Changing stroke rehab and research worldwide now.Time is Brain! trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.

What this blog is for:

My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.

Wednesday, July 25, 2018

Recanalization in Cerebral Venous Thrombosis

If you have a blood clot in a vein in your brain, they don't bother telling you what the results are; just a better chance of favorable outcome if you get recanalized. Once again missing the whole point of stroke research; what interventions get us to 100% recovery. Every research article should be written and evaluated in that light. Not this beating around the bush and quoting statistics like they are useful to stroke survivors.
https://www.ahajournals.org/doi/10.1161/STROKEAHA.118.022129?platform=hootsuite
A Systematic Review and Meta-Analysis
Originally publishedStroke. 2018;49:1828-1835

Abstract

Background and Purpose—

The role of recanalization of the occluded dural sinus or vein in the outcome of patients with cerebral venous thrombosis (CVT) is not established. We aimed to systematically review, in patients with CVT, (1) the recanalization rate and its association with (2) clinical outcome and (3) CVT recurrence.

Methods—

Systematic search in MEDLINE (Medical Literature Analysis and Retrieval System Online), Cochrane Library, and clinicaltrials.gov (inception to September 2017). We considered cohort studies reporting the recanalization rate in adult patients with CVT treated with anticoagulation. Reported rates of venous recanalization at the last follow-up, functional outcome defined using the modified Rankin scale at last follow-up dichotomized for favorable (0–1) and unfavorable (2–6) outcome, and recurrence rate of CVT according to recanalization status were extracted independently by 2 authors. Meta-analyses of proportions were performed using Freeman-Tukey double arcsine transformation. Functional outcomes according to the recanalization status were compared using meta-analysis and ordinal logistic regression. We conducted sensitivity analyses for time to assessment of recanalization and study quality.

Results—

Four hundred sixty-eight studies were identified, and 19 studies were included. (1) We found report of 694 patients with recanalization in the follow-up among 818 cases of CVT. The overall pooled proportion of patients achieving recanalization was 85% (95% confidence interval, 80–89; I2=58%). In studies with higher methodological quality, the recanalization rate was 77% (95% confidence interval, 70–82; I2=0%). (2) There was a significant increase in the chance of favorable outcome (modified Rankin scale, 0–1) in patients with recanalization with a pooled odds ratio of 3.3 (95% confidence interval, 1.2–8.9; I2=32%) in the random effects meta-analysis and a common odds ratio of 3.3 (95% confidence interval, 1.7–6.3) in the ordinal logistic regression. (3) Data on CVT recurrence according to recanalization was scarce.

Conclusions—

The overall rate of recanalization in patients receiving anticoagulation was 85%, but exclusion of severe patients from follow-up imaging is a plausible source of bias. Lack of venous recanalization was associated with worse clinical outcome.

Introduction

Thrombosis of the cerebral veins and sinuses (cerebral venous thrombosis [CVT]) is a distinct cerebrovascular disorder with a highly variable and unpredictable clinical course and in which, despite treatment, death or dependence occurs in ≈15% of patients with CVT.1
The clot itself is the primary target of current CVT treatments. However, although evidence from animal models of CVT suggests that early venous recanalization has an impact on brain tissue damage,2 the hypothesis that reopening of occluded sinuses and veins improves clinical outcome is not established in patients with CVT. Venous recanalization, that is, recanalization of sinuses or veins, may improve regional perfusion and, therefore, allow salvage of threatened tissues. However, several factors may weaken this relationship, particularly if this occurs too late to benefit affected tissues or if collateral circulation, common in the venous territories, protects perfusion. Besides, recanalization of sinuses may not restore drainage effectively if veins or microcirculation remain occluded.
Cohort studies evaluating rate and temporal profile of recanalization in patients with CVT receiving standard therapeutic anticoagulation have shown variable results. A prior systematic review published in 2006 highlighted the scarcity of data and the subsequent poor quality of the estimated recanalization rates.3 Importantly, studies assessing the relationship between venous recanalization and prognosis in patients with CVT have shown conflicting results.46 One possible explanation could be the variable extent and function of collateral circulation, which was not analyzed in these cohorts. However, an independent effect of venous collateral circulation on the prognosis of patients with CVT has not been shown previously.7
As described for low-extremity deep vein thrombosis,8 recanalization may also influence the risk of CVT recurrence. This association has already been suggested in a large cohort of pediatric patients with CVT9 but remains to be shown in adult patients.
We performed a systematic review of the published evidence to better estimate, in patients with CVT receiving standard anticoagulation treatment, (1) the recanalization rate and its association with (2) clinical outcome and (3) CVT recurrence.

