Patterns of cerebral glucose metabolism in patients with partial seizures

We analyzed local cerebral metabolic rates of glucose (LCMRglu) in 20 regions from 22 patients with complex partial seizures, who were taking neither phenytoin nor phenobarbital and who had normal CTs. Results were compared with data from 19 normal controls. Ten patients had left temporal, eight right temporal, and four bitemporal or generalized EEG discharges. There were no significant differences between patient and control values in any of 20 regions of interest. LCMRglu was depressed at the site of the epileptic focus: L/R ratio was 0.85 +/- 0.12 (p less than 0.003 compared with control), 0.92 +/- 0.08 (p less than 0.05), and 0.84 +/- 0.1 (p less than 0.001), respectively, in mesial, superior, and inferior temporal regions for patients with left temporal foci; 1.7 +/- 0.96 (p less than 0.04), 1.1 +/- 0.1 (NS), and 1.15 +/- 0.04 (p less than 0.001) for patients with right temporal foci. Patients with left temporal EEG foci had significantly lower values than patients with right temporal foci in left superior frontal and thalamic as well as left temporal regions, while patients with right-sided EEG foci had depressed LCMRglu (compared with patients with left temporal EEG foci) restricted to right mesial temporal lobe. The patients with left temporal foci tended to have longer seizure histories (22.7 +/- 5.4 versus 11 +/- 5.6 years; p less than 0.001). There was an inverse correlation between length of seizure history and mean LCMRglu (r = 0.38; 0.1 greater than p greater than 0.05). Our study suggests that LCMRglu is not depressed in regions beyond the epileptic focus when patients are not taking drugs known to decrease cerebral glucose metabolism.     

Changes in cerebral hemodynamics during simple partial motor seizures

Changes in cerebral perfusion were studied during nine short-lasting simple partial motor seizures (SPS) in an 11-year-old girl. Blood flow velocity changes in both middle cerebral arteries (MCAs) were assessed by transcranial Doppler sonography during simultaneous EEG monitoring. Within 7.4 +/- 1.4 s after electroencephalographic seizure onset, flow velocity in the MCA ipsilateral to the electrical discharges started to increase and then gradually rose up to 70% above baseline values. Spread of the epileptic activity to the other hemisphere in the late stage of seizure was associated with a slight increase in blood flow velocity (<30%) in the contralateral MCA. After the end of the seizure, flow velocities returned to baseline within 47 +/- 7 s. Our findings indicate that focal epileptic seizures evoke asymmetric perfusion increases which are closely related to the onset and cessation of the electroencephalographic seizure activity.     

Local cerebral blood flow with fentanyl-induced seizures

Local cerebral blood flow (LCBF) was evaluated with the [14C]iodoantipyrine quantitative autoradiographic technique in 29 brain structures in conscious control rats and during fentanyl-induced electroencephalographic (EEG) spike and/or seizure activity and in the postseizure EEG suppression phase. During spike activity, LCBF increased in all structures; the increase reached statistical significance (p less than 0.05) in the superior colliculus, sensorimotor cortex, and pineal body (+130%, +187%, and +185% from control, respectively). With progressive development of seizure activity, LCBF significantly increased in 24 brain structures (range, +58% to +231% from control). During the postseizure EEG suppression phase, LCBF remained elevated in all structures (+80% to +390% from control). The local cerebrovascular resistance (LCVR) significantly decreased in 10 of 29 structures with the onset of spike activity (range, -24% to -64%), and remained decreased in all brain structures during seizure activity (range, -34% to -67%) and during the EEG suppression phase (range, -24% to -74%). This reduction of LCVR represents a near maximal state of cerebrovasodilation during fentanyl-induced EEG seizure or postseizure suppression activity. The global nature of the LCBF elevation indicates that factors other than local metabolic control are responsible for CBF regulation during local seizure activity.     

Self-injection ictal SPECT during partial seizures

The authors compared ictal SPECT injection performed by medical personnel with self-injection ictal SPECT in six patients with refractory temporal lobe epilepsy. Self-injection was safe and started faster. Self-injection subtraction ictal SPECT coregistered to MRI (SISCOM) was localizing in three patients who had a complex partial seizure, but only one of three patients who had a simple partial seizure, which may limit its usefulness in clinical practice. The localizing information of self-injection was better in three patients, and obviated the need for depth-EEG studies in one patient.     

