Kawadler J.M.,Developmental Imaging and Biophysics Section |
Kirkham F.J.,University College London |
Clayden J.D.,Developmental Imaging and Biophysics Section |
Hollocks M.J.,University of Cambridge |
And 9 more authors.
Stroke | Year: 2015
Background and Purpose-Sickle cell anemia is associated with compromised oxygen-carrying capability of hemoglobin and a high incidence of overt and silent stroke. However, in children with no evidence of cerebral infarction, there are changes in brain morphometry relative to healthy controls, which may be related to chronic anemia and oxygen desaturation. Methods-A whole-brain tract-based spatial statistics analysis was carried out in 25 children with sickle cell anemia with no evidence of abnormality on T2-weighted magnetic resonance imaging (13 male, age range: 8-18 years) and 14 age-and race-matched controls (7 male, age range: 10-19 years) to determine the extent of white matter injury. The hypotheses that white matter damage is related to daytime peripheral oxygen saturation and steady-state hemoglobin were tested. Results-Fractional anisotropy was found to be significantly lower in patients in the subcortical white matter (corticospinal tract and cerebellum), whereas mean diffusivity and radial diffusivity were higher in patients in widespread areas. There was a significant negative relationship between radial diffusivity and oxygen saturation (P<0.05) in the anterior corpus callosum and a trend-level negative relationship between radial diffusivity and hemoglobin (P<0.1) in the midbody of the corpus callosum. Conclusions-These data show widespread white matter abnormalities in a sample of asymptomatic children with sickle cell anemia, and provides for the first time direct evidence of a relationship between brain microstructure and markers of disease severity (eg, peripheral oxygen saturation and steady-state hemoglobin). This study suggests that diffusion tensor imaging metrics may serve as a biomarker for future trials of reducing hypoxic exposure. © 2015 American Heart Association, Inc.
PubMed | Washington University in St. Louis, Methodist Houston, Albany Medical Center, Wessex Neurological Center and 6 more.
Type: Journal Article | Journal: Journal of neurointerventional surgery | Year: 2016
The low-profile visualized intraluminal support (LVIS) device is a new, braided, intracranial microstent designed for stent-assisted coiling.To present the results of a single-arm, prospective, multicenter trial of the LVIS for treatment of wide-necked intracranial aneurysms.31 patients with unruptured, wide-necked (neck 4mm or dome:neck ratio 2) intracranial aneurysms were treated with the LVIS device and bare platinum coils at six US centers (investigational device exemption G110014). Clinical follow-up was conducted at 30days and 6months. Angiographic follow-up was performed at 6months. The primary safety endpoint was any major stroke or death within 30days or major ipsilateral stroke or neurological death within 6months. Probable benefit was defined as 90% angiographic occlusion at 6months. An independent core laboratory adjudicated the angiographic results. An independent clinical events committee adjudicated the clinical endpoints.Average aneurysm size was 7.2mm (SD 3.8) and average neck width was 4.6mm (SD 1.8). 68% of patients had a dome:neck ratio 2. LVIS placement was technically successful in 29/31 patients (93.5%). No primary safety endpoints occurred during the study (0%). No patient had a higher modified Rankin Score at 6months than at baseline. 26/28 (92.9%) treated aneurysms with 6-month angiographic follow-up demonstrated 90% angiographic occlusion. 21/28 (75%) were completely occluded at follow-up.The LVIS device facilitated the coil embolization of wide-necked intracranial aneurysms with high rates of technical success, an excellent safety profile, and very high rates of complete and near-complete occlusion at follow-up.NCT01541254.
Varatharaj A.,Wessex Neurological Center |
Pinto A.,Wessex Neurological Center |
Manning M.,Whiston Hospital
Neurologist | Year: 2015
Finger drop is a useful clinical sign which is easy to elicit. This article presents a logical approach for assessing patients with finger drop and outlines the important causes, and how to differentiate them. Patients with finger drop may present either to orthopedic surgeons or to neurologists, and both specialists should be aware of important diagnoses in their complementary fields. © 2015 Wolters Kluwer Health, Inc.
Zakaria R.,Walton Center Foundation Trust |
Vajramani G.,Wessex Neurological Center |
Westmoreland L.,Walton Center Foundation Trust |
Fletcher N.,Walton Center Foundation Trust |
And 3 more authors.
