Radiation-Stimulated Translocation of CD166 and CRYAB to the Endothelial Surface Provides Potential Vascular Targets on Irradiated Brain Arteriovenous Malformations.

Vascular targeting with pro-thrombotic antibody-conjugates is a promising biological treatment for brain arteriovenous malformations (bAVMs). However, targeted drug delivery relies on the identification of unique or overexpressed markers on the surface of a target cell. In the absence of inherent biological markers, stereotactic radiosurgery may be used to prime induction of site-specific and targetable molecular changes on the endothelial surface. To investigate lumen-accessible, endothelial targets induced by radiation, we combined Gamma knife surgery in an AVM animal model with in vivo biotin-labeling and comparative proteomics. Two proteins, αB-crystallin (CRYAB)-a small heat shock protein that normally acts as an intracellular chaperone to misfolded proteins-and activated leukocyte cell adhesion molecule CD166, were further validated for endothelial surface expression after irradiation. Immunostaining of endothelial cells in vitro and rat AVM tissue ex vivo confirmed de novo induction of CRYAB following irradiation (20 Gy). Western analysis demonstrated that CRYAB accumulated intracellularly as a 20 kDa monomer, but, at the cell surface, a novel 65 kDa protein was observed, suggesting radiation stimulates translocation of an atypical CRYAB isoform. In contrast, CD166 had relatively high expression in non-irradiated cells, localized predominantly to the lateral surfaces. Radiation increased CD166 surface exposure by inducing translocation from intercellular junctions to the apical surface without significantly altering total protein levels. These findings reinforce the dynamic molecular changes induced by radiation exposure, particularly at the cell surface, and support further investigation of radiation as a priming mechanism and these molecules as putative targets for focused drug delivery in irradiated tissue.

Posttraumatic Intralaminar Hematoma Developing between Cranial Dural Layers: A Case Report.

We present a case of post-traumatic hematoma developing between the 2 layers of the cranial dura in a 2-year-old child following head injury. This child presented with history of fall from a height in altered sensorium with paucity of movements on the left side. Computerized tomography scan of the brain showed a right parietal linear fracture with an underlying hyperdense biconvex hematoma. Emergency evacuation of the hematoma was done. On elevation of the scalp flap, a fibrous membrane was seen protruding between the fracture lines. Following craniotomy, the hematoma was identified between the 2 layers of the dura and the fibrous membrane that protruded between the fracture lines was identified as the endosteal layer of dura. The hematoma was evacuated after opening the outer endosteal layer. After evacuation of the hematoma, the endosteal and meningeal layers could be identified separately and the point where these 2 layers split to enclose the hematoma was identified at the outer border of the hematoma. The child had no neurological sequel at the time of discharge.

Transient cortical blindness following a Hangman's fracture: a case report and review of literature.

We describe a case with transient cortical blindness after trauma with no obvious structural damage to the vertebral artery in the presence of a C2 spondylolisthesis. A patient complaining of blindness in a setting of polytrauma should always alert the possibility of a cervical spine injury with vertebral artery ischaemia.

Temporal progression and spatial distribution of "normal" prevertebral soft tissue swelling following central corpectomy for cervical spondylotic myelopathy.

OBJECTIVE: To document the temporal progression and spatial distribution of prevertebral soft tissue swelling (PSTS) after central corpectomy (CC) and to determine the variables affecting its severity. BACKGROUND: The natural attributes of PSTS following CC for cervical spondylotic myelopathy (CSM) have not been characterized in literature. MATERIALS AND METHODS: PSTS was measured at the C2 level and midpoint of the operated segment on lateral radiographs of the cervical spine taken pre-operatively and post-operatively (day 0, day 3/4, day 5 and day 6/7) in 93 patients with CSM undergoing one to three level uninstrumented CC. Patient's age, weight, Nurick's grade, number of corpectomy levels and intubation time were correlated with the PSTS. RESULTS: Proportionately, the swelling was maximal at the C2 level rather than at the level of CC, on all days, irrespective of the level of surgery. At the C2 level, the increase in PSTS was maximum by day 3/4 (P = 0.0001), whereas at the CC level, the PSTS continued to increase till day 5 (P = 0.0001). PSTS was higher in patients undergoing a three-level CC and in those with inclusion of C4 in the CC (P = 0.002). CONCLUSION: Patients undergoing CC are at risk for upper airway obstruction mainly at the C2 level in the first 3 days after surgery due to the PSTS. Those undergoing three-level CC, or having inclusion of C4 in the CC, have a greater degree of PSTS and have a higher risk of post-operative airway obstruction.

