Magic mushrooms for brain pain, new tech eases diagnosis for several neurological conditions, and a new link between PD and affective disorders

Psychedelics are emerging as a promising treatment for PTSD, and this week, we could be adding migraines to magic mushrooms’ list of new disease targets. It still makes sense to go with tried and true migraine therapies, though, because new research indicates one of the old standards could bring a side effect that might just save your life in the long run.

Neuro Flashback

Ever wonder who tops the list of coolest neurologists of all time? There are plenty of dashing doctors out there, but our vote goes to Oliver Sacks. Born in England to a surgeon mother and general practitioner father, Sacks moved to New York in 1965, where he practiced as a neurologist and was a prolific writer until his death in 2015. His accomplishments are too long to recap in a paragraph, but suffice it to say that if anything cool happened in the field of neurology between 1965 and 2015, there’s a good chance Dr. Sacks was involved. He may be best known for his ability to bring the complexities of neurology to the masses as a frequent contributor to The New Yorker and the author of 16 books. Still doubt he’s a cool guy? Check out the cover of his autobiography.

In the News

Another way to prevent migraines—open your mind. Sure, you can stay away from the culprit foods if you want to avoid triggering a migraine, but a new exploratory study suggests there’s also a far-out food that can help reduce the frequency of migraines: Magic mushrooms and their psychoactive ingredient, psilocybin. Side effects may include some audio-visual hallucinations.

The first-of-its-kind research, which was published in the journal Neurotherapeutics, was led by researchers at Yale School of Medicine and involved a double-blind, placebo-controlled cross-over study on the effects of a moderate psilocybin dose on migraine frequency and severity. Ten migraineurs took part in two sessions—one involving a dose of psilocybin and one involving a placebo. While the research is preliminary, its findings were surprising. During the two-week study period, the psilocybin appeared to reduce the number of migraines experienced by roughly 50%. In addition, any migraine experience during that period was around 30% less painful and debilitating. While more research is required to learn more about how psychedelic trips may help in the treatment of cluster headaches, the recent findings are certainly worth a deeper dive.

Brain protection from the gut. A new study has shown that, during multiple sclerosis flare-ups, the body’s defense system is bolstered by antibodies from a surprising place: The digestive system. The research, which was published in Science Immunology, found evidence that immune cells leave the gut and travel to the brain during multiple sclerosis relapses and help to push the symptoms into remission, adding to mounting evidence that suggests that the gut and its mind-boggling microbiome can affect just about everything. 

The cells in question express an antibody called IgA, which typically acts as a defense against foreign invaders and helps regulate the bacteria in our digestive microbiome. The recently published research, which was conducted by scientists in Canada, Germany, Sweden, and Switzerland, was the first to show that traces of the IgA antibody appear in the CSF of MS patients during flare-ups. The team also investigated which kinds of molecules the antibody reacted to. They found that the IgA was binding to harmful bacteria, which suggests that gut immune cells serve in a protective capacity with regard to MS. These findings align with other recent research, which highlights the dangerous role an unhealthy gut can play in multiple sclerosis.

If you want to go far, go together. Stress has been reported to trigger strokes, and there may be no greater stress than losing a spouse. According to a new study, the bereaved may in fact be at a higher risk of experiencing both ischemic stroke and intracerebral hemorrhage.

The study, which was published in the Journal of the American Heart Association, looked at all Danish people (roughly 280,000 individuals) who had lost a partner between 2002-2016, alongside a reference group. Over a 5-year study period, researchers found that 7,684 people had a stroke (aHR, 1.11 when compared with non-bereaved referents) and 1,139 experienced a brain hemorrhage (aHR, 1.13). In absolute numbers, the incidence of stroke at 30 days was 0.73 per 1000 people in bereaved individuals vs 0.63 in the reference group. Likewise, the incidence of brain hemorrhage at 30 days was 0.13 per 1000 in bereaved individuals vs 0.08 in those not bereaved. Researchers concluded that there are significant associations between partner bereavement and the risk of both having a stroke and brain hemorrhage, particularly in the short term. A broken heart may be a predictor of more pain to come.

Food and drink that don’t mix with migraines. Maybe you’ve found yourself in the midst of an intense headache, wondering if maybe the third cup of coffee you had that morning was the culprit. Well, according to a neurologist, you may be right. A recent article, which was medically reviewed by a California-based pain management specialist and medical director, provides a list of eight foods and drinks that are common migraine triggers, citing various studies.

Migraines impact a ton of people—more than one billion worldwide, including 39 million Americans. But there are a number of foods and beverages that lower the brain’s threshold to migraines. One of the key culprits is red wine, the imbibing of which can prompt the creation of inflammatory neurotransmitters, which make blood vessels around the brain dilate and result in nerve endings sending signals back to the brain that produce symptoms like pain, sensitivity to light, and nausea. Other possible migraine triggers include caffeine, cold cuts (tasty but also carcinogenic!), aged cheese, and chocolate.

