Abstract 2021 : Blood-based protein biomarkers have revolutionized several fields of medicine by enabling molecular level diagnosis, as well as monitoring disease progression and treatment efficacy. Traumatic brain injury (TBI) so far has benefitted only moderately from using protein biomarkers to improve injury outcome.
Because of its complexity and dynamic nature, TBI, especially its most prevalent mild form (mild TBI; mTBI), presents unique challenges toward protein biomarker discovery and validation given that blood is frequently obtained and processed outside of the clinical laboratory (e.g., athletic fields, battlefield) under variable conditions. As it stands, the field of mTBI blood biomarkers faces a number of outstanding questions. Do elevated blood levels of currently used biomarkers—ubiquitin carboxy-terminal hydrolase L1, glial fibrillary acidic protein, neurofilament light chain, and tau/p-tau—truly mirror the extent of parenchymal damage? Do these different proteins represent distinct injury mechanisms? Is the blood–brain barrier a “brick wall”? What is the relationship between intra- versus extracranial values? Does prolonged elevation of blood levels reflect de novo release or extended protein half-lives? Does biological sex affect the pathobiological responses after mTBI and thus blood levels of protein biomarkers?
At the practical level, it is unknown how pre-analytical variables—sample collection, preparation, handling, and stability—affect the quality and reliability of biomarker data.
The ever-increasing sensitivity of assay systems and lack of quality control of samples, combined with the almost complete reliance on antibody-based assay platforms, represent important unsolved issues given that false-negative results can lead to false clinical decision making and adverse outcomes.
This article serves as a commentary on the state of mTBI biomarkers and the landscape of significant challenges.
We highlight and discusses several biological and methodological “known unknowns”.
[The Known Unknowns: An Overview of the State of Stuart J. McDonald, Sandy R. Shultz, and Denes V. Agoston..Oct 2021. Journal of Neurotrauma, Volume: 38 Issue 19: September 14, 202, p. 2652-2666. http://doi.org/10.1089/neu.2021.0011 ]
Update 2018: FDA authorized marketing for the first blood test for the evaluation of concussion in adults Feb 13, 2018, but Blood-Based Protein Biomarkers for Mild Traumatic Brain Injury have known and unknown results. Peer review and further evaluations are in order.
"Research concluded that S100B, NSE, tau, and GFAP, provide contradictory results in regard to the overall utility in diagnostic and prognostic roles.
Most reviewed studies indicated that S100B measurement and use, either acutely or at several time points, can distinguish injured from noninjured patients with an uncertain degree of utility in predicting mortality. At present, S100B has largely become an acceptable biomarker of TBI; however, studies have begun to highlight the need to incorporate clinical symptoms instead of S100B concentration in isolation on the basis of inconsistent results across published studies.
Further research is needed to evaluate and validate the use of tau, NSE, and GFAP as a diagnostic aid in the management of concussion and TBI. Any diagnostic or prognostic information that can be obtained is important when managing athletes with concussion.
Unfortunately, at this time, biomarkers have only a limited role in the evaluation and management of concussion. Although several biomarkers of brain injury have been identified, continued research is required. S100B holds promise as the most clinically useful diagnostic biomarker. However, several biomarkers suffer from a lack of specificity, often being induced or released into the serum in response to other diseases or bodily injuries. This lack of specificity has hampered the effort to identify markers of mild TBI, especially in the context of trauma. A single biomarker may not have desired sensitivity and specificity for diagnosis nor for predicting outcome.
Biomarkers, in combination with other clinical data, such as head CT, would maximize the diagnostic accuracy. [Use of Blood Biomarkers in the Assessment of Sports-Related Concussion—A Systematic Review in the Context of Their Biological Significance Brendan O’Connell, BSc,*† Aine M. Kelly, PhD,‡ David Mockler,§ Matej Ore ˇ ´ si ˇc, PhD,{ Karl Denvir, MSc,† Garreth Farrell, MSc,† Damir Janigro, PhD,‖ and Fiona Wilson, PhD* Clin J Sport Med 2018;28:561–571)
FDA authorizes marketing of first blood test to aid in the evaluation of concussion in adults Feb 13, 2018
The U.S. Food and Drug Administration today permitted marketing of the first blood test to evaluate mild traumatic brain injury (mTBI), commonly referred to as concussion, in adults. The FDA reviewed and authorized for marketing the Banyan Brain Trauma Indicator in fewer than 6 months as part of its Breakthrough Devices Program.
