Game-changing neuro drug up for 3 indications, new therapeutic target for Alzheimer’s, and an unconventional therapy for Parkinson’s disease
As 2020 continues its relentless beatdown of our psyches, it’s never been harder to stay positive. It’s also never been more important to stay positive. In this edition of NeuroBrief, we’ll give you plenty of reasons to do just that—from a new neuro drug that may treat three separate conditions, to a potential new world of therapies for Alzheimer’s.
We’re going all the way back to the 17th century BCE to take a look at the earliest known recorded description of spinal injuries. The Edwin Smith Papyrus—named for the antiquities dealer who purchased it in 1862—is an ancient Egyptian text describing 48 typical presentations and treatments for fractures, wounds, tumors, and more. The document was most likely used as a manual for military surgery. While some of the treatments are a little outdated—when was the last time you stopped bleeding by applying raw meat?—the cases describe an astonishing level of medical understanding for the time. The document notes the influence of the brain on other parts of the body and identifies the relationship between the location of a cranial injury and the affected side of the body.
In the News
Dementia and dollar signs. Dementia’s burden on society is immense—it affects around 50 million people worldwide. Its burden on patients is scary—there’s no treatment to stop or slow its progression. And its burden on caregivers is exhausting—because beyond the emotional toll lies a heavy financial one. A new financial report from RBC Wealth Management finds that the lifetime cost of dementia care can exceed $750,000 in direct and indirect expenses, making it financially devastating for most people.
In a survey of 1,000 affluent and high-net-worth cognitive decline caregivers in the US, researchers found that making financial sacrifices, such as reducing working hours or leaving the workforce entirely, is common and can disrupt careers—particularly for women—and cost them about $35,000 in annual income. Caregivers also saw huge increases in monthly expenses—between $750 and $1,200 per month—depending on dementia severity. To make matters worse, the number of Americans with dementia is expected to double by 2040. The financial implications couldn’t be much more daunting.
Multiple sclerosis meets marijuana. A new nationwide survey of Americans with multiple sclerosis highlights a pretty alarming treatment gap—one that’s being filled by marijuana. Almost half of survey respondents endorsed marijuana-based products, which they reported relying on to help manage the symptoms of nerve-based pain and sleep disturbances. Interestingly, the reported scores for perceived pain were generally worse among recent or current cannabis users, according to the findings.
If the survey results paint an accurate picture, it’s a deeply concerning one. A 2020 Gallup poll found that only 12% of US adults reported smoking marijuana. The fact that nearly five times as many adults with multiple sclerosis use the drug suggests that problematic symptoms are either going untreated or are not helped by current therapies. And despite increasing public support for the clinical use of cannabis, evidence supporting its benefits in treating pain and sleep disturbances in general is scarce, as are specific guidelines on its use. Let’s hope we find a solid science-based way to close the gap.
COVID-19’s silent neurological wave is coming. More and more evidence suggests that the downstream neurological effects of SARS-CoV-2 infection are no joke. It’s leading researchers to speculate that we’ll soon face a “silent wave” of neurological disease—one that looks less like a resurgence of coronavirus infections and more like a massive increase in viral-associated cases of Parkinson’s disease, seeded by neuroinflammation, triggered in the brain as a response to the virus.
The specific risk of this actually occurring remains hypothetical, but the concerns are real and are rooted in evidence. In fact, a similar long-term effect was seen after the Spanish Flu pandemic in 1918, when a form of brain inflammation called encephalitis lethargica increased the risk of parkinsonism by up to three times. “We can take insight from the neurological consequences that followed the Spanish Flu pandemic in 1918,” a Florey Institute researcher said. “Given that the world’s population has been hit again by a viral pandemic, it is very worrying indeed to consider the potential global increase of neurological diseases that could unfold down track. The world was caught off guard the first-time, but it doesn’t need to be again.”
Don’t let all the bad news get you down. Seriously, please don’t. Negative thinking will only make things worse, but you don’t have to take our word for it. A new study published in BMC Psychiatry empirically corroborates the theoretical relationship between subjective cognitive decline (SCD) and repetitive negative thinking (RNT).
In a cross-sectional survey, 491 older adults completed measures of RNT, personality traits, purpose in life, worry, rumination, and meditation practice. Researchers assessed SCD continuously via self-perceived cognitive function (Neuro-QoL) and categorically via endorsement of memory complaints. A total of 24% of respondents reported memory complaints, and in the final prediction models, RNT was the only psychological variable associated with lower self-perceived cognitive function and a higher likelihood of memory complaints. More studies are needed to establish whether RNT is a prodromal symptom or an independent risk factor, but in the meantime, doing your best to stay positive can’t hurt.
