 months, there was no difference between domains. CONCLUSION: This study suggests that during the first year, development can be synchronous in the 2 areas evaluated by the Bayley Scales of Infant Development II, especially from the sixth month of age onward.

Episodic and semantic memory in children with mesial temporal sclerosis.

The aim of this study was to analyze semantic and episodic memory deficits in children with mesial temporal sclerosis (MTS) and their correlation with clinical epilepsy variables. For this purpose, 19 consecutive children and adolescents with MTS (8 to 16 years old) were evaluated and their performance on five episodic memory tests (short- and long-term memory and learning) and four semantic memory tests was compared with that of 28 healthy volunteers. Patients performed worse on tests of immediate and delayed verbal episodic memory, visual episodic memory, verbal and visual learning, mental scanning for semantic clues, object naming, word definition, and repetition of sentences. Clinical variables such as early age at seizure onset, severity of epilepsy, and polytherapy impaired distinct types of memory. These data confirm that children with MTS have episodic memory deficits and add new information on semantic memory. The data also demonstrate that clinical variables contribute differently to episodic and semantic memory performance.

Structural abnormalities of the thalamus in juvenile myoclonic epilepsy.

Studies have suggested that the thalamus is a key structure in the pathophysiology of juvenile myoclonic epilepsy. The objective of the present investigation was to examine the thalami of patients with juvenile myoclonic epilepsy using a combination of multiple structural neuroimaging modalities. The association between these techniques may reveal the mechanisms underlying juvenile myoclonic epilepsy and help to identify the neuroanatomical structures involved. Twenty-one patients with juvenile myoclonic epilepsy (13 women, mean age=30±9 years) and a control group of 20 healthy individuals (10 women, mean age=31±8 years) underwent MRI in a 2-T scanner. The volumetric three-dimensional sequence was used for structural investigation. Evaluation of the thalamus comprised voxel-based morphometry, automatic volumetry, and shape analysis. Comparisons were performed between patient and control groups. Voxel-based morphometry analysis identified areas of atrophy located in the anterior portion of the thalamus. Post hoc analysis of automatic volumetry did not reveal significant differences between the groups. Shape analysis disclosed differences between patients and controls in the anterior and inferior portions of the right thalamus and in the anterior portion of the left thalamus. The present investigation confirms that thalami of patients with juvenile myoclonic epilepsy are structurally abnormal with impairments located mainly in the anterior and inferior sections.

Correlation between quantitative EEG and MRI in idiopathic generalized epilepsy.

The objective of this study was to investigate the relationship between the focal discharges sometimes observed in the electroencephalogram of patients with idiopathic generalized epilepsies and subtle structural magnetic resonance imaging abnormalities. The main hypothesis to be assessed is that focal discharges may arise from areas of structural abnormality which can be detected by quantitative neuroimaging. Focal discharges were used for quantitative electroencephalogram source detection. Neuroimaging investigations consisted of voxel-based morphometry and region of interest volumetry. For voxel-based morphometry, volumetric MRI were acquired and processed. The images of each patient were individually compared with a control group. Statistical analysis was used to detect differences in gray matter volumes. Region of interest-based morphometry was automatically performed and used essentially to confirm voxel-based morphometry findings. The localization of the focal discharges on the electroencephalogram was compared to the neuroimaging results. Twenty-two patients with idiopathic generalized epilepsies were evaluated. Gray matter abnormalities were detected by voxel-based morphometry analysis in 77% of the patients. There was a good concordance between EEG source detection and voxel-based morphometry. On average, the nearest voxels detected by these methods were 19 mm (mm) apart and the most statistically significant voxels were 34 mm apart. This study suggests that in some cases subtle gray matter abnormalities are associated with focal epileptiform discharges observed in the electroencephalograms of patients with idiopathic generalized epilepsies.

Social cognition in childhood epilepsy with centrotemporal spikes.

