John Ragheb

Phase II clinical trial of moderate hypothermia after severe traumatic brain injury in children

OBJECTIVE:To determine whether moderate hypothermia (HYPO) (32–33°C) begun in the early period after severe traumatic brain injury (TBI) and maintained for 48 hours is safe compared with normothermia (NORM) (36.5–37.5°C). METHODS:After severe (Glasgow Coma Scale score ≤8) nonpenetrating TBI, 48 children less than 13 years of age admitted within 6 hours of injury were randomized after stratification by age to moderate HYPO (32–33°C) treatment in conjunction with standardized head injury management versus NORM in a multicenter trial. An additional 27 patients were entered into a parallel single-institution trial of excluded patients because of late transfer or consent (delayed in transfer >6 h but within 24 h of admission), unknown time of injury (e.g., child abuse), and adolescence (e.g., aged 13–18 yr). Assessments of safety included mortality, infection, coagulopathy, arrhythmias, and hemorrhage as well as ability to maintain target temperature, mean intracranial pressure (ICP), and percent time of ICP less than 20 mm Hg during the cooling and subsequent rewarming phases. Additionally, assessments of neurocognitive outcomes were obtained at 3 and 6 months of follow-up. RESULTS:Moderate HYPO after severe TBI in children was found to be safe relative to standard management and NORM in children of all ages and in children with delay of initiation of treatment up to 24 hours. Although there was decreased mortality in HYPO in both studies, there was an increased potential for arrhythmias with HYPO, although they were manageable with fluid administration or rewarming. Additionally, there was a reduction in mean ICP during the first 72 hours after injury in both studies, although rebound ICP elevations in HYPO compared with those in NORM were noted for up to 10 to 12 hours after rewarming. Although functional outcome at 3 or 6 months did not differ between treatment groups, functional outcome tended to improve from the 3- to 6-month cognitive assessment in HYPO compared with NORM, although the sample size was too small for any definitive conclusions. CONCLUSION:HYPO is likely a safe therapeutic intervention for children after severe TBI up to 24 hours after injury. Further studies are necessary and warranted to determine its effect on functional outcome and intracranial hypertension.

Different features of histopathological subtypes of pediatric focal cortical dysplasia

Focal cortical dysplasia (FCD) is the most frequent pathological finding in pediatric epilepsy surgery patients. Several histopathological types of FCD are distinguished. The aim of the study was to define distinctive features of FCD subtypes.

Epilepsy surgery in children with tuberous sclerosis complex: presurgical evaluation and outcome.

Summary: Purpose: Children with tuberous sclerosis complex (TSC) benefit from excisional surgery if seizures can be localized to a single tuber. We evaluated the role of noninvasive studies to localize the epileptogenic tuber/region (ET/R) and the outcome of focal resection.

Epilepsy surgery in patients with normal or nonfocal MRI scans: Integrative strategies offer long‐term seizure relief

Purpose: Excisional surgery achieves seizure freedom in a large proportion of children with intractable lesional epilepsy, but the outcome for children without a focal lesion on MRI is less clear. We report the outcome of a cohort predominantly of children with nonlesional intractable partial epilepsy undergoing resective surgery.

Surgery for Epilepsy Due to Cortical Malformations: Ten‐year Follow‐up

Summary:  Children with malformations of cortical development represent a significant proportion of pediatric epilepsy surgery candidates. From a cohort of 40 children operated on between 1980 and 1992 with malformation of cortical development, 38 were alive and had data 10 years after surgery. Age at surgery ranged from 6 months to 18 years (mean, 9.6 years). Thirty‐six had partial seizures, and two had infantile spasms; 20 were nonlesional. Pathologic diagnoses were cortical dysplasia (n = 31) and developmental tumor (n = 7). At 10‐year follow‐up, 15 (40%) were seizure free, 10 (26%) had >90% seizure reduction, and 13 (34%) were improved or unchanged. Children seizure free at two‐year follow‐up were likely to remain seizure free. Ten‐year seizure freedom was 72% in children with developmental tumors and 32% in the cortical dysplasia group. Complete resection was statistically significant for favorable outcome, and no patient with an incomplete resection was seizure free.

MR-guided laser interstitial thermal therapy for pediatric drug-resistant lesional epilepsy

To report the feasibility, safety, and clinical outcomes of an exploratory study of MR‐guided Laser Interstitial Thermal Therapy (MRgLITT) as a minimally invasive surgical procedure for the ablation of epileptogenic foci in children with drug‐resistant, lesional epilepsy.

The use of stereotactic radiosurgery to treat intractable childhood partial epilepsy.

