New COVID-19/neuro link, vitamin fights deadly brain cancer, and…common meds lead to Parkinson’s?
As the United States struggles under the weight of the COVID-19 pandemic, researchers fight to get ahead of the virus. It seems, almost daily, they are discovering new things about the virus that could lead to viable therapeutic options. Similarly, researchers in the field of neuroscience seem to constantly be making headway in their discoveries about neurological disorders, associated risk factors for development, and treatment options.
CSF levels and autism. In April 2017—only 3 years ago—researchers with the Brain Imaging Study Network, funded by the NIH, found a link between the amount of cerebrospinal fluid (CSF) in the body and autism. Specifically, they found greater quantities of CSF in 2-year-olds with newly diagnosed autism than non-autistic children of the same age. In addition, the greater the increase in CSF, the greater the severity of autistic symptoms. Extra-axial CSF volume at 6 months predicted which high-risk infants would develop autism spectrum disorders at 24 months, with an overall accuracy of 69% and corresponding 66% sensitivity and 68% specificity.
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Weathering the COVID-19 storm. The first case of COVID-19–associated acute necrotizing hemorrhagic encephalopathy has been documented by researchers from the Henry Ford Health System. Acute necrotizing encephalopathy is a known complication of viral infections, including the flu, and can break down the blood-brain barrier. The encephalopathy may have been caused by cytokine storm syndrome—the body’s overproduction of immune cells to fight an infection or cancer. According to researchers from China, cytokine storm syndrome has occurred in some patients with COVID-19.
The patient was a female airline worker who presented with a 3-day history of cough, fever, and altered mental state (ie, confusion, lethargy, and disorientation). The patient, in her late 50s, was given a diagnosis of COVID-19 via nasal swab and RT-PCR assay. On CT imaging, researchers found symmetric hypoattenuation within the bilateral medial thalami. CT angiograms and venograms were normal. MRI revealed T2-weight and fluid-attenuated inversion recovery (FLAIR) hyperintensity in the bilateral thalami, medial temporal lobes, and subinsular regions with hemorrhage. Postcontrast images showed rim enhancement as well.
The most characteristic imaging features of cytokine storm syndrome are symmetric, multifocal lesions with invariable thalamic involvement, according to the researchers. The brain stem, cerebral white matter, and cerebellum are often involved as well. Clinicians should be alert and watch for this condition in patients with COVID-19 who present with altered mental status, they warned.
Psychedelic revolution: Part 2? There’s a new movement afoot to revisit the use of psychedelic drugs like LSD and psilocybin for treatment of psychiatric disorders. In a commentary published in Cell, authors from the Imperial College London argue that brain imaging has given new insights into how these psychedelic drugs act on different areas of the brain. We now know that these drugs have powerful neuroplastic effects that can bring about long-term changes that may be beneficial in treating psychiatric disorders. In fact, researchers are now testing the safety and efficacy of psilocybin for recalcitrant depression, which has been granted breakthrough therapy designation by the FDA. Researchers have also set their sights on studying psilocybin for obsessive-compulsive disorder.
The activity of psychedelics is mediated through 5-HT2A receptor cells. Researchers say the war on drugs has discouraged the use and study of these drugs, which showed a lot of early potential, especially in treating alcoholism. They argue that it’s time to revisit these drugs in hopes of unlocking their potential to treat many psychiatric illnesses.
An Alzheimer gene? For the first time, researchers have identified two mutations in the endothelin-converting enzyme 2 (ECE2) gene that may increase the risk of Alzheimer disease (AD). The mutations hurt the gene’s ability to break down amyloid beta protein—a protein found more often in people with AD, making it a unique, defining characteristic of the condition. The researchers theorize that preventing or just mitigating amyloid beta protein build-up could prevent or treat AD.
