Training size predictably improves machine learning-based epileptic seizure forecasting from wearables

Antiseizure medication (ASM) treatment duration for acute symptomatic neonatal seizures is variable. A randomized clinical trial of phenobarbital compared with placebo after resolution of acute symptomatic seizures closed early owing to low enrollment. To assess whether ASM discontinuation after resolution of acute symptomatic neonatal seizures and before hospital discharge is associated with functional neurodevelopment or risk of epilepsy at age 24 months. This comparative effectiveness study included 303 neonates with acute symptomatic seizures (282 with follow-up data and 270 with the primary outcome measure) from 9 US Neonatal Seizure Registry centers, born from July 2015 to March 2018. The centers all had level IV neonatal intensive care units and comprehensive pediatric epilepsy programs. Data were analyzed from June 2020 to February 2021. The primary exposure was duration of ASM treatment dichotomized as ASM discontinued vs ASM maintained at the time of discharge from the neonatal seizure admission. To enhance causal association, each outcome risk was adjusted for propensity to receive ASM at discharge. Propensity for ASM maintenance was defined by a logistic regression model including seizure cause, gestational age, therapeutic hypothermia, worst electroencephalogram background, days of electroencephalogram seizures, and discharge examination (all P ≤ .10 in a joint model except cause, which was included for face validity). Functional neurodevelopment was assessed by the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) at 24 months powered for propensity-adjusted noninferiority of early ASM discontinuation. Postneonatal epilepsy, a prespecified secondary outcome, was defined per International League Against Epilepsy criteria, determined by parent interview, and corroborated by medical records. Most neonates (194 of 303 [64%]) had ASM maintained at the time of hospital discharge. Among 270 children evaluated at 24 months (mean [SD], 23.8 [0.7] months; 147 [54%] were male), the WIDEA-FS score was similar for the infants whose ASMs were discontinued (101 of 270 [37%]) compared with the infants with ASMs maintained (169 of 270 [63%]) at discharge (median score, 165 [interquartile range, 150-175] vs 161 [interquartile range, 129-174]; P = .09). The propensity-adjusted average difference was 4 points (90% CI, -3 to 11 points), which met the a priori noninferiority limit of -12 points. The epilepsy risk was similar (11% vs 14%; P = .49), with a propensity-adjusted odds ratio of 1.5 (95% CI, 0.7-3.4; P = .32). In this comparative effectiveness study, no difference was found in functional neurodevelopment or epilepsy at age 24 months among children whose ASM was discontinued vs maintained at hospital discharge after resolution of acute symptomatic neonatal seizures. These results support discontinuation of ASM prior to hospital discharge for most infants with acute symptomatic neonatal seizures.

Epileptic seizures (ES) and psychogenic nonepileptic seizures (PNES) are difficult to differentiate when based on a patient's self-reported symptoms. This study proposes review of objective data captured by a surface electromyography (sEMG) wearable device for classification of events as ES or PNES. This may help clinicians accurately identify ES and PNES. Seventy-one subjects were prospectively enrolled across epilepsy monitoring units at VA Epilepsy Centers of Excellence. Subjects were concomitantly monitored using video EEG and a wearable sEMG epilepsy monitor, the Sensing Portable sEmg Analysis Characterization (SPEAC) System. Three epileptologists independently classified ES and PNES that contained upper extremity motor activity based on video EEG. The sEMG data from those events were automatically processed to provide a seizure score for event classification. After brief training (60 minutes), the sEMG data were reviewed by a separate group of four epileptologists to independently classify events as ES or PNES. According to video EEG review, 17 subjects experienced 34 events (15 ES and 19 PNES with upper extremity motor activity). The automated process correctly classified 87% of ES (positive predictive value = 88%, negative predictive value = 76%) and 79% of PNES, and the expert reviewers correctly classified 77% of ES (positive predictive value = 94%, negative predictive value = 84%) and 96% of PNES. The automated process and the expert reviewers correctly classified 100% of tonic-clonic seizures as ES, and 71 and 50%, respectively, of non-tonic-clonic ES. Automated and expert review, particularly in combination, of sEMG captured by a wearable seizure monitor (SPEAC System) may be able to differentiate ES (especially tonic-clonic) and PNES with upper extremity motor activity.

