Chronic progressive multiple sclerosis patients will be randomised to home-based arm ergometry training for 12 weeks or a waitlist control group which will have access to the treatment after 12 weeks when primary endpoint assessment has been obtained. Assessments include clinical outcomes and questionnaires as well MRI imaging and transcranial magnetic stimulation paradigms. Primary endpoint will be the 6 minute walking test at week 12.

Short protocol Design: Patients with progressive MS (PPMS, SPMS) and moderate disability (Expanded Disability Status Scale 4-6.5) will be randomized to home-based arm ergometry or a waitlist control group. Home-based training will be supervised by SD-card documentation, telephone, email and personal contact.

Inclusion criteria: clinically definite MS according to Poser (1983), no progression in the last 6 months before starting, no acute relapse, age 18- 65 years, EDSS 4-6.5, able to perform all arm- and handfunctions in daily life, able to execute a daily Training.

Exclusion criteria: medical contraindications for exercise therapy like cardiovascular or major orthopedic disease, metal parts in body, substantial cognitive deficit, cardiac pacemaker or other electric implants, pregnancy, epilepsy.

Recruitment sample: n=50 Participants for analysis: n= 40 Control group: Intervention available after 3 months Duration: 3 months, data acquisition until 12 months after intervention Hypothesis: Arm ergometry improves walking ability (measured by 6-Minute Walk Test, 6MWT). Secondary endpoints include cognition, fatigue, depression, life quality and blood markers as BDNF.

Primary endpoint: Walking ability is evaluated before and after the training program (12 weeks) using the 6MWT by measuring the total walking distance within six minutes.

Secondary endpoints:

1. Walking abilities: 25FWT, TUG, 5SST, 9HPT, 7-day-accelerometry, MSWS- 12, Walking analysis on Gaitrite tapestry and with kinect camera with different tasks: normal speed, maximal speed, turning around and double tasking
2. EDSS (Expanded Disability status scale)
3. Fitness measures: areobic fitness (peak oxygen consumption VO2), bioimpedance analysis, DIERS-Myoline Muscle Strength Measurement, dynamic hand force measurement, spiroergometry, accelerometry
4. Neuropsychology: Test battery for Attentional Performance (TAP) including alertness, incompatibility and crossmodal integration, Verbal Learning- and Memory- Test (VLMT), Brief International Cognitive Assessment for MS (BICAMS), Symbol- Digit- Modalities Test (SDMT)
5. Questionnaires: HAQUAMS, Fatigue Scale for Motoric and Cognition (FSMC), Beck- Depressions- Inventar (BDI), Frenchay Activity Index (FAI)
6. cMRT
7. Blood: Neurofilament light, BDNF, Analysis with ELISA

Intervention:

Intervention will be a home-based, individual training with 5 -7 training sessions each week. Each individual training is based on the results of the spiroergometry of the participants. These tests will be conducted at the Competence Center for Sports and Exercise Medicine. The training sessions should be in the areobic exercise sector. In this sector intensity should be conducted at a power, which shows lactate values around 1.5 mmol, RER (Respiratory Exchange Ratio) should be around 0.91 and the subjective stress, measured on Borg-Scale, should be about 11. The V02max should be not higher than 65 %.

Before starting the training at home, patients have to come to the center for adaptation to the training machine, the "Motomed". We will test, if the power for the training estimated from stepwise arm ergometry is adeqaute. The patients will recieve an introduction for motomed as well as information on how to handle the chipcards. Patients will get 3 chipcards with one training program on each. The first card contains 10 training sessions. One training range includes 6 minutes active training followed by 2 minute passive rotation by the motomed. Every minute the direction of the crank changes. The frequency should not be higher than 60- 80 U/min. Patients have to repeat one training range (6min load, 2 minute rest) as often as possible. They will recieve one training plan for orientation. After 4 weeks the patients change the chipcard and they start their training with card number 2. Card number 2 includes the same training program as card number 1, but the power increases about 20-30 %. The results of everyday training will be saved automatically on the chipcards. Stored parameters will be heartrate, the power measured in Watt, the length of the training, the number of training ranges, and the frequency on the crank. Furthermore, patients make notes regarding their results and their perceived exertion during the training (measured by Borg-scaling) on a documentation sheet. If the training is too hard, the patients can either train for a shorter time, they can stop the training or they can use the chipcard with the lower power.

Procedure: After basline-examinations (walking ability, fitness, neuropsychology, blood draw, questionnaires, cMRT without contrast medium), instruction on "Motomed" and training at center, patients will be provided with the machines at their homes and start their training for 12 weeks under supervision (Email, telephone, home visit). Follow-up will be performed with the same assessments as at baseline including stepwise ergometry. For the assessments 2-3 appointments at the center are necessary.

Inclusion Criteria:

• proven multiple sclerosis
• stable disease
• EDD 4,0-6,5
• being able to perform arm ergometry

Exclusion Criteria:

• relapse situation
• cognitive deficit unable to understand study
• cardivascular disease
• contraindication for MRI

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