PURPOSE: Social cognition is involved in the perception, processing, and interpretation of social information. For this reason, social cognition is a crucial domain for successful communication and interpersonal relationships. With this in mind, we aimed to assess social cognition in children with Self-Limited Childhood Epilepsy with Centrotemporal Spikes (CECTS) and its association with traditional executive function tests and clinical variables of epilepsy. METHODS: We evaluated 23 patients with CECTS (65% male, mean age of 10.64 years) and 20 healthy children (75% male, mean age of 10.15 years). We used the Faux-Pas Child Task (FP) to analyze social cognition and a comprehensive battery of neuropsychological tests to evaluate domains of classic executive functions. RESULTS: Patients with CECTS had impairments in FP compared to healthy children [p < 0.001]. Impairments in some areas of traditional executive functions were related to worse social cognition in patients with CECTS. Epilepsy-related factors did not impair the performance on FP, except for the number of antiseizure medication [p = 0.016]. CONCLUSIONS: Social cognition is impaired in children and adolescents with CECTS. The presence of ongoing seizures and frequent epileptiform activity were not correlated with social cognition. Therefore, epilepsy per se was more relevant for social cognition than its severity.

Multimodal Analysis of SCN1A Missense Variants Improves Interpretation of Clinically Relevant Variants in Dravet Syndrome.

Objective: We aimed to improve the classification of SCN1A missense variants in patients with Dravet syndrome (DS) by combining and modifying the current variants classification criteria to minimize inconclusive test results. Methods: We established a score classification workflow based on evidence of pathogenicity to adapt the classification of DS-related SCN1A missense variants. In addition, we compiled the variants reported in the literature and our cohort and assessed the proposed pathogenic classification criteria. We combined information regarding previously established pathogenic amino acid changes, mode of inheritance, population-specific allele frequencies, localization within protein domains, and deleterious effect prediction analysis. Results: Our meta-analysis showed that 46% (506/1,101) of DS-associated SCN1A variants are missense. We applied the score classification workflow and 56.5% (286/506) of the variants had their classification changed from VUS: 17.8% (90/506) into "pathogenic" and 38.7% (196/506) as "likely pathogenic." Conclusion: Our results indicate that using multimodal analysis seems to be the best approach to interpret the pathogenic impact of SCN1A missense changes for the molecular diagnosis of patients with DS. By applying the proposed workflow, most DS related SCN1A variants had their classification improved.

A new missense mutation found in the FLNA gene in a family with bilateral periventricular nodular heterotopia (BPNH) alters the splicing process.

We describe the clinical and molecular evaluation of two patients, mother and daughter (proband), with bilateral periventricular nodular heterotopia (BPNH). The clinical evaluation revealed a more severe phenotype in the proband, with mental retardation and seizures. Imaging studies showed bilateral periventricular nodules in both patients. We identified a novel mutation, c.987G-->C mutation in exon 6 of the Filamin A (FLNA) gene in the genomic DNA of both patients. Complementary DNA (cDNA) sequencing revealed the maintenance of intron 6 in the mutated allele. Bioinformatics analysis indicates that the mutation identified in both patients probably destroyed the intron 6 donor-splicing site, which is likely to introduce a premature stop codon resulting in a truncated FLNA protein. In addition, X-chromosome inactivation studies in DNA of blood cells revealed a skewed pattern in the proband, and real time quantitative polymerase chain reaction (PCR) showed a higher expression of the mutated allele in the proband compared to that of the mother. This variation in expression of the mutated allele may be responsible for the differences in the clinical manifestations observed in both patients.

A new candidate locus for bilateral perisylvian polymicrogyria mapped on chromosome Xq27.

Polymicrogyria (PMG) is characterized by an excessive number of small and prominent brain gyri, separated by shallow sulci. Bilateral perisylvian polymicrogyria (BPP) is the most common form of PMG. Clinical signs include pseudobulbar paresis, mental retardation, and epilepsy. Familial forms of BPP have been described and a candidate locus was previously mapped to chromosome Xq28, distal do marker DXS8103. The objective of this study was to perform linkage analysis in one family segregating BPP. A total of 15 individuals, including 8 affected patients with BPP were evaluated. Family members were examined by a neurologist and subjected to magnetic resonance imaging scans. Individuals were genotyped for 18 microsatellite markers, flanking a 42.3 cM interval on ch Xq27-q28. Two-point and multipoint linkage analysis was performed using the LINKAGE package and haplotype reconstruction was performed by GENEHUNTER software. Our results showed a wide spectrum of clinical manifestations in affected individuals with BPP, ranging from normal to mild neurological abnormalities. Two-point linkage analysis yield a Zmax = 2.06 at theta = 0.00 for markers DXS1205 and DXS1227. Multipoint lod-scores indicate a candidate interval of 13 cM between markers DSXS1205 and DXS8043, on ch Xq27.2-Xq27.3. These results point to a new locus for BPP in a more centromeric location than previously reported.

