Multifocal hypometabolic correlates to deficits of verbal memory in mesial temporal lobe epilepsy.

BACKGROUND AND OBJECTIVES: Neuropsychological research on mesial temporal lobe epilepsy (MTLE) often highlights material-specific memory deficits, but a lesion-focused model may not accurately reflect the underlying networks that support episodic memory in these patients. Our study evaluated the pathophysiology behind verbal learning/memory deficits as revealed by hypometabolism quantified through 18-fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: This retrospective study included thirty presurgical patients with intractable unilateral MTLE who underwent interictal FDG-PET and verbal memory assessment (12 females, mean age: 38.73 years). Fluorodeoxyglucose-positron emission tomography mapping was performed with voxel-based mapping of glucose utilization to a database of age-matched controls to derive regional Z-scores. Neuropsychological outcome variables included scores on learning and recall trials of two distinct verbal memory measures validated for use in epilepsy research. Pearson's correlations evaluated relationships between clinical variables and verbal memory. Linear regression was used to relate regional hypometabolism and verbal memory assessment. Post hoc analyses assessed areas of FDG-PET hypometabolism (threshold Z ≤ -1.645 below mean) where verbal memory was impaired. RESULTS: Verbal memory deficits correlated with hypometabolism in limbic structures ipsilateral to language dominance but also correlated with hypometabolism in networks involving the ipsilateral perisylvian cortex and contralateral limbic and nonlimbic structures. DISCUSSION: We conclude that traditional models of verbal memory may not adequately capture cognitive deficits in a broader sample of patients with MTLE. This study has important implications for epilepsy surgery protocols that use neuropsychological data and FDG-PET to draw conclusions about surgical risks.

Direct and indirect costs associated with stereotactic radiosurgery or open surgery for medial temporal lobe epilepsy: Results from the ROSE trial.

OBJECTIVE: To determine whether a less-invasive approach to surgery for medically refractory temporal lobe epilepsy is associated with lower health care costs and costs of lost productivity over time, compared to open surgery. METHODS: We compared direct medical costs and indirect productivity costs associated with treatment with stereotactic radiosurgery (SRS) or anterior temporal lobectomy (ATL) in the ROSE (Radiosurgery or Open Surgery for Epilepsy) trial. Health care use was abstracted from hospital bills, the study database, and diaries in which participants recorded health care use and time lost from work while seeking care. Costs of use were calculated using a Medicare costing approach used in a prior study of the costs of ATL. The power of many analyses was limited by the sample size and data skewing. RESULTS: Combined treatment and follow-up costs (in thousands of US dollars) did not differ between SRS (n = 20, mean = $76.6, 95% confidence interval [CI] = 50.7-115.6) and ATL (n = 18, mean = $79.0, 95% CI = 60.09-103.8). Indirect costs also did not differ. More ATL than SRS participants were free of consciousness-impairing seizures in each year of follow-up (all P < 0.05). Costs declined following ATL (P = 0.005). Costs tended to increase over the first 18 months following SRS (P = 0.17) and declined thereafter (P = 0.06). This mostly reflected hospitalizations for SRS-related adverse events in the second year of follow-up. SIGNIFICANCE: Lower initial costs of SRS for medial temporal lobe epilepsy were largely offset by hospitalization costs related to adverse events later in the course of follow-up. Future studies of less-invasive alternatives to ATL will need to assess adverse events and major costs systematically and prospectively to understand the economic implications of adopting these technologies.

Visual field defects after radiosurgery versus temporal lobectomy for mesial temporal lobe epilepsy: Findings of the ROSE trial.

PURPOSE: Stereotactic radiosurgery (SRS) may be an alternative to anterior temporal lobectomy (ATL) for mesial temporal lobe epilepsy (MTLE). Visual field defects (VFD) occur in 9-100% of patients following open surgery for MTLE. Postoperative VFD after minimally invasive versus open surgery may differ. METHODS: This prospective trial randomized patients with unilateral hippocampal sclerosis and concordant video-EEG findings to SRS versus ATL. Humphries perimetry was obtained at 24 m after surgery. VFD ratios (VFDR = proportion of missing homonymous hemifield with 0 = no VFD, 0.5 = complete superior quadrantanopsia) quantified VFD. Regressions of VFDR were evaluated against treatment arm and covariates. MRI evaluated effects of volume changes on VFDR. The relationships of VFDR with seizure remission and driving status 3 years after surgery were evaluated. RESULTS: No patients reported visual changes or had abnormal bedside examinations, but 49 of 54 (91%) of patients experienced VFD on formal perimetry. Neither incidence nor severity of VFDR differed significantly by treatment arm. VFDR severity was not associated with seizure remission or driving status. CONCLUSION: The nature of VFD was consistent with lesions of the optic radiations. Effective surgery (defined by seizure remission) of the mesial temporal lobe results in about a 90% incidence of typical VFD regardless of method.

