Different relationships between epilepsy syndromes and autoimmune diseases.

OBJECTIVE: Our objective was to study the relationship between epilepsy and autoimmune diseases in two different types of epilepsy: idiopathic generalized epilepsies (IGEs) and mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). The contribution of the human leukocyte antigen (HLA) system to this relationship was analyzed. METHODS: Adult patients with IGEs and MTLE-HS at a tertiary epilepsy center were consecutively enrolled between January 2016 and December 2020. RESULTS: A total of 664 patients, 422 with IGEs and 242 with MTLE-HS, were included. Patients with IGEs were 15 years younger, on average, than patients with MTLE-HS (p < .001). The frequency of autoimmune diseases was 5.5% (n = 23) and 4.5% (n = 11) in patients with IGEs and MTLE-HS, respectively (p = .716). The mean age of autoimmune disease onset was 20 ± 15.6 years in patients with IGEs and 36.7 ± 16.5 years in patients with MTLE-HS (p < .05). Clinical manifestations of autoimmune diseases preceded epilepsy onset in 30.4% of patients with IGEs (i.e., in early childhood); in the other patients, epilepsy appeared before autoimmune disease onset. In all but one patient with MTLE-HS and autoimmune diseases, the autoimmune diseases appeared after epilepsy onset from adolescence onward. SIGNIFICANCE: Our study indicates two relationship patterns: a bidirectional association between IGEs and autoimmune diseases and a unidirectional relationship between MTLE-HS and autoimmune diseases. The involvement of genetic susceptibility factors (such as the HLA system), autoinflammatory mechanisms, female sex, and antiseizure medications in these relationships are discussed.

Mesial Temporal Lobe Epilepsy (MTLE) Drug-Refractoriness Is Associated With P2X7 Receptors Overexpression in the Human Hippocampus and Temporal Neocortex and May Be Predicted by Low Circulating Levels of miR-22.

Objective: ATP-gated ionotropic P2X7 receptors (P2X7R) actively participate in epilepsy and other neurological disorders. Neocortical nerve terminals of patients with Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (MTLE-HS) express higher P2X7R amounts. Overexpression of P2X7R bolsters ATP signals during seizures resulting in glial cell activation, cytokines production, and GABAergic rundown with unrestrained glutamatergic excitation. In a mouse model of status epilepticus, increased expression of P2X7R has been associated with the down-modulation of the non-coding micro RNA, miR-22. MiR levels are stable in biological fluids and normally reflect remote tissue production making them ideal disease biomarkers. Here, we compared P2X7R and miR-22 expression in epileptic brains and in the serum of patients with MTLE-HS, respectively. Methods: Quantitative RT-PCR was used to evaluate the expression of P2X7R in the hippocampus and anterior temporal lobe of 23 patients with MTLE-HS and 10 cadaveric controls. Confocal microscopy and Western blot analysis were performed to assess P2X7R protein amounts. MiR-22 expression was evaluated in cell-free sera of 40 MTLE-HS patients and 48 healthy controls. Results: Nerve terminals of the hippocampus and neocortical temporal lobe of MTLE-HS patients overexpress (p < 0.05) an 85 kDa P2X7R protein whereas the normally occurring 67 kDa receptor protein dominates in the brain of the cadaveric controls. Contrariwise, miR-22 serum levels are diminished (p < 0.001) in MTLE-HS patients compared to age-matched control blood donors, a situation that is more evident in patients requiring multiple (>3) anti-epileptic drug (AED) regimens. Conclusion: Data show that there is an inverse relationship between miR-22 serum levels and P2X7R expression in the hippocampus and neocortex of MTLE-HS patients, which implies that measuring serum miR-22 may be a clinical surrogate of P2X7R brain expression in the MTLE-HS. Moreover, the high area under the ROC curve (0.777; 95% CI 0.629-0.925; p = 0.001) suggests that low miR-22 serum levels may be a sensitive predictor of poor response to AEDs among MTLE-HS patients. Results also anticipate that targeting the miR-22/P2X7R axis may be a good strategy to develop newer AEDs.

Auditory verbal learning test can lateralize hippocampal sclerosis.

