Clinical outcome measures and their evidence base in degenerative cervical myelopathy: a systematic review to inform a core measurement set (AO Spine RECODE-DCM).

Funder: AO Foundation; FundRef: http://dx.doi.org/10.13039/501100001702OBJECTIVES: To evaluate the measurement properties of outcome measures currently used in the assessment of degenerative cervical myelopathy (DCM) for clinical research. DESIGN: Systematic review DATA SOURCES: MEDLINE and EMBASE were searched through 4 August 2020. ELIGIBILITY CRITERIA: Primary clinical research published in English and whose primary purpose was to evaluate the measurement properties or clinically important differences of instruments used in DCM. DATA EXTRACTION AND SYNTHESIS: Psychometric properties and clinically important differences were both extracted from each study, assessed for risk of bias and presented in accordance with the Consensus-based Standards for the selection of health Measurement Instruments criteria. RESULTS: Twenty-nine outcome instruments were identified from 52 studies published between 1999 and 2020. They measured neuromuscular function (16 instruments), life impact (five instruments), pain (five instruments) and radiological scoring (five instruments). No instrument had evaluations for all 10 measurement properties and <50% had assessments for all three domains (ie, reliability, validity and responsiveness). There was a paucity of high-quality evidence. Notably, there were no studies that reported on structural validity and no high-quality evidence that discussed content validity. In this context, we identified nine instruments that are interpretable by clinicians: the arm and neck pain scores; the 12-item and 36-item short form health surveys; the Japanese Orthopaedic Association (JOA) score, modified JOA and JOA Cervical Myelopathy Evaluation Questionnaire; the neck disability index; and the visual analogue scale for pain. These include six scores with barriers to application and one score with insufficient criterion and construct validity. CONCLUSIONS: This review aggregates studies evaluating outcome measures used to assess patients with DCM. Overall, there is a need for a set of agreed tools to measure outcomes in DCM. These findings will be used to inform the development of a core measurement set as part of AO Spine RECODE-DCM

Frailty and early mortality following intracerebral hemorrhage

Introduction: Prognostication in spontaneous intracerebral hemorrhage (ICH) is vital for effective clinical decision-making, but can be challenging. Frailty – the loss of physiological reserve to withstand stressor events – is a risk factor for poor outcomes after ischemic stroke, yet its role in ICH remains poorly understood. This study investigates whether frailty is independently associated with 28-day mortality following ICH. Methods: A validated pre-stroke frailty index (FI) was measured for individuals presenting with ICH, yielding a FI of 0-1. The relationship between 28-day mortality and FI was assessed using multivariable logistic regression adjusting for age, neurosurgical intervention, National Institutes of Health Stroke Scale (NIHSS), Glasgow Coma Score (GCS), and ICH volume. Results: Forty (34.5%) of 116 individuals with ICH died within 28 days. Frailty was independently associated with 28-day mortality, with each 0.1 increase in FI independently associated with an adjusted odds ratio of death of 1.09 (95% CI 1.01-1.18). ICH volume was also independently associated with mortality (aOR 1.04, 95% CI 1.02-1.06 per 10mL increase). In contrast, age and neurosurgical intervention was not independently associated with mortality in our cohort. Conclusion: Higher pre-stroke frailty is independently associated with early mortality following spontaneous ICH, indicating the potential of frailty evaluation to inform prognostication and clinical decision-making

Frailty reduces penumbral volumes and attenuates treatment response in hyperacute ischemic stroke

Background Frailty – the loss of physiological reserve to withstand a stressor event - is associated with poorer outcomes following acute stroke reperfusion therapies. However, the mechanisms underlying this relationship are poorly understood. This study investigated the association between frailty and penumbral volumes in hyperacute ischemic stroke. Methods Total ischemic lesion volumes (comprising infarct core and penumbral volumes) were measured using CT perfusion imaging to give the penumbral fraction within the ischemic lesion. Pre-stroke frailty was measured using a validated frailty index. The relationship between frailty and penumbral fraction was adjusted for age, onset-to-CT interval, collateral scores, small vessel disease burden, and vascular comorbidities. Stroke severity was measured using the National Institutes of Health Stroke Scale at baseline and after 24 hours. Results In 55 individuals receiving thrombolysis for ischemic stroke, increasing frailty was associated with a reduction in penumbral fraction (rs=-0.36, P<0.01). This remained significant after adjustment for age, onset-to-imaging time, and collateral score (beta=-1.16, P<0.001). Correspondingly, frailty was independently negatively associated with proportional improvement in stroke severity following treatment (beta=-2.00, P<0.01). C-reactive protein (CRP) on presentation was associated with frailty index (rs=0.38, P<0.01) and penumbral fraction (rs=-0.30, P=0.02). Discussion A reduction in salvageable penumbra in frailty may explain the treatment-attenuating effects of frailty on reperfusion therapies. The association with CRP motivates further research into a possible inflammatory component of this relationship. Conclusion Frailty is independently associated with reduced penumbra and poorer neurological recovery in acute stroke. These findings may explain the attenuated response to stroke reperfusion therapies seen in frailer individuals.ED reports no disclosures relevant to the manuscript; BL reports no disclosures relevant to the manuscript; SA is supported by the NIHR Cambridge Biomedical Research Centre [NIHR203312]; EAW is supported by the NIHR Cambridge Biomedical Research Centre [NIHR203312]; NRE is supported by the Stroke Association [SA-SCL-MED-22\100006], and NIHR Cambridge Biomedical Research Centre [NIHR203312]

