Epilepsy and stigma: an approach to understanding through the life and works of the Brazilian writer Machado de Assis (1839-1908).

Machado de Assis (1839-1908)-novelist, short story writer, essayist, and poet-is a fascinating personality. Had he written in French, English, German, or Italian, he would have achieved universal fame and would be in the same company as Balzac, Tolstoy, Dickens, and Dostoevsky. This article discusses stigma in epilepsy through Machado de Assis' life, literary work, and letters to other Brazilian writers. Founder of the Brazilian Academy of Letters, Machado offers an insoluble enigma to psychologists and essayists. Born in stark poverty, feeble, and ugly, he had to fight the taint of epilepsy. The documentation of epilepsy in Machado de Assis' texts and letters and the testimony of his contemporaries is unique, allowing the comprehension of scientific concepts and stigma related to epilepsy in the 19th century, when the positivist ideas of the Italian neuropsychiatrist Cesare Lombroso (1835-1909) permeated nascent Brazilian neuropsychiatry. Much of the stigma associated with epilepsy we witness today emerged from these concepts. Even today in Brazil, when barbaric crimes are committed, headlines in newspapers produced by forensic psychiatrists often attribute the conduct of the criminal to epileptic behavior.

Assessment of working memory in patients with mesial temporal lobe epilepsy associated with unilateral hippocampal sclerosis.

OBJECTIVE: The aim of the present study was to investigate whether working memory is impaired in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), a controversial and largely unexplored matter. METHODS: Twenty subjects with left MTLE-HS, 19 with right MTLE-HS, and 21 control right-handed subjects underwent neuropsychological assessment of episodic and semantic memory, executive functions, and specific working memory components. RESULTS: Left and right epileptogenic foci resulted in impairment of verbal and nonverbal episodic memory (verbal memory deficit greater in left MTLE-HS than in right MTLE-HS). In addition, patients with left MTLE-HS were impaired in learning paired associates, verbal fluency, and Trail Making. No differences were seen in the tests carried out to evaluate the working memory components (except visuospatial short-term memory in right MTLE-HS). CONCLUSION: In this study we did not detect reliable working memory impairment in patients with MTLE-HS with either a left or right focus in most tasks considered as tests of working memory components.

Provocative and inhibitory effects of a video-EEG neuropsychologic protocol in juvenile myoclonic epilepsy.

PURPOSE: Studies suggest that higher cognitive functions could precipitate seizures in juvenile myoclonic epilepsy (JME). The present study aimed to analyze the effects of higher mental activity on epileptiform discharges and seizures in patients with JME and compare them to those of habitual methods of activation. METHODS: Seventy-six patients with JME (41 female) underwent a video-EEG (electroencephalography) neuropsychologic protocol (VNPP) and habitual methods of activation for 4-6 h. RESULTS: Twenty-nine of the 76 (38.2%) presented provocative effect, and inhibition was seen in 28 of 31 (90.3%). A mixed effect was observed in 11 (35.5%), and 30 patients (39.5%) suffered no effect of VNPP. Action-programming tasks were more effective than thinking in provoking epileptiform discharges (23.7% and 11.0% of patients, respectively, p = 0.03). Inhibitory effect was observed equally in the various categories of tasks, except in mental calculation, which had a higher inhibitory rate. Habitual methods of activation were more effective than VNPP in provoking discharges. Anxiety disorders were diagnosed in 24 of 58 patients (41.4%); anxious patients had greater discharge indexes and no significant inhibitory effect on VNPP. DISCUSSION: Praxis exerted the most remarkable provocative effect, in accordance with the motor circuitry hyperexcitability hypothesis in JME. Inhibitory effect, which had no such task specificity, might be mediated by a widespread cortical-thalamic pathway, possibly involving the parietal cortex. The frequent inhibitory effect found under cortical activation conditions, influenced by the presence of anxiety, supports nonpharmacologic therapeutic interventions in JME.

Gastric secretion elicited by conditioning in rats.

