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[NEWS] Scientists can monitor brain activity to predict epileptic seizures few minutes in advance


Elizabeth Delacruz can’t crawl or toddle around like most youngsters nearing their second birthday.

A rare metabolic disorder that decimated her mobility has also led to cortical blindness – her brain is unable to process images received from an otherwise healthy set of brown eyes. And multiple times a day Elizabeth suffers seizures that continually reduce her brain function. She can only offer an occasional smile or make soft bubbly sounds to communicate her mood.

“But a few months ago I heard her say, ‘Mama,’ and I started to cry,” said Carmen Mejia, a subtle quaver in her voice as she recalled the joy of hearing her daughter. “That’s the first time she said something.”

Ms. Mejia realizes it may also be the last, unless doctors can find a way to detect and prevent the epileptic seizures stemming from a terminal disease called pyruvate dehydrogenase deficiency (PDHD) – which occurs when mitochondria don’t provide enough energy for the cells.

A UT Southwestern study gives parents like Ms. Mejia renewed hope for their children: By monitoring the brain activity of a specific cell type responsible for seizures, scientists can predict convulsions at least four minutes in advance in both humans and mice. The research further shows that an edible acid called acetate may effectively prevent seizures if they are detected with enough notice.

Although the prediction strategy cannot yet be used clinically – a mobile technology for measuring brain activity would have to be developed – it signifies a potential breakthrough in a field that had only been able to forecast seizures a few seconds ahead.

“Many of the families I meet with are not just bothered by the seizures. The problem is the unpredictability, the not knowing when and where a seizure might occur,” said Dr. Juan Pascual, a pediatric neurologist with UT Southwestern’s O’Donnell Brain Institute who led the study published in Science Translational Medicine. “We’ve found a new approach that may one day solve this issue and hopefully help other scientists track down the root of seizures for many kinds of epilepsy.”

Debunked theory

The critical difference between the study and previous efforts was debunking the long-held belief among researchers that most cells in epilepsy patients have malfunctioning mitochondria. In fact, Dr. Pascual’s team spent a decade developing a PDHD mouse model that enabled them to first discover the key metabolic defect in the brain and then determine only a single neuron type was responsible for seizures as the result of the metabolic defect. They honed in on these neurons’ electrical activity with an electroencephalogram (EEG) to detect which brainwave readings signaled an upcoming seizure.

“It’s much more difficult to predict seizures if you don’t know the cell type and what its activity looks like on the EEG,” Dr. Pascual said. “Until this finding, we thought it was a global deficiency in the cells and so we didn’t even know to look for a specific type.”

Predicting seizures

The study shows how a PDHD mouse model helped scientists trace the seizures to inhibitory neurons near the cortex that normally keep the brain’s electrical activity in check.

Scientists then tested a method of calculating when seizures would occur in mice and humans by reviewing EEG files and looking for decreased activity in energy-deficient neurons. Their calculations enabled them to forecast 98 percent of the convulsions at least four minutes in advance.

Dr. Pascual is hopeful his lab can refine EEG analyses to extend the warning window by several more minutes. Even then, live, clinical predictions won’t be feasible unless scientists develop technology to automatically interpret the brain activity and calculate when a seizure is imminent.

Still, he said, the discovery that a single cell type can be used to forecast seizures is a paradigm-shifting finding that may apply to all mitochondrial diseases and related epilepsies.

Potential therapy

Dr. Pascual’s ongoing efforts to extend the prediction time may be a crucial step in utilizing the other intriguing finding from the study: the use of acetate to prevent seizures.

The study showed that delivering acetate into the blood stream of PDHD mice gave their neurons enough energy to normalize their activity and decrease seizures for as long as the acetate was in the brain. However, Dr. Pascual said the acetate would probably need more time – perhaps 10 minutes or more – to take effect in humans if taken by mouth.

Acetate, which naturally occurs in some foods, has been used in patients for decades – including newborns needing intravenous nutrition or patients whose metabolism has shut down. But it had not yet been established as an effective treatment for mitochondrial diseases that underlie epilepsy.

Among the reasons, Dr. Pascual said, is that labs have struggled to create an animal model of such diseases to study its effects; his own lab spent about a decade doing so. Another is the widespread acceptance of the ketogenic diet to reduce the frequency of seizures.

But amid a growing concern about potentially unhealthy side effects of ketogenic diets, Dr. Pascual has been researching alternatives that may refuel the brain more safely and improve cognition.

Frequent seizures

Elizabeth, among a handful of patients whose EEG data were used in the new study, has been prescribed a ketogenic diet and some vitamins to control the seizures. Her family has seen little improvement. Elizabeth often has more than a dozen seizures a day and her muscles and cognition continue to decline. She can’t hold her head up and her mother wonders how many more seizures her brain can take.

Elizabeth was only a few months old when she was diagnosed with PDHD, which occurs when cells lack certain enzymes to efficiently convert food into energy. Patients who show such early signs often don’t survive beyond a few years.

Ms. Mejia does what she can to comfort her daughter, with the hope that Dr. Pascual’s work can someday change the prognosis for PDHD. Ms. Mejia sings, talks, and offers stuffed animals and other toys to her daughter. Although her little girl can’t see, the objects offer a degree of mental stimulation, she said.

“It’s so hard to see her go through this,” Ms. Mejia said. “Every time she has a seizure, her brain is getting worse. I still hope one day she can get a treatment that could stop all this and make her life better.”