The ability of the Auditory Verbal Learning Test (AVLT) to lateralize hippocampal sclerosis (HS) in mesial temporal lobe epilepsy (MTLE) was explored in a sample of 50 patients with MTLE-HS (23 right and 27 left). Patients' AVLT scores were adjusted to the demographic characteristics of each individual in accordance with the Portuguese normative data. The laterality of the HS was determined by consensus by two neuroradiologists. ROC curves were used to identify the best AVLT cutoff scores to differentiate right vs. left HS. Diagnostic statistics were applied to different AVLT measures. The study results revealed that four AVLT scores can correctly classify the laterality of HS in the total sample and a sub-group of 39 right-handed patients (Edinburgh Laterality Inventory +100): delayed recall trial (76 and 80%, respectively), delayed recognition trial (64 and 67%, respectively), learning over trials index (64 and 74%, respectively), and long-term percent retention index (68 and 72%, respectively). In right-handed patients, the diagnostic capability of the delayed recall trial was improved by pairing it with the learning over trials index (accuracy of 85%). In sum, AVLT measures of verbal memory differentiate left from right HS in MTLE. The delayed recall trial demonstrated good diagnostic capacity.

Long term outcome of functional hemispherectomy for refractory epilepsy: Experience from a single center.

BACKGROUND: Hemispherectomy has an established role as a treatment of last resort in patients with unilateral hemispheric lesions suffering from refractory epilepsy. METHODS: Seven patients were evaluated at our Epilepsy Unit. We compared the seizure outcome at 6 months, 1, 2, 5 years post-surgery, as well as at end follow-up (mean 7.1 years) using Engel classification. Reduction of antiepileptic drugs (AEDs) was also assessed utilizing equal time frames. RESULTS: The mean age of seizure onset was 5.4 years. Engel I was achieved in 5 patients at 6 months (71.4%). Engel at 1 year was predicted by the Engel at 6 months (p=0.013) with a similar number of patients being classified as Engel I outcome. Engel at 2 years was also predicted by Engel at 6 months and at 1 year (p=0.030). At end follow-up only 3 patients (42.9%) remained categorized as Engel I outcome. There was a trend toward a stability in Engel classification. All patients with developmental causes for their epilepsy experienced some deterioration of the surgical outcomes. Conversely, all patients with acquired causes were stable throughout follow-up. Seizure outcome at 6 months was worse in the patients who had post-op complications (p=0.044). Adult and pediatric populations did not differ significantly in any tested variable. CONCLUSIONS: Hemispherectomy is a valuable resource for seizure control in properly selected patients. Engel patient's evolution could be predicted at 6 months interval. Hemispherectomy could be considered a useful attitude in difficult cases.

Female preponderance in genetic generalized epilepsies.

INTRODUCTION: Epilepsy is more prevalent in men but Genetic Generalized Epilepsies (GGE) seem to be more common in women. A predominant maternal inheritance has been previously described in GGE. Our objective was to determine sex and inheritance patterns in a GGE population compared to mesial temporal lobe epilepsy with hippocampal sclerosis (MTLEHS). METHODS: We performed a prospective observational study including adult GGE and MTLEHS patients followed up at a tertiary epilepsy center from January 2016 to December 2019. Patients' familial history was obtained by a detailed questionnaire. Clinical and demographic data was retrieved from clinical notes. RESULTS: A cohort of 641 patients, 403 with GGE and 238 with MTLEHS, was analyzed. GGE was more common in women than MTLEHS (58.8% vs 44.5%, OR=1.63, p = 0.004). Compared to MTLEHS patients, more GGE patients had familial history of epilepsy (45.4% vs 25.2%; p<0.001). The GGE group had a higher percentage of female relatives with epilepsy (55% vs 37%; p = 0.006). The prevalence of maternal inheritance was not different between GGE and MTLEHS groups (62.9% vs 57.7%; p = 0.596). Photosensitivity was more common in females than in males (44.7% vs 34.3%, p = 0.036). CONCLUSION: There is a female preponderance in GGE when compared to MTLEHS, as both GGE patients and their affected relatives are more frequently women. The prevalence of maternal inheritance was not higher in GGE than in MTLEHS.

