HLA alleles and antiseizure medication-induced cutaneous reactions in Brazil: A case-control study.

In this observational case-control study, 107 cutaneous adverse reaction (CAR) cases (CAR+) manifesting up to 12 weeks after the start of treatment with antiseizure medication (ASM) were identified. Control groups consisted of 98 epilepsy patients without a history of CAR (CAR-) and 3965 healthy individuals in the Brazilian National Registry of Bone Marrow Donors. All participants were HLA typed by high-resolution Next Generation Sequencing for HLA-A, B, C, DQB1 and DRB1; HLA-DPA1, DPB1, DQA1, DRB3, DRB4 and DRB5 were also sequenced in samples from CAR+ and CAR- individuals. The relationship between the carrier frequency of each allele, CAR type and ASM for all participants was investigated. The ASMs most frequently associated with CAR were carbamazepine (48% of CAR+ subjects), lamotrigine (23%), phenytoin (18%), phenobarbital (13%) and oxcarbazepine (5%). The main alleles associated with a risk of CAR were HLA-A*02:05 (OR = 6.28; p = 0.019, carbamazepine or oxcarbazepine); HLA-DPA1*02:02 (OR = 4.16, p = 0.003, carbamazepine); HLA-B*53:01 (OR = 47.9, p = 0.014, oxcarbazepine), HLA-DPA1*03:01/DPB1*105:01 (OR = 25.7, p = 0.005, phenobarbital); HLA-C*02:10 (OR = 25.7, p = 0.005, phenobarbital) and HLA-DRB1*04:02 (OR = 17.22, p = 0.007, phenytoin). HLA-A*03:01 increased the risk for phenytoin-induced maculopapular exanthema 4.71-fold (p = 0.009), and HLA-B*35:02 was associated with a 25.6-fold increase in the risk of carbamazepine-induced Stevens-Johnson syndrome (p = 0.005). None of the 4170 subjects carried the HLA-B*15:02 allele, and HLA-A*31:01 was not associated with CAR. Hence, HLA-A*31:01 and HLA-B*15:02 were not associated with CAR in this population. Although other HLA class I and II alleles tested were associated with a risk of CAR, none of these associations were strong enough to warrant HLA testing before prescribing ASM.

Rey-Osterrieth complex figure test: Comparison of traditional and qualitative scoring systems after unilateral temporal lobectomy.

OBJECTIVE: We compared the performance on the Rey-Osterrieth Complex Figure Test (ROCF) of patients that had undergone unilateral anterior temporal lobectomy under both Taylor's and Loring's scoring systems to identify the sensitivity and specificity of each item for differentiating visuospatial memory deficits. METHOD: We administered the ROCF to evaluate the visual memory of 37 left anterior temporal lobectomy (LATL) and 38 right anterior temporal lobectomy (RATL) patients with unilateral temporal lobe epilepsy who had undergone a standard unilateral anterior temporal lobectomy between 1996 and 2010. Fisher's exact and Qui-Quadrado tests were used to analyze the relationships between the qualitative variables. The Mann-Whitney U test was used to compare the quantitative variables from the right and left sides. RESULTS: RATL patients performed worse than LATL patients based on the total score for delayed recall (DR) (p = 0.012). The scoring system's showed a specificity of 97.2% & 78.9% and sensitivity of 10.5% & 62.2% on DR, for the Taylor and Loring systems respectively. Our detailed analysis of certain items showed that some differed between the groups in terms of the presence/absence, correct reproduction, and errors of those items. Loring' errors I, IV, and X on DR and errors IV and X on immediate recall were more frequent in the RATL group. CONCLUSIONS: The use of these two scoring systems combined may help maximize sensitivity and specificity with clinical populations. Further, our analyses showed that items could be clustered better and different weights could be given to them to maximize sensitivity and specificity.

Relationship between hippocampal subfields and Verbal and Visual memory function in Mesial Temporal Lobe Epilepsy patients.

