Alcohol for seizure induction in the epilepsy monitoring unit.

RATIONALE: Seizure induction techniques are used in the epilepsy monitoring unit (EMU) to increase diagnostic yield and reduce length of stay. There are insufficient data on the efficacy of alcohol as an induction technique. METHODS: We performed a retrospective cohort study using six years of EMU data at our institution. We compared cases who received alcohol for seizure induction to matched controls who did not. The groups were matched on the following variables: age, reason for admission, length of stay, number of antiseizure medications (ASM) at admission, whether ASMs were tapered during admission, and presence of interictal epileptiform discharges. We used both propensity score and exact matching strategies. We compared the likelihood of epileptic seizures and nonepileptic events in cases versus controls using Kaplan-Meier time-to-event analysis, as well as odds ratios for these outcomes occurring at any time during the admission. RESULTS: We analyzed 256 cases who received alcohol (median dose 2.5 standard drinks) and 256 propensity score-matched controls. Cases who received alcohol were no more likely than controls to have an epileptic seizure (X2(1) = 0.01, p = 0.93) or nonepileptic event (X2(1) = 2.1, p = 0.14) in the first 48 h after alcohol administration. For the admission overall, cases were no more likely to have an epileptic seizure (OR 0.89, 95 % CI 0.61-1.28, p = 0.58), nonepileptic event (OR 0.97, CI 0.62-1.53, p = 1.00), nor require rescue benzodiazepine (OR 0.63, CI 0.35-1.12, p = 0.15). Stratified analyses revealed no increased risk of epileptic seizure in any subgroups. Sensitivity analysis using exact matching showed that results were robust to matching strategy. CONCLUSIONS: Alcohol was not an effective induction technique in the EMU. This finding has implications for counseling patients with epilepsy about the risks of drinking alcohol in moderation in their daily lives.

Clinical characteristics and surgical outcomes of epilepsy associated with temporal encephalocele: A systematic review.

Temporal encephaloceles (TE) are an under-identified, potentially intervenable cause of epilepsy. This systematic review consolidates the current data to identify the major clinical, neuroimaging, and EEG features and surgical outcomes of epilepsy associated with TE. Literature searches were carried out using MEDLINE, Embase, PsycINFO, Scopus, and Cochrane Library databases from inception to December 7, 2023. Studies were included if they described clinical, neuroimaging, EEG, or surgical data in ≥5 patients with TE and epilepsy. Of 562 studies identified in the search, 24 met the eligibility criteria, reporting 423 unique patients with both epilepsy and TE. Compared to epilepsy patients without TE, those with TE had a higher mean age of seizure onset and were less likely to have a history of febrile seizures. Seizure semiologies were variable, but primarily mirrored temporal lobe onset patterns. Epilepsy patients with TE had a higher likelihood of having clinical or radiographic features of idiopathic intracranial hypertension (IIH) than those without. Brain MRI may show ipsilateral mesial temporal sclerosis (16 %). CT scans of the skull base usually revealed bony defects near the TE (90 %). Brain PET scans primarily showed ipsilateral temporal lobe hypometabolism (80 %), mostly in the anterior temporal lobe (67 %). Scalp EEG mostly lateralized ipsilateral to the implicated TE (92 % seizure onset) and localized to the temporal lobe (96 %). Intracranial EEG revealed seizure onset near the TE (11 of 12 cases including TE-adjacent electrodes) with variable timing of spread to the ipsilateral hippocampus. After surgical treatment of the TE, the rate of Engel I or ILAE 1 outcomes at one year was 75 % for lesionectomy, 85 % for anterior temporal lobectomy (ATL), and 80 % for ATL with amygdalohippocampectomy. Further studies are needed to better elucidate the relationship between IIH, TE, and epilepsy, improve the identification of TE, and optimize surgical interventions.

A randomized phase 2b efficacy study in patients with seizure episodes with a predictable pattern using Staccato® alprazolam for rapid seizure termination.