How prevalent is autism spectrum disorder in the US?
According to estimates from the CDC’s Autism and Developmental Disabilities Monitoring Network, about 1 in 54 children has been diagnosed with ASD. That’s up from 1 in 150 in 2000 and 1 in 88 in 2008, although we’re not sure if that represents an increase in prevalence or better detection. The disorder is four times more common among boys than girls.
Good news and bad news for transient ischemic stroke. We’ll start with the good news first. A 5-decade analysis of incidence trends of ischemic stroke after transient ischemic attack (TIA) finds that rates of post-TIA stroke have probably decreased slightly during the past 2 decades. Good stuff!
The bad news? A new study shows that TIA is associated with a high risk of early stroke. In a systematic review and meta-analysis of more than 206,000 patients in 68 studies across 5 decades, researchers found that the subsequent risk of ischemic stroke was 2.4% within 2 days, 3.8% within 7 days, 4.1% within 30 days, and 4.7% within 90 days. The incidence among the study population recruited before 1999 was significantly higher, leading researchers to postulate that overall rates may have declined. Adding to this, researchers found that comorbidities, including hypertension, diabetes, atrial fibrillation, and coronary heart disease substantially contribute to the risk of stroke recurrence and mortality. Awareness and proper management of these comorbidities—as well as the new data from this study—may lead to a better prognosis for patients with TIA.
Three new biomarkers for cerebral venous thrombosis. In experimental studies, researchers have found that inflammation might contribute to blood barrier disruption and brain injury in patients with cerebral venous thrombosis (CVT). If that’s the case, could blood biomarkers of inflammation be associated with the evolution of brain lesions, persistent venous occlusion, or functional outcome in these patients?
Here’s what the data say about that. Researchers performed an evaluation of neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) concentrations on peripheral blood samples in 62 patients with newly diagnosed CVT in a multicenter prospective cohort study. Additional quantification of IL-6 was performed at days 1, 3, and 8 in 35 patients and 22 healthy controls. They found that IL-6 levels were increased in patients with CVT with a peak at baseline. IL-6, NLR, and CRP levels were not related to brain lesion outcomes or early recanalization, but had significant association with unfavorable functional outcome at 90 days. Researchers found that IL-6 had the best discriminative capacity. Overall, the research suggests that increased baseline levels of NLR, CRP, and IL-6 may serve as new predictive markers of worse functional prognosis at 90 days in patients with CVT. Keep an eye on these blood biomarkers of inflammation.
Speeding up TBI diagnosis. A lot is at stake when a patient presents with a head injury. Determining whether it’s TBI depends on the Glasgow Coma Scale, in which physicians use their subjective judgement based on the patient’s ability to open their eyes, their verbal responses, and their ability to move in response to instructions. We could definitely use a more reliable method. Now we may have one, thanks to scientists at the University of Birmingham in the UK.
Using chemical biomarkers released by the brain immediately after a head injury occurs, researchers were able to pinpoint when patients needed urgent medical attention for TBI. They reported that the method saved time and avoided unnecessary tests. Here’s how it works: Using a spectroscopic technique called surface enhanced Raman scattering, researchers fire a beam of light at the biomarker, taken from a pinprick blood sample, which is inserted into an optofluidic chip, where blood plasma is separated. Light causes the biomarker to vibrate or rotate, giving an accurate indication of the degree of injury. It’s pretty high-tech stuff, and it’s on its way to market. Following results of a proof-of-concept study, researchers completed the iCURE commercialization program and are looking for commercialization partners across eight countries.
One drug, three neurological indications. Eton Pharmaceuticals recently submitted a New Drug Application (NDA) to the FDA for topiramate oral solution (ET-101), for not just one, not even two, but three indications—monotherapy for treatment of partial-onset or primary general tonic-clonic seizures in patients 2 years of age or older; adjunctive therapy for the treatment of partial-onset seizures, including seizures associated with Lennox-Gastaut syndrome in patients 2 years of age and older; and as preventive treatment of migraine in patients 12 years of age and older.
Currently, the drug is FDA-approved only in its tablet and capsule form, but the product is expected to be the first and only FDA-approved liquid formulation of topiramate, according to an Eton statement. “Topiramate is one of the most widely compounded oral liquids, and our product addresses the unmet need for pediatric-friendly formulations of the molecule. We look forward to working with the FDA to bring a safe, effective, FDA-approved product to patients and caregivers as quickly as possible,” a spokesperson said. Results are expected in early 2021.