OBJECTIVE: To investigate whether interdigestive gastric acid secretion can be controlled by a possible memory-related cortical mechanism. MATERIAL AND METHODS: To evaluate gastric secretion in rats, we used a methodology that allows gastric juice collection in rats in their habitual conditions (without any restraining) by pairing sound as the conditioning stimulus (CS) and food as the unconditioning stimulus (US). The levels of gastric acid secretion under basal conditions and under sound stimulation were recorded and the circulating gastrin levels determined. RESULTS: When the gastric juice was collected in the course of the conditioning procedure, the results showed that under noise stimulation a significant increase in gastric acid secretion occurred after 10 days of conditioning (p<0.01). The significance was definitively demonstrated after 13 days of conditioning (p<0.001). Basal secretions of the conditioned rats reached a significant level after 16 days of conditioning. The levels of noise-stimulated gastric acid secretion were the highest so far described in physiological experiments carried out in rats and there were no significant increases in the circulating gastrin levels. CONCLUSIONS: The results point to the important role played by cortical structures in the control of interdigestive gastric acid secretion in rats. If this mechanism is also present in humans, it may be involved in diseases caused by inappropriate gastric acid secretion during the interprandial periods.

Personality traits related to juvenile myoclonic epilepsy: MRI reveals prefrontal abnormalities through a voxel-based morphometry study.

Studies involving juvenile myoclonic epilepsy (JME) patients have demonstrated an elevated prevalence of cluster B personality disorders (PD) characterized as emotional instability, immaturity, unsteadiness, lack of discipline, and rapid mood changes. We aimed to verify a possible correlation between structural brain abnormalities in magnetic resonance image (MRI) and the PD in JME using voxel-based morphometry (VBM). Sixteen JME patients with cluster B PD, 38 JME patients without psychiatric disorders, and 30 healthy controls were submitted to a psychiatric evaluation through SCID I and II and to a MRI scan. Significant reduction in thalami and increase in mesiofrontal and frontobasal regions' volumes were observed mainly in JME patients with PD. Structural alterations of the orbitofrontal cortex (OFC), involved in regulation of mood reactivity, impulsivity, and social behavior, were also observed. This study supports the hypothesis of frontobasal involvement in the pathophysiology of cluster B PD related to JME.

Validity and reliability of the Portuguese-Brazilian version of the Quality of Life in Epilepsy Inventory-89.

OBJECTIVE: The purpose of this article was to report the translation of the Quality of Life in Epilepsy Inventory-89 (QOLIE-89) into a Portuguese-Brazilian version and evaluate its reliability and validity. METHODS: This study involved 105 outpatients: 54 patients with refractory temporal lobe epilepsy (TLE) with mesial temporal sclerosis (MTS) and 51 with juvenile myoclonic epilepsy (JME). Reliability and test-retest reliability were assessed. Relationships between QOLIE-89 domains and other questionnaires (Nottingham Health Profile, Beck Depression Inventory, Adverse Event Profile, Neuropsychological Evaluation), and external measures such as demographic and clinical variables were analyzed to examine construct validity. RESULTS: Internal consistency (Cronbach's alpha=0.73-0.92) and test-retest reliability (intraclass correlation coefficient=0.60-0.84) for individual domains were acceptable. For construct validity, we verified high correlations between the QOLIE-89 and the Nottingham Health Profile, Beck Depression Inventory, Adverse Event Profile, and Neuropsychological Evaluation. For clinical characteristics, the patients with juvenile myoclonic epilepsy had better quality-of-life scores on 11 of 17 QOLIE-89 subscales compared with patients with temporal lobe epilepsy (P<0.05). CONCLUSION: These results support the reliability and validity of the Portuguese-Brazilian translation of QOLIE-89.

Correlation between memory, proton magnetic resonance spectroscopy, and interictal epileptiform discharges in temporal lobe epilepsy related to mesial temporal sclerosis.

