[Epilepsy and pregnancy]. / Epilepsie und Schwangerschaft.

BACKGROUND: Regarding treatment of women of childbearing potential with epilepsy, several aspects of family planning and desire to have children have to be taken into account. OBJECTIVE: Overview of current data on mutual implications of epileptic seizures, antiseizure medication (ASM), pregnancy and child development. METHOD: Review of the current literature, discussion and presentation of resulting treatment recommendations. RESULTS: Many ASMs bear the potential for clinically relevant interactions with both contraceptives and altered concentrations of sexual hormones and modified pharmacokinetics during pregnancy. All ASMs show an increased risk for congenital malformations; however, due to seizure-related risks for the mother and child effective ASM treatment during pregnancy is crucial. CONCLUSION: When considering the special aspects of consultation and treatment of women of childbearing potential with epilepsy most pregnancies are uncomplicated.

Clinical Course and Ophthalmologic Findings in Idiopathic Intracranial Hypertension and Pregnancy.

Idiopathic intracranial hypertension (IIH) has its highest prevalence among women of childbearing age and therefore frequently coincides with pregnancy. This retrospective cohort study aimed to explore the impact of pregnancy on the clinical course, ophthalmologic findings and on the therapeutic management of IIH patients. Individual patient records were reviewed for neuro-ophthalmologic findings, treatment strategy, adherence to therapy and pregnancy complications. Sixteen patients with 19 documented pregnancies were identified. The visual acuity, visual field defects and the grade of papilledema at baseline and after pregnancy were compared. The visual acuity and visual field mean deviation at baseline and at follow-up after pregnancy did not significantly differ. Papilledema at baseline was more pronounced in patients who had been diagnosed with IIH during pregnancy than in patients with established IIH. In this cohort, the visual acuity and the visual field were not lastingly impacted by pregnancy. The adherence to therapy was low, with 69% discontinuing treatment or medication.

Gender-specific outcomes of deep brain stimulation for Parkinson's disease - results from a single movement disorder center.

INTRODUCTION AND GOAL: The investigation of gender differences in treatment response is crucial for effective personalized therapies. With only 30%, women are underrepresented in trials for deep brain stimulation (DBS) in Parkinson's disease (PD). It is therefore important to evaluate gender-specific outcomes of DBS in PD in order to improve therapeutic counseling. METHODS: We analyzed clinical outcome parameters of 203 patients with PD that underwent DBS surgery targeting the subthalamic nucleus (STN) at our movement disorder center. A total of 27.6% of patients were female and 72.4% male. Motor and non-motor scores were compared before and 1 year after DBS surgery (1y FU) using Wilcoxon signed-rank tests and gender specific outcomes were analyzed with chi-square tests. RESULTS: At 1y FU, we found significant improvement in UPDRS II, UPDRS III (35.78 ± 36.14% MedOFF vs. StimON-MedOFF), UPDRS IV, depression (BDI-II), and health-related disability as (ADL) that showed no gender-specific differences. No significant change was revealed for UPDRS I, QUIP, and DemTect for the entire cohort. However, when analyzing both groups separately, only women improved in general cognition (plus 1.26 ± 3.03 DemTect points, p = 0.014*), whereas only men ameliorated in depression (minus 1.97 ± 6.92 BDI-II points, p = 0.002**) and impulsivity (minus 2.80 ± 7.27 QUIP points, p = 0.004**). Chi-square tests, however, revealed no significant differences between genders. CONCLUSION AND OUTLOOK: STN-DBS is a highly effective treatment for motor and non-motor symptoms of PD for both women and men but our study hints towards gender-specific outcomes in non-motor-domains like cognition, depressive symptoms, and impulsivity. To explore this in more detail, larger cohorts need to be investigated in multicenter trials.

Neurofilament light chain marks severity of papilledema in idiopathic intracranial hypertension.

