Hirotsugu Shiraki

Panencephalopathic type of Creutzfeldt-Jakob disease: primary involvement of the cerebral white matter

Eight necropsy cases of a “panencephalopathic” type of Creutzfeldt-Jakob disease (CJD) in the Japanese are reported. The reasons why this type should be discussed separately from other types of CJD are that there is primary involvement of the cerebral white matter as well as the cerebral cortex, and that the white matter lesion of one Japanese human brain with CJD similar to the present group has been successfully transmitted to experimental animals.

A study of the evolution of viral infection in experimental herpes simplex encephalitis and rabies by means of fluorescent antibody.

Introduction The mani fes ta t ions of v i ra l infect ions are the resul t of i n t eg ra t ion of focal effects caused b y v i rus mul t ip l i ca t ion in t a r g e t organs and the subsequen t genera l r eac t ions of the hos t ind iv idua ls . As far as v i rus infect ion of the cen t ra l ne rvous sys t em is concerned, the pa thogene t i c ana lys is depends on de ta i l ed in fo rma t ion a b o u t the sequence of the focal effects, since the neuroce l lu la r damage b r o u g h t a b o u t b y the v i rus re la tes d i r ec t ly to a d i s tu rbance of d i f ferencia ted ne rvous funct ions as an example of pol iomyel i t i s . One of the reasons w h y herpes s implex and rabies infect ions are discussed toge the r in th is p a p e r is because of t he con t r a s t be tween t h e m : the herpes s implex v i rus is p a n t r o p i c and has t he c a p a c i t y of forming nuclear inclusions as a morphological equ iva l en t to v i rus mul t ip l i ca t ion (McNAm SCOTT et el. 1953), while t he rubies v i rus is h igh ly neuro t rop ic and produces the classical Negr i bodies. l~ecent advances in the field of f luorescent a n t i b o d y technic have p e r m i t t e d v i sua l i za t ion of t he v i rus par t i c les in his tologic p repa ra t ions . Using this technic , our a t t e m p t s were d i r ec t ed to the inves t iga t ion of some fea tu res of v i rus p ropagat ion in he rpe t i c encepha lomyel i t i s of suckl ing mice, wi th sho r t t e rm expe r imen t s on v i rus infec t ion of cu l t i va t ed as t rocytes . W e also hoped to c lar i fy the va r i a t i ons of r ep l i ca t ion of rab ies v i rus which a p p e a r to be r e l a t ed to the different ce l lu lar cons t i t uen t s of the ne rvous sys t em and sa l iva ry g land of suckl ing mice.

Double encephalitis with herpes simplex virus and cytomegalovirus in an adult.

SummaryA 51-year-old housewife developed symptoms of a cold followed by high fever, delirium, coma, rigidity of extremity muscles, positive Babinski sign and generalized convulsions, while complement-fixing antibody titre to herpes simplex virus in the sera raised over 128x and declined to 8x in the course. She finally expired of bronchopneumonia following status epilepticus after 94 days of illness.Severe necrosis with extensive hemorrhage in the white matter was predominant in the temporal, insular and orbitofrontal cortex, thalamus and globus pallidus. Focal rarefaction of the cerebral cortex with a very few oesinophilic intranuclear inclusions in the oligodendroglia and nerve cells, nerve cell destruction in the substantia nigra with glial nodules and perivascular inflammatory cell cuffs were observed. Abundant cytomegalic inclusion cells, originating from hypertrophic astrocytes, were present in the necrotic areas of cerebrum as well as in the rarefied tissue in the subependymal layers of the brainstem and cerebellum. Electronmicroscopic study of the cytomegalic cells demonstrated the presence of numerous virions in both nucleus and cytoplasm.Fortuitous infection of the brain by cytomegalovirus with necrotizing encephalitis by herpes simplex virus is unique. The cause of double viral infections and severe lesions by less virulent strains is discussed.

