Dysport® Adult Upper Limb Spasticity Extension Study

Phase 3

Completed

Conditions: Nervous System Disorders

Interventions: Biological: Botulinum toxin type A

Registration Number: NCT01313312

Lead Sponsor: Ipsen

Brief Summary: The purpose of this research study is to assess the long term safety of Dysport® in hemiparetic subjects with upper limb spasticity due to stroke or traumatic brain injury over repeated treatment cycles.

Detailed Description: This was a phase III, multicentre, prospective, open label, repeat treatment cycles, extension to the double study Y-52-52120-145 (Study 145) . The study included both rollover subjects from Study 145 and de novo subjects. The primary study objective was to assess the long term safety of Dysport® in hemiparetic subjects with upper limb spasticity due to stroke or traumatic brain injury over repeated treatment cycles. The secondary study objective was to assess the long term efficacy of repeated treatment with Dysport®.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 258

Inclusion Criteria

Completion of the double blind study, Y-52-52120-145

Exclusion Criteria

Major limitation in the passive range of motion in upper limb

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Total Dysport®	Botulinum toxin type A	A total of 254 subjects in the open label study received between 1 and 5 intramuscular (i.m) injections of Dysport® according to their individual needs, for a period of up to 12 months. All subjects were administered an appropriate dosage of Dysport® (1000 Units \[U\] or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response. From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.

Primary Outcome Measures

Name	Time	Method
Mean Change From Baseline to End of Study/Early Withdrawal in Blood Urea Nitrogen (BUN) and Fasting Blood Glucose	Up to Week 52	Blood samples for analysis of BUN and fasting blood glucose levels were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal.
Mean Change From Baseline to End of Study/Early Withdrawal in Heart Rate (HR)	Up to Week 52	HR was recorded at screening, baseline and at each post baseline visit. Vital signs were measured with the subject in a sitting position after resting for 3 minutes. Outcome measure is reported for number of subjects with data available for analysis.
Mean Change From Baseline to End of Study/Early Withdrawal in Red Blood Cell (RBC) Count	Up to Week 52	Blood samples for RBC count were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.
Mean Change From Baseline to End of Study/Early Withdrawal in Haematocrit	Up to Week 52	Blood samples for haematocrit were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.
Mean Change From Baseline to End of Study/Early Withdrawal in Mean Corpuscular Volume (MCV)	Up to Week 52	Blood samples for MCV were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.
Mean Change From Baseline to End of Study/Early Withdrawal in Total Bilirubin and Creatinine	Up to Week 52	Blood samples for clinical chemistry analysis of total bilirubin and creatinine were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.
Mean Change From Baseline to End of Study/Early Withdrawal in 12 Lead ECG - HR	Up to Week 52	HR was measured by 12-lead ECG tracing, performed at baseline, at post treatment follow up visit Week 4, and at the end of study or early withdrawal visit. The 12-lead ECG recordings were performed at a paper speed of 25 mm/s, recorded with the subject in a supine position after 5 minutes rest.
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)	Up to Week 52	A TEAE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication. Adverse events of special interest (AESIs) were identified as those assessed as being due to remote spread of effect of Dysport®, or any adverse event (AE) that was assessed as a hypersensitivity reaction. TEAEs, AESIs, severe TEAEs, serious adverse events (SAEs), treatment related TEAEs, TEAEs leading to withdrawal and fatal SAEs are summarised by treatment cycle.
Mean Change From Baseline to End of Study/Early Withdrawal in Diastolic and Systolic Blood Pressure (BP)	Up to Week 52	Systolic and diastolic BP were recorded at screening, baseline and at each post baseline visit. Vital signs were measured with the subject in a sitting position after resting for 3 minutes. Outcome measure is reported for number of subjects with data available for analysis.
Mean Change From Baseline to End of Study/Early Withdrawal in Haemoglobin and Mean Corpuscular Haemoglobin Concentration (MCHC)	Up to Week 52	Blood samples for haemoglobin and MCHC were taken at baseline, at post treatment follow up visit Week 4, and at the end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.
Mean Change From Baseline to End of Study/Early Withdrawal in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets	Up to Week 52	Blood samples for WBC count with differentials (neutrophils, lymphocytes) and platelet count were taken at baseline, at post treatment follow up visit Week 4, and at end of study or early withdrawal.
Mean Change From Baseline to End of Study/Early Withdrawal in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT)	Up to Week 52	Blood samples for analysis of the following clinical chemistry parameters: ALP, GGT, SGOT and SGPT were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.
Mean Change From Baseline to End of Study/Early Withdrawal in 12-Lead Electrocardiogram (ECG)	Up to Week 52	12-lead ECG tracing was performed at baseline, post treatment at Week 4 and at the end of study/early withdrawal visit. The 12-lead ECG recordings were performed at a paper speed of 25 mm/s, recorded with the subject in a supine position after 5 minutes rest. The ECG parameters reported were QRS duration, PR duration, QT duration, QTcB (QT interval corrected for HR according to Bazett), and QTcF (QT interval corrected for HR according to Fridericia) at baseline and the change to end of study/early withdrawal visit (EOS).
Mean Change From Baseline to End of Study/Early Withdrawal in Mean Corpuscular Haemoglobin (MCH)	Up to Week 52	Blood samples for MCH were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.
Number of Subjects With Botulinum Toxin A Binding and Neutralising Putative Antibodies	Up to Week 52	Blood samples were collected at baseline, Week 4 of each cycle, and at the end of study/early withdrawal to test for the presence of Botulinum Toxin A Binding antibodies. Samples positive for the presence of binding antibodies were then analysed for the presence of neutralising putative antibodies. The number of subjects who were either positive (+ve) or negative (-ve) at baseline and then positive post baseline for binding or neutralising antibodies were reported.