Long term outcome of functional hemispherectomy for refractory epilepsy: Experience from a single center.

BACKGROUND: Hemispherectomy has an established role as a treatment of last resort in patients with unilateral hemispheric lesions suffering from refractory epilepsy. METHODS: Seven patients were evaluated at our Epilepsy Unit. We compared the seizure outcome at 6 months, 1, 2, 5 years post-surgery, as well as at end follow-up (mean 7.1 years) using Engel classification. Reduction of antiepileptic drugs (AEDs) was also assessed utilizing equal time frames. RESULTS: The mean age of seizure onset was 5.4 years. Engel I was achieved in 5 patients at 6 months (71.4%). Engel at 1 year was predicted by the Engel at 6 months (p=0.013) with a similar number of patients being classified as Engel I outcome. Engel at 2 years was also predicted by Engel at 6 months and at 1 year (p=0.030). At end follow-up only 3 patients (42.9%) remained categorized as Engel I outcome. There was a trend toward a stability in Engel classification. All patients with developmental causes for their epilepsy experienced some deterioration of the surgical outcomes. Conversely, all patients with acquired causes were stable throughout follow-up. Seizure outcome at 6 months was worse in the patients who had post-op complications (p=0.044). Adult and pediatric populations did not differ significantly in any tested variable. CONCLUSIONS: Hemispherectomy is a valuable resource for seizure control in properly selected patients. Engel patient's evolution could be predicted at 6 months interval. Hemispherectomy could be considered a useful attitude in difficult cases.

Immunogenetic protective factors in Genetic Generalized Epilepsy.

BACKGROUND: Genetic Generalized Epilepsies (GGEs) are a heterogeneous group of syndromes characterized by generalized seizure activity that affects both hemispheres, with mainly genetic causes. Neuroinflammation has been established as an important mechanism in epileptogenesis. The ability to develop an appropriated immune response is strongly determined by immunogenetic factors. In this setting, our aim was to evaluate potential associations between GGEs and immunogenetic factors. METHODS: The rs16944 (IL-1ß -511 T > C) polymorphism and the HLA-DRB1 locus were genotyped in a Portuguese GGE population. Association with two clinicopathological features, photosensitivity and refractoriness, was investigated. This case-control study included 323 GGE patients (187 F, 136 M, 34.0 ± 13.9 years of age), 145 of which with JME diagnosis (88 F, 57 M, 34.1 ± 14.0 years), and 282 healthy controls (174 F, 108 M, 37.7 ± 11.6 years). RESULTS: Decreased frequencies of the HLA-DRB1*09 and DRB1*13 alleles were observed in the GGE population. HLA-DRB1*07 frequency was increased in JME. Rs16944 allelic frequencies were similar between patients and controls. CONCLUSIONS: These results, not entirely consistent with previous reports, suggest that HLA molecules may have a complex role in epileptogenesis.

Social impairment and stigma in genetic generalized epilepsies.

INTRODUCTION: Patients with epilepsy have poor social outcome. Multifactorial factors are usually involved, but among them, stigma features may have an important role. Genetic generalized epilepsies (GGEs) were previously considered "benign" syndromes. The aim of our study was to assess social impairment and stigma in GGE and to evaluate differences between the following GGE subsyndromes: juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE), and generalized tonic-clonic seizures alone (GTCSA). Additionally, we compared these outcomes with outcomes from a cohort of patients with epilepsy with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), a severe and difficult-to-treat syndrome. Results were compared with social data from the general population. METHODS: Adult patients with epilepsy with a previously classified GGE or MTLE-HS were consecutively invited to fill in a sociodemographic and stigma questionnaire in outpatient clinic. Clinical data and psychiatric comorbidities were retrieved from clinical notes. RESULTS: Questionnaires from 333 patients were obtained: 226/67% from patients with GGE (JME: 106/31.8%, GTCSA: 74/22.2%, and JAE: 46/13.8%) and 107/32.1% from patients with MTLE-HS. We found that patients with GGE have a good academic achievement but they have increased difficulties in finding a partner, higher rates of divorce, and a reduced number of children per woman and per man when compared with general population. We also observed that patients with GGE have higher rates of unemployment (22.6%) and lower monthly income than general population. Severe problems in housing were only seen in GGEs. Of these, 3 patients (1.3%) were in homeless condition. Over half (52%) of patients with MTLE-HS and over a quarter (28%) of patients with GGE experienced felt stigma. Psychiatric comorbidity was highly prevalent among GGE (34.1%), especially in patients with refractory epilepsy. Mood and anxiety disorders were the most prevalent conditions. No other significant differences were found between GGE subsyndromes. DISCUSSION: We found an impairment in every social domain assessed (except in level of education) when compared with general population. Most of the social outcome parameters were unexpectedly close or similar to MTLE-HS or even worse as it was the prevalence of homelessness among GGE. Social impairment is underdiagnosed and might be considered in clinical practice even in syndromes for some time considered benign such as GGE.