‘Big questions’

Dr. Pascual is already conducting further research into acetate treatments, with the goal of launching a clinical trial for patients like Elizabeth in the coming years.

His lab is also researching other epilepsy conditions – such as glucose transporter type I (Glut1) deficiency – to determine if inhibitory neurons in other parts of the brain are responsible for seizures. If so, the findings could provide strong evidence for where scientists should look in the brain to detect and prevent misfiring neurons.

“It’s an exciting time, but there is much that needs to happen to make this research helpful to patients,” Dr. Pascual said. “How do we find an automated way of detecting neuron activity when patients are away from the lab? What are the best ways to intervene when we know a seizure is coming? These are big questions the field still needs to answer.”

via Scientists can monitor brain activity to predict epileptic seizures few minutes in advance

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[Abstract + References] Neuron–glia interactions in the pathophysiology of epilepsy


Epilepsy is a neurological disorder afflicting ~65 million people worldwide. It is caused by aberrant synchronized firing of populations of neurons primarily due to imbalance between excitatory and inhibitory neurotransmission. Hence, the historical focus of epilepsy research has been neurocentric. However, the past two decades have enjoyed an explosion of research into the role of glia in supporting and modulating neuronal activity, providing compelling evidence of glial involvement in the pathophysiology of epilepsy. The mechanisms by which glia, particularly astrocytes and microglia, may contribute to epilepsy and consequently could be harnessed therapeutically are discussed in this Review.


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via Neuron–glia interactions in the pathophysiology of epilepsy | Nature Reviews Neuroscience

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[Abstract + References] The Reverse Wrist Hinge to improve wrist range of motion


The wrist is often immobilized after trauma, potentially leading to subsequent stiffness.1 Static progressive wrist orthoses are sometimes used in rehabilitation when stiffness does not resolve with other techniques such as passive stretching, active exercise, and functional rehabilitation. Once the end-feel status of the wrist and the surrounding soft tissues is assessed,2 a low-load, prolonged stretch is an important factor to consider when attempting to regain wrist range of motion (ROM).3


  1. Lucado, A.M., Li, Z. Static progressive splinting to improve wrist stiffness after distal radius fracture: a prospective, case series study. Physiother Theory Pract2009;25:297–309.
  2. Porretto-Loehrke, A., Schuh, C., Szekeres, M. Clinical manual assessment of the wrist. J Hand Ther2016;29:123–135.
  3. Flowers, K.R., LaStayo, P. Effect of total end range time on improving passive range of motion.J Hand Ther1994;7:150–157.
  4. Schultz-Johnson, K. Static progressive splinting. J Hand Ther2002;15:163–178.
  5. Sueoka, S.S., Detemple, K. Static-progressive splinting in under 25 minutes and 25 dollars. J Hand Ther2011;24:280–286.
  6. Szekeres, M., Chinchalkar, S., LeBlanc, M. A low-tech alternative to static progressive wrist extension splinting: the wrist extension strap. J Hand Ther2002;15:375–376.

via The Reverse Wrist Hinge to improve wrist range of motion – Journal of Hand Therapy

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[ARTICLE] The validity of spatiotemporal gait analysis using dual laser range sensors: a cross-sectional study – Full Text



The spatiotemporal parameters were used for sophisticated gait analysis in widespread clinical use. Recently, a laser range sensor has been proposed as a new device for the spatiotemporal gait measurement. However, measurement using a single laser range sensor can only be used for short-range gait measurements because the device irradiates participants with lasers in a radial manner. For long-range gait measurement, the present study uses a modified method using dual laser range sensors installed at opposite ends of the walking path. The aim of present study was to investigate the concurrent validity of the proposed method for spatiotemporal gait measurement by comparison to a computer-based instrumented walkway system.


Ten healthy participants were enrolled in this study. Ten-meter walking tests at 100, 75, and 50% of the comfortable speed were conducted to determine the concurrent validity of the proposed method compared to instrumented walkway measurements. Frequency distributions of errors for foot-contact (FC) and foot-off (FO) estimated times between the two systems were also calculated to determine the adequacy of estimation of FC and FO from three perspectives: accuracy (smallness of mean error), precision (smallness of variability), and unambiguity (monomodality of histogram). Intra-class correlation coefficient (2,1) was used to determine the concurrent validity of spatiotemporal parameters between the two systems.


The results indicate that the detection times for FC and FO estimated by the proposed method did not differ from those measured by the instrumented walkway reference system. In addition, histogram for FC and FO showed monomodality. Intra-class correlation coefficients of the spatiotemporal parameters (stance time: 0.74; double support time: 0.56; stride time: 0.89; stride length: 0.83; step length: 0.71; swing time: 0.23) were not high enough. The mean errors of all spatiotemporal parameters were small.


These results suggest that the proposed lacks sufficient concurrent validity for spatiotemporal gait measurement. Further improvement of this proposed system seems necessary.


In gait disorder rehabilitation, gait analysis plays an important role in optimizing treatment for each patient [1234]. Conventionally, visual observation of gait analysis is easy and low cost and is commonly used in rehabilitation facilities. However, previous studies report that visual observation gait analysis has low inter-rater and test-retest reliability as well as low criterion concurrent validity in contrast to kinematic analyses using various instruments [45]. For highly accurate measurements with good inter-rater and test-retest reliability, a three-dimensional motion analysis system has been used. Although this system is able to measure whole-body joint motions, it has high costs and is time- and labor-intensive to set up [6].

