Localization of a gene for partial epilepsy to chromosome 10q.

There is strong evidence for a genetic contribution to epilepsy, but it is commonly assumed that this genetic contribution is limited to 'generalized' epilepsies, and that most forms of 'partial' epilepsy are nongenetic. In a linkage analysis of a single family containing 11 affected individuals, we obtained strong evidence for localization of a gene for partial epilepsy. This susceptibility gene maps to chromosome 10q, with a maximum two-point lod score for D10S192 of 3.99 at theta = 0.0. All affected individuals share a single haplotype for seven tightly linked contiguous markers; the maximum lod score for this haplotype is 4.83 at theta = 0.0. Key recombinants place the susceptibility locus within a 10 centimorgan interval.

Normal brain-stem auditory evoked potentials with abnormal latency-intensity studies in patients with acoustic neuromas.

Brain-stem auditory evoked potentials (BAEPs) are highly sensitive for detecting acoustic neuromas but false-negative results occur. We studied BAEPs preoperatively in 39 cases of acoustic neuroma. Absolute and interpeak latencies ipsilateral to the tumor, and interaural latency differences, were normal in four patients with small tumors. In three of these, however, results of latency-intensity studies were abnormal. In one patient, the latency-intensity result became normal postoperatively. If acoustic neuroma is suspected, and BAEPs are normal by usual criteria, latency-intensity functions should be examined to maximize chances of detecting a small tumor.

The role of extracellular potassium in hippocampal epilepsy.

It has been proposed that the notable capacity for epileptogenesis in the hippocampus may be related to potassium accumulation in extracellular spaces. To investigate this hypothesis more directly, we measured changes in extracellular potassium concentration ([K+]o) during focal hippocampal epilepsy using potassium-sensitive microelectrodes. Interictal and ictal electroencephalographic events were accompanied by increases in [K+]o that varied systematically with depth from the ependymal surface and lateral distance from the focus. Maximal [K+]o changes during interictal and ictal discharges occurred in the stratum pyramidale. Initiation of ictal activity did not correlate with a particular "threshold" [K+]o. Comparing these results with similar data from neocortex, we observed that interictal K+ responses in hippocampus lasted longer and had slower rise times, and that peak interictal and ictal [K+]o values were consistently lower. Increases in [K+]o cannot be the sole explanation for regional variations in seizure susceptibility, interictal-ictal transitions, or termination of ictal episodes.

Effect of cervical spinal cord lesions on early components of the median nerve somatosensory evoked potential.

Clinical interpretation of median somatosensory evoked potentials (SEPs) is usually based on latency measurements of selected waveforms. The "cervicomedullary" potential (N14) is commonly recorded by measuring the voltage difference between cervical spine and frontal electrodes. This cervicomedullary potential is actually a composite waveform that is generated by several distinct neural structures. We present evidence that placement of additional recording electrodes to delineate the multiple cervical components of the median SEP enhances ability to detect and localize cervical cord lesions.

Computerized cranial tomography in cerebral diseases of white matter.

Computerized tomographic scans were performed on 31 patients with primary diseases of the white matter. Among 18 patients with multiple sclerosis, acute lesions were visualized in five, all with symptomatic cerebral hemisphere disease. Characteristic white matter lesions were also demonstrated in adrenoleukodystrophy, spongiform encephalopathy, progressive multifocal leukoencephalopathy, disseminated necrotizing leukoencephalopathy, and an undiagnosed leukoencephalopathy associated with malignancy. Besides identifying white matter abnormalities, the CT scan patterns were often specific enough to help distinguish among the various etiologic possibilities for the abnormalities. Useful diagnostic characteristics included the anatomic distribution of lesions, mass effect, atrophic changes, and enhancement after contrast infusion.

Multiple sclerosis and narcolepsy: possible similar genetic susceptibility.

We have studied 2 patients with multiple sclerosis and narcolepsy. In both patients, the DR 2 histocompatibility antigen was positive. In each of the patients, the diagnosis of narcolepsy was confirmed by polygraphic testing.

Benign epileptiform transients of sleep. Clarification of the small sharp spike controversy.

Electroencephalograms were performed on 120 normal subjects sleep deprived for 24 hours. Twenty-four percent of the volunteers exhibited one or more epileptiform transients during stages 1 or 2 of non-rapid eye movement sleep. These potentials usually appeared as monophasic or diphasic spikes unaccompanied by sharp waves or focal slowing. When abundant, they occurred sporadically and independently over both hemispheres but were best developed in the anteromesial temporal regions. A 20 percent incidence of similar spikes was found in 599 consecutively referred patients recorded under the same conditions. We conclude that these epileptiform transients of sleep, which have been called "small sharp spikes," are normal and are of no diagnostic value in the evaluation of patients with seizures.