OBJECTIVE: Alprazolam administered via the Staccato® breath-actuated device is delivered into the deep lung for rapid systemic exposure and is a potential therapy for rapid epileptic seizure termination (REST). We conducted an inpatient study (ENGAGE-E-001 [NCT03478982]) in patients with stereotypic seizure episodes with prolonged or repetitive seizures to determine whether Staccato alprazolam rapidly terminates seizures in a small observed population after administration under direct supervision. METHODS: Adult patients with established diagnosis of focal and/or generalized epilepsy with a documented history of seizure episodes with a predictable pattern were enrolled. They were randomized 1:1:1 to double-blind treatment of a single seizure event with one dose of Staccato alprazolam 1.0 mg or 2.0 mg, or Staccato placebo in an inpatient unit. The primary end point of the study was the proportion of responders in each treatment group achieving seizure activity cessation within 2 min after administration of study drug and no recurrence of seizure activity within 2 h. RESULTS: A total of 273 patients were screened, and 116 randomized patients received treatment with the study drug in the double-blind part. The proportion of treated patients who were responders was 65.8% for each of Staccato alprazolam 1.0 mg (n = 38; p = .0392) and 2.0 mg (n = 38; p = .0392), compared with 42.5% for Staccato placebo (n = 40). Staccato alprazolam was well tolerated when administered as a single dose of 1.0 or 2.0 mg: cough and somnolence were the most common adverse events (AEs) (both 14.5%), followed by dysgeusia (13.2%). AEs were mostly mild or moderate in intensity; there were no treatment-related serious AEs. SIGNIFICANCE: Both 1.0 mg and 2.0 mg doses of Staccato alprazolam demonstrated efficacy in rapidly terminating seizures in an inpatient setting and were well tolerated. The next step is a Phase 3 confirmatory study to demonstrate efficacy and safety of Staccato alprazolam for rapid cessation of seizures in an outpatient setting.

Video quality using outpatient smartphone videos in epilepsy: Results from the OSmartViE study.

BACKGROUND AND PURPOSE: The aim of this study was to evaluate the quality of smartphone videos (SVs) of neurologic events in adult epilepsy outpatients. The use of home video recording in patients with neurological disease states is increasing. Experts interpretation of outpatient smartphone videos of seizures and neurological events has demonstrated similar diagnostic accuracy to inpatient video-electroencephalography (EEG) monitoring. METHODS: A prospective, multicenter cohort study was conducted to evaluate SV quality in patients with paroxysmal neurologic events from August 15, 2015 through August 31, 2018. Epileptic seizures (ESs), psychogenic nonepileptic attacks (PNEAs), and physiologic nonepileptic events (PhysNEEs) were confirmed by video-EEG monitoring. Experts and senior neurology residents blindly viewed cloud-based SVs without clinical information. Quality ratings with regard to technical and operator-driven metrics were provided in responses to a survey. RESULTS: Forty-four patients (31 women, age 45.1 years [r = 20-82]) were included and 530 SVs were viewed by a mean of seven experts and six residents; one video per patient was reviewed for a mean of 133.8 s (r = 9-543). In all, 30 patients had PNEAs, 11 had ESs, and three had PhysNEEs. Quality was suitable in 70.8% of SVs (375/530 total views), with 36/44 (81.8%) patient SVs rated as adequate by the majority of reviewers. Accuracy improved with the presence of convulsive features from 72.4% to 98.2% in ESs and from 71.1% to 95.7% in PNEAs. An accurate diagnosis was given by all reviewers (100%) in 11/44 SVs (all PNEAs). Audio was rated as good by 86.2% of reviewers for these SVs compared with 75.4% for the remaining SVs (p = 0.01). Lighting was better in SVs associated with high accuracy (p = 0.06), but clarity was not (p = 0.59). Poor video quality yielded unknown diagnoses in 24.2% of the SVs reviewed. Features hindering diagnosis were limited interactivity, restricted field of view and short video duration. CONCLUSIONS: Smartphone video quality is adequate for clinical interpretation in the majority of patients with paroxysmal neurologic events. Quality can be optimized by encouraging interactivity with the patient, adequate duration of the SV, and enlarged field of view during videography. Quality limitations were primarily operational though accuracy remained for SV review of ESs and PNEAs.

Statins for the Prevention of Post-Stroke Seizure and Epilepsy Development: A Systematic Review and Meta-Analysis.

