Faculty Bibliography

Epilepsy is a multilayered disorder complicated by numerous comorbid conditions and hormonal changes. More than 1.5 million girls and women with epilepsy face side effects that are compounded at different ages by menstruation, fertility, pregnancy, fetal health, bone health, and other health issues. Changes in hormonal balance during maturation, from menarche through menopause, affect seizure thresholds and antiepileptic drugs, and vice versa. This overview provides physicians with a background on the multiple issues relevant to women of all ages in the reproductive years, including those planning to conceive and those who are pregnant, and beyond the childbearing years

OBJECTIVE: Health-related quality of life (HRQOL) improves after resective epilepsy surgery, but data are limited to short follow-up in mostly retrospective reports, with minimal consideration of other potential factors that might influence HRQOL. METHODS: In a prospective multicenter study, 396 patients underwent resective epilepsy surgery. They completed the Quality of Life in Epilepsy Inventory-89 (QOLIE-89) before surgery, within 6 months, and at approximately yearly intervals after surgery. Seizure outcome was ascertained by phone calls every 3 months, and dates of postoperative seizures were chronicled. Overall HRQOL as measured by the QOLIE-89 was evaluated with respect to seizure outcome using logistic regression. RESULTS: QOLIE-89 scores increased significantly at the first postoperative measurement (within 6 months after surgery) in the cohort overall; subsequent changes over time were sensitive to seizure-free and aura-free status. After adjusting for baseline scores, the corresponding postsurgical QOLIE-89 overall, and four dimension scores, increased as a function of square root of time seizure-free, and independently as a function of square root of time aura free, leveling by 2 years of stable seizure (aura) status. HRQOL was not independently related to duration of epilepsy, duration of intractable epilepsy, or continuation of medications. INTERPRETATION: HRQOL improves early after surgery, regardless of seizure outcome. Subsequent changes parallel length of time seizure free or aura free, stabilize after 2 years, and are unrelated to duration of epilepsy, duration of intractable epilepsy, or continued medication use

Naming is mediated by perisylvian cortex in the left (language-dominant) hemisphere, and thus, left anterior temporal lobe resection for pharmacologically intractable temporal lobe epilepsy (TLE) carries risk for post-operative naming decline. Interestingly, this risk is lower in patients with hippocampal sclerosis (HS) relative to those without HS (non-HS). Although the hippocampus has traditionally been considered a critical structure for memory, without contribution to naming, this pattern might implicate direct hippocampal naming involvement. On the other hand, critical naming sites have been found in anterior, lateral temporal (i.e. extra-hippocampal) neocortex, the region typically removed with 'standard' TLE resection. We, therefore, speculated that the relative preservation of naming in post-operative HS patients might reflect cortical reorganization of language to areas outside this region. Using pre-resection electrical stimulation mapping, we compared the topography of auditory and visual naming sites in 12 patients with HS and 12 patients without structural brain pathology. Consistent with previous work, non-HS patients exhibited post-operative naming decline, whereas HS patients did not. As hypothesized, HS patients had proportionally fewer overall naming sites in anterior temporal cortex, the region typically removed with standard anterior temporal resection, whereas non-HS patients exhibited a more even distribution of naming sites in anterior and posterior temporal regions (P = 0.03). Although both groups exhibited the previously reported pattern of auditory naming sites anterior to visual naming sites, auditory naming sites had a significantly more posterior distribution in HS patients (P = 0.02). Additionally, non-HS patients exhibited a greater proportion of visual naming sites above the superior temporal sulcus, whereas visual naming sites in HS patients were scattered across superior and inferior temporal cortex. Results suggest that preserved naming ability in HS patients following anterior temporal resection might be attributable, at least in part, to intrahemispheric reorganization of language in response to the likely, early development of sclerosis in the medial temporal region. Furthermore, their more posterior distribution of naming sites is consistent with the more anterior propagation of EEG discharges in TLE. These results hold theoretical implications regarding the role of the dominant hippocampus in determining the cortical representation of semantic and lexical information, and raise questions regarding the specific roles of medial and lateral temporal cortex in targeted word retrieval. The different patterns of naming areas identified in patients with and without HS may also carry clinical implications, potentially improving efficiency during the time-constrained process of stimulation mapping

Abnormally strong functional linkage between cortical areas has been postulated to play a role in the pathogenesis of partial epilepsy. We explore the possibility that such linkages may be manifest in the interictal EEG apart from epileptiform disturbances or visually evident focal abnormalities. We analyzed samples of interictal intracranial EEG (ICEEG) recorded from subdural grids in nine patients with medically intractable partial epilepsy, measuring interelectrode synchrony using the mean phase coherence algorithm. This analysis revealed areas of elevated local synchrony, or 'hypersynchrony' which had persistent spatiotemporal characteristics that were unique to each patient. Measuring local synchrony in a subdural grid results in a map of the cortical surface that provides information not visually apparent on either EEG or structural imaging. We explore the relationship of hypersynchronous areas to the clinical evidence of seizure localization in each case, and speculate that local hypersynchrony may be a marker of epileptogenic cortex, and may prove to be a valuable aid to clinical ICEEG interpretation