Most patients with a suspected head injury are examined using a neurological scale, called the 15-point Glasgow Coma Scale, followed by a computed tomography or CT scan of the head to detect brain tissue damage, or intracranial lesions, that may require treatment; however, a majority of patients evaluated for mTBI/concussion do not have detectable intracranial lesions after having a CT scan. Availability of a blood test for concussion will help health care professionals determine the need for a CT scan in patients suspected of having mTBI and help prevent unnecessary neuroimaging and associated radiation exposure to patients.
“Helping to deliver innovative testing technologies that minimize health impacts to patients while still providing accurate and reliable results to inform appropriate evaluation and treatment is an FDA priority.
Today’s action supports the FDA’s Initiative to Reduce Unnecessary Radiation Exposure from Medical Imaging—an effort to ensure that each patient is getting the right imaging exam, at the right time, with the right radiation dose,” said FDA Commissioner Scott Gottlieb, M.D. “A blood-testing option for the evaluation of mTBI/concussion not only provides health care professionals with a new tool, but also sets the stage for a more modernized standard of care for testing of suspected cases. In addition, availability of a blood test for mTBI/concussion will likely reduce the CT scans performed on patients with concussion each year, potentially saving our health care system the cost of often unnecessary neuroimaging tests.”
According to the U.S. Centers for Disease Control and Prevention, in 2013 there were approximately 2.8 million TBI-related emergency department visits, hospitalizations and deaths in the U.S. Of these cases, TBI contributed to the deaths of nearly 50,000 people. TBI is caused by a bump, blow or jolt to the head or a penetrating head injury that disrupts the brain’s normal functioning. Its severity may range from mild to severe, with 75 percent of TBIs that occur each year being assessed as mTBIs or concussions. A majority of patients with concussion symptoms have a negative CT scan. Potential effects of TBI can include impaired thinking or memory, movement, sensation or emotional functioning.
“A blood test to aid in concussion evaluation is an important tool for the American public and for our Service Members abroad who need access to quick and accurate tests,” said Jeffrey Shuren, M.D., director of the FDA’s Center for Devices and Radiological Health. “The FDA’s review team worked closely with the test developer and the U.S. Department of Defense to expedite a blood test for the evaluation of mTBI that can be used both in the continental U.S. as well as foreign U.S. laboratories that service the American military.”
The Brain Trauma Indicator works by measuring levels of proteins, known as UCH-L1 and GFAP, that are released from the brain into blood and measured within 12 hours of head injury. Levels of these blood proteins after mTBI/concussion can help predict which patients may have intracranial lesions visible by CT scan and which won’t. Being able to predict if patients have a low probability of intracranial lesions can help health care professionals in their management of patients and the decision to perform a CT scan. Test results can be available within 3 to 4 hours.
The FDA evaluated data from a multi-center, prospective clinical study of 1,947 individual blood samples from adults with suspected mTBI/concussion and reviewed the product’s performance by comparing mTBI/concussion blood tests results with CT scan results. The Brain Trauma Indicator was able to predict the presence of intracranial lesions on a CT scan 97.5 percent of the time and those who did not have intracranial lesions on a CT scan 99.6 percent of the time. These findings indicate that the test can reliably predict the absence of intracranial lesions and that health care professionals can incorporate this tool into the standard of care for patients to rule out the need for a CT scan in at least one-third of patients who are suspected of having mTBI.
The Brain Trauma Indicator was reviewed under the FDA’s De Novo premarket review pathway, a regulatory pathway for some low- to moderate-risk devices that are novel and for which there is no prior legally marketed device.
