Saleem I. Malik

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.

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 Ohtaharas15 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.

Amantadine for the treatment of refractory absence seizures in children.

Amantadine has demonstrated efficacy in small series for absence and myoclonic type seizures. We examined the efficacy of amantadine for treating refractory absence seizures in a cohort of pediatric patients. We retrospectively reviewed medical records for patients with absence seizures treated with amantadine at Cook Childrens Medical Center after January 2007. Abstracted data included sex, age at initiation, concomitant antiepileptic drugs, amantadine dosing, and seizure frequency. Outcomes at 3, 6, and 12 months after initiation were categorized as >90%, ≥50%, or <50% reduction in seizure frequency. Of 13 patients included in the study, many were exposed to multiple antiepileptic drugs (median, 3; range, 1-6). Three were implanted with a vagus nerve stimulator. A response of at least 50% seizure reduction was reported in more than 50% of patients reviewed at 3, 6, and 12 months after initiating treatment. Among responders, a majority had >90% reduction in seizure frequency. Amantadine may constitute an efficacious alternative treatment for refractory absence seizures.

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.

Preservation of a subcutaneous pocket for vagus nerve stimulation pulse generator during magnetoencephalography. Technical note.

Patients with epilepsy and an implanted vagus nerve stimulation (VNS) device who are referred for consideration of definitive epilepsy surgery (removal of the epileptogenic cortex) may require magnetoencephalography (MEG), a study requiring explantation of the pulse generator, as part of their evaluation. Nonetheless, these patients may not wish to abandon palliative VNS therapy should definitive surgery prove unsuccessful or impossible. To avoid obliteration of the pocket by scar tissue after the pulse generator is explanted, the authors have preserved the dead space in several patients with insertion of a similarly sized silicone block. This block is easily replaced with the pulse generator if continued VNS therapy is appropriate, and is left in place in patients who appear to no longer require VNS therapy. Upon completion of MEG, if pulse generator replacement proves desirable, atraumatic retrieval of the electrode connector pin and body is easy. Silicone block implantation during what may prove to be temporary device explantation facilitates reuse of the original pulse generator implantation site and atraumatic distal electrode wire retrieval.

Clobazam for the Treatment of Intractable Epilepsy in Children

We describe our experience using clobazam, examining efficacy for individual seizure types and analyzing for factors contributing to initial and sustained response. We retrospectively reviewed medical charts of children treated with clobazam. We collected patient and treatment characteristics and compared response to therapy at 6, 12, and >12 months’ duration. One hundred eight patients with a variety of seizure types and etiologies of epilepsy were treated. Response rates for >50% seizure reduction were 59%, 39%, and 30% of patients at 6, 12, and >12 months’ therapy, respectively. No seizure type responded more favorably and there were no patient predictors of favorable response. Patients tended to respond early and at low dosing, and half the patients maintained this response for 15 months or more. Clobazam has efficacy against a wide spectrum of seizure types and epilepsy etiologies. An early, low-dose response is a favorable indicator for sustained response.

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 Childrens Medical Center and Dell Childrens 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.

Coregistration of multimodal imaging is associated with favourable two-year seizure outcome after paediatric epilepsy surgery*

Multimodal coregistration uses multiple image datasets coregistered to an anatomical reference (i.e. MRI), allowing multiple studies to be viewed together. Commonly used in intractable epilepsy evaluation and generally accepted to improve localization of the epileptogenic zone, data showing that coregistration improves outcome is lacking. We compared seizure freedom following epilepsy surgery in paediatric patients, evaluated before and after the use of coregistration protocols at our centre, to determine whether this correlated with a change in outcome. We included paediatric epilepsy surgery patients with at least one anatomical and one functional neuroimaging study as part of their presurgical evaluation. Preoperatively designated palliative procedures and repeat surgeries were excluded. Multiple pre-, peri-, and postoperative variables were compared between groups with the primary outcome of seizure freedom. In total, 115 were included with an average age of 10.63 years (0.12-20.7). All evaluations included video-EEG (VEEG) and MRI. Seven (6%) had subtraction single-photon emission CT (SPECT), 46 (40%) had positron emission tomography (PET), and 62 (54%) had both as part of their evaluation. Sixty (52%) had extratemporal epilepsy and 25 (22%) were MRI-negative. Sixty-eight (59%) had coregistration. Coregistered patients were less likely to undergo invasive EEG monitoring (p=0.045) and were more likely to have seizure freedom at one (p=0.034) and two years (p<0.001) post-operatively. A logistic regression accounting for multiple covariates supported an association between the use of coregistration and favourable post-surgical outcome. Coregistered imaging contributes to favourable postoperative seizure reduction compared to visual analysis of individual modalities. Imaging coregistration is associated with improved outcome, independent of other variables after surgery. Coregistered imaging may reduce the need for invasive EEG monitoring, likely due to improved confidence in presurgical localization. These findings support the use of multimodal coregistered imaging as part of the presurgical assessment in patients evaluated for surgical treatment of intractable epilepsy.

Dravet syndrome associated with cortical dysplasia of Taylor-type

Severe myoclonic epilepsy of infancy or Dravet syndrome is a catastrophic epilepsy of genetic origin that begins with febrile seizures in the first year of life and evolves to intractable epilepsy with cognitive decline and frequent episodes of status epilepticus. While multiple treatment strategies are employed, rarely are patients with Dravet syndrome considered for resective epilepsy surgery. We report a case of Dravet syndrome in which palliative resection of epileptogenic foci revealed cortical dysplasia of Taylor-type. We discuss the association of cortical dysplasia with Dravet syndrome and consider the utility of palliative surgical therapy in a genetically based epilepsy syndrome.