The cure for brain cancer? Plus, biomarkers predict Parkinson’s and the science behind daydreams

While the study of concussion management is advancing, there’s still a lot we don’t know about the actual mechanism of the brain injury. This week, we bring you a new study that enlisted the help of several Humpties Dumpty to get to the bottom of things. We’ve also got new research that found an ingredient in plastic bottles that contributes to the prevalence of male bias in autism spectrum disorder, a look at pre-existing drugs that could effectively “cut off the fuel supply” to certain brain cancers, insight into how a deficiency in fatty acids might be a trigger for multiple sclerosis symptoms, and more.

Neuro Flashback

Jean-Martin Charcot, MD, is often referred to as the father of modern neurology—and for good reason. He was the first physician to describe amyotrophic lateral sclerosis (ALS) in 1869, and he gave the condition its first name: Charcot disease. The condition subsequently became known as Lou Gehrig’s disease before taking on its modern name, although many francophone nations still refer to it as Charcot disease. Through studies conducted with a colleague between 1865-1869, Charcot discovered that lesions within the lateral column of the spinal cord resulted in chronic progressive paralysis and contractures, while lesions of the anterior horn of the spinal cord resulted in paralysis without contractures. While various discoveries have since resulted in a greater understanding of the disease, Charcot’s original clinical and pathological descriptions of ALS all remain essentially accurate.

In the News

Humpty Dumpty had a great scan. While we’ve come a long way in our understanding of concussions, there are still some fundamental questions we’ve yet to answer. One seemingly simple question has so far been unanswered: Are concussions caused by direct translational impact or by rotational impact? A new study may have answered that question with the help of an unlikely object: an egg.

Researchers opted to use an egg because of its structural resemblance to the human head. Both have a hard outer shell, and within the shell is a liquid layer (the whites in eggs; cerebrospinal fluid in people) surrounding a soft inner matter (yolk in eggs; brains in people). The team considered two types of impact: translational impact, which hits directly, and rotational, which occurs when the object accelerates or decelerates while rotating. The study found that direct translational impact does not tend to cause deformation to an egg yolk. However, rotational deceleration causes significant “scrambling.” The researchers hypothesize that rotational impact can result in more damage to the brain than translational impact. The findings could help helmet designers develop more effective shells.

Everyone’s mind wanders…but to where? What happens in our brains when our minds wander? A new study led by researchers at UC Berkeley might have uncovered a way to track the flow of our internal thought processes using an electroencephalogram (EEG). The work could help identify whether our minds are focused, fixated or wandering, based on brain signals.

The study, published in the Proceedings of the National Academy of Sciences, saw researchers monitor the brainwaves of 40 participants during four types of thinking: task-related, freely moving, deliberately constrained, and automatically constrained. Using an EEG, they found that these different types of thinking could be observed in the form of different brain waves. For example, increased alpha brain waves were detected in the prefrontal cortex when a participant’s thoughts jumped from one topic to another. Conversely, when participants didn’t pay attention to a task, weaker brain signals known as P3 appeared in the parietal cortex. The findings could be used to detect thought patterns linked to a spectrum of psychiatric and attention disorders.

Reach out and touch science. Patients who’ve experienced damage to the basal ganglia can end up with severely impacted motor abilities that can make common daily tasks like reaching and picking up objects nearly impossible. The specific neurons involved in these seemingly simple tasks were the focus of a newly published study, which stands to advance our understanding of basic cellular mechanisms in the brain.

The study, published in Cell Reports, examined basal ganglia neurons, which are involved in the development of diseases like Parkinson’s and Huntington’s. These striatal spiny projection neurons are involved in smooth motor functions and can be split into two types: D1 and D2. Prior research has indicated that the former is responsible for the “go” signal, while the latter executes the “stop” signal. Researchers sought to examine this process by monitoring mice while they reached through an opening to grab a food pellet. Researchers inhibited either the  D1 or D2 neurons of the mice by using a light. They found that both neurons are necessary for smooth motor function of all movement, and inhibition of either neuron resulted in failure at a different point in the movement. The researchers hope that the findings can contribute to a body of research that may one day lead to a cure for neurodegenerative diseases.

