A cognitive rehabilitation program to improve hot and cool executive dysfunction in juvenile myoclonic epilepsy: Preliminary findings.

OBJECTIVE: Executive and attentional deficits are often described in Juvenile Myoclonic Epilepsy (JME). We aimed to evaluate the short-term impact of rehabilitation developed for the most frequent cognitive deficits of persons with JME. METHODS: Thirty-three patients entered this study which consisted of 12 individual sessions once a 60-minute week, divided into planning/organization, attention, and impulsivity. Twenty-seven patients finished the protocol, and all patients had pre-and-post evaluations from neuropsychological tests and self-rating questionnaires. Generalized Estimating Equations (GEE) inferential statistics were used to verify the protocol's effect, and a 95% confidence interval was adopted. RESULTS: We found significant improvement in selective attention (TMT A [p < 0.01] and Stroop test 2 [p = 0.03]), inhibitory control (Stroop test 3 [p = 0.02], FAS [p < 0.01], CPT commissions [p < 0.01]), mental flexibility [WCST categories p < 0.01] and implicit decision making (IGT blocks A [p < 0.01], B [p = 0.02], C [p < 0.01] and D [p < 0.01]). All components of the Behavioral Rating Index of Executive Functions metacognition index and the general quotient had significant improvement (initiative [p ≤ 0.01], working memory [p ≤ 0.01], planning and organization [p ≤ 0.01], task monitor [p = 0.02] and organization of materials [p = 0.02]). Regarding the Behavioral Regulation Index, the "Emotional Control" was improved [p = 0.03]. The attentional component and general scores of the Adult Self-Report Scale for Adults also changed significantly [p ≤ 0.01]. SIGNIFICANCE: Executive function and attention had an improvement in objective and subjective tests. The context-dependent reactive mechanism of impulsivity improved in instruments based on the ecological evaluation. Our findings, though preliminary due to a lack of controls and practice effect corrections, support that cognitive rehabilitation may be a valuable resource to alleviate cognitive deficits in patients with JME.

The COVID-19 outbreak and PNES: The impact of a ubiquitously felt stressor.

OBJECTIVE: We aimed to assess frequency of functional seizures or psychogenic nonepileptic seizures (PNES) during the COVID-19 outbreak and to recognize possible factors associated with worsening in this population. METHODS: In this cross-sectional study conducted during the second phase of the pandemic, adult patients with PNES documented by video-EEG and followed up in two tertiary epilepsy centers responded to a structured telephone survey. Data were gathered on demographics, clinical features and frequency of PNES, history of psychiatric comorbidity, access to treatment, as well as on anxiety (GAD-7 items) and depressive symptoms (NDDI-E). RESULTS: Fifty-four patients (78% female; mean age of 31.36 years [SD = 10.6]) were contacted and 15 (28%) reported increased frequency of PNES during the pandemic. Higher scores of GAD-7 items (p < 0.001) and NDDI-E (p < 0.001) were associated with PNES worsening. There was strong evidence of a correlation between higher stress levels (p < 0.001) and poor sleep quality (p 0.005) with PNES aggravation. After regression, stress was the strongest predictor of PNES increased frequency. SIGNIFICANCE: Patients with functional neurological disorders are vulnerable during ubiquitously felt stressors. However, the atmosphere of uncertainty did not affect these patients equally. Patients with PNES showing symptoms of anxiety and depression are at higher risk of seizure worsening. Early identification of this subset of patients may prevent this detrimental outcome.

Genetic polymorphisms of the serotonin transporter are not related with depression in temporal lobe epilepsy caused by hippocampal sclerosis.

