Daniel Scoffings

Aetiological differences in neuroanatomy of the vegetative state: insights from diffusion tensor imaging and functional implications

Background An improved in vivo understanding of variations in neuropathology in the vegetative state (VS) may aid diagnosis, improve prognostication and help refine the selection of patients for particular treatment regimes. The authors have used diffusion tensor imaging (DTI) to characterise the extent and location of white matter loss in VS secondary to traumatic brain injury (TBI) and ischaemic–hypoxic injury. Methods Twelve patients with VS (seven TBI, five ischaemic/hypoxic injuries) underwent MRI including DTI at a minimum of 3 months postinjury. Mean apparent diffusion coefficient, fractional anisotropy and eigenvalues were obtained for whole-brain grey and white matter, the pons, thalamus, ventral midbrain, dorsal midbrain and the corpus callosum. DTI measures of supratentorial damage were compared with a summed measure from the JFK modified Coma Recovery Scale (CRS-R) and with a three-point scale of functional magnetic resonance imaging (fMRI) response to an auditory paradigm to assess whether residual integrity of supratentorial white matter connectivity correlated with cortical processing. Results Conventional radiological approaches did not detect lesions in regions where quantitative DTI demonstrated abnormalities. There was evidence of marked, broadly similar, abnormalities in the supratentorial grey- and white-matter compartments from both aetiologies. In contrast, discordant findings were found in the infratentorial compartment, with DTI abnormalities in the brainstem confined to the TBI group. Supratentorial DTI abnormalities correlated with the CRS-R as well as responses to an fMRI paradigm that detected convert cognitive processing. Conclusions DTI may help to characterise differences in patients in VS. These findings may have implications for response to therapies, and should be taken into account in trials of interventions aimed at arousal in VS.

A Comprehensive Study of Clinical, Biochemical, Radiological, Vascular, Cardiac, and Sleep Parameters in an Unselected Cohort of Patients With Acromegaly Undergoing Presurgical Somatostatin Receptor Ligand Therapy

CONTEXT Attainment of safe GH and IGF-1 levels is a central goal of acromegaly management. OBJECTIVE The aim of this study was to determine the extent to which reductions in GH and IGF-1 concentrations correlate with amelioration of radiological, metabolic, vascular, cardiac, and respiratory sequelae in a single unselected patient cohort. STUDY DESIGN This was a prospective, within-subject comparison in 30 patients with newly diagnosed acromegaly (15 women and 15 men: mean age, 54.3 years; range, 23-78 years) before and after 24 weeks of lanreotide Autogel (ATG) therapy. RESULTS Reductions in GH and IGF-1 concentrations and tumor volume were observed in all but 2 patients (median changes [Δ]: GH, -6.88 μg/L [interquartile range -16.78 to -3.32, P = .000001]; IGF-1, -1.95 × upper limit of normal [-3.06 to -1.12, P = .000002]; and pituitary tumor volume, -256 mm(3) [-558 to -72.5, P = .0002]). However, apnea/hypopnea index scores showed highly variable responses (P = .11), which were independent of ΔGH or ΔIGF-1, but moderately correlated with Δweight (R(2) = 0.42, P = .0001). Although systolic (P = .33) and diastolic (P = .76) blood pressure were unchanged, improvements in arterial stiffness (aortic pulse wave velocity, -0.4 m/s [-1.2 to +0.2, P = .046]) and endothelial function (flow mediated dilatation, +1.73% [-0.32 to +6.19, P = .0013]) were observed. Left ventricular mass index regressed in men (-11.8 g/cm(2) [-26.6 to -1.75], P = .019) but not in women (P = .98). Vascular and cardiac changes were independent of ΔGH or ΔIGF-1 and also showed considerable interindividual variation. Metabolic parameters were largely unchanged. CONCLUSIONS Presurgical ATG therapy lowers GH and IGF-1 concentrations, induces tumor shrinkage, and ameliorates/reverses cardiac, vascular, and sleep complications in many patients with acromegaly. However, responses vary considerably between individuals, and attainment of biochemical control cannot be assumed to equate to universal complication control.