OBJECTIVE: The aim of the study described here was to examine the relationship between memory function, proton magnetic resonance spectroscopy ((1)H-MRS) abnormalities, and interictal epileptiform discharge (IED) lateralization in patients with temporal lobe epilepsy (TLE) related to unilateral mesial temporal sclerosis. METHODS: We assessed performance on tests of memory function and intelligence quotient (IQ) in 29 right-handed outpatients and 24 controls. IEDs were assessed on 30-minute-awake and 30-minute-sleep EEG samples. Patients had (1)H-MRS at 1.5 T. RESULTS: There was a negative correlation between IQ (P=0.031) and Rey Auditory Verbal Learning Test results (P=0.022) and epilepsy duration; between(1)H-MRS findings and epilepsy duration (P=0.027); and between N-acetylaspartate (NAA) levels and IEDs (P=0.006) in contralateral mesial temporal structures in the left MTS group. (1)H-MRS findings, IEDs, and verbal function were correlated. CONCLUSIONS: These findings suggest that IEDs and NAA/(Cho+Cr) ratios reflecting neural metabolism are closely related to verbal memory function in mesial temporal sclerosis. Higher interictal activity on the EEG was associated with a decline in total NAA in contralateral mesial temporal structures.

Psychiatric comorbidity in epilepsy: a study comparing patients with mesial temporal sclerosis and juvenile myoclonic epilepsy.

We evaluated the frequency of psychiatric disorders (PDs) in a homogenous series of patients with temporal lobe epilepsy with mesial temporal sclerosis (TLE-MTS), as compared with patients with juvenile myoclonic epilepsy (JME), aiming to determine possible differences in psychiatric diagnoses between these two epileptic syndromes. Data from 170 patients with refractory TLE-MTS and from 100 patients with JME were reviewed and compared. The prevalence of PDs was high in both groups of patients with epilepsy: PDs were present in 85 patients with TLE-MTS (50%) and 49 patients with JME (49%). Among the TLE-MTS group, mood (25.8%), psychotic (15.8%), and anxiety (14.1%) disorders were the most frequent diagnoses, whereas anxiety and mood disorders (23 and 19%, respectively) were the most common among patients with JME. Psychoses were significantly associated with MTS (P<0.01) and anxiety disorders with JME (P<0.05). These findings suggest the existence of an anatomic correlation between PDs and brain structures involved in both epilepsy syndromes.

Quality of life and burden in caregivers of patients with epilepsy.

The purpose of this study was to compare quality of life and burden in 100 caregivers of adolescent and adult patients with epilepsy that started in adolescence. We invited caregivers of 50 patients with temporal lobe epilepsy (TLE) related to mesial temporal sclerosis and caregivers of 50 patients with juvenile myoclonic epilepsy (JME) to participate. After the caregivers answered a sociodemographic questionnaire, they answered the Brazilian version of the Burden Interview (BI) Scale and we assessed their quality of life using the 36-Item Short-Form Health Survey (SF-36). The mean ages of patients were 25.4 and 36.4 years and epilepsy duration was 14 and 25.6 years in the JME and TLE groups, respectively. We found a mild to moderate burden on caregivers in both groups, with a BI average score of 25.5 for JME and 30.7 for TLE. Caregivers in the JME group had lower scores in all domains of the SF-36 and reported higher burden. Low scores were also seen in three domains for the TLE group. These results suggest that caregivers of patients with both epileptic syndromes experience interference in their lives. When we compared the two groups, we found no difference between caregiver data on SF-36 and BI. Quality of life was significantly compromised in caregivers of patients with JME and TLE, and the two groups were burdened to a similar degree (mild to moderate). Nurses can carry out psychoeducative programs with the objective of diagnosing the impact of epilepsy in the family, decreasing burden, and improving quality of life for caregivers.

Ictal spitting in left temporal lobe epilepsy: report of three cases.

