Posts Tagged recovery

[ARTICLE] Transcranial Direct Current Stimulation to Facilitate Lower Limb Recovery Following Stroke: Current Evidence and Future Directions – Full Text HTML

Abstract

Stroke remains a global leading cause of disability. Novel treatment approaches are required to alleviate impairment and promote greater functional recovery. One potential candidate is transcranial direct current stimulation (tDCS), which is thought to non-invasively promote neuroplasticity within the human cortex by transiently altering the resting membrane potential of cortical neurons. To date, much work involving tDCS has focused on upper limb recovery following stroke. However, lower limb rehabilitation is important for regaining mobility, balance, and independence and could equally benefit from tDCS. The purpose of this review is to discuss tDCS as a technique to modulate brain activity and promote recovery of lower limb function following stroke. Preliminary evidence from both healthy adults and stroke survivors indicates that tDCS is a promising intervention to support recovery of lower limb function. Studies provide some indication of both behavioral and physiological changes in brain activity following tDCS. However, much work still remains to be performed to demonstrate the clinical potential of this neuromodulatory intervention. Future studies should consider treatment targets based on individual lesion characteristics, stage of recovery (acute vs. chronic), and residual white matter integrity while accounting for known determinants and biomarkers of tDCS response.

1. Introduction

Stroke is the second leading cause of death and third leading cause of adult disability globally [1]. With advancement in acute medical care, more people now survive stroke, but frequently require extensive rehabilitative therapy to reduce impairment and improve quality of life. For those that survive stroke, the damaging effects not only impact the individual and their family, but there is also increased burden on health unit resources and community services as the person leaves hospital, potentially requiring assistance to live in the community. Novel treatments that can enable restoration and enhance potential for stroke recovery are desperately needed and will have significant value for many aspects of stroke care.
True recovery from stroke impairment is underpinned by neuroplasticity. Neuroplasticity describes the brain’s ability to change in structure or function in order to help restore behavior following neural damage. Mechanisms of neuroplasticity are available throughout life but appear enhanced during critical periods of learning [2]. Across several animal studies, it has been shown that there is a period of heightened neuroplasticity that appears to open within several days following stroke [2,3,4] and correlates with rapid recovery [5]. In humans, the timing and duration of a similar critical period of heightened neuroplasticity are not clear, but it likely emerges early after stroke. Understanding the characteristics of a potential critical period of heightened neuroplasticity in humans is important for optimizing stroke rehabilitation and is the subject of current trials [6]. However, the importance of neuroplasticity for stroke recovery in humans is unequivocal, with imaging and physiological studies providing extensive evidence of brain changes correlating with improved behavior [7,8,9,10,11,12,13].
Transcranial direct current stimulation (tDCS) is a promising, non-invasive, method to induce neuroplasticity within the cerebral cortex and augment stroke recovery. Importantly, tDCS has potential to bidirectionally and selectively alter corticospinal excitability for up to one hour after stimulation [14,15]. Animal models indicate that tDCS modulates resting membrane potential, with anodal stimulation leading to neuronal depolarization and cathodal stimulation leading to neuronal hyperpolarization over large cortical populations [16]. Stimulation-induced changes may be potentiated by changes in intracellular calcium concentrations. For example, anodal tDCS applied to the surface of the rat sensorimotor cortex led to a rise in the intracellular calcium concentrations [17]. Local increases in calcium can result in short- and long-term changes in synaptic function [18]. In humans, pharmacological studies have also provided indirect evidence to suggest that tDCS after effects are mediated by changes in synaptic plasticity through mechanisms that resemble long-term potentiation (LTP) and long-term depression-like effects [19]. Oral administration of the NMDA-receptor antagonist dextromethorphan was found to suppress the post-tDCS effects of both anodal and cathodal stimulation, suggesting that tDCS after effects involve NMDA receptors [19]. Importantly, modulation of cortical activity with tDCS changes human behavior [20]. For example, in randomized sham-controlled trials, anodal stimulation of the motor cortex (M1) in the lesioned hemisphere was found to improve upper limb outcomes in chronic [21,22,23] and subacute stroke survivors [24,25,26], with behavior changes underpinned by increased cortical activity within the M1 [27]. Although much work remains to be performed regarding optimal stimulation doses, cortical targets and electrode montages, these studies provide some indication that tDCS may be beneficial in stroke recovery.
While there is indication that tDCS has potential to improve stroke recovery of the upper limb [28], there are comparatively fewer studies that have investigated tDCS for lower limb recovery after stroke. Lower limb rehabilitation is especially important, as the simple act of regaining the ability to walk has subsequent effects on the ability to engage in activities of daily living [29,30]. Furthermore, those receiving therapy targeting mobility have been shown to have reduced levels of depression and anxiety [31], which are important determinants of stroke recovery [32,33,34]. Therefore, novel interventions capable of enhancing lower limb recovery might improve not only lower limb motor performance but could have added benefit for stroke rehabilitation in general. The purpose of this review is to discuss tDCS as a technique to modulate brain activity and promote recovery of walking following stroke. Within this review, we will outline current studies that have investigated tDCS to improve lower limb motor performance in both healthy adults and people with stroke. Additionally, we propose a best-practice model of experimental design for lower limb tDCS to guide future application for lower limb stroke recovery.