OBJECTIVE: High-resolution protocols used in magnetic resonance imaging (MRI) currently enable the detailed analysis of the hippocampus along with its subfield segmentation. The relationship between episodic memory and the hippocampus is well established, and there is growing evidence that some specific memory processing steps are associated with individual hippocampal segments, but there are inconsistencies in the literature. We focused our analysis on hippocampal subfield volumetry and neuropsychological visual and verbal memory tests in patients with temporal lobe epilepsy (TLE) presenting with unilateral hippocampal atrophy. METHODS: The study involved a cohort of 62 patients with unilateral TLE, including unilateral hippocampal atrophy (29 on the left side) based on MRI and unequivocal ipsilateral ictal onsets based on surface video electroencephalography recordings. The hippocampal subfield volumes were evaluated using FreeSurfer version 7.1. We used the Rey-Auditory Verbal Learning Test to evaluate short-term (A1), learning (ΣA1-A5), immediate (A6), and delayed (A7) recall of episodic verbal memory. We used the Rey-Osterrieth Complex Figure Test to evaluate the immediate and delayed recall of visual memory. We analyzed the correlations between the asymmetry index scores for the hippocampal subfield volumes of thecornu ammonis (CA)1, CA2/3, and CA4 and memory test performance. RESULTS: Moderate associations were established between the CA2/3 asymmetry index scores and visual memory in TLE (both right and left hippocampal atrophy), as well as visual memory and CA4 in the right atrophy cases. The CA1 asymmetry index scores did not correlate with any of the memory test results. We did not find any significant correlation between verbal memory tests and specific hippocampal subfields. CONCLUSIONS: The use of high-resolution MRI protocols andin vivo automated segmentation processing revealed moderate associations between hippocampal subfields and memory parameters. Further investigations are needed to establish the utility of these results for clinical decisions.

Nonverbal fluency assessed by the five-point test in epilepsy patients with unilateral mesial temporal sclerosis-a Brazilian study.

OBJECTIVE: To investigate the performance of epilepsy patients diagnosed with unilateral mesial temporal sclerosis (MTS) on a nonverbal fluency measure using the five-point test (FPT). Our secondary aim was to investigate any differences in FPT and verbal fluency test (VFT) scores between left and right MTS. We hypothesized that scores on the FPT, commonly utilized in the assessment of individuals with presumed frontal lobe damage, would be lower in patients with temporal lobe dysfunction. METHOD: One hundred eighty patients diagnosed with temporal lobe epilepsy (TLE) and 150 healthy controls (HCs) were included in this retrospective study. We analyzed correlations between scores obtained from FPT and phonemic and semantic VFT, and scores according to the lateralization of epileptogenic focus in the TLE group. RESULTS: Overall, the TLE patients had lower performance than the HCs on the FPT, but no differences were observed on perseverance rates (p = 0.992). Statistically significant difference was found in both sections of the VFT in association with the lateralization of the epileptogenic zone (p < 0.001). As for the FPT, differences did not reach statistical significance (p = 0.0857). CONCLUSIONS: Our results support the hypothesis of involvement of the temporal areas on tasks such as the FPT, despite the lack of a lateralizing effect. Our findings also contribute to better understanding of the role of the FPT in assessment of executive function in patients with unilateral MTS, and provide further psychometric data on a native Brazilian population.

The First Unprovoked Seizure in Typically Developing Children: A Real-Life Setting in Southern Brazil.

