Brain CT signs and the effect of alteplase after stroke

The third International Stroke Trial (IST-3) is the largest (n=3035) randomised controlled trial of intravenous alteplase for acute ischaemic stroke to date. 1 Participants in IST-3 were older than in previous trials: 1617 (53%) were older than 80 years of age, whereas only 112 patients of this age were included in eight previous similar trials. 2 In IST-3, participants could be treated up to 6 h after stroke onset, but 849 (28%) were treated within 3 h. No signifi cant eff ect of alteplase was reported on the IST-3 primary endpoint—independence at 6 months (defi ned as an Oxford Handicap Scale score of 0–2). However, in a prespecifi ed ordinal analysis, a signifi cant shift was noted in functional outcome, in favour of alteplase. 1 A meta-analysis of individual patient data from nine randomised trials (including IST-3) showed that intravenous alteplase improved outcome when administered up to 4·5 h after stroke onset. 2 The proportional benefi t from alteplase increased with earlier treatment but was not modifi ed by age. 2 IST-3 is a landmark study because the eff ects of alteplase could be assessed reliably in older patients with acute ischaemic stroke. investigators, and this study includes a large population of patients with ALS and has a rigorous design. However, the same results need to be attained by less skilled investigators than those involved in this study, and the worldwide application of the technique will depend on the acquisition of new equipment and software. However, the study undoubtedly shows that detection of increased cortical excitability is a diagnostic biomarker in ALS, and that use of threshold tracking TMS with existing criteria might help to speed up the process of diagnosis. Nonetheless, despite these promising results, the question of disease onset is not yet resolved. Early signs of hyperexcitability are seen in the LMN pool; the presence of fasciculation potentials is the fi rst change detected in clinically non-aff ected muscles of patients with ALS. 9 This fi nding could be attributed to LMN activation due to increased cortical drive, but not all fasciculation potentials seen in the strong muscles of ALS patients originate in the anterior horn cell. Signs of corticomotoneuronal abnormality, as assessed by threshold tracking TMS, have been reported to precede signs of LMN dysfunction in the target muscle. 3 Altogether, we cannot reject the possibility that increased corticomotor excitability early in the disease course is a …