This study investigates the interdependence of inflammation, neurodegeneration, and disease progression in multiple sclerosis (MS) across different stages, with a focus on progressive MS. The research is based on detailed quantification of inflammatory cells in relation to axonal injury in 67 MS autopsies and 28 control cases. Key findings include: 1. **Inflammation and Neurodegeneration**: Inflammation is present in both acute/relapsing and progressive MS, with T- and B-cell infiltrates correlating with demyelinating lesion activity. Plasma cell infiltration is more pronounced in secondary progressive MS (SPMS) and primary progressive MS (PPMS), persisting even when T- and B-cell infiltrates decline. 2. **Association with Axonal Injury**: A significant association between inflammation and axonal injury is observed in all MS stages, including progressive MS. This correlation is maintained even when analyzing only progressive MS cases. 3. **Age and Disease Duration**: In older patients with long-disease duration, inflammatory infiltrates and axonal injury decline to levels similar to age-matched controls. Ongoing neurodegeneration in these patients is attributed to confounding pathologies like Alzheimer's or vascular disease. 4. **Pathologically Active and Inactive MS**: Among progressive MS patients, two distinct subgroups are identified: pathologically active progressive disease (with active or slowly expanding lesions) and pathologically inactive disease (with only inactive lesions). Pathologically active patients show higher densities of inflammatory infiltrates and axonal injury compared to pathologically inactive patients. 5. **Additional Pathologies**: In pathologically inactive MS patients, additional pathologies such as unusually thick demyelinated axons, synaptic patterns, and axonal or neuronal injury due to confounding diseases like Alzheimer's are observed. The study suggests that inflammation and neurodegeneration are closely linked in all MS lesions and stages, and that the disease processes may cease in aged patients with long-standing disease, provided there are no confounding age-related diseases.This study investigates the interdependence of inflammation, neurodegeneration, and disease progression in multiple sclerosis (MS) across different stages, with a focus on progressive MS. The research is based on detailed quantification of inflammatory cells in relation to axonal injury in 67 MS autopsies and 28 control cases. Key findings include: 1. **Inflammation and Neurodegeneration**: Inflammation is present in both acute/relapsing and progressive MS, with T- and B-cell infiltrates correlating with demyelinating lesion activity. Plasma cell infiltration is more pronounced in secondary progressive MS (SPMS) and primary progressive MS (PPMS), persisting even when T- and B-cell infiltrates decline. 2. **Association with Axonal Injury**: A significant association between inflammation and axonal injury is observed in all MS stages, including progressive MS. This correlation is maintained even when analyzing only progressive MS cases. 3. **Age and Disease Duration**: In older patients with long-disease duration, inflammatory infiltrates and axonal injury decline to levels similar to age-matched controls. Ongoing neurodegeneration in these patients is attributed to confounding pathologies like Alzheimer's or vascular disease. 4. **Pathologically Active and Inactive MS**: Among progressive MS patients, two distinct subgroups are identified: pathologically active progressive disease (with active or slowly expanding lesions) and pathologically inactive disease (with only inactive lesions). Pathologically active patients show higher densities of inflammatory infiltrates and axonal injury compared to pathologically inactive patients. 5. **Additional Pathologies**: In pathologically inactive MS patients, additional pathologies such as unusually thick demyelinated axons, synaptic patterns, and axonal or neuronal injury due to confounding diseases like Alzheimer's are observed. The study suggests that inflammation and neurodegeneration are closely linked in all MS lesions and stages, and that the disease processes may cease in aged patients with long-standing disease, provided there are no confounding age-related diseases.