Human spinal cord tissue is an underutilised resource in degenerative cervical myelopathy: findings from a systematic review of human autopsies.

STUDY DESIGN: Systematic review. BACKGROUND: Although degenerative cervical myelopathy (DCM) is the most prevalent spinal cord condition worldwide, the pathophysiology remains poorly understood. Our objective was to evaluate existing histological findings of DCM on cadaveric human spinal cord tissue and explore their consistency with animal models. METHODS: MEDLINE and Embase were systematically searched (CRD42021281462) for primary research reporting on histological findings of DCM in human cadaveric spinal cord tissue. Data was extracted using a piloted proforma. Risk of bias was assessed using Joanna Briggs Institute critical appraisal tools. Findings were compared to a systematic review of animal models (Ahkter et al. 2020 Front Neurosci 14). RESULTS: The search yielded 4127 unique records. After abstract and full-text screening, 19 were included in the final analysis, reporting on 150 autopsies (71% male) with an average age at death of 67.3 years. All findings were based on haematoxylin and eosin (H&E) staining. The most commonly reported grey matter findings included neuronal loss and cavity formation. The most commonly reported white matter finding was demyelination. Axon loss, gliosis, necrosis and Schwann cell proliferation were also reported. Findings were consistent amongst cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament. Cavitation was notably more prevalent in human autopsies compared to animal models. CONCLUSION: Few human spinal cord tissue studies have been performed. Neuronal loss, demyelination and cavitation were common findings. Investigating the biological basis of DCM is a critical research priority. Human spinal cord specimen may be an underutilised but complimentary approach

Clinical outcome measures and their evidence base in degenerative cervical myelopathy: a systematic review to inform a core measurement set (AO Spine RECODE-DCM)

OBJECTIVES To evaluate the measurement properties of outcome measures currently used in the assessment of degenerative cervical myelopathy (DCM) for clinical research. DESIGN Systematic review DATA SOURCES: MEDLINE and EMBASE were searched through 4 August 2020. ELIGIBILITY CRITERIA Primary clinical research published in English and whose primary purpose was to evaluate the measurement properties or clinically important differences of instruments used in DCM. DATA EXTRACTION AND SYNTHESIS Psychometric properties and clinically important differences were both extracted from each study, assessed for risk of bias and presented in accordance with the Consensus-based Standards for the selection of health Measurement Instruments criteria. RESULTS Twenty-nine outcome instruments were identified from 52 studies published between 1999 and 2020. They measured neuromuscular function (16 instruments), life impact (five instruments), pain (five instruments) and radiological scoring (five instruments). No instrument had evaluations for all 10 measurement properties and <50% had assessments for all three domains (ie, reliability, validity and responsiveness). There was a paucity of high-quality evidence. Notably, there were no studies that reported on structural validity and no high-quality evidence that discussed content validity. In this context, we identified nine instruments that are interpretable by clinicians: the arm and neck pain scores; the 12-item and 36-item short form health surveys; the Japanese Orthopaedic Association (JOA) score, modified JOA and JOA Cervical Myelopathy Evaluation Questionnaire; the neck disability index; and the visual analogue scale for pain. These include six scores with barriers to application and one score with insufficient criterion and construct validity. CONCLUSIONS This review aggregates studies evaluating outcome measures used to assess patients with DCM. Overall, there is a need for a set of agreed tools to measure outcomes in DCM. These findings will be used to inform the development of a core measurement set as part of AO Spine RECODE-DCM