Apolipoprotein E isoforms and susceptibility to genetic generalized epilepsies.

Background: Apolipoprotein E (ApoE) is the main lipoprotein secreted in brain. It has a critical immunomodulatory function, influences neurotransmission and it is involved in repairing damaged neurons. ApoE e4 is an isoform of ApoE with altered function, and was previously associated with early onset epilepsy and refractoriness, both in animal models and in patients with focal epilepsies. There is a limited knowledge on ApoE's role in Genetic Generalized Epilepsies (GGE).Aim: To determine if ApoE isoforms are risk factors for GGE development.Methods: A group of 337 GGE patients (193 F, 144 M, 33.6 ± 14.2 years) was compared with a group of 342 healthy individuals in a case-control genetic association study. ApoE genotyping was performed using PCR-RFLP.Results: The genotypic frequency of ApoE e3/e2 was lower in GGE patients relative to controls (6.5% in GGE vs. 11.7% in controls, p = 0.019, OR (95% CI) = 0.53 (0.305-0.905). No associations with other clinical data such as photosensitivity or age at disease onset were observed.Conclusion: Our results show that ApoE e3/e2 genotype may be a protective factor for GGE development. There is evidence that this genotype could be neuroprotective, preventing oxidative damage and promoting neuronal survival. Although replication studies are warranted, our data suggest that ApoE isoforms have a role in epileptogenic mechanisms regardless of the specific epileptic manifestations.

Immunogenetic predisposing factors for mesial temporal lobe epilepsy with hippocampal sclerosis.

PURPOSE: Neuroinflammation appears as an important epileptogenic mechanism. Experimental and clinical studies have demonstrated an upregulation of pro-inflammatory cytokines such as IL-1ß and TNF-α, in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Expression of these cytokines can be modulated by polymorphisms such as rs16944 and rs1800629, respectively, both of which have been associated with febrile seizures (FS) and MTLE-HS development. The human leukocyte antigen (HLA) system has also been implicated in diverse epileptic entities, suggesting a variable role of this system in epilepsy. Our aim was to analyse the association between immunogenetic factors and MTLE-HS development. For that rs16944 (-511 T>C, IL-1ß), rs1800629 (-308 G>A, TNF-α) polymorphisms and HLA-DRB1 locus were genotyped in a Portuguese Population. METHODS: We studied 196 MTLE-HS patients (108 females, 88 males, 44.7 ± 12.0 years, age of onset = 13.6 ± 10.3 years, 104 with FS antecedents) and 282 healthy controls in a case-control study. RESULTS: The frequency of rs16944 TT genotype was higher in MTLE-HS patients compared to controls (14.9% in MTLE-HS vs. 7.7% in controls, p = 0.021, OR [95% CI] = 2.20 [1.13-4.30]). This association was independent of FS antecedents. No association was observed between rs1800629 genotypes or HLA-DRB1 alleles and MTLE-HS susceptibility. Also, no correlation was observed between the studied polymorphisms and disease age of onset. CONCLUSION: The rs16944 TT genotype is associated with MTLE-HS development what may be explained by the higher IL-1ß levels produced by this genotype. High IL-1ß levels may have neurotoxic effects or imbalance neurotransmission leading to seizures.

Brain expression of inflammatory mediators in Mesial Temporal Lobe Epilepsy patients.