2. Is it Possible to Modify Lower Limb Motor Networks with Transcranial Direct Current Stimulation?

One approach to modify activity of the lower limb motor network with tDCS is to target the M1, similar to studies involving the upper limb. However, targeted application with tDCS is challenging as, compared with upper limb representations, the lower limb M1 representations are more medial and deeper within the interhemispheric fissure (Figure 1). This presents two notable difficulties. First, the ability of targeted stimulation to the lower limb M1 within one hemisphere (e.g., the lesioned hemisphere in stroke) is challenging, as tDCS electrodes can be relatively large compared to the size of cortical representations, resulting in current spread that may inadvertently lead to stimulation within the opposite hemisphere. Second, the depth of the lower limb M1 representations may present a challenge to current penetration and depth with traditional tDCS applications. However, there is evidence to indicate that it is possible to modulate activity of the lower limb M1 with tDCS. Computational modelling has revealed that traditional anodal tDCS electrode montages (anode overlying the lower limb M1 and cathode overlying the contralateral orbit; Figure 1) can lead to the expected cortical excitability enhancement in the target cortex [35]. Indeed, reducing the size of the anode (3.5 cm × 1 cm) was found to improve the specificity of the current delivered to the cortex, while positioning the return electrode (cathode) to a more lateral position (T7/8 on the 10–10 EEG system) further improved current specificity, leading to greater changes in cortical excitability [35]. Experimental evidence also suggests that tDCS targeting the lower limb M1 can modify excitability. Jeffrey and colleagues [36] utilized an anodal-tDCS montage (2 mA, 10 min) over the lower limb M1 and found that motor-evoked potentials (MEPs) of the tibialis anterior muscle increased by as much as 59% compared to sham conditions. Along similar lines, 10 sessions of anodal tDCS (2 mA, 10 min) targeting the lower limb M1 was found to increase the amplitude of MEPs recorded from the paretic tibialis anterior compared to sham stimulation [37]. This empirical evidence provides some support to the computational modelling to suggest that the use of tDCS targeting the lower limb M1 can modify corticospinal excitability.
Although M1 has received attention as a stimulation target to modify excitability of the lower limb M1, there is potential for cerebellar tDCS to induce similar, or possibly more prominent, behavioral and neurophysiological changes. It is noteworthy that a computational modelling study that compared electrode montages targeting M1 and the cerebellum found that cerebellar stimulation produced substantially higher electric field strengths in the target area compared to M1 stimulation, suggesting the cerebellum may indeed be a suitable target for tDCS [38]. Behaviorally, the cerebellum contributes to motor planning, learning, and control; this influence is in part mediated by connections to M1 via the cerebellothalamocortical tracts, previously reported to play a key role in motor skill learning in mice [39]. Although this stimulation technique has received comparatively little attention compared to M1 stimulation, there is some indication that it is possible to modify cerebellar excitability in a focal and polarity specific manner [40]. Whether cerebellar tDCS is required to modify excitability of M1 for behavioral change is unclear. However, if a desired outcome was to modify M1 excitability with cerebellar stimulation, a pertinent challenge would be whether cerebellar tDCS can achieve the specificity required to precisely target the lower limb M1 in one hemisphere. Although speculative, one approach could be to pre-activate M1 through a contralateral lower limb motor task in order to bias the effects of tDCS towards those networks activated to perform the task. In support, there is some evidence in the upper limb that performance of a task during cerebellar tDCS does interact with the change in M1 excitability [41].[…]

