The Copenhagen Stroke Study experience

The Copenhagen Stroke Study Experience Henrik Stig Jorgensen, MD

The Copenhagen Stroke (COST) Study was a prospective, consecutive, communitybased study of 1,197 patients with acute stroke who underwent acute stroke care and rehabilitation in a stroke unit setting. This article reviews the results of this study with respect to (1) the effect of organized stroke care and rehabilitation, (2) neurological outcome and functional outcome of stroke in relation to initial stroke severity and functional disability, (3) recovery of upper-extremity function and walking, (4) time course of neurological and functional recovery relative to initial stroke severity, (5) mechanisms of stroke recovery, and (6) the effect on stroke recovery of various demographic, medical, and pathophysiological factors, such as stroke in progression, spontaneous reperfusion age, diabetes, blood glucose on admission, stroke type (hemorrhage/infarction), silent infarction, and leuco-araiosis.

The Copenhagen Stroke (COST) Study 1-1swas a prospective, consecutive, community-based study of all patients with acute stroke, N = 1,197, admitted from a welldefined catchment area within the City of Copenhagen during a 25-month inclusion period from September 1, 1991, to September 30, 1993 (Table 1). All patients were given structured acute care and rehabilitation in a single, large stroke unit from the time of acute admission to the end of rehabilitation. Admission to the stroke unit took place regardless of age, stroke severity, and the patient's premorbid condition. Hospital care in Denmark is free, and all acute stroke patients are treated at their local community hospital. Almost all stroke patients (88%) in the Copenhagen area were admitted, except for some with very minor strokes and instantaneously fatal strokes, and some patients with stroke living in nursing homes) 6 The stroke unit under study was situated in the neurological ward at Bispebjerg hospital. During the study period there were 74 beds in the neurological ward, of which 63 beds (85%) were used for the stroke unit.

From the Department of Neurology, Bispebjerg Hospital, Copenhagen, Denmark. Address reprint requests to Henrik Stig Jorgensen, MD, Department of Neurology, Bispebjerg Hospital, Bispebjerg Bakke 23, DK2400 Copenhagen NV, Denmark. Copyright © 1996by National StrokeAssociation 1052-3057/96/0601-0000503.00/0

Median time from stroke onset to admission was 12 hours. Information was obtained regarding premorbid social and medical conditions, comorbidity, and risk factors. Initial care as well as all stages of rehabilitation were carried out within the unit by the permanently assigned staff. A standardized diagnostic evaluation program included routine blood tests, electrocardiogram on admission, chest radiograph, and CT scan. A Doppler examination of the carotid arteries and a single photon emission tomography (SPECT) was performed in most patients. Aspirin, 150 m g / d , was given to all patients with ischemic strokes. Ischemic stroke patients with atrial fibrillation were treated with warfarin (Nycomed DAK A/S, Lergravsvej, Denmark). Patients with stroke in progression were anticoagulated with heparin and warfarin unless contraindicated. Hoses were used for prophylaxis of deep venous thrombosis; low-dose heparin was not used. Rehabilitation began as early as possible. The rehabilitation program was individualized according to the needs of the patient and was given to all patients by a trained team of medical and nursing staff, physiotherapists, occupational therapists, speech therapists, and neuropsychologists. Weekly team conferences were held to evaluate the progress of the patient and to determine therapeutic goals. Patients were discharged to their own homes or to nursing homes when no further in-hospital improvement was expected. Initial (neurological) stroke severity was evaluated on

Journal of Stroke and Cerebrovascular Diseases, Vol. 6, No. 1, 1996: pp 5-16

5

H.S. ]ORGENSEN Table 1. Basic characteristics of the patients in the

Copenhagen stroke stud),

No. of patients Age (yr) Sex (M/F) Initial stroke severity Very severe (SSS 0-14 points) Severe (SSS 15-29 points) Moderate (SSS 30-44 points) Mild (SSS 45-58 points) Stroke type Infarct Hemorrhage Unknown

1197 74.3 ( 11.0) 547/650 223 (19%) 171 (14%) 316 (26%) 487 (41%) 912 (91%) 88 (9%) 197

admission with the Scandinavian Neurological Stroke Scale (SSS), and initial disability level (activity of daily living [ADL]) was evaluated with the Barthel Index (BI). Neurological recovery was monitored weekly using the SSS (performed by the same neurologist, H.S.J.), and functional recovery was monitored weekly by using the BI (performed by the nursing and rehabilitation staff). These measures were made from the acute admission until the end of rehabilitation and again at a 6-month follow-up visit.