Neuroinflammation may be central in epileptogenesis. In this study we analysed inflammatory reaction markers in brain tissue of Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (MTLE-HS) patients. TLR4, IL-1ß and IL-10 gene expression as well as the presence of activated HLA-DR+ microglia was evaluated in 23 patients and 10 cadaveric controls. Inflammation characterized by the presence of HLA-DR+ microglia and TLR4, IL-1ß overexpression was evident in hippocampus and anterior temporal cortex of MTLE-HS patients. Anti-inflammatory IL-10 was also overexpressed in MTLE-HS patients. Our results show that hippocampal neuroinflammation extends beyond lesional limits, as far as the anterior temporal cortex.

Age of onset of mesial temporal lobe epilepsy with hippocampal sclerosis: the effect of apolipoprotein E and febrile seizures.

PURPOSE: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is the most frequent pharmaco-resistant epilepsy. It has been associated with febrile seizures (FS) in childhood. Its aetiology remains unclear but genetic factors are involved. Apolipoprotein E (ApoE) is the main lipoprotein secreted in brain. It has a critical immunomodulatory function, influences neurotransmission and it is involved in repairing damaged neurons. ApoE ϵ4 is an isoform of ApoE with altered protein function, previously associated with refractoriness and early onset epilepsy. This study was undertaken to determine if ApoE isoforms are risk factors for MTLE-HS and influence clinical characteristics. METHODS: A group of 188 MTLE-HS patients (101 F, 87 M, mean age = 44.7 ± 11.6 years, 100 with FS antecedents) was studied and compared with a group of 342 healthy individuals in a case-control genetic association study. Data were analysed with Pearson Chi-squared Test or Student's t test, as appropriated. RESULTS: No differences in ApoE ϵ4 allelic frequencies between MTLE-HS patients and controls or between MTLE-HS subgroups were observed. Nevertheless, ApoE ϵ4 carriers had an earlier MTLE-HS onset (11.0 ± 7.9 years in ApoE ϵ4 carriers vs. 14.4 ± 11.2 years in ApoE ϵ4 non-carriers p < 0.05). Additionally, we observed that MTLE-HS patients with FS antecedents had a statistically significant early disease onset (11.5 ± 8.7 years in FS+ vs. 16.0 ± 12.1 years in FS-, p < 0.01). CONCLUSIONS: Our data show that ApoE ϵ4 and FS may not participate directly in etiopathogenic mechanisms of MTLE-HS but could hasten the disease development in predisposed individuals.

Obstructive sleep apnoea syndrome and HLA in the North of Portugal.

INTRODUCTION: The obstructive sleep apnoea syndrome (OSAS) is a common, complex and polygenic disease with diverse aetiologies interacting to produce a single phenotype. OSAS occurs throughout the entire lifespan and familial aggregation has been suggested. Several predisposing factors, as age, gender and obesity have been described. Associations between HLA polymorphisms and sleep disorders are confirmed, in European and Non-European descendent populations. However the associations found between HLA alleles and OSAS have not been consistent and have no informative value for sleep disorder classification. AIMS: To explore the genetic association of HLA with OSAS in a northern Portuguese population and to evaluate the role of obesity in the context of HLA in OSAS. PATIENTS AND METHODS: A cohort of 131 patients with OSAS was studied. Patients followed up in an Outpatient Sleep Clinic were assessed by clinical history, night sleep polygraphic recording, multiple sleep latency test (when necessary for differential diagnosis), laboratorial and demographic studies. A control population (CP) of 223 healthy individuals was used for comparison. HLA-DRB1 genotyping was performed using a polymerase chain reaction with sequence specific primers methodology. RESULTS: In this cohort, the HLA-DRB1*03 allele was identified as a susceptibility factor for OSAS (24% OSAS vs. 15% CP; p = 0.025; odds ratio = 1.861; 95% CI = 1.081-3.205). No significant differences were found for other HLA-DBR1* alleles. CONCLUSION: HLA-DRB1*03 is a susceptibility factor for OSAS in Portuguese population.

