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Kimford J Meador

Publications and source records attributed to Kimford J Meador.

At least 19 recordsLinked to original sources
PubMed2006

Structured cueing on a semantic fluency task differentiates patients with temporal versus frontal lobe seizure onset.

Patients with frontal lobe dysfunction (e.g., Huntington's disease) reportedly benefit more from cueing on measures of semantic fluency than do patients with damage to temporal lobe structures (e.g., Alzheimer's disease). This differential benefit from cueing suggests that different neurocognitive functions are impaired in these two groups. Patients with frontal lobe dysfunction are presumed to have difficulty with the executive aspects of this generative fluency task, whereas patients with temporal lobe impairment are limited by deficits in semantic memory. We studied the performance of patients with complex partial seizures of frontal or temporal lobe onset, as determined by video/EEG monitoring, on standard and cued measures of semantic fluency administered in a counterbalanced sequence across groups. These groups did not differ significantly in terms of age, education, gender, age at seizure onset, total number of antiepileptic drugs, or IQ, and all patients subsequently underwent surgery for intractable epilepsy. Patients with frontal lobe dysfunction (FL group) performed significantly worse than patients with temporal lobe impairment (TL group) on the standard semantic fluency paradigm (TL group: M=18.4, SD=4.7; FL group: M=11.1, SD=5.3), t(27)=-3.75, P<0.001. Nevertheless, results of an ANCOVA demonstrated that the FL group showed significantly greater performance improvement than the TL group when provided with a cued semantic fluency format, even after controlling for baseline differences in ability on the standard semantic fluency task (TL group: M=0.45, SD=3.8; FL M=9.4, SD=5.1), F(1,29)=12.37, P=0.002. These findings support previous research suggesting that frontal and temporal structures contribute uniquely to semantic generative fluency and suggest that using a combination of standard and cued semantic fluency tasks may help confirm localization of seizure onset in partial epilepsy by localizing the associated cognitive dysfunction.

Adult↗
PubMed2006

Antiepileptic drugs and neurodevelopment.

Clinical studies have documented the teratogenic potential of antiepileptic drugs (AEDs). More recent cohort studies have been trying to sort out which AEDs impose the highest risk of teratogenicity. Currently, there is evidence demonstrating an increased risk of major congenital malformations (MCMs) for valproate, phenobarbital, and polytherapy during pregnancy. Based on the current data from multiple studies, the risk for valproate is the highest. Additional studies are needed to fully delineate if differences exist for other AEDs, especially the newer AEDs. However, although MCMs are easy to recognize and have been shown to be more common after in utero exposure to AEDs, there are insufficient data regarding their long-term effects on cognition and behavior in exposed children. Although most children born to women with epilepsy are healthy, in recent years there has been increasing awareness of the long-term effects of in utero exposure to AEDs. Recent discovery of neuronal apoptosis following in utero AED exposure in animals during a period that corresponds to the third trimester and early infancy in humans raises further concerns. Prospective clinical studies seem necessary in order to better understand the long-term neurodevelopmental effects of in utero exposure to AEDs.

Abnormalities, Drug-Induced↗
PubMed2006

Cognitive and memory effects of the new antiepileptic drugs.

Problems with cognition are common in patients with epilepsy. A series of double-blind, randomized, crossover, healthy volunteer studies have been conducted to avoid a variety of the confounding effects on cognition such as those produced by changes in seizure frequency. All of the older AEDs produced cognitive effects compared to the non-drug conditions. The cognitive effects of several of the new AEDs are described although data are limited. Studies have demonstrated that in utero AED exposure in humans may affect cognitive development. Although the cognitive effects of AEDs are generally modest, these effects can have clinical significance. The available data suggest that some of the new AEDs have fewer effects on cognition and memory than the older AEDs, and these differences can have clinical impact.

Animals↗
PubMed2006

Rapid detection of major depression in epilepsy: a multicentre study.

