Shocking new results from an early-stage MS trial, a diet to protect against Parkinson’s, and 2 brain-related reasons to get better sleep

We put a lot of hope in the neurological therapy pipeline because—let’s face it—what’s available isn’t all that great. This week, an early-stage trial brings alarming new results for a hotly-anticipated multiple sclerosis therapy that we’re all rooting for. Plus, we’ve got plenty of good eats for Parkinson’s protection, a drug that will de-chronic your migraines, and two good reasons to go ahead and take a nap.

Neuro Flashback

Four centuries before the condition was recognized and years before the word “stress” even acquired its present usage, Shakespeare gave an accurate account of post-traumatic stress disorder in his play Henry IV. Kate, the wife of Hotspur, an English knight who fought in several campaigns against the Scots at the northern border and against the French in the Hundred Years’ War, describes her husband’s condition like this: “What is’t that takes from thee thy stomach, pleasure, and thy golden sleep? Why dost thou bend thine eyes upon the earth, and start so often when thou sit’st alone? Why has thou lost the fresh blood in thy cheeks, and given my treasures and my rights of thee to thick-eyed musing and curst melancholy?” Kate’s description covers many of the main features of PTSD and can be counted among the condition’s earliest descriptions.

In the News

Shocking results from a promising MS therapy. The world had high hopes for TEPP-46, an experimental drug that was supposed to make multiple sclerosis symptoms better. But the hard truth is that things don’t always work out as planned. And despite the fact that we desperately need any new treatment for multiple sclerosis, TEPP-46 probably isn’t exactly what we’re looking for. In fact, it may actually exacerbate multiple sclerosis symptoms, according to new data. Models used by researchers from the University of Virginia School of Medicine suggest that the drug can worsen the disease by redirecting inflammation from the spinal cord into the brain.

According to findings published in Science Signaling, researchers found that TEPP-46 worsened the disease in mouse models and determined that the drug caused harmful changes in T cells. They also reported that the drug had unintended, off-target effects. While TEPP-46 has not yet made it to human trials, the researchers were concerned by their findings and recommended that more research be conducted before TEPP-46 is tested on humans. All hope is not lost, but the future we were hoping for might be farther away than we thought.

Another reason to sleep more: Dementia prevention. According to a number of new studies, spending time in “deep sleep” can help protect you against Alzheimer’s disease. Deep sleep—the period when your body temperature drops and your brain starts to produce slow, electrical pulses—is a period of sleep during which the body disposes of waste products that increase the risk of developing dementia. Researchers believe that regular deep sleep can help reduce the levels of two biomarkers of Alzheimer’s disease: Beta-amyloid and tau. In one study published this month in Current Biology, a team of scientists studied the sleep of a group of 32 people in their 70s during the course of 6 years. The team looked at how much deep sleep each participant was getting and used brain scans to monitor their levels of beta-amyloid. They found that those who slept less had more of it.

Another study found an association between sleep deprivation and higher levels of tau, which also leads to Alzheimer’s. As such, scientists are now seeking ways to boost or even induce the slow rhythmic pulses that the brain produces during deep sleep. While there has been success in inducing these waves in the brains of rodents, the best we can currently do for people is to treat sleeping disorders like sleep apnea—or you can try listening to rhythmic sounds while you sleep, which may help to boost this process.

Links between inner mind and outer space. A new investigation has found a tantalizing degree of similarity between the organization of our brains and the universe, suggesting that the distribution of fluctuation within the cerebellum neural network follows the same progression of distribution of matter in the cosmic web. The study, which was published in Frontiers in Physics, explored the various properties of both the interconnected neurons of the human brain and the gravitational relationships between ordinary and dark matter across the universe.

Italy-based researchers applied methods from cosmology, neuroscience, and network analysis to see whether the two systems are shaped by similar principles of network dynamics. While the authors conceded their study had limitations, they concluded that some analogous configurations appear to emerge from the interaction of these two very different physical processes, resulting in similar levels of self-organization. The researchers hope that the analyses will motivate the development of more powerful and more discriminating algorithms to explore the comparison further, so that we can get a step closer to answering questions such as: How do our brains produce complex cognitive functions? Or, what is the exact nature of dark matter? Perhaps for us to understand the outer stretches of the universe, we’ll need to keep looking within ourselves.

Sleep deprivation really is traumatizing. Everyone knows that getting a full night’s sleep is important, but a new study has shown that sleep deprivation can interfere with the brain’s process of unlearning fear-related memories. The study, which appeared in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, concludes that getting only half a night’s sleep, as many healthcare workers often do, can put people at a greater risk of developing PTSD or an anxiety disorder.

