Nos2-/- mice infected with M. tuberculosis develop neurobehavioral changes and immunopathology mimicking human central nervous system tuberculosis.

BACKGROUND: Understanding the pathophysiology of central nervous system tuberculosis (CNS-TB) is hampered by the lack of a good pre-clinical model that mirrors the human CNS-TB infection. We developed a murine CNS-TB model that demonstrates neurobehavioral changes with similar immunopathology with human CNS-TB. METHODS: We injected two Mycobacterium tuberculosis (M.tb) strains, H37Rv and CDC1551, respectively, into two mouse strains, C3HeB/FeJ and Nos2-/- mice, either into the third ventricle or intravenous. We compared the neurological symptoms, histopathological changes and levels of adhesion molecules, chemokines, and inflammatory cytokines in the brain induced by the infections through different routes in different strains. RESULTS: Intra-cerebroventricular infection of Nos2-/- mice with M.tb led to development of neurological signs and more severe brain granulomas compared to C3HeB/FeJ mice. Compared with CDC1551 M.tb, H37Rv M.tb infection resulted in a higher neurobehavioral score and earlier mortality. Intra-cerebroventricular infection caused necrotic neutrophil-dominated pyogranulomas in the brain relative to intravenous infection which resulted in disseminated granulomas and mycobacteraemia. Histologically, intra-cerebroventricular infection of Nos2-/- mice with M.tb resembled human CNS-TB brain biopsy specimens. H37Rv intra-cerebroventricular infected mice demonstrated higher brain concentrations of inflammatory cytokines, chemokines and adhesion molecule ICAM-1 than H37Rv intravenous-infected mice. CONCLUSIONS: Intra-cerebroventricular infection of Nos2-/- mice with H37Rv creates a murine CNS-TB model that resembled human CNS-TB immunopathology, exhibiting the worst neurobehavioral score with a high and early mortality reflecting disease severity and its associated neurological morbidity. Our murine CNS-TB model serves as a pre-clinical platform to dissect host-pathogen interactions and evaluate therapeutic agents for CNS-TB.

Radiologic Findings in Polyarticular Amyloid Arthropathy and Myopathy in Multiple Myeloma: A Case Report.

BACKGROUND Amyloid arthropathy and myopathy are complications of amyloidosis that can be associated with non-specific imaging findings, which may be challenging to interpret. The report is of a case of polyarticular amyloid arthropathy and myopathy in a 56-year-old man with multiple myeloma and includes a description of the radiographic, computed tomography (CT), and magnetic resonance imaging (MRI) findings. CASE REPORT A 56-year-old man with multiple myeloma presented with chronic polyarticular pain and swelling. Soft tissue thickening of the wrist and knee were found on MRI to be of intermediate T1 weighted imaging (T1WI) and low to intermediate T2 weighted imaging (T2WI) signal intensity. Denervation muscle edema seen in the thenar muscles on the MRI of the right wrist were associated with carpal tunnel syndrome secondary to amyloid deposition. Soft tissue lesions in the periarticular regions of both hip joints were contiguous with subchondral bone lesions. Diffusely scattered myeloma lesions were shown as hyperintense on short tau inversion recovery (STIR) MRI imaging throughout the appendicular and axial skeleton, with vertebral compression fractures. Bilateral iliopsoas involvement with hypertrophy and abnormal surrounding fat reticulated signal intensity was consistent with amyloid myopathy. The patient had a pathological fracture of the right femoral neck and underwent surgical fixation. Histology of the right femoral head confirmed amyloid deposits. CONCLUSIONS Because the clinical presentation and imaging findings of musculoskeletal amyloidosis can be nonspecific, they can result in delay in diagnosis and treatment. Early radiologic identification of polyarticular amyloid arthropathy and myopathy should prompt confirmatory biopsy to confirm the diagnosis.