Irwin Feigin

A disease in infants resembling chronic Wernicke's encephalopathy

Summary 1. Three cases are reported of childrensuccumbing to a disease process resembling Wernickes encephalopathy. 2. There is no convincing evidence of a dietary inadequacy of thiamine or other vitamins, nor of a difficulty with intestinal absorption, nor of an abnormally high thiamine requirement in these cases. 3. Two of the patients were siblings of a consanguineous marriage. It is suggested that a congenital metabolic disorder, possibly involving the utilization of thiamine or in the enzymatic processes with which thiamine derivatives are concerned, may be present in these cases.

DEGENERATION OF WHITE MATTER IN HYPOXIA, ACIDOSIS AND EDEMA

In contrast to its usual effect, hypoxia appears at times to induce selective injury of the white matter with sparing of the gray. The factors involved were studied in the human brain at autopsy, with seven cases serving to illustrate the mechanisms though to be operative in this and related phenomena. It is suggested that such white matter injury results from the simultaneous effect of hypoxia and edema. The edema may be due to unrelated cause, such as trauma or hypertensive disease, but it may also be due to acidosis or other consequence of hypoxia, particularly generalized hypoxia which affects the body as a whole including the circulating blood. The uniformly diffuse, generalized cerebral edema that may result in such circumstances cannot be locally severe, even when producing severe swelling of the brain as a whole, and this results in difficulties in recognition and interpretation. With gold sublimate stains, the changes in astrocytes characteristic of edema are evident in generalized hypoxic states, and at times these may be the only recognizable histologic change. The pattern of change is like that in other cases of edema, and is thought to indicate that here too, the edema is essentially extracellular.

Tumors of neurons and their precursors.

A series of 10 central nervous system tumors thought to be composed of neurons and their multipotential precursors, are described and analyzed. Three are interpreted as hamartomas, seven as neoplasms. Six of the latter contained mature, well formed neurons, and of these, four contained anaplastic neurons, and two, and possibly a third, contained astrocytomatous tissues, as well. One neoplasm contained anaplastic neurons in the absence of well differentiated neurons. The observations suggest that these are embryonal tumors arising in nests of primitive multipotential neurectodermal cells which may mature and differentiate into neurons and neurologia, these being normal, malformed or neoplastic. Should neoplastic change supervene at any stage of maturation, either or both of two distinct processes may then operate to alter the appearance and biological activity of the tumor: the cells may continue to mature and differentiate, and grow more slowly, and the cells may become more anaplastic and grow more rapidly. Dedifferentiation, the concept that mature cells pass backward along the normal path of embryologic development to become immature cells, is thought not to be involved; if it occurred, the malignant neuronal tumors would tend to resemble neuroblastomas like those of the adrenal, but this is not the case. Much fibrous connective tissue is present in all of the neoplasms, and this is thought to be a product of Schwann cells formed from primitive reticular cells in response to the neuronal fibers present in such tumors, or which had been present prior to the onset of anaplastic changes.

Sarcoma Arising in Oligodendroglioma of the Brain

A case is reported of a tumor composed of both oligodendrogliomatous and sarcomatous elements. The interpretation is offered that the sarcoma arose secondarily by neoplastic transformation of the hyperplastic blood vessels formed in response to the presence of the oligodendroglioma. This tumor may be considered analogous to the astrocytoma-sarcoma, which is much more common, and to the metastatic carcinoma with secondary sarcoma, of which one case has been reported.

Schwann cells and regenerated peripheral myelin in multiple sclerosis: An ultrastructural study

Tissues of a multiple sclerosis plaque in the brachium conjunctivum of the pons known to contain peripheral myelin by light microscopic studies were removed from the paraffin block and processed for electron microscopic studies. The cells related to the peripheral myelin possessed the ultrastructural characteristics of Schwann cells, with basement membranes and associated collagen fibers. No continuity was seen with the peripheral nerve tissues of any cranial nerve. These Schwann cells probably arose within the central nervous tissues by selective maturation of multi potential primitive reticular cells, a phenomenon consistent with the view that Schwann cells are mesenchymal in character.

