Depressed cell-mediated immunity in patients with primary intracranial tumors. Characterization of a humoral immunosuppressive factor.

Tumor immunity in patients with primary intracranial tumors was assessed in relation to the general status of host immunocompetence. Lymphocyte sensitization to tumor-specific membrane antigens was demonstrated by the proliferative response of lymphocytes in the presence of autochthonous tumor cells. Paradoxically, one-half of the patients could not be sensitized to a primary antigen, dinitrochlorobenzene; existing delayed hypersensitivity was also depressed, as measured by skin tests and lymphocyte transformation in response to common antigens. A heat-stable factor in patients' sera blocked cell-mediated tumor immunity. In addition, these "enhancing" sera consistently suppressed the blastogenic response of autologous and homologous lymphocytes to phytohemagglutinin and to membrane antigens on allogeneic cells in the one-way mixed lymphocyte culture. When patients' leukocytes were washed and autologous plasma replaced with normal plasma, reactivity in the mixed lymphocyte culture increased to normal values. In vitro immunosuppressive activity in patients' plasma or sera correlated with depressed delayed hypersensitivity. After removal of the tumor, suppressor activity disappeared. IgG fractions of patient sera contained strong immunosuppressive activity. These data suggest that the suppressor factor may be an isoantibody elicited by the tumor that also binds to receptors on the lymphocyte membrane. In addition to specifically blocking cell-mediated tumor immunity, enhancing sera may broadly depress host immunocompetence.

Phagocytic astrocytes and neurons in old encephalomalacia.

Cytoplasmic accumulation of hemosiderin was observed within astrocytes and neurons as well as in other phagocytes associated with old encephalomalacia. The first patient was 3 years old when she died with malnutrition and superimposed infection. A cortical infarct had been caused by an old thrombus in a small artery. The second case was a 9-year-old girl who had old encephalomalacia in the pineal region after extirpation of a pineoloma. The third patient was a 22-year-old man who had a cortical infarct from an embolus associated with chronic rheumatic endocarditis. Granules of hemosiderin had accumulated within the perikaryon of many astrocytes and other phagocytes in all cases, and in a few neurons in the second instance. Review of the literature reveals that cytoplasmic accumulation of particulate matter has been described infrequently with regard to neuroepithelial derivatives. Our findings indicate that astrocytes and neurons as well as derivations of mesenchyme may act as phagocytes of old blood.

Melanotic neuroectodermal tumors of the brain and skull.

A case of melanotic neuroectodermal tumor in the cerebellum of a 21-year-old man is presented. Melanin was found mainly in small neoplastic cells rather than in large epithelioid cells. The tumor also contained neurons, as well as neoplastic tissue of ependyma, choroid plexus; and astrocytes. We propose that this neuroectodermal tumor resulted from a combination of cells originating in the neural crest and in the neural tube. The small cells have been described as medulloblasts, but they may be poorly differentiated ependymal cells, or, sympathicoblasts. The presence of pigment in these cells is compatible with an origin in the neural crest. The so-called melanotic progonoma, occurring most often in the maxilla of infants, is reviewed in relation to the melanotic neuroectodermal tumor of the brain. The tumor in facial bone occurs in adults as well as infants, in locations other than the maxilla, and has malignant forms. Melanotic neuroectodermal tumors, whether in brain or bone, are therefore similar in behavior as well as histologic appearance. The finding of similar tumors in these different locations is readily explained embryologically.

Pigmented ganglioneuroblastoma: relation of melanin and lipofuscin to schwannomas and other tumors of neural crest origin.

An unusual case of ganglioneuroblastoma containing melanin is presented. Electron microscopy revealed various stages of development of melanosomes in neoplastic cells of Schwann, the first direct demonstration in human material that these cells are malanogenic. The frequent occurrence of neuromelanin in autonomic ganglia and in ganglioneuromas is interpreted as the presence of altered lipofuscin. Review of ultrastructural and other observations indicates a relation between various pigmented tumors, the cell of Schwann, and other cells arising from the neural crest.

Subarachnoid spinal hemorrhage in a case of systemic lupus erythematosus.

