Can Pyridoxine Successfully Reduce Behavioral Side Effects from Levetiracetam?: A Critically Appraised Topic.

BACKGROUND: Levetiracetam is a commonly used anti-seizure medication, with the development of neuropsychiatric symptoms being the most common side effect. Preliminary literature describes the improvement of these symptoms with pyridoxine, mostly within the pediatric population. However, randomized control trial data investigating this relationship is sparse. OBJECTIVE: The objective of this study was to critically assess evidence regarding the role of pyridoxine in the treatment of neuropsychiatric symptoms from levetiracetam. METHODS: The objective was addressed through the development of a structured, critically appraised topic. This included a clinical scenario with a clinical question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, medical librarians, clinical epidemiologists, and content experts in the field of epilepsy. RESULTS: A randomized, placebo-controlled clinical trial was selected for critical appraisal. This trial compared pyridoxine versus placebo for the treatment of neuropsychiatric symptoms from levetiracetam in a pediatric population and included 105 patients (46/105 received pyridoxine, 59/105 received placebo). It found that both groups had a significant reduction in behavioral symptoms at the 2-,4-and 6-week time points ( P <0.05). However, the authors noted that the pyridoxine group had almost double the relative reduction when compared with the placebo group at all time points: 1.9 at 2 weeks, 2.0 at 4 weeks, and 1.8 at 6 weeks ( P =0.001). CONCLUSIONS: This study suggests that pyridoxine for the treatment of levetiracetam-induced behavioral side effects may result in modest improvement, although many limitations prevent conclusive results. There remains a need for a double-blinded, randomized control trial in both the adult and pediatric populations.

Diagnostic utility of the Minnesota Multiphasic Personality Inventory-2 Restructured Form in the epilepsy monitoring unit: Considering sex differences.

Psychological assessment measures are frequently used to evaluate patients in epilepsy monitoring units. One goal of that assessment is to contribute information that may help with differential diagnosis between epilepsy and psychogenic nonepileptic seizures (PNES). The Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF) is one such measure. Del Bene et al. (2017) recently published an analysis that was the first to compare MMPI-2-RF scale elevations between diagnostic groups stratified by sex. The purpose of the present study was to replicate that analysis in a larger sample. Similar to previous work, we found that both men and women with PNES were more likely than men and women with epilepsy to report high levels of somatic complaints (2 to 5 times greater odds of somatic symptom reporting) and a variety of types of complaints. Mood disturbance scales were not significantly elevated in our PNES sample. Results contribute to the small body of research on sex differences in patients with PNES and suggest that somatization is a key characterization across sexes.

Is Adjunctive Progesterone Effective in Reducing Seizure Frequency in Patients With Intractable Catamenial Epilepsy? A Critically Appraised Topic.

BACKGROUND: Catamenial epilepsy refers to cyclic seizure exacerbation in relation to the menstrual cycle. Three distinct patterns have been described: C1-perimenstrual, C2-periovulatory, and C3-inadequate luteal. There is experimental and clinical evidence that gonadal steroid hormones affect neuronal excitability with estrogens being mainly proconvulsant and progesterone anticonvulsant. If reproductive steroids have a role in seizure occurrence, they may also have a role in treatment. OBJECTIVE: The objective of this study was to critically assess current evidence regarding the efficacy of progesterone as adjunctive therapy in women with intractable catamenial epilepsy. METHODS: The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario with a clinical question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, medical librarian, and content experts in the fields of epilepsy and gynecology. RESULTS: A randomized, placebo-controlled clinical trial was selected for critical appraisal. This trial compared the efficacy of adjunctive cyclic natural progesterone therapy versus placebo for seizures in women with intractable partial epilepsy, stratified by catamenial and noncatamenial status. There was no significant difference in proportions of responders between progesterone and placebo in the catamenial and noncatamenial strata. Prespecified secondary analysis showed that the level of perimenstrual seizure exacerbation is a significant predictor of the responder rate for progesterone therapy. CONCLUSIONS: Cyclic natural progesterone is not superior to placebo in reducing seizure frequency in women with intractable partial epilepsy. Posthoc findings suggest that progesterone may benefit a subset of women with perimenstrually exacerbated seizures.

