[Show abstract][Hide abstract] ABSTRACT: Recent diagnostic and treatment advances in psychogenic nonepileptic seizures (PNES) have the potential to improve care for patients, but little is known about the current state of PNES care delivery in the Veterans Health Administration (VA). We conducted semistructured interviews with 74 health-care clinicians and workers in the VA, eliciting provider perceptions of PNES care. Data were analyzed according to principles of Grounded Theory. The results revealed variation in care and two emergent domain themes of frustration and hope. Frustration was manifest in subthemes including Complexity, Patient Acceptance, Uncertainty About Treatment, Need for Evidence-based Treatment, and Failure of Cross-Disciplinary Collaboration between neurologists and mental health providers. Hope encompassed subthemes of Positive Attitudes, Developing Cross-Disciplinary Treatment, and Specific PNES Care. Increased resources for diagnosing, treating, and researching PNES have improved awareness of the disorder. More research is needed to understand patients' and caregivers' perceptions of PNES care.
[Show abstract][Hide abstract] ABSTRACT: To evaluate a proposed seizure etiology of traumatic brain injury (TBI) as a risk factor for psychogenic nonepileptic seizures (PNESs), the effect of reported TBI severity on the diagnosis of PNES versus epileptic seizures (ESs), and the potential moderating role of posttraumatic stress disorder (PTSD).
The Journal of head trauma rehabilitation. 06/2014;
[Show abstract][Hide abstract] ABSTRACT: To examine the association of epilepsy with traumatic brain injury (TBI) in Afghanistan and Iraq (Operation Enduring Freedom [OEF]/Operation Iraqi Freedom [OIF]) Veterans.
Cross-sectional observational study.
A total 256284 OEF/OIF Veterans who received inpatient and outpatient care in the Veterans Health Administration in fiscal years 2009-2010.
We used algorithms developed for use with International Classification of Diseases, Ninth Revision, Clinical Modification, codes to identify epilepsy, TBI (penetrating TBI [pTBI]/other TBI), and other risk factors for epilepsy (eg, stroke). TBI and other risk factors were identified prior to the index date (first date of seizure or October 1, 2009) for primary analyses.
Epilepsy prevalence was 10.6 per 1000 (N = 2719) in fiscal year 2010; age-adjusted prevalence was 6.1. Of 37718 individuals with a diagnosis of TBI, 29297 Veterans had a diagnosis of TBI prior to the index date. Statistically significant associations were found between epilepsy and prior TBI diagnosis (pTBI: adjusted odds ratio = 18.77 [95% confidence interval, 9.21-38.23]; other TBI: adjusted odds ratio = 1.64 [1.43-1.89]).
Among OEF/OIF Veterans, epilepsy was associated with previous TBI diagnosis, with pTBI having the strongest association. Because war-related epilepsy in Vietnam War Veterans with TBI continued 35 years postwar, a detailed, prospective study is needed to understand the relationship between epilepsy and TBI severity in OEF/OIF Veterans.
The Journal of head trauma rehabilitation 04/2014; · 2.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Psychogenic non-epileptic seizures (PNES) are frequently encountered in epilepsy monitoring units (EMU) at Veterans Affairs Medical Centers (VAMCs) and cause significant long-term disability. An understanding of psychiatric factors associated with PNES could aid in earlier diagnosis and treatment. We studied 50 consecutive veterans diagnosed with PNES and 37 veterans diagnosed with epileptic seizures (ES), evaluated at a VAMC EMU. We reviewed all available mental health evaluations prior to EMU evaluation. Univariate comparisons included axis I diagnoses, axis II diagnoses, and psychiatric hospitalizations. Predictive models of seizure classification were evaluated by logistic regression. A diagnosis of post-traumatic stress disorder (PTSD) preceded the diagnosis of PNES in 58% of patients and the diagnosis of ES in 13.5% (p<0.001). On logistic regression, PTSD was the only significant psychiatric diagnosis (odds ratio 9.2). Major depression and alcohol abuse were common diagnoses but did not differentiate PNES and ES groups.
