Detethering of MRI-Demonstrated Tethered Cord Syndrome.

INTRODUCTION: Recognition of tethered cord syndrome (TCS) in children is important because as the child grows, the spinal cord is stretched, leading to ischemia and subsequent neurological deficits, including bowel or bladder dysfunction, back and leg pain, or lower extremity weakness. Imaging findings raising concerns for tethering include presence of a fatty and/or thickened filum or a conus medullaris located caudal to L2. OBJECTIVES: The objective of this study was to describe the symptomatic presentation of TCS in our institution, detect demographic and diagnostic predictors of signs and symptoms, assess changes in symptoms over time, and examine whether demographic and diagnostic variables affect changes in symptoms over time. METHODS: Using a retrospective chart review from patients who underwent detethering at our institution between April 1, 2015 and March 31, 2019, we report on the signs and symptoms of patients undergoing detethering surgery at presentation and examine possible demographic and diagnostic predictors of those symptoms and changes in symptoms over time. Logistic regression analyses were used to determine whether symptoms at presentation were related to demographic and diagnostic predictors and to assess a change in symptoms over time. RESULTS: A total of 273 patients underwent detethering and were analyzed. Of these, 144 (53%) were <5 years of age, 151 (55%) were male, 233 (85%) had a fatty filum, 179 (66%) had a thickened filum, and 106 (39%) had a low-lying conus. Patients <5 years of age were less likely to have urological, gastrointestinal, and neurological or orthopedic symptoms; patients with thickened fila (i.e., greater than 2 mm in diameter regardless of fat-infiltration) were less likely to have urological symptoms; and patients with low-lying coni were less likely to have gastrointestinal symptoms. Patients exhibiting symptoms at presentation had reduced rates of symptoms at the follow-up, but a reduction in rates of symptoms over time was unrelated to demographic or diagnostic variables. Surprisingly, 123 (45%) patients presented with intractable constipation. CONCLUSION: In the population studied, several presenting symptoms, particularly constipation, were commonly reported. Children <5 years old were less likely to manifest clinically evident neurological/orthopedic, urological, and gastrointestinal symptoms than the older cohorts. Patients were less likely to report symptoms at both their first and second postoperative visit compared to presentation.

Evaluation of pediatric glioma outcomes using intraoperative MRI: a multicenter cohort study.

BACKGROUND: The use of intraoperative MRI (iMRI) during treatment of gliomas may increase extent of resection (EOR), decrease need for early reoperation, and increase progression-free and overall survival, but has not been fully validated, particularly in the pediatric population. OBJECTIVE: To assess the accuracy of iMRI to identify residual tumor in pediatric patients with glioma and determine the effect of iMRI on decisions for resection, complication rates, and other outcomes. METHODS: We retrospectively analyzed a multicenter database of pediatric patients (age ≤ 18 years) who underwent resection of pathologically confirmed gliomas. RESULTS: We identified 314 patients (mean age 9.7 ± 4.6 years) with mean follow-up of 48.3 ± 33.6 months (range 0.03-182.07 months) who underwent surgery with iMRI. There were 201 (64.0%) WHO grade I tumors, 57 (18.2%) grade II, 24 (7.6%) grade III, 9 (2.9%) grade IV, and 23 (7.3%) not classified. Among 280 patients who underwent resection using iMRI, 131 (46.8%) had some residual tumor and underwent additional resection after the first iMRI. Of the 33 tissue specimens sent for pathological analysis after iMRI, 29 (87.9%) showed positive tumor pathology. Gross total resection was identified in 156 patients (55.7%), but this was limited by 69 (24.6%) patients with unknown EOR. CONCLUSIONS: Analysis of the largest multicenter database of pediatric gliomas resected using iMRI demonstrated additional tumor resection in a substantial portion of cases. However, determining the impact of iMRI on EOR and outcomes remains challenging because iMRI use varies among providers nationally. Continued refinement of iMRI techniques for use in pediatric patients with glioma may improve outcomes.

Clinically Significant Visual Deficits after Laser Interstitial Thermal Therapy for Mesiotemporal Epilepsy.

