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BackgroundNanoparticle siRNA-conjugates are promising clinical therapeutics as indicated by recent US-FDA approval. In glioma stem cells (GSC), multiple stemness associated genes were found aberrant. We report intracranially injectable, multi-gene-targeted siRNA nanoparticle gel (NPG) for the combinatorial silencing of 3 aberrant genes, thus inhibiting the tumorogenic potential of GSCs.MethodsNPG loaded with siRNAs targeted against FAK, NOTCH-1, and SOX-2 were prepared by the self-assembly of siRNAs with protamine–hyaluronic acid combination. Electron microscopy, DLS, and agarose gel electrophoresis were used for the physicochemical characterization. Cell transfection and gene-silencing efficiency were studied using human mesenchymal stem cells and rat C6 glioma-derived GSCs. Neurosphere inhibition was tested in vitro using GSCs derived from C6 cell line and glioma patient samples. Patient-derived xenograft model and orthotopic rat glioma model were used to test the effect of NPG on in vivo tumorigenicity.ResultsThe siRNA nanoparticles with an average size ~ 250 nm and ~ 95% loading efficiency showed cellular uptake in ~95.5% GSCs. Simultaneous gene silencing of FAK, NOTCH-1, and SOX-2 led to the inhibition of neurosphere formation by GSCs, whereas normal stem cells remained unaffected and retained neuronal differentiation capability. GBM PDX models manifested significant impairment in the tumorigenic potential of NPG treated GSCs. Intracranial injection of NPG inhibited tumor growth in orthotopic rat brain tumor model.ConclusionIntracranially injectable n-siRNA NPG targeted to multiple stem-cell signaling impairs glioma initiation capabilities of GSCs and inhibited tumor growth in vivo.

BACKGROUND The reevaluation and management of seizure relapse following resective surgery in magnetic resonance imaging (MRI)-negative pharmacoresistant epilepsy remains a significant challenge. OBSERVATIONS A 25-year-old right-handed male with medically refractory epilepsy presented with nonlocalizing electroencephalography (EEG) and MRI. Stereo-EEG (SEEG) implantation based on semiology and positron emission tomography imaging revealed a left frontal opercular focus with rapid bilateral insular ictal synchrony. The initial epileptogenic zone was resected and pathologically proven to be type 2A focal cortical dysplasia (FCD). Seizure relapse after 9 months was eventually reinvestigated, and repeat SEEG revealed a secondary epileptogenic focus in the contralateral insula. A novel technique of volumetric stereotactic radiofrequency ablation (vRFA) was utilized for the right insular focus, following which, the patient remains seizure-free for 20 months. He suffered a transient bilateral opercular syndrome following the second intervention that eventually resolved. LESSONS The authors present clinical evidence to suggest epileptogenic nodes distant from the primary focus as a mechanism for seizure relapse following FCD surgery and the importance of bilateral insular SEEG coverage. The authors also describe a novel technique of minimally invasive vRFA that allows ablation of a larger volume of cerebral cortex when compared to conventional bedside SEEG electrode thermocoagulation.

The management of ventriculoperitoneal (VP) shunt failure is a common problem in neurosurgical practice. On occasion, extraperitoneal sites for CSF diversion are required when shunting to the peritoneal cavity has failed after multiple attempts. The authors report a novel minimally invasive procedure allowing cannulation of the ureter for the purpose of ventriculo-ureteral (VU) shunting. Sixteen years prior to presentation, this 46-year-old woman had contracted tuberculous meningitis and had chronic hydrocephalus, with multiple distal shunt failures in recent months. A percutaneous nephrostomy was used to pass the distal catheter based on intraoperative retrograde pyelography. Following successful placement of the VU shunt, the patient's hydrocephalus stabilized and she returned to her regular functional status. The only long-term complication noted within 36 months of follow-up was a transient episode of electrolyte disturbance and dehydration associated with a diarrheal illness that responded to adequate hydration and salt supplementation. By its minimally invasive nature, this approach offers a reasonable extraperitoneal alternative after multiple distal shunt catheter failures have occurred.

