Deans' stroke musings

Changing stroke rehab and research worldwide now.Time is Brain!Just think of all the trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 438 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:

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's quite disgusting that this information is not available from every stroke association and doctors group.
My back ground story is here:http://oc1dean.blogspot.com/2010/11/my-background-story_8.html

Friday, July 3, 2015

Iterative Learning Control for Electrical Stimulation and Stroke Rehabilitation

A whole 123 page book for your doctor to know about. Ask him/her what changes to stroke protocols were made as a result of reading this book.
https://books.google.com/books?hl=en&lr=lang_en&id=0loICgAAQBAJ&oi=fnd&pg=PR5&dq=%22stroke+rehabilitation%22&ots=g_Zrjudxzj&sig=wDaja5cXLtcArZd5r3z4030ItSk#v=onepage&q=%22stroke%20rehabilitation%22&f=false

"All other difficulties are of minor importance"

Another great post from Seth Godin. This applies directly to our failing stroke associations. They are pushing easy research/press releases that identifies items that cause stroke risk. There is nothing controversial or hard about this. When they could work on the f*ckingly hard problems in stroke.

"All other difficulties are of minor importance" 

 

The Wright Brothers decided to solve the hardest problem of flight first.
It's so tempting to work on the fun, the urgent or even the controversial parts of a problem.
There are really good reasons to do the hard part first, though. In addition to not wasting time in meetings about logos, you'll end up getting the rest of your design right if you do the easy parts last.

Stroke rapid response alerts speeds pediatric stroke diagnosis

Faster and better diagnosis of stroke in the young is great. But they don't tell you the most important thing about this. 
WHAT ARE THE RESULTS?
Did they get appropriate treatment and recover completely? Or are they like most stroke patients, left with disabilities?
http://www.medpagetoday.com/Cardiology/Strokes/52427?xid=nl_mpt_DHE_2015-07-03&eun=g424561d0r

Thursday, July 2, 2015

Post-Stroke: Diffuse Spasticity activity - NSA

Note that none of this mentions curing spasticity.  I don't want my spasticity managed I want it cured. F*cking lazy assholes.
http://support.stroke.org/site/MessageViewer?em_id=29161.0&dlv_id=42101
Dear Dean,
Post-stroke Spasticity Case Study
Learn more
Before the accreditation runs out, we invite you to participate in part three of our Post-Stroke: Diffuse Spasticity activity. 
Through your participation you will be better able to:
  • Discuss the functional impact of post-stroke spasticity on recovery and rehabilitation
  • Apply evidence-based knowledge to diagnose and assess post-stroke spasticity
  • Identify evidence-based management strategies for post-stroke spasticity
  • Describe how to incorporate new knowledge and expertise around diagnosis and management of post-stroke spasticity into their respective clinical practice

Unbalanced metalloproteinase-9 and tissue inhibitors of metalloproteinases ratios predict hemorrhagic transformation of lesion in ischemic stroke patients treated with thrombolysis: results from the MAGIC study

