Dangerous effects of hypertension on neuro patients, a common neurological condition is often misdiagnosed, and a natural hormone could predict Alzheimer’s

As flu season ramps up, everyone’s keeping their eyes on COVID-19 numbers, especially patients with neurologic disease and the doctors who treat them. Every day our understanding of how the pandemic impacts these patients becomes clearer, and the image is pretty scary—fitting for the Halloween season. This week we offer insights into how the pandemic affects those with migraines, Parkinson’s disease, and ischemic stroke. But we also find that these patients and their physicians have plenty of room for optimism—we’ve got a new vitamin treatment for migraines, a new Parkinson’s biomarker, better stroke prognosis, plus a whole lot more.

Neuro Flashback

Imagine you’re living in the sleepy Long Island, NY, town of East Hampton way back in 1872. The Civil War is fresh in your memory, it’s super dark at night (the lightbulb won’t be patented for another 7 years), and something strange is happening to your fellow townsfolk: They’re having difficulty concentrating. Memory lapses are rampant, many seem depressed, and they’re stumbling around and going through wild mood swings.

This isn’t some made up Halloween horror story to get you hyped for Trick-Or-Treating (sorry, that’s probably cancelled this year anyway). It’s the real-life tale of George Huntingdon, MD, the physician who’s credited with the first detailed recounting of the symptoms of Huntington’s disease. Huntington wasn’t the first to describe his namesake disease, though—it had been endemic in the East Hampton community for several generations, afflicting many in the area whose ancestors had migrated from Suffolk, England—but he is rightfully credited with a detailed recounting of the hereditary condition’s telltale regression, which eventually leads to dementia. 

In the News

The comorbidity putting MS patients at higher neurocognitive risk. Lots of people with multiple sclerosis have hypertension. That’s not weird or surprising at all, considering that nearly half of all adults in the US have the condition. But what is weird and surprising is the fact that hypertension is 25% more common in patients with multiple sclerosis than it is in those without multiple sclerosis—even in age-, sex-, and race-matched cohorts.

Researchers discovered this after conducting a cross-sectional study of 37 million unique electronic health records across the US, where nearly 123,000 people with multiple sclerosis were identified. Hypertension was 25% more common in people with multiple sclerosis, and it increased in prevalence progressively with age. Males and Black Americans were more likely to be hypertensive across the MS and control cohort. So, what’s the key takeaway? We need to get serious about aggressive screening for (and management of) hypertension—which increases the risk of stroke and ischemic heart disease—among patients with multiple sclerosis.

Guess what else increases the risk of ischemic stroke? We’ll give you a hint: It’s been here for a long time, it shows no signs of going away, and yet some people don’t want to believe it’s real. No, we’re not talking about climate change or the adult children living in your basement—we’re talking about COVID-19. Thanks to a new study published in Neurology, everyone’s least favorite item on the 2020 highlight reel got even more harrowing. Results, which supported most neurologist’s suspicions, suggest that patients with COVID-19 develop a wide range of neurologic symptoms.

How bad can they get? Pretty bad. In a cohort of 43 men and 21 women, 56% of brain MRIs of patients with COVID-19 were considered abnormal. A total of 27% of these patients had ischemic strokes, 17% had leptomeningeal enhancement, and 13% had encephalitis. Confusion was another common symptom present in 53% of patients, while 39% had impaired consciousness, 31% experienced agitation, and 16% had headaches. These results add to the growing base of evidence that suggests that the neurological symptoms of COVID-19 are similar to the disease itself—deadly in some, mild in many, and altogether absent in others.

New neurological manifestations of obesity. Want the good news first? Obesity has a neuroprotective effect on dementia. But we covered that in a past edition of NeuroBrief. Today, we’re here to give you the bad news (sorry): A new meta-analysis published in NeuroImage: Clinical suggests that obesity is linked to reduced orbitofrontal cortex gray matter volume.  

How did we get here? Researchers dug up data in a meta-analysis of 25 voxel-based morphometry studies that included 7,612 patients. Patients who had higher BMI were more likely to have decreased gray matter volume in the right orbitofrontal cortex, an area associated with activity in the left frontal medial cortex, left temporal lobe, right precuneus cortex, posterior division of the left middle temporal gyrus, and right frontal pole. So what does this mean? Results are consistent with the understanding of obesity as a chronic medical condition that affects the brain and cognition. Lower orbitofrontal cortex gray matter volume can be disruptive, changing the way we process rewards and potentially affecting working memory function.

