Four-Way Wada: SEEG-based mapping with electrical stimulation, high frequency activity, and phase amplitude coupling to complement traditional Wada and functional MRI prior to epilepsy surgery.

Presurgical evaluation of refractory epilepsy involves functional investigations to minimize postoperative deficit. Assessing language and memory is conventionally undertaken using Wada and fMRI, and occasionally supplemented by data from invasive intracranial electroencephalography, such as electrical stimulation, corticortical evoked potentials, mapping of high frequency activity and phase amplitude coupling. We describe the comparative and complementary role of these methods to inform surgical decision-making and functional prognostication. We used Wada paradigm to standardize testing across all modalities. Postoperative neuropsychological testing confirmed deficit predicted based on these methods.

Longitudinal neurodevelopmental profile of a pediatric patient with de novo SPTAN1, epilepsy, and left hippocampal sclerosis.

Pathogenic variants in SPTAN1 result in abnormal neurodevelopment but limited information is available on the spectrum of neurodevelopmental profiles associated with variations in this gene. We present novel data collected at two time points over a three-year period in a nine-year-old patient with heterozygous de novo SPTAN1 variant, drug-resistant epilepsy, and left hippocampal sclerosis. Across evaluations, our patient's performance was highly variable, ranging from below age expectation to within age-expected range. The patient exhibited relative cognitive strengths at both time points on verbal-expressive tasks. Weaknesses were seen in her attention, executive function, psychomotor processing speed, fine motor, visual-motor integration, and social skills. Memory findings were consistent those associated with left hippocampal sclerosis. Evaluations resulted in diagnoses including attention deficit hyperactivity disorder and autism spectrum disorder.

Do atmospheric pressure changes influence seizure occurrence in the epilepsy monitoring unit?

In a prior study of epilepsy and atmospheric pressure, we were able to show a small association between changes in atmospheric pressure and increased seizure frequency in consecutive patients with epilepsy undergoing video telemetry. In this study, we used a larger data set of similar patients undergoing telemetry at another Seattle institution, and examined the possible impact of atmospheric pressure (AP) changes on seizure onset in subtypes of seizures (focal, generalized, and nonepileptic). Comparisons were made between AP score at time of seizure onset and AP score at selected time ranges prior to the event (hour of seizure and 3, 6, and 24 hours prior) and a random sample of AP scores collected over similar time frames using nonparametric testing with correction for multiple comparisons. We could find no evidence to suggest atmospheric pressure changes made seizure occurrence more likely in any of the seizure groups across any of the time periods.

An explanation for the association between specific language impairment and toxemia.

An association between specific language impairment (SLI) and toxemia has been detected in several studies. No clear explanation for this association has been identified to date. However, a number of potential explanations have been offered. These include: (1) toxemia causes fetal anoxia which leads to brain damage; (2) toxemia in the mother is an indication of maternal immune attack on the developing brain; (3) the association between toxemia and SLI is indirect and arises because both are consequences of a common but as yet unknown etiological factor. In this paper we present a fourth possible explanation for the association. That is, that both SLI and toxemia may be the consequence of low circulating levels of essential fatty acids. Evidence supporting this hypothesis is presented and four possible mechanisms underlying the association are discussed.

A critical evaluation of the evidence on the association between type of infant feeding and cognitive development.

This paper presents a critical evaluation of 24 studies on the association between type of infant feeding and cognitive development published over the past 20 years. Validity and generalisability of study findings were assessed according to three methodological standards: clearly defined outcome, specification of partial vs. exclusive breast feeding and control of confounding. Only six of the 24 investigations met all three standards. The most frequent study flaw was failure to distinguish between partial and exclusive breast feeding. Studies which made this distinction found larger IQ advantages to breast-fed infants than studies that did not. Four of the six studies meeting all three standards found an advantage in cognitive development to breast-fed infants of the order of two to five IQ points for term infants and eight points for low birthweight infants. We conclude that the question of whether breast feeding and formula feeding have differential effects on cognitive development has not yet been comprehensively answered. Research to date provides only an indication of the effect of relatively brief durations of partial breast feeding and even briefer durations of exclusive breast feeding. Future studies should measure breast feeding as a continuous dose-type variable, examine longer durations of breast feeding and control for a full range of confounders using techniques that deal appropriately with multicollinearity.

The Memory Assessment Scales and lateralized temporal lobe epilepsy.

We report Memory Assessment Scales (MAS) performance in 101 patients with unilateral temporal lobe epilepsy (TLE; left, n = 51; right, n = 50) with left cerebral language dominance. A significant multivariate group effect was present for the major summary indices (Verbal Memory, Visual Memory, and Global Memory, p < .04). Univariate analyses revealed no significant differences for either the Global Memory or Verbal Memory summary scores, although a significant group difference was present for Visual Memory (p < .04). The Verbal Memory-Visual Memory discrepancy score was significantly different between right and left TLE groups (p < .004). Verbal Memory scores were at least 14 points lower than Visual Memory scores in 34 patients (left = 20, 59%; right = 14, 41%). Visual Memory scores were at least 14 points lower than Verbal Memory performance in 20 patients (left = 5, 25%; right = 15, 75%). Diagnostic efficiency statistics show higher sensitivity but lower specificity in group classification for left TLE patients. These data suggest that the MAS is sensitive to material-specific memory deficits associated with a unilateral temporal lobe seizure focus. However, over one-third of the patients (19/54) with at least a 14-point Verbal Memory-Visual Memory discrepancy were classified incorrectly. The MAS, like other material-specific memory measures, should be interpreted within the context of other clinical findings.