Spatiotemporal gait measurement is another valuable method to identify gait deviations, make diagnoses, determine appropriate therapy, and monitor patient progress [23]. Frequently, parameters such stance time, swing time, double support time, stride time, stride length, and step length are evaluated [78910]. To calculate these spatiotemporal parameters, accurate detection of two events for switching between the stance and swing phases is essential: foot contact (FC) and foot off (FO). FC is defined as when any point of the foot first contacts and is the starting point of the stance phase. FO is when the sole is raised completely from the floor and is the onset of the swing phase. A measurement system for detection of FC and FO is a computer-based instrumented walkway system with pressure sensors and produces high inter-rater and test-retest reliability [278910]. Although this system has a relatively reasonable price as compared with a three-dimensional motion analysis system, it is still considerably expensive to become widely used. In addition, it occupies a large amount of floor space and greatly limits effective use of the exercise room. While this system is placed on the floor, the place is not able to be used for other purposes even though the exercise room has limited floor space.

Recently, spatiotemporal gait measurement using a laser range scanner has been proposed as easy to install and remove [11121314]. With a laser range scanner, both lower legs are measured using two best-fitting circles whose contours are defined by laser points. Although this method is useful for easy measurement of gait parameters in a clinical setting, the raw contour of the leg is incomplete because the sensor provides only one-sided information [11]. In addition, the number of laser points comprising the spheres decreases with long-range gait measurements because the lasers irradiate participants in a radial manner. Since the radial range decreases with increasing distance from the laser, this causes larger measurement errors.

For eliminating problems in long-range gait measurement, we proposed a method of spatiotemporal gait analysis using dual laser range sensors installed at opposite ends of the walking path. Because the measurement using laser range sensor is quick and easy method, this proposed method has a high degree of usability for clinical practice. However, it is not clear whether the proposed method has concurrent validity, which is defined as evaluation of an instrument against an already validated measure [15], for spatiotemporal gait measurement by comparison to a computer based instrumented walkway system (reference system) that was widely used for criterion-related validity. The aim of present study was to investigate the concurrent validity of the proposed method for spatiotemporal gait measurement by comparison to a reference system.



Ten healthy participants (7 males and 3 females, 20–24 years of age, 154-184 cm in height, 49-70 kg in weight) were enrolled in the present study. All participants have no history of orthopedic, neurophysiologic, and cardiovascular diseases. Informed consent was obtained from each participant before the experiments. The present study was approved by the ethics committee and was conducted according to the Declaration of Helsinki for human experiments.

Experimental procedures

This study used a cross-sectional design to assess the concurrent validity of the proposed method for spatiotemporal gait measurement by comparison to a reference system.

Participants wearing short pants were asked to get on a walking path and walk barefoot along a 12 m straight line including 3.5 m in front of the measured walking path and 3.5 m beyond the end of walking path. Each participant performed one trial at each speed: 100, 75, and 50% of the comfortable speed in a subjective manner. Before measurement, the order of the speed conditions was randomized for each participant. During the gait test, spatiotemporal measurements were carried out simultaneously using both the proposed method and the reference system. The inter-trial interval was set to 2 minutes to prevent fatigue.

Proposed method using laser range sensors

A two-dimensional radial scanning laser range sensor (UTM-30LX, Hokuyo Automatic Co., Ltd., Osaka, Japan) was used (Fig. 1a). The device has a scanning range from − 135° to 135° in steps of 0.25° (total of 1080 data points measuring the distance from the sensor to the target), and one scan is completed in 0.025 s (i.e., the sampling frequency is 40 Hz). In addition, the device exhibits very small test-retest variability and the relative error of a distance (0.1 to 10 m, σ < 0.01 m and ± 0.01 m, white Kent paper, respectively) in the repeated measurements using same laser range sensor unit (i.e. unit testing). Two devices were installed at opposite ends of a five-meter walking path at the level of the average shin height (0.25 m above the floor) [16] (Fig. 1b).


Continue —>  The validity of spatiotemporal gait analysis using dual laser range sensors: a cross-sectional study | Archives of Physiotherapy | Full Text

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[Abstract] Effectiveness of botulinum toxin treatment for upper limb spasticity after stroke over different ICF domains: a systematic review and meta-analysis.



To provide a comprehensive overview of reported effects and scientific robustness of botulinum toxin (BoNT) treatment regarding the main clinical goals related to post-stroke upper limb spasticity, using the ICF classification.

Data sources

Embase.com, PubMed, Wiley/Cochrane Library, and Ebsco/CINAHL were searched from inception up to 16 May 2018.

Study Selection

Randomized controlled trials comparing upper limb BoNT injections with a control intervention in stroke patients were included. A total of 1212 unique records were screened by two independent reviewers. Forty trials were identified, including 2718 stroke patients.

Data Extraction

Outcome data were pooled according to assessment timing (i.e. 4-8 and 12 weeks after injection), and categorized into six main clinical goals (i.e. spasticity-related pain, involuntary movements, passive joint motion, care ability, arm and hand use, and standing and walking performance). Sensitivity analyses were performed for the influence of study and intervention characteristics, involvement of pharmaceutical industry, and publication bias.

