Focal Spikes Research Articles

A propos d'une forme d'epilepsie hemiconvulsive avec hemiplegie chez l'enfant

Fifteen children between the age of 3 and 7 years who had had unilateral seizure followed by a transitory hemiplegia (without fever) were observed. This seizure was the only one in 13 of the children; a second fit appeared in 2 others. The average duration of the observation period was 10 years, 6 months. The evolution of the EEG shows that after a post-ictal delta focus contralateral to the hemiplegia, spike foci of variable localisations were formed in 12 cases. These cases, chosen because of their benign evolution, seem to be related closely to rolandic paroxysmal epilepsy (EPR).

Quantitative evaluation of anticonvulsant effects on penicillin‐induced spike foci in cats

We evaluated the effects of phenytoin, carbamazepine, phenobarbital, sodium valproate, and ethosuximide on penicillin-induced spike foci. Phenytoin, carbamazepine, and phenobarbital at blood levels within or slightly above the human therapeutic range in humans increased spike frequency, decreased spike duration, and abolished after discharges. Ethosuximide and sodium valproate had no statistically significant effect even at blood levels considered toxic in humans. The experimental spike focus and the method of analysis appear useful for: (1) detection of new potentially anticonvulsant drugs, (2) classifying new potentially anticonvulsant drugs according to the type of clinical seizure for which benefit is most likely, and (3) comparing different anticonvulsant drugs.

A clinical and electroencephalographical follow-up study for more than 10 years in patients with epilepsy.

A clinical and electroencephalographical follow-up study of 10 to 18 years was conducted on 147 patients with epilepsy. Generalized epilepsy was prognostically favorable, but petit mal absence with grand mal was not always good clinically and electroencephalographically as generally accepted. Paroxysmal discharges found in the initial EEGs tended to become more localized in the final EEGs recorded at least more than 10 years later. The migration of spike foci and bilateral independent spikes were found in many patients. Prognostically the EEG background was more important. Fourteen and six-per-second positive spikes and 6Hz spike and wave phantoms had an age dependence as well as 3 Hz spike and wave complexes and these discharges were regarded as prognostically the favorable patterns.

The independence of closely spaced discrete experimental spike foci.

Stable spike foci generated by weak penicillin solutions had a minimal area of distribution of 12.5 mm2. Two foci separated by 4 mm on the same gyrus were consistently dependent and simultaneous. An area of "positive surround" between the two spikes did not prevent dependency. This contradicts the hypothesis that "positive surround" prevents spreading of epileptiform discharges. Spike foci separated by 6 mm were almost always independent. Bursts of afterdischarges remained independent if the primary spikes were independent. Postafterdischarge suppression and spreading depression of Leao affected independent spike focus selectively. These experiments suggest that cross-talking between cortical columns is limited to column 1 to 2 mm apart.

Positron computed tomography studies of cerebral glucose metabolism in man: Theory and application in nuclear medicine

The capability of positron computed tomography (PCT) to delineate the substructures of the brain and its facility for accurately measuring the local tissue radioactivity concentration allow the application of tracer kinetic models for the study of local cerebral function in man. This principle and an adaptation of the 14C-deoxyglucose (DG) model of Sokoloff et al. with 18F-2-fluoro-deoxy-D-glucose (FDG) is being used at UCLA. Brookhaven National Laboratory, University of Pennsylvania, NIH, and the Massachusetts General Hospital to determine the local cerebral glucose metabolic rate (LCMRGIc) in normal man at rest and during sensory activation and the changes that occur in patients with a variety of cerebral disorders. Kinetic studies with PCT have been employed to measure the rate constants of the model in different gray and white matter structures of the brain in both normal and ischemic states. The precision of the method in normals has been shown to be about +/- 5% for 1.5-2.0 sq cm regions of the brain. Studies in normals have yielded values for hemispheric CMRGIc that are in agreement with measurement using the Kety-Schmidt technique and LCMRGIc values in agreement with values in monkeys using DG autoradiography. Studies in volunteers subjected to visual and auditory stimulation are demonstrating the potential of this technique for investigating the human brain's response to different stimuli. STudies in patients with stroke show excellent correlation between the degree, extent, and particular structures involved and the clinical symptoms. The method consistently detected hypometabolism in cortical, thalamic, and striatal tissues that were dysfunctional due to deactivation or damage but which appeared normal on x-ray CT. Studies in patients with partial epilepsy have shown hypometabolic zones that highly correlated anatomically with interictal EEG spike foci and were associated with normal x-ray CT studies in 77% of the patients studied. The studies on epilepsy at UCLA have resulted in the integration of the LCMRGIc study into the clinical workup of patients with partial epilepsy that are candidates for surgical resection of their epileptogenic focus (effective June 1979). Studies on Huntington's chorea, Parkinson's disease, aphasia, dementia, schizophrenia, and tumors are in early stage of investigation but also are providing exciting new results. Further studies are needed to determine the role of the local function information obtained with the PCT-FDG method in elucidating the basic mechanism and the potential to aid in improving the approach to medical therapy.