Local cerebral glucose utilization in newborn and pubescent monkeys during focal motor seizures

The [¹⁴C]deoxyglucose method was used to determine the rate of local cerebral glucose utilization (LCGU) in newborn and pubescent monkeys during focal motor seizures induced by injecting penicillin into the face-hand area of the right motro cortex. Seizures were studied in 3 newborn and 6 pubescent monkeys, and 3 newborn and 4 pubescent monkeys were used as controls. In controls, the pattern of glucose utiliztion within structures of the sensorimotor system was quite different at the two age levels; newborns showed far less activity, especially in the neocortex and striatum. In the monkeys with seizures, the unilateral increase in LCGU relative tot he controls was greater in newborn than in pubescent monkeys except in the cerebral and cereballar cortices. The increased glucose utilization in cortical and subcortical structures of the newborn was ipsilateral to the dischargin lesion and lacked the well-defined pattern seen in the pubescetn mmonkeys. In general, newborn brain was capable of supporting a focal motro seizure but lacked the precise clinical and electrographic expressions or efficient energy metabolism that accopany maturation of the brain at puberty.     

Change in cerebral glucose metabolism during limbic seizures elicited from lateral septal nucleus

The roles of the amygdala and hippocampus have been extensively studied in limbic seizures. Although the septal nuclei have a close connection to the hippocampus and affect emotional behavior, the effect on limbic seizures is still unclear. We have reported that characteristic sham-rage seizures were observed in cats, by administering a local injection of kainic acid (KA) into the lateral septal nucleus (LSN). This study investigated the electrophysiological features of KA-induced septal seizures in rats and analyzed the process in relation to the cerebral glucose metabolism using [¹⁴C]deoxyglucose autoradiography. On EEG, epileptic discharge eliciting from the LSN rapidly propagated to the hippocampus and the amygdala. Behavioral change was similar to that in limbic seizures induced by intraamygdaloid KA. Sham-rage seizure was not observed in rats. However, the local cerebral glucose metabolism during the seizures increased not only in the limbic structures including the LSN but also in the hypothalamus and periaqueductal grey matter of the midbrain. The findings were distinctive of septal seizures as compared with amygdaloid seizures. The results suggested that sham-rage seizures in cats might be caused by a secondary epileptogenic excitation in the hypothalamus or periaqueductal grey matter of the midbrain. The septal nuclei may play an important role in emotional behavior associated with limbic seizures even if there is a species difference in its function.     

Autonomic symptoms during childhood partial epileptic seizures

PURPOSE: To analyze systematically the occurrence and age dependence as well as the localizing and lateralizing value of ictal autonomic symptoms (ASs) during childhood partial epilepsies and to compare our results with those of earlier adult studies. METHODS: Five hundred fourteen video-recorded seizures of 100 consecutive children 12 years or younger with partial epilepsy and seizure-free postoperative outcome were retrospectively analyzed. RESULTS: Sixty patients produced at least one AS; 43 (70%) of 61 with temporal and 17 (44%) of 39 with extratemporal lobe epilepsy (p=0.012). Apnea/bradypnea occurred more frequently in younger children (p<0.01), whereas the presence of other ASs was neither age nor gender related. Postictal coughing (p<0.01) and epigastric aura (p<0.05) localized to the temporal lobe, whereas no ASs lateralized to the seizure-onset zone. CONCLUSIONS: Our study shows that ASs are common in childhood focal epilepsies, appearing in infants and young children, too. As in adults, childhood central autonomic networks might have a close connection to temporal lobe structures but do not lateralize the seizure-onset zone. To our knowledge, this is the first study comprehensively assessing ASs in childhood epilepsy.     

Neologistic speech automatisms during complex partial seizures

There are no documented cases of seizures causing reiterative neologistic speech automatisms. We report an 18-year-old right-handed woman with stereotypic ictal speech automatisms characterized by phonemic jargon and reiterative neologisms. Video-EEG during the reiterative neologisms demonstrated rhythmic delta activity, which was most prominent in the left posterior temporal region. At surgery, there was an arteriovenous malformation impinging on the left supramarginal gyrus and the posterior portion of the superior temporal gyrus. Though intelligible speech automatisms can result from seizure foci in either hemisphere, neologistic speech automatisms may implicate a focus in the language-dominant hemisphere.     

