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Biomedical subjects

K Meador

Publications and source records attributed to K Meador.

At least 19 recordsLinked to original sources

Cognitive effects of lamotrigine compared with topiramate in patients with epilepsy.

OBJECTIVE: To compare the cognitive effects of lamotrigine vs topiramate as adjunctive therapy in adults with epilepsy. METHODS: A multicenter, double-blind, randomized, prospective study was conducted in adults with partial seizures. Lamotrigine or topiramate was introduced as an adjunctive therapy to carbamazepine or phenytoin and titrated over 8 weeks to target doses. These drugs were maintained another 8 weeks (maintenance phase) without dosage changes. The primary endpoint was change from screening to the end of the maintenance phase in a combined analysis of standardized measures of cognition (Controlled Oral Word Association Task [COWA]; Stroop Color-Word Interference; Digit Cancellation; Lafayette Grooved Pegboard, dominant hand; Rey Auditory Verbal Learning Test, delayed recall; and Symbol-Digit Modalities test). RESULTS: For the primary endpoint, cognitive performance at the end of the maintenance phase was better with lamotrigine than with topiramate (415.3 vs 315.1; p < 0.001). On the individual cognitive tests, performance was better with lamotrigine than with topiramate in mean changes from screening on the COWA (p < 0.001), Stroop Color-Word Interference (p = 0.038), and Symbol-Digit Modalities tests (p < 0.001). The treatment effect exceeded the minimum clinically important difference for the COWA and the Symbol-Digit Modalities test. Mean changes from screening in the Performance-On-Line test simulating driving skills reflected better performance with lamotrigine than with topiramate (p = 0.021). The median percentage change from baseline in seizure frequency was lower with lamotrigine than with topiramate during the escalation phase (-80% vs -100%; p = 0.028) but not during the maintenance phase (-75% vs -100%; p = 0.062). The frequencies of cognitive adverse events and of premature withdrawals related to cognitive decline were higher with topiramate than with lamotrigine (6% vs 0%; p = 0.013). CONCLUSION: Lamotrigine had significantly less impact than topiramate on measures of cognition when used as adjunctive therapy for partial seizures.

Adolescent↗

Comparative cognitive effects of carbamazepine and gabapentin in healthy senior adults.

PURPOSE: This study compared the cognitive effects of carbamazepine (CBZ) and gabapentin (GBP) in healthy senior adults by using a randomized, double-blind crossover design. METHODS: Thirty-four senior adults were randomized to receive one of the two drugs followed by a 5-week treatment period. A 4-week washout phase preceded initiation of the second drug. Antiepileptic drugs (AEDs) were titrated to target doses of either CBZ (800 mg/day) or GBP (2,400 mg/day). Primary outcome measures were standardized neuropsychological tests of attention/vigilance, psychomotor speed, motor speed, verbal and visual memory, and the Profile of Mood State (POMS), yielding a total of 17 variables. Each subject received cognitive testing at predrug baseline, end of first drug phase, end of second drug phase, and 4 weeks after completion of the second drug phase. RESULTS: Fifteen senior adults (mean age, 66.5 years; range, 59-76 years) completed the study. Seniors completing the study did not differ significantly from noncompleting seniors in terms of demographic features or baseline cognitive performances. Fifteen of the 19 seniors not completing the study dropped out while receiving CBZ. Adverse events were frequently reported for both AEDs, although they were more common for CBZ. Mean serum levels for the completers were within midrange clinical doses (CBZ, 6.8 microg/ml; GBP, 7.1 microg/ml). Significant differences between CBZ and GBP were found for only one of 11 cognitive variables, with better attention/vigilance for GBP, although the effect was modest. Performances on the nondrug average were significantly better on 45% of cognitive variables compared with CBZ and 36% compared with GBP. The overall pattern of means favored GBP over CBZ on 15 of 17 (p < 0.001), nondrug over CBZ on 17 of 17 (p < 0.0000), and nondrug over GBP on eight of 17 (NS). CONCLUSIONS: Mild cognitive effects were found for both AEDs compared with the nondrug average condition. The magnitude of difference between the two AEDs across the cognitive variables was modest. Self-reported mood was not significantly affected by either AED. However, overall tolerability and side-effect profile of CBZ were poorer than those of GBP in senior adults at doses and titration rates reported in this study.