The Effect of Structured Stroke Rehabilitation Structured treatment of stroke patients in stroke units is a concept that has existed for several years, but in Denmark, and probably also worldwide, most patients with stroke do not receive this kind of treatment. They are instead given traditional routine treatment in neurologi-

caI and medical wards. For example, less than 1 of 10 Danish patients with stroke is offered treatment in a stroke unit. Traditionally, stroke is an area of low interest; patients are mostly elderly, a group whose treatment is often given a low priority, and no specific medical treatment for stroke is yet available. Accordingly, many doctors and medical staff adopt a nihilistic approach regarding stroke treatment. In the COST Study we compared mortality in 1,241 patients with acute stroke in two neighboring communities within Greater Copenhagen. 15 In one, all stroke patients were treated on a dedicated stroke unit from the time of acute admission to the end of rehabilitation. In the other, all stroke patients were provided with routine care on a general neurological ward (patients aged 70 or less) and on general medical wards with rehabilitation services. Both stroke populations were community based. The study was not biased by selection, because all patients regardless of age, stroke severity, and condition before stroke were treated in a dedicated acute stroke care and rehabilitation unit in the community offering that treatment and with routine acute care and rehabilitation on general wards in the community offering that treatment. The two poptflations were comparable in age, sex, marital status, living conditions before stroke, and stroke severity. Comorbidity rate was higher in patients treated on the stroke unit. In-hospital mortality as well as 1-year mortality in the COST study was significantly lower in patients treated on the stroke unit versus those treated on the general wards (Table 2). The case-fatality rate after 30 days was significantly lower in patients treated in the stroke unit (17% vs. 23%) as was the 6-month mortality (28% vs. 35%). The discharge rate to nursing homes did not increase as a

Table 2. Details of prospective studies comparing the effect of treatment at stroke units versus at general wards

n Jorgensen j~ Garmway 1~.18

1,241 297

Stroke population

Time of inclusion

Community Acute ba,~d Hospital

Acute

Exclusion criteria

Limitations on S U stay?

ADL function at discharge

ADL function after 1 yr

--

None

No

--

No

Improved. S

No

In-hospital moaality

l-yr mortality

Discharge to nursing home

Length of stay (d)

23% vs 29% (S)

32% vs 39% (S)

12% vs 15% IS)

38 vs. 55 (S)

Similar

19% vs, 28% (NS)

35% vs 40% (NS)

Not specified (NS)

55 vs. 75 (NS)

Improved, NS

Improved, NS

23% vs 2 8 % ( N S )

3 i % v s 4 1 % (NS)

13% vs 19%(NS)

--

Stevens 19

228

Hospital based

Subacute

Decreased consciousness/ no hemiplcgia None

Strand :'°

293

Hospital b&sed

Acute

None

No

Improved, S

Improved. S

22% vs 22% (NS)

39% vs 41% (NS)

22% vs 33% (S)'["

15 vs 18 (NS):~

Indredavik ~'~

206 Hospital based

Acute

Decreased consciousness/ omsing home

Yes

Improved, S

Improved, S

7% vs 16% (S)

25% vs 32% (NS)

1 I% vs 22% (S)§

--

Kalra'~"

246

Yes

Improved. S*

--

ba~d

Hospital based

recidcms Subacutc Death or discharge within 2 wk

Abbreviations: ADL. acitivity of daily living; S. statistically significant difference (P < .05); NS. not significant. *In patients with an "intermediate prognosis."