A 50-year-old woman with an 18-year history of systemic lupus erythematosus (SLE) died after an exacerbation of the illness, characterized by deteriorating mentation and right hemiplegia. Necropsy revealed massive spinal subarachnoid hemorrhage resulting from aneurysmal dilation and rupture of the posterior spinal artery, which was involved by vasculitis. The left parietal lobe and internal capsule contained recent infarcts. To our knowledge, this is the first reported case of SLE with spinal subarachnoid hemorrhage revealed by necropsy.

Combined congenital vascular anomalies and neuroepithelial (colloid) cysts.

We present two unique cases of intracranial congenital lesions of different origins. A 29-year-old woman had an angioma of the choroid plexus of the third ventricle and paraventricular region; a small neuroepithelia cyst was also included in the lesion. This case is the first known description of a choroidal angioma in the third ventricle. The other patient, a 39-year-old woman, had a ruptured saccular aneurysm at the junction of the anterior communicating and left anterior cerebral arteries, a cerebellar hemangioma, and a small neuroepithelial cyst with numerous papillary infoldings in the pineal region. The presence of choroid plexus in this cyst is further evidence of a developmental malformation. Review of the literature disclosed that vascular malformations and neuroepithelial cysts are occasionally associated with other congenital anomalies. The findings support the congenitally derived nature of these lesions.

Melanosis of the choroid plexua.

A unique case of melanosis of the choroid plexus in a 74-year-old man who died of hypertensive cardiovascular disease is described. The cerebral lesion did not cause symptoms. The proposed pathogenesis is the conversion of choroidal epithelial lipofuscin into melanin. Our findings also may explain the origin of a previously reported primary malignant melanoma of the choroid plexus and of black cortical adenomas of the adrenal gland.

Multiple neuroepithelial (colloid) cysts: association with other congenital anomalies.

A 4-year-old boy had three neuroepithelial cysts, one in the third ventricle and two in the supratentorial subarachnoid space, and also had stenosis of the cerebral aqueduct, obstructive internal hydrocephalus, frontoethmoidal meningoencephalocele, and right microphthalmia. The occurence of these combined lesions supports the congenitially derived nature of the cysts. The cysts originated from neuroepithelium including ectopic ependyma-lined structures. The exception may be those cysts arising in or near the floor of the third ventricle; these cysts could be derived from the cleft of Rathke's pouch, an endodermal derivative. Folding of the neuroepithelium in contact with mesenchyma or neuroglial tissue is proposed as the mode of formation of most "colloid" cysts. Review of the literature as well as our experience indicates that neuroepithelial cysts are widely distributed throughout the central nervous system.

Location of human pyramidal tract in the internal capsule: anatomic evidence.

A patient with a small infarct located posteriorly in the internal capsule had 9 years of weakness of the contralateral face, arm, and leg. At necropsy, it was found that degeneration of the corticospinal tract was almost complete in the midbrain and medullary pyramid. This case supports the increasing evidence that the human pyramidal tract is located in the third quarter of the posterior limb of the internal capsule.

Combined neuroepithelial (colloid) cyst and xanthogranuloma (xanthoma) in the third ventricle.

A case is reported of a combined neuroepithelial cyst and xanthogranuloma of the choroid plexus in the third ventricle of a 22-year-old woman. It is suggested that proliferated neuroepithelial cells lining the cyst enter the fibrous wall through the disrupted basal lamina, and then become xanthomatous cells. Disintegration of these foamy epithelial cells releases lipids and other materials into the cyst wall, provoking a response of macrophages and multinucleated giant cells of foreign-body type. A xanthogranuloma is then formed. The origin of "colloid" cysts is from neuroepithelium; these cysts arise from both ependyma and choroid plexus. Those cysts arising in or near the floor of the third ventricle may originate in stomodeal epithelium, but a distinction cannot be made from neuroepithelial cysts by presently available methods.

Pathogenesis of pigment and spheroid formation in Hallervorden-Spatz syndrome and related disorders.

