Can a deadly virus fight deadly brain tumors? Plus, eliminating Alzheimer’s; a vaccine for stroke; and more neuro news
Although this leap-year February is coming to a close, the output of new research in neurology is still going strong. Good thing we’ve got that extra day in February to catch up on the latest and greatest neuro news. Ready? This week, some tried-and-true therapeutics from across other specialties are getting a lot of airtime as researchers find they could provide applications for neurological diseases.
In 1988, Barry S. Fogel, MD, and Randolph Schiffer, MD, founded the American Neuropsychiatric Association (ANPA). The non-profit organization includes professionals from neuropsychiatry, behavioral neurology, and the clinical neurosciences. Its mission is to improve the lives of individuals with disorders “at the interface of psychiatry and neurology.”
In the News
Can statins do it all? Cardiovascular medications, including statins, may reduce the risk of Alzheimer disease by lowering arterial stiffness, increasing cerebral blood flow, and increasing clearance of beta-amyloids. Researchers found that patients who took medications for vascular conditions, including hypertension and hypercholesterolemia, had less beta-amyloid accumulation on PET. Vascular conditions are thought to contribute to the accumulation of beta-amyloids in the brain as well as cardiovascular disease, but previous researchers have failed to conclusively demonstrate the former.
These researchers assessed 215 cognitively healthy adults (mean age: 62.3 years). In all, 120 (56%) underwent PET, among whom 62% were not taking any vascular medications. In patients not taking vascular meds, the level of beta-amyloid deposits was higher on PET, which was associated with significantly higher total cholesterol and LDL levels, systolic blood pressure, and coronary risk profile scores. Researchers, however, found no statistically significant associations between vascular risk and beta-amyloid accumulation in those taking vascular medications. Statins, it seems, are great multitaskers. Now we can add neurological protection to their long list of benefits, which include activity against heart disease, cancer, liver disease, and inflammation. Let’s hear it for statins!
There’s more than one way to say it. By increasing cognitive reserve, bilingualism could delay the onset of Alzheimer disease (AD) symptoms in elderly patients (and no, medicine does not count as a second language). In the first study, to assess conversion time from mild cognitive impairment to AD in monolingual and bilingual individuals, researchers followed 158 patients with mild cognitive impairment. They wanted to see at what point a diagnosis changed from mild cognitive impairment to AD. For those who were bilingual, the conversion time was 1.8 years after their initial diagnosis, compared with 2.6 years for monolingual participants. While this sounds like it’s worse for bilinguals, it actually isn’t. Researchers found that bilingual patients had more neuropathology upon diagnosis of mild cognitive impairment compared with monolinguals, despite presenting with the same levels of cognitive function. So, although they progressed to AD faster, bilingual participants resisted AD longer than those who spoke only one language. Researchers concluded that bilinguals have a higher level of cognitive function due to their cognitive reserve.
Survival of the tallest? For men, being taller in young adulthood may lower the risk of dementia when they’re older, even after adjusting for education and intelligence. To reach this conclusion, researchers analyzed data from 666,333 Danish men, including 70,608 brothers and 7,388 twins, from Danish national registries. In all, 10,599 men developed dementia in later life. Researchers found that for every 6 cm of height over average height (which for Danish men, is 5 feet, 11.40 inches), men had a 10% reduction in their risk of developing dementia. Even after taking factors like intelligence and education into account, the reduction held. It also held when researchers looked at brothers of differing height, which suggests that genetics alone may not fully explain why shorter men have greater risk for dementia. Height linked to dementia risk? Who knew?
This time, don’t use your head. Subconcussive head impacts are no good for you—neurologically or neuro-ophthalmologically. (No surprises here!) In fact, researchers have now shown that heading a soccer ball may affect neuro-ophthalmologic function. They studied 67 soccer players (mean age: 20.6 years) who were randomized to either a heading group or a kicking group. Headers executed 10 soccer ball headers, which were projected at a speed of 25 mph. Kickers executed 10 soccer ball kicks. Using a triaxial accelerometer, researchers assessed peak linear and rotational head accelerations, and oculomotor function; and measured neuro-ophthalmologic function with the King-Devick test (KDT). Headers showed a mean peak linear acceleration and peak rotational acceleration per impact of 33.2 and 3.6 krad/s2, respectively. Kickers had no detectable levels of head acceleration. KDT speeds measuring neuro-ophthalmologic function gradually improved from 0 to 24 hours in both groups, but this improvement was faster in the kickers at all time points (0, 2, and 24 hours). Although researchers have come at this from a neurological perspective, this is the first study to examine it from a neuro-ophthalmologic point of view.
Which disorder mixes up sensory input, such that those afflicted can “see” sounds and “hear” colors?
Synesthesia is a condition in which one sense is simultaneously perceived by one or more additional senses. People with synesthesia can see sounds, taste words, or even feel certain smells on their skin. They may also “see” abstract constructs such as time projected in the space around them. One form of synesthesia causes people to connect things like letters, shapes, or names with a sensory perception like smell, flavor, or color. Once thought to be rare, synesthesia is now known to affect about 4% of the general population and tends to be genetic. People with synesthesia are called “synesthetes.”