Usage of EpiFinder clinical decision support in the assessment of epilepsy.

BACKGROUND: The diagnosis of epilepsy is at times elusive for both neurologists and nonneurologists, resulting in delays in diagnosis and therapy. The development of screening methods has been identified as a priority in response to this diagnostic and therapeutic gap. EpiFinder is a novel clinical decision support tool designed to enhance the process of information gathering and integration of patient/proxy respondent data. It is designed specifically to take key terms from a patient's history and incorporate them into a heuristic algorithm that dynamically produces differential diagnoses of epilepsy syndromes. OBJECTIVE: The objective of this study was to test the usability and diagnostic accuracy of the clinical decision support application EpiFinder in an adult population. METHODS: Fifty-seven patients were prospectively identified upon admission to the Epilepsy Monitoring Unit (EMU) for episode classification from January through June of 2017. Based on semiologic input, the application generates a list of epilepsy syndromes. The EpiFinder-generated diagnosis for each subject was compared to the final diagnosis obtained via continuous video electroencephalogram (cVEEG) monitoring. RESULTS: Fifty-three patients had habitual events recorded during their EMU stay. A diagnosis of epilepsy was confirmed (with cVEEG monitoring) in 26 patients while 27 patients were found to have a diagnosis other than epilepsy. The algorithm appropriately predicted differentiation between the presence of an epilepsy syndrome and an alternative diagnosis with 86.8% (46/53 participants) accuracy. EpiFinder correctly identified the presence of epilepsy with a sensitivity of 86.4% (95% confidence interval [CI]: 65.0-97.1) and specificity of 85.1% (95% CI: 70.2-96.4). CONCLUSION: The initial testing of the EpiFinder algorithm suggests possible utility in differentiating between an epilepsy syndrome and an alternative diagnosis in adult patients.

Predictive models in the diagnosis and treatment of autoimmune epilepsy.

OBJECTIVE: To validate predictive models for neural antibody positivity and immunotherapy response in epilepsy. METHODS: We conducted a retrospective study of epilepsy cases at Mayo Clinic (Rochester-MN; Scottsdale-AZ, and Jacksonville-FL) in whom autoimmune encephalopathy/epilepsy/dementia autoantibody testing profiles were requested (06/30/2014-06/30/2016). An Antibody Prevalence in Epilepsy (APE) score, based on clinical characteristics, was assigned to each patient. Among patients who received immunotherapy, a Response to Immunotherapy in Epilepsy (RITE) score was assigned. Favorable seizure outcome was defined as >50% reduction of seizure frequency at the first follow-up. RESULTS: Serum and cerebrospinal fluid (CSF) from 1,736 patients were sent to the Mayo Clinic Neuroimmunology Laboratory for neural autoantibody evaluation. Three hundred eighty-seven of these patients met the diagnostic criteria for epilepsy. Central nervous system (CNS)-specific antibodies were detected in 44 patients. Certain clinical features such as new-onset epilepsy, autonomic dysfunction, viral prodrome, faciobrachial dystonic seizures/oral dyskinesia, inflammatory CSF profile, and mesial temporal magnetic resonance imaging (MRI) abnormalities had a significant association with positive antibody results. A significantly higher proportion of antibody-positive patients had an APE score ≥4 (97.7% vs. 21.6%, p < 0.01). Sensitivity and specificity of an APE score ≥4 to predict presence of specific neural auto-antibody were 97.7% and 77.9%, respectively. In the subset of patients who received immunotherapy (77), autonomic dysfunction, faciobrachial dystonic seizures/oral dyskinesia, early initiation of immunotherapy, and presence of antibodies targeting plasma membrane proteins (cell-surface antigens) were associated with favorable seizure outcome. Sensitivity and specificity of a RITE score ≥7 to predict favorable seizure outcome were 87.5% and 83.8%, respectively. SIGNIFICANCE: APE and RITE scores can aid diagnosis, treatment, and prognostication of autoimmune epilepsy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Patients with psychogenic nonepileptic seizures report more severe migraine than patients with epilepsy.

