vEEG Monitoring Research Articles

Early Developmental EEG and Seizure Phenotypes in a Full Gene Deletion of Ubiquitin Protein Ligase E3A Rat Model of Angelman Syndrome.

Angelman syndrome (AS) is a neurodevelopmental disorder with unique behavioral phenotypes, seizures, and distinctive electroencephalographic (EEG) patterns. Recent studies identified motor, social communication, and learning and memory deficits in a CRISPR engineered rat model with a complete maternal deletion of the Ube3a gene. It is unknown whether this model recapitulates other aspects of the clinical disorder. We report here the effect of Ube3a maternal deletion in the rat on epileptiform activity, seizure threshold, and quantitative EEG. Using video-synchronized EEG (vEEG) monitoring, we assessed spectral power and epileptiform activity early postnatally through adulthood. While EEG power was similar to wild-type (WT) at 1.5 weeks postnatally, at all other ages analyzed, our findings were similar to the AS phenotype in mice and humans with significantly increased δ power. Analysis of epileptiform activity in juvenile and adult rats showed increased time spent in epileptiform activity in AS compared with WT rats. We evaluated seizure threshold using pentylenetetrazol (PTZ), audiogenic stimulus, and hyperthermia to provoke febrile seizures (FSs). Behavioral seizure scoring following PTZ induction revealed no difference in seizure threshold in AS rats, however behavioral recovery from the PTZ-induced seizure was longer in the adult group with significantly increased hippocampal epileptiform activity during this phase. When exposed to hyperthermia, AS rat pups showed a significantly lower temperature threshold to first seizure than WT. Our findings highlight an age-dependence for the EEG and epileptiform phenotypes in a preclinical model of AS, and support the use of quantitative EEG and increased δ power as a potential biomarker of AS.

Cycles of self-reported seizure likelihood correspond to yield of diagnostic epilepsy monitoring.

Video-electroencephalography (vEEG) is an important component of epilepsy diagnosis and management. Nevertheless, inpatient vEEG monitoring fails to capture seizures in up to one third of patients. We hypothesized that personalized seizure forecasts could be used to optimize the timing of vEEG. We used a database of ambulatory vEEG studies to select a cohort with linked electronic seizure diaries of more than 20 reported seizures over at least 8weeks. The total cohort included 48 participants. Diary seizure times were used to detect individuals' multiday seizure cycles and estimate times of high seizure risk. We compared whether estimated seizure risk was significantly different between conclusive and inconclusive vEEGs, and between vEEG with and without recorded epileptic activity. vEEGs were conducted prior to self-reported seizures; hence, the study aimed to provide a retrospective proof of concept that cycles of seizure risk were correlated with vEEG outcomes. Estimated seizure risk was significantly higher for conclusive vEEGs and vEEGs with epileptic activity. Across all cycle strengths, the average time in high risk during vEEG was 29.1% compared with 14% for the conclusive/inconclusive groups and 32% compared to 18% for the epileptic activity/no epileptic activity groups. On average, 62.5% of the cohort showed increased time in high risk during their previous vEEG when epileptic activity was recorded (compared to 28% of the cohort where epileptic activity was not recorded). For conclusive vEEGs, 50% of the cohort had increased time in high risk, compared to 21.5% for inconclusive vEEGs. Although retrospective, this study provides a proof of principle that scheduling monitoring times based on personalized seizure risk forecasts can improve the yield of vEEG. Forecasts can be developed at low cost from mobile seizure diaries. A simple scheduling tool to improve diagnostic outcomes may reduce cost and risks associated with delayed or missed diagnosis in epilepsy.

Immunization stress-related responses presenting as psychogenic non-epileptic seizures following HPV vaccination in Rio Branco, Brazil

ImportanceThe absence of a positive diagnosis of psychogenic non-epileptic seizures (PNES) in immunization stress-related response (ISRR) clusters may have not only a direct impact on affected patients’ health but may also reduce compliance to national vaccination programs. It is therefore crucial to develop efficient diagnostic tools and a feasible proposal for proper communication and treatment of ISRR. PurposeTo explore the psychogenic nature of patients’ convulsive seizures in a suspected outbreak of an ISRR cluster following human papillomavirus vaccination in Rio Branco, Brazil. MethodsTwelve patients with convulsive seizures were submitted to prolonged intensive video-electroencephalography monitoring, brain magnetic resonance imaging, cerebrospinal fluid diagnostic testing, laboratory subsidiary examinations, and complete neurological and psychiatric evaluations. ResultsTen patients received the positive diagnosis of PNES, and two patients received the diagnosis of idiopathic generalized epilepsy. No biological association was found between the HPV vaccine and the clinical problems presented by the patients. ConclusionsProlonged VEEG monitoring can contribute significantly to the positive diagnosis of PNES in ISRR clusters and to avoid hesitancy to vaccinate.