Blood test for dementia and PD? A simple blood test for biomarkers of inflammation and cell senescence could reliably predict cognitive decline. It may also help to identify people who may be at risk for early dementia and those with Parkinson disease (PD) at risk for motor progression. PD and inflammation are known to be close bedfellows, and previous researchers have shown that a pro-inflammatory serum profile can predict more rapid clinical progression.
Researchers of the Cognitive Impairments in Cohorts with Longitudinal Evaluation-Parkinson Disease (ICICLE-PD) study followed 150 patients with newly diagnosed PD and 99 controls for 36 months. After analyzing cellular senescence markers (like telomere length, and p16 and p21 expression) and inflammatory markers in the blood, they found that patients with PD had shorter telomeres both at baseline and 18 months later compared with controls. Patients who developed dementia after 3 years had significant shorter telomeres compared with those with no dementia. In addition, higher baseline p16 levels were associated with quicker motor and cognitive decline. Finally, researchers found that inflammatory scores at baseline were the best predictors of cognitive scores at 3 years in patients with PD. These markers need further study, but how great would it be to have a simple blood test to help manage and treat your patients with newly diagnosed PD?
A tale of two diseases. Can one of the world’s deadliest viruses actually be beneficial? A recently published studyfound that Ebola virus may be useful in treating one of the world’s deadliest brain cancers: glioblastoma. Researchers took advantage of one of the weaknesses of most cancer tumors—the inability to generate an innate immune response against viruses—and ran with it. Because viruses can expose patients to dangerous infections, the researchers used chimeric viruses or a combination of genes from multiple viruses, which can target cancer cells without harming patients. They used a chimeric virus with one Ebola virus gene—a glycoprotein with a mucin-line domain (MLD). MLD can hide Ebola from the immune system and protect normal cells from infection. When injected into the brains of mice with glioblastoma, the MLD helped to selectively target and kill glioblastoma tumors. Researchers hope to one day use Ebola virus in conjunction with surgery to eliminate and prevent the recurrence of glioblastomas. Talk about thinking outside the box!
New target for AD treatment. Preventing the pathological changes that occur in mild cognitive impairment, often a precursor to Alzheimer disease (AD), may help eliminate AD, once and for all! Researchers used a new biomarker—pSer46-MARCKS—to detect degenerative neurites surrounding dying neurons. This is a game changer because, currently, neuronal death is difficult to detect in real time—dying cells cannot be stained chemically or immunohistologically. The new biomarker gave researchers the ability to quantify cell necrosis at different stages of AD. And, surprisingly, they found that patients with mild cognitive impairment had much higher levels of necrosis than those with full-blown AD. In addition, neuronal death occurred earlier than thought. In yet another mind-blowing discovery, these researchers demonstrated that neuronal necrosis was dependent on YAP, a protein. By injecting mice with YAP—a protein with positive effects on neuronal necrosis—they found that they could prevent early-stage neuron loss, restore cognitive function, and prevent the formation of beta-amyloid plaques. Their discoveries have paved the way for new AD treatments that could prevent this leading cause of dementia. We say, the more the merrier!
Double threat for low-grade gliomas? Low-grade pediatric gliomas beware! Researchers from Johns Hopkins Kimmel Cancer Center have found—in laboratory models—that combining an experimental cancer medication (TAK228, or sapanisertib) with trametinib could be more effective than either drug used alone to decrease the growth of gliomas—the most common childhood neurological tumor. TAK228/sapanisertib is an mTOR pathway inhibitor and is currently in clinical trials. Trametinib is a MAPK pathway inhibitor approved for the treatment of melanoma. Mutations that increase the activity of both of these cell-signaling pathways have been implicated in pediatric low-grade gliomas. In mice, this combo therapy reduced tumor volume, decreased blood flow to the tumors, and increased survival. When researchers studied TAK228 and trametinib in patient-derived, pediatric, low-grade glioma cell lines grown in the lab, they found that combination therapy reduced tumor cell growth by 50%, suppressed mTOR and MAPK activity by over 50%, and reduced cell proliferation by over 90%. The researchers also saw a three-fold increase in the number of cancer cells killed compared with each agent used alone. Although much more preclinical work is needed, researchers are hopeful that the combination therapy may be a new treatment option for gliomas.
An “aha” moment for medulloblastoma. Over at the University of Virginia School of Medicine, researchers have found that medulloblastoma tumor cells may have the ability to turn into tumor-associated astrocytes, and then hijack microglia for the benefit of the tumor. By doing so, they force the microglia to produce insulin-like growth factor 1 (IGF1) that’s used for tumor proliferation. Medulloblastoma was previously thought to be a relatively simple cancer, but evidence of this complex process to drive growth opens the door to many potential treatments that could stop its progression. Researchers are now pondering how to reduce IGF1 production via these microglia. They’re also studying how to activate the microglia to attack the tumors or recruit T and B cells into the tumor to fight it. So many potential therapeutic targets from this one discovery! And not just for medulloblastoma—but other cancer types as well.
