Association Between Focal Dystonia and Complex Regional Pain Syndrome
Condition: Focal Dystonia; Peripheral Nervous System Disease
MeSH terms: Dystonia; Dystonic Disorders; Nervous System Diseases; Complex Regional Pain Syndromes; Reflex Sympathetic Dystrophy; Peripheral Nervous System Diseases; Syndrome
Study type: Observational

Summary: 
      This study will investigate differences among people with focal dystonia (FD), complex
      regional pain syndrome (CRPS) and people who have both conditions to learn more about the
      cause of both disorders.

      Participants undergo the following procedures in five visits:

        -  Electroencephalography (EEG). Electrodes (metal discs) are placed on the scalp with an
           electrode cap, a paste or a glue-like substance. The spaces between the electrodes and
           the scalp are filled with a gel that conducts electrical activity. Brain waves are
           recorded while the subject lies quietly and sensory stimulation is applied to the thumb
           or finger.

        -  Magnetic resonance imaging (MRI). This test uses a magnetic field and radio waves to
           obtain images of body tissues and organs. The patient lies on a table that can slide in
           and out of the scanner, wearing earplugs to muffle loud knocking and thumping sounds
           that occur during the scanning process. The procedure lasts about 45 minutes, during
           which time the patient will be asked to lie still for up to 15 minutes at a time.

        -  Transcranial magnetic stimulation (TMS). An insulated wire coil is placed on the scalp
           and a brief electrical current is passed through the coil. The current induces a
           magnetic field that stimulates the brain. There may be a pulling sensation on the skin
           under the coil and a twitch in muscles of the face, arm or leg. During the stimulation,
           subjects may be asked to keep their hands relaxed or to contract certain muscles.

        -  Peripheral electrical stimulation. In two experiments, TMS is combined with peripheral
           electrical stimulation, similar to what is used in nerve conduction studies, to the
           median nerve at the wrist. There may be muscle twitching.

        -  Surface electromyography. For TMS tests and peripheral electrical stimulation,
           electrodes are filled with a conductive gel and taped to the skin to record the
           electrical activity of three muscles on the right hand.

        -  Needle EMG. A needle is inserted into a muscle to record the electrical activity.

        -  Nerve conduction studies. A probe is placed on the skin to deliver a small electrical
           stimulus, and wires are taped to the skin record the nerve impulses. These studies
           measure the speed with which nerves conduct electrical impulses and the strength of the
           connection between the nerve and the muscles.

        -  Skin biopsy. Two sites are biopsied. A local anesthetic is given to numb the area and a
           1/4-inch piece of skin is removed with a special tool.

        -  JVP domes. Subjects are tested for their ability to discriminate sensory stimuli in the
           affected region and on the other side of it. They are asked to discriminate between
           stamps with grooves of different widths that are applied to the hands or feet.
    

Detailed description: 
      OBJECTIVE

      Dystonia is generally regarded as a motor execution abnormality due to a central nervous
      system dysfunction in the cortico-striato-thalamo-cortical motor loop. Regional traumas are
      considered to be risk factors for the development of focal dystonia (FD) in the affected
      limb. Since focal limb traumas are also associated with complex regional pain syndrome
      (CRPS), there may be a common underlying pathology in both conditions. In CRPS, many patients
      have a small fiber neuropathy. The goal of the proposed research is to distinguish
      (discriminate) among the three disease categories (FD, FD+CRPS, CRPS), to find out whether FD
      and CRPS share a common physiological substrate and represent two sides of a spectrum, and to
      see which clinical situations may be secondary to an underlying small fiber neuropathy.
      Independent studies will be conducted in patients with affected upper limbs and in those with
      affected lower limbs.

      STUDY POPULATION

      We intend to perform two studies on overall 90 subjects. One study will assess the affected
      upper limb in 15 patients with unilateral focal dystonia, 15 patients with CRPS and 15
      patients with focal dystonia and CRPS, while the second study will test the affected lower
      limb in 15 patients with unilateral focal dystonia, 15 patients with CRPS and 15 patients
      with focal dystonia and CRPS in the lower limb.

      DESIGN

      We propose to explore the central aspects (somatosensory evoked potentials, SEPS, and
      transcranial magnetic stimulation, TMS) in patients with upper limb disorders, because the
      cortical representation of hand muscles is easier to study than the lower limb muscle
      representations. In contrast, the peripheral studies (quantitative EMG and nerve conduction)
      will be performed in patients with lower limb disorders, due to length, accessibility and
      separation of pure motor and sensory nerves in the leg.

      OUTCOME MEASURES

      The primary outcome measure for the central nervous system features (the upper limb
      assessment) will be the difference in EEG dipole localization of the SEPs from thumb and
      index finger between the three groups to assess possible disturbances of cortical
      representation in the primary sensory cortex. TMS measures will be exploratory.

      The primary outcome measure of the lower limb testing will be the duration of motor unit
      action potentials (MUAP) to assess differences and subtle lesions, which were not picked up
      in clinical routine due to bigger confidence intervals of the single parameter.

      The unaffected side is the primary target of this study since we are looking for an
      underlying substrate; however, all clinical tests will be performed bilaterally (if tolerated
      by the subjects) and the comparison of both sides will be a secondary outcome measure.
    

Time perspective: Prospective
Keywords: Sensory Evoked Potentials (SEPs); Electromyogram; Transcranial Magnetic Stimulation (TMS); Complex Regional Pain Syndrome; Focal Hand Dystonia; Focal Dystonia; Chronic Regional Pain Syndrome; CRPS