Hippocampal 1H-MRSI correlates with severity of depression symptoms in temporal lobe epilepsy.

OBJECTIVE: To investigate the association of an indicator of hippocampal function with severity of depression symptoms in temporal lobe epilepsy. METHODS: We evaluated 31 patients with video/EEG-confirmed temporal lobe epilepsy using creatine/N-acetylaspartate ratio maps derived from a previously validated (1)H magnetic resonance spectroscopic imaging ((1)H-MRSI) technique at 4.1 T. We also assessed depression symptoms, epilepsy-related factors, and self-perceived social and vocational disability. We used conservative nonparametric bivariate procedures to determine the correlation of severity of depression symptoms with imaging and clinical variables. RESULTS: The extent of hippocampal (1)H-MRSI abnormalities correlated with severity of depression (Spearman rho = 0.65, p value < 0.001), but other clinical factors did not. CONCLUSION: The extent of hippocampal dysfunction is associated with depression symptoms in temporal lobe epilepsy and may be a more important factor than seizure frequency or degree of disability.

Implementation of talairach atlas based automated brain segmentation for radiation therapy dosimetry.

Radiotherapy for brain cancer inevitably results in irradiation of uninvolved brain. While it has been demonstrated that irradiation of the brain can result in cognitive deficits, dose-volume relationships are not well established. There is little work correlating a particular cognitive deficit with dose received by the region of the brain responsible for the specific cognitive function. One obstacle to such studies is that identification of brain anatomy is both labor intensive and dependent on the individual performing the segmentation. Automatic segmentation has the potential to be both efficient and consistent. Brains2 is a software package developed by the University of Iowa for MRI volumetric studies. It utilizes MR images, the Talairach atlas, and an artificial neural network (ANN) to segment brain images into substructures in a standardized manner. We have developed a software package, Brains2DICOM, that converts the regions of interest identified by Brains2 into a DICOM radiotherapy structure set. The structure set can be imported into a treatment planning system for dosimetry. We demonstrated the utility of Brains2DICOM using a test case, a 34-year-old man with diffuse astrocytoma treated with three-dimensional conformal radiotherapy. Brains2 successfully applied the Talairach atlas to identify the right and left frontal, parietal, temporal, occipital, subcortical, and cerebellum regions. Brains2 was not successful in applying the ANN to identify small structures, such as the hippocampus and caudate. Further work is necessary to revise the ANN or to develop new methods for identification of small structures in the presence of disease and radiation induced changes. The segmented regions-of-interest were transferred to our commercial treatment planning system using DICOM and dose-volume histograms were constructed. This method will facilitate the acquisition of data necessary for the development of normal tissue complication probability (NTCP) models that assess the probability of cognitive complications secondary to radiotherapy for intracranial and head and neck neoplasms.

Bilateral hippocampal atrophy: consequences to verbal memory following temporal lobectomy.

BACKGROUND: Bilateral hippocampal damage is a risk factor for memory decline after anterior temporal lobectomy (ATL). OBJECTIVE: To investigate verbal memory outcome in patients with temporal lobe epilepsy (TLE) with either unilateral or bilateral hippocampal atrophy as measured by MRI. METHODS: The authors selected 60 patients with TLE who had undergone ATL (left = 31, right = 29). They determined normalized MRI hippocampal volumes by cursor tracing 1.5-mm slices from three-dimensional MRI acquisition. Hippocampal volumes were defined as atrophic if the volumes were below 2 SD for control subjects. Bilateral hippocampal atrophy was present in 10 patients with left TLE and 11 patients with right TLE. The authors assessed acquisition, retrieval, and recognition components of verbal memory both before and after ATL. RESULTS: Groups did not differ across age, education, intelligence, age at seizure onset, or seizure duration. Seizure-free rates after ATL were 70% or higher for all groups. Before surgery, patients with left TLE displayed worse verbal acquisition performance compared with patients with right TLE. Patients with left TLE with bilateral hippocampal volume loss displayed the lowest performance across all three memory components. After surgery, both groups of patients with left TLE exhibited worse verbal memory outcome compared with patients with right TLE. Bilateral hippocampal atrophy did not worsen outcome in the patients with right TLE. A higher proportion of patients with left TLE with bilateral hippocampal atrophy experienced memory decline compared with the other TLE groups. CONCLUSION: Bilateral hippocampal atrophy in the presence of left TLE is associated with worse verbal memory before and after ATL compared with patients with unilateral hippocampal volume loss or right TLE with bilateral hippocampal volume loss.