TITLE: Sindrome de apnea obstructiva del sueño y HLA en el norte de Portugal.Introduccion. El sindrome de apnea obstructiva del sueño (SAOS) es una enfermedad frecuente, compleja y poligenica, con diversas etiologias que interaccionan originando un fenotipo unico. El SAOS puede ocurrir a cualquier edad del individuo y se presume la existencia de agregacion familiar. Han sido descritos diversos factores de predisposicion, como la edad, el sexo y la obesidad. La relacion entre los polimorfismos del antigeno leucocitario humano (HLA) y trastornos del sueño esta confirmada, tanto en poblaciones europeas como no europeas. No obstante, las relaciones descritas entre los alelos HLA y SAOS no han sido coherentes y carecen de valor informativo para la clasificacion del trastorno del sueño. Objetivo. Explorar la asociacion genetica del HLA con el SAOS en una poblacion del norte de Portugal y evaluar el papel de la obesidad en el contexto del HLA en el SAOS. Pacientes y metodos. Se estudio una cohorte de 131 pacientes con SAOS. Los pacientes fueron atendidos en una clinica del sueño ambulatoria donde se valoraron los antecedentes clinicos, se les practico una polisomnografia nocturna, una prueba de latencia multiple del sueño (si lo exigio el diagnostico diferencial), analiticas y estudios demograficos. A efectos comparativos, se utilizo una poblacion de control de 223 personas sanas. Se efectuo el genotipado del HLA-DRB1 con la reaccion en cadena de la polimerasa mediante cebadores de secuencia especifica. Resultados. En esta cohorte, el alelo HLA-DRB1*03 fue identificado como un factor de predisposicion para el SAOS (24% del SAOS frente a 15% de la poblacion de control; p = 0,025; odds ratio = 1,861; intervalo de confianza al 95% = 1,081-3,205). No hubo diferencias significativas en lo referente a otros alelos HLA-DBR1*. Conclusion. El HLA-DRB1*03 es un factor de predisposicion para el SAOS en la poblacion portuguesa.

Two-year follow-up with eslicarbazepine acetate: a consecutive, retrospective, observational study.

PURPOSE: Eslicarbazepine acetate (ESL) is a new generation voltage-gated sodium channel blocker. It has completed one phase II clinical trial and three phase III clinical trials, two of which with 1-year open label extensions. ESL was approved in 2009 by the European Medicines Agency as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization. It is marketed in Portugal since April 1st 2010. Despite good safety and efficacy shown in clinical trials, little is known about its effectiveness in a clinical day-to-day setting. Our purpose was to assess the post-marketing experience with ESL in our centre, in terms of safety and efficacy profile, and ascertain whether the results were comparable to the published data. METHODS: This is a retrospective, consecutive, single-centre 2-year observational study. All the patients who initiated treatment with ESL between April 1st 2010 and October 31st 2011 at Hospital de Santo António were consecutively included. Data was collected on demographics, clinical features, adverse events and treatment response, using a standardized data form. Follow-up data was considered until October 31st 2013. Efficacy analysis was performed using an "intention to treat" approach. KEY FINDINGS: We included 152 patients, 74 (48.7%) female. Mean age was 38.5 years-old (sd=14.2). Eight patients were less than 18 years old. Mean epilepsy duration was 26.8 (sd=13.1) years and mean seizure frequency in the previous 3 months was 19.7 seizures per month. At baseline, about 57.9% of all patients were taking ≤2 concomitant AEDs. The total adverse rate was 42.1% (64/152), with 50.0% (32/64) leading to treatment discontinuation. The most frequent adverse events were dizziness and somnolence/slowness. Adverse events were higher in regimens including carbamazepine, and mean age was higher in the patients reporting adverse events. Retention rates as estimated by Kaplan-Meyer curves were 82.9%, 71.3%, 65.1% and 62.8%, respectively, at 6, 12, 18 and 24 months. Retention time was not influenced by gender, diagnosis, age or epilepsy duration. Fifty-six patients (36.8%) dropped out of treatment, 32 (57.1%) due to adverse events, 19 (33.9%) due to lack of efficacy and 5 (8.9%) for other reasons. At 6,12,18 and 24 months, the responder rates were 25.7%, 25.7%, 19.0% and 17.1%, respectively and favourable global clinical impression rates were 27.7%, 19.7%, 17.8% and 16.5%. SIGNIFICANCE: This is the first study reporting follow-up data for up to 2 years in patients treated with ESL in the setting of daily clinical practice. The retention rates in our study are sustained throughout the 2 years of follow-up, and at 6 and 12 months are globally comparable to those of phase III trials and open-label extensions. The adverse event rate is also comparable to previous studies, and no new safety issues attributable to ESL were found. Responder rates were lower than those of previous studies, even though efficacy results must be interpreted with caution given the different study design. Thus, ESL appears to be a clinically useful add-on AED, with good safety profile and high retention rates, even in a very refractory group of patients like the presented cohort.