The FDA is permitting marketing of the Brain Trauma Indicator to Banyan Biomarkers, Inc
[FDA authorizes marketing of first blood test to aid in the evaluation of concussion in adults , FDA Press announcement; For Immediate Release, February 13, 2018]
SPECT Versus MRI/CT For Post-Concussion Syndrome May 18, 2016
Persistent Post-Concussion Syndrome (PPCS) is one of the most frustrating conditions to work with, simply because most imaging studies are not powerful enough to detect subtle brain tissue damage; MRI and CT scans usually show nothing in patients with long-term symptoms.
SPECT scans show promise in this arena; as we reported in the January and May, 1996, issues of the Soft-Tissue Review, researchers have found evidence of brain lesions in whiplash patients. Now some new research has been published that adds substantially to this work.
This study investigated 43 patients with "persistent post-concussion syndrome"—or patients with symptoms of PCS an average of 477 days since their injury. All of the patients had mild closed head injury: 47% from motor vehicle accidents; 19% from falls; and 30% from assaults or a falling object. Thirty-nine of these patients had been given an MRI scan, and 21 had been given a CT scan before this study began.
The researchers performed a SPECT scan on each patient, and then compared abnormal findings on this series to findings on MRI and CT. Of the 43 patients, SPECT found abnormalities in 53% of the subjects. MRI found abnormalities in just 9%, and CT only 4-6%. Thus, 23 patients had evidence of brain tissue damage on SPECT that was not detected by other imaging methods.
[Kant R, Smith-Seemiller L, Isaac G, Duffy J. Tc-HMPAO SPECT in persistent post-concussion syndrome after mild head injury: comparison with MRI/CT. Brain Injury 1997;11(2):115-124]
=========================================
SPECT Scans Use in Detecting Traumatic Brain Injuries
Fig. 1: The above is an example of a SPECT scan before and after common medical treatment used for a wide variety of treatments known as Hyperbaric Oxygen Treatment. The different colors represent the difference of perfusion before and after treatment. (Source Wikimedia Commons)
Traumatic brain injuries (TBIs) occur as a result of blunt force to the head or trauma and can range from mild concussions to severe and prolonged loss of consciousness. [1]
TBIs like Post Traumatic Stress Disorder both leave one a greater risk for developing depression, anxiety, or drug addiction. [1]
It is difficult to differentiate whether such symptoms are the result of physical trauma to the head or of psychological stress from the event. This distinction is particularly difficult to make in treating military men after a traumatic accident. [1]
The treatment for TBIs is also expensive estimated at $11,700 a year for a patient with a TBI the first year out of the military versus $2,400 a year for a military person without a TBI. [1] In addition, the long term repercussions of not treating even a mild TBI can lead to increased risk of depression and suicide. [1]
Clinically, it is important to distinguish PTSD from a traumatic brain injury, or to determine whether a patient suffers from both diagnoses to explore treatment options.
Imaging studies such as MRI and CT scans can detect TBIs, but recent research suggest SPECT scanning might be a more sensitive imaging alternative. [2] [Kaitlyn Merritt, April 28, 2018Submitted as coursework for PH241, Stanford University, Winter 2018]
New (2018) Blood Tests for Concussion:
C-terminal hydrolase (UCH-L1) and glial fibrillary acidic protein (GFAP)
"The newly approved blood test, called the Brain Trauma Indicator (BTI), helps determine whether a CT scan is needed in people with suspected concussion. The test measures two brain-specific proteins, ubiquitin C-terminal hydrolase (UCH-L1) and glial fibrillary acidic protein (GFAP), that are rapidly released by the brain into the blood within 12 hours of serious brain injury. Test results can be available within three to four hours.
"Low blood levels of these proteins indicate that, if the person has damage, it is likely too small to be seen on a CT scan. If these protein levels are high, healthcare practitioners could rule out mild concussion and order a CT scan to look for bleeding and damage that would require intervention.