PURPOSE: Clinical observations suggest that psychogenic non-epileptic seizure (PNES) patients often have severe migraine, more severe than epilepsy patients. Investigations into migraine characteristics in patients with PNES are lacking. In this study we tested the hypothesis that, compared to epilepsy patients, PNES patients have more severe migraine, with more frequent and longer duration attacks that cause greater disability. METHOD: In this observational study, 633 patients with video-EEG proven epilepsy or PNES were identified from the Mayo Clinic Epilepsy Monitoring Unit database. Contacted patients were screened for migraine via a validated questionnaire, and when present, data regarding migraine characteristics were collected. Two-sample t-tests, chi square analyses, and Mann-Whitney U tests were used to compare migraine characteristics in PNES patients to those of epilepsy patients. RESULTS: Data from 43 PNES patients with migraine and 29 epilepsy patients with migraine were available. Compared to epilepsy patients, PNES patients reported having more frequent headaches (mean 15.1 ± 9.8 vs. 8.1 ± 6.6 headache days/month, p<.001), more frequent migraine attacks (mean 6.5 ± 6.3 vs. 3.8. ± 4.1 migraines/month, p=.028), longer duration migraines (mean 39.5 ± 28.3 vs. 27.3 ± 20.1h, p=.035), and more frequently had non-visual migraine auras (78.6% vs. 46.7% of patients with migraine auras, p=.033). Migraine-related disability scores were not different between PNES and epilepsy patients (median 39, interquartile range 89 vs. 25, interquartile range 60.6, p=.15). CONCLUSION: Compared to epilepsy patients with migraine, PNES patients with migraine report having a more severe form of migraine with more frequent and longer duration attacks that are more commonly associated with non-visual migraine auras.

Fall prevention and bathroom safety in the epilepsy monitoring unit.

Falls are one of the most common adverse events occurring in the epilepsy monitoring unit (EMU) and can result in significant injury. Protocols and procedures to reduce falls vary significantly between institutions as it is not yet known what interventions are effective in the EMU setting. This study retrospectively examined the frequency of falls and the impact of serial changes in fall prevention strategies utilized in the EMU between 2001 and 2014 at a single institution. Overall fall rate was 2.81 per 1000 patient days and varied annually from 0 to 9.02 per 1000 patient days. Both seizures and psychogenic nonepileptic events occurring in the bathroom were more likely to result in falls compared with events occurring elsewhere in the room. With initiation of increased patient education, hourly nurse rounding, nocturnal bed alarms, having two persons assisting for high fall risk patients when out of bed, and immediate postfall team review between 2001 and 2013, there was a trend of decreasing fall frequency; however, no specific intervention could be identified as having a particular high impact. In late 2013, a ceiling lift system extending into the bathroom was put in place for use in all EMU patients when out of bed. In the subsequent 15 months, there have been zero falls. The results reinforce both the need for diligent safety standards to prevent falls in the EMU as well as the challenges in identifying the most effective practices to achieve this goal.

Quality of life in psychogenic nonepileptic seizures and epilepsy: the role of somatization and alexithymia.

It is clear that many individuals with psychogenic nonepileptic seizures (PNESs) often present with poorer quality of life compared with those with epileptic seizures (ESs). However, the mechanisms linking seizure diagnosis to quality-of-life outcomes are much less clear. Alexithymia and somatization are emotional markers of psychological functioning that may explain these differences in quality of life. In the current study, patients from an epilepsy monitoring unit with vEEG-confirmed diagnosis of PNESs or ESs were compared on measures of alexithymia, somatization, quality of life, and a variety of demographic and medical variables. Two models using alexithymia and somatization individually as mediators of the relations between diagnosis and quality of life were tested. Results indicated that patients with PNESs had significantly poorer quality of life compared with those with ESs. Alexithymia was associated with poor quality of life in both groups but did not differentiate between diagnostic groups. Further, alexithymia did not mediate the relationship between diagnosis and quality of life. Somatization was associated with poor quality of life, and patients with PNESs reported greater somatization compared with patients with ESs. Somatization also significantly mediated the relationship between diagnosis and quality of life. In conclusion, somatization may be one mechanism affecting poor quality of life among patients with PNESs compared with ESs and should be a target of comprehensive treatments for PNESs. Alexithymia proved to be an important factor impacting quality of life in both groups and should also be targeted in treatment for patients with PNESs and patients with ESs.

