Recent Updates in Migraine, Parkinson’s, and Stroke

This transcript has been edited for clarity. 
Dear colleagues, I’m Christoph Diener, from the Faculty of Medicine at the University of Duisburg-Essen in Germany. I would like to present to you five interesting studies in neurology that were published in September 2024. 
Let me start with migraine. We have a large amount of information now about the pathophysiology of migraine and, in particular, migraine attacks. Here, serotonin plays an important role, and we have triptans that target serotonin. 
For migraine prevention, we have two targets. One is calcitonin gene-related peptide (CGRP), and we have monoclonal antibodies targeting CGRP. We now have a new player, which is pituitary adenyl cyclase-activating polypeptide (PACAP). Intravenous administration of PACAP can induce migraine attacks in migraine patients. There is a new concept for the prevention of migraine, which is a monoclonal antibody targeting PACAP. 
In The New England Journal of Medicine, a research group from Denmark published a phase 2 trial in 237 patients in whom at least two previous prophylactic therapies were ineffective. They received one dose of the monoclonal antibody compared with placebo, and the antibody led to a significant reduction in migraine days over the next 4 weeks. However, the 50% responder rate had a strong trend but was not statistically significant. The treatment was well tolerated.
This means we need a much larger phase 3 study across 3 or 4 months to see whether this therapy really works. Potential patients for this new approach would be those in whom monoclonal antibodies targeting CGRP or the CGRP receptor are not effective. 
My second paper also deals with migraine — in this case, acute migraine attacks — published in the British Medical Journal. Migraine attacks are treated in most patients with analgesics or nonsteroidal anti-inflammatory drugs (NSAIDs), and we have seven different triptans that are available. Recently, we have available CGRP receptor antagonists, such as rimegepant, ubrogepant, or zavegepant, and the 5-HT1F agonist lasmiditan. So far, however, we have no head-to-head comparisons of the new migraine drugs with the triptans or NSAIDs. 
Therefore, a network meta-analysis analyzed 137 randomized controlled trials in almost 90,000 migraine patients. For the primary endpoint, which was being pain-free after 2 hours, eletriptan, rizatriptan, sumatriptan, and zolmitriptan were the most effective treatments. Gepants and lasmiditan were significantly less effective, and their efficacy is comparable to that of NSAIDs. The target group for lasmiditan includes patients who cannot use triptans owing to severe vascular diseases.
The bottom line is that triptans are prescribed far too rarely, and this is true for most European countries. In particular, the most effective triptan, which is eletriptan, is practically not prescribed at all. In terms of cost, triptans are now very affordable because they are off-patent.
My third paper deals with the prodromal phase of Parkinson’s disease and was published in Nature Communications. It is well known that REM sleep behavior disorders are a prodromal stage of Parkinson’s disease. The authors described two patients who were treated with acetyl-DL-leucine, and this improved REM sleep disorder in both patients.
They also checked DAT scan and FDG-PET, and found improvement in these two very important diagnostic features for incipient Parkinson’s disease. This could be a potential new modulating treatment that is well tolerated for the prodromal stage of Parkinson’s disease, but this also means we clearly need a large-scale randomized trial. 
Now, my next study is on stroke and it’s published in JAMA. We all know that elevated body temperature, or fever, is a negative predictor of outcome both in ischemic stroke and cerebral hemorrhage. This was an open-label, randomized study of almost 700 patients with severe stroke in the United States.
They compared the prevention of fever with surface temperature cooling vs standard therapy. They were able to decrease body temperature, but this had no impact on functional outcome. This is a whole series of randomized studies. They all showed it is possible to lower body temperature and also, for example, to treat pneumonia, but this has no impact on functional outcome.
My last study, also published in JAMA, deals with a very controversial issue : treatment of symptomatic intracranial stenosis, which is much more frequent in patients in Asia. This study performed in China compared balloon angioplasty in combination with dual-antiplatelet therapy vs drug treatment alone in 512 patients with symptomatic intracranial stenosis.
They clearly showed a benefit for the primary endpoint, which was stroke or death within the first 30 days or ipsilateral stroke between day 30 and month 12. The hazard ratio was 0.32. 
What is the problem? The problem is we already have three randomized trials, in this case, with stenting (SAMMPRIS, VISSIT, CASSISS), and these trials were either neutral or couldn’t show a benefit of stenting. The stenting group had a clearly higher complication rate. 
Is it only the difference in the method, which is balloon angioplasty compared with stenting, or is there another explanation? This means we need a second randomized trial with balloon angioplasty, preferentially perhaps in Europe and the United States.
Dear colleagues, we had five exciting studies in neurology in September 2024. I’m Christoph Diener, from the Faculty of Medicine at the University of Duisburg-Essen in Germany. Thank you very much for listening and watching.