Horner's syndrome secondary to T1-T2 intervertebral disc prolapse.

Background: T1-T2 intervertebral disc prolapse (IVDP) is a rare clinical condition. Horner's syndrome is an extremely rare clinical finding in these patients. Case Description: A 56-year-old man presented with the left C8 T1 radiculopathy, left hand grip weakness, and ipsilateral Horner's syndrome. Magnetic resonance imaging of the spine showed a contrast-enhancing lesion in the left T1 foramen compressing the left T1 nerve root. He underwent left T1 hemilaminectomy, upper half of left T2 hemilaminectomy and removal of the left foraminal lesion. A biopsy of the lesion was sent for histopathological diagnosis which revealed tissue consistent with disc material. Postoperatively, he had near-complete recovery with residual minimal Horner's syndrome. Conclusion: T1-T2 IVDP should be considered in the differential diagnosis when a patient presents with C8 T1 radiculopathy and Horner's syndrome.

Ceftriaxone-induced encephalopathy in a patient with multicentric glioma.

Background: Ceftriaxone is a commonly used antibiotic in a wide range of local and systemic infections. Encephalopathy is a rare complication of ceftriaxone, often seen in older adults and those with renal insufficiency. Case Description: A 73-year-old lady with prior history of hypertension and dyslipidemia presented with the complaints of slurred speech, gait imbalance, nocturnal vomiting, and progressively worsening headache. A magnetic resonance imaging of the brain revealed two intracerebral lesions involving the right frontal and temporal lobes, suggestive of multicentric glioma. She underwent craniotomy and excision of these lesions. The biopsy was reported as intra-axial tumors with features suggestive of the WHO Grade IV glioma. Postoperatively, she did not wake up. An electroencephalogram demonstrated triphasic waves suggestive of encephalopathy. The probable diagnosis of ceftriaxone-induced encephalopathy was made after ruling out other causes of delayed awakening after surgery. Ceftriaxone was discontinued and the patient improved within 2 days of withdrawal of ceftriaxone. Conclusion: Drug-induced encephalopathy should be considered in the differential diagnosis of patients with delayed awakening after surgery. Discontinuation of the drug leads to the recovery of these patients.

Cerebral venous sinus thrombosis as a complication of cranial melioidosis - a rare case report.

Cerebral venous sinus thrombosis is a rare complication of cranial melioidosis. We report a case of an adult male who presented with skull osteomyelitis, transverse sinus thrombosis and multiple brain abscesses. His blood cultures grew Burkholderia pseudomallei . The patient finally succumbed after multiple recurrences of the infection despite surgical excision of the osteomyelitic bone and the recommended antibiotic treatment. The management of cerebral venous sinus thrombosis in patients with cranial melioidosis is discussed along with a brief review of the literature.

Cognitive changes following surgery in intractable hemispheric and sub-hemispheric pediatric epilepsy.

