Pre-surgical mood disorders associated to worse post-surgical seizure outcome in patients with refractory temporal lobe epilepsy and mesial temporal sclerosis

OBJECTIVES: This study aims at verifying the impact of pre-surgical PD on seizure outcome in patients with refractory temporal lobe epilepsy and mesial temporal sclerosis (TLE-MTS). METHODS: After previous consent, retrospective data from 115 surgically treated (corticoamygdalohyppocampectomy) TLE-MTS patients (65 females; 56.5%) were analyzed. Psychiatric evaluations were performed through DSM-IV criteria. Engel IA was established as a favorable prognosis. RESULTS: Forty-five patients (41.6%) were classified as Engel IA, while 47 (40.8%) presented pre-surgical PD. Depression (OR=5.11; p=0.004) appeared as a risk factor associated to a non-favorable seizure outcome. CONCLUSION: In patients with refractory TLE-MTS, the presence of depression predicts an unfavorable outcome.

Epilepsy and electroencephalographic features: comparative study of Down syndrome and non-syndromic mental retardation

INTRODUCTION: Down syndrome (DS) is the most common chromosomal abnormality causing mental retardation and its association with epilepsy is highly variable in childhood. Although the first descriptions of the syndrome did not report seizures, their association with epilepsy is relatively common. METHODS: were evaluated 68 individuals with DS and 83 with non-syndromic mental retardation (N-SMR). All patients underwent digital EEG, lasting at least 30 minutes and electrodes positioned according to the International 10-20 System of Electrode Placement. Data were analyzed using descriptive statistics and proportions were compared with Student's t-test and test of Differences between Proportions with p<0.05 considered statistically significant. RESULTS: DS: 27.9% had epilepsy (first seizure with 2.2±3.7 years). Fifteen (22.1%) patients had epileptiform discharges, 5 (7.4%) hypsarrhythmia, 5 (7.4%) focal pattern, 3 (4.4%) generalized pattern and 2 (2.9%) multifocal pattern. N-SMR: 33.7% patients had epilepsy (first seizure with 1.2±4.5 years). Twenty-three (27.7%) patients had epileptiform discharges, 10 (12.0%) focal pattern, 5 (6.0%) generalized pattern and 8 (9.6%) multifocal pattern. CONCLUSION: The difference between the occurrence of epilepsy in DS and N-SMR was not statistically significant, as well as between normal EEG, EEGs with focal pattern, generalized pattern and multifocal pattern. In SD group 7.4% have shown hypsarrhythmia.The comparison with N-SMR was not possible because none of these has shown this EEG abnormality.

Different levels of MT-I/II between patients with MTLE with or without seizure generalization: does hippocampal MT-I/II affects seizure spread, or does seizure spread promotes differential expression of MT-I/II?

In the central nervous system, zinc is released along with glutamate during neurotransmission and, in excess, can promote neuronal death. Experimental studies have shown that metallothioneins I/II (MT-I/II), which chelate free zinc, can affect seizures and reduce neuronal death after status epilepticus. Our aim was to evaluate the expression of MT-I/II in the hippocampus of patients with temporal lobe epilepsy (TLE). Hippocampi from patients with pharmacoresistant mesial temporal lobe epilepsy (MTLE) were evaluated for expression of MT-I/II and for neuronal, astroglial, and microglial populations. Compared to control cases, MTLE group displayed widespread increase in MT-I/II expression, astrogliosis and reduced neuronal population. MT-I/II levels did not correlate with any clinical variables, but patients with secondary generalized seizures (SGS) had less MT-I/II than patients without SGS. In conclusion, MT-I/II expression was increased in hippocampi from MTLE patients and our data suggest that it may be associated with different seizure spread patterns.

Challenges in the surgical treatment of epilepsy: hypothalamic hamartoma in infancy - case report

INTRODUCTION: Hypothalamic hamartoma is a rare congenital malformation, characterized by epilepsy, especially gelastic seizures, psychomotor developmental delay, mental retardation, behavioral disorders and precocious puberty. Epilepsy has early onset and is usually medically refractory. Etiology and pathophysiological mechanisms are unclear. The EEG can present disorganization and slowing of background activity and multifocal and/or generalized epileptogenic discharges. OBJECTIVE: To report the difficulties and challenges of neurosurgical treatment of a hypothalamic hamartoma in an infant. CASE REPORT: Infant with seizures since eight months old of age. The neurological investigation revealed a lesion in tuber cinereum suggestive of hamartoma. The epilepsy evolved with resistance to antiepileptic drugs, requiring neurosurgical procedure. The endoscopic resection could not be performed because the hamartoma was firmly attached to the hypothalamus. Currently, the child remains with tonic, clonic and atonic seizures. DISCUSSION: Lesionectomy performed by microsurgery or radiosurgery seems to be the most effective treatment for seizure control in patients with hypothalamic hamartomas who do not respond to clinical treatment. Callosotomy may be effective in selected cases, and lobectomy/cortical resections are not related to seizure control. In some patients, particularly in infants, lesionectomy and radiosurgery may be technically unfeasible.