Time perception following unilateral amobarbital injection in patients with temporal lobe epilepsy.

Estimates of elapsed time were obtained from 53 patients with unilateral temporal lobe epilepsy (Left TLE = 27; Right TLE = 26) following Wada (intracarotid amobarbital) assessment. After resolution of drug effects, patients were asked to estimate how much time had passed since amobarbital administration. Estimates were also obtained from 24 healthy control subjects using the same cognitive tasks over a similar time frame. Elapsed time was significantly underestimated by both left and right TLE groups following right hemisphere injection. In addition, there was an interaction effect involving patient group, side of injection, and sequence of injection. Left TLE patients, consistent with normal controls, made more accurate time estimates when they could anticipate the estimation task following the second amobarbital administration. More accurate time estimates, however, occurred only when left hemisphere injection was second in sequence. In contrast, right TLE patients did not improve regardless of the order of injection. These results suggest that right hemisphere function plays a critical role in the accuracy of time estimations of intermediate temporal duration and that interhemispheric interaction may be required to make accurate retrospective temporal judgments. These findings are discussed in the context of the growing evidence for a right-hemispheric attentional network.

Using the neurobehavioral cognitive status examination as a screening measure for older adults.

We evaluated the ability of the Neurobehavioral Cognitive Status Examination (NCSE) to accurately distinguish between healthy older adults and geriatric patients suffering from dementia. Although the NCSE correctly identified all dementia patients, it produced an unacceptably high rate of false positives among the healthy elderly (70%). Despite the NCSE's lack of specificity when using the recommended classification criteria, significant group differences were found on several individual subscales and on the total number of subscales passed. These findings suggest the need to further evaluate the appropriateness of the geriatric norms for the NCSE and highlight some of the unique considerations involved in the assessment of older adults.

Epilepsy, anticonvulsant drugs and cognition.

The use of AEDs in the management of epilepsy requires an ongoing risk-benefit analysis that attempts to maximize seizure control while minimizing adverse cognitive side-effects. Although the effects of other factors on cognition are generally greater than AED effects in patients with epilepsy, the cognitive effects of AEDs are of special concern because they are iatrogenically induced. Baseline evaluation of mental functioning is essential and should be repeated whenever a change in cognitive performance is suspected. The cognitive effects of the major AEDs, including phenytoin, carbamazepine and valproate, appear modest when dosages are kept within standard therapeutic ranges and polypharmacy is avoided. Violation of these guidelines increases the risk of alterations in arousal, attention, memory and psychomotor functioning. In turn, dysfunction in these areas can contribute to deficits in higher cognitive processes. Evidence suggests that these primary and secondary deficits are relatively greater for benzodiazepines, bromide and phenobarbital. Initial studies involving the newer AEDs suggest that the cognitive profile of these drugs is favourable, but further research is required to determine their relative effects to each other and to the older AEDs. For some patients, optimal seizure management may require the use of polypharmacy or AED dosages that exceed the standard therapeutic range. In such cases, the physician should remain sensitive to the increased risk of cognitive side-effects. The impact of such effects will be greatest for those whose daily functioning requires sustained attention or psychomotor speed. Although the cognitive risks of AEDs appear rather modest for most adults, questions remain regarding the impact of AEDs on patients at extremes of age. Initial studies with children and older adults suggest that the effects of the major AEDs are comparable across the developmental lifespan. However, during the formative years of a child's intellectual development, close scrutiny should be paid to the possibility that subtle attentional or arousal deficits could contribute to cumulative deficits in learning or memory. Preliminary studies involving both animals and humans suggest that the impact of AEDs might be greatest during in utero exposure; however, additional research is required to fully delineate the long-term effects of AED exposure in this earliest period of neurodevelopment.

Amobarbital evaluation of neurobehavioral function prior to therapeutic occlusion of brain arteriovenous malformations: a new neuropsychological procedure.

Because untreated arteriovenous malformations (AVMs) frequently result in some form of permanent neurological complication, treatment of AVMs is aggressively pursued A relatively new treatment consists of sending micropellets into blood vessels supplying the AVM core to block blood flow and "shrink" the AVM When vessels supplying the AVM are thought to also irrigate vital portions of brain, evaluations of neurobehavioral function after injection of amobarbital into intracranial vessels (Wada testing) may be performed to prevent significant complications folIowing embolization This study details our preliminary experience with Wada testing and electroencephalography (EEG) prior to AVM embolization in seven patients Neurobehavioral functions were continuously monitored after injection of 50-75 mg of amobarbital into target cerebral vessels No change in sensorimotor, cognitive, or EEG functions were detected in any of the superselective Wada examinations Embolization was performed following all negative Wada evaluations The only irreversible complication after embolization was a superior quadrantanopia No other permanent neurobehavioral sequelae resulted from embolization These preliminary findings suggest that simultaneous Wada/EEG monitoring may be useful in predicting neurobehavioral complications prior to AVM embolization.