Preoperative Behavioral Health, Opioid, and Antidepressant Utilization and 2-year Costs After Spinal Fusion-Revelations From Cluster Analysis.

STUDY DESIGN: Retrospective administrative claims database analysis. OBJECTIVE: Identify distinct presurgery health care resource utilization (HCRU) patterns among posterior lumbar spinal fusion patients and quantify their association with postsurgery costs. SUMMARY OF BACKGROUND DATA: Presurgical HCRU may be predictive of postsurgical economic outcomes and help health care providers to identify patients who may benefit from innovation in care pathways and/or surgical approach. METHODS: Privately insured patients who received one- to two-level posterior lumbar spinal fusion between 2007 and 2016 were identified from a claims database. Agglomerative hierarchical clustering (HC), an unsupervised machine learning technique, was used to cluster patients by presurgery HCRU across 90 resource categories. A generalized linear model was used to compare 2-year postoperative costs across clusters controlling for age, levels fused, spinal diagnosis, posterolateral/interbody approach, and Elixhauser Comorbidity Index. RESULTS: Among 18,770 patients, 56.1% were female, mean age was 51.3, 79.4% had one-level fusion, and 89.6% had inpatient surgery. Three patient clusters were identified: Clust1 (n = 13,987 [74.5%]), Clust2 (n = 4270 [22.7%]), Clust3 (n = 513 [2.7%]). The largest between-cluster differences were found in mean days supplied for antidepressants (Clust1: 97.1 days, Clust2: 175.2 days, Clust3: 287.1 days), opioids (Clust1: 76.7 days, Clust2: 166.9 days, Clust3: 129.7 days), and anticonvulsants (Clust1: 35.1 days, Clust2: 67.8 days, Clust3: 98.7 days). For mean medical visits, the largest between-cluster differences were for behavioral health (Clust1: 0.14, Clust2: 0.88, Clust3: 16.3) and nonthoracolumbar office visits (Clust1: 7.8, Clust2: 13.4, Clust3: 13.8). Mean (95% confidence interval) adjusted 2-year all-cause postoperative costs were lower for Clust1 ($34,048 [$33,265-$34,84]) versus both Clust2 ($52,505 [$50,306-$54,800]) and Clust3 ($48,452 [$43,007-$54,790]), P < 0.0001. CONCLUSION: Distinct presurgery HCRU clusters were characterized by greater utilization of antidepressants, opioids, and behavioral health services and these clusters were associated with significantly higher 2-year postsurgical costs. LEVEL OF EVIDENCE: 3.

Prospective observational study: Fast ripple localization delineates the epileptogenic zone.

OBJECTIVE: To investigate spatial correlation between interictal HFOs and neuroimaging abnormalities, and to determine if complete removal of prospectively identified interictal HFOs correlates with post-surgical seizure-freedom. METHODS: Interictal fast ripples (FRs: 250-500 Hz) in 19 consecutive children with pharmacoresistant focal epilepsy who underwent extra-operative electrocorticography (ECoG) recording were prospectively analyzed. The interictal FRs were sampled at 2000 Hz and were visually identified during 10 min of slow wave sleep. Interictal FRs, MRI and FDG-PET were delineated on patient-specific reconstructed three-dimensional brain MRI. RESULTS: Interictal FRs were observed in all patients except one. Thirteen out of 18 patients (72%) exhibited FRs beyond the extent of neuroimaging abnormalities. Fifteen of 19 children underwent resective surgery, and survival analysis with log-rank test demonstrated that complete resection of cortical sites showing interictal FRs correlated with longer post-operative seizure-freedom (p < 0.01). Complete resection of seizure onset zones (SOZ) also correlated with longer post-operative seizure-freedom (p = 0.01), yet complete resection of neuroimaging abnormalities did not (p = 0.43). CONCLUSIONS: Prospective visual analysis of interictal FRs was feasible, and it seemed to accurately localize epileptogenic zones. SIGNIFICANCE: Topological extent of epileptogenic region may exceed what is discernible by multimodal neuroimaging.

Pathogenic Cav3.2 channel mutation in a child with primary generalized epilepsy.

Two paternally-inherited missense variants in CACNA1H were identified and characterized in a 6-year-old child with generalized epilepsy. Febrile and unprovoked seizures were present in this child. Both variants were expressed in cis or isolation using human recombinant Cav3.2 calcium channels in tsA-201 cells. Whole-cell patch-clamp recordings indicated that one variant (c.3844C > T; p.R1282W) caused a significant increase in current density consistent with a pathogenic gain-of-function phenotype; while the other cis-related variant (c.5294C > T; p.A1765V) had a benign profile.