Verbal retention lateralizes patients with unilateral temporal lobe epilepsy and bilateral hippocampal atrophy.

PURPOSE: To examine the lateralization utility of preoperative verbal retention in patients with and without bilateral hippocampal atrophy. METHODS: The sample consisted of 74 patients with EEG-defined unilateral temporal lobe epilepsy (TLE) who had also undergone volumetric magnetic resonance imaging (MRI). Verbal retention was operationalized by the Logical Memory percentage retention subtest (LM%) of the Wechsler Memory Scale. Patients were divided into groups with (a) bilaterally normal hippocampal volumes, (b) unilateral atrophy, or (c) bilateral atrophy. Two different thresholds (empirically derived vs. normative) were used to lateralize on the basis of LM%. LM% lateralization was then examined by group using chi2, sensitivity, positive predictive values, and odds ratios. Analyses were also conducted separately in the subset of patients who were seizure free after surgery. RESULTS: Mean LM% performance was significantly lower in patients with left versus right TLE in the subset with bilateral hippocampal atrophy (p = 0.018), but not in patients with a normal MRI (p = 0.918) or unilateral atrophy (p = 0.087). The odds of a correct lateralization by LM% increased from 1.67 in patients with normal MRI to 36.11 in patients with bilateral hippocampal atrophy. The power of a right and left lateralization prediction by LM% was 100% and 75%, respectively, in patients with bilateral hippocampal atrophy. Similar results were obtained when analysis was restricted to patients who were seizure free after surgery. CONCLUSIONS: Preoperative verbal retention as measured by LM% may provide meaningful lateralization information in patients who are difficult to lateralize via MRI.

Relationships among hippocampal volumetry, proton magnetic resonance spectroscopy, and verbal memory in temporal lobe epilepsy.

PURPOSE: To examine the relationship between hippocampal volumes, 1H magnetic resonance spectroscopy (MRS)-identified hippocampal metabolic function, and verbal memory in patients with unilateral mesial temporal lobe epilepsy (MTLE). METHODS: Hippocampal volumes, 1H MRS-derived hippocampal creatine to N-acetylaspartate (Cr/NAA), and verbal memory assessment were obtained preoperatively in 22 patients (six right, 16 left) with EEG-defined unilateral MTLE. RESULTS: Left hippocampal volume correlated significantly with left hippocampal Cr/NAA (r=-0.549, p < 0.01), whereas right volume correlated significantly with right Cr/NAA (r=-0.478, p < 0.05). Verbal memory correlated significantly with left hippocampal Cr/NAA (r=-0.594, p < 0.01), but not with left hippocampal volume or right hippocampal measures. CONCLUSIONS: Hippocampal volumes and 1H MRS-derived metabolite ratios are statistically related, but share only a small percentage of variance, suggesting separate but related pathophysiologic processes. Left hippocampal Cr/NAA appears to be more sensitive to verbal memory function than volumes.

Wisconsin Card Sorting performance in patients with temporal lobe epilepsy: clinical and neuroanatomical correlates.

PURPOSE: A sizable proportion of patients with temporal lobe epilepsy (TLE) display impairments on tests of executive function. Previous studies have suggested several factors that may explain such performance, including the presence of hippocampal sclerosis, electrophysiological disruption to extratemporal regions, and early age of seizure onset. However, no clear determinants have been found that consistently explain such executive dysfunction. The present study investigated the contribution of several clinical variables and temporal lobe neuroanatomic features to performance on the Wisconsin Card Sorting Test (WCST) in a series of patients with TLE. METHODS: Eighty-nine patients with lateralized TLE (47 left, 42 right) were examined. Seventy-two patients from this series underwent anterior temporal lobectomy (ATL). Regression analysis was used to examine the effects of age, education, age at seizure onset, seizure duration, seizure laterality, history of secondary generalized seizures, and MRI-based volumes of the right and left hippocampi on preoperative WCST performance (number of categories completed, perseverative errors). Further univariate analyses examined whether the presence of bilateral hippocampal sclerosis, mesial temporal lobe abnormalities beyond the hippocampus, or temporal neocortical abnormalities affected preoperative WCST performance. In addition, we examined whether becoming seizure free after ATL affected change in WCST performance. RESULTS: Overall regression analysis was not significant. However, an examination of individual partial correlations revealed that patients with a history of secondary generalized seizures performed more poorly on the preoperative WCST than did patients without such history. In addition, patients who were seizure free after ATL did not exhibit better WCST outcome than patients who did not become seizure free. The presence of bilateral hippocampal sclerosis, extrahippocampal mesial temporal atrophy, or temporal neocortical lesions did not affect WCST performance. CONCLUSIONS: These results indicate that the presence of temporal lobe structural abnormalities do not significantly affect executive function as measured by the WCST. The present study does suggests that the critical determinants of WCST performance in patients with TLE lie outside the temporal lobe and likely relate to metabolic disruption to frontostriatal neural network systems.

