Summary: Purpose:We report the development of a questionnaire to assess health-related quality-of-life (HRQOL) in people with epilepsy and the process of cross-cultural translations of the questionnaire.Methods: A sample of 304 adults with epilepsy from 25 seizure clinics in the United States was used to derive an abbreviated questionnaire focusing on epilepsy-related issues from a longer, 89-item instrument (QOLIE-89). A rigorous forward-backward-forward system was used for cross-cultural translation.Results: A 3 1 -item questionnaire (QOLIE-3 1, version 1 .O) resulted, comprising seven subscales covering general and epilepsy-specific domains. Subscale and total scores can be calculated. The subscales were grouped into two factors: EmotionallPsychological Effects (seizure worry, overall QOL, emotional well-being, energy/fatigue subscales) and Medical/Social Effects (medication effects, work-driving-social limits, cognitive function subscales). Cross-cultural translations were made from US.-English into Danish, Dutch, German, Canadian French, French, Italian, Spanish, Swedish, and U.K. English The individual patient's perspective has become an integral aspect of health care assessment (1). In epilepsy, clinicians are careful to obtain a social history along with physical and neurological examinations and medical history. The chronic nature of epilepsy, like that of most neurological disorders, often results in long-term relationships among the neurologist, the patient, and the patient's family. However, with recent changes in medical care delivery, less time is available to learn about the impact of the disorder on the patient's life. At the same time, the concept of quality of life (QOL) assessment has led to development of generic and disease-specific questionnaires to evaluate areas of concern to patients (2).The purpose of addressing QOL include improving the quality of patient care, differentiating among treatment Accepted July 17, 1997. options, and evaluating the allocation of health care resources. The major domains of QOL are physical, psychological, and social issues (3). These areas go well beyond the traditional assessment of seizure frequency and severity, and adverse effects of medications, toward an understanding of the impact of epilepsy on daily life (1).A variety of approaches have been used to assess QOL issues for people with epilepsy (2). Unified questionnaires [e.g., QOLIE-89 (4), ESI-55 ( 5 ) ] and batteries of tests [e.g., Liverpool QOL Battery (6)] have been used for detailed research programs. However, to conduct multinational epilepsy studies that include assessments of QOL requires an instrument that has been rigorously translated and adapted to the culture of each country in which it will be used. Such instruments will allow researchers to compile and aggregate QOL data across sample populations from different countries. The process is complicated not only by the wide differences in the concept of what constitutes "health" among cultures, 81

The motor manifestations of Parkinson's disease (PD) have been linked to an abnormal spatial covariance pattern involving basal ganglia thalamocortical pathways. By contrast, little is known about the functional networks that underlie cognitive dysfunction in this disorder. To identify such patterns, we studied 15 non-demented PD patients using FDG PET and a voxel-based network modeling approach. We detected a significant covariance pattern that correlated (p< 0.01) with performance on tests of memory and executive functioning. This PD-related cognitive pattern (PDCP) was characterized by metabolic reductions in frontal and parietal association areas and relative increases in the cerebellar vermis and dentate nuclei. To validate this pattern, we analyzed data from 32 subsequent PD patients of similar age, disease duration and severity. Prospective measurements of PDCP activity predicted memory performance (p<0.005), visuospatial function (p<0.01), and perceptual motor speed (p<0.005) in this validation sample. PDCP scores additionally exhibited an excellent degree of test-retest reliability (intraclass correlation coefficient, ICC=0.89) in patients undergoing repeat FDG PET at an 8-week interval. Unlike the PD-related motor pattern, PDCP expression was not significantly altered by antiparkinsonian treatment with either intravenous levodopa or deep brain stimulation (DBS). These findings substantiate the PDCP as a reproducible imaging marker of cognitive function in PD. Because PDCP expression is not altered by routine antiparkinsonian treatment, this measure of network activity may prove useful in clinical trials targeting the progression of non-motor manifestations of this disorder.