Impact of patient comorbidities on surgical site infection within 90 days of primary and revision joint (hip and knee) replacement.

BACKGROUND: The frequency of primary and revision total knee and hip replacements (pTKRs, rTKRs, pTHRs, and rTHRs, respectively) is increasing in the United States due to demographic changes. This study evaluated the impact of preoperative patient and clinical factors on the risk of surgical site infection (SSI) within the 90-day period after primary and revision total joint replacements (TJR). METHODS: A retrospective observational cohort study was designed using the IBM MarketScan and Medicare databases, 2009-2015. Thirty-four comorbidities were assessed for all patients, and multivariable logistic regression models were used to evaluate factors associated with higher odds of SSI after adjusting for other patient and clinical preoperative conditions. RESULTS: The study included a total of 335,134 TKRs and 163,547 THRs. SSI rates were 15.6% and 8.6% after rTKR and rTHR, respectively, compared with 2.1% and 2.1% for pTKR and pTHR, respectively. Comorbidities with the greatest adjusted effect on SSI across all TJRs were acquired immunodeficiency syndrome (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.06-2.34; P = .0232), paralysis (OR, 1.56; 95% CI, 1.26-1.94; P < .0001), coagulopathy (OR, 1.48; 95% CI, 1.36-1.62; P < .0001), metastatic cancer (1.48; 95% CI, 1.24-1.76; P < .0001), and congestive heart failure (OR, 1.39; 95% CI, 1.30-1.49; P < .0001). CONCLUSIONS: SSI occurred most commonly among patients after revision TJR and were related to many patient comorbidities, including diabetes, congestive heart failure, and coagulopathy, which were significantly associated with a higher risk of SSI after TJR.

Reoperations in intramedullary fixation of pertrochanteric hip fractures.

Objective: This study evaluated the frequency of reoperation within 1 year of initial intramedullary fixation for patients with pertrochanteric hip fracture and compared 1-year healthcare resource utilization and cost burden for patients with and without reoperation. Methods: This is a retrospective evaluation of medical claims from the US Centers for Medicare and Medicaid Standard Analytic File. Patients aged ≥65 years who underwent fixation with an intramedullary implant for a pertrochanteric fracture between 2013 and 2015 were included. Healthcare resources that were evaluated included skilled nursing facility (SNF), inpatient rehabilitation facility (IRF), readmissions, and outpatient hospital visits. All-cause payments for these services comprised overall cost burden. Generalized Linear Models were used to evaluate healthcare resources and cost burden over 1-year post-surgery and to adjust for confounding between patients with and without a reoperation. Results: A total of 6,423 Medicare patients were included in the analysis. Mean (SD) age was 82.4 (7.8) years, 76.0% were female, and 93.3% were white. A second hip surgery within 1 year after the index fixation procedure was performed in 414 patients (6.4%): 121 (29.2%) contralateral, 115 (27.8%) ipsilateral, and 178 (43.0%) without specified laterality. After adjusting for confounding factors, Medicare patients with ipsilateral reoperations had statistically significantly higher readmissions (100% vs 32.5%, p < 0.0001), outpatient hospital visits (96.4% vs 88.8%, p = 0.018), admissions to a SNF (88.5% vs 80.4%, p = 0.024), and admissions to an IRF (38.8% vs 22.0%, p < 0.0001) compared to patients without reoperations. The adjusted mean total all-cause payments ($90,162 vs $55,131, p < 0.0001) during the 1-year follow-up were statistically significantly higher among patients with reoperations as compared to patients without reoperations. Conclusions: Patients who require a second hip surgery after initial fixation with an intramedullary implant for pertrochanteric hip fractures have significantly higher 1-year healthcare resource utilization and 63.5% higher costs than patients without reoperation.

Comparative Analysis of Hospital Length of Stay and Discharge Status of Two Contemporary Primary Total Knee Systems.

