Brain lesions in chronic granulomatous disease

Abstract

In chronic granulomatous disease (CGD) enzyme-deficient neutrophils and mononuclear cells lack the respiratory burst required for biocidal activity. Recurrent infections lead to granulomas in various organs but brain lesions are rare. In the present case, a 23-year-old male with numerous infections since early childhood died of overwhelming pulmonary aspergillosis. He first began to experience neurological deficits at the age of 17. Computerized tomography and magnetic resonance imaging revealed fleeting white matter lesions that were interpreted as multiple sclerosis (MS). At post mortem, three types of brain lesions were found: (1) Pigmented macrophages in perivascular spaces and the leptomeninges similar to those reported previously. They contained fine, golden-brown, lipofuscin-like material whose chemical composition included a sulfur peak by X-ray analysis. (2) Focal, well-demarcated, "burnt out" white matter lesions with loss of both myelin and axons and intense sclerosis. (3) Diffuse areas of mild pallor in the centrum ovale which spared the U fibers. The pigmented macrophages are characteristic of those seen in the periphery in CGD. The origin of the discrete, destructive white matter lesions is unclear. They may have resulted from: (i) earlier activity by CGD macrophages; (ii) previous infections due to sepsis or embolism; or (iii) possibly post-infectious encephalomyelitis. The more diffuse, mild, white matter lesions are attributed to edema. Evidence for MS, progressive multifocal leukoencephalopathy, or human immunodeficiency virus encephalitis was lacking. This case is presented to alert us to look more carefully for brain lesions in CGD, characterize them and to help determine their cause.

Sarcoidosis in Chronic Granulomatous Disease

“…14 Unlike the chronic type of optic nerve involvement in sarcoidosis, the acute form responds well to corticosteroid therapy, 15 as seen in patient 1. In contrast, central nervous system inflammation unrelated to infections is rare in CGD, and other than 1 report of brain lesions from postmortem findings, 16 all reported cases to date are related to fungal infections. 17 The prevalence of chorioretinal lesions in CGD is 23% to 35%, but they typically appear "punched out" and are associated with pigment clumping.…”

Chronic granulomatous disease: a review of the infectious and inflammatory complications

“…Various pathogens have been associated with brain abscess development including Scedosporium prolificans [81], Alternaria infectoria [82], Salmonella enterica subspecies houtenae [83], and Aspergillus [84,85]. Other complications associated with CGD include white matter disease [86], CNS granulomatous disease [87] and leptomeningeal, and focal brain infiltration by pigmented, lipid-laden macrophages [88]. Several reports of fungal brain infection [89], Aspergillus abscess resembling a brain tumor [90], spinal cord infection by Aspergillus [91] and fungal granuloma of the brain have been described [92].…”

CNS granulomatosis in a child with chronic granulomatous disease

“…In this case there was also a widespread involvement of the reticuloendothelial system. Had® eld et al 15 described a case in which pigmented macrophages laden with lipofuscin similar to those reported in CGD were found in the perivascular spaces and the leptomeninges; however, no infectious focus was found. Gentile et al 16 reported a case of focal cerebral lesions caused by aspergillus infection in children in which the source of infection was in the chest.…”