Neuropathology of acquired immunodeficiency syndrome (AIDS): an autopsy review.

In the brains and spinal cords of 153 adult patients dying with acquired immunodeficiency syndrome (AIDS) at New York and Memorial Hospitals a subacute encephalitis with multinucleated cells was present in 28% of all patients. This encephalitis was characterized by multinucleated cells primarily located in the white matter and associated with myelin pallor and sparse infiltrates of rod cells, macrophages, gemistocytic astrocytes and lymphocytes. The incidence per 12 month period ranged from 0 to 43% and significantly increased between 1983-84 (14%) and 1984-85 (43%). Recent virologic and pathologic studies suggest that this encephalitis may be caused by direct LAV/HTLV-III infection of the central nervous system (CNS). Cytomegalovirus encephalomyelitis and toxoplasmosis were the most common opportunistic infections (26% and 10%, respectively). Progressive multifocal leukoencephalopathy, herpes simplex ventriculitis, varicella-zoster leukoencephalitis and fungal infections were infrequent (less than 3% each). A nonspecific encephalitis with microglial nodules and with mild white matter changes occurred in 17%, vacuolar myelopathy in 29% and CNS lymphoma in 6%. Less than 20% of patients had either normal brains or terminal metabolic encephalopathies. This survey shows that neuropathologic complications of AIDS are frequent. Infections are the most common complication and are caused by probable LAV/HTLV-III infection, or by opportunistic organisms.

Akinetic mutism in a bone marrow transplant recipient following total-body irradiation and amphotericin B chemoprophylaxis. A positron emission tomographic and neuropathologic study.

We describe a case of akinetic mutism associated with diffuse cerebral leukoencephalopathy, which developed in a bone marrow transplant recipient following total-body irradiation and amphotericin B chemoprophylaxis. A trial of high-dose bromocriptine did not stimulate purposeful verbal or motor activity. Fluorine 18-fluorodeoxyglucose/positron emission tomographic studies, performed before and during bromocriptine therapy, demonstrated cerebral hypometabolism and treatment-related decreases in regional cerebral blood volume. We conclude that whole-brain or total-body irradiation may increase blood-brain barrier permeability to polyene antibiotics, and that high-dose therapy with dopamine agonists is unlikely to benefit patients with akinetic mutism due to diffuse white-matter lesions.

Perforation of the gastrointestinal tract in patients receiving steroids for neurologic disease.

Between 1980 and 1984, of 107 patients receiving 16 mg/d of dexamethasone for spinal cord compression, three (2.8%) developed gastrointestinal (GI) perforation and two (1.9%) GI bleeding; of 226 being tapered from 100 mg/d of dexamethasone, perforation occurred in six (2.7%) and GI bleeding in eight (3.5%). Of 125 patients with GI perforations treated between 1979 and 1986, 41 (33%) were on steroids, 24 for neurologic disease. Median duration of steroid therapy was 24 days; 20 (91%) of the neurologic patients perforated within 30 days. The steroid group had more free peritoneal involvement (p less than 0.00001), but fewer signs and symptoms of peritonitis (p less than 0.000001) than the nonsteroid group. Seventeen patients were receiving steroids for cord compression; they had significantly more rectosigmoid perforations (p less than 0.014) and associated constipation (p less than 0.000001) than the 108 remaining patients. GI perforation is a less well-recognized complication of steroid therapy in neurologic patients than is GI bleeding though it occurs as frequently, is more difficult to diagnose, and far more serious. In steroid-treated patients, prevention of constipation might avert this serious complication, while early diagnosis will improve the outcome.

Evidence for a cortical projection to the magnocellular basal nucleus in the rat: an electron microscopic axonal transport study.

A potential reciprocal projection from the cerebral cortex to the nucleus basalis was studied in the rat using a new stabilization method to adapt tetramethylbenzidine-horseradish peroxidase histochemistry for electron microscopy. Following insular or cingulate cortical injections of wheat germ agglutinin-horseradish peroxidase conjugate, anterogradely labeled axon terminals were seen making symmetric synaptic contacts with retrogradely labeled nucleus basalis neurons. Labeled axon terminals contained round vesicles. Most of such contacts were located on distal dendrites, although a small number of synapses on proximal dendrites and cell somata were seen as well. These findings suggest that there is a reciprocal, excitatory projection from the cerebral cortex to the nucleus basalis in the rat.

Stabilization of TMB reaction product for electron microscopic retrograde and anterograde fiber tracing.

Use of the highly sensitive tetramethylbenzidine (TMB) method of horseradish peroxidase histochemistry for electron microscopy has been limited by the solubility of the reaction product in aqueous and alcoholic solutions. We have found that following the TMB reaction with a diaminobenzidine-cobalt (DAB-Co) step causes the TMB crystals to become coated with DAB-Co. The resultant reaction complex is insoluble, and easily localized using electron microscopy. By systematically varying the pH at which the TMB reaction is run, the size and shape of the reaction complex can be controlled. The pH 4.0 reaction complex was the most suitable for electron microscopic identification of labeled structures less than 1.0 micron in diameter (e.g., axon terminals).

Leukoencephalopathy complicating intraventricular catheters: clinical, radiographic and pathologic study of 10 cases.

Ten patients with implanted Ommaya devices developed pericatheter white matter lesions, apparent as focal lucenaries on computed tomographic scan sometimes with contrast enhancement and/or mass effect. Some of the patients had significant neurological signs that related to the lesion. Three of the patients had not received cytotoxic drugs through the reservoir, and two had received neither intrathecal chemotherapy nor cranial radiation therapy. The process appears to be related to back flow of cerebrospinal fluid, with or without contained cytotoxic drugs into the periventricular white matter. Patients with elevated intracranial pressure are at particular risk. Removal of the catheter relieves the condition.