[Show abstract][Hide abstract] ABSTRACT: Patients with epilepsy frequently experience depression and emotional stress and these may function as seizure triggers in epileptogenic frontotemporal cortex, which serves in emotional processing. Eight patients enrolled in a pilot trial of a 6-month epilepsy-specific behavioral approach comprising counseling and relaxation to recognize and eliminate emotional seizure triggers. Potential participants with psychogenic seizures were excluded by long-term EEG and/or the MMPI profile. One participant became seizure free, another had an approximately 90% reduction in seizures, and two additional participants achieved a greater than 50% reduction in seizure frequency (total responder rate=50%), stable during 6 months of observation after the intervention. All completers showed marked and stable improvement of quality of life (Quality of Life in Epilepsy-89 inventory) and temporary improvement in the Profile of Mood States. An adequately powered randomized controlled trial is needed to confirm our findings, which suggest that behavioral approaches may hold promise for motivated patients with epilepsy.
[Show abstract][Hide abstract] ABSTRACT: Psychogenic nonepileptic seizures (PNES) are frequently encountered in epilepsy monitoring units (EMU) and can result in significant long-term disability. We reviewed our experience with veterans undergoing seizure evaluation in the EMU to determine the time delay to diagnosis of PNES, the frequency of PNES, and cumulative antiepileptic drug (AED) treatment. We compared veterans with PNES to civilians with PNES studied in the same EMU.
We reviewed records of all patients admitted to one Veterans Affairs Medical Center (VAMC) EMU over a 10-year interval. These patients included 203 veterans and 726 civilians from the university affiliate. The percentage of patients with PNES was calculated for the veteran and civilian groups. Fifty veterans with only PNES were identified. Each veteran with PNES was matched to the next civilian patient with PNES. The 2 groups were compared for interval from onset of the habitual spells to EMU diagnosis, cumulative AED treatment, and other measures.
PNES were identified in 25% of veterans and 26% of civilians admitted to the EMU. The delay from onset of spells to EMU diagnosis averaged 60.5 months for veterans and 12.5 months for civilians (p < 0.001). Cumulative AED treatment was 4 times greater for veterans with PNES as compared to civilians (p < 0.01). Fifty-eight percent of veterans with PNES were thought to have seizures related to traumatic brain injury.
The results indicate a substantial delay in the diagnosis of PNES in veterans as compared to civilians. The delay is associated with greater cumulative AED treatment.
[Show abstract][Hide abstract] ABSTRACT: We describe seizure laterality and temporal seizure patterns in six subjects with bilateral temporal lobe epilepsy (bTLE) implanted with bilateral hippocampal depth electrodes and the NeuroPace RNS™ system over 84 consecutive days. Seizures were disproportionate in laterality in three subjects and disproportionate in time for two subjects. Clustering of seizures did not clearly affect laterality. Some but not all subjects with bTLE displayed nonrandom temporal or lateral clustering of seizures.
Epilepsy research 02/2011; 93(2-3):221-5. · 2.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Antiepileptic drugs (AEDs) can be associated with neurotoxic side effects including cognitive dysfunction, a problem of considerable importance given the usual long-term course of treatment. Pregabalin is a relatively new AED widely used for the treatment of seizures and some types of chronic pain including fibromyalgia. We measured the cognitive effects of 12 weeks of pregabalin in healthy volunteers.
Thirty-two healthy volunteers were randomized in a double-blind parallel study to receive pregabalin or placebo (1:1). Pregabalin was titrated over 8 weeks to 600 mg/d. At baseline, and after 12 weeks of treatment, all subjects underwent cognitive testing. Test-retest changes in all cognitive and subjective measures were Z scored against test-retest regressions previously developed from 90 healthy volunteers. Z scores from the placebo and pregabalin groups were compared using Wilcoxon tests.
