Multiple sulfatase deficiency: clinical, neuropathological, ultrastructural and biochemical studies.

We describe the clinical, pathological, ultrastructural and biochemical features in the case of a 15-year-old boy with multiple sulfatase deficiency. Clinical abnormalities included hypotonia, retarded psychomotor development, hepatosplenomegaly, pigmentary degeneration of the retina, myoclonic seizures, aortic insufficiency and quadriplegia. Urinalysis revealed increased heparan sulfate. At necropsy, aortic and mitral valves revealed nodular thickening and periodic acid-Schiff (PAS)-positive, metachromatic granules in renal proximal tubules. The brain weighed 400 g and demonstrated cerebral and cerebellar atrophy with a retrocerebellar meningeal cyst. Cortical neurons contained periodic acid-Schiff-positive and cresyl violet-reactive granules. White matter demonstrated brown metachromasia and intense fibrillary gliosis. Conjunctival fibroblasts contained amorphous vacuoles with dense osmiophilic nucleoid cores. Pleomorphic extracellular, intraneural and intraglial inclusions were noted in the brain. Activities of arylsulfatase A, B and C were diminished markedly in autopsied tissue from brain, liver, and kidney (0, 0 and less than 10% of control activities, respectively). Partial deficiencies of iduronate sulfatase and heparan sulfatase were noted in different tissues. Variable decreased enzyme activities were expressed in leukocytes: arylsulfatase A, less than 33%; B, 40%; and C, 90%; heparan sulfatase, 2%; and iduronate sulfatase was not detectable. Near normal activities were found in cultured fibroblasts.

Necrotizing vasculitis of the nervous system in a patient with AIDS-related complex.

A patient with AIDS-related complex (ARC) presented with a fulminant neurologic syndrome suggestive of ascending myelopathy, and died approximately 48 h after admission to hospital. At necropsy, there was evidence of a severe necrotizing vasculitis affecting the nervous system most severely, with multifocal haemorrhagic necroses of the spinal cord and cauda equina. Although a rare intranuclear inclusion suggestive of herpesvirus infection was seen in the predominantly lympho-histiocytic infiltrate in and around blood vessel walls, the precise aetiology of the angiitis was not apparent. It may represent a response to AIDS virus infection of one or more components of the blood vessel wall.

The neuropathology of AIDS. UCLA experience and review.

The central nervous system (CNS) has been examined at autopsy in 89 patients who died of the acquired immune deficiency syndrome (AIDS), including 14 patients who died primarily of neurologic complications of the disease. A total of 66 brains (74%) showed significant pathologic abnormalities, with opportunistic infections including cytomegalovirus (14) and cryptococcal (11) infections, progressive multifocal leukoencephalopathy (6), toxoplasmosis (6), and histoplasma microabscesses (1). Incidental Mycobacterium avium-intracellulare infection was found in 4 cases. Simultaneous CNS infection by more than one microorganism was encountered in 5 patients. Subacute (microglial nodule) encephalitis-related to cytomegalovirus infection or possibly brain infection by the causative agent of AIDS was present in 56 cases. Primary CNS lymphoma was noted in 3 patients. Secondary CNS deposits of lymphoma were found in 1 patient, and another patient had lymphomatoid granulomatosis. Vascular complications were not infrequently seen, and included infarcts secondary to vessel occlusion and disseminated intravascular coagulation in 4 patients and intracranial hemorrhage of variable severity in 13. White matter changes included vacuolar myelopathy (3 cases), central pontine myelinolysis (1 case), and foci of calcified, necrotizing leukoencephalopathy in pontocerebellar fibers of the basis pontis (2 cases). These findings highlight the variety of CNS complications in AIDS, some of which are not associated with clinical manifestations. Nevertheless, characterization of all lesions may be important in understanding the neurologic sequelae of AIDS.