INTRODUCTION: Comorbidities in persons with traumatic brain injury (TBI) may negatively impact injury recovery course and result in long-term disability. Despite the high prevalence of several categories of comorbidities in TBI, little is known about their association with patients’ functional outcomes. We aimed to systematically review the current evidence to identify comorbidities that affect functional outcomes in adults with TBI.
EVIDENCE ACQUISITION: A systematic search of Medline, Cochrane Central Register of Controlled Trials, Embase, and PsycINFO was conducted from 1997 to 2020 for prospective and retrospective longitudinal studies published in English. Three researchers independently screened and assessed articles for fulfillment of the inclusion criteria. Quality assessment followed the Quality in Prognosis Studies tool and the Scottish Intercollegiate Guidelines Network methodology recommendations.
EVIDENCE SYNTHESIS: Twenty-two studies of moderate quality discussed effects of comorbidities on functional outcomes of patients with TBI. Cognitive and physical functioning were negatively affected by comorbidities, although the strength of association, even within the same categories of comorbidity and functional outcome, differed from study to study. Severity of TBI, sex/gender, and age were important factors in the relationship. Due to methodological heterogeneity between studies, meta-analyses were not performed.
CONCLUSIONS: Emerging evidence highlights the adverse effect of comorbidities on functional outcome in patients with TBI, so clinical attention to this topic is timely. Future research on the topic should emphasize time of comorbidity onset in relation to the TBI event, to support prevention, treatment, and rehabilitation. PROSPERO registration (CRD 42017070033).
Accurate prediction of motor recovery after stroke is critical for treatment decisions and planning. Machine learning has been proposed to be a promising technique for outcome prediction because of its high accuracy and ability to process large volumes of data. It has been used to predict acute stroke recovery; however, whether machine learning would be effective for predicting rehabilitation outcomes in chronic stroke patients for common contemporary task-oriented interventions remains largely unexplored. This study aimed to determine the accuracy and performance of machine learning to predict clinically significant motor function improvements after contemporary task-oriented intervention in chronic stroke patients and identify important predictors for building machine learning prediction models.
This study was a secondary analysis of data using two common machine learning approaches, which were the k-nearest neighbor (KNN) and artificial neural network (ANN). Chronic stroke patients (N = 239) that received 30 h of task-oriented training including the constraint-induced movement therapy, bilateral arm training, robot-assisted therapy and mirror therapy were included. The Fugl-Meyer assessment scale (FMA) was the main outcome. Potential predictors include age, gender, side of lesion, time since stroke, baseline functional status, motor function and quality of life. We divided the data set into a training set and a test set and used the cross-validation procedure to construct machine learning models based on the training set. After the models were built, we used the test data set to evaluate the accuracy and prediction performance of the models.
Three important predictors were identified, which were time since stroke, baseline functional independence measure (FIM) and baseline FMA scores. Models for predicting motor function improvements were accurate. The prediction accuracy of the KNN model was 85.42% and area under the receiver operating characteristic curve (AUC-ROC) was 0.89. The prediction accuracy of the ANN model was 81.25% and the AUC-ROC was 0.77.
Incorporating machine learning into clinical outcome prediction using three key predictors including time since stroke, baseline functional and motor ability may help clinicians/therapists to identify patients that are most likely to benefit from contemporary task-oriented interventions. The KNN and ANN models may be potentially useful for predicting clinically significant motor recovery in chronic stroke.
Stroke is one of the leading causes of long-term disability . Most stroke patients suffer from upper limb hemiparesis that significantly impairs their functional abilities and quality of life . To help patients restore function, healthcare professionals have to provide rehabilitation interventions that are effective for each patient based on predicted outcomes. Nevertheless, making accurate prediction remains to be a challenging task due to the heterogeneous characteristics and recovery patterns among stroke patients .
With the recent advancement in technology, new techniques have been developed to assist clinicians/therapists in predicting patient recovery. One promising new technique is machine learning. Machine learning utilizes computerized algorithms to optimize prediction. It has several advantages including the ability to process large volumes of data, detection of complex interactions between multiple variables and easy incorporation of new attributes/data into models . These advantages make machine learning an ideal tool for processing complex healthcare informatics data to develop prediction models .
In stroke, machine learning techniques have been used for predicting motor and functional recovery in acute/subacute stroke patients. For example, Lin et al. evaluated whether machine learning models could predict recovery of activities of daily living in acute stroke patients . Other studies assessed whether machine learning models could predict motor and/or cognitive improvement in acute/subacute stroke patients [7,8,9]. Results of these studies were promising with moderate to high accuracy; however, these studies primarily involved inpatient rehabilitation in acute/subacute stroke. Whether the machine learning methods can predict responses of stroke patients to outpatient rehabilitation interventions, such as contemporary task-oriented interventions at chronic stage of stroke remain unknown.
Contemporary task-oriented rehabilitation interventions including the constraint-induced movement therapy (CIMT), bilateral arm training (BAT), robot-assisted therapy (RT) and mirror therapy (MT) are commonly used to address motor dysfunction in chronic stroke patients . Systematic reviews and meta-analysis studies showed that these contemporary interventions were effective in improving motor function in chronic stroke patients, and should be considered in clinical application [11,12,13,14]. Machine learning may be a useful tool to predict motor function improvement after contemporary task-oriented interventions, which may help to identify the responders to these interventions and facilitate practical use.
The purpose of this study was to determine the accuracy and performance of machine learning in predicting clinically significant motor function improvement after contemporary task-oriented interventions in chronic stroke patients and identify important predictors for building machine learning prediction models.[…]
Few studies have assessed the long-term functional outcomes of traumatic brain injury (TBI) in large, well-characterized samples. Using the Traumatic Brain Injury Model Systems cohort, this study assessed the maintenance of independence between years 5 and 15 post-injury and risk factors for decline. The study sample included 1381 persons with TBI who received inpatient rehabilitation, survived to 15 years post-injury, and were available for data collection at 5 or 10 years and 15 years post-injury. The Functional Independence Measure (FIM) and Disability Rating Scale (DRS) were used to measure functional outcomes. The majority of participants had no changes during the 10-year time frame. For FIM, only 4.4% showed decline in Self-Care, 4.9% declined in Mobility, and 5.9% declined in Cognition. Overall, 10.4% showed decline in one or more FIM subscales. Decline was detected by DRS Level of Function (24% with >1-point change) and Employability (6% with >1-point change). Predictors of decline factors across all measures were age >25 years and, across most measures, having less than or equal to a high school education. Additional predictors of FIM decline included male sex (FIM Mobility and Self-Care) and longer rehabilitation length of stay (FIM Mobility and Cognition). In contrast to studies reporting change in the first 5 years post-TBI inpatient rehabilitation, a majority of those who survive to 15 years do not experience functional decline. Aging and cognitive reserve appear to be more important drivers of loss of function than original severity of the injury. Interventions to identify those at risk for decline may be needed to maintain or enhance functional status as persons age with a TBI.
Psychiatric Definition of “Depression”: “When a person feels sad, blue, unhappy, miserable, or ‘down in the dumps.’ Most of us feel this way at one time or another for short periods. True depression is a mood disorder in which feelings of sadness, loss, anger, or frustration interfere with everyday life for an extended period of time.”