AIM: To describe the first unprovoked seizure in typically developing children, its clinical characteristics, recurrence rate, and possible risk factors in a real-life setting in Southern Brazil. METHOD: In this retrospective cohort study, medical records of typically developing children aged 28 days to 14 years who had a first unprovoked seizure in a single tertiary care center were reviewed, in a 10-year period (2006-2016). RESULTS: Seventy-four children were included, 41 males and 33 females. The most frequent age group of the first seizure was 5 to 10 years and seizure main type was focal (50%). Most seizures occurred while children were awake (70%). All patients underwent an electroencephalogram (EEG), which was normal in 44.6%. Neuroimaging was performed in 81%, in 2 cases the etiology was considered structural, the remaining was classified as unknown. Median follow-up period was 32.5 months. Seizure recurrence rate was 56.7% and age younger than 5 years was a possible risk factor. INTERPRETATION: In the subpopulation of Brazilian typically developing children with a first unprovoked epileptic seizure there is a high recurrence rate. An abnormal EEG was a common finding, although it was not associated with a higher risk of seizure recurrence. A possible risk factor was age younger than 5 years, which may suggest a more rigorous follow-up of these patients.

Mesial temporal lobe epilepsy: Revisiting the relation of hippocampal volumetry with memory deficits.

OBJECTIVE: Neuropsychological tests can infer the lateralization of the epileptogenic focus, associating verbal memory to mesial structures in the left temporal lobe and visual or nonverbal memory to the right side. High-field magnetic resonance imaging (MRI) with high-resolution protocols allows acquisitions suitable for advanced postprocessing with precise volumetry of brain structures, and functional MRI demonstrates evidence that epilepsy should be seen as a network pathology, involving several structures in the brain. Since the literature showing associations between the volumetry of brain structures in left and right mesial temporal lobe epilepsy (MTLE) and verbal and visual memory performance on neuropsychological tests is conflicting, we revisited these relationships, considering the hippocampal volumetry of patients with unilateral MTLE. METHODS: Automatized hippocampal volumes were obtained using FreeSurfer software from MRI exams of 35 patients with unilateral MTLE and hippocampal atrophy and homolateral ictal onset zone defined by video electroencephalography concordant to the side of hippocampal volume reduction (15 on the left side). Verbal memory was assessed using the Rey Auditory-Verbal Learning Test (RAVLT), and visual memory tests employed the Rey-Osterrieth Complex Figure Test (ROCFT). The statistical analysis explored relationships between hippocampal volumetry, lateralization, and performance on memory tests. RESULTS: In general, we observed deficits in both verbal and visual memory for patients with left and right hippocampal volume reduction. Patients with left hippocampal volume reduction had poorer performance on verbal memory tests compared with those with right hippocampal atrophy (t = -3.813, p < 0.001). Visual memory deficits were seen on both left and right MTLE without a statistically significant difference (t = 0.074, p = 0.942). The correlation between the Hippocampal Asymmetry Index (HAI) and visual and verbal Z-scores was significant only for visual Z-score in right MTLE (R = -0.45, p = 0.048). CONCLUSIONS: Verbal memory deficit seems to be more consistent in patients with left hippocampal volume reduction. Although it had only a moderate correlation to HAI, visual memory deficit is suggested as a poorer indicator for right MTLE. Considering that verbal and visual memory deficits are seen on both right and left MTLE, MTLE should not be regarded as a unilateral, focal, or local insult but as a multifactorial and network pathology, possibly involving several brain structures.

CYP2C9 polymorphisms in epilepsy: influence on phenytoin treatment.