OBJECTIVES: Cerebrovascular disease is the leading cause of seizures and incident epilepsy of known etiology in older adults. Statins have increasingly garnered attention as a potential preventive strategy due to their pleiotropic effects beyond lipid-lowering, which may include neuroprotective and anti-epileptogenic properties. We aim to assess the evidence on statin use for prevention of post-stroke early-onset seizures and post-stroke epilepsy. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines, which was prospectively registered with PROSPERO (CRD42019144916). PubMed and Embase were searched from database inception to 05/2020 for English-language, full-text studies examining the association between statin use in adults and development of early-onset seizures (≤7 days post-stroke) or post-stroke epilepsy. Pooled analyses were based on random-effects models using the inverse-variance method. RESULTS: Of 182 citations identified, 175 were excluded due to duplication or ineligibility. The 7 eligible publications were all cohort studies from East Asia or South America, with a total of 53,579 patients. Pre-stroke statin use was not associated with post-stroke epilepsy (3 studies pooled: OR 1.14, CI 0.91-1.42). However, post-stroke statin use was associated with lower risk of both early-onset seizures (3 studies pooled: OR 0.36, CI 0.25-0.53), and post-stroke epilepsy (6 studies pooled: OR 0.64, CI 0.46-0.88). CONCLUSIONS: Review of 7 cohort studies suggested post-stroke, but not pre-stroke, statin use may be associated with reduced risk of early-onset seizures and post-stroke epilepsy. Further research is warranted to validate these findings in broader populations and better parse the temporal components of the associations.

Safety and tolerability associated with chronic intermittent use of diazepam buccal film in adult, adolescent, and pediatric patients with epilepsy.

OBJECTIVE: Diazepam buccal film (DBF) is in development for treatment of patients experiencing bouts of increased seizure activity. We assessed safety, tolerability, and usability of self- or caregiver-administered DBF in the outpatient setting. METHODS: Patients aged 2-65 years needing treatment with a rescue benzodiazepine at least once monthly were eligible for the study. DBF (5-17.5 mg) was dispensed based on age and body weight. Patients/caregivers administered DBF for up to five seizure episodes per month. Adverse events (AEs) and usability assessments were recorded after the first dose, then every 3 months. RESULTS: Onehundred eighteen patients who used ≥1 DBF dose (adults, n = 82; adolescents, n = 19; children, n = 17) were enrolled. Eleven treatment-related AEs (10 being mild or moderate in severity) occurred in nine (7.6%) patients over a mean of 243 days of follow-up. No patient discontinued participation because of AEs. Mild local buccal discomfort, buccal swelling, and cheek skin sensitivity were reported by one patient each. Twenty-two serious AEs were reported; one was treatment-related. The three deaths reported, all unrelated to DBF, resulted from seizures or seizure with brain malignancy. Self-administration by adults was attempted on 23.6% (188/795) of use occasions. Administration of DBF occurred under ictal or peri-ictal conditions on 49.5% (538/1087) of use occasions, and DBF was successfully administered on a first or second attempt on 96.6% (1050/1087) of use occasions. Overall, patients received their dose of DBF on 99.2% (1078/1087) of use occasions. A second DBF dose was required within 24 hours after the first dose on 8.5% (92/1087) of use occasions. SIGNIFICANCE: In this observational study of chronic intermittent use, DBF was easy to administer, safe, and well tolerated in adult, adolescent, and pediatric patients with epilepsy experiencing seizure emergencies. DBF can be readily self-administered by adults with epilepsy, as well as successfully administered by a caregiver in seizure emergencies.

Cenobamate (YKP3089) as adjunctive treatment for uncontrolled focal seizures in a large, phase 3, multicenter, open-label safety study.