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[WEB SITE] Brain Injury News – CNS

RESEARCH UPDATES, INDUSTRY NEWS, SURVIVOR STORIES

The world of advancements in brain injury knowledge and treatment is a rich composite of the progress being made by scores of dedicated people. The articles and reports below reflect current research, industry analysis, and stories of recovery. Innovations in patient care and the evolution of best practices in rehabilitation are among the subjects addressed by thought leaders, universities, and institutes noted here.

Categories:  Survivor  Stories  Traumatic Brain Injury  Concussion  Stroke  Aneurysm  Coma

NEWS & EVENTS ARCHIVES

via Brain Injury News

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[Abstract] An interactive and innovative application for hand rehabilitation through virtual reality

Physiotherapy has been very monotonous for patients and they tend to lose interest and motivation in exercising. Introducing games with short term goals in the field of rehabilitation is the best alternative, to maintain patients’ motivation. Our research focuses on gamification of hand rehabilitation exercises to engage patients’ wholly in rehab and to maintain their compliance to repeated exercising, for a speedy recovery from hand injuries (wrist, elbow and fingers). This is achieved by integrating leap motion sensor with unity game development engine. Exercises (as gestures) are recognised and validated by leap motion sensor. Game application for exercises is developed using unity. Gamification alternative has been implemented by very few in the globe and it has been taken as a challenge in our research. We could successfully design and build an engine which would be interactive and real-time, providing platform for rehabilitation. We have tested the same with patients and received positive feedbacks. We have enabled the user to know the score through GUI.

 

via An interactive and innovative application for hand rehabilitation through virtual reality: International Journal of Advanced Intelligence Paradigms: Vol 15, No 3

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[Abstract] What is the potential of virtual reality for post-stroke sensorimotor rehabilitation?

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via What is the potential of virtual reality for post-stroke sensorimotor rehabilitation?: Expert Review of Neurotherapeutics: Vol 0, No 0

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[BLOG POST] Hope Clark on “My new normal” following her brain injury – Jumbledbrain

Today I want to introduce you to Hope Clark. She is a talented writer, who has written about learning disabilities and has written a couple of articles for some local newspapers. Plus there are plenty of articles written about her. These articles can be found archived at the National Library in Ottawa.

Since her brain injury she wrote few pieces as part of her therapy. However, she has now decided to share them publicly and hopes (no pun intended) that they will help others.

“I am from SW Ontario, Canada.  My past like is filled with Management positions, Event Planning, Fundraising and Marketing with a side of Communications. Writing for me is something I find very cathartic. I acquired my TBI in March of 2018 and have been trying to reinvent myself ever since. I am not sure what I am going to do when I grow up, but if I can help someone with my writing then I feel I have done my job.” – Hope Clark aka HM Lemon

This is an extract of one of her articles. You can read the full version of My new normal which she has published on Facebook here.


As the thick veil of trauma has slowly been dissolving over the past year, nine months, 5 days (you get the gist) my life has been interesting to say the least. I have been the most alone I have ever been even though, unlike before, I have a loving husband and two beautiful children. Don’t get me wrong, I have been treated with great empathy, compassion and caring.

My road to recovery has been met with other trauma victims, doctor’s, specialists, treatment providers: I am never alone, yet, I am the most alone I have ever been.

Living with a traumatic brain injury and trauma really does lend itself to the saying, ‘if you have never experienced it, you just won’t understand.’ You try to be like your old self, or your normal and no matter what happens…something you’ve never experienced before rears its ugly head. It is true what they say, ‘Don’t take things for granted because you never know what could happen”, is taken to the extreme!