Epileptic patterns of local cerebral metabolism and perfusion in humans determined by emission computed tomography of 18FDG and 13NH3

Seventeen patients with partial epilepsy had electroencephalographic (EEG) monitoring concurrent with cerebral positron emission computed tomography (PECT) after 18F-fluorodeoxyglucose (18FDG) and 13N-ammonia (13NH3) were given intravenously as indicators of local cerebral glucose utilization (LCMRglc) and relative perfusion, respectively. In 12 of 15 patients who had unilateral or focal electrical abnormalities, interictal 18FDG scan patterns clearly showed localized regions of decreased (14 to 58%) LCMRglc that correlated anatomically with the eventual EEG localization. These hypometabolic zones appeared normal on x-ray computed tomography in all but 3 patients and were unchanged on 18FDG scans repeated on different days. In 5 of 6 patients who underwent anterior temporal lobectomy the interictal 18FDG scan correctly detected the pathologically confirmed lesion as a hypometabolic zone, and removal of the lesion site resulted in marked clinical improvement. In contrast, the ictal 18FDG scan patterns clearly showed foci of increased (82 to 130%) LCMRglc that correlated temporally and anatomically with ictal EEG spike foci and were within the zones of interictal hypometabolism (three studies in 2 patients). 13NH3 distributions paralleled 18FDG increases and decreases in abnormal zones, but 13NH3 differences were of lesser magnitude. When the relationship of 13NH3 uptake to local blood flow found in dog brain was applied as a correction to the patients' 13NH3 scan data, local alterations in perfusion and glucose utilization were usually matched in both the interictal and the ictal state. We conclude that the interictal 18FDG-PECT scan is useful in aiding localization of the dysfunctional cerebral zone most likely to be responsible for seizures in patients being considered for anterior temporal lobectomy. With further development, emission computed tomography may help in better categorizing the various forms of the disorder and in elucidating the basic mechanisms of epilepsy in humans.

The local and remote effect of focal spikes on somatosensory evoked potential of the rat.

The local and remote effect of focal spikes on somatosensory evoked potential of the rat.

Electroencephalographic and pathophysiologic features of rat parenteral panicillin epilepsy

A multifocal epileptic pattern with secondary generalization, clinically characterized by mild myoclonic jerks, was evoked in the rat by the i.p. injection of 600,000 to 1,200,000 IU/kg penicillin. The development of clonic or tonic-clonic seizures was sometimes observed at that dose. Smaller doses of penicillin sometimes evoked focal spikes or bilateral synchronous bursts of atypical spike and wave complexes accompanied by vigilance reduction. Occasional and late involvement of thalamic structures in producing the paroxysmal activity was observed also with the largest doses. Diffuse bilateral application of a dilute penicillin solution (250 to 1,000 IU/hemisphere) produced EEG patterns which were very similar to those evoked by i.p. administration. Because of the larger doses of parenteral penicillin required to evoke epileptic activity compared with the cat model, both a more effective rat blood-brain barrier and/or a lesser sensitivity of rat cortex to the epileptogenic action of penicillin are suggested. In addition, other dissimilarities exist between epilepsies in the rat and cat after parenterally administered penicillin. Topical administration of the antibiotic to the thalamus did not induce any paroxysmal pattern, whereas epileptic responses were recorded when penicillin was topically applied to the hippocampus. No electroclinical pattern resembling the human epileptic syndrome was observed. Our data emphasize also in this model the primary role of the cortex in the genesis of the penicillin-induced epileptic activity.

Evoked parietal spikes and childhood epilepsy.

Parietal spikes can be evoked in some children by tactile stimulation of their feet or other parts. I investigated whether this curious phenomenon remains unchanged for several years and then disappears or whether it presages later epilepsy. Some children demonstrating this phenomenon may experience a spontaneous focus of spikes during sleep or waking and later a convulsive state. The cause of this condition may be hyperexcitability of a small cortical parietal area.

Psychological complications of temporal lobe epilepsy.

A series of young adults with temporal lobe epilepsy included 36% with psychological complications. The incidence of overt psychosis was 11%. Psychopathology was more common in subjects with left temporal lobe spike foci (43%) and in males (42%), but these trends did not attain statistical significance. Psychological complications became manifest in adolescence in 85% of the affected cases, and were more likely (p less than 0.01) to occur when seizures began in the second 5 years of life. Although seizures nearly always antedated psychological problems, the onsets of epilepsy and psychological complications did not directly correlated (p = 0.43).