"BTI developers say that use of their blood test could improve the accuracy of distinguishing between mild concussions and more serious brain injury in adults. They also say BTI could reduce the number of unnecessary CT scans by 33% in people suspected of having brain injury. CT scans can be expensive and time-consuming, and unnecessary scans expose patients to potentially harmful radiation.
"The FDA evaluated data and product performance from a study of 1,947 blood samples from adults suspected of having a concussion. When compared to CT scan results, the FDA found that BTI correctly identified the presence of damaged brain tissue in 97.5% of the individuals and correctly identified the absence of damage in 99.6% individuals. The FDA's review and approval of BTI took fewer than six months because it was part of the administration's Breakthrough Devices Program.
"BTI is only approved for use in adults, but plans are in the works to start a clinical trial to evaluate its use in children. Developers of the test are also working on a smaller, hand-held testing device that would be of interest to healthcare practitioners working in sports medicine, low-resource settings, or military installations.
"Some experts caution that head injuries can be complicated, and BTI does not replace CT scans in all cases. Also, CT scans, which were used to evaluate the effectiveness of BTI, do not detect all severe injuries. Thus, BTI does not eliminate the need for a full evaluation by a healthcare practitioner, including observation of the patient, neurological exam, and diagnosis.
"And while BTI has promise for evaluating concussions, it cannot be used to address the cumulative damage done by repeated head injuries. These repetitive traumas have been linked to degenerative brain disease—a condition that has received a lot of press because of its prevalence in football players who experience many hits to the head over the span of their careers. [Lab Tests On Line, HealthLabs.com,
CBS TV Football commentator, Gary Danielson, put it succinctly, “the defender (tackler) is responsible for moving their head and helmet (up-and-away or aside) to prevent spearing.” It doesn't matter if the ball carrier bends his head during the collision. [Auburn versus Florida, October 5, 2019, 3:30 PM CBS TV]
Athlete Concussion Neuropathology, Psychopathology, Morbidity and Mortality
Because there are no known treatments for Concussion Brain Disease aka Traumatic Brain Injuries (TBI), Chronic Traumatic Encephalopathy (CTE), prevention of Concussion and subconcussive blows are the only options. Prevention strategies must be sport specific.
The ICD-10-CM Concussion Diagnosis Code is SO6.O. There are several additional circumstances and perpetrator Modification Diagnosis Codes that can further describe and modify the baseline Concussion Diagnosis Code.
Targeting, when struck by a football helmet, (leading with the helmet, shoulder, forearm, fist, hand or elbow with forcible contact to the football oponents head or neck area [Targeting Rules, Ben Roberts,Sept. 16, 2019 Lex. Herald Leader], an ICD-10 modifier code is added:
The complete ICD-10-CM Concussion Diagnosis with Helmet modifier code:
ICD-10-CM Diagnosis Code = W21.81XA
An ominous medical sign of Concussion and/or Brain Trauma during a football game is the 'Fencing Response', which is recognized when the Football Athlete is knocked down on his/her back or side with arms flexed or extended into the air that lasts several seconds after impact in 'Fencing Response Position'. [Levin HS, Robertson CS. Mild traumatic brain injury J Neurotrauma. 2013;30(8):610–617] Please see the pictures above.
"Pittsburgh Steelers QB Mason Rudolph suffered what appeared to be a serious head injury during 2nd half Sunday Oct 6, 2019 against the Baltimore Ravens. Pleasae see picture above. [by Brian Batko, Oct 6, 2019 Pittsburgh Post-Gazette]
When the FootballAthlete goes down on his/her back extending his/her arms in 'Fencing Response' "it is a peculiar position of the arms following a concussion as described above after moderate forces traumatized the human brainstem.
