Once-daily USL255 as adjunctive treatment of partial-onset seizures: randomized phase III study.

OBJECTIVE: To evaluate the efficacy and safety of USL255, Qudexy(™) XR (topiramate) extended-release capsules, as an adjunctive treatment for refractory partial-onset seizures (POS) in adults taking one to three concomitant antiepileptic drugs. METHODS: In this global phase III study (PREVAIL; NCT01142193), 249 adults with POS were randomized 1:1 to once-daily USL255 (200 mg/day) or placebo. The primary and key secondary efficacy endpoints were median percent reduction in weekly POS frequency and responder rate (proportion of patients with ≥ 50% reduction in seizure frequency). Seizure freedom was also assessed. Safety (adverse events, clinical and laboratory findings), as well as treatment effects on quality of life (QOLIE-31-P) and clinical global impression of change (CGI-C), were evaluated. RESULTS: Across the entire 11-week treatment phase, USL255 significantly reduced the median percent seizure frequency and significantly improved responder rate compared with placebo. Efficacy over placebo was observed early in treatment, in patients with highly refractory POS, and in those with the most debilitating seizure types (i.e., complex partial, partial secondarily generalized). USL255 was safe and generally well tolerated with a low incidence of neurocognitive adverse events. USL255 was associated with significant clinical improvement without adversely affecting quality of life. SIGNIFICANCE: The PREVAIL phase III clinical study demonstrated that once-daily USL255 (200 mg/day) significantly improved seizure control and was safe and generally well tolerated with few neurocognitive side effects.

Efficacy of once-daily extended-release topiramate (USL255): a subgroup analysis based on the level of treatment resistance.

Results from a previously conducted global phase III study (PREVAIL; NCT01142193) demonstrate the safety and efficacy of once-daily USL255, Qudexy™ XR (topiramate) extended-release capsules, as adjunctive treatment of drug-resistant partial-onset seizures (POSs). In this study, we report a post hoc analysis of PREVAIL data according to patient level of treatment resistance (based upon the number of concomitant antiepileptic drugs [AEDs] and lifetime AEDs) at baseline, with patients defined as either having "highly" drug-resistant seizures (≥ 2 concurrent AEDs and ≥ 4 lifetime AEDs) or having "less" drug-resistant seizures (1 concurrent AED or <4 lifetime AEDs) at baseline. For each subgroup, median percent reduction in POS frequency (primary endpoint), responder rate, Clinical Global Impression of Change (CGI-C), and Quality of Life in Epilepsy--Problems (QOLIE-31-P) survey were assessed. Of 249 PREVAIL patients, 115 were classified as having highly drug-resistant seizures (USL255: n = 52, placebo: n = 63), and 134 were classified as having less drug-resistant seizures (USL255: n = 72, placebo: n = 62) at baseline. For the primary endpoint, USL255 resulted in significantly better seizure outcomes compared with placebo regardless of drug-resistant status (P = .004 and P = .040 for "highly" and "less", respectively). Responder rate was also significantly improved in patients with highly drug-resistant group (P = .023). The CGI-C scores indicated significant improvement in both subgroups (P = .003 and P = .013 for "highly" and "less", respectively). On the QOLIE-31-P, a significant improvement on the seizure worry subscale for the group with less drug-resistant seizures was noted in USL255-treated patients compared with placebo-treated patients (P = .003); the overall score and all other subscales were not significantly different for both subgroups. We conclude that USL255 led to significant improvements across multiple outcomes compared with placebo, including in those classified as having highly drug-resistant seizures to prior treatment, making it a valuable treatment option for patients with epilepsy.

Objective evaluation of personality and psychopathology in temporal lobe versus extratemporal lobe epilepsy.

Previous research has been equivocal on personality trait and psychopathology differences between temporal lobe and other types of epilepsy, as well as between patients with right and left temporal lobe seizure foci. In this study, personality differences between patients with right temporal (n=23), left temporal (n=21), and extratemporal (n=24) epilepsy were investigated using the NEO Personality Inventory-Revised (NEO-PI-R). No statistically significant differences were found on any of the NEO-PI-R domains or facet trait scales. There were also no significant differences between groups on the Minnesota Multiphasic Personality Inventory 2 (MMPI-2), a measure of psychopathology. However, mild elevations were seen in all groups on clinical scales related to physical symptoms, health concern, and depression. These data suggest there are no consistent personality or psychopathology differences, as measured by the NEO-PI-R and the MMPI-2, between patients with left temporal, right temporal, and extratemporal epilepsy whose seizures are localized using video/EEG monitoring.