Radiosurgery versus open surgery for mesial temporal lobe epilepsy: The randomized, controlled ROSE trial.

OBJECTIVE: To compare stereotactic radiosurgery (SRS) versus anterior temporal lobectomy (ATL) for patients with pharmacoresistant unilateral mesial temporal lobe epilepsy (MTLE). METHODS: This randomized, single-blinded, controlled trial recruited adults eligible for open surgery among 14 centers in the USA, UK, and India. Treatment was either SRS at 24 Gy to the 50% isodose targeting mesial structures, or standardized ATL. Outcomes were seizure remission (absence of disabling seizures between 25 and 36 months), verbal memory (VM), and quality of life (QOL) at 36-month follow-up. RESULTS: A total of 58 patients (31 in SRS, 27 in ATL) were treated. Sixteen (52%) SRS and 21 (78%) ATL patients achieved seizure remission (difference between ATL and SRS = 26%, upper 1-sided 95% confidence interval = 46%, P value at the 15% noninferiority margin = .82). Mean VM changes from baseline for 21 English-speaking, dominant-hemisphere patients did not differ between groups; consistent worsening occurred in 36% of SRS and 57% of ATL patients. QOL improved with seizure remission. Adverse events were anticipated cerebral edema and related symptoms for some SRS patients, and cerebritis, subdural hematoma, and others for ATL patients. SIGNIFICANCE: These data suggest that ATL has an advantage over SRS in terms of proportion of seizure remission, and both SRS and ATL appear to have effectiveness and reasonable safety as treatments for MTLE. SRS is an alternative to ATL for patients with contraindications for or with reluctance to undergo open surgery.

Quality of life in adults with epilepsy is associated with anticonvulsant polypharmacy independent of seizure status.

RATIONALE: Polypharmacy, sometimes necessary to control epilepsy, can result in adverse effects that may affect quality of life (QOL). Our purpose was to determine the association of polypharmacy with QOL. METHODS: Two hundred seven patients with epilepsy were surveyed on characteristics within the last 4weeks: QOL Quality of Life in Epilepsy-Patient-Weighted (QOLIE-10-P) and seizure status (seizure-free or not), demographics, epilepsy characteristics, insomnia, sleepiness, mood, sleep-wake timing, healthcare use, and employment. Those on polypharmacy (antiepileptic drug (AED)>1) were compared with controls (AED=1) with univariate comparisons and subsequent multivariate regression. RESULTS: Patients on polypharmacy had worse QOL scores (mean 33.3±6.9 versus 36.7±5.7), were less likely to be seizure-free (39 (44%) versus 82 (68%)), had more evening-weighted wakefulness, and were more likely unemployed (74% versus 49%). Polypharmacy was associated with worse QOL (odds ratio 1.068 and 95th CI 1.018-1.121) even after controlling for seizure status. Covariates offered no improvement to the model. CONCLUSION: Polypharmacy was associated with worse QOL in patients with epilepsy despite seizure control. Further investigation into specific etiology of polypharmacy's influence on QOL is warranted in order to develop paradigms for optimal treatment.

Visual field defects after radiosurgery for mesial temporal lobe epilepsy.

PURPOSE: Gamma knife radiosurgery (RS) may be an alternative to open surgery for mesial temporal lobe epilepsy (MTLE), but morbidities and the anticonvulsant mechanisms of RS are unclear. Examination of visual field defects (VFDs) after RS may provide evidence of the extent of a postoperative fixed lesion. VFDs occur in 52-100% of patients following open surgery for MTLE. METHODS: This multicenter prospective trial of RS enrolled patients with unilateral hippocampal sclerosis and concordant video-electroencephalography (EEG) findings. Patients were randomized to low (20 Gy) or high (24 Gy) doses delivered to the amygdala, hippocampal head, and parahippocampal gyrus. Postoperative perimetry were obtained at 24 months after RS. Visual field defect ratios (VFDRs) were calculated to quantify the degree of VFDs. Results were contrasted with age, RS dose and 50% isodose volume, peak volume of radiation-induced change at the surgical target, quality of life measurements, and seizure remission. KEY FINDINGS: No patients reported visual changes and no patients had abnormal bedside visual field examinations. Fifteen (62.5%) of 24 patients had postoperative VFDs, all homonymous superior quadrantanopsias. None of the VFDs were consistent with injury to the optic nerve or chiasm. Clinical diagnosis of VFDs correlated significantly with VFDRs (p = 0.0005). Patients with seizure remission had smaller (more severe) VFDRs (p = 0.04). No other variables had significant correlations. SIGNIFICANCE: VFDs appeared after RS in proportions similar to historical comparisons from open surgery for MTLE. The nature of VFDs was consistent with lesions of the optic radiations. The findings support the hypothesis that the mechanism of RS involves some degree of tissue damage and is not confined entirely to functional changes in neuromodulation.

