NO-GO TO TPA FOR TIA

Thrombolysis is not a rational or evidence-based therapeutic option for transient ischemia, irrespective of vascular status. Even with overt MCA occlusion, complete resolution of symptoms during evaluation does not warrant intravenous tissue-plasminogen activator (tPA). Symptom resolution may result from head-down positioning with improved hemodynamics and rapid improvement remains one of the most common reasons cited for withholding thrombolysis.^{1, 2} Multimodal CT and MRI have since enabled clinicians to rapidly depict proximal arterial occlusion, tissue status and perfusion through the brain. Identification of an MCA occlusion, however, dangles an elusive carrot that may incite harm with unnecessary thrombolysis.

The prevailing obsession with arterial occlusion has erroneously focused attention on clots rather than ischemia. Hemodynamic insufficiency, and not clots, causes symptoms when collaterals falter.³ The persistence of thrombolysis as the sole treatment for acute ischemic stroke perpetuates the notion that occlusion is a red flag for intervention, yet collaterals may offset or dissipate symptoms even in proximal arterial occlusion. Asymptomatic occlusion is often noted, with moyamoya serving as the ultimate example of collateral compensation. Robust downstream collateral perfusion may also accompany occlusion with atherosclerotic plaque unamenable to thrombolytics. Imaging of occlusion without consideration of clinical details or pathophysiological mechanisms may therefore be misleading.

Thrombolytic decisions should always integrate clinical aspects with vascular imaging features, resisting the temptation to treat imaging findings in isolation. Treating vascular lesions alone may be dangerous and based on incorrect assumptions about expected prognoses. The decision on thrombolysis has always been a synthesis of clinical severity, time from onset and imaging. In TIA with MCA occlusion, clinical severity is nil, time is reset and imaging patterns are variable. Others have reported TIA resulting from thrombolysis and the presence of minor deficits is radically dissimilar to TIA. Time is intangible as symptom onset is almost never synonymous with vascular occlusion. The seminal thrombolysis trials also demonstrated that time to presentation increases with diminishing severity and later “survivors” respond best to tPA, likely due to enhanced collateral flow.^{4, 5}

Collateral flow may or may not be sufficient to maintain perfusion, yet time will tell and provocative stimuli may presage subsequent events. Heads-up positioning may challenge collateral perfusion in MCA occlusion and even when sustained, serial examination of the patient may provide clues to optimal treatment strategies.⁶ Simply stated, the go/no-go nature of current thrombolytic triage is inappropriate for TIA and unnecessary as there is time to modernize this outdated paradigm. Close observation, frequent neurological assessments and supportive care are essential aspects of any patient with cerebral ischemia. Such elements form a cogent argument for admitting TIA patients not to be replaced by the unsubstantiated go/no-go of thrombolysis.

Thrombolysis may not prevent clinical worsening or early recurrence. Only a fraction of cases will recanalize, with even fewer to reperfuse. Opening an artery may be unwarranted, as some patients may never deteriorate. TIA cases may enjoy ischemic preconditioning that prevents later deterioration. The benefit of thrombolysis is purely theoretical with normal examination at baseline and subsequent worsening then provides impetus for rational revascularization.⁷ Thrombolytic risks and destabilization, however, must also be considered. Partial recanalization may expose more surface area and promote rethrombosis. Distal embolization into multiple branches may also not be tolerated or effectively offset by collaterals, resulting in focal cortical deficits. Finally, any asymptomatic tissue injury associated with TIA may be prone to reperfusion injury or hemorrhage.

Thrombolysis for TIA is an off-label use that eclipses other protocol violations such as acute anticoagulation. Clinical acumen and logic, not absolute rules, should be used to treat such complex cases. Thrombolysis was the nidus to orchestrate acute stroke systems of care, yet resulting systems now have the capacity to extend treatment strategies far beyond the go/no-go of tPA. Stroke units, clinical expertise and advanced diagnostic or therapeutic procedures offer more than simple protocol or cookbook approaches to stroke.

Although TIA should not be incorporated, minor deficits and many other aspects should be considered. Imaging should be utilized to increase and refine thrombolysis decisions around specific risk-benefit profiles, identifying robust collateral perfusion that improves outcome and factors that portend hemorrhage. The mere presence of MCA occlusion discloses nothing about downstream collateral flow and the corresponding evolution of ischemic injury in a particular case. When time allows, as in TIA with MCA occlusion, hasty and potentially erroneous thrombolysis decisions should be replaced with a modern paradigm that incorporates serial evaluation, imaging, and therapies.