Methods

For the purpose of this systematic review, we followed the MOOSE (Meta-Analysis of Observational Studies in Epidemiology)10 proposal and the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)11 guidelines. The authors declare that all supporting data are available within the article and its online-only Data Supplement.

Eligibility Criteria

We considered published observational cohort studies reporting original data on the recanalization status after acute CVT in adults, using noninvasive imaging (computed tomographic venography or magnetic resonance imaging). Cohort studies including at least 10 patients with evaluation for the recanalization status were accepted. We did not exclude studies a priori owing to poor quality. Articles in English, German, French, Spanish, Italian, and Portuguese were accepted. Series of pediatric patients or traumatic CVT were excluded. Cohorts in which >10% of patients received endovascular treatment or were not anticoagulated were also excluded.

Definitions

We considered imaging outcomes in follow-up, assessed using computed tomographic venography or magnetic resonance (complete recanalization, partial recanalization, and no recanalization), and clinical outcomes (full modified Rankin scale [mRS] score in the last available follow-up; recurrent CVT).
We used the following definitions of outcomes for data extraction and analysis:
To assess the quality of the author’s definitions of complete, partial, and absent recanalization of each individual occluded sinus or vein, we compared them with the following standard: complete recanalization defined as blood flow without any interruption, partial recanalization defined as small interruptions of continuous blood flow and narrowing of the venous lumen, and absent recanalization defined as interrupted blood flow.
Recanalization at the patient level was considered when there was recanalization of at least 1 sinus or vein in an individual patient with CVT. No recanalization was defined as total absence of any type of recanalization in any previously thrombosed sinus or vein in an individual patient with CVT. Complete recanalization was considered when all previously thrombosed structures met the criteria of complete recanalization. Whenever the criteria for complete recanalization were not fulfilled but at least 1 vessel displayed any type of recanalization, we considered this as partial recanalization.
We considered the earliest proof of recanalization in the imaging studies as the time point of recanalization.
Clinical outcomes were defined using the mRS in the last available follow-up. Favorable outcome was defined as complete recovery, demonstrated by mRS 0 to 1.
CVT recurrence was defined as new CVT diagnosis confirmed with imaging in a patient with prior CVT.

Search Strategy

A systematic search using combinations of keywords was performed in Pubmed, Cochrane Library, and clinicaltrials.gov from inception to September 10, 2017. The developed search strategy for all databases combined the terms sinus, thrombosis, cerebral, vein/venous or intracranial, and recanaliz* or recanalis*, as described in the online-only Data Supplement. Potential eligible studies and selected studies’ reference lists were crosschecked for additional studies.

Study Selection

Reports retrieved through electronic identification were screened for potential eligibility by title and abstract analysis. The full text of potentially eligible studies was screened for appropriateness for inclusion by 2 independent authors (D.A.d.S., L.L.N.). Disagreements were solved by consensus or by a third independent party (P.C., J.M.F.).

Data Collection Process

Two independent parties (D.A.d.S., L.L.N.) extracted data from included studies’ full text to a specially designed form. Disagreements were solved by consensus or by a third independent party (P.C., J.M.F.). Corresponding authors were contacted for additional information if needed.

Data Items

For the selected studies, we extracted the following data: country, study design, year of publication, study setting, number of patients, median/mean follow-up, number of patients with follow-up noninvasive imaging, imaging method used for assessment of recanalization, number of patients with recanalization (complete/partial) and no recanalization at the last follow-up, number of patients with recanalization (complete/partial) according to time point(s), mean/median time between diagnosis and last follow-up imaging, predictors of recanalization, number of patients with recurrent CVT according to recanalization status, clinical outcome (mRS) according to recanalization status, and mortality rate according to recanalization status.

Assessment of Study Quality

The studies eligible for inclusion in the meta-analysis were assessed for quality of study design and data reporting, according to the grading of recommendations, assessment, development, and evaluation approach12 (Table I in the online-only Data Supplement).

