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The relationship of the lock-step phenomenon and precipitous changes in mean arterial blood pressure.

The lock-step phenomenon (LSP) is the occurrence of postganglionic cardiac sympathetic discharge (PCSD) and cortical epileptiform activity (EA) in a time-locked fashion. The relationship between the LSP and precipitous changes in blood pressure (PCBP: greater than 23 mm Hg in 10 sec) was determined in 9 cats after EA was induced with pentylenetetrazol following pretreatment with phenobarbital (20 mg/kg, i.v.). Electrocorticogram (ECoG), PCSD, lead II EKG, and mean arterial blood pressure (MAP) were monitored. Since an interspike interval of 2.8 sec was frequently found to exist between ECoG spikes when the LSP was present, 4 categories of LSP were defined: LSP absent; stable LSP with 2.8 sec interval; stable LSP without 2.8 sec interval; and unstable LSP with increasing or decreasing rates of discharge. The duration of each LSP pattern and the proportion of time spent in PCBP were determined. A one-way repeated measures ANOVA and the Newman-Keuls post-hoc test showed that a higher mean proportion of time spent in PCBP was associated with the unstable LSP pattern (P less than 0.05). The LSP and associated patterns as related to precipitous changes in MAP are indicators of changes in autonomic function. Autonomic dysfunction with EA, causing cardiac arrhythmias, has been postulated as a cause of sudden unexplained death (SUD) in persons with epilepsy. Thus, an understanding of the autonomic changes, as indicated by PCBP associated with LSP, may contribute to the understanding and prevention of SUD in persons with epilepsy.

Animals↗

An automated seizure monitoring system for patients with indwelling recording electrodes.

An automated monitoring system has been developed to record from indwelling electrode arrays in patients undergoing evaluation for surgical treatment of intractable seizures. The functional aspects of this system's design are discussed and the range of electrical seizure patterns, other epileptiform events and artifacts that the system must handle are described. The system includes a flowing graphics image of as many as 32 channels of real-time ECoG, automatic seizure detection, recording of the ECoG for up to 6 min prior to seizure onset, and EEG for 792 clinical and subclinical seizures during 1578 h of monitoring with an artifact rate of 28% for all events recorded. However, system performance was judged upon the 86% accuracy for detection and recording of patient-specific seizure patterns (multiple seizures with the same pattern counted as 1) with 1.26 brief spike bursts and 0.67 artifacts/h.

Adolescent↗

Electrocorticography in patients with medically intractable temporal lobe seizures. I. Quantification of epileptiform discharges prior to resective surgery.

We studied retrospectively the intraoperative preresection electrocorticograms (ECoGs) of 72 patients undergoing surgery for medically intractable, mostly complex partial, temporal lobe seizures (TLS). Quantification of interictal epileptiform discharges (EDs) detected visually at each electrode location in 2 min recording epochs included computations of ED rates (EDs/min) and cumulative voltages (CuVs) (microV/min). Of 6388 EDs, 81% involved the infratemporal surface, 18% the lateral temporal surface and 1% the orbital frontal area. Forty-eight patients (67%) demonstrated multiple (up to 5 or more), temporally independent foci. Dominant foci in medial and lateral infratemporal locations were about equally common and were significantly more frequent than in lateral temporal locations. Rankings of ED CuVs and rates at individual cortical locations defined 4 areas of "relative interictal cortical epileptogenicity." These were arranged in an orderly pattern with the anterior parahippocampal gyrus and the inferomedial surface of the temporal tip displaying the highest and the lateral temporal and posterior infratemporal cortices showing the lowest propensity to the interictal epileptiform discharge. Individual areas were not characterized by distinct clinical seizure manifestations. Preresection ECoGs provide information on the epileptogenic dysfunction that involves most of the temporal lobe of patients with medically intractable TLS.

Adolescent↗

A specialised computer-based monitoring system for intraoperative electrocorticography.

We have developed a computer-based intraoperative ECoG monitoring system which offers the flexibility of digital recording and allows detailed review of recorded events without interrupting monitoring. In addition, a diagram showing the electrode positions on the brain can be generated on computer screen and subsequently displayed during monitoring--this allows automatic indication of the electrode positions corresponding to specific ECoG channels and can provide the surgeon with a clear visual impression of the area of spiking.

