Top Neurology Studies to Know

Hans-Christoph Diener, MD, PhD


December 15, 2022

This transcript has been edited for clarity.

Dear colleagues, I am Christoph Diener from the University of Duisburg-Essen in Germany. I would like to report what my literature search in September 2022 showed.

The first and most important message was not published in a journal, but was a press release by Biogen and Eisai. They reported the results of a study in patients with mild cognitive impairment, incipient Alzheimer's disease and beta-amyloid shown by amyloid PET. This study investigated a monoclonal antibody against beta-amyloid called lecanemab and compared it with placebo.

The drug was given at 10 mg/kg every 2 weeks. The study overall had 1,795 patients, and the primary endpoint was the Clinical Dementia Rating sum of boxes. The study was positive. For the primary outcome, there was a difference between active drug and placebo of 0.45 point.

This translates to a 27% risk reduction for preventing the progression of cognitive impairment. The study was also positive for amyloid PET, showing that less amyloid was seen in the active treatment group. The study was also positive for the secondary endpoints.

This will be a major breakthrough if the results are also shown in the final publication. The problem is related to adverse events. The study showed the typical adverse events of these antibodies, which include brain edema in some patients shown on MRI, microhemorrhages, and bleeding into the brain. We have to see, because the study was only 18 months, how the side effects develop if a patient is treated for several years.

The second study was published in Nature Medicine. This study looked at the neurologic consequences of COVID-19. The study had 154,000 people who had COVID-19 compared with 5.6 million controls and a follow-up of 12 months.

The study showed an odds ratio of 1.42, which is a 42% increase in the risk for neurologic diseases after COVID-19. This includes stroke, cerebral hemorrhage, cognitive impairment, memory dysfunction, polyneuropathy, migraine, epilepsy, disease of the musculoskeletal system, encephalitis, and encephalopathy.

The study was only done in Caucasian people, but I think it can also be translated to other people. This shows that neurologists have to know the possible long-term neurologic consequences of COVID-19.

The next spectacular study was published in Brain. We all know that misfolded alpha-synuclein is an important factor in the progression of Parkinson's disease. Until now, it was only possible to show alpha-synuclein in the cerebrospinal fluid.

A group in Kiel, Germany, has reported that they can show increased misfolded alpha-synuclein in plasma. This will be very important to identify patients in the future who could go into randomized treatment trials.

My next study was on asymptomatic carotid stenosis. A research group in Heidelberg, Germany, published the 5 year results of the SPACE-2 study. This study included 513 patients with asymptomatic carotid stenosis who were randomized to receive carotid endarterectomy or stenting, plus best medical treatment vs best medical treatment alone.

The primary endpoint was stroke or death within 30 days or ipsilateral ischemic stroke in 5 years. There was no difference between the treatment groups. My understanding is that this means that patients with asymptomatic carotid stenosis should receive the best medical treatment, and only those patients for whom it's not possible to control risk factors and concomitant diseases should undergo interventional treatment.

Let me now discuss secondary stroke prevention with anticoagulation. There is a very rare inherited disease, where people do not have the coagulation factor XIa. These people have a decreased risk for stroke and myocardial infarction and only a very small increased risk for bleeding.

Therefore, drugs that inhibit factor XIa were developed, like asundexian, which was investigated in people who had a noncardioembolic ischemic stroke. The study was published in The Lancet. The study included 1800 people and treated them with either 10, 20, or 50 mg of active drug or placebo. Patients were followed for 26 months.

The primary endpoint was clinically silent infarcts on MRI and clinically apparent ischemic strokes. Unfortunately, there was no difference between active drug and placebo. This was mostly due to the fact that the lacuna infarcts were not prevented, which I think is logical because anticoagulation does not work in preventing lacuna infarction. Bayer, however, announced they would do a further phase 3 study in a selected group of patients, in whom they hope to have a better result.

My final study looked at the initiation of non–vitamin K antagonist oral anticoagulants (NOACs) in people who had an ischemic stroke in atrial fibrillation. The TIMING study, which was published in Circulation, recruited 888 patients. They were either anticoagulation with a NOAC within 4 days or between 5 and 10 days.

The primary endpoint was recurrent ischemic stroke, intracranial bleeding, or mortality within 90 days. Statistically, there was no difference, but there was a strong trend toward benefit in people who were treated early. The good news is that no patient on a NOAC had intracranial bleeding within 10 days.

Ladies and gentlemen, these are spectacular new studies that came out in September 2022. I'm Christoph Diener from the University of Duisburg-Essen. Thank you very much for listening and watching.

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