OBJECTIVES: The objectives were to study the short and longitudinal changes in the cognitive skills of children with intractable epilepsy after hemispheric/sub-hemispheric epilepsy surgery. METHODS: Sixteen patients underwent surgery from September 2005 until March 2009. They underwent detailed presurgical evaluation of their cognitive skills and were repeated annually for 3 years. RESULTS: Their mean age was 6.6 years. Epilepsy was due to Rasmussen's encephalitis (n = 9), Infantile hemiplegia seizure syndrome (n = 2), hemimegalencephaly (n = 2), and Sturge Weber syndrome (n = 3). Fourteen (87.5%) patients underwent peri-insular hemispherotomy and two (12.5%) underwent peri-insular posterior quadrantectomy. The mental and social age, gross motor, fine motor, adaptive, and personal social skills showed a steady increase after surgery (p < 0.05). Language showed positive gains irrespective of the side and etiology of the lesion (p = 0.003). However, intelligence quotient (IQ) remained static on follow-up. Patients with acquired pathology gained more in their mental age, language, and conceptual thinking. Age of seizure onset and duration of seizures prior to surgery were predictive variables of postoperative cognitive skills. CONCLUSIONS: There are short- and long-term gains in the cognitive skills of children with intractable epilepsy after hemispherotomy and posterior quadrantectomy that was better in those patients with acquired diseases. Age of seizure onset and duration of seizures prior to surgery were independent variables that predicted the postoperative outcome.

Brain abscess in a non-penetrating traumatic intracerebral hematoma: case report and review of literature.

We report a 57-year-old man who presented one month after sustaining a traumatic right temporal intracerebral hematoma with history of headache, left hemiparesis and altered sensorium of two days duration. A diagnosis of right temporal resolving hematoma was made on computed tomography scan. However, his sensorium progressively deteriorated and he underwent craniotomy and partial excision of an abscess. He was treated with appropriate antibiotics for six weeks despite of which he did not improve and died nine months later. We conclude that there should be a high index of suspicion for brain abscess in patients with traumatic intracerebral hemorrhage if the clinical and radiological picture is different from the expected course of a resolving hematoma.

Role of surgery in pediatric epilepsy.

Twenty five percent of patients with intractable epilepsy have surgically remediable epilepsy syndromes. This article reviews the treatment paradigm for pediatric epilepsy and also the indications, methods, and surgical options for the subgroup of patients with surgically remediable epileptic disorders based on our experience in the management of these children. The article also discusses the rationale for offering surgery and the timing of surgery in these patients. The study of surgically remediable epilepsy can best be divided into focal, sub hemispheric, hemispheric and multifocal epileptic syndromes. These syndromes have both acquired and congenital etiologies and can be treated by resective or disconnective surgery. The surgical management of these conditions (with the exception of multifocal epilepsy) provides Engel's Class 1 outcome(complete seizure freedom) in approximately 80% of children. The consequences of seizure freedom leads to a marked improvement in the quality of life of these children. The benefits to society, of allowing a child to grow to adulthood with normal cognition to earn a livelihood and contribute actively to society, cannot be understated.

Radiosurgery Alters the Endothelial Surface Proteome: Externalized Intracellular Molecules as Potential Vascular Targets in Irradiated Brain Arteriovenous Malformations.

Stereotactic radiosurgery (SRS) is an established treatment for brain arteriovenous malformations (AVMs) that drives blood vessel closure through cellular proliferation, thrombosis and fibrosis, but is limited by a delay to occlusion of 2-3 years and a maximum treatable size of 3 cm. In this current study we used SRS as a priming tool to elicit novel protein expression on the endothelium of irradiated AVM vessels, and these proteins were then targeted with prothrombotic conjugates to induce rapid thrombosis and vessel closure. SRS-induced protein changes on the endothelium in an animal model of AVM were examined using in vivo biotin labeling of surface-accessible proteins and comparative proteomics. LC-MS/MS using SWATH acquisition label-free mass spectrometry identified 280 proteins in biotin-enriched fractions. The abundance of 56 proteins increased after irradiation of the rat arteriovenous fistula (20 Gy, ≥1.5-fold). A large proportion of intracellular proteins were present in this subset: 29 mitochondrial and 9 cytoskeletal. Three of these proteins were chosen for further validation based on previously published evidence for surface localization and a role in autoimmune stimulation: cardiac troponin I (TNNI3); manganese superoxide dismutase (SOD2); and the E2 subunit of the pyruvate dehydrogenase complex (PDCE2). Immunostaining of AVM vessels confirmed an increase in abundance of PDCE2 across the vessel wall, but not a measurable increase in TNNI3 or SOD2. All three proteins co-localized with the endothelium after irradiation, however, more detailed subcellular distribution could not be accurately established. In vitro, radiation-stimulated surface translocation of all three proteins was confirmed in nonpermeabilized brain endothelial cells using immunocytochemistry. Total protein abundance increased modestly after irradiation for PDCE2 and SOD2 but decreased for TNNI3, suggesting that radiation primarily affects subcellular distribution rather than protein levels. The novel identification of these proteins as surface exposed in response to radiation raises important questions about their potential role in radiation-induced inflammation, fibrosis and autoimmunity, but may also provide unique candidates for vascular targeting in brain AVMs and other vascular tissues.