BACKGROUND: Laser interstitial thermal therapy (LITT) has recently gained popularity as a minimally invasive surgical option for the treatment of mesiotemporal epilepsy (mTLE). Similar to traditional open procedures for epilepsy, the most frequent neurological complications of LITT are visual deficits; however, a critical analysis of these injuries is lacking. OBJECTIVES: To evaluate the visual deficits that occur after LITT for mTLE and their etiology. METHOD: We surveyed five academic epilepsy centers that regularly perform LITT for cases of self-reported postoperative visual deficits. For these patients all pre-, intra- and postoperative MRIs were co-registered with an anatomic atlas derived from 7T MRI data. This was used to estimate thermal injury to early visual pathways and measure imaging variables relevant to the LITT procedure. Using logistic regression, we then compared 14 variables derived from demographics, mesiotemporal anatomy, and the surgical procedure for the patients with visual deficits to a normal cohort comprised of the first 30 patients to undergo this procedure at a single institution. RESULTS: Of 90 patients that underwent LITT for mTLE, 6 (6.7%) reported a postoperative visual deficit. These included 2 homonymous hemianopsias (HHs), 2 quadrantanopsias, and 2 cranial nerve (CN) IV palsies. These deficits localized to the posterior aspect of the ablation, corresponding to the hippocampal body and tail, and tended to have greater laser energy delivered in that region than the normal cohort. The patients with HH had insult localized to the lateral geniculate nucleus, which was -associated with young age and low choroidal fissure CSF volume. Quadrantanopsia, likely from injury to the optic radiation in Meyer's loop, was correlated with a lateral trajectory and excessive energy delivered at the tail end of the ablation. Patients with CN IV injury had extension of contrast to the tentorial edge associated with a mesial laser trajectory. CONCLUSIONS: LITT for epilepsy may be complicated by various classes of visual deficit, each with distinct etiology and clinical significance. It is our hope that by better understanding these injuries and their mechanisms we can eventually reduce their occurrence by identifying at-risk patients and trajectories and appropriately tailoring the ablation procedure.

Temporal lobe pleomorphic xanthoastrocytoma and acquired BRAF mutation in an adolescent with the constitutional 22q11.2 deletion syndrome.

DiGeorge syndrome, or velocardiofacial syndrome (DGS/VCFS), is a rare and usually sporadic congenital genetic disorder resulting from a constitutional microdeletion at chromosome 22q11.2. While rare cases of malignancy have been described, likely due to underlying immunodeficiency, central nervous system tumors have not yet been reported. We describe an adolescent boy with DGS/VCFS who developed a temporal lobe pleomorphic xanthoastrocytoma. High-resolution single nucleotide polymorphism array studies of the tumor confirmed a constitutional 22q11.21 deletion, and revealed acquired gains, losses and copy number neutral loss of heterozygosity of several chromosomal regions, including a homozygous deletion of the CDKN2A/B locus. The tumor also demonstrated a common V600E mutation in the BRAF oncogene. This is the first reported case of a patient with DiGeorge syndrome developing a CNS tumor of any histology and expands our knowledge about low-grade CNS tumor molecular genetics.

Magnetic resonance imaging-guided laser interstitial thermal therapy as treatment for intractable insular epilepsy in children.

OBJECTIVE Seizure onset within the insula is increasingly recognized as a cause of intractable epilepsy. Surgery within the insula is difficult, with considerable risks, given the rich vascular supply and location near critical cortex. MRI-guided laser interstitial thermal therapy (LiTT) provides an attractive treatment option for insular epilepsy, allowing direct ablation of abnormal tissue while sparing nearby normal cortex. Herein, the authors describe their experience using this technique in a large cohort of children undergoing treatment of intractable localization-related epilepsy of insular onset. METHODS The combined epilepsy surgery database of Cook Children's Medical Center and Dell Children's Hospital was queried for all cases of insular onset epilepsy treated with LiTT. Patients without at least 6 months of follow-up data and cases preoperatively designated as palliative were excluded. Patient demographics, presurgical evaluation, surgical plan, and outcome were collected from patient charts and described. RESULTS Twenty patients (mean age 12.8 years, range 6.1-18.6 years) underwent a total of 24 LiTT procedures; 70% of these patients had normal findings on MRI. Patients underwent a mean follow-up of 20.4 months after their last surgery (range 7-39 months), with 10 (50%) in Engel Class I, 1 (5%) in Engel Class II, 5 (25%) in Engel Class III, and 4 (20%) in Engel Class IV at last follow-up. Patients were discharged within 24 hours of the procedure in 15 (63%) cases, in 48 hours in 6 (24%) cases, and in more than 48 hours in the remaining cases. Adverse functional effects were experienced following 7 (29%) of the procedures: mild hemiparesis after 6 procedures (all patients experienced complete resolution or had minimal residual dysfunction by 6 months), and expressive language dysfunction after 1 procedure (resolved by 3 months). CONCLUSIONS To their knowledge, the authors present the largest cohort of pediatric patients undergoing insular surgery for treatment of intractable epilepsy. The patient outcomes suggest that LiTT can successfully treat intractable seizures originating within the insula and offers an attractive alternative to open resection. This is the first description of LiTT applied to insular epilepsy and represents one of only a few series describing the use of LiTT in children. The results indicate that seizure reduction after LiTT compares favorably to that after conventional open surgical techniques.

