The use of MRI guided focused ultrasound for the management of focal hand dystonia

This trial aims to assess the efficacy and safety of MRgFUS in the treatment of focal hand dystonia. We aim to enrol 10 patients with focal hand dystonia, according to specific inclusion and exclusion criteria, and assess the benefit of MRgFUS in the treatment of this condition. All patients will undergo regular physical examination by a consultant neurologist and fellow with specialisation in movement disorders. Administration of standardised questionnaires, including the Arm Dystonia Disability Scale (ADDS), Michigan Health Outcome Questionnaire (MHOQ), Tubiana Musicians Dystonia Scale/Writer's Cramp Rating Scale (TMDS/WCRS), Short-Form 36 (SF-36) and pain numerical rating scale (NRS) will be administered at all visits except for the day of the procedure. Pre-procedure cognitive impairment will be screened using the mini-mental state examination (MMSE) and, similarly, pre- and post procedure depressive illness will be screened using the Beck Depression Inventory (BDI). If the participants meet all relevant inclusion, and no exclusion, criteria, a CT brain scan will be performed to measure the skull density ratio (SDR) using a low radiation dose CT scanner (at baseline only, not a treatment outcome). Further pre-procedural baseline screening will include assessment of neural pathways with MRI DTI tractography and resting state fMRI. Kinematic measures will be obtained using AMADEO upper extremity system and neurophysiological testing, using paired associative stimulation (PAS), will be used to measure cortical plasticity. The neurophysiological assessments are non-invasive (no recording needles are inserted) and the duration of neurophysiological testing is 60-90 minutes per study visit, with the patient seated comfortably in a neurophysiology laboratory with opportunities for rest breaks when needed. Participants will reviewed at baseline by an expert examiner in the field appropriate to their presenting complaint, that is, an expert musicologist for musician’s dystonia and a calligraphist for writer’s cramp. The MRgFUS intervention will be performed according to the standard protocol for MRgFUS at SVHNS and is delivered in a single session. The intervention is delivered by the senior consultant neurosurgeon involved in the study concept and protocol development. on the day of treatment, participants will undergo a head shave and the administration of local anaesthetic blocks prior to application of a stereotactic head frame. An elastic diaphragm is then placed over the scalp and affixed to the ultrasound transducer prior to being filled with cooled, degassed water. Participants are then placed into the 3-Tesla MRI scanner (SIGNA Architect, General Electric) and 3D T1 weighted imaging performed for localisation of the ventro-oral anterior and ventro-oral posterior nuclei. Lesions are created using an Exblate Neuro (InSightec) 650Hz, 1024-element, phased array ultrasound transducer. Initial operative planning is performed with a series of low power sonications producing temperatures of 40-45 °C to confirm accurate focusing in three orthogonal planes with magnetic resonance thermography. MR thermometry is utilised to measure the maximum temperature at target’s central voxel, centring on the target. Following confirmation of accurate targeting, therapeutic sonications are performed by gradually increasing the ultrasound energy and monitoring both the maximal and average temperatures at the target for each sonication. Clinical examinations are performed between each sonication to assess for focal hand dystonia and for the presence of side effects. This protocol is in keeping with the current TGA approved protocol for the use of MRgFUS in tremor treatment. The safety of this protocol is supported by the established safety profile of thalamic MRgFUS ablation for tremor syndromes and the existing body of literature for MRgFUS VOA/VOP thalamic ablation in focal hand dystonia as well as MRgFUS pallido-thalamic ablation for tremor syndromes. Treatment efficacy will be determined based administration of the ADDS, either the TMDS or WCRS based on the underlying syndrome, in addition to the SF-36 questionnaires at 1 month, 3 months, 6 months and 12 months post treatment. The pain NRS, MMSE and BDI will be administered at all follow up appointments. Kinematic hand function will be measured at 1, 3, 6 and 12 months using the specialised equipment that allows measurement of independent finger force and velocity in motor paradigms to assess manual dexterity required for high-level manual tasks. These assessments will allow defects of timing, force control (coordination), finger independence, and sequencing to be formally quantified to fully assess motor costs of treatment. Additionally, expert opinion by a musicologist, or calligraphist, will be sought at the baseline, 3, 6 and 12 month follow up appointments. Imaging outcomes will be collected at 3 and 12 months as in alignment with previous studies of MRgFUS in tremor. Repeat neurophysiological testing will be performed at 1, 3 and 12 months post treatment to assess for changes in cortical inhibition and neuroplasticity. Safety will be determined based on the incidence of predetermined adverse events experienced on the day of treatment, day 1 post procedure, 1 week post procedure (via phone call) and at each follow up appointment.