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Somatostatin, beta-endorphin, and prolactin levels in human cerebrospinal fluid during the gamma-vinyl-GABA treatment of patients with complex partial epilepsy.

The anticonvulsant action of the new anticonvulsant drug gamma-vinyl-GABA (GVG) is obviously mediated by elevation of the concentration of GABA in the brain. The effect of GVG administration on other transmitter systems is not fully known in humans. We studied the possible interactions of GVG administration with peptidergic systems. Included in this study were 67 patients with complex partial epilepsy (CPS). The first CSF sample was taken before GVG administration. The second CSF sample was taken after 3 months of GVG treatment (3 g/day). Thereafter half of the responders (50% decrease in seizure frequency or clear improvement in global performance) received 3 g/day and the other half received 1.5 g/day for the next three months, after which the third CSF sample was taken. Somatostatin (SLI), beta-endorphin (beta-EP), and prolactin (PROL) levels in CSF were measured by radioimmunoassay. Total GABA (tGABA) and GVG levels in CSF were measured by high performance liquid chromatography. After 3 months of GVG treatment there was a slight increase in the beta-EP (p = 0.027, Student's paired t-test), which was not found after 6 months of GVG administration. Both SLI and PROL were stable during the study. Peptide levels were not connected to the clinical response to GVG, GVG dosage, or to tGABA levels in the CSF. In conclusion, the elevation of GABA levels in the brain during GVG treatment apparently does not induce long-term interactions with the peptidergic systems studied.

Adult

Effect of gamma-vinyl GABA treatment on cholinergic and aminergic neurotransmission and on cyclic nucleotides in human complex partial epilepsy--a CSF study.

1. Gamma-vinyl GABA (GVG) is a new anticonvulsant drug that enhances levels of GABA in the brain by irreversibly inhibiting GABA transaminase. 2. To further evaluate the effects and mechanism of action of GVG in the human brain, we measured acetylcholinesterase (AChE) activity and levels of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), cyclic nucleotides (cAMP, cGMP), total GABA (TGABA), and GVG in CSF of 78 patients with complex partial epilepsy. The CSF samples were taken at baseline and after 3 months of GVG administration (3 g GVG per day). Thereafter, the responders (= 50% decrease in number of seizures) were divided (double-blind) into two groups that received either 1.5 g or 3 g of GVG per day for the next 3 months. The third CSF sample was taken after this double-blind period. 3. TGABA levels were increased during the GVG treatment (p less than 0.001). In the whole group of patients AChE, HVA, 5-HIAA, and cAMP did not differ from baseline values, cGMP levels were slightly elevated after 3 months of GVG administration (p = 0.019), but were no longer elevated after 6 months. Responders had slightly lower AChE activity than nonresponders (p = 0.041). After 6 months of drug treatment the cGMP levels of patients receiving 1.5 g of GVG did not differ from those receiving 3 g. 4. In conclusion, GVG administration elevates levels of TGABA in the CSF without any clear of constant change to cholinergic and aminergic transmission or effect on cyclic nucleotides. Our study further emphasizes the specific mechanism of action of GVG via GABAergic transmission.

Acetylcholinesterase

Phenacemide therapy of complex partial epilepsy in children: determination of plasma drug concentrations.

We used monotherapy with phenacemide to treat complex partial seizures in 13 children who were refractory to conventional antiepileptic drug therapy. Twelve patients responded with a reduction in seizure frequency, and 5 have been totally seizure free since the start of therapy. Phenacemide therapy was well tolerated with a minimum of untoward side effects and no evidence of irreversible drug toxicity. We developed a rapid and sensitive assay for the determination of plasma phenacemide concentrations by high performance liquid chromatography to monitor drug levels during therapy. Seizure control was achieved at plasma drug levels that ranged from 16 to 75 micrograms/ml. The median effective dose in our series was 52 micrograms/ml. The recurrence of seizures in three patients was, in each case, associated with trough plasma phenacemide levels below 50 micrograms/dl.

Adolescent

Fentanyl-induced electrocorticographic seizures in patients with complex partial epilepsy.

