Animal electricity from Bologna to Boston.

This is an appreciation of 3 scientists who made historic contributions toward understanding bio-electrical activity. The discoveries of Galvani and Volta, who were contemporaries two hundred years ago, continue as basic supports in advancing the strength and health of all mankind. They, nevertheless, had political and scientific disagreements that still linger. The third scientist was our contemporary, Alexander Forbes who, throughout most of the 20th century, continued to increase our understanding of electrical activity in the nervous system.

The risk of seizure recurrence after a first unprovoked afebrile seizure in childhood: an extended follow-up.

OBJECTIVE: To assess the long-term recurrence risks after a first unprovoked seizure in childhood. METHODS: In a prospective study, 407 children who presented with a first unprovoked seizure were then followed for a mean of 6.3 years from the time of first seizure. RESULTS: One hundred seventy-one children (42%) experienced subsequent seizures. The cumulative risk of seizure recurrence was 29%, 37%, 42%, and 44% at 1, 2, 5, and 8 years, respectively. The median time to recurrence was 5.7 months, with 53% of recurrences occurring within 6 months, 69% within 1 year, and 88% within 2 years. Only 5 recurrences (3%) occurred after 5 years. On multivariable analysis, risk factors for seizure recurrence included a remote symptomatic etiology, an abnormal electroencephalogram (EEG), a seizure occurring while asleep, a history of prior febrile seizures, and Todd's paresis. In cryptogenic cases, the risk factors were an abnormal EEG and an initial seizure during sleep. In remote symptomatic cases, risk factors were a history of prior febrile seizures and age of onset younger than 3 years. Risk factors for late recurrences (after 2 years) were etiology, an abnormal EEG, and prior febrile seizures in the overall group and an abnormal EEG in the cryptogenic group. These are similar to the risk factors for early recurrence. CONCLUSIONS: The majority of children with a first unprovoked seizure will not have recurrences. Children with cryptogenic first seizures and a normal EEG whose initial seizure occurs while awake have a particularly favorable prognosis, with a 5-year recurrence risk of only 21%. Late recurrences do occur but are uncommon.

Surface mapping of spike potential fields: experienced EEGers vs. computerized analysis.

An EEG epileptiform spike focus recorded with scalp electrodes is clinically localized by visual estimation of the point of maximal voltage and the distribution of its surrounding voltages. We compared such estimated voltage maps, drawn by experienced electroencephalographers (EEGers), with a computerized spline interpolation technique employed in the commercially available software package FOCUS. Twenty-two spikes were recorded from 15 patients during long-term continuous EEG monitoring. Maps of voltage distribution from the 28 electrodes surrounding the points of maximum change in slope (the spike maximum) were constructed by the EEGer. The same points of maximum spike and voltage distributions at the 29 electrodes were mapped by computerized spline interpolation and a comparison between the two methods was made. The findings indicate that the computerized spline mapping techniques employed in FOCUS construct voltage maps with similar maxima and distributions as the maps created by experienced EEGers. The dynamics of spike activity, including correlations, are better visualized using the computerized technique than by manual interpretation alone. Its use as a technique for spike localization is accurate and adds information of potential clinical value.

EEG abnormalities in children with a first unprovoked seizure.

We examined EEG findings from an ongoing study of 347 children with a first unprovoked seizure. EEGs were available in 321 (93%), and 135 (42%) had an abnormal EEG. EEG abnormalities included focal spikes (n = 77), generalized spike and wave discharges (n = 28), slowing (n = 43), and nonspecific abnormalities (n = 7). Abnormal EEGs were more common in children with remote symptomatic seizures (60%) than in those with idiopathic seizures (38%) (p < 0.003), more common in partial seizures (56%) than in generalized seizures (35%) (p < 0.001), and more common in children age > 3 years (52%) than in younger children (12%) (p < 0.001). Records including both awake and sleep tracings were available in 148 (46%) cases. For 122 (38%) only awake tracings and for 51 (16%) only sleep tracings were available. Fifty-nine (40%) of the 148 patients with both an awake and asleep tracing had abnormal EEGs. Of 50 such EEGs with epileptiform abnormalities, 15 (30%) demonstrated the abnormality either only while awake (n = 8) or only while asleep (n = 7). Of 17 patients with EEG slowing, 8 showed slowing only in the awake tracing and 9 showed slowing in both the awake and asleep tracing. Children with even a single unprovoked seizure have a high incidence of EEG abnormalities. Obtaining a combined awake and sleep EEG significantly increases the yield of EEG abnormalities. In children with an idiopathic first seizure, EEG abnormalities are associated with an increased risk of seizure recurrence.

Discontinuing antiepileptic drugs in children with epilepsy: a prospective study.

In a prospective study, antiepileptic drugs were discontinued in 264 children with epilepsy after a mean seizure-free interval of 2.9 years. They were then followed for a mean of 58 months to ascertain whether seizures recurred. Seizures recurred in 95 (36%) of the children. Etiology was a significant predictor of outcome (relative risk [RR] = 1.81). On multivariable analysis, significant factors in the idiopathic group included age at onset above 12 years (RR = 5.4), a family history of seizures (RR = 3.1), the presence of slowing on the electroencephalogram prior to medication withdrawal (RR = 2.4), and a history of atypical febrile seizures (RR = 2.8). Specific epileptic syndromes such as juvenile myoclonic epilepsy and benign rolandic epilepsy were also significant predictors of outcome. In the remote symptomatic group, significant predictors of outcome included age at onset older than 12 years (RR = 3.6), moderate to severe mental retardation (IQ < 50) (RR = 2.8), a history of atypical febrile seizures (RR = 2.0), and a history of absence seizures (RR = 0.4). The majority of children with epilepsy in remission while on antiepileptic drug therapy will remain seizure free when medications are withdrawn. A few readily available parameters distinguish those with a good prognosis from those in whom seizures are likely to recur. These data provide the framework for the clinical decision making for withdrawal of medications in these children.