Way out of my league, so you'll have to contact a genius somewhere to decipher this.
http://journal.frontiersin.org/article/10.3389/fneur.2015.00121/full?
imageBenedetta Piccardi1*, imageVanessa Palumbo2, imageMascia Nesi2, imagePatrizia Nencini2, imageAnna Maria Gori3, imageBetti Giusti3, imageGiovanni Pracucci1, imagePaolina Tonelli1, imageEleonora Innocenti1, imageAlice Sereni3, imageElena Sticchi3, imageDanilo Toni4, imagePaolo Bovi5, imageMario Guidotti6, imageMaria Rosaria Tola7, imageDomenico Consoli8, imageGiuseppe Micieli9, imageRossana Tassi10, imageGiovanni Orlandi11, imageFrancesco Perini12, imageNorina Marcello13, imageAntonia Nucera14, imageFrancesca Massaro15, imageMaria Luisa DeLodovici16, imageGiorgio Bono16, imageMaria Sessa17, imageRosanna Abbate3 and imageDomenico Inzitari1,18, On behalf of the MAGIC Study Group
  • 1Neuroscience Section, Department of Neurofarba, University of Florence, Florence, Italy
  • 2Stroke Unit, Department of Neurology, Careggi University Hospital, Florence, Italy
  • 3Department of Experimental and Clinical Medicine, Atherothrombotic Diseases Center, AOU Careggi, University of Florence, Florence, Italy
  • 4Emergency Department Stroke Unit, Department of Neurological Sciences, Sapienza University of Rome, Rome, Italy
  • 5SSO Stroke Unit, U.O. Neurologia d.O., DAI di Neuroscienze, Azienda Ospedaliera Integrata, Verona, Italy
  • 6Neurology Unit, Valduce General Hospital, Como, Italy
  • 7U.O. Neurologia, DAI Neuroscienze-Riabilitazione, Azienda Ospedaliera-Universitaria S. Anna, Ferrara, Italy
  • 8U.O. Neurologia, G. Jazzolino Hospital, Vibo Valentia, Italy
  • 9Istituto Neurologico Nazionale C. Mondino, Pavia, Italy
  • 10U.O.C. Stroke Unit, Dipartimento di Scienze Neurologiche e Neurosensoriali, Azienda Ospedaliera Universitaria Senese, Siena, Italy
  • 11Department of Neurosciences, Neurological Clinic, University of Pisa, Pisa, Italy
  • 12UOC di Neurologia e “Stroke Unit”, Ospedale San Bortolo, Vicenza, Italy
  • 13Neurology Unit, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy
  • 14Department of Clinical Neurological Sciences, London Health Sciences Centre, Western University, London, ON, Canada
  • 15Neurology Unit, Misericordia e Dolce Hospital, Prato, Italy
  • 16Stroke Unit, Department of Neurology, Ospedale di Circolo e Fondazione Macchi, Varese, Italy
  • 17Department of Neurology, Istituti Ospitalieri, Cremona, Italy
  • 18Institute of Neuroscience, Italian National Research Council, Florence, Italy
Background: Experimentally, metalloproteinases (MMPs) play a detrimental role related to the severity of ischemic brain lesions. Both MMPs activity and function in tissues reflect the balance between MMPs and tissue inhibitors of metalloproteinases (TIMPs). We aimed to evaluate the role of MMPs/TIMPs balance in the setting of rtPA-treated stroke patients.
Methods: Blood was taken before and 24-h after rtPA from 327 patients (mean age 68 years, median NIHSS 11) with acute ischemic stroke. Delta median values of each MMP/TIMP ratio [(post rtPA MMP/TIMP-baseline MMP/TIMP)/(baseline MMP/TIMP)] were analyzed related to symptomatic intracranial hemorrhage (sICH) according to NINDS criteria, relevant hemorrhagic transformation (HT) defined as confluent petechiae within the infarcted area or any parenchymal hemorrhage, stroke subtypes (according to Oxfordshire Community Stroke Project) and 3-month death. The net effect of each MMP/TIMP ratio was estimated by a logistic regression model including major clinical determinants of outcomes
Results: Adjusting for major clinical determinants, only increase in MMP9/TIMP1 and MMP9/TIMP2 ratios remained significantly associated with sICH (odds ratio [95% confidence interval], 1.67 [1.17–2.38], p = 0.005; 1.74 [1.21–2.49], p = 0.003, respectively). Only relative increase in MMP9/TIMP1 ratio proved significantly associated with relevant HT (odds ratio [95% confidence interval], 1.74 [1.17–2.57], p = 0.006) with a trend toward significance for MMP9/TIMP2 ratio (p = 0.007).
Discussion: Our data add substantial clinical evidence about the role of MMPs/TIMPs balance in rtPA-treated stroke patients. These results may serve to generate hypotheses on MMPs inhibitors to be administered together with rtPA in order to counteract its deleterious effect.

Introduction

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that are involved in extracellular matrix (ECM) degradation (1). The turnover of ECM is regulated by the balance between MMPs and a group of endogenous proteins called tissue inhibitor of metalloproteinases (TIMPs) (2). Active MMPs and some MMP proenzymes form 1:1 complexes with TIMPs and the unbalance between these two families of molecules appears implicated in a variety of diseases (3). A list of MMPs and TIMPs with their putative role in acute ischemic stroke is shown in Table S1 in Supplementary Material.
After cerebral ischemia, the general neuronal response to excitotoxic injury determines the release of pro-inflammatory cytokines that stimulate the local production of MMPs and TIMPs (4). In experimental models of brain ischemia, MMPs and MMP/TIMP unbalance play a detrimental role related to blood–brain barrier (BBB) disruption leading to hemorrhagic transformation and edema of an ischemic brain lesion (5). Circulating levels of MMP9 have been proved associated with poor outcomes in stroke patients treated with tissue plasminogen activator (rtPA) (6, 7). Furthermore, recent studies suggest that rtPA adverse effects may be mediated through MMPs upregulation and activation (2). No clinical study has hitherto considered selectively the effect of the balance between MMPs and their physiological inhibitor related to stroke outcomes after thrombolysis. Theoretical effects of rtPA on MMP/TIMP unbalance have been shown in Figure 1.
FIGURE 1
www.frontiersin.org Figure 1. Impact of tissue plasminogen activator on MMP/TIMP unbalance at the neurovascular unit level. After acute ischemic stroke, rtPA may cross blood–brain barrier (BBB), enter the brain parenchyma, and thereby damage neurovascular unit components by promoting metalloproteinase (MMPs) production and activation. Indeed, unbalance between MMPs and their natural inhibitors (tissue inhibitors of metalloproteinases, TIMPs) may exacerbate BBB disruption leading to hemorrhagic transformation and edema of an ischemic brain lesion.
The aim of this study was to evaluate the effect of MMPs/TIMPs ratio on outcomes of ischemic stroke in the same cohort of the biological markers associated with acute ischemic stroke (MAGIC) study. Because MMP inhibition is considered a possible therapeutic target for stroke patients (8), a clearer understanding of MMP/TIMP interplay, compared with the effect of MMPs only, would have important implications for acute stroke therapies.

More at link.

Editorial: The ischemic penumbra: still the target for stroke therapies?

