Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy.

One of the common neurological complications in patients with the acquired immune deficiency syndrome (AIDS) is a subacute encephalopathy with progressive dementia. By using the techniques of cocultivation for virus isolation, in situ hybridization, immunocytochemistry, and transmission electron microscopy, the identity of an important cell type that supports replication of the AIDS retrovirus in brain tissue was determined in two affected individuals. These cells were mononucleated and multinucleated macrophages that actively synthesized viral RNA and produced progeny virions in the brains of the patients. Infected brain macrophages may serve as a reservoir for virus and as a vehicle for viral dissemination in the infected host.

Is there a role for the autochthonous bubble in the pathogenesis of spinal cord decompression sickness?

Histological examination by light and electron microscopy of the spinal cords of four dogs rapidly perfusion-fixed after the onset of decompression sickness revealed the presence of numerous non-staining, space-occupying lesions that were absent in similarly prepared sections of control or ischemic spinal cords. We propose the hypothesis that these lesions are caused by the liberation of a gas phase. The possible significance of these lesions in the evolution of spinal cord dysfunction is discussed with reference to the principal theories of the pathogenesis of spinal cord decompression sickness.

Long-term changes in the spinal cords of patients with old poliomyelitis. Signs of continuous disease activity.

In a retrospective study, we reviewed sections from the spinal cords from eight patients, aged 36 to 61 years, who had had poliomyelitis and who died of nonneurologic diseases nine months to 44 years (mean, 20.7 years) after the acute poliomyelitis infection. Five patients had stable postpoliomyelitis deficits without new symptoms, and three patients had new slowly progressive muscle weakness defined as postpoliomyelitis progressive muscular atrophy (PPMA). Representative spinal cord sections matched the patients' clinical involvement in both groups. Control tissues from ten patients with amyotrophic lateral sclerosis and five with spinocerebellar degeneration were examined simultaneously. The spinal cord segments from all patients who had had poliomyelitis showed loss or atrophy of motor neurons, severe reactive gliosis (disproportional to the neuronal loss), and a surprising mild to moderate perivascular and interparenchymal inflammation. There was no difference in these pathologic changes between the patients with stable postpoliomyelitis deficits and those with PPMA. Additional findings were axonal spheroids (dystrophic axons) and occasional chromatolytic neurons in the spinal cord of patients with PPMA. Corticospinal tracts were spared.

Cerebral sparganosis.

Cerebral sparganosis is caused by the migrating larva of Spirometra mansonoides. Only seven cases have been reported worldwide. We here report the second known case in the United States. Including our case, ages ranged from 24 to 46 years. Men and women were equally affected. Headache, convulsions, focal neurologic signs, and peripheral eosinophilia were common. CT often revealed an enhancing mass. Surgical resection of the parasitic granuloma gave excellent results. often revealed an enhancing mass. Surgical resection of the parasitic granuloma gave excellent results.

Peripheral neuropathy in hypereosinophilic syndrome.

We evaluated seven patients with the hypereosinophilic syndrome (HES) to define the clinicopathologic spectrum of the peripheral neuropathy. Clinically, three had evident polyneuropathy; the others were asymptomatic, although they had electrophysiologic evidence of neuropathy. Nerve conduction studies and EMG were compatible with axonal neuropathy. Morphometry of sural nerves from four patients ranged from normal to marked axonal loss, more prominent in large myelinated fibers. Demyelination was rare, and there was no evidence of vasculitis. Neuropathy may be produced by an eosinophil-derived neurotoxin.

Peripheral neuropathy in abetalipoproteinemia.

We studied the peripheral neuropathy of three sisters with abetalipoproteinemia. Clinically, a sensory neuropathy progressively increased in severity. There was a diminution in the amplitude of sensory action potentials and a slight-to-moderate slowing in maximum sensory conduction velocity, initially most marked in distal portions of the nerves. Motor conduction was normal, although EMG indicated subclinical signs of partial chronic denervation. The sural nerves showed a decreased number of large fibers (greater than 7 micron); in the patient with the neuropathy of shortest duration, small fibers and clusters of regenerating fibers indicated regeneration. In the two patients with advanced neuropathy, one-half the segments of teased fibers showed paranodal demyelination. Also, unmyelinated fibers showed evidence of regeneration.

Clinical significance of types of cerebellar amyloid plaques in human spongiform encephalopathies.

