Vera C. Terra

Midbrain substrates of audiogenic seizures in rats

Audiogenic seizures (AS) are a rodent model of generalized tonic-clonic seizures, induced in susceptible (S) animals by high intensity (110 dB) acoustic stimulation. Resistant (R) animals do not respond to the sound with any seizure-related behavior, but they display facial automatisms and grooming clusters. Genetic selection and neuroethology are the basic tools used in our laboratory to perform behavioral analysis of AS S and R animals. Based upon selective lesion and microinjection (GABA, clobazam, NMDA) studies of substantia nigra (SN), inferior colliculus (IC), superior colliculus (SC), and on specific knife cuts at midcollicular levels, we have suggested differential roles for these substrates in the origin and spreading of AS. The IC central nucleus is suggested to be the most critical area involved in the afferent pathway whose activation is necessary for AS origin. IC cortical nuclei seem to be the most important structures involved in the transduction of sensory to motor activity. SC, SN and other reticular subnuclei are suggested to be modulators or components of the efferent pathway. Although the midbrain is considered to be the only network necessary for acute AS origin, both emotion-linked acoustic memories and plastic changes linked to audiogenic kindling involve midbrain-forebrain connections. This paper reviews the behavioral manifestations of acute and chronic AS, our contribution to the knowledge of some AS neurobiological midbrain substrates and the suggested implications of midbrain-forebrain interactions typical of AS kindling.

Do psychiatric comorbidities predict postoperative seizure outcome in temporal lobe epilepsy surgery

Clinical and demographic presurgical variables may be associated with unfavorable postsurgical neurological outcome in patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). However, few reports include preoperative psychiatric disorders as a factor predictive of long-term postsurgical MTLE-HS neurological outcome. We used Engels criteria to follow 186 postsurgical patients with MTLE-HS for an average of 6 years. DSM-IV criteria and psychiatric comorbidity criteria specific to epilepsy (interictal dysphoric disorder, postictal and interictal psychosis) were used to assess presurgical psychiatric disorders. Kaplan-Meier event-free survival and adjusted hazard ratios were estimated with unconditional logistic regression. Seventy-seven (41.4%) patients had a preoperative Axis I psychiatric diagnosis. Thirty-six patients had depression, 11 interictal dysphoric disorder, 14 interictal psychosis, 6 postictal psychosis, and 10 anxiety disorders. Twenty-three (12.4%) patients had Axis II personality disorders. Regarding seizure outcome, preoperative anxiety disorders (P=0.009) and personality disorders (P=0.003) were positively correlated with Engel class 1B (remaining auras) or higher. These findings emphasize the importance of presurgical psychiatric evaluation, counseling, and postsurgical follow-up of patients with epilepsy and psychiatric disorders.

New insights into behavioral evaluation of audiogenic seizures. A comparison of two ethological methods.

Wistar male rats were tested for susceptibility to audiogenic seizures (AS) and classified into sensitive (S) and resistant (R) groups by means of a severity index (SI). Susceptible animals were those which displayed wild running behavior (gyri, jumping and atonic falling) followed by generalized tonic-clonic seizures and consequently had an SI = 0.85 (maximum; n = 10). Resistant animals were considered those with no convulsive response to the acoustic stimulation having an SI = 0 (n = 10). Behavioral sequences of susceptible and resistant animals were recorded and analyzed using two ethological methods which basically considered behavior item frequency and statistical interactions of sequential patterns. Both methods include the concept of cluster analysis but do not include a simultaneous analysis of behavior frequency and time spent in each behavior. Thus, a third method is proposed to graphically display both frequency and temporal patterns in a more complex cluster analysis. The methods discussed here allow comparisons of behavioral sequences in a given experimental situation such as susceptible against resistant animals, acute and chronic seizures, comparison of pre- and postdrug effects, etc. Consequently, they may be the micro-behavioral substrate for correlation with contemporary molecular analysis of epileptic seizures.

