Posts Tagged diagnosis

[REVIEW ARTICLE] Blood Biomarkers for Traumatic Brain Injury: A Quantitative Assessment of Diagnostic and Prognostic Accuracy – Full Text

Blood biomarkers have been explored for their potential to provide objective measures in the assessment of traumatic brain injury (TBI). However, it is not clear which biomarkers are best for diagnosis and prognosis in different severities of TBI. Here, we compare existing studies on the discriminative abilities of serum biomarkers for four commonly studied clinical situations: detecting concussion, predicting intracranial damage after mild TBI (mTBI), predicting delayed recovery after mTBI, and predicting adverse outcome after severe TBI (sTBI). We conducted a literature search of publications on biomarkers in TBI published up until July 2018. Operating characteristics were pooled for each biomarker for comparison. For detecting concussion, 4 biomarker panels and creatine kinase B type had excellent discriminative ability. For detecting intracranial injury and the need for a head CT scan after mTBI, 2 biomarker panels, and hyperphosphorylated tau had excellent operating characteristics. For predicting delayed recovery after mTBI, top candidates included calpain-derived αII-spectrin N-terminal fragment, tau A, neurofilament light, and ghrelin. For predicting adverse outcome following sTBI, no biomarker had excellent performance, but several had good performance, including markers of coagulation and inflammation, structural proteins in the brain, and proteins involved in homeostasis. The highest-performing biomarkers in each of these categories may provide insight into the pathophysiologies underlying mild and severe TBI. With further study, these biomarkers have the potential to be used alongside clinical and radiological data to improve TBI diagnostics, prognostics, and evidence-based medical management.


Traumatic brain injury (TBI) is a common cause of disability and mortality in the US (1) and worldwide (2). Pathological responses to TBI in the CNS include structural and metabolic changes, as well as excitotoxicity, neuroinflammation, and cell death (34). Fluid biomarkers that may track these injury and inflammatory processes have been explored for their potential to provide objective measures in TBI assessment. However, at present there are limited clinical guidelines available regarding the use of biomarkers in both the diagnosis of TBI and outcome prediction following TBI. To inform future guideline formulation, it is critical to distinguish between different clinical situations for biomarker use in TBI, such as detection of concussion, prediction of positive and negative head computed tomography (CT) findings, and prediction of outcome for different TBI severities. This allows for comparisons to determine which biomarkers may be used most appropriately to characterize different aspects of TBI.

The identification of TBI severity has become a contentious issue. Currently, inclusion in TBI clinical trials is primarily based on the Glasgow Coma Scale (GCS), which stratifies patients into categories of mild, moderate, and severe TBI. The GCS assesses consciousness and provides prognostic information, but it does not inform the underlying pathologies that may be targeted for therapy (56). Furthermore, brain damage and persistent neurological symptoms can occur across the spectrum of TBI severity, limiting the use of GCS-determined injury severity to inform clinical management. Biomarkers in TBI have the potential to provide objective and quantitative information regarding the pathophysiologic mechanisms underlying observed neurological deficits. Such information may be more appropriate for guiding management than initial assessments of severity alone. Since the existing literature primarily focuses on applications of biomarkers in either suspected concussion, mild TBI (mTBI), or severe TBI (sTBI), we will discuss biomarker usage in these contexts.

Concussion is a clinical syndrome involving alteration in mental function induced by head rotational acceleration. This may be due to direct impact or unrestrained rapid head movements, such as in automotive crashes. Although there are over 30 official definitions of concussion, none include the underlying pathology. Missing from the literature have been objective measures to not only identify the underlying pathology associated with the given clinical symptoms, but also to indicate prognosis in long-term survival. Indeed, current practices in forming an opinion of concussion involve symptom reports, neurocognitive testing, and balance testing, all of which have elements of subjectivity and questionable reliability (7). While such information generally reflects functional status, it does not identify any underlying processes that may have prognostic or therapeutic consequences. Furthermore, because patients with concussion typically present with negative head CT findings, there is a potential role for blood-based biomarkers to provide objective information regarding the presence of concussion, based on an underlying pathology. This information could inform management decisions regarding resumption of activities for both athletes and non-athletes alike.