Summary Measures

The primary outcomes were recanalization rate in the last imaging follow-up in patients with CVT, functional outcome according to recanalization status and recurrence rate of CVT according to recanalization status. The secondary outcome was rate of partial and complete recanalization in the last imaging follow-up and mortality rate according to recanalization status.
Sensitivity analyses were conducted by excluding studies with recanalization assessment after <3 months and studies in which quality was classified as low.

Synthesis of Results/Statistical Analysis

We calculated the pooled incidence of recanalization per 100 individuals with CVT and 95% confidence intervals (CIs) using meta-analysis of proportions. A random effects model with Freeman-Tukey double arcsine transformation was used for pooling the proportions. Heterogeneity among studies was assessed with Cochran Q test. The percentage of total variation across studies because of heterogeneity was evaluated by the I2 measure. The presence of publication bias was interrogated by funnel plots. Extracted pooled incidences of dichotomized functional outcomes and recurrence rates according to recanalization status were pooled using a random effects model (DerSimonian Laird) owing to the presumed heterogeneity between individual study estimates and compared using odds ratio (OR). Overall incidences of functional outcomes according to the recanalization status were compared using proportional odds ordinal logistic regression to analyze shifts across the full range of the mRS. A P value of 0.05 was considered statistically significant. All analyses were conducted using Stata Statistical Software Release 14 (StataCorp, College Station, TX).

Results

We identified 468 nonduplicate references using our search strategy in Pubmed, Cochrane Library, and clinicaltrials.gov ( online-only Data Supplement), and 11 additional studies were obtained from manually reviewing references. We excluded 403 publications after evaluation of titles and abstracts using the predefined inclusion and exclusion criteria. We retrieved 65 studies in full text for detailed evaluation and verification of overlaps in study populations. Finally, we selected 19 studies.46,1328 A MOOSE/PRISMA flowchart summarizes study selection, including the reasons for exclusion (Figure 1). Details of the studies are displayed in the Table.

Stroke patients in Scotland left 'significantly disabled' amid lack of thrombectomy op

Even with this available your access to 'best possible care' doesn't exist. There are NO PROTOCOLS that will get you 100% recovered. Of course your lazy medical staff will use the tyranny of low expectations to assure you you are receiving the finest available care. 'CARE' NOT results. 

http://www.heraldscotland.com/news/16345513.stroke-patients-in-scotland-left-significantly-disabled-amid-lack-of-thrombectomy-op/

HUNDREDS of patients in Scotland are being left with "worse outcomes and significant disability" because a procedure to remove blood clots is unavailable in Scotland, charities have warned.
Only 13 patients underwent the operation, known as a thrombectomy, in 2017 despite estimates that 600 people a year who suffer a severe ischaemic stroke could be eligible for the treatment.
The procedure physically removes the clot to open up the artery and increase blood flow.
Read more: More middle-aged people are suffering strokes 
The figures emerged in the latest Scottish Stroke Care Audit.
It is estimated that routine access to thrombectomy in Scotland would result in around 300 patients having reduced disability and over 100 avoiding dependency on others, such as the need to live in a nursing home.
Thrombectomy is no longer offered at any hospital in Scotland, but is offered elsewhere in the UK.
The Scottish Government has established a national committee to plan the creation of a Scottish thrombectomy service, but campaigners said progress has been too slow.
Read more: Andrew Marr receives controversial new stroke treatment in US
Andrea Cail, Director Scotland of the Stroke Association said: "In 2017, only 13 people received thrombectomy, and currently no centre in Scotland is providing it.
"The Audit identifies around 600 Scots per year as potentially benefitting from this life changing treatment.
"A national committee has been established to plan a Scottish thrombectomy service, but the process is slow and the consequence again is that many patients have been left with worse outcomes and significant disability.
"We are calling alongside Chest, Heart and Stroke Scotland for the provision of thrombectomy in Scotland to be tackled as a priority by the Scottish Government, with national funding identified by the NHS.
"Those eligible stroke patients in Scotland deserve the same access to this life-changing treatment as in England.”
Paul Okroj, of charity Chest Heart & Stroke Scotland, added: “If thrombectomy is not carried out, those having the most severe types of stroke are likely to be more disabled when they leave hospital and less able to care for themselves than people who have had a thrombectomy.
"This will increase the length of their recovery and ultimately increase demand on health and social care resources.”
Read more: Cost of treating stroke and social care needs could triple by 2035
Overall, the Audit found that only one Scottish stroke care target had been achieved in 2017.
The target - for 80 per cent of patients to be seen at a specialist clinic within four days of referral - was exceeded at 82 per cent for the second year in a row.
A target to give thrombolysis - using drugs to break up clots - to 80 per cent of stroke patients within one hour of arrival was missed, averaging 59 per cent across Scotland.
However, two hospitals - Hairmyres Hospital in East Kilbride and Glasgow Royal Infirmary - became the first to achieve the thrombolysis target, and the total number of patients receiving thrombolysis was the highest since 2009.
Other targets - admission to a stroke unit within one day, a brain scan within 24 hours, a screening test in four hours and aspirin within a day - were missed.
Strokes are the third biggest killer in Scotland, but deaths have fallen.
Public health minister Joe FitzPatrick said: "These figures show that our strategy for stroke is delivering real improvements, with deaths from stroke down 39.5 per cent between 2007 and 2016.
"We know people who have had a stroke need access to the best possible care as quickly as possible and we are focused on providing that in acute settings as well as helping people's longer-term recovery in their own communities."