In a case of Hallervorden-Spatz syndrome, neuromelanin was found in neurons and, extracellularly, in the globus pallidus and pars reticulata of the substantia nigra. Some cells of pars compacta contained Lewey bodies. We propose that neuromelanin is formed by a metal-catalyzed pseudoperoxidation of lipofuscin, involving increased amounts of iron and copper in the affected regions. A similar mechanism of spheroid formation, often associated with neuromelanin, may result from pathologic accumulations of lipid peroxides during fatty acid oxidation of myelin. We suggest that neuromelanin is a late stage in the metabolism on intraneuronal and extraneuronal lipopigments. Discrepancies among the histochemical features of the pigment in different cases may be explained by differences in amounts of lipofuscin, neuromelanin, and their precursors. We propose relation of peroxidation to the pathogenesis of some related degenerative diseases.

Human tails and pseudotails.

A case of a tail in a 2-week-old infant is reported, and findings from a review of 33 previously reported cases of true tails and pseudotails are summarized. The true, or persistent, vestigial tail of humans arises from the most distal remnant of the embryonic tail. It contains adipose and connective tissue, central bundles of striated muscle, blood vessels, and nerves and is covered by skin. Bone, cartilage, notochord, and spinal cord are lacking. The true tail arises by retention of structures found normally in fetal development. It may be as long as 13 cm, can move and contract, and occurs twice as often in males as in females. A true tail is easily removed surgically, without residual effects. It is rarely familial. Pseudotails are varied lesions having in common a lumbosacral protrusion and a superficial resemblance to persistent vestigial tails. The most frequent cause of a pseudotail in a series of ten cases obtained from the literature was an anomalous prolongation of the coccygeal vertebrae. Additional lesions included two lipomas, and one each of teratoma, chondromegaly , glioma, and a thin, elongated parasitic fetus.

Familial gliomas: report of four families, with chromosome studies.

Four families having multiple family members with cerebral gliomas are presented. Genetic studies were done in some, but no chromosomal abnormalities were found in this group of patients or their families. The authors recommend that careful attention be given to the family history of all glioma patients and that more extensive genetic studies be done. The formation of a registry to report cases of familial gliomas is also suggested.

Combined neurilemmoma and angioma. Tumor of ectomesenchyme and a source of bleeding.

Eight cases are described of intracranial and peripheral neoplasms composed of mixed neurilemmoma and hemangioma. It is proposed that ectomesenchyme can differentiate into neurilemmoma and angioma. The latter may be related to recently described angiogenetic factors, or to developmental factors as in rare cases of arterial angiomas. The angiomatous part may be common, but has often been overlooked. The presence of abnormal vessels, whether in kind or in number, helps explain various biological features of neurilemmoma. These vessels frequently bleed within the tumor, which results in the characteristic hemosiderin-laden macrophages. Bleeding may also occur into the cerebrospinal fluid (CSF) to create xanthochromia. The frequent increase in CSF protein in cases of neurilemmoma is attributed to transudation of serum from abnormal vessels. Less commonly, bleeding may be sufficient to cause subarachnoid hemorrhage. The dense collagen usually associated with these angiomas accounts for the relative infrequence of major hemorrhages.

Relation of age and cerebral ventricle size to central canal in man. Morphological analysis.

The central canal of the spinal cord in man with and without hydrocephalus was studied histologically. The lumen was patent in most patients in the first two decades of life. Cells lining the canal in the prenatal and newborn state and in the first decade of life were predominantly pseudostratified ciliated epithelium. In the second decade, the epithelium became simple columnar or cuboidal. The central canal closed in most cases after the age of 20 years, secondary to proliferation of ependymal cells and astrocytes. Mechanisms whereby the number of glial cells increase are considered. The canal was closed in all adults with normal ventricular size, and in 94% of persons with various degrees of hydrocephalus. In the remaining 6% of cases with hydrocephalus, the lining of the canal resembled that seen in the first two decades, and could have acted as a pathway of cerebrospinal fluid (CSF) absorption. Three cases of severe hydrocephalus in the first two decades of life were encountered; the central canal was patent in one, and occluded in two. Based on these data, the canal was not a significant pathway of CSF absorption in most instances of hydrocephalus and in persons with dilated ventricles who were older than 20 years of age.

