Statins for stroke patients, alcohol for dementia prevention, and more

Now that Halloween is out of the way, it’s time to bring out the holiday cheer.

And, as always, there’s lots going on in the neurosciences. From MRI and genetics for better diagnostics in TBI and ALS, to the possible benefits of statins and even moderate drinking for the brain—just in time for Thanksgiving and Christmas—we’ve got it covered in this week’s Neuro Brief.

Neuro Flashback

At this time 20 years ago, researchers got the green light from the FDA to test a new spinal cord cell therapy—autologous macrophage therapy—in humans. Today, this therapy is still under development for acute, complete spinal cord injury, and is hoped to reverse the loss of motor and sensory functions in these patients.

In the News

Is there a doctor in the…helicopter? When a helicopter made an emergency landing on the Kamchatka Peninsula in Russia, good thing Konstantin Balashov, MD, PhD, professor, Department of Neurology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, was on board. Three passengers were injured after being flung to the back of the helicopter, and Dr. Balashov provided immediate medical assistance. In one passenger, after testing her cognitive abilities and other neurologic functions, he suspected a cervical fracture, and immobilized her using a piece of hard plywood. The fracture was later confirmed at a nearby hospital. Dr. Balashov also treated the other two injured passengers, one of whom sustained a tibial fracture, and the other, a deep skin and muscle laceration of the thigh. And you thought jet lag was bad.

Dementia doubles by 2040. According to a new report from the Milken Institute, the number of Americans living with Alzheimer disease and other dementia will double, totaling almost 13 million, over the next two decades. This means that by 2040, 8.5 million women and nearly 4.5 million men will have dementia. Experts also estimated that approximately 4.7 million women in the United States will have dementia by 2020, and account for nearly two-thirds of all cases. Further, by 2040, the economic burden of dementia will exceed $2 trillion, with over 80% of the costs carried by women. At least if you forget your anniversary, you’ll have a good excuse.

Weekly Trivia

Referred to by many as the “Father of Neurology,” Thomas Willis, born on January 27, 1621 in Wiltshire, England, was an Oxford professor of natural philosophy, and leader of the English iatrochemists. As such, he was interested in understanding how the body worked using current knowledge of chemical interactions. His 1664 book, “Cerebri Anatome, cui accessit Nervorum description et usus” or “Anatomy of the Brain, with a Description of the Nerves and Their Function,” was the most complete, accurate account of the nervous system of his time. Within its pages, he included the first description of the continuity of arteries at the base of the brain, a circulatory anastomosis that supplies blood to the brain and its surrounding structures. It was aptly named “the circle of Willis.” Dr. Willis was also the first to describe myasthenia gravis (1671) and puerperal (childbed) fever. He died on November 11, 1675, in London.

Novel Diagnostics

An MRI for a TBI? Yes please. After a traumatic brain injury (TBI), individuals with traumatic microbleeds on MRI may be twice as likely to experience disability. Researchers studied the brains of 439 individuals admitted to the emergency department with TBI who underwent MRI within 48 hours of initial injury. Roughly 31% of them had traumatic microbleeds—even those with mild TBI (27%) and moderate TBI (47%). Thirty to 90 days after injury, those with traumatic microbleeds were twice as likely to report disability. Because over 25% of those admitted to trauma centers with mild brain injuries have traumatic microbleeds, this may be an opportunity for clinicians to prevent further damage to brain tissues with treatment. This is important because the initial severity of TBI doesn’t always predict which patients will go on to experience disability.

It’s all in the genes. In individuals with amyotrophic lateral sclerosis (ALS), researchers have identified a genetic polymorphism that could predict more severe symptoms and faster diseases progression. They published their results in Neurology Neuroimmunology & Neuroinflammation. This commonly inherited variation in the interleukin-6 receptor gene was first identified in asthmatics as a marker of more severe asthma. Likewise, among those with ALS who had this polymorphism, disease progression was faster. Researchers are hopeful that their finding may provide a potential new therapeutic target for ALS. Currently, there are only two FDA-approved agents for the treatment of ALS, and no known cure.

Novel Treatments

Say buh-bye to migraine. The FDA has approved lasmiditan (Reyvow, Eli Lilly and Co.) for acute treatment of migraine with or without aura. Approval was based on positive findings from two randomized, double-blind, placebo-controlled trials in over 3,000 adults with a history of migraine. In both studies, pain and worst symptoms (including nausea, light sensitivity, and sound sensitivity) resolved within 2 hours of treatment in significantly more patients treated with lasmiditan compared with placebo. The most common side effects were dizziness, fatigue, paresthesia, and sedation.