Postinjury weight rather than cognitive or behavioral impairment predicts development of posttraumatic epilepsy after lateral fluid-percussion injury in rats.

To identify postinjury physiologic, behavioral, and cognitive biomarkers for posttraumatic epilepsy to enrich study populations for long-term antiepileptogenesis studies. The EPITARGET cohort with behavioral follow-up and 1-month 24/7 video-electroencephalography (vEEG) monitoring included 115 adult male Sprague-Dawley rats with lateral fluid-percussion-induced traumatic brain injury (TBI), 23 sham-operated controls, and 13 naive rats. Animals underwent assessment of somatomotor performance (composite neuroscore), anxiety-like behavior (elevated plus maze, open field), spatial memory (Morris water maze), and depression-like behavior (Porsolt forced swim, sucrose preference). Impact force, postimpact apnea time, postimpact seizure-like behavior, and body weight were monitored. TBI rats were impaired in the composite neuroscore (P<.001) on days (D) 2-14 and in the spatial memory test (P<.001) on D35-39 post-TBI. Differences in the elevated plus-maze (D28 and D126) and in the open field (D29 and D127) between TBI rats and controls were meager. No differences were observed in the Porsolt forced swim and sucrose preference tests as compared with sham-operated controls. Epilepsy developed in 27% of rats by the end of the sixth month. None of the behavioral or cognitive outcome measures discriminated rats with or without epilepsy. The receiver-operating characteristic analysis indicated that a decrease in body weight between D0 and D4 differentiated TBI rats with epilepsy from TBI rats without epilepsy (48% sensitivity, 83% specificity, area under the curve [AUC]0.679, confidence interval [CI] 95%0.56-0.80, P<.01). A 16% body weight decrease during D0-D4 could be used as a biomarker to enrich the study population from 27% (observed) to 50%. Single behavioral and cognitive outcome measures showed no power as prognostic/diagnostic biomarkers for posttraumatic epilepsy. A reduction in body weight during the first postinjury week showed some prognostic value for posttraumatic epileptogenesis and could serve as a subacute measure for selectively enriching the study population for long-term preclinical biomarker and therapy discovery studies of posttraumatic epileptogenesis.

Can commercially available wearable EEG devices be used for diagnostic purposes? An explorative pilot study

Electroencephalography (EEG) is a core element in the diagnosis of epilepsy syndromes and can help to monitor antiseizure treatment. Mobile EEG (mEEG) devices are increasingly available on the consumer market and may offer easier access to EEG recordings especially in rural or resource-poor areas. The usefulness of consumer-grade devices for clinical purposes is still underinvestigated. Here, we compared EEG traces of a commercially available mEEG device (Emotiv EPOC) to a simultaneously recorded clinical video EEG (vEEG). Twenty-two adult patients (11 female, mean age 40.2 years) undergoing noninvasive vEEG monitoring for clinical purposes were prospectively enrolled. The EEG recordings were evaluated by 10 independent raters with unmodifiable view settings. The individual evaluations were compared with respect to the presence of abnormal EEG findings (regional slowing, epileptiform potentials, seizure pattern). Video EEG yielded a sensitivity of 56% and specificity of 88% for abnormal EEG findings, whereas mEEG reached 39% and 85%, respectively. Interrater reliability coefficients were better in vEEG as compared to mEEG (ϰ = 0.50 vs. 0.30), corresponding to a moderate and fair agreement. Intrarater reliability between mEEG and vEEG evaluations of simultaneous recordings of a given participant was moderate (ϰ = 0.48). Given the limitations of our exploratory pilot study, our results suggest that vEEG is superior to mEEG, but that mEEG can be helpful for diagnostic purposes. We present the first quantitative comparison of simultaneously acquired clinical and mobile consumer-grade EEG for a clinical use-case.

