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ABSTRACT: Traumatic brain injury (TBI) remains a major public health problem. This review aims to present the principles upon which modern TBI management should be based. The early management phase aims to achieve haemodynamic stability, limit secondary insults (eg hypotension, hypoxia), obtain accurate neurological assessment and appropriately select patients for further investigation. Since 2003, the mainstay of risk stratification in the UK emergency departments has been a system of triage based on clinical assessment, which then dictates the need for a CT scan of the head. For patients with acute subdural or extradural haematomas, time from clinical deterioration to operation should be kept to a minimum, as it can affect their outcome. In addition, it is increasingly recognised that patients with severe and moderate TBI should be managed in neuroscience centres, regardless of the need for neurosurgical intervention. The monitoring and treatment of raised intracranial pressure is paramount for maintaining cerebral blood supply and oxygen delivery in patients with severe TBI. Decompressive craniectomy and therapeutic hypothermia are the subject of ongoing international multi-centre randomised trials. TBI is associated with a number of complications, some of which require specialist referral. Patients with post-concussion syndrome can be helped by supportive management in the context of a multi-disciplinary neurotrauma clinic and by patient support groups. Specialist neurorehabilitation after TBI is important for improving outcome.
Practical Neurology 03/2013;
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ABSTRACT: BACKGROUND:Up to two-thirds of patients report moderate to severe surgical site pain after craniotomy procedures, and there is understandable reluctance to manage these symptoms with systemic opioids that may impair neurological assessment. Furthermore, there is a lack of consensus and evidence concerning alternative analgesia strategies for cranial neurosurgery. Regional scalp block (RSB) is an established technique that involves infiltration of local anesthetic (LA) at well-defined anatomical sites targeting the major sensory innervation of the scalp. However, the efficacy of RSB in reducing postoperative pain remains unclear. In this study, we sought to systematically identify and review randomized controlled trials (RCTs) of RSB and synthesize an overall estimate of efficacy in a quantitative meta-analysis.METHODS:Medline, EMBASE, and the Cochrane Central Register of Controlled Trials databases were searched for all RCTs evaluating the effect of RSB on postoperative pain after craniotomy. Titles, abstracts, and papers were reviewed independently by 2 authors against predefined inclusion criteria. Two authors independently assessed the quality of included studies and extracted data on patient-reported pain scores, other analgesia requirements, and complications of RSB. Pain scores were scaled to a common 0 to 10 interval with higher scores indicating more severe pain. Meta-analysis of the pooled treatment effect was performed with a random-effects inverse-variance weighted model; heterogeneity was quantified with the I2 statistic.RESULTS:The literature search identified 138 unique citations, from which 7 RCTs with a total recruitment of 320 patients met the inclusion criteria. All studies used standard LA drugs (lidocaine, bupivacaine, or ropivacaine); in 3 studies, LA was combined with epinephrine. In 3 studies, RSB was performed preoperatively; in the other 4 studies, it was administered postoperatively after wound closure. No complications attributable to RSB were reported. Meta-analysis found a pooled reduction in pain score at 1 hour postoperatively (N = 5 studies; mean difference, -1.61; 95% confidence interval, -2.06 to -1.15; P < 0.001; I2 = 0%). Subgroup analysis of preoperative RSB showed significant reduction in pain scores at 2, 4, and 6 to 8 hours after surgery whereas postoperative RSB was associated with significant reduction in pain scores at 2, 4, 6 to 8 and 12 hours assessments. There was also an overall reduction in the opioid requirements over the first 24 hours postoperatively, although with significant heterogeneity among the studies (N = 6 studies; standardized mean difference, -0.79; 95% confidence interval, -1.55 to -0.03; P = 0.04; I2 = 86%).CONCLUSION:Published RCTs of RSB are small and of limited methodological quality but meta-analysis shows a consistent finding of reduced postoperative pain. This evidence supports the use of RSB for patients undergoing craniotomy.