Neuro Trivia

Which famous neurologist was given the title of “poet laureate of medicine” by The New York Times?

The one and only Oliver Sacks.

Novel Diagnostics

Weak magnetic brain signal, strong diagnostic potential. The brain is such a complex and extraordinary place that even its weakest signals contain the possibility of holding the next big neurological breakthrough. These weak signals are exactly where scientists at the University of Birmingham in the UK are hoping to detect signs of traumatic brain injury, dementia, and schizophrenia with newly developed sensors used in magnetoencephalography (MEG). The sensors use polarized light to detect changes in the orientation of the spin of atoms when exposed to a magnetic field.

Existing MEG sensors must be kept at constant cool temperatures, which requires bulky helium-cooling systems. That means they have to be arranged in a rigid helmet that doesn’t fit differently sized and shaped heads. They also require a zero-magnetic field environment to be able to pick up brain signals. But in recent tests, the new stand-alone sensors don’t require these conditions—plus, their performance surpasses existing sensors, discriminating between background magnetic fields and brain activity. “We know that early diagnosis improves outcomes, and this technology could provide the sensitivity to detect the earliest changes in brain activity in conditions like schizophrenia, dementia, and ADHD,” one study author said. “It also has immediate clinical relevance.” Investigators are currently working with clinicians to investigate its use in pinpointing the site of traumatic brain injuries.

Biomarkers and Down’s syndrome. One reason for the high incidence of Alzheimer’s disease in people with Down’s syndrome is that the gene coding for the production of amyloid is located on chromosome 21, of which people with Down’s syndrome have an extra copy. In previous studies, researchers have found that pathological forms of amyloid and tau can appear years before someone with Down’s syndrome shows signs of dementia. Now, researchers are studying the extent and distribution of tau and amyloid in the brain tissue of people with Down’s with or without an Alzheimer’s diagnosis in an effort to move toward earlier Alzheimer’s diagnosis for all patients.

Their analysis showed that the incidence of tau in the brain tissue of people with Down’s syndrome and Alzheimer’s disease was higher than in people who had Alzheimer’s but didn’t have Down’s syndrome. That suggests that tau is an early change in Down’s syndrome. Researchers also discovered that traces of tau could be detected in the brain tissues of fetuses with Down’s syndrome, suggesting that early prophylactic measures against tau accumulation could prevent the development of Alzheimer’s pathology in childhood. These new developments bring us a step closer to earlier diagnosis of Alzheimer’s—one of the most pressing needs in neurology.

Finding Parkinson’s in an unl-eye-kely place. To take your mind off of that terrible attempt at a pun, remember that 3 weeks ago we brought you news about an exciting new development: The eyes could be a promising new window into the risk of Parkinson’s disease. The research suggested that patients with Parkinson’s showed significant difference in several metrics as measured by optical coherence tomography. This week, we’re buttressing those findings with some new ones: A simple fundus eye exam combined with a powerful artificial intelligence (AI) machine learning technology could also provide early detection of Parkinson’s, according to new research presented at the annual meeting of the Radiological Society of North America.

Currently, we typically diagnose Parkinson’s via its motor symptoms, which only arrive after significant injury to dopaminergic neurons. This new technique, on the other hand, relies on support vector machine learning—a technique available since 1989—to classify Parkinson’s disease based on retina vasculature, with the key features being smaller blood vessels. The approach is much cheaper than traditional imaging approaches with MRI, CT, and nuclear medicine techniques, which can be very costly. In fact, this method relies on simple photos that can be captured by a smartphone with a special lens. “If we can make this a yearly screening, then the hope is that we can catch more cases sooner, which can help us better understand the disease and find a cure or a way to slow the progression,” researchers said.

A maternal biomarker for cerebral palsy. Scientists have pinned down a better way to predict cerebral palsy—as early as the first trimester of pregnancy. To investigate whether combined first-trimester screening (cFTS) biomarkers are associated with cerebral palsy, researchers matched mothers of 435 singleton children born with cerebral palsy from a population registry to the cFTS records and selected 10 singly-born pregnancy controls per case. Then, they compared mean and abnormal levels of pregnancy-associated plasma protein A (PAPP-A), beta subunit of human chorionic gonadotropin (ß-hCG), and nuchal translucency between cases and controls and between cerebral palsy subgroups.

Compared with control pregnancies, cerebral palsy pregnancies had lower mean levels of PAPP-A (0.95 vs 1.01) and ß-hCG (0.93 vs 0.99). Biomarker levels in cerebral palsy pregnancies were 1.8 times more likely to be associated with abnormally low levels of PAPP-A, 1.4 times for ß-hCG, and 2.6 times for low PAPP-A and ß-hCG together. In cases with CP, an abnormally low PAPP-A level was associated with a moderate preterm birth and low Apgar scores. Low ß-hCG, on the other hand, was associated with very low birth weight. All told, researchers found that low first-trimester biomarker levels suggest a role for early pregnancy factors in some causal pathways to cerebral palsy.

