Showing papers in "Journal of Neuropathology and Experimental Neurology in 1960"

Phase and electron microscopic studies of experimental demyelination. I. Variations in myelin sheath contour in normal guinea pig sciatic nerve.

Abstract: Phase and electron microscopic study of normal guinea pig sciatic nerves reveals numerous variations in the myelin sheath contour. For the most part, these variations consist of infoldings into axoplasm or protrusions into Schwann cell cytoplasm and can be seen as isolated myelin ovoids in a single plane of section. They are most numerous in the juxtanodal region of the largest fibers and are of particular importance to neuropathologists because of their resemblance to myelin forms seen with the light microscope in early demyelinative lesions. Several other features of peripheral nerve ultrastructure are briefly described.

The effects of subarachnoid injections of iron-containing substances on the central nervous system.

Abstract: Noetzel (1) was the first to describe in man an unusual condition characterized by an accumulation of iron-positive pigment in the subpial and subependymal layers of the central nervous system, without systemic manifestations of hemo-chromatosis. Similar cases have since been published by Lewey and Govans (2), Cammermeyer (3), Neumann (4 and 5), Noetzel (6) and Garcin and Lapresel (7). Two hypotheses have been proposed to explain the etiology of this remarkable neuropathological entity, which we propose to call “Subpial Cerebral Siderosis” (SCS). According to the first, the deposition of the iron-positive pigment is a result of subarachnoid hemorrhages; according to the second, it is a local manifestation of a generalized metabolic disorder, somehow similar to hemochromatosis. Since the evidence of subarachnoid hemorrhages in some of the cases described was not definite, it seemed warranted to investigate this problem experimentally by repeated injections of blood or iron-containing compounds into the subarachnoid spaces of dogs.

Central Nervous System Involvement in Whipple's Disease*

Abstract: The pathologic changes in the brains of two cases of Whipple's Disease have been described. The lesions are considered specific and, thus, constitute additional evidence of the systemic nature of the disease.

Xanthoma and cholesterol granuloma of the choroid plexus. Report of the pathological aspects in 29 cases.

Abstract: Only 9 cases of xanthoma or cholesterol granuloma were recorded in the literature prior to the report of 20 cases of xanthoma of the choroid plexus by Wolf, Cowen, and Graham (26), of which 1 (their case 8) was published separately (25). Cholesterol granuloma in the ventricular system of man was first described by Blumer (2) under the term \"cholestomatous endothelioma.\" Other terms employed were \"cholesteatoma\" (4, 5, 17), \"xanthoma\" (16, 18, 19), and \"angioreticuloma\" (7). Dandy (6) regarded the lesion in his Case 3 as \"perhaps [a] tumor of embryonal cells from which epithelium of the choroid plexus or ependyma is derived,\" but to us the lesion appears to be a clear-cut cholesterol granuloma. Stern and Levy (21) reported the presence of a cholesterol-containing tumor of the Illrd ventricle, but we doubt that it is of the same category as those reported in this paper. Henschen (13) distinguished between xanthomas and cholesterol granulomas of the choroid plexus, and Stewart (22) referred to xanthomas, but neither of these authors reported individual cases. Wolf, Cowen, and Graham (26), on the other hand, did not deal with xanthoma and cholesterol granulomas separately in their series, but did describe cholesterol granuloma in some of their xanthomas. Dunn and Kernahan (7a) found foam cells and evidence of cholesterol in degenerating parts of the connective-tissue core of the plexus, whereas cholesterol clefts were rare. In 24 cases of cholesterinosis of the choroid plexus, Trelles, Aranibar and Zevalloz (22a) described 3 histological forms: (I) Cystic, in which there was diffuse hyaline material which contained birefringent and clear zones, with reactive fibroblastic reaction around stored calcium and foci of foam (xanthoma) cells, (2) N odulo-cystic, similar to (I) but with a predominance of foam cells with cholesterol clefts, and (3) Nodular, characterized predominantly by foam cells, the central area of which contained cholesterol clefts with connective tissue and other reaction in such quantity as to constitute a cholesterol granuloma. The present article deals with 9 cases of xanthoma and 20 of cholesterol granuloma of the choroid plexus.

