Could new research unveil the mysteries of conversion disorder? Plus, a skin swab to diagnose Parkinson’s, and a drug to slow Alzheimer’s

Conversion disorder leaves patients abruptly unable to walk, talk, or see, and its causes have stumped scientists for years. But this week, we’re bringing you new findings that may have cracked this mystery. In this issue, you’ll also find a study that suggests a Parkinson’s diagnosis may be a simple skin swab away, research into how many steps you should walk daily after a stroke, how we can use AI and video game tech to classify Alzheimer’s disease, and more. 

Neuro Flashback

William Williams Keen is often cited as the forefather of neurosurgery in the United States. While serving in the Civil War, he worked with Silas Weir Mitchell in studying injuries sustained to the nervous system. Their studies were synthesized into the 1864 publication Gunshot Wounds and Other Injuries of the Nerves and Reflex Paralysis, which features the first descriptions of causalgia, reflex sympathetic dystrophy, and secondary paralysis. Later in his career, Keen treated patients with trigeminal neuralgia, performed cortical excisions for patients with epilepsy, and devised the procedure of posterior upper cervical root sections for spasmodic torticollis. He was also the first surgeon to perform and advocate for ventricular punctures. Keen’s most significant accomplishment, however, came in 1887, when he became the first surgeon in the United States to successfully remove a primary brain tumor and have the patient survive for more than 30 years. 

In the News

Researchers find one possible root of mystery neurological disorder. Conversion disorder (also known as functional neurological disorder) has been a mystery to researchers since it was first recognized as a disease. The condition leaves patients abruptly unable to walk, talk, or see, without any injury or physical issue, and its cause or causes have remained elusive. However, a research team now believes it’s discovered a possible cause of conversion disorder: a low-grade inflammation process that influences gene expression.

The findings of the study, published in Brain, Behavior, & Immunity—Health, suggest that the disorder is a result of the process by which the instructions in our DNA are converted into a functional product, like a protein. Researchers examined levels of inflammation in blood samples from patients with conversion disorder that mimicked stroke-like symptoms, and found that they were higher than normal. Researchers also noted that microRNA levels in the blood, which influence the expression of genes, seemed to play a role. While these preliminary results require further exploration and replication, researchers hope that the findings could lead to the development of treatments to ease symptoms.

New tool could bring unbiased autism screening. Tools used to screen children for autism spectrum disorder (ASD) often fail to identify the disorder in those from low-income families and racial/ethnic minority groups. This disparity is particularly harsh when English is not the family’s first language. Researchers have now developed a new visually based tool, which may reduce these disparities at a pivotal point during childhood development.

The tool, which was examined in a study published in Pediatrics, is called the Developmental Check-In (DCI) tool, and it includes 26 pictures that children are asked to respond to. Researchers tested it on 637 children aged 2 to 5 years; two-thirds of the children were Hispanic, and 86% were from uninsured families or those enrolled in Medicaid. Children who screened positive were then enrolled in an ASD evaluation from an expert clinician. Researchers found that the DCI tool was effective at distinguishing between children with ASD and children without. Significantly, they found that use of the DCI tool could lead to earlier and more accurate ASD diagnoses for Hispanic children, who are historically diagnosed at a lower rate than White children. 

Got high T? Chances are you’re more miserly. Past research has shown that elevated levels of testosterone in men can result in changes in decision-making, antisocial behavior, and even an increased desire for material possessions. Now, a new study has found another trend in those with higher levels of testosterone: a reduction in generosity through cortical and subcortical mechanisms.

The study, published in the Proceedings of the National Academy of Sciences, examined a cohort of 70 male volunteers aged 18 to 25 years. Half of the participants were given testosterone 150 mg, and the other half were given a placebo. Researchers then asked all the men to rate how close they felt to various people in their lives, and were asked to think about giving money to one of those people. Participants were then placed in an fMRI machine and told to think about one of their friends or relatives, before being asked whether they would like to keep all of the cash or split it with that person. Researchers found that volunteers tended to give the money away equally to those who were close to them, but those who’d been given testosterone were found to be less generous in sharing the cash with those less close to them. Additionally, researchers observed differences in activity in the temporoparietal junction in the brain—the part of the brain associated with empathy.

New light shed on subconscious stimuli could lead to treatments for neurological disorders. For the first time, researchers have mapped what happens in animals’ brains when they learn from subconscious visual stimuli. According to the authors of the new study, this understanding could lead to new treatments for a number of conditions, including Parkinson’s disease.