The study looked at 150 participants to establish whether sleeping only part of the night would result in a loss of REM sleep. This process, which typically occurs during the end of a normal sleep period, is when the brain consolidates memories. At this time, the brain also undergoes a process called “fear extinction,” which is essentially the unlearning of fear-related memories. One-third of the study’s participants were allowed a full night’s sleep, one-third were allowed a half-night’s sleep, and the final one-third were completely sleep deprived. Results from brain images of each enrollee during the following morning showed that those who had only gotten a half-night’s sleep had the most activity in brain regions associated with fear, and the least activity in areas associated with control of emotion. Surprisingly, the brain activity of those who were completely sleep deprived looked more similar to those who were given a full night’s sleep. So, you heard the scientists: Get a full night of sleep!

Neuro Trivia

Can you name the old monikers of PTSD?

It has been called shell shock, war neurosis, battle fatigue, soldier’s heart, and most recently, post-traumatic stress disorder. Some in the psychiatric community believe it should be renamed again to post-traumatic stress injury—an effort to reduce stigma and increase treatment.

Novel Diagnostics

Connecting the BBB mean and cognitive function. Are there links between blood-brain barrier (BBB) integrity, brain volume, and cognitive dysfunction in patients with systemic lupus erythematosus (SLE)? Researchers from Dalhousie University in Nova Scotia, Canada, set out to see if that’s the case in a new study published in BMJ. A total of 65 ambulatory patients with SLE and nine healthy controls underwent dynamic contrast-enhanced MRI scanning for quantitative assessment of the permeability of their BBB, as well as global cognitive function assessments.

Researchers found that patients with SLE had significantly higher levels of BBB leakage compared with controls. Extensive BBB leakage (affecting > 9% of brain volume) was only identified in patients with SLE, who also had smaller right and left cerebral grey matter volumes compared with controls. What’s more, extensive BBB leakage was associated with lower global cognitive scores and with impairment on one or more cognitive tasks. The key takeaway? The study provides evidence for a link between extensive BBB leakage and changes in brain structure and cognitive function in patients with SLE. The new data sets the groundwork for future studies that can validate the diagnostic utility of BBB imaging and determine the potential for targeting the BBB as a new therapeutic strategy.

Differentiating Parkinson’s from supranuclear palsy. Progressive supranuclear palsy is tough to diagnose. It’s uncommon and, because its symptoms are so similar to Parkinson’s disease (problems with walking, balance, and eye movement), it often ends up being misdiagnosed and mistreated. But there is one key indicator that could make diagnosis more accurate—the brain’s third ventricle. Previous studies have suggested that the third ventricle is enlarged in atypical parkinsonism. Could measuring it distinguish Parkinson’s from progressive supranuclear palsy?

In a new study, researchers measured third ventricle width and internal skull diameter in a training cohort of 268 participants—98 with Parkinson’s disease, 73 with progressive supranuclear palsy, and 98 controls—as well as a testing cohort of 291 participants (82 de novo Parkinson’s disease, 133 controls, and 76 early-stage progressive supranuclear palsy). In both cohorts, third ventricle/internal skull diameter values did not differ between Parkinson’s disease patients and controls, but they were significantly lower in Parkinson’s disease patients than in those with progressive supranuclear palsy. In Parkinson’s disease, third ventricle/internal skull diameter values did not change significantly between baseline and follow-up. What’s more, receiver operating characteristic analysis accurately differentiated Parkinson’s disease from progressive supranuclear palsy in the training cohort and the testing cohort (area under the curve 0.94 and 0.91, respectively). Good news in all—we may just have a new and reliable MRI measurement to help differentiate these very similar diseases.

Does this diagnostic exam work? Here’s a HINT. The HINTS exam is designed to distinguish between central and peripheral causes of dizziness in patients who complain of dizziness and vertigo. When trained specialists use it, the exam has excellent diagnostic accuracy. But what about emergency physicians—can they get the same results with the HINTS exam?

Apparently not. In a new study of 2,309 patients published in Academic Emergency Medicine, physician uptake of the HINTS exam was high, with 450 (19.5%) dizzy patients receiving all or part of the HINTS, even though a large majority of patients (96.9%) did not meet criteria for receiving the test as described in validation studies. This was because patients lacked documentation of nystagmus or described their symptoms as intermittent. What’s more, many patients received both HINTS and the Dix-Hallpike maneuver, which are intended for use in mutually exclusive patient populations. In all, even though the HINTS exam was widely used, its diagnostic value was limited, suggesting that additional training will be needed before emergency physicians can achieve higher reliability.

