Analgesic Effect of rTMS in Vasculitic Neuropathy

Vasculitic neuropathy (VN) results from inflammation and destruction of the walls of predominantly small vessels with subsequent ischemic damage of peripheral nerves. VN is painful in vast majority of patients and the pain is intractable with pharmacotherapy in about 40% of cases. Repetitive Transcranial Magnetic Stimulation (rTMS) is a noninvasive method of modulation of brain plasticity and is regarded as one of alternative methods to alleviate pain associated with various kind of neuropathies. The purpose of this study is to compare the effectiveness of analgesic effect of rTMS in vasculitic neuropathy with sham stimulation.

Vasculitic neuropathies (VN) are a group of disorders resulting from inflammation of predominantly small vessels with destruction of their walls and subsequent ischemic damage of peripheral nerves. Neural damage may or may not coexist with the damage of other organs. Examples of conditions associated with VN include diabetes, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis (Churg-Strauss), granulomatosis with polyangiitis (Wegener's), rheumatoid arthritis, systemic lupus erythematosus and others. VN is painful in about 80% of patients of whom 40% suffer from the pain intractable with pharmacological therapy. Repetitive Transcranial Magnetic Stimulation (rTMS) is a noninvasive method of modulation of brain plasticity. In this method, series of magnetic stimuli are delivered to the cerebral cortex, where they turn to electric current and depolarize repetitively the targeted neurons. If the stimulation is repeated during subsequent days it is capable to modify the activity of targeted cortical area for weeks or even months and by this way to achieve therapeutic effect. rTMS is widely regarded as one of alternative methods to alleviate pain associated with various kind of neuropathies. The purpose of this study is to compare the effectiveness of analgesic effect of rTMS in vasculitic neuropathy with sham stimulation.

Patients will be randomly assigned to active and then sham stimulation or to sham and then active stimulation.

Sham stimulation will be provided by holding the stimulating coil perpendicularly to the scalp, which assures similar impression as during active stimulation but prevents significant magnetic field to reach the brain tissue.

10 hertz (Hz) rTMS will be administered over the primary motor area. Therapy will include 5 daily sessions (on consecutive week days). In every sessions 1500 magnetic pulses of 90% of the resting motor threshold intensity will be elicited.

Sham stimulation will mimic the active one except that the stimulating coil will be held perpendicularly to the scalp, which assures similar impression as the active stimulation but prevents that significant magnetic field will reach brain tissue.

High frequency rTMS over the primary motor area to induce the long term potentiation of primary motor areas for the muscles of upper extremity.

Total score 10, with higher scores representing more severe pain. Change from baseline score in the Numeric Pain Severity Scale to the measurement taken after finishing rTMS.

Total score 10, with higher scores representing more severe pain. Change from baseline score in the Numeric Pain Severity Scale to the measurement taken two weeks after finishing rTMS.

Total score 10, with higher scores representing more severe pain. Change from baseline score in the Numeric Pain Severity Scale to the measurement taken four weeks after finishing rTMS.

An analog scale of the length of 100 milimeter. Total score of 100, with higher scores representing more severe pain. Change through the study.

Total score 64, with higher scores representing more severe depression. Change from baseline score in the Hospital Anxiety and Depression Scale to the measurement taken after finishing rTMS.

Total score 64, with higher scores representing more severe depression. Change from baseline score in the Hospital Anxiety and Depression Scale to the measurement taken two weeks after finishing rTMS.

Total score 64, with higher scores representing more severe depression. Change from baseline score in the Hospital Anxiety and Depression Scale to the measurement taken four weeks after finishing rTMS.

Total score, range 0 to 800, with lower values representing a worse outcome. Change from baseline score in the 36-Item Short Form Health Survey to the measurement taken after finishing rTMS.

Total score, range 0 to 800, with lower values representing a worse outcome. Change from baseline score in the 36-Item Short Form Health Survey to the measurement taken two weeks after finishing rTMS.

Total score, range 0 to 800, with lower values representing a worse outcome. Change from baseline score in the 36-Item Short Form Health Survey to the measurement taken four weeks after finishing rTMS.

Total score, range 0 to 100, with lower values representing a worse outcome. Change from baseline score in Neuro-Qol Upper Extremity Function to the measurement taken after finishing rTMS.

Total score, range 0 to 100, with lower values representing a worse outcome. Change from baseline score in Neuro-Qol Upper Extremity Function to the measurement taken two weeks after finishing rTMS.

Total score, range 0 to 100, with lower values representing a worse outcome. Change from baseline score in Neuro-Qol Upper Extremity Function to the measurement taken four weeks after finishing rTMS.

Electrocutaneus stimulation with gradually increasing intensity from 0mA until a patient reports that the sensation has become painful. Change from baseline pain threshold to the measurement taken after finishing rTMS.