Secondary Outcome Measures

Name	Time	Method
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Extrinsic Finger Flexors at Week 4	At Week 4	The MAS consists of 6 grades: 0, 1, 1+, 2, 3, or 4 that can be applied to muscles of both the upper and lower limbs. The MAS was applied by the rater by stretching the joint through its full available range over 1 second. The percentage of subjects with at least a 1 grade reduction and at least a 2 grades reduction from baseline in mean MAS in the extrinsic finger flexors at Week 4 are reported.
Mean Change From Baseline MAS in the Wrist Flexors at Week 4	At Week 4	The clinical assessment of muscle tone was performed using the MAS. The MAS consists of 6 grades: 0, 1, 1+, 2, 3, or 4 that can be applied to muscles of both the upper and lower limbs. The MAS was applied by the rater by stretching the joint through its full available range over 1 second. The mean changes from baseline to Week 4 in MAS in the wrist flexors are reported.
Mean Change From Baseline Modified Ashworth Scale (MAS) in the Overall Primary Targeted Muscle Group (PTMG) for Upper Limb at Week 4	At Week 4	The clinical assessment of muscle tone was performed using the MAS. The MAS consists of 6 grades: 0, 1, 1+, 2, 3, or 4 that can be applied to muscles of both the upper and lower limbs. The MAS was applied by the rater by stretching the joint through its full available range over 1 second. The mean changes from baseline to Week 4 in MAS in the overall PTMG (finger, wrist or elbow flexors) are reported.
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Overall PTMG	At Week 4	The MAS consists of 6 grades: 0, 1, 1+, 2, 3, or 4 that can be applied to muscles of both the upper and lower limbs. The MAS was applied by the rater by stretching the joint through its full available range over 1 second. The percentage of subjects with at least a 1 grade reduction and at least a 2 grades reduction from baseline in mean MAS in the overall PTMG at Week 4 are reported.
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Wrist Flexors at Week 4	At Week 4	The MAS consists of 6 grades: 0, 1, 1+, 2, 3, or 4 that can be applied to muscles of both the upper and lower limbs. The MAS was applied by the rater by stretching the joint through its full available range over 1 second. The percentage of subjects with at least a 1 grade reduction and at least a 2 grades reduction in mean MAS in the wrist flexors at Week 4 are reported.
Mean Change From Baseline MAS in the Shoulder Extensors at Week 4	At Week 4	The clinical assessment of muscle tone was performed using the MAS. The MAS consists of 6 grades: 0, 1, 1+, 2, 3, or 4 that can be applied to muscles of both the upper and lower limbs. The MAS was applied by the rater by stretching the joint through its full available range over 1 second. The mean changes from baseline to Week 4 in MAS in the shoulder extensors are reported.
Percentage of Subjects With at Least 1 Grade Reduction in DAS for PTT at Week 4	At Week 4	At baseline the subject and investigator together selected one of the four DAS domains as the PTT. The selected domain was required to have a rating of moderate or severe (≥2) at baseline. The DAS is a 4-point scale, the extent of functional impairment in 4 functional domains (dressing, hygiene, limb position and pain) was rated as follows: 0=no disability, 1=mild disability (noticeable but does not interfere significantly with normal activities), 2=moderate disability (normal activities require increased effort and/or assistance) and 3=severe disability (normal activities limited). The percentage of subjects with at least 1 grade reduction from baseline in DAS for PTT at Week 4 are reported.
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Extrinsic Finger Flexors as PTMG	At Week 4	The Tardieu Scale (TS) was used to measure spasticity in extrinsic finger flexors. The TS is administered by applying passive stretch to a muscle group at two velocities. Slow speed of muscle stretch measures the range of passive motion. During a slow stretching movement, the examiner determines the angle of movement arrest, either due to subject discomfort or a mechanical resistance. The same movement is repeated at high velocity (as fast as possible) to determine the angle of catch and release. The angle of movement arrest at slow velocity (XV1) and the angle of catch at fast speed (XV3) were recorded. The spasticity angle (X) was calculated as the difference between XV1 and XV3. Mean changes in Angles XV1, XV3 and X from baseline to Week 4 are reported.