Cerebral Cortex↗

Computer simulation of electrocortical activity at millimetric scale.

We report a simulation of electrocortical wave activity at millimetric scale, during the "desynchronised" state. Asymmetric sigmoid pulse/wave relations, short-range excitatory/inhibitory interactions and long-range excitatory couplings of pools of cortical cells were modelled. Frequency/wave number analysis of cat electrocorticogram was compared with the results of simulation. Local standing waves, with wave numbers from about 0.25/mm to 3.3/mm independent of temporal frequency, appeared in real and simulated ECoG. These arise from interactions of excitatory and inhibitory cells and reciprocal excitation of pyramidal cells. The simulation also exhibits long wave length activity consistent with that of the real ECoG. Serial relay of excitation gives rise to travelling waves with a velocity of about 0.6 m/sec, which approximates earlier experimental estimates based on coherence. Interaction of the local and travelling waves results in group waves with high phase velocities (32 m/sec at 5 Hz, to 0.6 m/sec at 50 Hz). Such group waves have not yet been experimentally identified and would be readily confused with effects of volume conduction. However, the frequency response characteristics of the simulation, along with the group waves, may account for experimental findings of action potential correlation with local field potentials at 40-50 Hz and long-range synchronisation of action potentials.

Animals↗

Usefulness of focal rhythmic discharges on scalp EEG of patients with focal cortical dysplasia and intractable epilepsy.

We examined the significance and frequency of occurrence of rhythmic epileptiform discharges (REDs) on the scalp EEGs of 74 patients with intractable partial epilepsy. We also analyzed the relationship of this abnormality to the continuous epileptiform discharges (CEDs) recorded on ECoG. Both REDs and CEDs had been found to be highly specific and sensitive indicators of focal cortical dysplastic lesions. Thirty-four patients (group I) had focal cortical dysplastic lesions (FCDLs) and 40 (group II) had non-dysplastic structural lesions. REDs were observed in 15 (44%) of the 34 patients of group I and in none of group II. REDs did not occur in isolation, were associated with more intermittent interictal spikes involving other regions, but had a greater (P < 0.05) significance for the localization of the epileptogenic area. A strong relationship was observed between the presence of REDs on scalp EEG and the occurrence of CEDs on ECoG recordings. Twelve (80%) of 15 patients with REDs had CEDs. Focal cortical dysplastic lesions are likely to be present when rhythmic epileptiform discharges are found.

Adolescent↗

Placental transfer of central nervous system depressants in sheep.

Continuous monitoring of the foetal electrocorticogram, eye movements and heart rate in ewes during the last month of gestation showed rapid placental transfer from the mother to the foetus of phenothiazine derivatives (acepromazine maleate), short-acting barbiturates (thiopental sodium) and narcotic analgesics (meperidine). Acepromazine and thiopental partially disrupted the foetal sleep cycle by synchronization of the ECoG for 1-2 h but increased the heart rate for 2-3 h. The effects of meperidine were similar but lasted only 5-10 min for the ECoG and less than 0.5 h for the heart rate.

Acepromazine↗

Slow wave sleep and a state resembling absence epilepsy induced in the rat by gamma-hydroxybutyrate.

The effect of gamma-hydroxybutyrate (GHB) in relatively low doses (12.5--200 mg/kg) on sleep stages, electrocorticogram (ECoG) patterns and behavior was investigated in the rat. 50-100 mg/kg GHB induced slow wave sleep but, in contrast to the cat, not paradoxical sleep. 200 mg/kg induced a hypersynchronous, bilaterally symmetrical ECoG pattern, which was different in amplitude and frequency distribution from normally occurring high amplitude patterns. When the hypersynchrony occurred in bursts, the rats displayed a sudden arrest of motor behavior. Convulsions were not induced. The results, together with the finding of others that GHB is a natural constituent of mammalian brain and our previous observation that the GHB-induced hypersynchrony can be antagonized by anti-absence (anti-petit mal) drugs are discussed in view of the possibility that GHB might play a role in the etiology of absence epilepsy in man.

