Carlos Alberto Mantovani Guerreiro

Antiepileptic drug response in temporal lobe epilepsy A clinical and MRI morphometry study

Objective: To investigate the relationship between brain MRI and clinical characteristics and patterns of antiepileptic drug (AED) response in patients with mesial temporal lobe epilepsy (MTLE). Methods: A total of 165 MTLE patients were divided into seizure-free with AED (AED responders, n = 50), pharmacoresistant (n = 87), and remitting-relapsing seizure control group (n = 28). All groups were evaluated regarding age, frequency of seizures, and age at epilepsy onset, duration of epilepsy, febrile seizures, presence and side of hippocampal atrophy (HA), and initial precipitating injuries. For gray matter (GM) MRI voxel-based morphometry (VBM) we selected only patients with unilateral HA on visual MRI analysis (n = 100). Comparisons were made between all groups and 75 healthy controls. Results: Age at epilepsy onset was lower (p = 0.005) and initial frequency of seizures was higher in the pharmacoresistant compared with the other 2 groups (p = 0.018). All groups showed GM atrophy compared to controls in ipsilateral hippocampus, bilateral parahippocampal gyri, frontal, occipital, parietal, and cerebellar areas. In the AED responders group, such findings were more restricted to areas ipsilateral to the epileptic focus and more widespread in the pharmacoresistant and remitting-relapsing groups. VBM pairwise comparisons showed areas with GM volume reduction in the pharmacoresistant and remitting-relapsing groups compared with AED responders in bilateral periorbital frontal (p < 0.01), cingulum (p < 0.05), and temporal lobe contralateral to the epileptic focus (p < 0.05). Conclusions: Pharmacoresistant and remitting-relapsing groups presented a similar pattern of GM atrophy, which was more widespread compared with AED responders. Conversely, age at epilepsy onset was lower and initial seizure frequency was higher in pharmacoresistant patients.

Dynamic changes in white and gray matter volume are associated with outcome of surgical treatment in temporal lobe epilepsy

BACKGROUND The reasons for surgical failure in 30% of patients with unilateral mesial temporal lobe epilepsy (MTLE) are still unclear. We investigated if different outcomes could be associated to different patterns of subtle gray matter atrophy (GMA) and white matter atrophy (WMA), and searched for postoperative magnetic resonance imaging (MRI) changes. METHODS We studied 69 controls and 67 operated patients with refractory unilateral MTLE. Patients were grouped as seizure-free (SF) group (34 patients Engels IA), worthwhile improvement group (23 patients, Engels IB-IIA) and failure group (10 patients Engels IIB-IV). We created a voxel-based morphometry/MATLAB code to mask the surgical lacuna, and performed t-test and paired t-test to evaluate preoperative and postoperative MRI scans. RESULTS Failure group showed a widespread pattern of preoperative GMA. On SF and improvement groups we identified a more restricted pattern of GMA. The three groups presented a widespread, bilateral pattern of WMA. In contrast, postoperative analyses showed bilateral hemispheric recovery (a relative increase of WM concentration) on SF and improvement groups, but few changes on failure group. We also identified areas with relative postoperative increase of GM on both SF and improvement groups, more widespread on SF group. CONCLUSION Areas of subtle GMA may be related to poorer surgical outcome. In addition, we demonstrated a postoperative relative increase of WM and GM concentration associated with seizure control. These changes may represent neuroplasticity related to improvement of brain function after seizure control. Further studies with a multimodal approach may help to predict surgical outcome and improve selection of patients for surgical treatment of MTLE.

Efficacy of clobazam as add-on therapy in patients with refractory partial epilepsy.

Summary:  Purpose: Clobazam (CLB) has an important antiepileptic effect and is less expensive than the new antiepileptic drugs (AEDs), but still has not been considered as first‐line drug in the treatment of epilepsy. We evaluated the efficacy of CLB as add‐on therapy in patients with refractory partial epilepsy.

Assessment of the epilepsy treatment gap in two cities of south-east of Brazil.

