Epilepsy phenotype and its reproducibility after lateral fluid percussion-induced traumatic brain injury in rats: Multicenter EpiBioS4Rx study project 1.

OBJECTIVE: This study was undertaken to assess reproducibility of the epilepsy outcome and phenotype in a lateral fluid percussion model of posttraumatic epilepsy (PTE) across three study sites. METHODS: A total of 525 adult male Sprague Dawley rats were randomized to lateral fluid percussion-induced brain injury (FPI) or sham operation. Of these, 264 were assigned to magnetic resonance imaging (MRI cohort, 43 sham, 221 traumatic brain injury [TBI]) and 261 to electrophysiological follow-up (EEG cohort, 41 sham, 220 TBI). A major effort was made to harmonize the rats, materials, equipment, procedures, and monitoring systems. On the 7th post-TBI month, rats were video-EEG monitored for epilepsy diagnosis. RESULTS: A total of 245 rats were video-EEG phenotyped for epilepsy on the 7th postinjury month (121 in MRI cohort, 124 in EEG cohort). In the whole cohort (n = 245), the prevalence of PTE in rats with TBI was 22%, being 27% in the MRI and 18% in the EEG cohort (p > .05). Prevalence of PTE did not differ between the three study sites (p > .05). The average seizure frequency was .317 ± .725 seizures/day at University of Eastern Finland (UEF; Finland), .085 ± .067 at Monash University (Monash; Australia), and .299 ± .266 at University of California, Los Angeles (UCLA; USA; p < .01 as compared to Monash). The average seizure duration did not differ between UEF (104 ± 48 s), Monash (90 ± 33 s), and UCLA (105 ± 473 s; p > .05). Of the 219 seizures, 53% occurred as part of a seizure cluster (≥3 seizures/24 h; p >.05 between the study sites). Of the 209 seizures, 56% occurred during lights-on period and 44% during lights-off period (p > .05 between the study sites). SIGNIFICANCE: The PTE phenotype induced by lateral FPI is reproducible in a multicenter design. Our study supports the feasibility of performing preclinical multicenter trials in PTE to increase statistical power and experimental rigor to produce clinically translatable data to combat epileptogenesis after TBI.

Factors affecting long-term prognosis in adult patients with psychogenic non-epileptic seizures.

Background and purpose:

Among epileptic patients who are monitored using the video-electroencephalography monitoring (VEM) technique, in some patients a psychogenic non-epileptic seizure (PNES) can be identified as a definitive diagnosis. The long-term prognosis of these patients is not well known. In this study, we aimed to determine the factors that affect the prognosis of PNES.

Forty-one PNES patients diagnosed using VEM between 2012 and 2022 were questioned about their PNES frequencies in the last 12 months. According to their semiological characteristics, PNES types were divided into motor and non-motor seizures. The effects of clinical characteristics (e.g. age, gender, marital status, education level and PNES type) on the prognoses were identified. 

Twenty-one PNES patients (51.2%) had long-term seizure freedom after VEM. Thirteen of them (31.7%) entered the seizure-free period immediately after VEM, and the other eight (19.5%) continued suffering from PNES for several years and became seizure free in the last 12 months. In the poor-prognosis group, female cases showed worse prognoses than male cases. The prognoses of motor and non-motor PNES types did not show significant differences. 

This study showed that 51.2% of the PNES patients examined had long-term seizure freedom and that female patients had worse prognoses than male patients.

A retrospective study of the correlation between duration of monitoring in the epilepsy monitoring unit and diagnostic yield.

OBJECTIVE: Long-term video-electroencephalographic (LTVEM) monitoring is a valuable tool in the evaluation of paroxysmal clinical events. However, vEEG itself is costly. Hence, we aimed to establish if longer duration of monitoring (DOM) is associated with higher diagnostic yield. METHOD: A retrospective review of patients admitted into the epilepsy monitoring unit (EMU) for the diagnostic evaluation of paroxysmal events was performed. Patients' demographic, clinical characteristics, and vEEG data were analyzed. In the cohort of patients with DOM > 7 days, the reasons for prolonged DOM were identified and the differences in clinical characteristics and vEEG data between conclusive and inconclusive studies were analyzed. RESULT: A total of 501 patients were included. Four hundred and thirty-six (87 %) patients had conclusive studies. Of these patients, 67.9 % patients with conclusive studies received diagnosis within the first 7 days of monitoring with the highest on day 7. The likelihood of conclusive studies decreased beyond 7 days. A total of 175 had DOM > 7 days, of which 140 (80 %) had conclusive studies. In the cohort with DOM > 7 days, patients with previous abnormal routine EEG, previous vEEG monitoring, first event recorded before day 5 of admission and ≥1 events recorded during vEEG monitoring were more likely to have conclusive studies. The most common reason for prolonging DOM beyond 7 days was to adequately record multiple semiologically distinctive events (76 %). CONCLUSION: Our study supports that longer DOM is associated with an increase in diagnostic yield. More than one-third of our cohort were monitored beyond 7 days with majority (80 %) being conclusive. Our findings may guide clinicians in planning the DOM and predicting the likelihood of conclusive vEEG studies in patients with prolonged DOM based on the clinical characteristics and vEEG data.