The fencing response is often observed during athletic competition involving contact, such as American football, hockey, rugby union, rugby league, [Newton, Phil (August 28, 2009). "YouTube helps identify a new tool in the evaluation of brain injury". Psychology Today. Retrieved April 4, 2015]
"Florida quarterback Tim Tebow had a 'Fencing Response' when knocked to ground during UK game in 2009 [Fencing response" key indicator of concussion, by Mike McCall, Alligator Staff writer Sep 29, 2009] Tebow "was taken to UK Medical Center by ambulance after taking a shot to the head while being sacked in the third quarter of the top-ranked Gators' 41-7 victory over Kentucky at Commonwealth Stadium on Saturday night..."We believe it is a concussion." See video [Mark Schlabach Sept 26, 2009 ESPN] See above Fencing Pictogram cThadius856
Post-concussion syndrome is a complex disorder in which various symptoms that last for weeks and sometimes months after the injury that caused the concussion.
So why are so many doctors, research scientists, public health officials, educators, advocates, families of Athletes and others in the athletic community so concerned about Concussion Brain Disease and preventing helmet to helmet trauma, reckless spearing and support stringent football penalties?
CONCUSSION CAN CAUSE THE FOLLOWING MILD, MODERATE, SEVERE AND CHRONIC MORBIDITY AND MORTALITY
PLEASE SAVE ATHLETES AND THE GAME OF FOOTBALL
====
Baum, Hedlund, Aristei & Goldman Attorneys with experience in Traumatic Brain Injuries have weighed in on Spearing Controversy with the following excellent history whidh they have allowed us to share:
“The drive for making the game smarter is nothing new, according to the Guardian. Programs similar to the Heads Up campaign date back to latter part of the 1800s.
“‘Butting,’ which is now commonly referred to as ‘spearing,’ caused an epidemic of head injuries in the 1880s (spearing is when a player hits another player using the crown of his head as a battering ram). In this era, Yale University’s football team had a reputation for an offensive line that headbutted their opponents to clear running lanes for their ball carriers.
“A few coaches of the time advised players to learn to tackle using a dummy, focusing on keeping one’s head to the side in order to avoid head collisions. These teachings would continue into the 20th century.
“Despite the best efforts Teddy Roosevelt’s movement to reform football i.e. revisions to the football rulebook, the creation of the National Collegiate Athletic Administration, football head injuries and concussions continued to occur in high numbers.
“A 1930s study looking into the cause of football injuries concluded that nearly 30 percent of injuries could be avoided. In the 1940s, many thought the advent of the plastic football helmet would reduce traumatic brain injury.
“In 1968, the media reported on 36 high school football players who lost their lives playing the game, and another 30 who were paralyzed. Rules changed, this time to combat spearing, even though a study at the time found that only 28% of concussions were caused by spearing.
“As football helmets improved in the 1970s, the sport’s nastiest head injury numbers went down. No longer were players sustaining skull fractures or paralysis in such high numbers, they were instead suffering concussions over and over again, the effects of which were largely dealt with in silence as many players and fans were unaware of the long-term health consequences.
“After news of Mike Webster’s death and subsequent chronic traumatic encephalopathy (CTE) diagnosis, the league again made moves in an attempt to improve the safety of the game and they again emphasized anti-spearing rules and created USA Football’s Heads Up Program to teach kids the same tackling concepts outlined more than a century ago. Which brings us to where we are today.
“We now have helmets and mouth pieces with high-tech sensors to detect concussions, and robots are patrolling the sidelines of football fields looking for potentially concussed players.