Effects of lamotrigine compared with levetiracetam on anger, hostility, and total mood in patients with partial epilepsy.

PURPOSE: To assess anger/hostility during treatment with lamotrigine adjunctive therapy versus levetiracetam adjunctive therapy in patients with partial seizures. METHODS: This randomized, double-blind, parallel-group study in adults with partial seizures included an 8-week escalation phase, during which adjunctive lamotrigine (n = 132) or adjunctive levetiracetam (n = 136) was titrated to a target dose, and a 12-week, double-blind maintenance phase, during which dosages of study medication and concomitant antiepileptic drugs were maintained. The primary endpoint was change from baseline to the end of the maintenance phase (week 20) in the Anger-Hostility subscale score of the Profile of Mood States (POMS). RESULTS: Improvement with lamotrigine relative to levetiracetam was observed for mean +/- SD (standard deviation) change from baseline to the end of the maintenance phase (week 20) on the Anger-Hostility subscale (lamotrigine -2.0 +/- 8.2, levetiracetam -0.3 +/- 8.4; p = 0.024) (the primary endpoint); the Anger-Hostility subscale on weeks 5, 6, 7, 8, 9, 11, 12, 14, 16, 18, and 19; and the Total Mood Disturbance score on weeks 6, 7, 8, 9, 11, 12, 17, 19, and 20. Improvement (p < 0.05) with lamotrigine relative to levetiracetam was also observed on the POMS subscales Depression-Dejection, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment. No difference in seizure frequency was observed between groups. The most common adverse events with both medications were headache and dizziness. DISCUSSION: Adjunctive lamotrigine significantly improved Anger-Hostility subscale scores relative to adjunctive levetiracetam in patients with partial seizures at the end of 20 weeks. This difference was consistently observed throughout the treatment period. Similar improvement with lamotrigine versus levetiracetam was observed for other mood symptoms.

Effects of lamotrigine on mood in older adults with epilepsy and co-morbid depressive symptoms: an open-label, multicentre, prospective study.

BACKGROUND: Both epilepsy and depressive symptoms are more prevalent in older individuals than in any other age group. Furthermore, depressive symptoms are among the most common interictal psychiatric co-morbid disorders in people with epilepsy. For these reasons, pharmacological treatment of epilepsy that might also confer antidepressant effects may be particularly beneficial in older patients. In this respect, lamotrigine is of considerable interest amongst antiepileptic drugs (AEDs) because it has proven thymoleptic activity. OBJECTIVE: These analyses, conducted on a data set drawn from a previously reported, open-label, multicentre, prospective study, examined the effect of lamotrigine on mood in adults aged>or=50 years with epilepsy and co-morbid depressive symptoms. All subjects were receiving background AED therapy at baseline. METHODS: Of the 158 subjects enrolled in the initial study, 40 adults (24 women, 16 men) met the age criterion for these analyses. The study consisted of a screening/baseline phase and four treatment phases over 36 weeks: lamotrigine escalation phase (7 weeks); lamotrigine maintenance or adjunctive therapy phase (12 weeks); concomitant AED withdrawal phase (5 weeks); and lamotrigine monotherapy phase (12 weeks). Psychometric evaluation of mood utilized the Beck Depression Inventory (BDI-II), Center for Epidemiological Studies Depression Scale (CES-D), the Neurological Disorders Depression Inventory in Epilepsy (NDDI-E) and the Profile of Mood States (POMS). Scores at the end of the adjunctive and monotherapy phases were compared with baseline scores. Lower scores on these scales indicate less depressive symptomatology. RESULTS: Mean baseline scores for the BDI-II, CES-D, NDDI-E and POMS were 15.8, 24.3, 13.8 and 57.7, respectively. Change scores were statistically significant (p<0.01) compared with baseline at the end of the adjunctive and monotherapy phases for all four psychometric measures of mood, with the exceptions of BDI-II and NDDI-E at the end of the adjunctive phase. CONCLUSIONS: The older adults in these analyses presented with low to moderate levels of depressive symptoms. Addition of lamotrigine to background AED therapy demonstrated antidepressant activity similar to that for the whole sample in the initial study. Given that the onset and prevalence of epilepsy are higher in older adults than in any other age group, pharmacological treatment for epilepsy in older patients that might also confer antidepressant therapy may be particularly beneficial.

