DTI Study of the Influence of Physiotherapy on Distribution of BoNT in Spastic Muscle
Condition: Spasticity
MeSH terms: Muscle Spasticity
Study type: Observational

Summary: 
      Intramuscular application of botulinum toxin (BoNT) is used as a successful therapy of muscle
      spasticity. Clinical practice shows, that even with the use of special guidance techniques to
      increase accuracy of targeting, BoNT may spread to adjacent sites by diffusion. This causes
      fluctuating treatment response, unintended side effects, and decrease of effect due to
      production of antibodies. Hence, clinicians require increase of efficacy and safety by dose
      reduction, improvement of injection technique, and additional treatment strategies. Referring
      to this, animal model showed increased efficacy and decreased systemic side effects of BoNT
      in the injected muscle after active or passive manipulation of muscle. The mechanism of this
      effect remain unclear.

      T2 and (Diffusion Tensor Imaging) DTI technique can evaluate the in-vivo distribution of
      fluids in human skeletal muscle. In addition, it allows to differentiate denervated muscle
      tissue, caused by BoNT injections, from surrounding unaffected muscle tissue.

      Up to the investigators knowledge, neither a human, in vivo measurement of the influence of
      passive muscle activity on the area of denervation, nor the primary, in-vivo distribution of
      BoNT within spastic human muscle tissue, been evaluated.

      The aim of this explorative study is:

        -  to monitor the inflow and regional distribution of the injection bolus by dynamic
           T2-weighted-, DTI-sequences;

        -  to assess the effect of passive muscle exercise on the area of denervated, caused by
           BoNT, measured by DTI-, T2-weighted and flair sequences.

      The investigators hypothesize, that

        -  intramuscular denervation area, measured by DTI-, T2-weighted and Fluid Attenuated
           Inversion Recovery (FLAIR) sequences, 3 weeks after routine BoNT injection, is
           facilitated by passive muscle exercise;

        -  primary distribution of the injected BoNT bolus can be non-invasively monitored by
           dynamic T2-, DTI- and T2 weighted sequences.

      Therefore, in this investigator blinded, cross-over study, 6 patients suffering from upper
      limb spasticity, including musculus biceps brachii, will be investigated. (Magnetic Resonance
      Tomography) MRI of the musculus biceps brachii will be performed at two consecutive, routine
      BoNT-injection days (baseline and week 16). Patients receive dosage as clinically indicated,
      due to routine treatment. Patients will be randomised to receive thirty minutes of
      physiotherapy of the affected arm, including exercise of the elbow flexors, at one of the
      injection days (baseline, or week 16, respectively). In addition, MRI will be repeated 3
      weeks after injection.
    

Detailed description: 
      -  At baseline and week 16, dynamic T2-, T2-,and DTI weighted sequences will be performed
           to monitor the injection of the BoNT-bolus. Immediate after MRI-scan, physiotherapy will
           be performed. Patients, who were randomised to the non-treatment group at baseline, will
           receive physiotherapy immediately after MRI at week 16.

        -  At week 3 and week 19, three weeks after BoNT injection, respectively, MRI will be
           repeated. T2-and DTI- weighted and FLAIR- sequences will be performed.
    

Intervention name(s): physiotherapy
Intervention type(s): Other
Intervention description(s): thirty minutes passive flexion and extension of the elbow joint by a physiotherapist
Other intervention name(s): physical therapy
Observational model: Case-Crossover
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        patients suffering from upper limb spasticity

        receiving routine BoNT injection
      
Keywords: spasticity; Diffusor tensor imaging; distribution; botulinum toxin; physiotherapy