Anesthesia and analgesia 03/2013; · 3.08 Impact Factor
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ABSTRACT: The ability to deliver drug molecules effectively across the blood-brain barrier into the brain is important in the development of central nervous system (CNS) therapies. Cerebral microdialysis is the only existing technique for sampling molecules from the brain extracellular fluid (ECF; also termed interstitial fluid), the compartment to which the astrocytes and neurones are directly exposed. Plasma levels of drugs are often poor predictors of CNS activity. While cerebrospinal fluid (CSF) levels of drugs are often used as evidence of delivery of drug to brain, the CSF is a different compartment to the ECF. The continuous nature of microdialysis sampling of the ECF is ideal for pharmacokinetic (PK) studies, and can give valuable PK information of variations with time in drug concentrations of brain ECF versus plasma. The microdialysis technique needs careful calibration for relative recovery (extraction efficiency) of the drug if absolute quantification is required. Besides the drug, other molecules can be analysed in the microdialysates for information on downstream targets and/or energy metabolism in the brain. Cerebral microdialysis is an invasive technique, so is only useable in patients requiring neurocritical care, neurosurgery or brain biopsy. Application of results to wider patient populations, and to those with different pathologies or degrees of pathology, obviously demands caution. Nevertheless, microdialysis data can provide valuable guidelines for designing CNS therapies, and play an important role in small phase II clinical trials. In this review, we focus on the role of cerebral microdialysis in recent clinical studies of antimicrobial agents, drugs for tumour therapy, neuroprotective agents and anticonvulsants.
Journal of Pharmacokinetics and Biopharmaceutics 03/2013; · 2.06 Impact Factor
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Acta Neurochirurgica 11/2012; · 1.52 Impact Factor
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ABSTRACT: Postoperative back pain is common after decompression surgery for lumbar stenosis and often delays discharge from hospital. Achieving regional analgesia by intraoperative delivery of epidural opiates after lumbar canal decompression is a promising approach to reduce postoperative pain and enhance early mobilization. However, there have been concerns about opiate-related complications, such as respiratory depression and urinary retention in what is generally an elderly population of patients.
To assess the analgesic efficacy of bolus epidural fentanyl administered intraoperatively after lumbar decompression for degenerative canal stenosis.
Patient-blinded randomized controlled trial conducted at two university neurosurgical centers.
Adults (older than 18 years) with neurogenic claudication and/or lower limb radiculopathy and concordant lumbar spinal canal stenosis demonstrated on magnetic resonance imaging. Patients with previous lumbar spinal surgery, a contraindication to fentanyl, or requiring instrumentation were excluded.
The primary outcome measure was patient-reported Visual Analogue Score (VAS) for pain recorded preoperatively, in recovery, and on the first and second postoperative days if the patient remained in the hospital. Secondary outcomes were duration of surgery, length of stay, and any side effects or complications.
Patients underwent a one to three level lumbar canal decompression as required, via a midline incision, under general anesthesia. Before wound closure either no drug (control) or a 100-μg bolus of fentanyl was administered via an epidural catheter inserted 10 cm rostral to the operated level. Patients were blinded to group allocation, and analysis was by intention to treat. The trial was approved by the National Health Service Research Ethics Service and the Medicines and Healthcare products Regulatory Agency. No commercial or other source of funding was received.
Sixty patients were randomized, 29 to fentanyl and 31 to control. Demographics, duration of surgery, and preoperative VAS were not significantly different between the groups. VAS in recovery was significantly lower in patients treated with fentanyl (mean [standard deviation]: 2.6 [2.7] vs. 4.7 [2.4]; p=.003). Later VAS and postoperative length of stay were similar between groups. More patients in the fentanyl group required temporary urinary catheterization, but there was no significant difference in the incidence of side effects.
Bolus epidural fentanyl provides effective short-term postoperative analgesia after lumbar canal decompression and may be a useful adjunct to pain management in patients undergoing lumbar spine surgery.
The spine journal: official journal of the North American Spine Society 08/2012; 12(8):646-51. · 2.90 Impact Factor
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ABSTRACT: Acute subdural haematomas (ASDH) occur commonly following traumatic brain injury and may be evacuated by either craniotomy (CR) or decompressive craniectomy (DC). We reviewed a series of consecutive patients undergoing evacuation of a traumatic ASDH at a regional centre, comparing observed clinical outcomes (assessed by Glasgow Outcome Scale at six months) with those predicted by the CRASH-CT prognostic model.
Retrospective review of prospectively collected data.