BACKGROUND: Mood disorders are the most frequent psychiatric disorders in patients with temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS). The pathophysiological mechanisms in common between TLE and mood disorders include abnormalities in the serotonergic pathway. We aimed to evaluate the association between serotonin transporter genetic polymorphisms - 5-HTTLPR and 5-HTTVNTR - and the presence of mood disorders in patients with TLE-HS. METHODS: We evaluated 119 patients with TLE-HS, with and without psychiatric disorder; 146 patients diagnosed with major depressive disorder (MDD), and 113 healthy volunteers. Individuals were genotyped for the 5-HTTLPR and 5-HTTVNTR polymorphisms. RESULTS: No difference was observed between the TLE-HS groups, healthy controls, and MDD without epilepsy. There was a correlation between the 12-allele of the 5-HTTVNTR and the family history of patients with epilepsy with TLE-HS (p = 0.013). CONCLUSIONS: In this study conducted in two Brazilian centers, the serotonin transporter polymorphisms evaluated cannot be associated with depressive disorder in patients with TLE-HS. Still, they do have some influence over some clinical characteristics of epilepsy in TLE-HS. These data may not be reproduced in other populations with distinct ethnic characteristics.

Clinical characteristics of psychogenic nonepileptic seizures across the lifespan: An international retrospective study.

PURPOSE: Previous studies from a few countries have reported semiological differences in younger children compared with adolescents or adults with psychogenic nonepileptic seizures (PNESs). This study tested the hypothesis that semiological, demographic, and historical risk factors vary with different ages of PNES onset in a large cohort from different countries. METHODS: In this retrospective study, we investigated patients consecutively referred for PNES, who were admitted to epilepsy monitoring units in Iran, Brazil, Venezuela, Canada, Argentina, and USA. Age, gender, age at seizure onset, seizure semiology, and factors predisposing to PNES (abuse, stressors) were documented according to routine diagnostic practices at each center. Participants were grouped according to their age at onset (i.e., childhood, adolescence, or adulthood). RESULTS: A total of 448 patients were studied. Female predominance was associated with adolescent- (85/122, 70%) and adult-onset (190/270, 70%) but not in childhood-onset PNES (28/56, 50%) (p = 0.011). Event frequency in the month preceding the diagnosis was higher in the childhood- [x¯â€¯= 50, standard deviation (sd) = 82, p = 0.025] versus adolescent- (x¯â€¯= 24, sd = 36) or adult-onset groups (x¯â€¯= 29, sd = 61). Significant between-group differences were observed for generalized body movements (p = 0.0001) and ictal injury (p = 0.027), suggesting more severe ictal presentations in adult-onset PNES compared with younger ages. Adult-onset patients were also more likely to be taking an unnecessary antiepileptic medication (p = 0.010). CONCLUSION: While PNES may present at any age, there appear to be notable differences across the lifespan with respect to some of the clinical characteristics. Further international and cross-cultural studies may reveal other interesting characteristics of PNES.

Dissociation between decision making under ambiguity and risk in patients with juvenile myoclonic epilepsy.

INTRODUCTION: Decision making (DM) is one aspect of impulsivity that can be defined by the ability to decide between two or more options in a given situation. To date, there are at least two types of DM that differ in the level of uncertainty, and how much information about consequences is provided. In this study, we aimed to evaluate the two domains of DM - under risk and ambiguous - with a comprehensive evaluation in a group of patients with juvenile myoclonic epilepsy (JME), and correlate with patients' characteristics, clinical variables, and neuropsychological evaluation for executive functions. METHODS: We evaluated 35 patients with JME and 39 healthy controls using the Iowa Gambling Task for DM under ambiguity and the Game Dice Task for DM under risk. We assessed the performance in Iowa Gambling Task and Game Dice Task through net scores, safe and risky choices, besides the type of decisions across time. RESULTS: Patients with JME had a higher number of risky choices compared to controls in the Game Dice Task. There was no significant difference between patients and controls in the Iowa Gambling Task. However, patients with higher seizure frequency had worse scores on decks C and D (safe choices) from the Iowa Gambling Task. CONCLUSION: Patients with JME have worse performance on DM under risk. The same was not observed for DM under ambiguity. Epilepsy-related factors and the presence of psychiatric disorders, but not executive dysfunction, were associated with a lower tendency for safe choices. These findings showed a dissociation between DM processes in patients with JME and a tendency to make disadvantageous decisions with measurable risks.