Photosensitive tonic-clonic seizures:a continuum between focal and generalized seizures

To investigate whether the tonic-clonic seizure (TCS) induced by intermittent photic stimulation (IPS)was generalized tonic-clonic seizure (GTCS)or partial secondarily tonic-clonic seizure (PGTCS),and to analyze the relationship between them. Video-electroencephalogram (VEEG)database of Peking University First Hospital from March 2010 to October 2018 were reviewed. Fifteen cases with idiopathic epilepsy who had TCS induced by IPS were included in this study, and their clinical and electroencephalogram (EEG)characteristics were retrospectively analyzed. In this study, 4 of the 15 cases were boys and 11 were girls. The age of seizure onset ranged from 1 to 13 years. According to the medical records: 12 cases were considered as GTCS,while the remaining 3 cases were considered as PGTCS. The age at VEEG monitoring ranged from 2.5 to 16.0 years. All backgrounds of the VEEG were normal. Interictal discharges:generalized discharges in 11 cases, of which 4 cases coexisted with posterior discharges, 2 cases coexisted with Rolandic discharges, the other 5 cases merely had generalized discharges; merely focal discharges in two cases, one in the Rolandic area and the other in the posterior area; no interictal discharge in the remaining 2 cases. IPS induced photoparoxysmal response (PPR)results: 2 cases without PPR,the remaining 13 cases with PPR of generalized discharges, and 6 of the 13 cases coexisted with posterior discharges. IPS induced photoconvulsive response (PCR)results: GTCS in one case (contradictory to medical history),PGTCS in 11 cases (consistent with medical history),and GTCS and PGTCS hardly to distinguish in the remaining 3 cases. Of the three conditions above, there were generalized myoclonic seizures induced by IPS before TCS in 7 cases. The medical history was unreliable in determining whether TCS was generalized or focal. Myoclonic seizures can coexist with PGTCS, and sometimes GTCS was indistinguishable from PGTCS, indicating that the dichotomy of seizure types need to be improved. Photosensitive TCS should be regarded as a continuum between focal and generalized seizures.

The Role of Interictal Epileptiform Discharges in Epilepsy Surgery Outcome.

Background:Epilepsy surgery is a fundamental treatment in refractory epilepsy. Video electroencephalographic (v-EEG) monitoring plays an essential role in presurgical evaluation of patients. However there are reports of favorable outcome based on interictal and magnetic resonance imaging (MRI) findings without any need for v-EEG monitoring in patients with temporal lobe epilepsy (TLE). This study aimed to investigate the prognostic effect of concordance between interictal findings and ictal and MRI data on postsurgical outcome of TLE and extratemporal lobe epilepsy (ETLE).Methods:A retrospective study was conducted on 199 patients with refractory focal epilepsy who were admitted for presurgical evaluation. The concordance between irritative zone (IZ) and seizure onset zone (SOZ) and also IZ and MRI lesion was registered, and subsequently the prognostic effect of relevancy on 1-year follow-up result based on Engel criteria was investigated.Results:In TLE and ETLE regarding relevancy between IZ and SOZ, 77.8% and 73.2% were concordant, 2.5% and 0% were discordant, and 19.6% and 26.8% had overlap, respectively. Concordance between IZ and MRI lesion was found in 76.6% and 51.2% of patients with TLE and ETLE while discordance was recorded in 2.5% and 12.2% and overlap registered in 20.9% and 36.6%, respectively. The concordance of interictal findings had no effect on postsurgical outcome of patients with TLE and ETLE.Conclusions:Our study showed that concordance of IZ with SOZ and MRI has no independent effect on postsurgical outcome of patients with TLE and ETLE. We suggest that excluding exceptional cases, v-EEG monitoring should be considered as the mainstay of presurgical evaluation.

Neuroimaging of Subacute Brain Inflammation and Microstructural Changes Predicts Long-Term Functional Outcome after Experimental Traumatic Brain Injury.

There is currently a lack of prognostic biomarkers to predict the different sequelae following traumatic brain injury (TBI). The present study investigated the hypothesis that subacute neuroinflammation and microstructural changes correlate with chronic TBI deficits. Rats were subjected to controlled cortical impact (CCI) injury, sham surgery, or skin incision (naïve). CCI-injured (n = 18) and sham-operated rats (n = 6) underwent positron emission tomography (PET) imaging with the translocator protein 18 kDa (TSPO) radioligand [18F]PBR111 and diffusion tensor imaging (DTI) in the subacute phase (≤3 weeks post-injury) to quantify inflammation and microstructural alterations. CCI-injured, sham-operated, and naïve rats (n = 8) underwent behavioral testing in the chronic phase (5.5-10 months post-injury): open field and sucrose preference tests, two one-week video-electroencephalogram (vEEG) monitoring periods, pentylenetetrazole (PTZ) seizure susceptibility tests, and a Morris water maze (MWM) test. In vivo imaging revealed pronounced neuroinflammation, decreased fractional anisotropy, and increased diffusivity in perilesional cortex and ipsilesional hippocampus of CCI-injured rats. Behavioral analysis revealed disinhibition, anhedonia, increased seizure susceptibility, and impaired learning in CCI-injured rats. Subacute TSPO expression and changes in DTI metrics significantly correlated with several chronic deficits (Pearson's |r| = 0.50-0.90). Certain specific PET and DTI parameters had good sensitivity and specificity (area under the receiver operator characteristic [ROC] curve = 0.85-1.00) to distinguish between TBI animals with and without particular behavioral deficits. Depending on the investigated behavioral deficit, PET or DTI data alone, or the combination, could very well predict the variability in functional outcome data (adjusted R2 = 0.54-1.00). Taken together, both TSPO PET and DTI seem promising prognostic biomarkers to predict different chronic TBI sequelae.

