Drug resistant epilepsy of the insular lobe: A review and update article.

Background: Epilepsy is a chronic disease that affects millions of people around the world generating great expenses and psychosocial problems burdening the public health in different ways. A considerable number of patients are refractory to the drug treatment requiring a more detailed and specialized investigation to establish the most appropriate therapeutic option. Insular epilepsy is a rare form of focal epilepsy commonly drug resistant and has much of its investigation and treatment involved with the surgical management at some point. The insula or the insular lobe is a portion of the cerebral cortex located in the depth of the lateral sulcus of the brain; its triangular in shape and connects with the other adjacent lobes. The insular lobe is a very interesting and complex portion of the brain related with different functions. Insula in Latin means Island and was initially described in the 18th century but its relation with epilepsy was first reported in the 1940-1950s. Insular lobe epilepsy is generally difficult to identify and confirm due to its depth and interconnections. Initial non-invasive studies generally demonstrate frustrating or incoherent information about the origin of the ictal event. Technological evolution made this pathology to be progressively better recognized and understood enabling professionals to perform the correct diagnosis and choose the ideal treatment for the affected population. Methods: A literature review was performed using MEDLINE/PubMed, Scopus, and Web of Science databases. The terms epilepsy/epileptic seizure of the insula and surgical treatment was used in various combinations. We included studies that were published in English, French, or Portuguese; performed in humans with insular epilepsy who underwent some surgical treatment (microsurgery, laser ablation, or radiofrequency thermocoagulation). Results: Initial search results in 1267 articles. After removing the duplicates 710 remaining articles were analyzed for titles and abstracts applying the inclusion and exclusion criteria. 70 studies met all inclusion criteria and were selected. Conclusion: At present, the main interests and efforts are in the attempt to achieve and standardize the adequate management of the patient with refractory epilepsy of the insular lobe and for that purpose several forms of investigation and treatment were developed. In this paper, we will discuss the characteristics and information regarding the pathology and gather data to identify and choose the best therapeutic option for each case.

Cutaneous adverse reactions associated with antiseizure medication: clinical characteristics and implications in epilepsy treatment.

OBJECTIVE: To describe the clinical characteristics of cutaneous adverse reactions and cross-sensitivity induced by antiseizure medications and compare the pattern of use of antiseizure medications in patients with epilepsy according to skin rash history. METHODS: We analysed patients with a history of skin rash presenting for up to 12 weeks after initiating antiseizure medication. The history of skin rash was verified by medical charts, interviews, and identification of skin lesions by patients based on illustrative images. The minimum follow-up period was eight months. The control group comprised epilepsy patients with regular antiseizure medication use for at least 12 weeks without skin rash. We included 109 cases and 99 controls. RESULTS: The median (interquartile range) period from the index rash was six years (2-11). Carbamazepine was the trigger medication in 48% of cases and induced skin rashes in all patients with cross-sensitivity and carbamazepine exposure. Stevens-Johnson syndrome, toxic epidermal necrolysis, or drug reactions with eosinophilia and systemic symptoms affected 36% of cases. Carbamazepine- or oxcarbazepine-induced maculopapular exanthema occurred earlier (median: one week) than that induced by other antiseizure medications (median: three weeks) (p=0.006). Cross-sensitivity was more common in patients with at least one episode of Stevens-Johnson syndrome (29%) and Stevens-Johnson/toxic epidermal necrolysis overlap (50%) than in patients with maculopapular exanthema (8%) (p=0.01). Although most cases were mild, the pattern of antiseizure medication use differed from that of controls, with a lower proportion of antiseizure medication typically associated with severe cutaneous adverse reactions (carbamazepine, phenytoin, phenobarbital, primidone, oxcarbazepine, and lamotrigine) (p<0.001). Most cases exposed to high-risk medication, however, did not develop cross-sensitivity. SIGNIFICANCE: Cutaneous adverse reaction history may influence antiseizure medication use. Cross-sensitivity is more common in severe cases and most patients are affected by mild, self-limited skin rashes. Further research should consider the relevance of mild skin rashes in lifelong epilepsy treatment.

Single-centre experience on genotypic and phenotypic features of southern Brazilian patients with McArdle disease.

