The Effectiveness of Individualized Physical Therapy and Functional Neurology Treatment Protocol in Conjunction With Optimizing Medication and Repetitive Transcranical Magnetic Stimulation in Patients With Complex Regional Pain Syndrome.

Complex Regional Pain Syndrome (CRPS) is a disabling and painful pain syndrome. It can be triggered by a very minor injury or a routine surgery, and the symptoms last much longer and are more difficult than the normal healing process would suggest. Symptoms of CRPS can include sensory and motor disorders, autonomic disorders, functional deficits, and major challenges in coping with daily activities. In addition, patients often have challenges with sleeping. Therefore, a multidisciplinary approach is required for treatment, even for several years. Treatment options include medication, rehabilitation (physiotherapy and occupational therapy), psychological interventions, surgical interventions, and alternative therapies. The best evidence currently exists for mirror therapy and Graded Motor Imaginery (GMI)-type rehabilitation interventions, although the evidence for these is based on a relatively small number of original studies. A new form of rehabilitation has emerged as functional neurological rehabilitation, which aims to optimize the functioning of the nervous system and thereby improve the symptoms and functional capacity of CRPS patients. This approach has not yet been extensively studied in CRPS patients.

Magnetic stimulation therapy (repetitive transcranial magnetic stimulation, rTMS) has been used effectively to treat many types of pain conditions (neuropathic pain, musculoskeletal pain, etc.) since the early 2000s. In rTMS therapy, a magnetic field is generated in the head area using an electromagnetic coil, which can affect the excitability level of the nerves in the stimulated area, but also in areas outside the magnetic field through extensive nerve connections. rTMS therapy can irritate or calm the excitability threshold of the nerves. There are also some studies conducted with a small sample size on the treatment of CRPS using rTMS with relatively good results. The effectiveness of the treatment seems to emerge with a slight delay. However, in a recent meta-analysis and recommendations for the use of rTMS therapy, the treatment is recommended for CRPS patients. (Chang et al 2020, Lefaucheur et al 2020.) The aim of the study is to investigate the significance of the timing of CRPS rehabilitation and functional neurological rehabilitation implemented at OYS in relation to rTMS treatment in alleviating symptoms and improving functional capacity in CRPS patients. The aim is also to monitor the effectiveness of the patients' treatment over a long period of time (1 and 3 years).

Study population and research methods The study population consists of patients from the OYS physiatry (or pain clinic) who have been referred for assessment from primary health care or other OYS clinics to make or confirm a CRPS diagnosis. After a CRPS diagnosis is made, the patient's possible initiation of rTMS treatment is discussed in a multidisciplinary pain working group. Patients for whom rTMS treatment is considered a suitable form of treatment will be asked about their willingness to participate in a treatment study for CRPS patients. The inclusion criteria are patients aged 18-70 who can understand Finnish fluently (reading and speaking) and who voluntarily participate in the study. In addition, the patient's CRPS symptom must be in 1-3 limbs. CRPS that has spread to the body or more than 3 limbs is an exclusion criterion. The patient's CRPS must also have developed within less than 5 years, even if the diagnosis is only made during the initial assessment by the OYS physiatrist, i.e. CRPS patients over 5 years old are excluded from the study.

All those receiving rTMS treatment who understand Finnish will be connected to the rTMS digital treatment pathway, which will allow their situation and symptoms and the effectiveness of the treatment to be monitored as part of the clinical work. Before the start of rTMS treatment, a magnetic resonance imaging (MRI) of the head will be taken from the patient to plan the treatment, as the treatment area(s) will be planned using this individual "brain map". The standard rTMS treatment protocol includes a 2-week intensive treatment period (5 + 5 days) and then maintenance treatments once a month for 5 times, i.e. the total treatment period is 6 months. If necessary, the patient is contacted by phone. As long as the patient is on rTMS treatment, he or she is followed up on the digital treatment path and the patient's situation is also inquired about 3 and 6 months after the end of treatment via the digital treatment path. The material collected on the digital treatment path is used as part of the study data collection from the patients participating in the study. The digital treatment path has been implemented and all rTMS treatments are connected to the digital treatment path. There are several surveys on the digital treatment path which include the following:

Before the start of the rTMS treatment period: Jenkins sleep questionnaire, Beck Depression Inventory, quality of life questionnaire, visual analogue scale (pain questionnaire), amount of sleep and changes in well-being.