ObjectiveProgressive multifocal leukoencephalopathy (PML) is a devastating demyelinating opportunistic infection of the brain caused by the ubiquitously distributed JC polyomavirus. There are no established treatment options to stop or slow down disease progression. In 2018, a case series of 3 patients suggested the efficacy of allogeneic BK virus-specific T-cell (BKV-CTL) transplantation.MethodsTwo patients, a bilaterally lung transplanted patient on continuous immunosuppressive medication since 17 years and a patient with dermatomyositis treated with glucocorticosteroids, developed definite PML according to AAN diagnostic criteria. We transplanted both patients with allogeneic BKV-CTL from partially human leukocyte antigen (HLA) compatible donors. Donor T cells had directly been produced from leukapheresis by the CliniMACS IFN-γ cytokine capture system. In contrast to the previous series, we identified suitable donors by HLA typing in a preexamined registry and administered 1 log level less cells.ResultsBoth patients' symptoms improved significantly within weeks. During the follow-up, a decrease in viral load in the CSF and a regression of the brain MRI changes occurred. The transfer seemed to induce endogenous BK and JC virus-specific T cells in the host.ConclusionsWe demonstrate that this optimized allogeneic BKV-CTL treatment paradigm represents a promising, innovative therapeutic option for PML and should be investigated in larger, controlled clinical trials.Classification of EvidenceThis study provides Class IV evidence that for patients with PML, allogeneic transplant of BKV-CTL improved symptoms, reduced MRI changes, and decreased viral load.

BACKGROUND AND PURPOSE: To detect brain morphological alterations in patients with early Parkinson's disease (PD) by using magnetic resonance imaging (MRI) morphometry under radiological diagnostic conditions. METHODS: T1-weighted brain images of 18 early PD patients and 18 age-sex-matched healthy controls (HCs) were analyzed with free software Computational Anatomy Toolbox (CAT12). Regional cortical thickness (rCTh) in 68 atlas-defined regionsof-interest (ROIs) and subcortical gray matter volume (SGMV) in 14 atlas-defined ROIs were determined and compared between patients and HCs by paired comparison using both ROI-wise and voxel-wise analyses. False-discovery rate (FDR) was used multiple comparison correction. Possible correlations between brain morphological changes in patients and clinical observations were also analyzed. RESULTS: Comparing to the HCs, the ROI-wise analysis revealed rCTh thinning significantly in left medial orbitofrontal (P = .001), by trend (P < .05 but not significant after FDR correction) in four other ROIs located in frontal and temporal lobes, and a volume decreasing trend in left pallidum of the PD patients, while the voxel-wise analysis revealed one cluster with rCTh thinning trend located between left insula and superior temporal region of the patients. In addition, the patients showed more distinct rCTh thinning in ipsilateral hemisphere and SGMV deceasing trends in contralateral hemisphere in respect of the symptom-onset body side. CONCLUSION: Brain morphological alterations in early PD patients are evident despite of their inconspicuous findings in standard MRI. Quantitative morphological measurements with CAT12 may be an applicable add-on tool for clinical diagnosis of early PD. These results have to be verified in future studies with larger patient samples.