Faculty Bibliography

OBJECTIVE: The analysis of the MR phase provides additional information on the tissue microstructure. In multiple sclerosis (MS) lesions phase alterations may reflect different stages of inflammatory activity. Here we investigated lesion morphology in MS patients with short and long disease duration on T2* weighted, phase, magnitude and susceptibility weighted imaging (SWI) at 7 Tesla (T). METHODS: 17 MS or clinically isolated syndrome patients with short (<60 months) and 11 with long (>60 months) disease duration underwent 7T MRI. Lesions were subsequently analyzed side-by-side with regard to morphology and visibility on T2* weighted, SWI, magnitude and SWI-filtered phase images. RESULTS: 126 of 192 T2* weighted lesions (65.6%) were characterized by a phase alteration pattern, and hence could be differentiated on phase images. In detail, a significantly reduced proportion of lesions showing phase alterations was detectable in patients with longer disease duration (mean+/-SD 51+/-37%, range 0-100%) compared to patients with short disease duration (mean+/-SD 90+/-19.5%, range 50-100%, p = 0.003). CONCLUSION: This cross-sectional study identified different patterns of phase changes in lesions of MS patients with short and long standing disease. Longitudinal studies are warranted to prove that MR phase imaging is useful in determining the activity and the developmental stage of individual MS plaques.

Neuromyelitis optica spectrum disorders, or neuromyelitis optica (NMO), is an autoimmune disease of the central nervous system that must be distinguished from multiple sclerosis. Therapeutic approaches to relapse prevention in NMO include immunosuppressants and monoclonal antibodies. Rituximab, a monoclonal antibody that targets CD20 antigen expressed on the surface of pre-B, mature B-lymphocytes and a small subset of T-lymphocytes, has been widely used for the treatment of NMO. In this review, we aim to summarize global experience with rituximab in NMO. We identified 13 observational studies that involved a total of 209 NMO patients treated with rituximab. Majority of rituximab-treated patients evidenced stabilization or improvements in their disability scores compared to pre-treatment period and 66% of patients remained relapse-free during treatment period. Monitoring rituximab treatment response with CD19+ or CD27+ cell counts appears to improve treatment outcomes. We offer clinical pointers on rituximab use for NMO based on the literature and authors’ experience, and pose questions that would need to be addressed in future studies.

OBJECTIVE: To describe the expanding clinical spectrum of a recently described hereditary leukoencephalopathy, hypomyelination with brainstem and spinal cord involvement and leg spasticity, which is caused by mutations in the aspartyl tRNA-synthetase encoding gene DARS, including patients with an adolescent onset. METHODS: Three patients with mutations in DARS were identified by combining MRI pattern recognition and genetic analysis. RESULTS: One patient had the typical infantile presentation, but 2 patients with onset in late adolescence had a disease mimicking an acquired inflammatory CNS disorder. Adolescent-onset patients presented with subacute spastic paraplegia and had positive response to steroids. They had only minor focal supratentorial white matter abnormalities, but identical spinal cord changes involving dorsal columns and corticospinal tracts. Clinical presentation included subacute spastic paraplegia with partial improvement on steroids. CONCLUSIONS: Focal T2 hyperintense white matter changes on brain MRI in combination with spinal cord signal abnormalities usually suggest acquired inflammatory conditions such as multiple sclerosis, especially in the context of relapsing course and a positive response to steroid treatment. Adolescents with mutations in DARS can present with a comparable clinical picture, broadening the clinical spectrum of hypomyelination with brainstem and spinal cord involvement and leg spasticity.