Measure
Abbreviation
Overview
Time to administer
Strengths
Weaknesses
Modified Rankin Scale
mRS
Degree of handicap is assigned on a scale depending on how severely affected activities of daily living are [16]. The scale ranges from no symptoms (a score of 0) to no significant disability despite symptoms (1), slight disability (2), moderate disability (3), moderately severe disability (4), severe disability (5), and death (6)
5–15 min
Some consider the categories in mRS to be broad/poorly defined [30]. There is high inter-rater variability [31], although a structured version (mRS-SI) is available [30] that decreases inter-rater variability [27]. A questionnaire is also available that improves inter-rater reliability [32]. The mRS is not ideal for proxy use due to it’s potential for variability [33]
National Institutes of Health Stroke Scale
NIHSS
Measures neurological impairment using a 15-item scale that considers levels of consciousness, pupillary response, gaze palsy, hemianopia, facial palsy, motor ability, limb ataxia, sensory loss, inattention and extinction (formerly neglect), dysarthria, and aphasia [34]
5–8 min
Some items are considered to be redundant or to not contribute meaningful information although a modified NIHSS (mNIHSS) has been created that is considered to be simpler and have improved reliability and continued validity [43, 44]. The mNIHSS can also be better estimated from medical charts than the original NIHSS [45]. It is not a hierarchical scale. Some ceiling effects have been noted with the NIHSS [46–48]
Functional Independence Measure
FIM
Thirteen measures of motor function and five measures of cognitive function including self-care, sphincter control, transfers, locomotion, communication, and social cognition [49]
30–40 min
Glasgow Outcome Scale
GOS
The GOS is a measure of global outcome categorized into 5 groups (death, persistent vegetative state, severe disability, moderate disability, and good recovery) [62]. The extended GOS divides severe disability, moderate disability, and good recovery into “upper” and “lower” subcategories
<5 min
Considered to be a fast and simple measure of morbidity/mortality. Both GOS and GOSE scores strongly correlate to self-report measures of outcome and therefore represent the perspective of the patient well [63]. GOS scores have been correlated to psychological test scores [64], and both GOS/GOSE scores have been found to correlate to quality of life [64, 65]. Reliable scores can also be obtained via GOS/GOSE questionnaires sent out by post [66]
Some categories in the GOS are considered broad/open to interpretation and insensitive to subtle changes in function [67–69]. However, the extended version of the GOS (GOSE) has eight distinct outcome categories (instead of 5) that increase sensitivity, validity, and efficacy [70, 71], and, more importantly, structured interviews that increase inter-rater reliability and comprehensiveness [72, 73]
EuroQoL
EQ-5D
Measure of health-related quality of life covering five dimensions: mobility, self-care, main activity, social relationships, pain, and mood [74]. Each dimension has 3 possible responses for the EQ-5D-3L (“no problems,” “some problems,” and “extreme problems”) and 5 responses for the EQ-5D-5L (“no problems,” “slight problems,” “moderate problems,” “severe problems,” and “unable to”)
<10 min
Barthel Index
BI
Measures disability in ten categories: feeding, bathing, grooming, dressing, bowels, bladder, toilet use, transfers, mobility, and stairs [86]
2–5 min (self-report), 20 min (observation)
High test–retest reliability [87]. The modified and original versions predict length of hospital stay [88–90] and the modified version predicts stroke recovery [91]. Can be used in telephone interviews reliably [92, 93]. The BI has been validated as an adequate measure of long-term outcome in stroke patients [94]
Ceiling/floor effects have been found [61, 95–97]. Cutoff scores are often chosen arbitrarily, although some have been suggested [98, 99]. The original BI (with a three-point scale per category) was considered to be insensitive, so a modified version that expanded the scoring of each category into a five-point scale was developed and was found to increase sensitivity and reliability [100]
WHO International Classification of Functioning, Disability, and Health
ICF
Health-related quality of life measured by three dimensions: body, activities, and participation
>60 min
Provides an exhaustive and wholesome international standard for assessing outcome. Good content validity [101]
Lengthy administration time. Moderate inter-rater reliability for the stroke core set of the WHO-ICF, though standardization has been suggested to increase the inter-rater agreement [102]
Stroke Impact Scale
SIS
Measures eight domains including strength, hand function, activities of daily living and instrumental activities of daily living, mobility, communication, emotion, memory and thinking, and participation [103]
15–20 min
Ceiling effects have been reported in the communication, memory and emotion domains [103, 104], memory, and emotion [104], and a floor effect has been reported in the hand function domain [103]. Although the measure can be mailed, telephone administration has been found to yield less bias and higher test–retest reliability than postal administration [109]