BACKGROUND: Depression is a common comorbid disorder in epilepsy but is not routinely assessed in neurology clinics. We aimed to create a rapid yet accurate screening instrument for major depression in people with epilepsy. METHODS: We developed a set of 46 items to identify symptoms of depression that do not overlap with common comorbid cognitive deficits or adverse effects of antiepileptic drugs. This preliminary instrument and several reliable and valid instruments for diagnosis of depression on the basis of criteria from the Diagnostic and Statistical Manual IV, depression symptom severity, health status, and toxic effects of medication were applied to 205 adult outpatients with epilepsy. We used discriminant function analysis to identify the most efficient set of items for classification of major depression, which we termed the neurological disorders depression inventory for epilepsy (NDDI-E). Baseline data for 229 demographically similar patients enrolled in two other clinical studies were used for verification of the original observations. FINDINGS: The discriminant function model for the NDDI-E included six items. Internal consistency reliability of the NDDI-E was 0.85 and test-retest reliability was 0.78. An NDDI-E score of more than 15 had a specificity of 90%, sensitivity of 81%, and positive predictive value of 0.62 for a diagnosis of major depression. Logistic regression showed that the model of association of major depression and the NDDI-E was not affected by adverse effects of antiepileptic medication, whereas models for depression and generic screening instruments were. The severity of depression symptoms and toxic effects of drugs independently correlated with subjective health status, explaining 72% of variance. Results from a separate verification sample also showed optimum sensitivity, specificity, and predictive power at a cut score of more than 15. INTERPRETATION: Major depression in people with epilepsy can be identified by a brief set of symptoms that can be differentiated from common adverse effects of antiepileptic drugs. The NDDI-E could enable rapid detection and improve management of depression in epilepsy in accordance with internationally recognised guidelines.

Adult↗
PubMed2006

Distinct cognitive neurophysiologic profiles for lamotrigine and topiramate.

PURPOSE: To contrast the effects of lamotrigine (LTG) and topiramate (TPM) on cognitive task-related and resting-state EEG and evoked potential (EP) measures. METHODS: We used a double-blind, randomized, crossover design. Healthy adults (N = 29) had two 8-week periods of dose escalation, 4 weeks of drug maintenance (300 mg daily), and 4 weeks of washout. EEG was recorded during working memory (WM) tasks and resting conditions at baseline, at the end of each maintenance phase, and after final washout. RESULTS. LTG did not affect overt performance on the tasks, although it reduced EEG power in both resting and WM task conditions, most prominently in the 6- to 12-Hz frequency range, and attenuated P300 evoked-potential amplitude equally in both WM task loads. TPM slowed responses and increased errors. It also increased EEG power below 6 Hz in all conditions, and reduced the amplitude of a slow wave observed in a difficult version of the WM task. CONCLUSIONS: The drugs produced both task-independent and task-related alterations in neurophysiologic measures. The EEG and EP changes produced by TPM are consistent with an impairment of WM, as evidenced by overt performance deficits on the behavioral tasks. By contrast, the reduction in synchronous cortical activity produced by LTG was not accompanied by cognitive impairment. It is unknown whether such effects would also be observed at lower doses, such as those that often are used in monotherapy for newly diagnosed patients.

Adult↗
PubMed2005

Subjective preference for lamotrigine or topiramate in healthy volunteers: relationship to cognitive and behavioral functioning.

OBJECTIVE: Outcomes research emphasizes patient self-assessment and preferences in optimizing treatment. We previously showed that lamotrigine produces significantly less cognitive and behavioral impairment compared with topiramate. In the current study we extend these observations to subject self-report of preference for lamotrigine or topiramate independent of potentially confounding effects of seizures or seizure control. Additionally, drug preference was related to effects of lamotrigine and topiramate on objective neuropsychological tests as well as self-perception on behavioral instruments. METHODS: Thirty-seven healthy volunteers completed a double-blind, randomized crossover design incorporating two 12-week treatment periods of lamotrigine and topiramate each titrated to a dose of 300 mg/day. Evaluation of 23 objective neuropsychological and 15 subjective behavioral measures occurred at four times: pretreatment baseline, first treatment, second treatment, and posttreatment baseline. Preference for lamotrigine or topiramate was assessed, while blinding was maintained, at the final study visit when each subject was asked which drug he or she would prefer to take. RESULTS: A large majority (70%) preferred lamotrigine, 16% stated preference for topiramate, and 14% had no preference (drugs equivalent). Consistent with preference, those preferring lamotrigine performed better on 19 of 23 objective and 13 of 15 subjective behavioral measurements while on lamotrigine. Inconsistent with preference, subjects preferring topiramate performed better on 19 of 23 objective and 9 of 15 subjective behavioral measures while on lamotrigine. Topiramate preference also did not correlate with IQ, serum concentration, body mass index, age, or gender. Topiramate preference did relate to responses on the Profile of Mood States. CONCLUSION: Lamotrigine was preferred by the majority of subjects, congruent with objective neuropsychological and subjective behavioral measures. In contrast, for those stating a preference for topiramate the results on objective neuropsychological measures were impaired while fewer complaints were noted on the Profile of Mood States. This suggests that preference for topiramate may be determined by an effect on mood.

