Daniel B. Hoch

PERIODIC LATERALIZED EPILEPTIFORM DISCHARGES : A CRITICAL REVIEW

It is the purpose of this review to critically consider and organize the literature dealing with the ephemeral electroencephalographic (EEG) pattern periodic lateralized epileptiform discharges (PLEDs). Although the retrospective nature of these studies limits their ability to discuss accurately the clinical and pathophysiological aspects of this EEG entity, the available data strongly emphasize stroke as the dominant etiology and its high association with seizures. Recent evidence, particularly from functional neuroimaging studies, strongly suggests that PLEDs might reflect a key pattern for focal hyperexcitability in the penumbra zone of ischemic stroke. The authors prefer to consider PLEDs as an EEG signature of a dynamic pathophysiological state in which unstable neurobiological processes create an ictal-interictal continuum, with the nature of the underlying neuronal injury, the patients preexisting propensity to have seizures, and the co-existence of any acute metabolic derangements all contributing to whether seizures occur or not. This review underlines the need for further sophisticated prospective controlled studies implementing early continuous EEG monitoring in order to contribute to an understanding of the incidence, dynamics, and relevance of this pattern.

Fatal puerperal cerebral vasospasm and stroke in a young woman

A woman who experienced postpartum cerebral infarction, brain edema, and death is described. Angiography implicated cerebral vasospasm as the primary etiology.

14C-dopamine microinjected into the brain-stem of the rat: dispersion kinetics, site content and functional dose.

A morphological analysis was undertaken of both the dispersion characteristics and tissue content of dopamine (DA) microinjected acutely into the brain-stem of the anesthetized rat. 14C-DA, with a specific activity of 56-62 mCi/mMol, was infused unilaterally into the pars compacta of the substantia nigra in one of four test volumes: 0.5, 1.0, 4.0 or 8.0 microliters. The concentration of the 14C-DA solution was 1.0 microCi/microliter, equivalent to 3.01 micrograms/microliters, which was delivered at an injection rate of 1.0 microliter per 45 sec. At an interval of either one min or 15 min following the microinjection, the rats brain was removed rapidly from its calvarium, flash frozen and then cut in the coronal plane on a freezing microtome in 500 micron slabs. After each of the respective serial slabs was mounted on glass, the Eik Nes-Brizzee trochar technique for the discrete removal of tissue samples was used to obtain 0.5 mm dia. cylindrical plugs of meso-diencephalic tissue at distances from the site of injection ranging from 0.5 to 2.5 mm, center to center. Each sample plug was subsequently solubilized and 14C-DA activity quantitated by liquid scintillation spectrometry. The results show that regardless of volume, the spatial patterning of the microinjected solution assumes a tear-drop or pear shape, not a sphere. Further, as the volume of the injection is increased from 0.5 to 8.0 microliters, the magnitude of the dispersion of 14C-DA is enhanced throughout the surrounding parenchyma, but not in a linear fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

Valproate and lamotrigine level variation with menstrual cycle phase and oral contraceptive use

Objective: To determine whether 1) combined oral contraceptive (COC) use affects serum levels of valproate (VPA) as well as lamotrigine (LTG) and 2) the naturally occurring high (mid-luteal) and low (early-mid follicular) reproductive steroid level phases of the menstrual cycle might affect antiepileptic drug levels as well. Methods: This investigation compared serum antiepileptic drug levels at two timepoints during a single menstrual cycle in four groups of women with epilepsy: 12 on VPA, 12 on VPA plus COC (VPA-COC), 12 on LTG, and 12 on LTG plus COC (LTG-COC). Results: Both VPA and LTG levels were lower (p < 0.01) on active COC than on inactive pill with median declines of 23.4% for the VPA-COC group and 32.6% for the LTG-COC group. Serum LTG levels showed a notable but not significant 31.3% median decline during the mid-luteal phase compared to the early-mid follicular phase in the non-COC group. The non-COC valproate group showed the least change of any group between the two measured timepoints with a decline of 8.3% (p = NS). Conclusions: The findings suggest that valproate (VPA), like lamotrigine (LTG), has substantially and significantly lower serum levels while women take active combined oral contraceptives as compared to inactive pills. Larger sample sizes will be required to determine whether LTG levels may drop significantly also during the luteal (high steroid) phase of natural menstrual cycles and whether VPA levels may show greater stability in levels across the phases of the menstrual cycle. AED = antiepileptic drug; BMI = basal metabolic index; COC = combined oral contraceptive; EIAED = enzyme-inducing antiepileptic drug; IGE = idiopathic generalized epilepsy; LRE = localization-related epilepsy; LTG = lamotrigine; VPA = valproate.