McArdle disease (MD) is a metabolic myopathy caused by deficiency of the myophosphorylase enzyme. The aim of our study was to analyse a series of MD patients in Brazil and the correlation between clinical findings, laboratory data, electromyography, muscle biopsy and genetic features. The PYGM gene was analysed by PCR/RLFP and Sanger sequencing. The sample included 12 patients, aged 18-57 years, from unrelated families. Exercise intolerance was present in all cases. Serum creatine kinase levels at rest were increased in all patients. Forearm ischaemic exercise testing in five patients revealed no increase in venous lactate. Needle electromyography presented 'myopathic pattern' in six patients. Muscle biopsy showed vacuolar myopathy in 10 patients and deficiency of myophosphorylase enzyme in all patients. The genetic analysis showed p.R50X as the most common mutation (allelic frequency: 56.25%), other known mutations (p.Y574X, p.G205S, p.W798R, IVS14 + 1G > A and IVS19-1G > A) and a new mutation (p.Asn168Lysfs*15) were also identified. Several features of the disorder were similar to the vast majority of patients worldwide. The genetic findings of this study revealed a range of mutations that are quite similar to the European cohort. The discovery of one novel mutation increases the genotypic heterogeneity of PYGM gene.

Brazilian guidelines for the application of transcranial ultrasound as a diagnostic test for the confirmation of brain death.

Neurosonological studies, specifically transcranial Doppler (TCD) and transcranial color-coded duplex (TCCD), have high level of specificity and sensitivity and they are used as complementary tests for the diagnosis of brain death (BD). A group of experts, from the Neurosonology Department of the Brazilian Academy of Neurology, created a task force to determine the criteria for the following aspects of diagnosing BD in Brazil: the reliability of TCD methodology; the reliability of TCCD methodology; neurosonology training and skills; the diagnosis of encephalic circulatory arrest; and exam documentation for BD. The results of this meeting are presented in the current paper.

Brazilian guidelines for the application of transcranial ultrasound as a diagnostic test for the confirmation of brain death / Diretrizes brasileiras para o uso do ultrassom transcraniano como teste diagnóstico de confirmação de morte cerebral

Neurosonological studies, specifically transcranial Doppler (TCD) and transcranial color-coded duplex (TCCD), have high level of specificity and sensitivity and they are used as complementary tests for the diagnosis of brain death (BD). A group of experts, from the Neurosonology Department of the Brazilian Academy of Neurology, created a task force to determine the criteria for the following aspects of diagnosing BD in Brazil: the reliability of TCD methodology; the reliability of TCCD methodology; neurosonology training and skills; the diagnosis of encephalic circulatory arrest; and exam documentation for BD. The results of this meeting are presented in the current paper.

Estudos neurossonológicos, especialmente o Doppler transcraniano (DTC) e o duplex transcraniano codificado a cores (DTCC), apresentam elevados níveis de especificidade e sensibilidade quando utilizados como exames complementares no diagnóstico de morte encefálica (ME). Um grupo de peritos do Departamento Científico de Doppler transcraniano da Academia Brasileira de Neurologia criou uma força-tarefa de forma a determinar os critérios neurossonológicos para os seguintes aspectos no diagnóstico de ME no Brasil: metodologia do DTC; metodologia do DTCC; treinamento e habilidades em Neurossonologia; diagnóstico de parada circulatória encefálica e documentação do exame para a ME. Os resultados deste encontro foram apresentados neste artigo.

MERRF: Clinical features, muscle biopsy and molecular genetics in Brazilian patients.

Myoclonic epilepsy with ragged red fibers (MERRF) is a mitochondrial disease that is characterized by myoclonic epilepsy with ragged red fibers (RRF) in muscle biopsies. The aim of this study was to analyze Brazilian patients with MERRF. Six patients with MERRF were studied and correlations between clinical findings, laboratory data, electrophysiology, histology and molecular features were examined. We found that blood lactate was increased in four patients. Electroencephalogram studies revealed generalized epileptiform discharges in five patients and generalized photoparoxysmal responses during intermittent photic stimulation in two patients. Muscle biopsies showed RRF in all patients using modified Gomori-trichrome and succinate dehydrogenase stains. Cytochrome c oxidase (COX) stain analysis indicated deficient activity in five patients and subsarcolemmal accumulation in one patient. Molecular analysis of the tRNA(Lys) gene with PCR/RFLP and direct sequencing showed the A8344G mutation of mtDNA in five patients. The presence of RRFs and COX deficiencies in muscle biopsies often confirmed the MERRF diagnosis. We conclude that molecular analysis of the tRNA(Lys) gene is an important criterion to help confirm the MERRF diagnosis. Furthermore, based on the findings of this study, we suggest a revision of the main characteristics of this disease.