Neurotrophins promote neurogenesis and help regulate synaptic reorganization. Their dysregulation has been implicated in a number of neurologic and psychiatric disorders. Previous studies have shown decreased levels of brain-derived neurotrophic factor (BDNF) in the serum of patients with psychiatric disorders such as major depressive disorder (MDD) and conversion disorder (CD). In human patients with temporal lobe epilepsy, there is an increase in both BDNF mRNA and protein levels in surgically resected hippocampi compared to controls. One study of children with epilepsy has found normal to increased serum BDNF levels compared to controls. Plasma [corrected] BDNF levels have not been investigated in adult patients with epileptic seizures (ES). We hypothesized that BDNF would differentiate between ES and psychogenic nonepileptic seizures (PNES). We assessed plasma [corrected] BDNF immunoreactivity in 15 patients with ES, 12 patients with PNES, and 17 healthy volunteers. Plasma [corrected] BDNF levels were measured using an enzyme-linked immunoassay. Healthy controls showed higher BDNF levels (4,289 ± 1,810 pg/mL) compared to patients with PNES (1,033 ± 435 pg/mL) (p < 0.001). However, unexpectedly, healthy controls also showed higher levels of BDNF compared to patients with ES without comorbid MDD (977 ± 565 pg/mL) (p < 0.001). Unlike children, adults with epilepsy appear to have decreased levels of plasma [corrected] BDNF. Reduced plasma [corrected] BDNF levels can be used to differentiate adult patients with ES or PNES from healthy controls. Further human studies are needed to better understand the pathophysiology explaining the decreased plasma [corrected] BDNF levels found in epilepsy and in PNES.

To identify characteristics, predictors, and outcomes of acute symptomatic seizures (ASS) in cerebral venous thrombosis (CVT), we investigated 1,281 consecutive adult patients with CVT included from 12 hospitals within the International CVT Consortium. We defined ASS as any seizure between symptom onset and 7 days after diagnosis of CVT. We stratified ASS into prediagnosis and solely postdiagnosis ASS. Status epilepticus (SE) was also analyzed separately. We analyzed predictors for ASS and the association between ASS and clinical outcome (modified Rankin Scale) with multivariable logistic regression. Of 1,281 eligible patients, 441 (34%) had ASS. Baseline predictors for ASS were intracerebral hemorrhage (ICH; adjusted odds ratio [aOR] 4.1, 95% confidence interval [CI] 3.0-5.5), cerebral edema/infarction without ICH (aOR 2.8, 95% CI 2.0-4.0), cortical vein thrombosis (aOR 2.1, 95% CI 1.5-2.9), superior sagittal sinus thrombosis (aOR 2.0, 95% CI 1.5-2.6), focal neurologic deficit (aOR 1.9, 95% CI 1.4-2.6), sulcal subarachnoid hemorrhage (aOR 1.6, 95% CI 1.1-2.5), and female-specific risk factors (aOR 1.5, 95% CI 1.1-2.1). Ninety-three (7%) patients had solely postdiagnosis ASS, best predicted by cortical vein thrombosis (positive/negative predictive value 22%/92%). Eighty (6%) patients had SE, independently predicted by ICH, focal neurologic deficits, and cerebral edema/infarction. Neither ASS nor SE was independently associated with outcome. ASS occurred in one-third of patients with CVT and was associated with brain parenchymal lesions and thrombosis of the superficial system. In the absence of prediagnosis ASS, no subgroup was identified with sufficient risk of postdiagnosis ASS to justify prophylactic antiepileptic drug treatment. We found no association between ASS and outcome.

<h3>Background</h3> There are three common causes of Transient Loss of Consciousness (TLOC), syncope, epileptic and psychogenic nonepileptic seizures (PNES). Many individuals who have experienced TLOC initially receive an incorrect diagnosis...