Data Synthesis

Robust evidence is shown for the effectiveness of BoNT in reducing resistance to passive movement, as measured with the (Modified) Ashworth Score, and improving self-care ability for the affected hand and arm after intervention (p<0.005) and at follow-up (p<0.005). In addition, robust evidence is shown for the absence of effect on ‘arm-hand capacity’ at follow-up. BoNT significantly reduced ‘involuntary movements’, ‘spasticity-related pain’, and ‘carer burden’, and improved ‘passive range of motion’, while no evidence was found for ‘arm and hand use’ after intervention.


In view of the robustness of current evidence, no further trials are needed to investigate BoNT for its favourable effects on resistance to passive movement of the spastic wrist and fingers, and on self-care. No trials are needed to further confirm the lack of effects of BoNT on arm-hand capacity, whereas additional trials are needed to establish the suggested favourable effects of BoNT on other ‘body functions’ which may result in clinically meaningful outcomes at ‘activity’ and ‘participation’ levels.

via Effectiveness of botulinum toxin treatment for upper limb spasticity after stroke over different ICF domains: a systematic review and meta-analysis – Archives of Physical Medicine and Rehabilitation

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[WEB SITE] How to stretch your hands and wrists – Videos

Wrist pain can be frustrating and inconvenient. It can also make work or basic day-to-day activities, such as using a computer or cooking a meal, more difficult.

Exercises can improve mobility and decrease the chance of injury or reinjury. Wrist stretches are easy to do at home or at the office. When done properly, they can benefit a person’s overall wrist and hand health.

Anyone experiencing chronic pain or pain with numbness should visit a doctor for a thorough diagnosis.

The following stretches can help improve strength and mobility:

Wrist and hand stretches

A person should do the exercises below slowly and gently, focusing on stretching and strengthening. If the stretch hurts, stop.

The following wrist and hand stretches may improve strength and mobility:

1. Raised fist stretch

Raised fist stretch

To do this stretch:

  1. Start with your arm up beside your head, with your hand open.
  2. Make a fist, keeping your thumb outside of it.
  3. Slide your fingers toward your wrist until you feel a stretch.

2. Wrist rotations

Wrist rotations

To do this stretch:

  1. Stretch your arm out in front of you.
  2. Slowly, point the fingers down until you feel a stretch. Use the other hand to gently pull the raised hand toward the body. Hold this position for 3–5 seconds.
  3. Point the fingers toward the ceiling until you feel a stretch. Use the other hand to gently pull the raised hand toward the body. Hold this position for 3–5 seconds.
  4. Repeat this three times.

3. Prayer position

Prayer position

To do this stretch:

  1. Sit with your palms together and your elbows on the table in a prayer position.
  2. Lower the sides of the hands toward the table until you feel a stretch. Keep your palms together. Hold this position for 5–7 seconds.
  3. Relax.
  4. Repeat this three times.

4. Hooked stretch

Hooked stretch

To do this stretch:

  1. Hook one elbow under the other and pull both arms towards the center of the torso. You should feel a stretch in your shoulders.
  2. Wrap one arm around the other so that the palms are touching.
  3. Hold the position for 25 seconds.
  4. Switch arms and repeat it on the other side.

5. Finger stretch

finger stretch

To do this stretch:

  1. Bring the pinky and ring fingers together.
  2. Separate the middle and index fingers from the ring finger.
  3. Repeat the stretch 10 times.

6. Fist-opener

Fist opener

To do this stretch:

  1. Make a fist and hold it in front of you.
  2. Stretch your fingers until your hand is flat and open, with the fingers together.
  3. Repeat the movements 10 times.

7. Sponge-squeeze

Sponge squeeze

To do this stretch:

  1. Squeeze a sponge or stress ball, making a fist.
  2. Hold the position for 10 seconds.
  3. Relax.
  4. Repeat this 10 times.

8. Windshield wiper wrist movement

To do this stretch:

  1. Start with your hand face down on a table.
  2. Gently, point the hand to one side as far as it can go without moving the wrist. Hold it there for 3–5 seconds.
  3. Do the same on the other side.
  4. Repeat the movement three times on each side.

9. Thumb pull

To do this stretch:

  1. Grab your thumb with the other hand.
  2. Gently pull the thumb backward, away from the hand.
  3. Hold the stretch for 25 seconds.
  4. Repeat it on the other thumb.

10. Flower stretch

To do this stretch:

  1. Stretch the arms in front of you, with the backs of the hands and wrists touching.
  2. Imagine an invisible force pulling the fingers further from the body. Feel the stretch.
  3. Hold it for 25 seconds.

11. Finger fan

To do this stretch:

  1. Make a fist.
  2. Stretch your fingers outwards as far as they can go, like a fan.
  3. Repeat the movements 10 times.

12. Imaginary piano

To do this stretch:

  1. Pretend to play a piano.
  2. Flip your hands over and play an upside-down piano.

13. Finger pulls

To do this stretch:

  1. Lay your hand flat on a table.
  2. Gently pull a finger upward so that it points toward the ceiling.
  3. Hold the position for 5 seconds.
  4. Release the finger.
  5. Repeat this on all the other fingers.

14. Alternate finger stretch

To do this stretch:

  1. Bring the middle and ring fingers together.
  2. Separate the pinky and index fingers from them.
  3. Repeat the stretch 10 times.