7% vs 12% (NS)

--

20% vs 30% (S)

40 vs 83 (S)

THE COPENHAGEN STROKE STUDY result of the lower mortality, but instead was lower in patients treated in the stroke unit (Table 2). In the COST study, multivariate regression analyses showed that when the difference in comorbidity and other factors of patients treated in the stroke unit and patients treated in the general wards were considered, the differences in outcome were even more pronounced. Patients treated in the stroke unit had a relative risk of death that was half that of patients treated on the general wards. Discharge to nursing home was reduced by 40%, and the chance of discharge to home was almost doubled. All these differences were statistically significant. Stroke unit treatment not only improved outcome in the COST study, it also reduced the length of hospital stay (Table 2). The number of bed days used for treatment of patients in the stroke unit compared with the general wards was significantly reduced with an estimated saving of 13 days per patient. These observations agree with the findings of most other studies, 17"22 but small numbers and selection bias have limited the applicability of their results (Table 2). Most previous studies report that stroke units decrease mortality, but the small number of patients included makes the results of these studies uncertain. One statistical review 23 estimated a mortality reduction of about 25% 3 months and 1 year after stroke in patients receiving organized acute stroke care and rehabilitation as compared with treatment on general medical wards. There was no increase in nursing home placement after organized stroke unit treatment despite reduced mortality. 24 Table 3 addresses the possible differences between stroke units and general neurological/medical wards, which may contribute to the superiority of stroke unit acute care and rehabilitation, t7-22,2s

Stroke Outcome In the COST study, organized stroke care and rehabilitation on a stroke unit were given to all patients) 2 Overall, 21% died, 15% were discharged to nursing homes after completed rehabilitation, and 64% were discharged to their own homes. At the end of rehabilitation, neurological deficits were absent or mild in 78% of survivors, moderate in 11%, and severe or very severe in 11%. Functional disability was still very severe in 14% of survivors, severe in 6 ° moderate in 8%, and mild in 26%, and 46% of survivors had normal ADL-function after completed rehabilitation.

Outcome and Initial (Neurological) Stroke Severity In the COST study, initial stroke severity was graded in four categories according to the Scandinavian Neurological Stroke Scale on admission26,27: very severe, SSS score 0

Table 3. A comparison of structure and function between stroke units and general wards Stroke Units Stroke physician? Nursing staff specialized in stroke patients? Multidisciplinary team work? Standardized program of investigation? Standardized program for initial observation? Focus on prevention/early treatment of complaint? Early mobilization? Early start of therapy? Intensified therapy? Total amount of therapy? Activities of daily living at ward part of rehabilitation? Close contact to relatives? Extended information to patient and family? Support from other stroke patients? Milieu facilitating stroke rehabilitation? Standardized, repetitive evaluation of course? Early planning of discharge?

General Wards

Yes

No

Yes Yes

No Not formal

Yes

No

Yes

No

Yes Yes Yes Yes Similar

Not formal Not formal No No Similar

Yes Yes

Not formal Not formal

Yes Likely

Not formal Unlikely

Yes

No

Yes Yes

Unlikely Not formal

to 14 points (19% of the patients); severe, SSS score 15 to 29 points (14%); moderate, SSS score 30 to 44 points (26%); mild, SSS score 45 to 58 points (41%). Patients (n = 223) with very severe strokes at presentation had in general a poor prognosis; 62% died and 24% were discharged to nursing home. However, almost half of the survivors improved their function to a higher level, and one third were discharged to their own homes after completed rehabilitation, most with no or only mild functional disability. One third of the patients (n = 171) who presented with severe stroke died, one third was discharged to a nursing home, and one third was discharged to their own homes after completing rehabilitation. More than half of the survivors had severe or very severe disability after completing rehabilitation; only about 10% reached full ADL function; 25% had only mild disability. Three fourths of the patients (n = 316) who presented with moderate stroke were discharged to their homes after completing rehabilitation and 12% died. Sixty-eight percent of the survivors had no or only mild disability at the end of rehabilitation. Practically all patients (n = 487) with initially mild strokes survived, had no or only mild

H.S. JORGENSEN

8 disability at discharge, and were discharged to their own homes.

Outcome According to Initial (ADL) Levelof Disability In the COST study, functional disability was graded in five categories according to the Barthel Index2a,29; very severe (0 to 20 points), severe (25 to 45 points), moderate (50 to 70 points), mild (75 to 95 points), and none (100 points). Half of the patients with initially very severe disability survived, and half of the survivors improved to a higher functional level during rehabilitation; 17% improved to no or only mild disability and could be discharged to their own homes. Seventeen percent of survivors with severe disability remained severely disabled, 83% improved to a higher level, and 65% improved to the level of no or only mild functional disability after completed rehabilitation. Almost all patients with moderate or mild disability survived. Improvement to a higher functional level was seen in 85% of the survivors with initially moderate disability, and one third reached full ADL function. Half of the patients with mild disability reached full ADL-function.