OBJECTIVE To assess the epilepsy treatment gap in Campinas and São Josédo Rio Preto, two cities in the State of São Paulo, Brazil. METHOD The treatment gap was estimated using the formula n1-n2/n1x100, where n1 was calculated using 1.86% prevalence and represented the number of individuals with epilepsy, while n2 represented the number of people who could be treated with an adult standard dose for a year utilizing the antiepileptic drugs supplied by the public health system. RESULTS Our estimates revealed that in 2001, approximately 50% of the population with epilepsy was treated with the recommended antiepileptic medication. CONCLUSION These results suggest that a relevant percentage of patients with epilepsy are not untreated. Further epidemiological studies are needed to investigate the reasons for this treatment gap so that interventions can reduce this gap and improve the quality of life of patients with epilepsy.

Quality of life in pregnant women with epilepsy versus women with epilepsy

It is assumed that 25% of patients with epilepsy are women of fertile age and 0.3% to 0.6% of all children are born of mothers with epilepsy. The aim of this study was to evaluate the quality of life on pregnant with epilepsy and compare with non-pregnant women with epilepsy. We evaluated two groups (Experimental Group--29 pregnant women with epilepsy and Control Group--30 women with epilepsy); they were attended at the HC/UNICAMP. The patients had three meetings to carry out and implement the anamnesis and the application of QQV-65. There were no significant differences in the measurement of quality of life when comparing both groups. However, when we analyzed individually in the pre- and post-partum periods, we observed significant differences in health aspects (p=0.0495), physical (p=0.02868) and emotional (p=0.0253) dimensions in QQV-65. This study shows that pregnancy could be interpreted as a stressor. In late pregnancy when this stressor was removed, women with epilepsy had improvement in their quality of life.

Vigabatrin in refractory childhood epilepsy. The Brazilian multicenter study

Children, 47, with various types of severe drug-resistant epilepsy were entered into a prospective, add-on, open trial with vigabatrin. Patients with West syndrome and idiopathic generalized epilepsies were excluded. Seven children had the drug withdrawn, five because of increase in seizure frequency and two because of adverse effects. Drug efficacy, measured according to seizure type, showed a 100% decrease in seizure frequency in 18.6% of partial seizures and 17.3% of the generalized seizures. There was a higher than 50% decrease in 39.5% of partial and 60.8% of generalized seizures, and less than 50% decrease or increase in seizure frequency in 41.8% and 21.8% of partial and generalized seizures, respectively. Vigabatrin mean dosage during phase 3 was 63.6 mg/kg per day (S.D. = 30.5), ranging from 19.3 to 110.5 mg/kg per day. Parametric statistical analysis (Students t-test) of seizure frequency between phases 1 and 3 showed a significant decrease in seizure frequency for partial (P = 0.022), and generalized seizures (P < 0.0001). Drug-related adverse effects were observed in 18/47 cases (38.3%), consisting mainly of irritability, hyperactivity, dizziness, somnolence and gastrointestinal symptoms.

Neurobrucelose: relato de três casos

Sao relatados dois casos de meningomielite brucelotica e um terceiro caso de hemorragia parenquimatosa e leptomeningite cronica com descricao anatomopatologica. Os autores destacam as formas clinicas e a importância das reacoes imunologicas no diagnostico, assim como a necessidade do diagnostico precose para o tratamento adequado.: Three cases of probable neurobrucellosis are reported. The diagnosis was made on the basis of immunological tests. Two patients with a clinical picture of meningomyelitis showed a definitive clinical improvement under tetracycline and streptomycin therapy. The immunological reactions found in the record case were even more positive in the spinal fluid than in the blood. In the case 3 with a clinical presentation of cerebral hemorrhage the histopathological studies demonstrated non specific chronic leptomeningitis and local hemorrhages in the caudate nucleus bilaterally. The diagnose and treatment of neurobrucellosis are discussed, stressing the importance of an early therapy.