American Heart Association Stroke Outcome Classification
AHA.SOC
Creates an outcome score based off of neurological impairment (motor, sensory, vision, language, cognition, affect)—which is calculated using other outcome scales—severity, and function [110]
Varies
It lacks specific guidelines as to which tests and scales to use for the neurological impairment domain. Does not capture differences in mental health after stroke [111]
Chedoke-McMaster Stroke Assessment
Chedoke Assessment
Measure of physical impairment and disability that assesses shoulder pain, postural control, arm, hand, leg, and foot based on motor recovery [112]
45–60 min
Cannot be used in patients younger than 19 years of age [114]
Frenchay Activities Index
FAI
Measures instrumental activities of daily living covering domestic chores, leisure/work, and outdoor activities [115]
5 min
Possible use with proxy respondents—there is high total and subscale agreement between patients and proxies [116]—which may lead to reduction in subjectivity [117], although caution is advised (see weaknesses). No ceiling effects [118, 119]. The FAI has been determined to provide information on activities of daily living not obtained from basic scales like the BI [120]. Can be administered as a postal version with good reliability [121]
Some evidence of gender bias [115, 122, 123] and potential for proxy biases that should be considered [116]. Two items from the original FAI (gainful work and reading books) have been considered to yield little informative and discriminative value; it has been suggested that removing the two would increase reliability [118]. Inter-rater reliability can be improved by specifying and clarifying scoring instructions [124, 125]
Stroke-Adapted Sickness Impact Profile
SA-SIP30
Measures quality of life by covering domains of body care and movement, social interaction, mobility, communication, emotional behavior, household management, alertness behavior, and ambulation [126]
5–10 min
Medical Outcomes Study Short Form-36
SF-36
Assessment of eight domains: limitations in physical activities due to health problems, limitations in social activities due to physical or emotional problems, limitations in usual role activities due to physical health problems, bodily pain, general mental health, limitations in usual role activities due to emotional problems, vitality, and general health perceptions [129]
10 min
Beck Depression Inventory –second version
BDI-II
Screening tool used as an indicator of depression (according to DSM-IV), though not intended as a tool for diagnosis (see weaknesses). Evaluation of 21 symptoms of depression covering emotion, behavioral changes, and somatic symptoms [137]
10–15 min
Sensitive to change in depression [138, 139]. Good internal consistency for assessing post-stroke depression [140]. The BDI is one of the most commonly used measures in post-stroke depression and has the advantage of relying more so on cognitive affective than somatic symptoms [141]. Can be used with proxies, although with caution since they tend to rate the patients as more depressive than the patients rate themselves [142]
There is a noted gender effect that should be taken into account; the BDI has greater accuracy in screening depression in males than females [140]. The BDI has been reported to have low specificity and high sensitivity, which leads to more false-positives [142, 143]. However, according to Berg et al. (2009), higher sensitivity is more important than high specificity in screening [142]. High specificity is more important for diagnosis and so the BDI is not suitable for diagnosing depression
Mini-Mental State Examination
MMSE
A brief measure of cognitive impairment that specifically examines arithmetic, memory, language, registration, attention, and orientation [144]
5–15 min
Both the MMSE and the modified MMSE (3MS) are adequate in detecting cognitive impairment in left-sided strokes [145]. The modified version is also considered to be more sensitive and a better predictor of functional outcome in stroke populations than the original [145]. Use of the MMSE in stroke patients has been advocated due to its simplicity to administer and brevity compared to other measures such as the FIM Cognitive Subscale and Loewenstein Occupational Therapy Cognitive Assessment [146, 147]. Lack of long-term change in MMSE score has previously been linked to lacunar infarction [148]. Poor performance on the MMSE is also predictive of long-term cognitive outcome [149]
Scores are affected by education, age, and cultural background [150–152], as well as language (minimal English is associated with low score). The MMSE and 3MS have previously been reported as inadequate for patients with right-sided cerebrovascular accidents [145], although the impact of hemisphere localization has been challenged [153]. The MMSE has been found to be insensitive (particularly in abstract reasoning, executive function, and visual perception/construction) when detecting cognitive impairment in acute stroke patients [154]. Ceiling effects have also been reported for the MMSE [155]
