Neuropathology Inflammation, Infection, Demyelination in the CNS
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1 Neuropathology Inflammation, Infection, Demyelination in the CNS PathoBasic Jürgen Hench
2 Inflammation in the CNS inflammation generally as a reaction against pathogen, substance, necrotic, or neoplastic cells if no causative agent found => idiopathic, autoaggressive
3 Most common "inflammatory reaction" encephalomalacia / ischemic brain necrosis "everything" dies in affected area phagocytic cells, mostly macrophages, infiltrate resorption takes place (weeks to months) hole remains (filled with CSF) astrogliosis at border ("glial scar") without connective tissue proliferation
4 Encephalomalacia - Neuropathological Diagnosis simple in autopsies (macroscopically soft) encephalo - malacia = brain softening histologically various stages of resorption examine the "borders" sometimes hemorrhagic component (lysis therapy, coumarin medication) sometimes septic infarcts granulocytes predominate potential histological detection of microbes
5 Encephalomalacia - Brain Biopsies should not be biopsied atypical infarct may present like tumor may mimic demyelination especially if very recent / white matter changes "atypical" astrocyte morphology at border Helpful stains: Holmes-Luxol: neurites, myelin (debris) neurofilament: neurites CNPase: oligodendrocytes, myelin GFAP: astrocyte morphology
6 Necrosis vs Demyelination no axons no myelin debris blood vessel necrosis, thrombosis sometimes hemorrhage, hemosiderin "naked" axons frequently spheroids myelin debris in macrophages CNPase loss more sensitive than luxol myelin staining
7 Infection of the CNS hard to diagnose requires extensive clinical and anamnestic workup bacteria fungi (immunosuppression) protozoa amoebae toxoplasma algae macroparasites cestodes nematodes
8 CNS Reactions to Infections General patters necrotizing purulent meningoencephalitis lymphocytic lymphohistiocytic histiocytic granulomatous Problem: unspecific necrotizing typical for toxoplasma (not specific!) purulent more common with (certain) bacteria lymphocytic more common with viruses little reaction / macrophage inclusion: T. whippelii
9 Most Important in Inflammatory CNS Disease Communicate with clinicians / radiologists! Serological / CSF markers may be more sensitive Native tissue microbiology / virology cultures DNA-based diagnostics typically higher sensitivity compared to anything based on FFPE don't "use up" specimen
10 "CNS Inflammation": Role of Neuropathologist Rule out an underlying brain infarct infection Wrong treatment possibly & quickly fatal! e.g. steroids and immunosuppressants + pathogen autoaggressive disorder without immunosuppression damage already caused hardly ever recovers fast & correct diagnosis important
11 CNS Infection: Special Stains PAS / DPAS microbial cell walls, parasitic extracellular matrix typically not glycogen => diastase resistant Grocott cell walls of bacteria, fungi, algae Brown-Brenn modified Gram's staining optimized for FFPE Fite / Ziehl-Neelsen acid-fast bacilli Warthin-Starry some bacteria invisible by other stains
12 CNS Infection: Immunohistochemistry Toxoplasma M. tuberculosis Spirochaete: several bacteria CMV VZV EBV (ISH)
13 Morphological Diagnosis in Inflammatory CNS Biopsies typically descriptive seldomly identification of pathogenesis / etiology less suited for frozen section examination high sampling bias pathogen density typically low
14 Helpful Stains - CNS Inflammation Leukocyte antigens to differentiate B/T-cells, histiocytes etc. mixed/reactive vs. "all the same": DD neoplastic Gömöri silver stain: blood vessel walls disrupted reticulin network in vasculitis lymphoma
15 Novelties cerebral protothecosis pathogenic algae, Prototheca spp., infect human brain case granulomatous encephalitis failure to diagnose = "neurosarcoidosis" always stain granulomas with Grocott necrotizing encephalitis under immune checkpoint inhibitor treatment possibly "over"-reaction of cytotoxic response seen in a case of lung cancer metastasis to brain
16 Conclusion of "CNS Inflammation" communicate with clinicians examine with every possibly methodology do it fast expect anything expect things not seen before! decide for treatment of cause infection, cancer immunosuppression / immunomodulation autoaggressive, demyelination no treatment infarct, drug side effect
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