Atlas of Neuropathology

By Nathan Malamud

This title is part of UC Press's Voices Revived program, which commemorates University of California Press’s mission to seek out and cultivate the brightest minds and give them voice, reach, and impact. Drawing on a backlist dating to 1893, Voices Revived makes high-quality, peer-reviewed scholarship accessible once again using print-on-demand technology. This title was originally published in 1957.

• Language: English
• Publisher: University of California Press
• Release date: Dec 22, 2023
• ISBN: 9780520323261

Nathan Malamud

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Atlas of Neuropathology

Nathan Malamud, M.D.

ASSOCIATE CLINICAL PROFESSOR OF PSYCHIATRY

AND NEUROPATHOLOGY, UNIVERSITY OF CALIFORNIA NEUROPATHOLOGIST, THE LANGLEY PORTER CLINIC, SAN FRANCISCO

Atlas of

Neuropathology

University of California Press P>erkeley and Los Angeles • 1957

UNIVERSITY OF CALIFORNIA PRESS • BERKELEY AND LOS ANGELES, CALIFORNIA

CAMBRIDGE UNIVERSITY PRESS • LONDON, ENGLAND

© I957 BY THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

LIBRARY OF CONGRESS CATALOG CARD NUMBER: 56-13133

PRINTED IN THE UNITED STATES OF AMERICA

BY THE UNIVERSITY OF CALIFORNIA PRINTING DEPARTMENT

DESIGNED BY JOHN B. GOETZ

To R.K.M.

Preface

The need for an atlas of neuropathology has long been apparent to workers in the fields of neurology, psychiatry, neurosurgery, and pathology. Precise and detailed knowledge of the gross and microscopic changes in the nervous system is a necessary prerequisite to the understanding of nervous and mental diseases. The purpose of this book is to provide a visual approach that is not usually provided by textbooks of neuropathology.

I have attempted to illustrate the various disorders of the nervous system as comprehensively as possible. Equal space has been given to all categories, but special attention has been paid to such neglected conditions as the heredodegenerative disorders and those pertaining to geriatrics, cerebral palsy, and mental deficiency. The case presentation method was used wherever possible, to afford a correlation between lesions and symptoms and to crystallize the clinical syndromes. Owing to lack of space, theoretical discussions and references to the literature were reduced to a minimum.

The material in the atlas represents approximately five thousand specimens collected from many sources, including general and mental hospitals, and personally examined by me in the laboratory of neuropathology at the Langley Porter Clinic.

Although it is not possible to list all sources, particular acknowledgment for the use of material is made to the following: the departments of Neurosurgery, Neurology, Psychiatry, and Pathology of the University of California Medical Center, San Francisco; Letterman Army Hospital, San Francisco; United States Naval Hospital, Oakland; and Veterans Administration Hospital, Palo Alto; the state hospitals of the Department of Mental Hygiene in California; and the Armed Forces Institute of Pathology, Washington, D. C.

In reproducing illustrations and certain data, I have indicated sources in suitable places throughout the book. I want to express gratitude to the following journals for granting permission to reproduce such material: Archives of Neurology and Psychiatry, Archives of Internal Medicine, American fournal of Diseases of Children, American fournal of Pathology y American fournal of Mental Deficiency, American fournal of Psychiatry, Archiv für Psychiatrie und Nervenkrankheiten, fournal of Nervous and Mental Diseases, fournal of Neurosurgery y fournal of Neuropathology and Experimental Neurology, fournal of Pediatrics, Neurology, Military Medicine, Transactions of the American Neurological Association, and to Charles C. Thomas, publisher.

My special thanks are extended to: Mrs. Irene Robley, for her untiring effort and excellent technique in preparing the microscopic slides; Mrs. Marie-Jeanne Angenent, for typing the manuscript; Dr. Herbert Herzon, for reading the text.

