BACKGROUND: Patients with space-occupying hemispheric infarctions have a poor 
prognosis, with case fatality rates of up to 80%. In a pooled analysis of 
randomised trials, surgical decompression within 48 h of stroke onset reduced 
case fatality and improved functional outcome; however, the effect of surgery 
after longer intervals is unknown. The aim of HAMLET was to assess the effect of 
decompressive surgery within 4 days of the onset of symptoms in patients with 
space-occupying hemispheric infarction.
METHODS: Patients with space-occupying hemispheric infarction were randomly 
assigned within 4 days of stroke onset to surgical decompression or best medical 
treatment. The primary outcome measure was the modified Rankin scale (mRS) score 
at 1 year, which was dichotomised between good (0-3) and poor (4-6) outcome. 
Other outcome measures were the dichotomy of mRS score between 4 and 5, case 
fatality, quality of life, and symptoms of depression. Analysis was by intention 
to treat. This trial is registered, ISRCTN94237756.
FINDINGS: Between November, 2002, and October, 2007, 64 patients were included; 
32 were randomly assigned to surgical decompression and 32 to best medical 
treatment. Surgical decompression had no effect on the primary outcome measure 
(absolute risk reduction [ARR] 0%, 95% CI -21 to 21) but did reduce case 
fatality (ARR 38%, 15 to 60). In a meta-analysis of patients in DECIMAL 
(DEcompressive Craniectomy In MALignant middle cerebral artery infarction), 
DESTINY (DEcompressive Surgery for the Treatment of malignant INfarction of the 
middle cerebral arterY), and HAMLET who were randomised within 48 h of stroke 
onset, surgical decompression reduced poor outcome (ARR 16%, -0.1 to 33) and 
case fatality (ARR 50%, 34 to 66).
INTERPRETATION: Surgical decompression reduces case fatality and poor outcome in 
patients with space-occupying infarctions who are treated within 48 h of stroke 
onset. There is no evidence that this operation improves functional outcome when 
it is delayed for up to 96 h after stroke onset. The decision to perform the 
operation should depend on the emphasis patients and relatives attribute to 
survival and dependency.