The Brazilian version of the Quality of Life in Epilepsy Inventory for Adolescents: translation, validity, and reliability.

OBJECTIVE: The aim of this study was to translate and adapt the Quality of Life in Epilepsy Inventory for Adolescents (QOLIE-AD-48) into Brazilian Portuguese, as well as to evaluate the psychometric properties of this Brazilian version. METHODS: The QOLIE-AD-48 Brazilian version was tested with respect to reliability and validity in 93 adolescents with epilepsy. Patients completed the Self-Esteem Inventory (SEI), Children's Depression Evaluation Scale (CDES), and Adverse Events Profile (AEP). A subset of these patients were reexamined after 3-4 weeks to evaluate the test-retest reliability of the inventory. We assessed validity by comparing the QOLIE-AD-48 Brazilian version with external measures. RESULTS: Internal consistency was satisfactory (Cronbach's alpha=0.87). Test-retest reliability was acceptable as well (intraclass correlation coefficient=0.52-0.81). Moreover, the QOLIE-AD-48 Brazilian version was highly correlated with other scales, demonstrating strong validity. CONCLUSIONS: We conclude that the QOLIE-AD-48 Brazilian version has psychometric properties equivalent to those of the original American-English version and is a valid and reliable instrument for assessment of health-related quality of life in adolescents with epilepsy in Brazil or other Portuguese-speaking countries.

Seizure related accidents and injuries in childhood.

Several studies show that the risk of accidents involving patients with epilepsy is much higher compared to the general population. The objective of this study was to identify the frequency and type of seizure related injuries in children diagnosed with epilepsy. In addition we also assessed possible risk factors associated with this seizure related accidents in childhood. This study was conducted at the pediatric epilepsy clinic of Unicamp, from January 2005 to August 2006. We evaluated 100 consecutive children with epilepsy. Parents were interviewed by one of the authors using a structured questionnaire that included questions about seizure related accidents and related injuries. Forty-four patients reported seizure related accidents. Eighteen patients needed medical assistance at an emergency room due the severity of their seizure related accident. Forty patients reported having a seizure related accident prevented by a bystander. Another 14 patients reported avoiding a seizure related accident by luck alone. Contusions and lacerations were the most common type of lesion associated with seizures. Patients with symptomatic/probable symptomatic epilepsy and those using higher numbers of anti-epileptic drugs (AEDs) were at greater risk for seizure related accidents (p<0.05). We conclude that patients with symptomatic/probable symptomatic epilepsy and on multiple AEDs are at increased risk of seizure related accidents. Parents and caretakers should be even more cautious about risk of injury in such patients.

Accident risk in patients with epilepsy.

OBJECTIVE: To compare the risk of accidents in patients with uncontrolled seizures, in seizure-free patients, and in patients with chronic headache. METHOD: This was a prospective longitudinal case-controlled study with interviews. A semi-structured questionnaire was used in the epilepsy and headache outpatient clinics of the Hospital das Clínicas of UNICAMP. RESULTS: Group I was composed of 48 patients with uncontrolled seizures, group II was composed of 24 seizure-free patients and group III was composed of 32 patients with headache. Thirty-nine patients (81%) in group I, 13 (54%) in group II, and 19 (59%) in group III reported accidents in the last two years. In the first group, 649 accidents (89%) were related to epileptic seizures and the average number of accidents not related to seizures was 1.7. The average number of accidents in groups II and III were both 2.4. CONCLUSION: Epileptic seizure was the most important factor determining the occurrence of accidents in people with epilepsy.