Glycolysis in energy metabolism during seizures

Studies have shown that glycolysis increases during seizures,and that the glycolytic metabolite lactic acid can be used as an energy source.However,how lactic acid provides energy for seizures and how it can participate in the termination of seizures remains unclear.We reviewed possible mechanisms of glycolysis involved in seizure onset.Results showed that lactic acid was involved in seizure onset and provided energy at early stages.As seizures progress,lactic acid reduces the pH of tissue and induces metabolic acidosis,which terminates the seizure.The specific mechanism of lactic acid-induced acidosis involves several aspects,which include lactic acid-induced inhibition of the glycolytic enzyme 6-diphosphate kinase-1,inhibition of the N-methyl-D-aspartate receptor,activation of the acid-sensitive 1A ion channel,strengthening of the receptive mechanism of the inhibitory neurotransmitter γ-aminobutyric acid,and changes in the intraand extracellular environment.     

31P NMR study of cerebral metabolism during prolonged seizures in the neonatal dog

The effects of prolonged bicuculline-induced seizures on cerebral blood flow and metabolism were determined in paralyzed, mechanically ventilated neonatal dogs. Transient changes occurring early in the course of status epilepticus included significant arterial hypertension, hypocarbia, elevation of plasma norepinephrine levels, and decline in brain glucose concentration. Cerebral blood flow remained elevated throughout the 45 minutes of seizure. Determination of cerebral metabolite values by in vivo phosphorus 31 nuclear magnetic resonance spectroscopy and by in vitro enzymatic analysis of frozen brain samples showed significant decreases in the level of phosphocreatine and relatively less change in ATP values. Progressive intracellular acidosis occurred, coincident with elevation of brain lactate concentrations. We conclude that the physiological and metabolic alterations that occur during prolonged seizures are not uniform, but change with time. Any hypothesis advanced to explain the mechanism of neuronal injury during prolonged seizures must take into account these temporally related changes.     

Local cerebral metabolism during enflurane anesthesia: identification of epileptogenic foci.

Electrocorticographic (ECoG) and depth recordings have previously demonstrated the epileptogenic nature of surgical concentrations of the volatile anesthetic enflurane. We contrasted ECoG activity with local cerebral glucose uptake [( 14C]2-deoxyglucose autoradiography) in 23 brain structures in order to identify the epileptogenic foci. Autoradiograms were obtained from sectioned rat brain following a 30 min period of steady-state anesthesia at 1, 1.5, or 2 MAC (minimum alveolar concentration) enflurane. Pseudo-epileptiform ECoGs were obtained at 1 MAC where bursts of slow waves and sharp waves were evoked by peripheral sensory stimulation. At 1.5 MAC, the ECoG displayed frank, spontaneous epileptiform activity with large amplitude spike-wave complexes; repetitive auditory stimulation occasionally precipitated grand-mal seizures. At 2 MAC, spike complexes were less frequent and could not be repetitively driven. At 1 MAC enflurane, regional cerebral metabolism was generally depressed approximately 14% from the awake controls. However, metabolism in the dentate gyrus of the hippocampus and other subcortical structures in the limbic brain was increased. At 1.5 MAC this dichotomy in local cerebral metabolic rate was maximal; we observed increased metabolism in the hippocampus, habenula, habenulo-interpeduncular tract and interpeduncular nucleus and pineal. Metabolism in all other structures was significantly depressed (P less than 0.05) compared to awake values. At 2 MAC, metabolism was decreased in all structures. We conclude that the low seizure threshold hippocampus and related structures associated with the limbic system and its pathways are the epileptogenic foci for seizures induced with enflurane in the rat. At 1.5 MAC, epileptiform activity spreads throughout the visceral brain when seizure threshold is at a minimum.     

Cognitive function and regional cerebral blood flow in partial seizures

Patients with partial seizures have cognitive function impairments that have been attributed to the toxic side effects of anticonvulsants and structural cerebral damage. However, even when these factors are absent, neuropsychological (NP) deficits have been demonstrated, although of milder degree than in structurally brain-damaged patients. Assessment of cerebral metabolism using positron emission tomography and cerebral blood flow with single photon emission computed tomography (SPECT) reveals focal physiologic deficits in structurally normal areas. Using both SPECT and NP assessment with the Halstead-Reitan Battery, we evaluated 50 patients with partial seizures. Comparison of the location of visually identified regional cerebral blood flow (rCBF) deficits in these patients with the location of the NP deficits revealed a significant correlation. Additional analyses indicated that rCBF quantification in visually identified areas of hypoperfusion was significantly lower than in "normal" areas and that quantified NP variables significantly discriminated patients with and without visual rCBF deficits in temporal and frontal brain regions.     