Mapping the visual cortex. In humans and other mammals, the visual cortex is organized into various functional maps for neural tuning. While correlations between the topographies of these maps have been observed, their apparent systematic organization remains something of a mystery to scientists. But new research has shed light on how the regularly structured topographic maps in the visual cortex of the brain arise spontaneously to efficiently process visual information.

The research, which was published in Cell Reports, found that the orthogonal organization in the primary visual cortex of the brain begins with the spatial organization in bottom-up, feed-forward projections. Researchers found that an orthogonal relationship among sensory modules already exists in the retinal mosaics, and the relationship is mirrored onto the primary visual cortex to initiate the clustered topography. Their findings offer new insights into the mechanisms of brain circuitry for the efficient tiling of sensory modules, paving the way for a new understanding of functional architectures in the visual cortex during early developmental stages.

Neuro Trivia

Question: What is the only known animal that has a skull but no vertebral column?

Answer: Hagfish. Widely considered to be the “most disgusting animal in the ocean,” this eel-shaped fish has a skull made of cartilage but no vertebrae. Fossil records show the fish hasn’t changed much in about 300 million years, so maybe these disgusting animals know something we don’t.

Novel Diagnostics

Does an ingredient in plastic bottles contribute to autism? Micro- and nanoplastics are a cause for concern for several environmental reasons, but a common ingredient might also play a role in autism spectrum disorder (ASD). A new study is the first to identify how gestational exposure to bisphenol A (BPA), a synthetic precursor to a number of plastics, could dysregulate the expression of several ASD candidate genes. Moreover, it suggests that BPA may serve as an environmental factor that contributes to the prevalence of male bias in ASD.

The study, published in Scientific Reports, focused on ASD, a neurodevelopmental disorder characterized by impaired social communication, restricted interests, and repetitive behaviors. BPA is used widely in plastic products and is found in micro- and nanoplastics that have seeped their way into the environment and even into our bodies. It impairs neurological functions known to be disrupted in ASD, as previous studies have found. The new research indicates that prenatal exposure to BPA can decrease neuronal viability and neuronal density in the hippocampus and impair learning and memory, but only in male offspring. While more research is required to understand the sex-specific molecular mechanisms of BPA, the findings suggest that changes in the policy regarding the use of BPA may be warranted.

Blood biomarkers signal PD prior to motor symptoms. The quicker we can diagnose a disease, the better chance we have of treating it successfully. That’s why new research from Nagoya University in Japan should excite those who work with Parkinson’s disease patients. Researchers found that blood pressure, hematocrit, and serum cholesterol levels change in patients with Parkinson’s long before the onset of motor symptoms, potentially leading to early diagnosis and treatment of the disease.

Prior studies have found that non-motor symptomslike constipation, REM sleep behavior disorder, impairment of the sense of smell, and depressionemerge in patients with Parkinson’s disease decades before motor symptoms do. The new research, published in Scientific Reports, focused on the results of general health checkups using data from 22 male and 23 female patients. In male patients, weight, BMI, hematocrit, total and LDL cholesterol levels, and serum creatinine levels were lower vs healthy controls. In females, blood pressure and aspartate aminotransferase activities were higher, while the other biomarker levels were lower vs healthy controls. The team is now conducting clinical trials of medication in patients considered to be at high risk for Parkinson’s to try to prevent development of the disease.

Eye test may predict dementia in Parkinson’s patients. Patients with Parkinson’s disease often develop debilitating dementia. Cognitive decline is estimated to affect roughly 50% of Parkinson’s patients within 10 years of their initial diagnosis. But a new study may have found a way to predict whether a patient will develop cognitive impairment and possible dementia within 18 months.

The study, which was conducted by researchers at the University College London and published in Movement Disorders, adds more evidence that vision changes precede cognitive impairment. The team’s research found that structural and functional connections of certain brain regions become decoupled throughout the entire brain in patients with Parkinson’s disease, and particularly in those with vision problems. The findings suggest that performance in simple tests using eye charts and images of animals indicated a higher degree of decoupling in some brain regions, particularly in memory-related regions in the temporal lobe, and correlated with their likelihood of impending cognitive decline. These tests could provide a window of opportunity to predict dementia before it takes hold, allowing time for treatment to slow its development.