Semiologic differences between bilateral tonic-clonic seizures of focal onset and generalized onset.

BACKGROUND: Focal semiologies have been described in idiopathic generalized epilepsies (IGE) and generalized-onset bilateral tonic-clonic seizures (GBTCS). These focal signs may lead to wrong diagnosis and inappropriate choice of antiseizure medications. We sought to investigate the differences in focal semiologic features between GBTCS and focal-onset bilateral tonic-clonic seizures (FBTCS). METHODS: We retrospectively reviewed video-EEG data of captured GBTCS and FBTCS over a period of five years. The presence or absence of 12 focal signs as well seizure duration and time to head version was tabulated for each seizure. We used the chi-square test for independence and Fisher's exact test to investigate the occurrence of each focal sign in FBTCS compared with GBTCS. Additionally, we used receiver operating characteristic (ROC) curves to explore if the seizure duration and time to head version from the ictal onset can reliably differentiate between FBTCS and GBTCS. Finally, we employed hierarchical cluster analysis to visualize how these focal signs appear in combination. RESULTS: Head version (p <.001), preceding automatisms (p <.001), eye version (p <.001), unilateral facial clonic activity (p <.001), and mouth deviation (p =.004) were found to be significantly more frequent in FBTCS. Longer seizures were highly in favor of FBTCS whereas shorter time to head version from the ictal onset indicated GBTCS in the ROC curve analysis. CONCLUSIONS: Though focal signs occur in GBTCS, careful evaluation of semiology can help the clinician distinguish FBTCS from GBTCS.

Surgery in intractable epilepsy-physicians' recommendations and patients' decisions.

OBJECTIVES: To identify demographic and clinical variables independently associated with patients' decisions against their physicians' recommendations for resective epilepsy surgery or further scalp video-EEG monitoring (sca-VEM), semi-invasive (sem-)VEM with foramen ovale and/or peg electrodes, and invasive (in-)VEM. METHODS: Consecutive patients, who underwent presurgical assessment with at least one sca-VEM between 2010 and 2014, were included into this retrospective analysis. Multivariate analysis was used to identify independent variables associated with patients' decisions. RESULTS: Within the study period, 352 patients underwent 544 VEM sessions comprising 451 sca-, 36 sem-, and 57 in-VEMs. Eventually, 96 patients were recommended resective surgery, and 106 were ineligible candidates; 149 patients denied further necessary VEMs; thus, no decision could be made. After sca- or additional sem-VEM, nine out of 51 eligible patients (17.6%) rejected resection. One hundred and ten patients were recommended in-VEM, 52 of those (47.2%) declined. Variables independently associated with rejection of in-VEM comprised intellectual disability (OR 4.721, 95% CI 1.047-21.284), extratemporal focal aware non-motor seizures ("aura") vs. no "aura" (OR 0.338, 95% CI 0.124-0.923), and unilateral or bilateral vs. no MRI lesion (OR 0.248, 95% CI 0.100-0.614 and 0.149, 95% CI 0.027-0.829, respectively). CONCLUSIONS: During and after presurgical evaluation, patients with intractable focal epilepsy declined resections and intracranial EEGs, as recommended by their epileptologists, in almost 20% and 50% of cases. This calls for early and thorough counseling of patients on risks and benefits of epilepsy surgery. Future prospective studies should ask patients in depth for specific reasons why they decline their physicians' recommendations.

Can semiology differentiate between bilateral tonic-clonic seizures of focal-onset and generalized-onset? A systematic review.

