Aminul I. Ahmed

Proposal for a prospective multi-centre audit of chronic subdural haematoma management in the United Kingdom and Ireland

Abstract Background. Chronic subdural haematoma (CSDH) is a common condition that increases in incidence with rising age. Evacuation of a CSDH is one of the commonest neurosurgical procedures; however the optimal peri-operative management, surgical technique, post-operative care and the role of adjuvant therapies remain controversial. Aim. We propose a prospective multi-centre audit in order to establish current practices, outcomes and national benchmarks for future studies. Methods. Neurosurgical units (NSU) in the United Kingdom and Ireland will be invited to enrol patients to this audit. All adult patients aged 16 years and over with a primary or recurrent CSDH will be eligible for inclusion. Outcome measures and analysis. The proposed outcome measures are (1) clinical recurrence requiring re-operation within 60 days; (2) modified Rankin scale (mRS) score at discharge from NSU; (3) morbidity and mortality in the NSU; (4) destination at discharge from NSU and (5) length of stay in the NSU. Audit standards have been derived from published systematic reviews and a recent randomised trial. The proposed standards are clinical recurrence rate < 20%; unfavourable mRS (4–6) at discharge from NSU < 30%; mortality rate in NSU < 5%; morbidity rate in NSU < 10%. Data will be submitted directly into a secure online database and analysed by the studys management group. Conclusions. The audit will determine the contemporary management and outcomes of patients with CSDH in the United Kingdom and Ireland. It will inform national guidelines, clinical practice and future studies in order to improve the outcome of patients with CSDH.

Endogenous GFAP-Positive Neural Stem/Progenitor Cells in the Postnatal Mouse Cortex Are Activated following Traumatic Brain Injury

Interest in promoting regeneration of the injured nervous system has recently turned toward the use of endogenous stem cells. Elucidating cues involved in driving these precursor cells out of quiescence following injury, and the signals that drive them toward neuronal and glial lineages, will help to harness these cells for repair. Using a biomechanically validated in vitro organotypic stretch injury model, cortico-hippocampal slices from postnatal mice were cultured and a stretch injury equivalent to a severe traumatic brain injury (TBI) applied. In uninjured cortex, proliferative potential under in vitro conditions is virtually absent in older slices (equivalent postnatal day 15 compared to 8). However, following a severe stretch injury, this potential is restored in injured outer cortex. Using slices from mice expressing a fluorescent reporter on the human glial fibrillary acidic protein (GFAP) promoter, we show that GFAP+ cells account for the majority of proliferating neurospheres formed, and that these cells are likely to arise from the cortical parenchyma and not from the subventricular zone. Moreover, we provide evidence for a correlation between upregulation of sonic hedgehog signaling, a pathway known to regulate stem cell proliferation, and this restoration of regenerative potential following TBI. Our results indicate that a source of quiescent endogenous stem cells residing in the cortex and subcortical tissue proliferate in vitro following TBI. Moreover, these proliferating cells are multipotent and are derived mostly from GFAP-expressing cells. This raises the possibility of using this endogenous source of stem cells for repair following TBI.

External ventricular drainage: Is it time to look at national practice?

Aimun A. B. Jamjoom 1 , Angelos G. Kolias 2 , Malik Zaben 3 , Aswin Chari 2 , John Kitchen 4 , Alexis Joannides 2 , Paul M. Brennan 1 , Jothy Kandasamy 1 , Silvia Gatscher 5 , William P. Gray 3 , Michael D. Jenkinson 4 , Diederik O. Bulters 6 , Conor L. Mallucci 7 , Helmut Schuster 8 , Peter J. Hutchinson 2 & Aminul I. Ahmed 6 ; UK Neurosurgical Research Network & British Neurosurgical Trainee Research Collaborative

Endoscopic Biopsy and Third Ventriculostomy for the Management of Pineal Region Tumors