I can’t drop my kids off at school because the commotion of the people, vehicles, movement, noise – it makes me so sick to the point my brain feels like it will explode. My ‘level of tolerance’ as the treatment providers call it is about 2 hours. When I meet a friend for a lunch, little do they know that I must sleep for 2 – 3 hours afterwards just to recover. This coming from a woman who would get up at 6 am to workout before getting the kids up at 7 am and then not stopping until around midnight. This schedule repeated day after day. Some other wonderful side effects of an MVA are, yet not limited to, screen time (computer and television) gives me headaches; my wonderfully intelligent brain now struggles with sentence structure, word recall and spelling and even executive functioning. My love of music has been put on mute and my awesome dance parties with the kids have been put on hold. I keep hearing the term, ‘new normal’ – and that is very difficult to wrap my head around. Living 44 years is a long time. You acquire certain traits, characteristics and now to be told that that isn’t you anymore is a struggle. At the same time, I am being told that I am extremely high functioning. What does that even mean!? Lol! Until recently I didn’t understand this until my OT said something of brilliance.
Living with a traumatic brain injury and trauma really does lend itself to the saying, ‘if you have never experienced it, you just won’t understand.’

You try to be like your old self, or your normal and no matter what happens…something you’ve never experienced before rears its ugly head.

It is true what they say, ‘Don’t take things for granted because you never know what could happen”, is taken to the extreme!

I can’t drop my kids off at school because the commotion of the people, vehicles, movement, noise – it makes me so sick to the point my brain feels like it will explode. My ‘level of tolerance’ as the treatment providers call it is about 2 hours. When I meet a friend for a lunch, little do they know that I must sleep for 2 – 3 hours afterwards just to recover. This coming from a woman who would get up at 6 am to workout before getting the kids up at 7 am and then not stopping until around midnight. This schedule repeated day after day. Some other wonderful side effects of an MVA are, yet not limited to, screen time (computer and television) gives me headaches; my wonderfully intelligent brain now struggles with sentence structure, word recall and spelling and even executive functioning. My love of music has been put on mute and my awesome dance parties with the kids have been put on hold. I keep hearing the term, ‘new normal’ – and that is very difficult to wrap my head around. Living 44 years is a long time. You acquire certain traits, characteristics and now to be told that that isn’t you anymore is a struggle. At the same time, I am being told that I am extremely high functioning. What does that even mean!? Lol! Until recently I didn’t understand this until my OT said something of brilliance.

‘We can go our whole lives living a certain way and one little bonk to the brain and yep, you have to relearn your whole way of life and living.’ Crazy enough it made me feel a bit better. I understood what people were trying to tell me about my ‘New Normal.’ 

Living with a TBI, (traumatic brain injury) is your brain telling you that you just can’t!

What does that mean exactly? When my level of tolerance has been met my brain begins to feel like it’s on fire. You are most likely saying once again, what does that mean? Well, it’s like when you begin to get the flu and your head feels like you’re starting get a fever, that is what my head feels like – yet, without the flu. I begin to get foggy. My concentration levels start to fade. My ability to understand let alone comprehend what the person I am with is saying it to is slim to none and I am unable to make eye contact with whom I am with because my brain is too busy trying to keep up. Oh yes, comprehension has left the building everyone and thank gawd for spell check. This coming from the woman who has been published, interviewed for television, print and radio more times than I can count. On Mother’s Day 2019, I dropped to the floor in front of my family. Out cold I was, and an ambulance had to be called. I spent the day in the ER. Just before I was released the doctor came and tried to explain what was going on. We had a conversation and when she walked away, my mom said – honey, you did NOT understand a word she was saying. I was mortified. This isn’t the only time this has happened, and I was oddly humbled by the experience. The great news is that my memory is completely shot so the likelihood of me remembering these highly embarrassing moments are unlikely. 