NOTE: I won’t be addressing in this teaching an illness similar to depression labeled “bi-polar disorder.” (formerly called Manic-Depressive Disorder) In some ways, a number of the symptoms of bi-polar disorder are similar to those of depression, but I’m not going to write about that illness in this teaching.
Also, I want to make very clear to you that I don’t have all the answers to all your questions about why you have depression. Depression is a very complex illness that often baffles professionals in the field of psychiatry, psychology, and behavioral science. I’m only going to be sharing with you a little bit about what I do know, some tips to aid in your own healing, and some thoughts about episodes of depression I have suffered. In addition, I want to tell you that I believe with all my heart that God is the Source of all healing, no matter what various means He may use to heal people having depression. And . . . if you are suffering with depression, God wants to heal you!
Depression is a dread, horrible, debilitating illness that has reached epidemic proportions in most industrialized nations of the world. Some aptly call it “the dark night of the soul.” It is a mental and emotional darkness of varying degrees in its victims. Some have mild depression, some have seasonal depression (SAD), some have situational depression, some have clinical depression, and some have a deep, dark, lingering, depression that causes the most hopeless feelings humans can experience, sometimes lasting for months and even years. In addition—for Jesus-believers—depression often involves a deep sense of utter abandonment by God.
Most of the time, people who suffer from any degree of depression feel that they are living in sort of a “dull-grey world.” If you’ve ever seen the movie Pleasantville” you know a little bit about what it’s like to live in a world that is all-grey most of the time—a world almost empty of any color other than dull grey.
Fortunately, by means of anti-depressant medication, counseling, prayer, etc., most depression can be cured, healed, or brought under control within a matter of weeks or months. It is rare, indeed, for depression to last longer than that—IF the depressed person seeks help. Sometimes, people will experience different episodes of depression throughout their lifetimes, but with enough information about the nature of the illness and its symptoms, most people can be healed and thereafter maintain their mental and emotional health.
The American Psychiatric Association (APA) provides the following information to aid in the diagnosis of depression. The following listing is of the indicators” of depression; if one experiences 5 or more of these indicators for more than 2 weeks, one is diagnosed with depression:
Sleep disturbances – especially sleeping too much.
Loss of appetite, or overeating; significant weight changes.
Difficulty in concentrating or remembering; inability to make decisions.
Physical pains that are hard to pinpoint.
Loss of self-esteem or attitude of indifference.
Loss of interest or pleasure in your job, family, life, hobbies, or sex; loss of pleasure in formerly enjoyable activities.
A downhearted period that worsens and won’t go away.
Frequent, unexplainable, or uncontrollable crying spells.
Feelings of loneliness.
Feelings of isolation.
Feelings of guilt.
Feelings of hopelessness and/or worthlessness.
Recurring thoughts about suicide or death.
Loss of energy; fatigue.
Feelings of extreme sadness.
And—for believers in Jesus–there is most often a sense of total abandonment by God.
I don’t pretend to be an expert on depression, nor am I presently a certified or licensed counselor. But I have experienced 3 distinct periods of depression in my life and I know how depression feels and its debilitating effects! And I know how God has healed me each time! I’ll tell you more about my depression later.
Furthermore, as a Jesus-believer I have learned much about events, circumstances, and situations which lead to depression—and about how prayer and the obedient “application” of the Bible, the Word of God, to the depressed person’s life can aid a great deal in healing from depression.
I advise any Jesus-believer suffering from depression to see your primary health care provider, take whatever medicine is prescribed, see a counselor or therapist if necessary (preferably a fellow Jesus-believer), and, in addition, give some thought to the ideas I will list later in this teaching that might help you see the origins of your depression and help in your complete healing.
Let me make this next point very clear right up front: Please, please get over your fear of seeing a counselor or therapist for fear they might expose some deep, dark secrets in your life! That’s what it’s often all about: exposing deep dark secrets that have caused or contributed to your depression. God cannot heal any area of our lives that we choose to keep hidden from Him (as if we could really hide anything from God . . . ) It’s probably some of those deep, dark secrets which are contributing to your depression in the first place.
Those hidden secrets need exposed and brought out into the light so God can deal with them. We all have deep, dark secrets. You’d probably be shocked at some of mine. But a good and competent counselor will not be shocked at anything; nothing will surprise or shock them; they’ve seen and heard it all. Get over your reluctance and make an appointment with a good counselor! Do it today!
First, I want to state again very clearly that—regardless of the causes of your depression—God can and does heal people who have depression! He heals through either prayer or medicine . . . or both, but He does heal depression! He is the Source of all healing; He will heal you!
Next, I want to tell you that nothing you have done has caused your depression. You don’t necessarily have depression because of some horrible sin you’ve committed. You don’t have depression because you’re a “weak” believer. You don’t have depression because you are an unfaithful Jesus-believer. And, God has not given you depression to punish you for something you’ve done wrong! It’s just an illness for which you need healing!
Also, you don’t need to be ashamed or humiliated because you’re a Jesus-believer with depression—and you think a “good” Jesus-believer shouldn’t get depression. Say this out loud to yourself very clearly and carefully: “I refuse to ‘should’ on myself!” You have no more responsibility for having depression than you are responsible when you catch a cold or because you are susceptible to migraine headaches.
And . . . this isn’t just a play on words: Refuse to see yourself as a depressed person; rather, see yourself as a person who happens to have an illness labeled depression. There’s a big difference in the two viewpoints. One viewpoint means you see yourself as a “walking depression” in every area of your life. The other viewpoint means you see yourself as a “whole” person who just happens to have depression in one area of your life—just as you might happen to have a cold at some time, but you are not your cold. You are not your depression.
Try to understand your depression in somewhat this way—some people are more susceptible to viruses than other people are; some people have chemical imbalances in their bodies; some people are more prone to certain infections; some people have immune system disorders; some people are more accident prone than others are; some people develop multiple sclerosis; some people have strokes; some people develop diabetes; some people have heart attacks; some people develop cancer. Some people happen to have depression.
None such physical illnesses and diseases are the faults of those people who have them. Some people have a genetic predisposition to having depression; that genetic predisposition is often triggered by something in one’s environment. But . . . you did not cause your depression because of something you’ve done wrong in your life!
You simply are a person who happens to have depression. Some people do. Some don’t. It’s that simple. If you can look at your depression in that way, that will serve you well as God begins to heal your depression.
Depression just happens to some people just because they are mortal, physical, and material human beings subject to sin, Satan, debility, corruption, and death. It’s not your fault that you happen to have depression at this time in your life! And—again—God has not given you your depression.
But—this is an important point!—Satan and his minions often oppress people . . . which can then lead to depression in people having a propensity for depression. “Oppression” means that if Satan knows you have a propensity for depression, sometimes he will transmit thoughts into your mind that weigh heavily on you in the sense that you begin to fret, worry, feel anger, feel loss, etc. Oppression is meant by Satan and his minions to terrorize you, to rule over your thoughts and emotions in a harsh, discordant manner.
Then—if and when he gains access to your mind and emotions by means of oppression, that can often lead to depression. Take heart: Acts 10: 38 in the Bible says that Jesus heals people who are oppressed by the devil!