Combined amyloid vascular changes and argyrophilic plaques in the central nervous system.

Abstract: In the course of an investigation on the prevalence of Alzheimer's disease at St. Elizabeths Hospital (1), a case was encountered in which the prominence of argyrophilic plaques and the lack of significant mental changes seemed in striking variance with the findings of other cases in the series. In contrast to the usual picture, the plaques in this case were visible with practically every staining method employed. Many of the plaques were larger, and the silver stained granules composing them coarser, than those seen in the brains of individuals showing progressive degenerative mental changes. Another interesting feature was the presence of hyaline-like changes in the walls of many small arteries; the large vessels in contrast were free from degenerative changes. Although the patient died as the result of a massive cerebral hemorrhage, and had suffered an earlier hemorrhage in the right motor area, there had been no clinical evidence of hypertension. Similar pathologic findings have been reported in the literature by Worster-Drought, Greenfield and McMenemey (2, 3) and by Corsellis and Brierly (4). In addition to the plaques and widespread vascular alterations, neurofibrillary changes were found in their cases, so that they were reported as unusual examples of presenile dementia. Because of the seeming rarity of the condition and the dissimilarity of the clinical signs in the reported case and those previously described, it is deemed of importance to add this case to the literature.

Mechanisms of brain damage in H. influenzae meningitis.

Abstract: In recent years H. injluenzae has become the most common cause of bacterial meningitis in infants in the United States of America (1, 2). Although, over the last two decades, with steady improvement in methods of treatment (2, 3) the mortality rate has declined from over 90 per cent to about 10 to 15 per cent, the sequelae in the survivors may be serious. As many as 10 to 20 per cent may be left with some degree of neurological deficit. The cause of this is still uncertain. Alexander (4) has suggested that arteritis with thrombosis, and cerebritis, are the causes of neuronal damage, and others (5, 6) have emphasized the importance of subdural effusions. It is claimed that such effusions become enclosed by membranes which lead to restriction of brain growth at a time when the latter is still rapid. The present study of 34 fatal cases examined at the Cincinnati General and Children's Hospitals between 1932 and 1958 is mainly oriented to this problem of the mechanism or mechanisms by which H. injluenzae meningitis sometimes results in significant permanent brain damage. Although this form of meningitis was recognized at the end of the 19th century (7), and numerom; cases were diagnosed soon after World War I (8), only one paper is known to us (9) in which detailed attention is given to the pathological lesions. This was based upon an analysis of 14 fatal cases from the Boston City and Massachusetts General Hospitals. It contains much valuable information about the evolution of the inflammatory process in the meninges, associated vascular lesions, and brain damage, as well as clinico-pathological correlations. However, the time of its publication, in 1948, was before complicating subdural effusions had received adequate recognition and this factor was not considered.

Acute effects of methoxypyridoxine on hippocampal end-blade neurons: an experimental study of "special pathoclisis" in the cerebral cortex.

Abstract: Architectonic fields in the hippocampus are defined largely in terms of the general histological characteristics of their pyramidal neurons (1–4), but these features do not account for the relative vulnerability of elements in different segments of the pyramidal band to various pathological conditions directly or indirectly affecting the central nervous system (5). To explain regional differences in hippocampal cellular pathology, two hypotheses have been suggested. One attributes neuronal damage in various sectors to local vascular and/or hemodynamic alterations (6) and is presumably supported by a variety of data (7–8). The other considers selective vulnerability or “special pathoclisis” a reflection of physico-chemical differences in neurons in different architectonic fields (4) and “remains in the nature of a statement of the problem” (5). In the present studies an antimetabolite of pyridoxine, methoxypyridoxine, has been employed as an analytical tool to attain a twofold objective: (a) to induce acute histopathological changes in neurons in different segments of the hippocampal pyramidal layer, and (b) to determine whether or not these selective changes may be interpreted primarily in terms of regional differences in the biochemical properties of the affected neurons. Analyses of the complex histopathological effects of methoxypyridoxine on elements in other parts of the central nervous system will be presented in a subsequent report. Some of the alterations in brain amino acid metabolism accompanying seizures induced by methoxypyridoxine have been considered elsewhere (9).