35 yr old steroid dependent lady with Pulmonary TB underwent debridement of epidural abscess & posterior stabilization for paraparesis. With histopathology and cultures showing Aspergillus fumigatus, voricanozole was started. By the fourth week, she developed persistent fever, and altered mental status. Brain MRI and CSF study including multiplex PCR evaluation confirmed cerebral aspergillosis. Voricanozole was changed to intravenous lipid complex Amphotericin B to achieve sustained clinical and radiological response after six months of therapy.

Subaxial spine injuries during infancy are uncommon. We present the case of an infant referred to our brachial plexus clinic with proximal weakness of both arms noted immediately following a complicated breech delivery. Nerve conduction studies were consistent with bilateral proximal upper plexus injury; however, radiological evaluation revealed a C4–C5 subluxation and MRI features of bilateral C5 root avulsions. He was immobilized in a cervical-body orthosis and underwent open reduction and posterior C4-C5-C6 fixation at 10 weeks age using luque rods, sublaminar wires, and rib graft. The spine was immobilized in a custom molded cervicothoracic brace for a total of 3 months, and a home exercise program prescribed. Follow-up radiographic evaluation showed good posterior bony fusion by 2 months but persistent bilateral proximal upper limb weakness with reduced compound motor action potential (CMAP) amplitudes of the axillary and musculocutaneous nerves. Bilateral supraclavicular exploration and C5 root neurotization using the ipsilateral C7 nerve roots were performed at 7 months of age. Voluntary biceps activity followed by voluntary external rotation with gravity eliminated was noted within the next 2–3 months. He progressed to develop near normal motor control of bilateral upper limbs within 1 year. We wish to report this rare entity and our favorable outcome using a strategy of early spinal stabilization and neurotization repair to restore function following proximal nerve root injury.

Background Robotic automation and haptic guidance have multiple applications in neurosurgery. Objective To define the spectrum of cranial procedures potentially benefiting from robotic assistance in a university hospital neurosurgical practice setting. Methods Procedures utilizing robotic assistance during a 24-mo period were retrospectively analyzed and classified as stereotactic or endoscopic based on the mode utilized in the ROSA system (Zimmer Biomet, Warsaw, Indiana). Machine log file data were retrospectively analyzed to compare registration accuracy using 3 different methods: (1) facial laser scanning, (2) bone fiduciary, or (3) skin fiduciary. Results Two hundred seven cranial neurosurgical procedures utilizing robotic assistance were performed in a 24-mo period. One hundred forty-five procedures utilizing the stereotactic mode included 33% stereotactic biopsy, 31% Stereo-EEG electrode insertion, 20% cranial navigation, 7% stereotactic catheter placement, 6% craniofacial stereotactic wire placement, 2% deep brain stimulation lead placement, and 1% stereotactic radiofrequency ablation. Sixty-two procedures utilizing the haptic endoscope guidance mode consisted of 48% transnasal endoscopic, 29% ventriculoscopic, and 23% endoport tubular access. Statistically significant differences in registration accuracies were observed with 0.521 ± 0.135 mm (n = 132) for facial laser scanning, 1.026 ± 0.398 mm for bone fiduciary (n = 22), and 1.750 ± 0.967 mm for skin fiduciary (n = 30; ANOVA, P Conclusion The combination of accurate, automated stereotaxy with image and haptic guidance can be applied to a wide range of cranial neurosurgical procedures. The facial laser scanning method offered the best registration accuracy for the ROSA system based on our retrospective analysis.

BACKGROUND AND IMPORTANCE The lateral suboccipital approach for microvascular decompression (MVD) of the trigeminal nerve has become a standard-of-care over the past several decades. Syndromic cranial base settling, a rare but known cause for trigeminal neuralgia (TN), poses significant dilemmas in clinical management. In such cases, distorted anatomy may render surgery via the suboccipital approach difficult or even impossible. CLINICAL PRESENTATION A 34-yr-old male with osteogenesis imperfecta and severe basilar invagination suffered from TN that was refractory to medication and stereotactic radiosurgery. MVD of the fifth nerve root was performed via a pterional trans-sylvian approach after 3-dimensional trajectory modeling suggested the feasibility of this approach. He experienced complete resolution of TN and remains free of both pain and medications after 18 mo of follow-up. CONCLUSION This microsurgical trajectory, previously undescribed for TN, provides good visualization of the trigeminal root entry zone, thereby offering an excellent surgical option for severe TN in the setting of abnormal posterior fossa anatomy.