Utilization of brain imaging in evaluating patients with psychogenic nonepileptic spells

BackgroundPsychogenic nonepileptic spells (PNES) are paroxysmal movements or sensory events that resemble epileptic seizures but lack corresponding ictal electrographic changes. A confirmed diagnosis of PNES is only accomplished via video electroencephalogram (vEEG) monitoring. Prior to diagnosis, patients are often assessed with neurodiagnostic imaging and their conditions treated with anticonvulsant medications, both of which are of limited clinical value and contribute to the higher cost of care. In this study, we assessed the relationship between the semiological features of PNES, medication regimen, or psychiatric comorbidities and the frequency of referrals for brain imaging tests prior to diagnosis of PNES. MethodsThis is a retrospective chart review of 224 adult patients diagnosed as having PNES at a level 4 epilepsy care center from 2012 to 2017. Patients with coexisting epilepsy were excluded. The 882 segments of vEEG records were reviewed for semiology of spells, and patients were categorized into one of seven distinct phenotypic classes according to the accepted clinical classification. The frequency of neurodiagnostic tests completed for each patient prior to vEEG was correlated with PNES phenotype and other clinical characteristics. ResultsThere were 68 (30%) males and 156 (70%) females diagnosed as having PNES with a median age of 36 years. Seventy-four percent of patients were receiving one or several anticonvulsant medications, and 67% of patients were treated with psychotropic medications other than benzodiazepines. The most prevalent PNES events were characterized by semirhythmic small amplitude movements in the extremities (class 2; 34%) followed by those resembling tonic–clonic seizures (class 4; 28%). Neurodiagnostic imaging tests including computed tomography (CT) and magnetic resonance imaging (MRI) of the brain were performed at least once in 60% of patients and 4 times or more in 11% prior to vEEG. There was a significant association between the frequency of neurodiagnostic tests and the PNES phenotype (p = 0.02). Specifically, patients with sensory changes (class 6) had more imaging tests than those with primitive gesturing and truncal posturing (classes 1 and 5, respectively). Additionally, patients diagnosed with 3 or more psychiatric disorders underwent significantly more neurodiagnostic tests relative to patients diagnosed with two or fewer psychiatric disorders (p = 0.03). Furthermore, patients whose conditions were treated with anticonvulsant medications tended to undergo more imaging scans prior to vEEG as compared with the patients whose conditions were not being treated with anticonvulsants. ConclusionsThese findings suggest that the frequency of brain imaging obtained prior to the definitive diagnosis of PNES is influenced by semiology of spells and the psychiatric health of patients. Patients who demonstrate minimal paroxysmal movements in the settings of multiple psychiatric comorbidities represent a particularly challenging patient phenotype which is linked to more frequent referrals for brain imaging. These patients should be promptly referred for vEEG to improve diagnostic accuracy and prevent treatment with anticonvulsants as well as referrals for serial neurodiagnostic tests.