Phenytoin (PHT) is an antiepileptic drug widely used in the treatment of focal epilepsy and status epilepticus, and effective in controlling focal seizures with and without tonic-clonic generalization and status epilepticus. The metabolization of PHT is carried out by two oxidative cytochrome P450 enzymes CYP2C9 and CYP2C19; 90% of this metabolization is done by CYP2C9 and the remaining 10% by CYP2C19. Genetic polymorphism of CYP2C9 may reduce the metabolism of PHT by 25-50% in patients with variants *2 and *3 compared to those with wild-type variant *1. The frequency distribution of CYP2C9 polymorphism alleles in patients with epilepsy around the world ranges from 4.5 to 13.6%, being less frequent in African-Americans and Asians. PHT has a narrow therapeutic range and a nonlinear pharmacokinetic profile; hence, its poor metabolization has significant clinical implications as it causes more frequent and more serious adverse effects requiring discontinuation of treatment, even if it had been effective. There is evidence that polymorphisms of CYP2C9 and the use of PHT are associated with an increase in the frequency of some side effects, such as cerebellar atrophy, gingival hypertrophy or acute cutaneous reactions. The presence of HLA-B*15:02 and CYP2C9 *2 or *3 in the same patient increases the risk of Stevens-Johnson syndrome and toxic epidermal necrolysis; hence, PHT should not be prescribed in these patients. In patients with CYP2C9 *1/*2 or *1/*3 alleles (intermediate metabolizers), the usual PHT maintenance dose (5-10 mg/kg/day) must be reduced by 25%, and in those with CYP2C9 *2/*2, *2/*3 or *3/*3 alleles (poor metabolizers), the dose must be reduced by 50%. It is controversial whether CYP2C9 genotyping should be done before starting PHT treatment. In this paper, we aim to review the influence of CYP2C9 polymorphism on the metabolization of PHT and the clinical implications of poor metabolization in the treatment of epilepsies.

Is there a relationship between narcolepsy, multiple sclerosis and HLA-DQB1*06:02?

We studied multiple sclerosis (MS) patients with the HLA-DQB1*06:02 allele and compared them with MS patients who did not carry the HLA-DQB1*06:02 allele. We analyzed clinical and neurophysiological criteria for narcolepsy in six MS patients with HLA-DQB1*06:02, compared with 12 MS patients who were HLA-DQB1*06:02 non-carriers. Only two patients with HLA-DQB1*06:02 allele scored higher than 10 on the Epworth Sleepiness Scale. Polysomnography recording parameters and the multiple sleep latency test showed an absence of narcolepsy in the study group. Our study suggested no significant correlation between narcolepsy, MS and HLA-DQB1*06:02. The HLA-DQB1*06:02 allele alone was not sufficient to cause MS patients to develop narcolepsy.

Is there a relationship between narcolepsy, multiple sclerosis and HLA-DQB1* 06: 02? / Existe relação entre narcolepsia, esclerose múltipla e HLA-DQB1* 06: 02?

ABSTRACT We studied multiple sclerosis (MS) patients with the HLA-DQB1*06:02 allele and compared them with MS patients who did not carry the HLA-DQB1*06:02 allele. We analyzed clinical and neurophysiological criteria for narcolepsy in six MS patients with HLA-DQB1*06:02, compared with 12 MS patients who were HLA-DQB1*06:02 non-carriers. Only two patients with HLA-DQB1*06:02 allele scored higher than 10 on the Epworth Sleepiness Scale. Polysomnography recording parameters and the multiple sleep latency test showed an absence of narcolepsy in the study group. Our study suggested no significant correlation between narcolepsy, MS and HLA-DQB1*06:02. The HLA-DQB1*06:02 allele alone was not sufficient to cause MS patients to develop narcolepsy.

RESUMO Pacientes com esclerose múltipla (EM) portadores do alelo HLA-DQB1*06:02 foram estudados e comparados com pacientes com EM mas que não são portadores do alelo HLA-DQB1*06:02. Os critérios clínicos e neurofisiológicos para narcolepsia foram analisados em pacientes com EM sendo 6 pacientes com o HLA-DQB1*06:02 comparados a 12 pacientes sem o HLA-DQB1*06:02. Somente 2 pacientes com EM e HLA-DQB1*06:02 tiveram escore maior que 10 na escala “Epworth Sleepiness Scale”. Os parâmetros da polissonografia e o teste de múltiplas latências do sono mostraram ausência de narcolepsia no grupo estudo. Nosso estudo não sugere correlações significantes entre narcolepsia, EM e HLA-DQB1*06:02. Somente o HLA-DQB1*06:02 não foi suficiente para desenvolver narcolepsia em pacientes com EM.