OBJECTIVE: Bilateral tonic-clonic seizures are encountered in both focal and generalized epilepsies. We reviewed the literature regarding the presence of focal signs in generalized-onset tonic-clonic seizures (GOTCS) and the utility of semiology in differentiating those from focal to bilateral tonic-clonic seizures (FBTCS). METHODS: We conducted a comprehensive literature search using four electronic databases (Medline, Embase, Web of Science, and Psychinfo) and constructed a systematic review in keeping with the Preferred Items for Systematic Reviews and Meta-analyses guidelines. RESULTS: We included 13 studies on focal semiological features of GOTCS. These studies included a total of 952 participants. The key focal signs described in GOTCS included: early head version, figure of four sign, asymmetric seizure termination, and a multitude of auras as well as automatisms. Additionally, we reviewed five studies that investigated the use of semiology to differentiate GOTCS from FBTCS; these studies had a total of 289 participants. Asymmetry in clonic phase, side-to-side axial movements, asymmetrical seizure termination, figure of four sign, index finger pointing, and fanning posture of the hand were found to be significantly more frequent in FBTCS compared with GOTCS. Furthermore, combinations of focal semiological features occurring in a single seizure were found to be suggestive of FBTCS rather than GOTCS. CONCLUSION: Focal signs are often evident in GOTCS. Though the observation of multiple focal signs within a given seizure may be in favor of an FBTCS, our findings caution against differentiating between the two seizure types based on semiology alone due to considerable overlap in focal features.

Psychiatric and cognitive characteristics of older adults admitted to a Video-EEG monitoring (VEM) unit.

OBJECTIVE: To compare the clinical, psychiatric, and cognitive characteristics of older with younger patients presenting to a video-EEG monitoring (VEM) unit. METHOD: This was a retrospective case-control study involving patients admitted for VEM over a two-year period (from April 2018 to April 2020) at two comprehensive epilepsy units. Patients were categorized into an older (≥60 years) and a younger (<60 years) group. Younger patients were individually matched to older adults to form a matched younger group. Diagnosis was determined by a consensus opinion of epileptologists, neurologists, and neuropsychiatrists. The main diagnostic categories were epilepsy, psychogenic nonepileptic seizures (PNES), and 'other' diagnosis (non-diagnostic and other nonepileptic diagnoses). Clinical psychiatric diagnoses were obtained from neuropsychiatric reports. Objective cognitive function was measured with the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG). Subjective cognitive function was assessed using the Quality of Life in Epilepsy Inventory-89 (QOLIE-89) cognitive subscales. RESULTS: Five-hundred and thirty three patients (71 older, 462 younger) aged 16-91 years were admitted to the VEM unit during the study period. There was a diagnosis of focal epilepsy in 55% of the older group and 48% of the younger group, generalized epilepsy in 3% of the older group and 10% of the younger group, and 'other' in 32% of the older group and 19% of the younger group. Ten percent (2 males and 5 females) of the older group were diagnosed with PNES compared to 22% of the younger group (p = 0.016). A depressive disorder was diagnosed in 34% of the older group and 24% of the younger group (p = 0.20). An anxiety disorder was diagnosed in 15% of the older group and 25% of the younger group (p = 0.15). Mild neurocognitive disorder was more common in the older group (34%) compared to the matched younger group (34% vs 3%, p < 0.001). The older group had lower mean NUCOG scores compared to the matched younger group (79.49 vs 87.73, p = <0.001). There was no evidence for a relationship between mean NUCOG score and overall subjective cognitive difficulties for the older group (r = 0.03, p = 0.83). Among older adults, those diagnosed with PNES had more experiences of childhood trauma. Measures of dissociation, depression, or general anxiety did not differ between PNES and non-PNES diagnoses in the older group. CONCLUSION: Psychiatric comorbidities are common among older adults admitted for VEM. The psychological impact of epilepsy and risk factors for PNES seen in younger patients are also applicable in the older group. The older group demonstrated more cognitive impairments than the younger group, although these were usually unrecognized by individuals. Older adults admitted to VEM will benefit from psychiatric and neuropsychological input to ensure a comprehensive care approach to evaluation and management.

Differentiating PNES from epileptic seizures using conversational analysis on French patients: A prospective blinded study.