Investigation of executive function change following anterior temporal lobectomy: selective normalization of verbal fluency.

The nociferous cortex hypothesis predicts that electrophysiological normalization to distal extratemporal brain regions following anterior temporal lobectomy (ATL) will result in improvements in executive functioning. The present study examined the effects of seizure laterality and seizure control on executive function change. The authors administered the Wisconsin Card Sorting Test (WCST), Trails B, and the Controlled Oral Word Association Test to 174 temporal lobe epilepsy patients who underwent ATL. No significant changes were found on the WCST or Trails B tests, regardless of surgery side or seizure-free status. However, verbal fluency significantly improved in seizure-free patients. Findings were consistent with the nociferous cortex hypothesis suggesting selective executive function improvement following ATL. These findings are discussed in terms of recent research demonstrating extrahippocampal metabolic normalization following surgery.

Assessing financial capacity in patients with Alzheimer disease: A conceptual model and prototype instrument.

OBJECTIVE: To investigate financial capacity in patients with Alzheimer disease (AD) using a new theoretical model and prototype psychometric instrument. DESIGN: Cross-sectional comparisons of older control subjects (n=23) and patients with mild (n=30) and moderate AD (n=20). MAIN OUTCOME MEASURES: Financial capacity was measured using the Financial Capacity Instrument, a prototype psychometric instrument that tests financial capacity using 14 tasks of financial ability comprising 6 clinically relevant domains of financial activity: basic monetary skills, financial conceptual knowledge, cash transactions, checkbook management, bank statement management, and financial judgment. RESULTS: The Financial Capacity Instrument tasks and domains showed adequate to excellent internal, interrater, and test-retest reliabilities. At the task level, patients with mild AD performed equivalently with controls on simple tasks such as counting coins/currency and conducting a 1-item grocery purchase, but significantly below controls on more complex tasks such as using a checkbook/register and understanding and using a bank statement. At the domain level, patients with mild AD performed significantly below controls on all domains except basic monetary skills. Patients with moderate AD performed significantly below controls and patients with mild AD on all tasks and domains. Regarding capacity status outcomes (capable, marginally capable, incapable) on domains, patients with mild AD had high proportions of marginally capable or incapable outcomes (range, 47%-87%), particularly on difficult domains like bank statement management (domain 5) and financial judgment (domain 6), but variability in individual outcomes. Patients with moderate AD had almost exclusively incapable outcomes across the 6 domains (range, 90%-100%). CONCLUSIONS: Financial capacity is already significantly impaired in mild AD. Patients with mild AD demonstrate deficits in more complex financial abilities and impairment in most financial activities. Patients with moderate AD demonstrate severe impairment of all financial abilities and activities. The Financial Capacity Instrument has promise as an instrument for assessing domain-level financial activities and task-specific financial abilities in patients with dementia. Arch Neurol. 2000.

Visual confrontation naming and hippocampal function: A neural network study using quantitative (1)H magnetic resonance spectroscopy.

