The size, burden and cost of disorders of the brain in the UK

Authors: Naomi A Fineberg, Peter M Haddad, Lewis Carpenter, Brenda Gannon, Rachel Sharpe, Allan H Young, Eileen Joyce, James Rowe, David Wellsted, David Nutt, Barbara J Sahakian

Aim: The aim of this paper is to increase awareness of the prevalence and cost of psychiatric and neurological disorders (brain disorders) in the UK.
Method: UK data for 18 brain disorders were extracted from a systematic review of European epidemiological data and prevalence rates and the costs of each disorder were summarized (2010 values).
Results: There were approximately 45 million cases of brain disorders in the UK, with a cost of €134 billion per annum. The most prevalent were headache, anxiety disorders, sleep disorders, mood disorders and somatoform disorders. However, the five most costly disorders (€ million) were: dementia: €22,164; psychotic disorders: €16,717; mood disorders: €19,238; addiction: €11,719; anxiety disorders: €11,687. Apart from psychosis, these five disorders ranked amongst those with the lowest direct medical expenditure per subject (<€3000). The approximate breakdown of costs was: 50% indirect costs, 25% direct non-medical and 25% direct healthcare costs.
Discussion: The prevalence and cost of UK brain disorders is likely to increase given the ageing population. Translational neurosciences research has the potential to develop more effective treatments but is underfunded. Addressing the clinical and economic challenges posed by brain disorders requires a coordinated effort at an EU and national level to transform the current scientific, healthcare and educational agenda.

Effects of xenon and hypothermia on cerebrovascular pressure reactivity in newborn global hypoxic-ischemic pig model

Authors: Chakkarapani E, Dingley J, Aquilina K, Osredkar D, Liu X, Thoresen M.

Autoregulation of cerebral perfusion is impaired in hypoxic-ischemic encephalopathy. We investigated whether cerebrovascular pressure reactivity (PRx), an element of cerebral autoregulation that is calculated as a moving correlation coefficient between averages of intracranial and mean arterial blood pressure (MABP) with values between -1 and +1, is impaired during and after a hypoxic-ischemic insult (HI) in newborn pigs. Associations between end-tidal CO2, seizures, neuropathology, and PRx were investigated. The effect of hypothermia (HT) and Xenon (Xe) on PRx was studied. Pigs were randomized to Sham, and after HI to normothermia (NT), HT, Xe or xenon hypothermia (XeHT). We defined PRx >0.2 as peak and negative PRx as preserved. Neuropathology scores after 72 hours of survival was grouped as 'severe' or 'mild.' Secondary PRx peak during recovery, predictive of severe neuropathology and associated with insult severity (P=0.05), was delayed in HT (11.5 hours) than in NT (6.5 hours) groups. Seizures were associated with impaired PRx in NT pigs (P=0.0002), but not in the HT/XeHT pigs. PRx was preserved during normocapnia and impaired during hypocapnia. Xenon abolished the secondary PRx peak, increased (mean (95% confidence interval (CI)) MABP (6.5 (3.8, 9.4) mm Hg) and cerebral perfusion pressure (5.9 (2.9, 8.9) mm Hg) and preserved the PRx (regression coefficient, -0.098 (95% CI (-0.18, -0.01)), independent of the insult severity.Journal of Cerebral Blood Flow & Metabolism advance online publication, 31 July 2013; doi:10.1038/jcbfm.2013.123.

Lessons from the Intracranial Pressure Monitoring-Trial in TBI patients

Authors: Sarrafzadeh AS, Smoll NR, Unterberg AW.

BACKGROUND: Monitoring of intracranial pressure (ICP) has been used for decades in patients with severe traumatic brain injury (TBI) and is recommended in the Guidelines of the Brain Trauma Foundation. It is the standard of care in most industrialized countries.
METHODS: Chesnut et al. have now performed the first randomized trial of ICP monitoring in patients with severe TBI. Patients were randomly assigned to one of two specific protocols - ICP monitoring (n=157) or imaging and clinical exam (n=167). The study was conducted in Latin America, where ICP-monitoring is not the standard of care in most hospitals.
RESULTS: Six months after injury, patients groups had similar scores on functional status and cognition and similar cumulative mortality. Patients who underwent ICP monitoring had a significantly lower intensity of brain-specific treatment and received fewer treatments for intracranial hypertension.
CONCLUSION: The benefit of this study is that ICP-monitoring - and more advanced multimodal monitoring allows a tailored treatment avoiding an overtherapy of drugs with unfavorable side effects. For low income countries, the results of this trial are encouraging, though efforts should be done to further improve after ICU-care and outcome. However, we guard against the use of this data to reform European and North American treatment guidelines. The authors have proven that neurosurgery can be studied in an elegant fashion. Thanks to their team of neurosurgeons and neurointensivists, the outcome of TBI-patients will continue to improve, driven by clinical practice guidelines.