The effect of selective serotonin reuptake inhibitors on the frequency of psychogenic nonepileptic seizures: a critically appraised topic.

BACKGROUND: Psychogenic nonepileptic seizures (PNES) are commonly encountered problem in neurological practice and usually are accompanied by other psychiatric comorbidities. Despite its prevalence and profound impact on patients and families, there have been few trials addressing treatment. Cognitive behavioral therapy may be effective but the role of pharmacologic therapy remains unclear. OBJECTIVE: To critically evaluate evidence that PNES frequency may be reduced by treatment with selective serotonin reuptake inhibitors. METHODS: The objective was addressed through the development of a structured, critically appraised topic. We incorporated a clinical scenario, background information, a structured question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, a medical librarian, epileptology, and psychiatry content experts. RESULTS: A pilot randomized control clinical trial was selected for critical appraisal. Thirty-eight PNES patients were randomized to flexible-dose sertraline (target dose, 200 mg/d) or placebo. Only 68% of patients contributed data to the primary analysis and baseline PNES frequency was notably dissimilar. Twelve-week seizure frequency rates, as compared with baseline, were 45% lower in the sertraline group (P=0.03) but unchanged in the placebo group (8% increase; P=0.78). After adjustment for baseline differences, between-treatment group comparison revealed a trend toward lower event frequency in the sertraline group (risk ratio 0.51; 95% confidence interval, 0.25-1.05; P=0.29). Psychosocial and quality of life measures did not differ between treatment groups. CONCLUSIONS: There is insufficient evidence to recommend routine treatment with sertraline to reduce PNES event frequency but these pilot data suggest a possible benefit worthy of further exploration.

The influence of impression management scales on the Personality Assessment Inventory in the epilepsy monitoring unit.

The Somatic Complaints scale (SOM) and Conversion subscale (SOM-C) of the Personality Assessment Inventory perform best in classifying psychogenic non-epileptic seizures (PNES) from epileptic seizures (ES); however, the impact of positive impression management (PIM) and negative impression management (NIM) scales on SOM and SOM-C classification has not been examined. We studied 187 patients from an epilepsy monitoring unit with confirmed PNES or ES. On SOM, the best cut score was 72.5 T when PIM was elevated and 69.5 T when there was no bias. On SOM-C, when PIM was elevated, the best cut score was 67.5 T and 76.5 T when there was no bias. Negative impression management elevations (n=9) were too infrequent to analyze separately. Despite similarities in classification accuracy, there were differences in sensitivity and specificity with and without PIM, impacting positive and negative predictive values. The presence of PIM bias generally increases positive predictive power of SOM and SOM-C but decreases negative predictive power.

Determination of hemispheric language dominance in the surgical epilepsy patient: diagnostic properties of functional magnetic resonance imaging.

BACKGROUND: Presurgical evaluation for refractory epilepsy typically includes assessment of cognitive and language functions. The reference standard for determination of hemispheric language dominance has been the intracarotid amobarbital test (IAT) but functional magnetic resonance imaging (fMRI) is increasingly used. OBJECTIVE: To critically assess current evidence regarding the diagnostic properties of fMRI in comparison with the IAT for determination of hemispheric language dominance. METHODS: The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario, structured question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the fields of epilepsy and neurosurgery. RESULTS: A systematic review and meta-analysis that compared the sensitivity and specificity of fMRI to IAT-determined language lateralization was selected for critical appraisal. The review included data from 23 articles (n=442); study methodology varied widely. fMRI was 83.5% sensitive and 88.1% specific for detection of hemispheric language dominance. CONCLUSIONS: There are insufficient data to support routine use of fMRI for the purpose of determining hemispheric language dominance in patients with intractable epilepsy. Larger, well-designed studies of fMRI for language and other cognitive outcomes as part of the presurgical and postsurgical evaluation of epilepsy patients are necessary.