Although electrical seizure activity in response to opioids such as fentanyl has been well described in animals, scalp electroencephalographic (EEG) recordings have failed to demonstrate epileptiform activity following narcotic administration in humans. The purpose of this study was to determine whether fentanyl is capable of evoking electrical seizure activity in patients with complex partial (temporal lobe) seizures. Nine patients were studied in whom recording electrode arrays had been placed in the bitemporal epidural space several days earlier to determine which temporal lobe gave rise to their seizures. The symptomatic temporal lobe was localized by correlating clinical and electrical seizure activity obtained during continuous simultaneous videotape and epidural EEG monitoring. In each patient, clinical seizures and electrical seizure activity were consistently demonstrated to arise unilaterally from one temporal lobe (four on the right, five on the left). During fentanyl induction of anesthesia in preparation for secondary craniotomy for anterior temporal lobectomy, eight of the nine patients exhibited electrical seizure activity at fentanyl doses ranging from 17.7 to 35.71 micrograms.kg-1 (mean 25.75 micrograms.kg-1). More importantly, four of these eight seizures occurred initially in the "healthy" temporal lobe contralateral to the surgically resected lobe from which the clinical seizures had been shown to arise. These findings indicate that, in patients with complex partial seizures, moderate doses of fentanyl can evoke electrical seizure activity. The results of this study could have important implications for neurosurgical centers where electrocorticography is used during surgery for the purpose of determining the extent of the resection.

Adult

The magnetic field of epileptic spikes agrees with intracranial localizations in complex partial epilepsy.

The magnetoencephalogram (MEG) and electroencephalogram (EEG) were measured during interictal epileptic spikes in nine patients with complex partial seizures. The MEG localization estimates were compared with localizations by intraoperative cortical electrodes, subdural electrodes, stereotaxic depth electrodes, anatomic imaging, postoperative pathologic analysis, and postoperative follow-up. In all patients, MEG localization estimates were in the same lobe as the epileptic focus determined by invasive methods and EEG. In two patients, it was possible to quantify precisely the accuracy of MEG localization by mapping a spike focus that was visually indistinguishable on MEG and cortical recordings. In both patients, MEG localization was approximately 12 mm from the center of the cortical spike focus on intracranial recordings. In eight patients, MEG showed tangential dipolar field patterns on the spontaneous record, but EEG did not. In one patient, a cortical epileptic discharge was detected only on MEG for some discharges and only on EEG for other discharges. The MEG did not detect deep spikes with present levels of environmental noise.

Brain

Auditory/verbal and visual/spatial memory in children with complex partial epilepsy of temporal lobe origin.

Two groups of epileptic children and a normal control group were administered a Comprehensive Children's Memory Scale (Experimental Edition) which is presently being developed by this author. The first experimental group consisted of 12 children having complex partial seizures of left temporal origin and the second group consisted of 12 children having partial complex seizures of right temporal lobe origin based upon clinical description and EEG/neuroimaging verification. Results indicated: (a) Children with left temporal lobe epilepsy demonstrated significantly lower performance than controls on auditory/verbal memory testing. (b) Children with right temporal lobe epilepsy demonstrated significantly lower performance than controls on visual/spatial memory testing. (c) For the most part, the right and left temporal lobe groups did not significantly differ from each other. However, their performance was in the expected direction; i.e., children with left temporal lobe epilepsy scored lower than right temporal lobe epileptics on auditory/verbal memory testing, and children with right temporal lobe epilepsy scored lower than left temporal lobe epileptics on visual/spatial memory testing.

Attention

Somatostatin-like immunoreactivity in cerebrospinal fluid of patients with complex partial epilepsy.

To investigate the role of somatostatin in human epilepsy, we measured somatostatin-like immunoreactivity (SLI) by radioimmunoassay of the cerebrospinal fluid (CSF) of 60 patients with complex partial seizures (CPS), 5 patients with other neurological diseases (OND), and 23 controls. The SLI levels were measured in groups of epileptic patients that differed in their history of disease, electroencephalogram (EEG), computerized tomography (CT) finding, psychological test scores, or anticonvulsant medication. SLI was lower in the epilepsy group (p less than 0.05) than in the controls. Patients with carbamazepine-clonazepam therapy had lower SLI than did other epileptics (p less than 0.02) or controls (p less than 0.005). Patients with central atrophy (p less than 0.01) in CT and infection (p less than 0.01) as an etiologic cause of epilepsy also seemed to have lower levels of SLI in the CSF than did other epileptics. No correlation was found between psychological memory scores and SLI levels in the CSF of patients with CPS. The present study shows that somatostatin levels are lowered in the CSF of epileptic patients, possibly owing to the lowered somatostatin content or the decreased number of somatostatinergic nerve cells in the epileptic human brain. However, studies in unmedicated patients with different types of seizures are needed to further clarify the possible role of somatostatin in human epilepsy.