15. Wrist-strengthener

To do this stretch:

  1. Get into position on your hands and knees, with the fingers pointing toward the body.
  2. Slowly lean forward, keeping your elbows straight.
  3. Hold the position for 20 seconds.
  4. Relax, then repeat the stretch.


Working with computers, writing, and doing manual labor put strain on the hands and wrists and can cause problems over time, such as tendonitis and carpal tunnel syndrome.

Taking frequent breaks and stretching before and while using the hands and wrists can help prevent strain. Improving flexibility and strength gradually can help people avoid wrist and hand injuries.

via Medical News Today: How to stretch your hands and wrists

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[Abstract] Investigation of multi-joint coordinated upper limb rehabilitation assisted with electromyography (EMG)-driven neuromuscular electrical stimulation (NMES)-robot after stroke


More than 80% of stroke survivors worldwide suffer from permanent upper limb motor deficits. Restoration of upper limb motor functions in conventional rehabilitation remains challenging; the main difficulties are as follows: 1) lack of intensive, repetitive practice in manually delivered treatment; 2) lack of coordination management of upper limb motor tasks, particularly those involving the distal joints, e.g., the wrist and the hand; and 3) lack of understanding of the optimal joint supportive scheme in task-oriented upper limb training. More effective training strategies are necessary for upper limb rehabilitation following stroke. Robots have proved to be valuable assistants in labour-demanding post-stroke rehabilitation, with a controllable mechanical design and repeatable dynamic support in physical training. A series of rehabilitation robots for multi-joint practices were successfully designed in our previous works. In this work, we proposed a device-assisted multi-joint coordinated strategy for post-stroke upper limb training. The objectives of the study were as follows: 1) To evaluate the rehabilitation effectiveness of multi-joint coordinated upper limb practice assisted by an electromyography (EMG)-driven neuromuscular electric stimulation (NMES)-robot for stroke survivors in both the subacute and chronic stages. 2) To compare different joint supportive schemes using NMES-robots and identify the optimized scheme for upper limb rehabilitation. The objectives were achieved through three independent clinical trials using common clinical assessments, namely, the Fugl-Meyer Assessment (FMA), Modified Ashworth Scales (MAS), Action Research Arm Test (ARAT), and Functional Independence Measurement (FIM), and cross-session EMG evaluations to trace the recovery progress of individual muscle activities (i.e. EMG activation level) and muscular coordination (i.e. Co-contraction Index, CI) between a pair of muscles.
The first clinical randomized controlled trial (RCT) was conducted to investigate the clinical effects and rehabilitation effectiveness of the new training strategy in the subacute stroke period. Subjects were randomly assigned to two groups and received either 20 sessions of NMES-robot-assisted training (NMES-robot group, n=14) or time-matched conventional treatments (control group, n=10). Significant improvements were achieved in FMA (full score and shoulder/elbow), ARAT, and FIM for both groups [P<0.001, effect sizes (EFs)>0.279], whereas significant improvements in FMA (wrist/hand) and MAS (wrist) after treatment were only observed in the NMES-robot group (P<0.05, EFs>0.145), with the outcomes maintained for 3 months. In the NMES-robot group, CIs of the muscle pairs of biceps brachii and flexor carpi radialis (BIC&FCR) and biceps brachii and triceps brachii (BIC&TRI) were significantly reduced and the EMG activation level of the FCR decreased significantly. The result indicated comparable proximal motor improvements in both groups and better distal motor outcomes and more effective release of muscle spasticity across the whole upper limb in the NMES-robot group. The second part of the work was a clinical trial with a single-group design. Recruited chronic stroke patients (n=17) received 20 sessions of NMES-robot-assisted multi-joint coordinated upper limb training. Significant improvements were observed in FMA (full score and shoulder/elbow), ARAT, and FIM (P<0.05, EFs>0.157) and maintained for 3 months. CIs of the FCR&TRI and BIC&TRI muscle pairs and EMG activation levels of the FCR and BIC significantly decreased. The results indicated that the new training strategy was effective for upper limb recovery in the chronic stroke, with the long sustainability of the motor outcomes. In the third trial, another clinical RCT was conducted to investigate the training effects of different joint supportive schemes. The recruited chronic subjects were randomly assigned to receive task-oriented multi-joint practices with NMES-robotic support either to the finger-palm (hand group, n=15) or to the wrist-elbow (sleeve group, n=15). Significant improvements in FMA (full score and shoulder/elbow) and ARAT (P<0.05, EFs>0.147) were observed in both groups, whereas significant improvements in FMA (wrist/hand) and MAS (finger, wrist, and elbow) (P<0.05, EFs>0.149) were only observed in the hand group. These results indicated that the distal supportive scheme was more effective in distal motor recovery and whole arm spasticity control than the proximal supportive one under the same training strategy. In conclusion, NME-robot-assisted multi-joint coordinated training was able to achieve significant motor outcomes and effective muscle spasticity control in the entire upper limb, especially at the distal segments, i.e., the wrist and the fingers, in both subacute and chronic stroke patients. Moreover, the distal supportive scheme proved more effective than the proximal supportive scheme in multi-joint coordinated upper limb training.

via Investigation of multi-joint coordinated upper limb rehabilitation assisted with electromyography (EMG)-driven neuromuscular electrical stimulation (NMES)-robot after stroke | PolyU Institutional Research Archive


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[ARTICLE] Effectiveness of Robot-Assisted Upper Limb Training on Spasticity, Function and Muscle Activity in Chronic Stroke Patients Treated With Botulinum Toxin: A Randomized Single-Blinded Controlled Trial


Background: The combined use of Robot-assisted UL training and Botulinum toxin (BoNT) appear to be a promising therapeutic synergism to improve UL function in chronic stroke patients.