Keep an eye out for calcified brain metastases. Among patients with calcifications within the brain parenchyma, metastases are considered uncommon. But a new study suggests that we may want to shift that assumption. According to the study, calcified brain metastases (CBM) are seen more frequently than previously thought. These findings indicate that intraparenchymal brain calcifications—particularly in patients with cancer—should not be overlooked by neuroradiologists.

The study sought to examine the incidence rate of calcified brain metastases as a means of mapping the various presentation patterns and primary tumor histologies. Researchers analyzed 1,002 consecutive brain CT scans of patients with known primary tumors. Of the 190 patients with brain metastatic disease, 34 (17.9%) had CBM. Most CBM patients had primitive lung adenocarcinoma (56%), followed by breast ductal invasive carcinoma (20%), and small cell lung carcinoma (11.8%). The data suggest that CBM are seen more frequently than previously thought, with an incidence of 9.5% ab initio in patients with brain metastases.

Novel Treatments

Virtual reality rehab could alleviate motor dysfunction in the real world. A researcher from Tohoku University in Japan has developed a new virtual reality (VR)-based method of rehabilitation for those suffering from motor dysfunction. The process works by increasing bodily awareness and improving basic movement control.

Japan’s rapidly aging population has prompted a sharp increase in patients with motor dysfunctions who are primarily treated with forms of movement rehabilitation. The new research, published in Scientific Reports, focused on the brain signals that give us a sense of where our limbs are and the ability to move them. Kazumichi Matsumiya, PhD, found that he could isolate these senses using a VR-based method. Participants viewed a computer-generated image of a hand while Dr. Matsumiya measured their sense of both ownership and agency over it. Participants’ motor control improved when they experienced a sense of agency over the VR limb, regardless of their sense of ownership of it. The findings suggest that by artificially enhancing the sense of agency, motor control rehabilitation becomes more effective. Turns out virtual worlds may be able to help us in the real world after all.

Existing drugs could “cut off fuel supply” to cancer. Glioblastoma is one of the most aggressive forms of brain cancer, and it has a very low survival rate. But a new study found that an already-existing class of mitochondria-inhibiting drugs could be effective in treating patients with certain types of glioblastoma.

A subset of glioblastoma, known as mitochondrial brain cancer, relies on overactive mitochondria to grow and spread. A new study published in Nature Cancer focused on cell cultures and found that this type of glioblastoma may respond to treatment with mitochondria-inhibiting drugs. While the published findings were based on experiments conducted on cell cultures grown in labs, the Columbia University Medical Center-based team has also found success testing the drugs on mice models. However, these results are yet to be published. Clinical trials on humans are now underway, and the researchers believe this could represent a breakthrough in cancer treatment.

Could activating a single protein be the route to curing cancer? Few people survive in the long term after being diagnosed with a glioblastoma, but a new study offers some hope. Researchers in Canada have identified a new cellular pathway—involving a protein called Rab35—which appears to limit the growth and spread of brain tumors, possibly opening up a new form of treatment.

The researchers used levels of a small GTPase known as Rab35 as a jumping-off point, as these levels are typically lower in patients with glioblastoma. The team performed tests on mice and found that reducing levels of Rab35 led to faster growth of a tumor and a shorter life span, and vice versa. Turns out that Rab35 is activated by a pathway involving a GTPase called Arf5. Together, Arf5 and Rab35 appear to affect the transport of various cell surface receptors and can restrict the ability of cells to migrate through tissues, limiting the ability of brain tumor-initiating cells to replicate. The findings could lead to the development of a new form of treatment by reactivating Rab35 to suppress the progression of glioblastomas.

Severe depression? Consider deep brain stimulation. Conditions like epilepsy and Parkinson’s disease are often the result of misfiring brain circuits. Targeted neuromodulation, which is tailored to the patient’s particular symptoms, is becoming an increasingly common form of treatment. But a new case study suggests that it might also help patients with severe depression. Recently, scientists at UC San Francisco’s Dolby Family Center for Mood Disorders tried neuromodulation on a patient with treatment-resistant depression and found that it provided relief from symptoms within minutes.

The study, published in Nature Medicine, involved mapping the effects of mild stimulation of several mood-related brain sites in the affected patient. Researchers implanted multi-site intracranial electrodes and systematically assessed the acute response to focal electrical neuromodulation. They found that this deep brain stimulation could alleviate symptoms like anxiety, low energy levels, or a lack of ability to experience pleasure in everyday activities. Notably, emotional responses were rapid in onset, reproducible, and context- and state-dependent. These findings provide proof of concept for personalized, circuit-specific medicine in psychiatry, researchers say.