Adult

Transient sensory, cognitive and affective phenomena in affective illness. A comparison with complex partial epilepsy.

Behavioural changes have often been noted in patients with epilepsy. This study investigated the converse phenomenon--the occurrence of transient sensory, cognitive and affective changes resembling those described by epileptics, in affectively ill patients. Forty-four patients with affective illness, 37 with complex partial seizures, and 30 hypertensive controls were interviewed to determine the lifetime occurrence of these phenomena. Such symptoms occurred frequently in association with episodes of affective illness and epilepsy, but were rare in controls. Visual, auditory, olfactory and epigastric symptoms, illusions, jumbled thoughts and amnesia were common to both epilepsy and affective illness. Greater numbers of symptoms were associated with better response to lithium and tricyclic antidepressants. Transient sensory, cognitive, and affective phenomena may be more common in affective illness and other psychiatric conditions than is generally recognised, and may be clues to the underlying pathophysiology of these conditions.

Adult

[Study of cerebral metabolism and blood flow in partial complex epilepsy and status epilepticus in man using positron emission tomography].

Positron Emission Tomography (PET) with the oxygen-15 steady state inhalation technique was used to provide quantitative values of regional cerebral blood flow (CBF), oxygen consumption (CMRO2) and oxygen extraction ratio (OER) in 25 patients with partial complex seizures during the interictal state, in 1 patient with recurrent temporal seizures and in 3 patients whose EEGs were characterized by periodic lateralized epileptiform discharges (PLEDs). Interictal scans showed temporal zone(s) of hypoperfusion and hypometabolism in 80% of patients with normal X-ray CT Scan. In all cases, ictal scans revealed a focal or multifocal increase in CBF and CMRO2. The localization of the most affected regions correlated well with the spatial distribution of the EEG abnormalities. Comparison of the different values of CBF, CMRO2 and OER showed that the increase in perfusion always exceeded that of oxygen consumption and hence was accompanied by a significant decrease in OER, the latter was always the most prominent in the region of the focus determined by serial EEG recordings. The observed imbalance between blood flow and oxidative glucose metabolism could suggest an impairment of O2 utilization by the mitochondria in the epilepticus focus during seizures or status epilepticus.

Brain

Detection of epileptiform activity by different noninvasive EEG methods in complex partial epilepsy.

The diagnostic utility of different noninvasive electrode placements for deriving the electroencephalogram and detecting interictal epileptiform discharges was compared. Anterior temporal and nasopharyngeal electrodes in combination with routine scalp electrodes detected over 97% of the spikes, whereas recording from only standard electrode placements detected 58%. Minisphenoidal and surface sphenoidal electrodes were generally not helpful. In some circumstances, however, the use of surface sphenoidal electrodes provided important confirmatory information. In no case did the minisphenoidal electrodes provide unique information, and their use seems unjustified, although the inclusion of other nonstandard electrodes in the recording montage is important to increase the yield.

Adolescent

[Electroclinical study of partial complex epilepsy. Paroxysmal need to drink].

A particular history of a man aged 51 with a right fronto-temporal tumor is analyzed. The main complaint is a paroxysmal need to drink water. Surface electrode electroencephalography and video-telemetry recordings sometimes demonstrated evidence of temporal epileptic abnormalities and therefore seem to have localizing significance. Waterdrinking may thus be added to the widening range of behavioral manifestations associated with epileptic discharges arising in man's temporal lobes.

Brain Neoplasms

Benign infantile epilepsy with complex partial seizures.