Intracranial Lipomas, Hydrocephalus and Other CNS Anomalies in Oculoauriculo-Vertebral Dysplasia (Goldenhar-Gorlin Syndrome)

13 cases of Goldenhar-Gorlin syndrome are presented in which numerous central nervous system anomalies have been found. These include occipital encephalocele, hydrocephalus, aqueductal stenosis, agenesis of corpus callosum, multiple congenital lipomas and many others. Pertinent literature has been reviewed. It is concluded that any part of the central nervous system can be involved in this condition and that careful evaluation is indicated in order to rule out a treatable intracranial anomaly.

The nerve sheath tumor, solitary and in von Recklinghausen's disease; A unitary mesenchymal concept

SummaryThe characteristic cell of peripheral nerves, the Schwann cell, is capable of forming peripheral myelin, but also of forming collagen and reticulin fibers and of being transformed into macrophages. This kind of cell has been demonstrated under circumstances in which its formation from pre-existing Schwann cells is precluded, as in regenerative foci within the brain in multiple sclerosis. It is suggested that this cell is a specilized mesenchymal element, and that it may be formed by maturation of the multipotential primitive reticular cells which give rise to other specialized mesenchymal elements in appropriate circumstances, and which are present in the brain as well as in most other tissues.It is suggested that only one type of neoplasm of specific Schwann cell origin exists, this being the same in the presence or absence of von Recklingshausens neurofibromatosis. It may most simply be designated as the nerve sheath tumor. Von Recklinghausens disease, however, is characterized by the occurrence of hamartomatous and degenerative phenomena, as well as the tendency to neoplasia, and these alter the appearnce of the specific nerve sheath tumor and of non-neoplastic segments of peripheral nerves. In addition, some neoplasms observed in this disease have been interpreted as of Schwann cell origin when, in fact, they are less specific fibromas originating in other connective tissue elements of a nerve, or in the extra-neural connective tissues. The term “neurofibroma” appears to have been applied to both of these phenomena, i.e., to degenerative, non-neoplastic changes in nerves, and to neoplasms which may not have originated in Schwann cells or even within peripheral nerves; its continued use is not warranted.ZusammenfassungDie für den peripheren Nerven kennzeichnende Zelle, die Schwannsche Zelle, ist imstande, sowohl Myelin vom peripheren Typ als auch Kollagen und Reticulin zu produzieren und als Makrophage tätig zu sein. Diese Fähigkeit der Zelle konnte unter solchen Umständen beobachtet werden, unter denen ihre Bildung aus autochthonen Schwannschen Zellen zwingend ausgenommen werden mußte, wie z.B. in den Foci der multiplen Sklerose im Gehirn. Es wird die Annahme vorgebracht, daß diese Zelle ein besonderes bindegewebiges Element ist, das sich durch Reifung von den multipotenten primitiven Reticulumzellen ableitet, die unter bestimmten Umständen auch andere spezielle mesenchymale Elemente produzieren, und die im Gehirn wie in den meisten anderen Geweben vorhanden sind.Ferner wird postuliert, daß es nur eine einzige Art von Geschwülsten der Schwannschen Zelle gibt, ungeachtet dessen, ob die von Recklinghausensche Neurofibromatose vorliegt oder nicht. Diese Geschwulst sollte einfach als Nervenscheidentumor bezeichnet werden. Die Recklinghausensche Krankheit ist jedoch durch das Vorkommen von Hamartomen und degenerativen Phänomenen sowie durch eine Bereitschaft zur Geschwulstbildung gekennzeichnet. Diese Momente ändern das Bild eines spezifischen Nervenscheidetumors sowie das der nichtneoplastischen Segmente des peripheren Nerven. Einige Geschwülste, die bei dieser Erkrankung vorkommen, wurden als Derivate der Schwannschen Zellreihe angesehen, während sie in Wirklichkeit weniger spezifische Fibrome sind, die ihren Ursprung von anderen Bindegewebselementen des Nerven oder des extraneuralen Gewebes nehmen. Die Bezeichnung “Neurofibrom” hat man anscheinend auf beide dieser Phänomene angewandt, d.h. auf Fälle, von regressiven, nicht-neoplastischen Veränderungen der Nerven und auf solche Geschwülste, die ihren Ursprung möglicherweise weder von der Schwannschen Zelle noch überhaupt im peripheren Nerven genommen hatten. Die weitere Anwendung dieser Bezeichnung erscheint unberechtigt.