Why the hell would we care about imaging the penumbra? Find something that stops all the causes of the neuronal cascade of death.
http://journal.frontiersin.org/article/10.3389/fneur.2015.00085/full?
  • 1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
  • 2Department of Physical Medicine and Rehabilitation, Johns Hopkins University School of Medicine, Baltimore, MD, USA
  • 3Department of Cognitive Science, Johns Hopkins University, Baltimore, MD, USA
  • 4Clinical Neurosciences, University of Cambridge, Cambridge, UK
  • 5INSERM U894, Centre de Psychiatrie et Neurosciences, Hôpital Sainte-Anne, Sorbonne Paris Cité, Paris, France
The ischemic penumbra refers to tissue at risk of infarction where perfusion is inadequate to support neuronal function, but just adequate to maintain cell viability (1). This dysfunctional, but salvageable tissue has been the target of all acute stroke therapies (2), and this concept underpinned the successful trials of intravenous thrombolysis using t-PA (3). Advanced imaging, including diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) MR and CT perfusion (CTp), was developed to rapidly identify stroke patients with still present penumbra, who were thought to be the best candidates for reperfusion therapies. However, early studies, using different methods for identifying penumbra, different measures of outcome, and different time-windows have not consistently confirmed the benefit of selecting treatment candidates on the basis of imaged penumbra. Therefore, some outstanding questions surround the optimal modality for imaging the penumbra, the most reliable thresholds in each modality, how long the penumbra can be maintained under what subject-specific circumstances, and the functional significance of persistent penumbra. These questions have taken on particular importance in light of the results of five recently completed randomized clinical trials showing benefit of endovascular treatment of stroke, when patients are carefully selected and treated on a timely basis. These trials include MR CLEAN (4), ESCAPE (5); EXTEND-IA (6), and two trials that have not been published, but the results of which have been presented at the International Stroke Conference [SWIFT PRIME (7) and REVASCAT1]. These trials have used different criteria to select patients for treatment, including different modalities of imaging (CT vs. MRI), but those that have shown the highest odds of favorable functional outcome have selected patients on the basis of having both a small core infarct, and either large volume of penumbral tissue (“tissue at risk”) (6, 7) or the presence of moderate–good collateral circulation (5) that would support penumbral tissue in the face of proximal occlusion.
These recent studies, together with an earlier successful pilot trial of another thrombolytic agent that used MR-based selection of target penumbral patients (8) have shown the importance of selecting patients on the basis of the presence of penumbral tissue, but underscore the urgency of defining appropriate thresholds with imaging that can be obtained swiftly in order to maximize the efficiency of intervention. While the gold standard for both irreversibly ischemic core and penumbra has been defined by PET (2), PET cannot be obtained rapid enough to provide a practical guide for acute stroke treatment. Some centers are able to obtain rapid MRI, while most will rely likely on multiphase CT angiogram and/or CTp to guide intervention. It is critical that the stroke field adopts valid and reliable thresholds using any of these modalities to select candidates for intervention. Toward this goal, two MR vs. PET back-to-back studies have proposed validated MR-perfusion thresholds, based on small samples (9, 10). This Research Topic consists of a set of papers that addresses some of the controversies and intriguing questions that remain.
Kaesemann and colleagues (11) evaluated the impact of severe extracranial ICA stenosis on MRI measures of penumbra in patients with middle cerebral artery occlusion who were imaged within 4.5 h of onset. They evaluated core infarct volumes, mean transit time (MTT), Tmax, cerebral blood volume (CBV), and cerebral blood flow (CBF) maps, as well as tissue at risk (Tmax >6 – infarct volume). The presence of the additional extracranial stenosis did not affect measured infarct volume, MTT, Tmax, or tissue at risk, but had a small influence on CBV. They hypothesized that extracranial stenosis may lead to ischemic preconditioning that results in improved collateral circulation and a consequent increase in CBV in the presence of acute stroke.
Wouters and co-workers (12) discuss proposed imaging criteria, including diffusion-FLAIR mismatch, for selecting patients who wake up with stroke and or have unknown onset. They point out that there are currently no data for selecting one set of criteria over another, but argue that identifying patients who have penumbral tissue with imaging should allow intravenous and/or endovascular treatment of many of these patients.
Leigh and colleagues (13) hypothesized that the conflicting conclusions from two large endovascular trials, MR RESCUE and DEFUSE 2, regarding the usefulness of MRI diffusion and perfusion imaging for selecting candidates for treatment were due to differences in definitions of core infarct and “tissue at risk.” MRI scans from patients evaluated for endovascular therapy were processed using the methods published in the two trials. The volume of core infarct was consistently smaller when defined by MR RESCUE criteria than DEFUSE 2 criteria. The volume of tissue at risk was consistently larger when defined by the MR RESCUE criteria than DEFUSE 2 criteria. When these volumes were used to classify MRI scans, 9 out of 12 patients (75%) were classified as having salvageable tissue by MR RESCUE, while only 4 out of 12 patients (33%) were classified as having salvageable tissue by DEFUSE 2 criteria.
Marsh and co-workers (14) present two patients who underwent endovascular treatment with very different outcomes. They argue that robust collateral circulation supported a prolonged penumbra in the patient who showed minimal progression to infarct and outstanding functional outcome despite a delay in treatment.
Agarwal and colleagues (15) compared quantitative hemodynamic measures of CTp (volumes of penumbra defined by CBF, or PenCBF, and penumbra defined by MTT, or PenMTT), a visually defined CBF/CBV ASPECTS ratio, and a visually rated collateral circulation on CTA. They found that both PenCBF and PenMTT showed trends to decrease with increased time since onset. The CBF/CBV ASPECTS ratio, which was related to the PenCBF, significantly decreased with increased time since onset. In contrast, the rating of collateral response was not related to time since onset. These results raise some questions as to whether the presence of collaterals can be used as a surrogate for the presence of penumbral tissue in selecting candidates for intervention.
Campbell and colleagues (16) discuss challenges of imaging the penumbra and provide useful guidelines. They also discuss scenarios in which recanalization and reperfusion are discordant: both cases in which there is recanalization without reperfusion and reperfusion without recanalization (via enhanced retrograde collateral flow). Finally, they discuss infarct growth and the fact that there is sometimes persistent hypoperfusion that accounts for clinical deficits.
Motta et al. (17) investigated the clinical consequences of persistent hypoperfusion. They found that uninfarcted but hypoperfused tissue, with a threshold of 4–5.9 s delay on time-to-peak (TTP) maps on PWI occasionally persists for days and is associated with cognitive deficits such as aphasia or neglect. Furthermore, change in volume of hypoperfused tissue of 4–5.9 s delay and change in volume of ischemic tissue on DWI over the first few days were independently associated with change in cognitive function. Sebastian et al. (18) also show that persistent cortical hypoperfusion caused by arterial stenosis can cause aphasia or neglect (in cases of purely thalamic infarct), although some cases of aphasia after thalamic stroke are likely due to cortical dysfunction (diaschisis) in the absence of hypoperfusion caused by arterial stenosis.
Finally, Scalzo and colleagues (19) argue that there are likely to be detailed features of CT and MRI that are not currently tapped, which may provide useful information for guiding stroke intervention. Use of computer vision and machine learning to incorporate aspects of imaging data that we may not realize are relevant may yield data-driven approaches to clinical decision-support.
This Research Topic thus addresses important and timely concerns surrounding the issue of how the ischemic penumbra can best be rapidly identified on imaging in order to contribute to management of acute stroke.

