Brain Physiology and Anatomy

This news story highlights new findings on how the brain clears waste products through a previously unknown paravascular lypmphatic-like system in the CSF. It contains a link to the original research publication.  The findings are also discussed in Nature.

A Science article shows that metabolic waste products in mice were cleared out of the sleeping brain at a faster rate; the glymphatic system was ten times more active when the mice were asleep vs. awake. Researchers also found that when asleep, the brain’s cells reduce in size, with 60% increase in the interstitial space, resulting in a striking increase in convective exchange between CSF and interstitial fluid.

This Science article discusses the discovery of cilia in the 3rd ventricle, which control and direct the flow of CSF.

Recent research has proposed re-characterizing sacral autonomic nerves as part of the sympathetic nervous system, rather than the parasympathetic system, based on 15 phenotypic and ontogenetic features.

This JAMA article includes MRI showing an “incidental finding” in a patient presenting the palsy of CN VI, with left-sided enhancement of the dura in the region of Dorello’s canal (where the abducens nerve travels from the pontine cistern to the cavernous sinus under the petrosphenoid ligament and over the tip of the petrous ridge).

A new ultrahigh-resolution 3D model of a human brain has been created as part of the European Human Brain Project. “BigBrain” is a free, publicly available tool that provides considerable neuroanatomical insight into the human brain, thereby allowing the extraction of microscopic data for modeling and simulation.

Autistic changes in brain begin prenatally. A study in NEJM found focal disruption of cortical laminar architecture in the cortexes of 10 of 11 young children with autism (based on autopsy findings). The data suggest a probable dysregulation of layer formation and layer-specific neuronal differentiation during prenatal development.

Stanford scientists have revolutionized a method of looking at brain anatomy that pulls off the fat that covers neurons, to see the vast interconnected network underneath.

Research published in the Proceedings of the National Academy of Science found direct connections from activity in the cerebral cortex to the adrenal medulla.  Cortical areas involved in the control of movement, cognition, and affect are all potential sources of central commands to influence sympathetic arousal. These results provide an anatomical basis for a direct mind-body connection.

Researchers published a spectacular new map of the brain detailing nearly 100 previously unknown regions. Using multi-modal MRI images from the Human Connectome Project (HCP), they characterized 97 new areas of the cerebral cortex, and more precisely delineated 83 areas that had been previously identified.

Concussion

American Academy of Neurology has issued concussion guidelines, available on their website with resources for clinicians and patients and even an quick reference app.

This systematic review from the journal Neurosurgery aimed to create evidence-based definition of concussion.  The authors identified 4 “prevalence indicators” of concussion.
1. Observed and documented disorientation or confusion immediately after the event;
2. Impaired balance within 1 day after injury;
3. Slower reaction time within 2 days after injury; and
4. Impaired verbal learning and memory within 2 days after injury.
Loss of consciousness occurred in only between 1-14% of patients.

Radiology research has found that patients may have persistent brain atrophy after even a single concussion.

In addition to OMT for traumatic brain injury, you may want to instruct your patients to avoid sodas and other sources of added fructose after a TBI. Researchers at UCLA found that fructose “promoted plasma membrane lipid peroxidation” in TBI. In addition, “fructose consumption disrupts hippocampal energy homeostasis” and worsens spatial memory. These findings suggest that fructose exacerbates brain trauma further through metabolic mechanisms, though it is unclear whether it lowers the threshold for TBI in the first place.

Researchers have identified a possible biomarker for concussion in a study of 600 head injury patients, tracking how blood levels glial fibrillary acidic protein (GFAP) changed over time. The results showed that GFAP peaked at 20 hours after injury and slowly declined over 72 hours but continued to be detectable for seven days.

Post-traumatic stress disorder (PTSD) in soldiers with exposure to blast injuries may be from a physical injury to the brain, rather than a psychological disorder. Researchers have found a distinctive, consistent, and unique pattern of dustlike scarring on autopsy of soldiers with known blast injuries, often at the border between gray matter (where synapses reside) and the white matter that interconnects it.

Migraine and Headaches

A JAMA article discussed the association between infant colic and childhood/adolescent migraine.

A Lancet article highlights some findings that pain from migraines may be due to more than simple arterial dilation.

