Dendritic pathology: an overview of Golgi studies in man.

Study of dendritic morphology through Golgi impregnation techniques has significantly furthered our understanding of neuronal development, maturation, and senescence. It has also provided insight into the pathogenesis of a wide spectrum of disease processes ranging from brain malformations to degenerative disorders. Golgi impregnation remains virtually the only method for demonstrating dendritic morphology. It delineates the profile of the individual neuron and its dendritic ramifications with unsurpassed clarity. Although it has been widely applied to experimental neuroscience involving animal tissue, its application to human material has been limited. This review summarizes the information on dendritic development and pathology in the human brain revealed by the use of the Golgi method.

Lymphadenopathy in an inner-city population consisting principally of intravenous drug abusers with suspected acquired immunodeficiency syndrome.

Generalized lymphadenopathy in intravenous drug abusers (IVDAs) at risk for AIDS has not been well studied. We have retrospectively analyzed the results of lymph node biopsies obtained from 27 patients referred to the Infectious Diseases Service for evaluation of generalized lymphadenopathy and suspected AIDS during a recent 18-month period. Fourteen of the patients were heterosexual IVDAs, 7 were male homosexual IVDAs, and 6 were male homosexual non-IVDAs. All of the patients were residents of the Bronx, New York. Mycobacterium tuberculosis (TB) was the most frequent diagnosis established on lymph node biopsies from IVDAs, in 12 out of 21 (57%). Tuberculous adenitis was not diagnosed in the 6 non-IVDAs. All TB patients were febrile, 11 (91%) had lost weight, and 10 (84%) had an abnormal chest roentgenogram. The 5TU PPD skin test, however, was reactive in only 2 (16%) of 12 patients. Tuberculosis is important to consider in patient populations with exposure histories to both AIDS and TB. The alarmingly high prevalence of TB in this drug addict population emphasizes the importance of lymph node biopsies with acid-fast smears and mycobacterial cultures in symptomatic IVDAs. Preventive antituberculosis therapy for HIV-positive persons, especially IVDAs, with a history of positive tuberculin reactions or of recent household contact should be seriously considered.

Brain morphology in Duchenne muscular dystrophy: a Golgi study.

Intellectual impairment associated with Duchenne muscular dystrophy is well recognized, although no consistent anatomic central nervous system lesions have been reported. The autopsy findings of 13 patients, ages 13-18 years, were reviewed. Intelligence quotients, ascertained in 5 patients, ranged from 46-79. Gross and microscopic examinations of brain and spinal cord revealed no consistent pattern of abnormalities. Neuropathology included neuronal loss and gliosis in spinal gray matter and tegmental brainstem, extensive Purkinje cell loss, mononuclear perivascular cuffing with cortical and subcortical gliosis, and cerebral heterotopia. Quantitative analysis of rapid Golgi impregnations of the visual cortex revealed significantly reduced dendritic length and branching of apical and basal dendrites from pyramidal neurons in 1 patient and less striking attenuation of dendritic arborization in 2 others. The literature suggests that the intellectual deficit in Duchenne muscular dystrophy is nonprogressive and unrelated to age or severity of muscle disease, although performance intelligence quotient may deteriorate with progressive muscle weakness. Golgi analysis suggested that abnormal dendritic development and arborization may underlie intellectual impairment. Although the pathogenesis of the cellular defect is not fully known, the coexistence of central nervous system and muscle pathology raises the possibility of a common molecular mechanism.

The association of infantile osteopetrosis and neuronal storage disease in two brothers.

