BackgroundAutologous haematopoietic stem cell transplantation (AHSCT) has been explored as a therapeutic intervention in multiple sclerosis (MS) over the last two decades; however, prospective clinical trials of the most common myeloablative conditioning regimen, BEAM, are limited. Furthermore, patient selection, optimal chemotherapeutic regimen and immunological changes associated with disease response require ongoing exploration. We present the outcomes, safety and immune reconstitution (IR) of patients with active, treatment refractory MS.MethodsThis study was a single-centre, phase II clinical trial of AHSCT for patients with active relapsing remitting (RRMS) and secondary progressive MS (SPMS). Patients underwent AHSCT using BEAM (carmustine, etoposide, cytarabine, melphalan)+antithymocyte globulin chemotherapeutic regimen.OutcomesThe primary outcome was event-free survival (EFS); defined as no clinical or radiological relapses and no disability progression. Multiparameter flow cytometry was performed for evaluation of post-transplant IR in both MS and lymphoma patients receiving the same chemotherapy regimen.ResultsThirty-five patients (20 RRMS, 15 SPMS) completed AHSCT, with a median follow-up of 36 months (range 12–66). The median Expanded Disability Status Scores (EDSS) was 6 (2–7) and patients had failed a median of 4 (2–7) disease modifying therapies. 66% failed treatment with natalizumab. EFS at 3 years was 60%, (70% RRMS). Sustained improvement in EDSS was seen in 15 (44%) of patients. There was no treatment-related mortality. A sustained rise in CD39+ T regulatory cells, immunosuppressive CD56hi natural killer cells and ablation of proinflammatory mucosal-associated invariant T cells was seen for 12 months following AHSCT in patients with MS. These changes did not occur in patients with lymphoma receiving the same chemotherapy for AHSCT.ConclusionsThe EFS in our MS cohort is significantly greater than other high-efficacy immunosuppressive therapies and similar to other AHSCT studies despite a more heavily pretreated cohort.Trial registration numberACTRN12613000339752.

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Background Whilst MRI guided Focused Ultrasound (MRgFUS) thalamotomy is an effective treatment option for tremor disorders, there are reports of tremor recurrence in patients with tremor dominant Parkinson's disease (PD). The mechanisms for tremor recurrence are unknown but likely relate to the duality of tremor network pathways with ramifications for subsequent treatment options. Cases We report two cases of tremor dominant PD who experienced tremor recurrence following MRgFUS thalamotomy with subsequent successful subthalamic nucleus deep brain stimulation (DBS). Tremor scores were measured at baseline, 1‐ and 3‐months post MRgFUS and at least 18 months post DBS in both patients. Both cases evidenced immediate improvement in tremor, after MRgFUS, followed by subsequent tremor recurrence. STN DBS resulted in almost complete long‐term tremor alleviation in both cases. Conclusions These cases demonstrate the efficacy and feasibility of STN DBS in patients with tremor dominant PD with tremor recurrence following MRgFUS thalamotomy. We discuss the dualism of tremor outflow pathways that may have implications for single target lesional therapies.