1. Early decompressive surgery for stroke
Malignant cerebral oedema has 80% mortality
Analysis of 3 RCTs (DECIMAL*, DESTINY*, HAMLET-ongoing) n=93
Age with space occupying MCA infarction
Decompressive surgery within 48 h of stroke onset
Reduces mortality
Does not increase the number of severely disabled survivors
NNT=2 for survival with mRS<4 (able to walk)
Vahedi et al, Lancet Neurol. 2007;6:
*Stopped early due to significant between-group differences in mortality, favoring surgery
BACKGROUND: Malignant infarction of the middle cerebral artery (MCA) is associated with an 80% mortality rate. Non-randomised studies have suggested that decompressive surgery reduces this mortality without increasing the number of severely disabled survivors. To obtain sufficient data as soon as possible to reliably estimate the effects of decompressive surgery, results from three European randomised controlled trials (DECIMAL, DESTINY, HAMLET) were pooled. The trials were ongoing when the pooled analysis was planned. METHODS: Individual data for patients aged between 18 years and 60 years, with space-occupying MCA infarction, included in one of the three trials, and treated within 48 h after stroke onset were pooled for analysis. The protocol was designed prospectively when the trials were still recruiting patients and outcomes were defined without knowledge of the results of the individual trials. The primary outcome measure was the score on the modified Rankin scale (mRS) at 1 year dichotomised between favourable (0-4) and unfavourable (5 and death) outcome. Secondary outcome measures included case fatality rate at 1 year and a dichotomisation of the mRS between 0-3 and 4 to death. Data analysis was done by an independent data monitoring committee. FINDINGS: 93 patients were included in the pooled analysis. More patients in the decompressive-surgery group than in the control group had an mRS<or=4 (75%vs 24%; pooled absolute risk reduction 51% [95% CI 34-69]), an mRS<or=3 (43%vs 21%; 23% [5-41]), and survived (78%vs 29%; 50% [33-67]), indicating numbers needed to treat of two for survival with mRS<or=4, four for survival with mRS<or=3, and two for survival irrespective of functional outcome. The effect of surgery was highly consistent across the three trials. INTERPRETATION: In patients with malignant MCA infarction, decompressive surgery undertaken within 48 h of stroke onset reduces mortality and increases the number of patients with a favourable functional outcome. The decision to perform decompressive surgery should, however, be made on an individual basis in every patient.

2. Indications for decompressive hemicrainectomy
Age < 60 years***
Severe MCA infarct (NIHSS>15)
Fall of conscious level to drowsy (e.g. a score of 1 or greater on NIHSS 1a or GCS E+M <=9)
Signs on CT of an infarct of at least 50% of MCA territory or infarct volume >145 cm3
Referral within 24 h of stroke onset, surgery no later than 48 h after stroke onset
NICE (guidance)
NICE (evidence table)
RCP
based on Vahedi et al Lancet Neurology 2007.
****See DESTINY II 2012: age limit no longer applies
Comments:
Early referral seems the key.
Refer young patients with large MCA infarcts as soon as they become drowsy.
Do not wait until loss of consciousness or dilation of pupil.
Operate within 48 h of stroke onset (not within 48 h of onset of drowsiness).
RCP guidance is woolly on this ‘within 48 h of symptom onset’, but checking NICE tables and Vahedi publication this guidance is based in it appears clear that 48 h refers to stoke onset.
Vahedi et al (counducted the pooled analysis of the main three Euopean trials DESTINY, DECIMAL, HAMLET) :
“Data from a large non-randomised series have suggested that outcome is substantially improved if treatment is initiated within 24 h of stroke onset as compared with longer time window….’
“Similar observations were made in a recent series of patients in which the mean interval from stoke onset to surgery was 47 hours”
“In most patients, clinical signs of herniation appear after 2 days of stroke onset. Whether decompressive surgery is also beneficial if undertaken after the first 48 h is currently being tested in HAMLET”
Neuroscience Paper
“of the three randomised trials only HAMLET allowed a delayed surgery (up to 99 h after stroke onset) ….”
So all the trial data refer to stroke onset rather than onset of symptoms of oedema. – especially as the pooled analysis of HAMLET, DESTINY AND DECIMAL used similar inclusion criteria.
Vibbert and Mayer review paper :
“The optimal timing of hemicraniectomy remains uncertain. There has been an ongoing debate over whether to opeate as soon as the diagnosis of MCA infarction is made, or to wait for signs of early symptomatic mass effect, which might perhaps spare some patients if they have a stable course”
Worse outcome in hamlet than destiny and decimaal even if only pts within 48 h inlcuded. Mean time sx to surgery 24 h in Dest and dec, but 31 h in hamlet. All support earlier rather than later surgery. Also subgroup analysis does not show that dominant hemisphere does worse than non dominant hemisphere stroke, or that are worse than < 50 yo.
Drowsiness may also be defined as combined GCS motor and weye scores of <=9 (bibbert mayer 2010)

3. HEMICRANIECTOMY
Baseline MRI scans (A) of a 22-year-old woman in the surgery group with a DWI infarct volume of 173 cm3. A large right hemicraniectomy including temporal, frontal, parietal, and occipital bone ipsilateral to the stroke was performed (B). At 1-year follow-up, 6 months after reconstruction of the large bone defect, her mRS score was 3, and fluid-attenuated inversion recovery imaging revealed right hemisphere atrophy (C).
Vahedi, K. et al. Stroke 2007;38:
Copyright ©2007 American Heart Association