Lamotrigine in patients with epilepsy and comorbid depressive symptoms.

PURPOSE: This open-label study evaluated the antidepressant qualities of lamotrigine (LTG) in people with epilepsy. METHODS: Eligible patients exhibited low to moderate depressive symptoms and required a change in antiepileptic drug (AED) therapy, but were excluded if they had a major depressive disorder (MDD). Lamotrigine was added onto a stable AED regimen, and self-report instruments were administered to evaluate changes in mood states. Evaluations were conducted at baseline, at the end of 19 weeks of adjunctive treatment, and 36 weeks following conversion to monotherapy. RESULTS: One hundred and fifty-eight patients with epilepsy participated; 96 patients completed adjunctive treatment, and 66 patients completed monotherapy. Intent-to-treat analyses for all instruments showed improvement in depression scores after adjunctive LTG treatment. Improvement was maintained for those converted to monotherapy. CONCLUSIONS: These data suggest that LTG may have antidepressant activity for patients with epilepsy and comorbid low to moderate depressive symptoms, and warrant a randomized controlled trial for validation.

Correlation of lamotrigine concentrations between serum and saliva.

STUDY OBJECTIVE: To compare the relationship between serum and salivary concentrations of lamotrigine in pediatric and adult epilepsy populations. DESIGN: Paired-sample pharmacokinetic study. SETTING: University neurology clinic. PATIENTS: Thirty-seven patients with epilepsy, aged 2-60 years, who were taking lamotrigine and whose physicians had ordered a lamotrigine serum concentration. MEASUREMENTS AND MAIN RESULTS: Patients spit a minimum of 0.25 ml into a cup to provide saliva samples. Blood samples were obtained by phlebotomy. Serum and salivary lamotrigine concentrations were determined by high-performance liquid chromatography. Linear regression analysis was used to evaluate correlations. Six patients' results were omitted due to the lack of a serum or saliva specimen or clearly erroneous results, leaving 31 patients for analysis. There was a strong correlation between the serum results reported by two reference laboratories (coefficient of correlation [r] = 0.988). The correlations between salivary and serum lamotrigine concentrations were similar for reference laboratory A (r = 0.81) and reference laboratory B (r = 0.84). Saliva:serum concentration ratios ranged from 0.41-1.26 (mean +/- SD 0.62 +/- 0.19) for reference laboratory A and from 0.40-1.19 ((mean +/- SD 0.64 +/- 0.18) for reference laboratory B. CONCLUSION: There is a good correlation between salivary and serum concentrations for lamotrigine. However, there is wide interpatient variability in the saliva:serum ratio. The data suggest that salivary monitoring may play a role in the monitoring of lamotrigine for adult and pediatric patients.

Continuous spikes and waves during slow sleep in an adult.

Continuous spikes and waves during slow wave sleep (CSWS) is rare and is considered to be an age-related epileptic syndrome occurring only in children. We report the case of a 21-year-old patient diagnosed with this syndrome. The patient had a history of seizures since the age of 3 and was admitted for continuous video/EEG monitoring to evaluate seizure exacerbation and unprovoked outbursts of anger. During 3 days of monitoring, awake EEG recordings showed focal slow wave activity in the right temporal region. CSWS were observed. After a change in his antiepileptic drug regimen, subsequent EEG recordings showed resolution of CSWS. As shown in our patient, CSWS can be observed in adults. In addition, continuous video/EEG monitoring including sleep is important in the evaluation of patients with sudden deterioration of seizure control accompanied by behavioral changes.

