Recent Studies in Alzheimer’s, MS, and Headache

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. Today, I would like to tell you about seven studies in neurology. 
I would like to start with the diagnosis of Alzheimer’s disease using biomarkers. A study in Sweden investigated how accurate plasma-based biomarkers are for the diagnosis of Alzheimer’s disease. They recruited 600 patients with cognitive impairment, and they measured plasma phosphorylated tau 217, amyloid-beta 42, and amyloid-beta 40. They validated the biomarkers with the clinical diagnosis of Alzheimer’s disease and with cerebrospinal fluid samples.
Overall, 23% of the patients had cognitive impairment, 44% had mild cognitive impairment, and 33% had dementia. These blood tests had a very high sensitivity and accuracy, although in people who simply had cognitive disturbances. 
Now, what is the consequence? What about people with incipient disease? Do you really want to know whether you will have Alzheimer’s disease 5 years from now? In an area where we do not have really effective therapy, this is an ethical dilemma. 
My next study deals with the antidiabetic drugs glucagon-like peptide 1 (GLP-1) receptor agonists and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists, for the treatment of diabetes. This study, published in the European Stroke Journal, investigated in a meta-analysis whether these new drugs also have an impact on vascular events. 
They analyzed 13 randomized studies with more than 65,000 patients with diabetes. Compared with placebo, the new antidiabetic drugs reduced major vascular events by 13%, all-cause mortality by 22%, the risk for stroke by 16%, and the risk for ischemic stroke by 25%.
It is highly relevant because the traditional antidiabetic drugs were able to treat diabetes, but they did not dramatically reduce the risk for vascular events. The real dilemma is the availability of these drugs, and the even more important limitation is the high costs. 
My next study deals with multiple sclerosis (MS). The question here was whether vaccination against COVID-19 increases the risk for a new manifestation of MS. This study, published in Neurology, was a national study from France with more than 1 million MS patients, of whom 82% were vaccinated. The study observed no increased risk for MS relapses. This important observation also is valid for other vaccinations. 
My next study is related to epilepsy and migraine prevention, and it’s about valproic acid. There is no doubt that valproic acid given during pregnancy increases the risk for major congenital defects, and in the long run, neurodevelopment disturbances. There was recently advice from the European Medicines Agency (EMA) that men should avoid valproic acid during spermatogenesis, which is 3 months before conception. 
This study from Denmark, published in JAMA Network Open, analyzed more than 1 million newborns between 1997 and 2017. In 1330 of these children, the fathers took valproic acid during spermatogenesis. 
The mean observation period was 10 years, and there was no increased risk for major congenital malformations or neurologic developmental disorders. These data are in contrast to the recommendations of the EMA and its Pharmacovigilance Risk Assessment Committee, and we have to see how the guidelines will be adapted. 
My next three studies deal with headache. The International Headache Society published practice recommendations for the acute treatment of migraine attacks in Cephalalgia. Guidelines are usually based on randomized, placebo-controlled trials, but these trials often cannot give advice for everyday clinical problems. For example, what do you do if one triptan doesn’t work, what do you do about recurrence, can we combine acute therapy, and so on. Therefore, an expert panel has set up 17 practical questions on the acute treatment of migraine attacks and gives practice recommendations for everyday clinical use. 
The next question is, is there a difference between atogepant and rimegepant, the calcitonin gene-related peptide (CGRP) receptor antagonists, for the treatment of acute migraine attacks? At present, we do not have a head-to-head comparison, but the study group in Italy did an indirect comparison of patients in the studies on the prophylaxis of episodic and chronic migraine. They found that atogepant was significantly more effective for the reduction of monthly migraine days. There was no difference in tolerability and safety. 
We have to wait until these drugs are on the market to see whether there is really a difference between atogepant and rimegepant. 
Finally, a very important population includes people with migraine and medication overuse or medication overuse headache. An observational, retrospective study in 291 patients in Germany, published in TheJournal of Headache and Pain, showed that treating these patients with erenumab, fremanezumab, or galcanezumab is highly effective. These patients do not require pausing acute medication or medication withdrawal.
This means that sequencing in these patients with medication overuse is advised. If they are not able to reduce their intake days, then the next step would be prevention with a monoclonal antibody, which includes eptinezumab. Only if this fails would we recommend pausing acute medication or withdrawal of therapy.
Dear colleagues, dear friends, these were seven interesting studies. I am Christoph Diener, from the Medical Faculty of the University of Duisburg-Essen. Thank you very much for listening and watching.