Please understand that much (not all) depression is triggered by a sense of real or imagined loss of some sort. It may be the loss of a friend, loved one, or pet either by death or separation of some kind. It may be the “loss” of a marriage by divorce or death. It may be the loss of a job or a prized “possession.” It may be the loss of one’s “ministry” as a Jesus-believer. It may be the loss of self-esteem or self-worth. It may be the loss of money or reduced income. It may be having to “downsize” one’s home to move into a smaller apartment or nursing home. It may be the loss of one’s early dreams for life as the realities of day-to-day life have overshadowed those dreams.
It may be the loss of a child who has grown up and left home for the first time. It may be the loss of prestige. It may be the temporary or permanent loss of one’s good health because of disease, illness, or disablement. Perhaps you still suffer the loss of innocence or purity you suffered in an untimely or painful way as a child or teenager. It may be the loss of one’s beauty or good looks due to advancing age. It may be the loss of rank or advancement because someone else was promoted instead of you. It may be the loss of romantic, fanciful “school girl” expectations about marriage. It could be the loss of a sense of security in marriage because of a spouse’s adultery. Or . . . any similar loss.
It doesn’t have to be a real, tangible loss either; it can also be an imagined or perceived loss of something, such as a feeling that one has “lost” one’s reputation—whether or not that is really the case. It could be the feeling of loss of respect by one’s co-workers or by others in one’s profession—such as a lawyer losing a high-profile case and feeling he has lost his reputation and the esteem of his colleagues.
Yes, most depression (again, not all) originates with a real or perceived loss of some type, tangible or intangible.
In a nutshell, here is how a real or imagined sense of loss works. If you attempt to superimpose real or imagined past losses upon the present, it results in depression in the present. On the other hand—just by way of information—if you attempt to superimpose the future upon the present, it leads to anxiety and stress in the present—and panic attacks sometimes. Our past losses (real or perceived) superimposed upon the present = depression. Our worries about the future superimposed upon the present = anxiety and stress.
So . . . you (and your counselor) must search for and identify what you feel you have “lost.” That could very well be the starting point in your healing—the point of diagnosis. Ask the Holy Spirit who lives inside you to help reveal the loss(es) to you and to your counselor; He will do so if you ask Him to. And, of course, ask Him to reveal other causes for your depression.
My Healing From Depression
The story I’m about to tell you of God healing me from depression isn’t one of those hyped instant healings where someone placed their hands on my head, prayed for me, and then proclaimed “Be healed!” while I thrashed around on the floor. Nope, nothing like that. But . . . my healing is just as miraculous as that type of supernatural, instant healing. Healing is healing, no matter what shape or form it takes, no matter how it happens.
If you’ve never battled depression as I have for most of my adult years, you can’t possibly know the l-o-n-n-g days of depression that just seem to go on and on forever . . . without end—days of unnameable hopelessness, deep despair, overwhelming worthlessness, total exhaustion, sadness beyond sadness, wanting to give up, obsessive suicidal thoughts . . . feeling utterly abandoned by God . . .
Yes, I’ve battled depression off and on most of my adult life—with bouts of varying lengths and intensity. I may even have had it during my late childhood and teen years, choosing to numb its effects with alcohol. In those days, depression was seldom diagnosed in adults, much more rarely in children and teenagers.
Clearly, my depression began with perceived losses I experienced in childhood. The first was when I began to realize how mean and brutal my dad was. For example, one of my earliest memories is of Dad throwing down a flight of stairs when I was only about two years old! Even with my thought patterns underdeveloped at that stage, I remember asking myself in my child mind what was wrong with me that Dad would do that to me. I felt a sense of loss as a child having no worth—or that something was wrong with me.
Dad’s brutality continued throughout my childhood with horrible whippings with a leather belt or razor strap, and most of the time I was left wondering what was wrong with me that I deserved that sort of punishment. Please don’t misunderstand me: I’m not blaming my dad for my problems and depression; I’ve simply tried to explore and understand what led to my adult depressive episodes. In actual fact, Dad was a victim of his own harsh childhood.
Another factor contributing to my depression was that at age four, my kindergarten teacher sexually abused me in the boy’s bathroom. I couldn’t articulate how I felt at the time, but I know it was a feeling that I had “lost” something—my innocence, my “purity”—something like that. I knew what she had done to me was wrong and that it had “robbed” me of something.
That perception—along with always wondering what was wrong with me that caused Dad to spank me so much and so hard—left me with a deep sense of sadness, “loss” of my childhood, and a deep sense that I wasn’t really worth much as a human being.
Along with those feelings, throughout my childhood and early teens, Dad and his father (my grandfather “Baba”) often told me I would never amount to much, called me dumb and stupid, told me I could never do anything right, called me retarded, and the like. I didn’t understand why they felt that way about me, but for years I believed what they told me was true. That’s one of the reasons I began drinking at age nine—just to numb myself from the horrible feelings I had about my lack of worth as a person . . . that for some reason I was an incomplete person.
Again, I no longer blame Dad or Baba for what they did to me; I forgave them long ago. I know this sounds weird, but I actually look forward to seeing them again beyond this mortal journey and talking through all that made them the way they were and the way they treated me. They know I’ve forgiven them, but we still need to talk through some matters in order to bring final closure. Long ago, I also forgave that kindergarten teacher for abusing me; I hope I get to meet her again some day and offer her my forgiveness in person.
My first episode of depression in my adulthood occurred as a result of a very bad situation of my own making that occurred in my life at age 33. Because at first I didn’t know what was happening to me or how to deal with it, I made an aborted suicide attempt; of course, it failed or I wouldn’t be writing these words.
That scared my wife and me enough so that I decided I needed to see a counselor; fortunately, I was employed at the time at a nearby Veterans Administration Psychiatric Hospital with plenty of psychiatrists and psychologists to choose from. My supervisor was very sympathetic and let me see my counselor whenever I felt I needed to. It so happens that my counselor at the time, Dr Ching, was a pioneer in a new counseling procedure known as “Cognitive Restructuring.” That means quite simply, replacing old negative thoughts about oneself with positive thoughts. Along with Dr Ching’s counseling and with a mild anti-depressant medication I took, the three-year period of depression began to quickly be healed. Within just a matter of weeks after beginning to see Dr Ching and taking a mild anti-depressant, I was completely healed.
I’ll mention more about this later, but it is important for a Jesus-believer having depression to apply the Word of God to one’s life and rely upon the inner empowerment of the Holy Spirit to aid in the healing process. I began to do that with more diligence upon seeing Dr Ching and taking my medication, and it wasn’t long before I was healed. I give God the ultimate credit for the healing, believing he used Dr Ching, the medication, and the application of his Word, the Bible to my life. God heals through many means—through both prayer and medicine and counseling, but ultimately He is the Healer.
My second episode of depression began—again—with a very negative situation of my own making resulting in situational depression. Fortunately, the negative situation changed very quickly, thanks very much to the quick action at the time by my wife to totally change the negative situation. That episode of depression lasted only about six weeks. Again, I was depression-free and hoped I would remain so for the remainder of my life.
The third—and longest—episode of depression lasted six long years! It, too, began with a very bad situation I found myself in . . . of my own making. Unfortunately, the relatively mild situational depression developed quickly into a very deep period of depression lasting six years. I won’t even begin to describe the sense of abandonment by God, the hopelessness, the “darkness,” the sense of aloneness . . . Only someone who has had similar depression can even begin to understand what that type of depression is like.