Autosomal dominant partial epilepsy with auditory features: defining the phenotype.

The authors previously reported linkage to chromosome 10q22-24 for autosomal dominant partial epilepsy with auditory features. This study describes seizure semiology in the original linkage family in further detail. Auditory hallucinations were most common, but other sensory symptoms (visual, olfactory, vertiginous, and cephalic) were also reported. Autonomic, psychic, and motor symptoms were less common. The clinical semiology points to a lateral temporal seizure origin. Auditory hallucinations, the most striking clinical feature, are useful for identifying new families with this synome.

State-dependent changes in the N20 component of the median nerve somatosensory evoked potential.

Short-latency components of median nerve somatosensory evoked potentials are generally assumed to be unaffected by sleep and level of arousal. We found that sleep prolongs the latency and alters the morphology of the N20 component in normal subjects. These changes may represent differential effects of sleep on various elements contributing to generation of the N20. Failure to control for patient state may degrade the reliability of clinical somatosensory evoked potential testing.

Reliability of seizure classification using a semistructured interview.

Methods for standardized classification of epileptic seizures are important for both clinical practice and epidemiologic research. In this study, we developed a strategy for standardized classification using a semistructured telephone interview and operational diagnostic criteria. We interviewed 1,957 adults with epilepsy ascertained from voluntary organizations. To confirm and expand the seizure history, we also interviewed a first-degree relative for 67% of subjects and obtained medical records for 59%. Three lay reviewers used all available information to classify seizures. To assess reliability, each reviewer classified a sample of subjects assigned to the others. In addition, an expert physician classified a sample of subjects assigned to two of the reviewers. Agreement was "moderate-substantial" for generalized-onset seizures, both for the comparisons between pairs of lay reviewers and for the neurologist versus lay reviewers. Agreement was "substantial-almost perfect" for partial-onset seizures, both for pairs of lay reviewers and for the neurologist versus lay reviewers. These results suggest that seizures can be reliably classified by lay reviewers, using operational criteria applied to symptoms ascertained in a semistructured telephone interview.

Electrophysiologic features of abetalipoproteinemia: functional consequences of vitamin E deficiency.

We performed electrophysiologic testing in 10 patients with abetalipoproteinemia (ABL). Peripheral nerve studies implied an axonal disorder. Visual evoked potentials demonstrated prolonged P100 latency in three patients and abnormal electroretinograms in six. Somatosensory evoked potentials indicated dorsal column dysfunction in eight patients. Brainstem auditory evoked potentials were normal. Findings were consistent with the known neuropathology of ABL and of experimental vitamin E deficiency. Stabilization or improvement in electrophysiologic findings occurred with vitamin E supplementation. Neurophysiologic tests document retinal, central somatosensory and peripheral nerve lesions in vitamin E deficiency and provide an objective indication of response to treatment.

The role of transcranial Doppler in confirming brain death: sensitivity, specificity, and suggestions for performance and interpretation.

We performed transcranial Doppler (TCD) examinations on 54 comatose patients over a 1-year period. Of 49 patients with technically adequate TCD examinations, 23 met criteria for determination of brain death by clinical and EEG criteria (21) or clinical criteria alone (2; EEG not performed). A TCD waveform abnormality, consisting of absent or reversed diastolic flow, or small early systolic spikes, in at least 2 intracranial arteries, occurred in 21 brain-dead patients, but in none of the other patients in coma. With appropriate guidelines for performance and interpretation, TCD could be incorporated into institutional protocols as a rapid and convenient alternative to EEG for confirmation of brain death.

Glial cells and extracellular potassium: their relationship in mammalian cortex.

Simultaneous recordings were made of glial cell potentials and the extracellular potassium concentration ([K+]O) in cat cortex in an attempt to provide more quantitative information about the sensitivity of mammalian neuroglia to changes in [K+]O. A penicillin epileptogenic focus served to generate both transient and sustained elevations in [K+]O, thus allowing measurement of glial membrane potential (Vm) at both resting and increased [K+]O levels many times during the same experiment. Resting Vm averaged--92.6 +/- 10.9 mV for 33 glial cells. With each surface interictal spike, glial cells exhibited slow depolarizations averaging 18.4 +/- 6.5 mV which mirrored rises in [K+]O in many respects. Several discrepancies were found, however, between transient and focal rises in [K+]O and the associated glial cell depolarizations which made it difficult to determine accurately the effect of changes in [K+]O on glial Vm. For example, the amplitude of the glial depolarization caused by a single interictal discharge showed no constant relationship to depth below the cortical surface in contrast to the consistent laminar profile recorded by the K+ electrode. Thus, large glial membrane depolarizations could be recorded at times when there was little or no increase in measured [K+]O. Agreement between changes in [K+]O and glial cell depolarizations was closer to that predicted by the Nernst equation during sustained elevations in [K+]O such as occurred during ictal episodes ('seizures'). These findings may be related in part to methodology as a consequence of the different spatial relationships which exist between glial membrane, K+-electrode tip and released K+. In addition, though, they may indicate the presence of a functional glial syncytium.