Thirty subjects completed the study (94%). Three of 6 target cognitive measures (Digit Symbol, Stroop, Controlled Oral Word Association) revealed significant test-retest differences between the pregabalin and placebo groups, all showing negative effects with pregabalin (p < 0.05). These cognitive effects were paralleled by complaints on the Portland Neurotoxicity Scale, a subjective measure of neurotoxicity (p < 0.01).
At conventional doses and titration, pregabalin induced mild negative cognitive effects and neurotoxicity complaints in healthy volunteers. These effects are one factor to be considered in the selection and monitoring of chronic AED therapy. Class of Evidence: This study provides Class I evidence that pregabalin 300 mg BID negatively impacts cognition on some tasks in healthy volunteers.
[Show abstract][Hide abstract] ABSTRACT: Non-epileptic seizures (NES) are not infrequent in the elderly. However, the data on NES in the elderly is likited.
To study the demographic and historical background of eldely patients with NES and compare the same with the data in the younger patients with NES.
Patients with NES over 55 years of age and the next two consecutive patients with NES between ages 18 and 45 were compared in terms of demographic and historical features, psychiatric evaluation and MMPI testing.
Of all the 128 patients with NES, 13 (10.6%) were over 55 years of age. History of physical/sexual abuse was high in both the groups. The mean length of time for NES diagnosis was longer in the elderly (13.38 +/- 15.33 vs. 6.15 +/- 8.04 years; P < 0.05). Majority of the patients with NES were on AEDs without evidence of epilepsy and almost half in both the groups were using benzodiazepines.
In demographic and historical aspects old and young patients do not display major differences; however, the diagnosis is significantly delayed in the elderly. Early diagnosis with video EEG is recommended to avoid potential long-term risks associated with inappropriate treatments.
Neurology India 01/2010; 58(1):48-52. · 1.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We compared MMPI-2 profiles of Gulf War veterans with fibromyalgia (FM) to epileptic seizure (ES) patients, psychogenic non-epileptic seizure (PNES) patients, and Gulf War veteran healthy controls. Both PNES and FM are medically unexplained conditions. In previous MMPI-2 research PNES patients were shown to have significantly higher Hs and Hy clinical scales than ES patients. In the present research the FM group had significantly higher Hs and Hy scale scores than both the ES group and the healthy control group. There was no significant difference between the FM and PNES Hs scale scores; however, the FM Hy scale score was significantly lower than the PNES Hy scale score. Present findings indicate a high level of psychological distress in the FM group.
The Clinical Neuropsychologist 10/2009; 24(2):220-34. · 1.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Neurological, neurodiagnostic, and neuropsychological aspects of psychogenic nonepileptic seizures (PNES) are reviewed, including psychosocial, psychiatric, cognitive, and MMPI-2 findings.
[Show abstract][Hide abstract] ABSTRACT: Previous quantitative EEG (QEEG) studies of carbamazepine (CBZ), oxcarbazepine (OXC), and phenytoin (PHT) revealed a pattern of EEG slowing and an increase in drowsiness on the awake maintenance task (AMT). EEG slowing has been shown to correlate with negative effects on cognitive tests. Topiramate (TPM) is a novel AED with relatively large negative effects on cognitive function. We tested the hypothesis that TPM would induce significant slowing of EEG background rhythms and an increase in AMT drowsiness.
Forty healthy volunteers were randomized to TPM, gabapentin (GBP), or placebo. Doses were escalated as tolerated to a maximum of 400mg/day for TPM or 3600 mg/day for GBP, over a 10-week period, followed by a minimum 2-week plateau period. Volunteers underwent an EEG, cognitive tests, and the AMT prior to starting an AED and again 12 weeks later. The EEG was captured using a structured recording protocol and quantified using the fast Fourier transform. Four target measures were derived from the averaged occipital electrodes (peak frequency of the dominant posterior rhythm, median frequency, percentage theta, and percentage delta). Test-retest changes for all measures were scored against similar test-retest distributions previously obtained from untreated healthy volunteers.