Adult↗
PubMed2005

Lamotrigine therapy in patients requiring a change in antiepileptic drug regimen.

INTRODUCTION: The tolerability of lamotrigine as adjunctive and monotherapy in patients requiring a change in antiepileptic drug (AED) therapy was assessed in this multicenter, open-label study. Open-label studies conducted in the clinic setting may provide additional drug tolerability and effectiveness information that may not be evident in pre-approval clinical trials. METHODS: Adult patients with partial seizures received adjunctive lamotrigine for 16 weeks. Patients taking a single enzyme-inducing AED could convert to lamotrigine monotherapy for an additional 12 weeks. Patients were assessed at baseline, end of adjunctive therapy, and end of monotherapy using the Liverpool Adverse Experience Profile (AEP), Quality of Life in Epilepsy-31, a patient satisfaction rating, and a subjective investigator global assessment. RESULTS: Of the 547 patients enrolled (mean age 42.7 years, 58% female), 421 (77%) completed adjunctive therapy. Upon completion of the adjunctive phase, mean improvement from baseline was 4.3 points on the AEP, and investigators rated 71% of patients as improved in global status. Overall score on the QOLIE 31 improved by 10 points from baseline. One hundred and seventy-eight patients entered and 143 (80%) patients completed the monotherapy phase. In patients completing lamotrigine monotherapy, mean improvement from baseline was 5.9 points on the AEP, and investigators rated 92% as improved in global status. Overall score on the QOLIE 31 score improved by 15 points from baseline. CONCLUSION: Lamotrigine as adjunctive treatment and monotherapy may improve side effect burden and quality of life in patients requiring a change in AED therapy.

Adolescent↗
PubMed2005

Dimensions of the epilepsy foundation concerns index.

We performed principal component analysis (PCA) of the Epilepsy Foundation Concerns Index scale in 189 patients undergoing evaluation for epilepsy surgery. We identified a five-factor solution in which there were no varimax-rotated factors consisting of fewer than two questions. Factor 1 reflects affective impact on enjoyment of life, Factor 2 reflects general autonomy concerns, Factor 3 reflects fear of seizure recurrence, Factor 4 reflects concern of being a burden to one's family, and Factor 5 reflects a perceived lack of understanding by others. Multiple regression using the Quality of Life in Epilepsy--89 question version; Minnesota Multiphasic Personality Inventory--2; Wechsler Adult Intelligence Scale--third edition; and verbal and visual memory tests as predictors demonstrated a different pattern of association with the factor and summary scores. We conclude that the Epilepsy Foundation Concerns Index is multidimensional, and using a global score based on all items may mask specific concerns that may be relevant when applied to individual patients.

Adult↗
PubMed2005

Victoria symptom validity test performance in non-litigating epilepsy surgery candidates.

We report Victoria Symptom Validity Test (VSVT) performance in 120 epilepsy patients undergoing neuropsychological assessment as part of their evaluation as epilepsy surgery candidates. Patients were grouped according to their performance on hard VSVT stimuli. Scores of at least 21/24 on the hard VSVT items were classified as valid (n=86), scores of 18/24-20/24 were considered questionably valid (n=20), and scores of 17/24 and below were designated as invalid (n=14). Significant group effects were observed for WAIS-III Full Scale IQ, Verbal IQ, Performance IQ, Digit Span, Rey 3x5 Memory, Selective Reminding Recognition, and Complex Figure Immediate Recall; poorer cognitive scores were associated with lower VSVT scores. Age was also related to VSVT performance, with patients older that 40 years of age (16/42) more likely to fail the VSVT (i.e., hard scores < or = 20/24) than their younger counterparts (8/78) (p=.0006, Fisher's Exact Test). These results indicate that VSVT may identify cases of incomplete effort in patients being evaluated for strictly clinical purposes in which no external incentive to perform poorly has been identified, although the potential confound of low IQ on VSVT cannot be determined from this sample. Older patients also appear to be at increased risk for suboptimal performance, and may need additional encouragement or education regarding the need to perform to the best of their ability, and thereby maximize the likelihood of obtaining valid neuropsychological test results.

Adult↗
PubMed2005

Screening for major depression in epilepsy with common self-report depression inventories.