Arthrogryposis multiplex congenita. Report of two cases of a radicular type with familial incidence.

ARTHROCRYPOSIS MULTIPLEX CONGENITA has been classified from the pathogenetic point of view in 2 main categories:’ [A] cases due t o degeneration and loss of motor neurons in the anterior horns of the spinal cord and [B] cases due to an infantile muscular dystrophy. Only very recently a third type of congenital familial arthrogryposis has been observed, which is associated with a peculiar focal collagenous proliferation in the anterior spinal roots.2 It is the purpose of this communication to focus attention on this radicular form by reporting 2 cases that we have recently had the opportunity to study.

The influence of the ground substance on the extracellular water of normal and edematous human brain: focal edema and the demyelinating diseases, including multiple sclerosis.

The presence of a ground substance in brain provides a mechanism by which edema localized to one region of the white matter might occur without spreading diffusely into the adjacent tissues. The most common such localization is the sparing of the arcuate white matter when the deeper white matter is markedly edematous. This may be related to the higher concentration of mucopolysaccharides in the former. Petechial hemorrhages in the white matter may be surrounded by a zone free of edema, although the hemorrhagic zone itself is almost certainly edematous. This, and the presence of a central zone within some of the petechiae forming a ring hemorrhage may reflect the influence of the ground substance. Focal lesions of the dorsum of the corpus callosum and similar lesions of the basal surface of the ports, these probably due to traumatization by the contiguous falx or arteries, are characterized by myelin loss and axon preservation, a characteristic of edema; the surrounding tissues are not edematous. Severe hypertension is sometimes associated with the presence of clusters of focal perivenous demyelinating lesions in the white matter, the axons being preserved. These resemble the lesions of acute disseminated encephalomyelitis and may be due to edema; they are surrounded by nonedematous white matter. It is suggested that the same concept may apply to the focal demyelinating lesions of acute disseminated encephalomyelitis, multifocal leukoencephalopathy, central pontine myelinolysis and of multiple sclerosis i.e. the “true” demyelinating diseases, just as has already been suggested for diffuse sclerosis.

A modification for paraffin sections of silver carbonate impregnation for microglia

SummaryA technique is described whereby the cytoplasm of microglia is stained in routinely fixed paraffin embedded sections, greatly facilitating the study of these cells in normal and pathological sites. Of interest is the apparent paucity of these cells in normal tissues and their rapid and intensive proliferation in pathological states. The changes observed may be correlated with changes recognized with other stains on companion paraffin sections of the same tissue.ZusammenfassungEs wird eine Methode beschrieben, mittels welcher das Cytoplasma der Mikrogliazellen in den routinemäßig fixierten und paraffineingebetteten Schnitten zur Darstellung gebracht wird. Diese Methode erleichtert die Untersuchung dieser Zellen in normalen und pathologischen Zuständen. Von Interesse ist die augenscheinliche Seltenheit dieser Zellen im normalen Gewebe und ihre schnelle und mächtige Proliferation in pathologischen Zuständen. Die beobachteten Veränderungen können mit den Ergebnissen von anderen Färbemethoden an benachbarten Schnitten von demselben Block korreliert werden.