Mean Change From Baseline MAS in the Extrinsic Finger Flexors at Week 4	At Week 4	The clinical assessment of muscle tone was performed using the MAS. The MAS consists of 6 grades: 0, 1, 1+, 2, 3, or 4 that can be applied to muscles of both the upper and lower limbs. The MAS was applied by the rater by stretching the joint through its full available range over 1 second. The mean changes from baseline to Week 4 in MAS in the extrinsic finger flexors are reported.
Physician's Global Assessment (PGA) of Treatment Response at Week 4	At Week 4	The PGA is a 9-point rating scale: -4=markedly worse, -3=much worse, -2=worse, -1=slightly worse, 0=no change, +1=slightly improved, +2=improved, +3=much improved, +4=markedly improved. An assessment of overall treatment response was conducted by the investigator and the mean PGA scores during long-term open label treatment with Dysport were reported.
Percentage of Subjects With at Least One Grade Reduction in DAS for Individual Domains at Week 4	At Week 4	The DAS is a 4-point scale. The extent of functional impairment in 4 functional domains (dressing, hygiene, limb position and pain) was rated as follows: 0=no disability, 1=mild disability (noticeable but does not interfere significantly with normal activities), 2=moderate disability (normal activities require increased effort and/or assistance) and 3=severe disability (normal activities limited). The percentage of subjects with at least one grade reduction in DAS for each of the individual domains at Week 4 is reported.
Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Elbow Flexors as PTMG	At Week 4	The TS was used to measure spasticity in elbow flexors.The TS is administered by applying passive stretch to a muscle group. The spasticity grade (Y) assesses quality of muscle reaction on a 5-point scale (measured at fast speed): 0 =No resistance throughout passive movement, 1=slight resistance throughout passive movement, 2=clear catch at precise angle, interrupting passive movement, followed by release, 3=fatigable clonus (less than 10 seconds when maintaining pressure) occurring at a precise angle, followed by release. 4=unfatigable clonus (more than 10 seconds when maintaining pressure) occurring at precise angle. Mean changes in spasticity grade (Y) from baseline to Week 4 are reported.
Mean Change From Baseline at Week 4 in Ease of Applying a Splint	At Week 4	The ease of applying a splint was evaluated on a 6-point scale (0= no splint needed, -1= splint needed and applied with no difficulty, -2= splint needed and applied with mild difficulty, -3= splint needed and applied with moderate difficulty, -4= splint needed and applied with severe difficulty, -5= splint needed,but unable to apply). Mean change in ease of applying a splint from baseline to Week 4 was reported.
Mean Change From Baseline MAS in the Elbow Flexors at Week 4	At Week 4	The clinical assessment of muscle tone was performed using the MAS. The MAS consists of 6 grades: 0, 1, 1+, 2, 3, or 4 that can be applied to muscles of both the upper and lower limbs. The MAS was applied by the rater by stretching the joint through its full available range over 1 second. The mean changes from baseline to Week 4 in MAS in the elbow flexors are reported.
Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Extrinsic Finger Flexors as PTMG	At Week 4	The TS was used to measure spasticity in extrinsic finger flexors. The TS is administered by applying passive stretch to a muscle group. The spasticity grade (Y) assesses quality of muscle reaction on a 5-point scale (measured at fast speed): 0 =No resistance throughout passive movement, 1=slight resistance throughout passive movement, 2=clear catch at precise angle, interrupting passive movement, followed by release, 3=fatigable clonus (less than 10 seconds when maintaining pressure) occurring at a precise angle, followed by release. 4=unfatigable clonus (more than 10 seconds when maintaining pressure) occurring at precise angle. Mean changes in spasticity grade (Y) from baseline to Week 4 are reported.