Past research has shown that when people are rewarded during the presentation of visual stimuli that are not consciously perceivable, they can still perceive these stimuli subsequently. The new study, published in Neuron, aimed to clarify how this subconscious learning occurs. Researchers studied the brains of two rhesus monkeys both before and after they were exposed to subconscious visual stimuli. While the ventral tegmental area—which includes the cells that produce dopamine—was stimulated, the monkeys performed complicated tasks while being shown nearly invisible images of human faces and bodies. The monkeys could not consciously perceive these images. Afterward, the monkeys again received subconscious visual stimuli while the ventral tegmental area was stimulated. Results showed that the monkeys remembered details about the first subconscious images. The findings could lead to targeted treatments for disorders like Parkinson’s or depression, which are linked to disturbances in the dopaminergic system.

Neuro Trivia

Which mammal has the largest brain-to-body ratio?

Answer: The tree shrew, whose brain makes up 10% of its body weight. No word if they’ll use those big brains to suggest that we stop calling them shrews.

Novel Diagnostics

Can Parkinson’s be diagnosed with a skin swab? As it stands, there is no definitive test to diagnose this disease. But a new study has shown that identifying Parkinson’s may be possible through a simple and painless skin swab. Findings suggest that Parkinson’s disease could be diagnosed based on compounds found on the surface of skin––a potential breakthrough for earlier, less-invasive diagnosis.

The study, published in Nature Communications, examined samples from a cohort of 500 participants. Researchers used high-resolution mass spectrometry to profile the chemical signature in the sebum of people with Parkinson’s and observed changes in these patients’ lipid processing and mitochondria, which are hallmarks of the disease. Moreover, they observed subtle changes in the sebum as the disease progressed. In all, researchers have identified 10 chemical compounds in sebum that are elevated or reduced in people with Parkinson’s. This allowed researchers to distinguish people with the disease with 85% accuracy. The findings could lead to a definitive test to diagnose Parkinson’s accurately, quickly, and cost-effectively. 

First diagnostic criteria for CTE published. Chronic Traumatic Encephalopathy (CTE) is a degenerative brain disease that tends to be associated with a history of repetitive head impacts. This means it’s often found in former athletes in sports like football and boxing. In the past, CTE could only be diagnosed after death through a neuropathological examination of brain tissue. Now, however, consensus diagnostic criteria for Traumatic Encephalopathy Syndrome (TES) have been published by the National Institute of Neurological Disorders and Stroke (NINDS). They are the first-ever expert consensus criteria developed for the clinical disorder associated with CTE brain pathology. 

The “First NINDS Consensus Workshop to Define the Diagnostic Criteria for TES” was held in 2019 in Phoenix, AZ, as part of the ongoing NINDS-funded multicenter DIAGNOSE CTE Research Project. After an 8-month process of drafting, reviewing, commenting, voting, and revising the criteria, consensus was reached by the panel of 20 clinician-scientists and seven observers from 11 academic institutions across the country. Published in Neurology, the criteria include: substantial exposure to repetitive head impacts and a progressive course of cognitive impairment or neurobehavioral dysregulation, or both. The publication of the criteria will help researchers and clinicians to better understand CTE’s clinical features, as well as causes and risk factors for developing the disease.

Turning to AI and video games to classify Alzheimer’s. Generative adversarial networks (GANs) are machine-learning systems in which two neural networks competing in a zero-sum-game can produce high quality images. These AI systems are used in various fields, from astronomy to gaming. Recently a team of researchers used a GAN to process brain images to generate a model that was able to classify Alzheimer’s disease with improved accuracy.

The research, published in Alzheimer’s Research & Therapy, saw researchers using a modified GAN to learn from a series of T1-weighted brain MRI scans from 151 participants of the Alzheimer’s Disease Neuroimaging Initiative. The model they generated was trained with a three-dimensional fully convolutional network using the generated images as inputs to predict Alzheimer’s status. While further work is needed before models like this can be used to predict Alzheimer’s, the researchers found that image quality was greatly improved, and concluded that the study demonstrated a proof of principle that GAN frameworks can be used to augment Alzheimer’s classification performance.

MRI scans are the key to prognosis for kids with cerebral palsy. In patients with cerebral palsy, brain abnormalities are known to relate to motor function. Researchers, however, have been unclear on whether these abnormalities have any association with cognitive functioning. But now, a new study has found that brain MRI characteristics and Gross Motor Function Classification System (GMFCS) level at a young age can each help identify children with cerebral palsy at risk for impaired cognition at school age, and could be used as a prognostic tool. 

The study, published in the European Journal of Paediatric Neurology, examined the prognostic value of brain abnormalities for cognitive function. Using a cohort of 75 children with cerebral palsy, researchers analyzed MRI scans looking for patterns in brain abnormalities, and measured cognitive functioning using the nonverbal intelligence quotient. They found that 27% of the participants had a nonverbal IQ below 70, and 36% of the participants were classified as “having impaired cognition.”They also found that a higher degree of white matter damage and a more severe GMFCS level measured early in life are risk factors for impaired cognition at 4 to 7 years of age. The model was successful in predicting 89% of cases, and researchers found that while using the brain abnormalities alone, they were able to predict impaired cognition in 71% of cases.