Longitudinal study of epileptiform EEG patterns in normal children.

EEG were recorded in 3,726 children, from 6 to 13 years of age who were neurologically normal and had no history of epileptic seizures. The records were taken during wakefulness, at rest, and during hyperventilation. In 131 cases (3.54%) epileptiform patterns were found. They consisted of 3 count/sec spike and slow waves discharges (4 cases), multiple spike and slow wave complexes (37 cases), midtemporal spikes (50 cases), rolandic or parietal spikes (27 cases), occipital spikes (2 cases), and multifocal spikes (11 cases). Half of the subjects with EEG abnormalities had behavior problems and/or slight psychomotor ability disturbances. Follow-up studies over an 8 to 9 year period were performed. These demonstrated the spontaneous disappearance of the EEG abnormalities, usually within school age or, at the latest, during adolesence. Only seven individuals developed epileptic seizures of the primary generalized type which responded well to anticonvulsant drug treatment. From this study we can deduce that the epileptiform EEG patterns that often are found in children during school age have no clinical relationship to epilepsy in the great majority of cases. The relationship with epilepsy exists probably on a genetic level for the generalized discharges. The spike foci are non-epileptic in nature in all probability, especially if they emerge from a fairly normal background activity and their duration is very similar to that of the constituents of the background activity, as found in the majority of these subjects. On the contrary, it is probable that these alterations express difficulties in affective or motor adaptation during childhood.

Epidemiology of different types of epilepsy in school age children of Modena, Italy.

An epidemiologic study of epilepsy in school age children has been carried out in Modena, Italy, during the period 1968 to 1973. The prevalence of epileptics aged 5 to 14 years varied between 3.98% and 4.91%. The accession rate varied between 60 and 98 cases /100,000. The primary generalized epilepsies represent 30.8%, the epilepsies with rolandic spike foci 23.9%, the other types of partial epilepsy 42.1%, and the Lennox-Gastaut syndrome 3.2%. Of the 178 epileptics diagnosed during school age, 159 have been followed for at least 4 years, with recovery in 55% of the cases and tendency to improve in 24%.

Quantitative studies of spike foci induced by minimal concentrations of penicillin

The minimal concentrations of penicillin which induce stable recurrent spikes (20,000 U/ml) and which elicit stable recurrent after-discharges (100,000 U/ml) were determined. A quantitative study of the inter-relationships, variability and changes with time of a number of spike parameters (spike latency, spike amplitude, amplitude of prepositivity, spike duration and spike frequency) was performed. The study adds new information on the pathogenesis of the experimental spike focus and serves as baseline for quantitative evaluation of the effects of anticonvulsants on the characteristics of the primary spike focus and on after-discharges.

The effects of phenytoin on the penicillin-induced spike focus

A quantitative evaluation of the effects of phenytoin on penicillin-induced spike foci is reported. Phenytoin at blood levels considered within therapeutic range in humans increased spike frequency, decreased spike duration and abolished after-discharges. Spiking at weak foci was completely abolished when high concentrations of phenytoin were used. It is concluded that phenytoin affects mainly the long chain pathways whether the ultimate effects of these pathways are excitatory or inhibitory.

Histopathology of the ferric-induced chronic epileptic focus in cat: A Golgi study

Five cats were rendered chronically epileptic via subpial injection of saturated FeCl 3 solution. Six weeks postinjection, electrocorticographic recording demonstrated focal epileptiform spiking in the region of the injection. This finding was not observed in saline-injected controls. Histopathological analysis of the epileptic focus using Nissl and Golgi-Cox techniques revealed (i) depopulation of Golgi-impregnated neurons, (ii) astocytic gliosis, (iii) loss of dendritic spines, (iv) decreased dendritic branching, and (v) dendritic varicosities. These are similar to the pathological findings which have been described for human epileptogenic foci. These results, in combination with the frequent observation of hemosiderosis in regions of human epileptogenic foci, implicate the release of iron from extravasated blood elements as a possible etiologic mechanism. Therefore, we believe the FeCl 3 experimental epileptogenic focus accurately models the human clinical entity (posttraumatic epilepsy) with respect to both electrophysiology and histopathology.

Focal epileptogenesis after intracortical hemoglobin injection

Intracortical injection of purified bovine hemoglobin produced chronic focal spike activity in 89% of rats tested; 50% of the animals evidenced spike activity within 48 h. The lesions produced were pathologically similar to those seen in post-traumatic epilepsy. Evidence is presented suggesting that the neural effect of iron released from hemoglobin may be causally related to the development of a trauma-induced epileptiform focus in humans.