Blood-based biomarkers have utility far beyond a simple detection of concussion by elucidating specific aspects of the injury that could drive individual patient management. For example, biomarkers may aid in determining whether a mTBI patient presenting to the emergency department requires a CT scan to identify intracranial pathology. The clinical outcome for a missed epidural hematoma in which the patient is either discharged or admitted for routine observation is catastrophic; 25% are left severely impaired or dead (8). The Canadian CT Head Rule (9) and related clinical decision instruments achieve high sensitivities in predicting the need for CT scans in mild TBI cases. However, they do this at specificities of only 30–50% (10). Adding a blood biomarker to clinical evaluation may be useful to improve specificity without sacrificing sensitivity, as recently suggested (11). In addition, given concern about radiation exposure from head CT scans in concussion cases, particularly in pediatric populations, identification of patients who would be best assessed with neuroimaging is crucial. Thus, the use of both sensitive and specific biomarkers may serve as cost-effective tools to aid in acute assessment, especially in the absence of risk factors for intracranial injury (12). S-100B, an astroglial protein, has been the most extensively studied biomarker for TBI thus far and has been incorporated into some clinical guidelines for CT scans (1314). However, S-100B is not CNS-specific (1516) and has shown inconsistent predictive capacity in the outcome of mild TBI (1718). Given that several other promising biomarkers have also been investigated in this context, it is important to evaluate and compare the discriminative abilities of S-100B with other candidate blood-based biomarkers for future use.

Blood biomarkers also have the potential to help predict unfavorable outcomes across the spectrum of TBI severity. Outcome predication is difficult; in mTBI, existing prognostic models performed poorly in an external validation study (19). Identifying biomarkers that best predict delayed recovery or persistent neurological symptoms following mTBI would help with the direction of resources toward patients who may benefit most from additional rehabilitation or prolonged observation. In sTBI, poorer outcome has often been associated with a low GCS score (20). However, factors such as intoxication or endotracheal intubation may make it difficult to assess GCS reliably in the acute setting (2122). The addition of laboratory parameters to head CT and admission characteristics have improved prognostic models (23). Thus, prognostic biomarkers in sTBI could help determine whether patients are likely to benefit from intensive treatment. Several candidate biomarkers that correlate with various pathologies of mild and severe TBI have been studied (24), but their relative prognostic abilities remain unclear.

Existing reviews on biomarkers in TBI have provided valuable insight into the pathologic correlates of biomarkers, as well as how biomarkers may be used for diagnosis and prognosis (2531). However, there has been no previous quantitative comparison of the literature regarding biomarkers’ discriminative abilities in specific clinical situations. Here, we compare existing studies on the discriminative abilities of serum biomarkers for four commonly studied clinical situations: detecting concussion, predicting intracranial damage after mTBI, predicting delayed recovery after mTBI, and predicting adverse outcome after sTBI.[…]


Continue —-> Frontiers | Blood Biomarkers for Traumatic Brain Injury: A Quantitative Assessment of Diagnostic and Prognostic Accuracy | Neurology

Figure 2. Anatomical locations of potential TBI biomarkers. The biomarkers included in this schematic all rated as “good” (AUC=0.800.89) or better for any of the four clinical situations studied (detecting concussion, predicting intracranial damage after concussion, predicting delayed recovery after concussion, and predicting adverse outcome after severe TBI). Biomarkers with a pooled AUC <0.8 are not shown. 1Also found in adipose tissue; 2synthesized in cells of stomach and pancreas; may regulate HPA axis; 3found mostly in pons; 4also found extracellularly; 5lectin pathway of the complement system; 6also found in endothelial cells. BBB, blood brain barrier. ECM, Extracellular matrix. Image licensed under Creative Commons Attribution-ShareAlike 4.0 International license. See Supplementary Material for image credits and licensing.