And now to the disappointing conclusion: “What do these products have in common? They all promise that their products are helping to improve the safety of the game, which is a good thing. But as we’ve seen, this is a promise they can’t possibly keep—teaching players how to tackle isn’t going to stop concussions any more than a high-tech helmet will. Smarter football won’t reduce traumatic brain injuries. The only sure way to do that is to not play." The End. [Baum, Hedlund, Aristei & Goldman Attorneys with experience in Traumatic Brain Injuries]
====
CONCUSSION, TAU PROTEIN MISFOLDING AND AGGREGATION, DYSTONIA, TAU BLOOD TEST
Tau proteins (or τ proteins, after the Greek letter with that name) are proteins that stabilize microtubules (the cytoskelton in neurons, brain cells, and axons) are abundant in neurons of the central nervous system and are less common elsewhere, but are also expressed at very low levels in CNS astrocytes and oligodendrocytes.[5] Pathologies and dementias of the nervous system such as Alzheimer's disease and Parkinson's disease[6] are associated with tau proteins that have become defective and no longer stabilize microtubules properly. [Goedert M, Spillantini MG (May 2017). "Propagation of Tau aggregates". Molecular Brain. 10 (1): 18. doi:10.1186/s13041-017-0298-7. PMC 5450399. PMID 28558799]
Pictured above, following Traumatic Brain Injury, Concussion and other trauma and disorders, Tau protein (green) aggregates abnormally in and on brain cells (blue) and around axons and Tau protein can entangle the axons and cause misdirection of the nerve cell axon signals, depending on the NeuroNetworks affected in the region. function and action of the Brain afflicted or traumatized, and cause abnormal movements, other mental and motor pathologies. Tau proteins, after certain cncentrations, spill out of the cell and extracellular space and enter the bloodstream (red). Research shows that antibodies (blue) can capture tau in the blood, be measured and reflect Tau levels in the brain.
Dystonia is neurological movement disorder that causes muscles to contract or spasm involuntarily. Dystonia is caused by defect in mechanisms that allow muscles to relax when they are not in use. Dystonia muscle spasms distort the body into awkward, irregular, uncomfortable positions and affects about 300,000 people in North America with varying degrees of disability and pain. [Surgeons Trying Pacemaker Procedure For The Brain, Doctors Find Deep Brain Stimulation Can Help Patients Deal With Neurological Disorder, ABC 7 News, Denver, Apr 14, 2010]
Sudden Athlete failure to execute easy athletic motor actions is often caused by Dystonia and aka YIPS. For example, when an Athletes suddenly cannot execute i.e. throwing baseball, shooting basketball, swimming, kicking football. Dysphonia is a dystonia that affects the both focal vocal cords and the generalized entire body and “Caused by genetic disorder which is a defect in a protein called Torsin A.[1]
Torsion A is a Mutation the DYT1 gene characterized by a loss of the amino acid, glutamic acid, in the Torsin A protein. The Defective protein creates disruption in communication in neurons control muscle movement control [2] Torsin A is a Dominant Allele, when a person needs 1 copy of mutated DYT1 gene [3].
30 to 40% who have the gene have symptoms [4]. Dystonia is prevalent among the Jewish population and populations of immigrants to America and common among Polish Ashkenazi Jews. Torsion dystonia in Ashkenazi Jewish was found by Department of Epidemiology / Public Health Yale Univ. School Medicine in New Haven, CT.
“Reports beginning this century reveal Ashkenazi Jewish families with multiple cases Inherited Torsional Dystonia (ITD) in siblings or parents and offspring. [Schwalbe 1908; Bernstein 1912; Abrahamson 1920) (Wechsler and Brock 1922; Mankowsky and Czerny 1929; Regensberg 1930)]1st evaluation of mode of inheritance ITD in Jewish and non-Jewish families was described by Zeman and Dyken (1967), who found it was an inherited autosomal dominant with incomplete penetrance in both Jewish and non-Jewish families. Although they concluded that the gene frequency was higher in the AJ population than in non-Jews, no difference in mode of inheritance or disease mechanism was construed.
REFERENCES
THAP1 gene was fond in 3 Amish-Mennonite families with mixed-onset primary torsion dystonia is DYT6 dystonia. Another German family mutatuion with primary torsion dystonia had THAP1 mutations which also caused dystonia in other ancestry groups.
‘Missense mutation’ impairs DNA binding and causes transcriptional dysregulation and the DYT6 dystonia phenotype (observable characteristics, how a person appears) a primary torsion dystonia. [Mutations in the THAP1 gene are responsible for DYT6 primary torsion dystonia, Tania Fuchs et al, Nature Genetics 41, 286 – 288 (2009) 1 February 2009]
Dystonia is prevalent among the Jewish population and populations of immigrants to America, Common among Polish Ashkenazi Jews. Torsion dystonia in Ashkenazi Jewish was found by Department of Epidemiology / Public Health Yale Univ. School Medicine in New Haven, CT.