This study compares the differences in hospital length of stay (LOS), operating room time (ORT), discharge status, and total hospital costs among primary total knee arthroplasty (TKA) patients implanted with one of two contemporary primary total knee systems. A retrospective cohort analysis of elective inpatient, primary, unilateral TKA patients in the United States from 2013 to 2014 was conducted using the Premier Perspective® hospital billing database. The included patients had a diagnosis for osteoarthritis and received an ATTUNE® Knee (Gradually Reducing Radius Knee) or Triathlon™ (Single Radius Knee) from a hospital where both devices were used. Patient, provider, and procedure characteristics were included in generalized estimating equation (GEE) models to explore the impact of device on LOS, ORT, discharge status, and costs accounting for clustering within hospitals. A 1:1 propensity score-matched sensitivity analysis was also conducted. There were 1,178 patients who received gradually reducing radius knee and 5,707 patients who received single radius knee. GEE models indicated that the adjusted mean LOS and ORT for patients who received gradually reducing radius knee were significantly shorter than those who received single radius knee (p < 0.001). The adjusted odds ratios for gradually reducing radius knee patients being discharged to a skilled nursing facility (SNF) or other facility were 39% lower than that for single radius knee patients (odds ratio = 0.61; 95% confidence interval: 0.50-0.75; p < 0.001). The adjusted mean costs for gradually reducing radius knee patients were significantly lower than the single radius knee patients ($12,824 [1,813] vs. $18,713 [1,505]; p < 0.01). Findings were similar in the propensity-matched cohort of 2,044 patients, which was balanced on baseline covariates between devices (standardized differences were ≤ 8%). Patients who received gradually reducing radius knee had a shorter LOS and ORT, were less likely to be discharged to a SNF or other facility, and had lower total hospital cost than those who received single radius knee. These outcomes are increasingly relevant as hospitals bear the financial burden for episodes of care, and will require optimization to achieve success under the Centers for Medicare and Medicaid Services' Comprehensive Care for Joint Replacement model.

Medical resource utilization and costs for total hip arthroplasty: benchmarking an anterior approach technique in the Medicare population.

AIMS: The anterior approach (AA) for total hip arthroplasty (THA) is associated with more rapid recovery when compared to traditional approaches. The purpose of this study was to benchmark healthcare resource utilization and costs for patients with THA via AA relative to matched patients. MATERIALS AND METHODS: This study queried Medicare claims data (2012-2014) to identify patients who received THA via an AA from experienced surgeons, and matched these patients to a control cohort (all THA approaches). Direct and propensity-score matching were employed to maximize similarity between patients and hospitals in the two cohorts. Hospital length of stay (LOS), the proportion of patients discharged to home or home health, and post-acute claim payments during the 90-day episode were assessed. Generalized estimating equations were applied to control for imbalances between the cohorts and clustering of outcomes within hospitals. RESULTS: A total of 1,794 patients were included after patient matching. Patients who received AA had significantly lower mean hospital LOS vs patients in the control group (2.06 ± 1.36 vs 2.98 ± 1.58 days, p < .0001). The adjusted proportion of patients discharged to home was nearly 20 percentage points higher in the AA cohort vs the control cohort (87.3% vs 68.7%, p < .0001). Post-acute claim payments for AA patients were nearly 50% lower than those for control patients ($4,139 vs $7,465, p < .0001). CONCLUSION: AA patients had significantly lower post-acute care resource use when compared to control patients. Further research is warranted to evaluate the cost effectiveness of AA among surgeons of varying experience levels.

AR2, a novel automatic muscle artifact reduction software method for ictal EEG interpretation: Validation and comparison of performance with commercially available software.

Objective: To develop a novel software method (AR2) for reducing muscle contamination of ictal scalp electroencephalogram (EEG), and validate this method on the basis of its performance in comparison to a commercially available software method (AR1) to accurately depict seizure-onset location. Methods: A blinded investigation used 23 EEG recordings of seizures from 8 patients. Each recording was uninterpretable with digital filtering because of muscle artifact and processed using AR1 and AR2 and reviewed by 26 EEG specialists. EEG readers assessed seizure-onset time, lateralization, and region, and specified confidence for each determination. The two methods were validated on the basis of the number of readers able to render assignments, confidence, the intra-class correlation (ICC), and agreement with other clinical findings. Results: Among the 23 seizures, two-thirds of the readers were able to delineate seizure-onset time in 10 of 23 using AR1, and 15 of 23 using AR2 (p<0.01). Fewer readers could lateralize seizure-onset (p<0.05). The confidence measures of the assignments were low (probable-unlikely), but increased using AR2 (p<0.05). The ICC for identifying the time of seizure-onset was 0.15 (95% confidence interval (CI), 0.11-0.18) using AR1 and 0.26 (95% CI 0.21-0.30) using AR2.  The EEG interpretations were often consistent with behavioral, neurophysiological, and neuro-radiological findings, with left sided assignments correct in 95.9% (CI 85.7-98.9%, n=4) of cases using AR2, and 91.9% (77.0-97.5%) (n=4) of cases using AR1. Conclusions: EEG artifact reduction methods for localizing seizure-onset does not result in high rates of interpretability, reader confidence, and inter-reader agreement. However, the assignments by groups of readers are often congruent with other clinical data. Utilization of the AR2 software method may improve the validity of ictal EEG artifact reduction.