Objective: To evaluate the effects of Robot-assisted UL training on UL spasticity, function, muscle strength and the electromyographic UL muscles activity in chronic stroke patients treated with Botulinum toxin.

Methods: This single-blind, randomized, controlled trial involved 32 chronic stroke outpatients with UL spastic hemiparesis. The experimental group (n = 16) received robot-assisted UL training and BoNT treatment. The control group (n = 16) received conventional treatment combined with BoNT treatment. Training protocols lasted for 5 weeks (45 min/session, two sessions/week). Before and after rehabilitation, a blinded rater evaluated patients. The primary outcome was the Modified Ashworth Scale (MAS). Secondary outcomes were the Fugl-Meyer Assessment Scale (FMA) and the Medical Research Council Scale (MRC). The electromyographic activity of 5 UL muscles during the “hand-to-mouth” task was explored only in the experimental group and 14 healthy age-matched controls using a surface Electromyography (EMGs).

Results: No significant between-group differences on the MAS and FMA were measured. The experimental group reported significantly greater improvements on UL muscle strength (p = 0.004; Cohen’s d = 0.49), shoulder abduction (p = 0.039; Cohen’s d = 0.42), external rotation (p = 0.019; Cohen’s d = 0.72), and elbow flexion (p = 0.043; Cohen’s d = 1.15) than the control group. Preliminary observation of muscular activity showed a different enhancement of the biceps brachii activation after the robot-assisted training.

Conclusions: Robot-assisted training is as effective as conventional training on muscle tone reduction when combined with Botulinum toxin in chronic stroke patients with UL spasticity. However, only the robot-assisted UL training contributed to improving muscle strength. The single-group analysis and the qualitative inspection of sEMG data performed in the experimental group showed improvement in the agonist muscles activity during the hand-to-mouth task.

Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03590314


Upper limb (UL) sensorimotor impairments are one of the major determinants of long-term disability in stroke survivors (). Several disturbances are the manifestation of UL impairments after stroke (i.e., muscle weakness, changes in muscle tone, joint disturbances, impaired motor control). However, spasticity and weakness are the primary reason for rehabilitative intervention in the chronic stages (). Historically, spasticity refers to a velocity-dependent increase in tonic stretch reflexes with exaggerated tendon jerks resulting from hyperexcitability of the stretch reflex () while weakness is the loss of the ability to generate the normal amount of force.

From 7 to 38% of post-stroke patients complain of UL spasticity in the first year (). The pathophysiology of spasticity is complicated, and new knowledge has progressively challenged this definition. Processes involving central and peripheral mechanisms contribute to the spastic movement disorder resulting in abnormal regulation of tonic stretch reflex and increased muscle resistance of the passively stretched muscle and deficits in agonist and antagonist coactivation (). The resulting immobilization of the muscle at a fixed length for a prolonged time induces secondary biomechanical and viscoelastic properties changes in muscles and soft tissues, and pain (). These peripheral mechanisms, in turn, leads to further stiffness, and viscoelastic muscle changes (). Whether the muscular properties changes may be adaptive and secondary to paresis are uncertain. However, the management of UL spasticity should combine treatment of both the neurogenic and peripheral components of spasticity ().

UL weakness after stroke is prevalent in both acute and chronic phases of recovery (). It is a determinant of UL function in ADLs and other negative consequences such as bone mineral content (), atrophy and altered muscle pattern of activation. Literature supports UL strengthening training effectiveness for all levels of impairment and in all stages of recovery (). However, a small number of trials have been performed in chronic subgroup patients, and there is still controversy in including this procedure in UL rehabilitation ().

Botulinum toxin (BoNT) injection in carefully selected muscles is a valuable treatment for spastic muscles in stroke patients improving deficits in agonist and antagonist coactivation, facilitating agonist recruitment and increasing active range of motion (). However, improvements in UL activity or performance is modest (). With a view of improving UL function after stroke, moderate to high-quality evidence support combining BoNT treatment with other rehabilitation procedures (). Specifically, the integration of robotics in the UL rehabilitation holds promise for developing high-intensity, repetitive, task-specific, interactive treatment of upper limb (). The combined use of these procedures to compensate for their limitations has been studied in only one pilot RCT reporting positive results in UL function (Fugl-Meyer UL Assessment scale) and muscular activation pattern (). With the limits of the small sample, the results support the value of combining high-intensity UL training by robotics and BoNT treatment in patients with UL spastic paresis.

Clinical scales are currently used to assess the rehabilitation treatment effects, but these outcome measures may suffer from some drawbacks that can be overcome by instrumental assessment as subjectivity, limited sensitivity, and the lack of information on the underlying training effects on motor control (). Instrumental assessment, such as surface electromyography (sEMG) during a functional task execution allows assessing abnormal activation of spastic muscles and deficits of voluntary movements in patients with stroke.