Novel cellular mechanisms for neuroprotection in ischemic preconditioning: a view from inside organelles

So the real question is; After your first stroke should you initiate TIAs in order to precondition the rest of your brain to survive the next stroke?
http://journal.frontiersin.org/article/10.3389/fneur.2015.00115/full?
  • 1Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatological Science, School of Medicine, Federico II University of Naples, Naples, Italy
  • 2Fondazione IRCSS SDN, Naples, Italy
Ischemic preconditioning represents an important adaptation mechanism of CNS, which results in its increased tolerance to the lethal cerebral ischemia. The molecular mechanisms responsible for the induction and maintenance of ischemic tolerance in the brain are complex and not yet completely clarified. In the last 10 years, great attention has been devoted to unravel the intracellular pathways activated by preconditioning and responsible for the establishing of the tolerant phenotype. Indeed, recent papers have been published supporting the hypothesis that mitochondria might act as master regulators of preconditioning-triggered endogenous neuroprotection due to their ability to control cytosolic calcium homeostasis. More interestingly, the demonstration that functional alterations in the ability of mitochondria and endoplasmic reticulum (ER) managing calcium homeostasis during ischemia, opened a new line of research focused to the role played by mitochondria and ER cross-talk in the pathogenesis of cerebral ischemia in order to identify new molecular mechanisms involved in the ischemic tolerance. In line with these findings and considering that the expression of the three isoforms of the sodium calcium exchanger (NCX), NCX1, NCX2, and NCX3, mainly responsible for the regulation of Ca2+ homeostasis, was reduced during cerebral ischemia, it was investigated whether these proteins might play a role in neuroprotection induced by ischemic tolerance. In this review, evidence supporting the involvement of ER and mitochondria interaction within the preconditioning paradigm will be provided. In particular, the key role played by NCXs in the regulation of Ca2+-homeostasis at the different subcellular compartments will be discussed as new molecular mechanism proposed for the establishing of ischemic tolerant phenotype.

Introduction

Cerebral ischemia is a multifactorial and complex disease (1, 2). Indeed, the intracellular events activated by the loss of perfusion of the brain and responsible for neuronal damage range from impairment of intracellular homeostasis to mitochondrial dysfunction and free radical production (35). The complexity of these events explains the great discrepancy between the frequency of cerebral ischemic accidents and the lack of effective treatments able to inhibit or slow neuronal demise following the ischemic insult. Hence, the urgent need to identify new potential targets for the development of innovative therapeutic strategies able to defend the ischemic brain.
On these premises, in the recent years, the attention of the researchers focused on ischemic tolerance a phenomenon, also known as ischemic preconditioning (IPC), which consists of a sub-lethal anoxic insult that makes the tissue in which it occurs more resistant to a subsequent and potentially lethal ischemia (611). The relevance of this phenomenon is to correlate to the study of the endogenous mechanisms activated in neurons to allow cell survival after a sub-lethal ischemic stimulus. By this way, it is possible to identify new molecular targets useful to develop alternative therapeutic strategies to treat the ischemic disease. The great interest in the cerebral IPC and in the tolerance evoked by itself also comes from the similarity of this phenomenon with those clinical situations occurring in the human brain. Indeed, it is well known that transient ischemic attacks (TIAs) do not cause structural damage but appear to protect brain against a subsequent “stroke” (12, 13).
Therefore, IPC or ischemic tolerance of the brain lie in a natural adaptive process that can be mimicked by a variety of sub-lethal insults, such as transient hypoxia, spreading depression, oxidative stress, hyperthermia, or heat shock, and that increases the tissue tolerance to a subsequent, potentially lethal ischemia. This adaptive cytoprotection is a fundamental property of living cells, which allows them to survive to the exposure to potentially recurrent stressors. This phenomenon was clearly identified in the heart by Murry et al. (14) as preconditioning, or subsequently as ischemic tolerance, and in 1990 it was described also in the brain by Kitagawa et al. (15). Since then, it immediately attracted the interest of clinical and basic neuroscientists for several reasons. First, this biological process became widely recognized as a pertinent and effective experimental instrument to understand how the brain protects itself against ischemia, thereby providing an innovative approach for the discovery of novel neuroprotective strategies. Second, retrospective case-control studies showed a clinical correlate of the phenomenon discovered experimentally.