NMDA-dependent audiogenic seizures are differentially regulated by inferior colliculus subnuclei.

Wistar rats were classified as susceptible (S) and resistant (R) to audiogenic seizures (AS) by evaluation of their response to high intensity sound stimulation (110.3 dB). R rats usually do not respond with any convulsive behavior to sound stimulation, whereas S animals develop a complex wild running sequence plus tonic-clonic seizure patterns after sound stimulation. Thus, R rats were injected with phosphate buffer (PB; 0.2 microliter) or N-methyl-D-aspartate (NMDA) in three different doses (2.0 micrograms, 2.5 micrograms and 3.0 micrograms/0.2 microliter) into central ventral or cortical dorsal inferior colliculus (IC) nuclei. Dose-response curves were evaluated by means of an ethological method in which behavioral sequences typical of S and R animals were quantitated. Animals displayed more severe spontaneous audiogenic-like seizures with the dose of 2.5 micrograms/0.2 microliter NMDA, which were potentiated by the acoustic stimulus. Significant differences were apparent between central and cortical nuclei and more severe seizures were observed in IC cortical microinjected animals. These audiogenic seizures were blocked with microinjections of 2-amino-7-phosphono-heptanoate (AP7) applied just before 2.5 micrograms NMDA microinjections into central or cortical nuclei. In S rats, AP7 totally blocked AS when microinjected into the central IC and partially, but significantly, blocked AS when applied into the cortical IC nucleus. In the last case, wild running was still present in 100% of the animals after AP7 treatment. These data may suggest an NMDA-dependent differential participation of IC subnuclei in the development of AS.

Sudden unexpected death in epilepsy: From the lab to the clinic setting

Sudden unexpected death in epilepsy (SUDEP) is defined as sudden, unexpected, witnessed or unwitnessed, non-traumatic, and non-drowning death in a patient with epilepsy. Sudden unexpected death in epilepsy is probably the most common cause of epilepsy-related deaths. Many predisposing and initiating factors may coexist and contribute to SUDEP, but the mechanisms are poorly understood. Cardiac and respiratory deregulation seems to have a major role in SUDEP. Here, we review several advances in understanding the mechanisms involved in SUDEP.

Qualitative analysis of hippocampal plastic changes in rats with epilepsy supplemented with oral omega-3 fatty acids

Studies have provided evidence of the important effects of omega-3 fatty acid on the brain in neurological conditions, including epilepsy. Previous data have indicated that omega-3 fatty acids lead to prevention of status epilepticus-associated neuropathological changes in the hippocampal formation of rats with epilepsy. Omega-3 fatty acid supplementation has resulted in extensive preservation of GABAergic cells in animals with epilepsy. This study investigated the interplay of these effects with neurogenesis and brain-derived neurotrophic factor (BDNF). The results clearly showed a positive effect of long-term omega-3 fatty acid supplementation on brain plasticity in animals with epilepsy. Enhanced hippocampal neurogenesis and BDNF levels and preservation of interneurons expressing parvalbumin were observed. Parvalbumin-positive cells were identified as surviving instead of newly formed cells. Additional investigations are needed to determine the electrophysiological properties of the newly formed cells and to clarify whether the effects of omega-3 fatty acids on brain plasticity are accompanied by functional gain in animals with epilepsy.

Neuroethological evaluation of audiogenic seizures and audiogenic-like seizures induced by microinjection of bicuculline into the inferior colliculus. I. Effects of midcollicular knife cuts.