PURPOSE: Ictal spitting is rarely reported in patients with epilepsy. More often it is observed in patients with temporal lobe epilepsy (TLE) and is presumed to be a lateralizing sign to language nondominant hemisphere. We report three patients with left TLE who had ictal spitting registered during prolonged video-EEG monitoring. METHODS: Medical charts of all patients with medically refractory partial epilepsy submitted to prolonged video-EEG monitoring in the Epilepsy Unit at UNIFESP during a 3-year period were reviewed, in search of reports of ictal spitting. The clinical, neurophysiological and neuroimaging data of the identified patients were reviewed. RESULTS: Among 136 patients evaluated with prolonged video-EEG monitoring, three (2.2%) presented spitting automatisms during complex partial seizures. All of them were right-handed, and had clear signs of left hippocampal sclerosis on MRI. In two patients, in all seizures in which ictal spitting was observed, EEG seizure onset was seen in the left temporal lobe. In the third patient, ictal onset with scalp electrodes was observed in the right temporal lobe, but semi-invasive monitoring with foramen ovale electrodes revealed ictal onset in the left temporal lobe, confirming false lateralization in surface records. The three patients became seizure-free following left anterior temporal lobectomy. CONCLUSIONS: Ictal spitting is a rare finding in patients with epilepsy, and may be considered a localizing sign of seizure onset in the temporal lobe. It may be observed in seizures originating from the left temporal lobe, and thus should not be considered a lateralizing sign of nondominant TLE.

Iatrogenic Creutzfeldt-Jakob disease following human growth hormone therapy: case report.

We report the case of a 41-year-old man with iatrogenic Creutzfeldt-Jakob disease (CJD) acquired after the use of growth hormone (GH) obtained from a number of pituitary glands sourced from autopsy material. The incubation period of the disease (from the midpoint of treatment to the onset of clinical symptoms) was rather long (28 years). Besides the remarkable cerebellar and mental signs, the patient exhibited sleep disturbance (excessive somnolence) from the onset of the symptoms, with striking alteration of the sleep architecture documented by polysomnography. 14-3-3 protein was detected in the CSF, and MRI revealed increased signal intensity bilaterally in the striatum, being most evident in diffusion-weighted (DW-MRI) sequences. This is the second case of iatrogenic CJD associated with the use of GH reported in Brazil.

Magnetic fields in noninvasive brain stimulation.

The idea that magnetic fields could be used therapeutically arose 2000 years ago. These therapeutic possibilities were expanded after the discovery of electromagnetic induction by the Englishman Michael Faraday and the American Joseph Henry. In 1896, Arsène d'Arsonval reported his experience with noninvasive brain magnetic stimulation to the scientific French community. In the second half of the 20th century, changing magnetic fields emerged as a noninvasive tool to study the nervous system and to modulate neural function. In 1985, Barker, Jalinous, and Freeston presented transcranial magnetic stimulation, a relatively focal and painless technique. Transcranial magnetic stimulation has been proposed as a clinical neurophysiology tool and as a potential adjuvant treatment for psychiatric and neurologic conditions. This article aims to contextualize the progress of use of magnetic fields in the history of neuroscience and medical sciences, until 1985.

Gender and hemispheric differences in temporal lobe epilepsy: a VBM study.

PURPOSE: Gender differences are recognized in the functional and anatomical organization of the human brain. Differences between genders are probably expressed early in life, when differential rates of cerebral maturation occur. Sexual dimorphism has been described in temporal lobe epilepsy with mesial temporal sclerosis (TLE-MTS). Several voxel-based morphometry (VBM) studies have shown that TLE-MTS extends beyond mesial temporal structures, and that there are differences in the extent of anatomical damage between hemispheres, although none have approached gender differences. Our aim was to investigate gender differences and anatomical abnormalities in TLE-MTS. METHODS: VBM5 was employed to analyze gender and hemispheric differences in 120 patients with TLE-MTS and 50 controls. RESULTS: VBM abnormalities were more widespread in left-TLE; while in women changes were mostly seen in temporal areas, frontal regions were more affected in men. CONCLUSIONS: Our study confirmed that gender and laterality are important factors determining the nature and severity of brain damage in TLE-MTS. Differential rates of maturation between gender and hemispheres may explain the distinct areas of anatomical damage in men and women.

Does the patient's hand hold the key to preventing secondary generalization in mesial temporal lobe epilepsy?