Memory: I did have one almost 2 years ago. I had a great memory and my jobs reflected by ability to hold large amounts of information. Now, I forget to turn off the stove or close the fridge. I lose my thought(s) in mid-sentence, knowing there was something there and at the same time not having a clue what I was saying, doing, or what the topic was. Grabbing and putting the wrong lid on something is day after day. I forget my children’s names. In my defence, it is mostly when I am upset of my tolerance levels have been met and asking them to go brush their teeth or get ready for bed. My daughter just looks at me as says, ‘Mom, why are you telling me to go to the kitchen!? Don’t you want me to go to the bathroom, cause we’re already in the kitchen?’ My response, ‘Om-goodness, you understood what I am trying to say so please just go,’ Lol.

Honestly, looking at your brain injury with a positive outlook is the only way to be. The truth is that you can not control the future, only your present. You have no idea when and if you will be 100% and that is okay. It is okay because you can begin to reinvent yourself and how many people really get the chance to do that? Every step forward is a victory. Each and every day you can manage the pain, headaches and nausea is a bonus! You just push forward with whatever you have left. Be thankful for every moment you get to spend with your children and jump for joy that they were not in the car with you. And, even though you miss experiences and moments with your children – you get to be there with them in the small moments: putting them to bed, helping them brush their teeth, making dinner because all moments and experiences are important. You cherish and laugh out loud when your 6-yr old tells you to piss off; and, when your 8-yr-old daughter wants to just sit and cuddle with you for hours. And, this is where I leave you 1 year, 9 months, 15 days,…for now.

Other articles you may like:

Does this sound familiar to you? What has it been like having to accept what is your new normal following a brain injury?

via Guest post: Hope Clark on “My new normal” following her brain injury. | Jumbledbrain

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[VIDEO] Recovery from Brain Injury Occurs for the Rest of a Person’s Life – YouTube

The human brain is a wonderful organ with amazing flexibility. Learn more about recovery.

via Recovery from Brain Injury Occurs for the Rest of a Person’s Life – YouTube

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[BLOG] PROMOTING A BRAIN HEALING LIFESTYLE

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[Brochure] Understanding TBI Part 4: The impact of a recent TBI on family members and what they can do to help with recovery

How does brain injury affect family members?

For most family members, life is not the same after TBI. We want you to know that you are not alone in what you are feeling. While everyone’s situation is a bit different, there are some common problems that many family members experience such as less time for yourself, financial difficulties, role changes of family members, problems with communication, and lack of support from other family members and friends. These are just some of the problems that family members may face after injury. Sometimes these problems can seem too much and you may become overwhelmed, not seeing any way out. Family members have commonly reported feeling sad, anxious, angry, guilty, and frustrated.[…]

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[ARTICLE] Recovery of upper limb function is greatest early after stroke but does continue to improve during the chronic phase: a two-year, observational study – Full Text

Abstract

Objectives

Investigate upper limb (UL) capacity and performance from <14-days to 24-months post-stroke.

Design

Longitudinal study of participants with acute stroke, assessed ≤14-days, 6-weeks, 3-, 6-, 12-, 18-, and 24-months post-stroke.

Setting

Two acute stroke units.

Main outcome measures: Examination of UL capacity using Chedoke McMaster Stroke Assessment (combined arm and hand scores, 0 to 14), performance using Motor Activity Log (amount of movement and quality of movement, scored 0 to 5), and grip strength (kg) using Jamar dynamometer. Random effects regression models were performed to explore the change in outcomes at each time point. Routine clinical imaging was used to describe stroke location as cortical, subcortical or mixed.

Results

Thirty-four participants were enrolled: median age 67.7 years (IQR 60.7 to 76.2), NIHSS 11.5 (IQR 8.5 to 16), female n = 10 (36%). The monthly rate of change for all measures was consistently greatest in the 6-weeks post-baseline. On average, significant improvements were observed to 12- months in amount of use (median improvement 1.81, 95% CI 1.35 to 2.27) and strength (median improvement 8.29, 95% CI 5.90 to 10.67); while motor capacity (median improvement 4.70, 95% CI 3.8 to 5.6) and quality of movement (median improvement 1.83, 95% CI 1.37 to 2.3) improved to 18-months post-stroke. Some individuals were still demonstrating gains at 24-months post-stroke within each stroke location group.