TPM produced no significant change in any of the four target EEG measures or on the AMT, even though several target cognitive tests revealed moderate or greater negative effects. There were also no significant changes in the placebo group. GBP slowed the peak and median frequency EEG measures and increased the percentage of theta and delta activity. Neither TPM, GBP, nor placebo caused a significant increase in drowsiness on the AMT.
TPM has a unique neurotoxicity profile. It has no effect on EEG background measures or on the AMT, but induces moderate to large negative changes in many cognitive test scores. This profile differs from those of CBZ, OXC, PHT, and GBP.
[Show abstract][Hide abstract] ABSTRACT: We compared the MMPI-2 profiles of adults with multiple chemical sensitivity (MCS), epileptic seizures (ES), and nonepileptic seizures (NES). Both NES and MCS are medically unexplained conditions. In previous studies profiles associated with NES were elevated on scales Hs and Hy, compared with profiles associated with ES. We predicted that profiles associated with MCS would be elevated on Hs and Hy compared with the ES group. Patients with ES and NES were diagnosed after intensive EEG monitoring using published criteria. MCS was diagnosed if there was a complaint of illness in response to multiple common odors at levels that are not noxious to most people. All the MCS cases had legal claims for injury related to chemical exposures. The results showed that on MMPI-2 scales Hs, D, and Hy the MCS group had means significantly higher than both the ES and NES groups. Fake Bad Scale scores were elevated in 11 MCS cases, and regression-based estimates of Fake Bad Scale scores showed elevation in the MCS group compared with both seizure groups. We conclude that MMPI-2 data, obtained from people seeking financial compensation, indicate that there is a strong psychological component to MCS symptoms.
The Clinical Neuropsychologist 01/2007; 20(4):848-57. · 1.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vigilance is a term with varied definitions but the most common usage is sustained attention or tonic alertness. This usage of vigilance implies both the degree of arousal on the sleep-wake axis and the level of cognitive performance. There are many interacting neural and neurotransmitter systems that affect vigilance. Most studies of vigilance have relied on states where the sleep-wake state is altered, e.g. drowsiness, sleep-deprivation, and CNS-active drugs, but there are factors ranging from psychophysics to motivation that may impact vigilance. While EEG is the most commonly studied physiologic measure of vigilance, various measures of eye movement and of autonomic nervous system activity have also been used. This review paper discusses the underlying neural basis of vigilance and its assessment using physiologic tools. Since, assessment of vigilance requires assessment of cognitive function this aspect is also discussed.
[Show abstract][Hide abstract] ABSTRACT: Vagus nerve stimulation (VNS) has demonstrated a significant anticonvulsant effect in preclinicalstudies, in pilot studies in humans, and in the acute phaseof a multicenter, double-blinded, randomized study. After completion of a 14–week, blinded, randomized study, with 31 receiving high (therapeutic) VNS and 36 receiving low (less or noneffective) VNS, 67 patients elected tocontinue in an open extension phase. During the extension phase, all 67 patients received high VNS. Seizurefrequency during the 3-month treatment blocks was compared with a 12–week baseline. For both groups, all periods of high VNS demonstrated a significant decrease inseizure frequency (p < 0.01 level) as compared with baseline. For the 16–18–month period of VNS, data wereavailable for 26 of the 31 patients randomized to highVNS. This group achieved a 52.0% mean seizure frequency percentage réduction as compared with baseline. For those converted from low to high VNS, data wereavailable for 24 of the 36 patients at the 16–18-month timeperiod. This group reported a mean seizure frequency percentage reduction of 38.1% as compared with