Novel Treatments

Get excited for reduced excitability. Cortical and spinal motor neuron excitability—or, the ability to generate a large, rapid change of membrane voltage in response to a small stimulus—is increased in patients with amyotrophic lateral sclerosis (ALS). That’s not a good thing. We need treatments to reduce that excitability. Enter ezogabine, an anticonvulsant used as an adjunctive treatment for partial epilepsies in treatment-experienced adult patients.

In a new study published in JAMA Network, researchers tested whether ezogabine could reduce cortical and spinal motor neuron excitability in 65 patients with ALS, and found that it reduced both in a dose-dependent manner. These 65 patients were randomized to placebo (23), 600 mg/d of ezogabine (23), and 900 mg/d ezogabine (19). The change in short-interval intracortical inhibition (SICI–1) increased by 53% in the 900-mg/d ezogabine group vs placebo group, but the SICI–1 did not change in the 600-mg/d ezogabine group vs placebo. Alternatively, the resting motor threshold increased in the 600-mg/d ezogabine group vs placebo, but not the 900-mg/d ezogabine group. Ezogabine caused a dose-dependent decrease in excitability by several other metrics, including strength-duration time constant in the 900-mg/d ezogabine group vs placebo. All told, ezogabine decreased cortical and spinal motor neuron excitability in participants with ALS, suggesting that these neurophysiological metrics may be used as pharmacodynamic biomarkers in future trials.

Putting severe nausea to good use. Nausea is one of the most common side effects of drugs, and erenumab, a proven treatment for migraine, is no exception. But in a clever twist of fate, researchers have figured out a way to turn erenumab-induced nausea into a positive—it may be able to help people quit smoking.

In a new multicenter retrospective review, researchers looked at three cases of patients who were suffering from chronic migraine, resistant to multiple preventive therapies, and also smokers. Each was prescribed monthly injections of erenumab 70 mg. Out of three patients, two reported reduced headache frequency and intensity, but all three patients developed severe nausea while smoking cigarettes after their first dose of erenumab, which led to smoking cessation. One patient who co-smoked marijuana did not get nauseated after smoking it. To the best of the authors’ knowledge, this is the first report of severe nausea secondary to erenumab administration and smoking cigarettes, which finally resulted in patients being able to completely quit smoking. It seems that erenumab may be able to help knock the literal and metaphorical headaches out of your life.

Neflamapimod tries, tries again. After failing to curb cognitive decline in people with Alzheimer’s disease last year, neflamapimod, an alpha isoform of p38 MAP kinase inhibitor, has achieved that goal in patients with dementia with Lewy bodies, according to new data from a small phase 2 trial presented at this year’s virtual Clinical Trials in Alzheimer’s Disease meeting. Conducted at 22 centers in the United States and at two in the Netherlands, the placebo-controlled trial tested the efficacy of neflamapimod in people who had a clinical diagnosis of mild-to-moderate probable dementia with Lewy bodies, as well as reduced dopamine transporter protein as measured by a DAT scan. Participants were split 1:1 to receive either 40 mg neflamapimod or placebo. 

At baseline, the study enrolled 91 participants, including 45 in the placebo group, 26 in the twice-daily group, and 20 who took it three times per day. The trial met its primary endpoint in participants who took three 40 mg capsules of neflamapimod per day, but for those in the placebo or twice-daily groups, scores did not improve. Overall, patients who took three 40 mg capsules of neflamapimod per day posted improvements in a neuropsychological test battery focused on executive function and attention—two cognitive domains most affected in people with the disease.

Collateral lethality is coming for brain cancer. Collateral lethality is not some long-forgotten Arnold Schwarzenegger film or yet another video game. It is, however, among the most promising new developments in the treatment of brain cancer. In collateral lethality, an important protein is lost through genetic deletion as a bystander near a tumor suppressor gene, and a redundant protein is blocked therapeutically. Researchers at the University of Texas MD Anderson Cancer Center have achieved this with the development of a novel targeted therapy, called POMHEX. It is a small-molecule enolase inhibitor that’s effective in killing brain cancers cells that were missing EN01—one of the two genes encoding the enolase enzyme.