Acta Neurochirurgica | Year: 2013
Background Tremor is an important cause of disability and poor quality of life amongst multiple sclerosis (MS) patients. We assessed the outcomes of ventral intermediate (VIM) nucleus deep brain stimulation for the treatment of multiple sclerosis (MS)-associated tremor at a single centre in a prospective fashion. Methods Sixteen patients (9 female, 7male) with a mean age of 41.7 years (range 24-59) underwent surgery. The median duration ofMSprior to surgery was 6.5 years and median duration of tremor prior to surgery was 4 years. Case selection was by multidisciplinary assessment with carers, therapists, neurosurgeons and movement disorder neurologists. Tremor was scored pre-operatively and at 6 to 12 months post operatively using Bain and/or Fahn-Tolosa-Marin systems. The Euro-Qol 5D tool was used to assess quality of life before and after surgery. Results The mean tremor reduction was 39 % with a range between 0 and 87%. Five of 16 patients achieved at least 50% tremor reduction and 11 of 16 achieved at least 30 % tremor reduction at last follow up, mean 11.6 months (range 3-80). Tremor was significantly reduced as rated by Bain scores (Wilcoxon matched pairs, Z =3.07, p =.002) and tended to significance as rated by Fahn scores (Wilcoxon matched pairs, Z =1.85, p =0.06). Sub-analysis of activities of daily living measures from the Fahn system showed post operative improvement in feeding (statistically significant), hygiene, dressing, writing and working. Mean visual analogue scores (0-100) of patient reported well-being increased from 54.6 to 57.4 post operatively with a trend to significance (Student's t-test, t =1.26, p =0.2). Euro-Qol 5D utility values increased following surgery with a trend to significance which was greater in the group with at least 50%tremor reduction than in those with none or at least 30 % tremor reduction. Conclusions VIM DBS may reduce severe, disabling tremor in patients with MS. This tremor reduction tends to be associated with improved quality of life and function in those who respond. Patient reported outcome measures may not correlate with physician rated clinical outcome such as tremor scoring systems and more subtle assessment of these patients is required. © Springer-Verlag Wien 2013.
Skrzypiec A.E.,University of Exeter |
Shah R.S.,University of Leicester |
Shah R.S.,Wessex Neurological Center |
Schiavon E.,University of Leicester |
And 5 more authors.
PLoS ONE | Year: 2013
Behavioural adaptation to psychological stress is dependent on neuronal plasticity and dysfunction at this cellular level may underlie the pathogenesis of affective disorders such as depression and post-traumatic stress disorder. Taking advantage of genome-wide microarray assay, we performed detailed studies of stress-affected transcripts in the amygdala - an area which forms part of the innate fear circuit in mammals. Having previously demonstrated the role of lipocalin-2 (Lcn-2) in promoting stress-induced changes in dendritic spine morphology/function and neuronal excitability in the mouse hippocampus, we show here that the Lcn-2 gene is one of the most highly upregulated transcripts detected by microarray analysis in the amygdala after acute restraint-induced psychological stress. This is associated with increased Lcn-2 protein synthesis, which is found on immunohistochemistry to be predominantly localised to neurons. Stress-naïve Lcn-2-/- mice show a higher spine density in the basolateral amygdala and a 2-fold higher rate of neuronal firing rate compared to wild-type mice. Unlike their wild-type counterparts, Lcn-2-/- mice did not show an increase in dendritic spine density in response to stress but did show a distinct pattern of spine morphology. Thus, amygdala-specific neuronal responses to Lcn-2 may represent a mechanism for behavioural adaptation to psychological stress. © 2013 Skrzypiec et al.
Hall S.,University of Southampton |
Kumaria A.,Wessex Neurological Center |
Belli A.,University of Birmingham
British Journal of Neurosurgery | Year: 2014
Nosocomial infections, pneumonia in particular, are well-known complications of traumatic brain injury (TBI), which are associated with a worse neurological outcome. This review aims to explore the role of vagus nerve activity in immunomodulation as a causative factor. A MEDLINE search revealed numerous reports published over the last decade describing the "cholinergic anti-inflammatory pathway" between the vagus nucleus and leukocyte activity. Using a combination of lipopolysaccharide stimulation and vagotomy, it has been shown that the parasympathetic fibres terminating in the spleen reduce tumour necrosis factor production. Further pharmacological and receptor knockout studies have identified the α7 subtype of nicotinic receptors as the likely target for this. Vagal activity also induces changes in neutrophil chemotaxis through altered expression of the CD11b integrin which is abolished by splenectomy. By extrapolating this evidence we suggest a possible mechanism for immunosuppression following TBI which also has the potential to be targeted to reduce the incidence of pneumonia. Whilst there is strong supporting evidence for the role of vagal nerve overactivity in post-TBI pneumonia, there have yet to be any clinical investigations and further study is required. © 2014 The Neurosurgical Foundation.
Smith J.E.,Institute of Research and Development |
Smith J.E.,Derriford Hospital |
Kehoe A.,Derriford Hospital |
Harrisson S.E.,Royal Center for Defence Medicine Research and Academia |
And 3 more authors.