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Shoulder Extensors	At Week 4	The TS was used to measure spasticity in shoulder extensors. The TS is administered by applying passive stretch to a muscle group at two velocities. Slow speed of muscle stretch measures the range of passive motion. During a slow stretching movement, the examiner determines the angle of movement arrest, either due to subject discomfort or a mechanical resistance. The same movement is repeated at high velocity (as fast as possible) to determine the angle of catch and release. The angle of movement arrest at slow velocity (XV1) and the angle of catch at fast speed (XV3) were recorded. The spasticity angle (X) was calculated as the difference between XV1 and XV3. Mean changes in Angles XV1, XV3 and X from baseline to Week 4 are reported.
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Elbow Flexors at Week 4	At Week 4	The MAS consists of 6 grades: 0, 1, 1+, 2, 3, or 4 that can be applied to muscles of both the upper and lower limbs. The MAS was applied by the rater by stretching the joint through its full available range over 1 second. The percentage of subjects at least a 1 grade reduction and at least a 2 grades reduction from baseline in mean MAS in the elbow flexors at Week 4 are reported.
Mean Change From Baseline in Disability Assessment Scale (DAS) Score for the Principal Target of Treatment (PTT) at Week 4	At Week 4	At baseline the subject and investigator together selected one of the four DAS domains as the PTT. The selected domain was required to have a rating of moderate or severe (≥2) at baseline. The DAS is a 4-point scale, the extent of functional impairment in 4 functional domains (dressing, hygiene, limb position and pain) was rated as follows: 0=no disability, 1=mild disability (noticeable but does not interfere significantly with normal activities), 2=moderate disability (normal activities require increased effort and/or assistance) and 3=severe disability (normal activities limited). The mean changes in DAS at Week 4 are reported.
Mean Change From Baseline in Active Range of Motion (AROM) at Week 4 in the 3 Possible PTMGs	At Week 4	The AROM was assessed by the range of extension achieved by the subject moving each joint in the PTMGs (extrinsic finger flexors, elbow flexors and wrist flexors) without assistance. A goniometer was used for measurements in the elbow and wrist flexors but not for measurements in the extrinsic finger flexors. Mean changes in AROM in the 3 possible PTMGs from baseline to Week 4 are reported.
Mean Change From Baseline in Modified Frenchay Scale (MFS) at Week 4	At Week 4	The MFS was used to measure upper limb active function. Each subject was video taped while performing specific tasks. The videos were sent to a central provider and were read and scored by two independent readers blinded to the timing of the video and to treatment. These central assessments were used for the analysis of efficacy endpoints. The MFS consists of 10 tasks asking the subject to reach, grasp, carry and release different objects of different sizes which subjects are likely to use in their daily life. Each of these tasks was rated on a 10 point scale ranging from no movement to normal movement; for each task, the score 5 is used to rate a task barely accomplished. Mean change in MFS from baseline to Week 4 was reported.
Mean Change From Baseline in Short Form (36) Health Survey (SF-36) Quality of Life (QoL) at End of Study/Early Withdrawal Visit	Up to Week 52	Subjects were asked to complete the SF-36 questionnaires prior to the study treatment at baseline and at the end of study/early withdrawal visit. The SF-36 is a generic non-preference based health status measure. This instrument assessed subject health across 8 variable dimensions, which are specific health domains such as physical functioning, social functioning and vitality. Each variable item score is coded and turned into a 0-100 scale where 0 indicates the worst and 100 indicates the best possible health state for both the Physical Component Summary (PCS) and Mental Component Summary (MCS) of the questionnaire. Baseline results and the change from baseline to end of study/early withdrawal for the PCS and MCS are reported.