BACKGROUND: Neurofilament light chain (NfL) reflects axonal damage in neurological disorders. It has recently been evaluated in idiopathic intracranial hypertension (IIH). A biomarker indicating the severity of optic nerve damage in IIH could support diagnostic accuracy and therapeutic decisions. METHODS: We retrospectively reviewed NfL concentrations in the cerebrospinal fluid (CSF) of 35 IIH patients and 12 healthy controls, who had received diagnostic workup for IIH in our clinic. The diagnosis of IIH was made according to the modified Friedman criteria for IIH and for IIH without papilledema Friedman DI et al Neurol 81:1159-1165 (2013) [1]. NfL in the CSF (CSF-NfL) was correlated with the severity of papilledema and with CSF opening pressure. RESULTS: CSF-NfL correlated with CSF opening pressure at the time of collection. In patients with IIH and moderate or severe papilledema, CSF-NfL was significantly increased compared to patients with mild or no papilledema. Healthy controls with raised intracranial pressure showed no relevant elevation of CSF-NfL. CONCLUSION: CSF-NfL appears to correlate with the severity of papilledema in IIH and with CSF opening pressure and may therefore be a predictor of optic nerve damage in IIH patients.

Valproic acid use in fertile women with genetic generalized epilepsies.

OBJECTIVES: In genetic generalized epilepsies (GGE), valproic acid (VPA) is the most efficacious compound. However, due to teratogenicity and increased risk for impaired cognitive development after intrauterine exposure, its use in women of fertile age is strictly regulated but sometimes unavoidable. METHODS: All patients with GGE treated at the outpatient clinic of a tertiary epilepsy center with at least one visit between January 2015 and April 2020 were included in this retrospective study. The rate of women aged 18 to 49 years taking VPA was compared to that of men of the same age group and to women > 49 years. Furthermore, in each group, clinical variables associated with VPA use were sought. RESULTS: Twenty-eight out of 125 women of fertile age (22%) were treated with VPA, compared to 28 out of 56 men ≤ 49 years (50%; p = .002) and to 22 out of 40 female patients > 49 years (55%; p < .001). VPA dose was lower in fertile women compared to men, with no difference in seizure freedom rates. In women ≤ 49 years, multivariate analysis demonstrated age as the only variable independently associated with VPA use (OR 1.095; 95% CI 1.036-1.159). In the other two groups, no associated variables were identified. CONCLUSIONS: Despite warnings with respect to teratogenicity and impaired cognitive development with VPA, from 2015 to 2020, almost every fourth women of fertile age with GGE received this compound. Inevitably lower VPA doses in these women seem sufficient for favorable seizure freedom rates.

Specific adverse effects of antiepileptic drugs--A true-to-life monotherapy study.

BACKGROUND: In patients taking antiepileptic drugs (AEDs) for epilepsy, adverse effects (AEs) often lead to unfavorable quality of life, impaired adherence, and, eventually, discontinuation of pharmacological treatment. In a true-to-life sample of subjects from our academic epilepsy outpatient clinic, we aimed to identify predictors for overall high AE burden and for specific AEs focusing on patients on monotherapy. METHODS: All patients ≥16years of age with epilepsy for ≥12months were routinely asked to complete the Liverpool Adverse Event Profile (LAEP) just before their appointment. Demographic, epilepsy, and treatment variables were derived from our comprehensive outpatient database. RESULTS: Out of 841 patients, 438 (61% female, mean age: 44.7±17.1years) on monotherapy were included in this study. Levetiracetam (n=151), lamotrigine (n=167), valproic acid (n=73), or controlled-release carbamazepine (n=47) were the most commonly used antiepileptic drugs (AEDs). Independent predictors for general high AE burden (LAEP score≥45) were duration of epilepsy, lack of 12-month seizure freedom, and partial epilepsy, but none of the four individual AEDs. The most frequent LAEP-defined specific AEs were sleepiness, difficulty concentrating, tiredness, and memory problems. The three most frequent independent predictors for each of the 19 AEs were lack of 12-month seizure freedom (13/19 AEs), individual AED (7/19 AEs), and partial epilepsy (6/19 AEs). Levetiracetam was independently associated with anger/aggression, nervousness/agitation, upset stomach, depression, and sleep disturbance; lamotrigine with nervousness/agitation, upset stomach, and difficulty concentrating; and valproic acid with upset stomach and shaky hands. CONCLUSION: Individual AEDs independently predicted some specific AEs, but not overall high AE burden. Our findings may help to characterize patients with epilepsy who are at high risk for specific AEs. Dose reduction or change to another AED may reduce LAEP score and potential nonadherence.