Conversion to lamotrigine monotherapy from valproate monotherapy in older adolescent patients with epilepsy.

BACKGROUND: Pharmacokinetic interactions can make necessary anti-epileptic medication (AED) changes hazardous for children with epilepsy. We report the utility of a dosing algorithm designed to maintain stable trough lamotrigine (LTG) concentrations during conversion from valproate (VPA) to LTG monotherapy in adolescents aged 16-20 years. METHODS: Patients were enrolled into the study if they required a change in their AED regimen due to lack of efficacy or intolerable side effects. Conversion to LTG monotherapy took place in a four part treatment algorithm. Lamotrigine was escalated according to a target dose of 200 mg/day over 8-weeks. Valproate was withdrawn over a period of 2-6 weeks, depending on the initial dose. Lamotrigine dose was further escalated to 500 mg/day and continued for four weeks as mono therapy. Trough serum concentrations of LTG were measured during each phase of the trial. RESULTS: Twelve of 16 patients completed the study. After the LTG escalation to 200 mg/day, mean trough serum concentrations of 8.0 microg/mL did not differ significantly from the 9.5 microg/mL after VPA withdrawal or the 9.2 microg/mL after 4 weeks of monotherapy at 500 mg/day. Adverse events led to premature discontinuation for one subject. Two subjects withdrew due to worsening seizures during LTG monotherapy possibly due to non-compliance. Limitations of the trial include the open label design and small sample size of the sub-analysis. CONCLUSION: In adolescent patients, this algorithm produces stable LTG serum concentrations with favorable tolerability during a transition from VPA to LTG mono therapy.

Performance of patients with epilepsy or psychogenic non-epileptic seizures on four measures of effort.

Exaggeration of cognitive symptoms or poor effort on cognitive testing has been addressed primarily in the traumatic brain injury literature. The present investigation aims to extend the evaluation of effort to the epilepsy monitoring setting, where base rates of failure on effort testing remain unknown for patients with intractable epilepsy (ES), psychogenic nonepileptic seizures (PNES), or both conditions (ES+PNES). In addition, this investigation explores how well four measures of effort (DMT, LMT, TOMM, PDRT) distinguish between these diagnostic groups. Results show that 20% of the combined sample failed one or more effort measure. When examining failure rates for each diagnostic group, 22% of epilepsy patients, 24% of PNES patients, and 11% of ES+PNES patients performed suboptimally on one or more measure of effort. The utility of these effort measures to differentiate between these diagnostic groups appears limited. Further research is needed to clarify the base rate of poor effort in the epilepsy monitoring unit setting in general and in these three diagnostic groups specifically.

Relationship of indicators of neuropathology, psychopathology, and effort to neuropsychological results in patients with epilepsy or psychogenic non-epileptic seizures.

Previous research suggests epilepsy and psychogenic non-epileptic seizure (PNES) patients do not show consistent group differences on neuropsychological measures. However, both groups of patients show decreased neuropsychological performance when compared to a normal population (Cragar, Berry, Fakhoury, Cibula, & Schmitt, 2002). Swanson, Springer, Benbadis, and Morris (2000) have suggested epilepsy patients show decreased neurocognitive functioning due to neuropathology whereas PNES patients show decreased neurocognitive functioning due to psychopathology. Effort has also been implicated as an important factor in neuropsychological test results in general (Green, 2003). The purpose of this study was to investigate the relationships of medical history variables (e.g., duration of disorder), neuropathology, psychopathology, and effort to neuropsychological findings in epilepsy and PNES patients. Neuropsychological functioning was divided into six domains: intelligence, memory, language, executive functions, visual-spatial, and motor. Results indicated that medical history variables were related to intellectual, memory, language, and motor functioning. Psychopathology was associated with all cognitive domains except executive functioning. Effort was related to intellectual, memory, language, visual-spatial, and motor functioning. Neuropathology and diagnosis were related only to memory.

Cluster analysis of normal personality traits in patients with psychogenic nonepileptic seizures.