OBJECTIVE: During the development of cenobamate, an antiseizure medication (ASM) for focal seizures, three cases of drug reaction with eosinophilia and systemic symptoms (DRESS) occurred. To mitigate the rate of DRESS, a start-low, go-slow approach was studied in an ongoing, open-label, multicenter study. Also examined were long-term safety of cenobamate and a method for managing the pharmacokinetic interaction between cenobamate, a 2C19 inhibitor, and concomitant phenytoin or phenobarbital. METHODS: Patients 18-70 years old with uncontrolled focal seizures taking stable doses of one to three ASMs were enrolled. Cenobamate 12.5 mg/d was initiated and increased at 2-week intervals to 25, 50, 100, 150, and 200 mg/d. Additional biweekly 50 mg/d increases to 400 mg/d were allowed. During titration, patients taking phenytoin or phenobarbital could not have their cenobamate titration rate or other concomitant ASMs adjusted; phenytoin/phenobarbital doses could be decreased by 25%-33%. RESULTS: At data cutoff (median treatment duration = 9 months), 1347 patients were enrolled, of whom 269 (20.0%) discontinued, most commonly due to adverse events (n = 137) and consent withdrawn for reason other than adverse event (n = 74); 1339 patients received ≥1 treatment dose (median modal dose = 200 mg). The most common treatment-emergent adverse events (TEAEs) were somnolence (28.1%), dizziness (23.6%), and fatigue (16.6%). Serious TEAEs occurred in 108 patients (8.1%), most commonly seizure (n = 14), epilepsy (n = 5), and pneumonia, fall, and dizziness (n = 4 each). No cases of DRESS were identified. In the phenytoin/phenobarbital groups, 43.4% (36/114) and 29.7% (11/51) of patients, respectively, had their doses decreased. At the end of titration, mean plasma phenytoin/phenobarbital levels were generally comparable to baseline. SIGNIFICANCE: No cases of DRESS were identified in 1339 patients exposed to cenobamate using a start-low (12.5 mg/d), go-slow titration approach. Cenobamate was generally well tolerated in the long term, with no new safety issues found. Phenytoin/phenobarbital dose reductions (25%-33%), when needed during cenobamate titration, maintained stable plasma levels.

Trends in oral anticoagulant co-prescription with antiepileptic drugs among adults with epilepsy, 2010-2018.

Treatment considerations for epilepsy patients requiring anticoagulation are changing, and actual prescribing practices have not been characterized. We used the 2010-2018 Optum Clinformatics® Data Mart Database to estimate the annual prevalence and distinguish the patterns of oral anticoagulants (OACs) co-dispensed with antiepileptic drugs (AEDs) among adults with epilepsy. Monotonic trends were assessed using the Spearman rank correlation coefficient (ρ). Multivariable logistic regression models were built to evaluate the associations of sociodemographic characteristics. Among 345,892 adults with epilepsy (56.5% female; median age 61, IQR 46-74) on studied AEDs, the prevalence per thousand of concurrent OACs increased from 58.4 in 2010 to 92.0 in 2018 (OR 1.63, CI 1.58-1.69). Direct-acting oral anticoagulant (DOAC) use rapidly increased from 2010 to 2018 (ρ = 1.00; P < 0.001), with a corresponding decrease in warfarin use (ρ = -0.97; P < 0.001). Among OAC/AED dispensings in 2018, warfarin was more likely to be co-dispensed with potentially interacting, enzyme-inducing antiepileptic drugs (EI-AEDs) versus presumably non-interacting, non-enzyme inducing antiepileptic drugs (OR 1.48, CI 1.38-1.59). Characteristics independently associated with concurrent OAC/EI-AED use included younger age, female sex, white race, net worth <$250 K, and lower education levels. Our findings demonstrate the expanding use and evolving patterns of OAC/AED co-dispensing, and ensuing critical need to further understanding regarding postulated interactions.

Fidaxomicin Compared With Oral Vancomycin for the Treatment of Severe Clostridium difficile-Associated Diarrhea: A Retrospective Review.

Purpose: The most recent published guidelines on Clostridium difficile-associated diarrhea (CDAD) developed by the Infectious Diseases Society of America (IDSA) were released in 2017 and outline its treatment based on severity of the disease and recurrence; however, a clear first-line agent has not been recommended specifically for severe CDAD. Methods: This retrospective chart review was approved by the institutional review board and consisted of three community hospitals and one academic medical center. To be included, patients need to meet criteria for severe CDAD and receive at least 72 hours of therapy. Patients received either oral vancomycin or fidaxomicin, in addition to other therapies for CDAD, and differences in outcomes such as cost obtained from a common charge center, rates of recurrence, time to recurrence as measured at time of positive to negative polymerase chain reaction (PCR) test, and mortality were assessed. Results: Of the 147 patients, 74 patients received fidaxomicin and 73 patients received oral vancomycin. The average hospitalization cost for patients receiving fidaxomicin was $129,338.69 and for patients receiving vancomycin was $153,563.81 (P = .26). Recurrence rates were lower with fidaxomicin compared with vancomycin (6.8% vs 17.6%; P = .047), and time to recurrence was longer with fidaxomicin versus vancomycin, but not statistically significant (96.8 ± 45.9 days vs 63.2 ± 66.9 days; P = .321). Mortality, length of stay in the intensive care unit, and overall length of stay were similar between the two therapies. Conclusions: In the treatment of severe CDAD, recurrence rates were lower and time to recurrence was higher with fidaxomicin compared with oral vancomycin. A clear financial benefit has yet to translate from these known findings.