Psychogenic nonepileptic seizures (PNES) resemble epileptic seizures (ES) but are not caused by the occurrence of excessive cortical neuronal discharge. Previous studies in German-, English-, and Italian-speaking patients showed that patients used a different communicative style to talk about their seizures. They demonstrated that the diagnosis between PNES and ES could be predicted using qualitative assessment and a diagnostic scoring aid (DSA). The objective of our study was to evaluate the contribution of linguistic analysis in the differential diagnosis between ES and PNES in a French patient population. During an extended video-electroencephalogram (video-EEG) monitoring, 13 patients presented PNES and 19 patients with ES. Two neurologists blindly and independently analyzed the interview of each patient. Rater 1 predicted the correct diagnosis in 27 of 32 patients (84%) and Rater 2 in 28 of 32 patients (88%). Interrater reliability of qualitative analysis was satisfactory (k = 0.68, interrater agreement = 84.4%). Using a simplified DSA, Rater 1 and Rater 2 would have correctly diagnosed 88% (28/32 patients) and 91 % (29/32) of the cases, respectively. Our blinded prospective study confirms the diagnostic value of conversational analysis, performed by neurologists, to differentiate PNES from ES in French-speaking patients.

Development of a Rat Model for Glioma-Related Epilepsy.

Seizures are common in patients with high-grade gliomas (30-60%) and approximately 15-30% of glioblastoma (GB) patients develop drug-resistant epilepsy. Reliable animal models are needed to develop adequate treatments for glioma-related epilepsy. Therefore, fifteen rats were inoculated with F98 GB cells (GB group) and four rats with vehicle only (control group) in the right entorhinal cortex. MRI was performed to visualize tumor presence. A subset of seven GB and two control rats were implanted with recording electrodes to determine the occurrence of epileptic seizures with video-EEG recording over multiple days. In a subset of rats, tumor size and expression of tumor markers were investigated with histology or mRNA in situ hybridization. Tumors were visible on MRI six days post-inoculation. Time-dependent changes in tumor morphology and size were visible on MRI. Epileptic seizures were detected in all GB rats monitored with video-EEG. Twenty-one days after inoculation, rats were euthanized based on signs of discomfort and pain. This study describes, for the first time, reproducible tumor growth and spontaneous seizures upon inoculation of F98 cells in the rat entorhinal cortex. The development of this new model of GB-related epilepsy may be valuable to design new therapies against tumor growth and associated epileptic seizures.

Rapid discontinuation of sodium channel-blocking antiseizure drugs evokes focal edema in the splenium corporis callosi: A matched case-control study.

OBJECTIVE: Focal edema of the splenium of the corpus callosum (FESCC) is infrequently seen in patients with epilepsy who are undergoing video-electroencephalography (EEG) monitoring. It is diagnosed by qualitative visual inspection of the magnetic resonance imaging (MRI) and is usually assumed to be a dichotomous phenomenon. Rapid reduction of anticonvulsants has been proposed as a cause. In this study we investigate the relationship between dose reduction of anticonvulsants and the occurrence of FESCC, based on absolute drug doses. METHODS: We examined in detail the anticonvulsive therapy of all patients during video-EEG monitoring between 2014 and 2018. We compared patients with a radiologically diagnosed FESCC to controls in a 1:2 case-control analysis matched by age, epilepsy syndrome, and adjacent time of admission. In a separate correlation analysis, we examined quantitative effects of reduction of antiseizure drugs on diffusion restriction in the corpus callosum. RESULTS: Of 326 patients who had an MRI following video-EEG monitoring, 12 (3.7%) had FESCC. Antiseizure drugs were reduced to a significantly greater extent in FESCC patients than in the 24 controls (P < 0.001). Sodium channel-blocking antiseizure drugs were reduced (P < 0.001) and reintroduced (P < 0.001) significantly faster in FESCC patients, and the duration of anticonvulsant discontinuation was longer in FESCC patients (P < 0.001). The separate correlation analysis in 325 patients shows a weak correlation between diffusion restriction in the splenium and the reduction rate of sodium channel-blocking anticonvulsants (r = -0.15, P = 0.03) as well as the duration of their discontinuation (r = -0.16, P = 0.01). No such effects were found for anticonvulsants with other modes of action. SIGNIFICANCE: Our findings substantiate that FESCC is associated with high rates of dose reduction of anticonvulsants, specifically those acting on sodium channels. Our results cautiously suggest that reducing sodium-channel blockers has a small effect on diffusivity in the splenium below the visual threshold.

Localization value of subclinical seizures on scalp video-EEG in epilepsy presurgical evaluation.

