Magnetic Resonance Imaging Correlates of Multiple Sclerosis Immunopathological Patterns.

OBJECTIVE: Histology reveals that early active multiple sclerosis lesions can be classified into 3 main interindividually heterogeneous but intraindividually stable immunopathological patterns of active demyelination (patterns I-III). In patterns I and II, a T-cell- and macrophage-associated demyelination is suggested, with pattern II only showing signs of a humoral immune response. Pattern III is characterized by inflammatory lesions with an oligodendrocyte degeneration. Patterns suggest pathogenic heterogeneity, and we postulated that they have distinct magnetic resonance imaging (MRI) correlates that may serve as biomarkers. METHODS: We evaluated in an international collaborative retrospective cohort study the MRI lesion characteristics of 789 conventional prebiopsy and follow-up MRIs in relation to their histopathologically classified immunopathological patterns (n = 161 subjects) and lesion edge features (n = 112). RESULTS: A strong association of a ringlike enhancement and a hypointense T2-weighted (T2w) rim with patterns I and II, but not pattern III, was observed. Only a fraction of pattern III patients showed a ringlike enhancement, and this was always atypical. Ringlike enhancement and T2w rims colocalized, and ringlike enhancement showed a strong association with macrophage rims as shown by histology. A strong concordance of MRI lesion characteristics, meaning that different lesions showed the same features, was found when comparing biopsied and nonbiopsied lesions at a given time point, indicating lesion homogeneity within individual patients. INTERPRETATION: We provide robust evidence that MRI characteristics reflect specific morphological features of multiple sclerosis immunopatterns and that ringlike enhancement and T2w hypointense rims might serve as a valuable noninvasive biomarker to differentiate pathological patterns of demyelination. ANN NEUROL 2021;90:440-454.

Neuroaxonal regeneration is more pronounced in early multiple sclerosis than in traumatic brain injury lesions.

The extent of irreversible neuroaxonal damage is the key determinant of permanent disability in traumatic and inflammatory conditions of the central nervous system (CNS). Structural damage is nevertheless in part compensated by neuroplastic events. However, it is unknown whether the same kinetics and mechanisms of neuroaxonal de- and regeneration take place in inflammatory and traumatic conditions. We analyzed neuroaxonal degeneration and plasticity in early multiple sclerosis (MS) lesions and traumatic brain injury (TBI). Neuroaxonal degeneration identified by the presence of SMI31+ chromatolytic neurons and SMI32+ axonal profiles were characteristic features of leukocortical TBI lesions. Axonal transport disturbances as determined by amyloid precursor protein (APP)+ spheroids were present in both TBI and MS lesions to a similar degree. Neurons expressing growth-associated protein 43 (GAP43) and synaptophysin (Syn) were found under both pathological conditions. However, axonal swellings immunopositive for GAP43 and Syn clearly prevailed in subcortical MS lesions, suggesting a higher regenerative potential in MS. In this context, GAP43+/APP+ axonal spheroid ratios correlated with macrophage infiltration in TBI and MS lesions, supporting the idea that phagocyte activation might promote neuroplastic events. Furthermore, axonal GAP43+ and Syn+ swellings correlated with prolonged survival after TBI, indicating a sustained regenerative response.

A 76-year-old woman with paraplegia.

A-76-year old woman was admitted to the hospital with paraplegia after a collapse at home. Magnetic resonance imaging showed white matter lesions from Th4 to L2 as well as large confluent white matter lesions in the cerebrum. Within 3 days, the patient's mental status decreased dramatically and she finally died on day 16 after her fall. Autopsy examination revealed an acute myeloid leukemia, which had not previously been diagnosed and which had never been treated. In the CNS, we found spread of myeloblasts in combination with acute demyelinating lesions which corresponded to the antibody- and complement-mediated pattern II of multiple sclerosis lesions. This case implies that association of acute myeloid leukemia and acute CNS demyelination needs to be discussed and suggests that AML patients need to be strictly monitored for CNS functions.

Persistence of immunopathological and radiological traits in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a heterogeneous autoimmune disease of the central nervous system. The identification of 4 different immunopathological subtypes of MS raises the question of whether these subtypes represent different patient subgroups that can be distinguished according to their leading mechanism of myelin destruction or whether this is a stage-dependent process in the development of lesions in a given patient. OBJECTIVE: To document intraindividual immunopathological and radiological homogeneity of 2 different lesions in a single patient with relapsing-remitting MS over time. DESIGN: Case report. SETTING: A neuropathological referral center for inflammatory demyelinating diseases of the central nervous system. PATIENT: A 49-year-old woman with clinically definite relapsing-remitting MS. MAIN OUTCOME MEASURES: Radiological and immunopathological analysis of MS lesions. RESULTS: Identical pathological findings in 2 different MS lesions separated by more than 2 years were identified. These lesions displayed similar and distinct radiological features on cranial imaging. CONCLUSIONS: In this patient we were able to show the same antibody/complement-mediated lesion pathological findings with compatible identical ring enhancement on T1-weighted magnetic resonance images and hypointense rims on T2-weighted images after an interval of 26 months. Our observations support the concept of intraindividual homogeneity of a given immunopathological MS subtype.