N. M.

Contents 1

Contents 1

I Cytology and Cellular Pathology

II Inflammatory Disorders

III Toxic and Nutritional Disorders

IV Demyelinating Disorders

V Vascular Disorders

VI Traumatic Disorders

VII Degenerative Disorders

VIII Neoplastic Disorders

IX Developmental Disorders

X Sequelae of Paranatal and Postnatal Disorders

Bibliography

Index

I

Cytology and Cellular Pathology

Pathologic processes are based ultimately on cellular pathology. The nature of a particular disorder is determined by the manner in which nerve cells and fibers are altered, the type of reaction of the supporting cells evoked, and the kind of catabolic products produced.

Different staining methods may be required to demonstrate such changes, since the various nerve structures have specific staining properties.

STAINING METHODS

Nissl Method. Aniline dyes, such as thionin, toluidine blue, or cresyl violet, stain the Nissl bodies of neurons and the chromatin of all nuclei varying shades of blue to purple (Fig. ia).

Hematoxylin-Eosin Method. This nonspecific method stains the cytoplasm purplish red and the nucleus blue-black. In neurons undergoing ischemic or anoxic change, the cytoplasm stains a bright red that contrasts with the deep blue pyknotic nucleus (Fig. ib).

Bielschowsky Method (or its von Braunmühl modification). Silver nitrate stains the neurofibrils, and such argyrophilic pathologic structures as senile plaques, black against a slightly purplish background (Fig. ic).

Davenport Method. Silver nitrate (similar to the Bielschowsky) stains the axis cylinders black against a purplish background (Fig. id).

Weigert Method (or any of its modifications). Iron hematoxylin, in tissue previously mordanted with chrome and copper salts, stains the myelin sheaths blue-black in contrast to the slightly yellowish color of normally unmyelinated or demyelinated areas (Fig. le).

Weil Method. A solution of iron alum and hematoxylin stains the normal myelin sheaths a bluish gray against the light gray of unmyelinated and demyelinated structures, as in a degenerating peripheral nerve (Fig. if).

Laidlaw Connective Tissue Method. A solution of lithium silver stains reticulin fibers black, as in a gumma (Fig. ig).

Hematoxylin-van Gieson Method. A solution of iron hematoxylin and picric acid-fuchsin stains collagen fibers red, and nerve tissue and hemosiderin pigment yellowish brown, as in the capsule of a brain abscess (Fig. ih).

STAINING METHODS (continued)

Hortega Silver Carbonate Method. The microglia stain black against a purplish background (Fig. 2a).

Cajal Gold Sublimate Method. The astrocytes and their processes stain black against a reddish-brown background (Fig. 2b).

Holzer Method. Crystal violet stains the glial fibers of astrocytes a deep blue, as in a glial scar (Fig. 2c).

Scarlet-Red Method. Sudan IV, counterstained with alum hematoxylin, stains droplets of neutral fat deposited in gitter cells a brilliant red and the nuclei blue, as in a demyelinating lesion (Fig. 2d).

Nile Blue Sulfate Method. This method stains prelipoids (fatty acids and lipids other than neutral fats) varying shades of blue to violet, as in the neurons of cases of amaurotic family idiocy (Fig. 2e).

Turnbull Blue Method. A solution of yellow-ammonium sulphide and potassium ferricyanide-hydrochloric acid, counterstained with carmine, stains iron blue, and the background purplish red, as in a hemorrhagic infarct (Fig. 2f).

Kossa Method. Silver nitrate stains calcium black against a slightly yellowish background, as in cerebral calcification (Fig. 2g).

in Nissl preparations the normal neuron consists of Nissl bodies evenly distributed in the cell body and its dendrites, and of a clear spherical nucleus that contains a central nucleolus (Fig. 3a). In Bielschowsky preparations neurofibrils form the content of the cell (see Fig. ic).

Under pathologic conditions various changes occur in the nerve cell that are mostly nonspecific, differing only as the underlying disease process is acute or chronic, reversible or irreversible. These changes may be classified as follows:

Swelling. Under acute injurious conditions the cell may undergo swelling of the cytoplasm and dendrites and pulverization of the Nissl bodies, but the nucleus remains intact (Fig. 3b) and the neurofibrils are generally preserved. This process is considered reversible.