Conclusion

This study highlights that the greatest rate of improvement of UL capacity and performance occurs early post-stroke. At the group level, improvements were evident at 12- to 18-months post-stroke, but at the individual level improvements were observed at 24-months.

Introduction

Up to 70% of individuals experience difficulties using their upper limb (UL, arm and hand) to perform meaningful activities after stroke [1]. There is an assumption that when a stroke survivor demonstrates a change in activity, it is underpinned by an improvement in their capacity (i.e., what a person can do in the clinical environment) and performance (i.e., does a person actually use their UL in real world environments outside of the clinic) [2]. However, UL recovery post-stroke is unlikely to be this simplistic [3]. Understanding how capacity and performance change over years post-stroke might help to identify which patients to target and when during their recovery.

Previous research has noted distinct recovery profiles during inpatient [4][5] and outpatient [6] rehabilitation. Firstly, survivors may demonstrate improvements in both capacity and performance after stroke. Secondly, survivors may demonstrate an improvement in capacity but not performance. Lastly, survivors may demonstrate little or no change in both capacity and performance. An improvement in performance but not capacity has not been documented in the literature. Combined, these profiles support our rationale that UL capacity and performance are interrelated, yet are different constructs that must be measured separately.

Stroke recovery is a long-term goal. It is important to complete observational studies that track recovery to establish whether there is a discrepancy between capacity and performance in the long-term. To date, longitudinal tracking of recovery has largely lacked investigation of natural recovery from an acute time point post-stroke (first 7- to 14-days), long-term follow up of patients beyond 3- to 6-months post-stroke, and characterisation of stroke variables such as lesion type and location that may modify or interact with observed recovery profiles [7].

In this exploratory study our objectives were to determine 1) whether UL capacity and performance improve over the first 24-months after stroke; and 2) if there is a window of greatest improvement in UL capacity and performance. This information is important to develop an understanding of the longterm timecourse of recovery after stroke to support evidence-based clinical practice guidelines to inform upper limb rehabilitation services.

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Continue —-> Recovery of upper limb function is greatest early after stroke but does continue to improve during the chronic phase: a two-year, observational study – ScienceDirect

Fig. 2

Fig. 2. Upper limb motor capacity (Chedoke), performance (quality of movement & amount of use), and grip strength over 24-months post-stroke (n = 28)

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[ARTICLE] What the Proportional Recovery Rule Is (and Is Not): Methodological and Statistical Considerations – Full Text

In 2008, it was proposed that the magnitude of recovery from nonsevere upper limb motor impairment over the first 3 to 6 months after stroke, measured with the Fugl-Meyer Assessment (FMA), is approximately 0.7 times the initial impairment (“proportional recovery”). In contrast to patients with nonsevere hemiparesis, about 30% of patients with an initial severe paresis do not show such recovery (“nonrecoverers”). Hence it was suggested that the proportional recovery rule (PRR) was a manifestation of a spontaneous mechanism that is present in all patients with mild-to-moderate paresis but only in some with severe paresis. Since the introduction of the PRR, it has subsequently been applied to other motor and nonmotor impairments. This more general investigation of the PRR has led to inconsistencies in its formulation and application, making it difficult to draw conclusions across studies and precipitating some cogent criticism. Here, we conduct a detailed comparison of the different studies reporting proportional recovery and, where appropriate, critique statistical methodology. On balance, we conclude that existing data in aggregate are largely consistent with the PRR as a population-level model for upper limb motor recovery; recent reports of its demise are exaggerated, as these excessively focus on the less conclusive issue of individual subject-level predictions. Moving forward, we suggest that methodological caution and new analytical approaches will be needed to confirm (or refute) a systematic character to spontaneous recovery from motor and other poststroke impairments, which can be captured by a mathematical rule either at the population or at the subject level.