This pandemic is quite the headache. Seven months, constant devastation, no end in sight—it’s pretty grueling. Well, it turns out that for many of us, this pandemic has been as much a metaphorical headache as a literal one. A new survey published in The Journal of Headache and Pain suggests that in comparison to the pre-pandemic period (remember that?), 60% of respondents reported an increase in migraine frequency and 10% saw their headaches progress to chronic migraines.

Despite this, the majority of respondents (62%) didn’t communicate this increase with their doctors, while just 47% complied with their migraine treatments, and 59% reported overusing analgesics to compensate. Several patients went without their standard Botox injections, and among the 4% who got COVID-19, 63% said their headaches got worse during the infection period. Researchers say we ought to put plans in place to ensure these patients get the care they need if a similar pandemic or another wave sweeps across the globe again soon.

Neuro Trivia

Can you name a neurologic disease where higher BMI actually has a protective effect? Psst! The answer’s “In the News!”

It may seem counterintuitive, but studies have shown that obesity strengthens the protective effect of serum urate on risk of dementia.

Novel Diagnostics

Delirium detection ≠ dementia diagnosis. The findings of a new study suggest that among adults not previously diagnosed with dementia in a skilled nursing facility (SNF), a positive screen for delirium was significantly associated with a higher risk of being diagnosed with Alzheimer’s disease and related dementias (ADRD). But that’s not the big news. What’s even more interesting is that the risk was highest for patients in the first days of their stay and with the least cognitive impairment—this suggests that their ADRD diagnosis was probably made in error.

In the study, which included 1,175,550 Medicare enrollees, a positive screen for delirium was identified in 7.7% of patients. Most of these positive screens (62.5%) occurred within the first 7 days of SNF admission, and nearly all new diagnoses of ADRD (93.5%) occurred within the first 30 days of SNF admission. Patients who screened positive on the Confusion Assessment Method (CAM) for delirium had a nearly threefold increased risk of receiving an incident ADRD diagnosis on the same day. Among patients who screened CAM positive for delirium, those who were cognitively intact or who had mild cognitive impairments were, on average, six times more likely to receive an incident ADRD diagnosis relative to those testing CAM negative. The study gives us a glimpse into the extent to which delirium screening leads to an inappropriate diagnosis of ADRD, and provides an opportunity for us to course-correct.

Detecting Alzheimer’s with the ‘stress hormone.’ When we wake up in the morning, our adrenal glands secrete cortisol, also known as the stress hormone, as part of the process that shifts our bodies from a resting to an active state (coffee also helps). A new study finds patients with Alzheimer’s disease secrete much more cortisol in the morning than healthy controls, and that people with mild cognitive impairment have higher cortisol in their CSF than healthy controls.

What does this mean? The data, published in a systematic review and meta-analysis in Ageing Research Reviews, suggests that high cortisol is associated with accelerated cognitive decline in people with mild cognitive impairment, and that cortisol levels may hold predictive value for cognitive decline in preclinical adults. Study authors found that patients with Alzheimer’s had moderately increased morning cortisol in their blood, saliva, and CSF, and that higher morning cortisol may accelerate cognitive decline. More studies are needed to replicate these results, but in the meantime, try not to stress too hard.

New biomarker for Parkinson’s in the skin. Here’s the deal: We know that deposits of pathological α-synuclein (αSynP) in the brain is the hallmark of synucleinopathies like Parkinson’s disease, Lewy body dementia, and multiple system atrophy. What we don’t know is whether real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA) assays can sensitively detect skin biomarkers for these synucleinopathies, including Parkinson’s disease.

Here’s the good news: it appears that they can. In a new study published in JAMA Neurology, researchers provide the first-ever evidence and proof-of-concept that skin αSynP seeding activity may serve as a novel biomarker for antemortem diagnosis of Parkinson’s disease and other synucleinopathies. “Given that skin punch biopsy is relatively easier to perform and much less invasive, skin αSynP seeding activity may be a more practical antemortem diagnostic biomarker for PD and synucleinopathies,” the authors wrote.

Stroke prognosis may have just gotten a bit simpler. Ischemic stroke outcomes usually aren’t great, but predicting how they’ll unfold can help reduce the burden and ensure patients get the personalized care they need. That ideal is coming closer to reality—new research has revealed for the first time that the combination of C-C chemokine receptor 5 T cells (CCR 5+Tregs) and Treg cells can achieve an excellent prediction effect on the prognosis of patients with ischemic stroke.