More at link.

Fatigue in multiple sclerosis compared to stroke

There is no 'suggestion' that fatigue is a problem in stroke. Don't any of you high faluting scientists ever talk to survivors?  Fatigue and spasticity are my top two problems. Solve them and I would be fully recovered in no time.
http://journal.frontiersin.org/article/10.3389/fneur.2015.00116/full?
Claudia Lukoschek1, imageAnnette Sterr2,3,4, imageDolores Claros-Salinas1,5, imageRolf Gütler1 and imageChristian Dettmers1,5,6*
  • 1Kliniken Schmieder Konstanz, Konstanz, Germany
  • 2University of Surrey, Guildford, UK
  • 3University of Freiburg, Freiburg im Breisgau, Germany
  • 4Department of Neurology, University of São Paulo, São Paulo, Brazil
  • 5Lurija Institute, Kliniken Schmieder Allensbach, Allensbach, Germany
  • 6Department of Psychology, University of Konstanz, Konstanz, Germany
Objectives: Fatigue is typically associated with multiple sclerosis (MS), but recent studies suggest that it is also a problem for patients with stroke. While a direct comparison of fatigue in, e.g., Stroke and MS is desirable, it is presently not easily possible because of different definitions and assessment tools used for the two conditions. In the present study, we therefore assessed fatigue in Stroke and MS using a generic, not disease-specific instrument to allow transdiagnostic comparison.
Method: A total of 137 patients with MS and 102 patients with chronic stroke completed the SF-36, a generic questionnaire assessing health related quality of life. Fatigue was measured through the vitality scale of the SF-36. The vitality scale consists of two positive items (“lot of energy,” “full of life”) and two negative ones (“worn out,” “tired”). The two negative ones were scaled in reverse order. The vitality scale has been recommended as reciprocal index of fatigue.
Results: Normalized vitality scores in MS (35.3) and stroke (42.1) were clearly lower than published reference values from the SF-36 in age-matched healthy controls. The sum score of the vitality items was lower in MS than in stroke patients. This difference could not be explained by age, gender, or the Physical Functioning Scale of the SF-36. Both patient groups showed no positive correlation between fatigue and physical functioning. Fatigue – as determined with the vitality scale of the SF-36 – correlated with the estimated working capacity in MS patients, but not in stroke patients.
Conclusion: These findings confirm high fatigue in MS and stroke patients with higher values in MS. Fatigue has a higher impact on working capacity in MS than in stroke(really? have you talked to survivors?). Fatigue in both patient groups is not a direct consequent of physical functioning/impairment. Vitality score of the SF-36 is a suitable transdiagnostic measure for the assessment of fatigue in stroke and MS.

Introduction

Fatigue is a prominent and frequent symptom in multiple sclerosis (MS), and affects 60–90% of patients (1, 2). Fatigue is often experienced as the most disabling and limiting symptom, and greatly contributes to the degradation of general well-being, quality of life, and social participation (3, 4). Moreover, the impact of fatigue in the workplace can be severe and frequently triggers early retirement, even in the early phase of the disease (5). In contrast to the importance of fatigue for patients, treatment options are limited and efficacy varies substantively across patients (6) (see also Khan et al., this special issue). Understanding and distinguishing different pathophysiological mechanisms might improve individually tailored treatment options.
While fatigue is most prominent in MS, it is also observed in other conditions. This is particularly for patients with Stroke, where fatigue has been identified as “a major yet neglected issue” (7). This perspective has spearheaded more research in this arena (810), but the characteristics of fatigue in stroke have yet to be fully determined. It is further unclear to what extent fatigue in MS and Stroke share similarities in their impact on the individual, and whether fatigue is equally prevalent in the two conditions.
Because fatigue is by far best characterized in MS, benchmarking fatigue characteristics of other conditions against MS is important. However, such comparisons are challenging because the majority of assessment instruments, such as the Fatigue Severity Scale (11) and the Fatigue Scale for Motor and Cognitive Functions (FSMC) (12), have been specifically developed for MS, and might therefore not be equally sensitive in other neurological conditions. Moreover, a recent review on fatigue measures in neurological conditions concluded that the FSMC and the Unidimensional Fatigue Impact Scale (13, 14) are best suited for measuring fatigue in MS, while the Profile of Mood States Fatigue subscale (POMS-F) is the optimal measure for stroke (15).
If fatigue characteristics and fatigue prevalence are to be compared across neurological conditions, it is necessary to use a generic, disease-unspecific measure, which allows the transdiagnostic comparison of fatigue prevalence. Such a generic measure has been derived from the vitality subscale of the short form SF-36 (15). The SF-36 is a well-validated and accepted measure of health, which is used in a wide range of health care settings and research (16). Its vitality subscale has already been used to assess fatigue in patients with myocardial infarction (17). The present study therefore used the vitality subscale to contrast fatigue in 137 MS and 102 Stroke patients. Based on the prevailing notion that the fatigue affects the majority of MS patients, we predicted a more severe manifestation and a higher impact on working capacity in MS compared to Stroke.