Association of MRI findings and visual outcome in idiopathic intracranial hypertension

Authors: Saindane AM, Bruce BB, Riggeal BD, Newman NJ, Biousse V.

OBJECTIVE. Patients with idiopathic intracranial hypertension (IIH) have elevated intracranial pressure (ICP) without an identifiable cause. The clinical course is variable, resulting in irreversible vision loss in some and a benign course in others. Although MRI findings have been described in IIH, their association with visual outcome has not been evaluated to date. MATERIALS AND METHODS. Forty-six patients with IIH underwent funduscopic evaluation, visual field testing, lumbar puncture with opening pressure (OP) measurement, and MRI. Patients were stratified into the following groups by visual outcome: group 1, no vision loss (n = 28); group 2, some vision loss (n = 10); and group 3, severe vision loss (n = 8). MRI findings in the orbits, pituitary gland, and optic canals and the frequency of skull base cephaloceles and of transverse sinus (TS) stenosis were assessed by a reviewer blinded to the patients' visual outcome. Demographic, clinical, and MRI findings were evaluated for association with visual outcome. RESULTS. Patients in group 3 (worst visual outcome) were significantly younger (p = 0.03) and had higher OP (p = 0.04) than patients in the other groups. There were no significant differences in sex, race, or body mass index. Despite worse visual outcomes and sometimes fulminant vision loss, there were no differences in the frequency of orbital MRI findings or TS stenosis, optic canal diameter, and pituitary appearance among the three groups. Group 3 had significantly lower cephalocele frequency than the other groups (p = 0.04). CONCLUSION. Although MRI findings may suggest elevated ICP and the diagnosis of IIH, they are not predictive of visual outcome in patients with IIH.

Non-invasive intracranial pressure estimation by orbital subarachnoid space measurement: the Beijing intracranial and intraocular pressure (iCOP) study

Authors: Xie X, Zhang X, Fu J, Wang H, Jonas JB, Peng X, Tian G, Xian J, Ritch R, Li L, Kang Z, Zhang S, Yang D, Wang N.

INTRODUCTION: The orbital subarachnoid space surrounding the optic nerve is continuous with the circulation system for cerebrospinal fluid (CSF) and can be visualized using magnetic resonance imaging (MRI). We hypothesized that the orbital subarachnoid space width (OSASW) is correlated with and can serve as a surrogate for intracranial pressure (ICP). Our aim was to develop a method for a non-invasive measurement of the intracranial CSF-pressure (CSF-P) based upon MRI-assisted OSASW.

Patterns of Retinal Hemorrhage Associated With Increased Intracranial Pressure in Children

Authors: Binenbaum G, Rogers DL, Forbes BJ, Levin AV, Clark SA, Christian CW, Liu GT, Avery R.

OBJECTIVE:Raised intracranial pressure (ICP) has been proposed as an isolated cause of retinal hemorrhages (RHs) in children with suspected traumatic head injury. We examined the incidence and patterns of RHs associated with increased ICP in children without trauma, measured by lumbar puncture (LP).METHODS:Children undergoing LP as part of their routine clinical care were studied prospectively at the Children's Hospital of Philadelphia and retrospectively at Nationwide Children's Hospital. Inclusion criteria were absence of trauma, LP opening pressure (OP) ≥20 cm of water (cm H2O), and a dilated fundus examination by an ophthalmologist or neuro-ophthalmologist.RESULTS:One hundred children were studied (mean age: 12 years; range: 3-17 years). Mean OP was 35 cm H2O (range: 20-56 cm H2O); 68 (68%) children had OP >28 cm H2O. The most frequent etiology was idiopathic intracranial hypertension (70%). Seventy-four children had papilledema. Sixteen children had RH: 8 had superficial intraretinal peripapillary RH adjacent to a swollen optic disc, and 8 had only splinter hemorrhages directly on a swollen disc. All had significantly elevated OP (mean: 42 cm H2O).CONCLUSIONS:Only a small proportion of children with nontraumatic elevated ICP have RHs. When present, RHs are associated with markedly elevated OP, intraretinal, and invariably located adjacent to a swollen optic disc. This peripapillary pattern is distinct from the multilayered, widespread pattern of RH in abusive head trauma. When RHs are numerous, multilayered, or not near a swollen optic disc (eg, elsewhere in the posterior pole or in the retinal periphery), increased ICP alone is unlikely to be the cause.


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