During the process of resolution, the inflammatory cells disappear in almost the reverse order as they had appeared. Neutrophils begin to disintegrate by the fourth to fifth day, and soon thereafter, with treatment, no new ones appear. Lymphocytes, plasma cells, and macrophages disappear more slowly, and a few lymphocytes and mononuclear cells may remain in small numbers for several months. The completeness of resolution depends on the stage at which the infection is arrested. If it is controlled in the very early stages, there may not be any residual change in the arachnoid; following an infection of several weeks’ duration, there is a permanent fibrous overgrowth of the meninges, resulting in a thickened, cloudy, or opaque arachnoid and often in adhesions between the pia and arachnoid and even between the arachnoid and dura.
From the earliest stages of meningitis, changes are also found in the small and medium-sized subarachnoid arteries. The endothelial cells swell, multiply, and crowd into the lumen. This reaction appears within 48 to 72 h and increases in the days that follow. The adventitial connective tissue sheath becomes infiltrated by neutrophils. Foci of necrosis of the arterial wall sometimes occur. Neutrophils and lymphocytes migrate from the adventitia to the subintimal region, often forming a visible layer. Later there is subintimal fibrosis. This vascular reaction is a striking feature of nearly all types of subacute and chronic infections of the meninges but most notably of tuberculous and syphilitic meningitis (Heubner arteritis). In the veins, swelling of the endothelial cells and infiltration of the adventitia also occur. Subintimal layering, as occurs in arterioles, is not observed in veins, but there may be a diffuse infiltration of the entire wall of the vessel. It is in veins so affected that focal necrosis of the vessel wall and mural thrombi are most often found. Thrombophlebitis of the larger cortical veins, which may be part of this process, does not usually develop before the end of the second week of the infection.
The unusual prominence of the vascular changes may be related to their anatomic peculiarities. The adventitia of the subarachnoid vessels, both of arterioles and venules, is actually formed by an investment of the arachnoid membrane, which is invariably involved by the infectious process. Thus, in a sense, the outer vessel wall is affected from the beginning by the inflammatory process—an infectious vasculitis. The much more frequent occurrence of thrombosis in veins than in arteries is probably accounted for by the thinner walls and the slower current of blood flow in the former.
Although the spinal and cranial nerves are surrounded by purulent exudate from the beginning of the infection, the perineurial sheaths become infiltrated by inflammatory cells only after several days. Exceptionally, there is infiltration of the endoneurium and degeneration of myelinated fibers, leading to the appearance of fatty macrophages and fibroblasts. More often, there is little or no acute damage to nerve fibers traversing the subarachnoid space. Occasionally cellular infiltrations may be found in the optic nerves or olfactory bulbs.
The arachnoid membrane tends to serve as an effective barrier to the spread of infection into the adjacent subdural compartment, but some secondary reaction in this space may occur nevertheless (subdural effusion). Subdural effusions occur far more often in infants than in adults; according to Snedeker and coworkers, approximately 40 percent of infants with meningitis younger than 18 months of age develop effusions. As a rule, there is no subdural pus and no bacteria, only a sterile yellowish exudate. In proportion of cases, small amounts of fibrinous exudate are found in microscopic sections that include the spinal dura.