OBJECTIVE: To evaluate the localization value and prognostic significance of subclinical seizures (SCSs) on scalp video-electroencephalography monitoring (VEEG) in comparison to clinical seizures (CSs) in patients who had epilepsy surgery. METHODS: We included 123 consecutive patients who had SCSs and CSs during scalp-VEEG evaluation. All patients had subsequent epilepsy surgery and at least 1-year follow-up. Concordance between SCSs and CSs was summarized into five categories: complete, partial, overlapping, no concordance, or indeterminate. Using the same scheme, we analyzed the relationship between resection and SCS/CS localizations. The concordance measures, along with demographic, electroclinical, and other presurgical evaluation data, were evaluated for their associations with postoperative seizure outcome. RESULTS: Sixty-nine patients (56.1%) had seizure-free outcome at 1-year follow-up. In 68 patients (55.3%), the localizations of SCSs and CSs were completely concordant. Multivariate logistic analysis showed that complete SCS/CS concordance was independently associated with seizure-free outcome at 1-year (P = .020) and 2-year follow-up (P = .040). In the temporal lobe epilepsy (TLE) seizure-free group, SCS localization was completely contained within the resection in 44.4% and CS localization was completely contained within the resection in 41.7%; in the extratemporal lobe epilepsy (ETLE) seizure-free group, SCS localization was completely contained within the resection in 54.5% and CS localization was completely contained within the resection in 57.6%. SIGNIFICANCE: Complete concordance between CS and SCS localization is a positive prognostic factor for 1-year and 2-year postoperative seizure-free outcome. Localization value of SCSs on scalp VEEG is similar to that of CSs for TLE and ETLE. Although SCSs cannot replace CSs, localization information from SCSs should not be ignored.

Referral to evaluation for epilepsy surgery: Reluctance by epileptologists and patients.

OBJECTIVE: Despite the obvious advantages of resective surgery in patients with drug-resistant focal epilepsy, namely high probability of seizure freedom, decreased mortality, and increased quality of life, referral rates from physicians and approval rates by patients for presurgical assessment remain constantly low. METHODS: In the outpatient clinics of a tertiary epilepsy center, checklists were implemented asking treating epileptologists whether they recommended presurgical evaluation with noninvasive video-electroencephalographic monitoring to adult patients with drug-resistant focal epilepsy and asking respective patients whether they followed this recommendation. RESULTS: Of 185 eligible patients, 80 (43%) were recommended presurgical evaluation by their epileptologists, and 24 (30%) of these patients consented. Nineteen of all patients (10%) actually underwent noninvasive presurgical assessment, and nine of these eventually proceeded to resection. The most frequent reason for nonreferral by epileptologists was their subjective appraisal of seizure frequency as low (31%), whereas patients declined most often due to overall fear of brain surgery (50%). Variables independently associated with nonreferral by epileptologists comprised older age of patients at questioning (odds ratio [OR] = 1.03), no previous evaluation for epilepsy surgery (OR = 4.04), the presence of legal guardianship (OR = 4.29), and ≥11 years of professional experience by the treating epileptologist (OR = 4.62). Independent predictors for patients' rejection of presurgical evaluation were older age at questioning (OR = 1.08), lifetime number of antiepileptic drugs ≥ 5 (OR = 4.47), presence of focal aware seizures (OR = 4.37), and absence of focal seizures with impaired awareness (OR = 11.24). SIGNIFICANCE: In both epileptologists and patients with difficult-to-treat epilepsy, we found high decision rates against presurgical assessment. Some reasons given by physicians for not recommending presurgical evaluation to patients may be understandable; others need further exploration. On the patients' side, early and thorough counseling on risks and benefits of epilepsy surgery is necessary to increase understanding and acceptance.

Long-term seizure outcome in frontal lobe epilepsy surgery.