An allele for Alzheimer’s. Right now, our best effort at Alzheimer’s drug discovery is to directly target the ß-amyloid (Aß) pathway. Clearly, though, that hasn’t been going very well. There have been no new treatments approved for Alzheimer’s disease years. So what else can we do? Researchers think there may be a new therapeutic target to slow Aß accumulation—the high prevalence of apolipoprotein E ε4 (APOE ε4) in Alzheimer’s disease. It’s easy to identify ε4 carriers (they make up two-thirds of patients with Alzheimer’s), which makes the APOE genotype and its corresponding protein (apoE) a pretty appealing target.
In a cross-sectional study that included 4,432 participants with a positive Aß level, researchers found that APOE ε2 was associated with a reduction in both the overall and age-dependent level of Aß in the presence of ε4, with Aß levels in the APOE ε24 group increasing at less than half the rate with respect to increasing age, compared with the APOE ε34 group. All told, the findings suggest that the protective outcome of carrying an ε2 allele in the presence of an ε4 against Aß accumulation could be important for new treatments, which could attempt to biochemically mimic the function of the ε2 allele in order to facilitate Aß clearance in ε4 carriers.
Suppressing MS symptoms sooner. That’s the promise of a potential new therapeutic modality identified by researchers at the University of Chicago Pritzker School of Molecular Engineering. The big idea? Fuse a cytokine to a blood protein. In mice, this combination prevented destructive immune cells from infiltrating the central nervous system and decreased the number of cells that play a role in the development of multiple sclerosis, leading to fewer symptoms and even disease prevention.
Several multiple sclerosis treatments sequester Th17 cells in the lymph nodes and prevent them from targeting tissues, but these drugs can have serious adverse events (and, as you read in our story on MS and marijuana, also leave much to be desired). Instead, researchers bound IL-4, an anti-inflammatory cytokine, to a blood protein and injected it into mice that had mouse models of multiple sclerosis. The result? Reduced infiltration of Th17 cells into the spinal cord, suppressed disease, and fewer symptoms. “This treatment could potentially be self-administered by MS patients at home with an injector pen,” a researcher said. “We think this is imminently translatable and could lead to better quality of life, with fewer symptoms, for those with the disease.” We’re a long way from the promised land, but there’s plenty of reason to be excited.
A treatment that crushes multiple sclerosis symptoms. Wouldn’t it be great if we had a multiple sclerosis treatment that could ease clinical symptoms while reducing inflammation, weight loss, and myelin loss? We do—but so far, it’s only been tested for these indications in mice. The treatment, human placental extract, is already in use in several Asian countries to treat a variety of other conditions. The treatments contain hundreds of compounds, including hormones, growth factors, immune signaling proteins, and amino acids.
Studies have suggested that these extracts have a broad range of biological activities that can modulate immune response, improve healing, and reduce inflammation. A team at the Iran University of Medical Sciences tested that hypothesis in mice with induced multiple sclerosis symptoms. In an analysis of the spinal cords at the study’s end, researchers found that mice treated with human placental extract showed significantly less demyelination and showed less weight loss over time. On top of that, there were no significant side effects noted during the treatment period. The fact that the study was conducted in mice means human placental extract is a long way from achieving the kind of validity needed for human use, but further research is warranted, and we’ll be there to let you know how it goes.
Perampanel for seizure control. Perampanel, also known by its brand name Fycompa, is adding more solid study results to its résumé, thanks to a new study published in Seizure. The study found that the drug demonstrated a strong efficacy and safety profile when used as a first add-on therapy in patients who didn’t respond to monotherapy.
In a study of 149 patients with a mean age of 41 years, 118 were still receiving perampanel as first add-on treatment after 12 months. Mean perampanel dose was 6.2 mg/day. At 12 months, 45.6% were seizure-free with an 84.6% response rate. Researchers identified a significant difference in seizure freedom rate between patients with idiopathic generalized epilepsy (IGE) and patients with focal epilepsy, but not in responders. What’s more, reduced seizure control was observed when perampanel was administered alongside strong enzyme-inducing anti-seizure drugs, but increased seizure control was seen when the same dose of perampanel was combined with enzyme-inhibiting anti-seizure drugs. Altogether, results demonstrated a solid efficacy and safety profile for this drug, which is already approved for partial seizures and as an add-on therapy for those with generalized onset tonic-clonic seizures.