Electrocutaneus stimulation with gradually increasing intensity from 0mA until a patient reports the first nonpainful tactile sensation. Change from baseline sensory threshold to the measurement taken after finishing rTMS.

Electrocutaneus stimulation with gradually increasing intensity from 0mA until a patient reports that the sensation has become painful. Change from baseline pain threshold to the measurement taken two weeks after finishing rTMS.

Electrocutaneus stimulation with gradually increasing intensity from 0mA until a patient reports the first nonpainful tactile sensation. Change from baseline sensory threshold to the measurement taken two weeks after finishing rTMS.

Electrocutaneus stimulation with gradually increasing intensity from 0mA until a patient reports that the sensation has become painful. Change from baseline pain threshold to the measurement taken four weeks after finishing rTMS.

Electrocutaneus stimulation with gradually increasing intensity from 0mA until a patient reports the first nonpainful tactile sensation. Change from baseline sensory threshold to the measurement taken four weeks after finishing rTMS.

Stimulation with cold temperature stimuli, gradually colder, starting from from 32 degree Celcius until patient will report that he feels cold. Change from baseline cold sensation threshold to the measurement taken after finishing rTMS.

Stimulation with cold temperature stimuli, gradually colder, starting from 32 degree Celcius until patient starts to perceive stimuli as painful. Change from baseline pain threshold to the measurement taken after finishing rTMS.

Stimulation with cold temperature stimuli, gradually colder, starting from from 32 degree Celcius until patient will report that he feels cold. Change from baseline cold sensation threshold to the measurement taken two weeks after finishing rTMS.

Stimulation with cold temperature stimuli, gradually colder, starting from 32 degree Celcius until patient starts to perceive stimuli as painful. Change from baseline pain threshold to the measurement taken two weeks after finishing rTMS.

Stimulation with cold temperature stimuli, gradually colder, starting from from 32 degree Celcius until patient will report that he feels cold. Change from baseline cold sensation threshold to the measurement taken four weeks after finishing rTMS.

Stimulation with cold temperature stimuli, gradually colder, starting from 32 degree Celcius until patient starts to perceive stimuli as painful. Change from baseline pain threshold to the measurement taken four weeks after finishing rTMS.

Stimulation with warm temperature stimuli, gradually warmer, starting from from 32 degree Celcius until patient will report that he feels warmth. Change from baseline warmth sensation threshold to the measurement taken after finishing rTMS.

Stimulation with warm temperature stimuli, gradually warmer, starting from 32 degree Celcius until patient starts to perceive stimuli as painful. Change from baseline pain threshold to the measurement taken after finishing rTMS.

Stimulation with warm temperature stimuli, gradually warmer, starting from from 32 degree Celcius until patient will report that he feels warmth. Change from baseline warmth sensation threshold to the measurement taken two weeks after finishing rTMS.

Stimulation with warm temperature stimuli, gradually warmer, starting from 32 degree Celcius until patient starts to perceive stimuli as painful. Change from baseline pain threshold to the measurement taken two weeks after finishing rTMS.

Stimulation with warm temperature stimuli, gradually warmer, starting from from 32 degree Celcius until patient will report that he feels warmth. Change from baseline warmth sensation threshold to the measurement taken four weeks after finishing rTMS.

Stimulation with warm temperature stimuli, gradually warmer, starting from 32 degree Celcius until patient starts to perceive stimuli as painful. Change from baseline pain threshold to the measurement taken four weeks after finishing rTMS.

Change from baseline strength of the index finger flexion to the measurement taken after finishing rTMS.

Change from baseline strength of the index finger flexion to the measurement taken two weeks after finishing rTMS.

Change from baseline strength of the foot extension to the measurement taken two weeks after finishing rTMS.

Change from baseline strength of the index finger flexion to the measurement taken four weeks after finishing rTMS.

Change from baseline strength of the index foot extension to the measurement taken four weeks after finishing rTMS.

Inclusion Criteria: Diagnosis of vasculitic neuropathy Neuropathic pain of constant severity since not less than a month and requiring use of analgesics more than once a week Score of 30 milimeter or more on the 100 milimeter visual analog scale of pain intensity at inclusion Exclusion Criteria: Severe depression Personality disorders and other psychiatric conditions, which could disturb the participation in the study Cognitive deficits, which could disturb the participation in the study Contraindications for rTMS as listed by the Guidelines of the International Federation of Clinical Neurophysiology (Rossi et al. 2009) i.e. seizure in the past, epilepsy, presence of magnetic material in the reach of magnetic field, pregnancy, likelihood to get pregnant, intracranial electrodes, cardiac pacemaker or intracardiac lines, frequent syncopes

After completing the study, the age and gender of participants as well as the scores and results of all outcome measurements made at baseline, after rTMS, at the first and at the second follow up will be made available to other researchers on request.

Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14.