Moreover, the hand-to-mouth task is representative of Activities of Daily Life (ADL) such as eating and drinking. Kinematic analysis of the hand-to-mouth task has been widely used to assess UL functions in individuals affected by neurological diseases showing adequate to more than adequate test-retest reliability in healthy subjects (). The task involves flexing the elbow a slightly flexing the shoulder against gravity, and it is considered to be a paradigmatic functional task for the assessment of spasticity and strength deficits on the elbow muscles (). Although sEMG has been reported to be a useful assessment procedure to detect muscle activity improvement after rehabilitation, limited results have been reported ().

The primary aim of this study was to explore the therapeutic synergisms of combined robot-assisted upper limb training and BoNT treatment on upper limb spasticity. The secondary aim was to evaluate the treatment effects on UL function, muscle strength, and the electromyographic activity of UL muscles during a functional task.

The combined treatment would contribute to decrease UL spasticity and improve function through a combination of training effects between BoNT neurolysis and the robotic treatment. A reduction of muscle tone would parallel improvement in muscle strength ought to the high-intensity, repetitive and task-specific robotic training. Since spasticity is associated with abnormal activation of shortening muscles and deficits in voluntary movement of the UL, the sEMG assessment would target these impairments ().

Materials and Methods

Trial Design

A single-blind RCT with two parallel group is reported. The primary endpoint was the changes in UL spasticity while the secondary endpoints were changes in UL function, muscle strength and the electromyographic activity of UL muscles during a functional task. The study was conducted according to the tenets of the Declaration of Helsinki, the guidelines for Good Clinical Practice, and the Consolidated Standards of Reporting Trials (CONSORT), approved by the local Ethics Committee “Nucleo ricerca clinica–Research and Biostatistic Support Unit” (prog n.2366), and registered at clinical trial (NCT03590314).


Chronic post-stroke patients with upper-limb spasticity referred to the Neurorehabilitation Unit (AOUI Verona) and the Physical Medicine and Rehabilitation Section, “OORR” Hospital (University of Foggia) were assessed for eligibility.

Inclusion criteria were: age > 18 years, diagnosis of ischemic or hemorrhagic first-ever stroke as documented by a computerized tomography scan or magnetic resonance imaging, at least 6 months since stroke, Modified Ashworth Scale (MAS) score (shoulder and elbow) ≤ 3 and ≥1+ (), BoNT injection within the previous 12 weeks of at least one of muscles of the affected upper limb, Mini-Mental State Examination (MMSE) score ≥24 () and Trunk Control Test score = 100/100 ().

Exclusion criteria were: any rehabilitation intervention in the 3 months before recruitment, bilateral cerebrovascular lesion, severe neuropsychologic impairment (global aphasia, severe attention deficit or neglect), joint orthopedic disorders.

All participants were informed regarding the experimental nature of the study. Informed consent was obtained from all subjects. The local ethics committee approved the study.


Each patient underwent a BoNT injection in the paretic limb. The dose of BoNT injected into the target muscle was based on the severity of spasticity in each case. Different commercial formulations of BoNT were used according to the pharmaceutical portfolio contracts of our Hospitals (Onabotulinumtoxin A, Abobotulinumtoxin A, and Incobotulinumtoxin A). The dose, volume and number of injection sites were set accordingly. A Logiq ® Book XP portable ultrasound system (GE Healthcare; Chalfont St. Giles, UK) was used to inject BoNT into the target muscle.

Before the start of the study authors designed the experimental (EG) and the control group (CG) protocols. Two physiotherapists, one for each group, carried out the rehabilitation procedures. Patients of both groups received ten individual sessions (45 min/session, two sessions/week, five consecutive weeks). Treatments were performed in the rehabilitative gym of the G. B. Rossi University Hospital Neurological Rehabilitation Unit, or “OORR” Hospital.

Robot-Assisted UL Training

The Robot-assisted UL Training group was treated using the electromechanical device Armotion (Reha Technology, Olten, Switzerland). It is an end-effector device that allows goal-directed arm movements in a bi-dimensional space with visual feedback. It offers different training modalities such as passive, active, passive-active, perturbative, and assistive modes. The robot can move, drive or oppose the patient’s movement and allows creating a personalized treatment, varying parameters such as some repetitions, execution speed, resistance degree of motion. The exercises available from the software are supported by games that facilitate the functional use of the paretic arm (). The robot is equipped with a control system called “impedance control” that modulates the robot movements for adapting to the motor behavior of the patient’s upper limb. The joints involved in the exercises were the shoulder and the elbow, is the wrist fixed to the device.

The Robot-assisted UL Training consisted of passive mobilization and stretching exercises for affected UL (10 min) followed by robot-assisted exercises (35 min). Four types of exercises contained within the Armotion software and amount of repetitions were selected as follows: (i) “Collect the coins” (45–75 coins/10 min), (ii) “Drive the car” (15–25 laps/10 min), (iii) “Wash the dishes” (40–60 repetitions/10 min), and (iv) “Burst the balloons” (100–150 balloons/5 min) (Figure 1). All exercises were oriented to achieving several goals in various directions, emphasizing the elbow flexion-extension and reaching movement. The robot allows participants to execute the exercises through an “assisted as needed” control strategy. For increment the difficulty, we have varied the assisted and non-assisted modality, increasing the number of repetitions over the study period.

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Figure 1
The upper limb robot-assisted training setting.

