Improving strain diagnosis of prion disease by diffusion MRI and biophysical modelling

Sporadic Creutzfeldt–Jakob disease (sCJD) is the most common form of prion disease, characterized by five different strains, presenting intracellular vacuoles with different diameter/distribution. Unfortunately, no reliable non-invasive method for strain identification currently exists. Here we provide the first quantitative maps of MR-measured vacuolar diameter/density in five sCJD patients, using multishell diffusion MRI and biophysical modelling. Results show distribution of small and larger vacuoles in the brain lesions of each patient, presumably corresponding to different sCJD strains, and absence of vacuoles in five age-matched healthy controls. If validated, this method would be extremely valuable for non-invasive diagnosis of sCJD strain

Association of asymptomatic spinal cord lesions and atrophy with disability 5 years after a clinically isolated syndrome.

Spinal cord pathology is an important substrate for long-term disability in multiple sclerosis (MS). To investigate longitudinal changes in spinal cord lesions and atrophy in patients with a non-spinal clinically isolated syndrome (CIS), and how they relate to the development of disability. In all, 131 patients with a non-spinal CIS had brain and spinal cord imaging at the time of CIS and approximately 5 years later (median: 5.2 years, range: 3.0-7.9 years). Brain magnetic resonance imaging (MRI) measures consisted of T2-hyperintense and T1-hypointense lesion loads plus brain atrophy. Spinal cord MRI measures consisted of lesion number and the upper cervical cord cross-sectional area (UCCA). Disability was measured using the Expanded Disability Status Scale (EDSS). Multiple linear regression was used to identify independent predictors of disability after 5 years. During follow-up, 93 (71%) patients were diagnosed with MS. Baseline spinal cord lesion number, change in cord lesion number and change in UCCA were independently associated with EDSS (R(2) = 0.53) at follow-up. Including brain T2 lesion load and brain atrophy only modestly increased the predictive power of the model (R(2) = 0.64). Asymptomatic spinal cord lesions and spinal cord atrophy contribute to the development of MS-related disability over the first 5 years after a non-spinal CIS

Spinal cord involvement in multiple sclerosis and neuromyelitis optica spectrum disorders

Spinal cord involvement is an important cause of disability in patients with multiple sclerosis or neuromyelitis optica spectrum disorders (NMOSDs). Multiple sclerosis and NMOSDs can be distinguished from other disorders that cause myelopathy by results from laboratory and radiological investigations. However, limitations in the sensitivity and specificity of spinal cord imaging and poor correlation with disability megasures have impeded the understanding of the relationship between spinal cord involvement and clinical manifestations. Nevertheless, studies of the pathological features of multiple sclerosis and NMOSDs have shown that quantitatively different mechanisms lead to differences in clinical course and pattern of accrual of permanent disability in the two dis-orders. Better understanding of these mechanisms is necessary to develop more informative clinical measures, electrophysiological methods, fluid biomarkers, and imaging techniques to detect and monitor spinal cord involvement in the diagnosis and management of patients with multiple sclerosis or NMOSDs, and as outcome measures in clinical trials

Spinal cord involvement in multiple sclerosis and neuromyelitis optica spectrum disorders

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