John Caird

Loss-of-function mutations in SMARCE1 cause an inherited disorder of multiple spinal meningiomas

One-third of all primary central nervous system tumors in adults are meningiomas. Rarely, meningiomas occur at multiple sites, usually occurring in individuals with type 2 neurofibromatosis (NF2). We sequenced the exomes of three unrelated individuals with familial multiple spinal meningiomas without NF2 mutations. We identified two individuals with heterozygous loss-of-function mutations in the SWI/SNF chromatin-remodeling complex subunit gene SMARCE1. Sequencing of SMARCE1 in six further individuals with spinal meningiomas identified two additional heterozygous loss-of-function mutations. Tumors from individuals with SMARCE1 mutations were of clear-cell histological subtype, and all had loss of SMARCE1 protein, consistent with a tumor suppressor mechanism. Our findings identify multiple-spinal-meningioma disease as a new discrete entity and establish a key role for the SWI/SNF complex in the pathogenesis of both meningiomas and tumors with clear-cell histology.

Foramen magnum decompression for Chiari I malformation: A procedure not to be underestimated

Abstract Objective. Chiari I malformation may be treated with foramen magnum decompression (FMD). We aim to describe the symptoms with which patients initially present, and to determine the number and type of complications occurring after FMD for Chiari I malformation. Methods. Retrospective review of medical records for patients who had FMD performed for Chiari I malformation between January 2009 and December 2011. Post-operative outcomes were recorded and analysed. Patient demographic details and other relevant medical conditions were also noted. Results. Between January 2009 and December 2011, 54 FMDs were performed for Chiari I malformation. Among them, 40(74%) patients were female and 14 patients (26%) were male. The majority of patients (42.6%) were aged 16–39 years and 24.07% of patients were children aged < 16 years. A total of 30(55.6%) patients had documented evidence of a syrinx pre-operatively. 18(33.3%) patients developed complications. Nine of these developed multiple complications while nine had a single problem. One mortality was reported. Ten (18.5%) patients developed hydrocephalus requiring shunting. Two patients developed subdural collections requiring evacuation associated with hydrocephalus. Six (11.1%) patients developed post-operative infections: two CNS infections; one wound infection; and three other infections. Conclusions. FMD for Chiari I malformation is a procedure which carries risk. In particular, the risk of developing post-operative hydrocephalus requiring permanent shunting is relatively high. ICP monitoring prior to FMD may be required to definitively rule out raised intracranial pressure.

Spontaneous knot; a rare cause of ventriculoperitoneal shunt blockage

A 14-year old X linked congenital hydrocephalus presented with unexplained headaches and vomiting. He had external ventricular drain and intracranial pressure monitoring (ICP). Subsequently, he underwent exploration and removal of previously inserted ventriculoperitoneal (VP) shunts. On retrieval of peritoneal catheters a double knot was noted between his two distal catheters. This case illustrates a rare cause of ventriculoperitoneal shunt malfunction.

Craniotomy with prosthetic heart valves: a clinical dilemma

The authors report two cases of spontaneous intracranial haemorrhage after elective craniotomy for resection of cerebral tumour. Both patients had mechanical aortic valve prostheses and were on regular warfarin therapy. In both cases, warfarin therapy was discontinued 5 days prior to surgery and unfractionated heparin administered intravenously until 12 h before surgery. Both patients were re-anticoagulated with subcutaneous low molecular weight heparin within the first week postcraniotomy—both developed life-threatening intracranial haemorrhage requiring urgent evacuation. The authors emphasize the risk of re-anticoagulation without postoperative imaging and the disadvantages of therapeutic dose, low molecular weight heparin in the postoperative period.

Self-inflicted head trauma using a captive bolt pistol : report of three cases

Three cases of self-inflicted head trauma using a captive-bolt pistol are described. This is a rarely reported phenomenon and presents with an unique pattern of brain injury.Three cases of self-inflicted head trauma using a captive-bolt pistol are described. This is a rarely reported phenomenon and presents with an unique pattern of brain injury.

Preoperative cervical traction in cases of cranial settling with halo ring and Mayfield skull clamp.

Rheumatoid cervical myelopathy presents one of the most daunting challenges in neurological surgery. Preoperative cervical traction can help to distract the dens from the brainstem prior to performing occipitocervical fusion in cases of cranial settling. Valuable millimetres gained in preoperative traction can be lost in placing the patient in the prone position after removing the halo to allow application of the Mayfield skull clamp. The authors have found that traction can be adequately maintained during surgery by applying the Mayfield skull clamp with skull pins to the halo ring itself.

Radiation-Induced Moyamoya Syndrome after Proton Beam Therapy in the Pediatric Patient: A Case Series

Minimizing normal-tissue radiation exposure is especially important in the pediatric population as children appear to be particularly sensitive to postradiation vasculopathies after conventional photon radiotherapy. Given the limited scattering effect and low-dose radiation delivery to the surrounding tissues with proton beam radiotherapy, this modality is considered to be an effective treatment for pediatric skull-base tumors compared to conventional radiotherapy, and to have fewer adverse side effects. We report 2 cases of radiation-induced moyamoya syndrome following proton beam therapy in pediatric patients. To our knowledge, only a few other reported cases of radiation-induced moyamoya syndrome following proton beam therapy exist in the current literature. While rare, radiation-induced moyamoya syndrome can occur in the pediatric population with newer techniques like proton beam radiotherapy. Accordingly, patients and their families should be informed about this potential complication prior to all forms of radiation treatment.

