Faculty Bibliography

The prolonged QT syndrome is associated with ventricular tachyarrhythmias and sudden death. We report two patients and review eight previously reported cases of this syndrome, presenting as epilepsy. The average age at the time of the first convulsion was 4.7 years. Episodes were often infrequent, and the time to correct diagnosis ranged from 1 to 28 years. Only one-half the patients had histories suggestive of a familial syndrome. Presyncopal complaints and 'lifelessness' prior to seizure activity were common findings in retrospect. Beta-blockade was effective in preventing recurrences in all patients who received treatment

We studied 120 generalized tonic-clonic seizures (GTCSs) in 47 patients with video-EEG telemetry. GTCSs were preceded by antecedent seizures, including 13 simple partial, 70 complex partial, 17 simple partial leading to complex partial, seven tonic, seven clonic, and one typical absence. We divided GTCSs into the following phases: onset of generalization, pretonic clonic, tonic, tremulousness, and clonic. The mean GTCS duration was 62 seconds. There was a non-significant trend toward longer duration on reduced antiepileptic drug doses. Marked heterogeneity in GTCS phenomenology was present; only 27% of seizures included all five phases. Individual phase duration and clinical expression, including tonic and clonic phases, was highly variable. The clinical phenomena suggest that multiple cortical and subcortical routes of spread may exist. When GTCSs last longer than 2 minutes, intravenous antiepileptic drug treatment should be initiated

Changes in gene expression after kindled seizures were examined using microdissection of discrete brain areas and Northern and slot blot analyses. Experimental animals were kindled with either of two protocols: (1) a paradigm in which 50 Hz/10 s stimulus trains were delivered every 30 min through hippocampal electrodes (12 stimulations every other day for 4 days) and (2) a traditional approach in which 50 Hz/10 s stimulus trains were given to the hippocampus three times daily for 16 days. Rats were sacrificed 24 h or 30 days after the last kindled seizure. We first examined the possibility that kindling may affect transcription of mRNA for neurotransmitter receptors. We found significant decreases (22-58%) in AMPA/kainate activated glutamate receptor mRNAs (GluR1, -2, -3 mRNAs) in hippocampus, amygdala/entorhinal cortex and in frontoparietal cortex 24 h but not 30 days after rapidly kindled seizures. However, changes in GABA receptor alpha 1, alpha 2, alpha 4 or beta 1 mRNAs were not observed in any brain region 30 days after traditional kindling or 24 h after rapidly kindled seizures. In addition, we tested whether changes in the expression of proenkephalin could be detected after kindling. We found significant increases (1.7-10 fold) in proenkephalin mRNA in the frontoparietal cortex, hippocampus and in the amygdala/entorhinal cortex 24 h but not 30 days after rapidly kindled seizures. Our findings suggest that changes in glutamate receptor and proenkephalin gene expression are robust, acute sequelae to kindled seizures and may be involved in kindling

Adult patients with left, right, or bilateral temporal lobe epilepsy or absence epilepsy, and normal controls completed the Buss-Durkee Hostility Inventory (BDHI), a standardized questionnaire of aggressive tendencies. Patients with left temporal lobe seizure foci scores higher on the Suspicion scale than did other patients or controls (p < 0.05). Factor analysis scale scores identified three factors: hostile feelings, covert aggression, and overt aggression. The groups differed on their pattern of factor scores (p < 0.01): patients with left temporal lobe epilepsy scored higher than other groups on hostile feelings, normal controls scored higher on Covert aggression, and bitemporal patients scores higher on Overt aggression. Patients with absence seizures did not differ from controls. Lateralization of the seizure focus in patients with temporal lobe epilepsy may alter expression of aggressive behavior