In the study, researchers used flow cytometry to measure Tregs and CCR5+ Tregs in patients’ blood. Then, they analyzed their effects on ischemic stroke and used a receiver operating characteristic (ROC) curve to assess predictive values for Treg cells and CCR5+ Tregs. They found that Tregs in patients with severe ischemic stroke were higher than those in mild ischemic stroke, while the expression of CCR5+ in Tregs was reversed. Tregs and CCR5+ Tregs had a good predictive effect on ischemic stroke prognosis, and the ROC curve showed that the combination of Tregs and CCR+ Tregs achieved a better prediction effect.

Novel Treatments

A vitamin for migraines. You’ll find it in milk, liver, eggs, and green veggies. You can also find it being synthesized by our gut bacteria, because it’s essential for metabolic energy production. So what is this mystery vitamin? It’s riboflavin, and thanks to a new study, it’s adding a new benefit to its list: children can take it prophylactically to treat their migraines. 

Here are the data: researchers conducted a retrospective observational study on 42 patients with migraine between 6 to 18 years of age who were recommended weight-based dosing of riboflavin for migraine prevention. These patients had a significant reduction in headache days per month at the first follow-up visit at 2 to 4 months compared to baseline. Mean headache intensity decreased from 8.85 to 2.30 on a 0 to 10 scale. Headache duration also reduced significantly from 18.23 h ±17.07 (T0) to 10.18 h ±10.49 (T1). There was a positive correlation between riboflavin efficacy and reduced utilization of acute medications. All told, the authors recommend riboflavin as a safe, inexpensive, and effective nutraceutical for the treatment of pediatric migraine—one that serves the dual purpose of helping pediatric patients avoid symptoms and side-effect laden medications.

Ponesimod vs teriflunomide. These two treatments—both for adults with relapsing multiple sclerosis—faced off in a recently published phase 3 study in adults with relapsing multiple sclerosis. Of course, only one came out on top—the winner was ponesimod, Janssen’s investigational selective S1P1 receptor modulator, which showed superior efficacy to teriflunomide 14 mg in the phase 3 OPTIMUM study’s primary endpoint, and most secondary endpoints, too.

Compared with teriflunomide, patients who took ponesimod saw a statistically significant reduction of annualized relapse rate (ARR), the study’s primary endpoint, by up to 30.5% up to week 108. Several pre-specified secondary endpoints also landed in favor of ponesimod, including an improvement in fatigue symptoms. “This is the first large controlled head-to-head study comparing two oral compounds for the treatment of relapsing MS,” Professor Ludwig Kappos, MD, of the Department of Neurology at University Hospital of Basel, Switzerland, said in a statement. “These data, in conjunction with the observed safety profile, underline the potential of ponesimod as a new treatment option for MS.”

Low dose or high dose, rituximab gets it done. Using the standard 1000 mg treatment of rituximab for your patients with multiple sclerosis? A new study suggests you can probably use half that amount and still get the same results. The data, presented at MSVirtual2020, found that the annualized relapse rate in patients who were treated with low-dose rituximab (500 mg) was 0.05, compared with an annualized relapse rate of 0.03 in patients receiving the standard dose—that’s statistically insignificant in the good kind of way.

The study was conducted at two centers in Spain—one in Barcelona, where 249 patients were given high-dose therapy, and one in Girona, where 54 patients received low-dose therapy. After two intravenous infusions of 1000 mg of rituximab at baseline, patients in the high-dose group (Barcelona) received two more infusions every six months for the first year, and then 1000 mg every six months. In the low dose group (Girona), after the two initial 1000 mg doses at baseline patients were treated with 500 mg every six months. After three years of dosing, during which patients were followed up every six months with lab tests and with yearly brain MRI scans, researchers concluded that lower doses of rituximab could have similar efficacy but lower adverse event risk than higher doses. More studies that measure long-term risk are needed, but initial results are promising, suggesting that less might be more when it comes to this treatment for multiple sclerosis.

Put some pepinemab in your step. Or don’t—the data from a new phase 2 study isn’t super convincing just yet. But we’re sharing it nonetheless, because it’s trending in the right direction and future studies may push this treatment past the statistical-significance finish line for Huntington’s disease, a condition where treatments are limited (there are literally none, so even small wins in this treatment space are huge).

The study had two co-primary endpoints—the results of two cognitive assessments from the Huntington’s Disease Cognitive Assessment Battery and Clinical Global Impression of Change (CGIC). The bad news is that the study did not meet either pre-specified co-primary endpoint. The good news is that results of both tests demonstrated a strong trend for beneficial change in cognition. On top of that, pepinemab was well-tolerated, with remarkably low treatment discontinuation and study drop-out rates over the extended 18-month treatment period. The bottom line: while pepinemab didn’t earn the most impressive results, they were decent enough to warrant additional studies. For a disease where new treatments are so desperately needed, that’s reason to keep hope alive.

