Symposium on Neuropathology Harry M. Zimmerman, M.D., Guest Editor*
INTRODUCTION In very recent )'ears the progress that has been made in advancing knowledge c o n c e r n i n g mechanisms o f disease affecting the nervous s)'stem in man has been p h e n o m e n a l . From a plodding discipline preoccupied with classifications based excluslvely on morphologic alterations, n e u r o p a t h o l o g y has become t r a n s f o r m e d by the search for and discovery o f pathogenetic agents. T h e s e include not only living agents, such as bacteria and tkmgi, as well as many classes o f viruses, but also chemical and physical agents, genetically conditioned defects, and i n b o r n errors o f metabolism. Most o f the advances in neuropatlmlogy were made possible, o f course, by conc u r r e n t advances in related disciplines, such as genetics, neurobiochemistry, histochemistry and microchemistry, enzymology, virology,, and imnmnologv,, to cite an incontplete list. T h e n , fortuitously, certain instrumelatS and techniques became available that hitherto did not even exist. A m o n g them should be m e n t i o n e d transmission anti scanning electron microscopy, imnmnolluorescence, anti electrophoresis. Again this is but a partial list. T h e summary effect o f the almost s u d d e n availability o f ntethods and apparatus in a field replete with problems awaiting solution was to attract young investigators. Neuropathologists who a little over a generation ago were perhaps rift)' in n u m b e r now can be c o u n t e d in the h u n d r e d s in this country alone. It should be realized that in the selec-
tion o f articles for a symlmsium m x ~ pathology, in which so much actMty is now in progress, a certain arbitrariness is inevitable. T h e additional limitations of space that p r e c l u d e a fifli display o f the new "wares" in n e u r o p a t h o l o g y also c o n t r i b u t e to a less than impartial selectivity. In the selection o f papers for this symposium it was the aim to provide a sampling o f the new orientation in a few o f the conditions that affect the nervous system. T h e r e is no single unifying topic that was chosen as a central thenae. It will be n o t e d that concepts o f disease Imve often been subjected to e x p e r i m e n t a l p r o o f and to new methods o f attack in the contributions to this s)'mposium. One o f the age-old problems in n e u r o pathology, as yet unresolved, is c o n c e r n e d with the demyelinative process as seen in multiple sclerosis. A vast body o f work o f an experimental n a t u r e has been perf o r m e d in recent years in this field. Many investigators have utilized the mammalian nerwms system as the animal model for multiple sclerosis in experiments on allergic encephalomyelitis. Dr. l'rineas has studied the earl)" lesion o f multiple sclerosis in Imman autopsy material and correlates his findings with those obtained in anilnal models. Equally baffling for most o f this century has been the problem o f the so-called lipid storage diseases, such as amaurotic family idiocy. A l t h o u g h it can by no means be claimed that with progress in recent )'ears there has resulted a simplification o f
*Professor of l'admhN.v, Emeritus, Albert Einstein College of Medicine. l'roli2ssori;d l.ecturcr. The Mount Sinai School of Medicine of tile City University of New York. Consultant. l)el>artment of l'athology, Montcfiore llospital and Medical Center, New York, New York.
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tlUMAN I ' A T H O L O G Y - - V O L U M E 6, NUMBER 5 September 1975 concepts r e g a r d i n g this very large g r o u p of conditions, a clearer u n d e r s t a n d i n g o f the m a n y p r o b l e m s involved has b e e n aclfieved." T h e complexities o f n e u r o n a l storage diseases are p r e s e n t e d in a specilic e x a m p l e o f tltis class o f n e u r o n a l disease treated in detail, the gangliosidoses by Volk and his collal)orators. Brat the last word has not vet been written on the lipid storage diseases. T h i s is a p p a r e n t f r o m a p a p e r that has j u s t a p p e a r e d by Fishman et al., ~ who r e p o r t a novel type o i ' h u m a n sphingolipidosis characterized by the acctmmlatioll o f G.~).~ as the r e s u h o f a deficiency in ganglioside biosynthesis, l)revious cases were described as resulting fi'otu a defective catabolic reaction. T h e r a n g e o f interest o f n e u r o p a t h o l ogy has not been lintited to the obvious or suspected "organi(~" disorders of the nervous svstent., Neurol)sychiatric conditions lmve also been subjected to scrutiny with tire n e w e r techniques. An e x a m p l e o f such a study is supplied by Doctors Gonatas a n d Moss, who have f o u n d fine structure changes in axons a n d synapses in certain psychiatric disorders. In a concise p a p e r on stroke Dr. Julio Garcia has defined this ternt and has out-
530
lined most o f the c u r r e n t concel)tS conc e r n i n g it that have been f o u n d valid I)y laboratory COllfirmation. O n e f o r m o f stroke is p r o d u c e d by cerebral embolization, a n d u n u s u a l ex]mH)les of embolization by nontln-ombotic agents are supplied by Dr. Nitva G h a t a k . For s o m e years I)r. Asao H i r a n o has I)ecn in tile f o r e f r o n t o f investigations on cerebral e d e m a a n d swelling u n d e r a variety of circumstances, including the l)resence o f brain tumors. This led him naturally to a study o f the fine s t r u c t u r e o f the cerebral blood vessels and the bloodbrain barrier. As an examl)le o f the work by him and o t h e r s in this iml)ortant lield o f investigation t h e r e is included his latest contribution with a coworker, Dr. Matsui, on "Vascular Structures in Brain T u m o r s . " HARRY M. ZIMMERMAX, M.D.
REFERENCE 1. Fishman, I'. It., Max, S. R., Tallman J. F., Brady, P,. O., Maclaren, N. K., ,rod Cornblath, M.: Deficient gangliosidc biosynthesis: a novel human sphingolipidosis. Science, 187:68-71), 1975.