Absence of early epileptiform abnormalities predicts lack of seizures on continuous EEG

Objective: To determine whether the absence of early epileptiform abnormalities predicts absence of later seizures on continuous EEG monitoring of hospitalized patients. Methods: We retrospectively reviewed 242 consecutive patients without a prior generalized convulsive seizure or active epilepsy who underwent continuous EEG monitoring lasting at least 18 hours for detection of nonconvulsive seizures or evaluation of unexplained altered mental status. The findings on the initial 30-minute screening EEG, subsequent continuous EEG recordings, and baseline clinical data were analyzed. We identified early EEG findings associated with absence of seizures on subsequent continuous EEG. Results: Seizures were detected in 70 (29%) patients. A total of 52 patients had their first seizure in the initial 30 minutes of continuous EEG monitoring. Of the remaining 190 patients, 63 had epileptiform discharges on their initial EEG, 24 had triphasic waves, while 103 had no epileptiform abnormalities. Seizures were later detected in 22% (n = 14) of studies with epileptiform discharges on their initial EEG, vs 3% (n = 3) of the studies without epileptiform abnormalities on initial EEG (p < 0.001). In the 3 patients without epileptiform abnormalities on initial EEG but with subsequent seizures, the first epileptiform discharge or electrographic seizure occurred within the first 4 hours of recording. Conclusions: In patients without epileptiform abnormalities during the first 4 hours of recording, no seizures were subsequently detected. Therefore, EEG features early in the recording may indicate a low risk for seizures, and help determine whether extended monitoring is necessary.

The probability of seizures during EEG monitoring in critically ill adults

OBJECTIVE To characterize the risk for seizures over time in relation to EEG findings in hospitalized adults undergoing continuous EEG monitoring (cEEG). METHODS Retrospective analysis of cEEG data and medical records from 625 consecutive adult inpatients monitored at a tertiary medical center. Using survival analysis methods, we estimated the time-dependent probability that a seizure will occur within the next 72-h, if no seizure has occurred yet, as a function of EEG abnormalities detected so far. RESULTS Seizures occurred in 27% (168/625). The first seizure occurred early (<30min of monitoring) in 58% (98/168). In 527 patients without early seizures, 159 (30%) had early epileptiform abnormalities, versus 368 (70%) without. Seizures were eventually detected in 25% of patients with early epileptiform discharges, versus 8% without early discharges. The 72-h risk of seizures declined below 5% if no epileptiform abnormalities were present in the first two hours, whereas 16h of monitoring were required when epileptiform discharges were present. 20% (74/388) of patients without early epileptiform abnormalities later developed them; 23% (17/74) of these ultimately had seizures. Only 4% (12/294) experienced a seizure without preceding epileptiform abnormalities. CONCLUSIONS Seizure risk in acute neurological illness decays rapidly, at a rate dependent on abnormalities detected early during monitoring. This study demonstrates that substantial risk stratification is possible based on early EEG abnormalities. SIGNIFICANCE These findings have implications for patient-specific determination of the required duration of cEEG monitoring in hospitalized patients.