PURPOSE: The purpose of this study was to report long-term seizure outcome in patients who underwent frontal lobe epilepsy (FLE) surgery. METHOD: This retrospective study included 44 consecutive subjects who underwent resective surgery for intractable FLE at IRCCS NEUROMED (period 2001-2014), followed up for at least 2 years (mean: 8.7 years). All patients underwent noninvasive presurgical evaluation and/or invasive electroencephalography (EEG) monitoring when nonconcordant data were obtained or epileptogenic zone was hypothesized to be close to the eloquent cortex. Electroclinical, neuroimaging, surgical data, and histology were compared to seizure outcome. RESULTS: Mean epilepsy duration was 19 years; mean age at surgery was 31.6 years. Preoperative magnetic resonance imaging (MRI) showed a frontal lesion in 86.4 % of cases. Scalp video-electroencephalography (VEEG) monitoring detected a focal ictal onset in 90% of cases. Twenty-seven patients (61.4%) underwent invasive recordings. Resections involved dorsolateral (47.7%), medial (9%), orbital (13.6%), and rolandic (13.6%) region. Lobectomy within functional boundaries was performed in the remaining 7 cases (16%). Transient and permanent neurological deficits were observed in 2 and 3 cases, respectively. Histology revealed focal cortical dysplasia (45.5%), World Health Organization (WHO) I-II grade tumors (15.9%), gliosis (22.7%), vascular malformations (4.5%), Rasmussen encephalitis (6.8%), and normal tissue (4.5%). At last observation 68.1% of patients were in Engel's class I, 11.4% in class II, 9% in class III, and 11.4% in class IV. A favorable outcome was associated with focal ictal scalp EEG onset (p = 0.0357). CONCLUSION: Surgery is a safe treatment option in drug-resistant FLE with a satisfying long-term outcome. These data highlight the importance of an appropriate selection of potential surgical candidates.

Randomized controlled study comparing the efficacy of rapid and slow withdrawal of antiepileptic drugs during long-term video-EEG monitoring.

OBJECTIVE: Antiepileptic drugs (AEDs) are routinely withdrawn during long-term video-electroencephalography (EEG) monitoring (LTM), to record sufficient number of seizures. The efficacy of rapid and slow AED taper has never been compared in a randomized control trial (RCT), which was the objective of this study. METHODS: In this open-label RCT, patients aged 2-80 years with drug-resistant epilepsy (DRE) were randomly assigned (1:1) to rapid and slow AED taper groups. Outcome assessor was blinded to the allocation arms. Daily AED dose reduction was 30% to 50% and 15% to <30% in the rapid and slow taper groups, respectively. The primary outcome was difference in mean duration of LTM between the rapid and slow AED taper groups. Secondary outcomes included diagnostic yield, secondary generalized tonic-clonic seizure (GTCS), 4- and 24- hour seizure clusters, status epilepticus, and need for midazolam rescue treatment. The study was registered with Clinical Trial Registry-India (CTRI/2016/08/007207). RESULTS: One hundred forty patients were randomly assigned to rapid (n = 70) or slow taper groups (n = 70), between June 13, 2016 and February 20, 2017. The difference in mean LTM duration between the rapid and slow taper groups was -1.8 days (95% confidence interval [CI] -2.9 to -0.8, P = .0006). Of the secondary outcome measures, time to first seizure (2.9 ± 1.7 and 4.6 ± 3.0 days in the rapid and slow taper groups respectively, P = .0002) and occurrence of 4-hour seizure clusters (11.9% and 2.9% in the rapid and slow taper groups, respectively, P = .04) were statistically significant. None of the other safety variables were different between the 2 groups. LTM diagnostic yield was 95.7% and 97.1%, in rapid and slow taper groups respectively (P = .46). SIGNIFICANCE: Rapid AED tapering has the advantage of significantly reducing LTM duration over slow tapering, without any serious adverse events.

Phase-amplitude coupling between interictal high-frequency activity and slow waves in epilepsy surgery.

OBJECTIVE: We hypothesized that the modulation index (MI), a summary measure of the strength of phase-amplitude coupling between high-frequency activity (>150 Hz) and the phase of slow waves (3-4 Hz), would serve as a useful interictal biomarker for epilepsy presurgical evaluation. METHODS: We investigated 123 patients who underwent focal cortical resection following extraoperative electrocorticography recording and had at least 1 year of postoperative follow-up. We examined whether consideration of MI would improve the prediction of postoperative seizure outcome. MI was measured at each intracranial electrode site during interictal slow-wave sleep. We compared the accuracy of prediction of patients achieving International League Against Epilepsy class 1 outcome between the full multivariate logistic regression model incorporating MI in addition to conventional clinical, seizure onset zone (SOZ), and neuroimaging variables, and the reduced logistic regression model incorporating all variables other than MI. RESULTS: Ninety patients had class 1 outcome at the time of most recent follow-up (mean follow-up = 5.7 years). The full model had a noteworthy outcome predictive ability, as reflected by regression model fit R2 of 0.409 and area under the curve (AUC) of receiver operating characteristic plot of 0.838. Incomplete resection of SOZ (P < 0.001), larger number of antiepileptic drugs at the time of surgery (P = 0.007), and larger MI in nonresected tissues relative to that in resected tissue (P = 0.020) were independently associated with a reduced probability of class 1 outcome. The reduced model had a lower predictive ability as reflected by R2 of 0.266 and AUC of 0.767. Anatomical variability in MI existed among nonepileptic electrode sites, defined as those unaffected by magnetic resonance imaging lesion, SOZ, or interictal spike discharges. With MI adjusted for anatomical variability, the full model yielded the outcome predictive ability of R2 of 0.422, AUC of 0.844, and sensitivity/specificity of 0.86/0.76. SIGNIFICANCE: MI during interictal recording may provide useful information for the prediction of postoperative seizure outcome.