Anatomic localization of topically applied [14C]penicillin during experimental focal epilepsy in cat neocortex.

14C-labeled penicillin was topically applied to the suprasylvian gyri of adult cats in order to study the distribution of the convulsant agent at the onset of focal epileptogenesis. Using radioassay and autoradiographic techniques, a steep gradient of penicillin was found. At the time interictal EEG spike discharges appeared, 95% of the labeled drug was in the uppermost cortical layers (laminae I-III). Analysis of the concentration profiles obtained by scintillation counting showed that penetration of penicillin into brain occurs primarily by passive diffusion. An apparent diffusion coefficient for penicillin in neocortex of 1.5 sq. mm/h was calculated using modifications of standard diffusion equations. It is apparent that with a rapidly acting topical convulsant such as penicillin, the dimensions of the neuronal pool actually in contact with the drug will change significantly over time. The changing boundaries of the epileptic neuronal aggregate must be taken into account when interpreting observations made within and around such experimentally produced epileptic foci.

Kinetics of potassium movement in norman cortex.

Artificial CSF containing 12mEq/1 of potassium (4 times normal concentration) was perfused over the surface of normal neocortex in 10 locally or barbiturate anesthetized cats. Extracellular potassium concentrations ([K+]OS) were measured as a function of time to 8 h and of depth to 3 mm. Analysis of the [K+]O versus depth and [K+]O versus time profiles showed that the distribution of extracellular potassium could be modelled by a process of diffusion with diffusion coefficient = 1.03 +/- 0.16 sq.mm/h, and a surface barrier to diffusion with magnitude given by a barrier constant 0.8 +/- 0.2 mm-1, and with a small correction for active uptake into cells and blood vessels. The profiles obtained differ considerably from those which could be predicted from kinetic properties of potassium in aqueous solution.

Regional cerebral blood flow in the rat during prolonged seizure activity.

In order to evaluate the possible contribution of regional insufficiency in blood flow to the development of epileptic brain damage, we have measured changes in total and regional cerebral blood flow (tCBF and rCBF) during the course of prolonged sustained seizures. We have used both a particle distribution method (radioactively labelled microspheres) and a diffusible tracer method (iodo [14C]antipyrine). Seizures were induced with bicuculline (1.2 mg/kg, i.v.) in rats with neuromuscular paralysis, mechanically ventilated with 70% N2O/30% O2, rCBF was determined in 13 brain regions after 10, 30, 60 and 120 min of seizure activity. Microsphere and iodo[14C]antipyrine methods gave identical control values for tCBF (0.88 +/- 0.02 vs 0.86 +/- 0.07 ml/g brain/min) and closely similar rCBF values. The increases in tCBF after 10 and 30 min seizure activity were less as measured with microspheres than with iodo [14C]antipyrine (2.42 +/- 0.29 vs. 4.99 +/- 0.94 and 1.79 +/- 0.18 vs 3.05 +/- 0.30 mg/g brain/min, respectively). With microspheres, rCBF values showed considerable interhemisphere variability, but did not do so with iodo [14C]antipyrine. The regional pattern of flow changed during seizures. Changes in neocortical rCBF tended to match changes in tCBF. Consistent decreases in rCBF relative to tCBF were seen in the pons-medulla and cerebellum at all seizures times. Relative increases in rCBF were seen at all seizure times in the thalamus, and at 10 and 30 min in colliculi and midbrain. In the hippocampus, rCBF was unchanged (relative to tCBF) at 10 and 30 min, but was increased at 60 and 120 min of seizure activity. Thus, regions developing epileptic brain damage in this model of status epilepticus (hippocampus, thalamus, neocortex) show increases in rCBF greater than those in regions not showing brain damage (cerebellum, brain stem).

Reversible signal abnormalities in the hippocampus and neocortex after prolonged seizures.