Introduction: The Philadelphia chromosome (Ph) is the most common cytogenetic abnormality associated with adult acute lymphoblastic leukemia (ALL) occurring in 20% to 40% of patients. It is also detected in 2% to 5% of children with ALL. Historically, patients with Ph-positive ALL carried a dismal prognosis, with poor response to most chemotherapy combinations, short remission durations, and long-term disease-free survival rates of 10% to 20%. The advent of tyrosine kinase inhibitors (TKIs) has revolutionized therapy of Ph-positive ALL. Materials and Methods: This retrospective and descriptive single center study was carried out based on data retrieved of 508 patients treated for ALL from 2007 to 2014. Of these thirty patients were Ph-positive ALL and were available for analysis, and these patients were included in the study. Ph-positive ALL was defined as ALL carrying the t(9;22) translocation on standard karyotype and/or fluorescent in situ hybridization analysis and/or positivity for BCR-ABL fusion transcript detection by real-time quantitative polymerase chain reaction (RQ-PCR) analysis. Patients were treated with combination chemotherapy and oral TKIs and responses were classified as either CR defined by the absence of circulating blasts and

The authors present the case of an 11-year-old boy with an intraventricular chordoid meningioma, which is a rare presentation of prolonged fever of unknown origin due to a rare tumor in a rare location. The fever resolved after excision of the lesion. Subsequent imaging revealed recurrence at 1 year. After a repeat excision and fractionated radiotherapy, the patient has remained disease free 5 years after the first surgery. Very few cases of intraventricular chordoid meningioma have been reported to date. The pathological features and clinical course are described. A review of the literature describing management options for this tumor type, recently found to have a higher recurrence rate, is described herein.

We report a seven-year-old girl who presented with a sudden tumor apoplexy due to a parasagittal hemangiopericytoma. Following tumor excision, the child was noted to have bilateral optic nerve dysfunction and progressive papilledema, despite rapid overall neurological improvement. Based on the clinical features, we feel that this case represents an unusual form of visual deterioration related to impaired CSF absorption somehow precipitated by the acute tumour apoplexy. This unusual case of blindness responded significantly to CSF shunting. Several reports exist describing raised intracranial pressure with papilledema caused by nonthrombotic sinus occlusion due to tumors in proximity to the posterior superior sagittal sinus, torcular herophili and the jugular outlet. Communicating hydrocephalus, pseudotumor syndrome or intracranial venous sinus obstruction should be considered when otherwise inexplicable visual loss coexists with optic nerve dysfunction and papilledema. We emphasize the importance of a thorough search for the cause of visual loss.

Object Middle cerebral artery infarction often occurs at a younger age than other strokes and is associated with significant rates of mortality and morbidity. After a period of pessimism regarding decompressive hemicraniectomy in the management of acute stroke, the method has reemerged in the past decade. The present study was undertaken to assess the immediate and long-term outcome of this intervention and to help better define the selection criteria for surgery. Methods The authors conducted a nonrandomized prospective study using decompressive hemicraniectomy with duraplasty in patients at various stages of clinical deterioration due to a space-occupying middle cerebral artery infarct. Patients were assessed at 6 and 12 months postinfarction by using functional scales. Subjective reconsideration was assessed using a questionnaire. Twenty-six patients were included in the study. The mean age was 48.4 ± 11.2 years, and the mean preoperative Glasgow Coma Scale score was 9.9 ± 3.2. The median time from ictus to surgery was 54 hours (range 13–288 hours). The rate of survival at 1 year postsurgery was 73%. Among survivors, 33.3% were independent (Barthel Index [BI] > 95) and 55.6% were partially dependent (BI 60–95) at 1 year postsurgery, with 72% attaining the ability to walk independently by 1 year postsurgery. No patient remained in a vegetative state. The 1-year BI score was inversely related to patient age (r = − 0.47, p = 0.048). Conclusions Survival after decompressive hemicraniectomy was better than previously reported using medical management alone. A vegetative state was avoided and functional independence was possible, especially in younger patients. Increasing age was a statistically significant predictor of disability and long-term functional dependence.