Inflammatory processes may provoke epileptic seizures and seizures may promote an immune reaction. Hence, the systemic immune reaction is a tempting diagnostic and prognostic marker in epilepsy. We explored the immune response before and after epileptic and psychogenic non-epileptic seizures (PNES). Serum samples collected from patients with videoEEG-verified temporal or frontal lobe epilepsy (TLE or FLE) or TLE + PNES showed increased interleukin-6 (IL-6) levels in between seizures (interictally), compared to controls. Patients with PNES had no increase in IL-6. The IL-6 levels increased transiently even further within hours after a seizure (postictally) in TLE but not in FLE patients. The postictal to interictal ratio of additionally five immune factors were also increased in TLE patients only. We conclude that immune factors have the potential to be future biomarkers for epileptic seizures and that the heterogeneity among different epileptic and non-epileptic seizures may be disclosed in peripheral blood sampling independent of co-morbidities.

Technetium-99m-ethyl cysteinate dimer brain perfusion loss in pediatric postictal psychosis

Background Due to their semiological similarities, psychogenic nonepileptic seizures (PNESs) can occasionally hardly be differentiated from epileptic seizures (ESs), and long-term video-electroencephalographic monitoring (VEM) is needed for the differential diagnosis.Objective To investigate the time of the first clinical event and its distribution on the days of VEM in ES and PNES patients.Methods In total, a consecutive series of 48 PNES and 51 ES patients matched for gender and age were retrospectively and consecutively evaluated. The time distribution of the seizures during the day was noted. Seizure latency was determined as the time in hours from the start of the video-electroencephalographic recording to the first clinical event.Results The seizure latency was significantly shorter in PNES patients compared to ES patients (p < 0.001). Seventy-two percent of PNES patients and 49.1% of ES patients had their first seizure in the 24 hours of video-EEG recording (p = 0.023). Recording longer than 48 hours was required for 12.5% of PNES patients and 37.3% of ES patients (p = 0.006). While ESs were almost evenly distributed throughout the day, most PNESs occurred during the evening hours (p = 0.011).Conclusion We observed that the PNESs appeared earlier than the ESs in the VEM and were concentrated during daylight hours. Although not strictly reliable, seizure latency can contribute to the differential diagnosis of ES and PNES.

Objective To explore the relevance between the level changes of serum neuron⁃specific enolase (NSE) and neuronal damage in various seizure types of children with epilepsy. Methods According to the classification criteria of seizure types formulated by International League Against Epilepsy (ILAE) in 1981, 190 children with epilepsy were enrolled including tonic⁃clonic seizure group (41 cases), tonic seizure group (34 cases), clonic seizure group (22 cases), myoclonic seizure group (12 cases), atonic seizure group (17 cases), absence seizure group (22 cases), simple partial seizure group (21 cases) and complex partial seizure group (21 cases), and 64 healthy children were enrolled as control group. The long⁃ range vedio⁃electroencephalogram (VEEG) was operated and the blood samples were collected from these cases within 72 h after their seizures. Results The serum NSE levels of epileptic children were significantly higher than control group (P = 0.000). Among these seizure groups, serum NSE in myoclonic seizure group [(32.42 ± 6.62) ng/ml] was significantly higher than the other types, except for tonic⁃clonic seizure group (P = 0.062). There was no significant difference among the other types (P > 0.05, for all). According to rank correlation analysis, there was positive corrlation between serum NSE levels and VEEG abnormal intensity (rs = 0.613, P = 0.000). Conclusion The serum NSE were markedly increased in children with epilepsy after seizures, suggesting that a certain degree of neuronal damage may result from seizures; the higher NSE levels were, the more serious neuronal damage caused by epileptiform discharges was. The serum NSE levels in myoclonic seizure group and tonic⁃clonic seizure group were significantly higher than other seizure types, indicating the two kinds of seizures may result in greater neuronal damage. DOI：10.3969/j.issn.1672⁃6731.2012.05.013