“Reports beginning this century found Ashkenazi Jewish (AJ) families with multiple cases Inherited Torsional Dystonia in siblings or parents and offspring Schwalbe 1908; Bernstein 1912; Abrahamson 1920) (Wechsler and Brock 1922; Mankowsky and Czerny 1929; Regensberg 1930)
1st evaluation of mode of inheritance ITD in Jewish and non-Jewish families was described by Zeman and Dyken (1967), and was inherited autosomal dominant with incomplete penetrance in both. TAU Protein Pathology occurs in football athletes’ with Traumatic Brain Injury (TBI) and Concussion, in addition to Dystonia.
“Traumatic brain injury (TBI) from contact sports involve TAU protein entanglement of neuron cells and cause chronic behavioral, mood, severe depression + cognitive disturbances with pathological tau protein deposition found on brain autopsy” particularly Pro Football Players.
PET scans after IV injections of FDDNP (2-(1-{6-[(2-[fluorine-18]fluoroethyl)(methyl)amino]-2-naphthyl}-ethylidene)malononitrile) found TAU protein brain was deposited where brain lit-up.In the paset, only autopsy was indicative for TAU deposition and was the only means for identification prior to death of neurodegeneration in contact-sports athletes. [Gary W. Small, M.D., et al Am J Geriatric Psychiatry 21:2, February 2013]
FDDNP-PET may offer a means for premorbid identification of neurodegeneration in contact-sports athletes. [Am J GeriatrPsychiatry 2013; 21:138e144]
Dystonia will not fit into one diagnostic box and sometimes very difficult to diagnose. Because are no pathognomonic tests for the disease. “New research presented at this year’s International Early Psychosis Association (IEPA) meeting in Milan, Italy (20-22 October) shows that levels of a certain type of the Alzheimer’s disease-related TAU protein are higher in patients aged 18 years and under suffering Early Onset Psychosis (EOP).
“This finding suggests that tau protein metabolism may be altered in EOP. EOP, including early onset of schizophrenia (EOS) and affective non-schizophrenia psychotic disorders, are devastating mental disorders with an onset age before 18 years and an unknown cause.
“Previous studies have shown that when these conditions develop, the person affected suffers a severe loss of neurocognitive functions, such as attention, executive function, coordinating thoughts and working memory. Researchers have suggested this could indicate neurodegeneration.
“In neurodegenerative disorders such as Alzheimer’s disease, the deterioration is associated with increased neurodegenerative biomarkers (such as TAU protein) in blood and cerebrospinal fluids. [Antibody Makes Alzheimer’s Protein Detectable in Blood,May 2, 2017 by Dr. Francis Collins]
Age can bring moments of forgetfulness. It can also bring concern that the forgetfulness might be a sign of early Alzheimer’s disease. For those who decide to have it checked out, doctors are likely to administer brief memory exams to assess the situation, and medical tests to search for causes of memory loss. Brain imaging and spinal taps can also help to look for signs of the disease.
But an absolutely definitive diagnosis of Alzheimer’s disease is only possible today by examining a person’s brain postmortem. A need exists for a simple, less-invasive test to diagnose Alzheimer’s disease and similar neurodegenerative conditions in living people, perhaps even before memory loss becomes obvious.
One answer may lie in a protein called tau, which accumulates in abnormal tangles in the brains of people with Alzheimer’s disease and other “tauopathy” disorders. In recent years, researchers have been busy designing an antibody to target tau in hopes that this immunotherapy approach might slow or even reverse Alzheimer’s devastating symptoms, with promising early results in mice [1, 2].