A study of some physiological mechanisms underlying susceptibility to audiogenic seizures in mice.

Abstract: One of the difficulties in studying the pathogenesis of epileptiform convulsions is due to the fact that a great variety of apparently heterogeneous causes such as trauma, cerebral edema, anoxemia, and disturbance of acid-base equilibrium may induce convulsions. If some similarity can be found between various factors such as genetic constitution, biochemical or physiological changes and disturbances, and epileptogenic agents, all of which can bring on convulsive behavior, some progress in the understanding of the pathogenesis of convulsions may be expected. A fruitful approach to an understanding of the physiology of convulsions may be provided by a study of rabbits and mice genetically predisposed to convulsive behavior in response to auditory stimulation. The extensive literature on these strains has been reviewed by Antonitis, Crary, Sawin and Cohen (4), Bevan (5), Finger (10), Ginsburg (15), and Vicari (27, 28). At the present time two main approaches are being followed in studies exploring the physiological mechanisms underlying audiogenic seizures. It has been suggested that oxidative processes supplying energy for the nervous system lag behind energy expenditure during convulsive activity. Whether or not this theory is applicable also to audiogenic seizures cannot be decided, since neurochemical studies of the type performed during and after convulsions induced by various pharmacological epileptogens are still lacking in mice suffering from audiogenie seizures (19, 23). However, the protective effect against recurrence of audiogenic seizures exerted by such substances as glutamic acid, glucose, pyruvate, thiouracil, and a number of citric acid cycle intermediates has been interpreted to mean that the differential susceptibility to audiogenic seizures in different strains of mice is a function of different metabolic capacities of the central nervous system (Ginsburg and Hovda (16); Ginsburg, Ross, Zamis and Perkins, (18); Vieari, (27); Vieari, Tracy and Jongbloed, (28)). This view has.

Hyperplasia of the Skull Associated with Intra-Osseus Meningioma in the Absence of Gross TumorRetort of Three Cases

Abstract: 1. Three cases of hyperostosis of the skull associated with intra-osseus meningioma in the absence of gross, tumor have been presented. 2. Two of these 3 cases, represent examples of familial meningioma.

Specific cord damage at the atlas level as a pathogenic mechanism in cerebral concussion.

Abstract: Significant changes in the neurons of some of the brain stem nuclei were found following experimentally induced brain concussion (Windle, Groat, and Fox, (5), Windle, Groat, and Magoun, (fi)). A chromatolysis was found in the neurons of the reticular formation of the medulla oblongata, in the lateral vestibular nucleus (Deiter's nucleus), the red nucleus, the nucleus of the spinal trigeminal tract, and certain other nuclei. The motor nuclei of the cranial nerves remained unchanged. The number of damaged cells in the affected nuclei was in relation to the severity of the trauma. A reduction of the cell population of the affected nuclei was found in longer follow-ups (7, 2). The present report describes the neuropathology of cats in which an abrupt stretch of the cervical vertebral column was produced by dropping the anaesthe-tized cats with the heads fixed in a restraining collar (Hollister, Jolly, and Horne (3)). This experimental technique resulted in the same type of cell degeneration in the brain stem as described by Windle et al. in animals which had received a blow to the skull, or true head injury. In addition and in contradiction to prior studies, a specific fiber damage was resolved confined to the first segments of the spinal cord. The thick fibers were specifically affected. The damage was localized and required a special investigation of the cervical cord; it was apparently produced by the intimate cord-bone relationship at the atlas level. Fiber damage and chromatolysis in the axons were related phenomena. In controls , exactly the same type of injury was found also in cats which had received true head injuries by a blow on the head. The brains and spinal cords of 32 cats were studied, 24 of which were used for the drop experiment. The injury caused by the dropping procedure induced temporary loss of respiration and corneal reflex, indiscernible from the results of an experimental concussion by head injury. Such an experimentally induced impairment of brain stem reflexes is termed hereafter \"concussion\"; the definition has to be emphasized, since the relationship of the experimental syndrome to the clinical picture of concussion still has to be defined. A description of the experimental arrangement and findings is reported separately by Hollister, Jolly and Horne (3). It was the author's intention to determine if a relationship existed between neurohisto-pathological findings and duration of \"concussion\". Therefore, it was decided to group the cats according to …

Central nervous system lipidosis in an adult with atrophy of the cerebellar granular layer: a case report.