Antiseizure Medication Use and Outcomes After Suspected or Confirmed Acute Symptomatic SeizuresZafar SF, Sivaraju A, Rubinos C, Ayub N, Awodutire PO, McKee Z, Chandan P, Byrnes M, Bhansali SA, Rice H, Smith-Ayala A, Haider MA, Tveter E, Erlich-Malona N, Ibanhes F, DeMarco A, Lewis S, Dhakar MB, Punia V. JAMA Neurol. 2024;81(11):1159–69. doi: 10.1001/jamaneurol.2024.3189.Importance: Antiseizure medications (ASMs) are frequently prescribed for acute symptomatic seizures and epileptiform abnormalities (EAs; eg, periodic or rhythmic patterns). There are limited data on factors associated with ASM use and their association with outcomes. Objectives: To determine factors associated with ASM use in patients with confirmed or suspected acute symptomatic seizures undergoing continuous electroencephalography, and to explore the association of ASMs with outcomes. Design, Setting, and Participants: This multicenter cohort study was performed between July 1 and September 30, 2021, at 5 US centers of the Post Acute Symptomatic Seizure Investigation and Outcomes Network. After screening 1717 patients, the study included 1172 hospitalized adults without epilepsy who underwent continuous electroencephalography after witnessed or suspected acute symptomatic seizures. Data analysis was performed from November 14, 2023, to February 2, 2024. Exposure: ASM treatment (inpatient ASM continuation ≥48 h). Main Outcomes and Measures: Factors associated with (1) ASM treatment, (2) discharge ASM prescription, and (3) discharge and 3-month Glasgow Outcome Scale score of 4 or 5 were ascertained. Results: A total of 1172 patients (median [IQR] age, 64 [52-75] years; 528 [45%] female) were included. Among them, 285 (24%) had clinical acute symptomatic seizures, 107 (9%) had electrographic seizures, and 364 (31%) had EAs; 532 (45%) received ASM treatment. Among 922 patients alive at discharge, 288 (31%) were prescribed ASMs. The respective frequencies of inpatient ASM treatment and discharge prescription were 82% (233 of 285) and 69% (169 of 246) for patients with clinical acute symptomatic seizures, 96% (103 of 107) and 95% (61 of 64) for electrographic seizures, and 64% (233 of 364) and 48% (128 of 267) for EAs. On multivariable analysis, acute and progressive brain injuries were independently associated with increased odds of inpatient ASM treatment (odds ratio [OR], 3.86 [95% CI, 2.06-7.32] and 8.37 [95% CI, 3.48-20.80], respectively) and discharge prescription (OR, 2.26 [95% CI, 1.04-4.98] and 10.10 [95% CI, 3.94-27.00], respectively). Admission to the neurology or neurosurgery service (OR, 2.56 [95% CI, 1.08-6.18]) or to the neurological intensive care unit (OR, 7.98 [95% CI, 3.49-19.00]) was associated with increased odds of treatment. Acute symptomatic seizures and EAs were significantly associated with increased odds of ASM treatment (OR, 14.30 [95% CI, 8.52-24.90] and 2.30 [95% CI, 1.47-3.61], respectively) and discharge prescription (OR, 12.60 [95% CI, 7.37-22.00] and 1.72 [95% CI, 1.00-2.97], respectively). ASM treatment was not associated with outcomes at discharge (OR, 0.96 [95% CI, 0.61-1.52]) or at 3 months after initial presentation (OR, 1.26 [95% CI, 0.78-2.04]). Among 623 patients alive and with complete data at 3 months after discharge, 30 (5%) had post-discharge seizures, 187 (30%) were receiving ASMs, and 202 (32%) had all-cause readmissions. Conclusions and Relevance: This study suggests that etiology and electrographic findings are associated with ASM treatment for acute symptomatic seizures and EAs; ASM treatment was not associated with functional outcomes. Comparative effectiveness studies are indicated to identify which patients may benefit from ASMs and to determine the optimal treatment duration.

Ictal crying in epileptic seizures and psychogenic nonepileptic seizures: What are the hints to differentiate them?