Tolerability of a comprehensive cardiorespiratory monitoring protocol in an epilepsy monitoring unit.

BACKGROUND: Recent reports of fatal or near-fatal events in epilepsy monitoring units (EMUs) and an increasing awareness of the effects of seizures on breathing have stimulated interest in cardiorespiratory monitoring for patients undergoing video-electroencephalography (EEG) recording. Patient and provider acceptance of these extra recording devices has not previously been studied and may represent a barrier to widespread adoption. METHODS: We queried EMU subjects regarding their experiences with a monitoring protocol that included the continuous measurement of oral/nasal airflow, respiratory effort (chest and abdominal respiratory inductance plethysmography), oxygen saturation, and transcutaneous CO2. Surveys were returned by 71.4% (100/140) of eligible subjects. RESULTS: Overall, 73% of participants reported being moderately to highly satisfied with the monitoring, and 82% reported moderate to strong agreement that advance knowledge of the monitoring would not have changed their decision to proceed with the video-EEG study. Except for nasal airflow, none of the additional monitoring devices caused more discomfort than EEG electrodes. CONCLUSION: Patient acceptance of an EMU comprehensive cardiorespiratory monitoring protocol is high. The information obtained from "multimodality recording" should help clinicians and investigators understand the effect of seizures on both cardiac and respiratory physiology, may enhance safety in the EMU, and may aid in the identification of biomarkers for sudden unexpected death in epilepsy (SUDEP).

Implementation of Continuous Video-Electroencephalography at a Community Hospital Enhances Care and Reduces Costs.

BACKGROUND: Despite data indicating the importance of continuous video-electroencephalography (cvEEG) monitoring, adoption has been slow outside major academic centers. Barriers to adoption include the need for technologists, equipment, and cvEEG readers. Advancements in lower-cost lead placement templates and commercial systems with remote review may reduce barriers to allow community centers to implement cvEEG. Here, we report our experience, lessons learned, and financial impact of implementing a community hospital cvEEG-monitoring program. METHODS: We implemented an adult cvEEG service at Duke Regional Hospital (DRH), a community hospital affiliate, in June of 2012. Lead placement templates were used in the implementation to reduce the impact on technologists by using other bedside providers for EEG initiation. Utilization of the service, study quality, and patient outcomes were tracked over a 3-year period following initiation of service. RESULTS: Service was implemented at essentially no cost. Utilization varied from a number of factors: intensive care unit (ICU) attending awareness, limited willingness of bedside providers to perform lead placement, and variation in practice of the consulting neurologists. A total of 92 studies were performed on 88 patients in the first 3 years of the program, 24 in year one, 27 in year two, and 38 in year three, showing progressive adoption. Seizures were seen in 25 patients (27%), 19 were in status, of which 18 were successfully treated. Transfers to the main hospital, Duke University Medical Center, were prevented for 53 patients, producing an estimated cost savings of $145,750. The retained patients produced a direct contribution margin of about $75,000, and the margin was just over $100,000 for the entire monitored cohort. CONCLUSION: ICU cvEEG service is feasible and practical to implement at the community hospital level. Service was initiated at little to no cost and clearly enhanced care, increased breadth of care, increased ICU census, and reduced transfers. The system allowed for successful management of ICU patients with underlying seizures and eliminated interfacility transfers, producing a savings of $145,750. The savings combined with the retained patient revenue produced a total revenue of over $250,000 with additional revenue in professional services as well. These results suggest expansion of cvEEG monitoring to community ICUs is practical, financially sustainable, improves the level and quality of care, and reduces costs.

Drug taper during long-term video-EEG monitoring: efficiency and safety.