More Canadian stroke patients could get clot-grabbing treatment

They may have saved your life doing this but they left you with no way to get 100% recovered. That is the ONLY stroke goal.
http://www.cbc.ca/news/health/stroke-guidelines-blood-clot-treatment-1.4753969

People in remote areas or who suffer a stroke while sleeping could benefit from new 24-hour window


Endovascular thrombectomy, a procedure in which doctors pull a blood clot out of a stroke patient's artery to restore blood flow to the brain, could benefit more Canadian patients than previously thought, the Heart and Stroke Foundation says. (Akkalak Aiempradit/Shutterstock )
A procedure that allows doctors to pull stroke-causing blood clots out of patients' arteries could now save more lives and prevent more disabilities in Canada, the Heart and Stroke Foundation says.
The procedure, endovascular thrombectomy (EVT), was previously OK'd for use up to only six hours after a stroke. But on Thursday, the foundation announced it had changed its guidelines, extending that window to 24 hours.
New research suggests EVT could benefit one in five Canadian stroke patients, said Patrice Lindsay, stroke director for the Heart and Stroke Foundation. Previously, experts thought the treatment was only viable for 10 to 15 per cent of patients.




How a thrombectomy works
00:00 00:22

Watch how a clot in the brain of a person having a stroke is cleared with a device 0:22
Last February, when the American Heart Association announced it was changing its maximum timeline for EVT (also called mechanical thrombectomy) to 24 hours, the foundation confirmed it was also planning to change the guidelines in Canada. The results of the new studies, which were announced at a European conference in May, offered compelling evidence that even more patients could benefit from EVT many hours after having a stroke, Lindsay said.
During the procedure, physicians insert a stent into the patient's groin and thread it up through the blood vessels to reach a clot — that is blocking a major artery supplying blood to the brain — and pull it out.
EVT is only useful in cases of ischemic strokes (strokes caused by a blood clot), as opposed to those caused by a bleed in the brain. Health-care providers assess whether to use EVT on a case-by-case basis, using an advanced CT scan to see exactly where the clot is and whether it can be removed with minimal risk of causing additional damage.
Doctors also use CT imaging to see how much brain tissue has died in the area where the stroke occurred, and how much can be saved. It was previously thought that after six hours, there wasn't enough surviving tissue left to justify doing an EVT —  but there's now evidence to the contrary, prompting the extension to 24 hours.

