Joan Grieve

External ventricular drain insertion accuracy: is there a need for change in practice?

OBJECTIVEFree-hand insertion of an external ventricular drain (EVD) is a common emergency neurosurgical procedure, mostly performed for critically ill patients. Although EVD complications have been studied thoroughly, the accuracy of EVD positioning has been audited only occasionally. METHODSPost-EVD insertion computed tomographic scans performed in our unit over a 2-year period were analyzed for EVD tip location and intracranial catheter length. RESULTSA total of 183 post-EVD insertion scans were reviewed. Of those, 73 EVD tips (39.9%) were in the ipsilateral frontal horn of the lateral ventricle (the desired target); of those, 18 (25%) required EVD revision/reinsertion. Of the others, 35 (19.1%) were in the third ventricle, 33 (18%) in the body of the lateral ventricle, 19 (10.4%) in the subarachnoid space, 5 (2.7%) in the contralateral frontal horn, and 18 (9.8%) within the brain parenchyma. When the EVD tip was outside the desired target, 44 of the patients (40%) required EVD revision/reinsertion procedure (P = 0.0383). CONCLUSIONFree-hand insertion of an EVD is an inaccurate procedure, and further studies are required to assess the accuracy and feasibility of the routine use of neuronavigation, ultrasonography, or other guidance techniques and the possible implication of the decreasing revision rate, complications, and length of hospital stay.

Brain biopsy in dementia: clinical indications and diagnostic approach

Brain biopsy may be performed to make a definitive diagnosis in patients with rapidly progressive dementia. To assess the value of this procedure, we previously studied 90 consecutive cerebral biopsies performed in the tertiary referral centre of the National Hospital for Neurology and Neurosurgery, Queen Square between 1989 and 2003 (6 biopsies/year). Fifty-seven percent of all biopsies were diagnostic with Alzheimer’s disease (18%), Creutzfeldt–Jakob disease (CJD) (12%) and inflammatory disorders (9%) being the most frequent. In the non-diagnostic group and for the series as a whole non-specific gliosis was the commonest diagnosis (37%). Treatment was altered because of information obtained from neuropathological findings in 11% of cases. To identify changes in practice that may have occurred due to recent advances in clinical assessment and improved histopathological techniques, we performed a follow-up study of 19 brain biopsies (~3 cases/year) carried out for a dementing illness in the same centre between 2004 and 2009. These data suggest that brain biopsy may be less frequently used to help clinical diagnosis whilst its diagnostic yield increased from 57 to 74%. The commonest diagnosis was CJD, mostly suspected during life. Amongst the diagnoses, there were two cases of vasculitis and two cases of primary neurodegenerative dementia. These data suggest that improved clinical selection criteria supported by advances in diagnostic testing may result in brain biopsy being less frequently required, although it may still provide useful diagnostic information in difficult cases. We propose algorithms to aid the clinician in selecting appropriate patients for a biopsy and the neuropathologist in assessing a biopsy specimen.

Epigenetic Regulation of Survivin by Bmi1 is Cell Type Specific During Corticogenesis and in Gliomas

Polycomb group proteins are essential regulators of stem cell function during embryonic development and in adult tissue homeostasis. Bmi1, a key component of the Polycomb Repressive Complex 1, is highly expressed in undifferentiated neural stem cells (NSC) as well as in several human cancers including high‐grade gliomas—highly aggressive brain tumors. Using a conditional gene activation approach in mice, we show that overexpression of Bmi1 induces repressive epigenetic regulation of the promoter of Survivin, a well‐characterized antiapoptotic protein. This phenomenon is cell type‐specific and it leads to apoptotic death of progenitor cells exclusively upon commitment toward a neuronal fate. Moreover, we show that this is triggered by increased oxidative stress‐induced DNA damage. In contrast, undifferentiated NSC as well as glioma‐initiating cells display an open chromatin configuration at the Survivin promoter and do not undergo apoptotic death. These findings raise the possibility that normal and neoplastic stem cells depend on the same mechanism for surviving the hyperproliferative state induced by increased Bmi1 expression. STEM Cells2013;31:190–202

Stability of ruptured intracranial aneurysms treated with detachable coils: is delayed follow-up angiography warranted?

The optimal strategy for monitoring the stability of ruptured intracranial aneurysms following coil embolisation is unclear. The value of delayed follow-up angiography in detecting new recurrences or progression of residual lesions visualised on earlier angiographic studies was determined in the light of the increasing use of non-invasive imaging techniques such as time of flight magnetic resonance angiography (TOF-MRA) for the evaluation of intracranial aneurysm occlusion. Ninety-seven patients with 105 ruptured aneurysms treated with detachable coils in 2005 and 2006 were included. The presence of a residual neck or aneurysm was assessed on catheter angiograms performed at 6 months and 2 years using the Raymond criteria (Class I = completely occluded, class II = small residual neck, class III = aneurysm sac filling). At 6-month follow-up, 32% of class I aneurysms progressed to class II and 6% of these aneurysms required re-treatment. A further 2-year angiogram was obtained in 59 patients with 65 aneurysms. Ninety-six per cent of class I, 100% of the class II and class III aneurysms remained unchanged at 2 years compared to 6 months. In our series, most recurrences were apparent at 6-month follow-up. The vast majority of coiled ruptured aneurysms that were class I or II at 6 months remained stable at 2-year follow-up. In the absence of a residual lesion in the early angiographic study, a further delayed catheter angiogram may not be warranted. The use of non-invasive strategies such as TOF-MRA should be considered.