In murine models, mice with the ECE2 mutations had increased amyloid beta protein levels and formed more plaques. Some even had memory loss, a sign of AD. On the flip side, mice given the nonmutated ECE2 gene had decreased amyloid beta protein levels, and some recovered learning and memory deficits. Maybe in the future, targeting this gene and increasing its expression could be a way to treat AD
Dirty air and dementia. Would you believe us if we told you that continuously breathing polluted air may up your risk of dementia—by as much as 50%—, especially if you have cardiovascular disease (CVD)? That’s exactly what researchers from The Karolinska Institutet in Sweden found after following nearly 3,000 adults (mean age: 74 years) living in central Stockholm for up to 11 years. For every interquartile range difference in mean PM2.5—the annual average level of particular matter 2.5 microns or less in width—the risk of dementia increased by over 50% for the last 5 years of exposure. Furthermore, the risk increased by 14% per interquartile range difference in nitrogen oxide as well. What’s good is that earlier life exposures had less impact on the risk of dementia.
Researchers also found that ischemic heart disease and heart failure also increased the risk of dementia, and stroke accounted for nearly 50% of air-pollution related dementia cases. Air pollution’s effects on cognition are probably indirect, they say, and the most likely link may be cardiovascular health; CVD increases the rate of cognitive decline. CVD and dementia? All the more reason to push for cleaner air.
Which part of the brain is named after its resemblance to a seahorse?
The hippocampus derived its name from the Greek hippocampus (hippo meaning “horse” and kampos meaning “sea monster” because, structurally, it resembles a sea horse). Located in the medial region of the temporal lobe, it forms part of the limbic system, a cortical region responsible for regulating emotion, motivation, learning, and memory. The role of the hippocampus is somewhat debated; some believe it’s involved in storing long-term memories while others think it may play a role in spatial processing and navigation.
Quick and easy diagnosis of OPMD. Diagnosis of oculopharyngeal muscular dystrophy (OPMD) is often difficult, so it’s great that researchers from Italy have found that measuring the accumulation of insoluble PABPN1 muscle fiber nuclei in these patients can lead to an accurate and quick diagnosis. They used immunofluorescence to study muscle biopsies from 423 adults with OPMD. Thirty were from patients with genetically proven OPMD; 30 from those not affected by a neuromuscular disorder; 220 from patients with non-specific muscle disease who presented with ptosis or difficulties swallowing, progressive lower proximal weakness or isolated rimmed vacuoles at muscle biopsy; and 143 from those affected by other neuromuscular diseases. Detecting insoluble nuclear PABPN1 accumulations was fast, had 100% sensitivity, and 96% specificity. Researchers were able to discover 23 new cases of OPMD among the 220 patients with non-specific disease.
Vitamin promises. Could a simple vitamin be effective against glioblastoma, the bad boy of neurologic cancers? Niacin—aka vitamin B3—combined with chemotherapy could give much needed support to immune cells attacking glioblastoma. In preclinical trials, this combination dramatically slowed the progression of glioblastoma. In mice with glioblastoma treated with the combo therapy, lifespan increased more than three-fold, from 40 days to 150 days. What’s more, even niacin alone lengthened survival. Glioblastoma basically hijacks the immune system, suppressing it and “convincing” immune cells to work in tandem with tumors instead of against them.
Researchers from the University of Calgary explained that since glioblastoma tumor stem cells are resistant to treatment, the research group chose to target the immune system instead. When given in combination with a temozolomide chemo regimen, niacin lengthened survival via immune cell stimulation and reeducation. In short, it “convinced” immune cells to do what they’re supposed to do—attack and kill tumor stem cells. Niacin was chosen after researchers screened 1,040 compounds because it had what it takes to activate myeloid cells and inhibit the growth of brain-tumor initiating stem cells. Researchers have gotten the go-ahead for a clinical trial and are hopeful for positive results, especially since niacin and temozolomide are both well-known treatments.
PROMISE-2 promising for migraine prevention. A new treatment to prevent migraines? We have it! In February of this year, eptinezumab—a humanized anti-calcitonin gene related peptide monoclonal antibody—became the first FDA-approved IV medication for migraine prevention. Researchers studied eptinezumab in the Prevention of Migraine via IV ALD403 Safety and Efficacy-2 (PROMISE-2) multicenter, randomized, double-blind, placebo-controlled, parallel-group study. After just one dose of intravenous eptinezumab (100 or 300 mg), patients with chronic migraine had greater and significant reductions in monthly migraine days from week 1 to 12 compared with placebo. Treatment-emergent adverse events were common (43.5%), but nasopharyngitis was the only one reported for more than 2% of patients treated with the 300-mg dose. Put that in your doctor’s bag and use it!