It lasted for six years because—feeling so utterly helpless—I neglected to apply the principles I had previously learned through the years in dealing with depression. I have even counseled many persons having depression—and have seen amazing results in many instances—but I simply felt so hopeless and helpless this time that I didn’t do what I needed to do to “trigger” God’s healing.
I was treated by three separate counselors at various times, and I took numerous anti-depressant medications (which for the most part made me even more of a “zombie” than I was by the depression alone). But, I neglected to apply many of the principles I learned earlier. I knew what I needed to do, but simply could not bring myself to take any positive action toward my healing. It was a horrible “catch 22” situation: the more depressed I was, the more I neglected to apply “healing principles” to my life; the more I neglected to apply those principles, the more depressed I became. It’s often the case that deep depression such as I was experiencing leads to a hopeless sense of inertia, immobilization, and paralysis where one just doesn’t have the inner resources to move off “dead center.”
Finally, one day during the early part of my sixth l-o-n-n-n-g year of depression, the counselor I was then seeing (a spiritual person, but not necessarily a Jesus-believer) got real angry with me in our afternoon session and said, “Bill, you know what you need to do in order for God to heal you. If you don’t get off your butt and start doing what you know to do, then I’m through counseling you. You can just go home and lay on the couch all day and rot!”
Somehow that angry outburst got through to me and I knew that I had to take at least one tiny little step that God could then follow through on and begin to heal me. I knew that I needed to take a tiny step—do anything—that would serve to “activate” God’s healing power in me. So . . . one day I forced myself to get cleaned up and go to the local library and volunteer a couple of hours a week; I secretly hoped they couldn’t use me, but they signed me up right away as a volunteer to work with their “Homebound Program.” That was the tiny action—the trigger—that God needed me to take so that He could then do what He needed to do in order to heal me.
I stopped taking all my medications “cold turkey” and, instead, began “taking” the Bible as my “medicine,” developing a new, ravenous hunger for the Bible. I read it for hours and hours each day and night. Whenever I came to a passage or verse that “spoke” to me I would immediately ask the Holy Spirit to use it to heal me, restore me, and transform my life. I believed (rightly or wrongly) that I would die if I didn’t read, study, and apply the Bible to my life once again.
Also, I began attending church services again; oh, I had been going sporadically, but the services held little meaning for me. I was simply attending because I felt it might help in my healing process . . . and because my wife convinced me to regularly begin attending church again. And, attending church did help. One Sunday morning, I experienced a “magic”moment” when I knew that I knew that I knew I was going to be completely healed and set free from the depression that had enslaved me for six years! When that magic moment occurred, my healing was speeded up exponentially and it was only a couple of months or so after that when I could say I was completely healed.
Who healed me? God! How? In my case, through prayer, by means of a very “directive” counselor, by renewed attendance at church, and by seriously taking the Bible as my daily medication.
To recap, I’ve had three episodes of depression in my adult life. It began with deep feelings of “loss” during my childhood—loss of self, loss of worth, loss of feeling I was valued by anyone (except maybe by my mother and sister). I did not become a Jesus-believer until age 18, so before that time I had no inner spiritual resources with which to deal with the depression. And, at age nine I began drinking very heavily and stayed drunk almost daily for the next nine years—in order to numb the feelings of loss.
If I were to attempt to put “in a nutshell” how God healed me of all three episodes of depression, I would say it like this. First, I learned to forgive anyone and anything that had caused me to feel loss and—and anger at the loss. Then, I had to realize that it seemed like I had a propensity for depression—just like some people have a propensity to be overweight, to develop diabetes, or to have migraine headaches or osteoperosis. It’s not that I was created by God to be that way, but simply because of the results of my sinful fallen nature, I had a propensity to be a depressed person. I repeat: God does not cause illness, sickness, accidents . . . or depression. They are caused by Satan and by our fallen, sinful condition.
But . . . I believe that sometimes God allows us to become ill or to have accidents so that He can then heal us for his glory . . . and his alone! And, so that we can learn more about ourselves and about his grace, mercy, and sovereign healing in our lives. God allows many of his children to be broken at their weakest points so that afterwards we are strong at the broken places—strong with his inner strength!
I praise God for healing me from depression three times in my adult life. Each healing has resulted in my being able to share with others God’s grace, mercy, and healing power in my life! Bottom line . . . well, I haven’t figured that out yet. But I believe it has something to do with a biblical principle that when we are weak He is strong; when we are ill, He is our Healer; when we are Broken, He is the Potter Who puts the broken pieces back together.
I readily admit I don’t understand all there is to know about depression; I don’t understand why I have had 3 horrible episodes of depression—one of them resulting in six seemingly wasted and lost years. I just don’t understand. And I don’t understand God’s healing processes. But I do know that God is a good God and absolutely everything He does is good (Psalm 119: 68). I also know that God is love (1 John 4: 8) and everything that happens to me is always filtered through his great and deep love for me. So . . . yes, there’s much I don’t understand about my years of depression. But what I do understand about God’s love and goodness is enough.
All I know is that I never, ever, ever want to have depression again, and I pray daily that it will never return.
As I hinted earlier, when God healed me just a little over a year ago from that last long bout of depression, I developed a new, ravenous, voracious hunger for the Bible once again, and since then have read it completely through almost 4 more times. I’m not trying to impress you—simply to inform you about the supreme importance of the Bible in my life and for my healing and health. I simply cannot live this mortal life I have been sent here to live without the Bible. I crave it more than food!
There’s a song that sort of sums up what I have written about my healing from depression; it’s entitled “I Will Go On.” I wish I could sing it to you, but I can’t so here are the words:
“I repent [change my mind] for the moments I have spent Recalling all the pain And failures of my past. I repent for dwelling on the things Beyond my power to change– The chains that held me fast.
CHORUS: I will go on. My past I leave behind me. I gladly take His mercy and His love. He is joy and He is peace. He is strength and sweet release. I know He is and I am His. I will go on.
I give up the bitterness and hate; And blaming men and fate For all my discontent. The guilt and pain I empty from my cup So God can fill it up With peace and sweet content.
I accept the promise of the dawn– A place to build upon, To make a brand new day. I will begin convinced that Jesus lives; Assured that He forgives And that He’s here to stay.
There you have it, dear friend struggling with the dark night of your soul. Take heart! There is sweet release and peace. Day is dawning. Deliverance will come. You will be free of the depression. You will go on!
See a health care provider. If you need medication, take it. See a good and godly counselor, if at all possible; otherwise, any caring counselor can help even if he or she is not an authentic Jesus-believer—they still want to work with you within your faith-system to help you get well. Read the LIFE-giving Bible and obediently apply it to your life. Keep a journal, writing down important events in your recovery process. Trust the Holy Spirit Who lives within you to “rise up” and help you find total and complete recovery from your depression. I assure you, you will be well and whole again!