The literature on patients with psychogenic nonepileptic seizures (PNES) suggests that they are a heterogeneous population. This study addresses this heterogeneity by describing subtypes of PNES based on a cluster analysis of normal personality traits in patients with PNES. In addition, the identified PNES subtypes are further described on dimensions of psychopathology as measured by the Minnesota Multiphasic Personality Inventory, Second Edition (MMPI-2), and cognition. Three personality clusters emerged: (1) very high neuroticism, low extraversion, low openness, high agreeableness, low conscientiousness; (2) average on all domains; (3) very high neuroticism, average extraversion, low openness, low agreeableness, average conscientiousness. Patients in clusters 1 and 3 appear to exhibit more severe psychopathology and a broader range of symptoms than those in cluster 2. Based on NEO-PI-R and MMPI-2 findings, tentative descriptions of the clusters are offered. Cluster 1 comprises "depressed neurotics"; cluster 2, "somatic defenders"; and cluster 3, "activated neurotics." Clusters 1 and 3 also differ significantly on neurocognitive testing, with cluster 1 significantly lower than cluster 3 in memory functioning, while cluster 2 individuals show generally average cognition across domains. These results suggest the existence of personality subtypes in patients with PNES that should be considered in the design of interventions for them.

Stability of salivary concentrations of the newer antiepileptic drugs in the postal system.

Saliva antiepileptic drug (AED) concentrations strongly correlate with serum concentrations. Saliva collection is painless and noninvasive, and untrained personnel can easily be taught the collection process. Remote patients could mail saliva samples to a laboratory for monitoring, and samples could be obtained in the immediate postictal state to provide a "real-time" concentration. The objectives of this study were to assess the stability of saliva lamotrigine (LMT), levetiracetam (LEV), oxcarbazepine (OXC), topiramate (TPM), and zonsiamide (ZNS) concentrations sent through the United States Postal Service (USPS) and to quantify the amount of time needed for patients and the USPS to return samples to clinic. Saliva samples were obtained from patients currently taking 1 of the targeted AEDs. Samples were split into 2 storage vials. One sample was sealed in an addressed envelope, which the patient mailed from home, whereas the other sample was frozen immediately. Postmark date and day returned were collected for mailed samples. Saliva concentrations were determined using HPLC. Wilcoxon rank sum tests were used to compare the immediately-frozen and mailed sample means. Correlations were determined by the Spearman test. Thirty-seven patients were enrolled in the study. The median time between collection and postmark was 1 day (range 0-6 days); and between collection and receipt was 4 days (range 1-160 days). The mean concentrations for mailed and immediately frozen samples were similar for each AED (P > 0.15). Spearman rank order correlations between mailed and immediately frozen aliquots were strong (LMT rs = 1, LEV rs = 1, OXC rs = 0.964, TPM rs = 0.90, and ZNS rs = 1). Saliva samples mailed by patients maintain stability and can be returned in a reasonable length of time. Further studies are needed to assess patient/caretaker capability of obtaining an adequate sample.

Topiramate and status epilepticus: report of three cases.

OBJECTIVE: The goal of this study was to report the effectiveness of topiramate in treating status epilepticus. METHODS: Three patients with status epilepticus were treated with topiramate 500 mg twice daily for 2-5 days, with the dose gradually tapered thereafter to 200 mg twice daily. The patients' clinical status and EEG recordings were followed. RESULTS: Patient 1 was admitted for subacute encephalopathy that was complicated by secondarily generalized status epilepticus resistant to lorazepam, fosphenytoin, and pentobarbital coma. Topiramate was added and, 2 days later, pentobarbital was tapered with no recurrence of ictal discharges as the patient improved clinically. Patient 2 had end-stage liver disease and was hospitalized for peritonitis, and his course was complicated by partial status epilepticus. Topiramate was started and, 2 days later, his mental status improved as repeat EEG showed no further ictal discharges although periodic epileptiform discharges were seen in the left centroparietal area. The patient later died from complications of variceal bleeding. Patient 3 suffered cardiopulmonary arrest, and developed postanoxic seizures, which did not respond to lorazepam, fosphenytoin, valproate, and propofol coma as continuous EEG recordings showed recurrent generalized ictal discharges. Two days after topiramate was started, propofol was tapered and discontinued and EEG showed generalized slow wave activity and no ictal discharges. The patient was discharged to another facility 12 days later. CONCLUSIONS: Topiramate was effective in treating two patients with refractory generalized status epilepticus and one with complex partial status epilepticus. It should therefore be considered as an option in these situations, especially when other medications cannot be used.