Adult-onset psychogenic nonepileptic seizures: A multicenter international study.

PURPOSE: The aim of this multicenter international cross-cultural study was to compare clinical variables in a large sample of people with adult-onset psychogenic nonepileptic seizures (PNES). METHODS: In this retrospective study, we evaluated persons with documented PNES, who were older than 16 years of age at the onset, from four countries (i.e., Iran, Brazil, Venezuela, and Argentina) regarding their age, gender, PNES semiology, and possible predisposing factors. RESULTS: We included 389 patients (244 from Iran, 66 from Brazil, 51 from Venezuela, and 28 from Argentina). Age at diagnosis was 32 ±â€¯9 years (range: 17-64 years), and age at the onset of seizures was 27 ±â€¯8 years (range: 17-49 years). There was a female predominance in all countries. The demographic characteristics and factors associated with PNES were similar among the countries. However, there were significant semiological differences among the countries. CONCLUSION: This study corroborates the notion that PNES share more similarities than differences cross-culturally and across international borders. However, the background determined by cultural, ethnic, and religious differences may influence the semiology of PNES. Further cross-cultural studies involving more than two continents may advance our understanding of PNES.

Sex differences in demographic and clinical characteristics of psychogenic nonepileptic seizures: A retrospective multicenter international study.

PURPOSE: Sex-related differences have been reported in patients with neurological and psychiatric disorders. It is also plausible to assume that there might be differences between females and males with psychogenic nonepileptic seizures (PNES). METHODS: In this retrospective study, we investigated patients with PNES, who were admitted to the epilepsy monitoring units at centers in Iran, the USA, Canada, Brazil, Argentina, and Venezuela. Age, sex, age at seizure onset, seizure semiology, factors potentially predisposing to PNES, and video-electroencephalography recording of all patients were registered routinely. RESULTS: Four hundred and fifty-one patients had PNES-only and were eligible for inclusion; 305 patients (67.6%) were females. We executed a logistic regression analysis, evaluating significant variables in univariate analyses (i.e., age, age at onset, aura, presence of historical sexual or physical abuse, and family dysfunction). The only variables retaining significance were historical sexual abuse (p = 0.005) and presence of aura (p = 0.01); physical abuse was borderline significant (p = 0.05) (all three were more prevalent among females). CONCLUSION: Similarities between females and males outweigh the differences with regard to the demographic and clinical characteristics of PNES. However, notable differences are that females more often report lifetime adverse experiences (sexual and probably physical abuse) and auras. While social, psychological, and genetic factors may interact with lifetime adverse experiences in the inception of PNES, the link is not yet clear. This is an interesting avenue for future studies.

Genetic polymorphisms of the 5HT receptors are not related with depression in temporal lobe epilepsy caused by hippocampal sclerosis.

BACKGROUND: Temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS) is the most frequent form of drug-resistant epilepsy in adults. Mood disorders are the most frequent psychiatric comorbidities observed in these patients. Common pathophysiological mechanisms of epilepsy and psychiatric comorbidities include abnormalities in the serotonin pathway. The primary goal of this study was to determine the possible association between polymorphisms of genes encoding the serotonin receptors 5HT1A (rs6295), 5HT1B (rs6296), and 5HT2C (rs6318) and the presence of mood disorders in patients with TLE-HS. Our secondary goal was to evaluate the possible association between these variants and susceptibility to develop seizures in TLE-HS. METHODS: We assessed 119 patients with TLE-HS, with and without psychiatric comorbidities; 146 patients with major depressive disorder; and 113 healthy volunteers. Individuals were genotyped for the rs6295, rs6296, and rs6318 polymorphisms. RESULTS: No difference was observed between the group with TLE-HS, healthy controls, and the group with major depressive disorder without epilepsy regarding the polymorphisms that were evaluated. There was no correlation between rs6318, rs6295, rs6296, and epilepsy-related factors and history of psychiatric comorbidities. CONCLUSIONS: Our work suggests that the studied polymorphisms were not related to the presence of TLE, psychiatric comorbidities in TLE, and epilepsy-related factors.

