COMMENTARY

2022's Most Important Neurology Studies

Hans-Christoph Diener, MD, PhD

Disclosures

December 30, 2022

This transcript has been edited for clarity.

Dear colleagues, I am Christoph Diener from the University of Duisburg-Essen in Germany. The goal of my video this month is to summarize the most important clinical studies in neurology published in 2022.

A Caveat With Lecanemab

I would like to start by discussing a publication in The New England Journal of Medicine on Alzheimer's disease.

The study investigated lecanemab, a monoclonal antibody, against beta-amyloid in people with mild cognitive impairment or incipient Alzheimer's disease. Results showed that a monoclonal antibody against beta-amyloid was effective for both primary and secondary endpoints of cognition and function.

The data on amyloid on PET were most impressive. The load of amyloid in the brain was unchanged in placebo-treated patients. However, in the monoclonal antibody treatment group, the amyloid concentration in the brain decreased by 60%-70% within 18 months.

Now, we don't know how this would translate into clinical efficacy across many years. But the most important message here is that for the first time in history, we have a drug that slows the progression of early Alzheimer's disease.

There is also a caveat, which is the adverse event profile. These monoclonal antibodies can lead to brain edema, which requires MRI every 3 months. They can also lead to microbleeds, which are usually asymptomatic. No one knows what will happen if these drugs are given long-term to patients who need anticoagulation because they have atrial fibrillation.

COVID-19 and Somatic Symptoms

Let's move to the post–COVID-19 setting.

We now have many studies that looked at people who had COVID-19 and controls, and who were monitored for somatic symptoms. Most of the somatic symptoms are in the neurologic domain. They include headache, fatigue, dizziness, back pain, muscle pain, and nausea.

One of the studies in the Netherlands was the first to report the nature and prevalence of post–COVID-19 condition while correcting for individual symptoms present before COVID-19 and the symptom dynamics in the population without SARS-CoV-2 infection during the pandemic. About 20% of people who had COVID-19 had somatic symptoms 90-150 days after the infection, compared with only 9% of the controls.

Unfortunately, we don't know the pathophysiology of this post–COVID-19 syndrome and we have no real effective therapy.

A Need for New Sleep Medications

Let's now move to sleep disorders.

In the past, we had benzodiazepines, which were replaced by the Z substances. The Z substances were not supposed to lead to addiction, but in some patients they have. Therefore, there is a pressing need for new sleep drugs that do not carry the risk for addiction.

The new class of drugs is the orexin antagonists. Daridorexant is a dual orexin antagonist that showed efficacy in two large, phase 3 trials. The good news here is that this drug not only improved the latency until patients fell asleep, but also had no hangover effect the next day.

Epstein-Barr Virus and Multiple Sclerosis

The most debated aspect in multiple sclerosis research came from a large study using a Veterans Administration database. It showed that an Epstein-Barr virus infection clearly increased a person's risk of developing multiple sclerosis. By contrast, this was not the case for the cytomegalovirus virus.

Unfortunately, this is a very prevalent infection, as 70%-80% of adults have Epstein-Barr virus. To date, we don't have a vaccine and whether a vaccine would really decrease the likelihood of multiple sclerosis remains unknown.

Parkinson's Disease Treatment Hits a Roadblock

Let's move to Parkinson's disease.

We know that alpha-synuclein aggregates in the brain are obviously a driving pathophysiological force in this disease. A group in Kiel, Germany, developed a blood test to identify alpha-synuclein in serum. That's the good news.

The bad news is that we had two randomized, placebo-controlled trials in incipient Parkinson's disease with monoclonal antibodies against alpha-synuclein that were both negative. This means at the moment, we do not have a treatment with disease-modifying action in Parkinson's disease.

In Stroke, Mechanical Thrombectomy Found to Be Superior

For stroke, there are two important updates.

Several randomized studies showed that adding thrombolysis to mechanical thrombectomy in the anterior circulation improves functional outcome, reduces mortality, and increases the rate of reperfusion.

We now have two randomized trials that clearly show mechanical thrombectomy is superior to pure medical treatment in people with thrombosis or occlusion of the basilar artery.

A Step Forward in Migraine Preventive Therapy

Finally, headache.

The good news here is that the monoclonal antibodies against CGRP or the CGRP receptor are effective in treating chronic migraines. They work in people who have had prior treatments that failed, and also in people with medication overuse headache. They also have almost no side effects.

Beyond the high cost, this is really a step forward in a specific treatment for migraine in terms of preventive therapy.

Dear colleagues, 2022 was an exciting year. These are only a few of the highlights. I thank you very much for listening and watching.

See you in 2023!

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