S92. Outcome of prolonged EEG-video monitoring in a new V.A. monitoring unit

Introduction For patients with refractory seizures or seizure-like activity, prolonged inpatient video-EEG (v-EEG) monitoring is standard of care to guide diagnosis and management. With the advent of the “Epilepsy Centers of Excellence (ECOE)” in the VA system, many V.A. hospitals have developed an epilepsy monitoring unit (EMU). The purpose of this study was to describe the outcome of v-EEG monitoring in a new VA EMU. Methods In this retrospective study, we reviewed the diagnoses of all prolonged (>24 h) inpatient v-EEGs performed in our EMU at the James A Haley VA in Tampa, Florida. A total of 195 prolonged inpatient v-EEGs were performed over a four-year period (11/2013–10/2017). The patient population consisted of adult veterans (171 males, 24 females) ranging of 22–84 years old. The duration of monitoring ranged from 24 h to 7 days (mean 3 days). The outcomes of monitoring were then categorized as epileptic seizures (ES) (generalized versus focal ), interictal epileptiform abnormalities without a clinical event (IIAE), psychogenic nonepileptic seizures (PNES), other non-epileptic seizures (NES), non-diagnostic events (event captured was not the event in question or milder form of the typical event), and lastly those which were inconclusive (no event captured and no IIAE). Results Of the 195 studies, 44 (23%) had exclusively epileptic seizures (ES). Of these, 42 (95%) had focal seizures, and 2 (5%) had generalized seizures. Of the 42 cases with focal seizures, all but 2 had clear ictal changes on EEG. Both of the generalized seizures had clear ictal correlates on EEG. Twenty-two (11%) EEG studies revealed interictal epileptiform abnormalities without a clinical event. Fifty-three (27%) of the v-EEGs had exclusively non-epileptic events. Of these, 21 (∼11%) were psychogenic non-epileptic seizures (PNES) and 32 (16%) were other non-epileptic seizures (NES) such as syncope, hypnic jerks or subjective non-motor symptoms such as head pain or dizziness. There was only one case of mixed ES and PNES. Seventy-five (38%) of the studies were inconclusive, either due to lack of events captured (52) or because the events recorded were not the patient’s typical episodes (23). Conclusion A significant portion of the prolonged inpatient v-EEGs done during this time period was inconclusive. A possible explanation is that patients with infrequent events were often referred for v-EEG, and a longer monitoring period may be needed. The criteria of selecting patients for video-EEG may have to be better defined. There were less PNES than expected even within the NES group. This could be a result of the sample population, which consisted predominantly of males, whereas PNES occur more commonly in females. Another possible explanation is that at our center PNES are often captured during outpatient v-EEGs performed prior to EMU admission. The main limitation is that this study represents a single center. Future studies compiling data from all 16 VA ECOEs may help to better refine this data.

Paroxysmal non-epileptic motor phenomena in newborns

A variety of paroxysmal motor phenomena often occur in newborns, including physiological events(immaturity of the central nervous system)and pathological events(epileptic and non-epileptic). The clinician should be able to properly identify and diagnose the paroxysmal motor phenomena with various etiologies.There are some clinical features that may help clinicians with the differentiation among physiological and pathological, epileptic and non-epileptic events.However, VEEG monitoring is still the gold standard for differentiating the paroxysmal motor phenomena of epileptic and non-epileptic seizures, which can help to further clarify the etiology.In this paper, the clinical features, underlying pathophysiological mechanisms and differential diagnoses of non-epileptic paroxysmal motors in newborns were reviewed. Key words: Neonate; Non-epileptic seizures; Tremor; Myoclonus; Dystonia

Persistent seizure control in epileptic mice transplanted with gamma-aminobutyric acid progenitors.

A significant proportion of the more than 50 million people worldwide currently suffering with epilepsy are resistant to antiepileptic drugs (AEDs). As an alternative to AEDs, novel therapies based on cell transplantation offer an opportunity for long-lasting modification of epileptic circuits. To develop such a treatment requires careful preclinical studies in a chronic epilepsy model featuring unprovoked seizures, hippocampal histopathology, and behavioral comorbidities. Transplantation of progenitor cells from embryonic medial or caudal ganglionic eminence (MGE, CGE) were made in a well-characterized mouse model of status epilepticus-induced epilepsy (systemic pilocarpine). Behavioral testing (handling and open field), continuous video-electroencephalographic (vEEG) monitoring, and slice electrophysiology outcomes were obtained up to 270 days after transplantation (DAT). Post-hoc immunohistochemistry was used to confirm cell identity. MGE progenitors transplanted into the hippocampus of epileptic mice rescued handling and open field deficits starting at 60 DAT. In these same mice, an 84% to 88% reduction in seizure activity was observed between 180 and 210 DAT. Inhibitory postsynaptic current frequency, measured on pyramidal neurons in acute hippocampal slices at 270 DAT, was reduced in epileptic mice but restored to naïve levels in epileptic mice receiving MGE transplants. No reduction in seizure activity was observed in epileptic mice receiving intrahippocampal CGE progenitors. Our findings demonstrate that transplanted MGE progenitors enhance functional GABA-mediated inhibition, reduce spontaneous seizure frequency, and rescue behavioral deficits in a chronic epileptic animal model more than 6 months after treatment. Ann Neurol 2017;82:530-542.