Injury | Year: 2014
Background Penetrating intracranial injuries are common in the deployed military medical environment. Early assessment of prognosis includes initial conscious level. There has been no previous identification of different outcomes depending on mechanism of penetrating injury. The aim of this study was to define outcome from penetrating head injury in our population, and to compare outcome between gunshot wound (GSW) and blast fragment injury, in order to detect a difference in survival. Methods A retrospective database review was undertaken using the UK Joint Theatre Trauma Registry (JTTR) between the dates 2003 and 2011 to identify all cases of penetrating head injury. Data collected included mechanism of injury, first recorded GCS, injury severity score (ISS), abbreviated injury scale (AIS) head score, concomitant extracranial injury, surgical intervention, hospital length of stay, and survival. Results 813 patients sustained a penetrating head injury, of whom 625 were injured by blast fragmentation and 188 were injured by GSW; overall 336 patients (41.3%) died. There was a significant difference between survival from GSW (41.5%) and blast fragment (63.8%; p < 0.001). In addition, the GCS in patients injured by GSW was significantly lower than that in patients injured by blast fragment. 157 cases sustained isolated head injury (79 GSW, 78 blast). The difference in injury severity between these groups was marked; median AIS was higher in the GSW group, survival lower (42% vs. 88%; p < 0.001) and distribution of GCS categories less favourable (p < 0.001). 338 of 343 patients (98.5%) with a best recorded GCS > 5, survived to discharge. Conclusion Most patients who present following penetrating intracranial injury, who have a GCS > 5, survive to discharge. There is a significant difference in survival to hospital discharge following penetrating injury caused by blast fragment compared to those caused by GSW, partly attributable to a difference in injury severity. This is the first study to specifically highlight and define this difference. © 2013 Elsevier Ltd.
The SILVER (silver impregnated line versus evd randomized trial): A double-blind, prospective, randomized, controlled trial of an intervention to reduce the rate of external ventricular drain infection
Keong N.C.H.,University of Cambridge |
Bulters D.O.,Wessex Neurological Center |
Richards H.K.,University of Cambridge |
Farrington M.,Public Health England |
And 4 more authors.
Neurosurgery | Year: 2012
BACKGROUND: Cerebrospinal fluid (CSF) infections associated with external ventricular drain (EVD) placement attract major consequences. Silver impregnation of catheters attempts to reduce infection. OBJECTIVE: To assess the efficacy of silver catheters against CSF infection. METHODS: We performed a randomized, controlled trial involving 2 neurosurgical centers (June 2005 to September 2009). A total of 356 patients requiring an EVD were assessed for eligibility; 325 patients were enrolled and randomized (167 plain, 158 silver); 278 patients were analyzed (140 plain, 138 silver). The primary outcome measure was CSF infection as defined by organisms seen on Gram stain or isolated by culture. Secondary outcome measures included ventriculoperitoneal (VP) shunting. RESULTS: There was a significant difference in infection risk between the 2 study arms: 21.4% (30/140) for plain catheters vs 12.3% (17/138) for silver catheters (P = .0427; 95% confidence interval [CI]: 1.015-3.713). Patients who had an EVD infection had more than double the risk of requiring a VP shunt compared with patients without an EVD infection (45.7% [21/46] vs 19.7% [45/229], respectively, P = .0002; 95% CI: 1.766-6.682). There was also a significant difference in VP shunt risk with infection: plain (55.2%; 16/29) vs the silver arm (29.4%; 5/17); P = .0244 (95% CI: 1.144-11.695). A multivariate analysis demonstrated that infection risk was increased by duration of EVD placement (odds ratio: 1.160), spontaneous intracranial hemorrhage (odds ratio 4.958) and decreased by silver catheters (odds ratio: 0.423). CONCLUSION: The study provides Class I evidence that silver-impregnated catheters reduce CSF infection. Copyright © 2012 by the Congress of Neurological Surgeons.
PubMed | Wessex Neurological Center
Type: Journal Article | Journal: Restorative neurology and neuroscience | Year: 2011
Two cases are described in which spinal cord stimulation was effective in abolishing previously intractable deafferentation pain for a number of years, but in which late failure occurred for non-technical reasons. A possible explanation for this is advanced; namely that the dorsal column fibres have altered electrical properties due to a form of transganglionic degeneration.
PubMed | Wessex Neurological Center
Type: Journal Article | Journal: British journal of neurosurgery | Year: 2012
This paper aims to review the current literature on vagus nerve stimulation (VNS) use in animal models of traumatic brain injury (TBI) and explore its potential role in treatment of human TBI. A MEDLINE search yielded four primary papers from the same group that demonstrated VNS mediated improvement following fluid percussion models of TBI in rats, seen as motor and cognitive improvements, reduction of cortical oedema and neuroprotective effects. The underlying mechanisms are elusive and authors attribute these to attenuation of post traumatic seizures, a noradrenergic mechanism and as yet undetermined mechanisms. Reviewing and elaborating on these ideas, we speculate other potential mechanisms including attenuation of peri-infarct depolarisations, attenuation of glutamate mediated excitotoxicity, stabilisation of intracranial pressure, enhancement of synaptic plasticity, upregulation of endogenous neurogenesis and anti-inflammatory effects may have a role. Although this data unequivocally shows that VNS improves outcome from TBI in animal models, it remains to be determined if these findings translate clinically. Further studies are warranted.