Semiology of psychogenic nonepileptic seizures: An international cross-cultural study.

PURPOSE: We compared the semiology of psychogenic nonepileptic seizures (PNES) between patients from the USA and Brazil. This international cross-cultural comparative study may expand understanding of PNES across the borders. METHODS: We retrospectively investigated all patients with PNES admitted to one epilepsy center in the USA and one in Brazil. We classified their seizures into four classes: generalized motor, akinetic, focal motor, and subjective symptoms. All patients were interviewed by an epileptologist in both countries and were administered psychological assessment measures, including questions about PNES risk factors. For the statistical analyses, we compared patients from the two nations. RESULTS: Eighty-nine patients (49 from the USA and 40 from Brazil) were studied. Patients from the two countries were not significantly different with regard to sex and age, but patients from Brazil had earlier age at onset (26years vs. 34years; P=0.004) and a significantly greater delay in diagnosis (9.9years vs. 5.6years; P=0.001). Some characteristics of PNES were different between the two groups; patients from the USA had generally more seizure types and more often reported subjective seizures (55% in the USA vs. 10% in Brazil; P=0.0001). Clinical and historical characteristics of the patients were not significantly different. CONCLUSION: Delay in diagnosis of PNES may represent a major factor in resource-limited countries. Large multicenter cross-cultural studies may reveal subtle but significant cross-cultural differences with respect to the semiological, clinical, and historical aspects of PNES; however, patients with PNES share more similarities than differences.

The approach to patients with psychogenic nonepileptic seizures in epilepsy surgery centers regarding diagnosis, treatment, and education.

Previous studies, using surveys, provided an understanding about how health-care providers address patients with PNES. To date, there is limited information on the management of patients with PNES by tertiary referral centers for epilepsy. In this study, we surveyed 11 Brazilian epilepsy center directors about diagnosis, treatment, education and research on PNES. Respondents reported that patients with PNES represented 10-20% of all adult patients recorded by video-EEG (VEEG). All respondents recognized VEEG as the method to confirm the diagnosis, and 81.8% used this approach for confirmation. Most centers had a standard protocol for diagnosis. None of the centers had a particular protocol to treat PNES, but 90.9% had a uniform treatment approach including therapy and educational measures. Psychotherapy was not easily obtained in nine centers (81.8%). Seven (63.3%) centers reported ongoing research projects with PNES. Five centers referred to an educational PNES program discussing diagnosis, but only one reported an educational program for treatment. This study showed a commitment to PNES diagnosis; however, some gaps remain regarding treatment and training, namely implementing a psychotherapy approach for patients and providing educational curricula for clinicians.

Psychogenic non-epileptic seizures at a tertiary care center in Brazil.

Although psychogenic non-epileptic seizures (PNES) are a worldwide phenomenon, most of our knowledge addressing clinical characteristics is based on studies conducted in the USA, Europe, and Australia. There are scarce data about PNES in South American countries. This study provided a detailed analysis of the demographic, clinical, and psychosocial characteristics of 102 Brazilian patients with PNES. Seventy-eight patients (76.4%) were female with mean age of 35.27 years. Mean age at onset was 27.85 years; mean time to diagnosis was 7.89 years; 87.25% lived with their families; 56.89% were single; and only 33 (39.75%) worked on a regular basis. Depression was diagnosed in 48.03%. Thirty-three patients misdiagnosed as having epilepsy were using antiepileptic drugs. Stress factors were identified in 57.84%. This is the first Brazilian study that involves a large sample of patients with video-EEG-documented PNES and corroborates the idea that PNES are a worldwide phenomenon sharing several similarities, despite cultural and socioeconomic differences.

Semiology of psychogenic nonepileptic seizures: age-related differences.