We developed an instrument to measure health-related quality of life (HRQOL) in epilepsy. A 99-item inventory was constructed from the RAND 36-Item Health Survey (generic core), with 9 additional generic items, 48 epilepsy-targeted items, and 6 other items concerning attitudes toward epilepsy and self-esteem. We administered the 99-item inventory to 304 adults with epilepsy at 25 epilepsy centers. Patients and patient-designated proxies completed the inventory and were retested 1-91 days later. A multitrait scaling analysis of these data led to retention of 86 items distributed in 17 multiitem scales (Cronbach's alpha ranged from 0.78 to 0.92). Factor analysis of the 17 multiitem scales yielded four underlying dimensions of health: an epilepsy-targeted dimension, a cognitive factor, mental health, and physical health. Construct validity was supported by significant patient-proxy correlations for all scales and correlations between neuropsychologic tests and self-reported emotional and cognitive function (all p values < 0.05). There were significant negative correlations between the four factor scores derived from the HRQOL scales and neurotoxicity, systemic toxicity, and health care utilization (except for the correlation between mental health factor and health care utilization; all p values < 0.05). Patients who were seizure-free in the preceding year reported better HRQOL for the overall score, three of the four factor scores, and 8 of the 17 scale scores than did patients with a high frequency of seizures. Relative validity analysis showed that the epilepsy-targeted factor and three of its four component scales were more sensitive to categorization of patients by severity of seizure frequency and type than scales tapping physical health, mental health, or cognitive function. These cross-sectional data support the reliability and validity of this measure of HRQOL in epilepsy. The addition of an epilepsy-targeted supplement to the generic core improved the sensitivity to severity of epilepsy. The 86 items included in the field testing were supplemented by three additional items to form the Quality of Life in Epilepsy (QOLIE-89) inventory.

Objective-To use 18 F-fluorodeoxyglucose (FDG) and PET to investigate changes in regional metabolism associated with mild cognitive impairment (MCI) in Parkinson disease (PD). Cognitive abnormalities are common in PD. However, little is known about the functional abnormalities that underlie the manifestations of MCI in this disorder.Methods-We used FDG PET to measure regional glucose metabolism in patients with PD with multiple-domain MCI (MD-MCI; n = 18), with single-domain MCI (SD-MCI; n = 15), and without MCI (N-MCI; n = 18). These patients were matched for age, education, disease duration, and motor disability. Maps of regional metabolism in the three groups were compared using statistical parametric mapping (SPM). We also computed the expression of a previously validated cognition-related spatial covariance pattern (PDCP) in the patient groups and in an age-matched healthy control cohort (n = 15). PDCP expression was compared across groups using analysis of variance.Results-SPM revealed decreased prefrontal and parietal metabolism (p < 0.001) in MD-MCI relative to N-MCI, as well as an increase in brainstem/cerebellar metabolism (p < 0.001) in this group. In these regions, SD-MCI occupied an intermediate position between the two other groups. PDCP expression was abnormally elevated in the N-, SD-, and MD-MCI groups (p < 0.05), increasing stepwise with worsening cognitive impairment (p < 0.01).Conclusions-Early cognitive decline in Parkinson disease as defined by mild cognitive impairment is associated with discrete regional changes and abnormal metabolic network activity. The quantification of these alterations with 18 F-fluorodeoxyglucose PET may allow for the objective assessment of the progression and treatment of this disease manifestation.Cognitive decline in Parkinson disease (PD) constitutes a well-defined behavioral syndrome characterized by difficulties in executive and visuospatial functions, as well as deficits in Copyright © 2008 The use of MCI criteria in patients already diagnosed with PD has been shown to have some prognostic value in that 64% of patients with MCI converted to dementia over a 4-year follow-up period as compared with only 20% of those without MCI. 5 Contrary to prodromal Alzheimer disease, PD patients with SD-MCI without memory impairment, as well as those with MD-MCI, appear more likely to progress to dementia. 3 However, the clinical characterization of MCI in PD has not been validated and the underlying pathology is not known.Metabolic imaging with 18 F-fluorodeoxyglucose (FDG) PET, an in vivo assay of synaptic activity in the brain, can potentially be used to identify regional changes in brain function that differentiate PD patients with and without cognitive dysfunction. The presence of specific metabolic abnormalities in patients with PD fulfilling diagnostic criteria for MCI can be used to validate this syndrome as a distinct diagnostic entity. Moreover, these scans can be used to quantify the activity of a distinct spatial covariance pattern associated with co...

The QOLIE-10 can be completed by a patient in several minutes and reviewed rapidly by the physician. This screening tool could provide potentially useful information for initial assessment or follow-up of problem areas that are not commonly evaluated during routine clinical visits with patients with epilepsy.