The kynurenine pathway metabolites, quinolinic acid (QUIN) and L-kynurenine are convulsants, whereas kynurenic acid (KYNA) is an antagonist of excitatory amino acid receptors. Imbalances in the concentrations of these metabolites have been implicated in the etiology of human seizure disorders. In the present study, L-kynurenine and QUIN concentrations in both cerebrospinal fluid (CSF) and serum were reduced in patients with intractable complex partial seizures (CPS) in both the postictal period (15-75 min after a seizure) and the interictal period (absence of seizure for > 24 h) as compared with neurologically normal control subjects. Linear regression analyses and analysis of covariance showed that the reductions in serum QUIN and L-kynurenine were correlated to blood antiepileptic medication. L-Tryptophan (L-TRP) levels also tended to be lower in both CSF and serum of the seizure patients. CSF KYNA and serum 3-hydroxykynurenine concentrations were not affected in seizure patients, whereas serum levels of KYNA were reduced. 3-Hydroxykynurenine was not detected in the CSF of either control or seizure patients. The results do not support a role for a generalized reduction in KYNA concentrations or an increased ratio of QUIN:KYNA, or increases in CSF L-kynurenine in initiation and maintenance of intractable CPS humans

OBJECTIVE: To examine postictal behaviors after temporal lobe complex partial seizures (CPSs) and to correlate these behavioral phenomena with side of origin and ictal spread pattern. DESIGN: Review language and other behavioral phenomena after seizures defined by subdural electroencephalography. SETTINGS: A surgical epilepsy center. PATIENTS: We studied postictal behavior following 65 CPSs in 18 patients with left hemisphere language dominance using subdural electrode recordings. INTERVENTION: Subdural electrodes. MAIN OUTCOME MEASURES: Language function, affect, orientation, and postictal automatisms. RESULTS: Following the CPS ictal discharge, the mean interval for initial nonreflexive response to an environmental stimulus was 43 seconds (left foci, 57 seconds; right foci, 29 seconds; not significantly) and for first correct verbal response was 219 seconds (left foci, 275 seconds; right foci, 167 seconds; not significant). Impaired comprehension with fluent but unintelligible speech, as well as anomia, occurred after seizures arising from either temporal lobe. All nine seizures followed by global or nonfluent aphasia originated on the left side. Paraphasic errors were significantly more common after left temporal CPSs. Prolonged disorientation for place and flat affect were significantly more common after right temporal CPS. Postictal automatisms were frequent and included rubbing of the face, fumbling and picking hand movements, and repetitive oral movements. CONCLUSIONS: Postictal paraphasias, disorientation for place, and flat affect most likely reflect the functions of the area from which seizures arise but not the areas involved by spread

We reviewed the seizure frequencies of 38 patients with medically refractory epilepsy 6 weeks before (baseline) and 3 weeks after withdrawing their antiepileptic drugs (AEDs) for video-EEG monitoring. Seizure frequency during the first 3 weeks after restarting AEDs was diminished compared with baseline (P < 0.05). We found no correlation between seizure frequency and patient age, specific antiepileptic drugs, number of seizures during the video-EEG monitoring, number of days without AEDs, or partial vs total withdrawal of AEDs. Medication tachyphylaxis, functional tolerance, or long term post-ictal depression of the seizure threshold is hypothesized. The diminished seizure frequency after reinstitution of medications in four of five patients who did not have seizures during their hospitalization suggests that drug tachyphylaxis is a relevant mechanism

We studied 24 patients with partial seizures receiving carbamazepine (CBZ) monotherapy and 40 normal controls, 17 of whom were tested with and without CBZ therapy. Autonomic nervous system assessment included baseline heart rate (HR) and blood pressure (BP); BP and HR changes during orthostasis and cold pressor test (CPT); and HR changes during sinus arrhythmia, Valsalva maneuver, and cold face test with apnea (CFTA). Our study demonstrated normal interictal autonomic function in patients with epilepsy, but, variations in BP and HR during orthostasis and CPT were significantly (p < 0.05) higher in epilepsy patients than in controls with or without CBZ. Epilepsy patients had higher initial increases in BP and greater subsequent decreases in BP than did nonmedicated controls during CPT. Controls with CBZ had higher HR during orthostasis and CFTA than did those without CBZ. CBZ levels correlated with baseline and orthostatic BP and HR during deep breathing (sinus arrhythmia). Our results showed that patients with epilepsy have greater BP and HR variability and reactivity than controls, attributable in part to CBZ levels