Thinking outside the shunt-sterile CSF malabsorption in pilocytic astrocytomas: case series and review of the literature.

IntroductionVentriculoperitoneal (VP) shunt insertion is the most common cerebrospinal fluid (CSF) diversionary procedure used for the treatment of chronic hydrocephalus. Sterile CSF ascites is a rare complication of VP shunt insertion. This can arise from either an overproduction of CSF or inadequate filtration of CSF at the level of the peritoneum. By either mechanism, the development of CSF ascites requires an intact VP shunt.ObjectiveThe authors discuss two paediatric cases diagnosed with suprasellar pilocytic astrocytomas treated with platinum-based chemotherapy, who subsequently developed sterile CSF ascites. We review the literature with regard to CSF malabsorption and discuss it as a contributing factor to shunt malfunction.ConclusionCSF malabsorption with resultant ascites is a rare complication of VP shunting with many etiologies. Two common predisposing factors included the use of platinum-based chemotherapeutic agents, as well as the specific neuropathology. Further analysis of these two entities is needed in order to elucidate their role in contributing to the development of CSF ascites in this patient cohort.

Comment on: recurrent subdural hygromas after foramen magnum decompression for Chiari type I malformation

We read with interest the case report by Pereira et al. in the last issue of the Journal. It is now clear that hydrocephalus after foramen magnum decompression for Chiari I malformation should no longer be considered as an unusual complication. Our series published in the same issue reported a hydrocephalus rate of 18.5% while the oft-quoted paper by Zakaria et al. reported a rate of 8.7%. Two patients with hydrocephalus in our series had symptomatic subdural collections requiring burrhole evacuation, while Zakaria et al. reported five with subdural collections, two of whom required evacuation. Attention must now turn to elucidating a cause for post-operative hydrocephalus in foramen magnum decompression. Both the authors and Zakaria et al. suggest pin-hole tears in the arachnoid layer as a possible cause of patients subsequently developing hydrocephalus post-operatively. The authors also performed a larger than usual 3 4 cm suboccipital craniotomy. In the postoperative sagittal CT image, the cerebellar tonsils can be seen at the level of the superior border of C2 suggesting they have migrated inferiorly compared to the pre-operative MRI. It is possible that this may have obstructed cerebrospinal fluid (CSF) circulation at this level, contributing to a rise in pressure. In addition, this downward movement may have contributed to the formation of subdural hygromas by the tearing of small bridging vessels. A meta-analysis performed in 2008 suggested that there was a greater risk of CSF-related complications if duraplasty was performed after the decompression. This is also suggested by our figures – seven cases in the duraplasty group versus two cases in the non-duraplasty group. In addition, it has been suggested that the use of bovine-derived collagen matrix grafts in the posterior fossa can result in hydrodynamic complications. While the authors in this case did not use any duraplasty material, they mentioned the overlaying of Surgicel (a cellulose-based haemostatic material) and Spongostan (a porcine gelatin sponge). It is possible these agents may have played a role in the disruption of normal CSF flow dynamics at the foramen magnum, leading to hydrocephalus. Another possibility, as the authors have mentioned, is that the patient had pre-existing idiopathic intracranial hypertension. It is known that a subgroup of Chiari patients can have raised intracranial pressure (ICP) with normal ventricles. Based on our experience, we recommended pre-operative ICP monitoring prior to Chiari surgery and we support the authors’ policy of doing so. Post-Chiari decompression hydrocephalus can be difficult to manage, with patients often requiring multiple procedures including wound resuturing or exploration, external ventricular or lumbar drainage, multiple lumbar punctures or permanent CSF diversion. The authors are to be commended for successfully avoiding shunting this patient. However, given the difficulty in managing such patients, the treatment should be tailored to the individual and shunting should not be ruled out as a management option in such cases.

CNS metastasis secondary to malignant-mixed Müllerian tumor: case report and review of therapeutics

This paper reviews CNS involvement secondary to malignant-mixed Müllerian tumor or uterine carcinosarcoma, a rare aggressive biphasic Müllerian tumor. We report a cerebellar metastasis with epithelial and mesenchymal components, demonstrating heterologous rhabdomyogenic and chondroblastic differentiation. The patient had undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy for palliation of symptomatic chemotherapy-resistant node-positive disease. CNS involvement is rare, and prognostically poor, and suggestively poorer in predominantly sarcomatous metastases. Multimodal therapy is indicated; in solitary metastases, surgical resection or stereotactic radiosurgery is included, followed by whole brain radiotherapy. In unresectable brain metastases, stereotactic radiosurgery and whole brain radiotherapy warrant consideration in up to 2-3 metastases. In multiple metastases, palliative steroid therapy or cranial irradiation may be considered. Combination or platinum-based chemotherapy (i.e., ifosfamide-paclitaxel or carboplatin-paclitaxel) is indicated in all stages, with a role in both disease cure and control-directed management. Targeted therapeutics have thus far not demonstrated significant clinical efficacy.