Recovery of Upper Extremity Function In the COST study, hall upper-extremity function defined as full Barthel Index score in grooming and feeding (15 points = independence) was reached during rehabilitation by 79% of survivors. 4 A similar rate was found by others. 3° Partial upper extremity function (5 or 10 points in BI) was reached by 15%, but 6% remained nonfunctional. Recovery of upper extremity function was closely related to the degree of upper extremity paresis on admission as also found by others. 3°'33 One third of the survivors who had initial severe upper-extremity paresis reached full function, and almost 80% with mild paresis reached full upper-extremity function.

Recovery of Walking Function Recovery of walking function was also monitored in the COST study. 1° Initially, 51% of patients could not walk, 12% could walk with assistance, and 37% walked independently. At the end of rehabilitation 22% of survivors could not walk, 14% could walk with assistance, and 64% were independent in walking. Friedman 3a found a similar frequency of independent walking but Wade et a129 and Skilbeck et a135 reported a higher frequency of independent walking in survivors, approximately 85%, possibly attributable to a higher mortality. In the COST study, the degree of recovery was found related to both the degree of initial impairment of walking and the severity of lower extremity paresis. Independent walking was achieved by 15% of the survivors who

initially could not walk and by 60% of those who initially could walk with assistance. Independent walking was achieved by 24% of the survivors with initial paralysis of the leg, by 55% with severe paresis, by 61% with moderate paresis, by 89% with mild paresis, and by 92% with no initial paresis of the leg.

The Time Course of Recovery From Stroke Functional recovery from stroke occurs mainly within the first 6 months after stroke. 21,32,35"41In the COST study, the time course of both neurological and functional recovery was monitored by weekly neurological examinations and functional assessments from the time of acute admission to the end of rehabilitation and again 6 months poststroke. 13 Figure I shows the time course of functional recovery in relation to initial neurological stroke severity (stratified according to the SSS score on admission, as previously described). Functional recovery was completed within 13 weeks from stroke onset in 95% of the patients, but 80% of the patients had reached their best function within 6 weeks. The time course of recovery was strongly related to initial neurological stroke severity (Fig 1). Best function was reached within 9 weeks in patients with initially mild strokes, within 13 weeks in patients with initially moderate strokes, within 17 weeks in patients with initially severe strokes, and within 20 weeks in patients with initially very severe strokes. After these time points no significant changes in function occurred. A valid prognosis could be made much earlier, because best function was reached by 80% of the patients with initially mild strokes within 3 weeks, within 7 weeks for the patients with moderate strokes, and within 12 weeks for the patients with initially severe or very severe strokes (Fig 1). Overall, functional recovery from stroke usually occurs within the first 13 weeks from stroke onset. Patients with the longest period of recovery (ie, those with very severe strokes) should not expect further functional recovery after the first 5 months: such late recovery was seen in only 9 of the 1,197 patients. The time course of recovery of the neurological deficit followed a pattern similar to that of functional recovery, but preceded functional recovery by 2 weeks on average. In the COST study, best upper-extremity function was reached within 6 weeks in patients with initially mild upper-extremity paresis and within 11 weeks in patients with initially severe paresis? Best walking was reached within 4 weeks in patients with initially mild paresis of the affected lower extremity, within 6 weeks in patients with moderate paresis, and within 11 weeks in patients with initially severe paresis or paralysis of the affected lower extremity. 1° Patients initially unable to walk reached best function within 11 weeks, but 80% had reached best function within 6 weeks. Patients who initially could walk

THE COPENHAGEN

STROKE STUDY Mild

%

Stroke

lOO

80

~

.

.

.

.

.

.

.

.

.

Moderate

% ~

~

~

~

100

80 ~

.

• -I . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I I 40 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I I 2o . . . . I. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . J

60-

Stroke

. . . . . . . . . . . . . . . . . . .

60 ,

. . . . . . . .

. . . . . . . .

[. . . . . . . . . . . . .

I

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I. . . . . . . . . . . . .

] . . . . . . . . . .

J. . . . . . . . . . . . .

I I

I I

1

I

20

0 1

2

3

4

5

6

7

8

2

10 11 12 13 14 15 16 17 10 19 20>20

3

4

5

6

7

8

9 10 11 12 13 14 15 16 17 18 19 20>20

Weeks From Stroke Onset

Weeks From Stroke Onset

Severe

%

Stroke

.~I

100

Very Severe

%

Stroke

100

80.