Simultaneous occurrence of nonepileptic and epileptic seizures during a single period of in-patient video-electroencephalographic monitoring.

SummaryEpilepsy and psychogenic nonepileptic seizures (PNES) can coexist and may present in two forms: sequential and simultaneous. In sequential presentations, epileptic seizures (ES) are treated and PNES emerge later. Simultaneous recording of ES and PNES by video‐electroencephalogram (vEEG) is less well described. We retrospectively reviewed all patients diagnosed with PNES by vEEG following standard seizure induction practices over a 21‐month period. Within this cohort, we established the prevalence of coexisting epilepsy using clinical and electrographic data acquired from our epilepsy‐specific patient record. We identified patients with simultaneous PNES and ES recorded during a single vEEG admission, establishing the frequency and emergent timing of each type. Of our 262 monitored patients, 59 were diagnosed with PNES. Nineteen of the patients with PNES had coexisting epilepsy (prevalence rate of 7.3% or 32% of those with PNES). Sixteen patients had PNES and ES recorded during the same admission, and the remaining three patients had sequential PNES following successful treatment of ES. PNES occurred earlier (mean, within 1.21 days), with ES occurring later (mean, within 4.86 days). The simultaneous occurrence of PNES and ES recorded during a single admission is more common than previously reported. Identifying this group of patients may require a significantly longer period of vEEG monitoring and a detailed analysis of each individual's historical seizure events.

P327 Nonconvulsive status epilepticus caused by herpes encephalitis: Neurophysiological findings and contribution to intensive care unit management

Objectives Herpes simplex virus is a common form of sporadic encephalitis with a poor prognosis. Many patients require prolonged ICU management. We aim to underline the usefulness of V-EEG monitoring and qEEG for the management of acute encephalitis. Methods We report the case of a healthy 36 year old female with severe herpetic encephalitis requiring prolonged ICU stay. She was presented to our emergency department with diffuse myalgia, polyarticular pain and disorganized behaviour. We review relevant literature to HSV encephalitis and non-convulsive status epilepticus and we report the short-term and long term outcome and serial neurophysiological findings on this patient to this moment. Results V-EEG studies showed diffuse slow waves which decreased their amplitude and focalized on temporal areas when clonazepam was administered. qEEG studies showed diffuse high voltage slow waves generated in both temporal lobes that suggested non-convulsive status epilepticus. The patient suffered from tonic-clonic seizures and mandibular stereotyped movements that correlated with generalized and focal spikes patterns on the EEG. Subsequently the patient‘s condition ameliorated and electrographic abnormalities progressively disappeared with no residual findings. Discussion HSV-1 acute encephalitis is a severe neurological condition that may require long term V-EEG monitoring to provide a better outcome. Conclusion V-EEG monitoring may be a key tool for the correct management and treatment assessment of acute encephalitis. Different antiepileptic drugs combinations were used concomitantly to neurophysiological evaluation of their effectiveness. The patient is now seizure free with mild memory impairment and impulse control disorder.

Increased odds and predictive rates of MMPI-2-RF scale elevations in patients with psychogenic non-epileptic seizures and observed sex differences.

The Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) is a self-report instrument, previously shown to differentiate patients with epileptic seizures (ES) and psychogenic non-epileptic seizures (PNES). At present, the odds of MMPI-2-RF scale elevations in PNES patients, as well as the diagnostic predictive value of such scale elevations, remain largely unexplored. This can be of clinical utility, particularly when a diagnosis is uncertain. After looking at mean group differences, we applied contingency table derived odds ratios to a sample of ES (n=92) and PNES (n=77) patients from a video EEG (vEEG) monitoring unit. We also looked at the positive and negative predictive values (PPV, NPV), as well as the false discovery rate (FDR) and false omission rate (FOR) for scales found to have increased odds of elevation in PNES patients. This was completed for the overall sample, as well as the sample stratified by sex. The odds of elevations related to somatic concerns, negative mood, and suicidal ideation in the PNES sample ranged from 2 to 5 times more likely. Female PNES patients had 3-6 times greater odds of such scale elevations, while male PNES patients had odds of 5-15 times more likely. PPV rates ranged from 53.66% to 84.62%, while NPV rates ranged from 47.52% to 90.91%. FDR across scales ranged from 15.38% to 50%, while the FOR ranged from 9.09% to 52.47%. Consistent with prior research, PNES patients have greater odds of MMPI-2-RF scale elevations, particularly related to somatic concerns and mood disturbance. Female PNES patients endorsed greater emotional distress, including endorsement of suicide related items. Elevations of these scales could aid in differentiating PNES from ES patients, although caution is warranted due to the possibility of both false positives and the incorrect omissions of PNES cases.

