Effect of repetitive trans-cranial magnetic stimulation (rTMS) of lower limb motor cortex on Lower extremity spasticity in patients with hereditary spastic paraplegia (HSP): A randomized sham-controlled double-blind study

1. Effectiveness of rTMS on improvement of lower limb spasticity 2. Effectiveness of rTMS on improvement of modified Ashworth scale (MAS) of knee 3. Effectiveness of rTMS on improvement of 10-meter walking test 4. Effectiveness of rTMS on improvement of Fugl-Meyer lower limb functional assessment (FMA-LE) 5. Effectiveness of rTMS on improvement of quality of life based on SF-36

Double blind, randomized, Sham-controlled trial

Place of study: Neurology department of Shariati hospital Patients with familial or sporadic hereditary spastic paraplegia who are classified as definitely affected or probably affected based on Fink's criteria will be registered between 2016-18. designated sample size for the study is 10 patients, 5 in each group. patients would be randomized to either receive active 5 Hz rTMS or sham rTMS. Patients will be evaluated for following outcomes at baseline, upon completion of the intervention and 1 month after intervention: Average score of modified Ashworth scale in both knees Gait based on 10-meter walking test Lower limb motor function based on Fugl-Meyer lower extremity functional assessment (FMA-LE) Quality of life based on short form survey 36 (SF-36)

Inclusion: Patients with minimum age of 18 who are classified as definitely affected or probably affected based on Fink's criteria. Exclusion: History of seizure, uncontrolled hypertension, History of head trauma during 1 month prior to study, artificial heart valve or pacemaker, metallic body in head

Active group: 5-Hz rTMS) 5 sessions on 5 consecutive days. Sham group: Sham rTMS, similar sessions and duration to active group but with coil placed perpendicular, hence, no stimulation.

Effect of high frequency rTMS on lower limb spasticity of HSP patients based on average modified Ashworth scale

We used computer-generated blocks for randomization. We asked a third party with no role in patient registration or data analysis to generate a number of blocks with 4 spots, 2 for intervention and 2 for sham. When the patient registration started, the person in charge of randomization was asked to start choosing a random block and inform the operator (who was an independent person with no role in patient registration and analysis) of the type of intervention for each patient in order of registration. in total 2 blocks of 4 were used for our 8 patients.

For patient's in sham group, we used the same coil in active group but we placed it perpendicular to patient's scalp, therefore we were able to reproduce the somatic vibration sensation and acoustic artifact without stimulating motor cortex. As patients would receive intervention in separate appointments and there was no contact between patients, apart from the operator of rTMS, everyone -including the clinician who evaluated the outcomes and the analyst- was blind to the intervention for each patients.

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