Kelly A. McNally

Ictal neocortical slowing in temporal lobe epilepsy

Background: Temporal lobe epilepsy (TLE) may affect brain regions outside the temporal lobe, causing impaired neocortical function during seizures. Methods: The authors selected 11 consecutive patients with mesial TLE and hippocampal sclerosis who underwent intracranial EEG monitoring and had no seizures during a follow-up period of at least 1 year after temporal lobe resection. Secondarily generalized seizures were excluded, and up to three seizures were analyzed per patient (31 seizures total). Electrode contacts were assigned to one of nine cortical regions based on MRI surface reconstructions. EEG during seizures was analyzed for specific patterns including low-voltage fast (LVF), rhythmic polyspike, spike-wave, irregular slowing, and postictal suppression. Results: Mesial and lateral temporal contacts on the side of seizure onset showed significant increases in ictal patterns such as LVF and polyspike activity, followed by postictal suppression. Bilateral frontal and ipsilateral parietal cortex exhibited large amplitude irregular slow waves during seizures. This frontoparietal slowing persisted into the postictal period. Perirolandic and occipital cortex were relatively spared. These EEG patterns were accompanied by bland staring, minor automatisms, and unresponsiveness or amnesia in the majority of patients studied. Conclusions: Prominent irregular slowing occurs in bilateral frontal and ipsilateral parietal association cortex during and after temporal lobe seizures. EEG slowing in the frontoparietal association cortex may signify physiologic impairment that contributes to widespread altered cerebral function during partial seizures.

Localizing Value of Ictal–Interictal SPECT Analyzed by SPM (ISAS)

Summary:  Purpose: The goal of neuroimaging in epilepsy is to localize the region of seizure onset. Single‐photon emission computed tomography with tracer injection during seizures (ictal SPECT) is a promising tool for localizing seizures. However, much uncertainty exists about how to interpret late injections, or injections done after seizure end (postictal SPECT). A widely available and objective method is needed to interpret ambiguous ictal and postictal scans, with changes in multiple brain regions.

Focal network involvement in generalized seizures: new insights from electroconvulsive therapy

Generalized seizures are commonly thought to involve the entire brain homogeneously. However, recent evidence suggests that selective cortical-subcortical networks may be crucial for the initiation, propagation, and behavioral manifestations of generalized seizures, while other brain regions are relatively spared. Here we review previous studies, and describe a new human model system for the investigation of generalized seizures: single-photon emission computed tomography, ictal-interictal difference imaging of generalized tonic-clonic seizures induced by electroconvulsive therapy (ECT). Bitemporal ECT activates focal bilateral frontotemporal and parietal association cortex, sparing other regions; bifrontal ECT activates mainly prefrontal cortex; while in right unilateral ECT the left frontotemporal region is relatively spared. Associated midline subcortical networks are also involved. Focal verbal memory deficits parallel the focal regions involved in these neuroimaging studies. Further studies of this kind may elucidate specific networks in generalized tonic-clonic seizures, providing targets for new therapeutic interventions in epilepsy.

Imaging Onset and Propagation of ECT‐induced Seizures

Summary:  Purpose: Regions of seizure onset and propagation in human generalized tonic–clonic seizures are not well understood. Cerebral blood flow (CBF) measurements with single photon emission computed tomography (SPECT) during electroconvulsive therapy (ECT)‐induced seizures provide a unique opportunity to investigate seizure onset and propagation under controlled conditions.

Adherence to Pediatric Asthma Treatment in Economically Disadvantaged African-American Children and Adolescents: An Application of Growth Curve Analysis

OBJECTIVES The primary aims of the study were to: (a) describe the trajectories of adherence to daily inhaled corticosteroid (ICS) medication for a year in economically disadvantaged, African-American youth with asthma based on growth curve modeling; and (b) test the relationship of treatment adherence to symptom control, quick-relief medication, and healthcare utilization. METHODS This prospective study measured adherence to daily ICS treatment using electronic monitoring in 92 children and adolescents with moderate to severe asthma for 9-12 months and assessed clinical outcomes, including asthma-related symptoms, quick-relief medication, and healthcare utilization. RESULTS Youth showed a decrement in treatment adherence to less than half of prescribed corticosteroid treatment over the course of the study, which related to increased healthcare utilization (p < .04), but not to asthma symptoms or albuterol use. CONCLUSION Economically disadvantaged youth with asthma demonstrate high rates of chronic nonadherence that warrant identification and intervention to reduce asthma-related healthcare utilization.