80

60.

60

40

40-

20

20-

1 . . . . . . . . . . . . . . . .

i

. . . . . . . . . . . . . .

0

0 2

3

4

5

8

7

8

9 10 11 12 13 14 15 16 17 18 19 20>20

Weeks From Stroke Onset

2

3

4

5

6

7

8

9 10 11 12 13 14 15 16 17 18 19 20>20 Weeks

From

Stroke Onset

Figure 1. Graphs depict the time course of maximal~mctional recovery strat~ed according to initial neuro~ogical stroke severity~ shozon as the accumulated rate of patients having reached their bestfunctional level (ADL). The Copenhagen Stroke Study. Mild stroke: 45 to 58 points on the SSS. Moderate stroke: 30 to 44 points in SSS. Severe stroke: 15 to 29 points. Very severe stroke: 0 to 14 points.

only with assistance reached best function within 5 weeks, but 80% had reached best function within 3 weeks. Factors other than initial stroke severity and disability may influence the time course of recovery. In the COST study stroke in progression was found to double the length of the recovery period, 6 and the presence of diabetes also slowed recovery,8 but age, 3 sex,3 a history of stroke or other disabling disease, 3 stroke type, 14 the presence of silent infarction, 1 and leuco-araiosis u had no independent influence on the time course of recovery.

Mechanisms of Recovery Recovery from stroke occurs in the neurological and functional domain. Functional recovery occurs through adaptive and intrinsic mechanisms42; rehabilitation recovery is primarily accomplished by adaptive mechanisms. Recovery occurs in part by education in the use of uninvolved body parts to perform impaired function, ie, compensation.

Compensation is an important mechanism of recovery in rehabilitation. In the COST study of acute stroke patients with upper extremity paresis so severe that the affected extremity was nonfunctional. More than half of thse patients remained severely paretic. 5 Forty percent, however, had improved upper extremity function through compensation using the uninvolved upper extremity. Compensation was greater at a younger age, in patients with less severe strokes, and in patients with more intact higher cortical functions. Randomized, controlled studies of rehabilitation methods have compared the effect of integrated behavioral physical therapy (electromyographic feedback) versus the Bobath method, 43conventional therapy versus proprioceptive neuromuscular facilitating (PNF) versus the Bobath method, 44 conventional versus the Bobath method, 40 conventional versus PNF, 46 and functional occupational therapy versus sensorimotor integrative occupational therapy. 47 No method proved superior to another. That recovery achieved by rehabilitation seems independent of

10 the method used was further confirmed by Wagenaar et al, who compared two methods based on very contrasting principles, neurodevelopmental treatment and the Brunnstrom method, and found no difference in outcome. 48 In addition, no specific speech therapy proved superior to another. 49 Intrinsic neurological recovery m a y be attributable to at least three different mechanismsS°; restoration of cerebral blood flow by spontaneous reperfusion, resolution of edema or hemorrhage, and transfer of lost neural function to intact part(s) of the brain. Spontaneous recanalization of an occluded artery has been known for several decades. 5~-53In the COST study, spontaneous reperfusion occurred in about 80% of the patients with cortical infarcts. 7 Approximately 30% of the infarcts reperfused within the first 3 days from onset, 60% within the first week, and 80% within the first 2 weeks from stroke onset. Early spontaneous reperfusion improves both neurological 7 and functional 54 outcome by restoring neuronal function in the ischemic penumbra surrounding the infarcted area. 55~6 Edema peaks 3 to 4 days after stroke onset, 57 resolves within four weeks, 5s and may cause late stroke in progression. 6 In hemorrhagic strokes the hemorrhagic process itself m a y compromise neuronal function. Resorption of the hematoma is often accomplished within the first few weeks after stroke. 59 Functionally compromised but still viable neurons may be restored by resorption of the edema or blood products in the early phase of stroke. In the COST study, recovery was dependent on the systemic blood pressure because there was a clear relation between decreasing systemic blood pressure on admission and the development of early stroke in progression. Clinical evidence is increasing for the transfer of brain function from the affected area to other brain areas. This has been shown in reports of recovery after hemispherectomy, 6° loss of recovered speech after amytal injection in the right carotid artery, 6~ activation on a positron emission tomography scan of the unaffected hemisphere by motor exercise of recovered hand or linguistic tasks, 62~ and loss of recovered ffmction after new stroke in the opposite hemisphere. 6s