Seeing the future of stroke with VEGF. If inflammation can tell us how a stroke patient is likely to fare post-stroke, it’s possible that growth factors with neurotrophic and angiogenesis-regulating properties can provide reliable information about sequelae. In a new study, researchers measured the prognostic performance of four factors related to stroke—vascular endothelial growth factor (VEGF), placental growth factor (PLGF), IL-6, and CRP. The winner? VEGF.

In ischemic stroke patients who died or had moderate-to-severe disability at 6 months, researchers found that VEGF was elevated. There were correlations between VEGF and HbA1c, triglycerides, erythrocyte sedimentation rate (ESR), and NIHSS and Rankin scores, with VEGF being identified as a major loading factor that discriminated a good from a poor prognosis. Approximately 24 to 48 hours after acute ischemic stroke, circulating VEGF was elevated, conveying notable prognostic information about moderate-to-severe disability at 6 months.

Novel Treatments

From chronic to episodic migraine. If you have to have a headache, you’d be much better off with episodic migraines than with chronic migraines. In fact, in patients with migraines, reversion from chronic migraine to episodic migraine is an important treatment milestone—one that fremanezumab can help them achieve, according to new data from a phase 3, randomized, double-blind, placebo-controlled, parallel-group trial published in Headache.

The analysis included data from 1,088 chronic migraine patients, and found that a higher proportion of fremanezumab‐treated patients reverted from CM to EM relative to patients who received placebo, when reversion was defined either as < 15 monthly headache days per month over 3 months on average or, more stringently, as < 15 headache days during each month (measured at months 1, 2, and 3) of the treatment period. The bottom line? Fremanezumab was shown to be an efficacious preventive therapy for chronic migraine, based on its ability to significantly reduce headache frequency and migraine days compared with placebo.

Phones giveth headaches, and phones taketh headaches away. Ever got a headache after hours and hours of doomscrolling through your phone? We have good news. Smartphones can also help reduce headaches, according to new data published in the aptly-named journal Headache. In a study of adults with migraine and 4 or more headache days per month, participants were given the RELAXaHEAD app, which included an electronic headache diary, and randomized to receive one of two versions of the app—one with progressive muscle relaxation (PMR) software and one without.

For the first 6 weeks, participants practiced PMR 2-4 days per week. Mean session duration was about 11 minutes. Relative to the diary-only group, the PMR group showed a greater non-significant decline in mean MIDAS scores (–8.7 vs –22.7), corresponding to a small-to-moderate mean effect size. At the end of the trial, patients reported that the app was easy to use, giving it a mean score of 4.2 on a scale of 1 to 5, and stated that they would be happy to engage in the PMR intervention again. With such a dearth of effective therapies for migraine, alternative therapies like PMR may hold some serious promise.

Busting up cluster headaches. When it comes to cluster headaches (CH), treatment with galcanezumab makes a big difference. But just how big is “big” really? A post-hoc analysis of a phase 3, randomized double-blind, placebo-controlled study in patients diagnosed with episodic cluster headache has characterized outcomes in the preventive treatment of episodic cluster headache, and identified better definitions of clinically meaningful attack frequency reduction based on galcanezumab’s efficacy.

In the analysis, the median time-to-first occurrence of a ≥ 50%, ≥ 75%, or 100% reduction from baseline in CH attacks was consistently shorter (9‐10 days sooner) with galcanezumab vs placebo: ≥ 50%, 5 days vs 14 days; ≥ 75%, 11 days vs 21 days; 100%, 22 days vs 32 days. Mean reduction from baseline in the overall frequency of weekly pooled acute medication use across weeks 1-3 was significantly greater with galcanezumab vs placebo. The odds of achieving an attack reduction threshold of 43% across weeks 1-3 was significantly higher in the galcanezumab group. Overall, faster median time-to-first occurrence of response rates, lower frequency of pooled acute medications use, and a greater proportion of patients achieving a response anchored by patient-reported improvement were observed for galcanezumab vs placebo.

Electroconvulsive therapy for Parkinson’s? Electroconvulsive therapy is widely accepted as an effective treatment for psychiatric disorders, including depression and psychosis. You know who has those exact symptoms sometimes? Patients with Parkinson’s disease. So is it possible that electroconvulsive therapy can help patients with Parkinson’s tackle their psychiatric symptoms? Yes. But that’s not the coolest part about a new systematic review and meta-analysis published in Movement Disorders—it can also help them tackle their motor symptoms, too.