Many migraine patients are interested in alternatives to pharmaceuticals for prevention of headaches. The American Headache Society/American Academy of Neurology 2012 guidelines include recommendations for: Butterbur (Level A);  Feverfew, Histamine (subQ), Riboflavin (B2), and Magnesium (Level B), and CoQ10 (Level C). A 2016 study found that a high percentage of pediatric migraine patients may be deficient in riboflavin, coenzyme Q10, vitamin D, and folate and  may benefit from supplementation.

A 2013 presentation at theAmerican Academy of Pain Management conference demonstrated how chronic tension headaches in teens dramatically improve with osteopathic treatment and qi gong (from 22.3 down to 4.9 headaches per month), compared to pharmacological therapy (from 23.9 to 16.4 headaches per month).

Embryology

This  NY Times article summarizes several recent embryological findings on how the human body begins the process of right/left differentiation at the midline node. It includes references to several original research papers.

The Virtual Human Embryo created thousands of restored, digitized, and labeled serial sections and used them to create animations, fly-throughs, and 3-D reconstructions.  Building on that work, researchers in the Netherlands have created the 3-D Atlas of Human Embryology (also available for download as an App).

A study in Nature Genetics finds the embryologic development steps that form the diaphragm and how genetic mutations can lead to congenital hernias. The first phase of diaphragm development is pleuroperitoneal folds of connective tissue that migrate outward, toward the sides of the body. Then these cells fan out toward the front and back. Muscle cells follow the trail of the connective tissue to form the diaphragm, sandwiched between the 2 sheets of connective tissue. It is mutations in the first (the PPF connective tissue fibroblasts) that leads to hernias; mutations in the muscle tissue cells do not.

Anatomy News

Researchers confirmed the anatomy of the interstitium that osteopaths have described physiologically for decades.   The layers of the body previously thought by anatomists to be dense, connective tissues are in fact interconnected compartments filled with fluid, creating an organ in its own right and one of the largest in the body. Supported by a mesh of strong and flexible connective tissue proteins, the interstitium is a series of connected, fluid-filled spaces found under skin as well as throughout the gut, lungs, blood vessels and muscles, and drains into the lymphatic system.  

The mesentery has also been classified as an organ, although the function is less well understood.

Pain Management

This meta-analysis published in the British Medical Journal found “high-quality evidence” that Tylenol is ineffective in treatment of low back pain and provides only minimal short term benefit for people with osteoarthritis. In the meantime, the risk of abnormal liver function quadruples. The authors urge updating of clinical practice guidelines for patients with low back pain and osteoarthritis to reduce recommendations of acetaminophen (paracetamol).

Among patients with acute, nontraumatic, nonradicular low back pain presenting to the ED, adding cyclobenzaprine (Flexeril) or oxycodone/acetaminophen (Norco) did not improve functional outcomes or pain at 1-week follow-up, relative to naproxen alone. These findings do not support use of these additional medications.

As medical marijuana becomes more available, it’s useful for all physicians to become familiar with appropriate indications for use, although research has been sparse to date. This JAMA systematic review found moderate-quality evidence supporting use of cannabinoids for chronic pain and spasticity. Low-quality evidence suggested improvements in nausea and vomiting from chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome. Cannabinoids were associated with an increased risk of short-term adverse effects, ranging from dry mouth to drowsiness, euphoria, and hallucinations.

Effects of Medications and Supplements

Delirium and other brain problems have been linked to 54 antibiotics from 12 different classes of drugs, according to a study published this month in Neurology. Effects included: encephalopathy with seizures or myoclonus (cephalosporins or penicillin); encephalopathy characterized by psychosis (quinolones, macrolides, and procaine penicillin); and encephalopathy with cerebellar signs and MRI abnormalities (weeks after metronidazole).

Certain antibiotics taken during pregnancy, especially in the first trimester, may increase the risk for birth defects.  In utero exposure to clindamycin, doxycycline, quinolones, macrolides and phenoxymethylpenicillin was linked to organ specific malformations. Amoxicillin, cephalosporins and nitrofurantoin were not associated with any major congenital malformations.

Two systematic reviews from the British Medical Journal looked at calcium supplementation for treatment or prevention of osteoporosis and concludes that calcium supplements had no effect on risk of fractures at any site (the only exception being if serum calcium levels were below normal). The accompanying editorial states that evidence currently available gives a strong signal that calcium supplements do not protect older people from fractures, and they also increase risks of adverse events such as constipation, cardiovascular events, kidney stones, or admission for acute GI symptoms.