Ninety-one patients were identified (51 DC and 40 CR ). Eighty-five had available admission data sets from which predicted outcome could be calculated. The DC group were younger than the CR group (p = 0.015). The DC group also had a greater proportion of patients whose pre-intubation GCS was ≤8 (p = 0.001), with significant extracranial injuries (p = 0.001) and obliterated basal cisterns (p = 0.001) on their pre-operative CT scan. Bone flaps in the DC group (n = 45) were longer (mean 11.6 cm; 95 % CI: 11.1-12.1) in comparison to bone flaps in the CR (n = 34) group [(mean 10.2 cm; 95 % CI: 9.35 - 10.9); p = 0.0024] The mean CRASH-CT predicted risk of 14-day mortality and of unfavourable outcome at six months was significantly higher in the DC group compared with the CR group. Eighty-eight patients had available 6-month Glasgow Outcome Scale scores. Favourable outcomes were observed in 42 % of DC versus 45 % of CR (p = 0.83). The overall mortality rate was 38 % in DC versus 32 % in CR (p = 0.65). The standardised morbidity ratio (observed/expected unfavourable outcomes) was 0.75 (95 % CI: 0.51-1.07) for DC and 0.90 (95 % CI: 0.57-1.35) for CR.
CR and DC for traumatic ASDH are both commonly used for primary evacuation of ASDH. Primary DC may be more effective than CR for selected patients with ASDH. Class I evidence is required in order to refine the indications for DC following evacuation of ASDH.
Acta Neurochirurgica 06/2012; 154(9):1555-61. · 1.52 Impact Factor
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ABSTRACT: Abstract We report the case of a ruptured internal carotid artery (ICA) aneurysm that demonstrated significant persistent filling despite management with a common carotid to middle cerebral artery saphenous vein extracranial-intracranial bypass and subsequent permanent ICA balloon occlusion. The residual aneurysm was successfully embolised with detachable coils using a novel endovascular approach via the bypass graft.
British Journal of Neurosurgery 01/2012; 26(5):759-62. · 0.88 Impact Factor
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ABSTRACT: There is a growing realisation that neuro-inflammation plays a fundamental role in the pathology of Traumatic Brain Injury (TBI). This has led to the search for biomarkers that reflect these underlying inflammatory processes using techniques such as cerebral microdialysis. The interpretation of such biomarker data has been limited by the statistical methods used. When analysing data of this sort the multiple putative interactions between mediators need to be considered as well as the timing of production and high degree of statistical co-variance in levels of these mediators. Here we present a cytokine and chemokine dataset from human brain following human traumatic brain injury and use principal component analysis and partial least squares discriminant analysis to demonstrate the pattern of production following TBI, distinct phases of the humoral inflammatory response and the differing patterns of response in brain and in peripheral blood. This technique has the added advantage of making no assumptions about the Relative Recovery (RR) of microdialysis derived parameters. Taken together these techniques can be used in complex microdialysis datasets to summarise the data succinctly and generate hypotheses for future study.
PLoS ONE 01/2012; 7(6):e39677. · 4.09 Impact Factor
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ABSTRACT: There is an increasing recognition that following traumatic brain injury, a cascade of inflammatory mediators is produced, and contributes to the pathological consequences of central nervous system injury. This review summarises the key literature from pre-clinical models that underlies our understanding of innate inflammation following traumatic brain injury before focussing on the growing evidence from human studies. In addition, the underlying molecular mediators responsible for blood brain barrier dysfunction have been discussed. In particular, we have highlighted the different sampling methodologies available and the difficulties in interpreting human data of this sort. Ultimately, understanding the innate inflammatory response to traumatic brain injury may provide a therapeutic avenue in the treatment of central nervous system disease.
Progress in Neurobiology 09/2011; 95(3):352-72. · 8.87 Impact Factor
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ABSTRACT: Intracranial neurenteric cysts are rare congenital lesions that typically occur in the posterior fossa. We report a case of a 70-year-old gentleman presenting with gait disturbance, found to have a neurenteric cyst primarily arising from and expanding the sella turcica. A review of the literature revealed 27 reports of supratentorial neurenteric cysts. Clinical presentation, radiological characteristics, treatment, prognosis and embryological origin are discussed. Intracranial neurenteric cysts should be included in the differential with any well-demarcated cystic lesion without enhancement on magnetic resonance imaging (MRI). Complete surgical excision is the treatment of choice, with good prognosis.