This study aimed to analyze the impact of ictal dystonic posturing (DP) in postoperative seizure outcome and to assess the influence of DP in generalized tonic-clonic seizure (GTCS) occurrence during video-EEG monitoring of patients with temporal lobe epilepsy with mesial temporal sclerosis. The impact of DP on surgical outcome remains controversial. Moreover, DP has been recently associated with brain networks avoiding GTCS occurrence. Five hundred twenty-seven seizures of 171 patients who were submitted to standard anterior temporal lobectomy (ATL) between 2002 and 2010, with at least one year of post-surgical follow-up, were retrospectively analyzed and classified as with or without DP and as evolving or not to GTCS. The ictal semiologic correlates of DP, timing elapsed since precedent seizure and antiepileptic drug (AED) intake before each seizure were evaluated. Seizure outcome after ATL was assessed according to Engel's scale. Fifty-eight out of 171 patients (34%) exhibited ictal DP, of which 91.5% were always unilateral and contralateral to the operated side. DP was related to shorter seizures (p=0.007) and a much lower likelihood of the seizure evolving to GTCS (p=0.001), even during AED withdrawal (p=0.002). There was no association between DP and prognosis regarding seizure control as the result of the surgical resection, either in patients with shorter or in those with longer period of follow-up. Our data support the hypothesis that DP reflects a brain network activation that helps avoid GTCS, even during AED withdrawal.

Pre-surgical predictors for psychiatric disorders following epilepsy surgery in patients with refractory temporal lobe epilepsy and mesial temporal sclerosis.

Psychiatric outcomes of patients submitted to epilepsy surgery have gained particular interest given the high prevalence of pre-surgical psychiatric disorders (PD) in this population. The present study aimed to verify the possible pre-surgical predictors for psychiatric disorders following epilepsy surgery in a homogeneous series of patients with refractory temporal lobe epilepsy and mesial temporal sclerosis (TLE-MTS). Data from 115 TLE-MTS patients (65 females; 56.5%) who underwent cortico-amygdalohippocampectomy were included. Pre- and post-surgical psychiatric evaluations were performed using DSM-IV criteria. Pre-surgical PD - particularly mood, anxiety and psychotic disorders - were diagnosed in 47 patients (40.8%). Twenty-seven patients (54% of those with pre-surgical PD) demonstrated a remission of psychiatric symptoms on post-surgical psychiatric evaluation. Eleven patients (9.6%) developed de novo PD. The presence of pre-surgical depression (OR=3.32; p=0.008), pre-surgical interictal psychosis (OR=4.39; p=0.009) and epileptiform discharges contralateral to the epileptogenic zone (OR=2.73; p=0.01) were risk factors associated with post-surgical PD. Although epilepsy surgery is considered to be the best treatment option for patients with refractory TLE-MTS, the relatively high psychiatric comorbidities observed in surgical candidates and their possible negative impact on post-surgical outcomes require a careful pre-surgical evaluation of clinical, sociodemographic and psychiatric factors.

Major depressive disorder as a predictor of a worse seizure outcome one year after surgery in patients with temporal lobe epilepsy and mesial temporal sclerosis.

PURPOSE: The association between pre-surgical psychiatric disorders (PDs) and worse seizure outcome in patients with refractory epilepsy submitted to surgery has been increasingly recognized in the literature. The present study aimed to verify the impact of pre- and post-surgical PD on seizure outcome in a series of patients with refractory temporal lobe epilepsy and mesial temporal sclerosis (TLE-MTS). METHOD: Data from 115 TLE-MTS patients (65 females; 56.5%) who underwent cortico-amygdalohippocampectomy (CAH) were analyzed. Pre- and post-surgical psychiatric evaluations were performed using DSM-IV and ILAE criteria. The outcome subcategory Engel IA was considered as corresponding to a favorable prognosis. A multivariate logistic regression model was applied to identify possible risk factors associated with a worse seizure outcome. RESULTS: Pre-surgical PDs, particularly major depressive disorder (MDD), anxiety and psychotic disorders, were common, being found in 47 patients (40.8%). Fifty-six patients (48.7%) were classified as having achieved an Engel IA one year after CAH. According to the logistic regression model, the presence of pre-surgical MDD (OR=5.23; p=0.003) appeared as the most important risk factor associated with a non-favorable seizure outcome. CONCLUSION: Although epilepsy surgery may be the best treatment option for patients with refractory TLE-MTS, our findings emphasize the importance of performing a detailed psychiatric examination as part of the pre-surgical evaluation protocol.