Novel Treatments

Promising new drug may slow the progression of Alzheimer’s. The FDA hasn’t approved a new drug for Alzheimer’s disease in roughly 18 years, but pharmaceutical company Eli Lilly is hoping to bring something new to the table. Newly published results from a phase 2 trial indicate that the firm’s drug donanemab can slow the progression of Alzheimer’s disease.

The research, published in the New England Journal of Medicine, involved 257 patients with early stages of Alzheimer’s during the course of 76 weeks. Half of the cohort were given donanemab, an antibody designed to clear deposits of amyloid-β peptides that form plaques in the brains of patients with Alzheimer’s. Disease progression was measured through two systems that involved having the patients complete cognitive tasks and perform daily activities, like getting dressed or using a phone. Researchers found that those taking the drug exhibited a 32% lower rate of cognitive decline compared with those given the placebo. That said, the clearance of amyloid plaques and slowing of tau pathology observed in the patients on the drug was not statistically significant vs those on the placebo. Phase 3 trials may yet determine whether the FDA moves toward approving donanemab.

Walking away from disability after a stroke. For those recovering from stroke, a regular dose of evening strolls may be the key to better post-stroke outcomes. That’s according to a new study, which found that the strongest predictors of future mobility were measures of daily steps and balance at 2 months after a stroke. The findings suggest it may be important to improve daily physical activity and target balance early on to boost chances of physical activity at 1 year.

The study, published in Stroke, looked at data from 206 participants with a mean age of 63 years. Researchers tracked their number of daily steps and their balance over a follow-up period of 1 year. The aim was to create a model that can predict daily steps at 1-year post-stroke using data collected at 2 months. Researchers found that participants who were taking more than 1,600 daily steps at 2 months were 1.86 times more likely to reach more than 6,000 daily steps at 1-year post-stroke. The authors of the study noted that reaching a point where patients can walk more than 6,000 daily steps significantly decreases their chances of having a subsequent stroke. As such, early identification of those with a low step count following stroke could facilitate interventions that lead to improved health and outcomes.

Clues found in the gut point to microbe-inspired therapies for neurological disorders. For a long while, researchers believed that the symptoms of many neurological disorders are caused by genetic variants affecting brain development and function. But a new study may upend this school of thought. The research suggests that microbes in the gut may contribute to certain symptoms associated with complex neurological disorders, which indicates that microbe-inspired therapies may one day help to treat them.

The study, published in Cell, saw researchers examining the gut microbiome—which is another important source of genetic variants—using mouse models of Autism Spectrum Disorder (ASD). Researchers found that certain maladaptive behaviors are interdependently regulated by the microbiome and host genes for neurodevelopmental disorders. Specifically, they found that the hyperactivity phenotype of Cntnap2−/− mice is caused by host genetics, whereas the social-behavior phenotype is mediated by the gut microbiome. Additionally, they found that microbial intervention selectively rescued social deficits in Cntnap2−/− mice through upregulation of metabolites in the tetrahydrobiopterin synthesis pathway. The findings indicate that behavioral abnormalities associated with ASD could have two distinct origins, which suggests that the gut may be a target for future treatments.

Kids with migraine: Say no to drugs. Treating migraines can be tough, but a new systematic review may have opened up Pandora’s Box. The new study has found that a wide range of nonpharmacological interventions may be effective in treating pediatric migraine.

In the review, researchers pooled data from 12 randomized controlled trials that included 576 children and adolescents who suffered from migraines. Half of the participants received interventions including self-administered treatments, biofeedback, relaxation, and psychological therapy. Control groups received psychological placebo, sham biofeedback, or were put on a waiting list for other interventions. Researchers found that all interventions were more effective than the waiting list. The smallest effect measured was from long-term psychological placebos and the greatest effect was observed for short-term, self-administered treatments. The findings indicate that some of these interventions could be integrated into a treatment plan involving both pharmacological and behavioral management.

New in Patient Management

A lack of “good” cholesterol may lead to Parkinson’s. High-density lipoprotein cholesterol (HDL-C) is known as the “good” cholesterol because it can help remove other kinds of cholesterol from the blood. Now, new research has found yet another reason to keep up your HDL-C levels. The findings of the new study suggest there’s a link between low HDL-C levels and greater HDL-C variability and an increased risk of developing Parkinson’s disease.