GABAergic neurons in rat hippocampal culture

The experiments described here were designed to study biochemical and histological measures of gamma-aminobutyric acid (GABA) uptake and glutamic acid decarboxylase (GAD) in primary dissociated cell cultures prepared from 17-21-day fetal rat hippocampus. Preparations from all ages of animals, except 21-day fetuses, were enriched in GABAergic neurons, when compared to the adult hippocampus in situ. These cells comprise 30-50% of the large, phase-bright, process-bearing cells in hippocampal cultures as estimated by autoradiography of GABA uptake and GAD immunocytochemistry. Neurons concentrate GABA by a relatively slow but high-affinity process (Km = 2.6 microM) that has considerably higher maximum velocity than glial uptake (Vmax = 479 pmol/mg protein/min for neurons and 31 pmol/mg protein/min for glia). No low-affinity uptake process was noted in neurons or glia. GABA uptake into neurons was competitively inhibited by cis-4-OH-nipecotic acid (Ki = 39 +/- 11 microM). These cultures also possess considerable GAD activity, up to 6 nmol/mg protein/min in one-month-old cultures, which approximates that of the adult hippocampus. Both GABA uptake and GAD activity increased with time in culture. The enrichment of GABAergic markers indicates that this preparation may be useful for the detailed study of hippocampal GABAergic neurons.

Monitoring carotid test occlusions with continuous EEG and clinical examination.

We routinely monitor invasive neuroradiologic carotid balloon test occlusions with continuous polygraph and quantitative EEG along with repeated detailed clinical examinations. Four of 17 consecutive cases showed changes during carotid occlusion. In one instance, an immediate delta increase was accompanied by slurred speech and aphasia. Another showed alpha attenuation without clinical change. A third patient had significant clinical change without EEG change. Nine of the 17 cases underwent permanent therapeutic carotid occlusion as treatment of an intracerebral vascular abnormality. Seven of these nine had no EEG or clinical changes during monitoring and have had no functional abnormalities on follow-up. The patient with focal alpha attenuation had an accidental balloon detachment but has had no functional or structural neurologic abnormalities. The patient with minor regional increased delta received a permanent carotid occlusion and went on to develop clinical signs 24 h later. We believe that continuous EEG monitoring and repeated clinical examinations provide useful ways of evaluating cerebral circulation during carotid test occlusions.

Stroke and Epilepsy: Critical Review of the Literature

Stroke-associated seizures and epilepsy provide an excellent clinical model to study both acute hyperexcitability after stroke and long-term tissue changes responsible for epileptogenic scar formation

Spectrogram screening of adult EEGs is sensitive and efficient

Objective: Quantitatively evaluate whether screening with compressed spectral arrays (CSAs) is a practical and time-effective protocol for assisting expert review of continuous EEG (cEEG) studies in hospitalized adults. Methods: Three neurophysiologists reviewed the reported findings of the first 30 minutes of 118 cEEGs, then used CSA to guide subsequent review (“CSA-guided review” protocol). Reviewers viewed 120 seconds of raw EEG data surrounding suspicious CSA segments. The same neurophysiologists performed independent page-by-page visual interpretation (“conventional review”) of all cEEGs. Independent conventional review by 2 additional, more experienced neurophysiologists served as a gold standard. We compared review times and detection rates for seizures and other pathologic patterns relative to conventional review. Results: A total of 2,092 hours of cEEG data were reviewed. Average times to review 24 hours of cEEG data were 8 (±4) minutes for CSA-guided review vs 38 (±17) minutes for conventional review (p < 0.005). Studies containing seizures required longer review: 10 (±4) minutes for CSA-guided review vs 44 (±20) minutes for conventional review (p < 0.005). CSA-guided review was sensitive for seizures (87.3%), periodic epileptiform discharges (100%), rhythmic delta activity (97.1%), focal slowing (98.7%), generalized slowing (100%), and epileptiform discharges (88.5%). Conclusions: CSA-guided review reduces cEEG review time by 78% with minimal loss of sensitivity compared with conventional review. Classification of evidence: This study provides Class IV evidence that screening of cEEG with CSAs efficiently and accurately identifies seizures and other EEG abnormalities as compared with standard cEEG visual interpretation.