New in Patient Management

What about the kids? Data has shown that the frequency of hypertension increases in adults with migraine, but what about kids? No studies have figured out whether they’re in the same boat—until now, that is. Researchers performed ambulatory blood pressure monitoring (ABPM) on 37 children diagnosed with migraine and 30 healthy controls. Office blood pressure was also measured for all children and the two groups were compared.

Results suggest that, although the frequency of hypertension wasn’t higher, abnormal ABPM patterns were found to be significantly more frequent in the migraine group (45.9% vs 16.7%, respectively). What’s more, nighttime mean arterial blood pressure, nighttime diastolic blood pressure, and non-dipping pattern were higher in children with migraine than those in the control group. It’s not clear yet whether kids are the same as adults when it comes to the link between hypertension and migraine, but the data suggest ambulatory blood pressure abnormalities may be present in about half of patients with migraine, so ABPM should be performed, even if the office blood pressure measurements of children diagnosed with migraine are normal.

Less than ideal side effect of dopamine agonists. Dopamine agonists are some of the most common treatments for Parkinson’s disease. Side effects can be pretty serious, including hallucinations, sleepiness, and compulsive behaviors, like hypersexuality, gambling, and eating. According to a new study, increased BMI is another side effect, highlighting the health consequences of the drug’s propensity to induce compulsive eating.

In the study, published in Parkinsonism & Related Disorders, researchers studied a cohort of 356 patients with Parkinson’s who had annual follow-ups for up to 6 years, and who had their BMI, antiparkinsonian drug use, and impulse control disorders assessed at each visit. In the follow up, BMI increased in dopamine agonist users compared to non-users. It also decreased in those who were taking levodopa. In fact, the incidence of weight gain of ≥ 6 kg was 2.10-fold higher in dopamine agonist users than non-users, while levodopa users were less likely to gain weight (HR = 0.60). Those associations decreased in analyses adjusted for compulsive eating or impulse control disorders. The takeaway? Keep a close eye on compulsive eating behaviors and weight gain in patients with Parkinson’s disease taking dopamine agonists.

Exercise, diet, and stroke. We know that a poor diet and lack of physical activity increase the risk of recurrent stroke. We also know that that risk can be compounded by obesity and diabetes. But here’s what we don’t know: whether there’s an association of obesity and diabetes with poor diet and insufficient physical activity in stroke survivors. Fortunately, researchers are getting to the bottom of the issue. In a new study, they compared the prevalence of low fruit and vegetable consumption (< 1 fruit and < 1 vegetable daily) and low physical activity (< 150 minutes of weekly moderate-intensity physical activity) in stroke survivors, stratified by obesity-diabetes status.

Here’s what they found: The prevalence of low fruit and vegetable consumption and low physical activity exceeded 50% across all obesity-diabetes categories. Compared with respondents who didn’t have obesity or diabetes, adjusted odds ratios for low physical activity were increased for respondents with both obesity and diabetes (2.02) and respondents with obesity only (1.31). AORs for low fruit and vegetable consumption, on the other hand, did not differ across categories. The key—we need more targeted interventions to help modify unhealthy behaviors in stroke survivors.

A rock and a hard place for those with Parkinson’s. If you read our “In the News” section above, you know how rough the pandemic has been on migraine sufferers. Well, there’s not much good news when it comes to COVID-19, so we might as well share some more disconcerting data: In a new cross-sectional survey of 568 Spanish patients with Parkinson’s disease, more than half reported worsening of their symptoms during confinement—a true lesser-of-two-evils situation for those choosing whether to quarantine and for how long.

Survey results found that among these patients, 68.8% were concerned about the pandemic and 95.6% took preventive measures to avoid becoming infected. About 85% of these patients had no contact with people who had confirmed COVID-19 infection, and only 2.6% had contracted the infection themselves. But safety came at a cost—even though 72.7% remained active during quarantine, 65.7% perceived worsening of their symptoms. The results highlight yet another way the pandemic is having negative impacts on people living with neurological disease.

Latest in Journal Summaries

Gut microbiota associated with Alzheimer’s, MDD, and schizophrenia.

COVID-19-related intracranial imaging findings.

ENBIND study: Cognitive performance in midlife type 2 diabetes.

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Upcoming Medical Meetings

The following meetings are entirely virtual:

2020 Barrow Acquired Brain Injury & Spinal Cord Injury Symposium. October 10-11, 2020.

American Academy of Neurology (AAN) Fall Conference. October 16-17, 2020.

28th Annual Update: Neurology 2020. October 12-16, 2020.

 

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