More migraine prevention. And speaking of migraine prevention, multiple cranial nerve blocks (MCNBs) may be an alternative preventive option for your patients. In a small, single-center study, researchers found that about 66% of patients with chronic migraine or chronic migraine with aura responded to MCNBs with at least a 30% reduction in headache days. Patients had either repetitive occipital nerve blocks or occipital and trigeminal nerve blocks. The MCNBs also had great staying power, lasting for a mean of 5.7 weeks. Another new option to add to your migraine armamentarium!
Small but mighty. Treating patients with late-onset myasthenia gravis is a bit different that treating younger patients, what with the comorbidities and the risks posed by immunotherapy. So, researchers set out to determine the safety of rituximab, a chimeric monoclonal antibody used to treat rheumatoid arthritis and B-cell non-Hodgkin lymphoma, in older patients. They studied a retrospective series of seven patients with late-onset myasthenia gravis, with a mean age of onset of 66 years of age. Three patients didn’t respond to previous therapy, and six had side effects to prednisone. All were treated with at least one dose of rituximab, and were able to reduce or even discontinue their maintenance medications. Importantly, no significant adverse events were seen. But, the study was small, and more studies are needed.
New in Patient Management
Say ‘no’ to that second drink? Unfortunately, if you’re a woman, that extra martini will not lower your risk of Parkinson disease (PD)—at least according to researchers of the Million Women Study, who found no association between alcohol intake and the risk of PD in women.
Results from previous studies on the effects of alcohol on PD were mixed, like a good cocktail. Some had suggested that increasing alcohol intake may be slightly protective and lower the risk of PD, while other studies found no such protective effect. To put the debate to rest, UK researchers studied data on alcohol intake, lifestyle factors, and medical history from 1.3 million women (mean age: 56 years) in the United Kingdom. After 17.9 years of follow-up, there were no differences in the development of PD between women who drank more than 14 alcoholic beverages/week and those who drank only 1 to 2 alcoholic beverages/week. On the bright side, increased alcohol intake did not seem to increase the risk of PD.
Too many trips to the ER. Many adults with cerebral palsy require hospitalization more than once a year; these patients also use acute inpatient services for emergency healthcare rather than for planned care, according to a recent study. Researchers assessed 5 years of data and identified 2,922 hospital admission among people with cerebral palsy. Of these, 29% constituted adult admissions. Adult hospitalizations were primarily for respiratory illnesses and gastrostomy dysfunction. Although children were more frequently hospitalized, lengths of stay were longer for adults.
More proof of the gut-brain connection. Could it be that some of the most useful and commonly used medicines in the world predispose people to developing Parkinson disease (PD)? It’s true, according to researchers from the University of Helsinki, who found that certain antibiotics may be associated with an increased risk of PD. They assessed the effect of prior antibiotic exposure on PD risk via conditional logistic regression in a nationwide, register-based, case-control study. After comparing antibiotics taken by 13,976 patients with PD and 40,697 controls, they found the strongest association between increased PD risk and exposure to macrolides and lincosamides. Importantly, these associations were there even though these antibiotics were taken many, many years before the study.
There were also positive associations between elevated PD risk and the use of the following antibiotics: anti-anaerobics and tetracycline 10 to 15 years before the study, sulfonamides and trimethoprim 1 to 5 years before, and antifungal medications 1 to 5 years before. As if that weren’t enough, they found further positive association with broad-spectrum antibiotics in a post hoc analysis. These results lend even more credence to the gut-brain connection. The researchers concluded: “The pattern of associations supports the hypothesis that effects on gut microbiota could link antibiotics to PD, but further studies are needed to confirm this.”
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Upcoming Medical Meetings
Please note that, in the interests of containing the current COVID-19 pandemic, the following meetings have been cancelled. Please contact these organizations for details and specifics on refunds and rescheduling:
World of Neurosurgery: American Association of Neurological Surgeons (AANS) 2020 Annual Scientific Meeting, in Boston, MA, April 25-29, 2020.
American Academy of Neurology 71st Annual Meeting (AAN 2020), in Toronto, ON, Canada, April 25-May 1, 2020.
The following conference has not yet been cancelled. Please check website for up-to-the-minute information:
The 24th Annual Children’s Neuroscience Symposium, in Phoenix, AZ, March 20-21, 2020.