Mapping Traumatic Axonal Injury Using Diffusion Tensor Imaging: Correlations with Functional Outcome

Background Traumatic brain injury is a major cause of morbidity and mortality worldwide. Ameliorating the neurocognitive and physical deficits that accompany traumatic brain injury would be of substantial benefit, but the mechanisms that underlie them are poorly characterized. This study aimed to use diffusion tensor imaging to relate clinical outcome to the burden of white matter injury. Methodology/Principal Findings Sixty-eight patients, categorized by the Glasgow Outcome Score, underwent magnetic resonance imaging at a median of 11.8 months (range 6.6 months to 3.7 years) years post injury. Control data were obtained from 36 age-matched healthy volunteers. Mean fractional anisotropy, apparent diffusion coefficient (ADC), and eigenvalues were obtained for regions of interest commonly affected in traumatic brain injury. In a subset of patients where conventional magnetic resonance imaging was completely normal, diffusion tensor imaging was able to detect clear abnormalities. Significant trends of increasing ADC with worse outcome were noted in all regions of interest. In the white matter regions of interest worse clinical outcome corresponded with significant trends of decreasing fractional anisotropy. Conclusions/Significance This study found that clinical outcome was related to the burden of white matter injury, quantified by diffusivity parameters late after traumatic brain injury. These differences were seen even in patients with the best outcomes and patients in whom conventional magnetic resonance imaging was normal, suggesting that diffusion tensor imaging can detect subtle injury missed by other techniques. An improved in vivo understanding of the pathology of traumatic brain injury, including its distribution and extent, may enhance outcome evaluation and help to provide a mechanistic basis for deficits that remain unexplained by other approaches.

Resolution of transverse sinus stenoses immediately after CSF withdrawal in idiopathic intracranial hypertension

The cause of idiopathic intracranial hypertension (IIH) remains unknown but catheter venography has shown that many patients have intracranial venous hypertension proximal to transverse sinus stenoses. These stenoses have subsequently been demonstrated on magnetic resonance and CT venography and it has been proposed that by reducing the passive resorption of CSF, intracranial venous hypertension due to these stenoses might be the cause of IIH. However, CSF withdrawal reduces venous sinus pressures, implying that venous hypertension is a secondary phenomenon.1 Moreover, resolution of transverse sinus stenoses has been reported in three patients with IIH treated by CSF diversion procedures.2,3 We report a patient with IIH in whom catheter and CT venography showed transverse sinus stenoses which resolved immediately after CSF withdrawal by lumbar puncture (LP). A 35 year old woman presented with a 2 year history of headache and transient visual obscurations. She had papilloedema and constricted visual fields but no focal neurology. MRI of the brain was normal. At LP, the opening pressure was 35 cm H2O with normal CSF constituents. IIH was diagnosed and treatment started with acetazolamide 250 mg three times daily. One year later the patient was referred to our institution with persistent headaches and papilloedema for consideration of a CSF diversion procedure. Magnetic resonance venography at this time suggested stenoses in the anterior part of …

Interaction of age with the ischaemic penumbra, leptomeningeal collateral circulation and haemodynamic variables in acute stroke: a pilot study

Background Increasing age is the single largest non-modifiable risk factor for ischaemic stroke. Animal models have substantiated the view that age related neuron vulnerability to ischaemia plays a role in stroke and other age related neurological diseases. Given the key role of the ischaemic penumbra in stroke pathophysiology, we hypothesised that age has an impact on penumbral tissue and its acute determinants. Methods We studied a prospective cohort of patients (n=39) at a mean time of 154.7 min from stroke onset, using state of the art whole brain perfusion CT and CT angiography. Penumbral and core were defined using quantitative voxel based thresholds for mean transit time and cerebral blood volume (CBV). Collateral vessel scores were assessed and haemodynamic variables (ie, cerebral blood flow and CBV) were measured in affected and unaffected tissues. Results While age correlated negatively with normalised penumbral volume (Kendalls τ b=−0.234, p=0.048) and lesion volume (Kendalls τ b=0.238, p=0.045), core volume remained unchanged, accompanied by an incremental collateral response with age (Kendalls τ b=0.496, p<0.0001). Haemodynamic variables remained unaffected by age in our cohort. Conclusions These findings, described for the first time in a clinical cohort using whole brain CT perfusion and concomitant vascular imaging, suggest that age has a differential effect on acute tissue compartments in the wake of a preserved collateral vascular response and haemodynamic parameters. In agreement with the preclinical literature, the results point to a distinct tissue response to acute ischaemia in the ageing brain and merit validation studies in larger cohorts, particularly in relation to clinical outcomes.