Audiogenic seizures (AS) are a model of generalized tonic-clonic seizures. The inferior colliculus (IC) and the GABAergic neurotransmission seems to be the most critical site and neurotransmitter system, respectively, of the auditory midbrain involved in AS origin and development. Thus, audiogenic-like seizures are evoked by GABAA antagonists such as bicuculline (BIC). Wistar audiogenic AS resistant (R) rats were sham-transected through the midcollicular line and microinjected with IC bicuculline (BIC; 80 ng/0.2 microliters) (n = 8); transected through the midcollicular line and microinjected with IC saline 0.9% (n = 8); transected through the cortex above the midcollicular line and microinjected with IC BIC (n = 3); transected through the midcollicular line up to 6.0 mm depth and microinjected with IC BIC (80 ng/0.2 microliters or 120 ng/0.3 microliters (n = 8). Wistar AS susceptible (S) rats were submitted to cortical transections (n = 8) and midcollicular transections (n = 7). Animals were studied by means of an ethological method before and after microinjections and/or transections in order to evaluate possible pathways in the AS-like evoked seizures. Bicuculline-evoked seizures were very similar to those evoked by acoustic stimulation, but lacked the tonic-clonic component. No modification in animal behavior was observed in the presence of sound, once the AS-like behavior was initiated. A small percentage of the animals, however, presented procursive behavior which was increased by sound. The IC BIC-evoked patterns were almost totally blocked by midcollicular but not cortical transections. Furthermore, midcollicular but not cortical transections blocked the tonic-clonic component of AS in genetically S animals without modifying the wild running component. These data suggest that the inferior colliculus-superior colliculus connection may be involved in the sensorimotor transduction necessary for AS-like behaviors.

Neuroethological evaluation of audiogenic seizures and audiogenic-like seizures induced by microinjection of bicuculline into the inferior colliculus. II: Effects of nigral clobazam microinjections

Male Wistar rats were classified as susceptible (S) and resistant (R) to audiogenic seizures (AS) by evaluation of their response to high-intensity sound stimulation (110.3 dB). R rats injected with bicuculline into the inferior colliculus (IC) preferentially displayed audiogenic-like seizures with gyri, jumping and atonic falling, without important tonic-clonic components but with postictal contralateral asymmetry and hyperreactivity. These audiogenic-like seizures were blocked by clobazam microinjection into the substantia nigra (SN) and partially modified by SN vehicle injection. Injection of vehicle or clobazam into the SN of susceptible rats (S) did not modify the occurrence of AS. This may suggest the participation of GABAergic regulation in the development of audiogenic-like seizures in R rats and a defect in GABAergic neurotransmission in S rats.

Notificação compulsória da cisticercose em Ribeirão Preto - SP

Cysticercosis is a severe public health problem in several regions of Asia, Africa and Latin America. Epidemiologic studies based on the frequency of cases observed in specialized neurology, neurosurgery and computed tomography services, at autopsy and in seroepidemiologic studies do not permit the determination of the true prevalence of the disease in the population. The objective of the present study was to investigate the prevalence of cysticercosis by compulsory notification. The coefficient of prevalence was 54 cases/100000 inhabitants in the municipality of Ribeirao Preto. The results also indicated that cysticercosis is not under control in our region since 21% of cases presented the active form of the disease. Compulsory notification proved to be a valuable resource for the epidemiologic study of cysticercosis, also permitting the mapping of more affected areas for a better direction of prevention strategies.

Mothers of children with cerebral palsy with or without epilepsy: a quality of life perspective

Purpose. Disability in a child affects not only the childs life but also the familys life. The aim of our study is to verify the quality of life (QOL) of mothers of disabled children with cerebral palsy (CP) with epilepsy compared with non-epilepsy children evaluated in a Brazilian center. Methods. Thirty mothers of disabled children participated in the study. The control group comprised of 18 healthy mothers of children without disabilities. All mothers agreed to participate in the study. They completed the evaluation forms of the SF-36 health survey, a well-documented, self-administered QOL scoring system. Results. The results of our study support the premise that mothers of children with CP, as a group, have poorer QOL than mothers of not disabled children. Conclusions. We also observed that mothers of children with CP and epilepsy have poorer QOL than mothers of children with CP without epilepsy.