Acetates↗

Patient-oriented outcome assessment after temporal lobectomy for refractory epilepsy.

OBJECTIVE: To determine patient-oriented outcome after anterior temporal lobectomy (ATL) for refractory epilepsy. BACKGROUND: Health-related quality of life (HRQOL) is an important component of the assessment of outcome from epilepsy surgery, but prior controlled studies of the effect of surgery on HRQOL are inconclusive. Direct assessment of the effect of surgery on patient concerns of living with epilepsy has not been reported. METHODS: We used reliable and valid instruments to compare HRQOL and patient concerns of 125 patients who had received an ATL more than than one year previously to a clinically similar group of 71 patients who were awaiting ATL. All patients were selected for surgery based on similar criteria. We also used bivariate correlation analysis and multivariate regression modeling to determine the association of traditional outcome variables with HRQOL. RESULTS: Patients who had undergone ATL reported significantly less concern of living with epilepsy in 16 of 20 items of the EFA Concerns Index and better HRQOL in 8 of 11 scales of the Epilepsy Surgery Inventory-55. Regression analysis in the postoperative group demonstrated that mood status, employment, driving, and antiepileptic drug (AED) cessation, but not seizure-free status or IQ, were associated with better HRQOL. CONCLUSIONS: Our findings support a positive affect of ATL on patient concerns and HRQOL in refractory temporal lobe epilepsy, although longitudinal studies are needed to corroborate these results. Mood, employment, driving ability, and AED use are important postoperative predictors of HRQOL.

Adult↗

The relationship between memory performance, perceived cognitive function, and mood in patients with epilepsy.

OBJECTIVE: The low correlations between memory performance and subjective memory may be attributable to disparities between tasks in neuropsychological tests and cognitive experiences of day-to-day living. This study evaluated the relationship between everyday memory performance, perceived cognitive functioning, and mood among patients with epilepsy. METHODS: From three epilepsy centers in the USA, 138 patients were recruited. Everyday memory performance was measured using the Rivermead Behavioural Memory Test (RBMT). Questionnaires assessed perceived cognitive function (cognitive domain, Quality of Life in Epilepsy Inventory, QOLIE-89) and mood (Profile of Mood States, POMS). RESULTS: Memory performance scores were weakly correlated with perceived cognitive functioning (r =0.22, P < 0.01). Perceived cognitive functioning was strongly correlated with mood (r = - 0.75, P < 0.0001). Multiple regression analysis indicated memory performance (RBMT) and mood (POMS) were independent predictors of perceived cognitive functioning (P < 0.02); however, the explained variance for RBMT and POMS combined (R2 = 0.58) is only slightly higher than the predictive value for the POMS score alone (R2 = 0.56). CONCLUSIONS: Memory performance tests provide qualitatively different information than patients' self-reported cognitive difficulties, thus it is important to assess memory performance, perceived cognitive function, and mood separately because the constructs are related but not redundant.

Adult↗

Development and cross-cultural translations of a 31-item quality of life in epilepsy inventory.

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 31-item questionnaire (QOLIE-31, version 1.0) resulted, comprising seven subscales covering general and epilepsy-specific domains. Subscale and total scores can be calculated. The subscales were grouped into two factors: Emotional/Psychological 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 U.S.-English into Danish, Dutch, German, Canadian French, French, Italian, Spanish, Swedish, and U.K. English Versions 1.1. CONCLUSIONS: Our results support the reliability and validity of the QOLIE-31 (U.S.-English version 1.0) as a measure of HRQOLIE. Cross-cultural translations into nine other languages make it feasible to use the QOLIE-31 (version 1.1) in multinational clinical trials after validation in each population or concurrent with the clinical trial.

Adolescent↗

A comparison of health-related quality of life in patients with epilepsy, diabetes and multiple sclerosis.