Best Practices for Outpatient Anterior Cervical Surgery: Results From a Delphi Panel.

STUDY DESIGN: Delphi Panel expert panel consensus and narrative literature review. OBJECTIVE: To obtain expert consensus on best practices for patient selection and perioperative decision making for outpatient anterior cervical surgery (anterior cervical disc fusion (ACDF) and cervical total disc replacement (CTDR)). SUMMARY OF BACKGROUND DATA: Spine surgery in ambulatory settings is becoming a preferred option for both patients and providers. The transition from traditional inpatient environments has been enabled by innovation in anesthesia protocols and surgical technique, as well as favorable economics. Studies have demonstrated that anterior cervical surgery (ACDF and CTDR) can be performed safely on an outpatient basis. However, practice guidelines and evidence-based protocols to inform best practices for the safe and efficient performance of these procedures in same-day, ambulatory settings are lacking. METHODS: A panel of five neurosurgeons, three anesthesiologists, one orthopedic spine surgeon, and a registered nurse was convened to comprise a multidisciplinary expert panel. A three-round modified-Delphi method was used to generate best-practice statements. Predetermined consensus was set at 70% for each best-practice statement. RESULTS: A total of 94 consensus statements were reviewed by the panel. After three rounds of review, there was consensus for 83 best-practice statements, while 11 statements failed to achieve consensus. All statements within several perioperative categories (and subcategories) achieved consensus, including preoperative assessment (n = 8), home-care/follow-up (n = 2), second-stage recovery (n = 18), provider economics (n = 8), patient education (n = 14), discharge criteria (n = 4), and hypothermia prevention (n = 6). CONCLUSION: This study obtained expert-panel consensus on best practices for patient selection and perioperative decision making for outpatient anterior cervical surgery (ACDF/CTDR). Given a paucity of guidelines and a lack of established care pathways for ACDF/CTDR in same-day, ambulatory settings, results from this study can supplement available evidence in support of local protocol development for providers considering a transition to the outpatient environment. LEVEL OF EVIDENCE: 4.

Electroencephalographic patterns during sleep in children with chromosome 15q11.2-13.1 duplications (Dup15q).

Our objective was to define the EEG features during sleep of children with neurodevelopmental disorders due to copy number gains of 15q11-q13 (Dup15q). We retrospectively reviewed continuous EEG recordings of 42 children with Dup15q (mean age: eight years, 32 with idic15), and data collected included background activity, interictal epileptiform discharges, sleep organization, and ictal activity. Three patterns were recognized: Pattern 1: Alpha­delta sleep was noted in 14 children (33%), not associated with any clinical changes. Pattern 2: Electrical status epilepticus in sleep was noted in 15 children (35%), all diagnosed with treatmentresistant epilepsy. Thirteen of the 15 children had clinical seizures. Pattern 3: Frequent bursts of high amplitude bifrontal predominant, paroxysmal fast activity (12­15 Hz) during non-REM sleep was noted in 15 children (35%). All 15 children had treatment-resistant epilepsy. This is the first report of electroencephalographic patterns during sleep of children with Dup15q reporting alpha-delta rhythms, CSWS, and high amplitude fast frequencies. Alpha-delta rhythms are described in children with dysautonomia and/or mood disorders and CSWS in children with developmental regression. The significance of these findings in cognitive function and epilepsy for the children in our cohort needs to be determined with follow-up studies.

Conductive Plastic Electrodes Reduce EEG Artifact During Pediatric ECMO Therapy.