We report three patients with both spongiform encephalopathy and cerebellar amyloid plaques; one showed kuru-like plaques and was diagnosed as having Creutzfeldt-Jakob disease (CJD), and two had multicentric plaques and were diagnosed as having Gerstmann-Sträussler-Scheinker disease (GSSD). Evaluation of these cases and review of others previously reported suggests a clinicopathologic correlation between type of cerebellar plaque and neurologic clinical course. CJD patients who showed kuru-like plaques generally had disease with early onset (average age, 49.1 years) and long duration (average, 34 months), as compared with CJD patients without kuru-like plaques. GSSD patients usually had multicentric cerebellar plaques, and cases were usually familial, had early age of onset (average, 42.7 years), and were of long duration (average, 73 months). Myoclonus was infrequent in GSSD patients and pathologically spongiform change was minimal; spinal tract degeneration was common.

AIDS-associated progressive multifocal leukoencephalopathy (PML): comparison to non-AIDS PML with in situ hybridization and immunohistochemistry.

We studied brain sections from 10 patients with the acquired immunodeficiency syndrome (AIDS) and progressive multifocal leukoencephalopathy (PML) by in situ hybridization with a biotin-labeled JC virus (JCV) DNA probe and by immunohistochemistry using antibody against the JCV capsid antigen. We compared the results with brain sections studied in the same fashion from 10 PML patients without AIDS. The pathology of JCV infection in AIDS was similar to non-AIDS PML except for minor differences in degree. AIDS-associated pathologic material showed a greater tendency toward necrosis and a higher density of JCV-infected cells. Replication of JCV was restricted to glial cells in all tissue studied. Bizarre astrocytes were less frequent in the AIDS patients, and perivascular inflammatory cells were more frequent. We could not demonstrate JCV in macrophages or microglial cells known to harbor HIV infection. In situ hybridization with nonradioactive probes serves as a useful technique for the confirmation of PML in AIDS.

Hemangiopericytoma of the central nervous system: a review of 94 cases.

Ninety-four cases of central nervous system hemangiopericytoma (CNS-HPC) are reported. Hemangiopericytoma was found more commonly in men than in women. The mean age at diagnosis was 40.9 years for men and 47 years for women. The tumor was found throughout the entire CNS, usually superficially and closely related to the meninges. Based on multiple histologic variables, the original tumors were divided into differentiated (n = 67) and anaplastic (n = 27). Anaplastic HPC was characterized by the presence of necrosis and/or greater than five mitoses per ten 400x microscopic fields, and at least two of the following microscopic features: hemorrhage, moderate to high nuclear atypia, and moderate to high cellularity. For those patients known to be dead, median survival time was 144 months for differentiated HPC and 62 months for anaplastic HPC. Fifty-seven (60.6%) patients had one or more recurrences and metastasis developed in 22 (23.4%). Thirty-five of 56 patients with differentiated HPC had recurrence, while 22 of 26 patients with anaplastic HPC had recurrence. Bone, liver, lung, central nervous system, and abdominal cavity were the most common sites of metastasis. Postoperative radiotherapy and/or chemotherapy were significantly associated with increased patient survival time.

Bubble-induced dysfunction in acute spinal cord decompression sickness.

Five anesthetized dogs undertook a chamber dive, on air, to 300 feet of seawater for 15 min. After the dive, spinal cord decompression sickness was detected by recording a reduced amplitude of the somatosensory evoked potential compared with predive base-line values. After the diagnosis of decompression sickness and rapid perfusion fixation of the animal, the spinal cord was removed and examined histologically. Numerous space-occupying lesions (SOL) that disrupted the tissue architecture were found in each cord, mainly in the white matter. The size and distribution of the SOL were determined using computerized morphometry. Although SOL occupied less than 0.5% of the white matter volume, we tested a number of algorithms to assess whether the SOL may have been directly involved in the loss of spinal cord function that followed the dive. We determined that the loss of somatosensory evoked potential amplitude may be attributed to the SOL if 30-100% of the spinal cord fibers that they displaced were rendered nonconducting. A number of possible mechanisms by which SOL may interfere with spinal nerve conduction are discussed.

Optic neuropathy due to brain abscess.

A 26-year-old man went blind as part of a multifocal central nervous system disease. Bilateral optic nerve head pallor developed four weeks later. There had been no papilledema. In this setting, the appearance of optic atrophy without preceding papilledema in part led to the clinical diagnosis of severe disseminated encephalomyelitis. At autopsy multiple brain abscesses were found, including an area of inflammation within the chiasm.

Ethnic distribution of primary central nervous system tumors in Washington, DC, 1971 to 1985.