Early single centre experience of flow diverting stents for the treatment of cerebral aneurysms.

Abstract Introduction. The flow diverting stent (FDS) is a relatively new endovascular therapeutic tool specifically designed to reconstruct the parent artery and divert blood flow along the normal anatomical course and away from the aneurysm neck and dome. Methods. Retrospective review of prospectively built clinical and imaging database of patients treated with FDS at the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK was done. Results. Between 18/03/2008 and 10/11/2011, 80 patients underwent 84 FDS insertion procedures for various indications. Mean duration of clinical follow-up was 11.3 ± 9.3 months and of imaging follow-up was 10.6 ± 9.3 months. Sixty-seven had anterior circulation aneurysms while 17 had posterior circulation aneurysms. Seven (8.3%) patients died (two probably not related, giving a procedure-related mortality of 5.9%), eight had permanent new deficit (9.5%), 20 had transient deficit (23%) and 49 (58%) had no complications. There was a trend towards bad outcome with larger posterior circulation aneurysms. Angiographic follow-up showed 38% cure rate at 6 months and 61% at 12 months. Conclusion. FDS should only be used following multidisciplinary discussion in selected patients. Further data is required regarding long-term safety, efficacy and indications.

Diagnostic implications of histological analysis of neurosurgical aspirate in addition to routine resections

Many neurosurgical centers use surgical aspirators to remove brain tumor tissue. The resulting aspirate consists of fragmented viable tumor, normal or tumor‐infiltrated brain tissue as well as necrotic tissue, depending on the type of tumor. Typically, such fragmented aspirate material is collected but discarded and not included when making the histopathological diagnosis. Whereas the general suitability of surgical aspirate for histological diagnosis and immunohistochemical staining has been reported previously, we have systematically investigated whether the collection and histological examination of surgical aspirate has an impact on diagnosis, in particular on the tumor grading, by providing additional features. Surgical and aspirate specimens from 85 consecutive neurosurgical procedures were collected and routinely processed. Sixty‐five of the 85 specimens were intrinsic brain tumors and the remainder consisted of metastatic tumors, meningiomas, schwannomas and lymphomas. Important diagnostic features seen in surgical aspirate were microvascular proliferation (n = 3), more representative necrosis (n = 2), and gemistocytic component (n = 2). In one case, microvasular proliferations were seen in the aspirate only, leading to a change of diagnosis. Collection of surgical aspirate also generates additional archival material which can be microdissected and used for tissue microarrays or for molecular studies.

Association of functional MMP-2 gene variant with intracranial aneurysms: case-control genetic association study and meta-analysis

Abstract Introduction: Abnormalities in Matrix Metalloproteinase (MMP) genes, which are important in extracellular matrix (ECM) maintenance and therefore arterial wall integrity are a plausible underlying mechanism of intracranial aneurysm (IA) formation, growth and subsequent rupture. We investigated whether the rs243865 C > T SNP (single nucleotide polymorphism) within the MMP-2 gene (which influences gene transcription) is associated with IA compared to matched controls. Materials and Methods: We conducted a case-control genetic association study, adjusted for known IA risk factors (smoking and hypertension), in a UK Caucasian population of 1409 patients with intracranial aneurysms (IA), and 1290 matched controls, to determine the association of the rs243865 C > T functional MMP-2 gene SNP with IA (overall, and classified as ruptured and unruptured). We also undertook a meta-analysis of two previous studies examining this SNP. Results: The rs243865 T allele was associated with IA presence in univariate (OR 1.18 [95% CI 1.04–1.33], p = .01) and in multi-variable analyses adjusted for smoking and hypertension status (OR 1.16 [95% CI 1.01-1.35], p = .042). Subgroup analysis demonstrated an association of the rs243865 SNP with ruptured IA (OR 1.18 [95% CI 1.03–1.34] p = .017), but, not unruptured IA (OR 1.17 [95% CI 0.97–1.42], p = .11). Conclusions: Our study demonstrated an association between the functional MMP-2 rs243865 variant and IAs. Our findings suggest a genetic role for altered extracellular matrix integrity in the pathogenesis of IA development and rupture.

Tablets or scalpel: Pituitary hyperplasia due to primary hypothyroidism.

We describe a patient with pituitary hyperplasia due to primary hypothyroidism. Pituitary hyperplasia and pituitary masses cannot be reliably differentiated on imaging alone, despite significant improvement in imaging quality in recent years.