Objective To investigate the brain protection of intermittent hypoxia preconditioning (IHP) on rats with seizures induced by lithium-pilocarpine (Li-pilo). Methods 96 rats were randomly divided into control group, seizure group and four IHP-seizure group. The animal model of epilepsy was established by Li-pilo intraperitoneal injection in seizure group and four IHP-seizure groups (Li-pilo was injected 1, 3, 7, or 14 days after a 5-day regimen of IHP). Subsequently, 240 min video data of seizure behavior was tested, histological grade (HG) and neuronal density (ND) in rat hippocampal CA1 subfield via terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labeling (TUNEL) and Nissl’s staining. Results Modified Racine scales of induced seizure peaked on average between 50-150 min after Li-pilo administration. The average peak score in IHP-3 d seizure group [(1.42±0.50) points, P=0.007] was significantly lower than seizure group [(4.15±0.72) points] and IHP-1 d [(2.16±0.69) points, P=0.028]; 7 d [(2.26±0.53) points, P=0.030] seizure group. The average escape latency in seizure rats [(54.33±3.90) s was significantly longer than Control group [(36.95±15.71) s, P=0.011], IHP-1 d seizure group [(44.83±11.68) s, P=0.047], IHP-3 d seizure group [(38.75±15.32) s, P=0.012] and IHP-7 d seizure group [(44.73±11.18) s, P=0.045]. The neuronal apoptosis rate and HG in seizure group were also higher than the other groups. The average percentage of time in the probe quadrant and ND value in seizure rats [(29.63±4.95)%; (35.25±8.37) cells/HP] were obviously lower than Control group [(41.13±19.09)%, P=0.013; (110.35±9.87) cells/HP, P=0.000], IHP-1 d seizure group [(36.13±13.97)%, P=0.037; (65.31±7.25) cells/HP, P=0.007], IHP-3 d seizure group [(42.38±20.15)%, P=0.011; (98.50±14.20) cells/HP, P=0.000] and IHP-7 d seizure group [(33.94±8.75)%, P=0.040; (54.80±11.68) cells/HP, P=0.010]. Conclusion The results indicate that 5-day IHP manipulation can afford definite anti-epileptic functions to epileptic model rats. Key words: Hypoxia preconditioning; Epilepsy; Apoptosis; Neuroprotection; Rat

Clinical Neurophysiology: EEG–Video Monitoring

Validation of a predictive calculator to distinguish between patients presenting with dissociative versus epileptic seizures

Diffuse low-grade gliomas are highly epileptogenic brain tumours. We aimed to explore the natural course of epileptic seizures, their predictors and the prognostic significance of their occurrence in adult patients harbouring a diffuse low-grade glioma. An observational retrospective multicentre study examined 1509 patients with diffuse low-grade gliomas to identify mutual interactions between tumour characteristics, tumour course and epileptic seizures. At diagnosis, 89.9% of patients had epileptic seizures. Male gender (P = 0.003) and tumour location within functional areas (P = 0.001) were independent predictors of a history of epileptic seizures at diagnosis. Tumour volume, growth velocity, cortical location, histopathological subtype or molecular markers did not significantly affect epileptic seizure occurrence probability. Prolonged history of epileptic seizures (P < 0.001), insular location (P = 0.003) and tumour location close to functional areas (P = 0.038) were independent predictors of uncontrolled epileptic seizures at diagnosis. Occurrence of epileptic seizures (P < 0.001), parietal (P = 0.029) and insular (P = 0.002) locations were independent predictors of uncontrolled epileptic seizures after oncological treatment. Patient age (P < 0.001), subtotal (P = 0.007) and total (P < 0.001) resections were independent predictors of total epileptic seizure control after oncological treatment. History of epileptic seizures at diagnosis and total surgical resection were independently associated with increased malignant progression-free (P < 0.001 and P < 0.001) and overall (P < 0.001 and P = 0.016) survivals. Epileptic seizures are independently associated with diffuse low-grade glioma prognosis. Patients diagnosed with epileptic seizures and those with complete and early surgical resections have better oncological outcomes. Early and maximal surgical resection is thus required for diffuse low-grade gliomas, both for oncological and epileptological purposes.