Intracerebral delivery of the M2 polarizing cytokine interleukin 13 using mesenchymal stem cell implants in a model of temporal lobe epilepsy in mice.

Neuroinflammation plays a critical role in the pathophysiology of mesialtemporal lobe epilepsy. We aimed to evaluate whether intracerebral transplantation of interleukin 13-producing mesenchymal stem cells (IL-13 MSCs) induces an M2 microglia/macrophage activation phenotype in the hippocampus with an epileptogenic insult, thereby providing a neuroprotective environment with reduced epileptogenesis. Genetically engineered syngeneic IL-13 MSCs or vehicle was injected within the hippocampus 1week before the intrahippocampal kainic acid-induced status epilepticus (SE) in C57BL/6J mice. Neuroinflammation was evaluated at disease onset as well as during the chronic epilepsy period (9weeks). In addition, continuous video-electroencephalography (EEG) (vEEG) monitoring was obtained during the chronic epilepsy period (between 6 and 9weeks after SE). Evaluation of vEEG recordings suggested that IL-13 MSC grafts did not affect the severity and duration of SE or the seizure burden during the chronic epilepsy period, when compared to the vehicle treated SE mice. An M2-activation phenotype was induced in microglia/macrophages that infiltrated the -13 MSC graft site, as evidenced by the arginase1 expression at the graft site at both the 2-week and 9-week time-points. However, M2-activated immune cells were rarely observed outside the graft site and, accordingly, the neuroinflammatory response or cell loss related to SE induction was not altered by IL-13 MSC grafting. Moreover, an increase in the proportion of F4/80+ cells was observed in the IL-13 MSC group compared to the controls. Our data suggest that MSC-based IL-13 delivery to induce M2 glial activation does not provide any neuroprotective or disease-modifying effects in a mouse model of epilepsy. Moreover, use of cell grafting to deliver bioactive compounds for modulating neuroinflammation may have confounding effects in disease pathology of epilepsy due to the additional immune response generated by the grafted cells.

Effective withdrawal of antiepileptic drugs in premonitoring admission to capture seizures during limited video‐EEG monitoring

SummaryObjectiveWithdrawal of antiepileptic drugs (AEDs) is commonly applied to capture seizures in video‐EEG (vEEG) monitoring for patients with infrequent but intractable seizures. Because of the half‐life of AEDs, AED withdrawal during only vEEG tends to be inadequate to provoke seizures within the vEEG admission. We hypothesize that prewithdrawal of long‐half‐life AEDs in premonitoring admission (PMA) is safe and effective to capture seizures in the limited time of vEEG. We determined the effect of half‐life on the interval between AED withdrawal and seizure occurrence.MethodsWe collected 87 patients with three criteria: (1) seizure occurrence ≤3 per month; (2) AEDs ≥2; (3) AED withdrawal during their admission, among 126 consecutive patients who underwent vEEG in the Department of Neurosurgery, Hiroshima University Hospital between 2011 and 2014. We divided patients into two groups on the basis of half‐life of AED: Group A (23 patients) with phenobarbital (PB) and/or zonisamide (ZNS); Group B (64 patients) with other AEDs. In Group A, PB and ZNS were withdrawn during 4‐day PMA before vEEG started. Further AED withdrawal was performed during vEEG, depending on the seizure occurrence.ResultsThe number of AEDs on admission was significantly higher in Group A (2–6, 3.5 ± 0.9; range, mean ±SD) than in Group B (2–5, 2.8 ± 0.8) (p < 0.01). All 23 Group A patients and 13 (20%) Group B patients underwent AED withdrawal during PMA. Seizures occurred during PMA in two patients in both Group A (9%) and Group B (15%). The first seizure occurred significantly longer after the start of withdrawal in Group A (6.1 ± 2.0 days) than in Group B (2.8 ± 1.3 days) (p < 0.01). Seizures were equally captured between both groups: 96% in Group A and 92% in Group B during vEEG.SignificanceFor epilepsy patients who are treated with PB and/or ZNS, we recommend the planning of AED withdrawal during PMA before the start of vEEG to succeed in capturing seizures during the limited time of vEEG monitoring.