Liquefaction. Under more intense pathologic conditions the neuron undergoes an irreversible change with ringlet and droplet formations in the cytoplasm, disintegration of the Nissl bodies and neurofibrils, pyknosis of the nucleus, dissolution of the cell membrane, and pericellular incrustations (Fig. 3c).

Shrinkage. Although generally found in chronic disease states, shrinkage may also accompany the previously described acute changes. It is characterized by shrinkage of the cell body, tortuosity of the dendrites, and hyperchromatosis whereby the Nissl substance and the neurofibrils fuse with the deeply staining nucleus (Fig. 3d).

Coagulation. Under conditions of ischemia and/or anoxia the nerve cell becomes pale, shrunken, and may be surrounded by incrustations, the cytoplasm hyalinized, and the nucleus small and pyknotic (Fig. 3e; also Fig. 3c, large neuron at the left). This change is particularly well demonstrated in hematoxylin-eosin preparations, since the cytoplasm assumes a diffuse pinkish-red color (see Fig. ib). As an end stage of ischemic as well as other conditions the neurons may undergo calcification (Fig. 3!).

Fatty degeneration. In some acute toxic disorders the cytoplasm of the neuron becomes alveolar or granular as a result of deposits of sudanophilic fat droplets (Fig. 3g). In chronic involution’ states pathologic increase of the normal lipochrome pigment may result in a somewhat similar appearance, known as pigment atrophy.

Retrograde or axonal degeneration. After disease of, or injury to, axis cylinders, either peripheral or central, the cells of origin undergo swelling, central chromatolysis, and eccentricity of the nucleus (Fig. 3h). Such a change may or may not be reversible.

The peripheral nerve fiber comprises a central axis cylinder enclosed in a myelin sheath composed of a complex network (Fig. 4a). The myelin sheath is surrounded by the neuri- lemmal sheath of Schwann, which is enclosed by endoperineurial connective tissue.

Disease of the peripheral nerves causes a successive series of changes, known as Wallerian degeneration. After swelling, the result of edema, the axons and myelin sheaths fragment and disappear. The cells of the sheath of Schwann and endoperineurium react by proliferation, resulting in the formation of numerous round and fusiform cells between the degenerating myelin sheaths (Fig. 4b). The reacting elements act as phagocytes of the axon-myelin breakdown products. At the end of the first week after injury their lipid content stains black with osmic acid (Marchi stage), and at the end of the second week red with sudan for neutral fats (scarlet-red stage, Fig. 4c).

The outstanding feature of lesions of the peripheral nerves is their regenerative capacity. In this process axons proliferate from the proximal end of the severed fiber to reunite with the distal end along reformed sheaths of Schwann, separated by variable amounts of connective tissue (Fig. 4d).

In the central nervous system the myelin sheath is thinner and of simpler structure, has no sheath of Schwann, and is surrounded by satellite oligodendroglia.

In central lesions similar Wallerian degeneration takes place, but at a slower tempo, and there are only feeble or no regenerative phenomena.

Swelling, beading, fragmentation, and disappearance of myelin sheaths (Fig. 4e) are accompanied by similar changes in the axons (Fig. 4f). Phagocytic activity is carried out by microglia, which become transformed into fat-laden gitter cells (Fig. 4g). The Marchi stage (third week) is followed by the scarlet-red stage (fourth week). Repair is a function of the astrocytes; the end stage is an astroglial scar (Fig. 4h).

The glia are the principal reacting elements to lesions of the central nervous system. Within limits of their own susceptibility to degenerate under noxious influences, they—unlike nerve cells and fibers—are capable of proliferation. There are three types of glia: microglia, astrocytes, and oligodendroglia.

MICROGLIA

According to the generally accepted theories, the microglia are derived from mesoderm, have the ability to migrate and to act as phagocytes, and thus represent the reticulo-endothelial elements of the central nervous system.

In the resting phase the cells are sparse, small, with trabeculated unipolar or bipolar processes and oval or rodlike nuclei, which stain specifically with the silver carbonate method of Hortega (Fig. 5a).