[Endocrine and metabolic effects of antiepileptic drugs]. / Efeitos endócrinos e metabólicos das drogas antiepilépticas.

The antiepileptic drugs (AED) have been widely used for a great deal of people--in the treatment of epilepsy and other diseases--throughout the world. Continuous and prolonged use of AED may be associated with adverse effects in different systems, including a variety of endocrine and metabolic abnormalities. In this review, the relationship of AED with alterations in bone mineral metabolism, energy balance and body weight, gonadal function and thyroid metabolism was revised, as well as their clinical utility in the treatment of diabetic neuropathy.

Efeitos endócrinos e metabólicos das drogas antiepilépticas / Endocrine and metabolic effects of antiepileptic drugs

As drogas antiepilépticas (DAE) são utilizadas por um enorme contingente de pessoas em todo o mundo - tanto no tratamento das epilepsias como para outros fins - frequentemente por um longo tempo. Por essas razões, torna-se fundamental o conhecimento sobre os potenciais efeitos adversos desses medicamentos, muitos deles envolvendo vários aspectos hormonais e metabólicos que devem ser do conhecimento do endocrinologista. Nesta revisão, foi abordada a relação das DAE com anormalidades no metabolismo mineral ósseo, balanço energético e peso corporal, eixo gonadal e função tireoideana, além de ter sido revisado o papel terapêutico dessas medicações no tratamento da neuropatia diabética.

The antiepileptic drugs (AED) have been widely used for a great deal of people - in the treatment of epilepsy and other diseases - throughout the world. Continuous and prolonged use of AED may be associated with adverse effects in different systems, including a variety of endocrine and metabolic abnormalities. In this review, the relationship of AED with alterations in bone mineral metabolism, energy balance and body weight, gonadal function and thyroid metabolism was revised, as well as their clinical utility in the treatment of diabetic neuropathy.

Menkes' disease: case report.

Menkes disease is a rare neurodegenerative disorder due to an intracellular defect of a copper transport protein. We describe a 7 months male patient who presented with seizures, hypoactivity and absence of visual contact. The investigation disclosed pilli torti and thrycorrexis nodosa in the hair, low serum levels of both copper and ceruloplasmin, brain magnetic resonance study showed atrophy and white matter hypointensities on T1-weighted images, electroencephalogram reveals moderate background activity disorganization and epileptiform activity, and muscle biopsy with type 2 fiber atrophy. The clinical, laboratorial, genetic, muscle biopsy and neurophysiological findings in Menkes disease are discussed.

Menkes' disease: case report

Menkes disease is a rare neurodegenerative disorder due to an intracellular defect of a copper transport protein. We describe a 7 months male patient who presented with seizures, hypoactivity and absence of visual contact. The investigation disclosed pilli torti and thrycorrexis nodosa in the hair, low serum levels of both copper and ceruloplasmin, brain magnetic resonance study showed atrophy and white matter hypointensities on T1-weighted images, electroencephalogram reveals moderate background activity disorganization and epileptiform activity, and muscle biopsy with type 2 fiber atrophy. The clinical, laboratorial, genetic, muscle biopsy and neurophysiological findings in MenkesÆ disease are discussed.

A doença de Menkes é uma rara desordem neurodegenerativa causada por defeito intracelular na proteína transportadora do cobre. Descrevemos um paciente de 7 meses, masculino, com crises convulsivas, hipoatividade e ausência de contato visual. A investigação demonstrou pilli torti e thrycorrexis nodosa; níveis séricos baixos de ceruloplasmina e cobre; RNM de crânio com atrofia e redução de sinal da substância branca (imagens em T1); eletroencefalograma com moderada desorganização da atividade de base e atividade irritativa; e biópsia muscular com atrofia de fibras do tipo 2. As características clínicas, laboratoriais, genéticas, biópsia muscular e estudo neurofisiológico na doença de Menkes são discutidas.

Creutzfeldt-Jakob's disease: case report with emphasis on the electroencephalographic features

Creutzfeld-Jakob's disease is a rare neurodegenerative disorder that is included among the transmissible spongiform encephalopathies. The clinical features are those of a rapid progressive dementia with mioclonic jerks, which pregoresses to death is less than one year. We report the case of a 79 years old woman, with initial complaints of vertigo, visual and gait compromise, with an initial brain MR1, EEG and CSF tha had no specific features of CID. After 12 days she was again admitted to the hospital with a worsening of her symptoms, along with global spasticity, inability to walk and a further deterioration of speech and swallowing. A new EEG disclosed periodic triphasic complexes, typical of the disease. CSF had a positive 14-3-3 protein. Sha later evolved with mioclonic jerks, coma, multiple infectius complications and, ultimately death 45 days after her second admission. We focus on the role of the EEG as an adjuctive eletrophysiological tool for the presumptive in vivo diagnosis of the disease

Bone mineral density and serum levels of 25 OH vitamin D in chronic users of antiepileptic drugs.