Overnight Polygraphic Studies of Infantile Spasms — Influence of Hormone Therapy on Sleep States, Pulse, Respiration and Seizure Activities

The influence of hormone therapy on sleep states, pulse, respiration and seizure activities of infantile spasms was examined by means of overnight sleep polygraphy. Also the correlation between the changes of these parameters and the prognosis was investigated. The results were as follows: 1) In all cases, the awake time of TIB during hormone therapy was longer than before hormone therapy. The reduction of REM sleep time of SPT and lowering of REM density were remarkable during hormone therapy in cases with delayed psychomotor development as compared with cases with a considerable degree of psychomotor development. During hormone therapy, the NREM sleep time of SPT was shortened in cases with ACTH therapy, and prolonged in case with hydrocortisone therapy. 2) During hormone therapy, the pulse rate increased significantly in cases with a considerable degree of psychomotor development, but decreased significantly in cases with delayed psychomotor development. The change of respiratory rate by hormone therapy was not remarkable in all cases. 3) In cases with hypsarhythmic EEG records, the number of spikes decreased drastically by hormone therapy. In the case with EEG record of focal spikes, the number of spikes increased by hormone therapy. From the results mentioned above, the mechanism for effectiveness of hormone therapy and correlation between the administration of hormone therapy and prognosis was discussed.

Longitudinal study of EEG-spike appearance in long-term follow-up patients with epilepsy.

Summary Fluctuations of the spike component on EEG were studied in 66 epileptic patients under clinical observations for six years or more. During this time five or more EEG recordings were taken once a year. 1. There was no statistical correlation between the number of well controlled cases in the last three years (27.3%) and the disappearance rate of EEG spike on the three most recent EEG recordings. In the group of patients still having seizures, the incidence of the spike on the three recent EEGs was more and inconsistent. 2. When the cases were divided into primary generalized and partial epilepsies, there was no significant difference in the incidence of spike between the two groups with and without seizures. 3. As for the type of spike appearance, 34 cases were of the focal type (51.5%). In 11 cases, spike was not seen even once (16.7%). There were five cases (7.5%) where it was difficult to determine whether the spike belonged to the centrencephalic or focal type. 4. The incidence (presence or absence) of the spike per one EEG record fluctuated and ranged from 0–100% in each case. 5. In 21 cases (31.8% of the total; 61.7% of the focal spike group) there was a shift of the localized area. 6. The effectiveness of provocation by hyperventilation and photic stimulation was poor.

Functional anatomy of occipital lobe seizures: an experimental study in rats.

Small amounts of penicillin were used to create a seizure focus in the primary visual cortex (area 17), extrastriate cortex (area 18 and 18a), and neighboring somatosensory and temporal areas in rats. Autoradiography with 14C-deoxyglucose was used to map the focus and the local cortical and long subcortical circuits. Mild seizures from area 17 were associated with focal spiking without behavioral manifestations. There was restricted utilization of local U-fiber circuits and ipsilateral subcortical visual system nuclei. Stronger seizures filled up the visual cortex and projected into adjacent neocortex and limbic cortex, the contralateral 17-18a border, and additional subcortical nuclei. Seizures originating in the posterior visual cortex were associated with prolonged afterdischarges and stereotyped behavioral manifestations, with spread into the posterior cingulum, the subicular complex, and the bilateral hippocampus. After analyzing the electrographic discharges, behavior, and seizure pathways in each animal, we conclude that ictal symptoms associated with seizures would not be the expression of the function of a cortical focus, but rather of the dysfunction of excessive discharges through many local and long circuits.

Electroclinical and ultrastructural changes associated with subconvulsant doses of pentylenetetrazol

A series of rats was subjected to subconvulsant and convulsant doses of pentylenetetrazol (PTZ) and the brains were examined electronmicroscopically. After establishing baseline dose effects, rats were chronically implanted bilaterally with cortical bipolar electrodes in frontal and parietal regions. One week postoperatively, they received on either 3 or 4 successive days subconvulsant doses (10 to 20 mg/kg) of PTZ. The following electroclinical evolution was characteristic: Focal spike activity in some of the sampled regions was followed by asymptomatic low-voltage “spike-wave” bursts, which were in turn followed by higher voltage more diffuse “spike-wave” bursts associated with whisker twitching. The animals were killed on the third, fourth, or fifth day when the full clinical picture was present, but before a generalized convulsive seizure had occurred. Electron micrographs showed swollen glial processes around capillaries. No change could be detected in the endothelial basement membrane and the neurons appeared intact. We conclude that ultrastructural changes can be demonstrated prior to overt major seizures and that they are similar to some results in the literature on animals which received convulsant doses. Repeated subconvulsant doses of PTZ also led to a “kindling” effect.