Prognosis: Your Healing from Depression
To begin using the Bible in your healing, please read Hebrews 4: 12 in the New Testament. This reference teaches that the Bible actually gives LIFE to those who read and obey it. I can’t explain how that happens, but the Bible is, in actual fact, God’s LIFE-giving “medicine” for healing and wholeness. Moreover, the Bible is full of power. I can’t explain that either; the Bible is God’s instrument of super-natural power in the life of the Jesus-believer (any pre-believer, too) who reads and obeys the Bible, the Word of the Living God. And, only the Bible can plunge like a “sharp sword” deep into our psyches and spirits to diagnose the losses that have led to our depression. There are other biblical references that teach much the same, but we won’t look at them at this time.
Now, let’s turn to a specific biblical reference that will help us see how the Bible “works” to aid in our healing from depression. I invite you to turn to only one pertinent reference (there are many) that we will use to show you how reading and obeying the Bible works in our healing processes. That reference is Psalm 37.
The reference begins by urging us not to fret or be envious (of evil doers or evil doing). For purposes of this teaching, let’s think of the evil-doing as something or someone that has “robbed” us, causing our loss. To fret is to have something (our loss) eat away or gnaw at us; a loss that wears us down because we continually focus on it day after day, almost to the exclusion of everything else going on in our lives. If we continually fret about our losses day after day, week after week, it eats away at us, gnaws at us, and wears us down.
We must turn our fretting over to the Holy Spirit by a conscious act of our will—by a quality decision—by a firm resolve—asking Him to super-naturally empower us from within to stop the endless cycle of fretting—to “let go” of the losses and not dwell upon them any longer. To trust God that He will “make up” for our losses in a miraculous manner, turning “bad” past losses into “good” present or future results. Some of that letting go may involve forgiveness of someone else or yourself.
Forgiveness is not something you necessarily feel; it is an act of your will; it is something you do. Forgiveness doesn’t necessarily set the forgiven person free (if it’s someone besides yourself you must forgive), but it sets you—the forgiver—free! Forgiveness is not about the other person; it’s about you. You can free yourself of many past losses by the simple act of forgiving yourself or others.
Next in Psalm 37, we find envy. Envy is a feeling of discontent and ill will because of another’s “gains” of advantages or possessions while we have suffered losses. We mistakenly compare ourselves with others and what they “have” with what we don’t have—with our losses. It’s the age-old matter of not being able to “keep up with the Joneses.” It’s seeing others doing well while we feel we are suffering losses. The Joneses will always be a part of our mortal lives here on planet earth. We must learn to ask God to help us see that the “riches” we have in Jesus are far more than anything the Joneses possess or could ever hope to possess. That’s not an ethereal, spiritual play on words; it’s a truism that we must learn to recognize and accept our “riches in Jesus” if we are authentic believers in God and in the truths of the Bible.
Next, Psalm 37 says we must trust in the Lord. What exactly does that mean? Trust is a many-faceted word used throughout the Bible. It means to have a firm belief in the reliability, trustworthiness, honesty, integrity, and justice of God and his revealed truth in the Bible. It means to have confidence in God without fear of the outcome simply because He is God. It means to trust that God is good and that all He does is good (Psalm 119: 68). It means we believe without reservation that He is faithful to carry out all his good plans and purposes (not ours’) in our lives.
We are to “feed on” his faithfulness, that is, we are to daily meditate upon and dwell upon his faithfulness. How do we do that? We are to read, meditate upon, and study the Bible daily—and apply it to our lives by obeying what we read. As we do that, our sense of loss is slowly diminished as we see that God truly is good and everything He does (or allows to happen) in our lives is for our good.
Next, in Psalm 37 we are to “delight ourselves” in the Lord. What does that mean? We are to understand that our relationship with God should give us joy and pleasure. One earmark of depression, of course, is that we often feel very sad—sometimes over something specific, but sometimes it is a generalized feeling of overall sadness for which we can’t necessarily pinpoint the cause: we’re just sad and have no joy at all. Most of the time we often feel that life has no reason for pleasure. It takes an act of our wills—again, a quality decision, a firm resolve—that we will find something (even a very small thing) in our relationship with God that we can delight in—that we can find joy and pleasure in.
It may be something as insignificant as making ourselves take a moment to find joy in seeing a beautiful bird in our backyard. Maybe, it’s just a fleeting moment of joy that quickly goes away, but those moments will build up as we find them—perhaps only one fleeting moment a day or perhaps a few each day.
The same holds true for pleasure. If we will look for brief moments of pleasure and acknowledge their reality, they, too, will have a cumulative effect in overcoming our depression. Find a moment of pleasure in your relationship with your spouse or children; find a brief few seconds of pleasure in seeing a beautiful baby in the supermarket. Then find another moment of pleasure . . . and another . . . and another. Let them build up.
At this point, I encourage you to start keeping a written journal of such moments of joy or pleasure so that when things seem so sad you can hardly stand it, you can turn to your journal and remind yourself that you have found just a few moments or seconds of joy and pleasure. As mentioned above, such moments that you have felt and recorded in your journal will have a cumulative effect in driving back the darkness of the depression. It won’t happen overnight (in some cases it does, but not always). Let your journal be a written record of your arduous climb up and out of the deep pit of depression.
Yes, make a quality decision that you will find moments of joy and pleasure in your life, record them in your journal, and it will help to drive away the deep darkness of your depression. Of course, continue taking your medication and working with your counselor.
Next, Psalm 37 tells you to commit your way to the Lord. The word “commit” means to actually take your burdens of depression and sort of “roll them over” from your weak shoulders onto God’s strong shoulders. Again, this takes moment-by-moment acts of your will to do that. For example, take a specific loss you are feeling or a specific thing or event that causes you to feel sadness, and then in a moment of time, roll that specific loss, thing, or event from your shoulders over onto God’s shoulders. Actually picture in your imagination yourself doing that. Actually “see” yourself rolling it over from your bent shoulders onto God’s strong shoulders.
Then, when you have accomplished that (and it might take a very hard effort on your part to do that) be sure to note the event in your journal, noting the exact time and date you rolled it over onto God’s shoulders. Keep a cumulative written record as you do that; maybe you can only come up with the inner strength to do it once a day or even once a week, but when you do, note it in your journal so that when that particular loss comes back to haunt you, you can know that on a certain date and time you rolled it over onto God’s shoulders and it’s a “done deal.” Also, keep records in your journal of other positive events in your journey, such as a date and time when your forgave someone, etc.
Do not record negative events in your journal, only good, positive events!
Verse 7 of Psalm 37 encourages us to rest in the Lord and wait patiently for Him. What does that mean? In terms of your depression, it means to take time now and then just to stop working so hard to overcome your depression; it means to take a period of inactivity when you just sort of “give up” working so hard to come out of the depression. It’s like stopping at a “rest stop” on the interstate highway system. It’s when you just put your mind in neutral and “take a break” from the depression. During that rest stop or period of inactivity, you are giving the Holy Spirit (Who lives within you in your spirit) a brief period of time when you sort of “free Him up” to do some of his own work inside your mind and emotions to further set you free from the depression.
As to waiting patiently for God, it means that during your rest stop, you are essentially giving God permission to do some work of his own inside you that He sometimes can’t do because there’s so much turmoil and frantic activity going on inside you that you are simply not giving Him an opportunity to do what He needs to do to help you overcome your depression. It’s simply giving yourself a “time out” to allow the Holy Spirit to do some things inside you that He ordinarily “can’t” do because you’re not giving Him a “chance” to do so while your mind is churning and going “100 miles an hour” and you just can’t seem to stop.