Resective surgery in the treatment of super-refractory partial status epilepticus secondary to NMDAR antibody encephalitis.

BACKGROUND: Anti-NMDAR encephalitis is an increasingly described clinical entity in children, comprising 40% of all cases. We present a case of super-refractory status epilepticus secondary to anti-NMDAR encephalitis treated with emergent resective surgery. CASE STUDY: A 7 years-old boy presented with progressive abnormal irritability. On the day after admission he had multiple seizures, characterized by head and eye version to the right. EEG revealed left parietal-occipital continuous paroxysmal activity. Anti-NMDAR antibodies were positive in CSF and serum. After almost 3 months in the Intensive Care Unit, in barbituric coma, and given the failure of all treatment regimens, a preoperative evaluation was conducted. Ictal SPECT showed significant hiperperfusion and brain FDG-PET a cortical hypometabolism in the left occipital lobe; a left occipital lobectomy was performed. In the next days it was possible to progressively suspend Thiopental. Currently, patient presents right homonymous hemianopsia, eats by his own hand but needs help in almost all other activities. DISCUSSION: Status epilepticus (SE) in the setting of anti-NMDAR encephalitis is unusual but described. Whilst the role of surgery in the management of refractory focal epilepsy is established, it is seldom used in the treatment of SE. In the patient with refractory SE (RSE), awareness of surgery as a potentially life saving treatment is an important issue. To our knowledge, this is the first report of a partial RSE secondary to anti-NMDAR encephalitis treated with resective surgery and illustrates the need to consider anti-NMDAR encephalitis as a cause of super-refractory SE.

Usefulness of genetic characterization of narcolepsy and hypersomnia on phenotype definition: a study in Portuguese patients.

INTRODUCTION: The determination of human leukocyte antigen (HLA) class II genotype is widely used to confirm the diagnosis of narcolepsy with or without cataplexy. The HLA genotyping is reliable, easy to perform and reassures the clinician. It is also less invasive than other methodologies and is in accordance with the autoimmune hypothesis for the origin of narcolepsy. AIM. To assess the usefulness of genetic markers (HLA) in the differential diagnosis between different sleep disorders and their relevance in the context of our population. SUBJECTS AND METHODS: We analyzed a cohort of 113 patients with episodes of daytime sleepiness, 38 patients were classified as narcolepsy with cataplexy, 13 as narcolepsy and 62 as hypersomnia/idiopathic hypersomnia. A control population of 206 reportedly healthy individuals from the same geographic origin was used. RESULTS: The HLA-DQB1*06:02 allele frequency was overrepresented in patients with narcolepsy and narcolepsy with cataplexy (46% and 71% respectively vs. 16% in control population), with a value of p = 4.53-13 for narcolepsy with cataplexy. The HLA-DQB1*02 frequency was increased in the population with hypersomnia when compared with the control population (55% vs. 34%; p = 0.004). CONCLUSIONS: Genetic characterization has the potential to enhance the ability to carry out differential diagnosis among diverse excessive daytime sleepiness phenotypes, corresponding to diverse entities with different biological mechanisms.