Awake craniotomy and electrophysiological mapping for eloquent area tumours.

OBJECTIVE: An awake craniotomy facilitates radical excision of eloquent area gliomas and ensures neural integrity during the excision. The study describes our experience with 67 consecutive awake craniotomies for the excision of such tumours. METHODS: Sixty-seven patients with gliomas in or adjacent to eloquent areas were included in this study. The patient was awake during the procedure and intraoperative cortical and white matter stimulation was performed to safely maximize the extent of surgical resection. RESULTS: Of the 883 patients who underwent craniotomies for supratentorial intraaxial tumours during the study period, 84 were chosen for an awake craniotomy. Sixty-seven with a histological diagnosis of glioma were included in this study. There were 55 men and 12 women with a median age of 34.6 years. Forty-two (62.6%) patients had positive localization on cortical stimulation. In 6 (8.9%) patients white matter stimulation was positive, five of whom had responses at the end of a radical excision. In 3 patients who developed a neurological deficit during tumour removal, white matter stimulation was negative and cessation of the surgery did not result in neurological improvement. Sixteen patients (24.6%) had intraoperative neurological deficits at the time of wound closure, 9 (13.4%) of whom had persistent mild neurological deficits at discharge, while the remaining 7 improved to normal. At a mean follow-up of 40.8 months, only 4 (5.9%) of these 9 patients had persistent neurological deficits. CONCLUSION: Awake craniotomy for excision of eloquent area gliomas enable accurate mapping of motor and language areas as well as continuous neurological monitoring during tumour removal. Furthermore, positive responses on white matter stimulation indicate close proximity of eloquent cortex and projection fibres. This should alert the surgeon to the possibility of postoperative deficits to change the surgical strategy. Thus the surgeon can resect tumour safely, with the knowledge that he has not damaged neurological function up to that point in time thus maximizing the tumour resection and minimizing neurological deficits.

Outcomes of disconnective surgery in intractable pediatric hemispheric and subhemispheric epilepsy.

OBJECTIVES: To study the outcome of disconnective epilepsy surgery for intractable hemispheric and sub-hemispheric pediatric epilepsy. METHODS: A retrospective analysis of the epilepsy surgery database was done in all children (age <18 years) who underwent a peri-insular hemispherotomy (PIH) or a peri-insular posterior quadrantectomy (PIPQ) from April 2000 to March 2011. All patients underwent a detailed pre surgical evaluation. Seizure outcome was assessed by the Engel's classification and cognitive skills by appropriate measures of intelligence that were repeated annually. RESULTS: There were 34 patients in all. Epilepsy was due to Rasmussen's encephalitis (RE), Infantile hemiplegia seizure syndrome (IHSS), Hemimegalencephaly (HM), Sturge Weber syndrome (SWS) and due to post encephalitic sequelae (PES). Twenty seven (79.4%) patients underwent PIH and seven (20.6%) underwent PIPQ. The mean follow up was 30.5 months. At the last follow up, 31 (91.1%) were seizure free. The age of seizure onset and etiology of the disease causing epilepsy were predictors of a Class I seizure outcome. CONCLUSIONS: There is an excellent seizure outcome following disconnective epilepsy surgery for intractable hemispheric and subhemispheric pediatric epilepsy. An older age of seizure onset, RE, SWS and PES were good predictors of a Class I seizure outcome.