In the review, researchers pooled data from 14 studies—one randomized controlled trial, nine prospective observational studies, and four retrospective studies. Electroconvulsive therapy was found to significantly improve motor manifestations in patients with Parkinson’s disease, and the improvement was significant in the subpopulation without psychiatric symptoms. The therapy significantly improved depression and psychosis, and significantly relieved wearing-off phenomenon without worsening cognitive function. All in all, electroconvulsive therapy appears to be a promising treatment for the psychiatric and motor symptoms of Parkinson’s disease, even in difficult-to-treat subgroups.

New in Patient Management

Can a Mediterranean diet help stop Parkinson’s? Even if we can’t fly to the Mediterranean right now, we can still enjoy their cuisine—which we all ought to do if we want to achieve better health. Despite it being identified as a catalyst for good health decades ago, researchers continue to uncover new positives associated with the Mediterranean diet. Just last month, a new large-scale study found that Mediterranean diet adherence can likely protect against Parkinson’s disease.

The study, published in Movement Disorders, analyzed the eating habits of 47,000 middle-aged Swedish women and sought to establish whether following a Mediterranean dietary pattern was associated with protection against neurodegeneration later in life. The decades-spanning study found that the more participants followed a Mediterranean-style diet, the lower their chances of developing Parkinson’s disease. In fact, sticking to the diet during mid-life was associated with a 29% lower risk of developing Parkinson’s after turning 65. Researchers found that dietary and nutritional factors could additionally improve symptoms and quality of life among patients with the disease. So, on your next trip to the grocery store, don’t forget to grab some fish, olive oil, and fresh tomatoes.

The leading cause of death for cerebral bleed survivors. If you have a patient who survived an intracerebral hemorrhage and who suddenly gets readmitted to the hospital, there’s a good chance you’ll need to treat an infection, according to a new multistate longitudinal study. The research, which was published in Neurology, aimed to establish the leading causes of death in spontaneous intracerebral hemorrhage survivors who are readmitted to the hospital. 

Using data provided from hospitals in California, New York, and Florida, researchers looked at 72,000 elderly patients. Of the roughly 12,500 patients who died within 4 years of their initial hospitalization, a little over one-third died of infection. The other leading causes of death were intracranial hemorrhage (14%), cardiac disease (8%), respiratory failure (8%), and ischemic stroke (5%). The authors hope that the study’s findings will help physicians to prioritize interventions and improve the long-term survival rates for those who experience cerebral bleed.

Who says you can’t run from your problems? Migraines can be debilitating, but the results of new research suggest that women may be able to prevent the onset of these severe recurring headaches simply by exercising more often. The recent cross‐sectional survey, which was published in Headache, looked at almost 400 students, monitoring them for migraines and analyzing the level of physical activity they incorporated into their lifestyles.

It’s worth pointing out that the relationship between athletics and migraines remains controversial, with several studies actually identifying sports as a trigger of migraines, rather than something that can help prevent them. And even according to the authors of this study, the role of exercise in affecting migraines remains unclear. Still, the results indicated a protective effect of sports on the risk of migraines in women, as well as an increased risk of migraines when compared to men. For men, on the other hand, the same effect was not observed. While the researchers concluded that further studies are required to deepen knowledge of the subject, the study suggests that working out could be women’s path to fewer headaches.

Dementia patients at higher risk of COVID-related death. More and more data are coming to light about COVID-19, as the global scientific community rushes to learn more about the virus and how to best prioritize and treat patients. Various risk factors associated with a poor prognosis for COVID‐19 patients have already been publicly established. For example: Those with chronic obstructive pulmonary disease or cancer. Earlier this month, a newly published study indicated that those who suffer from dementia are also at a greater risk of dying after contracting COVID.

The study, which was published in Geriatric Psychiatry, analyzed several pieces of literature dating from the past year. The researchers found that, among COVID-19 patients, the prevalence of dementia was higher in those who died as a result of the disease than in survivors (17.5% vs 5.4%). The pooled analysis performed using a random-effect model showed an increase in the risk of death in COVID-19 patients with dementia (OR=3.75), and the Eggers regression test confirmed that there was no statistical evidence of publication bias to alter the results. The conclusion? Because of their intrinsic frailty, those with dementia likely require more aggressive treatment and immediate isolation to improve their short‐term outcomes.

Latest in Journal Summaries

First-trimester maternal serum biomarkers and the risk of CP.

Difficulties in the prehospital assessment of patients with TIA/stroke.

Subjective cognitive complaints in early Parkinson’s are associated with affective symptoms.

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