EKG abnormalities during partial seizures in refractory epilepsy

SUMMARY: PURPOSE: This study assessed the frequency and character of ictal cardiac rhythm and conduction abnormalities in intractable epilepsy. Sudden unexpected death in epilepsy (SUDEP) is a major cause of excess mortality in people with refractory epilepsy, and cardiac arrhythmias during seizures may be responsible. The frequency of cardiac abnormalities during seizures in patients with refractory epilepsy must be determined. METHODS: Fifty-one seizures in 43 patients with intractable partial epilepsy were analyzed prospectively from CCTV-EEG monitoring with one ECG channel. Arrhythmias, repolarization abnormalities, and PR and QTc intervals were determined for preictal (3 min), ictal, and postictal (3 min) periods for one or more seizures per patient. Parametric statistics were used for continuous variables, and nonparametric statistics were used for categoric variables. RESULTS: Of the patients, 39% had one or more abnormalities of rhythm and/or repolarization during or immediately after seizures. Abnormalities included asystole (one), atrial fibrillation (one), marked or moderate sinus arrhythmia (six), supraventricular tachycardia (one), atrial premature depolarizations (APDs; eight), ventricular premature depolarizations (VPDs; two), and bundle-branch block (three). Mean seizure duration was longer in patients with abnormalities than in those without (204 vs. 71 s; p < 0.001). Generalized tonic-clonic seizures were also associated with increased occurrence of ictal ECG abnormalities (p = 0.006) as compared with complex partial seizures. There were no clinically significant differences in mean preictal and ictal/postictal PR and QTc intervals. CONCLUSIONS: Cardiac rhythm and conduction abnormalities are common during seizures, particularly if they are prolonged or generalized, in intractable epilepsy. These abnormalities may contribute to SUDEP.     

Profiles of instant heart rate during partial seizures

Instant heart rate (R-R intervals) can be readily studied during spontaneous seizures recorded with ambulatory cassette AEEG/AECG techniques. Ninety-three seizures were recorded in 32 patients with complex partial epilepsy. Instant R-R interval plots showed that 74% of seizures were associated with a dominant tachycardia, the most characteristic features of which were the initial steep acceleration phase at seizure onset and the wide fluctuations in heart rate ('exaggerated sinus arrhythmia') which occurred during and immediately after the seizure. Five percent of seizures were associated with a dominant but transient phase of heart rate slowing during or towards the end of the seizure. Nineteen percent of seizures showed equivocal or negative ictal effects on the heart rate and rhythm despite unequivocal AEEG seizure discharges. Conversely, other patients had characteristic heart rate changes despite equivocal AEEG abnormality. The heart rate profiles showed striking seizure-to-seizure similarities when multiple fits were recorded in the same patient. Ratemeter profiles may be clinically useful to locate epileptic seizures in long duration records; they can help to locate seizures which are either inaccurately timed or poorly identified by the event marker, or not clearly associated with definite AEEG changes. The secondary cardiac effects of epilepsy may be misdiagnosed if their primary cerebral origin is not suspected.     

Local cerebral glucose utilization in rats with petit mal-like seizures

The quantitative 2-[14C]deoxyglucose autoradiographic method was applied to the measurement of local cerebral metabolic rates for glucose in a model of genetic petit mal-like seizures in a strain of Wistar rats. During the experimental period, epileptic rats exhibited synchronous spike-and-wave discharges recorded from the cerebral cortex, whereas the electroencephalographic pattern of control animals was normal. An overall consistent increase in local cerebral metabolic rates for glucose was observed in epileptic rats as compared to nonepileptic control rats. This increase was statistically significant in 52 of the 59 cerebral structures studied and concerned all cerebral functional systems. These results are in accordance with positron emission tomography measurements in humans with typical childhood absence epilepsy. There is a lack of anatomical correlation between areas demonstrating hypermetabolism and areas where spike-and-wave discharges are recorded. Thus, the diffuse increase in cerebral energy metabolism in epileptic rats as compared to controls is not directly related to the occurrence of spike and wave discharges.