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Elbow Flexors as PTMG	At Week 4	The TS was used to measure spasticity in elbow flexors. The TS is administered by applying passive stretch to a muscle group at two velocities. Slow speed of muscle stretch measures the range of passive motion. During a slow stretching movement, the examiner determines the angle of movement arrest, either due to subject discomfort or a mechanical resistance. The same movement is repeated at high velocity (as fast as possible) to determine the angle of catch and release. The angle of movement arrest at slow velocity (XV1) and the angle of catch at fast speed (XV3) were recorded. The spasticity angle (X) was calculated as the difference between XV1 and XV3. Mean changes in Angles XV1, XV3 and X from baseline to Week 4 are reported.
Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Shoulder Extensors	At Week 4	The TS was used to measure spasticity in shoulder extensors. The TS is administered by applying passive stretch to a muscle group. The spasticity grade (Y) assesses quality of muscle reaction on a 5-point scale (measured at fast speed): 0 =No resistance throughout passive movement, 1=slight resistance throughout passive movement, 2=clear catch at precise angle, interrupting passive movement, followed by release, 3=fatigable clonus (less than 10 seconds when maintaining pressure) occurring at a precise angle, followed by release. 4=unfatigable clonus (more than 10 seconds when maintaining pressure) occurring at precise angle. Mean changes in spasticity grade (Y) from baseline to Week 4 are reported.
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Wrist Flexors as PTMG	At Week 4	The TS was used to measure spasticity in wrist flexors. The TS is administered by applying passive stretch to a muscle group at two velocities. Slow speed of muscle stretch measures the range of passive motion. During a slow stretching movement, the examiner determines the angle of movement arrest, either due to subject discomfort or a mechanical resistance. The same movement is repeated at high velocity (as fast as possible) to determine the angle of catch and release. The angle of movement arrest at slow velocity (XV1) and the angle of catch at fast speed (XV3) were recorded. The spasticity angle (X) was calculated as the difference between XV1 and XV3. Mean changes in Angles XV1, XV3 and X from baseline to Week 4 are reported.
Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Wrist Flexors as PTMG	At Week 4	The TS was used to measure spasticity in wrist flexors. The TS is administered by applying passive stretch to a muscle group. The spasticity grade (Y) assesses quality of muscle reaction on a 5-point scale (measured at fast speed): 0 =No resistance throughout passive movement, 1=slight resistance throughout passive movement, 2=clear catch at precise angle, interrupting passive movement, followed by release, 3=fatigable clonus (less than 10 seconds when maintaining pressure) occurring at a precise angle, followed by release. 4=unfatigable clonus (more than 10 seconds when maintaining pressure) occurring at precise angle. Mean changes in spasticity grade (Y) from baseline to Week 4 are reported.
Mean Change From Baseline in European 5 Dimensions, 5 Level (EQ-5D-5L) QoL at End of Study/Early Withdrawal Visit	Up to Week 52	Subjects were asked to complete the EQ-5D-5L QoL questionnaires prior to the study treatment at baseline and at the end of study/early withdrawal visit. The EQ-5D-5L index is a generic preference based measure of health related QoL producing utility scores that represent subject preferences for particular health states. This instrument rated subject health state looking at 5 specific dimensions such as mobility, self-care, usual activity, pain/discomfort and anxiety/depression and scored their general health state. Each dimension has 5 levels of severity (no problems, slight problems,moderate problems, severe problems and extreme problems). In addition, a visual analogue scale (VAS) ranging from 0 to 100 was also included for the patients to summarize their overall health status, where 0 is the worst and 100 the best possible health state. The mean values for each dimension and the VAS scores at baseline and at the end of-study /early withdrawal are reported.