Objectives We present a case series of patients who underwent perirolandic resection for medically refractory focal epilepsy due to focal cortical dysplasia (FCD). Our aim was to specifically evaluate the outcome of a surgical strategy intended for seizure freedom while preserving primary motor cortex function. Materials and methods Thirteen patients undergoing perirolandic resection for pharmacoresistant focal epilepsy between 2010 and 2015 who demonstrated histological evidence of FCD were selected from a prospectively maintained database. Presurgical evaluation included video EEG telemetry and 3T MRI brain for all patients. Eight patients underwent interictal FDG PET scan. Intracranial EEG monitoring was done for 8 patients – six by conventional subdural grid and depth electrodes and two by Stereo EEG. Additional techniques included extraoperative cortical stimulation mapping, intraoperative electrocorticography (ECoG), intraoperative motor cortex mapping and awake surgery in various combinations. In all cases (lesional and nonlesional), resection was intentionally limited for anatomic preservation of the primary motor cortex. Results Amongst the thirteen patients with age ranging 14–44 years (mean 26.8 ± 9.2) 62% of them had daily seizures. MRI abnormalities were identified in 8 patients (62%), PET showed concordant findings in 7 patients (88%). When utilized, the mean duration of intracranial EEG recordings was 8.0 ± 7.2 days (range 2–23 days). All patients underwent a primary motor cortex-sparing resection of the suspected epileptogenic cortex. The mean postoperative follow up period was 23 months (range 7.5–62 months). Twelve out of 13 (92%) were seizure free (Engel 1) outcome at the last follow-up assessment; one patient had Engel 2a outcome at 28 months. Six patients (46%) had immediate new focal neurological deficits, however all six patients had recovered completely within three months. Conclusion The surgical strategy of a primary motor cortex-sparing resective surgery for perirolandic FCD is associated with an excellent early seizure-freedom rate and no permanent neurological deficits. Since the ultimate goal of resective epilepsy surgery is seizure freedom with simultaneous functional preservation, similar long term outcome studies should ultimately guide the resection strategy.

Neurofibromatosis type 1 (NF-1) is a heterogeneous autosomal dominant disease with an incidence ranging from 1 in 2500 to 1 in 3000. Rare intrathoracic vascular disorders resulting in massive spontaneous hemothorax with fatal consequences may occur in these patients, so also are various types of skeletal dysplasia which may result in dramatic presentations, posing management challenges to the attending physicians. We report the case of a 43-year-old woman with NF-1 who developed spontaneous massive hemothorax and was discovered to have a concurrent giant intrathoracic meningocele and thoracic kyphoscoliosis with severe vertebral dysplastic changes. Surgical treatment via a right thoracotomy with primary repair of the meningocele and spinal fusion with fibula graft resulted in good outcome. This case represents an extreme manifestation of this otherwise indolent disease in clinical practice.

A seven-month-old infant presented with a generalized seizure. The radiological evaluation revealed a large arteriovenous fistula in the left sylvian region. The fistula connected the left middle cerebral artery and the vein of Trolard. A giant varix was present at the venous end. The child underwent craniotomy, complete disconnection of the fistula and excision of the varix. Except for recurrent seizures, which were eventually controlled on anticonvulsants, the child's neurological development has been good on long-term follow-up of three years. Pial arteriovenous fistulae are rare intracranial vascular malformations. Though significant operative risks exist, they can be successfully managed surgically with good long-term prognosis.

Introduction Intracranial arachnoid cysts are considered to be congenital malformations with a predilection for the temporal fossa. They are often asymptomatic but can sometimes be symptomatic due to enlargement or hemorrhage. There are multiple case reports of arachnoid cysts becoming symptomatic with hemorrhagic complications following head trauma. In such cases, the bleeding is often confined to the side ipsilateral to the arachnoid cyst. Occurrence of contralateral subdural hematomas in patients with temporal fossa arachnoid cysts has rarely been observed and is reported less frequently in the medical literature. Case presentation We report two cases of people (a 23-year-old man and a 41-year-old man) with temporal fossa arachnoid cysts complicated by a subdural hematoma following head injury. Both patients developed a subdural hematoma contralateral to the side of a temporal fossa arachnoid cyst. It is likely that lack of adequate intracranial cushioning in the presence of an intracranial arachnoid cyst may result in injury not only to ipsilateral but also to contralateral bridging veins, following head trauma. Conclusion It is important to identify and report such rare complications with intracranial arachnoid cysts, so that asymptomatic patients with an intracranial arachnoid cyst can be counseled about such possibilities following head trauma.