Acta Neurochirurgica 07/2011; 153(7):1519-25. · 1.52 Impact Factor
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Neurosurgery 06/2011; 69(4):E1029-30. · 2.79 Impact Factor
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ABSTRACT: Serum albumin is an established predictor of survival in numerous cancers but its prognostic value in central nervous system tumours has not been established. Here we have examined prognostic factors in 685 patients with histologically proven glioblastoma multiforme (GBM), the majority of which (n = 549) had pre-operative serum albumin assayed. Mean serum albumin was 34.7 g/l (SD 5.2). Post-operative survival was significantly less for patients with hypoalbuminaemia (<30 g/l, n = 82) than for patients with normal albumin level (median 2.3 vs. 5.6 months, P < 0.001 Log-rank test). Furthermore, patients with lower normal albumin (30-40 g/l, n = 371) had significantly shorter survival compared against patients with albumin in the upper normal range (40-50 g/l, n = 96; median 5.1 vs. 8.8 months, P < 0.001). Multivariate Cox regression showed the independent predictors of survival were age, debulking surgery, chemoradiotherapy, and serum albumin (Hazard Ratio 0.97 per g/l, P < 0.005). This study suggests pre-operative serum albumin level is a significant predictor of survival in patients with GBM. Further studies are needed to examine the relationship between albumin and other known prognostic factors, and to determine if pre-operative serum albumin is a clinically useful predictor of survival.
Journal of Neuro-Oncology 03/2011; 105(1):77-81. · 3.21 Impact Factor
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ABSTRACT: Measuring health-related quality of life (HRQoL) has an important role in the comprehensive assessment of patient recovery following traumatic brain injury (TBI). We examined the validity of domain and summary scores derived from the Medical Outcomes Survey 36-Item Short Form Health Questionnaire (SF-36) as outcome measures for TBI in a prospective study of 514 patients with a range of functional impairment (Glasgow Outcome Scale-Extended [GOSE] scores 3-8). Item scaling criteria for the eight domain scores were tested and principal component analysis was used to examine if physical and mental component summary scores were valid. External validity was assessed by comparison with GOSE. Mean response, variance, and distribution of the items were largely equivalent, and item-own scale correlations corrected for overlap all exceeded the threshold for equivalent contribution to domain scores and convergent validity. All corrected item-own scale correlations were greater than the respective item-other correlations indicating no scaling failures, and reliability coefficients for the domain scores were high and substantially more than the inter-domain correlations. Overall, criteria for summing items into domain scores were satisfied, and there was a significant relationship of increasing score with more favorable GOSE class across all domains. However, there were floor and/or ceiling effects in four of the eight domains, and principal component analysis of the domain scores demonstrated only a unidimensional structure to the data. We conclude that individual SF-36 domain scores are valid measures of HRQoL in TBI patients, but that the physical and mental component summaries should be interpreted with caution.
Journal of neurotrauma 10/2010; 27(12):2173-81. · 4.25 Impact Factor
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ABSTRACT: We describe the case of a patient with known Wegener's Granulomatosis who developed a spontaneous intradural haematoma in the thoracic spine against a background of a recent relapse in her vasculitis. Decompression resulted in a rapid recovery of lower limb function. We propose involvement of the spinal meninges in the systemic vasculitis as the cause of haemorrhage.
Clinical neurology and neurosurgery 05/2010; 112(4):341-3. · 1.30 Impact Factor
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ABSTRACT: The Roland-Morris disability scale (RMS) for disability secondary to low back pain is a validated and popular instrument in clinical practice and research. We have made a simple modification to the questionnaire to increase sensitivity to sciatica (RMS-L) and validated this in patients with lumbar disc prolapse and radiculopathy.
The original RMS and modified RMS-L were prospectively administered to 203 patients presenting with lumbar radiculopathy and intervertebral disc prolapse demonstrated on MRI. Scores at pre-operative assessment and follow-up at 3 months and 12-24 months were compared against visual analogue scores (VAS) and Short Form 36 generic health domains.
Correlation between RMS-L and VAS leg pain was significantly greater than between original RMS and VAS leg pain pre-operatively (r = 0.57 vs. 0.17, p < 0.001) and at 3 months follow-up (r = 0.78 vs. 0.49, p < 0.001). Conversely, correlation between RMS and VAS back pain was significantly higher (r = 0.58 vs. 0.15, p < 0.001). Compared with RMS, at pre-operative assessment, RMS-L showed greater correlation with SF-36 physical function (PF; r = -0.57 vs. -0.32, p < 0.001) and bodily pain (r = -0.58 vs. -0.35, p < 0.001). Similarly, the change in PF to 3 months follow-up showed significantly higher correlation with change in RMS-L compared with the change in RMS (r = -0.60 vs. -0.37, p < 0.001). Effect sizes were good for RMS-L (1.19-1.24) but only moderate for RMS (0.69-0.79).
The original and modified RMS can discriminate disability due to low back pain and sciatica, respectively. Separate assessment of these symptoms and their contribution to functional impairment is useful in assessing suitability for surgery and predicting outcome.