Structural lesions of the frontal lobe. Manifestations, classification, and prognosis.

Newer imaging methods, particularly MRI, are recognizing increasing numbers of frontal static and progressive lesions in patients in whom recurrent seizures are the presenting and only symptoms. Surgical results in terms of controlling frontal seizures are improving and becoming comparable to those achieved in the temporal lobe. The results following removal of discrete frontal lesions are superior to those with more diffuse lesions or without demonstrable lesions. Stereotaxic surgery and microsurgical techniques are allowing safer excisions from formerly inaccessible areas or adjacent to areas of essential function. These advances have increased the number of candidates who benefit from successful frontal lobe surgery. The types of clinical seizures in patients with discrete local frontal lesions usually conform with five of the seven anatomically named seizure types described in the 1989 International Classification of Epilepsies and Epileptic Syndromes (supplemental motor seizures, anterior frontopolar region, dorsolateral, and motor cortex). Too few cases with discrete lesions were found with sufficiently detailed seizure descriptions of possible orbitofrontal and cingulate origin to allow separate categorizations. In those cases symptoms and signs, such as autonomic, mood and affect, gestural automatisms, and versive movements preceding the automatisms, did not seem to differentiate orbitofrontal and anterior cingulate lesion cases from each other or from those in other areas of the anterior third of the frontal lobe.

Risk of seizure recurrence following a first unprovoked seizure in childhood: a prospective study.

In a prospective study, 283 children who presented with a first unprovoked seizure were followed for a mean of 30 months from the time of first seizure. Subsequent seizures were experienced by 101 children (36%). The cumulative risk of seizure recurrence for the entire study group was 26% at 12 months, 36% at 24 months, 40% at 36 months, and 42% at 48 months. The cumulative risk of recurrence in the 47 children with a remote symptomatic first seizure was 37%, 53%, and 60% at 12, 24, and 36 months, respectively, compared with a cumulative risk of 24%, 33%, and 36% at 12, 24, and 36 months, respectively, in the 236 children who had had an idiopathic first seizure (P less than .01). In children with an idiopathic first seizure, the electroencephalogram was the most important predictor of recurrence. The cumulative risk of recurrence in the 81 children with abnormal electroencephalograms was 41%, 54%, and 56% at 12, 24 and 36 months, respectively, but only 15%, 23%, and 26% at 12, 24, and 36 months, respectively, in the 138 children with normal electroencephalograms (P less than .001). A history of epilepsy in a first-degree relative was a significant risk factor only in idiopathic cases with abnormal electroencephalograms. In children with a remote symptomatic first seizure, either a history of prior febrile seizures or the occurrence of a partial seizure were significant predictors of recurrence. Age at first seizure and duration of seizure did not affect recurrence risk in either the idiopathic or remote symptomatic group. A total of 84% of the children were not treated with antiepileptic drugs or were treated for less than 2 weeks. Only 9% were treated for longer than 3 months. Treatment did not affect the risk of recurrence. The results suggest that, even without treatment, the majority of children with a first unprovoked seizure will not experiment a recurrence. Children with an idiopathic first seizure and a normal electroencephalogram have a particularly favorable prognosis.

Temporal and spatial distribution of intracellular potentials during generation and spread of epileptogenic discharges.

This chapter addresses the characteristics and spatial distribution of intracellular potentials, the spread of paroxysmal depolarization shifts (PDSs) through the cortex, the extracellular field potentials in three dimensions, and the concentrations of penicillin in direct contact with elements in the epileptogenic focus. Data are presented that show that there are several types or gradations of PDS intensities within each focus; PDS types are distributed in groups related to their distance from the center of the focus and to the concentration of the epileptogenic drug; the morphology and repetition rate of electroencephalogram (EEG) spikes are related to features of the intracellular potentials; a mathematical model can estimate the distribution of concentrations of penicillin within the focus over long periods; no barriers impede diffusion of penicillin either at the cortical surface or at the boundary between gray and white matter; the potential field of the EEG spike is defined in three dimensions; and PDSs spread through the focus at the rate of 0.25 m/sec.

The relevance of secondary epileptogenesis to the treatment of epilepsy: kindling and the mirror focus.

Human beings with partial epilepsy and demonstrable cerebral lesions show, in addition to ipsilateral epileptiform EEG discharges, apparently independent epileptiform discharges from the opposite hemisphere. Patients with apparent unilateral focal onset of their partial seizures but without demonstrable lesions also frequently display what appear to be bilaterally independent EEG foci. When surgical treatment or medical prognosis is considered and there is no demonstrable lesion, the decision of which of the two apparent foci is primarily responsible for the seizures is often difficult. Even with a known structural lesion the question arises whether, following its removal, the contralateral focus will persist and will be epileptogenic. Two related experimental phenomena bear directly on these questions- kindling and the mirror focus. This presentation looks critically at existing evidence and finds that it fails to support the idea that kindling and the mirror focus have roles in human epilepsy that currently should influence clinical decisions.

Symptomatology of nonconvulsive seizures: ictal and postictal.

Nonconvulsive seizures were divided into the two major classes used in the International Classification of Seizures (partial and generalized). Of the patients with nonconvulsive seizures reported, four had complex partial seizures and two had generalized absences. An analysis of the simultaneous recordings of EEG activity and the behavior of patients with nonconvulsive seizures on closed circuit television (CCTV) led to improved recognition and management of the seizures by providing information essential for making proper diagnoses and classification. Some anatomical and physiological factors are offered to explain the limited ability of scalp EEG to register epileptogenic spike activity occurring at the cortex.

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.

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.

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.