Abstract: Cases of central nervous system lipidosis unaccompanied by retinal abnormality that is visible by funduscopy and surviving into or beyond the third decade of life are rare. The majority have had onset in adolescence or adulthood, although in occasional instances (2, 9, 12) symptoms have been manifest from childhood. The authors have been able to find 18 cases (1 to 17) in which there is full histologic description (table 1). These cases have had no distinctive clinical pattern that would permit an ante mortem diagnosis, and anatomically the degree and site of involvement have been variable. The present report is concerned with the clinical and anatomical features of a sporadic case of central nervous system lipidosis in an adult. the clinical course was characterized by cerebellar dysfunction and muscular atrophy. The major histologic features were enlargement of neurons at various levels of the nervous system by lipid deposits, and atrophy of the granular layer of the cerebellum.

Influenza virus infections in pregnant mice.

Abstract: The pregnancy rate of mice infected intranasally with PR8 influenza A virus (0.7 and 1.0 LD50) was significantly reduced, but litter sizes were unaffected. Immune animals challenged with large doses were similar to controls in all respects. Intraperitoneal and intravenous routes of inoculation failed to reduce pregnancy rates or litter sizes. Influenza virus crossed the placenta late in the gestational period as evidenced by recovery of virus from fetuses. However, the possibility of virus recovery in newborn pups is unlikely, and maze studies tend to confirm the failure of the influenza virus to cross the placental barrier when pregnant mice are infected early in pregnancy.

Localized cerebral gliosis with giant neurons histologically resembling tuberous sclerosis.

Abstract: There are many pathological states which give rise to mental deficiency and convulsive seizures starting at or near birth. Some of these are related to injury at birth; others consist of malformations either genetic in origin, or resulting from injury in the early stages of embryonic development. One group of such pathological states is characterized histologically by the presence in the central nervous system of abnormal, giant, deformed neurons, and/or giant, deformed astrocytes. Most commonly, such abnormal neurons and astrocytes are found in the form of discrete gross nodules, and this entity has been designated tuberous sclerosis (1, 2). Abnormal giant neurons have been described in pachygyria (3, 4), in some cases of von Recklinghausen's disease (5), and in one case of Albright's disease (6). More recently Crome (7) has reported the pathological changes in two cases in which the abnormal cells were present in large numbers distributed diffusely in one broad area of one cerebral hemisphere. The purpose of this paper is to describe the clinical and pathological features of a patient with progressive mental deficiency and convulsions since birth in which the similarities to these other conditions and to Crome's cases, are readily apparent.

Experimental study of diphtheritic polyneuritis in the rabbit and guinea pig. II. The effect of diphtheria toxin on lipide biosynthesis by guinea pig nerve.

Abstract: Diphtheritic polyneuritis was induced in guinea pigs by injection of incompletely neutralized toxin-antitoxin mixture. At varying intervals after the injection, simples of peripheral nerves from these animals were incubated in Warburg vessels in the presence of a labelled lipide precursor (acetate or phosphate); the total lipides were then extracted and counted. Nerve preparations from litter mate pair-fed animals served as controls. Histologically, no damage was observed until 6 or 7 days after the injection, at which time some fibers began to show segmental demyelination. From the fifth day onward there was a slow decrease in total nerve lipide content and a slight decrease in percentage dry weight. Oxygen uptake was slightly depressed at 5 days, and moderately elevated from 15 days onwards. The incorporation of acetate into the total lipides was profoundly and persistently depressed, a measurable decrease being apparent as early as 24 hours. The incorporation of phosphate into the lipides tended to increase only in the later stages of the disease, when fibers undergoing Wallerian degeneration were found admixed with those showing the characteristic segmental demyelination. These biochemical changes were interpreted as a manifestation of an early and persistent depression of the function of myelin maintenance, in the absence of any stimulus to the Schwann cell. This situation was contrasted with the changes previously found in Wallerian degeneration, in which the depression of myelin maintenance is accompanied by hypertrophy and hyperplasia of the Schwann cells. When liver slices from normal and treated animals were incubated under the same conditions as the nerves, no significant difference was found in the rates of incorporation of the label. Normal nerves and white matter, incubated for 4 hours in the presence of large amounts of toxin, were not demonstrable affected. Starvation alone was found to have considerable effect on lipide biosynthesis in peripheral nerves. After 5 days of partial food restriction, the rate of incorporation of acetate was reduced to one-half the control value, while histologically the nerves appeared normal.

