As far as I'm aware, tPA is currently the only approved therapy for ischemic stroke in USA and Europe, which was introduced almost 20 (!) years ago. Even so, many patients do not fit the inclusion criteria for this treatment. Where is the field for acute stroke treatment evolving too? Which new treatments are on the rise or tested in the clinic?
Thanks Mahtab. Indeed, that is I think one reason why not all patients can be included to receive tPA, besides other factors. I wonder whether this therapeutic window is determined by the disease itself or the treatment.
Current cutting-edge research in stroke treatment is aimed to 3 targets:
1. Pre-hospital Stroke Treatment, including protocols for the administration of novel drugs, CT scans mounted in ambulances among others.
2. Interventional Stroke Treatment (endovascular techniques) including intra-arterial thrombolysis, mechanical thrombectomy and flow augmentation devices and,
3. Pharmacological and non-pharmacological interventions to aid recovery of remaining neural tissue after stroke (cryotherapy, transcranial laser therapy, transcranial magnetic stimulation, transcranial direct current stimulation, sphenopalatine ganglion stimulation, among others)
Very interesting Juan. Have these novel drugs specifically been developed and tested for stroke, or is there also repurposing of recently approved drugs for other ischemic diseases, such as myocardial ischemia (neprilysin inhibitors), and possibly even hypertension (PDE inhibitors and sGC stimulators). At least judging from preclinical studies, these drugs might also be promising for stroke, and interestingly all center on a similar pathway to modulate cGMP levels.
The only agent I am sure has been proved by this approach is magnesium sulfate (Stroke. 2004 May;35(5):e106-8. Epub 2004 Mar 11.) Even though this was a negative trial it proved the point of the feasibility of prehospital administration of potential neuroprotective agents
Most of it will probably involve service design to deliver hyperacute treatment earlier and earlier.
Ultrasound shows promise:
Alexandrov et Al. 2004 NEJM 351(21)
I agree with Juan's statement. Secondary prevention (and primary) are still the most effective ways to avoid a (recurrent) stroke.
Thank you Stefanos. I remember this study well, I spent my PhD at Karolinska Institutet and know some of the authors.
Thank you also Mahtab for that article, and everyone for commenting on this question!
Hi all, Jeroen,
apart from specific new treatments, what about considering this point as well.
Your discussion starts off with rt-PA inclusion/exclusion criteria: actually, some of them (above all exclusion) can be consider as "suggestions" rather than absolute contraindications and, with growing experience in intravenous rtPA, the proportion of treatable patients is increasing. For example:
age (consider over 80), glucose levels (should be corrected before i.v. thrombolysis), INR (limit changed from 1.4 to 1.7), timing (should therapeutic windows be tailored to the specific patient if a DWI/PWI mismatch is detected?...looking forward to ECASS IV trial for patients with an unknown stroke onset for example), etc...
This opinion is not intended at all to diminish the possible role of new treatments, rather to make clear that in the future, the majority of acute patients would probably be found to benefit from rt-PA, even alone, and that the most promising new treatments seems to be the ones which demonstrated to protect brain from rt-PA side effect (mainly edema and haemorrage) followed by endovascular procedures.
don't know if you agree...it was just to provoke discussion
Controversial indeed... I agree to a degree - increasing thrombolysis eligibility is the low hanging fruit in hyperacute stroke treatments.
but when 50% of patients present >12 hours after onset, thrombolysis isn't going to be an option for the majority of patients. There has to be continued efforts in:
- secondary injury
- neuro protection
- identification of high-risk populations for earlier alerting systems (AF screening programmes)
The search for advances in stroke management could be newer thrombolytics with short administration protocols, and further refinement of inclusion and exclusion criteria as suggested by Janes. The analysis of ICH in thrombolysed patients may throw additional light on the problem
There are several reports on EC-IC bypass application in patients with cerebral arteries occlusive diseases, which stops neurologic deterioration and even improves overall condition (in few cases) in acute brain ischemia
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