Inhaled alprazolam rapidly suppresses epileptic activity in photosensitive participants.

OBJECTIVE: Treatment options for seizure clusters are limited; the need for easy-to-administer treatments remains. The Staccato system delivers drug deep into the lung via inhalation. In this phase 2a study, we investigated the ability of three different doses of Staccato alprazolam to suppress the electroencephalographic (EEG) photoparoxysmal response (PPR) compared with placebo in participants with photosensitive seizures. METHODS: Adults (18-60 years) with a diagnosis and history of PPR on EEG with or without an epilepsy diagnosis were eligible to participate. Participants received Staccato alprazolam 0.5, 1.0, and 2.0 mg, and Staccato placebo (twice) in random order. Intermittent photic stimulation and clinical assessments were performed at one predose and seven postdose time points. The primary endpoint of the study was the change in standardized photosensitivity range (SPR) in participants receiving each dose of Staccato alprazolam. RESULTS: Fifteen participants with a prior epilepsy diagnosis were screened; five were enrolled, randomized, and completed the study. All participants were white females with a mean (SD) age of 27.2 (6.8) years. All doses of Staccato alprazolam reduced the SPR at 2 minutes; the effect was sustained through 4 hours for the 0.5-mg dose and 6 hours for the 1.0- and 2.0-mg doses. The magnitude and duration of sedation and sleepiness were dose-related. Four participants (80%) experienced ≥1 adverse event (AE); none was severe or serious. Cough, diarrhea, dysgeusia, oral dysesthesia, sedation, and somnolence were experienced by two participants (40%) each. SIGNIFICANCE: This proof-of-concept study demonstrated that Staccato alprazolam 0.5, 1.0, and 2.0 mg rapidly suppressed epileptiform activity in photosensitive participants with epilepsy. The AE profile of Staccato alprazolam was similar to what has been reported for alprazolam for other indications. The results support further development of Staccato alprazolam as a rescue medication for the acute treatment of seizures.

Sentinel lymph node biopsy in head and neck rhabdomyosarcoma.

Head and neck rhabdomyosarcoma lymph node staging is challenging due to varied patterns of lymphatic drainage and the suboptimal predictive value of available imaging modalities. Furthermore, regional relapse rates are unacceptably high, and the toxicity of empiric radiation is undesirable in the pediatric and young adult population. In an attempt to improve locoregional control without excess morbidity, we have adopted routine sentinel lymph node biopsy in head and neck rhabdomyosarcoma, which is safe and feasible in pediatric patients. Of six procedures reported here, pathologic findings led to intensification of regional and/or systemic therapy in two patients.

Poor concordance among drug compendia for proposed interactions between enzyme-inducing antiepileptic drugs and direct oral anticoagulants.

PURPOSE: To assess concordance regarding proposed interactions between enzyme-inducing antiepileptic drugs (EI-AEDs) and direct oral anticoagulants (DOACs) in leading, international drug compendia. METHODS: We measured consistency of interaction reporting for each DOAC with a group of potent EI-AEDs among eight provider and consumer-focused drug compendia. Discrepant severity ranking systems were consolidated on a 0 to 4 scale. Percent agreement (PA) and Scott/Fleiss' Kappa (к) were used to quantify inter-compendia agreement on interaction listings, with linear weighting when consolidated severity rankings were taken into account (wPA and wк, respectively). RESULTS: For dabigatran, rivaroxaban, apixaban, and edoxaban, poor inter-compendia concordance was observed for interaction listings with EI-AEDs, with and without accounting for severity rankings (wPA: 0.54-0.72/wк: -0.08-0.03, and PA 0.47-0.79/к: -0.09-0.09, respectively). Conversely, betrixaban was consistently listed as not interacting with EI-AEDs in almost all assessed compendia, despite overlap in P-glycoprotein-based transport with other DOACs. Only 6/20 (30%) EI-AED/DOAC interactions were listed in all eight databases, and even in these six cases, severity rankings were universally discordant. Extreme inconsistencies in interaction reporting (some compendia assigning the highest possible severity ranking, while others reported no interactions) were observed in half of the individually examined interactions (10/20). CONCLUSIONS: Drug compendia are highly inconsistent in the inclusion and reported severity of interactions between EI-AEDs and DOACs. Generation of high-quality, real-world evidence from large-scale outcome studies is imperative to resolve discordance and provide clarity for clinical guidelines.