INTRODUCTION In very recent )'ears the progress that has been made in advancing knowledge c o n c e r n i n g mechanisms o f disease affecting the nervous s)'stem in man has been p h e n o m e n a l . From a plodding discipline preoccupied with classifications based excluslvely on morphologic alterations, n e u r o p a t h o l o g y has become t r a n s f o r m e d by the search for and discovery o f pathogenetic agents. T h e s e include not only living agents, such as bacteria and tkmgi, as well as many classes o f viruses, but also chemical and physical agents, genetically conditioned defects, and i n b o r n errors o f metabolism. Most o f the advances in neuropatlmlogy were made possible, o f course, by conc u r r e n t advances in related disciplines, such as genetics, neurobiochemistry, histochemistry and microchemistry, enzymology, virology,, and imnmnologv,, to cite an incontplete list. T h e n , fortuitously, certain instrumelatS and techniques became available that hitherto did not even exist. A m o n g them should be m e n t i o n e d transmission anti scanning electron microscopy, imnmnolluorescence, anti electrophoresis. Again this is but a partial list. T h e summary effect o f the almost s u d d e n availability o f ntethods and apparatus in a field replete with problems awaiting solution was to attract young investigators. Neuropathologists who a little over a generation ago were perhaps rift)' in n u m b e r now can be c o u n t e d in the h u n d r e d s in this country alone. It should be realized that in the selec-
tion o f articles for a symlmsium m x ~ pathology, in which so much actMty is now in progress, a certain arbitrariness is inevitable. T h e additional limitations of space that p r e c l u d e a fifli display o f the new "wares" in n e u r o p a t h o l o g y also c o n t r i b u t e to a less than impartial selectivity. In the selection o f papers for this symposium it was the aim to provide a sampling o f the new orientation in a few o f the conditions that affect the nervous system. T h e r e is no single unifying topic that was chosen as a central thenae. It will be n o t e d that concepts o f disease Imve often been subjected to e x p e r i m e n t a l p r o o f and to new methods o f attack in the contributions to this s)'mposium. One o f the age-old problems in n e u r o pathology, as yet unresolved, is c o n c e r n e d with the demyelinative process as seen in multiple sclerosis. A vast body o f work o f an experimental n a t u r e has been perf o r m e d in recent years in this field. Many investigators have utilized the mammalian nerwms system as the animal model for multiple sclerosis in experiments on allergic encephalomyelitis. Dr. l'rineas has studied the earl)" lesion o f multiple sclerosis in Imman autopsy material and correlates his findings with those obtained in anilnal models. Equally baffling for most o f this century has been the problem o f the so-called lipid storage diseases, such as amaurotic family idiocy. A l t h o u g h it can by no means be claimed that with progress in recent )'ears there has resulted a simplification o f
*Professor of l'admhN.v, Emeritus, Albert Einstein College of Medicine. l'roli2ssori;d l.ecturcr. The Mount Sinai School of Medicine of tile City University of New York. Consultant. l)el>artment of l'athology, Montcfiore llospital and Medical Center, New York, New York.
629
tlUMAN I ' A T H O L O G Y - - V O L U M E 6, NUMBER 5 September 1975 concepts r e g a r d i n g this very large g r o u p of conditions, a clearer u n d e r s t a n d i n g o f the m a n y p r o b l e m s involved has b e e n aclfieved." T h e complexities o f n e u r o n a l storage diseases are p r e s e n t e d in a specilic e x a m p l e o f tltis class o f n e u r o n a l disease treated in detail, the gangliosidoses by Volk and his collal)orators. Brat the last word has not vet been written on the lipid storage diseases. T h i s is a p p a r e n t f r o m a p a p e r that has j u s t a p p e a r e d by Fishman et al., ~ who r e p o r t a novel type o i ' h u m a n sphingolipidosis characterized by the acctmmlatioll o f G.~).~ as the r e s u h o f a deficiency in ganglioside biosynthesis, l)revious cases were described as resulting fi'otu a defective catabolic reaction. T h e r a n g e o f interest o f n e u r o p a t h o l ogy has not been lintited to the obvious or suspected "organi(~" disorders of the nervous svstent., Neurol)sychiatric conditions lmve also been subjected to scrutiny with tire n e w e r techniques. An e x a m p l e o f such a study is supplied by Doctors Gonatas a n d Moss, who have f o u n d fine structure changes in axons a n d synapses in certain psychiatric disorders. In a concise p a p e r on stroke Dr. Julio Garcia has defined this ternt and has out-
530
lined most o f the c u r r e n t concel)tS conc e r n i n g it that have been f o u n d valid I)y laboratory COllfirmation. O n e f o r m o f stroke is p r o d u c e d by cerebral embolization, a n d u n u s u a l ex]mH)les of embolization by nontln-ombotic agents are supplied by Dr. Nitva G h a t a k . For s o m e years I)r. Asao H i r a n o has I)ecn in tile f o r e f r o n t o f investigations on cerebral e d e m a a n d swelling u n d e r a variety of circumstances, including the l)resence o f brain tumors. This led him naturally to a study o f the fine s t r u c t u r e o f the cerebral blood vessels and the bloodbrain barrier. As an examl)le o f the work by him and o t h e r s in this iml)ortant lield o f investigation t h e r e is included his latest contribution with a coworker, Dr. Matsui, on "Vascular Structures in Brain T u m o r s . " HARRY M. ZIMMERMAX, M.D.
REFERENCE 1. Fishman, I'. It., Max, S. R., Tallman J. F., Brady, P,. O., Maclaren, N. K., ,rod Cornblath, M.: Deficient gangliosidc biosynthesis: a novel human sphingolipidosis. Science, 187:68-71), 1975.