Summary:  Purpose: Although conventional surgery is presently used to treat seizures of temporolimbic and neocortical origin, deep‐seated lesions are often associated with morbidity. Stereotactic radiosurgery is a noninvasive procedure that effectively treats patients with vascular malformations and brain tumors, but its efficacy for epileptogenic foci is limited, especially in children.

Unique Clinical Presentation of Pediatric Shunt Malfunction

Introduction: A cerebrospinal fluid (CSF) shunt is the primary treatment for most etiologies of hydrocephalus in the pediatric population. Malfunction of the shunt may present with unique symptoms and signs. This retrospective review investigates the presenting signs and symptoms of pediatric patients with shunt malfunction. Clinical Material and Method: One-hundred-and-thirty CSF diversion procedures were performed at two affiliated pediatric hospitals over a 2-year period. Seventy consecutive cases of CSF shunt revision were reviewed. These 70 operations were performed on 65 patients. Their medical records and radiographic studies were reviewed, and supplemented with a telephone interview to obtain a minimum of 3 months follow-up. Results: The 65 patients’ age ranged from 3 months to 16 years. The original etiology of the hydrocephalus was Chiari II malformation in 17, idiopathic in 15 and intraventricular hemorrhage in 10, neoplasm in 8 patients and meningitis in 5 patients. The most frequent presenting symptoms were headache (39 admissions), nausea/vomiting (28) and drowsiness (21). Seven Chiari patients (41%) presented with neck pain, 2 (12%) presented with lower cranial nerve palsy, and 2 (12%) presented with symptomatic syrinx, complaints not reported by non-Chiari patients (p < 0.01, χ2 analysis). Four myelodysplastic patients presented with a new-onset or recurrent seizure episode, which was significantly more frequent than in nonmyelodysplastic patients (p < 0.05, χ2 analysis). On examination, increased head circumference was noted in 17 patients. Parinaud’s syndrome was noted more prominently in patients with a history of intracranial neoplasm (4 of 8 cases) than in patients with nonneoplastic diseases (2 of 62 cases; p < 0.05, χ2 analysis). Other interesting presenting signs were pseudocyst (2), syringomyelia (2), hemiparesis (2) and Parkinson-like rigidity (2). Conclusion: Pediatric shunt malfunction generally presents with headache, nausea/vomiting, altered mental status, increased head circumference and bulging fontanelle. Other less frequent but unique presenting signs and symptoms, such as neck pain, syringomyelia and lower cranial nerve palsy in the myelodysplastic population, and Parinaud’s syndrome in patients with a history of intracranial neoplasm are frequently associated with shunt malfunction and should prompt a radiographic workup.

Outcomes in pediatric patients with Chiari malformation Type I followed up without surgery: Clinical article

OBJECT The natural history of untreated Chiari malformation Type I (CM-I) is poorly defined. The object of this study was to investigate outcomes in pediatric patients with CM-I who were followed up without surgical intervention. METHODS The authors retrospectively reviewed 124 cases involving patients with CM-I who presented between July 1999 and July 2008 and were followed up without surgery. The patients ranged in age from 0.9 to 19.8 years (mean 7 years). The duration of follow-up ranged from 1.0 to 8.6 years (mean 2.83 years). Imaging findings, symptoms, and findings on neurological examinations were noted at presentation and for the duration of follow-up. RESULTS The mean extent of tonsillar herniation at presentation was 8.35 mm (range 5-22 mm). Seven patients had a syrinx at presentation. The syrinx size did not change in these patients on follow-up imaging studies. No new syrinxes developed in the remaining patients who underwent subsequent imaging. The total number of patients with presenting symptoms was 81. Of those 81 patients, 67 demonstrated symptoms that were not typical of CM-I. Of the 14 patients with symptoms attributed to CM-I, 9 had symptoms that were not severe or frequent enough to warrant surgery, and surgery was recommended in the remaining 5 patients. Chiari malformation Type I was also diagnosed in 43 asymptomatic patients who had imaging studies performed for various reasons. No new neurological deficits were noted in any patient for the duration of follow-up. CONCLUSIONS The majority of patients with CM-I who are followed up without surgery do not progress clinically or radiologically. Longer follow-up of this cohort will be required to determine if symptoms or new neurological findings develop over the course of many years.

Medically intractable epilepsy in Sturge‐Weber syndrome is associated with cortical malformation: Implications for surgical therapy

Purpose:  Anecdotal reports have described cortical malformations in epileptic patients with Sturge‐Weber syndrome (SWS). No data are available regarding the prevalence and significance of this association.