Under acute toxidegenerative or inflammatory conditions the cells multiply and undergo various changes. They may elongate and lose their trabeculae, at which time they are known as rod cells (Fig. 5b), or they may be polyblastic and attach themselves to neurons that they digest in the process designated as neuronophagia (Fig. 5c). This is particularly common in poliomyelitis (Fig. 5d). In other forms of encephalitis of viral origin the microglia tend to aggregate in the tissue as glial nodes or rosettes (Fig. 5e), or about degenerating dendrites of Purkinje cells as glial shrubberies (Fig. 5f).

Under conditions of tissue necrosis, as in infarcts, the microglia undergo a change from rod (A) forms to rounded (B) forms (Fig. 6a). Ultimately they become spherical cells with small eccentric nuclei and granular-reticulated cytoplasm, known as compound granular corpuscles, scavenger cells, or gitter cells (Figs. 6b, 6c).

Various phagocytosed products can be found in the cells, such as hemosiderin pigment in old hemorrhage (Fig. 6d), fat droplets (see Fig. 2d), iron (see Fig. 2f) or other catabolic elements. The microglia thus rid the tissue of waste and breakdown products, ultimately transporting these to the blood stream, where they are absorbed.

ASTROCYTES

Unlike microglia, the astrocytes are true ectodermal elements. Their function under pathologic conditions is that of repair.

In a resting state the astrocytes appear in Nissl preparations as vesicular naked nuclei, which are larger and paler than the small hyperchromatic oligodendroglial and microglial nuclei (Fig. 7a; see also Fig. ia). Cajal’s gold sublimate stain reveals the spider-shaped cell bodies with multipolar branching processes, having single foot-plate attachments to blood vessels (Fig. 7b). Astrocytes occur as protoplasmatic and fibrillary forms, the latter because of their production of glial fibers.

Under pathologic conditions the astrocytes undergo hyperplasia and hypertrophy. The first step is the swelling of nucleus and cytoplasm, which assumes a finely granular appearance and becomes visible in Nissl preparations (Fig. 7c). In Cajal preparations the cells demonstrate an increase in their branching processes and foot plates (Fig. 7d). The second step is the multiplication of fibrous astrocytes and the increased production of glial fibers (Figs. 7e, 70. Finally the cells disappear as the lesions become purely fibrous scars.

Since astrocytes are less resistant than microglia are to toxic influences, the former frequently show degenerative forms. There may be either acute ameboid glia with fragmentation of expansions or chronic plump astrocytes with hyalinization of cytoplasm and eccentricity of nucleus (Fig. 7g).

OLIGODENDROGLIA

The oligodendroglia are small round cells that are diffusely distributed in the central nervous system as satellites of nerve cells and fibers. Their nuclei resemble lymphocytes and their cytoplasm and processes are scanty, giving the appearance of perinuclear halos. Their normal function and role in disease remain uncertain.

Under acute pathologic conditions the oligodendroglia multiply about but do not digest neurons (Fig. 8a)—the process being known as satellitosis, which is to be distinguished from true neuronophagia by microglia.

Oligodendroglia may undergo degeneration, whereby the cytoplasm at first swells with the nucleus becoming pyknotic (A) followed by hydropic (B) and/or mucinous degeneration (Fig. 8b).

PATHOLOGIC CHANGES IN CONNECTIVE TISSUE

The connective tissue of the nervous system, as found in blood vessels, meninges, and endoperineurium, reacts to pathologic conditions in much the same way as in tissues of the body. Thus, proliferation of histiocytes and macrophages takes place in inflammatory and degenerative states. In reparative processes, silver-impregnated reticulin fibers (Fig. 8c) or fuchsinophilic collagen fibers (Fig. 8d; see also Fig. ih) are produced.

II

Inflammatory Disorders

Infectious diseases manifest themselves by an inflammatory reaction characterized by primary hematogenous and mesodermal tissue response to invading microorganisms. This inflammatory reaction is to be distinguished from symptomatic inflammation secondarily provoked by tissue damage as in infarcts and neoplasms.

Diseases caused by microorganisms may be classified, according to the type of inflammatory reaction, as: purulent, granulomatous, and nonpurulent.

PURULENT INFECTIONS

Pyogenic microorganisms induce a reaction characterized principally by exudation of polymorphonuclear leucocytes in the formation of pus.