Surgical and postmortem pathology studies: contribution for the investigation of temporal lobe epilepsy.

Pathology studies in epilepsy patients bring useful information for comprehending the physiopathology of various forms of epilepsy, as well as aspects related to response to treatment and long-term prognosis. These studies are usually restricted to surgical specimens obtained from patients with refractory focal epilepsies. Therefore, most of them pertain to temporal lobe epilepsy (TLE) with mesial temporal sclerosis (MTS) and malformations of cortical development (MCD), thus providing information of a selected group of patients and restricted regions of the brain. Postmortem whole brain studies are rarely performed in epilepsy patients, however they may provide extensive information on brain pathology, allowing the analysis of areas beyond the putative epileptogenic zone. In this article, we reviewed pathology studies performed in epilepsy patients with emphasis on neuropathological findings in TLE with MTS and MCD. Furthermore, we reviewed data from postmortem studies and discussed the importance of performing these studies in epilepsy populations.

Temporal lobe epilepsy with mesial temporal sclerosis: hippocampal neuronal loss as a predictor of surgical outcome.

OBJECTIVE: To analyze retrospectively a series of patients with temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS), and the association of patterns of hippocampal sclerosis with clinical data and surgical prognosis. METHOD: Sixty-six patients with medically refractory TLE with unilateral MTS after anterior temporal lobectomy were included. Quantitative neuropathological evaluation was performed on NeuN-stained hippocampal sections. Patient's clinical data and surgical outcome were reviewed. RESULTS: Occurrence of initial precipitating insult (IPI), as well as better postoperative seizure control (i.e. Engel class 1), were associated with classical and severe patterns of hippocampal sclerosis (MTS type 1a and 1b, respectively). CONCLUSION: Quantitative evaluation of hippocampal neuronal loss patterns predicts surgical outcome in patients with TLE-MTS.

Granule cell dispersion is associated with memory impairment in right mesial temporal lobe epilepsy.

PURPOSE: We analyzed the association of granule cell dispersion (GCD) with memory performance, clinical data and surgical outcome in a series of patients with mesial temporal lobe epilepsy (MTLE) and mesial temporal sclerosis (MTS). METHOD: Hippocampal specimens from 54 patients with MTLE (27 patients with right MTLE and 27 with left MTLE) and unilateral MTS, who were separated into GCD and no-GCD groups and thirteen controls were studied. Quantitative neuropathological evaluation was performed using hippocampal sections stained with NeuN. Patients' neuropsychological measures, clinical data, type of MTS and surgical outcome were reviewed. RESULTS: GCD occurred in 28 (51.9%) patients. No correlation between GCD and MTS pattern, clinical data or surgical outcome was found. The presence of GCD was correlated with worse visuospatial memory performance in right MTLE, but not with memory performance in left MTLE. CONCLUSION: GCD may be related to memory impairment in right MTLE-MTS patients. However, the role of GCD in memory function is not precisely defined.

Intracranial depth electrodes implantation in the era of image-guided surgery.

The advent of modern image-guided surgery has revolutionized depth electrode implantation techniques. Stereoelectroencephalography (SEEG), introduced by Talairach in the 1950s, is an invasive method for three-dimensional analysis on the epileptogenic zone based on the technique of intracranial implantation of depth electrodes. The aim of this article is to discuss the principles of SEEG and their evolution from the Talairach era to the image-guided surgery of today, along with future prospects. Although the general principles of SEEG have remained intact over the years, the implantation of depth electrodes, i.e. the surgical technique that enables this method, has undergone tremendous evolution over the last three decades, due the advent of modern imaging techniques, computer systems and new stereotactic techniques. The use of robotic systems, the constant evolution of imaging and computing techniques and the use of depth electrodes together with microdialysis probes will open up enormous prospects for applying depth electrodes and SEEG both for investigative use and for therapeutic use. Brain stimulation of deep targets and the construction of "smart" electrodes may, in the near future, increase the need to use this method.