Cytokines in cerebrospinal fluid of children with West syndrome

In this study we aimed to determine the levels of tumor necrosis factor beta (TNF-b), interleukin (IL) 1-beta (IL-1b), IL-5, IL-10, and interferon gamma (IFN-g ) in CSF from children during the onset of West syndrome (WS). We observed elevated levels of IL-1b and IFN-g correlated to clinical, EEG, therapeutic response, and follow-up suggesting the involvement of immune response in WS. These results suggest that inflammatory and immunologic mediators may play a role in the pathophysiologic mechanisms of infantile spasms. Our findings may explain the perfusion and cognitive disfunctions and actions of adrenocorticotropic hormone (ACTH), corticosteroids, and intravenous immunoglobulin (IVIg) observed in WS. In conclusion, WS results from association of neurophysiological mechanisms and structural abnormalities with participation of cytokines mainly in symptomatic group.

Genotype-Phenotype correlation in Dravet Syndrome with SCN1A mutation increase efficiency of molecular diagnosis

OBJECTIVES: The purpose of this study was to advance the knowledge on the clinical use of SCN1A testing for severe epilepsies within the spectrum of generalized epilepsy with febrile seizures plus by performing genetic screening in patients with Dravet and Doose syndromes and establishing genotype-phenotype correlations. METHODS: Mutation screening in SCN1A was performed in 15 patients with Dravet syndrome and 13 with Doose syndrome. Eight prediction algorithms were used to analyze the impact of the mutations in putative protein function. Furthermore, all SCN1A mutations previously published were compiled and analyzed. In addition, Multiplex Ligation-Dependent Probe Amplification (MLPA) technique was used to detect possible copy number variations within SCN1A. RESULTS: Twelve mutations were identified in patients with Dravet syndrome, while patients with Doose syndrome showed no mutations. Our results show that the most common type of mutation found is missense, and that they are mostly located in the pore region and the N- and C-terminal of the protein. No copy number variants in SCN1A were identified in our cohort. CONCLUSIONS: SCN1A testing is clinically useful for patients with Dravet syndrome, but not for those with Doose syndrome, since both syndromes do not seem to share the same genetic basis. Our results indicate that indeed missense mutations can cause severe phenotypes depending on its location and the type of amino-acid substitution. Moreover, our strategy for predicting deleterious effect of mutations using multiple computation algorithms was efficient for most of the mutations identified.

Metabolic differences in the contralateral hippocampus of concordant and discordant mesial temporal sclerosis (MTS) patients: evaluation with proton magnetic resonance spectroscopy (1H-MRS)

PURPOSE: Patients with mesial temporal sclerosis (MTS) are clinically classified as concordant or discordant according to the extent of epileptogenic activity. The aim of this study is to determine whether the metabolic changes in the hippocampus are different in the two groups. MATERIALS AND METHODS: 33 patients diagnosed with MTS, 23 concordant (33±9 years old) and 10 discordant (33±10 years old) and 28 controls (33±10 years old) were evaluated. We obtained magnetic resonance spectroscopy of both hippocampi (ipsilateral and contralateral) on a 3T scanner with single voxel PRESS sequence with TE/TR=135/1500ms. The main metabolites were quantified with LC Model. For comparison between groups statistical tests were performed with a significance level of 0.05. RESULTS: In all patients a reduction of NAAipsi and Cr ipsi was observed, when compared to the contralateral side, but this difference was only significant for the group of concordant patients. In comparison with controls a significant reduction of Cr ipsi and NAAipsi was observed for both groups and for Naa/Cr ipsi in the group of concordant patients while NAA/Cr contra was reduced only in the group of discordant patients. CONCLUSION: Our findings suggest a stronger decline of NAA/Cr ipsi in the group of concordant patients and of NAA/Cr contra in discordant patients, suggesting a slightly different metabolic pattern for both groups. However, we need to increase the sample size to confirm these findings.