Gender differences in depression, but not in anxiety in people with epilepsy.

PURPOSE: Anxiety and depression are frequent comorbidities in people with epilepsy (PWE), but possible gender differences are often neglected. The aim of the present study was to analyze if men and women with epilepsy differ with regard to anxiety and depressive symptoms and to identify possible predictors. METHODS: Adult consecutive PWE (N=302; 53% women) completed self-report questionnaires, including the depression module of the Patient Health Questionnaire (PHQ-9), the anxiety module of the Hospital Anxiety and Depression Scale (HADS-A) and the subscales "medication effects" and "seizure worry" of the Patient-weighted Quality of Life in Epilepsy Inventory-31-P (QOLIE-31-P). RESULTS: There was no gender difference in extent of anxiety (p=.532), which was mainly due to higher anxiety levels in men compared to the general population. The gender difference in depressive symptoms was significant (p=.009), with female patients being more affected. The most important predictors for anxiety and depressive symptoms were detrimental effects of medication (QOL medication effects) and of seizure worry (QOL seizure worry). Moreover, these predictors were more closely associated with anxiety and depressive symptoms in men. CONCLUSION: Future intervention studies could show whether providing more information about the illness and medication effects may improve anxiety and depression. Our results suggest that such interventions should be tailored to the different needs of men and women.

Burden analysis of rare microdeletions suggests a strong impact of neurodevelopmental genes in genetic generalised epilepsies.

Genetic generalised epilepsy (GGE) is the most common form of genetic epilepsy, accounting for 20% of all epilepsies. Genomic copy number variations (CNVs) constitute important genetic risk factors of common GGE syndromes. In our present genome-wide burden analysis, large (≥ 400 kb) and rare (< 1%) autosomal microdeletions with high calling confidence (≥ 200 markers) were assessed by the Affymetrix SNP 6.0 array in European case-control cohorts of 1,366 GGE patients and 5,234 ancestry-matched controls. We aimed to: 1) assess the microdeletion burden in common GGE syndromes, 2) estimate the relative contribution of recurrent microdeletions at genomic rearrangement hotspots and non-recurrent microdeletions, and 3) identify potential candidate genes for GGE. We found a significant excess of microdeletions in 7.3% of GGE patients compared to 4.0% in controls (P = 1.8 x 10-7; OR = 1.9). Recurrent microdeletions at seven known genomic hotspots accounted for 36.9% of all microdeletions identified in the GGE cohort and showed a 7.5-fold increased burden (P = 2.6 x 10-17) relative to controls. Microdeletions affecting either a gene previously implicated in neurodevelopmental disorders (P = 8.0 x 10-18, OR = 4.6) or an evolutionarily conserved brain-expressed gene related to autism spectrum disorder (P = 1.3 x 10-12, OR = 4.1) were significantly enriched in the GGE patients. Microdeletions found only in GGE patients harboured a high proportion of genes previously associated with epilepsy and neuropsychiatric disorders (NRXN1, RBFOX1, PCDH7, KCNA2, EPM2A, RORB, PLCB1). Our results demonstrate that the significantly increased burden of large and rare microdeletions in GGE patients is largely confined to recurrent hotspot microdeletions and microdeletions affecting neurodevelopmental genes, suggesting a strong impact of fundamental neurodevelopmental processes in the pathogenesis of common GGE syndromes.

Gender differences in social support in persons with epilepsy.