The aim of this cross sectional study was to evaluate bone mineral density (BMD) and serum levels of 25-hydroxy vitamin D (25OHD) in a group of patients taking antiepileptic drugs (AED) for a seizure disorder. Between May-2001 and January-2003, we evaluated 58 patients (40 women/18 men), 34.4+/-6 years old living in Curitiba or in its metropolitan area, on antiepileptic therapy for 2 to 38 years (10 on monotherapy /48 on multiple drugs regime). The group was matched by age, gender, and bone mass index to 29 healthy subjects (20 women/ 9 men); 34.2+/-5.9 years old. Medical history and physical exam were performed on all subjects with particular information sought about fractures and risks factors for osteoporosis. Blood samples were collected for total serum calcium, albumin, phosphorus, creatinine, total alkaline phosphatase, and liver function tests. BMD of the lumbar spine, femur and forearm was determined by dual energy X-ray absorptiometry (DXA, Hologic QDR 1000). Between February and April-2003, other blood samples were collected to measure 25OHD, intact paratohormone (PTH) and calcium. Unemployment and smoking history were more frequent among patients than among controls (p<0.05). Fifteen patients had a fracture history, all of which occurred during a seizure. The BMD of the lumbar spine (0.975+/-0. 13 g/cm2 vs. 1.058+/-0.1 g/cm2; p<0.03) and of the total femur (0.930+/-0.1 g/cm2 vs. 0.988+/-0.12 g/cm2; p<0.02) was lower in patients than in controls. In 63.5% of patients and in 24.1 % of controls a T-score < -1.0 in at least one site was seen. The AED users had higher total alkaline phosphatase and lower 25OHD (p<0.02). No correlations between BMD and 25OHD were found. The use of phenytoin was correlated with a greater incidence of fractures (RR: 2.38). We conclude that patients on chronic use of AED have alterations in bone metabolism characterized in this study by lower BMD of the lumbar spine and total femur and lower serum concentrations of 25OHD.

Bone mineral density and serum levels of 25 OH vitamin D in chronic users of antiepileptic drugs

O objetivo deste estudo transversal foi avaliar a densidade mineral óssea (DMO) e os níveis de 25hidroxi vitamina D (25OHD) em um grupo de pacientes com epilepsia e usuários crônicos de drogas antiepilépticas (DAE). Entre maio-2001 e janeiro-2003 avaliamos 58 pacientes (40 mulheres/18 homens) residentes em Curitiba ou região metropolitana da cidade, com média de idade 34,4±6 anos e tempo de tratamento entre 2 e 38 anos (10 em monoterapia/48 em politerapia). O grupo de pacientes foi emparelhado por idade, sexo e índice de massa corpórea com 29 indivíduos aparentemente sadios (20 mulheres/9 homens; 34,2±5,9 anos). Pacientes e controles foram submetidos a anamnese e exame clínico, com ênfase na história de fraturas e fatores de risco para osteoporose. Nas visitas foram coletadas amostras de sangue para dosagens de cálcio, albumina, fósforo, creatinina, fosfatase alcalina, transaminases e gama GT. Foi avaliada também a DMO na coluna lombar, fêmur e antebraço (DEXA, Hologic QDRW1000®). Entre fevereiro e abril-2003, pacientes e controles foram chamados para nova coleta de sangue para dosagem da 25OHD e parato-hormônio (PTH) intact. Desemprego e tabagismo foram mais comuns nos pacientes do que nos controles (p<0,05). Quinze pacientes relataram fraturas durante as crises epilépticas. A DMO da coluna lombar (0,975±0,13 g/cm2 vs 1,058±0,1 g/cm2; p<0,03) e do fêmur total (0,930±0,1 g/cm2 vs 0,988±0,12 g/cm2; p<0,02) foi menor nos pacientes do que controles. Em 63,5% dos pacientes e em 24,1% dos controles foi registrado escore T < -1.0 desvio-padrão em pelo menos um dos sítios avaliados. Os usuários crônicos de DAE apresentaram níveis de fosfatase alcalina mais elevados (p<0,01) e níveis de 25OHD mais baixos (p<0,02 vs controles). Não houve correlação entre a DMO e os níveis de 25OHD. O uso de fenitoína correlacionou-se positivamente com maior incidência de fraturas (RR: 2,38). Concluímos que usuários crônicos de DAE apresentam importantes alterações do metabolismo mineral ósseo, demonstrada no presente estudo através de valores menores da DMO em coluna lombar e fêmur e níveis séricos diminuídos de 25OHD.