In the study, published in Neurology, researchers examined 382,391 patients aged 65 years or older, none of whom had a history of Parkinson’s. The HDL-C variability of patients, along with any signs of Parkinson’s, were monitored over a 5-year follow-up period. Researchers found that 2,733 individuals were newly diagnosed with Parkinson’s over that time, and those with the lowest levels of HDL-C were more likely to develop the disease. Additionally, the group with the highest levels of HDL-C variability had increased rates of Parkinson’s incidence when compared to those with the least variability. The findings indicate that we should all be paying attention to how much “good” cholesterol we’re consuming if we want to keep Parkinson’s at bay. 

RNAs tell us about Parkinson’s progression. Parkinson’s disease is the second most common neurodegenerative disease in the world, but researchers are still somewhat in the dark as to the exact causes of the disease and what prompts its progression. But recently published research may have uncovered a piece of the puzzle. The new study has found that the level of non-coding RNAs in the blood of a Parkinson’s patient can be used to track the progression of the disease.

In the Nature Aging study, researchers examined circulating small noncoding RNAs (sncRNAs) across two cohorts of Parkinson’s patients, and monitored their effect on the transcriptome. After sequencing the sncRNAs from blood samples of 1,614 individuals, researchers found that dysregulated microRNAs associated with Parkinson’s and its progression occur in two distinct waves in the third and seventh decades of life. They observed that these molecules, which originate predominantly from immune cells, resembled a systemic inflammatory response and mitochondrial dysfunction, which are two hallmarks of Parkinson’s. They validated these findings using samples from an additional 1,024 individuals in the second cohort. Results suggest that levels of these RNAs in the blood could be used as diagnostic and prognostic tools for Parkinson’s patients. 

Looking to avoid stroke? Go vegetarian. We all have that one friend who spends their time trying to convert the rest of us to a plant-based diet. Well, that friend’s argument just got a little stronger, thanks to new research that suggests eating a diet based on foods like vegetables, whole grains, and beans, and decreasing intakes of foods with meat, refined grains or added sugars, may reduce your risk of having a stroke by up to 10%.

The study, published in Neurology, examined the diets of 73,890 women in the Nurses’ Health Study (NHS; 1984 to 2016), 92,352 women in NHSII (1991 to 2017), and 43,266 men in Health Professionals Follow-Up Study (1986 to 2012). None of the participants had cardiovascular disease at the beginning of the study. The cohorts were grouped into vegetarians (those who reported their meat and/or fish intake was zero or < 1 serving per month) and non-vegetarians. While no associations were observed for hemorrhagic stroke, researchers found that those who ate a plant-based diet had a marginally lower risk of ischemic stroke and total stroke than non-vegetarians. They concluded that a healthful plant-based diet can lower your risk of stroke. We’ll never hear the end of this one from our vegetarian friends. 

Statins could save the lives of AF-related stroke patients. Patients with atrial fibrillation (AF) who suffer a stroke have higher mortality and morbidity rates than those who have other types of stroke. While statins are commonly prescribed in cases of stroke, this treatment hasn’t been studied for cases of specifically AF-related stroke. This prompted a study, the findings of which were recently published in European Neurology. The researchers found that the use of statins before a stroke improved the clinical outcomes in patients with atrial fibrillation by upregulating the level of SOCS-3 and decreasing the plasma MMP-9 level.

The study looked at a cohort of 453 AF-associated acute ischemic stroke patients from four medical centers. The patients were split into two groups, one of which was prescribed statins prior to a stroke occurrence. Researchers examined all patients over a 3-month period, measuring plasma suppressor of cytokine signaling-3 (SOCS-3) and matrix metalloproteinase-9 (MMP-9) levels on admission and after 3 and 7 days. They found that plasma SOCS-3 levels were significantly higher and MMP-9 levels lower in patients in the prestroke statin group. They also found that these patients had a lower risk of 3-month mortality and major disability. The findings suggest that the prestroke use of statins can improve clinical outcomes in stroke patients with AF.

Latest in Journal Summaries

Hemodynamic responses to in-bed cycle exercise in the acute phase after moderate-to-severe stroke.

High occurrence of dementia in older adults returning to community from prison.

The effect of cumulative lifetime estrogen on cognition in depressed vs non-depressed older women.

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Upcoming Medical Meetings

The following meeting is entirely virtual:

American Academy of Neurology 73rd Virtual Annual Meeting (AAN 2021). April 17-22, 2021.

The following meetings are scheduled to be entirely in-person:

2021 Congress of Neurological Surgeons (CNS) Annual Meeting. Austin, TX. October 16-20, 2021.

Neuroscience 2021: The Society for Neuroscience (SfN) Annual Meeting. Chicago, IL. November 13-17, 2021.

 

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