PURPOSE: Extracorporeal membrane oxygenation (ECMO) is a life-saving heart and lung bypass procedure that can cause substantial EEG artifact. Continuous EEG monitoring is nonetheless a helpful neuromonitoring tool for patients receiving ECMO therapy because neurologic complications are frequent, but factors such as sedation, neuromuscular blockade, and hemodynamic instability limit clinical and radiographic evaluation. We examined whether using conductive plastic electrodes in place of conventional gold electrodes reduces artifact in clinical EEG studies of pediatric ECMO patients. METHODS: Four masked electroencephalographers assessed artifact and its impact on overall EEG interpretation in samples from 21 consecutive EEGs recorded during ECMO therapy (14 gold and 7 plastic). A spectral power analysis then quantified 50- to 70-Hz artifact in a larger group of 14 gold and 34 plastic electrode studies during ECMO and 4 non-ECMO gold electrode studies. RESULTS: The masked electroencephalographers identified less artifact (P < 0.001) and indicated greater confidence in the accuracy of EEG interpretation (P < 0.001) among studies recorded with plastic electrodes. In quantitative analyses, ECMO was associated with greater 50- to 70-Hz power among studies using gold electrodes (P < 0.001) and gold electrodes exhibited greater 50- to 70-Hz power than plastic electrodes (P < 0.001). Contrasting studies in which most of the electroencephalographers believed that interpretation was (n = 12; 7 gold and 5 plastic) or was not (n = 7; all gold) compromised by artifact, 50- to 70-Hz power was similarly higher among the compromised studies (P < 0.001). CONCLUSION: Plastic electrodes substantially reduce the burden of electrical artifact in EEG studies performed on pediatric ECMO patients and improve confidence in EEG interpretation.

Seven-year cost-effectiveness of ProDisc-C total disc replacement: results from investigational device exemption and post-approval studies.

OBJECTIVE The purpose of this study was to evaluate the 7-year cost-effectiveness of cervical total disc replacement (CTDR) versus anterior cervical discectomy and fusion (ACDF) for the treatment of patients with single-level symptomatic degenerative disc disease. A change in the spending trajectory for spine care is to be achieved, in part, through the selection of interventions that have been proven effective yet cost less than other options. This analysis complements and builds upon findings from other cost-effectiveness evaluations of CTDR through the use of long-term, patient-level data from a randomized study. METHODS This was a 7-year health economic evaluation comparing CTDR versus ACDF from the US commercial payer perspective. Prospectively collected health care resource utilization and treatment effects (quality-adjusted life years [QALYs]) were obtained from individual patient-level adverse event reports and SF-36 data, respectively, from the randomized, multicenter ProDisc-C total disc replacement investigational device exemption (IDE) study and post-approval study. Statistical distributions for unit costs were derived from a commercial claims database and applied using Monte Carlo simulation. Patient-level costs and effects were modeled via multivariate probabilistic analysis. Confidence intervals for 7-year costs, effects, and net monetary benefit (NMB) were obtained using the nonparametric percentile method from results of 10,000 bootstrap simulations. The robustness of results was assessed through scenario analysis and within a parametric regression model controlling for baseline variables. RESULTS Seven-year follow-up data were available for more than 70% of the 209 randomized patients. In the base-case analysis, CTDR resulted in mean per-patient cost savings of $12,789 (95% CI $5362-$20,856) and per-patient QALY gains of 0.16 (95% CI -0.073 to 0.39) compared with ACDF over 7 years. CTDR was more effective and less costly in 90.8% of probabilistic simulations. CTDR was cost-effective in 99.8% of sensitivity analysis simulations and generated a mean incremental NMB of $20,679 (95% CI $6053-$35,377) per patient at a willingness-to-pay threshold of $50,000/QALY. CONCLUSIONS Based on this modeling evaluation, CTDR was found to be more effective and less costly over a 7-year time horizon for patients with single-level symptomatic degenerative disc disease. These results are robust across a range of scenarios and perspectives and are intended to support value-based decision making.

Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: A potential role for infantile spasms and Lennox-Gastaut syndrome.