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[WEB SITE] What one piece of advice would you give to someone who has just been diagnosed? – Epilepsy Society

21 November 2018

In September 2018, we asked our Facebook community what was the one piece of advice they would want to give to someone who had just been diagnosed with epilepsy. Our Marketing and Communications Executive, Paige Dawkins, talks more about the responses we received.


What one piece of advice would you give to someone who has just been diagnosed?

How can a diagnosis feel?

Everyone will have their own unique reaction to being diagnosed with epilepsy. Some people will feel scared, some people will feel confused as to where the epilepsy came from, possibly seemingly out of the blue. Some people will feel relief, as they finally have an answer to the seizures they have been experiencing. Coming to terms with a diagnosis can depend on someone’s own personal life experiences, as well as the support and information they have available to them at the time, from family, friends, and healthcare professionals.

One thing that we learnt from our Facebook post was for certain – a diagnosis of epilepsy does not necessarily mean the end of an enjoyable and fulfilling life. For some people, their experiences with epilepsy have actually taught them valuable lessons, and for others, epilepsy has not stopped them from achieving their dreams. Below is a selection from over 130 comments we received on the post; here is the advice that our followers would give to someone who has just been diagnosed with epilepsy.

Our follower’s advice

‘Actually I have 2, 1 to the person and the 2nd to the care givers:  1) The biggest problem with Epilepsy is not seizures its other people and their perceptions/attitude. 2) parents,guardians & carers go against you natural instincts and dont wrap someone up in cotton wool. Give them space to grow learn and make mistakes the usual way. Yes its tough on you as you will invariably have to pick up the pieces but it will be invaluable to the child/individual as they will learn not to be defined and constrained by their condition.’

‘never let your epilepsy beat you I got diagnosed 8 years ago I have a one year old baby I work and live a normal everyday life I’ve ran half marathons done the tough mudder and more events I thought things were going to be awful and went to a size 16 I’m now a size 10.’

‘I hate it !! But I’ve learnt to live with it. Don’t let it dictate your life x’

‘Don’t panic. Work with it, not against it.’

‘I have just recently been diagnosed with TLE and the hardest thing I’ve had to deal with is losing my driving licence which has been a complete life changer and very stressful at times. But I still believe you can still be happy as anyone else. You are just going to be living a bit differently from now on. And it’s ok to feel crap about it xxx’

‘Take each day as it comes and treat today as the gift it is…the present.’

‘That it’s not the end of the world. It just feels like it. But you will come to accept it and manage it the best that you can. That it’s more common than you think. And that it does not define who you are x’

‘Don’t fight the people around you who are trying to help, my big mistake.’

‘I’ve had epilepsy all my life, from the age of 18 months and I’m 34 this week. The one thing I would say is. Epilepsy is part of who you are. It’s a sucker, we learn differently and act differntly but we still human. Don’t let people think epilepsy is a big tabo to talk about. Coz it’s not.’

‘Make sure you get an appointment with a neurologist. They have a much better chance of helping you control your epilepsy than a GP.’

‘it means you have to do some thing differently sometimes but it will only stop you living your life if you let. You find your own coping mechanisms, I have a dark sense of humour that freaks people out sometimes if they aren’t used to me.’

‘Always look for the positive, get to know your body & brain. Stay away from booze.’

‘Just roll with it as best you can! The more you stress or get frustrated it just makes it worse and doesn’t get you anywhere. It’s hard when others don’t understand but don’t push them away most of the time they are doing there best x’

‘Do not let it take over your life. You will learn to adapt to certain restrictions life brings with epilepsy…but you can still have a fulfilled life in other ways. Just take care of yourself and be sensible with your decisions’

‘Remember to take the meds…and on time. ‘

‘People don’t understand what its like to think is it going to happen today, that feeling of just wanting to stay at home just incase, but you have to get past this and get help from others in the same position as yourself, joining my local epilepsy coffee and chat group has made me realise that there are people worse off than me and that I’ve just got to get on with it, not being able to drive is crap, it effects the whole family not just myself, I have really low days but just put on a brave face and get on with it! Don’t let it stop you living!’