Differentiated Thyroid Cancer in the Pediatric/Adolescent Population: Evolution of Treatment.

Differentiated thyroid cancer (DTC) is the most common cancer in adolescents and young adults. In 2015, the American Thyroid Association published guidelines for management of pediatric DTC. We report our institutional experience and highlight changing practices and new opportunities. A retrospective analysis of all patients diagnosed with DTC from 2001 to 2016 was performed. Among 59 eligible patients, 31 (53%), 15 (25%), and 13 (22%) had low-risk, intermediate-risk, and high-risk disease, respectively. Half (15/31) of low-risk and all intermediate-risk/high-risk patients received radioactive iodine (I-131) ablation. For low-risk patients, average I-131 dose decreased from 80 to 42.05 mCi, and the percentage of patients who received I-131 decreased over time. Eleven of 16 patients with tumor genomic data were found to have somatic targetable (n=6) or germline (n=5) mutations. Persistent/recurrent disease was only present in high-risk (n=8) and intermediate-risk (n=1) patients. Two patients with iodine-refractory disease received trametinib to enhance radioiodine uptake. All patients were alive at follow-up (median, 5 y; range, 1 to 15 y). Coincident with the recent American Thyroid Association guidelines, the use of I-131 in low-risk patients has decreased over time in our practice. Tumor sequencing and cancer genetic evaluation may help redefine opportunities for treatment of high-risk patients and family counseling.

Validation of the mIBG skeletal SIOPEN scoring method in two independent high-risk neuroblastoma populations: the SIOPEN/HR-NBL1 and COG-A3973 trials.

BACKGROUND: Validation of the prognostic value of the SIOPEN mIBG skeletal scoring system in two independent stage 4, mIBG avid, high-risk neuroblastoma populations. RESULTS: The semi-quantitative SIOPEN score evaluates skeletal meta-iodobenzylguanidine (mIBG) uptake on a 0-6 scale in 12 anatomical regions. Evaluable mIBG scans from 216 COG-A3973 and 341 SIOPEN/HR-NBL1 trial patients were reviewed pre- and post-induction chemotherapy. The prognostic value of skeletal scores for 5-year event free survival (5 yr.-EFS) was tested in the source and validation cohorts. At diagnosis, both cohorts showed a gradual non-linear increase in risk with cumulative scores. Several approaches were explored to test the relationship between score and EFS. Ultimately, a cutoff score of ≤3 was the most useful predictor across trials. A SIOPEN score ≤ 3 pre-induction was found in 15% SIOPEN patients and in 22% of COG patients and increased post-induction to 60% in SIOPEN patients and to 73% in COG patients. Baseline 5 yr.-EFS rates in the SIOPEN/HR-NBL1 cohort for scores ≤3 were 47% ± 7% versus 26% ± 3% for higher scores at diagnosis (p < 0.007) and 36% ± 4% versus 14% ± 4% (p < 0.001) for scores obtained post-induction. The COG-A3973 showed 5 yr.-EFS rates for scores ≤3 of 51% ± 7% versus 34% ± 4% for higher scores (p < 0.001) at diagnosis and 43% ± 5% versus 16% ± 6% (p = 0.004) for post-induction scores. Hazard ratios (HR) significantly favoured patients with scores ≤3 after adjustment for age and MYCN-amplification. Optimal outcomes were recorded in patients who achieved complete skeletal response. CONCLUSIONS: Validation in two independent cohorts confirms the prognostic value of the SIOPEN skeletal score. In particular, patients with an absolute SIOPEN score > 3 after induction have very poor outcomes and should be considered for alternative therapeutic strategies.

