Iron Deposition in the Brain After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: After aneurysmal subarachnoid hemorrhage (SAH), thrombus forms over the cerebral cortex and releases hemoglobin. When extracellular, hemoglobin is toxic to neurones. High local hemoglobin concentration overwhelms the clearance capacity of macrophages expressing the hemoglobin-haptoglobin scavenger receptor CD163. We hypothesized that iron is deposited in the cortex after SAH and would associate with outcome. METHODS: Two complementary cross-sectional studies were conducted. Postmortem brain tissue from 39 SAH (mean postictal interval of 9 days) and 22 control cases was studied with Perls' staining for iron and immunolabeling for CD163, ADAM17 (a disintegrin and metallopeptidase domain 17), CD68, and Iba1 (ionized calcium binding adaptor molecule 1). In parallel, to study the persistence of cortical iron and its relationship to clinical outcome, we conducted a susceptibility-weighted imaging study of 21 SAH patients 6 months postictus and 10 control individuals. RESULTS: In brain tissue from patients dying soon after SAH, the distribution of iron deposition followed a gradient that diminished with distance from the brain surface. Iron was located intracellularly (mainly in macrophages, and occasionally in microglia, neurones, and glial cells) and extracellularly. Microglial activation and motility markers were increased after SAH, with a similar inward diminishing gradient. In controls, there was a positive correlation between CD163 and iron, which was lost after SAH. In SAH survivors, iron-sensitive imaging 6 months post-SAH confirmed persistence of cortical iron, related to the size and location of the blood clot immediately after SAH, and associated with cognitive outcome. CONCLUSIONS: After SAH, iron deposits in the cortical gray matter in a pattern that reflects proximity to the brain surface and thrombus and is related to cognitive outcome. These observations support therapeutic manoeuvres which prevent the permeation of hemoglobin into the cortex after SAH.

A subarachnoid haemorrhage-specific outcome tool.

Functional outcome after subarachnoid haemorrhage has traditionally been assessed using scales developed for other neurological conditions. The modified Rankin score and Glasgow Outcome Scale are most commonly used. Employment of these scales in subarachnoid haemorrhage is hampered by well recognized limitations. We set out to develop and validate a new condition-specific subarachnoid haemorrhage outcome tool (SAHOT). Items addressing diverse aspects of the impact of subarachnoid haemorrhage were collected during focus groups involving patients, next-of-kin and multidisciplinary professionals involved in subarachnoid haemorrhage management. After a series of iterative revisions, the resultant questionnaire was applied to patients and their next-of-kin at 1, 3 and 6 months post-subarachnoid haemorrhage. Rasch methodology was used to finalize the structure of the questionnaire and explore the extent to which SAHOT scores met Rasch-based criteria of successful measurement. The SAHOT was further assessed using traditional scale evaluation techniques, and validated in a second separate subarachnoid haemorrhage patient cohort. The final SAHOT included 56 items dealing with cognitive, physical, and behavioural/psychological consequences of subarachnoid haemorrhage. Rasch analysis indicated the scale successfully measured functional outcome post-subarachnoid haemorrhage. Three item scoring categories produced the best scale performance. There was no evidence of differential item functioning between patients and next-of-kin. The SAHOT was found to be acceptable, have good convergent and divergent validity, good discrimination and excellent responsiveness. It was successfully validated in a second subarachnoid haemorrhage patient cohort. The SAHOT offers the first subarachnoid haemorrhage-specific scientifically robust outcome measure with potential utility in neurovascular clinical services and research studies.

Re-evaluating the National Subarachnoid Haemorrhage study (2006) from a Patient-Related-Outcome-Measure perspective: comparing fiscal outcomes of Treatment-as-Usual with an enhanced service.

BACKGROUND: Subarachnoid haemorrhage (SAH) is neurological catastrophe, creating major disruption for patient and family, hence the importance of considering Patient-Related-Outcome-Measures (PROM). This study uses the National Study of SAH (2006) to explore any fiscal benefits to patients and NHS if they had an enhanced Neuro-Vascular-Specialist-Nurse (NVSN) service compared to Treatment-as-Usual (TAU). METHOD: Ensuring total confidentiality, clinical data from the National Study (n=2397) were matched with regional clinical data of a TAU (n=137) and prospective NVSN service (n=184) patients. The TAU and NVSN fiscal outcomes were projected onto the National Study patients to provide estimates of the potential benefits that could accrue nationally from a NVSN service based upon length of stay and earlier return to work of patients and carers. RESULTS: There were substantial benefits for NVSN cohort related to shorter time in hospital, reduced family disruption, earlier return to work and fiscal benefits to family and the NHS. NVSN patients and carers potential savings were estimated at £ 8.097 million and £ 2.492 million to the service, £ 10.497 million overall. PRACTICE IMPLICATIONS: This PROM approach allows the 'patient's voice' to be heard, which facilitates speedier patient and family recovery, showing that an integrated treatment approach in 'high tech' neuro-surgery is cost-effective.