TITLE: Utilidad de la caracterizacion genetica de la narcolepsia y la hipersomnia en la definicion del fenotipo: estudio en pacientes portugueses.Introduccion. La determinacion del genotipo de los antigenos leucocitarios humanos (HLA) de clase II es un metodo muy difundido para confirmar el diagnostico de la narcolepsia, con y sin cataplejia. El genotipado del HLA es fiable, sencillo y proporciona seguridad al medico. Tambien es menos invasivo que otros metodos y entronca con la hipotesis autoinmunitaria sobre el origen de la narcolepsia. Objetivo. Evaluar la utilidad de los marcadores geneticos (HLA) en el diagnostico diferencial de diferentes trastornos del sueño y su relevancia en el contexto de nuestra poblacion. Sujetos y metodos. Se analizo una cohorte de 113 pacientes con episodios de somnolencia diurna, 38 de los cuales fueron clasificados como afectados por narcolepsia con cataplejia, 13 con narcolepsia y 62 con hipersomnia/hipersomnia idiopatica. La poblacion de control estaba integrada por 206 individuos sanos del mismo origen geografico. Resultados. La frecuencia del alelo HLA-DQB1*06:02 era superior a la habitual en los pacientes con narcolepsia y narcolepsia con cataplejia (46% y 71%, respectivamente, frente al 16% en la poblacion control), con un valor de p = 4,53­13 en el caso de la narcolepsia con cataplejia. La frecuencia del alelo HLA-DQB1*02 era mas elevada en la poblacion con hipersomnia en comparacion con la poblacion control (55% frente a 34%; p = 0,004). Conclusiones. La caracterizacion genetica tiene posibilidades de mejorar el diagnostico diferencial entre varios fenotipos de somnolencia diurna excesiva, que corresponden a diversas entidades con diferentes mecanismos biologicos.

Polissonografia: aspectos técnicos e clínicos / Polysomnography: technical aspects and clinical use

O sono pode ser estudado por registro em poligrafia (registro combinado de vários sinais biológicos) geralmente chamado de polissonografia (PSG). Neste artigo comparam-se os resultados dos achados da PSG, segundo Rechtshaffen and Kales sleep scoring manual, 1968 ("R and K" rules), com American Academy of Sleep Medicine Manual for Scoring Sleep and Associated Events, 2007, mas se enfatiza o uso do segundo manual. Sumariamente, e com uso de ilustrações, resumem-se a aplicação prática da PSG; o estudo dos potenciais bioelétricos e suas bases; os sensores e transdutores usados nesta poligrafia; as características dos estágios do ciclo sono-vigília. Associadamente, apresentam-se alguns achados normais e anormais da PSG, avaliam-se parâmetros do estudo do ciclo sono-vigília.

Sleep can be studied by a polygraph registration (registration of various combined biological signals) commonly called polysomnography (PSG). In this paper we compare the results of the PSG, according to the Rechtshaffen and Kales sleep scoring manual of 1968 ("R and K" rules), to the American Academy of Sleep Medicine Manual for Scoring Sleep and Associated Events, 2007, however it is emphasized the second manual. Briefly, and with the help of illustrations, we summarize: practical application of the PSG and the study of bioelectric potential and its bases; sensors and transducers used in this polygraph; the characteristics of the stages of sleep-wake cycle. In addition, we present some PSG normal and abnormal findings, and we evaluate the parameters of the study of sleep-wake cycle.

Distrofia miotônica de Steinert e hipersonia primária: relato de caso / Myotonic dystrophy of Steinert and primary hypersomnia: case report

Este artigo apresenta o caso de uma paciente com distrofia miotônica tipo 1 (DM1) (doença de Steinert) e faz a revisão de literatura sobre sonolência excessiva diurna (SED) nestes pacientes. Paciente de 36 anos, portadora de (DM1), apresenta SED e testes múltiplos de latência com média de latências de 1 minuto e 22 segundos. DM1 e SED podem ter várias etiologias, a ressaltar as devidas à disfunção no sistema nervoso central ou à miopatia. No caso da paciente, provavelmente predomina a SED de origem central.

This article presents the case of a myotonic dystrophy type 1 - Steinert's disease (DM1) patient and reviews the literature on excessive daytime sleepiness (EDS) in these patients. Patient of 36 years of age, with DM1, presents EDS and mean multiple sleep latency test of 1 minute and 22 seconds. DM1 and EDS can have some etiologies, mainly due to central nervous system dysfunction or to the myopathy. In the present case, probably predominate the SED of central origin.