‘Keep positive…life gets better x’

‘To know your not alone and to know it is good to talk. Xx’

‘Trust yourself and your body. You know your body better than anyone else possibly could. Try not to blame yourself. And for me that’s still really hard. Don’t give up. It’s not easy and is most definitely a life changer. But just love yourself as much as you can with all the trials and all the not knowings. The brain is a largely uncharted map and in hard times lean on that, on the people who truly love you and peace wherever it may be. And through your journey, as hard as it may be eliminate those who are negative and unsupportive. Educate yourself and others in your life and last but not least; the brain is a muscle too and it needs to be worked out. Keep on keeping on’

‘Don’t bottle your feelings up, talk to people who have epilepsy, it really helps a lot. Join epilepsy groups xx’

‘Take your meds regularly. Don’t skip them but if the side effects are unbearable, you CAN request to try a new drug. What is great for one person is terrible for another. Get the right drug for you.’

‘You are not alone x’

‘Get your free bus pass!’

‘It is still who you are. It teaches you to respect your body and pay attention to its signs. It makes you stronger while you have to talk about it to several people, sometimes ask for help… You can live a perfect life with epilepsy :)’

‘Don’t let it define you as a person, it’s only a part of you not all of you’

‘Be kind to yourself.’

‘Take your meds at the same time each day, get enough sleep and keep stress as low as possible. Don’t live in fear of having a seizure (easy to say but hard in reality) and try and live your life to the full.’

‘Try take it all in and learn about the medication and your triggers what starts it off and after that live your life to the best you can do. Dont let it become a label and drag you down rise above it and be yourself xxxx’

‘Talk , cry , love but most of all laughter has helped us stay positive’

‘Take every day as it comes! But don’t let epilepsy define you. The epilepsy society packs are amazing too so definately get yourself a few of those, and especially the just diagnosed pack – they help so much!!’

‘Just don’t give up on anything. You can live a full life with the right medication. And the most important thing: here you’re not alone.’

‘Patience. It’s a bumpy ride so keep strong. ‘

‘Research other people’s triggers. What’s okay for one person may not be for you. Sewing actually triggers me. (Focusing on Fast patterns)’

‘Sleep is important! Too little sleep can make seizures worse. While sleep can really help post siezure recovery.’

‘I know it’s hard, but please don’t give up. Don’t let epilepsy rule your life! ‘

‘You have just started a new chapter in your life. Epilepsy is not how you are, it is what you have. Be patient and learn what your body is telling you’

‘Hey plenty of rest and keep a regular routine with eating / sleeping xo’

‘Don’t panic. it’s not the end of the world and you can live a normal life’

‘It isn’t always life changing. The right meds might be the first you try x’

‘There are always better days. Relax and accept the dark days and know they’ll not last forever.’

‘Do not let it change your dreams goals & plans in life. It’s a condition we have to live with not let it rule our life. I have never let it get the better of me or my dreams goals & plans. I am a husband a dad run my own businesses stood as an independent candidate in last years general election! A personal goal from a young age. Epilepsy is not the end of your life journey it’s part of it!’

Our online social community

On our social media pages, we share information about epilepsy, news stories, blogs, personal stories and community posts such as the above. If you would like to join our online community, follow us on FacebookTwitterInstagram and LinkedIn.

via What one piece of advice would you give to someone who has just been diagnosed?

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[ARTICLE] Poststroke Depression Biomarkers: A Narrative Review – Full Text