baseline. No significant change in the safetyhde effect profilewas reported during longterm followup. The previouslyreported side effects of hoarsenesslvoice change, coughing, and paresthesia (sensation in neck and jaw) continued to occur during VNS. These side effects were well tolerated. During the follow-up period, 1 patient died of thrombotic thrombocytopenic purpura (TTP) and 5 patients discontinued treatment because of unsatisfactory efficacy.RéSUMé: La stimulation du nerf vague (SNV) a demontre un effet anticonvulsivant significatif lors l'études pre-clinique, d'études pilotes chez l'homme et pendant la phase aigue d'une étude randomisée multicentrique en double-aveugle. Après avoir termine une étude randomisée aveugle de 14 semaines, 67 patients ont choisi de continuer au cours d'une phase d'extension ouverte, 31 recevant la SNV haute (therapeutique) et 36 une SNV basse (moins ou non efficace). Pendant cette phase d'extension les 67 patients ont tous re y la stimulation haute. La friquence des crises pendant les periodes de traitement de 3 mois etait comparée avec la période de base de 12 semaines. Toutes les périodes de SNV haute, pour les deux groupes, ont mis en évidence une diminution significative de la fréquence des crises (p < 0.01) par comparaison a la période de base. Pour la périodes de 16 18 mois de SNV, des données étaient disponibles pour 26 et 31 patients randomists en SNV haute. Ce groupe a obtenu une réduction moyenne de la frequence des crises de 52.0% par rapport B la période de base. Pour les patients passes de la SNV basse a la SNV haute, les données étaient disponibles pour 24 des 36 patients la période de 16 a 18 mois. Ce groupe a signale une réduction de la fréquence moyenne des crises de 38.1% par rapport a la ligne de base. Le profil du rapport securité sur effets secondaires n'a pas été modifie de façon significative pendant l'étude de suivi a long terme. Les effets secondaires signales auparavant (raucité de la voix, toux, paresthesies du cou ou de la mrichoire) ont continue survenir pendant la SNV. Ces effets secondaires ont été bien toléres. Pendant la période de suivi un patient est decede d'un purpura thromotique thrombocytopenique et 5 patients ont arr été le traitement en raison d'une efficacite non satisfaisante.RESUMEN: La estimulación del nervio vago (VNS) ha demostrado efectos anticonvulsivantes significativos en estudios preclinicos, en estudios piloto en humanos y en la fase aguda de un ensayo multicentrico y doble ciego. DespuéS de la finalización de un estudio randomizado ciego de 4 semanas, 67 pacientes decidieron prolongar la fase de estudio abierto y 31 casos recibieron VNS ALTA (terapeutica) y 36 VNS BAJA (poco o no eficaz). Durante la fase de amplkación todos los 67 casos recibieron VNS ALTA. La frecuencia de ataques durante dos bloques terapeuticos de 3 meses, se comparo con 12 semanas basales. Todos los periodos de VNS ALTA para ambos grupos, demostraron una reducción significativa de la frecuencia de ataques (p < 0.01) comparada con el periodo basal. Durante los meses 16–18 la VNS, consiguió información en 26 de los 31 casos randomizados para VNS ALTA. Este grupo alcanzó una reducción promedio del 52.0% de reduction de ataques comparandola con la fase basal. En los enfermos que pasaron de VNS BAJA a ALTA se consiguió information en 24 de los 36 enfermos durante un periodo de 16–18 meses. Este grupo reveló un 38.1% de reducción de los ataques comparandola con los periodos basales. Se observaron cambios de perfil de los efectos sobre la seguridad durante un seguimiento prolongado. Los efectos colaterales previarnente publicados ronquerdcarnbios de la voz, tos y parestesias (sensaciones en el cuello y en la rnandfbula), continuaron observandose durante la VNS aunque fueron bien tolerados. Durante el period0 de seguirniento un enferrno fallecio de una purpura trombocitopknica y 5 enferrnos interrurnpieron el tratarniento debido a resultados poco satisfactorios.ZUSAMMENFASSUNG: Die Vagusstirnulation (VNS) hat einen signifikanten antikonvulsiven Effekt in vorklinischen Studien, in Pilotstudien bei Menschen und in der