4. Age Limit?
Destiny II showed NNT = 4 for patients>60 years (no upper age limit!)
Stopped by DSMB at n=80 b/o efficacy
24.9% absolute difference between the groups in favour of decompressive surgery
20 of 49 (40.8%) vs 10 of 63 (15.9%) in the non-surgical cohort ( P = .0038) had an mRS 0-4 ( P = 0.004)
Hacke et al , European Stroke Conference 2013
When the DSMB did its 6-month interim analysis on 80 patients, it found a 24.9% absolute difference between the groups in favor of decompressive surgery. In the ICU plus decompressive surgery cohort, 20 of 49 (40.8%) patients had an mRS of vs 10 of 63 (15.9%) in the ICU only cohort ( P = .0038).
That makes...a number needed to treat of 4. Dr. Werner Hacke  
"That makes...a number needed to treat of 4," Dr. Hacke reported. The remaining patients in each group had an mRS of
A shift analysis of the mRS distribution showed that there was a significant shift of mRS scores to lower categories in the surgery group compared with the conservative management group ( P < .001). The shift in the surgery group was mainly from mRS to mRS 4. (mRS 5 denotes severe disability, and 6 denotes death.)

5. TIMING
Time is brain
Earlier hemicraniectomy (within 24 h ) has more independent survivors than late hemicraniectomy
Vibbert and Mayer

6. Hemisphere Effect?
Updated Metaanalysis of DESTINY, DECIMAL and HAMLET (n=109)
Outcome is similar in dominant and non-dominant hemisphere strokes
Vibbert and Mayer

7. Lay Summary
Large cortical infarcts (strokes) are invariably associated with brain swelling
The brain shrinks with age and in older people there is usually enough space in the skull for the brain to swell
In young patients there is no spare space in the skull and therefore the brain swelling causes compression of vital centres in the brain stem
Young patients with very large strokes are therefore at high risk of rapid deterioration and death within the first 48 hours.
Surgery may be required. This may be life saving, but will not reverse the damage the of the initial stroke.

8. Results expected at 1 year for every 10 patients undergoing decompressive hemicraniecomty
Slide designed by Zubair Iqbal

9. Inclusions
DESTINY
Juettler 2007
N=32
DECIMAL
Vahedi 2007
N=38
HAMLET
Hofmeijer 2009
N=64
18-60
18-55
and
12-36 h from symptom onset to OP
<30 h from stroke onset to OP
<96 h from stroke onset to OP
NIHSS 1a ≥ 1
GCS
≤13 L hemiparesis
≤9 R hemiparesis
NIHSS
≥18 L hemiparesis
≥21 R hemiparesis
NIHSS≥16
≥16 L hemiparesis
≥ ¾ MCA incl. at least part of basal ganglia (involvement of ACA or PCA allowed)
≥ 50% MCA
≥ ¾ MCA (involvement of ACA or PCA allowed) -
DWI≥145mm3
Exclusions
mRS≥2 or
BI ≤ 95
GCS ≤6
Fixed dilated pupil bilaterally
Any other clinically relevant brain lesion
Signif contralat. Infarct
ACA MCA and PCA infarcted
Space occupying brain haemorrhagic transformation
Haemorrhagic transformation >50% of MCA
Coagulopathy
Thrombolysis
Thrombolysis ≤12 h ago
Other severe comorbidities limiting life expectancy
Other severe comorbidities or life expectancy <3y
Outcome
Mortality 30 d
47% vs. 88% p=0.02
mRS<4 at 12 mo 47% vs. 27% p=0.2
Mortality 12 mo
25% vs. 78% p<0.0001
mRS<4 at 12 mo 50% vs. 22% p=0.1
Mortality at 12 month red by 38%
No difference in mRS<4

10. Reassessment of the HAMLET study
Figure 2
Reassessment of the HAMLET study
Patrick Mitchell, Barbara A Gregson, John Crossman, Chris Gerber, Alastair Jenkins, Claire Nicholson, Nick V Todd, Nick Ross, Parameswaran Bhattathiri, Justin Nissen, Peter J Crawford, Guy Wynne-Jones, Robin P Sengupta, Laura Graham, Akif Gani, Michelle Davis, Chris Gray, David Barer, Paul Dorman, David Millar, Julia Williamson, Holly Durham, Alison Jones, Helen Hastie and A David Mendelow
The Lancet Neurology Volume 8, Issue 7, Pages (July 2009)
DOI: /S (09)
Outcome at 1 year by treatment group for all three studies combined
mRS=modified Rankin scale. Comparison of surgical patients with medical patients for good outcome (mRS of 0–3) versus bad outcome (mRS of 4–5, or dead) using Fisher's exact test for all 134 patients gives a p value of 0·14, and for patients treated within 48 h (for 109 patients) gives a p value of 0 ·10.
Source: The Lancet Neurology 2009; 8: (DOI: /S (09) )
Terms and Conditions

11. Figure 1
Meta-analysis of the three trials with data from all 134 patients
DECIMAL=DEcompressive Craniectomy In MALignant middle cerebral artery infarction. DESTINY=DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY. df=degrees of freedom. HAMLET=Hemicraniectomy After Middle cerebral artery infarction with Life-threatening Edema Trial. M–H=medical minus hemicraniectomy.
Source: The Lancet Neurology 2009; 8: (DOI: /S (09) )
Terms and Conditions