Conventional Training

The conventional training consisted of UL passive mobilization and stretching (10 min) followed by UL exercises (35 min) that incorporated single or multi-joint movements for the scapula, shoulder, and elbow, performed in different positions (i.e., supine and standing position). The increase of difficulty and progression of intensity were obtained by increasing ROM, repetitions and performing movements against gravity or slight resistance (). Training parameters were recorded on the patient’s log. […]


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[Abstract + References] Synergy-Based FES for Post-Stroke Rehabilitation of Upper-Limb Motor Functions


Functional electrical stimulation (FES) is capable of activating muscles that are under-recruited in neurological diseases, such as stroke. Therefore, FES provides a promising technology for assisting upper-limb motor functions in rehabilitation following stroke. However, the full benefits of FES may be limited due to lack of a systematic approach to formulate the pattern of stimulation. Our preliminary work demonstrated that it is feasible to use muscle synergy to guide the generation of FES patterns.In this paper, we present a methodology of formulating FES patterns based on muscle synergies of a normal subject using a programmable multi-channel FES device. The effectiveness of the synergy-based FES was tested in two sets of experiments. In experiment one, the instantaneous effects of FES to improve movement kinematics were tested in three patients post ischemic stroke. Patients performed frontal reaching and lateral reaching tasks, which involved coordinated movements in the elbow and shoulder joints. The FES pattern was adjusted in amplitude and time profile for each subject in each task. In experiment two, a 5-day session of intervention using synergy-based FES was delivered to another three patients, in which patients performed task-oriented training in the same reaching movements in one-hour-per-day dose. The outcome of the short-term intervention was measured by changes in Fugl–Meyer scores and movement kinematics. Results on instantaneous effects showed that FES assistance was effective to increase the peak hand velocity in both or one of the tasks. In short-term intervention, evaluations prior to and post intervention showed improvements in both Fugl–Meyer scores and movement kinematics. The muscle synergy of patients also tended to evolve towards that of the normal subject. These results provide promising evidence of benefits using synergy-based FES for upper-limb rehabilitation following stroke. This is the first step towards a clinical protocol of applying FES as therapeutic intervention in stroke rehabilitation.

I. Introduction

Muscle activation during movement is commonly disrupted due to neural injuries from stroke. A major challenge for stroke rehabilitation is to re-establish the normal ways of muscle activation through a general restoration of motor control, otherwise impairments may be compensated by the motor system through a substitution strategy of task control [1]. In post-stroke intervention, new technologies such as neuromuscular electrical stimulation (NMES) or functional electrical stimulation (FES) offer advantages for non-invasively targeting specific groups of muscles [2]–[4] to restore the pattern of muscle activation. Nevertheless, their effectiveness is limited by lack of a systematic methodology to optimize the stimulation pattern, to implement the optimal strategy in clinical settings, and to design a protocol of training towards the goal of restoring motor functions. This pioneer study addresses these issues in clinical application with a non-invasive FES technology.

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[Abstract] How effective is physical therapy for gait muscle activity in hemiparetic patients who receive botulinum toxin injections?


BACKGROUND: Administration of botulinum neurotoxin A (BoNT-A) to the ankle plantar flexors in patients with hemiplegia reduces the strength of knee extension, which may decrease their walking ability. Studies have reported improvements in walking ability with physical therapy following BoNT-A administration. However, no previous studies have evaluated from an exercise physiology perspective the efficacy of physical therapy after BoNT-A administration for adult patients with hemiplegia.

AIM: To investigate the effects of physical therapy following BoNT-A administration on gait electromyography for patients with hemiparesis secondary to stroke.

DESIGN: Non-randomized controlled trial.

SETTING: Single center.

POPULATION: Thirty-five patients with chronic stroke with spasticity were assigned to BoNT-A monotherapy (N.=18) or BoNT-A plus physical therapy (PT) (N.=17).

METHODS: On the paralyzed side of the body, 300 single doses of BoNT-A were administered intramuscularly to the ankle plantar flexors. Physical therapy was performed for 2 weeks, starting from the day after administration. Gait electromyography was performed and gait parameters were measured immediately before and 2 weeks after BoNT-A administration. Relative muscle activity, coactivation indices, and walking time/distance were calculated for each phase.

RESULTS: For patients who received BoNT-A monotherapy, soleus activity during the loading response decreased 2 weeks after the intervention (P<0.01). For those who received BoNT-A+PT, biceps femoris activity and knee coactivation index during the loading response and tibialis anterior activity during the pre-swing phases increased, whereas soleus and rectus femoris activities during the swing phase decreased 2 weeks after the intervention (P<0.05). These rates of change were significantly greater than those for patients who received BoNT-A monotherapy (P<0.05).
CONCLUSIONS: Following BoNT-A monotherapy, soleus activity during the stance phase decreased and walking ability either remained unchanged or deteriorated. Following BoNT-A+PT, muscle activity and knee joint stability increased during the stance phase, and abnormal muscle activity during the swing phase was suppressed.

CLINICAL REHABILITATION IMPACT: If botulinum treatment of the ankle plantar flexors in stroke patients is targeted to those with low knee extension strength, or if it aims to improve leg swing on the paralyzed side of the body, then physical therapy following BoNT-A administration could be an essential part of the treatment strategy.


via How effective is physical therapy for gait muscle activity in hemiparetic patients who receive botulinum toxin injections? – European Journal of Physical and Rehabilitation Medicine 2019 February;55(1):8-18 – Minerva Medica – Journals

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