An ethnic analysis was made of 8947 cases of primary central nervous system (CNS) tumors seen at the Armed Forces Institute of Pathology (AFIP), Washington, DC, from 1971 to 1985. Results showed a slightly higher frequency of primary CNS tumors in whites than in blacks with a white:black case ratio of 9:1 against the white:black population ratio in the United States of 7.4:1. Gliomas appeared to be twofold more frequent in whites than in blacks with a white:black case ratio of 12.1:1. However, meningiomas and pituitary adenomas were more common in blacks with a white:black case ratio of 6.7:1 and 4.2:1, respectively. When these results were compared with the results of a previous identical study using similar materials collected at AFIP from 1958 to 1970, the relative paucity of gliomas and higher frequency of meningiomas and pituitary adenomas in American blacks is again confirmed, thus re-emphasizing the importance of genetic factors in the genesis of primary CNS tumors. The remarkable decreasing white:black case ratio of primary CNS tumors as a whole (9:1 compared with 13.7:1) since 1970 probably reflects the socioeconomic improvement of American blacks during the same period.

Neuromuscular diseases associated with human immunodeficiency virus infection.

The types of neuromuscular diseases associated with human immunodeficiency virus (HIV) infection are described. Our classification includes: (1) six subtypes of peripheral neuropathies--namely, acute Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, mononeuritis multiplex, an axonal, predominantly sensory, painful polyneuropathy, a sensory ataxic neuropathy due to ganglioneuronitis, and an inflammatory polyradiculoneuropathy presenting as cauda equina syndrome; (2) inflammatory myopathies (e.g., polymyositis); and (3) other less common neuromuscular manifestations, such as type II muscle fiber atrophy and nemaline myopathy. Although the exact incidence of clinical and subclinical neuromuscular diseases in HIV-positive and acquired immunodeficiency syndrome (AIDS) patients is unknown, estimates vary from 15 to almost 50% of such individuals. The type of neuropathy or myopathy related to the specific stage of HIV infection, the pathogenetic mechanisms involved, and effective therapies are discussed. A neuromuscular disease not only occurs in patients with AIDS and AIDS-related complex, but it can coincide with HIV seroconversion or it can be the only clinical indication of a chronic silent HIV infection. Chronic asymptomatic HIV infection should be considered in the differential diagnosis of certain acquired inflammatory polyneuropathies or myopathies. Precautions needed when doing electromyographic studies are discussed.

Myosin ATPase intermediate density fibers for diagnosis of reinnervation.

Myosin ATPase (pH 9.4) differentiates two muscle fiber types in healthy human muscle, while diseased muscle often contains intermediate density fibers (IDFs). We evaluated the possibility that, since almost all IDFs in pathologic muscle biopsies are changing type after reinnervation by a motor axon of the opposite type, IDFs are useful in diagnosis. In a retrospective study of 208 muscle biopsies, IDFs were seen as often as were esterase-positive angular atrophic fibers (EPAAFs). In denervation identified by EMG and by histopathology, EPAAFs and IDFs were found much more often than were other indicators. Of biopsies diagnosed without use of IDFs as minimal histologic change or no pathologic diagnosis, 16% had IDFs with sparse EPAAFs and 21% had IDFs without EPAAFs, suggesting mild denervation with rapid reinnervation. IDFs correlate well with EPAAFs, identifying reinnervated versus denervated fibers. Type grouping reveals completed reinnervation change that may be many years old, while IDFs are changing type when biopsied and thus reveal recent reinnervation and preceding denervation. IDFs usefully belong with the histochemical indicators used to evaluate muscle disease.

Conduction studies in peripheral cat nerve using implanted electrodes: III. The effects of prolonged constriction on the distal nerve segment.

Electrophysiological properties were monitored in detail in chronically constricted peripheral nerves by implanted, multicontact nerve cuff electrodes and correlated with morphometric histology in selected cases. The physiological and histological responses in nerve to a range of constricting cuffs of standard sizes were readily graded. The initial response to any significant constriction was a transient, focal conduction slowing or block at the constriction, followed by more protracted distal effects; the latter ranged from loss of excitability consistent with "dying-back" degeneration to reductions in conduction velocity consistent with histologically observed atrophy. Smaller myelinated fibers tended to have similar but less pronounced changes than larger diameter fibers. Recordings from ventral and dorsal roots showed that distal degeneration was more pronounced in motor than in sensory fibers of similar caliber. Electronmicroscopical measurements showed that basal laminas were relatively preserved around even the most atrophic and demyelinated axons. Perimeter measurements of the basal lamina could be used to estimate the diameter of the original nerve fiber.

Arterial gas embolism as a pathophysiologic mechanism for spinal cord decompression sickness.