Neurological manifestations in infantile osteopetrosis are common and varied, and not always attributable to the skeletal pathology. An unusual association of osteopetrosis with neuronal storage of ceroid lipofuscin is reported in two infant brothers born of nonconsanguinous parents. The first child became symptomatic at age 5 days with weight loss and vomiting. He had poor head control, hypertonia, and persistent fisting, and died at age 2 months. In the second infant, the diagnosis of osteopetrosis was confirmed at age 2 days. His neurological symptoms included blindness, deafness, and recurrent seizures. The infant died at 7 months of age. In both cases, autopsy confirmed the diffuse bony sclerosis with hepatosplenomegaly and extramedullary hematopoiesis. Neuropathological examination revealed cerebral atrophy with ventricular dilation, neuronal loss, and astrogliosis. The most striking finding was widespread accumulation of neuronal ceroid lipofuscin associated with formation of axonal spheroids. The optic nerves were compressed at the optic foramina and showed loss of myelinated axons and gliosis. Rapid Golgi impregnations of neurons from the calcarine cortex in the second infant were analyzed quantitatively, showing a reduction in the total dendritic length and number of branches. The primary defect in osteopetrosis is thought to be a lysosomal dysfunction involving the monocyte cell line from which osteoclasts are derived. Thus, the association in two brothers of osteopetrosis with accumulation of neuronal ceroid lipofuscin may not be fortuitous. The neuronal storage disorder in this instance probably reflects lysosomal dysfunction.

Massive cerebral edema associated with meningioma.

Cerebral edema is a well-known complication of malignant astrocytoma and metastatic brain tumour. Though far less frequent, the association of cerebral edema with meningioma is also recognized; this is unpredictable and sometimes out of proportion to tumour size. We describe three cases where the mass effect was due to severe edema, rather than the tumour itself and was responsible for a catastrophic clinical presentation. The mechanisms responsible for the development of severe edema with meningioma which have been previously proposed are reviewed. They include tumour size, location, histologic subtype, cellularity, mitotic activity, vascularity and the presence of excretory-secretory activity. None of these consistently correlate with cerebral edema. Our cases suggest that spontaneous hemorrhage into the tumour may be the common factor responsible for severe cerebral edema. It is stressed that though a decidedly rare complication, cerebral edema secondary to meningioma should be entertained in the differential diagnosis of acute neurologic deterioration of these patients.

Wernicke's encephalopathy in patients on peritoneal dialysis or hemodialysis.

Although the occurrence of Wernicke's encephalopathy (WE) in patients on dialysis is frequently alluded to, review of the literature reveals only 3 described cases. We describe 5 patients on dialysis who developed WE in the absence of alcoholism or other predisposing factors. The clinical diagnoses included uremic encephalopathy (2 patients), dysequilibrium syndrome (1), dialysis dementia (1), and brainstem hemorrhage (1). At postmortem examination, classic findings of WE were evident. The rarity of WE in patients on dialysis may in part be explained by studies indicating a genetic defect in transketolase activity. Patients on dialysis are also potentially at risk for thiamine deficiency because of anorexia, vomiting, and intravenous alimentation. Other factors altering thiamine requirements, such as glucose load or infections, may also contribute. Preventable and potentially curable, WE should be suspected in all patients on dialysis who have an unexplained neurological picture.

Glial fibrillary acidic protein (GFAP) in oligodendrogliomas: a reflection of transient GFAP expression by immature oligodendroglia.

Fourteen pure oligodendrogliomas were studied by light- and electronmicroscopy and immunohistochemistry to examine glial fibrillary acidic protein (GFAP) positivity in the tumors. To compare the immunohistochemical staining patterns of neoplastic oligodendroglia and immature oligodendroglia, myelination glia in the white matter of eight normal brains from children under 6 months of age were studied. The tumors possessed light microscopic and ultrastructural features characteristic of oligodendrogliomas. Microtubules were found in the cytoplasm of nine tumors on electronmicroscopy. In one, intermediate filaments and microtubules were observed in occasional tumor cells with polygonal crystalline structures in the cytoplasm. Using the peroxidase-antiperoxidase technique, all specimens were stained for GFAP, vimentin, S-100 and neuron-specific enolase (NSE). In nine tumors, variable numbers of cells with an oligodendroglial morphology reacted positively for GFAP. All tumors were positive for S-100 and negative for vimentin and NSE. The myelination glia in the eight normal brains stained positively for GFAP but not for vimentin. Vimentin is expressed by developing, reactive and neoplastic astrocytes. Thus, GFAP positivity combined with vimentin negativity in both neoplastic and immature oligodendroglia suggests that GFAP positivity in oligodendrogliomas may reflect the transient expression of this intermediate filament by immature oligodendroglia.