Use of proton pump inhibitors (PPIs) may increase risk of dementia by 42% (women) to 52% (men), according to a report in JAMA Neurology, after adjusting for pre-defined confounding factors of age, sex, polypharmacy (> 5 prescription drugs),and comorbidities (stroke, depression, ischemic heart disease, and diabetes).  Previous studies have proposed various mechanisms that may be involved.  PPIs also carry an known increased risk of kidney disease, fracture, low magnesium levels, gastrointestinal infections and pneumonia.

Musculoskeletal Issues

A series of studies have shown that surgery for meniscus repair — either with or without accompanying osteoarthritis — has almost no benefit over physical therapy.

Autonomic Nervous System

New research uses anatomical and molecular analyses to re-assign neurons in the sacral autonomic nervous system as part of the sympathetic nervous system. Researchers used 15 phenotypic and ontogenetic features to show that the sacral outflow is indistinguishable from the thoracolumbar (sympathetic) outflow.

Pediatrics

A new AAP study estimates the rate of positional plagiocephaly in young infants at almost 50%, as an indirect result of the “Back to Sleep” campaign.

OMT reduced NICU average length of stay for premies by 5 days (26.1 vs. 31.3 days) in this randomized control trial in Italy, and published by American Academy of Pediatrics Grand Rounds. Each of the 101 infants received an osteopathic exam, and all other NICU staff were blinded as to which babies were treated.

The British Medical Journal found that helmets are no better than normal growth and development in reducing plagiocephaly in children, and they come with side effects.

No. 1 on AAP’s list of unnecessary tests/treatments  in newborn medicine: avoid routine use of antireflux medications for treatment of symptomatic gastroesophageal reflux in infants. According to the Choosing Wisely campaign, “Parents should be counseled that GER is normal in infants and not associated with anything but stained clothes.”

OB/Gyn

JAMA Pediatrics showed an association between autism and a history of induced or augmented labor. In a review of over 1000 charts, there was an increase in the odds of autism in patients with induced/augmented labor, particularly in males.

This special open MRI scanner that allowed doctors in Germany to capture video and images of what it looks like inside a woman’s uterus during childbirth. The 24-year-old volunteer entered the scanner during the pushing stage of her labor. During the final contraction of the 45 minutes the mother spent in the scanner, the baby’s head is seen emerging and the video suddenly stops, as the machine was cut off in order to protect the child from the loud noise of the MRI.

Microbiome

Markers of systemic inflammation and gut epithelial cell damage (“leaky gut”) have been found in individuals who do not have celiac disease but report sensitivity to wheat in their diet (Non Celiac Wheat Sensitivity). Cytotoxic T cells found in those with celiac disease were not present in these patients.

Research published in Gastroenterology shows changes in brain activity (as measured by fMRI) in patients taking probiotics.

The microbiome is important for more than just gut health. Chronic sinusitis appears to be associated with both an overgrowth of a non-pathogen bacteria and a lack of a particular strain of lactobacillus.

Researchers have found reversal of autistic-like behavior in mice from changing their gut flora. In one study, the mice had lower levels of B. fragilis in their guts, and dramatically higher serum levels of 4EPS. After the mice guts were colonized with B. fragilis, symptoms improved.  Original research at http://www.cell.com/abstract/S0092-8674(13)01473-6.   In another study, the mothers were fed with a high fat diet and the offspring mice had altered biome, with deficient synaptic plasticity and low oxytocin levels.  Symptoms improved after being colonized with L. reuteri.

A vast, varied system exists where gut microbes influence the brain through hormones, immune molecules and the specialized metabolites that they produce.  Researchers have drawn links between GI pathology and conditions such as anxiety, depression, autism, schizophrenia and neurodegenerative disorders — but it’s very difficult to tell if microbial differences are causes or consequences of the disease.

For infants at risk for developing Type 1 diabetes, adding a probiotic to feeding within the first month of life significantly reduced incidence of islet autoimmunity, compared to those infants who did not receive the probiotic. The risk reduction was primarily observed in children with the highest-risk HLA genotype of DR3/4, giving us a glimpse of microbial power in preventive medicine.

Endocrinology

Endocrine-disrupting chemicals found in plastic bottles, flame retardants, detergents, cosmetics and pesticides cost the U.S. more than $340 billion a year in health costs and lost earnings;  the largest single cost comes from chemical effects on children’s developing brains.

This article puts forward the idea that bones are hormone secreting organs, influencing physiology in ways never before considered.  Original research is available at http://www.cell.com/abstract/S0092-8674(13)01073-8