PURPOSE: To investigate the phenomenon of reversible increased signal intensity of medial temporal lobe structures and cerebral neocortex seen on MR images of six patients with recent prolonged seizure activity. METHODS: After excluding patients with known causes of reversible signal abnormalities (such as hypertensive encephalopathy), we retrospectively reviewed the clinical findings and MR studies of six patients whose MR studies showed reversible signal abnormalities. MR pulse sequences included T2-weighted spin-echo coronal views or conventional short-tau inversion-recovery coronal images of the temporal lobes. RESULTS: All six MR studies showed increased signal intensity within the medial temporal lobe, including the hippocampus in five studies. All follow-up MR examinations showed partial or complete resolution of the hyperintensity within the medial temporal lobe and the neocortex. In one patient, results of a brain biopsy revealed severe cerebral cortical gliosis. Temporal lobectomy performed 4 years later showed moderate cortical gliosis and nonspecific hippocampal cell loss and gliosis. CONCLUSION: Significant hyperintensity within the temporal lobe is demonstrable on MR images after prolonged seizure activity, suggestive of seizure-induced edema or gliosis. Damage to medial temporal lobe structures by prolonged seizure activity indicates a possible mechanism of epileptogenic disorders.

Electroencephalography in lacunar infarction.

To determine the occurrence and clinical implications of electroencephalographic (EEG) abnormalities in patients with acute lacunar infarction, we conducted a single-blinded EEG study in 55 patients. Twenty-nine (53%) had mild EEG abnormalities, which were focal and ipsilateral to the side of infarction in 7 patients (13%). Abnormalities were more common in patients with evidence of a prior stroke (10 of 12 patients, 83%). However, 43% (16 of 37 patients) of those without historical or radiologic evidence of a prior stroke also had mild EEG abnormalities. This represents a higher incidence of routine EEG abnormalities in lacunar infarction than is generally assumed. Indeed, these findings are more consistent with recent quantitative EEG studies that consistently have shown high rates of abnormalities in lacunar infarction. We did not find major EEG abnormalities, such as continuous or nearly continuous focal delta activity, in any patient with first lacunar infarction. We conclude that within the first 48 h after a first ischemic infarction, when computed tomography often fails to show abnormalities, an EEG that shows lateralized major abnormalities is useful in excluding the diagnosis of either lacunar infarction or infarction limited to the brain stem. Mild abnormalities occur more often than previously thought in lacunar infarction and do not exclude this diagnosis.

The predictive value of intraoperative electrocorticography in resections for limbic epilepsy associated with mesial temporal sclerosis.

OBJECTIVE: Prior studies on the predictive value of intraoperative electrocorticography (ECoG) have been performed on heterogeneous groups of patients with both temporal and extratemporal interictal spikes, lesional and nonlesional pathological findings, and variably extensive resections by different surgeons. METHODS: We performed both pre- and postresection intraoperative ECoG on 29 consecutive patients with medial temporal lobe epilepsy (17 left-sided) who underwent standard nontailored resections by one surgeon (RRG). All patients had only temporal interictal spikes (six bitemporal) and mesial temporal sclerosis diagnosed by preoperative magnetic resonance imaging and confirmed by pathological examination of resected tissue. RESULTS: After a mean follow-up of 24.8 months, there were 15 (52%) patients who were seizure-free, 6 (21%) who were seizure-free except for auras, and 8 (28%) who had any seizure after the 1st postoperative month. Fourteen patients (48%) had active interictal discharges outside the area of planned resection revealed by preresection ECoG. Neither the presence of these spikes nor their mean frequency correlated with seizure outcome. Eleven patients (38%) had residual spike discharges after resection, and 18 patients (62%) had new spikes revealed by the postresection ECoG. Neither of these findings nor the mean spike frequency of residual or new spikes related to seizure outcome. Persistent spikes increased in frequency after resection in all outcome groups. CONCLUSIONS: Electrocorticographic monitoring of interictal epileptiform activity intraoperatively is not useful in the surgical treatment of patients undergoing standard resection for medial temporal lobe epilepsy with magnetic resonance imaging evidence of mesial temporal sclerosis.

Subacute sclerosing panencephalitis and acquired immunodeficiency syndrome: role of electroencephalography and magnetic resonance imaging.

Subacute sclerosing panencephalitis (SSPE) had largely disappeared from the United States because of nearly universal measles vaccination, but it has reemerged in children infected with human immunodeficiency virus (HIV). Two children with SSPE are described. The first was HIV positive and presented with seizures and encephalopathy at the age of 21 months. The second developed myoclonus and dementia at age 4 years; she was not infected with HIV, but her mother had acquired immunodeficiency syndrome. Magnetic resonance imaging findings were nonspecific and could have been compatible with HIV encephalopathy. Electroencephalography was characteristic of SSPE, showing high-voltage, periodic slow-wave complexes and background slowing. The diagnosis of SSPE was confirmed by brain biopsy or high measles antibody titers in the cerebrospinal fluid.