An inflammatory cell reaction may be present in the histopathological profile of virtually all diseases of the central nervous system (CNS), including neoplasms, and hypoxic/ischemic, neurodegenerative, and metabolic diseases. Preneoplastic or neoplastic inflammatory cell diseases may be difficult to distinguish from purely reactive infiltrates. Some of the most common pitfalls in dealing with inflammatory lesions lie in the failure to recognize primary demyelinating disease from atypical or neoplastic lymphoproliferative disease.

The nature of the inflammatory infiltrate may provide a clue as to the type of inflammatory disease. Neutrophils predominate in abscesses, most forms of meningitis except viral and fungal infections, and in toxoplasmosis and acute hemorrhagic leukoencephalitis. Lymphocytes predominate in viral meningitis, encephalitis, some chronic bacterial infections including rickettsial and Lyme disease and a number of immune-mediated disorders including Rasmussen's encephalitis, paraneoplastic encephalitis, lymphocytic hypophysitis, and others. Plasma cells are frequent in neurosyphilis, subacute sclerosing panencephalitis (SSPE), inflammatory pseudotumor and Castleman's disease. Epithelioid cells, giant cells, and granulomas should provoke the consideration of infections such as tuberculosis, mycotic infections, amebiasis due to Acanthameba, human immunodeficiency virus (HIV), and other immunologic disorders including sarcoidosis, granulomatous angiitis, rheumatoid nodules, particularly in paraspinal lesions, and Wegener's granulomatosis. Macrophages are frequent in demyelinating processes, progressive multifocal leukoencephalopathy, Whipple's disease, histoplasmosis, Rosai–Dorfman disease, and various xanthomatous lesions. Eosinophils are sometimes but all not always indicative of parasitic diseases, Langerhans cell histiocytosis, and are found in subdural hematomas. Microglial activation is common in viral encephalitis, Rasmussen's encephalitis but may also be conspicuous histologic component of infiltrating gliomas.