Poststroke depression (PSD) is the most prevalent psychiatric disorder after stroke, which is independently correlated with negative clinical outcome. The identification of specific biomarkers could help to increase the sensitivity of PSD diagnosis and elucidate its pathophysiological mechanisms. The aim of current study was to review and summarize literature exploring potential biomarkers for PSD diagnosis. The PubMed database was searched for papers published in English from October 1977 to December 2017, 90 of which met inclusion criteria for clinical studies related to PSD biomarkers. PSD biomarkers were subdivided into neuroimaging, molecular, and neurophysiological. Some of them could be recommended to support PSD diagnosing. According to the data, lesions affecting the frontal-subcortical circles of mood regulation (prefrontal cortex, basal nuclei, and thalamus) predominantly in the left hemisphere can be considered as neuroimaging markers and predictors for PSD for at least 1 year after stroke. Additional pontine and lobar cerebral microbleeds in acute stroke patients, as well as severe microvascular lesions of the brain, increase the likelihood of PSD. The following molecular candidates can help to differentiate PSD patients from non-depressed stroke subjects: decreased serum BDNF concentrations; increased early markers of inflammation (high-sensitivity C-reactive protein, ferritin, neopterin, and glutamate), serum pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-18, IFN-γ), as well as pro-inflammatory/anti-inflammatory ratios (TNF-α/IL-10, IL-1β/IL-10, IL-6/IL-10, IL-18/IL-10, IFN-γ/IL-10); lowered complement expression; decreased serum vitamin D levels; hypercortisolemia and blunted cortisol awakening response; S/S 5-HTTLPR, STin2 9/12, and 12/12 genotypes of the serotonin transporter gene SLC6A4, 5-HTR2a 1438 A/A, and BDNF met/met genotypes; higher SLC6A4 promoter and BDNF promoter methylation status. Neurophysiological markers of PSD, that reflect a violation of perception and cognitive processing, are the elongation of the latency of N200, P300, and N400, as well as the decrease in the P300 and N400 amplitude of the event-related potentials. The selected panel of biomarkers may be useful for paraclinical underpinning of PSD diagnosis, clarifying various aspects of its multifactorial pathogenesis, optimizing therapeutic interventions, and assessing treatment effectiveness.


Poststroke depression (PSD) is the most prevalent psychiatric disorder after stroke, which affects nearly one-third of the survivors during first 5 years after disease onset (13). The diagnosis of PSD includes the following characteristics: (1) presence of major/minor depressive episode according to DSM-III-IV-5 or other valid approaches; (2) evidence of stroke from history, physical examination, and/or neuroimaging data; and (3) onset of PSD is temporally related to the stroke (3). Several epidemiological findings have demonstrated that PSD is independently linked to negative clinical outcomes, such as significantly longer hospitalization; more severe functional disability (36); profound diminutions in physical, psycho-social, cognitive, and eco-social domains of quality of life (37); unsatisfactory results of poststroke rehabilitation (8); elevated rates of mortality (3911); higher risks of recurrent stroke at 1 year (12); as well as considerable strain for caregivers (13). Data mentioned above highlight the importance of identifying PSD among stroke survivors.

The detection of depressive symptoms at early stroke stages and recognition subjects at risk for PSD diagnosis remains challenging. Clinical measures currently used to assess PSD, especially in the acute poststroke patients, may lack the specificity necessary to detect symptoms (1415). From this point of view, the identification of specific biomarkers might help to increase the sensitivity of PSD diagnosis. Moreover, it could be helpful for elucidating the pathophysiological mechanisms of PSD and ultimately lead to choosing specific targeted treatment (16).

Thus, we aimed to review and summarize the literature exploring potential biomarkers for PSD diagnosis.[…]


Continue —>  Frontiers | Poststroke Depression Biomarkers: A Narrative Review | Neurology

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[WEB SITE] One Woman, 10 MRI Scans, 10 Different Diagnoses

Cultura RM Exclusive/Sigrid Gombert/Getty Images

An MRI scan is a lot more like a Rorschach test to your radiologist than you’d probably like to imagine.

That’s the summary of a study recently published in The Spine Journal. Researchers sent a 63-year-old woman with lower back pain and a specific set of other symptoms to MRI appointments with ten different radiologists. The radiologists collectively made 49 distinct findings. Zero, however, made it into all ten diagnoses, and only one was reported in nine out of the ten.

Even more alarming: The average report contained between nine and 16 errors, both false-positives and missed diagnoses (which were later found by experts in her specific spinal problem, the comparison points for the study’s researchers). Overall, the study found “poor overall agreement” in radiologists’ opinions of the woman’s condition.