Efficacy and tolerability of conversion to monotherapy with lamotrigine compared with valproate and carbamazepine in patients with epilepsy.

OBJECTIVE: This randomized, open-label study was designed to compare the efficacy and tolerability of lamotrigine monotherapy with those of valproate and carbamazepine monotherapy in patients with epilepsy whose seizures were uncontrolled on their prestudy antiepileptic drug monotherapy. METHODS: Patients meeting eligibility criteria were randomized 2:1 to lamotrigine:carbamazepine or lamotrigine:valproate. The treatment phase was divided into a 4-week dose-escalation phase (Weeks 1-4), during which lamotrigine, carbamazepine, or valproate was added to patient's prestudy monotherapy; an 8-week add-on phase (Weeks 5-12), during which patients were stabilized on both the study medication and their prestudy antiepileptic therapy; an 8-week withdrawal phase (Weeks 13-20), during which prestudy antiepileptic therapy could be withdrawn if clinically appropriate; and an 8-week monotherapy phase (Weeks 21-28), during which patients could be treated with study medication as monotherapy. RESULTS: The numbers of patients randomized to the carbamazepine and valproate arms of the study were 144 (98 lamotrigine, 46 carbamazepine) and 158 (105 lamotrigine, 53 valproate), respectively. Successful monotherapy sustained for at least 7 weeks was achieved in comparable percentages of patients in the lamotrigine group (56%) and the carbamazepine group (54%) and in more patients in the lamotrigine group (49%) than the valproate group (40%). Among monotherapy completers, the percentage of patients with zero seizures during the monotherapy phase was comparable for lamotrigine (41%) and carbamazepine (30%) and significantly higher (P<0.05) with lamotrigine (32%) than with valproate (11%). No differences between treatments were observed with respect to time to treatment failure or time to first seizure. Lamotrigine was also better tolerated than carbamazepine or valproate. CONCLUSION: Lamotrigine monotherapy was as effective as and better tolerated than carbamazepine or valproate monotherapy in patients whose seizures were uncontrolled on their prestudy antiepileptic drug monotherapy.

A review of diagnostic techniques in the differential diagnosis of epileptic and nonepileptic seizures.

The diagnosis of psychogenic nonepileptic seizures (PNES) is complex. Long-term electroencephalogram monitoring with video recording (video EEG) is the most common method of differential diagnosis of epilepsy and PNES. However, video EEG is complex, costly, and unavailable in some areas. Thus, alternative diagnostic techniques have been studied in the search for a diagnostic method that is as accurate as video EEG, but more cost effective, convenient, and readily available. This paper reviews the literature regarding possible diagnostic alternatives and organizes findings into 7 areas of study: demographic and medical history variables, seizure semiology, provocative testing, prolactin levels, single photon emission computed tomography, psychological testing, and neuropsychological testing. For each area, the literature is summarized, and conclusions about the accuracy of the technique as a diagnostic tool are drawn. Overall, it appears unlikely that any of the reviewed alternative techniques will replace video EEG monitoring; rather they may be more successful as complementary diagnostic tools. An important focus for further investigations involves combinations of diagnostic techniques for the differential diagnosis of epilepsy and PNES.

Correlation of levetiracetam concentrations between serum and saliva.

