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.

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.

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.

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.

Everyday memory impairment in patients with temporal lobe epilepsy caused by hippocampal sclerosis.

OBJECTIVE: Patients with temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS) have episodic memory impairment. Memory has rarely been evaluated using an ecologic measure, even though performance on these tests is more related to patients' memory complaints. We aimed to measure everyday memory of patients with TLE-HS to age- and gender-matched controls. METHODS: We evaluated 31 patients with TLE-HS and 34 healthy controls, without epilepsy and psychiatric disorders, using the Rivermead Behavioral Memory Test (RBMT), Visual Reproduction (WMS-III) and Logical Memory (WMS-III). We evaluated the impact of clinical variables such as the age of onset, epilepsy duration, AED use, history of status epilepticus, and seizure frequency on everyday memory. Statistical analyses were performed using MANCOVA with years of education as a confounding factor. RESULTS: Patients showed worse performance than controls on traditional memory tests and in the overall score of RBMT. Patients had more difficulties to recall names, a hidden belonging, to deliver a message, object recognition, to remember a story full of details, a previously presented short route, and in time and space orientation. Clinical epilepsy variables were not associated with RBMT performance. Memory span and working memory were correlated with worse performance on RBMT. SIGNIFICANCE: Patients with TLE-HS demonstrated deficits in everyday memory functions. A standard neuropsychological battery, designed to assess episodic memory, would not evaluate these impairments. Impairment in recalling names, routes, stories, messages, and space/time disorientation can adversely impact social adaptation, and we must consider these ecologic measures with greater attention in the neuropsychological evaluation of patients with memory complaints.

Delineating behavioral and cognitive phenotypes in juvenile myoclonic epilepsy: Are we missing the forest for the trees?

INTRODUCTION: Patients with juvenile myoclonic epilepsy (JME) have executive dysfunction and impulsive traits. There are lines of evidence that JME is a heterogeneous epilepsy syndrome considering outcome. In this study, we aimed to analyze this heterogeneity beyond seizure control. The objective was to identify whether the pattern of cognitive dysfunction and impulse control is also heterogeneous, in an attempt to establish possible differences in patients with easy- and hard-to-control epilepsies. METHODS: Essentially, 57 patients with JME were compared with 44 controls. Patients and controls were assessed with a neuropsychological battery for executive, attention, and memory functions. The expression of impulsive traits was evaluated with the Temperament and Character Inventory - novelty seeking domain. Then, patients were categorized according to seizure control as having easy- and hard-to-control JME. RESULTS: Patients with hard-to-control JME showed worse performance in 12 out of 25 neuropsychological tests than those with easy-to-control JME. Patients with hard-to-control JME also demonstrated significantly higher scores in novelty seeking - subfactor impulsiveness (p=0.002). SIGNIFICANCE: Our study demonstrated the existence of distinct or more severe cognitive and psychiatric profiles in a subset of patients with JME. Patients with treatment-refractory seizures seem to present a broader impairment related to both cognitive deficits and impulsive traits. These findings suggest that patients with JME are not equally compromised by executive and memory deficits or dysfunction, neither by their impulsive traits. Thus, there is a need for a better characterization of patients with JME to include diverse phenotypes since our results suggest a possible existence of distinct groups of patients with JME.

Decision-making in patients with temporal lobe epilepsy: Delay gratification ability is not impaired in patients with hippocampal sclerosis.