There is a great need for safe and effective therapies for treatment of infantile spasms (IS) and Lennox-Gastaut syndrome (LGS). Based on anecdotal reports and limited experience in an open-label trial, cannabidiol (CBD) has received tremendous attention as a potential treatment for pediatric epilepsy, especially Dravet syndrome. However, there is scant evidence of specific utility for treatment of IS and LGS. We sought to document the experiences of children with IS and/or LGS who have been treated with CBD-enriched cannabis preparations. We conducted a brief online survey of parents who administered CBD-enriched cannabis preparations for the treatment of their children's epilepsy. We specifically recruited parents of children with IS and LGS and focused on perceived efficacy, dosage, and tolerability. Survey respondents included 117 parents of children with epilepsy (including 53 with IS or LGS) who had administered CBD products to their children. Perceived efficacy and tolerability were similar across etiologic subgroups. Eighty-five percent of all parents reported a reduction in seizure frequency, and 14% reported complete seizure freedom. Epilepsy was characterized as highly refractory with median latency from epilepsy onset to CBD initiation of five years, during which the patient's seizures failed to improve after a median of eight antiseizure medication trials. The median duration and the median dosage of CBD exposure were 6.8 months and 4.3mg/kg/day, respectively. Reported side effects were far less common during CBD exposure, with the exception of increased appetite (30%). A high proportion of respondents reported improvement in sleep (53%), alertness (71%), and mood (63%) during CBD therapy. Although this study suggests a potential role for CBD in the treatment of refractory childhood epilepsy including IS and LGS, it does not represent compelling evidence of efficacy or safety. From a methodological standpoint, this study is extraordinarily vulnerable to participation bias and limited by lack of blinded outcome ascertainment. Appropriately controlled clinical trials are essential to establish efficacy and safety.

Development and validation of a seizure prediction model in critically ill children.

PURPOSE: Electrographic seizures are common in encephalopathic critically ill children, but identification requires continuous EEG monitoring (CEEG). Development of a seizure prediction model would enable more efficient use of limited CEEG resources. We aimed to develop and validate a seizure prediction model for use among encephalopathic critically ill children. METHOD: We developed a seizure prediction model using a retrospectively acquired multi-center database of children with acute encephalopathy without an epilepsy diagnosis, who underwent clinically indicated CEEG. We performed model validation using a separate prospectively acquired single center database. Predictor variables were chosen to be readily available to clinicians prior to the onset of CEEG and included: age, etiology category, clinical seizures prior to CEEG, initial EEG background category, and inter-ictal discharge category. RESULTS: The model has fair to good discrimination ability and overall performance. At the optimal cut-off point in the validation dataset, the model has a sensitivity of 59% and a specificity of 81%. Varied cut-off points could be chosen to optimize sensitivity or specificity depending on available CEEG resources. CONCLUSION: Despite inherent variability between centers, a model developed using multi-center CEEG data and few readily available variables could guide the use of limited CEEG resources when applied at a single center. Depending on CEEG resources, centers could choose lower cut-off points to maximize identification of all patients with seizures (but with more patients monitored) or higher cut-off points to reduce resource utilization by reducing monitoring of lower risk patients (but with failure to identify some patients with seizures).

Hypsarrhythmia assessment exhibits poor interrater reliability: a threat to clinical trial validity.

OBJECTIVE: Hypsarrhythmia is the classic interictal electroencephalographic pattern associated with infantile spasms, and characterized by high voltage, disorganization, and multifocal independent epileptiform discharges. Given this seemingly simple definition, one might expect excellent interrater reliability (IRR) in the identification of this pattern. Alternatively, it may be argued that assessments of voltage and disorganization are fairly subjective, and thus quite challenging in borderline cases. We sought to test the IRR of hypsarrhythmia assessment in a systematic fashion. METHODS: Six blinded pediatric electroencephalographers from four centers reviewed 22 electroencephalography (EEG) samples from patients with infantile spasms. Each sample was 5 min in duration and included only wakefulness. Raters determined if each EEG was abnormal and if hypsarrhythmia was present/absent, and characterized relevant features: voltage, organization, epileptiform discharges, slowing, interictal attenuations, symmetry, and synchrony. In addition, raters indicated their level of confidence for each assessment. Multirater kappa statistics (κ) were calculated for the assessment of hypsarrhythmia and each feature. RESULTS: Although IRR was favorable in determining whether a study was normal or abnormal (κ=0.89), reliability was unfavorable for assessment of hypsarrhythmia (κ=0.40), modified hypsarrhythmia (κ=0.47), high voltage (κ=0.37), disorganization (κ=0.22), multifocal epileptiform discharges (κ=0.68), interictal voltage attenuations (κ=0.21), slowing (κ=0.20), asymmetry (κ=0.26), and asynchrony (κ=0.08). Despite generally unsatisfactory interrater agreement, raters consistently reported high confidence in assessments. SIGNIFICANCE: This study contradicts the view that hypsarrhythmia assessment is straightforward. Even small variability in the identification of hypsarrhythmia has potentially deleterious consequences for clinical care, as its presence or absence impacts decisions to pursue high-risk and high-cost therapies. These inconsistencies may similarly confound studies in which abolition of hypsarrhythmia is an outcome measure. There is a great need for practical, reliable, and unbiased measures of hypsarrhythmia.