Prior research on the relationship between visual confrontation naming and hippocampal function has been inconclusive. The present study examined this relationship using quantitative (1)H magnetic resonance spectroscopy ((1)H-MRS) to operationalize the function of the left and right hippocampi. The 60-item Boston Naming Test (BNT) was used to measure naming. Our sample included 46 patients with medically intractable, focal mesial temporal lobe epilepsy who had been screened for all pathology other than mesial temporal sclerosis. Statistics included Pearson correlations and neural network analysis (multilayer perceptron and radial basis function). Baseline BNT performance correlated significantly with left (1)H-MRS hippocampal ratios. Thirty-six per cent of the variance in baseline BNT performance was explained by a neural network model using left and right (1)H-MRS ratios(creatine/N-acetylaspartate) as input. This was elevated to 49% when input from the right hippocampus was lesioned mathematically. In a second model, left (1)H-MRS hippocampal ratios were modelled using measures of semantic and episodic memory as input (including the BNT). Explained variance in left (1)H-MRS hippocampal ratios fell from 60.8 to 3.6% when input from BNT and another semantic memory measure was degraded mathematically. These results provide evidence that the speech-dominant hippocampus is a significant component of the overall neuroanatomical network of visual confrontation naming. Clinical and theoretical implications are explored.

Subjective versus objective memory change after temporal lobe epilepsy surgery.

OBJECTIVE: To examine subjective versus objective memory change after anterior temporal lobectomy (ATL). METHODS: A prospective, controlled study. Controls included 39 unoperated patients with intractable temporal lobe epilepsy (TLE) who were administered a series of cognitive and health-related quality of life measures at baseline and at 12-month follow-up intervals. The surgery sample included 65 patients with intractable, focal TLE who had undergone either a right or left ATL. These patients were tested preoperatively and at 6-month follow-up intervals. Subjective and objective memory change was quantified using a newly developed methodology to control for practice effect and regression to the mean. RESULTS: Measures of subjective and objective memory change were not significantly related in the surgery sample. Prevalence of significant subjective memory decline 1 year after surgery ranged from 3 to 7%, whereas prevalence of significant objective memory decline ranged from 26 to 55%. Postoperative levels of emotional distress significantly predicted self-reported memory decline 1 year after ATL. Postoperative medication side effect and seizure outcome were also related significantly to subjective memory change in patients who had undergone left ATL. CONCLUSIONS: Subjective and objective memory change after temporal lobectomy are not related. Complaints of significant memory decline after ATL are infrequent and may serve as a marker for depression or other mood disorder rather than organically based memory decline.

A method for assessing clinically relevant individual cognitive change in older adult populations.

The evaluation of individual cognitive change has relied heavily upon the raw change score, defined simply as the difference between follow-up and baseline scores. However, raw changes scores are susceptible to the confounding effects of both regression-to-the-mean and practice effect. The clinical relevance of raw change scores for the older adult is also obscured by normal, age-related cognitive change. The present study illustrates the use of a standardized regression-based (SRB) methodology to generate an alternative to the raw change score; the SRB change score. SRB change scores provide a standardized alternative to the raw change score, allowing the clinician to evaluate the magnitude of change on one or more variables along a common metric that controls for practice effect, regression-to-the-mean, and normal cognitive decline. Case data illustrate how SRB change scores can identify clinically relevant cognitive change in the individual older adult patient.

Individual memory change after anterior temporal lobectomy: a base rate analysis using regression-based outcome methodology.

PURPOSE: To characterize patterns of base rate change on measures of verbal and visual memory after anterior temporal lobectomy (ATL) using a newly developed regression-based outcome methodology that accounts for effects of practice and regression towards the mean, and to comment on the predictive utility of baseline memory measures on postoperative memory outcome. METHODS: Memory change was operationalized using regression-based change norms in a group of left (n = 53) and right (n = 48) ATL patients. All patients were administered tests of episodic verbal (prose recall, list learning) and visual (figure reproduction) memory, and semantic memory before and after ATL. RESULTS: ATL patients displayed a wide range of memory outcome across verbal and visual memory domains. Significant performance declines were noted for 25-50% of left ATL patients on verbal semantic and episodic memory tasks, while one-third of right ATL patients displayed significant declines in immediate and delayed episodic prose recall. Significant performance improvement was noted in an additional one-third of right ATL patients on delayed prose recall. Base rate change was similar between the two ATL groups across immediate and delayed visual memory. Approximately one-fourth of all patients displayed clinically meaningful losses on the visual memory task following surgery. Robust relationships between preoperative memory measures and nonstandardized change scores were attenuated or reversed using standardized memory outcome techniques. CONCLUSIONS: Our results demonstrated substantial group variability in memory outcome for ATL patients. These results extend previous research by incorporating known effects of practice and regression to the mean when addressing meaningful neuropsychological change following epilepsy surgery. Our findings also suggest that future neuropsychological outcome studies should take steps towards controlling for regression-to-the-mean before drawing predictive conclusions.

