Four Neurology Studies to Know

Hans-Christoph Diener, MD, PhD


January 25, 2019

Dear colleagues, I am Christoph Diener, a neurologist from the University Duisburg-Essen in Essen, Germany. Today I would like to report four randomized studies that were published in August [2018] and then [discuss three practical recommendations].

Let me start with melanoma and brain metastases. This is a traumatic condition and the usual survival time used to be 2-4 months, but now we have very potent new drugs. This study was published in the New England Journal of Medicine.[1] The open-label trial evaluated combination treatment with nivolumab and ipilimumab, which are checkpoint inhibitors, and an anti-programmed death agent in 94 patients who had asymptomatic brain metastases of melanoma.

The mean follow-up was 14 months. Benefit in intracranial growth of metastases was seen in 57% of patients, 64% of patients did not show any progression of the disease, and the 6-month survival was 80%. I think this is very dramatic progress in the treatment of this disease.

The next study was published in JAMA Neurology.[2] I think you all know that there is now a hypothesis that the gut and bacteria in the bowel have something to do with Parkinson disease. Using insurance claims databases in the United States, the investigators identified more than 144,000 individuals with inflammatory bowel disease and matched them with 720,000 controls without bowel disease. When they looked at the incidence of Parkinson disease over 15 years, the incidence was increased by 28% in patients with inflammatory bowel disease.

If these patients were treated with anti–tumor necrosis factor, the incidence of Parkinson disease was 70% lower compared with patients who were untreated. This is indirect evidence that the bowel system has something to do with the pathophysiology of Parkinson disease.

Now, let us move to primary prevention of vascular diseases with aspirin. The ARRIVE study was presented at the European [Society of Cardiology] congress in Munich.[3] This trial recruited 12,546 patients with vascular risk factors, and they were randomized to aspirin or placebo. After 60 months, there was no benefit for the prevention of the primary endpoints, which were vascular events, including myocardial infarction, stroke, and vascular death. However, there was a twofold higher risk of GI bleeding.

The second trial presented was the ASCEND trial.[4] This trial included 15,480 participants with diabetes and no vascular events who were also randomized to aspirin or placebo and followed up for about 7.4 years. There was a 19% risk reduction for vascular events for aspirin, but there was a 30% increase in the risk of major bleeds. Therefore, the benefit in preventing vascular events is counterbalanced by major bleeding.

There was an interesting study in Annals of Neurology, where the investigators from the SITS registry investigated whether people who received thrombolysis who were on dual antiplatelet therapy have a higher risk of bleeding complications than people who are not on antiplatelet therapy.[5] The investigators included approximately 1000 patients with thrombolysis and dual antiplatelet therapy, and approximately 1000 patients who received only thrombolysis. They assessed the rates of symptomatic intracranial hemorrhage, mortality, and functional outcome, and there was no difference. The good news is that people who are on clopidogrel plus aspirin can undergo thrombolysis.

There is a statement from the European [Medicines] Agency and European Headache Federation that valproic acid should not be used for migraine prevention in women of childbearing age due to the toxicity of this drug.[6]

There is a published recommendation on PFO closure in patients with cryptogenic stroke, promoting PFO closure under these conditions.[7]

Finally, erenumab, which is an antibody against the CGRP receptor, was approved in Europe.[8] This is a new therapy that has almost no side effects; it is very well tolerated. It is as effective, in indirect comparison, with beta-blockers and topiramate, but the treatment costs are relatively high. This will probably be used primarily in patients with chronic migraine or frequent migraine who do not respond to available therapies or cannot tolerate them.

Ladies and gentlemen, we discussed four randomized trials, one registry, and three practical recommendations. I am Christoph Diener from the medical faculty of the University of Duisburg-Essen in Essen, Germany. Thank you very much for listening and watching.


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