Montreal Cognitive Assessment
MoCA
Tool used to assess cognitive impairment in short-term memory, visuospatial abilities, executive function, attention, concentration, working memory, language, and orientation [156]
5–10 min
Higher sensitivity than the MMSE at detecting subtle cognitive impairment [156–160]. Lower ceiling effects and higher internal reliability than the MMSE have been reported for the MoCA in stroke patients [158]. The MoCA has also been able detect cognitive impairment in aneurysmal subarachnoid hemorrhage patients in domains including verbal learning, executive function, working memory, visuospatial function, and motor function wherein the MMSE failed to detect any [160], and similar findings were reported in stroke and transient ischemic attack patients [155]
The MoCA has been found to have lower specificity than the MMSE for stroke patients [161] as well as other patient groups [159], although the opposite has been reported as well for cognitively impaired patients [157]. Scores are affected by age and education [162]. The development of an abbreviated version has been suggested, with the naming domain removed (due to evidence of a ceiling effect) and the word recall removed (due to evidence of a floor effect) [157]
Stroke-Specific Quality of Life
SS-QOL
A measure of health-related quality of life by assessing 49 items in domains covering energy, family roles, language, mobility, mood, personality, self-care, social roles, thinking, upper extremity function, vision, and work/productivity
10–15 min
Key Stroke Trials
Ginsberg categorized stroke trials into two categories [172]. The first category tested drugs or strategies that were trying to achieve neuroprotection, which he defined as a treatment designed to slow or stop the biochemical and molecular events leading to irreversible ischemic brain injury [172]. There were about 160 ongoing or completed as of 2007. The other category of stroke trials includes those that target the blood supply to the brain where the treatment is designed to maintain patency of or prevent or reverse occlusion or reduction in blood supply to the brain. There were about 100 listed by Ginsberg in 2008. They include treatments such as thrombolytics (tissue plasminogen activator), anti-thrombotic, and antiplatelet drugs. Another example is devices to remove clots or dilate stenosis. The Internet stroke center lists 2,344 clinical trials in stroke [173] (www.Strokecenter.org) and www.clinicaltrials.gov returned 3,516 studies when searching “stroke” [174].
Trials with Functional Activity Measures Alone
International Stroke Trial
The International Stroke Trial was a randomized trial of ASA, subcutaneous heparin, both, or neither among 19,435 patients with acute ischemic stroke [175]. The primary endpoint was death from any cause within 14 days and death or dependency (defined as needing help from another person with daily activities) at 6 months. The trial found no difference in mortality between groups, although there were fewer recurrent ischemic strokes and more hemorrhages with heparin or ASA at 6 months. Secondary endpoints were symptomatic intracranial hemorrhage or ischemic strokes within 14 days, major extracranial hemorrhage, death from any cause by 6 months, and dependency or incomplete recovery from stroke at 6 months. The main conclusion was that ASA should be started as soon as possible after ischemic stroke.
British Aneurysm Nimodipine Trial
The British Aneurysm Nimodipine Trial randomized 554 adults with aneurysmal SAH at four medical centers in the United Kingdom [176]. The primary endpoint was the incidence of cerebral infarction and secondary endpoints were poor functional outcome on the GOS 3 months after SAH and incidence of rebleeding. The GOS was dichotomized into good recovery/moderate disability vs. severe disability/vegetative/dead. The study found that patients who received nimodipine had a 34 % reduction in cerebral infarction from 33 % in the placebo to 22 % in the nimodipine group. Poor outcome on the GOS also was reduced by nimodipine by 40 %. There were no important side effects observed. This trial was important in establishing oral nimodipine for use in almost all patients with aneurysmal SAH.
International Subarachnoid Aneurysm Trial
The International Subarachnoid Aneurysm Trial (ISAT) was a RCT that compared neurosurgical clipping to endovascular coiling in 2,143 patients with ruptured intracranial aneurysms from 42 centers [177]. The primary endpoint was death or dependence at 1 year (mRS of 3–6) and secondary endpoints were rate of rebleeding and seizures. Endovascular coiling was associated with a 7 % absolute and 23 % relative risk reduction in poor outcome to 24 %, compared to 31 % in the neurosurgical-clipping group at 1 year. The EuroQol was collected also, as well as neurocognitive outcomes in a subset of patients from the eight United Kingdom centers who had mRS of 0–2 12 months after SAH [178]. Cognitive impairment was less likely in patients treated by coiling compared to clipping (odds ratio 0.58, 95 % confidence interval 0.38–0.87, p = 0.0055). The outcomes on the EuroQol seemed similar between groups.