The few studies addressing semiology of psychogenic nonepileptic seizures (PNES) in children showed that this group differs from adults, considering the classical signs described. Our study with systematic assessment provides a direct comparison of the classical signs of psychogenic nonepileptic seizures (PNESs) in children and adults in order to establish the usefulness of the most important signs described for adults in children. Video-EEG recordings of patients with PNESs from 2006 to 2011 were analyzed. Twenty-five signs were selected as the most prevalent in literature, and their presence was evaluated. Events were categorized as either of the following: catatonic, major motor, minor motor, and subjective (Griffith et al., 2007 [11]). One hundred and fifteen patients were included; 63.5% were adults, 73.2% were females, and 14.4% had epilepsy. Adults presented more ictal eye closure (p=0.006), convulsions lasting >2 min (p<0.001), postictal speech change (p=0.021), vocalization during the "tonic-clonic" phase (p=0.005), and pelvic thrust movement (p=0.035). Biting the tip or side of the tongue and opisthotonos were rare and only present in adults. As for the semiological categories, major motor activity was the main feature in adults, and minor motor activity was more prevalent among children (52.9% and 38.1%, respectively; p=0.01). Our data showed that research about the distinct ictal features of PNESs, such as minor motor events that are more typical in children, is likely to be useful in promoting earlier recognition of PNESs in this population.

Seizure control and anxiety: Which factor plays a major role in social adjustment in patients with Juvenile Myoclonic Epilepsy?

PURPOSE: This study aimed to determine the presence of anxiety disorder and severity of anxiety symptoms in an extensive series of consecutive patients with JME and its association with epilepsy-related factors. In addition, we evaluated the impact of anxiety and clinical variables on social adjustment. METHODS: We prospectively evaluated 112 (56.2 % females, mean age 27.2 years) patients with an electroclinical diagnosis of JME and 61 (52.4 % females, mean age 29.3 years) healthy controls. Anxiety symptoms were assessed by the State and Trait Anxiety Inventory (STAI). Social functioning was addressed with Self-Report Social Adjustment Scale (SAS). The patient group was also evaluated with a psychiatric interview. RESULTS: Patients with JME presented more severe anxiety symptoms and worse social adjustment compared with controls. The presence of anxiety disorder and the severity of anxiety symptoms was associated with frequent seizures - generalized tonic-clonic seizures (p = 0.008) and drug-resistant epilepsy (p = 0.021). Regarding social adjustment, the severity of anxiety symptoms was associated with lower economic adjustment (p = 0.039), while the presence of anxiety disorder impacted family relationships (p 0.025). The presence of hard-to-control myoclonic seizure was associated with lower scores on work (p = 0.019), leisure activities (p = 0.008), family relationship (p = 0.022) and overall social adjustment (p = 0.038). CONCLUSION: Patients with JME have severe anxiety symptoms and worse social adjustment. Anxiety disorder and symptoms were associated with frequent seizures and drug-resistant epilepsy. Epilepsy-related factors and anxiety impaired distinct aspects of social functioning.

Association between the Occurrence of Primary Hypothyroidism and the Exposure of the Population Near to Industrial Pollutants in São Paulo State, Brazil.

BACKGROUND: Environmental agents interfere with thyroid function at multiple levels. This study was to investigate the association between pollutant concentrations and the primary hypothyroidism (PH) occurrence odds in residents living in the Capuava Petrochemical Complex (CPC) influence area. METHODS: This area was evaluated with the combination of the AERMOD dispersion model with the Weather Research Forecast (WRF) meteorological model (2016). The concentration of atmospheric pollutants were analyzed in 2017 using meteorological data on the period from 2005 to 2009, correlating this data with the research done in 2003 to 2005. A home-based questionnaire was applied to evaluate 2004 residents, of both sexes, aged from 8 to 72 years, based on their proximity to the industrial areas; were select residents with PH. RESULTS: Volatile organic compounds (VOCs), carbon monoxide (CO), and nitrogen dioxide (NO2) concentrations presented the highest correlations between the PH odds and pollutant concentrations. CONCLUSION: Air pollution associated with the presence of the CPC is an important environmental factor contributing to the development of PH in the nearby population. As the first study showing this association in Brazil, research should be continued to better understand the mechanisms and to find ways to compensate for or remedy to avoid health impacts in future populations.