PURPOSE: More than 100 drugs have been evaluated for salivary therapeutic drug monitoring since the 1970s. The most studied drugs are the anticonvulsants phenytoin, phenobarbital, and carbamazepine, demonstrating strong correlations between serum and saliva concentrations. No published data exist for levetiracetam (LEV) to the authors' knowledge. This study's objective is to determine the correlation between LEV serum and saliva concentrations. METHODS: Investigators identified subjects seen in neurology clinics at the University of Kentucky. Patients were eligible if they agreed to participate in this study, were taking LEV for a minimum of 4 weeks, and if a serum LEV concentration had been ordered by their physician. Patients spit a minimum of 0.25 mL into a cup to obtain saliva samples. Blood samples were obtained by phlebotomy. RESULTS: Serum and saliva LEV concentrations were determined via high-performance liquid chromatography (HPLC) in two separate reference laboratories. Linear regression analysis was used to evaluate correlations. Serum and saliva samples were obtained from 40 patients (22 female, 18 male), ranging from 3 to 57 years of age. The mean +/- SD serum LEV concentration for reference laboratory A was significantly lower (P < 0.0001) than reference laboratory B, 23.6 +/- 13.8 microg/mL and 27.0 +/- 16.9 microg/mL, respectively. The mean +/- SD saliva to serum concentration fraction was also different for the two laboratories, i.e., 41.0% +/- 0.15% for lab A and 36.0% +/- 0.15% for lab B (P = 0.001). The correlation coefficients for the two laboratories were similar, 0.87 and 0.86 (both P < 0.0001) for labs A and B, respectively. CONCLUSION: A significant positive correlation exists between LEV saliva and serum concentrations. The ability to monitor LEV therapy using saliva may provide benefits that include facilitating sample collection and improving the quality of life for persons with epilepsy. Patients with poor venous access, such as children and elderly patients, and persons afraid of needles may particularly benefit from this method.

A comparison of MMPI-2 decision rules in the diagnosis of nonepileptic seizures.

The differential diagnosis of epileptic seizures (ES) and psychogenic nonepileptic seizures (PNES) continues to be a common concern in epilepsy treatment centers. The MMPI/MMPI-2 is the most commonly studied psychological measure in the differential diagnosis of ES and PNES. Wilkus, Dodrill, and Thompson (1984) and Derry and McLachlan (1996) both developed decision rules for use with the MMPI and MMPI-2 to assist in this diagnostic discrimination. Both sets of decision rules were evaluated in a sample of ES (n=58), PNES ( n=29) and epilepsy plus PNES (n=19) patients. Validity of the epilepsy diagnosis was established with 24-hr video-EEG monitoring in all cases. The two sets of decision rules applied to the MMPI-2 showed sensitivities of 68% and 48% and specificity values of 55% and 58%. Calculation of positive and negative predictive power for both sets of rules at three different base rates suggests that use of these rules can result in a large number of false positive diagnoses of PNES.

Feasibility and limitations of oxcarbazepine monitoring using salivary monohydroxycarbamazepine (MHD).

The purpose of this study is to determine the feasibility of using 10-hydroxy-10,11-dihydrocarbazepine (MHD) concentration in saliva as an alternative to serum for the therapeutic monitoring of oxcarbazepine (OXC) treatment. Investigators identified subjects seen in neurology clinics at the University of Kentucky Chandler Medical Center. Patients were eligible if they agreed to participate in this study, were taking oxcarbazepine, and if a serum MHD concentration had been ordered by their physician. Unstimulated saliva specimens (0.25 mL minimum) were collected in the clinic and frozen until analysis. Blood samples were obtained by phlebotomy. Serum specimens were analyzed by a reference laboratory. Saliva MHD concentrations were determined by high-performance liquid chromatography in the Clinical Laboratory at the Cincinnati Children's Hospital Medical Center. Linear regression analysis was used to evaluate correlations. Saliva and blood specimens were collected from 28 epilepsy patients, but usable samples were obtained from only 23. The mean serum MHD concentration was 23.9 +/- 10.0 microg/mL, and the mean saliva concentration was 23.1 +/- 10.1 microg/mL. There was a significant positive correlation between the serum and saliva concentrations: saliva (y) = 0.95 serum (x) + 0.39; r = 0.941; n = 23; P < 0.001). The mean saliva:serum MHD concentration ratio was 0.96 +/- 0.15. The results of the current study indicate that the relationship between freely flowing (unstimulated) saliva and serum concentrations of MHD is sufficient for therapeutic drug monitoring. A limitation of saliva MHD monitoring is that individuals who have difficulty producing small quantities of saliva or who have viscous saliva should generally be avoided for this type of monitoring. It is also recommended to avoid saliva collection within 8 hours after OXC dosing to allow complete absorption and transformation of the parent drug.