PURULENT MENINGITIS

Inflammation of the dura mater—or pachymeningitis—usually develops as a direct extension from infection of adjacent tissues, as for example from an osteomyelitis or leptomeningitis.

Inflammation of the pia-arachnoid membrane—or leptomeningitis—is an independent infection caused by a great variety of pyogenic microorganisms that gain entrance into the subarachnoid space either from adjacent infection, such as otitis media, or by way of the blood stream.

Grossly, the exudate consists of grayish-green pus that fills the subarachnoid space and obscures the underlying nervous and vascular structures. The exudate does not differ in appearance in accordance with the specific etiologic agent, but may vary in location. Thus such organisms as the meningococcus induce primarily a basilar meningitis (Fig. 9a), whereas other organisms may affect principally the convexities of the hemispheres either unilaterally or bilaterally.

Microscopically, in the acute phase of the meningitis, polymorphonuclear leucocytes (A) predominate, accompanied by scattered histiocytes (B) and lymphocytes (C) (Figs. 9b, 9c).

PURULENT MENINGITIS (continued)

If the exudate is not absorbed, it becomes organized. At first a central zone (A) of disintegrating polymorphonuclear leucocytes separates from a peripheral zone (B), adjacent to the nervous tissue, that consists of lymphocytes, plasma cells, and histiocytes (Fig. ioa). Later, if the exudate becomes organized, an adhesive arachnoiditis results by laying down of dense reticulin and collagen fibers (Fig. lob).

If this is located at the base of the brain (Fig. IOC), the adhesions will tend to obstruct the cisterns and the foramina of Luschka, resulting in internal hydrocephalus, which is visible externally by ballooning of the cerebral tissue.

PURULENT EPENDYMITIS

Leptomeningitis is usually accompanied by an ependymitis, because of direct communication of the subarachnoid spaces with the ventricles. In some cases the ependymitis may be the predominant seat of the infection.

In the acute stage polymorphonuclear leucocytes accumulate in the ventricles, choroid plexus, ependymal, and subependymal layers (Fig. 11a). In chronic stages lymphocytes and plasma cells (A) supervene associated with subependymal gliosis (B) (Fig. 11b).

The gliosis may be so marked as to occlude the narrowest parts of the ventricular system, particularly the aqueduct of Sylvius and the fourth ventricle. The atresia in turn results in obstructive hydrocephalus.

Case: A female infant developed, on the third day following a normal birth, recurrent convulsive attacks, opisthotonus, and fever. Initially a blood calcium level of 7.6 mg. per 100 cc. led to a diagnosis of hypocalcemic tetany of the newborn. Later, with increasing evidence of hydrocephalus despite specific treatment, meningitis was suspected. A ventricular tap revealed 5,000 cells per cu. mm., predominantly polymorphonuclear leucocytes, total protein of 480 mg. per 100 cc. and glucose of 22 mg. per 100 cc. The fluid cultured E. coli. After treatment with sulfonamides and penicillin, the culture became sterile. A ventriculogram disclosed enlarged lateral ventricles. The condition progressed further, and by the age of 2 months the child showed marked hydrocephalus, spasticity of all extremities, and mental retardation. Death occurred at the age of 4 months.

The significant findings were chronic arachnoiditis occluding the cisterna magna (A), enlargement of the foramina of Luschka (B), complete atresia of the fourth ventricle (C) (Fig. ne), atresia of the third ventricle (D), enlargement of the lateral ventricles (E), pressure atrophy of the corpus callosum, septum pellucidum and fornix, and cysts (F) in the cerebral white matter (Fig. nd).

Microscopically, gliosis and remnants of inflammatory cells filled the stenosed fourth ventricle.

In this case of E. coli infection the principal lesion was thus an ependymitis that, by inducing atresias in various parts of the cerebrospinal fluid channels, accounted for the internal hydrocephalus.

COMPLICATIONS OF LEPTOMENINGITIS

Usually meningitis does not extend into the underlying nervous tissue. The latter undergoes diffuse edematous and toxic changes that are usually reversible.