H.S. ]ORGENSEN

Table 4. The influence o f various factors on stroke outcome Time InNeurocourse hospital logical ADL of mortality deficits function recovery Stroke in progression Early spontaneous reperfusion Diabetes Blood glucose in diabetics* Blood glucose in nondiabetics* Age Sex Hemorrhage/infarct Silent infarction Leuco-araiosis Hypertension Cardiac disease Previous stroke

1

T

1

]"

? T

J. ~

1" "-'

? '--'

--.

?

?

?

? ---. -----, . . . ? ? ?

? J, --.

? ---.

T ---, ---, . . . . . . l---'? l 1-*

. . . -"? 1 ?

? ? ?

Abbreviations: 1, reduced; ---,, no influence; T, increased; ?, unknown/unsettled. *Elevated levels on admission. Stroke in Progression

A marked deterioration develops in one third of stroke patients in hospital during the first few days after stroke onset. 6,66"69In the COST study, Jorgensen et al 6 found that early progression within the first 36 hours from onset was related to admitting blood pressure (Fig 2). The risk of developing stroke in progression (SIP) decreased with increasing systolic blood pressure on admission (odds, 0.66 per 20 m m Hg). Only I of 22 patients with a systolic S t r o k e In P r o g r e s s i o n ,

%

50

40

30

The Effect of Some Demographic,

20

Medical, and P a t h o p h y s i o l o g i c a l Factors on the O u t c o m e of Stroke

10-

The outcome of stroke is diverse even for patients with similar initial stroke severity or disability. Despite the large number of outcome studies, few have studied factors influencing the outcome of organized stroke rehabilitation, and even fewer of these studies have been performed in unselected stroke populations. Table 4 summarizes present knowledge.

0

_< 140

-160

i

J

-180

-200

-220

>220

systolic Blood Pressure on Admission

Figure2. Thefrequency of patients developing early stroke in progression as afimction of the systolic blood pressure on admission in the Copenhagen Stroke Study.

11

THE C O P E N H A G E N STROKE S T U D Y

admission blood pressure of 220 m m Hg or more developed SIP. The risk of early SIP was almost doubled in stroke patients with diabetes. Impaired autoregulation 5s during the acute stroke, to which patients with diabetes may be especially vulnerable, 7° may explain these relations. Late progression (within the first week from onset) was not related to blood pressure or diabetes but to initial stroke severity.6 The risk of SIP increased by 1.4 times per 20-point deterioration on the Scandinavian Stroke Scale. Asplund 69 also found SIP related to stroke severity, but patients were not stratified according to whether progression occurred early or late. Cerebral edema and hemorrhagic transformation of stroke may contribute to late progression. 7-s7 The impact of SIP on the rehabilitation process and rehabilitation outcome is severe and lasting. 6,6s In the COST study SIP doubled mortality rate, discharge rate to nursing home, and the length of hospital stay.6 Survivors had markedly more severe neurological deficits and ffmctional disabilities at the end of rehabilitation.

Spontaneous Reperfusion In ischemic stroke, spontaneous reperfusion of the affected area occurs in about 80% of all cortical infarcts within the first 14 days after stroke onset. 7 In a PET study of 18 patients, there was better functional outcome in those with early spontaneous reperfusion, s4 Of 36 acute stroke patients studied by SPECT, 7 marked improvement in the neurological deficit at 2 weeks and at the end of rehabilitation was present only in those with early spontaneous reperfusion (Fig 3). Normalization of neuronal

Difference in Gain, 95% CI 20Reperfusion

15 p<0.02

10

<0,0~ I p

No Reperfuslon

L Day of onset

-

49

p=O.eS

4847 46 45

=

~

Admission

Day 1

44

43 42

p=0.79

41 40

I

I

I

Week l

I

Discharge

Figure 4. Neurotogic recovery (SSS score) as afimction of time in patients with (A) and without ( I ) diabetes. The Copenhagen Stroke Study. function in the ischemic penumbra, ie, the peri-infarct region, most likely explains this. ss

Diabetes Diabetes doubles the risk of ischemic stroke, 7L72 but reduces the risk of primary hemorrhagic stroke. 8,7],72 There is an increased stroke mortality. 8,73-7s Diabetes almost doubled the risk of dying of stroke, s Initial stroke severity, lesion size, and site did not differ in patients with and without diabetes. 8 Differences in the distribution of other risk factors such as coronary heart disease, hypertension, etc, did not explain this increased mortality, 8,76 and the cause of death did not differ between stroke patients with and without diabetes. 8 Prognosis for recovery is reportedly poor in patients with diabetesT 79 but in the COST study, 8 neurological and functional outcomes were similar in survivors with and without diabetes, although rehabilitation in diabetic patients took longer (Fig 4).