A drug for Alzheimer disease? Let’s try this again, again. After halting two large studies of aducanumab—an investigational agent—for the treatment of Alzheimer disease (AD), the folks at Biogen announced that they will now request FDA approval for aducanumab to treat those with mild cognitive impairment and the earliest signs of AD. While aducanumab cannot prevent or cure AD, Biogen claims it may slow cognitive decline in some. As a monoclonal antibody, aducanumab appears to clear accumulations of beta amyloid. Biogen now has additional results from the two halted studies, including data from an additional subgroup of patients who received high doses of aducanumab, which they have yet to publish, let’s hope they don’t forget.

Chemo for muscle contractures? Bortezomib—a chemotherapeutic agent—may reduce shoulder and elbow contractures, according to results from a mouse model developed to mimic the contractures that are typical in childhood paralysis (caused by conditions such as cerebral palsy or brachial plexus injury at birth). In their preclinical model, researchers discovered that these contractures are caused by the inability of the paralyzed muscles to grow to normal lengths due to a lack of critical signaling input from normal nerve fibers during early development. Talk about not wanting to go the extra mile. Because bortezomib inhibits protein breakdown, it may actually re-balance muscle growth at the cellular level, which relies on a balance between the synthesis and breakdown of muscle proteins.

FDA halts STRONG study. The FDA has halted the STRONG trial of onasemnogene abeparvovec-xioi—yeah, we can’t pronounce it either—(Zolgensma) after concerns raised by a preclinical study. Onasemnogene is currently approved—and is the world’s most expensive drug treatment, with the first year of treatment far exceeding half a million dollars—for children up to age 2 years with spinal muscular atrophy with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene. The drug’s manufacturer, Novartis, had planned to expand its use to older children with spinal muscular atrophy. Now, researchers reported dorsal root ganglia mononuclear cell inflammation with higher study drug doses. The FDA’s partial hold will halt enrollment of patients aged 5 years and older with spinal muscular atrophy who were to receive a higher dose of the therapy via spinal infusion.

New in Patient Management

Excess protein could be bad for you. In a post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), researchers found that baseline albuminuria was associated with a higher risk of incident stroke in patients with diabetes. (The original SPRINT trial was designed to assess the effects of higher vs lower intensity blood pressure (BP) management on mortality in almost 9,000 participants.) Researchers also observed, however, that the association differed according to treatment—and was insignificant in those in the intensive BP treatment arm (unadjusted HR: 1.25) but significant in the standard treatment arm (unadjusted HR: 3.44). Therefore, they concluded, intensive BP treatment may reduce the risk of stroke in patients with albuminuria.

Too much, too little, or juuuust right? Good news is, your brain is safe if you drink; heck, your brain might even thank you. Bad news is, you can’t drink too much. In a recent study published in JAMA, researchers found that both complete abstention from drinking alcohol and drinking more than 14 drinks per week were associated with lower cognitive scores in those aged 72 years and older, compared with those who drank less than 1 drink per week. They concluded that drinking alcohol—in low quantities—may be associated with a lower dementia risk compared with sporadic heavier drinking.

More positives to statin use. Pre-stroke statin use was associated with significant decreases in 3-month mortality, major disability, and composite outcome in patients with atrial fibrillation-related acute ischemic stroke in a recent multicenter prospective study. Researchers postulated that treatment with statins in these patients before stroke actually decreases plasma oxidized LDL levels to improve outcomes.

CSF vs blood testing. Cerebrospinal fluid (CSF) levels of neuron-specific enolase (NSE) increase before serum NSE levels do in patients with severe brain injury. Researchers used this knowledge as the basis for their study, in which they assessed and compared the prognostic value and performance of CSF NSE vs serum NSE levels in out-of-cardiac arrest patients after target temperature management. Indeed, CSF NSE values were highly predictive and sensitive markers of poor neurological outcomes at 6 months in these patients. Thus, concluded researchers, measuring CSF NSE levels even 1 day after return of spontaneous circulation could be a useful prognosticating tool.

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Upcoming Medical Meetings

Headache Symposium 2019: The Art of Headache Medicine in Cleveland, OH, November 9, 2019

International Society for Traumatic Stress Studies (ISTSS) 35th Annual Meeting in Boston, MA, November 14-16, 2019

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