Give yourself a rest period, and while you’re resting simply wait for God to work in you whatever miracles He needs to perform to help in your healing from the depression. Jot down in your journal what you feel God does when you are resting—even if it seems to be very insignificant. Again, these episodes of resting and waiting on God will have a cumulative effect in your healing.
Finally, Psalm 37 encourages you to cease from anger and wrath. Much of our depression is often caused by anger and wrath we have toward real or imagined loss, past situations over which we had no control, people whom we feel have caused us to incur or suffer loss. The Bible says that anger itself is not sin; it’s merely one of the many emotions God has created us with. However, the Bible says we should not go to bed at night still harboring anger. We simply need to go ahead and let ourselves feel the emotion of anger (we can’t deny our feelings), give vent to it, express it, but then let it go before we go to sleep at night. Anger, left unresolved, can burn inside us, leading to bitterness and crippling of our mental and emotional wellbeing. Again, the emotion of anger in and of itself is not wrong; the Bible simply cautions us not to sin while we are angry.
If we let anger fester in our conscious and subconscious minds (especially during the night while we sleep) it can grow and grow and just overwhelm us the next day. Again, by an act of your will, by a conscious choice, by a quality decision, by a firm resolve, let the anger go before going to bed each night. You can do it, but sometimes it will be one of the hardest things you will ever do.
When we are depressed, sometimes it’s hard enough just to make a decision to get out of bed, to eat, or even to go to the bathroom. For example, one depressed client of mine attempted to explain to me that no matter how urgently she sometimes needed to go to the bathroom, she just couldn’t make the decision to go—sometimes resulting in her wetting herself; yes, depressive indecision can get that bad! But down inside you—at the core of your being—there is that little spark of life where you can make decisions like I have noted above. You can do it. You must do it. For your own wellbeing, you must draw upon that little spark of life down inside you and make such quality decisions as I have described above. Being able to make such decisions, along with taking your medication, and working with your counselor or therapist will go a long way in cooperating with God to rid you of your of the depression.
I’m not writing about “gritting your teeth” and conjuring up the inner strength to make such quality decisions; that won’t work. You may feel that you’re just too “dead” inside to make such decisions, but deep down inside you there is a tiny “spark of life” from where you can make such acts of your will, such quality decisions, such firm resolve. You can do it by drawing upon God’s strength within you!
There is one other element I want to suggest you bring into play as you work toward your healing from your dark night of the soul; I’ve already alluded to it. Jesus lives inside you in his “unbodied form” of the Holy Spirit. He took up permanent residence within you when you became an authentic Jesus-believer. Often, when we are depressed, He just remains deep within us in sort of a “dormant” state because we are too ill to even acknowledge his presence within us.
The Holy Spirit is a strong “untapped resource” we can call upon to help us be healed of the depression. The Bible says that He is a “power source” within us which we can tap into to help us in our healing. Again, it’s very difficult to make any decision when we are depressed, but we must make a quality decision to ask Him to empower us to help us overcome the depression. He will do so, but we must ask Him to do so; He will seldom, if ever, do anything within us that we do not ask Him to do.
Try daily to make a quality decision to ask Him for assistance in your healing. Simply say something like this: “Holy Spirit, I know you live inside me and want as much as I do for me to be healed of this depression. Please empower me to make the decisions I need to make and the actions I need to take; please empower me to read and apply the Bible to my depression; please empower me to take my medication; please empower me to cooperate with my counselor. You are the ‘power of God’ within me. I ‘release’ you to empower me in any way you want to help heal me of this depression.”
There you have it: how to apply the Bible to aid you in your healing. Take your medication. Cooperate with your counselor. Keep a written journal. Read, apply, and obey the Bible. Ask the Holy Spirit to empower you in ways that will aid you in the healing process. Draw on that spark of life deep within you to make quality decisions that will bring you out of your depression. Pray, even if sometimes it’s only a one-word plea to God for help.
Helpful Tips For Healing
Now I want to give you some practical tips that will help you “free up” God the Holy Spirit to heal your depression.
First, it is vital that you take some small step to begin to crawl up and out of the dark pit of depression you find yourself in. Any small step will do—just some small move off dead center that you would not ordinarily do while you are depressed. What do I mean? Well, for example, if you’ve been laying in bed or on the couch in the back bedroom for days, weeks, or even months, make a quality decision that you will do whatever you need to do so that you lay down one hour later tomorrow. Or, if it’s a decent day outside, go out into your back yard, and just take 5 or 10 deep breaths. Or, get up and make yourself a cup of tea—anything that you would not ordinarily feel like doing while you are depressed.
Why make one small move like that? Well, that’s an outward “sign” that inwardly you are “releasing” your faith toward God, allowing the Holy Spirit to rise up from within you where He lives in your spirit and begin to empower you from within to begin climbing out of the pit of depression. Whatever small move you make will serve as a “trigger” to “unleash” the Holy Spirit from within you and activate the healing power of God. Just do anything to start moving and get you off the “dead center” of depression. Such a small move or decision serves as a “point of contact” for you to tap into the Holy Spirit’s power within you. It’s like the simple act of turning on a light switch “releases” tremendous electrical power to light up a darkened room.
I’ve alluded to the following hints and tips for your healing above, but now I want to try to put them together in a meaningful way as sort of “steps” you can follow to cooperate with God in your healing. God heals through the “twin streams” of both prayer and medicine. Continue seeing your health care professional and/or counselor; continue taking your prescribed medication. But . . . begin to look at these other means God will use to heal you as well.
First, you need to make a steady and persistent application of the Bible to your life. Here are some tips about how to do that—tips that have worked with me and with many others whom I have counseled who have depression. How can you do that?
Purchase a little packet of 3 x 5 cards. Then, as you read your Bible from day to day and a verse or reference sort of leaps out at you and gives you some hope, either write down that reference on a 3 x 5 card or write out a “positive” thought for yourself based on the Bible reference. So . . . you are going to be writing on 3 x 5 cards either actual Bible references word-for-word, or, you’re going to be writing positive, personalized thoughts based on Bible references. I call either of these “Bible Decrees, Bible Declarations, or Positive Proclamations.”
Here’s an example of what I mean. Look up Jeremiah 29: 11 in your Bible. Either write it down word-for-word (from a modern English version of the Bible) or write yourself a positive thought based on that verse. Here’s how such a thought might read on your 3 x 5 card: “God’s plans for me are to give me a future with hope beyond this depression!”
The next step is my “prescription” for you. Carry such 3 x 5 cards with you throughout the day (or make multiple copies to affix to your bathroom mirror, to keep in your vehicle, to keep on your desk at work) and then 3 to 5 times each day say the words on the card OUT LOUD. There are important medical reasons why you must say them aloud 3 to 5 times every day, but I won’t go into those reasons in this teaching; it’s just important to know you must say them out loud. As you accumulate more and more cards, break them down into sets where you only carry 6 to 8 cards with you at any given time; maybe have 6 cards you’ll read aloud on Monday, 6 more on Tuesday, and so on. Eventually, you might have 30 or 40 cards (or more), but use only 6 to 8 of them each day. “Take” your “prescription cards” OUT LOUD regularly and consistently every day just like you take your prescription medication.