Higher transcription alleles of the MAOA-uVNTR polymorphism are associated with higher seizure frequency in temporal lobe epilepsy.

BACKGROUND: There is evidence of an imbalance in the neuromodulatory system mediated by serotonin (5-HT) in patients with drug-resistant temporal lobe epilepsy (TLE). This study analyzed the monoamine oxidase A promoter variable number of tandem repeats (MAOA-uVNTR) polymorphism in patients with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). Therefore, we assessed the association between this genetic variant and seizure predisposition and severity in patients with TLE-HS. METHODS: One hundred nineteen patients with TLE-HS and 113 healthy volunteers were assessed. First, we genotyped all individuals for the MAOA-uVNTR genetic polymorphism. Second, we compared patients and controls and evaluated clinical variants of epilepsy. RESULTS: There was no difference between the TLE-HS and control groups regarding genotypic and allelic distributions of MAOA-uVNTR polymorphism (p = 1.000). Higher transcription alleles of the MAOA-uVNTR were associated with higher seizure frequency (p = 0.032) and bilateral tonic-clonic seizures (p = 0.016). CONCLUSIONS: In a selected group of patients with TLE-HS, the polymorphism MAOA-uVNTR was associated with some aspects of epilepsy severity, namely seizure frequency and bilateral tonic-clonic seizures.

Pediatric-onset psychogenic nonepileptic seizures: A retrospective international multicenter study.

PURPOSE: We compared various clinical characteristics of pediatric-onset psychogenic nonepileptic seizures (PNES) between patients from five countries. The purpose of this study was to advance our understanding of pediatric-onset PNES cross-culturally. METHODS: In this retrospective study, we compared consecutive patients with PNES with an age at onset of 16 years and younger from epilepsy monitoring units in Iran, Brazil, the USA, Canada, and Venezuela. Age, gender, age at seizure onset, seizure semiology, predisposing factors, and video-EEG recordings of all patients were extracted. Pearson Chi-Square, one-way ANOVA and Bonferroni correction tests were used for statistical analyses. RESULTS: Two hundred twenty-nine patients were studied (83 from Iran, 50 from Brazil, 39 from Canada, 30 from the USA, and 27 from Venezuela). Mean age at the onset of seizures was 12.1 ±â€¯3.2 years (range: 4-16 years). The sex ratio of the patients was 1.83: 1 (148 females and 81 males). Clinical characteristics of pediatric-onset PNES showed some significant differences among the nations. However, factors associated with pediatric-onset PNES in these five nations were similar. CONCLUSION: This study underscores how international cross-cultural studies can make important contributions to our understanding of PNES. Patients with pediatric-onset PNES from different countries were similar on many risk factors associated with PNES. This suggests universality in many features of PNES. However, intriguing differences were also noted with regard to seizure semiology, which might be the result of cultural factors.

Validation of fecal elastase-1 determination using immunoenzymatic assay in HIV-infected patients.

Pancreatic elastase-1 is a proteolytic enzyme exclusively produced in the pancreas, is stable when passing through the bowel, and its determination is associated with chronic pancreatitis. The clinical diagnosis of pancreatitis is based on anamnesis, physical examination, radiological, sonographic, endoscopic, and laboratory findings. Nowadays, there is a test for the determination of fecal elastase-1, by enzymatic reaction (enzyme-linked immunosorbent assay, ELISA), which specifically determines human elastase-1, promoting the pancreatic function evaluation. Parameters such as linearity, calibration curve, sensitivity, specificity, precision, accuracy, recovery, and receiver operator characteristic (ROC) curve are used to evaluate the test. The aim of this study was the validation of the immunoenzymatic assay (ELISA) and the use of its results in patients with HIV, alcoholics, and under antiretroviral therapy. The study involved 157 patients, 95 of them were HIV-infected, and 62 were completely healthy. The elastase-1 ELISA kit from Bioserv was used, and we noted that the obtained results were linear, sensitive, precise, and accurate. Moreover, our results suggest that this test can be a laboratory evaluation to determine the relationship of pancreatitis with alcohol use, but not its association with antiretroviral use in HIV patients (P=0.424). This test is useful to diagnose pathologies related to pancreatic insufficiency.