Guidelines for the assessment and acceptance of potential brain-dead organ donors. / Diretrizes para avaliação e validação do potencial doador de órgãos em morte encefálica.

Organ transplantation is the only alternative for many patients with terminal diseases. The increasing disproportion between the high demand for organ transplants and the low rate of transplants actually performed is worrisome. Some of the causes of this disproportion are errors in the identification of potential organ donors and in the determination of contraindications by the attending staff. Therefore, the aim of the present document is to provide guidelines for intensive care multi-professional staffs for the recognition, assessment and acceptance of potential organ donors.

Diretrizes para avaliação e validação do potencial doador de órgãos em morte encefálica / Guidelines for the assessment and acceptance of potential brain-dead organ donors

RESUMO O transplante de órgãos é a única alternativa para muitos pacientes portadores de algumas doenças terminais. Ao mesmo tempo, é preocupante a crescente desproporção entre a alta demanda por transplantes de órgãos e o baixo índice de transplantes efetivados. Dentre as diferentes causas que alimentam essa desproporção, estão os equívocos na identificação do potencial doador de órgãos e as contraindicações mal atribuídas pela equipe assistente. Assim, o presente documento pretende fornecer subsídios à equipe multiprofissional da terapia intensiva para o reconhecimento, a avaliação e a validação do potencial doador de órgãos.

ABSTRACT Organ transplantation is the only alternative for many patients with terminal diseases. The increasing disproportion between the high demand for organ transplants and the low rate of transplants actually performed is worrisome. Some of the causes of this disproportion are errors in the identification of potential organ donors and in the determination of contraindications by the attending staff. Therefore, the aim of the present document is to provide guidelines for intensive care multi-professional staffs for the recognition, assessment and acceptance of potential organ donors.

Improving first responders' psychogenic nonepileptic seizures diagnosis accuracy: Development and validation of a 6-item bedside diagnostic tool.

OBJECTIVE: Epileptic seizures (ES) are often seen as a medical emergency, and their immediate and accurate recognition are pivotal in providing acute care. However, a number of clinical situations may mimic ES, potentially leading to misdiagnosis at the emergency room and to inappropriate prescription of antiepileptic drugs (AED) in the acute and chronic settings. Psychogenic nonepileptic seizures (PNES) play a major role in this scenario and often delay the correct diagnosis and increase treatment morbidity and cost. First responders often conduct the initial assessment of these patients, and their impression may be decisive in the prehospital approach to seizures. We sought to investigate and improve the accuracy of PNES diagnosis among professionals involved in the initial assistance to patients with seizures. METHODS: Fifty-three registered nurses, 34 emergency physicians, 33 senior year medical students, and 12 neurology residents took a short training program consisting of an initial video-based seizure assessment test (pretest), immediately followed by a 30-minute presentation of a 6-item bedside diagnostic tool and then a video-based reassessment (posttest). Baseline status and learning curves were determined. RESULTS: The distinct professional categories showed no significant differences in their ability to diagnose PNES on both pretests and posttests. All groups improved diagnostic skills after the instructional program. SIGNIFICANCE: The findings helped determine the best identifiable PNES clinical signs and to provide initial validation to a novel diagnostic instrument. In addition, our results showed that educational measures might help in the identification of PNES by first responders, which may decrease the treatment gap.

Reactivation of herpes simplex virus-1 following epilepsy surgery.

PURPOSE: The present study reports a case of encephalitis due to herpes simplex virus-1 (HSV-1), following surgical manipulation of the site of a primary infection. METHODS: Herpes simplex virus-1 infection was confirmed by CSF PCR and DNA sequencing. RESULTS: The patient was an 11-year-old girl who required temporal lobe surgery for epilepsy. She had meningoencephalitis due to HSV at the age of 20 months, and she was treated with acyclovir. Three years later, the patient developed uncontrolled seizures that became more frequent and changed in character at 11 years of age. On the 12th postoperative day, she developed fever and seizures, and she was diagnosed with HSV-1 by positive CSF PCR. She was treated with acyclovir (30 mg/kg/day for 21 days). In this report, we describe the patient and review the relevant literature. CONCLUSION: The authors stress the potential risk of reactivation of HSV encephalitis after intracranial surgery. Herpes simplex virus encephalitis must be considered in neurosurgical patients who develop postoperative seizures and fever.

