A Breakthrough in Parkinson Disease and New Data on Treating Stroke

This transcript has been edited for clarity.

Dear colleagues, I'm Christoph Diener, a neurologist from the University of Duisburg-Essen in Germany, presenting six very interesting publications from February 2020 in the fields of stroke, multiple sclerosis (MS), and Parkinson disease.

New Data on NOACs, Antiplatelet Therapy, and Endovascular Intervention

Dual-antiplatelet therapy is now used in many patients, in particular after an acute coronary syndrome. This has led to the question of whether these patients can be safety treated with thrombolysis if they have an ischemic stroke.

In a meta-analysis published in Neurology, researchers presented data from nine studies investigating dual-antiplatelet therapy in 66,675 total patients who had acute ischemic stroke treatment with intravenous (IV) thrombolysis. Dual-antiplatelet therapy was associated with an increased chance of symptomatic intracranial hemorrhage (odds ratio [OR], 2.26), but had no significant impact on mortality and functional outcome after 3 months. This is very good news, because it probably means that most patients on dual-antiplatelet therapy can safely receive IV thrombolysis if they have an ischemic stroke.

An observational study published this February in Stroke investigated the risk for symptomatic intracranial hemorrhage in patients who have had a large stroke, require endovascular therapy, and are anticoagulated because they have atrial fibrillation. Investigators included 1932 patients, of whom 222 were on vitamin K antagonists, 98 were on novel oral anticoagulants (NOACs), and the remaining 1612 were not anticoagulated.

Compared with NOACs, vitamin K antagonists significantly increased the risk for symptomatic intracranial hemorrhage and mortality (OR, 2.5 and 1.6, respectively) after mechanical thrombectomy. The authors replicated this result with a meta-analysis of 15 studies including 855 patients on vitamin K antagonists and 318 patients on NOACs. This is another argument to use NOACs, and not vitamin K antagonists, in people with a high risk for ischemic stroke or a recurrent stroke who have atrial fibrillation.

Results from the open-label, randomized BEST trial were published in Lancet Neurology. This study compared endovascular treatment within an 8-hour window with best medical care alone in patients with distal occlusions of the vertebral artery and a majority with basilar artery occlusion. The study was prematurely terminated after 133 patients were randomized, because it didn't show a difference in functional outcome. This was not surprising, as the study was clearly underpowered and probably lost its clinical equipoise. Nonetheless, I think it is completely fine to perform thrombectomy in patients with basilar artery thrombosis, because they have nothing to lose given that the prognosis is otherwise so poor.

The observational SAMURAI study investigated the efficacy and safety of early versus later initiation of anticoagulation in 499 patients who had an ischemic stroke. NOACs were initiated within 3 days or less or within 4 days or more in the early and late groups, respectively. Unsurprisingly, the authors couldn't find differences between the groups in recurrent stroke, bleeding complications, deaths, and functional outcome after 3 months. Remember that all of these registries are biased, given that patients who are severely disabled and have had large-volume strokes are usually later anticoagulated.

A Failed MS Study and a Breakthrough in Parkinson Disease

The next study I want to discuss dealt with secondary progressive MS. From a pathophysiologic perspective, demyelination is not a major issue in these patients so much as axonal loss is. Investigators identified three approved drugs that were effective in preclinical models at acting on different axonal pathobiologies: the diuretic amiloride; fluoxetine, an antidepressant also studied in ischemic stroke; and riluzole, which is approved for amyotrophic lateral sclerosis. They randomized 445 patients to these three treatments or placebo, and followed them for 96 weeks to assess the primary outcome of volumetric MRI percentage brain volume change. Unfortunately, there was no neuroprotective benefit to any of the therapies. This means we are still in desperate need of neuroprotective therapy in secondary progressive MS.

The absolute highlight of the February neurology literature was a paper published in Nature. This study investigated whether it is possible to differentiate strands of alpha-synuclein in Parkinson disease and multiple system atrophy (MSA) using a method called "protein misfolding cyclic amplification." Researchers tested cerebrospinal fluid samples from 94 patients with Parkinson disease, 75 with MSA, and 56 control patients with other neurologic diseases. In fact, they were truly able to discriminate Parkinson disease and MSA with an overall sensitivity of 95.4%.

This is a major breakthrough. Treatment trials have to start early to be effective, and this gives us the possibility of using this in the future to discriminate Parkinson disease from incipient MSA. This is definitely a major step forward in our knowledge about the pathophysiology of neurodegenerative disorders.

Ladies and gentlemen, February 2020 was an exciting month for neurology. I'm Christoph Diener from the University of Duisburg-Essen, and I thank you very much for listening and watching.

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