Effects of the endogeneous cannabinoid, anandamide, on neuronal activity in rat hippocampal slices. (57/4971)

1. The arachidonic acid derivative arachidonylethanolamide (anandamide) is an endogeneous ligand of cannabinoid receptors that induces pharmacological actions similar to those of cannabinoids such as delta9-tetrahydrocannabinol (THC). We examined whether anandamide can influence excessive neuronal activity by investigating stimulation-induced population spikes and epileptiform activity in rat hippocampal slices. For this purpose, the effects of anandamide were compared with those of the synthetic cannabinoid agonist WIN 55,212-2 and its inactive S(-)-enantiomer WIN 55,212-3. 2. Both anandamide (1 and 10 microM) and WIN 55,212-2 (0.1 and 1 microM) decreased the amplitude of the postsynaptic population spike and the slope of the field excitatory postsynaptic potential (field e.p.s.p.) without affecting the presynaptic fibre spike of the afferents. At a concentration of 1 microM, WIN 55,212-2 completely suppressed the postsynaptic spike, whereas the S(-)-enantiomer WIN 55,212-3 produced only a slight depression. The CB1 receptor antagonist SR 141716 blocked the inhibition evoked by the cannabinoids. SR 141716 had a slight facilitatory effect on neuronal excitability by itself. 3. Anandamide shifted the input-output curve of the postsynaptic spike and the field e.p.s.p. to the right and increased the magnitude of paired-pulse facilitation indicating a presynaptic mechanism of action. 4. Anandamide and WIN 55,212-2, but not WIN 55,212-3, attenuated both stimulus-triggered epileptiform activity in CA1 elicited by omission of Mg2+ and spontaneously occurring epileptiform activity in CA3 elicited by omission of Mg2+ and elevation of K+ to 8 mM. The antiepileptiform effect of these cannabinoids was blocked by SR 141716. 5. In conclusion, cannabinoid receptors of the CB1 type as well as their endogeneous ligand, anandamide, are involved in the control of neuronal excitability, thus reducing excitatory neurotransmission at a presynaptic site, a mechanism which might be involved in the prevention of excessive excitability leading to epileptiform activity.  (+info)

Actions of brain-derived neurotrophic factor in slices from rats with spontaneous seizures and mossy fiber sprouting in the dentate gyrus. (58/4971)

This study examined the acute actions of brain-derived neurotrophic factor (BDNF) in the rat dentate gyrus after seizures, because previous studies have shown that BDNF has acute effects on dentate granule cell synaptic transmission, and other studies have demonstrated that BDNF expression increases in granule cells after seizures. Pilocarpine-treated rats were studied because they not only have seizures and increased BDNF expression in granule cells, but they also have reorganization of granule cell "mossy fiber" axons. This reorganization, referred to as "sprouting," involves collaterals that grow into novel areas, i.e., the inner molecular layer, where granule cell and interneuron dendrites are located. Thus, this animal model allowed us to address the effects of BDNF in the dentate gyrus after seizures, as well as the actions of BDNF on mossy fiber transmission after reorganization. In slices with sprouting, BDNF bath application enhanced responses recorded in the inner molecular layer to mossy fiber stimulation. Spontaneous bursts of granule cells occurred, and these were apparently generated at the site of the sprouted axon plexus. These effects were not accompanied by major changes in perforant path-evoked responses or paired-pulse inhibition, occurred only after prolonged (30-60 min) exposure to BDNF, and were blocked by K252a. The results suggest a preferential action of BDNF at mossy fiber synapses, even after substantial changes in the dentate gyrus network. Moreover, the results suggest that activation of trkB receptors could contribute to the hyperexcitability observed in animals with sprouting. Because human granule cells also express increased BDNF mRNA after seizures, and sprouting can occur in temporal lobe epileptics, the results may have implications for understanding temporal lobe epilepsy.  (+info)

Activity of neurons in human temporal cortex during identification and memory for names and words. (59/4971)

Extracellular recordings of human temporal cortical neuronal activity during identification and memory for object names or words were obtained from 31 neurons at 18 sites in 12 left language dominant patients undergoing left (10) or right (2) awake craniotomy for epilepsy under local anesthesia. Frequency of activity during identification was compared with perceptual controls, that during the encoding phase of recent memory to identification of the same material. Statistically significant changes in one or more temporal epoch (p < 0.005) of one or more comparisons were present for 27 of the 31 neurons in either hemisphere. Few neurons changed activity in the same direction for both words and names. The instruction to retain an item in recent memory changed activity in most neurons from that during identification of the same material, although the items presented were identical and overtly identified in each task. Any individual neuron usually changed activity in one direction for only one task. There are separate, widely distributed neural networks for identification or recent memory for each type of material. The majority of nearby neurons recorded through the same extracellular microelectrode were related to the networks for different tasks. The temporal characteristics of these changes were also investigated; 31% of the changes were "phasic": temporally related to presentation or response to the item. Most of the remaining neuron changes were sustained throughout a task, often for several minutes. These task-specific sustained changes may reflect effects of thalamo-cortical attentional systems. Individual neurons had both sustained and phasic changes to different tasks.  (+info)

Safe use of valproic acid during pregnancy. (60/4971)