Carotid Surgery Trials
The North American Symptomatic Carotid Endarterectomy Trial (NASCET) included 659 patients from 50 center, with included patients experiencing transient ischemic attack or non-disabling stroke within 120 days due to 70–99 % carotid stenosis [179]. Patients were randomized to undergo medical management plus carotid endarterectomy or medical management only. The primary endpoint was fatal or nonfatal ipsilateral stroke, any stroke, or death with follow-up to 12 months. Significantly fewer strokes (any, major or fatal) were noted in the surgical arm.
The Asymptomatic Carotid Surgery Trial randomized 3,120 patients from 126 centers to carotid endarterectomy or medical management with endarterectomy only if it became necessary [180]. Patients were symptomatic or asymptomatic. The results showed that younger patients with asymptomatic carotid stenosis of greater than 70 % benefitted from reduction in stroke risk after carotid endarterectomy, if the perioperative stroke and mortality rate from surgery was low (<3 %). This trial excluded patients with previous ipsilateral carotid endarterectomies, poor surgical risk (including coronary artery disease, potential embolic strokes), and poor life expectancy precluding long-term follow-up. The primary endpoints were any perioperative morbidity and mortality (including stroke and myocardial infarction). The results in asymptomatic patients were similar to the Asymptomatic Carotid Atherosclerosis Study (ACAS) [181].
The European Carotid Surgery Trial was similar to NASCET and randomized patients to medical management plus endarterectomy versus medical management for recently symptomatic carotid stenosis [182]. The trial enrolled 3,204 patients from 96 centers, including those of any age, who recently had a transient ischemic attack or mild stroke in the distribution of the carotid artery (within previous 6 months) and internal carotid stenosis responsible for the patients’ symptoms. Those with cardiac conditions likely causing embolic events and more severe disease of distal rather than proximal ICA were excluded. The primary endpoint was major stroke or death. Secondary endpoints were death or major stroke within 30 days of carotid endarterectomy, estimated gain in stroke-free life expectancy. Significantly fewer strokes or deaths were noted in the surgical arm.
The carotid endarterectomy studies have not included cognitive outcomes. Emerging evidence suggests carotid stenosis, endarterectomy, and carotid stenting are associated with cognitive impairment and that endarterectomy may affect this [183].
Trials with Both Functional Activity and Other Measures
International Surgical Trial in Intracerebral Hemorrhage
The International Surgical Trial in Intracerebral Hemorrhage (STICH) entered 1,033 patients at 107 centers with spontaneous supratentorial intracerebral hematomas who were randomized to early surgery (within 24 h of randomization) vs. initial conservative treatment [184]. The primary endpoint was the extended GOS, with secondary endpoints being mortality, Barthel Index, and mRS at 6 months. Surgery did not confer any functional or survival benefit. An individual patient data analysis of 2,186 cases from eight RCTs of surgery for intracerebral hemorrhage found that clinical outcome was better if patients underwent surgery within 8 h of hemorrhage, the hematoma volume was 20–50 mL, the Glasgow coma score was 9 to 12, or the patient was 50 to 69 years old [185].
Acute Stroke Ischemic NXY-059 Treatment
The Acute Stroke Ischemic NXY-059 Treatment (SAINT) Trial investigated the free radical trapping agent, NXY-059, in 1,722 adult patients with acute ischemic stroke in 158 hospitals, enrolling those with acute stroke within 6 hours who were conscious, had limb weakness, and NIHSS score of at least 6 [186]. The agent was administered within 6 hours of ischemic stroke onset. The study had multiple outcome measures, including the mRS, Barthel Index, SIS, and EuroQol EQ-5D, with the primary outcome being the mRS. The mRS was not dichotomized but analyzed by Cochran-Mantel-Haenszel test across the whole range of scores, adjusting for various baseline variables. NXY-059 significantly improved the primary outcome (reduced disability at 90 days on the mRS), but did not significantly improve secondary outcomes (NIHSS to 90 days). The second major clinical trial of NXY-059 for ischemic stroke, however, showed no evidence of efficacy based on the mRS [187].