Blood Glucose

p=0,4

-5

SSS Score 50-

i

1 reek 2 weeks Time From Stroke Onset

Discharge

Figure 3. Differencein gain in the SSS scoreand 95% Ct between patients zoith spontaneous reperfi~sion (reperfusion) and without spontaneous reperfilsion (no reper~tsion) within the first week from stroke onset. The Copenhagen Stroke Study.

There is an association between high levels of blood glucose and an increased mortality rate in nondiabetic stroke patients. 8,7s,77.79~ In the COST study, multivariate regression analyses were used to assess the relationship between admission blood glucose and mortality rate independently from initial stroke severity and other influencing factors. 8 Most of the relationship was explained by initial stroke severity, but high admission glucose levels increased mortality rate independently from initial stroke severity, by odds 1.2 per 1 m m o l / L

H.S. Jf~RGENSEN

12 Mortality in Non-Diabetics, %

Sex "

/

35 30

9.'//////.

25

~//'//~ / /

.......

20

;;;;;;;.

15

~/,/././,/.d

Stroke Type

. . . . . .

~.'//////~ ,/ . . . . . .

,///////. ////////

~/////,,

///////A ,

-<5

>5-6

>6-7

>7-8

/

/

>8-9

As in other studies, 87.92.93 the COST study found no independent influence of sex on neurological and functional outcome, speed of recovery, or mortality rate of stroke. 3

>9

Admission Glucose, mmol/I Figure 5. Plasma-glucose on admission in relation to mortality in nondiabetic stroke patients. The Copenhagen Stroke Study.

above 6 mmol/L (Fig 5). Therefore, whether or not a stress response reflecting stroke severity, increased blood glucose levels contributed to poor prognosis in these patients. In contrast, no independent influence of admission glucose levels was found regarding initial stroke severity and mortality in diabetic stroke patients. Age

Most studies have shown a negative influence of age on various outcome measures of stroke, but methodological problems such as selection bias, the use of unvalidated scoring systems, and studies based on small numbers have limited their validity. Wade and Hewer 87 found that age was related to increases in initial disability, disability 6 months after stroke, hospital stay, mortality rate, and need for institutional care. More recent studies ~-9° also report an age-dependent increase in mortality rate after stroke. Increased age is associated with a higher frequency of comorbidity and disability. Therefore, elderly stroke patients have a worse prognosis than young stroke patients. An evaluation of the influence of age per se on outcome should consider age independent of age-associated factors. In the COST study Nakayama et aP studied the independent influence of age on outcome. They found that age per se does not influence type or size of the stroke, length of hospital stay, time course of recovery, 3-month mortality, or the discharge rate to nursing homes after completed rehabilitation. Age did influence stroke outcome in ADL-related measures, but not neurological recovery. This indicates a limited compensatory ability in elderly stroke patients. This influence of age on ADL was confirmed by Kalra et al. 91

Strokes caused by primary hemorrhages generally are believed to carry a worse prognosis than strokes caused by ischemic infarction because mortality rate is higher. 14,94"1°1In the COST study after controlling for the difference in initial stroke severity, the type of stroke carried no prognostic information. ~4 This was true for mortality, neurological and functional outcome in survivors, and time course of recovery. In general, stroke type adds no prognostic information to the bedside evaluation of the patient. The generally worse outcome found in stroke patients with a primary intracerebral hemorrhage, as compared with patients with ischemic infarction, seems entirely caused by the severity of intracerebral hemorrhage. Only 4% of mild strokes were caused by hemorrhage, whereas 25% of the severe strokes are hemorrhagic 14 (Fig 6). These results are corroborated in a

% of Patients with ICH 40

30

20

10

Mild

Moderate

Severe

Very severe

Initial Stroke Severity Figure 6. The relative frequency (%) of intracerebral hemorrhage (ICH) as a Jimction of stroke severity (stratified according to the SSS score on admission). Ninety-five percent cot~dence intervals are shown. The Copenhagen Stroke Study. Mild stroke: 45 to 58 points on the SSS. Moderate stroke: 30 to 44 points on SSS. Severe stroke: 15 to 29 points. Very severe stroke: 0 to 14 points.

