Summary No single outcome measure can describe or predict all dimensions of recovery and disability after acute stroke. Several scales have proven reliability and validity in stroke trials, including the National Institutes of Health stroke scale (NIHSS), the modified Rankin scale (mRS), the Barthel index (BI), the Glasgow outcome scale (GOS), and the stroke impact scale (SIS). Several scales have been combined in stroke trials to derive a global statistic to better define the effect of acute interventions, although this composite statistic is not clinically tenable. In practice, the NIHSS is useful for early prognostication and serial assessment, whereas the BI is useful for planning rehabilitative strategies. The mRS and GOS provide summary measures of outcome and might be most relevant to clinicians and patients considering early intervention. The SIS was designed to measure the patient's perspective on the effect of stroke. Familiarity with these scales could improve clinicians' interpretation of stroke research and their clinical decision-making.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474442206704951.pdf

Clinical interpretation and use of stroke scales

National Institutes of Health Stroke Scale (NIHSS)

Background. Motor recovery after stroke is predicted only moderately by clinical variables, implying that there is still a substantial amount of unexplained, biologically meaningful variability in recovery. Regression diagnostics can indicate whether this is associated simply with Gaussian error or instead with multiple subpopulations that vary in their relationships to the clinical variables. Objective. To perform regression diagnostics on a linear model for recovery versus clinical predictors. Methods. Forty-one patients with ischemic stroke were studied. Impairment was assessed using the upper extremity Fugl-Meyer Motor Score. Motor recovery was defined as the change in the upper extremity Fugl-Meyer Motor Score from 24 to 72 hours after stroke to 3 or 6 months later. The clinical predictors in the model were age, gender, infarct location (subcortical vs cortical), diffusion weighted imaging infarct volume, time to reassessment, and acute upper extremity Fugl-Meyer Motor Score. Regression diagnostics included a Kolmogorov-Smirnov test for Gaussian errors and a test for outliers using Studentized deleted residuals. Results. In the random sample, clinical variables explained only 47% of the variance in recovery. Among the patients with the most severe initial impairment, there was a set of regression outliers who recovered very poorly. With the outliers removed, explained variance in recovery increased to 89%, and recovery was well approximated by a proportional relationship with initial impairment (recovery ≅ 0.70 × initial impairment). Conclusions. Clinical variables only moderately predict motor recovery. Regression diagnostics demonstrated the existence of a subpopulation of outliers with severe initial impairment who show little recovery. When these outliers were removed, clinical variables were good predictors of recovery among the remaining patients, showing a tight proportional relationship to initial impairment.

https://journals.sagepub.com/doi/pdf/10.1177/1545968307305302

Inter-individual Variability in the Capacity for Motor Recovery After Ischemic Stroke:

Background: Rapid and easy clinical assessments for volumes of infarction and perfusion mismatch are needed. We tested whether simple geometric models generated accurate estimates of these volumes. Methods: Acute diffusion-weighted image (DWI) and perfusion (mean transit time [MTT]) in 63 strokes and established infarct volumes in 50 subacute strokes were measured by computerized planimetry. Mismatch was defined as MTT/DWI ≥ 1.2. Observers, blinded to planimetric values, measured lesions in three perpendicular axes A, B, and C. Geometric estimates of sphere, ellipsoid, bicone, and cylinder were compared to planimetric volume by least-squares linear regression. Results: The ABC/2 formula (ellipsoid) was superior to other geometries for estimating volume of DWI (slope 1.16, 95% confidence interval [CI] 0.94 to 1.38; R 2 = 0.91, p = 0.001) and MTT (slope 1.11, 95% CI 0.99 to 1.23; R 2 = 0.89, p = 0.001). The intrarater and interrater reliability for ABC/2 was high for both DWI (0.992 and 0.965) and MTT (0.881 and 0.712). For subacute infarct, the ABC/2 formula also best estimated planimetric volume (slope 1.00, 95% CI 0.98 to 1.19; R 2 = 0.74, p = 0.001). In general, sphere and cylinder geometries overestimated all volumes and bicone underestimated all volumes. The positive predictive value for mismatch was 92% and negative predictive value was 33%. Conclusions: Of the models tested, ABC/2 is reproducible, is accurate, and provides the best simple geometric estimate of infarction and mean transit time volumes. ABC/2 has a high positive predictive value for identifying mismatch greater than 20% and might be a useful tool for rapid determination of acute stroke treatment.

ABC/2 for rapid clinical estimate of infarct, perfusion, and mismatch volumes.

Spontaneous behavioral recovery is usually limited after stroke, making stroke a leading source of disability. A number of therapies in development aim to improve patient outcomes not by acutely salvaging threatened tissue, but instead by promoting repair and restoration of function in the subacute or chronic phase after stroke. Examples include small molecules, growth factors, cell-based therapies, electromagnetic stimulation, device-based strategies, and task-oriented and repetitive training-based interventions. Stage of development across therapies varies widely, from preclinical to late-phase clinical trials. The optimal methods to prescribe such therapies require further studies, for example, to best identify appropriate patients or to guide features of dosing. Likely, anatomic, functional, and behavioral measures of brain state, as well as measures of injury, will each be useful in this regard. Considerations for clinical trials of restorative therapies are provided, emphasizing both similarities and points of divergence with acute stroke clinical trial design.