The present study focused on social support as a key feature of the enhancement and maintenance of mental health. So far, literature on gender differences in social support and its effects on the experience of stress in individuals with epilepsy is scarce. We hypothesized that in individuals with epilepsy, social support buffers detrimental effects of stressors (e.g., unpredictable occurrence of seizures) on mental health. Additionally, we explored the role of gender in this process. In 299 individuals with epilepsy, data from validated questionnaires on seizures in the last 3months, perceived support, social network size, and depressive symptoms were analyzed. Women reported higher depressive symptoms (t=2.51, p<.01) and higher perceived support (t=2.50, p<.01) than men. Women and men did not differ in social network size (t=-0.46, p=64), nor in experiencing seizures (χ(2)=0.07, p=.82). Regression analyses revealed no buffer effects. Perceived support was negatively associated with depressive symptoms (B=-0.49, p<.001, 95% CI [-0.67; -0.32]). With regard to depressive symptoms, social integration was slightly more beneficial for women (Bcond.=-0.06, p<.001; 95% CI [-0.09; -0.03]) than for men (Bcond.=-0.02, p=.09; 95% CI [-0.04; 0.01]). Findings present perceived support and social integration as general health resources in individuals with epilepsy regardless of previously experienced seizures. They also encourage further research on gender-specific effects in individuals with epilepsy and move towards recommendations for practitioners and gender-specific interventions. Future aims will be to enhance social integration in order to support adjustment to the chronic condition of epilepsy and to improve individuals' confidence in support interactions.

Genome-wide association analysis of genetic generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32.

Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% and account for 20-30% of all epilepsies. Despite their high heritability of 80%, the genetic factors predisposing to GGEs remain elusive. To identify susceptibility variants shared across common GGE syndromes, we carried out a two-stage genome-wide association study (GWAS) including 3020 patients with GGEs and 3954 controls of European ancestry. To dissect out syndrome-related variants, we also explored two distinct GGE subgroups comprising 1434 patients with genetic absence epilepsies (GAEs) and 1134 patients with juvenile myoclonic epilepsy (JME). Joint Stage-1 and 2 analyses revealed genome-wide significant associations for GGEs at 2p16.1 (rs13026414, P(meta) = 2.5 × 10(-9), OR[T] = 0.81) and 17q21.32 (rs72823592, P(meta) = 9.3 × 10(-9), OR[A] = 0.77). The search for syndrome-related susceptibility alleles identified significant associations for GAEs at 2q22.3 (rs10496964, P(meta) = 9.1 × 10(-9), OR[T] = 0.68) and at 1q43 for JME (rs12059546, P(meta) = 4.1 × 10(-8), OR[G] = 1.42). Suggestive evidence for an association with GGEs was found in the region 2q24.3 (rs11890028, P(meta) = 4.0 × 10(-6)) nearby the SCN1A gene, which is currently the gene with the largest number of known epilepsy-related mutations. The associated regions harbor high-ranking candidate genes: CHRM3 at 1q43, VRK2 at 2p16.1, ZEB2 at 2q22.3, SCN1A at 2q24.3 and PNPO at 17q21.32. Further replication efforts are necessary to elucidate whether these positional candidate genes contribute to the heritability of the common GGE syndromes.

Genome-wide linkage meta-analysis identifies susceptibility loci at 2q34 and 13q31.3 for genetic generalized epilepsies.

PURPOSE: Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% with heritability estimates of 80%. A considerable proportion of families with siblings affected by GGEs presumably display an oligogenic inheritance. The present genome-wide linkage meta-analysis aimed to map: (1) susceptibility loci shared by a broad spectrum of GGEs, and (2) seizure type-related genetic factors preferentially predisposing to either typical absence or myoclonic seizures, respectively. METHODS: Meta-analysis of three genome-wide linkage datasets was carried out in 379 GGE-multiplex families of European ancestry including 982 relatives with GGEs. To dissect out seizure type-related susceptibility genes, two family subgroups were stratified comprising 235 families with predominantly genetic absence epilepsies (GAEs) and 118 families with an aggregation of juvenile myoclonic epilepsy (JME). To map shared and seizure type-related susceptibility loci, both nonparametric loci (NPL) and parametric linkage analyses were performed for a broad trait model (GGEs) in the entire set of GGE-multiplex families and a narrow trait model (typical absence or myoclonic seizures) in the subgroups of JME and GAE families. KEY FINDINGS: For the entire set of 379 GGE-multiplex families, linkage analysis revealed six loci achieving suggestive evidence for linkage at 1p36.22, 3p14.2, 5q34, 13q12.12, 13q31.3, and 19q13.42. The linkage finding at 5q34 was consistently supported by both NPL and parametric linkage results across all three family groups. A genome-wide significant nonparametric logarithm of odds score of 3.43 was obtained at 2q34 in 118 JME families. Significant parametric linkage to 13q31.3 was found in 235 GAE families assuming recessive inheritance (heterogeneity logarithm of odds = 5.02). SIGNIFICANCE: Our linkage results support an oligogenic predisposition of familial GGE syndromes. The genetic risk factor at 5q34 confers risk to a broad spectrum of familial GGE syndromes, whereas susceptibility loci at 2q34 and 13q31.3 preferentially predispose to myoclonic seizures or absence seizures, respectively. Phenotype- genotype strategies applying narrow trait definitions in phenotypic homogeneous subgroups of families improve the prospects of disentangling the genetic basis of common familial GGE syndromes.