Benign infantile epilepsy with complex partial seizures is characterized by a high incidence of family history of benign childhood convulsions, normal development prior to onset, infantile onset, no underlying disorders, no neurological abnormalities, normal interictal EEGs, good response to treatment, and complete remission with normal developmental outcome. Seizures often occur in clusters, consisting of motion arrest, decreased responsiveness, staring or blank eyes mostly with simple automatisms, and mild convulsive movements associated with focal paroxysmal discharges, most frequently in the temporal area.

Electroencephalography

Organic disorders in children with epileptic seizures.

1) Brain C-T scan was done in 1,005 epileptic children as one of the diagnostic methods, and 32% showed abnormal findings. 2) Infantile spasm showed abnormal scan most frequently at 52.9%, persistent subtle seizure 46.7%, simple partial epilepsy 37.7%, and myoclonic epilepsy 37.5%, in order of frequency. 3) In partial epilepsy the positive scan detection rate was 35.2% of the total, with simple partial epilepsy 37.7%, complex partial epilepsy 36.1% and secondary generalized epilepsy 33.5%. These rates are higher than those of generalized epilepsy (27.1%). 4) In generalized epilepsy, generalized tonic clonic showed abnormal scan in 26.1%, generalized tonic in 23.6%, generalized clonic in 20.5%, atypical absence in 15% and typical absence in none. 5) Brain tumor was detected in 2.18%. 6) Positive scan is commonly detected in seizures starting in young age group, and in epileptic patients with focal neurologic signs as well as focal EEG abnormality. 7) The curable lesions were brain tumor, some granulomas, and arachnoid cyst. 8) Brain C-T scan is an effective diagnostic method in epileptic children to identify structural abnormalities of the brain and to make sure that the abnormality does not progress, but it would be better to perform C-T scan case by case rather than as a routine diagnostic procedure.

Adolescent

Mental aspects of temporal lobe epilepsy. Follow-up of 74 patients after resection of a temporal lobe.

Psychiatric disorders were investigated in 74 patients with drug-resistant temporal lobe epilepsy (complex partial epilepsy). In all cases unilateral anterior temporal lobectomy had been performed during the period 1960-69. At follow-up in 1970-71, 45 patients were free from seizures, and in a further group of 15 patients seizure frequency had been substantially reduced. There were four postoperative deaths. Six patients were psychiatrically normal and had no history of any such disorder. Behavioural disturbances were observed in 55 patients. Before operation 11 patients displayed schizophrenia-like psychoses, and nine others became psychotic during follow-up. Fourteen patients attempted suicide on one or more occasions. Half the patients had diminished sexual drive. Improvement in psychiatric status was clearly correlated with relief from seizures and, in those cases with only a few or no seizures after operation, led directly to social rehabilitation. The presence or absence of a psychiatric disorder was not useful as a criterion for or against surgery.

Adolescent

Interictal brain 99Tc-HM-PAO SPECT hypoperfusion in patients with unstable partial epilepsy and normal CT.

Brain perfusion was studied interictally with 99mTc-HM-PAO SPECT in 47 adult patients with partial epilepsy and normal brain CT. Epilepsy was classified as secondarily generalized in 24 patients, as complex partial in 17 patients and as simple partial in 6 patients. In 24 patients good seizure control was not achieved as these patients had a median number of 78 seizures during the preceding month, while in the rest of the patients seizure control was relatively good (less than 6 seizures during preceding month). Local brain hypoperfusion was observed in 41 or 87% of the patients. Hypoperfusion was located close to the EEG foci in 76% and equally often with temporal and frontal foci. Hypoperfusion and the EEG focus were located on the same side in 83%. Hypoperfusion was more frequent in secondarily generalized epilepsy and simple partial epilepsy than in complex partial epilepsy. Left-sided hypoperfusion was especially associated with complex partial epilepsy. It is likely that the significant epileptogenic brain area was revealed in patients with SPECT focus and EEG focus in the same brain area. In one of our patients MRI showed a small temporal lesion which on successful removal was identified as a low-grade oligodendroglioma. Abnormalities of regional brain uptake of HM-PAO demonstrated by SPECT in patients with partial epilepsy and normal brain CT give further information about pathophysiology in partial epilepsy; this may be of use both for selecting appropriate therapy and in presurgical localization of foci.

Adult