Animals↗

Relationship between focal penicillin spikes and cortical spindles in the cerveau isolé cat.

Using the unanesthetized, cerveau isolé preparation in the cat, the association between artificially induced penicillin (PCN) spikes and spontaneously occurring electrocorticographic (ECoG) spindles was investigated. Spikes were elicited by surface application of small pledgets of PCN. After the application of PCN, there was a decrease in spindle amplitude but no change in frequency, duration, or spindle wave frequency in the area of the focus. Examination of the times of occurrence of the spikes and spindles disclosed that in the majority of cases, within a few minutes of the initiation of the foci, there was very high simultaneity, usually 100% between the occurrences of these two events. Examination of the times of occurrence of the spikes within the ECoG spindles failed to disclose any compelling evidence which would favor either the hypothesis that spikes "trigger" spindles or the hypothesis that spindles predispose to focal spikes. Thus, whether spikes trigger spindles, or spikes simply occur in a nonspecific manner during the occurrence of the spindle, or whether it is a combination of both these explanations, must remain an open question on the basis of the data available.

Animals↗

A novel protein induced in cortical epileptic focus of rat cerebrum: a possible linkage to epileptogenesis.

To precisely evaluate a protein-related mechanism of epileptogenesis, we quantitatively analyzed the 70-kDa protein (namely, P70), a specific protein found in the cobalt-induced epileptic focus, and examined its effect on the electrocorticogram (ECoG) and cortical neurons in cerebral slices and its immunocytochemical localization in rats. Cobalt-induced cortical epileptogenic cortex exhibited a marked induction of P70. Its initiation time was ahead of the generation of epileptogenic activities. The anticonvulsant phenytoin (PHT) attenuated the cobalt-induced epileptogenic activities, but failed to suppress protein induction. Injection of this protein into the motor region of normal rat cerebral cortex elicited an epileptic ECoG and behavioral seizures. It also caused epileptiform activity with paroxysmal depolarization shifts in cortical neurons. These epileptogenic phenomena elicited by P70 were abolished by prior treatment with PHT or phenobarbital. Immunocytochemical analysis with an antiserum against P70 revealed that the reactivity was confined to pyramidal cells only in the region of the focus and was mainly localized on somatic, dendritic, and nuclear membranes and microtubles. These findings suggest that P70 may be linked to epileptogenesis.

Animals↗

The pattern of breathing of fetal sheep in graded hypoxia.

We examined the effects on fetal breathing movements (FBM) and electrocortical activity (ECoG) of maintaining fetal arterial PO2 (PaO2) at 16.9 +/- 1.9 mmHg for 20 min in unanaesthetized, chronically instrumented fetal sheep in utero at 122-132 days gestation. In 82% of trials, a pattern of regular FBM occurred characterised by its large (35 +/- 7 mmHg) excursions in tracheal pressure and its low frequency (ca. 3 per min) compared to the irregular FBM occurring during normoxia (ca. 5 mmHg and ca. 90 per min, respectively) (PaO2 ca. 23 mmHg). The occurrence of FBM in mild hypoxia was independent of the ECoG state of the fetus and it also occurred in fetuses in which the carotid sinus nerves and cervical vagosympathetic trunks had been sectioned bilaterally. Reducing PaO2 to between 16 and 11 mmHg produced a cessation of FBM, as reported by other workers. The FBM in mild hypoxia were distinct from 'gasping', which occurs only when PaO2 was reduced to much lower levels. The FBM in mild hypoxia are discussed in terms of central respiratory mechanisms excited by hypoxia, as opposed to the well-documented mechanisms which inhibit FBM in more intense hypoxia.

Animals↗

Tremor at rest episodes in unilaterally 6-OHDA-induced substantia nigra lesioned rats: EEG-EMG and behavior.

Twenty male adult Wistar rats were unilaterally lesioned in the substantia nigra (SN) with 6-hydroxydopamine (6-OHDA), and prepared with chronic cortical (ECoG) and neck muscle (EMG) electrodes. Longitudinal study over a period of up to 18 months demonstrated the emergence, in about two-thirds of the rats, of spontaneous repetitive episodes of head and neck tremor during awake at rest, of up to 20 seconds duration each, that were associated with spike and wave-like ECoG activities. These episodes of tremor at rest disappeared during sleep and REM sleep episodes, and also following the i.p. administration of L-DOPA. It is assumed that these tremor at rest episodes are analogous to those reported to occur in primates after experimentally induced dysfunction of the nigro-striatal, extrapyramidal system.