PURPOSE: Major depression is a common psychiatric comorbidity in chronic epilepsy that is frequently unrecognized and untreated. A variety of self-report mood inventories are available, but their validity as well as ability to detect major depression in epilepsy remains uncertain. The purpose of this study was to determine the ability of two common depressive symptom inventories to identify major depression in people with epilepsy. METHODS: In total, 174 adult patients with epilepsy underwent standardized psychiatric interview techniques [Mini International Neuropsychiatric Interview (MINI) and Mood Disorders module of the Structured Clinical Interview for DSM-IV Axis I Disorders-Research Version (SCID-I)] to determine the presence of current major depression. Subjects completed two self-report depression inventories [Beck Depression Inventory-II (BDI-II), Center for Epidemiological Study of Depression (CES-D)]. The ability of these self-report measures to identify major depression as identified by the gold standard structured interviews was examined by using diagnostic efficiency statistics. RESULTS: Both the BDI-II and the CES-D exhibited significant ability to identify major depression in epilepsy. All ROC analyses were highly significant (mean area under the curve, 0.92). Mean sensitivity (0.93) and specificity (0.81) were strong, with excellent negative predictive value (0.98) but lower positive predictive value (0.47). CONCLUSIONS: Common self-report depression measures can be used to screen for major depression in clinical settings. Use of these measures will assist in the clinical identification of patients with major depression so that treatment can be initiated.

Adult↗
PubMed2005

Clinical assessment of Axis I psychiatric morbidity in chronic epilepsy: a multicenter investigation.

This study characterizes the rate of current Axis I DSM-IV disorders using a brief standardized psychiatric interview procedure, the Mini International Neuropsychiatric Interview (v5.0) (MINI), and determined the validity of MINI diagnoses of current depressive episodes to the research standard (Structured Clinical Interview for DSM-IV Disorders [SCID]). One hundred seventy-four patients with chronic epilepsy from five tertiary medical centers were interviewed using the MINI and the mood disorders module of the SCID. Current Axis I disorders were evident in one-half the sample (49%), with prevalent anxiety (30.4%) and mood (21.8%) disorders. Major depressive episode was the most common individual diagnosis (17.2%). Concordance was high between the MINI and SCID for diagnoses of current depression, especially for major depression. Of those with current major depression, less than one-half were treated with antidepressant medications. Current Axis I DSM-IV diagnoses can be effectively and accurately identified in clinical settings using shorter standardized psychiatric interview techniques. Issues regarding recognition and treatment of psychiatric morbidity in epilepsy are discussed.

Adult↗
PubMed2004

Cognitive side effects of antiepileptic drugs in children.

Cognitive impairment associated with antiepileptic drug (AED) therapy in children is an important concern given the potential negative effects of treatment on school learning and performance. Unfortunately, there have been few studies examining the cognitive effects of AEDs in this population and no adequate studies of newer AEDs. This article will discuss the effects of the traditional and newer AEDs on neuropsychological function in children. Because of various limitations in the designs of these studies, however, many of the studies report inconclusive findings. Although it will be necessary to overcome many programmatic and procedural hurdles, well-designed randomized prospective studies that are of adequate length to determine how AEDs ultimately relate to school performance and social adjustment are needed to firmly establish the cognitive and behavioral effects of AEDs in children.

Adolescent↗
PubMed2004

Role of cerebral lateralization in control of immune processes in humans.

Cerebral lateralization may be important in neural control of immune function. Animal studies have demonstrated differential effects of left and right brain lesions on immune function, but human studies are inconclusive. Here, we show that resections in the language dominant hemisphere of patients with epilepsy reduce lymphocytes, total T cells, and helper T cells. In contrast, resections in the language nondominant hemisphere increased the same cellular elements. T-cell responses to mitogens and microbial antigens were not differentially affected. Left/right arm histamine skin response ratios were altered in patients with left cerebral epileptic focus, and flare skin responses were reduced by left cerebral resections in contrast with an increase after right cerebral resections. The findings demonstrate a differential role of the left and right cerebral hemispheres on immune functions in humans.

Adult↗
PubMed2004

Cognitive side effects of antiepileptic drugs.

Antiepileptic drugs produce global changes in the excitation levels in the central nervous system and often lead to cognitive and behavioral deficits. These deficits vary and must be considered independently in every patient. A number of consistent risk factors have been established. Polypharmacy and high blood levels of an antiepileptic drug (AED) increase the risk of cognitive side effects. Different effects have been demonstrated for some AEDs, but comparative data are incomplete across all of them. Other factors such as patient age and type/frequency of seizures may also be important contributors to the patient's cognitive state. AEDs can have positive or negative effects on mood, providing another consideration in choosing the course of treatment.

Adult↗