Empty sella secondary to suprasellar colloid cyst of foregut (respiratory) origin. Case report.

An enlarged sella turcica was discovered in a 40-year-old man who had bitemporal headaches. A pneumoencephalograph revealed a third ventricular cyst, dilated lateral ventricles, and an empty sella. The colloid cyst was lined by foregut epithelium, probably originating in the respiratory tract, and dense connective tissue. This case is the first instance of an empty sella associated with a colloid cyst of the third ventricle. It is proposed that enlargement of the mass in the third ventricle caused increased pulsation pressure of the cerebrospinal fluid, and that in the presence of an incompetent diaphragma sellae the subarachnoid space expanded into the sella. The origin of third ventricle cysts is reconsidered. It is concluded that suprasellar colloid cysts may arise from endoderm, ectoderm, neuroepithelium, or a combination of these epithelia.

Nonketotic hyperglycemic hyperosmolar coma. Report of neurosurgical cases with a review of mechanisms and treatment.

Seventy-eight critically ill patients who died while on the neurosurgical service were studied retrospectively to establish the prevalence of nonketotic hyperglycemic hyperosmolar coma (NHHC). All the patients had been comatose before death, and all underwent necropsy. Criteria for the diagnosis of NHHC included moderate-to-severe hyperglycemia with glucosuria, absence of significant acetonuria, hyperosmolarity with dehydration, and neurological dysfunction. This study revealed seven cases of unequivocal NHHC (9%), and six of hyperosmolarity but with incomplete records. Five of the seven confirmed cases of NHHC demonstrated no evidence of cerebral edema transtentorial herniation, or brain-stem damage, and showed central nervous system (CNS) lesions compatible with survival. Fatal complications of this syndrome, such as acute renal failure, terminal arrhythmias, and vascular accidents, both cerebral and systemic, were common in this series. The mechanism of coma in NHHC is believed related to shifts of free water from the cerebral extravascular space to the hypertonic intravascular space, with subsequent intracellular dehydration, accumulation of metabolic products of glucose, and brain shrinkage. It is uncertain whether injury to specific areas in the CNS is a predisposing factor to the development of NHHC. Factors documented to be significant in its development include nonspecific stress to primary illnesses, hyperosmolar tube feedings, dehydration, diabetes and mannitol, Dilantin, or steroid administration.

Late appearance of meningioma at the site of partially removed oligodendroglioma. Case report.

A case is presented in which a meningioma and a glioma grew in the region where, 23 years before, a glial tumor had been partially removed and irradiated. The authors suggest that surgical trauma and ionizing radiation may have influenced the tumor's development.

Differentiation of Medulloblastoma. Studies including immunohistochemical localization of glial fibrillary acidic protein.

A series of medulloblastomas was studied by light microscopy. The tumors were variable; astrocytic, ependymal, neuronal, and probable oligodendroglial differentiation was present. Features of glioblastoma multiforme occurred in one case. Immunoperoxidase staining for glial fibrillary acidic protein (GFAP), an antigen found only in astrocytes and ependymal cells, revealed astrocytic differentiation in 11 of 13 cases. The two GFAP-negative tumors were histologically undifferentiated. A new classification of medulloblastomas is presented, based on the multiple types of differentiation of these tumors. Neuronal, astrocytic, ependymal, and small-cell types are described. Undifferentiated tumors were more frequent in younger children. The differentiation of medulloblastoma is correlated with recent experimental studies of gliogenesis and neurogenesis. A hypothesis that medulloblastoma is a stem-cell neoplasm is presented, based on these comparative data.

Disseminated intravascular coagulation following cranial trauma. Case report.

Cranial and spinal trauma resulted in disseminated intravascular coagulation (DIC) in a 78-year-old man, causing widespread bleeding and incoagulable blood. Traumatized brain tissue was found in the lumina of dural venous sinuses. The mechanisms of DIC are reviewed. It is suggested that intravascular release of potent cerebral thromboplastin contributed to the severity of DIC in this patient, by causing activation of the extrinsic clotting system. Intrasinus brain tissue in cases of human trauma has not previously been reported.