Correlating optic nerve sheath diameter with opening intracranial pressure in pediatric traumatic brain injury.

Introduction:The use of clinical markers to predict intracranial pressure (ICP) is desirable as a first-line measure to assist in decision making as to whether invasive monitoring is required. Correlations between ICP and optic nerve sheath diameter (ONSD) using CT and MRI have been observed in adult populations. However, data on this modality in children is less well documented.Methods:ONSD was measured by independent observers and correlated with opening ICP at insertion of invasive monitoring probes in pediatric traumatic brain injury patients admitted to Addenbrookes Hospital between January 2009 and December 2013.Results:Thirty-six patients with a mean age of 8.2 y were admitted to the Pediatric Intensive Care Unit (PICU) with a traumatic head injury and required invasive neurosurgical monitoring. The median ICP was 18 ± 10 mmHg (median ± IQR), the median right ONSD was 5.6 ± 2.5 mm and the left was 5.9 ± 3.2 mm. The Intraclass correlation between observers was 0.91 (P < 0.0001). The correlation of mean ONSD and max ONSD with ICP was 0.712 (P < 0.0001) and 0.713 (P < 0.0001), respectively. Area under ROC curve for both mean and max ONSD is 0.85 (95% CI: 0.73–0.98).Conclusion:Where pediatric patients present with an ONSD of over 6.1 mm following a traumatic brain injury (TBI), ICP monitoring should be implemented.

Radiological Correlates of Raised Intracranial Pressure in Children: A Review.

Radiological assessment of the head is a routine part of the management of traumatic brain injury. This assessment can help to determine the requirement for invasive intracranial pressure (ICP) monitoring. The radiological correlates of elevated ICP have been widely studied in adults but far fewer specific pediatric studies have been conducted. There is, however, growing evidence that there are important differences in the radiological presentations of elevated ICP between children and adults; a reflection of the anatomical and physiological differences, as well as a difference in the pathophysiology of brain injury in children. Here in, we review the radiological parameters that correspond with increased ICP in children that have been described in the literature. We then describe the future directions of this work and our recommendations in order to develop non-invasive and radiological markers of raised ICP in children.

Analysis of Heterogeneity in T2-Weighted MR Images Can Differentiate Pseudoprogression from Progression in Glioblastoma

Funded by Medical Research Council/ Royal College of Radiologists (UK) Clinical Research Fellowship (G1000265); Cancer Research UK Clinical Research Fellowship; Addenbrookes Charitable Trust Award to TCB. Cancer Research UK Programme grant (C197/ A3514) to KMB.

Isolated oculomotor nerve palsy in patients with mild head injury

Abstract Isolated oculomotor nerve palsy following head injury is uncommon. It can only be diagnosed with confidence if it is known to have developed immediately following trauma and if adequate investigations exclude secondary causes. The recovery is only partial and this has repercussion on patients’ quality of life.

PO.12 Perfusion CT based thrombolysis in acute ischaemic stroke

Background Despite use in clinical practice and trials of thrombolysis, a non-contrast CT is not sensitive for identifying penumbral tissue in acute stroke. This study evaluated how it compares with physiological imaging using CT perfusion. Methods 40 imaging datasets with non-contrast CT (NCCT) and perfusion CT (CTP) were retrospectively identified. 2 sets of observers (n=6) and a neuroradiologist made a blind evaluation of the images. Inter-observer agreement was calculated for identifying ischaemic change on NCCT, and abnormalities on cerebral blood flow, time to peak and cerebral blood volume maps. A prospective cohort of 73 patients with anterior circulation cortical strokes were thrombolysed based on qualitative assessment of penumbral tissue on CTP within 3 h of stroke onset. Functional outcome was assessed at 3 months. Results Inter-rater agreement was moderate (k=0.54) for early ischaemic change on NCCT. Perfusion maps improved this to substantial for deficit in cerebral blood volume (k=0.67) and almost perfect for time to peak and cerebral blood flow (both k=0.87). In the prospective arm, 58.9% of patients with cortical strokes were thrombolysed. There was no significant difference in attainment of complete recovery (p=0.184) between the thrombolysed and non-thrombolysed group. Conclusions We demonstrate how perfusion CT aids clinical decision-making in acute stroke. Good functional outcomes from thrombolysis can be safely achieved using this physiologically informed approach.