The purpose of this investigation was to compare self-reported health-related quality of life (HRQOL) in epilepsy compared to another neurological condition or a non-neurological chronic illness. Patients with epilepsy (N = 271), multiple sclerosis (N = 85) and diabetes (N = 555) completed a generic measure of HRQOL (RAND 36-Item Health Survey 1.0 (SF-36)), and the eight SF-36 scale scores were compared across groups, adjusting for differences in sociodemographic characteristics and co-morbid medical conditions. Patients with multiple sclerosis reported significantly worse HRQOL compared to both the epilepsy and diabetes groups (who did not differ from one another) on the Physical Functioning, Role Limitations-Physical, Energy, and Social Function scales. Patients with epilepsy and multiple sclerosis did not differ from one another but reported significantly lower HRQOL scores than the diabetes group on the Emotional Well-Being and Role Limitations-Emotional scales. However, the epilepsy group reported better health perceptions compared to the diabetes and multiple sclerosis patients. Generic measures of HRQOL appear useful in identifying some effects of neurological disease, but disease-targeted supplements may be required to more clearly identify the impact of epilepsy on quality of life.

Adult↗

A brief questionnaire to screen for quality of life in epilepsy: the QOLIE-10.

PURPOSE: To evaluate a brief questionnaire to screen aspects of health-related quality of life for persons with epilepsy. METHODS: A study of 304 adults with epilepsy was undertaken at 25 seizure clinics in the United States. It was used for derivation of a brief screening tool from a longer instrument (QOLIE-89). RESULTS: The 10-item questionnaire (QOLIE-10) covers general and epilepsy-specific domains, grouped into three factors: Epilepsy Effects (memory, physical effects, and mental effects of medication), Mental Health (energy, depression, overall quality of life), and Role Functioning (seizure worry, work, driving, social limits). Scale scores were significantly different among seizure groups (p = 0.003). CONCLUSIONS: 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.

Adolescent↗

Optimum stimulus parameters for lateralized suppression of speech with magnetic brain stimulation.

Rapid-rate transcranial magnetic brain stimulation produces lateralized suppression of speech output over the frontal lobe, consistent with cerebral dominance for language. But the sensitivity of magnetic speech localization has been limited, and reports are imprecise concerning the amount of discomfort involved. Using a focal magnetic coil, we evaluated the effectiveness and pain of stimulation at different intensities, orientations, and repetition rates (2 to 32 Hz) in six normal volunteers. We obtained complete and clearly lateralized speech arrest in all subjects. The best ratio of efficacy to pain occurred using slower repetition rates of 4 to 8 Hz with a horizontal alignment of the induced electric field. Lower stimulation frequency also allowed clearer distinction between speech arrest and dysarthria from tonic contraction of cranial muscles. The relative comfort and safety of stimulation at 4 Hz should allow more widespread use of magnetic speech localization in clinical and research applications.

Adult↗

Agreement between self reports and proxy reports of quality of life in epilepsy patients.

Agreement between self reports and proxy reports of quality of life was examined in a sample of 292 patients with epilepsy and their designated proxies. Patients and proxies completed an 89-item Quality of Life Inventory (QOLIE-89), with the items rephrased for the proxy. Results reveal moderate correlations (product-moment r ranging from 0.29 to 0.56 for 17 multi-item scales) between self reports and proxy reports. Agreement was good for measures of function that are directly observable and relatively poor for more subjective measures. Mean scale scores were significantly different between patients and proxies for only five of 17 multi-item scales. Proxy respondents systematically reported better functioning than did patients in three scales assessing cognitive functioning (all p < 0.001). By contrast, patients reported more positive health perceptions and less seizure distress than proxies. Patient educational attainment correlated inversely with degree of disagreement between patient and proxy reports for six of the 17 QOL scales and for the overall score. In addition, proxy educational attainment correlated positively with agreement for four scales. This study indicates that for group level comparisons, proxy respondents can be substituted for adults with epilepsy having low to moderate seizure frequency. However, for individual level assessments proxies should be used with caution.

Adolescent↗

Development of the quality of life in epilepsy inventory.

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.

Adolescent↗

Computerized seizure detection of complex partial seizures.

In this study, we describe a computerized method that uses 3 quantified EEG features and discriminant analysis to automatically detect seizure EEG. The quantified EEG features were relative amplitude, dominant frequency and rhythmicity. Using EEGs recorded from intracranial electrodes, the seizure detection method was applied to consecutive non-overlapping 2-channel EEG epochs. A seizure detection sensitivity, ranging from 90% to 100%, was associated with a false positive detection rate of 1.5-2.5/h. The performance of the seizure detection method remained stable for EEG recorded over variable time periods.