When should MELAS (Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes) be the diagnosis? / Quando o diagnóstico deveria ser MELAS (Miopatia mitocondrial, encefalopatia, acidose lática, e episódios semelhantes a acidente vascular cerebral)?

ABSTRACTMitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) is a rare mitochondrial disorder. Diagnostic criteria for MELAS include typical manifestations of the disease: stroke-like episodes, encephalopathy, evidence of mitochondrial dysfunction (laboratorial or histological) and known mitochondrial DNA gene mutations. Clinical features of MELAS are not necessarily uniform in the early stages of the disease, and correlations between clinical manifestations and physiopathology have not been fully elucidated. It is estimated that point mutations in the tRNALeu(UUR) gene of the DNAmt, mainly A3243G, are responsible for more of 80% of MELAS cases. Morphological changes seen upon muscle biopsy in MELAS include a substantive proportion of ragged red fibers (RRF) and the presence of vessels with a strong reaction for succinate dehydrogenase. In this review, we discuss mainly diagnostic criterion, clinical and laboratory manifestations, brain images, histology and molecular findings as well as some differential diagnoses and current treatments.

RESUMOMiopatia mitocondrial, encefalopatia, acidose lática, e episódios semelhantes a acidente vascular cerebral (MELAS) é uma rara doença mitocondrial. Os critérios diagnósticos para MELAS incluem as manifestações típicas da doença: episódios semelhantes a acidente vascular cerebral, encefalopatia, evidência de disfunção mitocondrial (laboratorial ou histológica) e mutação conhecida em genes do DNA mitocondrial. Na fase inicial da doença, as manifestações clínicas podem não ser uniformes, e sua correlação com a fisiopatologia não está completamente elucidada. Estima-se que as mutações de ponto no gene tRNALeu(UUR) do DNAmt, principalmente a A3243G, sejam responsáveis por cerca de 80% dos casos de MELAS. As alterações morfológicas na biópsia muscular incluem uma grande proporção de fibras vermelhas rasgadas (RRF) e presença de vasos com forte reação para succinato desidrogenase. Nesta revisão, são discutidos os principais critérios diagnósticos, manifestações clínicas e laboratoriais, imagens cerebrais, padrões eletrofisiológicos, histológicos e alterações moleculares, bem como alguns dos diagnósticos diferenciais e tratamentos atuais.

When should MELAS (Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes) be the diagnosis?

Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) is a rare mitochondrial disorder. Diagnostic criteria for MELAS include typical manifestations of the disease: stroke-like episodes, encephalopathy, evidence of mitochondrial dysfunction (laboratorial or histological) and known mitochondrial DNA gene mutations. Clinical features of MELAS are not necessarily uniform in the early stages of the disease, and correlations between clinical manifestations and physiopathology have not been fully elucidated. It is estimated that point mutations in the tRNALeu(UUR) gene of the DNAmt, mainly A3243G, are responsible for more of 80% of MELAS cases. Morphological changes seen upon muscle biopsy in MELAS include a substantive proportion of ragged red fibers (RRF) and the presence of vessels with a strong reaction for succinate dehydrogenase. In this review, we discuss mainly diagnostic criterion, clinical and laboratory manifestations, brain images, histology and molecular findings as well as some differential diagnoses and current treatments.

When should MERRF (myoclonus epilepsy associated with ragged-red fibers) be the diagnosis?