More at link.

Therapeutic Argentine Tango Dancing for People with Mild Parkinson’s Disease: A Feasibility Study

I don't see why this couldn't be duplicated for stroke survivors. Challenging exercises help us to recover faster.
http://journal.frontiersin.org/article/10.3389/fneur.2015.00122/full?

  • College of Science, Health and Engineering, School of Allied Health, La Trobe University, Bundoora, VIC, Australia
Background: Individuals living with Parkinson’s disease (PD) can experience a range of movement disorders that affect mobility and balance and increase the risk of falls. Low health-related quality of life, depression, and anxiety are more common in people with PD than age-matched comparisons. Therapeutic dance is a form of physical activity believed to facilitate movement and therapy uptake. As well as being enjoyable, dancing is thought to improve mobility, balance, and well-being in some people living with PD. The primary objective of this study was to evaluate the feasibility and safety of a 4-week Argentine tango dance program for people with PD.
Methods: Six community dwelling individuals with mild to moderate PD were recruited from Parkinson’s support groups, movement disorder clinics, and the PD association in Australia. To minimize falls risk, participants were required to be <75 years of age and physically independent (Hoehn and Yahr stages I–III). They were also required to speak English. Participants attended a 1-hour dance class at a dance studio twice per week for 4 weeks. A professional dance instructor led and choreographed the Argentine tango dance classes. Physiotherapists were present to assist participants during the class and served as dance partners as necessary. The primary outcome was feasibility, which was determined by measures of recruitment, adherence, attrition, safety (falls, near misses and adverse events), and resource requirements. Secondary measures included the Beck Depression Inventory and the Euroqol-5D, administered at baseline and post intervention. Therapy outcomes pre- and post-intervention were analyzed descriptively as medians and interquartile ranges and using Wilcoxon matched pair signed-rank tests.
Results: The Argentine tango dance intervention was shown to be safe, with no adverse events. Adherence to the dance program was 89%. Depression scores improved after intervention (p = 0.04). Some challenges were associated with the need to quickly recruit participants and physiotherapists to act as dance partners during classes and to monitor participants.
Conclusion: The 4-week, twice weekly Argentine tango dancing program was shown to be feasible and safe for people with mild-to-moderately severe PD.

Introduction

Idiopathic Parkinson’s disease (PD) is a progressive neurological disorder associated with reduced mobility, falls, and reduced quality of life (QOL) (1). International guidelines endorse exercise therapy to retrain balance and preserve physical capacity for individuals living with PD (2). Meta-analyses have also shown exercise therapy to have positive effects with regards to physical functioning, balance, and health-related QOL (3, 4). Despite the potential benefits of movement rehabilitation, long-term adherence to traditional exercise programs can be problematic (5). A systematic review evaluating exercise adherence in PD reported that reduced motivation was a common reason for reduced participation (6). This demonstrates a need for community-based physical activity programs that facilitate uptake and enjoyment (7).
Emerging evidence suggests that therapeutic dance may be an appropriate and enjoyable form of physical activity for some individuals with PD (8). Dance may address some of the physical impairments in PD through teaching movement strategies, challenging balance, and improving physical fitness (9, 10). The musical rhythm could become an auditory cue to engage cortical control of movement, which in turn might potentially enhance motor learning (11). Preliminary trials suggest dance can facilitate improvements in gait, balance, and motor impairment in comparison to exercise (12), physiotherapy (13), and control conditions (8, 1416). It has been proposed that therapeutic dance may also facilitate QOL and well-being through enabling movement expression and building social connections (17).
The Argentine Tango dance genre is arguably one of the most suitable dance forms for people with PD (8, 14, 15). It has been proposed to target the movement impairments of PD with strong musical rhythms that trigger movement and enable greater amounts of physical activity. Compared to other dance genres, the choreography can be designed to train specific movement strategies such as walking backwards and turning (18). Furthermore, as a partnered form of dance, tango may facilitate interpersonal connections that positively affect QOL and mood (18).
While a growing number of pilot studies have explored the effects of dance on movement disorders in PD, there is a paucity of feasibility data and recommendations that allow researchers to design future protocols (19). Comprehensive exploration of the safety of specific dance genres is still required given that individuals with PD have a propensity to fall (20). This research also focused on QOL and depression outcomes, as there is little published literature on the effects of therapeutic dance on perceived QOL and mood for adults with PD.
The primary purpose of the current study was to evaluate the feasibility and safety of an Argentine tango dance intervention and to provide recommendations for future research. The specific aims were to: (i) determine if 4 weeks of twice weekly Argentine tango dance classes were feasible and safe for people with PD, allowing the development of recommendations for a future research protocol and (ii) measure the within-group change for depressive symptoms and health-related quality of life (HRQOL) following participation in the dance classes.