Animals↗

Onset of insensibility at slaughter in calves: effects of electroplectic seizure and exsanguination on spontaneous electrocortical activity and indices of cerebral metabolism.

Cerebral venous and femoral arterial blood samples were collected from 21 young calves either during electrical stunning and recovery or electrical stunning and slaughter by carotid severance or slaughter without stunning. The blood samples were analysed for PO2, PCO2, pH, glucose and lactate. The results were compared with simultaneous recordings of spontaneous electrocortical (ECOG) activity. Calves subjected to head-only electrical stunning and slaughter became permanently insensible at the time of the stun. The six calves slaughtered without stunning lost sensibility within 10 seconds. One calf, in which a clot formed in the carotid arteries inhibiting bleeding, maintained some evidence of cortical activity beyond 52 seconds; this was high amplitude low frequency activity and analysis by Fast Fourier Transform showed sensibility was not regained. In the remaining calves the ECOG activity was lost on average within 49 +/- 3.5 (SEM) seconds after slaughter. The cerebral extraction of metabolites increased after carotid severance, indicating inadequacy of cerebral bloodflow after slaughter. No correlations were found between indices of cerebral metabolism and the time of loss of cortical function.

Abattoirs↗

Central and peripheral cardio-respiratory effects of saxitoxin (STX) in urethane-anesthetized guinea-pigs.

Effects of saxitoxin (STX; 10 micrograms/kg; i.p.) on cardio-respiratory activities were evaluated in urethane-anesthetized guinea-pigs. Concurrent recordings were made of electrocorticogram (ECoG), bulbar respiratory-related unit activities, diaphragmatic electromyogram (DEMG), electrocardiogram (Lead II ECG), blood pressure, heart rate, end-tidal CO2, arterial O2/CO2 tensions, and arterial pH. The average time to STX-induced respiratory failure was about 10 min. The most striking effect prior to apnea was a state of progressive bradypnea which emerged 5-7 min after the toxin administration. Other noteworthy responses included (i) a time-dependent decrease in ECoG amplitudes which typically began before the development of a bradypneic profile; (ii) an increasing degree of diaphragm neuromuscular blockade; (iii) a state of combined hypercapnia and uncompensated acidemia; (iv) a declining blood pressure; (v) an incrementally dysfunctional myocardial performance; and (vi) an increasingly degenerative central respiratory activity profile which ultimately culminated in a complete loss of central respiratory drive. The therapeutic effect of intratracheally administered oxygen was equivocal in that the cardio-respiratory activities, be they of central of peripheral nature, remained conspicuously dysfunctional and precarious despite 100% oxygen ventilation. What can be inferred from this study is two-fold. First, STX-induced ventilatory insufficiency can be attributed to a loss of functional integrity of both central and peripheral respiratory system components. That is, although diaphragm blockade contributes significantly to STX-induced respiratory failure, analyses of single respiratory unit activity data revealed that the central respiratory rhythmogenic mechanism also appeared to play a pivotal role in the development of a bradypneic profile which promotes, and directly causes, a complete loss of respiratory drive. Second, a state of unabating depression of central respiratory activities, which seemed to be refractory to the effect of O2, suggests STX has a direct and persistent action on medullary rhythmogenic mechanisms. In conclusion, these findings indicate that both central and peripheral cardio-respiratory components are critically involved in STX-induced apnea, dysfunctional cardiovascular performance, and lethality.

Anesthesia↗

Adriamycin and cisplatin in the treatment of stage III and IV epithelial ovarian carcinoma.