Myoclonic epilepsy associated with ragged red fibers (MERRF) is a rare mitochondrial disorder. Diagnostic criteria for MERRF include typical manifestations of the disease: myoclonus, generalized epilepsy, cerebellar ataxia and ragged red fibers (RRF) on muscle biopsy. Clinical features of MERRF are not necessarily uniform in the early stages of the disease, and correlations between clinical manifestations and physiopathology have not been fully elucidated. It is estimated that point mutations in the tRNALys gene of the DNAmt, mainly A8344G, are responsible for almost 90% of MERRF cases. Morphological changes seen upon muscle biopsy in MERRF include a substantive proportion of RRF, muscle fibers showing a deficient activity of cytochrome c oxidase (COX) and the presence of vessels with a strong reaction for succinate dehydrogenase and COX deficiency. In this review, we discuss mainly clinical and laboratory manifestations, brain images, electrophysiological patterns, histology and molecular findings as well as some differential diagnoses and treatments.

When should MERRF (myoclonus epilepsy associated with ragged-red fibers) be the diagnosis? / Quando o diagnóstico deveria ser MERRF (epilepsia mioclônica associada com fibras vermelhas rasgadas)?

Myoclonic epilepsy associated with ragged red fibers (MERRF) is a rare mitochondrial disorder. Diagnostic criteria for MERRF include typical manifestations of the disease: myoclonus, generalized epilepsy, cerebellar ataxia and ragged red fibers (RRF) on muscle biopsy. Clinical features of MERRF are not necessarily uniform in the early stages of the disease, and correlations between clinical manifestations and physiopathology have not been fully elucidated. It is estimated that point mutations in the tRNALys gene of the DNAmt, mainly A8344G, are responsible for almost 90% of MERRF cases. Morphological changes seen upon muscle biopsy in MERRF include a substantive proportion of RRF, muscle fibers showing a deficient activity of cytochrome c oxidase (COX) and the presence of vessels with a strong reaction for succinate dehydrogenase and COX deficiency. In this review, we discuss mainly clinical and laboratory manifestations, brain images, electrophysiological patterns, histology and molecular findings as well as some differential diagnoses and treatments.

Epilepsia mioclônica associada com fibras vermelhas rasgadas (MERRF) é uma rara doença mitocondrial. O critério diagnóstico para MERRF inclui as manifestações típicas da doença: mioclonia, epilepsia generalizada, ataxia cerebelar e fibras vermelhas rasgadas (RRF) na biópsia de músculo. Na fase inicial da doença, as manifestações clínicas podem não ser uniformes, e correlação entre as manifestações clínicas e fisiopatologia não estão completamente elucidadas. Estima-se que as mutações de ponto no gene tRNALys do DNAmt, principalmente a A8344G, sejam responsáveis por quase 90% dos casos de MERRF. As alterações morfológicas na biópsia muscular incluem uma grande proporção de RRF, fibras musculares com deficiência de atividade da citocromo c oxidase (COX) e presença de vasos com forte reação para succinato desidrogenase e deficiência da COX. Nesta revisão, são discutidas as principais manifestações clínicas e laboratoriais, imagens cerebrais, padrões eletrofisiológicos, histológicos e alterações moleculares, bem como, alguns dos diagnósticos diferenciais e tratamentos.

Are children affected by epileptic neuropsychiatric comorbidities?

Childhood-onset epilepsy is associated with psychiatric and cognitive difficulties and with poor social outcomes in adulthood. Some antiepileptic drugs adversely affect behavior in susceptible children with easy-to-control or refractory epilepsies, contributing to a high risk of psychological and psychiatric disturbance. Studies had demonstrated that patients with benign rolandic epilepsy and absence epilepsy had more aggressive behavior, depression, and anxiety disorders than control children. Psychiatric comorbidities are strongly associated with a poor long-term health-related quality of life in childhood-onset epilepsy, which suggests that comprehensive epilepsy care must include screening and long-term treatment for these conditions, even if seizures remit.