Acute Ischemic Stroke Treatment, Part 2: Treatment “Roles of Capillary Index Score, Revascularization and Time”

More bloviating and talking about what they don't know. You're fucking screwed if you have a stroke right now. The authors need to read up on the neuronal cascade of death. They wouldn't be allowed to receive any funding from my organization with that lack of knowledge.
http://journal.frontiersin.org/article/10.3389/fneur.2015.00117/full?
  • 1Department of Neuro Interventional Surgery, Akron General Medical Center, Akron, OH, USA
  • 2Department of Research, Akron General Medical Center, Akron, OH, USA
Due to recent results from clinical intra-arterial treatment for acute ischemic stroke (IAT-AIS) trials such as the interventional management of stroke III, IAT-AIS and the merit of revascularization have been contested. Even though intra-arterial treatment (IAT) has been shown to improve revascularization rates, a corresponding increase in good outcomes has only recently been noted. Even though a significant percentage of patients achieve good revascularization in a timely manner, results do not translate into good clinical outcomes (GCOs). Based on a review of the literature, the authors suspect limited GCOs following timely and successful revascularization are due to poor patient selection(wrong, wrong, wrong) that led to futile and possibly even harmful revascularization. The capillary index score (CIS) is a simple angiography-based scale that can potentially be used to improve patient selection to prevent revascularization being performed on patients who are unlikely to benefit from treatment. The CIS characterizes presence of capillary blush related to collateral flow as a marker of residual viable tissue, with absence of blush indicating the tissue is no longer viable due to ischemia. By only selecting patients with a favorable CIS for IAT, the rate of GCOs should consistently approach 80–90%. Current methods of patient selection are primarily dependent on time from ischemia. Time from cerebral ischemia to irreversible tissue damage seems to vary from patient to patient; so focusing on viable tissue based on the CIS rather than relying on an artificial time window seems to be a more appropriate approach to patient selection.

Introduction

The interventional management of stroke (IMS) III trial (1) showed non-superiority of intra-arterial (IA) revascularization combined with intra venous (IV) tissue plasminogen activator (tPA) treatment over IV tPA alone, and the systemic thrombolysis for acute ischemic stroke (SYNTHESIS) trial demonstrated similar lack of favorable clinical outcomes for IA versus IV tPA therapy (2). This is despite the high revascularization rate in the IA arms in these trials. The role of intra-arterial treatment for acute ischemic stroke (IAT-AIS) has been contested. Paradoxically, however, the benefit of revascularization to clinical outcomes is convincingly attested to in prior literature. In a recent meta-analysis of 998 patients with clinical follow-up at 3 months, good clinical outcome was found in 58% of revascularized patients as compared to 24.8% in non-revascularized patients (3). When revascularization occurred within the first 6 h, good clinical outcomes (GCOs) were found in 50.9% of revascularized patients as compared to 11.1% in non-revascularized patients. Other authors reached similar conclusions. Even in the IMS III trial, better revascularization using the modified thrombolysis in cerebral infarction (mTICI) score led to better outcomes than those for patients who achieved lesser revascularization (1). This data were recently resolved with the publication of newer trials. In MR CLEAN, EXTEND-IA, and ESCAPE, good recanalization rates were achieved in 58.7, 86, and 72.4% of patients, respectively, with accompanying GCO rates at 32.6, 71, and 53%, respectively (46). While these results demonstrate IA superiority with higher recanalization rates than with IVT, there are still a significant number of patients who achieved good and timely revascularization that did not also achieve GCOs. So if better revascularization improves outcome and IA treatment has a better revascularization rate than IV treatment, how can we explain the lack of GCOs in some of these patients?

Revascularization and Outcome

Revascularization is defined as the restoration of anterograde blood flow to the ischemic area through the recently occluded artery. Currently, this is reported using the mTICI score, with mTICI of 2b or 3 being considered successful revascularization (7). The aim of revascularization is to produce clinical improvement through restoring the cerebral blood flow (CBF) level to greater than the critical threshold of 23 ml/100 g/min of viable brain tissue (8). This should translate into a permanent resolution of AIS symptoms by saving the ischemic tissue before it progresses to irreversible damage. So if perfect revascularization is achieved (mTICI = 3) in a timely manner, i.e., before ischemia becomes irreversible, clinical improvement should be achieved for almost all patients, as well as for the majority of patients with less effective revascularization (mTICI = 2b). However, review of the literature reveals that only around 50% of patients in whom we obtained timely recanalization (mTICI 2b, 3) will achieve a good clinical outcome (Table 1) (1, 2, 913). Attempting to solve the paradox regarding why all technically successful revascularizations do not translate into GCOs should help us improve our revascularization strategy.

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Acute ischemic stroke treatment, part 1: patient selection “The 50% barrier and the capillary index score”

This current strategy misses the whole problem of the neuronal cascade of death. Their assumption is wrong.  Doesn't ANYONE  in stroke read at all?
http://journal.frontiersin.org/article/10.3389/fneur.2015.00083/full?
  • 1Summit Neurovascular Specialists, Akron, OH, USA
  • 2Department of Research, Akron General Medical Center, Akron, OH, USA
  • 3Department of Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
The current strategy for intra-arterial treatment (IAT) of acute ischemic stroke focuses on minimizing time from ictus to revascularization and maximizing revascularization. Employing this strategy has yet to lead to improved rates of successful outcomes. However, the collateral blood supply likely plays a significant role(Why?) in maintaining viable brain tissue during ischemia. Based on our prior work, we believe that only approximately 50% of patients are genetically predisposed to have sufficient collaterals for a good outcome following treatment, a concept we call the 50% barrier. The Capillary Index Score (CIS) has been developed as a tool to identify patients with a sufficient collateral blood supply to maintain tissue viability prior to treatment. Patients with a favorable CIS (f CIS) may be able to achieve a good outcome with IAT beyond an arbitrary time window. The CIS is incorporated into a proposed patient treatment algorithm. For patients suffering from a large stroke without aphasia, a non-enhanced head CT should be followed by CT angiography (CTA). For patients without signs of stroke mimics or visible signs of structural changes due to large irreversible ischemia, CTA can help confirm the vascular occlusion and location. The CIS can be obtained from a diagnostic cerebral angiogram, with IAT offered to patients categorized as f CIS.