Trial Locations

Locations (34): Malopolskie Centrum Medyczne
🇵🇱
Krakow, Poland
State University
🇷🇺
St Petersburg, Russian Federation
Derer's Hospital
🇸🇰
Bratislava, Slovakia
Medical Rehabilitation Center
🇷🇺
Moscow, Russian Federation
Krakowska Akademia Neurologii
🇵🇱
Warszawa, Poland
Vanderbilt University
🇺🇸
Nashville, Tennessee, United States
Design Neuroscience Miami
🇺🇸
South Miami, Florida, United States
Associated Neurologist of Southern CT, PT
🇺🇸
Fairfield, Connecticut, United States
Parkinson's Disease & Movement Disorders Center of Boca Raton
🇺🇸
Boca Raton, Florida, United States
Rancho Los Amigos National Rehabilitation Center
🇺🇸
Downey, California, United States
The Rehabilitation Institute of Chicago
🇺🇸
Chicago, Illinois, United States
Weill Cornell Medical College
🇺🇸
New York, New York, United States
Wake Forest Medical Center
🇺🇸
Winston-Salem, North Carolina, United States
Southwestern Medical Center at Dallas University of Texas
🇺🇸
Dallas, Texas, United States
CHU Brest
🇫🇷
Brest, France
Clinique Universitaire
🇧🇪
Yvoir, Belgium
Charles University in Prague
🇨🇿
Praha 2, Czechia
Université catholique de Louvain av Hippocrate 10
🇧🇪
Bruxelles, Belgium
Hôpital Sébastopol
🇫🇷
Reims, France
Hopital Rangueil
🇫🇷
Toulouse, France
Centre Hospitalier Albert Chenevier-Hopital Henri Mondor
🇫🇷
Créteil, France
Hopital Raymond Poincarré
🇫🇷
Garches, France
CHU Strasbourg
🇫🇷
Strasbourg, France
National Institute for Medical Rehabilitation
🇭🇺
Budapest, Hungary
Azienda Hospedaliero
🇮🇹
Catania, Italy
Petz Aladar County Hospital
🇭🇺
Gyor, Budapest, Hungary
Mount Sinai School of Medicine
🇺🇸
New York, New York, United States
Univ of North Carolina - Chapel Hill
🇺🇸
Chapel Hill, North Carolina, United States
Centre de Réadaptation de Coubert
🇫🇷
Coubert, France
University of North Texas HSC at Ben Hogan Center
🇺🇸
Fort Worth, Texas, United States
University of Utah School of Medicine
🇺🇸
Salt Lake City, Utah, United States
Policlinico Universitario Agostino Gemelli
🇮🇹
Roma, Italy
Samodzielny Publiczny Centralny Szpital Kliniczny
🇵🇱
Warszawa, Poland
Scientific Center of Neurology of RAMS
🇷🇺
Moscow, Russian Federation