13

THE COPENHAGEN STROKE STUDY

case-controlled study of 240 patients that showed no difference between types of stroke in survivors and the frequency of patients being functionally independent 1 year after the ictus} m

Silent Infarction Silent cerebral infarction is a common finding on CT and MRI in stroke patients; frequency ranges from 10% to 38%) A°2-1°5Ricci et aP °5 studied 209 patients with firstever stroke and found that silent infarctions did not influence mortality rate and persistence of handicap. In the COST study, silent infarcts did not influence the frequency of prestroke home care, admission mini-mental state examination score, functional score (Barthel Index), and admission neurological score (Scandinavian Stroke Scale)) Functional and neurological scores remained the same after completed rehabilitation. The speed of recovery, length of hospital stay, mortality, and discharge rate to nursing home were also similar in patients with and without silent infarcts. Silent infarcts do not seem to influence the rehabilitation process and they do not affect the outcome of rehabilitation. Any subtle, negative influence of the silent infarct on the intellectual performance of the patient with stroke remains to be determined. 2

Leuco-araiosis Leuco-araiosis is the rarefaction of white matter in the brain as seen on CT or MRI. m6 This condition has been related to higher cortical dysfunction in the healthy elderly, to dementia, and to cerebrovascular disease. In stroke patients the frequency of leuco-araiosis increases with age. 11,1°7In the COST study, moderate daily alcohol consumption was related to a reduced risk of leucoaraiosis. Multivariate analyses found no relation between leuco-araiosis and mortality, neurological and functional outcome, and the length of hospital stay. u

Hypertension Hypertension, present in about one third of all stroke patients, is the single most important treatable risk factor in both ischemic and hemorrhagic stroke34 Whether hypertension influences the outcome of stroke rehabilitation remains to be determined. Solzi et aP °s retrospectively studied late survival in 1,369 patients referred to rehabilitation within 6 months poststroke and reported an adverse effect of hypertension on late survival, but initial stroke severity was not considered. Wade et al 1°9 studied late survival in 162 patients referred for rehabilitation and found no independent influence of hypertension. Also Censori et a193 who studied 172 patients admitted to a stroke unit, and Shah et al n° who studied 258 patients receiving comprehensive rehabilitation, reported no rela-

tion between hypertension and functional outcome. Most stroke studies giving traditional treatment 97,gs,m,n2 have also reported no relation between hypertension and both short- and long-term mortality. The Framingham study found hypertension associated with a reduced survival in men, but not in women. H3

Cardiac Disease The presence of heart disease increases both functional disability after stroke rehabilitation n° as well as late mortality, 1°8,1°9 but Censori et a193 fotmd no relation between heart disease and functional outcome. Most nonrehabilitation stroke studies 97,98,m,u2 report a poorer short- and long-term survival in patients with heart disease. Sacco et al u2 found an increased risk ratio of 2.6 for both short- and long-term mortality in patients with congestive heart failure.

Previous Stroke A study of 1,566 patients found that a history of previous stroke independently increased 1-year mortality, m but another smaller study found no independent influence of a history of previous stroke on late survival) °9 Sacco et al u2 reported no independent relationship between a history of previous stroke and short- and long-term mortality. In contrast, Chambers et al9~ reported from a study of 1,013 patients that a history of stroke reduced both short- and long-term survival. In conclusion, the general nihilistic approach to rehabilitation of stroke patients that has dominated the past no longer seems warranted. There is established benefit from treating stroke patients from the time of admission to the end of rehabilitation on dedicated stroke units. Even with future advances in the medical treatment of stroke by thrombolysis and neuroprotective agents, the need for structured stroke rehabilitation will increase. General criteria for the selection of patients for stroke unit treatment should be avoided, especially age. Patients with the most severe strokes may often be those who benefit most from dedicated stroke unit care. A benefit for this management strategy should be available to all stroke patients.

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101.

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