Decompressive Craniectomy Trials for Ischemic Stroke
Major published decompressive craniectomy trials included the French DECIMAL [188], German DESTINY [189], and Dutch HAMLET trials [190], with a subsequent pooled analysis that was possible due to the similar design of the studies. When combined, 93 patients were available for analysis. The primary outcome was the mRS, which was dichotomized at 0–3 vs. 4–6, which is different from that used in many ischemic stroke trials that used 0–2 vs. 3–6. The surgical technique used was very similar in all three trials, with all patients having at least a 12-cm diameter bone flap removed from the side of stroke. Medical management was also very similar in all three trials. Patients were intubated in the intensive care unit (ICU) with no initial intracranial pressure monitoring. Management of cerebral edema included restriction of intravenous fluids to 500 mL per day, use of osmotic diuretics, antihypertensives to keep systolic blood pressure <220 and diastolic blood pressure <120, treatment of hyperthermia and hyperglycemia, elevation of the head of the bed, and the option of anticonvulsant use.
The pooled analysis showed that significantly fewer patients who underwent craniectomy had unfavorable outcome (mRS > 3 at 12 months). Other important data to emerge from these studies were that the quality of life as measured by the SIS was the same in patients who did or did not have decompressive craniectomy in DECIMAL. There was no statistically significant difference in depression between groups in HAMLET.
Summary
The most common primary endpoint for stroke trials is the mRS, although different authorities have recommended various other scales. The advantages of the mRS include that it had the lowest amount of ceiling effect compared to other outcome scales [24]. The mRS focuses on physical deficits but does address some cognitive and communication issues. Because of this, it may not detect important cognitive, mood, and quality of life deficits, especially in severely affected stroke patients. There is no outcome scale with good psychometric properties, which captures both functional and cognitive behavioral outcomes and that is validated and meets other criteria as an outcome measure for stroke. While recent reviews of stroke outcome scales emphasize use of the mRS, these trials were mostly ischemic stroke and intracerebral hemorrhage. There is less information on outcome scales for SAH, and since these patients tend not to have the same focal neurological deficits, cognitive behavioral outcomes might be important to assess after SAH.
References
1.
Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2011 update: a report from the American Heart Association. Circulation. 2011;123:e18–209.
2.
Feigin VL, Lawes CM, Bennett DA, Barker-Collo SL, Parag V. Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review. Lancet Neurol. 2009;8:355–69.PubMed
3.
Mohr JP, editor. Stroke: pathophysiology, diagnosis and management. 5th ed. Philadelphia: Elsevier/Saunders; 2011.
4.
Gillen G, editor. Stroke rehabilitation: a functional-based approach. 3rd ed. St. Louis, Mo: Mosby/Elsevier; 2011.
5.
Umphred D, editor. Neurological rehabilitation. 5th ed. St. Louis, Mo: Mosby; 2007.
6.
Rosengart AJ, Huo JD, Tolentino J, Novakovic RL, Frank JI, Goldenberg FD, et al. Outcome in patients with subarachnoid hemorrhage treated with antiepileptic drugs. J Neurosurg. 2007;107:253–60.PubMed
7.
Morgenstern LB, Hemphill JC III, Anderson C, Becker K, Broderick JP, Connolly ES Jr, et al. American Heart Association Stroke Council and Council on Cardiovascular Nursing. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2010;41:2108–29.
8.
Lew HL, Lee E, Date ES, Zeiner H. Influence of medical comorbidities and complications on FIM change and length of stay during in patient rehabilitation. Am J Phys Med Rehabil. 2002;81(11):830–7.PubMed
9.
Miller FG, Joffe S. Equipoise and the dilemma of randomized clinical trials. N Engl J Med. 2011;364:476–80.PubMed
10.
Guyatt G, editor. Users’ guides to the medical literature: a manual for evidence-based clinical practice. 2nd ed. New York: McGraw-Hill; 2008.
11.
Ahn C, Ahn D. Randomized clinical trials in stroke research. J Investig Med. 2010;58:277–81.PubMed
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Spatial Neglect: Not Simply Disordered Attention
Cognitive Dysfunction After Intracerebral Hemorrhage, Vasculitis, and Other Stroke Syndromes
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