Discriminant Analysis↗

MR imaging in patients with intractable complex partial epileptic seizures.

Detailed neurologic studies, high-field-strength MR imaging, and CT scanning were performed preoperatively in 53 patients with intractable complex partial seizures who underwent surgical treatment for epilepsy. Macroscopic structural (tumoral or vascular) lesions were found in 28% of patients. The remainder had pathologic findings consistent with mesial temporal gliosis. Tumors were found in 22% of the patients and were benign or of low-grade malignancy in every case. MR was accurate in the preoperative diagnosis of structural lesions, including very small occult tumors and cryptic vascular malformations. In patients with mesial temporal gliosis, there was correlation between the MR observation of a unilaterally dilated anterior temporal horn and the EEG-identified seizure focus and side of temporal lobectomy. However, MR demonstrated T2-weighted signal abnormalities correlating with the epileptogenic focus in only 8% of cases of mesial temporal gliosis. MR provided useful information in 28% of patients who underwent surgery for refractory complex partial epilepsy. MR obviated invasive EEG monitoring in 93% of the patients with structural lesions. MR was useful in only 8% of the patients with pathologic changes of mesial temporal gliosis.

Adolescent↗

Tribulin in post-traumatic stress disorder.

Tribulin (endogenous monoamine oxidase inhibitor/benzodiazepine receptor binding inhibitor) output was measured in the urine of 18 patients with post-traumatic stress disorder (PTSD) and 13 controls. The level of the two inhibitory activities was highly significantly correlated in the group as a whole. There was no difference between output of either inhibitor in patients and controls. However, when the PTSD group was subdivided according to various psychometric ratings, a pattern of output did emerge. Levels of both inhibitory activities were higher in agitated compared with non-agitated subjects, and lower in extroverts compared with introverts. This finding supports the view that tribulin output is raised in conditions of greater arousal.

Arousal↗

The DST and posttraumatic stress disorder.

The dexamethasone suppression test (DST) was administered to 28 male combat veterans with posttraumatic stress disorder. Six subjects (21%) were nonsuppressors. The nonsuppression rates for the subgroups with and without major depressive disorder according to the Research Diagnostic Criteria were 50% and 6%, respectively. The authors conclude that cortisol nonsuppression is rare in posttraumatic stress disorder unless there is concomitant major depression.

Adolescent↗

Irreversible neurologic complications of metrizamide myelography.

Metrizamide, a major contrast agent for myelographic procedures, has rarely been reported to cause irreversible neurologic complications. The major transient neurologic alterations include neuropsychological reactions, generalized tonic-clonic seizures, and headaches. Two cases of irreversible spinal neurologic deficits resulting from metrizamide myelography are reported, and the factors that may increase the risks of complications in metrizamide myelographic studies are discussed, including preexisting dehydration, patient positioning, and the concentration of contrast agent.

Adult↗

Diabetes mellitus in the elderly.

Diabetes mellitus, because of its prevalence and inherent chronicity, represents a major health threat to the elderly. However, some of the risk of diabetes-associated morbidity and mortality can be diminished with a regimen that takes into account special features of the disease in this age-group.

Adult↗

Preliminary findings of high-dose thiamine in dementia of Alzheimer's type.

Thiamine is important not only in the metabolism of acetylcholine but also in its release from the presynaptic neuron. Pathologic, clinical, and biochemical data suggest that thiamine deficiency is detrimental to the cholinergic system and that thiamine-dependent enzymes may be altered in Alzheimer's disease. Two previous studies reported contradictory results in patients with dementia of Alzheimer's type treated with 3 g/day of thiamine. In the present study, we examined the effects of 3 to 8 g/day thiamine administered orally. Our results suggest that thiamine at these pharmacologic dosages may have a mild beneficial effect in dementia of Alzheimer's type. The mechanism of the observed effect is unknown, but the findings warrant further investigation, not only for their therapeutic implications but for their possible etiologic clues. In addition, the results suggest long-term carry-over effects that should be considered in the design of future studies.

Aged↗