My second tip for you concerns prayer. Maybe you are so depressed that you can’t even pray. That’s okay . . . for now. But find no more than two people (friends, your Pastor, etc.) whom you can ask to pray for you—and whom you know will do just that! Someone to pray for you regularly and consistently for God to heal you from your depression. They must be two people who are very positive people, not pray-ers who are negative. I’m sure you know they type of negative people I mean. Ask them to report to you at least once a day (in person, by telephone, or by e-mail) what they have prayed about that day and perhaps what God has “told” them about you while they have prayed (if you and your praying friends believe in that sort of thing . . . that God “speaks” to people). It’s important that they’re in touch with you each day and tell you specifically what they prayed about for you that day.
Next, if you’re not already doing so, please, please find a good, concerned, compassionate counselor to work with you. It would be best if the counselor is a Bible-believing counselor, but that’s not absolutely necessary if you can’t locate one. The very best type of counselor would be a Jesus-believer who uses a method of counseling labeled theophostic counseling, but there aren’t as many of those types of counselors as there are other types. Incidentally, you can find out if there’s a theophostic counselor near you by going to http://www.theophostic.com on the internet.
My next tip for you is to find someone ( Jesus-believing friends, a pastor or priest, etc.) who is willing to share Communion (the Eucharist, the Lord’s Supper, the Table of the Lord—whatever you choose to call it) with you regularly and consistently—preferably a minimum of once a week. Each time while you are taking Communion, either specifically ask God yourself (or have those who are with you) to apply the “healing benefits” of Communion to your depression.
My final tip is to find someone who will be willing to pray for you and place their hands on you for healing according to the principles found in James 5: 14 – 16 in the New Testament portion of the Bible. Someone who will be willing to do that for you regularly and consistently, again, a minimum of once a week.
Understand this final point: once God has healed you of the depression—for most people who have once suffered with it and been healed—very often the depression will still sort of “linger” around you or “hover” around you attempting to come back. I can’t explain that phenomenon, only that it has happened to me and to many others I have worked with towards their healing. Don’t be fearful when that happens; just be vigilant and be aware that it can and might happen. Just don’t let it “get it’s foot in the door” of your life again.
I don’t have all the answers about healing from depression. I don’t even have many of the questions! I don’t know why some people are healed more readily and more quickly than others. I simply believe that God heals people from depression, and that He will heal YOU!
I assure you that if you will do all that I mentioned in the above paragraphs, you will be healed of your depression! I know. I have had 3 episodes of depression in my adult life. God has healed me of all three of them. I remain totally free of depression today and by God’s grace I will continue to be free, whole, and well!
This approach will also work with a pre-Jesus-believer, but it will generally take longer because a pre-believer is generally not as sensitive and “open” to the work of the Holy Spirit or to the life-giving power of the Bible, prayer, Communion etc. The Holy Spirit is not limited in any way from working in the life of a pre-believer, however.
By the way . . . this is an important point: if you have family members or friends who have never had depression, don’t expect them necessarily to understand what you’re going through. If they’ve not had depression they most likely won’t understand your suffering. Get help outside your circle of family and friends. Consider yourself fortunate if you do happen to have family members and friends who are sympathetic; if so, they may try to help, but in most cases they can’t. Get some outside help!
Unfortunately, often family members and friends will say things to you like: “Hey, just get over it; you can do it. Snap out of it! Just be more positive about things. Look on the bright side of things. Think more positive thoughts. Stop being around negative people who bring you ‘down.’” You’ll hear lots of statements like that; just ignore them. Such family members, friends, and acquaintances mean well, but they just don’t understand your depression. Don’t even try to explain your depression to them; if you do that, many times they will simply think you are a negative “whiner.”
Well, there you have it: the definition of depression, it’s diagnosis, its causes, the story of how God has healed me from depression on three separate occasions, and—finally—your own prognosis of how God is going to heal you from your depression, with some tips for you to use in cooperating with Him in your healing. God is a loving, good God who wants to heal you of your depression even more than you want Him to! And, He will heal you!
The recovery of walking capacity is one of the main aims in stroke rehabilitation. Being able to predict if and when a patient is going to walk after stroke is of major interest in terms of management of the patients and their family’s expectations and in terms of discharge destination and timing previsions. This article reviews the recent literature regarding the predictive factors for gait recovery and the best recommendations in terms of gait rehabilitation in stroke patients. Trunk control and lower limb motor control (e.g. hip extensor muscle force) seem to be the best predictors of gait recovery as shown by the TWIST algorithm, which is a simple tool that can be applied in clinical practice at 1 week post-stroke. In terms of walking performance, the 6-min walking test is the best predictor of community ambulation. Various techniques are available for gait rehabilitation, including treadmill training with or without body weight support, robotic-assisted therapy, virtual reality, circuit class training and self-rehabilitation programmes. These techniques should be applied at specific timing during post-stroke rehabilitation, according to patient’s functional status.
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de Rooij IJM, van de Port IGL, Visser-Meily JMA, Meijer JG (2019) Virtual reality gait training versus non-virtual reality gait training for improving participation in subacute stroke survivors: study protocol of the ViRTAS randomized controlled trial. Trials 20(1):89
There is growing interest in using biomarkers to predict motor recovery and outcomes after stroke. The PREP2 algorithm combines clinical assessment with biomarkers in an algorithm, to predict upper limb functional outcomes for individual patients. To date, PREP2 is the first algorithm to be tested in clinical practice, and other biomarker-based algorithms are likely to follow.
This review considers how algorithms to predict motor recovery and outcomes after stroke might be implemented in clinical practice.
There are two tasks: first the prediction information needs to be obtained, and then it needs to be used. The barriers and facilitators of implementation are likely to differ for these tasks. We identify specific elements of the Consolidated Framework for Implementation Research that are relevant to each of these two tasks, using the PREP2 algorithm as an example. These include the characteristics of the predictors and algorithm, the clinical setting and its staff, and the healthcare environment.
Active, theoretically underpinned implementation strategies are needed to ensure that biomarkers are successfully used in clinical practice for predicting motor outcomes after stroke, and should be considered in parallel with biomarker development.
To demonstrate the feasibility of algorithmic prediction utilizing a model of baseline arm movement, genetic factors, demographic characteristics, and multi-modal assessment of the structure and function of motor pathways. To identify prognostic factors and the biological substrate for reductions in arm impairment in response to repetitive task practice.
This prospective single-group interventional study seeks to predict response to a repetitive task practice program using an intent-to-treat paradigm. Response is measured as a change of ≥5 points on the Upper Extremity Fugl-Meyer from baseline to final evaluation (at the end of training).
Anticipated enrollment of 96 community-dwelling adults with chronic stroke (onset ≥6 months) and moderate to severe residual hemiparesis of the upper limb as defined by a score of 10-45 points on the Upper Extremity Fugl-Meyer.
The intervention is a form of repetitive task practice using a combination of robot-assisted therapy coupled with functional arm use in real-world tasks administered over 12 weeks.
Main outcome measures
Upper extremity Fugl-Meyer Assessment (primary outcome), Wolf Motor Function Test, Action Research Arm Test, Stroke Impact Scale, questionnaires on pain and expectancy, magnetic resonance imaging, transcranial magnetic stimulation, arm kinematics, accelerometry, and a saliva sample for genetic testing.