Involuntary Movement Disorders Following Basal Ganglia Surgery in Man

Abstract: During the course of a series of more than 850 consecutive basal ganglia operations (7, 8, 9) for involuntary movement disorders, 21 patients developed a postoperative dyskinesia differing from that which had been relieved by the surgery. The operatively-induced involuntary movements took the form of a ballismus, chorea or athetosis, alone or in combination. They varied in intensity from mild to severe, and in duration from a single day to 5 months. Two of the patients who underwent anterior choroidal artery ligation developed transient contralateral choreiform movements which cleared spontaneously within 7 days. In both of these cases, parkinsonian tremor and rigidity were relieved and have not recurred in more than 5 years since surgery. Only one patient (Case No. 198) in the entire series of over 500 chemopallidec-tomies manifested a dyskinesia post-operatively: He is a 34 year-old bilateral parkinsonian who presented a chorea of the right upper extremity the first day after left chemopallidectomy was performed. The abnormal movements disappeared within 24 hours and the patient was discharged after 3 weeks with complete remission of tremor and rigidity on the operated side. All of the other patients who developed involuntary movements were operated upon during the evolution of the target areas situated more posteriorly: pallido-fugal complex and ventrolateral thalamus, especially the latter. Eleven of these patients developed a contralateral dyskinesia following initial surgery. In one case, however, a 34 year-old woman (case No. 435) with dystonia musculorum deformans who had a right chemothalamectomy, a transient athetosis appeared on the ipsilateral side. Thus far, in the group of patients which were reoperated on the same side because of incomplete results initially, there are no examples of consequent hyperkinesis. Eight patients who had previously undergone unilateral chemosurgery developed abnormal involuntary movements after placement of a lesion in the opposite hemisphere. Included in this bilateral series are the 2 patients previously mentioned: The patient with parkinsonism (case No. 198) returned one year later (still

The effect of x-irradiation on the perineuronal satellite cells in the cortex of aging brains.

Abstract: A great deal of information pertaining to the cytological effects of ionizing irradiation of the central nervous system has begun to indicate a certain selective sensitivity of the interstitial cell system. Arnold and Bailey (1) have pointed out that the type and manner of the response demonstrated by neuroglial elements (oligodendroglia, astroglia and microglia) to x-irradiation correlated well with 1. the total dose of irradiation, 2. the intensity of dose administration, 3. the uniformity of the dose distribution within the tissue, and 4. the duration of time of observation after irradiation. These investigators reported that glia in the monkey brain did not undergo significant acute reactions following dosages of 1500–3000 r. It was only after months had passed that they observed intense gliosis. They concluded that initially there was inhibition of glia, recovery and terminally intense gliosis. The degree of glial reaction was directly related to the rate of delivery and intensity of irradiation. Hicks and Montgomery (2) have reported specific sensitivity of glial elements. These authors found that rat and mice brains underwent degeneration of oligodendroglia elements approximately 9 to 11 days after being exposed to various levels of x-irradiation between 50 and 20,000 r. They also reported oligodendroglia were necrotic within 6 to 24 hours after receiving 1200 r to the head. It is believed that further efforts should be undertakne to determine the sublethal effects of irradiation during short and long term programs emphasizing the importance of age variations. In view of present differences in information regarding neuroglial radiosensitivity, a simple approach to quantitating some of these changes is under investigation. It is the author's opinion that basic quantitative evaluation of specific alterations are most essential in seeking to arrive at an understanding of the underlying mechanisms involved.