OBJECTIVE To assess the histologic accuracy of endoscopic biopsy samples of the pineal region. Pineal region tumors usually present with acute hydrocephalus. Histologic diagnosis is paramount, as it greatly influences treatment. Endoscopic techniques can combine histologic diagnosis with relief of the obstructive hydrocephalus in a single operation. Because pineal region tumors can be heterogeneous, initial biopsy samples may not represent the most aggressive portion of the tumor. METHODS This retrospective study reviews our experience of endoscopic third ventriculostomy combined with biopsy of the lesion. The histologic diagnosis as a result of the initial biopsy was compared with the final histologic diagnosis to establish the accuracy of the endoscopic biopsy sample in aiding diagnosis. RESULTS Forty-seven patients underwent an endoscopic third ventriculostomy. All but 1 patient underwent a concurrent biopsy of the space-occupying lesion and 39 of 46 patients (85%) had a histologic diagnoses. In the remaining 7 patients (15%), the histology was negative; in 6 cases, the second attempt to obtain a histologic diagnosis was successful (2 repeat endoscopic biopsy samples, 2 resections, 2 stereotactic biopsy samples). In 1 patient a presumed low-grade tectal tumor was followed up with sequential scanning. Twenty-eight patients underwent subsequent operations (24 resections, 4 stereotactic biopsies). In 6 of 28 patients (21%), the histologic report was amended after the second procedure. CONCLUSIONS The endoscopic biopsy sample yields an accurate histologic diagnosis for most pineal region tumors, with a positive histologic sample in about 85% of patients. However, the results must be interpreted cautiously, as the heterogeneous nature of these tumors may lead to an approximately 21% error rate in the initial tumor diagnosis.

Prospective, multicentre study of external ventricular drainage-related infections in the UK and Ireland

Objectives External ventricular drain (EVD) insertion is a common neurosurgical procedure. EVD-related infection (ERI) is a major complication that can lead to morbidity and mortality. In this study, we aimed to establish a national ERI rate in the UK and Ireland and determine key factors influencing the infection risk. Methods A prospective multicentre cohort study of EVD insertions in 21 neurosurgical units was performed over 6 months. The primary outcome measure was 30-day ERI. A Cox regression model was used for multivariate analysis to calculate HR. Results A total of 495 EVD catheters were inserted into 452 patients with EVDs remaining in situ for 4700 days (median 8 days; IQR 4–13). Of the catheters inserted, 188 (38%) were antibiotic-impregnated, 161 (32.5%) were plain and 146 (29.5%) were silver-bearing. A total of 46 ERIs occurred giving an infection risk of 9.3%. Cox regression analysis demonstrated that factors independently associated with increased infection risk included duration of EVD placement for ≥8 days (HR=2.47 (1.12–5.45); p=0.03), regular sampling (daily sampling (HR=4.73 (1.28–17.42), p=0.02) and alternate day sampling (HR=5.28 (2.25–12.38); p<0.01). There was no association between catheter type or tunnelling distance and ERI. Conclusions In the UK and Ireland, the ERI rate was 9.3% during the study period. The study demonstrated that EVDs left in situ for ≥8 days and those sampled more frequently were associated with a higher risk of infection. Importantly, the study showed no significant difference in ERI risk between different catheter types.

Stem cells in the adult human brain

The rapidly advancing field of stem cell research holds great promise for regenerative medicine. Regenerating brain tissue, while technically the most challenging application of stem cell biology, is also likely to reap the most reward for patients. Here, we review the current state of stem cell research in the field of human neuroscience and highlight aspects that will be of relevance to neurosurgeons.

Role of proinflammatory cytokines in the inhibition of hippocampal neurogenesis in mesial temporal lobe epilepsy

Abstract Background In mesial temporal lobe epilepsy, reduced hippocampal neurogenesis correlates with severe impairment in declarative learning and memory. The proinflammatory cytokines interleukin 1β and high-mobility group box 1 (HMGB1) and their receptors have key roles in generating and perpetuating seizures. This study aimed to assess their potential role in inhibiting neurogenesis in patients with mesial temporal lobe epilepsy and whether any effect would be pharmacologically reversible as a possible mechanism to restore learning and memory deficits. Methods We generated three-dimensional (3D) stem-cell cultures (Hi-Spot, Capsant Neurotechnologies Ltd, UK), preserving the inflammatory microenvironment and key features of the in-vivo stem-cell niche, from sclerotic tissue obtained from patients undergoing surgery for epilepsy (n=23). Concentrations of interleukin 1β and HMGB1 and their receptors in sclerotic tissue were determined with PCR, western blot, ELISA, and immunohistochemistry and compared with normal cortical tissue. Neurogenesis in the presence or absence of interleukin 1β or HMGB1 antagonists was examined by quantifying the number of newly born neurons. Findings We expanded the use of air–liquid interphase technology previously used to generate Hi-Spots from the cortex of rats to generate 3D Hi-Spots from the adult human hippocampus. Using ELISA, we demonstrated that interleukin 1β concentrations were significantly elevated in sclerotic hippocampal Hi-Spots compared with control (mean 24·4 pg/mL [SD 2·3] vs 3·6 [1·4], p 2 [SD 1·13] vs 4·8 [0·7], p vs 7·7 [0·29], p Interpretation We provide a novel in-vitro molecular model that relies on the interleukin 1β–interleukin 1 receptor–HMGB1 axis. Whereas previous studies have elegantly shown that blockade of this axis renders epileptic animals free of seizures, our observations support the development of therapeutic interventions that counteract the microenvironment to promote hippocampal neurogenesis. This possibility could lead to pharmacological strategies to treat learning and memory deficits in mesial temporal lobe epilepsy. Funding Epilepsy Research UK.