BACKGROUND: Decision-making abilities have rarely been examined in patients with temporal lobe epilepsy related to hippocampal sclerosis (TLE-HS). We aimed to investigate the ability to delay gratification, a decision-making subdomain, in patients with intractable TLE-HS and to verify the association of delay gratification performance and cool executive function tests. METHODS: We evaluated 27 patients with TLE-HS (mean age: 35.46 [±13.31] years; 7 males) and their cognitive performance was compared with that of 27 age- and gender-matched healthy controls (mean age: 35.33 [±12.05] years; 7 males), without epilepsy and psychiatric disorders. Patients were assessed using the delay discounting task (DDT) and tests of attention, shifting, inhibitory control, and concept formation. Results were correlated with clinical epilepsy variables such as age of onset, epilepsy duration, AED use, history of status epilepticus, febrile seizures, and the presence of generalized seizures. Statistical analysis was performed using one-way ANCOVA with years of education as a confounding factor. RESULTS: Patients and controls demonstrated similar performance on DDT, showing similar discount rate (p=0.935) and probability rate (p=0.585). Delay gratification was not related to cool executive function tests (Digit Span, Stroop Color Test, Trail Making Test, Wisconsin Card Sorting Test, and Connors' CPT). History of status epilepticus, presence of generalized seizures and higher seizure frequency, age at onset, and epilepsy duration had a significant impact on DDT. CONCLUSION: Patients with intractable TLE-HS showed unimpaired delay gratification abilities, being able to accept a higher delay and a lower amount of chance for receiving a higher reward in the future. Clinical variables related to the epilepsy severity impacted the performance on delay gratification. Impairment on cool aspects of executive function was unrelated to this decision-making domain.

Distinct domains of impulsivity are impaired in juvenile myoclonic epilepsy but not in temporal lobe epilepsy.

OBJECTIVE: The Barratt Impulsiveness Scale (BIS-11) is the most widely used questionnaire to study impulsivity in persons with psychiatric disorders, but it has rarely been applied to persons with epilepsy. The present study aimed to evaluate the usefulness of BIS-11 as a tool to explore impulsivity in two distinct epilepsy syndromes. METHOD: The BIS-11 was applied to 20 patients with juvenile myoclonic epilepsy (JME) (32.5±8.95years old), 20 patients with temporal lobe epilepsy (TLE) (37.7±13.25years old), and 26 healthy controls (31.86±11.25years old). The scores in motor, attentional, and lack of planning impulsivity were compared between groups. RESULTS: Patients with JME showed higher scores than patients with TLE and controls in all domains: motor (JME vs TLE: 28.60 vs 13.25 (mean score), p<0.001 and JME vs controls: 28.60 vs 14.12, p<0.001), attentional (JME vs TLE: 21.55 vs 13.45, p<0.001 and JME vs controls: 21.55 vs 14.88, p<0.001) and nonplanning (JME vs TLE: 28.05 vs 13.10, p<0.001 and JME vs controls: 28.05 vs 16.15, p<0.001). CONCLUSION: Higher BIS-11 scores in all domains of impulsivity [i.e., motor, attentional, and lack of planning] corroborated previous findings described in patients with JME. On the other hand, BIS-11 could not demonstrate problem solving and inhibitory control deficits related to impulsive behavior, which were described in patients with TLE. Other behavioral measures may be more sensitive to some aspects of impulsivity in TLE. Our results reinforce the concept that distinct epileptic syndromes require different neuropsychological approaches, especially considering a complex construct such as impulsivity.

The long odyssey for the DEE-CDKL5 diagnosis: A call for action.

OBJECTIVES: This study aims to determine the current state of CDD diagnosis and epilepsy treatment in an upper-middle-income country. METHODS: Forty-seven families of the Brazilian CDD Association were invited to participate in an online survey to gather information about the diagnosis and treatment of epilepsy. RESULTS: Forty-three families (91.5%) of unrelated patients with confirmed genetic diagnosis of CDD participated. The median age was 7 years (ranging from 1.3-25 years) and the male: female ratio was 1:6. Early and severe epilepsy started during infancy in 74.4%. Seizures occurred daily in 61.9% and 83.7% had clusters of seizures. The mean age of diagnosis was 3.3 years (ranging from 37 days to 16 years), and younger patients had an earlier diagnosis (p < 0.001). Patients were seen by an average of 4.4 physicians (1-15) before the diagnosis. The most relevant obstacles to genetic testing were cost (55.8%) and late requests by physicians (27.9%). At the moment of the assessment, patients received a mean of 3.6 ASMs/day (ranging from 1 to 5). Thirty-four (79.1%) caregivers reported side effects throughout life, including life-threatening events in 16.3%. SIGNIFICANCE: Based on our findings, a sense of urgency for genetic assessment implementation is evident since the delay in the diagnosis with unnecessary use of resources and excessive polytherapy with serious side effects cause a higher burden to the healthcare system, caregivers, and patients. PLAIN LANGUAGE SUMMARY: In this study, we assessed the diagnosis and treatment of patients with genetically confirmed DEE-CDKL5 from the Brazilian Association of CDD with an online survey. Caregivers reported a long delay in the diagnosis associated with cost and late referral to genetic testing, considered the last resource for one-third of the patients. Patients received a high number of ASM, mainly under polytherapy, with serious side effects. Although it is promising that younger patients received earlier diagnosis, public policies for genetic testing are needed to improve CDD patients' care.

