Jaderson da Costa

AM251, a selective antagonist of the CB1 receptor, inhibits the induction of long-term potentiation and induces retrograde amnesia in rats

Long-term potentiation (LTP) has a long history as putative mechanism of memory formation, specially in the hippocampus, a structure essential for memory formation. Endocannabinoids are one of the endogenous systems that modulate this plasticity event: the activation of hippocampal CB1 receptors may inhibit local GABA release. Here, we have studied both (1) the role of the selective CB1 antagonist AM251 upon LTP induction in a hippocampal slice preparation, and (2) the effect of its intrahippocampal administration in the step-down inhibitory avoidance (IA) and the open field habituation tasks (OF). Standard extracellular electrophysiology techniques were used to record field excitatory postsynaptic potentials from the dendritic region of CA1 neurons in response to a high frequency stimulation of Schaffers collaterals; a micropipette ejected 0.2 microM of AM251 (in DMSO/PBS) 2 min before the stimulus: LTP was induced and lasted more than 30 min in the control, but not in the AM251-treated group. Immediately after training, either in IA (footshock, 0.5 mA) or OF, animals received a bilateral infusion of 0.55 or 5.5 ng/side of AM251 or its vehicle in the CA1 region, and test was performed 24 h later. AM251 has caused a significative decrease in the test step-down latency when compared to the control group, but no differences were detected in the OF task, including the number of crossings, i.e., there were no motor effects. The LTP supression could be caused by AM251 acting over GABAergic interneurons that modulate the LTP-bearing glutamatergic neurons. Endocanabinoids would then be the natural dis-inhibitors of local plasticity in the dorsal hippocampus, and the amnestic action of AM251 would be due to a disruption of this endogenous modulatory system.

Functional variability of the human cortical motor map: Electrical stimulation findings in perirolandic epilepsy surgery

&NA; The purpose of this study was to assess the cortical representation of sensorimotor functions in patients undergoing perirolandic epilepsy surgery, focusing on somatotopy, mosaicism, and variability of function in relation to the classic motor homunculus. The authors studied 36 patients in whom intraoperative or extraoperative electrical cortical stimulation to map motor functions was performed. A computer program was devised to register electrode number, stimulation parameters, and response to each stimulus. Electrode position was represented graphically whenever a stimulus was delivered. A total of 43 maps from 36 patients were analyzed. The authors found variations in the organization of M1 (primary motor cortex) in seven patients (19.4%). Four patients (11.1%) presented mosaicism (overlapping of functional areas), two (5.6%) presented variability (inverted disposition of M1 functional areas), and one (2.8%) had both. The results of this study challenge the notion of orderly topographic relationships between the human sensorimotor functions and their representation in the primary motor cortex. These results confirm those of other studies with animals and humans using novel imaging techniques, suggesting that the motor homunculus may not always be considered a definite and absolute representation of M1.

Duration of rhythmic EEG patterns in neonates: new evidence for clinical and prognostic significance of brief rhythmic discharges.

OBJECTIVEnThis study aimed at identifying the characteristics - especially the duration - of rhythmic discharges in neonatal EEG, and their association with clinical neonatal problems. Specifically, we aimed at testing the diagnostic and prognostic validity of using 10 s as minimal duration for defining electroencephalographic seizures.nnnDESIGN AND METHODSnThe polysomnographies of 340 neonates were reviewed, and episodes of rhythmic discharges were identified, analyzed, and quantified. The study sample was divided into 3 groups: one in which the maximal duration of rhythmic discharges was shorter than 10 s (brief rhythmic discharges, BRD), a second one in which there were rhythmic discharges longer than 10 s (long rhythmic discharges, LRD), and finally a group in which no rhythmic discharge was found (No-RD). These 3 groups of subjects were compared for the baseline and outcome clinical data.nnnRESULTSnFrom the 340 neonates studied, 210 did not present any form of rhythmic discharge, 67 (19. 7%) had only BRD episodes, and 63 (18.5%) had at least one LRD episode. Prevalence of rhythmic discharges was low among healthy full term newborns, and was significantly higher among preterm and high-risk newborns. Electrophysiological characteristics of rhythmic discharges did not differ between healthy neonates and high-risk ones. Accompanying clinical manifestations were present in 26.3% of the LRD group, but also in 15.9% of the BRD group. The presence of BRD was significantly associated with leukomalacia and with hypoglycemia in the cross-sectional analysis of baseline data, and with an increased risk for abnormal neurodevelopmental outcome after a mean follow-up period of 47 months (adjusted relative risk=4.90, P<0.01).nnnCONCLUSIONSnThe present data demonstrate an association between BRD and clinical history of hypoxic-ischemic encephalopathy, especially when complicated by leukomalacia, and also with a prognosis of increased risk for abnormal neurodevelopmental outcome. The clinical and prognostic significance of isolated BRD justifies the need to include these brief episodes in future studies of neonatal seizures.

Localization of the Epileptogenic Zone by Ictal and Interictal SPECT with 99mTc‐Ethyl Cysteinate Dimer in Patients with Medically Refractory Epilepsy

Summary: Purpose: To evaluate the accuracy, feasibility and clinical value of both ictal and interictal 99mTc‐ethyl cysteinate dimer (ECD) single photon emission computed tomography (SPECT) in patients with medically refractory epilepsy.

Polysomnography in neonatal seizures

Seizures are one of the most frequent problems in the neonatal period, and are frequently associated with high mortality and morbidity rates. On the other hand, neonatal seizures may represent a first or even the only sign of central nervous system dysfunction. However, establishing the diagnosis of neonatal seizures poses several problems, and clinical observation is not sufficient in many cases. Neonatal polysomnography is a valuable tool both in the diagnostic and in the prognostic assessment of neonatal seizures. The present text reviews some technical aspects related to neonatal polysomnographies, and its usefulness in the area of suspected neonatal seizures. Moreover, some questions are raised regarding rhythmic discharges and their significance as a possible ictal and interictal epileptic pattern in the neonate.