Clinical use of ictal SPECT in secondarily generalized tonic–clonic seizures

Partial seizures produce increased cerebral blood flow in the region of seizure onset. These regional cerebral blood flow increases can be detected by single photon emission computed tomography (ictal SPECT), providing a useful clinical tool for seizure localization. However, when partial seizures secondarily generalize, there are often questions of interpretation since propagation of seizures could produce ambiguous results. Ictal SPECT from secondarily generalized seizures has not been thoroughly investigated. We analysed ictal SPECT from 59 secondarily generalized tonic-clonic seizures obtained during epilepsy surgery evaluation in 53 patients. Ictal versus baseline interictal SPECT difference analysis was performed using ISAS (http://spect.yale.edu). SPECT injection times were classified based on video/EEG review as either pre-generalization, during generalization or in the immediate post-ictal period. We found that in the pre-generalization and generalization phases, ictal SPECT showed significantly more regions of cerebral blood flow increases than in partial seizures without secondary generalization. This made identification of a single unambiguous region of seizure onset impossible 50% of the time with ictal SPECT in secondarily generalized seizures. However, cerebral blood flow increases on ictal SPECT correctly identified the hemisphere (left versus right) of seizure onset in 84% of cases. In addition, when a single unambiguous region of cerebral blood flow increase was seen on ictal SPECT, this was the correct localization 80% of the time. In agreement with findings from partial seizures without secondary generalization, cerebral blood flow increases in the post-ictal period and cerebral blood flow decreases during or following seizures were not useful for localizing seizure onset. Interestingly, however, cerebral blood flow hypoperfusion during the generalization phase (but not pre-generalization) was greater on the side opposite to seizure onset in 90% of patients. These findings suggest that, with appropriate cautious interpretation, ictal SPECT in secondarily generalized seizures can help localize the region of seizure onset.

Preliminary fMRI findings in experimentally sleep-restricted adolescents engaged in a working memory task

Here we report preliminary findings from a small-sample functional magnetic resonance imaging (fMRI) study of healthy adolescents who completed a working memory task in the context of a chronic sleep restriction experiment. Findings were consistent with those previously obtained on acutely sleep-deprived adults. Our data suggest that, when asked to maintain attention and burdened by chronic sleep restriction, the adolescent brain responds via compensatory mechanisms that accentuate the typical activation patterns of attention-relevant brain regions. Specifically, it appeared that regions that are normally active during an attention-demanding working memory task in the well-rested brain became even more active to maintain performance after chronic sleep restriction. In contrast, regions in which activity is normally suppressed during such a task in the well-rested brain showed even greater suppression to maintain performance after chronic sleep restriction. Although limited by the small sample, study results provide important evidence of feasibility, as well as guidance for future research into the functional neurological effects of chronic sleep restriction in general, the effects of sleep restriction in children and adolescents, and the neuroscience of attention and its disorders in children.

Targeted prefrontal cortical activation with bifrontal ECT.

The anatomical brain regions involved in the therapeutic and adverse actions of electroconvulsive therapy (ECT) are unknown. Previous studies suggest that bifrontal vs. bitemporal ECT differ in therapeutic efficacy and cognitive side effects. We therefore performed cerebral blood flow (CBF) imaging during bitemporal vs. bifrontal ECT-induced seizures to identify regions crucial for the differences between these treatments. Patients with major depression, undergoing bitemporal or bifrontal ECT, were studied. Ictal-interictal SPECT images were analyzed with statistical parametric mapping for bitemporal (n=11 image pairs in 8 patients) and bifrontal (n=4 image pairs in 2 patients) ECT-induced seizures to identify regions of ictal CBF changes. Bifrontal ECT was found to cause increases in CBF in prefrontal and anterior cingulate regions. Bitemporal ECT, however, caused CBF increases in the lateral frontal cortex and in the anterior temporal lobes. In bifrontal ECT, a greater increase in prefrontal activation, while sparing the temporal lobes, may result in a better therapeutic response and fewer adverse effects on memory than bitemporal ECT.

Adherence to Combined Montelukast and Fluticasone Treatment in Economically Disadvantaged African American Youth with Asthma

High rates of asthma treatment nonadherence have been reported, particularly in economically disadvantaged African American youth. The relationship between adherence to combined medication treatment and asthma outcomes has potential clinical significance but is not well understood. Using electronic monitoring, we describe the pattern of adherence to daily corticosteroid (fluticasone) and leukotriene receptor antagonist (montelukast) medication over the course of 1 year in a population of African American youth with moderate to severe asthma. On average, adherence to montelukast was higher than adherence to fluticasone (p < 0.01); however, for both medications, adherence rates significantly declined over the course of the study. After 1 year, participants took only 31% of prescribed doses of montelukast and 23% of prescribed doses of fluticasone. The decline in adherence to both fluticasone (p < 0.05) and montelukast (p < 0.001) was related to increased healthcare utilization. Furthermore, asthma symptom ratings were related montelukast (p < 0.001), but not fluticasone adherence. These results suggest that adherence promotion intervention strategies are warranted to improve health-related outcomes in families who are at-risk for treatment nonadherence.

Relationship between semiology of psychogenic nonepileptic seizures and Minnesota Multiphasic Personality Inventory profile.

Subtypes of psychogenic nonepileptic seizures (PNES) have emerged via classification of seizure semiology, psychological variables, or both. PNES subtypes that differ with respect to etiology may be amenable to targeted treatment strategies. The aim of the present study was to investigate the relationship between semiology type and Minnesota Multiphasic Personality Inventory-2 (MMPI-2) profile among patients with PNES. We did so by modifying a classification scheme proposed by Selwa et al. Our main hypothesis was that there would be significant associations of semiology-based subtypes with psychological profiles among patients with PNES. We found significant differences in mean scores on MMPI-2 clinical scales 1 (Hypochondriasis) and 3 (Hysteria) and Harris-Lingoes subscales D5 (Brooding) and Sc5 (Lack of Ego Mastery, Defective Inhibition) across PNES subtypes (catatonic, minor motor, major motor). The results of the present study enhance understanding of the nosology of PNES by identifying psychopathological correlates of semiology-based subtypes of PNES. Our study also may inform the methodology of future investigations of psychopathology among patients with PNES by providing support for content-based interpretation of the MMPI.