Akutphase einer rnultizentrischen doppelblind randomisierten Untersuchung gezeigt. Nach Beendigung einer 14-wochigen blinden randornisierten Studie wurden 67 Patienten für eine offene Erweiterungsphase ausgewahlt, von denen 31 Patienten eine starke (therapeutische) VNS und 36 eine schwache (geringer oder nicht effektive) VNS erhalten hatten. Wahrend der Erweiterungsphase erhielten alle 67 Patienten eine starke VNS. Die Anfällsfrequenz wahrend des 3 Monate dauernden Behandlungsblocks wurde rnit einer 12-wochigen Ausgangsperiode verglichen. FÜR beide Gruppen zeigten alle Perioden rnit starker VNS einen signifkanten Abfall in der Anfällsfrequenz (p < 0.01), verglichen rnit der Ausgangsphase. FÜR die 1618 Monatsperiode rnit VNS wurden Daten für 26 von 31 Patienten gewonnen, die in die “starke” VNS-Gruppe randornisiert waren. Diese Gruppe erzielte eine 52%ige mittlere Anfällsfrequenzreduktion irn Vergleich zurn Ausgangsbefund. FÜR Patienten, die von schwacher zu starker VNS karnen, waren die Ergebnisse für 24 von 36 Patienten über eine 16 bis 18 Monate dauernde PéRiode erhaltlich. Diese Gruppe berichtete über eine mittlere Anfällsfrequenzreduktion von 38.1% irn Vergleich zurn Ausgangsbefund. Es wurden keine signikanten Anderungen bezogen auf Sicherheit oder Nebenwirkungsprofile wahrend des Langzeit Follow-up berichtet. Die fruher berichteten Nebenwirkungen von Heiserkeit oder Stirnrnanderung, Husten und Paraesthesien (irn Nacken und Kieferbereich) hielten wahrend der VNS an. Diese Nebenwirkungen wurden jedoch gut toleriert. wahrend der Follow-Up Période starb ein Patient an einer thrornbotishcen thrombozytopenischen Purpura (TTP), funf Patienten brachen die Behandlüng wegen ünbefriedigender Wirkung ab.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the cognitive effects of topiramate (TPM) and gabapentin (GBP).
Forty healthy volunteers were randomized to a 12-week course of TPM, GBP, or placebo. Doses were gradually escalated over 10 weeks to a maximum of 400 mg/day of TPM or 3,600 mg/day of GBP or to the highest tolerated dose. Subjects were interviewed and examined biweekly. Cognitive testing was performed prior to initiating the drug and again 12 weeks later, at least 2 weeks after achieving plateau dosing. For each subject and cognitive measure, test-retest Z scores were calculated based on regression equations derived from 73 healthy volunteers. Group comparisons utilized the Wilcoxon test.
There were significant TPM vs GBP and TPM vs placebo differences in test-retest Z scores for four of six target cognitive measures (Digit Symbol, Story Recall, Selective Reminding, Controlled Oral Word Association), always indicating worse retest performance for subjects receiving TPM. Overall, 12 of 24 cognitive measures were similarly affected. TPM effects were large, and several target measures averaged >2 SD of negative change. One measure was significantly affected by GBP.
Topiramate (TPM) impaired cognitive test performance, whereas gabapentin had minimal effects. The effects of TPM were of sufficient magnitude potentially to affect daily and occupational function.
[Show abstract][Hide abstract] ABSTRACT: The Portland Neurotoxicity Scale (PNS) is a brief patient-based survey of neurotoxicity complaints commonly encountered with the use of antiepileptic drugs (AEDs). The authors present data on the validity of this scale, particularly when used in longitudinal studies. Participants included 55 healthy controls, 23 epilepsy patient controls, and 86 healthy volunteers who took various AEDs or placebos for 12 weeks as part of randomized, double-blind studies of AED effects on cognitive abilities. Test-retest reliability in the control groups averaged .80 (total score). Test-retest changes in the PNS were sensitive to AED usage in general (p < .001) and to each of the five AEDs tested but not to placebo. Test-retest changes in the PNS were strongly correlated with several scales of the Profile of Mood States but only weakly correlated with objective cognitive test measures. The PNS has satisfactory psychometric properties and is sensitive to AED usage in test-retest studies.