OBJECTIVES: Anti-epileptic drugs (AED) are often tapered to reduce the time needed to record a sufficient number of seizure during long-term video-EEG monitoring (LTM). Fast AED reduction is considered less safe, but few studies have examined this. Our goal is to examine whether the rate of AED reduction affects efficiency and safety. MATERIALS & METHODS: We performed a retrospective observational study of patients referred for presurgical evaluation. Each patient was categorized by two dichotomous parameters of AED tapering: (i) fast vs slow AED reduction the first 24 h of LTM and (ii) complete vs partial AED discontinuation during LTM. RESULTS: Of 79 patients, 51% underwent a fast AED reduction and 58% ended up with AEDs completely discontinued. Complete AED discontinuation was associated with three times increased likelihood of receiving rescue therapy during LTM and double risk of having secondary generalized tonic-clonic seizures (sGTCS) compared to the group partially discontinued. Fast vs slow AED reduction had no effect on the safety of LTM. The fast AED reduction group and the complete AED discontinuation group had a significantly longer time to first seizure and total recording time compared to the slow AED reduction and partial discontinuation groups, respectively. CONCLUSIONS: Fast AED reduction was found safe in patients undergoing presurgical video-EEG monitoring. Patients completely discontinued from AEDs had more sGTCS than patients partially discontinued. Further studies are suggested to confirm this finding and to evaluate whether fast reduction is safe and efficient in other subgroups of patients referred for LTM.

Quality and safety in adult epilepsy monitoring units: A systematic review and meta-analysis.

OBJECTIVE: The epilepsy monitoring unit (EMU) is a valuable resource for optimizing management of persons with epilepsy, but may place patients at risk for adverse events due to withdrawal of treatment and induction of symptoms. The purpose of this study was to synthesize data on the safety and quality of care in EMUs to inform the development of quality indicators for EMUs. METHODS: A systematic review was conducted according to the Preferred Reporting and Items for Systematic Review and Meta-Analysis (PRISMA) statement. The search strategy, which included broad search terms and synonyms pertaining to the EMU, was run in six medical databases and included conference proceedings. Data abstracted included patient and EMU demographics and quality and safety variables. Study quality was evaluated using a modified 15-item Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. Descriptive statistics and meta-analyses were used to describe and synthesize the evidence. RESULTS: The search yielded 7,601 references, of which 604 were reviewed in full text. One-hundred thirty-five studies were included. The quality and safety data came from 181,823 patients and reported on 34 different quality and safety variables. Included studies commonly reported the number of patients (108 studies; median number patients, 171.5), age (49 studies; mean age 35.7 years old), and the reason for admission (34 studies). The most common quality and safety data reported were the utility of the EMU admission (38 studies). Thirty-three studies (24.4%) reported on adverse events, and yielded a pooled proportion of adverse events of 7% (95% confidence interval [CI] 5-9%). The mean quality score was 73.3% (standard deviation [SD] 17.2). SIGNIFICANCE: This study demonstrates that there is a great deal of variation in the reporting of quality and safety measures and in the quality and safety in EMUs. Study quality also varied considerably from one study to the next. These findings highlight the need to develop evidence-based, consensus-driven quality indicators for EMUs.

Quality indicators for the adult epilepsy monitoring unit.

OBJECTIVE: Quality and safety in epilepsy monitoring units (EMUs) are of great importance because patients' seizures are induced rather than prevented in this hospital setting. However, the measurement and evaluation of quality and safety in EMUs are heterogeneous, as are practices and processes of care. To improve the measurement of quality and safety in EMUs, we sought to develop evidence-based and consensus-driven quality indicators, adhering to previously described methodologic standards. METHODS: Candidate quality indicators were identified using a recent systematic review on quality and safety indicators in EMUs. These were supplemented by expert opinion to identify other indicators that had not been reported previously. The candidate quality indicators were then evaluated using a modified Delphi technique among a multidisciplinary EMU quality improvement team. Candidate indicators identified as important and feasible through the Delphi technique were then developed into quality metrics. RESULTS: Thirty-four candidate indicators were abstracted from 135 studies included in the earlier systematic review, and two additional candidate indicators were suggested through consensus from experts. Consensus was reached after two modified Delphi rounds for 25 quality indicators identified as important. These 25 indicators were then developed into quality metrics using a standardized data collection form and were deployed in an online database for systematic data capture and further analyses. SIGNIFICANCE: These quality indicators have the potential to improve the reporting of quality and safety in EMUs through standardized measurement and evaluation of the quality and safety of care. The ultimate goal is improved patient care and clinical outcomes through safer and better care for people with epilepsy in the EMU.