BDNF Val66Met polymorphism is not related with temporal lobe epilepsy caused by hippocampal sclerosis in Brazilian population.

PURPOSE: Some variants of the brain derived neurotrophic factors (BDNF) gene, namely the Val66Met (rs6265), may contribute the risk for epilepsy development. We aimed to investigate if this polymorphism was associated with the risk for epilepsy development in TLE-HS and its correlation with epilepsy-related factors and the presence of psychiatric disorders. METHODS: We assessed 119 patients with unequivocal TLE-HS and 112 healthy controls. Individuals were genotyped for the polymorphisms of the gene encoding BDNF Val66Met. RESULTS: There was no difference between TLE-HS and healthy controls, for the genotypic distribution (p = 0.636) and allelic distribution (p = 0.471). There was no correlation between Val66Met and epilepsy-related factors and for psychiatric comorbidities (p = 0.888). CONCLUSIONS: Our findings demonstrated that polymorphism Val66Met is not associated with TLE-HS, epilepsy-related factors and psychiatric comorbidities in this selected group of patients.

Risk Factors for Diagnostic Delay in Psychogenic Nonepileptic Seizures Among Children and Adolescents.

BACKGROUND: This study aims to analyze a series of pediatric patients with psychogenic nonepileptic seizures (PNES) to establish the diagnostic gap and possible risk factors for the delayed diagnosis in this age group. METHODS: We evaluated all children with PNES documented by video electroencephalography. None had a previous diagnosis of PNES. In total, we included 53 children (interquartile range: seven to 17 years; mean age 12.81 years [S.D. 3.15]; 60.4% girls) who underwent a protocol consisting of neurological and psychiatric interviews. RESULTS: The average time between seizure onset and referral was 17.76 months (interquartile range: 0.5 to 48 months; S.D. ± 12.62). Earlier age of onset correlated with a later diagnosis (P < 0.001). The late referral group also presented with a history of psychological abuse (P = 0.018). CONCLUSION: Youth with PNES represent a diagnostic challenge. Identification of children at risk might lead to earlier diagnosis of PNES.

Psychogenic nonepileptic seizures: should we use response to AEDS as a red flag for the diagnosis?

PURPOSE: Lack of response to anti-epileptic drugs (AEDS) is considered a "red flag" pointing to a diagnosis of Psychogenic Nonepileptic Seizures (PNES). On the other hand, placebo effects are relevant in any medical condition with a complex psychosocial component. We aimed to evaluate the presence and frequency of a placebo response in patients with sole PNES and explore its impact on diagnostic delay. METHODS: We reviewed the medical records of 102 patients referred for video EEG monitoring and diagnosed with PNES. Patients with PNES and epilepsy were excluded. The response to AEDs was analyzed according to patients' reports and medical records. Patients were classified, according to the response to AEDs, in two groups: responders (patients achieving remission) and non-responders. Then, we compared the diagnostic delay from the first event to the final diagnosis between these groups. RESULTS: Forty-seven patients (79.7%) with sole PNES who were using AEDs were identified. Twenty-two patients (46.8%) had reported complete or partial remission of PNES with mean response duration of 7.2 months (SD+9.6 months). The time delay of the diagnosis in the AED responder group was 10.6 years; the delay in non-responders was 5.6 years (p=0.035). CONCLUSION: Patients with sole PNES receiving AEDs can go into PNES remission. A favorable response to AEDs is likely to be interpreted as supporting a diagnosis of epilepsy and is associated with diagnostic delay. Physicians should bear in mind that patients with PNES may be particularly vulnerable to placebo effects.