5 New Neurology Studies to Know

This transcript has been edited for clarity.

Dear colleagues, I am Christoph Diener, a neurologist from the Faculty of Medicine at the University of Duisburg-Essen in Germany. In April, I identified five interesting studies in neurology. Let me start with Alzheimer's disease.

There is a class of drugs that has an impact on the production of amyloid beta. One of these drugs is verubecestat, which is an oral, beta-site amyloid precursor protein-cleaving enzyme 1 inhibitor. [Verubecestat inhibits the production of beta amyloid and can be given orally.]

Verubecestat was tested in a study published in the New England Journal of Medicine in 1455 patients with memory impairment and elevated brain amyloid on PET.^[1] The purpose was to look at incipient Alzheimer's disease because this drug failed in patients who already had moderate to severe Alzheimer's disease.

The investigators used two doses of 12 or 40 mg daily for 104 weeks. The trial was stopped for futility when 40% of the patients reached the follow-up of 104 weeks. There was no difference in score on the Clinical Dementia Rating Scale-Sum of Boxes and there was even a worse outcome in the higher-dose group.

The transition from cognitive impairment to dementia was about 20%-25% per year, and this was, again, not different. Ladies and gentlemen, we now have dozens of negative trials in Alzheimer's disease, and in particular, in studies that target beta amyloid.

It is likely that beta amyloid is not the cause of disease but simply a biomarker. We have more than 100 randomized trials ongoing and we are still hopeful that perhaps, one day, we will have a treatment for Alzheimer's disease.

The second dementia study had a different approach. One of the hypotheses is that inflammation plays an important role in degenerative brain diseases. This study from the Prevent-AD group investigated naproxen 220 mg twice daily to slow the progression of presymptomatic Alzheimer's disease.^[2]

The investigators identified 195 patients from families with Alzheimer's disease who had cognitive imaging and biomarkers. Naproxen, unfortunately, had no impact on progression. Naproxen treatment led to significantly more adverse events in terms of vascular events, hypertension, and constipation. NSAIDs, obviously, are not a good choice to prevent Alzheimer's disease.

The third study is focused on migraine prevention. We have a new class of drugs for the prevention of migraine, which are the monoclonal antibodies against CGRP or the CGRP receptor. Erenumab is one of these drugs. One of the trials investigated the drug in people with chronic migraine, which is defined as more than 15 days of headache per month with at least 8 days fulfilling criteria for a migraine attack.

This trial recruited 667 adults with chronic migraine and compared 70 and 140 mg of erenumab with placebo for 3 months.^[3] The endpoint was monthly migraine days in the last month of treatment.

Of these patients, 41% (274 patients) fulfilled the criteria for medication overuse headache, which means they took a specific migraine drug on more than 10 days per month, and nonspecific migraine drugs or simple analgesics for more than 15 days per month.

Although erenumab was as effective in people with and without medication overuse, the majority of patients reverted from chronic migraine to episodic migraine. The percentage of patients who achieved this was significantly higher for erenumab compared with placebo. This, ladies and gentlemen, means that we should treat people with chronic migraine who overuse medication with topiramate, botulinum toxin, or the new monoclonal antibody erenumab.

The last two studies have to do with thrombectomy. There is an interesting meta-analysis in JAMA Neurology, which was designed to assess the time interval between stroke and the beginning of recanalization, and the effect of this time interval on recanalization rate and outcomes.^[4]

This meta-analysis was based on seven randomized studies, which compared thrombectomy with thrombolysis in 728 patients who had a mean age of 65 years. There is a near linear relationship between the time interval between stroke and time to recanalization, in terms both of recanalization rate and outcome. This means that there is a 20% relative reduction in benefit per additional hour.

Despite the fact that we currently have a time window for treatment of up to 24 hours, these results clearly demonstrate that we don't have time to wait to do mechanical thrombectomy. This must be done as quickly as possible.

The last paper came out as a joint guideline between the European Stroke Organisation (ESO) and the European Society for Minimally Invasive Neurological Therapy (ESMINT).^[5] These are the guidelines for mechanical thrombectomy in acute ischemic stroke in 2019.

Within a time window of 6 hours, thrombolysis should be combined with thrombectomy. Beyond 6 hours and up to 24 hours, thrombectomy is recommended with imaging selection criteria, as in DAWN or DEFUSE-3.

Mechanical thrombectomy plus thrombolysis is preferred over mechanical thrombectomy alone. Stent retrievals are preferred over aspiration. There is obviously no upper age limit and there is no upper limit for the severity of strokes; however, there is a lower limit of stroke severity, based on a National Institutes of Health Stroke Scale (NIHSS) score between 0 and 5.

The systolic blood pressure should be kept below 180 mm Hg. At the moment, there is no clear recommendation about whether thrombectomy should be done under general anesthesia or sedation.

Ladies and gentlemen, we have discussed five interesting studies published in April 2019 that were related to Alzheimer's disease, migraine, and stroke.

I am Christoph Diener from the University of Duisburg-Essen in Germany. Thank you very much for listening and watching.

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