New in Patient Management

Breast milk proves its worth once again. While scientists have long known that exosomes are a key therapeutic treatment for patients with conditions like muscular dystrophy and heart failure, the question remained: What’s the best way to deliver them? A little over a decade ago, human trials involved injecting exosomes directly into the hearts of patients. Now, a new study has found that mixing the exosomes with the dominant protein in breast milk and administering them orally could be the answer.

The research is focused on human cardiosphere-derived cells that secrete exosomes, a type of extracellular vesicle that contains various biomolecules. The study involved mixing the exosomes with casein—the major protein in breast milk—and feeding the mixture to mice with muscular dystrophy. Mice that were fed exosomes exhibited improved heart function, mobility, and exercise capacity, but mice that were fed exosomes mixed with casein saw significantly enhanced effects. The research might point to a treatment that could vastly improve the quality of life for muscular dystrophy patients.

Brain changes sketch a road map for relapsing MS. Many studies of multiple sclerosis (MS) focus on single biomarkers. While these provide useful pieces of the overall puzzle in understanding the progression of the neurodegenerative disease, the puzzle pieces can be hard to place. Recent research, however, has attempted to track the sequence of events in the progression of relapsing MS, shedding light on brain changes that could provide a road map for the development of the disease.

During the study, published in NeuroImage: Clinical, researchers analyzed the records of 295 relapsing MS patients. The researchers examined the sequence of three elements: disease progression, changes from low to high disability, and cognitive decline. They found that changes in levels of gray matter in specific regions of the brain tend to occur early, while structural changes in white matter happen later in disease progression. The findings offer a greater understanding of the order of events in MS, which researchers hope will provide a context for study results based on single biomarkers and ultimately help physicians monitor patients with more precision.

Pick a category: MS cognitive phenotypes. Cognitive impairment is common in patients with MS, but there is no established characterization of cognitive phenotypes in MS, which can make it tricky to determine the best treatment options. But a new study has taken steps to address this. The study identified five cognitive phenotypes in MS patients, which could help clinicians define the disability in a clinical way, thereby guiding treatment choices and tailoring cognitive rehabilitation strategies.

The study, published in JAMA Neurology, examined 1,212 patients with MS. Using specific clinical and MRI features, researchers identified five distinct cognitive phenotypes: preserved cognition; mild—verbal memory/semantic fluency; mild—multidomain; severe—executive/attention; and severe—multidomain. The researchers hope their findings can be used with the Expanded Disability Status Scale score, empowering clinicians to more accurately define levels of disability in MS patients.

In defense of fatty acids. When we discuss fatty acids, it’s often in the context of dieting. But a new study suggests that their benefits might be more wide-ranging. The abnormal immune system response that causes MS symptoms can be triggered by the lack of a specific fatty acid in fat tissue, according to a new Yale study.

The researchers analyzed the fat tissue of patients diagnosed with MS and found that participants lacked normal levels of oleic acid. This monounsaturated fatty acid is found in high levels in cooking oils, meats like beef and pork, cheese, nuts, eggs, milk, pasta, and other foods. The lack of oleic acid leads to a loss of the metabolic sensors that activate T cells, which mediate the immune system’s response to infectious diseases. Without these cells, the immune system can attack central nervous system cells, causing MS symptoms like vision loss, pain, and lack of coordination. Could a change in eating habits help to treat certain people with autoimmune disease? Could be, according to the findings.

Latest in Journal Summaries

Stimulating brain pathways shows origins of human language and memory.

Stress and lack of sleep can lead to concussion-type symptoms.

Good clinical outcome decreases with number of retrieval attempts in stroke thrombectomy.

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Upcoming Medical Meetings

The following meeting is entirely virtual:

54th Annual Recent Advances in Neurology. February 10-12, 2021.

The following meeting is scheduled to have an in-person and virtual component:

American Academy of Neurology 73rd Annual Meeting (AAN 2021). San Francisco, CA. April 17-23, 2021.

The following meeting is scheduled to be entirely in-person:

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


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