OBJECTIVE: To report the technique of subpectoral (SP) implantation of the vagus nerve stimulator (VNS) generator. METHODS: We retrospectively reviewed and compared demographics and complications from patients receiving either subcutaneous (SQ; n = 107) or SP (n = 138) VNS implants, performed by one surgeon (WKD) between 1999 and 2003. Selection of implant location was made during the preoperative surgeon-patient consultation on the basis of surgeon recommendation and patient preference. RESULTS: The standard VNS generator implantation is performed within a SQ pocket in the left infraclavicular region of the chest. We have modified this technique by placing the generator into a deeper pocket SP, beneath the pectoralis major muscle, while tunneling the electrodes SQ in the usual fashion. The SP group was substantially younger (median age 19 yr) compared with the SQ group (median age 29 yr). At an average follow-up of 52 months for SQ implants and 28.4 months for SP implants, there were 2.9% infections per patient in the SQ group and 2.5% infections per patient in the SP group. There were three cases of excessive generator mobility in the SQ group; no cases occurred in the SP group. CONCLUSION: The SP implantation technique provides an attractive alternative to SQ VNS implantation. With increased soft tissue coverage, we provide improved cosmesis, increased wound durability to tampering and trauma, and a comparable infection rate with the SQ group

A card ordering task was developed to evaluate the role of the temporal lobe in perceiving subtle featural displacements of faces that contribute to judgments of facial expression and identity. Individuals with varying degrees of temporal lobe damage and healthy controls were required to manually sort cards depicting morphs of facial expressions or facial identities so that the cards were sequentially ordered from one morph endpoint to another. Four morph progressions were used-three emotion morphs (neutral-to-anger, neutral-to-fear, and fear-to-anger) and an identity morph. Five exemplars were given per morph type. Debriefing verified that participants were using feature-level cues to sort the cards. A patient with bilateral amygdala damage due to epilepsy did not differ in her sorting abilities from unilateral temporal lobectomy patients or controls. In contrast, a post-encephalitic patient with widespread left temporal lobe damage showed impairments that were most marked on the fear-to-anger and identity sorts. These results show that amygdala-damaged individuals can use information contained in facial expressions to solve tasks that rely on feature-level analysis, which recruits processing in other temporal lobe regions involved in making fine featural distinctions

Changes of cardiovascular function are frequent in temporal lobe epilepsy (TLE). The baroreflex - the most important reflex for cardiovascular stability - has not been studied systematically in TLE. We evaluated cardiovascular variability and baroreflex function in TLE.In 22 TLE patients and 20 controls, we continuously monitored heart rate (HR) and blood pressure (BP). Time-domain parameters were derived from recordings at rest and from standard cardiovascular reflex tests. Spectral analysis determined sympathetic and parasympathetic modulation of HR and BP in the low (LF-power) and high frequency range (HF-power). We calculated the relative LF- and HF-powers of HR in relation to the sum of LF- and HF-powers. LF/HF-ratio of HR was assessed as a parameter of sympatheticovagal balance. LF-transfer function gain between BP and HR determined baroreflex function.Time-domain parameters did not differ between TLE patients and controls. Spectral analysis showed decreased absolute LF- and HF-powers but increased relative LF-power and LF/HF-ratio of HR in TLE. LF-transfer function gain between BP and HR was reduced in TLE (p<0.05).The reduction of absolute LF- and HF-powers indicates decreased total autonomic variability in TLE. However, increased relative LF-power and LF/HF-ratio of HR in TLE show a relative increase of sympathetic tone. Most importantly, we demonstrate an impaired baroreflex function in TLE. These cardiovascular autonomic abnormalities may contribute to cardiac arrhythmia in TLE

Ventromedial prefrontal cortex (VMPFC) lesions can alter emotional and autonomic responses. In animals, VMPFC activation results in cardiovascular sympathetic inhibition. In humans, VMPFC modulates emotional processing and autonomic response to arousal (e.g. accompanying decision-making). The specific role of the left or right VMPFC in mediating somatic responses to non-arousing, daily-life pleasant or unpleasant stimuli is unclear. To further evaluate VMPFC interaction with autonomic processing of non-stressful emotional stimuli and assess the effects of stimulus valence, we studied patients with unilateral VMPFC lesions and assessed autonomic modulation at rest and during physical challenge, and heart rate (HR) and blood pressure (BP) responses to non-stressful neutral, pleasant and unpleasant visual stimulation (VES) via emotionally laden slides. In 6 patients (54.0 +/- 7.2 years) with left-sided VMPFC lesions (VMPFC-L), 7 patients (43.3 +/- 11.6 years) with right-sided VMPFC lesions (VMPFC-R) and 13 healthy volunteers (44.7 +/- 11.6 years), we monitored HR as R-R interval (RRI), BP, respiration, end-tidal carbon dioxide levels, and oxygen saturation at rest, during autonomic challenge by metronomic breathing, a Valsalva manoeuvre and active standing, and in response to non-stressful pleasant, unpleasant and neutral VES. Pleasantness versus unpleasantness of slides was rated on a 7-point Likert scale. At rest, during physical autonomic challenge, and during neutral VES, parameters did not differ between the patient groups and volunteers. During VES, Likert scores also were similar across the three groups. During pleasant and unpleasant VES, HR decreased (i.e. RRI increased) significantly whereas BP remained unchanged in volunteers. In VMPFC-L patients, HR decrease was insignificant with pleasant and unpleasant VES. BP slightly increased (P = 0.06) with pleasant VES but was stable with unpleasant VES. In contrast, VMPFC-R patients had significant increases in HR and BP during pleasant and not quite significant HR increases (P = 0.06) with only slight BP increase during unpleasant VES. Other biosignals remained unchanged during VES in all groups. Our results show that VMPFC has no major influence on autonomic modulation at rest and during non-emotional, physical stimulation. The paradoxical HR and BP responses in VMPFC-R patients suggest hemispheric specialization for VMPFC interaction with predominant parasympathetic activation by the left, but sympathetic inhibition by the right VMPFC. Valence of non-stressful stimuli has a limited effect with more prominent left VMPFC modulation of pleasant and more right VMPFC modulation of unpleasant stimuli. The paradoxical sympathetic disinhibition in VMPFC-R patients may increase their risk of sympathetic hyperexcitability with negative consequences such as anxiety, hypertension or cardiac arrhythmias