Frustrations and Victories in 5 New Neurology Studies

This transcript has been edited for clarity.

Dear colleagues, I'm Christoph Diener from the University of Duisburg-Essen in Germany. Today I'd like to make you familiar with five studies published in August 2022.

Monoclonal Antibodies for Early Parkinson's Disease

In the past 10 years, we've learned about the important role of alpha-synuclein in the pathophysiology of Parkinson's disease. It is likely that a change in the gut microbiome leads to the absorption of alpha-synuclein from the gut into the wall of the intestinal system, and from there, via retrograde transport through the vagus nerve into the brain. Neuropathological studies have shown an accumulation of alpha-synuclein aggregates in important areas for Parkinson's disease.

This led to the idea of developing monoclonal antibodies against the alpha-synuclein aggregates in the brain. There was high hope that this treatment would improve the progression of Parkinson's disease, particularly in the early phases of the disease.

Two studies were recently published on such monoclonal antibodies in The New England Journal of Medicine. The first study was with the compound prasinezumab, which was used in early Parkinson's disease in two doses, 1500 mg or 4500 mg, given every 4 weeks, and compared with placebo for 52 weeks. The second study was with cinpanemab and used a similar design of comparing three different doses — 250 mg, 1250 mg, or 3500 mg — against placebo for 52 weeks.

Both studies were negative for the primary endpoint and for all secondary endpoints. This was also true in the second study of cinpanemab for single-photon-emission computed tomography imaging.

This is extremely disappointing, because we were so hopeful that finally we would have a treatment to delay the progression of Parkinson's disease, which is similar to the frustrations we've experienced in trying to treat Alzheimer's disease.

Lack of Effect for Stenting in Symptomatic Intracranial Stenosis

People who have symptomatic intracranial stenosis have a higher risk for recurrent stroke after an initial stroke or transient ischemic attack (TIA).

Initially we had two studies, which are almost 10 years old, that showed that stenting is not superior to optimal medical therapy in these patients. A criticism lodged against these studies was that perhaps the selection of patients was not optimal and that the interventional neuroradiologists were not experienced enough.

Now we have a third study undertaken in China, which included 380 patients with TIA or symptomatic high-degree intracranial stenosis or ischemic stroke. Patients were randomized either to balloon dilatation and stenting plus medical therapy or medical therapy alone. The primary endpoint was stroke or death within 30 days, or stroke, ipsilateral stroke, and death from 30 days to 1 year.

The study was unable to show a significant benefit of stenting compared with optimal medical therapy, and this was also true for mortality.

This means, ladies and gentlemen, that we now have three negative studies on stenting in symptomatic intracranial stenosis.

Diabetic Peripheral Neuropathic Pain: Different Therapies, Similar Results

Painful diabetic polyneuropathy is a frequently encountered problem in everyday clinical practice.

In a great study performed in the United Kingdom, patients were randomized initially to a monotherapy with pregabalin, amitriptyline, or duloxetine. After 16 weeks, they were then also randomized to receive a second therapy — for example, a combination of pregabalin plus amitriptyline, duloxetine plus pregabalin, or amitriptyline plus pregabalin.

The overall duration of the study was 1 year, which is amazing.

The results are very clear: All therapies are equally effective. And in patients in whom the initial monotherapy is not really effective, it makes sense to add a second drug because then the benefit is higher.

This is a very important study for everyday clinical practice.

Vitamin K Antagonists Show Promise in Rheumatic Heart Disease

My last study is a little bit out of the scope of neurology, but it's very important for people who work in low- and middle-income countries where rheumatic heart disease is still prevalent.

We all know that novel oral anticoagulants (NOACs) are superior to vitamin K antagonists for stroke prevention in patients with atrial fibrillation. But what about people who have rheumatic heart disease and a high degree of mitral stenosis?

This was investigated in a study with approximately 4500 patients who were randomized to either rivaroxaban or a vitamin K antagonist. The primary endpoint was a combination of stroke, systemic embolism, myocardial infarction, or death.

To the surprise of everyone, vitamin K antagonists were superior to rivaroxaban, which was true for the vascular endpoints and also for mortality. There was no difference in the risk for major bleeding.

This means we have two groups of patients in whom NOACs should not be used: those with mechanical heart valves and now those with atrial fibrillation due to rheumatic heart disease.

Dear colleagues, these were five very important studies. Unfortunately, three of them were also frustrating because they were negative. But we shouldn't give up and must continue our efforts to develop treatment, for example, for Parkinson's disease.

I'm Christoph Diener from the medical faculty of the University of Duisburg-Essen. Thank you very much for listening and watching.

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