'Catastrophic' strokes 

The extension will especially affect people who live in remote and rural communities, Lindsay said.
Because EVT is a highly specialized procedure, it is only performed in 23 hospitals across Canada. That means many stroke victims who live far from an urban centre, and who had to be transferred, "would never have made the six-hour time window," she said.
That's been a worry for Dr. Ayman Hassan, a neurologist at Thunder Bay Regional Health Sciences Centre in northern Ontario.
The hospital has one neurosurgeon who does EVT, but if he's not there, patients who need the procedure have to be transferred to Winnipeg or to health-care centres in southern Ontario. Stroke patients also come to Thunder Bay from remote communities.
In the past, some patients who would have been eligible for EVT have run out of time before being able to get the treatment, Hassan said. With the new 24-hour time frame, he expects about 30 patients a year at his hospital will escape the "catastrophic" disability or death that this type of stroke brings.
The neurologist has seen the difference EVT can make, recalling a patient in his 60s who suffered a "significant stroke" last spring.
"He was able to walk on his own and no residual weakness, no residual visual change, no residual sensory dysfunction," Hassan said. "So he almost recovered like it was a minor, non-disabling stroke."
Had that patient not had the treatment, he likely would have been left with serious disabilities, including trouble walking, speaking and swallowing, he said.
The new time frame for EVT will also affect patients who have an ischemic stroke while sleeping.
"We now have opportunity for people who went to bed feeling fine and at whatever time they woke up, they were showing stroke symptoms, but there was no way of pinpointing exactly when that stroke occurred," Lindsay said.
But the Heart and Stroke Foundation acknowledges the new guidelines have implications for Canada's already stressed health-care system.
It's been working with provincial and territorial health ministries to prepare, Lindsay said, noting that screening more stroke patients to see if EVT is appropriate for them means an increased demand for immediate CT scans.
"All of the sudden everybody in that [24-hour] time window is critically urgent because we still have a chance to do something," she said.
Although that extra time is "great" in circumstances in which delays getting treatment are unavoidable, Lindsay emphasized that "sooner is still better" when it comes to stroke.
"We still lose 1.9 million brain cells a minute [after a stroke], and the longer you wait, the more harm and damage and less positive recovery," she said.

Growth Differentiation Factor 11 Promotes Neurovascular Recovery After Stroke in Mice

Mouse models, so you'll have to see if your doctor contacts these researchers doing human testing.  And no real hurry to get it done.
https://www.frontiersin.org/articles/10.3389/fncel.2018.00205/full?
  • Department of Translational Neuroscience, Jing’an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology and Institutes of Brain Science, Fudan University, Shanghai, China
Background: Growth differentiation factor 11 (GDF11), a member of transforming growth factor-β (TGF-β) superfamily, was shown to rejuvenate cardiac and skeletal muscle function and to improve cerebral vasculature and neurogenesis in old mice. However, recent experimental data reported that raising GDF11 levels inhibited skeletal muscle regeneration and had no effect on cardiac hypertrophy. Our aim was to investigate the effects of GDF11 on brain repair during the recovery phase after stroke.
Methods: Mice were subjected to distal middle cerebral artery occlusion, and recombinant GDF11 (rGDF11) was injected intraperitoneally once a day during days 7–13 after stroke. Neuronal precursor cells (NPCs) proliferation and angiogenesis were assayed at 14 days. Neuronal regeneration was assayed at 42 days. The beam-walking test and CatWalk were used to evaluate behavioral functions. Downstream pathways of GDF11 were also investigated.
Results: GDF11 was upregulated in the ipsilateral peri-infarct cortex and subventricular zone (SVZ) at 14 days after stroke. Treatment with rGDF11 enhanced the number of newborn NPCs and endothelial cells, microvascular length and area, and brain capillary perfusion. Western blots showed that rGDF11 upregulated brain-derived neurotrophic factor (BDNF) and increased the levels of proangiogenic factor angiopoietin-2 (Ang-2) and phosphorylation of vascular endothelial growth factor receptor-2 (VEGFR-2). We also found that rGDF11 upregulated the transcription factors Smad2 and Smad3 phosphorylation, but these activations were blocked by a TGF-β receptor inhibitor SB431542. Moreover, rGDF11-induced angiogenic remodeling and NPCs proliferation were reversed by injection of SB431542, suggesting that GDF11 may exert its effect via the TGF-β/Smad2/3 signaling pathway. Finally, treating mice with rGDF11 resulted in a significant increase in neuronal regeneration and functional recovery.
Conclusion: GDF11 promoted neurogenesis and angiogenesis and contributed to functional recovery after stroke in mice.