Association study of TRPC4 as a candidate gene for generalized epilepsy with photosensitivity.

Photoparoxysmal response (PPR) is characterized by abnormal visual sensitivity of the brain to photic stimulation. Frequently associated with idiopathic generalized epilepsies (IGEs), it might be an endophenotype for cortical excitability. Transient receptor potential cation (TRPC) channels are involved in the generation of epileptiform discharges, and TRPC4 constitutes the main TRPC channel in the central nervous system. The present study investigated an association of PPR with sequence variations of the TRPC4 gene. Thirty-five single nucleotide polymorphisms (SNP) within TRPC4 were genotyped in 273 PPR probands and 599 population controls. Association analyses were performed for the broad PPR endophenotype (PPR types I-IV; n = 273), a narrow model of affectedness (PPR types III and IV; n = 214) and PPR associated with IGE (PPR/IGE; n = 106) for each SNP and for corresponding haplotypes. Association was found between the intron 5 SNP rs10507456 and PPR/IGE both for single markers (P = 0.005) and haplotype level (P = 0.01). Three additional SNPs (rs1535775, rs10161932 and rs7338118) within the same haplotype block were associated with PPR/IGE at P < 0.05 (uncorrected) as well as two more markers (rs10507457, rs7329459) located in intron 3. Again, the corresponding haplotype also showed association with PPR/IGE. Results were not significant following correction for multiple comparisons by permutation analysis for single markers and Bonferroni-Holm for haplotypes. No association was found between variants in TRPC4 and other phenotypes. Our results showed a trend toward association of TRPC4 variants and PPR/IGE. Further studies including larger samples of photosensitive probands are required to clarify the relevance of TRPC4 for PPR and IGE.

Role of GRM4 in idiopathic generalized epilepsies analysed by genetic association and sequence analysis.

BACKGROUND: GRM4 encoding the group III metabotropic glutamate receptor 4 (mGluR4), is located on the chromosomal segment 6p21.3 where tentative susceptibility loci for Juvenile Myoclonic Epilepsy (JME) and Photoparoxysmal Response (PPR) have been mapped. The present candidate gene study examined if variation in GRM4 confers susceptibility to IGE. PATIENTS AND METHODS: The case-control association sample included 564 unrelated IGE patients and 733 population controls of German descent. Association analysis was carried out for 17 single nucleotide polymorphisms (SNPs) covering the genomic GRM4 sequence for all IGE patients as well as for two common IGE subsyndromes [Juvenile Myoclonic Epilepsy (JME, n=215) and Childhood Absence Epilepsy (CAE, n=175)]. Sequence analysis was performed in 85 IGE and 42 PPR cases and 44 controls. RESULTS: Nominally significant associations were detected between IGE and seven GRM4 SNPs (with P-values ranging from 0.037 to 0.0036), between JME and five SNPs (P=0.042-0.0106), and between CAE and two SNPs (P=0.0466-0.0021). Four novel SNPs were identified by sequence analysis. CONCLUSIONS: Our association findings support the hypothesis that GRM4 sequence variants might confer low-risk effects to the etiology of IGE. A minor pathogenetic contribution of the examined variants is possible. These exploratory findings warrant further replication analyses.