Circadian rhythm and profile in patients with juvenile myoclonic epilepsy and temporal lobe epilepsy

OBJECTIVE This study intended to compare the circadian rhythm and circadian profile between patients with juvenile myoclonic epilepsy (JME) and patients with temporal lobe epilepsy (TLE). METHOD We enrolled 16 patients with JME and 37 patients with TLE from the Outpatient Clinic of UNICAMP. We applied a questionnaire about sleep-wake cycle and circadian profile. RESULTS Fourteen (87%) out of 16 patients with JME, and 22 out of 37 (59%) patients with TLE reported that they would sleep after seizure (p < 0.05). Three (19%) patients with JME, and 17 (46%) reported to be in better state before 10:00 AM (p < 0.05). CONCLUSION There is no clear distinct profile and circadian pattern in patients with JME in comparison to TLE patients. However, our data suggest that most JME patients do not feel in better shape early in the day.

Surgery for refractory mesial temporal lobe epilepsy: prognostic factors and early, rather than late, intervention.

Mesial temporal lobe epilepsy (MTLE) is the most prevalent refractory epilepsy in adolescents and adults, and its pathologic hallmark is classic hippocampal sclerosis. There is the strongest level of evidence (Level A) to indicate surgical treatment for refractory unilateral MTLE1. The study presented by Jardim et al.2 is important because it confirms the relationship between prognostic factors of surgery for unilateral MTLE and the pathologic findings. The best postoperative seizure control (i.e. Engel class 1) was associated with classic and severe patterns of hippocampal sclerosis (types 1a and 1b, respectively), as well as the presence of an initial precipitating injury2. The three patients with normal hippocampal findings were associated with poor outcome. This point is still controversial in the literature. In general, outcome is poorer in patients without hippocampal neuronal cell loss (no hippocampal sclerosis). Nowadays, modern imaging with resonance techniques offers a very useful and safe way to check this point. The study also reassures in that more than two thirds of the patients became seizure free for at least six months, which is considered a short follow-up. This outcome is compatible with the literature and it is considered a very successful outcome. The concept of a medical refractory epilepsy patient is defined as the failure of adequate trials of two tolerated, appropriately chosen and used, antiepileptic drug schedules (either as monotherapies or in combination) to achieve sustained seizure freedom3. Therefore, it is possible to make the diagnosis of refractory MTLE relatively quickly. Unfortunately, patients are operated on after 20 years of seizures, as confirmed by data in the article by Jardim et al.2. This astonishing fact occurs not only in Brazil, but also in other organized countries, such as the USA. A recent study has shown that early referral for surgery is tremendously advantageous for the patients in order to avoid irreversible, disabling social, and psychological consequences of recurrent seizures, as well as minimizing the risk of premature death4. We do hope that our fellow neurologists are aware of this important information and that all patients with refractory epilepsy are referred to an epilepsy center to determine if they might be candidates for surgery. Professor Titular do Departamento de Neurologia da Faculdade de Ciências Médicas da Universidade de Campinas (UNICAMP), Campinas SP, Brazil.

Hippocampal dysplasia with balloon cells: case report and discussion on classification

The International League Against Epilepsy (ILAE) has proposed a classification for focal cortical dysplasia (FCD), in which lesions with cortical dyslamination, dysmorphic neurons and balloon cells are considered as Type IIB. Blurring of gray–white matter junction and subcortical hyperintense T2/FLAIR signal are the main MRI findings of FCD Type IIB [1]. This classification, however, focuses mainly on neocortical alterations. Here, we report a case of hippocampal dysplasia with balloon cells (HD-bc) and discuss its valuation based on ILAE classification. A 12-year-old boy presented with short daily episodes of epigastric pain over 4 years, subsequently followed by episodes of confusion and oral automatisms identified as seizures. There was no history of perinatal complications, acquired deficits, febrile seizures or head trauma. Physical and neurological exams were normal. Electroencephalography showed interictal epileptiform discharges over the right temporal region. MRI revealed increased volume of right hippocampus with T2-weighted hyperintense signal (Fig. 1). Neuropsychological testing showed normal intelligence quotient and bilateral language representation. Based on these findings and refractoriness to four antiepileptic drugs (AEDs), a temporal lobectomy was performed. After 1 year of follow-up, he initially reported auras only and has been seizure-free for 6 months on AEDs. On neuropathological examination, hematoxylin and eosin-stained (HE however, it may be underdiagnosed. To our knowledge, four cases were previously F. Rogerio and M. E. Morita contributed equally to the manuscript.