Fatal subarachnoid hemorrhage due to traumatic rupture of the vertebral artery.

Massive fatal subarachnoid hemorrhage maximal in the posterior fossa following minor trauma to the head and neck was first attributed to rupture of a vertebral artery (VA) in 1971. Typically, a young, healthy, but intoxicated man receives a minor blow and immediately collapses and dies within minutes. Early reports suggested an extracranial site of rupture with upward tracking of blood into the subarachnoid space. In few cases has this site of rupture been histologically verified, and more recent reports have drawn attention to intracranial rupture of the VA. We describe herein six cases in which the intracranial segment of the VA was the site of traumatic rupture, a site which can be demonstrated by careful examination of the most proximal segment of the VA attached to the brain in the course of routine brain removal.

Granulomatous inflammation in the acquired immune deficiency syndrome.

Granulomas were found in 16 biopsied specimens from eight patients with the acquired immune deficiency syndrome (AIDS), a disease characterized by a profound suppression of the T-cell arm of immunity. The pathogens were Mycobacterium avium-intracellulare (1), Mycobacterium tuberculosis (3), Histoplasma capsulatum (2), Candida albicans (1), and unidentified in one patient. The sites of granuloma formation included the lung in two, the pleura in one, the liver in three, the bone marrow in six, the skin in one, and the lymph node in three cases. The granulomas were epithelioid in nature, with aggregates of epithelioid histiocytes and macrophages. They were by and large small and loosely formed, with minimal or absent lymphocytic cuffing. Although it is a well-recognized concept that T-cell and macrophage interaction plays an important role in the granulomatous inflammatory response, granulomas have been produced in experimental animals independent of cell-mediated immune mechanisms. Granuloma formation in AIDS patients may well represent a clinical example of such a phenomenon.

Diffuse alveolar damage and interstitial fibrosis in acquired immunodeficiency syndrome patients without concurrent pulmonary infection.

Patients with acquired immunodeficiency syndrome (AIDS) characteristically present with repeated pulmonary infections. We present the pathologic findings in lung biopsy specimens from 12 patients with AIDS in whom the histologic spectrum ranged from mild diffuse alveolar damage to frank interstitial fibrosis. In all of these patients, there was no evidence of any concurrent infectious process in the lung. Diffuse alveolar damage is a pattern of response of the lung to many kinds of infectious processes and immunologic injury, both of which are potential possibilities in patients with AIDS. This study underscores the development of diffuse alveolar damage or interstitial fibrosis and their presentation as the sole histologic findings in lung biopsy specimens from patients with AIDS. We discuss the possibility that these changes may be long-term sequelae to repeated pulmonary infections with or without an immunologic defect.

A testicular tumor resembling the sex cord with annular tubules in a case of the androgen insensitivity syndrome.

Sex cord tumor with annular tubules (SCTAT) is a distinctive neoplasm with indifferent cells of sex cord derivation in a characteristic arrangement of ring-like tubules. Much attention has been drawn to its association with the Peutz-Jeghers syndrome (PJS) with reported occurrence of the tumor in the testis of a boy with PJS. The authors present two cases of the androgen insensitivity syndrome (AIS), one of the cases being distinctive in having a large multicystic tumor resembling the SCTAT in the immature gonad. Additionally, the focal areas of the tumor, the large Sertoli cells lining the tubules, resembled those of a large cell calcifying Sertoli cell tumor (LCCSCT) although no calcific areas were discernible. Although the occurrence of neoplasms like germinomas and tubular adenomas is well known in the AIS, SCTAT has hitherto not been reported in a gonad of the AIS. SCTAT has been placed under an "unclassified sex cord-stromal" category in the World Health Organization (WHO) Classification, yet, opinions are divided as to its origin from a granulosa or Sertoli cell, although an overlap in the histologic features of the two cell categories is to be anticipated in view of their homologous nature. In the case presented, the close resemblance of the tumor cells to the Sertoli cells of the uninvolved gonad would further support the concept of a Sertoli line of differentiation of the SCTAT.