A total of 342 eligible, previously untreated patients with Stage III or IV epithelial ovarian carcinoma were treated with Adriamycin and cisplatin, both at 50 mg/m2, for nine courses. Of the 210 patients who had clinically detectable disease after initial surgery, 85 (41%) had a complete clinical response and 45 (21%) had a partial clinical response. A total of 197 were clinically free of disease at the completion of chemotherapy and 175 of these had a second-look laparotomy; 55 had no macroscopic or microscopic evidence of residual disease after multiple random biopsies were examined histologically (complete surgical/histologic response). The major determinants of complete surgical/histologic response were diameter of largest residual tumor prior to treatment, ECOG performance status, and grade, patients with grade 3 tumors having a higher complete response rate than those with grade 1 or 2 tumors. The major determinants of survival were ECOG performance status and diameter of largest residual tumor prior to treatment. Median survival of the total group was 1.8 years.

Adult↗

Effects of nicotine on beta-endorphin, alpha MSH, and ACTH secretion by isolated perfused mouse brains and pituitary glands, in vitro.

The effects of nicotine on secretion of the pituitary peptides beta-endorphin, alpha MSH, and ACTH were studied using the isolated perfused mouse brain (IPMB) and isolated superfused pituitaries of C3H mice. Nicotine (6.1 microM) stimulated secretion of beta-endorphin immunoreactivity from C3H IPMB approximately twofold. Secretion of alpha MSH immunoreactivity was stimulated approximately two- and sixfold by 6.1 microM and 12.2 microM nicotine, respectively. However, nicotine (6.1 microM) had no direct effect on the secretion of beta-endorphin, alpha MSH, or ACTH immunoreactivities from the isolated superfused pituitaries. The data suggest nicotine acts in the brain to stimulate pituitary secretion of alpha MSH and beta-endorphin. Electrocorticographic (ECoG) activity of the IPMB was monitored. Nicotine induced characteristic ECoG changes including a reduction of input voltage, a biphasic response of rapid desynchronization followed by prolonged synchronization, and seizure at high doses (12.2 microM).

Adrenocorticotropic Hormone↗

Human hand and lip sensorimotor cortex as studied on electrocorticography.

We investigated functional topography of human hand and lip sensorimotor cortex using somatosensory evoked potentials (SEPs) from chronically indwelling subdural grid electrodes (ECoG) in 3 epilepsy patients during stimulation of median nerve, ulnar nerve, and lower lip. We used dipole modeling to determine the cortical location of each peripheral sensory field. The cortical locations were in the postcentral gyrus and showed a clear somatotopic organization from medial superior to lateral inferior in the order: ulnar nerve, median nerve, and lip. The source localizations agreed with the results of cortical stimulations and anatomical features on intraoperative photographs. The cortical regions of median and ulnar nerve each could be modeled by sequential tangential and radial dipoles. The cortical region of lip was different and could be explained mostly by tangential dipoles. These findings suggest a difference in the cortical organization of human lip and hand sensory cortex and are consistent with a larger representation of lip in the posterior bank of central fissure in area 3b than on the gyral surface in area 1, similar to findings in macaque. Further studies in a larger population of patients with ECoG or normal subjects with scalp-EEG and MEG are warranted to test this hypothesis.

Brain Mapping↗

Somatotopy of human hand somatosensory cortex as studied in scalp EEG.

We recorded somatosensory evoked potentials (SEPs) in scalp EEGs during stimulation of the median nerve, the ulnar nerve and the individual digits in 3 normal subjects and in 1 epilepsy patient. In this patient we also measured SEPs from chronically indwelling subdural grid electrodes during electrocorticography (ECoG). We applied dipole modelling technique to study the 3-dimensional intracerebral locations and time activities of the neuronal sources underlying stimulation of different peripheral receptive fields. The sources underlying median nerve SEPs were located an average of 10.8 mm lateral inferior to those underlying ulnar nerve SEPs. Digit SEP sources showed a somatotopic arrangement from lateral inferior to medial superior in the order thumb, index finger, middle finger, ring finger and little finger, with some overlap or reversal for adjacent digits. The average distance between thumb and little finger was 12.5 mm. Thumb, index finger and middle finger were clustered around median nerve cortical representation, whereas ring finger and little finger were arranged around ulnar nerve cortex. In the epilepsy patient, the source localizations obtained in scalp EEGs showed good agreement with those on ECoGs. We conclude that SEPs recorded in scalp EEGs can be used to study functional topography of human somatosensory cortex non-invasively.

Adult↗