Contribution of neuropsychological data to the prediction of temporal lobe epilepsy surgery outcome.

PURPOSE: We empirically examined the contribution of neuropsychological data to the prediction of postoperative seizure control relative to base rate information in an existing series of patients undergoing anterior temporal lobectomy (ATL). METHODS: A discriminant function predicting surgery outcome (seizure-free vs. non-seizure-free) was computed separately for samples of patients with left (n = 79) and right (n = 62) temporal lobectomy (LATL, RATL). Predictor variables included 14 measures tapping five neurocognitive domains. The predicted base rates were compared with the actual base rates in the two samples. Finally, overall predictive accuracy was examined in optimal versus suboptimal ATL patients. RESULTS: The base rate of seizure freedom in the LATL group was 74.70%; that in the RATL group was 66.10%. The predictive function for the LATL group achieved a hit rate of 80.00% and a positive predictive power of 92.11%. The function for the RATL group achieved a hit rate of 83.33% and a positive predictive power (PPP) of 89.66%. The overall predictive accuracy for the optimal group was only 55%, but that in the suboptimal group was 72%. CONCLUSIONS: Neuropsychological data used in a multivariate statistical fashion may be able to offer an incremental increase in the prediction of postoperative seizure freedom relative to existing base rates of surgery success in patients with ATL epilepsy. The use of neuropsychological data may be of greatest predictive value in a population of ATL candidates with suboptimal findings with a lower base rate of postoperative seizure freedom, but may actually reduce predictive accuracy in a group of ATL candidates from an optimal population with an already high base rate of surgical success.

Empirical methods for assessing meaningful neuropsychological change following epilepsy surgery.

Traditional methods for assessing the neurocognitive effects of epilepsy surgery are confounded by practice effects, test-retest reliability issues, and regression to the mean. This study employs 2 methods for assessing individual change that allow direct comparison of changes across both individuals and test measures. Fifty-one medically intractable epilepsy patients completed a comprehensive neuropsychological battery twice, approximately 8 months apart, prior to any invasive monitoring or surgical intervention. First, a Reliable Change (RC) index score was computed for each test score to take into account the reliability of that measure, and a cutoff score was empirically derived to establish the limits of statistically reliable change. These indices were subsequently adjusted for expected practice effects. The second approach used a regression technique to establish "change norms" along a common metric that models both expected practice effects and regression to the mean. The RC index scores provide the clinician with a statistical means of determining whether a patient's retest performance is "significantly" changed from baseline. The regression norms for change allow the clinician to evaluate the magnitude of a given patient's change on 1 or more variables along a common metric that takes into account the reliability and stability of each test measure. Case data illustrate how these methods provide an empirically grounded means for evaluating neurocognitive outcomes following medical interventions such as epilepsy surgery.

Internal structure of the MMPI-2 Addiction Potential Scale in alcoholic and psychiatric inpatients.

Recently, Weed, Butcher, McKenna, and Ben-Porath (1992) introduced two new scales for assessing alcohol and drug abuse with the Minnesota Multiphasic Personality Inventory-2 (MMPI-2; Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989): the Addiction Potential Scale (APS), an empirically derived measure similar to the MacAndrew Alcoholism Scale (MAC; MacAndrew, 1965), and the Addiction Acknowledgement Scale. Like the MAC, the APS was designed to identify the personality dimensions associated with substance abuse. Although there has been evidence to support the discriminative validity of the APS among samples of abusers, nonabusers, and psychiatric inpatients (Greene, Weed, Butcher, Arrendondo, & Davis, 1992; Weed et al., 1992), there has been no attempt to determine the personality dimensions tapped by the APS. Thus our study investigated the internal complexities of the APS. Using MMPI-2 protocols from a sample of alcoholic and psychiatric inpatients, we subjected the APS to a principal components analysis with subsequent varimax rotation. Both qualitative and quantitative methods were used to name the components that were identified. Five components consistently emerged across settings: Satisfaction/Dissatisfaction with Self, Powerlessness/Lack of Self-Efficacy, Antisocial Acting-Out, Surgency, and Risk-Taking/Recklessness, Clinical advantage gained from a knowledge of the internal structure of the APS was illustrated using 6 patients from the alcoholic sample. A rational approach to validating the empirical structure of the APS was discussed as a potential avenue for future research.