And now for something totally new. The FDA has approved lumateperone (Caplyta), an oral antipsychotic medication, for the treatment of schizophrenia in adults. Unlike many recent second-generation antipsychotics, which act on only serotonin and dopamine receptors, lumateperone acts on those receptors plus glutamate receptors. Lumateperone’s unique effects on the glutamate receptors is a novel characteristic that may give current research of antipsychotic medications a new boost and a new direction. Labeling includes a boxed warning that treatment with antipsychotics increases risk of death in older patients with dementia-related psychosis. Lumateperone is not approved for the treatment of patients with dementia-related psychosis.
New in Patient Management
Shingles vaccine for stroke? A type of shingles vaccination—zoster vaccine live—could have preventive effects against stroke in older adults, according to preliminary research being presented at the American Stroke Association’s International Stroke Conference 2020. Researchers reviewed Medicare records of over 1 million Medicare beneficiaries aged 66 years and older with no history of stroke who received the zoster vaccine live between 2008 and 2014. They matched them with controls who did not receive the vaccine, and followed them for nearly 4 years. Receiving the shingles vaccine lowered the risk of stroke by roughly 16%, lowered the risk of ischemic stroke by about 18%, and lowered the risk of hemorrhagic stroke by about 12%. The greatest protective benefits were seen in those aged 66 to 79 years. In those over 80 years of age, the risk of stroke was reduced by about 10%, compared with 20% in those younger than 80 years. Researchers postulated that the cause of increased stroke risk after shingles infection may be the inflammation caused by the virus. The newest shingles vaccine—adjuvanted, non-live recombinant shingles vaccine—could afford even greater protection against stroke. A simple vaccine to reduce the risk of both shingles and stroke? Wünderbar!
Wearable tech preferred. Wearable tech should replace motor diaries to track motor fluctuations in patients with Parkinson disease (PD), researchers concluded. The need for data in these patients is critical to not only effectively manage the disease, but also to develop new therapies. Technology helps capture accurate data in large quantities. The current standard for identifying and monitoring motor and nonmotor fluctuations in patients with PD remains to be questionnaires and motor diaries. But there are concerns about the accuracy and reliability of these measures due to the effects of fatigue on patient adherence, recall bias, limited time resolution, and inability to identify the severity of impairments and magnitudes of improvements in response to treatment.
Thus, researchers studied 95 patients with PD and 60 healthy controls who were asked to record their activities and symptoms in electronic diaries. A full 38% of participants missed 25% of possible entries. Their entries were often made hours after the events occurred, leading to 35% false negatives and 15% false positives. These results put an emphasis on the need for objective, high-resolution, continuous monitoring via wearable technologies to improve the monitoring of PD symptoms. Encourage your patients with PD to go high-tech.
A double whammy. After a stroke, one in five survivors suffer from anxiety. Researchers conducted a review of nearly 100 global studies that included 22,262 stroke survivors from 34 countries. They found that almost 20% of survivors were given a diagnosis of anxiety. Although the manifestation of depression after a stroke has been well documented and addressed in the literature, the problem of anxiety has not. These results confirm that anxiety is common after stroke and is a call for clinicians to be vigilant of symptoms of anxiety in their patients recovering from stroke.
New AAN guideline issued. Ah, a good night’s sleep. Is anything more important? Children and teens with autism spectrum disorder often struggle with sleep, having problems falling asleep, staying asleep, or simply refusing to go to sleep. These sleep problems are common and can cause poor health and quality of life. The American Academy of Neurology (AAN) has issued a new guideline for sleep problems in children and teens with autism. The guideline addressed refusing to go to bed, trouble falling asleep and staying asleep, not getting enough total sleep each night, and daytime behavior problems associated with insufficient nighttime sleep. It provides a basis for clinicians to identify the causes of sleep problems (medications, medical conditions, or behavioral). Behavioral strategies are offered, but if these are not enough, melatonin is recommended. The guideline is endorsed by the American Academy of Sleep Medicine, Autism Speaks, the Child Neurology Society, and the Society for Developmental and Behavioral Pediatrics.
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Upcoming Medical Meetings
5th Annual Americas Committee for Treatment and Research in Multiple Sclerosis Forum (ACTRIMS 2020), in West Palm Beach, FL, February 27-29, 2020
American Society for Experimental Neurotherapeutics (ASENT) 2020 Annual Meeting , in Bethesda, MD, March 2-5, 2020
Multidisciplinary Neuro-Oncology Symposium: Updates in Medical and Surgical Management of Brain Tumors 2020, in Orlando, FL, March 6-7, 2020
North American Neuro-Ophthalmology Society (NANOS) 2020 Annual Meeting, in Amelia Island, FL, March 7-12