Introduction

Stroke is the leading cause of disability around the world (Murray et al., 2012). However, currently there is no effective treatment to facilitate the recovery in stroke patients. Stroke triggers the proliferation of the neural progenitor cells (NPCs) in the subventricular zone (SVZ) and the subgranular zone (SGZ) and the migration of NPCs toward the stroke areas (Arvidsson et al., 2002; Teng et al., 2008; Osman et al., 2011). Recent studies have suggested that stroke also induces angiogenesis in the peri-infarct region (Jiang et al., 2016). In stroke patients, there is a significant correlation between the vessel density in the brain and delayed mortality, suggesting that the angiogenesis is important for stroke recovery (Krupinski et al., 1993; Krupinski, 1994). Furthermore, angiogenic vessels were reported to release growth factors and chemokines to promote the migration of neuroblasts and the survival of new neurons, indicating that angiogenesis is highly linked with neurogenesis (Tsai et al., 2006). Therefore, therapeutic approaches to promote both neurogenesis and angiogenesis process may provide promising opportunities for stroke recovery.
Growth differentiation factor 11 (GDF11), a member of the transforming growth factor-β (TGF-β) superfamily, participates various biological processes in mammals. GDF11 has been identified as a rejuvenation factor which could reverse age-related cardiac hypertrophy and improve muscle and brain function (Loffredo et al., 2013; Katsimpardi et al., 2014; Sinha et al., 2014). The major findings of these studies were that circulating levels of GDF11 decreased with aging and recombinant GDF11 injection could improve the vascular remodeling and increase neurogenesis in aging mice (Katsimpardi et al., 2014). However, a recent report questioned the conclusion and suggested that circulating GDF11 levels increased with age and reduced muscle regeneration (Egerman et al., 2015). Another study also demonstrated a negative effect of GDF11 on age-related cardiac hypertrophy (Smith et al., 2015). Furthermore, in vitro experiments found that GDF11 treatment could increase the peripheral blood endothelial progenitor cells migration and the sprout formation (Finkenzeller et al., 2015), while showed no significant effect on the human umbilical vein endothelial cells proliferation and migration (Zhang et al., 2016).
In this study, we investigated the role of GDF11 on stroke recovery in a mouse model of distal occlusion of middle cerebral artery. We found that delayed treatment with recombinant GDF11 (rGDF11) at 7 days after stroke promoted neurogenesis and angiogenesis and improved behavioral outcome by regulating the TGF-β/Smad2/3 signaling pathway.

Exoskeleton-Robot Assisted Therapy in Stroke Patients: A Lesion Mapping Study

I'm sure that someplace in the joining of these three sets this research was already accomplished and no protocols came out of it. Just like NO PROTOCOLS will come out of this one either. 
https://www.frontiersin.org/articles/10.3389/fninf.2018.00044/full?
Antonio Cerasa1,2*†, Loris Pignolo1†, Vera Gramigna2, Sebastiano Serra1, Giuseppe Olivadese2, Federico Rocca2, Paolo Perrotta2, Giuliano Dolce1, Aldo Quattrone2,3 and Paolo Tonin1*
  • 1
S. Anna Institute and Research in Advanced Neurorehabilitation (RAN) Crotone, Crotone, Italy

  • 2Neuroimaging Unit, IBFM-CNR, Catanzaro, Italy
  • 3Neuroscience Research Centre, University Magna Græcia, Catanzaro, Italy

  • Background: Technology-supported rehabilitation is emerging as a solution to support therapists in providing a high-intensity, repetitive and task-specific treatment, aimed at improving stroke recovery. End-effector robotic devices are known to positively affect the recovery of arm functions, however there is a lack of evidence regarding exoskeletons. This paper evaluates the impact of cerebral lesion load on the response to a validated robotic-assisted rehabilitation protocol.
    Methods: Fourteen hemiparetic patients were assessed in a within-subject design (age 66.9 ± 11.3 years; 10 men and 4 women). Patients, in post-acute phase, underwent 7 weeks of bilateral arm training assisted by an exoskeleton robot combined with a conventional treatment (consisting of simple physical activity together with occupational therapy). Clinical and neuroimaging evaluations were performed immediately before and after rehabilitation treatments. Fugl-Meyer (FM) and Motricity Index (MI) were selected to measure primary outcomes, i.e., motor function and strength. Functional independance measure (FIM) and Barthel Index were selected to measure secondary outcomes, i.e., daily living activities. Voxel-based lesion symptom mapping (VLSM) was used to determine the degree of cerebral lesions associated with motor recovery.
    Results: Robot-assisted rehabilitation was effective in improving upper limb motor function recovery, considering both primary and secondary outcomes. VLSM detected that lesion load in the superior region of the corona radiata, internal capsule and putamen were significantly associated with recovery of the upper limb as defined by the FM scores (p-level < 0.01).
    Conclusions: The probability of functional recovery from stroke by means of exoskeleton robotic rehabilitation relies on the integrity of specific subcortical regions involved in the primary motor pathway. This is consistent with previous evidence obtained with conventional neurorehabilitation approaches.