Monomorphous angiocentric glioma: a distinctive epileptogenic neoplasm with features of infiltrating astrocytoma and ependymoma.

We present 8 examples of a neoplasm with features of both astrocytoma and ependymoma that may represent a distinct clinicopathologic entity. The cerebral hemispheric tumors occurred in patients that were 3, 4, 12, 14, 15, 26, 30, and 37 years of age. All presented with seizures that, with the exception of 2, began in childhood. Magnetic resonance imaging studies showed ill-defined, T2-hyperintense, generally noncontrast-enhancing lesions that, although centered on the cortex or amygdala, extended into the underlying white matter for a short distance. Histologically, the variably infiltrative tumors were distinctively angiocentric with well-developed perivascular pseudorosettes in some cases. Longitudinal and/or circumferential orientations of perivascular cells were common also. The cells were uniform in their cytologic features from case to case and were bipolar in all but one case. A glial nature was inferred from immunoreactivity for GFAP, and ependymal differentiation was suggested by positivity for EMA in three cases and ultrastructural features in one. Overall, the tumors were biologically indolent except for one that recurred and ultimately proved fatal.

Epilepsy surgery for early infantile epileptic encephalopathy (ohtahara syndrome).

Early infantile epileptic encephalopathy or Ohtahara syndrome is the earliest form of the age-dependent epileptic encephalopathies. Its manifestations include tonic spasms, focal motor seizures, suppression burst pattern, pharmaco-resistance, and dismal prognosis. The purpose of this study was to evaluate the effectiveness of epilepsy surgery in selected infants. We identified 11 patients, 9 from the literature and 2 from our institution that fulfilled diagnostic criteria of Ohtahara syndrome and had undergone epilepsy surgery in infancy. Seven of the 11 infants have remained seizure free (Engel class IA) and four are reportedly having rare to infrequent seizures (Engel class IIB). All patients experienced "catch up" development. In contrast to Ohtahara's15 pharmacotherapy managed patients, who had a mortality rate of approximately fifty percent, and those that survived continued to have seizures and were severely impaired, the outcome of selected surgically managed patients is much more favorable.

Atypical imaging evolution of sturge-weber syndrome without facial nevus.

We report a patient with Sturge-Weber syndrome without facial angioma, who presented with seizures and normal initial imaging results. The patient experienced several years without seizures before a sudden increase in seizure frequency, followed by an atypical evolution of imaging findings prompting biopsy to establish the diagnosis. This case highlights not only the rare presentation of isolated leptomeningeal angiomatosis, but also the potential for atypical evolution of imaging findings through the course of the disease. We detail the imaging findings of our case and review the potential pathophysiological basis for this appearance. Our experience suggests that repeat imaging is warranted in patients with suspected Sturge-Weber syndrome or those with intractable cryptogenic epilepsy, because some imaging features of Sturge-Weber syndrome may manifest over time.

Lorcaserin (APD356), a selective 5-HT(2C) agonist, reduces body weight in obese men and women.

Lorcaserin (APD356) is a potent, selective 5-HT(2C) agonist with ~15-fold and 100-fold selectivity vs. 5-HT(2A) and 5-HT(2B) receptors, respectively. This study evaluated the safety and efficacy of lorcaserin for weight reduction in obese patients during a 12-week period. The randomized, double-blind, placebo-controlled, parallel-arm study enrolled 469 men and women between ages 18 and 65 and with BMI 30-45 kg/m(2). Patients received placebo, lorcaserin 10 mg q.d., lorcaserin 15 mg q.d., or lorcaserin 10 mg b.i.d. for 12 weeks, and were counseled to maintain their usual diet and activity. The primary end point was change in weight from baseline to day 85 by completer analysis. Safety analyses included echocardiograms at Screening and day 85/study exit. Lorcaserin was associated with progressive weight loss of 1.8 kg, 2.6 kg, and 3.6 kg at 10 mg q.d., 15 mg q.d., and 10 mg b.i.d., respectively, compared to placebo weight loss of 0.3 kg (P < 0.001 for each group). Similar results were seen by intent-to-treat last observation-carried forward (ITT-LOCF) analysis. The proportions of completers achieving > or =5% of initial body weight were 12.8, 19.5, 31.2, and 2.3% in the 10 mg q.d., 15 mg q.d., 10 mg b.i.d., and placebo groups, respectively. The most frequent adverse events (AEs) were transient headache, nausea, and dizziness. Echocardiograms showed no apparent drug-related effects on heart valves or pulmonary artery pressure (PAP). Lorcaserin was well tolerated and efficacious for weight reduction in this 12-week study. Longer-term trials employing behavior modification will be needed to more fully assess its safety and efficacy.