Hearing impairment after subarachnoid hemorrhage.

Background: Subarachnoid hemorrhage (SAH) survivors experience significant neurological disability, some of which is under-recognized by neurovascular clinical teams. We set out to objectively determine the occurrence of hearing impairment after SAH, characterize its peripheral and/or central origin, and investigate likely pathological correlates. Methods: In a case-control study (n = 41), participants were asked about new onset hearing difficulty 3 months post-SAH, compared with pre-SAH. Formal audiological assessment included otoscopy, pure tone audiometry, a questionnaire identifying symptoms of peripheral hearing loss and/or auditory processing disorder, and a test of speech understanding in noise. A separate cohort (n = 21) underwent quantitative susceptibility mapping (QSM) of the auditory cortex 6 months after SAH, for correlation with hearing difficulty. Results: Twenty three percent of SAH patients reported hearing difficulty that was new in onset post-SAH. SAH patients had poorer pure tone thresholds compared to controls. The proportion of patients with peripheral hearing loss as defined by the World Health Organization and British Audiological Society was however not increased, compared to controls. All SAH patients experienced symptoms of auditory processing disorder post-SAH, with speech-in-noise test scores significantly worse versus controls. Iron deposition in the auditory cortex was higher in patients reporting hearing difficulty versus those who did not. Conclusion: This study firmly establishes hearing impairment as a frequent clinical feature after SAH. It primarily consists of an auditory processing disorder, mechanistically linked to iron deposition in the auditory cortex. Neurovascular teams should inquire about hearing, and refer SAH patients for audiological assessment and management.

Cost-benefit analysis of an integrated approach to reduce psychosocial trauma following neurosurgery compared with standard care: two-year prospective comparative study of enhanced specialist liaison nurse service for aneurysmal subarachnoid hemorrhage (ASAH) patients and carers.

BACKGROUND: Dysfunctional psychosocial stress often follows standard treatment for aneurysmal subarachnoid hemorrhage (ASAH). An enhanced Specialist Liaison Nurse (SLN) service sought to reduce this stress in a 2-year comparative prospective study, and was designed to determine if such a service would be cost-effective? METHOD: Clinical data based on consultant notes, included Glasgow Coma Scale (GCS) and high-risk bleed score. Psychosocial outcomes used a standardized patient/carer designed questionnaire to compare outcomes of the SLN cohort (n = 184) with retrospective 18/12 control ASAH cohort (n = 142). Costs-benefits analysis identified savings in reduced need for subsequent medical care, time-off-work, and contributions to the economy. RESULTS: The cohorts were socio-clinically well matched; 54% aged less than 55 years, 83% were middle-class and 32% had children still in school; 65% of SLN patients had high risk bleeds, and 81% were Grade 1 and 2 on the G.C.S. The SLN patients and carers had statistically significantly reduced psychosocial trauma compared to controls, with early and easy accessibility being the key to success of SLN. Net savings of $280,000 per annum at 2003 prices, from reduced time-off work, re-admissions and saved medical time. Prospectively, more than $3.03 million is added to the national economy by the 80% of employed patients returning to work. CONCLUSIONS: We conclude that an integrated ASAH treatment yields major psychosocial and economic benefits. Dysfunctional stress after an ASAH is not inevitable in the majority of patients. High-technology neurosurgery is not just a public cost but also improves and saves lives and generates revenue.

Comparison of cohorts of elective and emergency neurosurgical patients: psychosocial outcomes of acoustic neuroma and aneurysmal sub arachnoid hemorrhage patients and carers.

OBJECTIVES: To compare the psychosocial outcomes of cohorts of elective [Acoustic Neuroma (AN)] and emergency [Aneu-rysmal Sub Arachnoid Hemorrhage (ASAH)] Neurosurgical patients and carers. METHODS: The standardized Wessex Patient Carer Questionnaire was designed with patients and carers and provided psychosocial and economic outcome data following elective or emergency surgery. Clinical data on size of tumor and size of bleed, respectively, were extracted from Consultant notes. RESULTS: Both cohorts were generally satisfied with neurosurgical in-patient care but both suffered high-economic costs and were predominately very dissatisfied with community care. There were significant psychosocial differences between elective and emergency patients, and despite greater relative physical disability among elective patients, it was the emergency cohort who had worse psychosocial outcomes. CONCLUSIONS: Despite many common psychosocial features, the differences between the cohorts were mainly psychological rather than physiological, because of greater 'post-traumatic-stress-reaction' in the emergency cohort, indicating the need for appropriate psychosocial care immediately after neurosurgery to reduce unnecessary distress and costs to patients, carers, and community.