Neuropsychological outcomes after Gamma Knife radiosurgery for mesial temporal lobe epilepsy: a prospective multicenter study.

PURPOSE: To assess outcomes of language, verbal memory, cognitive efficiency and mental flexibility, mood, and quality of life (QOL) in a prospective, multicenter pilot study of Gamma Knife radiosurgery (RS) for mesial temporal lobe epilepsy (MTLE). METHODS: RS, randomized to 20 Gy or 24 Gy comprising 5.5-7.5 ml at the 50% isodose volume, was performed on mesial temporal structures of patients with unilateral MTLE. Neuropsychological evaluations were performed at preoperative baseline, and mean change scores were described at 12 and 24 months postoperatively. QOL data were also available at 36 months. KEY FINDINGS: Thirty patients were treated and 26 were available for the final 24-month neuropsychological evaluation. Language (Boston Naming Test), verbal memory (California Verbal Learning Test and Logical Memory subtest of the Wechsler Memory Scale-Revised), cognitive efficiency and mental flexibility (Trail Making Test), and mood (Beck Depression Inventory) did not differ from baseline. QOL scores improved at 24 and 36 months, with those patients attaining seizure remission by month 24s accounting for the majority of the improvement. SIGNIFICANCE: The serial changes in cognitive outcomes, mood, and QOL are unremarkable following RS for MTLE. RS may provide an alternative to open surgery, especially in those patients at risk of cognitive impairment or who desire a noninvasive alternative to open surgery.

The relationship between psychological distress and baseline sports-related concussion testing.

OBJECTIVE: This study examined the effect of psychological distress on neurocognitive performance measured during baseline concussion testing. DESIGN: Archival data were utilized to examine correlations between personality testing and computerized baseline concussion testing. Significantly correlated personality measures were entered into linear regression analyses, predicting baseline concussion testing performance. Suicidal ideation was examined categorically. SETTING: Athletes underwent testing and screening at a university athletic training facility. PARTICIPANTS: Participants included 47 collegiate football players 17 to 19 years old, the majority of whom were in their first year of college. INTERVENTIONS: Participants were administered the Concussion Resolution Index (CRI), an internet-based neurocognitive test designed to monitor and manage both at-risk and concussed athletes. Participants took the Personality Assessment Inventory (PAI), a self-administered inventory designed to measure clinical syndromes, treatment considerations, and interpersonal style. MAIN OUTCOME MEASURES: Scales and subscales from the PAI were utilized to determine the influence psychological distress had on the CRI indices: simple reaction time, complex reaction time, and processing speed. RESULTS: Analyses revealed several significant correlations among aspects of somatic concern, depression, anxiety, substance abuse, and suicidal ideation and CRI performance, each with at least a moderate effect. When entered into a linear regression, the block of combined psychological symptoms accounted for a significant amount of baseline CRI performance, with moderate to large effects (r = 0.23-0.30). When examined categorically, participants with suicidal ideation showed significantly slower simple reaction time and complex reaction time, with a similar trend on processing speed. CONCLUSIONS: Given the possibility of obscured concussion deficits after injury, implications for premature return to play, and the need to target psychological distress outright, these findings heighten the clinical importance of screening for psychological distress during baseline and post-injury concussion evaluations.

A multicenter, prospective pilot study of gamma knife radiosurgery for mesial temporal lobe epilepsy: seizure response, adverse events, and verbal memory.