Treatment of infantile spasms with very high dose prednisolone before high dose adrenocorticotropic hormone.

PURPOSE: This study investigated the short-term response to a standardized hormonal therapy protocol for treatment of infantile spasms. METHODS: Twenty-seven children with video electroencephalography (EEG)-confirmed infantile spasms received very high dose (8 mg/kg/day, max 60 mg/day) oral prednisolone for 2 weeks. Response (absence of both hypsarrhythmia and spasms) to prednisolone was ascertained by repeat overnight video-EEG. Responders were tapered over 2 weeks and nonresponders were immediately transitioned to high dose (150 IU/m(2)/day) intramuscular adrenocorticotropic hormone (ACTH) for two additional weeks. Response was again determined by overnight video-EEG after ACTH therapy. KEY FINDINGS: Sixty-three percent (17/27) of patients responded completely to prednisolone. Subsequently, 40% (4/10) of prednisolone nonresponders exhibited a complete response after an additional 2-week course with ACTH. Among 27 subjects with median follow-up of 13.5 months (interquartile range [IQR] 4.8-25.9), 12% (2/17) of prednisolone responders and 50% (2/4) of ACTH responders experienced a relapse between 2 and 9 months after initial response. SIGNIFICANCE: Very high dose prednisolone demonstrated significantly higher efficacy than previously reported for lower doses in prior studies. High dose ACTH may be superior to very high dose prednisolone, and in lieu of a definitive clinical trial, the choice between prednisolone and ACTH for initial treatment of infantile spasms remains controversial.

Electrographic seizures after convulsive status epilepticus in children and young adults: a retrospective multicenter study.

OBJECTIVE: To describe the prevalence, characteristics, and predictors of electrographic seizures after convulsive status epilepticus (CSE). STUDY DESIGN: This was a multicenter retrospective study in which we describe clinical and electroencephalographic (EEG) features of children (1 month to 21 years) with CSE who underwent continuous EEG monitoring. RESULTS: Ninety-eight children (53 males) with CSE (median age of 5 years) underwent subsequent continuous EEG monitoring after CSE. Electrographic seizures (with or without clinical correlate) were identified in 32 subjects (33%). Eleven subjects (34.4%) had electrographic-only seizures, 17 subjects (53.1%) had electroclinical seizures, and 4 subjects (12.5%) had an unknown clinical correlate. Of the 32 subjects with electrographic seizures, 15 subjects (46.9%) had electrographic status epilepticus. Factors associated with the occurrence of electrographic seizures after CSE were a previous diagnosis of epilepsy (P = .029) and the presence of interictal epileptiform discharges (P < .0005). The median (p25-p75) duration of stay in the pediatric intensive care unit was longer for children with electrographic seizures than for children without electrographic seizures (9.5 [3-22.5] vs 2 [2-5] days, Wilcoxon test, Z = 3.916, P = .0001). Four children (4.1%) died before leaving the hospital, and we could not identify a relationship between death and the presence or absence of electrographic seizures. CONCLUSIONS: After CSE, one-third of children who underwent EEG monitoring experienced electrographic seizures, and among these, one-third experienced entirely electrographic-only seizures. A previous diagnosis of epilepsy and the presence of interictal epileptiform discharges were risk factors for electrographic seizures.

Subclinical early posttraumatic seizures detected by continuous EEG monitoring in a consecutive pediatric cohort.