    Introduction

    Several systematic and meta-analytic reviews have confirmed that robotic-assisted devices elicit robust motor recovery in patients with stroke, mainly in relation to the upper limb intervention (Masiero et al., 2007; Bertani et al., 2017; Lo et al., 2017). Early research on robotic therapy for the upper limb was based on end-effector robots, which hold the patient’s hand or forearm at one point and generate forces at the interface. Recently this field of study has shifted towards an exoskeleton device, which overcomes many of the inherent limitations of end-effector robots (Lo and Xie, 2012). Compared to conventional therapy, exoskeletons have the potential to provide intensive rehabilitation consistently for a longer duration and irrespective of the skills and fatigue level of the therapist (Huang and Krakauer, 2009; Lo and Xie, 2012).
    The Automatic Recovery Arm Motility Integrated System (ARAMIS) is a concept robot and prototype for the neurorehabilitation of the paretic upper limb developed at the Institute S. Anna—Crotone, Italy. ARAMIS was designed with two computer-controlled, symmetric and interacting exoskeletons, which compensate for the inadequate strength and accuracy of the paretic arm movements and the effect of gravity during rehabilitation. The basic idea is to exploit proprioceptive inputs using passive, repetitive, interactive, high-intensive bilateral movement training, which has been demonstrated to enhance motor recovery in stroke patients (Stinear et al., 2008; Choo et al., 2015; Saleh et al., 2017; Gandolfi et al., 2018). This device has been widely validated (Colizzi et al., 2009; Dolce et al., 2009; Pignolo et al., 2012) with respect to conventional neurorehabilitation approaches, demonstrating high degree of upper limb recovery as assessed by the Fugl-Meyer (FM) scale (Fugl-Meyer et al., 1975). The FM is a performance-based impairment index designed to assess motor functioning, balance, sensation and joint functioning in patients with post-stroke hemiplegia. Overall, FM together with the Modified Ashworth Scale (MAS) and functional independance measure (FIM) (Keith et al., 1987), are the most reliable clinical scales employed to unravel motor recovering after robotic-treatment in stroke patients (Bertani et al., 2017).
    Despite this large amount of evidence confirming the effectiveness and robustness of robotic-assisted rehabilitation in promoting motor recovery the underlying pathophysiology is still unclear. In fact, some biomarkers have been effectively demonstrated to predict therapeutic response or recovery following stroke (Burke Quinlan et al., 2015). Generally, research has focused on the neural substrate of motor recovery obtained with a conventional neurorehabilitation approach (Shelton and Reding, 2001; Murphy and Corbett, 2009; Carrera and Tononi, 2014; Choo et al., 2015; Lee et al., 2017; Siegel et al., 2018), whereas little attention has been paid to robotic-assisted therapy with exoskeleton devices (Formaggio et al., 2013; Fan et al., 2016; Gandolfi et al., 2018). Overall, preservation of the corticospinal tract is considered as a hallmark for good recovery of impaired motor function in patients with brain injury (Hendricks et al., 2002; Swayne et al., 2008; Stinear, 2010). Within this pathway there are several critical hubs that have been associated with functional recovery after conventional therapy. Mounting evidence from functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI) as well as resting-state functional connectivity studies have demonstrated that the increased activity in ipsilateral primary motor cortex and the morphological integrity of the posterior limb of the capsula interna predict the positive clinical outcome (Shelton and Reding, 2001; Stinear et al., 2012; Stinear and Ward, 2013; Favre et al., 2014; Rehme et al., 2015). Moreover, lesions in the globus pallidus, and putamen (together with corona radiata, internal capsule) were also associated with poor recovery (Lee et al., 2017).
    This study, thus, assesses the effects of lesion location on the response to rehabilitation training obtained with an exoskeleton robot device. The aim is to expand knowledge of the neural basis of stroke rehabilitation and the prognosis of upper limb disorders.