Code blue: seizures.

Eyewitnesses frequently perceive seizures as life threatening. If an event occurs on the hospital premises, a "code blue" can be called which consumes considerable resources. The purpose of this study was to determine the frequency and characteristics of code blue calls for seizures and seizure mimickers. A retrospective review of a code blue log from 2001 through 2008 identified 50 seizure-like events, representing 5.3% of all codes. Twenty-eight (54%) occurred in inpatients; the other 22 (44%) events involved visitors or employees on the hospital premises. Eighty-six percent of the events were epileptic seizures. Seizure mimickers, particularly psychogenic nonepileptic seizures, were more common in the nonhospitalized group. Only five (17.9%) inpatients had a known diagnosis of epilepsy, compared with 17 (77.3%) of the nonhospitalized patients. This retrospective survey provides insights into how code blues are called on hospitalized versus nonhospitalized patients for seizure-like events.

Indeterminate EMU admissions: does repeating the admission help?

Epilepsy monitoring unit (EMU) admissions during 2007-2009 at Mayo Clinic Hospital Arizona were reviewed. Of the 106 indeterminate admissions, 13 (12%) went on to have a second admission. During the second admission, 8 (62%) were diagnosed. Five patients went on to have a third or fourth admission, with none of them receiving a diagnosis. Nineteen (18%) patients had ambulatory EEG monitoring after an indeterminate admission, with only one (5%) receiving a diagnosis after ambulatory EEG monitoring. Even in patients who were initially indeterminate, medication management changed 37% of the time. Admission to the EMU was helpful for spell classification, with 80% of the patients receiving a diagnosis after the first admission. Based on this study, a second admission should be considered if no diagnosis is reached after the first admission. If no diagnosis is made after the second EMU admission, subsequent admissions are unlikely to produce a definitive diagnosis.

Olfactory and gustatory hallucinations presenting as partial status epilepticus because of glioblastoma multiforme.

Olfactory and gustatory hallucinations are not often encountered in the acute care setting but may represent the subtle presenting features of a significant underlying disease process. We describe a patient whose most striking presenting symptoms were of olfactory and gustatory hallucinations and in whom the diagnosis and treatment of a new brain tumor and partial status epilepticus occurred entirely in the emergency department. The lesion was subsequently identified as glioblastoma multiforme involving the hippocampus and amygdala.

Clinical predictors of psychogenic nonepileptic seizures: a critically appraised topic.

BACKGROUND: Psychogenic nonepileptic seizures (PNES) are often disabling and usually associated with psychiatric disorders and reduced quality of life. Although often suspected based on historical and clinical features, the gold standard for diagnosis of PNES is video electroencephalography. Identification of clinical features that reliably distinguish PNES from ES would be valuable in acute care settings, for patients that have coexisting disorders, and those with multiple event types. OBJECTIVE: To determine the diagnostic value of putative clinical symptoms or signs of PNES against the gold standard of video electroencephalography. METHODS: We addressed the objective through development of a structured critically appraised topic that included a clinical scenario, structured question, search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of epileptology. RESULTS: There were wide variations in the rates of coexisting PNES and epilepsy and study methodology. Ictal stuttering and the "teddy bear" sign were associated with moderate specificity for PNES. However, the presence of pelvic thrusting or ictal eye closure did not accurately distinguish PNES from ES. CONCLUSIONS: The presence of either ictal stuttering or the teddy bear sign is moderately specific but poorly sensitive for PNES. Pelvic thrusting and ictal eye closure are not reliable indicators of PNES. Future studies should establish more precise and reliable definitions of clinical signs and evaluate combinations of such signs in a broad spectrum of patients with PNES and ES spell phenotypes that may be difficult to distinguish, such as spells of unresponsiveness with motor manifestations. Because PNES and ES may coexist, analysis of diagnostic accuracy of clinical features should be performed for individual spells.