A First Report of Secondary Hemophagocytic Lymphohistiocytosis Associated With Papillary Thyroid Carcinoma.

Secondary hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal immune-deficiency disorder that develops in response to diseases that produce strong immunologic activation, such as infection and malignancy. Although secondary HLH is reported to occur in association with various malignancies, there is no report of its association with thyroid cancer. We evaluated a 19-year-old man who presented with HLH. During investigation for an underlying cause of his HLH computed tomographic scan of the neck discovered thyroid nodules that were confirmed with biopsy to be papillary thyroid carcinoma. He was treated with surgery followed by radioactive iodine therapy and remains without any recurrence of malignancy or his secondary HLH. This report documents the first observation of HLH associated with thyroid cancer, and illustrates the need to include imaging of the neck while evaluating patients with secondary HLH for an underlying malignancy.

Detection of lymph node metastases in pediatric and adolescent/young adult sarcoma: Sentinel lymph node biopsy versus fludeoxyglucose positron emission tomography imaging-A prospective trial.

BACKGROUND: Lymph node metastases are an important cause of treatment failure for pediatric and adolescent/young adult (AYA) sarcoma patients. Nodal sampling is recommended for certain sarcoma subtypes that have a predilection for lymphatic spread. Sentinel lymph node biopsy (SLNB) may improve the diagnostic yield of nodal sampling, particularly when single-photon emission computed tomography/computed tomography (SPECT-CT) is used to facilitate anatomic localization. Functional imaging with positron emission tomography/computed tomography (PET-CT) is increasingly used for sarcoma staging and is a less invasive alternative to SLNB. To assess the utility of these 2 staging methods, this study prospectively compared SLNB plus SPECT-CT with PET-CT for the identification of nodal metastases in pediatric and AYA patients. METHODS: Twenty-eight pediatric and AYA sarcoma patients underwent SLNB with SPECT-CT. The histological findings of the excised lymph nodes were then correlated with preoperative PET-CT imaging. RESULTS: A median of 2.4 sentinel nodes were sampled per patient. No wound infections or chronic lymphedema occurred. SLNB identified tumors in 7 of the 28 patients (25%), including 3 patients who had normal PET-CT imaging of the nodal basin. In contrast, PET-CT demonstrated hypermetabolic regional nodes in 14 patients, and this resulted in a positive predictive value of only 29%. The sensitivity and specificity of PET-CT for detecting histologically confirmed nodal metastases were only 57% and 52%, respectively. CONCLUSIONS: SLNB can safely guide the rational selection of nodes for biopsy in pediatric and AYA sarcoma patients and can identify therapy-changing nodal disease not appreciated with PET-CT. Cancer 2017;155-160. © 2016 American Cancer Society.

FDG PET/CT appearance of local osteosarcoma recurrences in pediatric patients.

BACKGROUND: Osteosarcoma is the most common pediatric malignant bone tumor, frequently surgically managed with limb salvage rather than amputation. Local recurrences are seen in up to 9% of osteosarcoma patients, with CT and MRI imaging often limited by metal artifacts. OBJECTIVE: To describe the [F-18]2-fluoro-2-deoxyglucose (FDG) PET/CT appearance of local osteosarcoma recurrences with correlation to findings on other imaging modalities. MATERIALS AND METHODS: A retrospective review of pediatric osteosarcoma patients imaged with FDG PET/CT was performed in patients with pathologically proven local recurrences. FDG PET/CT findings were reviewed and correlated with available comparison imaging studies. RESULTS: Ten local osteosarcoma recurrences in eight pediatric osteosarcoma patients were imaged with FDG PET/CT. All eight patients had a local recurrence after limb salvage; two patients had a second local recurrence after amputation. All local recurrences were seen with FDG PET/CT, demonstrating solid (n=5) or peripheral/nodular (n=5) FDG uptake patterns. Maximum standard uptake values (SUVs) ranged from 3.0 to 15.7. In five recurrences imaged with FDG PET/CT and MRI, MRI was limited or nondiagnostic in three. In four recurrences imaged with FDG PET/CT and bone scan, the bone scan was negative in three. CONCLUSION: Local osteosarcoma recurrences are well visualized by FDG PET/CT, demonstrating either solid or peripheral/nodular FDG uptake with a wide range of maximum SUVs. FDG PET/CT demonstrates the full extent of local recurrences, while MRI can be limited by artifact from metallic hardware. PET/CT appears to be more sensitive than bone scan in detecting local osteosarcoma recurrences.