Now, an NIH-funded research team that developed one such antibody have found it might also open the door to a simple blood test [3]. Scientists know that tau loosened from abnormal tangles exits the brain and enters the bloodstream. Testing for the protein in blood has been extremely difficult because it disappears almost immediately.
But the team has discovered that tau proteins bound to antibodies remain in the bloodstream much longer, allowing them to reach easily detectable levels. Importantly, they show that those blood levels of tau provide a good indication of abnormal tau levels in the brain. The discovery suggests a simple blood test for tau could one day be used to screen patients for early signs of tau-associated conditions, including Alzheimer’s disease and a brain injury known as chronic traumatic encephalopathy (CTE) that can affect football players and boxers who have suffered repeated concussions.
In a study published in Science Translational Medicine, the team led by David Holtzman at Washington University, St. Louis, showed that an infusion of its anti-tau antibody into people and mice causes blood levels of tau to rise within a day or two. In fact, during studies of three people with a rare neurodegenerative disease called progressive supranuclear palsy, they found that a single dose of antibody caused tau levels to remain high for up to 2 weeks.
Further study showed that the antibody increases blood levels of tau by stabilizing the protein and not allowing it to disappear so quickly. When tau alone was injected into the bloodstream, half of it vanished in less than 10 minutes. But when tau was injected along with the antibody, the protein remained in the blood for more than 3 hours. In other words, the antibody acts like a caretaker, making tau easier to measure by amplifying the time it stays in the bloodstream. Of course, tau levels in the blood would only be useful if they provide an accurate indication of what’s going on in the brain.
To find out, the researchers tested tau levels in mice with brain injuries. The injuries caused an increase in tau in the brain fluid that also appeared in their blood. Similarly, in mice genetically modified to develop less tau in brain fluid with age, the researchers found that blood levels of the protein indeed declined as the animals got older. While lots of work remains to be done, Holtzman notes that the next logical step is to pair this promising new blood test with clinical trials to prevent or slow Alzheimer’s disease. One promising partner would be the Accelerating Medicines Partnership-Alzheimer’s Disease (AMP-AD) Biomarkers Project, which has brought together four pharmaceutical companies and NIH’s National Institute on Aging.
AMP-AD is already incorporating tau imaging into trials of several promising therapies, and adding the blood test could be a powerful way to assess its clinical utility.
LARYNGEAL DYSTONIA
Spasmodic dysphonia (SD), a focal form of dystonia, is a neurological voice disorder that involves "spasms" of the vocal cords causing interruptions of speech and affecting the voice quality. SD can cause the voice to break up or to have a tight, strained, or strangled quality.[2019 National Spasmodic Dysphonia Association, NSDA], NSDA,300 Park Boulevard, Suite 335 Itasca, Illinois 60143, Email: nsda@dysphonia.org [NORD (National Organization of Rare Disorders) gratefully acknowledges H A Jinnah, MD, PhD, Professor, Departments of Neurology, Human Genetics, & Pediatrics, Emory University School of Medicine, for assistance in the preparation of this report. Copyright ©2018 NORD - National Organization for Rare Disorders]
Laryngeal Dystonia Subdivisions
Summary: Laryngeal dystonia (LD) is a chronic voice disorder characterized by momentary periods of uncontrolled spasms of the muscles of the voice box (larynx). These muscles control speech. The spasms can result in tightness in the throat, recurrent hoarseness, and changes in voice quality and/or difficulty speaking.
At certain times, affected individuals must make a conscious effort in order to speak. The most frequent sign of this disorder is a sudden, momentary lapse or interruption of the voice. When affected individuals speak, their voice may sound strained, forced, strangled, breathy, or whispery. In severe cases, an affected individual may be barely able to speak. LD can potentially cause significant quality of life issues for affected individuals impacting both work and social situations.
The disorder can be associated with depression and anxiety. There is no cure for LD, but the disorder can be treated. In most cases, the cause of LD is not significantly progressive and not fatal.
Copyright © 2024 Athlete Safety 1st Education - All Rights Reserved.
Powered by GoDaddy Website Builder