Bizarre behavior during intracarotid sodium amytal testing (Wada test): are they predictable?

The intracarotid sodium amytal test (ISAT or Wada Test) is a commonly performed procedure in the evaluation of patients with clinically refractory epilepsy candidates to epilepsy surgery. Its goal is to promote selective and temporary interruption of hemispheric functioning, seeking to define language lateralization and risk for memory compromise following surgery. Behavioral modification is expected during the procedure. Even though it may last several minutes, in most cases it is subtle and easily manageable. We report a series of patients in whom those reactions were unusually bizarre, including agitation and aggression. Apart of the obvious technical difficulties (patients required physical restraining) those behaviors potentially promote testing delay or abortion and more importantly, inaccurate data. We reviewed those cases, seeking for features that might have predicted their occurrence. Overall, reactions are rare, seen in less than 5% of the ISAT procedures. The barbiturate effect, patients' psychiatric profiles, hemisphere dominance or selectiveness of the injection were not validated as predictors. Thorough explanation, repetition and simulation may be of help in lessening the risk of those reactions.

Cerebellar hemorrhage as a complication of temporal lobectomy for refractory medial temporal epilepsy: report of three cases.

Cerebellar hemorrhage is listed among the potential complications following neurosurgical procedures. In this scenario it is usually reported as a rare condition. However, it seems that epilepsy surgery patients are somewhat more prone to this kind of complication, compared to other surgical groups. Head positioning, excessive cerebral spinal fluid draining and the excision of non-expanding encephalic tissue (or combinations among the three) are likely to be cause underlying remote cerebellar hemorrhage. Out of the 118 ATL/AH performed at our institution, between 1996 and 2002, we identified 3 (2.5%) patients presenting with cerebellar hemorrhage. We report on such cases and review the literature on the topic.

Bizarre behavior during intracarotid sodium amytal testing (Wada test): are they predictable?

O teste do amital sódico intracarotídeo (TASI ou teste de Wada) é procedimento comum na avaliação de pacientes portadores de epilepsia clinicamente refratária candidatos a cirurgia de epilepsia. Tem por objetivo promover interrupção seletiva e temporária da função hemisferial, definindo lateralização de linguagem e risco de comprometimento de memória no pós-operatório. São esperadas mudanças comportamentais durante o teste, as quais podem durar vários minutos, porém, em geral, são sutis e facilmente manejáveis. Relatamos uma série de casos em que ocorreram comportamentos pouco usuais, bizarros, incluindo agitação e agressividade. Estes comportamentos comprometem o teste (paciente deve ser contido), podendo levar a atrasos ou mesmo abortamento do mesmo, além de produzir dados menos confiáveis. Os casos foram revisados, visando a definição de preditores de sua ocorrência. Estas reações são raras (5% dos casos). Efeito barbitúrico, perfil psiquiátrico, dominância cerebral e seletividade da injeção não puderam ser validados como preditores. Explicações detalhadas, repetição e simulações podem ser utéis na prevenção deste tipo de ocorrência.

Cerebellar hemorrhage as a complication of temporal lobectomy for refractory medial temporal epilepsy: report of three cases

A hemorragia cerebelar faz parte das potenciais complicações dos procedimentos neurocirúrgicos. De forma geral, é considerada uma condição rara. Entretanto, há aparente propensão dos pacientes sub metidos ao tratamento cirúrgico de epilepsia em apresentar este tipo de complicação, quando compara dos com outros grupos cirúrgicos. O posicionamento da cabeça, excessiva drenagem de líquido cefalorraquidiano e a excisão de tecido cerebral não expansível (ou talvez combinações entre os três) constituem as po ten ciais causas da hemorragia cerebelar remota. Entre os 118 pacientes em nossa série de LTA » AH, identifi camos 3(2.5%) casos de hemorragia cerebelar. Relatamos os três casos desta natureza, com revisão da lite ratura pertinente a esta complicação.