A continuous infusion of air (1.0 ml.min-1) was delivered via a fine aortic cannula into the arterial circulation of 7 anesthetized dogs until no spinal cord function could be elicited by somatosensory evoked potentials. The animals were then rapidly perfusion-fixed and the spinal cords removed for histological examination. The appearance of the embolized cords differed substantially from eight spinal cords injured by fulminant decompression sickness (DCS). The embolized cords appeared essentially normal whereas the DCS cords featured extravascular, nonstaining, space-occupying lesions (SOLs) scattered throughout the cord, mainly in the white matter. Two spinal cords injured by DCS with a delayed onset (30 min from surfacing) appeared similar to the embolized cords. These findings are compatible with the hypothesis that two mechanisms are involved in the onset of spinal cord DCS. Fulminant disease is associated with SOLs, which are probably caused by the in situ evolution of a gas phase. Disease with a delayed onset is more likely to be caused by an ischemic mechanism, which in the acute phase is histologically indistinguishable from gas embolism.

Conduction studies in peripheral cat nerve using implanted electrodes: II. The effects of prolonged constriction on regeneration of crushed nerve fibers.

Arrays of chronically implanted electrodes were used to examine the time course of elongation and maturation of peripheral nerve fibers in the cat after crush of the tibial nerve in the proximal calf. Regeneration after crush alone was compared with crush 5 mm proximal to a tight constriction of the nerve. Regeneration was monitored by the progression of excitability along the electrode arrays on the tibial and plantar nerves. The sensitivity was sufficient to record the averaged activity in single nerve fibers allowing detection of the earliest regeneration. The diameters of the fastest regenerating fibers were estimated from the conduction velocity proximal to the site of crush. Both after crush alone, and after crush constriction, small myelinated fibers regenerated in front of large fibers. The rate of elongation after crush alone was 3.2 mm/day, whereas it was slower (P less than 0.02) distal to crush + constriction (2.2 mm/day). In both lesions, the extrapolated delay to onset of regeneration was 8 days. In observations up to 300 days after crush, maturation was delayed or impaired by the constriction, and the compound nerve action potential had a smaller amplitude and a dispersed shape. Transverse sections of nerves after crush + constriction showed a diminished number of large and an increased number of small fibers compared with crush alone, possibly due to persistent branching of regenerated fibers. After both crush alone and crush + constriction, regenerated fibers had similar g ratios, suggesting that myelination developed fully in fibers of diminished diameters.

Spinal metastases. A rare mode of presentation of brain tumors.

An analysis of more than 18,000 primary central nervous system (CNS) tumors revealed only 18 cases (0.01%) in which dropped spinal metastases had caused the presenting symptoms. This group included 11 males and 7 females in whom there was no history of surgical intervention or irradiation. Primitive neuroectodermal tumors ( PNET , medulloblastoma), comprised the largest group (11 patients) followed by high-grade astrocytomas (anaplastic and glioblastoma) (5 patients). One case each of germinoma and ependymoma were also identified. The clinicopathologic data of these cases, and a brief review of the literature are presented.

Polymyositis associated with AIDS retrovirus.

Two homosexual men were initially seen with polymyositis as the only manifestation of the acquired immunodeficiency syndrome (AIDS) retrovirus infection. They developed AIDS-related complex a few weeks later and typical AIDS two to six months after onset of muscle weakness. By use of anti-human T-cell lymphotropic virus type III antiserum and monoclonal antibodies to lymphocyte subsets in an immunofluorescence technique, viral antigens were found in the OKT4-positive lymphoid cells surrounding muscle fibers and invading the endomysia septa. We concluded that an initial infection with the AIDS retrovirus can be associated with polymyositis, which may be the first clinical manifestation of an impending AIDS-related complex or AIDS.

Slow virus-macrophage interactions. Characterization of a transformed cell line of sheep alveolar macrophages that express a marker for susceptibility to ovine-caprine lentivirus infections.

Visna-maedi of sheep and arthritis encephalitis of goats are slowly progressive diseases caused by serologically related lentiviruses. Lesions are inflammatory and can occur at one or many sites including the central nervous system, lungs, joints, and mammary glands. The viruses replicate in macrophages, and in the animal large numbers of infected macrophages can be obtained from inflamed tissues. To study virus-macrophage interactions we transformed sheep alveolar macrophages, which are natural virus target cells, with simian virus 40 and produced a macrophage cell line. The transformed cells grew into density-dependent monolayers and were subcultured after trypsin dissociation. They maintained histochemical and physiologic properties of macrophages as well as the ability to support replication of the lentiviruses. Rabbit antisera to these cells reacted with blood monocytes and only selected populations of tissue macrophages, including those in lung, synovium, mammary gland, and spleen. Microglia, Kupffer cells, and connective tissue histiocytes were not recognized by the sera. Since the tissues in which virus localizes in infected animals are the same as those recognized by the sera, the antimacrophage serum may provide an immunologic marker for virus-susceptible macrophages in the animal.