OBJECTIVE: The safety, efficacy, and morbidity of radiosurgery (RS) must be established before it can be offered as an alternative to open surgery for unilateral mesial temporal lobe epilepsy. We report the 3-year outcomes of a multicenter, prospective pilot study of RS. METHODS: RS was randomized to 20 or 24Gy targeting the amygdala, hippocampus, and parahippocampal gyrus. Seizure diaries evaluated the final seizure remission between months 24 and 36. Verbal memory was evaluated at baseline and 24m with the Wechsler Memory Scale-Revised (WMS-R) and California Verbal Learning Test (CVLT). Patients were classified as having "significant improvement," "no change," and "significant impairment" based on relative change indices. RESULTS: Thirteen high-dose and 17 low-dose patients were treated. Both groups showed significant reductions in seizures by 1 year after treatment. At the 36-month follow-up evaluation, 67% of patients were free of seizures for the prior 12 months (high dose: 10/13, 76.9%; low dose: 10/17, 58.8%). Use of steroids, headaches, and visual field defects did not differ by dose or seizure remission. The prevalence of verbal memory impairment was 15% (4/26 patients); none declined on more than one measure. The prevalence of significant verbal memory improvements was 12% (3/26). INTERPRETATION: RS for unilateral mesial temporal lobe epilepsy offers seizure remission rates comparable with those reported previously for open surgery. There were no major safety concerns with high-dose RS compared with low-dose RS. Additional research is required to determine whether RS may be a treatment option for some patients with mesial temporal lobe epilepsy.

Depression in intractable partial epilepsy varies by laterality of focus and surgery.

PURPOSE: Depression sometimes occurs after surgical treatment for medically intractable partial epilepsy. The risk of pre- and postsurgical depression may vary by laterality of seizure focus. We reviewed the pre- and postsurgical psychological assessments and clinical courses of patients to identify those at highest risk for postsurgical mood disorders. METHODS: Depression status was assessed in a consecutive series of epilepsy patients before and 1 year after epilepsy surgery with the use of Scale 2 of the MMPI-2 and a clinical depression index (CDI) scoring the occurrence of depressive symptoms, psychiatric referral, or attempted/completed suicide. Outcome at 1 year was modeled by regression techniques as functions of preoperative mood measurements, side of epilepsy surgery, and preoperative verbal intelligence. RESULTS: The CDI and Scale 2 MMPI-2 correlated significantly (r = 0.341; p < or = 0.01). Left (n = 54 subjects) and right (n = 53) surgery groups did not differ by sex, seizure outcome, age, education, age at first seizure, duration of epilepsy, or intellect. Higher presurgical depressive morbidity (p = 0.0037) and right-sided surgery (p = 0.0003) predicted higher postoperative CDI. Higher preoperative Scale 2 scores, indicating worse depressive traits, predicted worse postoperative Scale 2 scores (p < 0.0001). Although side of surgery did not predict Scale 2 scores, Scale 2 scores of patients with preoperative right-sided foci tended to have worse postsurgical Scale 2 scores (p = 0.08). Findings for the temporal lobectomy subgroup (n = 90) were similar to those of the overall sample. CONCLUSIONS: Patients undergoing right hemispheric epilepsy surgery, especially those with high presurgical depression-related morbidity, may be particularly susceptible to clinical depression. Our findings support other studies that show an interhemispheric modulation of depressive traits and symptoms.

Assessing cognitive dysfunction in breast cancer: what are the tools?

The goal of adjuvant chemotherapy in the treatment of breast cancer is to reduce recurrence and mortality. With respect to quality of life and morbidity, however, such treatments come at a cost. Decreased cognitive functioning, development of fatigue, and mood alterations are common during chemotherapy and persist after its conclusion as evidenced by subjective self-reports and objective neurocognitive performance records. Few efforts, however, have used standardized neuropsychological measures, and no study has empirically selected those measures that best distinguish women in active chemotherapy from those who have previously completed it. Perhaps the most glaring deficit in the literature is that no study has used baseline data to track individual neurocognitive changes across treatment phases and after completion. This article provides an overview of the field of neuropsychology and the cognitive domains theorized to be affected by chemotherapy and the measures typically used, including validated computerized tests, which are tools for future studies; briefly summarizes existing research on the cognitive effects that chemotherapy has on breast cancer patients; compares data resulting from an ongoing pilot study of the cognitive performance of women actively undergoing anthracycline-containing chemotherapy with that of women 6-12 months post chemotherapy completion; and provides a preliminary analysis of the relationship between cognitive and emotional functioning. Future uses of these data to refine the ideal tools that efficiently, accurately, and validly detect short-term and persistent chemotherapy effects are proposed.