It has been appreciated since Hippocrates that the strongest predictor of final motor impairment after stroke is initial impairment (Aphorisms of Hippocrates, Section 2: 42). A prominent poststroke motor impairment in humans is the intrusion of unwanted synergies, with synergy referring to a systematic pattern of either joint co-articulation or muscle co-activation. The Fugl-Meyer Assessment (FMA) was explicitly developed to track progression of recovery from such synergies. A seminal study tracking the recovery of patients using the upper extremity subscale of the Fugl-Meyer Assessment (FMA-UE) demonstrated that more severely affected patients saw greater recovery in this outcome, on average, than more mildly affected patients in the immediate poststroke recovery period1; however, the average final score of the FMA-UE among the severly affected still trailed behind the mildly affected. The authors of this study stated, “The most dramatic recovery in motor function occurred over the first 30 days, regardless of the initial severity of the stroke.” On the basis of this study and other considerations, Krakauer et al2 sought to investigate the nature of this FMA-UE change early after stroke; work that led to the formulation of the proportional recovery rule (PRR).2 The PRR states that patients recover approximately 70% of their maximal potential reduction in impairment as measured by the FMA.2

Since it was introduced, the PRR has been applied in a broad range of studies that involve recovery from stroke, both for FMA-UE and for other outcomes. Claims related to the PRR have been made for upper and lower limb impairment measured by the FMA,310 aphasia measured with the Western Aphasia Battery (WAB),11 the resting motor threshold (RMT) of the extensor carpi radialis,6 and visuospatial neglect measured with the Letter Cancellation Test (LCT),12 among others. Applications of the PRR typically distinguish between two distinct subgroups of patients, referred to as “recoverers” and “nonrecoverers”: the former subgroup is composed of patients who recover a significant amount of lost function, and the latter is composed of those who do not. The PRR is thought to usefully characterize the recovery process among recoverers only. Although the methods by which the PRR was applied and evaluated have differed substantially across publications, many authors have argued that their findings are evidence for a PRR that accurately describes an underlying biological process that arises across neurolocical domains. Recently, however, the PRR has been the subject of criticism related to the validity of the statistical methods underlying its implementation and to the degree to which data are consistent with claims in support of the PRR.13,14 Much of the critique on the PRR articulated by these articles was focused on specific statements associated with the PRR followed by a general dismissal of all findings.

Our goal in this work is to provide a critical reexamination of the literature pertaining to the PRR. We focus first on the interpretation and implementation of PRR as a statistical model, and on data-driven concerns about the use of the PRR in studies of recovery. We then reexamine data reported in the literature and the extent to which past studies provide evidence for the PRR with these considerations in mind. Our hope is that this will serve as an instructive overview of issues that can arise in the application of the PRR to studies of recovery, aiming to improve future investigations into the PRR. Although our primary purpose is not to provide direct response to recent critiques,13,14 we are mindful of the concerns raised and address these directly in the Discussion section.

The breadth of work on the PRR introduces a commensurate range of methodological concerns one might consider. We attempt to be complete in our discussion but prefer to focus on overarching concerns regarding the statistical validity of the PRR instead of point-by-point inspections of the existing literature. Two themes we will revisit while pursuing the main goals of this paper are the identification of recoverers and the distinction between describing biological mechanisms and making patient-level predictions. The manner in which nonrecoverers are identified is a point of legitimate concern, as some statistical approaches can artifactually create evidence for the PRR. The PRR was originally intended to describe biological mechanisms at the population level, although implicitly it is expected that the PRR may be useful for predicting recovery of individual patients. Both of these are related to recent concerns regarding the PRR.

The next section provides an overview of the statistical formulation of the PRR and introduces three simulated datasets to illustrate scenarios over which the PRR shows varying degrees of validity. Subsequent sections conduct a selective review of the literature, reevaluating specific articles in the light of the three scenarios, comment on recent criticisms of the PRR, and end with our current view on the veracity of the PRR.

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Continue —>  What the Proportional Recovery Rule Is (and Is Not): Methodological and Statistical Considerations – Robinson Kundert, Jeff Goldsmith, Janne M. Veerbeek, John W. Krakauer, Andreas R. Luft,

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