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.

Anxiety symptoms are the strongest predictor of quality of life in temporal lobe epilepsy.

PURPOSE: It is established that the severity of depressive and anxiety symptoms is associated with poorer quality of life (QOL) in persons with drug-resistant epilepsy. We aimed to verify the presence of subsyndromic depressive episodes (SDEs) and subsyndromic anxiety episodes (SAEs) in persons with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) compared to healthy controls and to determine the impact of depressive and anxiety symptoms on patients' QOL. METHODS: We prospectively evaluated 35 persons with TLE-HS and 90 healthy controls. QOL was assessed by the Epilepsy Surgery Inventory (ESI) and QOL in Epilepsy Inventory-31 (QOLIE-31). The Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI-X) were used to assess symptoms, and SDEs and SAEs diagnosis were made considering the total scores of BDI (<9) and STAI-Trait (<49), respectively. RESULTS: Persons with TLE-HS had higher symptoms on BDI, STAI-S, and STAI-T. They have 3.011 greater odds of presenting SDEs and 7.056 times odds, SAEs. The depressive and anxiety symptoms, added in the model with epilepsy-related factors, accounted for a significant increase in the variance in several aspects of QOL. Anxiety-trait symptoms are the most critical individual determinant of the QOL. CONCLUSION: Our results demonstrated that persons with TLE-HS had greater odds of presenting SDE and SAE than healthy controls. Besides, there was a relationship between anxiety and depressive symptoms and worse QOL in TLE-HS. It is essential to be aware of psychiatric symptoms, even though these symptoms do not meet the criteria to be considered a "disorder."

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.

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.

Sexuality in teenagers with epilepsy.

OBJECTIVES: In adults with epilepsy it is well known that the epileptic syndrome, seizure frequency and antiepileptic drug use may influence sexual function and behavior. However, knowledge acquired with adult populations has been extrapolated to teenagers, based on the supposition that these patients are influenced by similar factors. This study aimed to evaluate aspects related to sexuality obtained from female adolescents with epilepsy. METHODS: We carried out a prospective study of 35 female adolescents, with epilepsy, with ages from 10 to 20 years, and epileptic syndromes diagnosed according to ILAE criteria (1989). Information on sexual function and behavior of adolescents with epilepsy was evaluated by use of a standard questionnaire. Exclusion criteria were lack of menarche, previous endocrine or chronic clinical disorders, and moderate to severe mental retardation. RESULTS: No differences were observed between the age at first sexual intercourse, sexual activity, libido and orgasm of adolescents with epilepsy when compared to controls. Epilepsy clinical variables such as age of onset, duration and severity had no significant relationship with distinct aspects of sexual function and behavior. CONCLUSION: Adolescents with epilepsy represent a special patient group because, even with their chronic disorder, they have an active sexual life, despite the severity of their disorder. Therefore, aspects related to sexuality require special attention by health professionals when attending to adolescents with epilepsy.

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.

Severe epilepsy and pachygyria associated with peculiar facial traits characterize Fryns-Aftimos syndrome.