Introduction

The current strategy for acute ischemic stroke (AIS) treatment is based on two pillars: time from ictus to revascularization (TIR) and revascularization success as measured by the modified thrombolysis in cerebral ischemia scale (mTICI). The assumption is that clinical outcome following AIS is dependent on the interaction of these two factors. The shorter the TIR and the higher the mTICI, the better the outcome. It follows that the strategy behind current intra-arterial treatment for acute ischemic stroke (IAT-AIS) is the faster and more complete the revascularization, the better the clinical outcome. However, despite the recent impressive improvement in revascularization rates and decrease in time to revascularization, until recently the clinical improvement rate remained unchanged at approximately 40–45% (Table 1) with a ratio of good clinical outcome (GCO) in treatment vs. control arms of approximately 1.7 (111). Recent trials have published GCOs above 50% in the treatment arm, but with the same ratio of GCOs between the treated and untreated arms around 1.7 (12, 13). How we can explain this consistency? A fresh look at our strategy and selection criteria is obviously warranted.
TABLE 1
www.frontiersin.org Table 1. Clinical outcomes across IAT-AIS trials.

Physiological Background and the 50% Barrier
Normal cerebral blood flow (CBF) is 50–55 ml/100 g/min (14, 15). AIS induces a rapid and sustained reduction in CBF. Clinical signs of ischemia generally become apparent when CBF drops below 23 ml/100 g/min (16). If residual CBF (rCBF) further decreases to 15–16 ml/100 g/min, the cortical-evoked potential ceases within seconds (16). The rate of depression of the evoked potential (EP) amplitude (expressed in units of percent of control/min) is highly correlated with the residual flow, following a linear relationship with the regression line intercepting the flow axis at 15.2 ml/100 g/min (17). The data strongly suggest a threshold-like relationship also exists between the amplitude of the EP and local blood flow. If flow is greater than approximately 16 ml/100 g/min the EP is not affected, but at flows less than approximately 12 ml/100 g/min the EP is abolished (17). Neither the clinical signs of ischemia nor cessation of the EP is synonymous with cell death, but cessation of the EP is one of the final stages before irreversible injury (infarction). Its physiological purpose is to conserve energy by decreasing cell metabolism to the minimal level possible; however, cell death ensues thereafter.
Similarly, the relationship between time to irreversible damage and rCBF is well-documented (18). In one study, rCBF in monkeys was measured in the ischemic area with time after occlusion until irreversible tissue damage occurred (16). An infarction threshold was observed relating the rCBF to time between the initial drop in CBF to irreversible ischemia (Figure 1). This work confirmed prior studies using the neuronal EP and showed that when rCBF reached a low level of around 10 ml/100 g/min, the available time to salvage the brain tissue was extremely short (<1 h) (16).
 
FIGURE 1
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Figure 1. Depth of ischemia and time to irreversible cerebral damage: time to irreversible cerebral damage depends on the depth of ischemia, which depends on the pial collateral supply to the ischemic territory. Since different patients have different collaterals, the depth of ischemia will vary among patients, as will the time available for therapy to salvage the tissue (16).
 
 
The depth of ischemia, i.e., the level of rCBF, will vary from patient to patient depending on the available retrograde pial collaterals to the ischemic area. The major determinants of the amount of collateral perfusion are the number and diameter of these pial collaterals, plus perfusion pressure and resistance above and below the collateral network. Greater collateral numbers and diameters sustain a higher rCBF, thus more salvageable brain and a smaller final infarct volume.
Following AIS, rCBF stays virtually unchanged if spontaneous recanalization of the occluded blood vessels does not occur (16, 18, 19). While the clinical symptoms of ischemia will often resolve if CBF is restored promptly, prolonged low levels of rCBF leads to irreversible brain tissue damage. Since the time of ischemia that the brain tissue can tolerate before irreversible damage ensues depends on the rCBF value, which is patient-specific and highly dependent on the collaterals, it follows that every patient has his or her own time (Figure 1) (16, 18, 19). Hence, if we correctly select patients that are optimal candidates (patients with ischemic but viable tissue) and are able to achieve safe, full, and timely revascularization (prior to irreversible ischemic damage occurring), the clinical symptoms of a stroke should improve significantly and rather quickly.
Given this information, the most logical explanation for the remarkably consistent results of the different IAT-AIS trials, with <50% GCOs (modified Rankin Score, or mRS, ≤2), is that around half of treated patients have poor pial collaterals, thus causing them to have a relatively low rCBF such that they enter into irreversible ischemia before therapy can be administered, even when timely (within 6 h) revascularization is achieved. This observation implies a potential ceiling effect for IAT-AIS; we call this phenomenon the 50% barrier (Figure 2).
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