Methods for this trial are outlined and an illustration of inter-individual variability is provided by example of two participants who present similarly at baseline but achieve markedly different outcomes.
This article presents the design, methodology, and rationale of an ongoing study to develop a predictive model of response to a standardized therapy for stroke survivors with chronic hemiparesis. Applying concepts from precision medicine to neurorehabilitation is practicable and needed to establish realistic rehabilitation goals and to effectively allocate resources.
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 (3, 4). 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 (5, 6). 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 (13, 14). However, S-100B is not CNS-specific (15, 16) and has shown inconsistent predictive capacity in the outcome of mild TBI (17, 18). 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 (21, 22). 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 (25–31). 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.[…]
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. https://creativecommons.org/licenses/by-sa/4.0/deed.en. See Supplementary Material for image credits and licensing.
Background. Many persons with stroke experience physical, cognitive, and emotional problems that contribute to restrictions in social participation. There is, however, a lack of knowledge on the long-term course of participation over time post-stroke.
Objective. To describe the time course of participation up to 2 years post-stroke and to identify which demographic and stroke-related factors are associated with this time course.
Methods. This was a multicenter, prospective cohort study following 390 persons with stroke from hospital admission up to 2 years (at 2, 6, 12, and 24 months). Multilevel modeling with linear and quadratic time effects was used to examine the course of the frequency of vocational and social/leisure activities, experienced restrictions, and satisfaction with participation.
Results. The frequency of vocational activities increased up to 1 year post-stroke and leveled off thereafter. Older and lower-educated persons showed less favorable courses of participation than younger and higher-educated persons, respectively. The frequency of social/leisure activities decreased post-stroke. Participation restrictions declined up to 1 year post-stroke and leveled off thereafter. Persons dependent in activities of daily living (ADL) kept experiencing more restrictions throughout time than independent persons. Satisfaction with participation increased slightly over time.
Conclusions. Changes in participation occurred mostly in the first year post-stroke. Particularly older and lower-educated persons, and those dependent in ADL showed less favorable courses of participation up to 2 years post-stroke. Clinicians can apply these findings in identifying persons most at risk of long-term unfavorable participation outcome and, thus, target rehabilitation programs accordingly.
Stroke can lead to long-lasting physical problems such as mobility limitations,1cognitive problems such as attention or memory deficits,2 and emotional problems such as anxiety,3,4 depressive symptoms,3–5 and fatigue.4,6 The population of persons surviving a stroke7,8 increases, consistent with major improvements in acute stroke care (eg, stroke units, thrombolysis, and thrombectomy9,10), but this also means that more people have to deal with the long-lasting consequences of stroke.11,12 These consequences contribute to the deterioration of social participation post-stroke.13–17 Importantly, persons with stroke view social participation (participation hereafter) as a central aspect of their recovery.18,19
Participation can be defined as involvement in a life situation such as paid work, family, or community life,17 which consists of actual performed activities,20 such as the frequency of observable actions and behaviors,21–23 and the subjective experience of persons,20 such as experienced restrictions and satisfaction.21–23
In previous studies, it was observed that the frequency of activities decreases in persons with stroke, relative to their premorbid levels.16,24–28 This particularly applies to vocational activities (work, unpaid work, and household activities), but social activities decrease after stroke, too.28 Four months after discharge from outpatient rehabilitation, 50% of persons with stroke still experienced participation problems.29Social activity levels have been reported to be lower in persons with stroke at 1 year post-stroke than in healthy controls,30 a level that remained stable up to 3 years.31Past studies showed that only 39% of persons with stroke were satisfied with their lives as a whole after 1 year,16 which might be even lower up to 3 years post-stroke,32 especially in socially inactive persons.33
Although studies have shed some light on the course of participation over time post-stroke, it is difficult to get a good understanding of how levels of participation develop and change over time. This is a result of the use of cross-sectional designs,16,24,26,27,33 longitudinal designs limited to either only the first 6 months13,25,28,29 or only the long-term levels of participation after stroke,31,32,34studies only incorporating 2 time points,35 and many different participation measures, some measuring the frequency of activities and others the subjective experience of participation.36
Research into factors associated with participation post-stroke could lead to identifying possible risk factors of an unfavorable outcome. Earlier studies showed that demographic factors such as older age at stroke onset,14,37 lower levels of education,29,38 and female sex37 were related to a less favorable outcome in terms of participation, along with stroke-related factors such as dependence in activities of daily living (ADL),39,40 more severe stroke,37 and lower levels of cognitive functioning.26,29 However, these factors are yet to be examined in relation to the course of participation over time and as such to be identified as possible risk factors.
To get a more detailed and comprehensive understanding of participation over time, it is necessary to include repeated measurements of objective (ie, frequency of activities) as well as subjective (ie, experienced restrictions and satisfaction) aspects of participation. Furthermore, it is important to identify persons in the early stage after stroke, who are at risk of an unfavorable outcome in the long term. At this point in time, potential risk factors can be easily determined through available information, including demographics and stroke-related information, and rehabilitation care can be provided. Consequently, we studied participation over a 2-year follow-up in a clinical cohort of persons with stroke in order to answer the following research questions: how does participation develop over the first 2 years after stroke in terms of frequency, restrictions, and satisfaction? Moreover, which demographic and stroke-related factors are associated with this time course?[…]
For patients surviving serious traumatic brain injury (TBI), families and other stakeholders often desire information on long-term functional prognosis, but accurate and easy-to-use clinical tools are lacking. We aimed to build utilitarian decision trees from commonly collected clinical variables to predict Glasgow Outcome Scale (GOS) functional levels at 1, 2, and 5 years after moderate-to-severe closed TBI. Flexible classification tree statistical modeling was used on prospectively collected data from the TBI-Model Systems (TBIMS) inception cohort study. Enrollments occurred at 17 designated, or previously designated, TBIMS inpatient rehabilitation facilities. Analysis included all participants with nonpenetrating TBI injured between January 1997 and January 2017. Sample sizes were 10,125 (year-1), 8,821 (year-2), and 6,165 (year-5) after cross-sectional exclusions (death, vegetative state, insufficient post-injury time, and unavailable outcome). In our final models, post-traumatic amnesia (PTA) duration consistently dominated branching hierarchy and was the lone injury characteristic significantly contributing to GOS predictability. Lower-order variables that added predictability were age, pre-morbid education, productivity, and occupational category. Generally, patient outcomes improved with shorter PTA, younger age, greater pre-morbid productivity, and higher pre-morbid vocational or educational achievement. Across all prognostic groups, the best and worst good recovery rates were 65.7% and 10.9%, respectively, and the best and worst severe disability rates were 3.9% and 64.1%. Predictability in test data sets ranged from C-statistic of 0.691 (year-1; confidence interval [CI], 0.675, 0.711) to 0.731 (year-2; CI, 0.724, 0.738). In conclusion, we developed a clinically useful tool to provide prognostic information on long-term functional outcomes for adult survivors of moderate and severe closed TBI. Predictive accuracy for GOS level was demonstrated in an independent test sample. Length of PTA, a clinical marker of injury severity, was by far the most critical outcome determinant.