We describe an 18-year-old boy with a frontofacial syndrome. The presence of severe epilepsy led to a neuroimaging investigation, which revealed a diffuse pachygyric (normal thickness and simplified folding) cortex that was bilateral and affected all supratentorial regions, sparing the medial and inferior aspects of the frontal lobe plus the posterior occipital region. In addition, an unusual skull base presentation with small posterior fossa, narrowed foramen magnum, and low torcular and tentorial insertions was documented. Dysmorphic ventricles and enlarged cavi of the septi pellucidum, vergae, and velum interpositum were also noted. This case shares many similarities with two patients formerly described by Fryns and Aftimos, who were previously classified as having mental retardation and multiple congenital anomalies syndrome. The existence of a new case corroborates the idea of a distinct condition with particular characteristic dysmorphic facial features and the presence of a specific malformation of cortical development associated with severe epilepsy. We believe that epilepsy and pachygyria play a central role in distinguishing this syndrome from others classified as frontofacial or cerebrofrontofacial syndromes, and we propose the term "Fryns-Aftimos syndrome" to name it.

Hippocampal serotonin depletion is related to the presence of generalized tonic-clonic seizures, but not to psychiatric disorders in patients with temporal lobe epilepsy.

OBJECTIVE: Previous studies suggest that concentration of serotonin ([5-HT]) plays a pathogenic role in various types of epilepsy inhibiting seizures. However, most have not considered the clinical variables of epilepsy, and all of these studies included small and heterogeneous samples with refractory epilepsy, regardless of etiology. In this work, we measured [5-HT]s in hippocampal tissues from a large series of patients with refractory temporal lobe epilepsy caused by hippocampal sclerosis who underwent epilepsy surgery and evaluated the relationship between [5HT] and epilepsy-related clinical variables and psychiatric disorders. METHODS: We included 44 patients with refractory unilateral TLE-HS who underwent surgical treatment for epilepsy. Hippocampal samples were collected, and serotonin concentrations were measured with high-pressure liquid chromatography (HPLC). RESULTS: Lower [5-HT]s were correlated with a history of GTC seizures (Student's t-test: p 0.041). There were no differences in [5-HT]s according to the other clinical variables and the presence of psychiatric disorders. SIGNIFICANCE: Our findings demonstrated that serotonin depletion in the hippocampus play an important role in some aspects of the severity of epilepsy (i.e., the presence of GTC seizures) in a homogeneous sample of patients with refractory temporal lobe epilepsy determined by hippocampal sclerosis, but not with the presence of psychiatric disorders.

Polymicrogyria in glycogenosis type III: an incidental finding?

The purpose of the present report is to document a 20-year-old woman with glycogenosis type III who presented a malformation of cortical development, in this case a polymicrogyria over bilateral perisylvian regions. Association of a malformation of cortical development in this type of glycogenosis has not been previously reported. The existence of previous cases of glycogenosis associated with malformations of cortical development led us to believe that glycogen storage during pregnancy may act as a harmful prenatal event. On the other hand, the presence of a lesion associated with severe neurologic deficits in one patient with a milder form of glycogenosis is in disagreement with the idea that there is a strong correlation between the severity of the central nervous system lesion and that of the disease.

Correlation between platelet and brain PLA(2) activity.

The phospholipase A2 (PLA2) enzymes have been implicated in several neuropsychiatry disorders and activity alterations have been described in brain and platelet. Since brain tissue is not readily available for the measurement of PLA2 activity, it would be of interest to test directly whether PLA2 activities in both tissues are correlated. We performed this task assessing PLA2 activity in platelets and hippocampus collected simultaneously from 19 patients undergoing temporal lobectomy for treatment of refractory epilepsy. Our findings suggest that total PLA2 activity in platelets may reflect the total activity of the enzyme in the brain (rs=0.59, p=0.008). However in our sample no correlations were found between the subgroups of the enzyme in brain and in platelets. This lack of correlations may be due to different effects of drug treatment on the PLA2 subtypes. In face of the difficulty to obtain brain tissues from living patients, further studies with larger drug-free samples are warranted to clarify whether the use of platelets is a reliable strategy to reflect the subtypes of PLA2 activity in the brain.