Acta Neurochirurgica 05/2010; 152(9):1549-53; discussion 1553. · 1.52 Impact Factor
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ABSTRACT: Herpes simplex is a common human pathogen that has rare but severe manifestations including encephalitis.
A 44-year-old man underwent uneventful resection of an acoustic neuroma. Postoperatively, he developed swinging pyrexia, vomiting, and episodic confusion. Analysis of cerebrospinal fluid showed a lymphocytosis, and polymerase chain reaction revealed herpes simplex DNA. After treatment of herpes encephalitis with acyclovir, the patient made a good recovery.
Herpes encephalitis is a rare complication of neurosurgical procedures, and the most likely etiology is reactivation of latent infection from manipulation of cranial nerves.
Surgical Neurology 08/2009; 72(5):502-4. · 1.67 Impact Factor
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ABSTRACT: Health-Related Quality of Life (HRQoL) assessments in spinal disease offer the potential of outcome measures that better represent patients' disability and response to treatment. The Short Form 36 Health Survey (SF-36) is a generic HRQoL questionnaire that has been extensively used in primary and secondary care, but before it can be routinely applied in patients with spinal disease must be validated against traditional specific measures of physical and mental morbidity. Patients with lumbar disc prolapse, lumbar canal stenosis, and cervical spondylotic radiculomyelopathy were identified from a prospectively maintained database. Visual Analogue Scales (VAS) and condition-specific questionnaires including the Roland Morris Disability Score (RMDS), Myelopathy Disability Index (MDI), and Hospital Anxiety and Depression Scales (HADS), were completed alongside the SF-36 survey at baseline and following surgery. Convergent, discriminant, and predictive validity were assessed by computing correlations between the specific and generic scores. In addition, responsiveness (Standardised Response Mean, SRM) and floor and ceiling effects were examined. Data from 1623 assessments of 620 patients were available. Convergent validity was shown by strong correlations between condition-specific physical scores (MDI or RMDS) and the Physical Function and Bodily Pain domains of SF-36 (rho = -0.52 to -0.76, all p < 0.01). VAS for leg or arm pain were also strongly correlated with Bodily Pain domain scores (rho = -0.54 to -0.77, all p < 0.01). Discriminant validity was confirmed by non-significant partial correlations between Physical Function and Mental Health SF-36 domains when controlled for HADS scores (r = -0.01 to 0.02, p > 0.05). Predictive validity was demonstrated by similar correlations between pre- and post-operative scores for specific and generic instruments. Physical Function, Bodily Pain, and Mental Health domains were all free of significant floor or ceiling effects and showed moderate to good responsiveness (SRM 0.54-1.72). SF-36 domain scores are valid for measuring morbidity and surgical outcomes in common spinal disorders.
British Journal of Neurosurgery 08/2009; 23(4):401-5. · 0.88 Impact Factor
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Neurology 07/2007; 68(24):2155. · 8.31 Impact Factor
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ABSTRACT: We report the unexpected adjustment of a Strata shunt valve by a vagus nerve stimulator-activating magnet, resulting in symptomatic under-drainage of CSF. Implantable devices using magnets for calibration and activation are becoming more prevalent within neurosurgery and the present case highlights the potential for adverse interactions.
British Journal of Neurosurgery 03/2007; 21(1):41-2. · 0.88 Impact Factor
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ABSTRACT: There is an increasing recognition that following traumatic brain injury, a cascade of inflammatory mediators is produced, and contributes to the pathological consequences of central nervous system injury. This review summarises the key literature from pre-clinical models that underlies our understanding of innate inflammation following traumatic brain injury before focussing on the growing evidence from human studies. In addition, the underlying molecular mediators responsible for blood brain barrier dysfunction have been discussed. In particular, we have highlighted the different sampling methodologies available and the difficulties in interpreting human data of this sort. Ultimately, understanding the innate inflammatory response to traumatic brain injury may provide a therapeutic avenue in the treatment of central nervous system disease.Highlights► A wide range of cytokines and growth factors are produced as a result of traumatic brain injury. ► There is evidence for both beneficial and damaging consequences of cytokine production, depending on the concentration and context in which they are produced. ► Blood brain barrier dysfunction is a common consequence of several central nervous system pathologies. ► Cytokine production in blood, cerebrospinal fluid and brain extracellular space is distinct both qualitatively and quantitatively. ► Cytokine action provides a novel and promising therapeutic target following traumatic brain injury.
Progress in Neurobiology. 95(3):352-372.