Activation of endogenous neural stem cells after traumatic brain injury

Abstract Background Interest in promoting regeneration of the injured nervous system has recently turned to the use of endogenous stem cells. Elucidating cues implicated in driving these precursor cells out of quiescence after injury and the signals that drive them towards neuronal and glial fates will help harness these cells for repair. In the cortex, cells expressing the astrocytic marker, glial acidic fibrillary protein (GFAP), generate both neurons and glia, but only after a stab injury to the cortex. This observation raises the possibility that a source of potential endogenous stem cells resides in the cortex. We have focused on the mechanisms that underly this injury induced activation in traumatic brain injury. Methods Using a biomechanically validated in-vitro organotypic stretch injury model, we cultured cortico-hippocampal slices from postnatal mice. A stretch injury, equivalent to a severe traumatic brain injury, was applied to the slices and the neurogenic potential of the tissue in both the cortex and the hippocampus was measured. Findings In uninjured cortex, proliferative potential under in-vitro conditions was virtually absent in older slices (equivalent postnatal day 15 vs 8). However, after a severe stretch injury, this potential was restored in injured outer cortex. Using slices from mice expressing a fluorescent reporter on the human GFAP promoter, we showed that GFAP-positive cells accounted for the majority of the proliferating neurospheres formed, and that these cells were likely to arise from the cortical parenchyma and not the subventricular zone. Upregulation of Sonic Hedgehog signalling, a pathway known to regulate stem-cell proliferation, correlated with restoration of regenerative potential after traumatic brain injury. We found an increase in mRNA expression of transforming growth factor β, a cytokine known to increase the number of GFAP-expressing cells in the cortex. Interpretation Our results indicate that a source of quiescent endogenous stem cells residing in the cortex proliferate in-vitro after traumatic brain injury. Moreover, these proliferating cells are multipotent and are derived mostly from GFAP-expressing cells. We are investigating the contribution of signalling pathways to this stem-cell activation. Our findings raise the possibility of using this endogenous source of stem cells for repair after traumatic brain injury. Funding The Royal College of Surgeons of England, Wessex Medical Research, Academy of Medical Sciences.

The British Neurosurgical Trainee Research Collaborative: Five Years On

Since its inception in 2012, the British Neurosurgical Trainee Research Collaborative (BNTRC) has established itself as a robust example of a trainee-led research collaborative. This article summarises the work of the collaborative over its first 5 years of existence, outlining the structure, its research projects, impact and future directions.

Assessment of precision and reproducibility of a new myograph

BackgroundThe physiological characteristics of muscle activity and the assessment of muscle strength represent important diagnostic information. There are many devices that measure muscle force in humans, but some require voluntary contractions, which are difficult to assess in weak or unconscious patients who are unable to complete a full range of voluntary force assessment tasks. Other devices, which obtain standard muscle contractions by electric stimulations, do not have the technology required to induce and measure reproducible valid contractions at the optimum muscle length.MethodsIn our study we used a newly developed diagnostic device which measures accurately the reproducibility and time-changed-variability of the muscle force in an individual muscle. A total of 500 in-vivo measurements of supra-maximal isometric single twitch contractions were carried out on the musculus adductor pollicis of 5 test subjects over 10 sessions, with ten repetitions per session. The same protocol was performed on 405 test subjects with two repetitions each to determine a reference-interval on healthy subjects.ResultsUsing our test setting, we found a high reproducibility of the muscle contractions of each test subject. The precision of the measurements performed with our device was 98.74%. Only two consecutive measurements are needed in order to assess a real, representative individual value of muscle force. The mean value of the force of contraction was 9.51 N and the 95% reference interval was 4.77–14.25 N.ConclusionThe new myograph is a highly reliable measuring device with which the adductor pollicis can be investigated at the optimum length. It has the potential to become a reliable and valid tool for diagnostic in the clinical setting and for monitoring neuromuscular diseases.