The study differs from past ones in which radiologists viewed MRI results in a research setting and made diagnoses, says co-author Daniel Elgort, vice president of healthcare data analytics and research at the Spreemo Quality Research Institute. “[In those studies] they knew they were being studied, so they made a more careful diagnosis.” Radiologists seeing an average patient are apparently less thorough.

The point of the exercise was to disprove a common misconception among medical consumers. “There is this notion that there are no differences in quality in radiology services,” Elgort says, “that [one] should always decide by price and convenience.”

Radiologists, however, are not the oil change technicians or dry cleaners of the medical world— professions where there is not much difference in performance once one achieves professional-level competency. Instead, the results suggest that some radiology offices are in fact better than others.

While they do not have enough data to prove it, Elgort theorizes that the difference is in cost. Cheaper radiology offices probably employ less experienced staff, use older equipment, cram in appointments, and cut other corners.

“The takeaway should not be, ‘go get the most expensive MRI possible,'” Elgort says. “Healthcare in general isn’t a necessarily a correlation between price and quality. It should definitely be that not every healthcare provider is equally suited to give you the most accurate diagnosis.” He added that patients should seek out radiology labs with specialists in their specific issues.

As for where they found a middle-aged woman willing to get MRI after MRI for weeks, Elgort says they recruited the subject from contacts at the Hospital for Special Surgery in New York City, adding, “She’s a former nurse, so she knows the value of this kind of science.


via One Woman, 10 MRI Scans, 10 Different Diagnoses – Tonic

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[WEB SITE] Dataiku and Bioserenity team up to develop wearable device for improving epilepsy diagnosis.

Dataiku and Bioserenity, two European based companies, have partnered to create a wearable device which is aimed to improve the diagnosis of epilepsy. Dataiku, the maker of predictive analytics software, has created a data analysis application that has been combined with a wearable device developed by Bioserenity. The result monitors patients in real-time to help doctors effectively diagnose epilepsy.

Epilepsy affects over 50 million people worldwide, or roughly 0.7% of the global population, but diagnosing and monitoring the condition can be difficult because seizures often occur in the absence of medical staff.

To help solve this issue, Dataiku and Bioserenity collaborated in June of 2015 to create a consortium called MEData.lab, whose work focuses on the evolution of the digital hospital and connected devices. MEData.Lab allows operational and reliable implementation of tools to promote the use of connected devices (IoT) in the medical community. Its main project is to revolutionize the diagnosis of epilepsy by combining online clothing technology platforms and predictive analytics.

Bioserenity has since developed a connected wearable device called NEURONAUTE®, which is the first diagnostic solution for Epilepsy using smart clothing, a smartphone application, and a Cloud platform for remote analysis and dashboard views. The system which has received CE Marking in Europe but is not yet available in the US Market, will allow for a mobile and continuous electroencephalogram (EEG) recording with the objective of giving neurologists a tool for reducing the time for an accurate Epilepsy diagnosis.

In turn, Dataiku has delivered an analysis application that can process and analyze the incredible amount of real-time data from the NEURONAUTE devices. They designed a system that could accommodate for each of the Bioserenity units to produce 126 million measurements and 1 GB of data per unit per hour. The platform also had to be scalable, so a system was built that could accommodate 10,000 devices running simultaneously. The end result can interpret and analyze 90 terabytes of daily data production and 10,000 BILLION daily measurements.

“The MEData.Lab project is particularly important to us because it’s enabled us to take part in the development of what could be major transformations for the healthcare industry,” said Florian Douetteau, CEO of Dataiku. “With Bioserenity, we’re showing that the appropriate use of data could lead to tomorrow’s ever more effective world of medicine and health.”

The MEData.lab project has already won 3 major awards in the French Big Data community.

Bioserenity received ISO 13485 certification and CE Marking for the Neuronaute in May of 2016 and the solution is currently being deployed in several University Hospitals across Europe.


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