Cellular injury and neuroinflammation in children with chronic intractable epilepsy

<p>Abstract</p> <p>Objective</p> <p>To elucidate the presence and potential involvement of brain inflammation and cell death in neurological morbidity and intractable seizures in childhood epilepsy, we quantified cell death, astrocyte proliferation, microglial activation and cytokine release in brain tissue from patients who underwent epilepsy surgery.</p> <p>Methods</p> <p>Cortical tissue was collected from thirteen patients with intractable epilepsy due to focal cortical dysplasia (6), encephalomalacia (5), Rasmussen's encephalitis (1) or mesial temporal lobe epilepsy (1). Sections were processed for immunohistochemistry using markers for neuron, astrocyte, microglia or cellular injury. Cytokine assay was performed on frozen cortices. Controls were autopsy brains from eight patients without history of neurological diseases.</p> <p>Results</p> <p>Marked activation of microglia and astrocytes and diffuse cell death were observed in epileptogenic tissue. Numerous fibrillary astrocytes and their processes covered the entire cortex and converged on to blood vessels, neurons and microglia. An overwhelming number of neurons and astrocytes showed DNA fragmentation and its magnitude significantly correlated with seizure frequency. Majority of our patients with abundant cell death in the cortex have mental retardation. IL-1beta, IL-8, IL-12p70 and MIP-1beta were significantly increased in the epileptogenic cortex; IL-6 and MCP-1 were significantly higher in patients with family history of epilepsy.</p> <p>Conclusions</p> <p>Our results suggest that active neuroinflammation and marked cellular injury occur in pediatric epilepsy and may play a common pathogenic role or consequences in childhood epilepsy of diverse etiologies. Our findings support the concept that immunomodulation targeting activated microglia and astrocytes may be a novel therapeutic strategy to reduce neurological morbidity and prevent intractable epilepsy.</p

Pediatric Pineal Region Tumors: Institutional Experience of Surgical Managements with Posterior Interhemispheric Trans-Tentorial Approach

Abstract Purpose Resecting pineal region tumors in children is often challenging. Several approaches have been proposed and practiced. A personal series of pediatric pineal region tumor resected through craniotomy with posterior interhemispheric occipital transtentorial (OT) approach are reviewed. We present the surgical techniques and pitfalls, and their results. Material and Methods Eighty patients ranging in age from 3 months to 21 years old, and treated over 3 decades were reviewed. Hydrocephalus caused the main presenting symptoms and was noted in 74 patients. It was treated prior to the craniotomy for tumor resection with endoscopic third ventriculostomy (ETV) in 33, external ventricular drainage in 26 and precraniotomy shunt in 15. Nine patients had ETV together with endoscopic biopsy. All patients had parieto-occipital craniotomy in a prone position. Through a tentorial section, a gross total resection of the tumor was attempted except for germinomas Results . The tumor pathology showed 32 germ cell tumors (GCT), 22 benign astrocytomas 13 pineal parenchymal tumors, 5 ATRTs, 3 papillary tumors and 5 others. Of GCTs, 18 were teratomas. The extent of resection consisted of 55 gross total resection, 13 subtotal resection, 10 partial and 2 biopsy with one postoperative death. Hemiparesis in 2, cerebellar ataxia in another 2 and hemiballismus in 1 were transient and improved overtime. One had permanent hemisensory loss and another patient had bilateral oculomotor palsy. Postoperative homonymous hemianopia occurred in 2 patients but subsided over a short period of time. Parinaud’s sign was noted in 24 patients, of which 16 were transient. Conclusion The posterior interhemispheric OT approach provides a safe route and comfortable access to the pineal region in children. A great majority of postoperative neurological complications are the results of direct manipulations of the midbrain at tumor resection. Identification and preservation of the tumor-brain interface is of paramount importance. GCTs other than teratomas are treated with neoadjuvant chemotherapy and may eliminate the need of craniotomy. Exophytic midbrain JPAs are amenable to resection.</jats:p

Spring-Assisted Distraction Osteogenesis for the Treatment of Shunt-Induced Craniosynostosis

Shunt-induced craniosynostosis is a rare complication of ventricular shunting for hydrocephalus in pediatric patients. Although the exact pathophysiology of this form of secondary craniosynostosis is not well understood, the current understanding is that persistent drainage of the ventricular shunt causes decreased dural tension, resulting in decreased expansile force on the cranium and premature sutural fusion. Due to the low incidence of this complication, there is no consensus on the ideal treatment for shunt-induced craniosynostosis. In recent years, distraction osteogenesis has been employed with greater frequency, as it is felt to counter the fundamental problem of decreased expansile force on the cranium. However, in a patient with a ventricular shunt, placement of external hardware in close proximity to the shunt could cause significant morbidity due to the increased risk of shunt infection. We present the management of a patient with shunt-induced craniosynostosis who continued to be shunt-dependent. We chose to use fully buried springs to create an expansile force on the cranium as an alternative to external distractors so as to mitigate the risk of infection. We demonstrate that spring-assisted distraction osteogenesis can be an effective treatment modality for patients with shunt-induced craniosynostosis. This method should be considered in patients with contraindications to external distraction devices, such as ongoing shunt dependency. </jats:p