New in Patient Management
Pushing QoL for Parkinson’s disease. They say art is good for the soul, but can it be good for the mind too? Quality of life (QoL) is a huge metric—one that often goes way down for patients with Parkinson’s disease. Between loss of control, declining independence, and, in many cases, isolation, things can get pretty rough. But a new lifestyle therapy addresses all three of these measures, and a new study suggests it can make a big difference. The therapy in question? Performing arts.
There’s been increasing interest in performing arts as a therapeutic medium in Parkinson’s disease, but little research into the matter until this new systematic review, published in BMC Neurology, reviewed its merit by measurements of QoL, functional communication, speech, motor function, and cognitive status. In the review, 56 studies, published from 1989 to 2020, including a total of 1,531 people with Parkinson’s from 12 countries, found a beneficial effect to four performing arts modalities—dance, singing, music therapy, and theatrical interventions. Until more research is conducted it’s not possible to say which modalities are most beneficial, but there’s nothing wrong with encouraging patients to sing and dance their hearts out in the meantime.
More on post-COVID-19 parkinsonism. Earlier we spotlighted increasing speculation that a “silent wave” of Parkinson’s disease could follow the coronavirus pandemic (See “COVID-19’s silent neurological wave is coming” above). New evidence suggests it may have already begun. In a new case study, researchers identified a patient with severe SARS-CoV-2 who acutely developed a hypokinetic-rigid syndrome, or parkinsonism, a rare disorder characterized by Parkinsonian features but secondary to conditions in addition to Parkinson’s disease that have different diagnostic criteria.
Pulling data from medical records from a hospital in Madrid, Spain, researchers examined a previously healthy 58-year-old man who developed hyposmia, generalized myoclonus, fluctuating and transient changes in level of consciousness, opsoclonus, and asymmetric hypokinetic-rigid syndrome with ocular abnormalities, all following infection with COVID-19. They confirmed a bilateral decrease in presynaptic dopamine uptake that asymmetrically involved both putamina. The good news? Significant improvement in the parkinsonian symptoms was observed without any specific treatment. The bad news? This case study provides clinical and functional neuroimaging evidence to support the hypothesis that SARS-CoV-2 gains access to the central nervous system, affecting midbrain structures and leading to neurological signs and symptoms.
Can’t we all just get along? According to a new study published in Neurology Clinical Practice, patients would be much happier if doctors did. The research focused on synchronous collaboration—defined by a simultaneous encounter between primary care providers (PCPs) patients, and neurologists—and found that it may significantly improve access to neurologic expertise, care value, and satisfaction of PCPs and patients.
In a series of synchronous collaborations and report outcomes in an outpatient collaborative primary care–neurology care model, scientists implemented synchronous video consultations and assessed PCP experience in a post-collaboration survey. In 58 synchronous encounters, the most common outcome was neurologists reassuring PCPs (40%) and patients (38%). Another benefit—test utilization was avoided in 40% of encounters. On the other hand, neurologists changed the treatment plan 40% of the time. Still, most PCPs said they were very satisfied with the ease of access and quality of care, and reported that they were likely to continue to use synchronous collaborations in the future. Go team!
Disease-modifying drugs and COVID-19 risk. Things change quickly with a novel virus like SARS-CoV-2, so what was true yesterday might not be true today. That seems to be the case when it comes to disease-modifying drugs (DMD), multiple sclerosis, and the risk of COVID-19 infection. Previously it was thought that DMDs may alter immune status and increase susceptibility to COVID-19 in patients with multiple sclerosis or neuromyelitis optica spectrum disorders (NMOSD). But a new survey published in Neuroimmunology & Neuroinflammation suggests that may not be true.
The survey, conducted through the Chinese Medical Network for Neuroinflammation, included patients in 10 multiple sclerosis centers from eight cities, including Wuhan, where the virus originated. Researchers found that 882 of 1,804 (48.89%) patients with multiple sclerosis and 2,129 of 3,060 (69.58%) patients with NMOSD were receiving DMDs without any alteration to their regimen from January 15 to March 15, 2020. None of the patients with MS treated with DMDs had COVID-19, while two patients with relapsing NMOSD were diagnosed with COVID-19-related pneumonia. After treatment, both patients recovered and neither experienced new attacks due to predisposing SARS-CoV-2 in the following 2 months. No increased risk of COVID-19 infection was observed in these patients, but neurologists may have had a hand in the measure—a battery of stringent preventive measures to reduce infection in these patients may have contributed to the low risk.
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