Prevalence and predictors of subclinical seizures during scalp video-EEG monitoring in patients with epilepsy

Objective: This study first aimed to establish the prevalence and predictors of subclinical seizures in patients with epilepsy undergoing video electroencephalographic monitoring, then to evaluate the relationship of sleep/wake and circadian pattern with subclinical seizures. Methods: We retrospectively reviewed the charts of 742 consecutive patients admitted to our epilepsy center between July 2012 and October 2014. Demographic, electro-clinical data and neuroimage were collected. Results: A total of 148 subclinical seizures were detected in 39 patients (5.3%) during video electroencephalographic monitoring. The mean duration of subclinical seizures was 47.18 s (range, 5–311). Pharmacoresistant epilepsy, abnormal MRI and the presence of interictal epileptiform discharges were independently associated with subclinical seizures in multivariate logistic regression analysis. Subclinical seizures helped localizing the presumed epileptogenic zone in 24 (61.5%) patients, and suggested multifocal epilepsy in five (12.8%). In addition, subclinical seizures occurred more frequently in sleep and night than wakefulness and daytime, respectively, and they were more likely seen between 21:00–03:00 h, and less likely seen between 09:00–12:00 h. Thirty patients (76.9%) had their first subclinical seizures within the first 24 h of monitoring while only 7.7% of patients had their first subclinical seizures detected within 20 min. Conclusion: Subclinical seizures are not uncommon in patients with epilepsy, particularly in those with pharmacoresistant epilepsy, abnormal MRI or interictal epileptiform discharges. Subclinical seizures occur in specific circadian patterns and in specific sleep/wake distributions. A 20-min VEEG monitoring might not be long enough to allow for their detection.

Postictal ammonia as a biomarker for electrographic convulsive seizures: A prospective study.

Transient hyperammonemia (THA) was reported to follow generalized convulsions without sufficient evidence to confirm the epileptic nature of those events. We aimed to determine if postictal THA can differentiate between different types of events as confirmed electroencephalographically using video-electroencephalography (vEEG) monitoring. In our prospective cohort, we screened all consented adults (>18 years) admitted to the epilepsy monitoring unit. Ammonia was checked at baseline, within 60 min of the event (for all patients) and 24 h after event (whenever possible). Patients were grouped into generalized convulsive seizures (GCS), psychogenic nonepileptic seizures with convulsions (PNES-C), or focal seizures (FS) based on vEEG. Data were analyzed using descriptive statistics and parametric/nonparametric methods. Of 78 patients enrolled, 13 had GCS, 8 had FS, and 9 had PNES-C. The groups were different with regard to gender (p = 0.04) and baseline ammonia (p = 0.02), but not age. The change in ammonia postictally from baseline was significantly different among the three groups (p = 0.004). The area under the receiver operator characteristic (ROC) curve for postictal ammonia to distinguish GCS from other groups was 0.88 (95% confidence interval [CI] 0.69-0.96) suggesting ammonia to be a good test differentiating epileptic GCS from other events. An ammonia level of ≥80 μmol/L correctly classified 80% of our patients (sensitivity 53.9%, specificity 100%). Our results provide objective evidence for the association between THA and GCS seizures utilizing vEEG monitoring, and a basis for future studies to determine the role of postictal ammonia as an inexpensive diagnostic test to diagnose GCS.

Number of patient-reported allergies helps distinguish epilepsy from psychogenic nonepileptic seizures.

Psychogenic nonepileptic seizures (PNES) are relatively common, accounting for 5-40% of visits to tertiary epilepsy centers. Inpatient video-electroencephalogram (vEEG) monitoring is the gold standard for diagnosis, but additional positive predictive tools are necessary given vEEG's relatively scarce availability. In this study, we investigated if the number of patient-reported allergies distinguishes between PNES and epilepsy. Excessive allergy-reporting, like PNES, may reflect somatization. Using electronic medical records, ICD-9 codes, and text-identification algorithms to search EEG reports, we identified 905 cases of confirmed PNES and 5187 controls with epilepsy but no PNES. Patients with PNES averaged more self-reported allergies than patients with epilepsy alone (1.93 vs. 1.00, p<0.001). Compared to those with no allergies, each additional allergy linearly increased the percentage of patients with PNES by 2.98% (R(2)=0.71) such that with ≥12 allergies, 12/28 patients (42.8%) had PNES compared to 349/3368 (11.6%) of the population with no allergies (odds ratio=6.49). This relationship remained unchanged with logistic regression analysis. We conclude that long allergy lists may help identify patients with PNES. We hypothesize that a tendency to inaccurately self-report allergies reflects a maladaptive externalization of psychologic distress and that a similar mechanism may be responsible for PNES in some patients with somatic symptom disorder.