Recent Studies in Parkinson's, Headache, Stroke, and Obesity

Hans-Christoph Diener, MD, PhD


September 27, 2023

This transcript has been edited for clarity.

Dear colleagues, I'm Christoph Diener from the University Duisburg-Essen in Germany. Today, I would like to show you the results of a number of studies that were recently published not only in neurology but also internal medicine.

Parkinson's Disease Smokers Paradox

Let me start with Parkinson's disease. Epidemiologic studies clearly showed that people who smoke have a lower risk for Parkinson's disease than do nonsmokers. A study group in Germany, therefore, did a randomized, prospective study, which was published in The New England Journal of Medicine Evidence where they compared transdermal nicotine vs placebo in 100 patients with incipient Parkinson's disease, who at the time of randomization did not need dopaminergic medication.

Over 1 year, there was no difference in the course of the disease. About one third of patients in both groups needed dopaminergic therapy. This means that nicotine is not effective in preventing the progression of Parkinson's disease, and this also shows that we cannot make conclusions from epidemiologic studies on how we treat patients. We always have to wait for the results of properly conducted randomized placebo-controlled studies.

Headache Genes

My next study published in Annals of Neurology deals with the genetics of cluster headache. We have good evidence that in migraine, genetics plays a very important role, and there are more than 70 gene loci that have been identified in migraine. This study is the largest genome-wide analysis in over 4700 patients with cluster headache and 21,000 controls. The heritability of cluster headache is about 14%.

The investigators were able to identify 20 gene loci, and they found an association genetically with cigarette smoking, risk behavior, attention-deficit/hyperactivity disorder, depression, and musculoskeletal pain. Three of the gene loci were shown in migraine. I think the most important results of these genetic studies are that risk-taking behavior and smoking are associated with cluster headache.

Thrombectomy +/- Thrombolysis

The next study, published in The Lancet, deals with the question of whether people who have large artery occlusion and ischemic stroke undergoing mechanical thrombectomy should first receive systemic thrombolysis or direct thrombectomy. The investigators analyzed six studies with 2313 patients, and they found no difference in outcome.

This is not what reality shows. I think whenever a patient comes with, for example, a left vertebral artery occlusion into a stroke center and the angio suite is available, the patient will immediately go to thrombectomy. If there is a waiting time or the patient has to be transported to a large stroke center, then they should receive systemic thrombolysis.

The End of Extraintracranial Bypass Surgery

My next topic is extraintracranial bypass surgery in people with occlusion of the internal carotid artery or occlusion or high-degree stenosis of intracranial arteries. This study was performed in China and published in JAMA. They randomly assigned about 160 patients to extraintracranial bypass surgery and the same number to medical treatment. The inclusion criteria was a perfusion deficit on the side of the vascular occlusion.

This study was negative for the primary outcome and all secondary outcomes. This replicates what has already been shown in two other studies. To my understanding, this is the end of this technically demanding surgery. I don't think we should perform extraintracranial bypass surgery anymore.

Obesity Drugs for Vascular Health

Finally, let me move to internal medicine. I think you all know that diabetes and obesity are major health problems. Until a few years ago, we didn't have effective therapy both for diabetes and obesity. We were not able to decrease the risk for vascular endpoints in these diseases. This has dramatically changed.

The new class of glucagon-like peptide 1 (GLP-1) analogs, were not only highly effective in diabetes but they also showed as a kind of side effect a dramatic decrease in body weight in people who were obese, both with and without diabetes. A new development here is now that one of these drugs, semaglutide, is not only available as a regular subcutaneous injection but also in an oral form with 50 mg. This drug, taken over a year in people with obesity, reduces body weight by about 15%.

Novo Nordisk made a very important press release because they had a 5-year study, the SELECT study, with 17,600 obese patients who were treated with 2.4-mg semaglutide subcutaneously or placebo. They showed a 20% reduction in major vascular events like stroke, myocardial infarction, and vascular death. This shows that the decrease in body weight is not only cosmetic but that it also has a major impact on healthcare systems in reducing vascular diseases.

There is still progress. We have now new drugs, which combine two modes of action: GLP-1 agonism, and at the same time, they work on the glucose-dependent insulinotropic polypeptide. One of these new drugs is tirzepatide, which has shown also a decrease in body weight in obesity by about 15% in 1 year. Beyond this, the drug also resulted in decreased blood pressure, lower cholesterol, and a number of improved metabolic parameters. These are good news.

The not-so-good news is that these drugs are not approved yet for obesity treatment in all countries. They are very expensive. They have side effects. Obviously, you need to treat lifelong because when you stop the treatment the body weight increases again.

Dear colleagues, I'm Christoph Diener from the University Duisburg-Essen in Germany. Thank you very much for listening and watching.

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