QUESTION: I have an epileptic patient who plans pregnancy. It took us years to control her seizures, and valproic acid seems to be the only way to control them. What is the risk to her fetus? ANSWER: Neural tube defects (NTDs) are the most common of the major anomalies associated with in utero exposure to valproic acid. About 1% to 2% of exposed fetuses suffer adverse effects.  (+info)

Measuring quality of care with routine data: avoiding confusion between performance indicators and health outcomes. (61/4971)

OBJECTIVE: To investigate the impact of factors outside the control of primary care on performance indicators proposed as measures of the quality of primary care. DESIGN: Multiple regression analysis relating admission rates standardised for age and sex for asthma, diabetes, and epilepsy to socioeconomic population characteristics and to the supply of secondary care resources. SETTING: 90 family health services authorities in England, 1989-90 to 1994-5. RESULTS: At health authority level socioeconomic characteristics, health status, and secondary care supply factors explained 45% of the variation in admission rates for asthma, 33% for diabetes, and 55% for epilepsy. When health authorities were ranked, only four of the 10 with the highest age-sex standardised admission rates for asthma in 1994-5 remained in the top 10 when allowance was made for socioeconomic characteristics, health status, and secondary care supply factors. There was also substantial year to year variation in the rates. CONCLUSION: Health outcomes should relate to crude rates of adverse events in the population. These give the best indication of the size of a health problem. Performance indicators, however, should relate to those aspects of care which can be altered by the staff whose performance is being measured.  (+info)

Epilepsy surgery : overview Of forty years experience. (62/4971)

Although many patients with epilepsy achieve control of their seizures with medication, a substantial number ultimately develop intractable epilepsy. Patients with intractable epilepsy form the group for whom surgical procedures may be beneficial. We retrospectively analyzed the clinical profile and outcome of 141 patients operated for intractable epilepsy at Vellore between 1949 and 1990. The operative procedures done for suprasylvian epilepsy were topectomy (24 cases) and lobectomy (2 cases). For temporal lobe epilepsy the surgical procedures done were topectomy (28 cases), temporal lobectomy with amygdalectomy (25 cases), temporal lobectomy with amygdalectomy and hippocampectomy (10 cases), amygdalectomy (15 cases) and topectomy with amygdalectomy in one case. Hemispherectomy was done for 12 cases with multilobe epilepsy. For multifocal epilepsy, four patients underwent stereotactic ansotomy. Post operative complications included infections (10 cases) and acute post operative haematoma in one patient. There was transient neurological deterioration in ten patients. Three patients operated prior to 1960 died due to peri operative complications. Follow up data of 80 patients, ranging from 1 to 42 years (mean 10 years) was analysed. Total or near total seizure control was obtained in 53% patients and a worthwhile outcome in 20% patients. Mental retardation, pre operative scalp electroencephalography and post excision electrocorticography has been shown to be predictors of outcome with respect to seizures.  (+info)

Epileptic psychoses and anticonvulsant drug treatment. (63/4971)

Forty four consecutive patients with epilepsy and psychoses were studied retrospectively for psychotic episodes associated with changes in antiepileptic drug therapy. Twenty seven patients (61%) developed their first episode of psychosis unrelated to changes in their antiepileptic drug regimen. Twenty three of these patients developed psychoses with temporally unrelated changes in seizure frequency. Many patients had chronic schizophrenia-like psychotic symptoms. Seventeen patients (39%) developed their first episode of psychosis in association with changes in their antiepileptic drug regimen. Twelve patients developed psychoses temporally related to seizure attenuation or aggravation. Many of their psychotic symptoms were polymorphic with a single episode or recurrent episodes. No marked differences were found in the various clinical backgrounds between the two groups. In the drug-related group, seven patients developed psychoses after starting add-on therapy with a new antiepileptic drug, six after abruptly discontinuing their drugs, and four after taking an overdose of antiepileptic drugs. Based on the present findings, drug regimens should be changed gradually and compliance should be maintained to prevent epileptic psychoses.  (+info)

Clinical significance of intracranial developmental venous anomalies. (64/4971)

OBJECTIVES: Venous angiomas, or developmental venous anomalies (DVAs), represent the most often occurring cerebral vascular malformation. The clinical significance of a DVA is, however, at present unclear. METHODS: A retrospective analysis was carried out on two series of consecutive cranial MRIs performed between January 1990 and August 1996 in a university department of neuroradiology and in a large radiological private practice. The medical records of all patients in whom a DVA was diagnosed were screened to identify the specific complaint which necessitated the imaging procedure. RESULTS: A total of 67 patients with DVA could be identified. In 12 patients an associated cavernoma was found. The main reason for performing the MRI was the evaluation of seizures or of headaches. In all patients with DVA in whom an intracerebral haemorrhage was diagnosed an associated cavernoma was present at the site of the haemorrhage. None of the 67 patients showed an association between the complaints that led to the MRI and the location of the DVA. CONCLUSIONS: DVAs do not seem to be associated with a specific clinical presentation. In a significant percentage of cases, however, coexisting cavernomas are found which have a defined bleeding potential and should be treated independently of the DVA. This study supports the hypothesis that DVAs are a congenital abnormality of venous drainage without clinical significance.  (+info)