Enolase is an essential enzyme involved in glycolysis, a metabolic pathway that is elevated in many cancers to fuel their increased growth. Two genes, EN01 and EN02, encode different but redundant versions of enolase, and several cancers, especially glioblastoma, are missing the EN01 gene because of chromosomal loss. This leaves the cancer cells with only EN02 to continue glycolysis, making them highly sensitive to enolase inhibitors. With that in mind, the research team worked to generate an enolase inhibitor, called HEX, which preferentially targets EN02 over EN01. To improve its ability to enter cells, the team created the prodrug POMHEX, which is biologically inactive until it is metabolized into HEX within cells. In cancer cell lines lacking EN01, treatment with POMHEX blocked glycolysis, inhibited cell growth, and stimulated cell death. Conversely, treatment of cells with normal EN01 showed minimal effects. The bottom line? Collateral lethality and HEX have shown significant clinical activity against EN01-deleted cancers, including glioblastoma.

New in Patient Management

Memory loss concerns may indicate depression in PD. Research shows that subjective cognitive complaints (SCCs)—or concerns over general memory loss that aren’t backed by any objective evidence of cognitive impairment—are highly prevalent in those experiencing the early stages of Parkinson’s disease. But that’s not the big news. New research shows that these concerns may be an indicator of an underlying affective disorder.

The main types of affective disorder, which are also known as mood disorders, are depression and bipolar disorder. The new study involved 120 participants, all in the early stages of Parkinson’s disease. Researchers found that, independent of underlying cognitive status, 38.8% of all participants exhibited SCC. Prevalence of SCC in cognitively impaired and cognitively normal participants was 10.7% and 28.1% respectively. In the cognitively normal participants, multivariable linear regression analysis revealed that SCC was significantly associated with anxiety, depression, and apathy. Keep an eye on these complaints—they may foreshadow underlying pathology.

SMS for MS? According to a recent study, the way you type on your smartphone may offer clues as to how your multiple sclerosis disease is progressing. The results of the study—published in Chaos: An Interdisciplinary Journal of Nonlinear Science—may represent a step toward using keystrokes and other typing patterns to help detect clinical changes in patients with chronic diseases like multiple sclerosis, according to its authors.

Researchers used an app to record the smartphone keystrokes of a group of patients with multiple sclerosis and a control group over the course of a year. They analyzed how quickly or slowly an individual’s typing was and the number of mistakes made and corrected, as well as other behaviors. The study found that the typing patterns of those with multiple sclerosis changed over time, in a way that those in the control group didn’t. The authors of the study believe that, with more research, this approach could be used to monitor the progression of the disease, which in turn could assist physicians with treatments and intervention. Finally, a way to put all that screen time to good use!

Childhood lead exposure may lead to a smaller brain later in life. At this point, we don’t need a study to tell us that lead exposure is bad for children. Nevertheless, a new study has shed light on one of the ways childhood lead exposure can lead to poor health later in life. Researchers found that a higher childhood blood lead level was associated with lower structural brain integrity in midlife. 

The study, which was published this month by JAMA Network, followed a group of more than 560 children in New Zealand into adulthood. Researchers tested their lead blood levels at age 11 and then examined their brains using an MRI once they’d reached the age of 45. Researchers found that those who’d experienced a greater exposure to lead in childhood exhibited noticeable brain structure differences in mid-life, including smaller cortical surface area, smaller hippocampal volume, lower global fractional anisotropy, and an older estimated brain age. Another reason to avoid lead paint and check your children’s toys for the stuff!

Diabetes, hypertension may increase risk of COVID-19 brain complications. As COVID-19 continues to rage, researchers are working around the clock to figure out who’s at risk of which complications. According to a new study, COVID patients with diabetes or hypertension—two of the most common chronic conditions in the US—may be at a higher risk of experiencing bleeding in the brain and stroke. 

The study saw researchers at the Perelman School of Medicine at the University of Pennsylvania analyze COVID patients in their health system who underwent a brain scan between January and April. A total of 81 patients had a brain scan performed, most commonly due to the development of symptoms like speech and vision problems. A little over 20% of those patients were found to have had a stroke, brain bleed, blocked blood vessels, or some other emergency or critical condition. In at least half of these cases, the patient had a pre-existing history of high blood pressure or type 2 diabetes. More research is being conducted, but these findings represent a step toward a better understanding of how COVID-19 affects our bodies beyond its more well-known symptoms.

Latest in Journal Summaries

Risk factors for minor hallucinations in Parkinson’s disease.

Ticagrelor plus aspirin in acute ischemic stroke or TIA of atherosclerotic origin.

Diagnostic accuracy of MR planimetry in clinically unclassifiable Parkinsonism.

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Upcoming Medical Meetings

The following meetings are entirely virtual:

8th Annual Shaping the Management of Parkinson’s Disease: Debating the Most Controversial Issues and Discussing the Latest Breakthroughs. January 23-24, 2021.

9th Annual Brain Tumor Symposium: Maintaining Excellence in the COVID-19 Pandemic Era. January 15, 2021.

Mayo Clinic Multiple Sclerosis and Autoimmune Neurology Update 2021 – Livestream. February 5-6, 2021.





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