Selective posterior callosotomy for drop attacks: A new approach sparing prefrontal connectivity

Objective: To evaluate a novel approach to control epileptic drop attacks through a selective posterior callosotomy, sparing all prefrontal interconnectivity. Methods: Thirty-six patients with refractory drop attacks had selective posterior callosotomy and prospective follow-up for >4 years. Falls, episodes of aggressive behavior, and IQ were quantified. Autonomy in activities of daily living, axial tonus, and speech generated a functional score ranging from 0 to 13. Subjective effect on patient well-being and caregiver burden was also assessed. Results: Median monthly frequency of drop attacks decreased from 150 to 0.5. Thirty patients (83%) achieved either complete or >90% control of the falls. Need for constant supervision decreased from 90% to 36% of patients. All had estimated IQ below 85. Median functional score increased from 7 to 10 (p = 0.03). No patient had decrease in speech fluency or hemiparesis. Caregivers rated the effect of the procedure as excellent in 40% and as having greatly improved functioning in another 50%. Clinical, EEG, imaging, and cognitive variables did not correlate with outcome. Conclusions: This cohort study with objective outcome assessment suggests that selective posterior callosotomy is safe and effective to control drop attacks, with functional and behavioral gains in patients with intellectual disability. Results are comparable to historical series of total callosotomy and suggest that anterior callosal fibers may be spared. Classification of evidence: This study provides Class III evidence that selective posterior callosotomy reduces falls in patients with epileptic drop attacks.

Neuropatologia das epilepsias de difícil controle: estudo de 300 casos consecutivos

We report histopathological findings in 300 consecutive surgical specimens from epilepsy surgery during 6 years. Our material was mainly from temporal lobe epilepsy (70.33%). In 44% the diagnosis was hippocampal sclerosis. There were tumors in 15% of cases and neuronal migration disorders in 10%. The most common tumors were gangliogliomas (42.22%) and dysembryoplastic neuroepithelial tumors (20%). We review the more frequent diagnosis in epilepsy surgery based on this series and comparing with literature.We report histopathological findings in 300 consecutive surgical specimens from epilepsy surgery during 6 years. Our material was mainly from temporal lobe epilepsy (70.33%). In 44% the diagnosis was hippocampal sclerosis. There were tumors in 15% of cases and neuronal migration disorders in 10%. The most common tumors were gangliogliomas (42.22%) and dysembryoplastic neuroepithelial tumors (20%). We review the more frequent diagnosis in epilepsy surgery based on this series and comparing with literature.

Corpora amylacea in temporal lobe epilepsy associated with hippocampal sclerosis

UNLABELLEDnHippocampal sclerosis (HS) is the commonest pathology in epileptic patients undergoing temporal lobe epilepsy surgery. Beside, there are an increased density of corpora amylacea (CA) founded in 6 to 63% of those cases.nnnOBJECTIVEnverify the presence of CA and the clinical correlates of their occurrence in a consecutive series of patients undergoing temporal surgery with diagnosis of HS.nnnMETHODnWe reviewed 72 hippocampus specimens from January 1997 to July 2000. Students t test for independent, samples, ANOVA and Tukey test were performed for statistical analysis.nnnRESULTSnCA were found in 35 patients (49%), whose mean epilepsy duration (28.7 years) was significantly longer than that group of patients without CA (19.5 years, p=0.001). Besides, when CA were found, duration was also significantly correlated with distribution within hippocampus: 28.7 years with diffuse distribution of CA, 15.4 with exclusively subpial and 17.4 years with distribution subpial plus perivascular (p=0.001).nnnCONCLUSIONnOur findings corroborate the presence of CA in patients with HS and suggest that a longer duration of epilepsy correlate with a more distribution of CA in hippocampus.

Associated and prognosis in apparent life threatening events (ALTE)

OBJECTIVE: To verify the etiology and prognosis of ALTE in infancy and its possible relationship to Sudden Infant Death Syndrome (SIDS). METHODS: We studied a group of infants that presented ALTE episodes and were evaluated in our hospital. First we reviewed their clinical history and polysomnographies, then we sent a letter to the families with questions regarding the outcome. RESULTS: 56 patients were included. 92% had ALTE during their first 6 months and 83% in the first trimester. Symptomatic ALTE predominated (71%). The disease most frequently associated was gastroesophageal reflux, followed by neurological diseases. The follow up showed 51.5% of normal outcome, 4 children repeated ALTE, no cases of SIDS were registered. CONCLUSIONS: Our results showed that multifactorial etiologies can be associated to ALTE, and the outcome is generally related to the associated disease. We did not observe any relationship between ALTE and SIDS considering a predominantly symptomatic ALTE population.

Seizures in the neonatal period

OBJECTIVE: To characterize and differentiate neonatal seizures from those that occur at different ages, based on a critical assessment of the available literature and also on the authorś clinical experience. SOURCES: Literature review, including up-to-date and classical studies that helped us to better understand clinical, neurophysiological and physiopathological aspects related to seizures in the newborn. SUMMARY OF THE FINDINGS: The authors present clinical and electroencephalographic characteristics of neonatal seizures, discuss their classification, treatment and prognosis. CONCLUSIONS: Neonatal seizures have a distinct clinical pattern, which justifies the necessity of an appropriate classification. The etiology is predominantly symptomatic and multifactorial; the treatment should follow a routine protocol, and the prognosis seems to be closely related to etiology.