Interictal dysphoric disorder and periictal dysphoric symptoms in patients with epilepsy.

PURPOSE: The issue of phenomenology of mood disorders in epilepsy still remains controversial. It has been suggested that a subgroup of patients may develop an affective syndrome also known as interictal dysphoric disorder (IDD). However, the number of behavioral changes that may occur around the ictus needs to be taken into account for an accurate distinction between "true" psychiatric phenomenology and periictal phenomena. This study aimed at identifying clinical correlates of the IDD, with special attention to the relationship between symptoms and seizures. METHODS: A sample of 142 consecutive adult outpatients with epilepsy were assessed using the Interictal Dysphoric Disorder Inventory (IDDI), a 38-item, self-report questionnaire specifically developed to evaluate presence and severity of IDD symptoms as well as their habitual association with seizures (coded as before, after, during, or when seizure-free) and their duration. RESULTS: IDD was diagnosed in 31 subjects but symptoms showed a clear-cut relationship with epileptic seizures in 54.8% of cases, leading to an operative distinction between true IDD and periictal dysphoric symptoms (PDS). There was no significant difference among patients with IDD, PDS, or those without psychopathology. In the IDD group, symptoms were chronic and unremitting in one-third of cases, with labile affective symptoms being correlated with age at onset of seizures (rho = -0.612, p = 0.020) and duration of the epilepsy (rho = 0.833, p < 0.001). DISCUSSION: An operative distinction between IDD and PDS bears the opportunity to identify different clinical endophenotypes that may have different prognoses and require different treatment strategies.

Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies.

Idiopathic generalized epilepsies account for 30% of all epilepsies. Despite a predominant genetic aetiology, the genetic factors predisposing to idiopathic generalized epilepsies remain elusive. Studies of structural genomic variations have revealed a significant excess of recurrent microdeletions at 1q21.1, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 in various neuropsychiatric disorders including autism, intellectual disability and schizophrenia. Microdeletions at 15q13.3 have recently been shown to constitute a strong genetic risk factor for common idiopathic generalized epilepsy syndromes, implicating that other recurrent microdeletions may also be involved in epileptogenesis. This study aimed to investigate the impact of five microdeletions at the genomic hotspot regions 1q21.1, 15q11.2, 16p11.2, 16p13.11 and 22q11.2 on the genetic risk to common idiopathic generalized epilepsy syndromes. The candidate microdeletions were assessed by high-density single nucleotide polymorphism arrays in 1234 patients with idiopathic generalized epilepsy from North-western Europe and 3022 controls from the German population. Microdeletions were validated by quantitative polymerase chain reaction and their breakpoints refined by array comparative genomic hybridization. In total, 22 patients with idiopathic generalized epilepsy (1.8%) carried one of the five novel microdeletions compared with nine controls (0.3%) (odds ratio = 6.1; 95% confidence interval 2.8-13.2; chi(2) = 26.7; 1 degree of freedom; P = 2.4 x 10(-7)). Microdeletions were observed at 1q21.1 [Idiopathic generalized epilepsy (IGE)/control: 1/1], 15q11.2 (IGE/control: 12/6), 16p11.2 IGE/control: 1/0, 16p13.11 (IGE/control: 6/2) and 22q11.2 (IGE/control: 2/0). Significant associations with IGEs were found for the microdeletions at 15q11.2 (odds ratio = 4.9; 95% confidence interval 1.8-13.2; P = 4.2 x 10(-4)) and 16p13.11 (odds ratio = 7.4; 95% confidence interval 1.3-74.7; P = 0.009). Including nine patients with idiopathic generalized epilepsy in this cohort with known 15q13.3 microdeletions (IGE/control: 9/0), parental transmission could be examined in 14 families. While 10 microdeletions were inherited (seven maternal and three paternal transmissions), four microdeletions occurred de novo at 15q13.3 (n = 1), 16p13.11 (n = 2) and 22q11.2 (n = 1). Eight of the transmitting parents were clinically unaffected, suggesting that the microdeletion itself is not sufficient to cause the epilepsy phenotype. Although the microdeletions investigated are individually rare (<1%) in patients with idiopathic generalized epilepsy, they collectively seem to account for a significant fraction of the genetic variance in common idiopathic generalized epilepsy syndromes. The present results indicate an involvement of microdeletions at 15q11.2 and 16p13.11 in epileptogenesis and strengthen the evidence that recurrent microdeletions at 15q11.2, 15q13.3 and 16p13.11 confer a pleiotropic susceptibility effect to a broad range of neuropsychiatric disorders.