PURPOSE: Traumatic brain injury (TBI) is an important cause of morbidity and mortality in children, and early posttraumatic seizures (EPTS) are a contributing factor to ongoing acute damage. Continuous video-EEG monitoring (cEEG) was utilized to assess the burden of clinical and electrographic EPTS. METHODS: Eighty-seven consecutive, unselected (mild - severe), acute TBI patients requiring pediatric intensive care unit (PICU) admission at two academic centers were monitored prospectively with cEEG per established clinical TBI protocols. Clinical and subclinical seizures and status epilepticus (SE, clinical and subclinical) were assessed for their relation to clinical risk factors and short-term outcome measures. KEY FINDINGS: Of all patients, 42.5% (37/87) had seizures. Younger age (p = 0.002) and injury mechanism (abusive head trauma - AHT, p < 0.001) were significant risk factors. Subclinical seizures occurred in 16.1% (14/87), while 6.9% (6/87) had only subclinical seizures. Risk factors for subclinical seizures included younger age (p < 0.001), AHT (p < 0.001), and intraaxial bleed (p < 0.001). SE occurred in 18.4% (16/87) with risk factors including younger age (p < 0.001), AHT (p < 0.001), and intraaxial bleed (p = 0.002). Subclinical SE was detected in 13.8% (12/87) with significant risk factors including younger age (p < 0.001), AHT (p = 0.001), and intraaxial bleed (p = 0.004). Subclinical seizures were associated with lower discharge King's Outcome Scale for Childhood Head Injury (KOSCHI) score (p = 0.002). SE and subclinical SE were associated with increased hospital length of stay (p = 0.017 and p = 0.041, respectively) and lower hospital discharge KOSCHI (p = 0.007 and p = 0.040, respectively). SIGNIFICANCE: cEEG monitoring significantly improves detection of seizures/SE and is the only way to detect subclinical seizures/SE. cEEG may be indicated after pediatric TBI, particularly in younger children, AHT cases, and those with intraaxial blood on computerized tomography (CT).

Electroencephalography monitoring in critically ill children: current practice and implications for future study design.

PURPOSE: Survey data indicate that continuous electroencephalography (EEG) (CEEG) monitoring is used with increasing frequency to identify electrographic seizures in critically ill children, but studies of current CEEG practice have not been conducted. We aimed to describe the clinical utilization of CEEG in critically ill children at tertiary care hospitals with a particular focus on variables essential for designing feasible prospective multicenter studies evaluating the impact of electrographic seizures on outcome. METHODS: Eleven North American centers retrospectively enrolled 550 consecutive critically ill children who underwent CEEG. We collected data regarding subject characteristics, CEEG indications, and CEEG findings. KEY FINDINGS: CEEG indications were encephalopathy with possible seizures in 67% of subjects, event characterization in 38% of subjects, and management of refractory status epilepticus in 11% of subjects. CEEG was initiated outside routine work hours in 47% of subjects. CEEG duration was <12 h in 16%, 12-24 h in 34%, and >24 h in 48%. Substantial variability existed among sites in CEEG indications and neurologic diagnoses, yet within each acute neurologic diagnosis category a similar proportion of subjects at each site had electrographic seizures. Electrographic seizure characteristics including distribution and duration varied across sites and neurologic diagnoses. SIGNIFICANCE: These data provide a systematic assessment of recent CEEG use in critically ill children and indicate variability in practice. The results suggest that multicenter studies are feasible if CEEG monitoring pathways can be standardized. However, the data also indicate that electrographic seizure variability must be considered when designing studies that address the impact of electrographic seizures on outcome.

Electrographic seizures in pediatric ICU patients: cohort study of risk factors and mortality.

OBJECTIVES: We aimed to determine the incidence of electrographic seizures in children in the pediatric intensive care unit who underwent EEG monitoring, risk factors for electrographic seizures, and whether electrographic seizures were associated with increased odds of mortality. METHODS: Eleven sites in North America retrospectively reviewed a total of 550 consecutive children in pediatric intensive care units who underwent EEG monitoring. We collected data on demographics, diagnoses, clinical seizures, mental status at EEG onset, EEG background, interictal epileptiform discharges, electrographic seizures, intensive care unit length of stay, and in-hospital mortality. RESULTS: Electrographic seizures occurred in 162 of 550 subjects (30%), of which 61 subjects (38%) had electrographic status epilepticus. Electrographic seizures were exclusively subclinical in 59 of 162 subjects (36%). A multivariable logistic regression model showed that independent risk factors for electrographic seizures included younger age, clinical seizures prior to EEG monitoring, an abnormal initial EEG background, interictal epileptiform discharges, and a diagnosis of epilepsy. Subjects with electrographic status epilepticus had greater odds of in-hospital death, even after adjusting for EEG background and neurologic diagnosis category. CONCLUSIONS: Electrographic seizures are common among children in the pediatric intensive care unit, particularly those with specific risk factors. Electrographic status epilepticus occurs in more than one-third of children with electrographic seizures and is associated with higher in-hospital mortality.