MIBG in Neuroblastoma Diagnostic Imaging and Therapy.

Neuroblastoma is a common malignancy observed in infants and young children. It has a varied prognosis, ranging from spontaneous regression to aggressive metastatic tumors with fatal outcomes despite multimodality therapy. Patients are divided into risk groups on the basis of age, stage, and biologic tumor factors. Multiple clinical and imaging tests are needed for accurate patient assessment. Iodine 123 ((123)I) metaiodobenzylguanidine (MIBG) is the first-line functional imaging agent used in neuroblastoma imaging. MIBG uptake is seen in 90% of neuroblastomas, identifying both the primary tumor and sites of metastatic disease. The addition of single photon emission computed tomography (SPECT) and SPECT/computed tomography to (123)I-MIBG planar images can improve identification and characterization of sites of uptake. During scan interpretation, use of MIBG semiquantitative scoring systems improves description of disease extent and distribution and may be helpful in defining prognosis. Therapeutic use of MIBG labeled with iodine 131 ((131)I) is being investigated as part of research trials, both as a single agent and in conjunction with other therapies. (131)I-MIBG therapy has been studied in patients with newly diagnosed neuroblastoma and those with relapsed disease. Development and implementation of an institutional (131)I-MIBG therapy research program requires extensive preparation with a focus on radiation protection.

Prospective detection of cortical dysplasia on clinical MRI in pediatric intractable epilepsy.

BACKGROUND: Cortical dysplasia is the most common cause of pediatric refractory epilepsy. MRI detection of epileptogenic lesion is associated with good postsurgical outcome. Additional electrophysiological information is suggested to be helpful in localization of cortical dysplasia. Educational measures were taken to increase the awareness of cortical dysplasia at our institution in the context of a recent International League Against Epilepsy (ILAE 2011) classification of cortical dysplasia. OBJECTIVE: To determine changes in the rate of prospective identification of cortical dysplasia on an initial radiology report and also evaluate the benefit of MRI review as part of a multidisciplinary epilepsy conference in identifying previously overlooked MRI findings. MATERIALS AND METHODS: We retrospectively evaluated surgically treated children with refractory epilepsy from 2007 to 2014 with cortical dysplasia on histopathology. We analyzed the initial radiology report, preoperative MRI interpretation at multidisciplinary epilepsy conference and subsequent retrospective MRI review with knowledge of the resection site. We recorded additional electrophysiological data and the presence of lobar concordance with the MRI findings. RESULTS: Of 78 children (44 MRI lesional) evaluated, 18 had initially overlooked MRI findings. Comparing 2007-2010 to 2011-2014, there was improvement in the rate of overlooked findings on the initial radiology report (54% vs. 13% of lesional cases, respectively; P = 0.008). The majority (72%) were identified at a multidisciplinary conference with lobar concordance of findings with at least one additional electrophysiological investigation in 89%. CONCLUSION: Awareness of current classification schemes of cortical dysplasia and image review in the context of a multidisciplinary conference can lead to improved MRI detection of cortical dysplasia in children.

Spondylolysis and Beyond: Value of SPECT/CT in Evaluation of Low Back Pain in Children and Young Adults.

Single photon emission computed tomography (SPECT)/computed tomography (CT) is ideally suited for assessment of low back pain in children and young adults. Spondylolysis is one of the most common structural causes of low back pain and is readily identified and characterized in terms of its chronicity and likelihood to heal. The value of SPECT/CT extends to identification and characterization of other causes of low back pain, including abnormalities of the posterior elements, developing vertebral endplate, transverse processes, and sacrum and sacroiliac joint. Some of the disease processes that are identifiable at SPECT/CT are similar to those that occur in adults (eg, facet hypertrophy) but may be accelerated in young patients by high-level athletic activities. Other processes (eg, limbus vertebrae) are more unique to children, related to injury of the developing spine. The authors review the spectrum of pars interarticularis abnormalities with emphasis on the imaging features of causes of pediatric low back pain other than spondylolysis.