Manic/hypomanic symptoms and quality of life measures in patients with epilepsy.

PURPOSE: Although several studies pointed out an association between depression and quality of life (QoL) of patients with epilepsy, data about manic/hypomanic symptoms (MHS) remain scanty. In this study, we sought to investigate their relationship with social and health-related QoL measures in patients with epilepsy. METHODS: Consecutive adult outpatients with epilepsy were assessed using the M.I.N.I. Plus version 5.0.0 and the QOLIE-31. RESULTS: Among 117 evaluated patients, 17 fulfilled DSM-IV criteria for manic/hypomanic episodes. Patients with MHS, as compared to those without, showed lower scores in emotional well-being, energy and fatigue, medication effects, social function and total QOLIE score. However, there was no between-groups difference in educational achievements, employment status, living situation, comorbid psychiatric disorders, history of suicide or abuse of illicit drugs. CONCLUSIONS: MHS are associated with poor QoL measures in patients with epilepsy, though without differences in educational achievements, employment status and independent living.

15q13.3 microdeletions increase risk of idiopathic generalized epilepsy.

We identified 15q13.3 microdeletions encompassing the CHRNA7 gene in 12 of 1,223 individuals with idiopathic generalized epilepsy (IGE), which were not detected in 3,699 controls (joint P = 5.32 x 10(-8)). Most deletion carriers showed common IGE syndromes without other features previously associated with 15q13.3 microdeletions, such as intellectual disability, autism or schizophrenia. Our results indicate that 15q13.3 microdeletions constitute the most prevalent risk factor for common epilepsies identified to date.

Clinical and psychopathological definition of the interictal dysphoric disorder of epilepsy.

PURPOSE: Different authors suggested the occurrence of a pleomorphic affective syndrome in patients with epilepsy named interictal dysphoric disorder (IDD). We sought to investigate whether IDD occurs only in patients with epilepsy and to validate IDD features against DSM-IV criteria. METHODS: Consecutive patients with a diagnosis of epilepsy (E) or migraine (M) have been assessed using the BDI, MDQ, and the Interictal Dysphoric Disorder Inventory (IDDI), a questionnaire specifically created to evaluate IDD symptoms. Diagnosis of current and lifetime DSM-IV Axis I disorders was established using the MINI Plus version 5.0.0. RESULTS: A total of 229 patients (E = 117; M = 112) were evaluated. Females were significantly more represented in the migraine group (E = 46.5% vs. M = 73.3% p = 0.009), but there was no difference in age, duration of the disease, or education level. Patients with epilepsy were more likely to screen positively at MDQ (E = 17% vs. M = 5.3% p = 0.006) and to have a diagnosis of bipolar disorder (E = 14.5% vs. M = 4.5% p = 0.013) as compared to migraine patients. There was no between-groups difference in IDD prevalence (E = 17%; M = 18.7%) and IDDI total scores (E = 4.1 +/- 2.0 vs. M = 3.8 +/- 2.0). Validation of IDD against DSM-IV categories showed current major depression being the foremost diagnostic category correlated with IDD in both epilepsy (OR = 0.32-0.12-0.88, p = 0.028) and migraine (OR = 0.10, 95% CI = 0.02-0.49, p = 0.004) samples. Current anxiety disorder correlated with IDD only in migraine patients (OR = 0.19, 95% CI = 0.05-0.77, p = 0.02). CONCLUSION: IDD represents a homogenous construct that can be diagnosed in a relevant proportion of patients but it is not typical only of epilepsy, occurring in other central nervous system disorders such as migraine.