Repairing the human brain after stroke. II. Restorative therapies.

Background The 'vascular depression' hypothesis states that brain changes located in frontal-subcortical pathways increase vulnerability for specific depressive symptom profiles, but studies examining locations of small-vessel and degenerative changes with individual symptoms are scarce. We examined whether location and progression of white-matter lesions (WMLs), lacunar infarcts and atrophy were associated with motivational and mood symptoms in patients with symptomatic atherosclerotic disease. Method In 578 patients [63 (s.d.=8) years] of the Second Manifestations of ARTerial disease (SMART)-Medea study, volumes of WMLs and atrophy and visually rated infarcts were obtained with 1.5 T magnetic resonance imaging at baseline and after 3.9 (s.d.=0.4) years' follow-up. Depressive symptoms were assessed with Patient Health Questionnaire-9 at follow-up and categorized into motivational and mood symptoms. Results Regression analyses adjusted for age, gender, education, Mini-Mental State Examination, physical functioning, antidepressant use and vascular risk factors showed that location in mainly deep white-matter tracts and progression of WMLs were associated with symptoms of anhedonia, concentration problems, psychomotor retardation and appetite disturbance. Lacunar infarcts in deep white matter were associated with greater motivational [Incidence rate ratio (IRR) 1.7, 95% confidence interval (CI) 1.2-2.4] and mood (IRR 1.7, 95% CI 1.1-2.6) sumscores, and with symptoms of psychomotor retardation, energy loss and depressed mood; lacunar infarcts in the thalamus were associated with psychomotor retardation only. Cortical atrophy was associated with symptoms of anhedonia and appetite disturbance. Excluding patients with major depression did not materially change the results. Conclusions Our findings suggest that disruption of frontal-subcortical pathways by small-vessel lesions leads to a symptom profile that is mainly characteristic of motivational problems, also in the absence of major depression.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S0033291711001383

Location and progression of cerebral small-vessel disease and atrophy, and depressive symptom profiles: The Second Manifestations of ARTerial disease (SMART)-Medea study

PURPOSE Previous studies investigating relationships between stroke lesion volume and outcome were restricted to short follow-up periods (3-6 months) and outcome measures of stroke severity and activities only, whereas functional improvement has been found to extend far beyond six months. Therefore, this study investigated relationships between infarct volume and a broad range of outcomes of stroke survivors at a long follow-up period. METHODS Correlations between lesion volumes (determined by conventional MRI scans in the second week post-stroke) and outcomes after one year of 75 first-ever ischemic stroke survivors were investigated. RESULTS Moderate Spearman Rank correlation coefficients were found between lesion volume and motor impairment (Motricity Index (MI): -0.43, p < 0.01; Fugl Meyer Motor Assessment Scale (FM): -0.43; p < 0.01). Correlation coefficients with activities of daily living were moderate but low associated with Barthel Index (r(s) = 0.30; p < 0.01), modified Rankin Scale (r(s) = 0.39; p < 0.01) and Frenchay Activities Index (r(s) = -0.35; p < 0.01). Lesion volume had a significant but low association (r(s) = 0.27; p = 0.02) with patient's health status measured with Sickness Impact Profile 68 (SIP68)) and a moderate correlation with well-being assessed with Life Satisfaction Questionnaire (LSQ; r(s) = -0.45; p < 0.01). Found correlation coefficients were slightly stronger after correction for mixed (cortical/subcortical) and purely subcortical lesion location. CONCLUSIONS It can be concluded that infarct volume moderately correlates with long-term motor impairment, functional outcome and quality of life of patients surviving stroke.

Ischemic lesion volume correlates with long-term functional outcome and quality of life of middle cerebral artery stroke survivors.

Objective. To examine the relationship between the volume of the middle cerebral artery stroke lesion and functional status in the subacute phase of stroke. Methods. Infarctvolumes of 94 patients with a 1st middle cerebral artery stroke assessed on conventional MRI scans obtained in the 2nd week poststroke were related to a clinical measure of stroke severity (National Institutes of Health Stroke Scale [NIHSS]) and to functional status: motor impairment (Motricity Index [MI]) and limitation in activities (Barthel Index [BI] and modified Rankin Scale). Separate correlations were computed for patients with large (>30 ml) and small (30 ml) lesions, and to investigate the influence of lesion location on the relationship between volume and functional status, correlations were computed for patients with left and right hemisphere lesions and for patients with cortical and subcortical lesions. Results. Lesion volume correlated strongly with NIHSS scores (R = 0.61) and moderately with the patient’s functional stat...

Relationship between ischemic lesion volume and functional status in the 2nd week after middle cerebral artery stroke.

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Location and progression of cerebral small-vessel disease and atrophy, and depressive symptom profiles: The Second Manifestations of ARTerial disease (SMART)-Medea study

Ischemic lesion volume correlates with long-term functional outcome and quality of life of middle cerebral artery stroke survivors.

Relationship between ischemic lesion volume and functional status in the 2nd week after middle cerebral artery stroke.