Interventional neurology: a personal road map.

The foundation of thrombolytic therapy for acute stroke rests on the NINDS IV tPA trial published in 1995 [1] and the PROACT II intra-arterial trial published in 1999 [2] . Based on NINDS and PROACT II, virtually all major stroke centers now routinely perform IV and IA thrombolysis in patients with acute ischemic stroke. The early road to thrombolytic stroke therapy had many twists and turns, some of which I now retravel with you in my strokemobile ( fig. 1 , 2 ). In 1990 there were 2 major groups in the world working on stroke thrombolysis: the angiography-based group, spearheaded by Gregory Del Zoppo and funded by Burroughs Wellcome (BW), and the NINDS group led by Tom Brott and supported by Genentech. The angiographic group, of which I was a charter member, argued (sometimes vehemently) that all thrombolysis candidates must first undergo angiography to determine the site of occlusion and whether recanalization had occurred. Our seminal angiographic dose escalation study published in 1992 [3] established that the site of vascular occlusion in acute stroke was highly variable and could not be reliably determined by the clinical neurological examination. Moreover, recanalization varied by site of occlusion with only distal M3 MCA occlusion reliably opening with IV tPA. The NINDS group made the seminal insight that time is brain (prior to 1990 almost all stroke trials used up to a 48-hour window). For the first time NINDS established a very aggressive treatment window of ! 3 h. NINDS argued that pretreatment vascular imaging information was neither feasible nor necessary. The NINDS group arrived at the final IV tPA dose of 0.9 mg/kg by performing 2 dose escalation trials which were halted when excessive brain hemorrhages occurred, i.e. the final dose of 0.9 mg/kg IV tPA was based solely on safety; recanalization rates for IV tPA were never established [4, 5] . In 1990, after 5 years of legal action, Genentech obtained a permanent injunction against BW tPA. The injunction was announced to our team by the CEO of BW while we were sitting in an airplane in Frankfurt, Germany, having just presented the initial results of the BW Published online: April 23, 2012