Ultrastructure of herpes simplex virus infection of the nervous system of mice

SummaryThe nervous system and small intestine of mice infected with herpes simplex virus were examined by electron microscopy from the viewpoint of virus-host interaction.The host cells examined included the neuron, astrocyte, oligodendrocyte, and Schwann cell. The susceptibility of the latter was not less than that of the neuron. The endothelial cell, perineural fibrocyte and smooth muscle cell were also host cells. Replication of herpes virus in the nervous system was proven to be identical to that occurringin vitro; initial reproduction of nucleocapsids in the nucleus and subsequent maturation at the nuclear membrane with envelope formation, followed by discharge into the cytoplasmic reticular cavities and finally release from the host cell. Inconsistency in the distribution of virus particles and viral antigen was chiefly concerned with the host cell nucleus and the glial cytoplasm.Herpes virions, though few, were identified in the axons of peripheral nerves, and in the periaxonal space of myelinated fibres in the brain and the nerve ganglia. Virions were present in tiny vesicles in the perikarya or as naked particles. In the distal parts of peripheral nerve, there was marked dissociation in the amount of virions between Schwann cells and the axon. The significance of the endoneural space and the axon in the neural speread of infection is discussed briefly.

Clinico-Pathological and Histochemical Studies of Hallervorden-Spatz Disease with Torsion Dystonia with Special Reference to Diagnostic Criteria of the Disease from the Clinico-Pathological Viewpoint

Publisher Summary This chapter presents clinico-pathological and histochemical studies of Hallervorden-Spatz disease with torsion dystonia with special reference to diagnostic criteria of the disease from the clinico-pathological viewpoint. Hallervorden-Spatz disease or syndrome is a rare clinico-pathological condition that affects hitherto normally developing children around 10 years of age, who are then doomed to death after a clinical course of 10 to 20 years. Stiffness of the extremities and mental retardation of a progressive nature, and the frequent familial incidence of the disease, constitute the main clinico-epidemiological features. The report concerns two siblings in whom the neuropathological features corresponded well with the classical criteria of Hallervorden-Spatz disease, while the clinical pictures consisted of typical torsion dystonia the nature of which was analyzed by electromyography. The histochemical analysis was concurrently done to clarify the nature of the increased pigmentary granules, the spheroid structures and the widespread lipid accumulation in neuronal cells. The histochemical studies encompassed both spheroids and pigmentary granules of the globus pallidus and substantia nigra, and the intraneuronal pigmentary granules of both cerebral and cerebellar cortex.

A case of demyelinating encephalomyelitis with some resemblance to collagen disease.

SummaryA woman, aged 26 years, who died of progressively worsening demyelinating encephalomyelitis in the course of 4 years is reported. The neuropathological findings included large subcortical softenings in the cerebral hemispheres, tiny perivenous demyelinated foci in their neighborhood and scattered in the white matter. There was an acute vasculitis with fibrinoid exudation in the affected as well as unaffected areas. Focal perivenous mononuclear cell infiltrations are conspicuous in the white matter. The laboratory and postmortem examinations suggested a collagen disease like SLE. The abnormalities included marked increase of serum γ-globulin, especially of IgG, and elevation of CRP, RA, and ANA titer, moderate thickening of the basement membranes of the renal glomeruli, onion skin-like periarteriolar fibrosis in the spleen, fibrous pericarditis and periadventitial fibrosis of myocardial arteries. Bilateral degeneration of the spinal posterior columns and dorsal roots was also observed. A probable relationship of the modified features in this example of demyelinating encephalomyelitis with abnormal immune mechanisms in the background is discussed.ZusammenfassungEs wird ein Autopsiefall von Entmarkungsencephalomyelitis bei einer 26jährigen Hausfrau berichtet, die nach mehreren Remissionen in einem rasch progredienten Krankheitsschub verstarb. Die Krankheit dauerte etwa 4 Jahre. Die eindrücklichsten neuropathologischen Befunde sind ausgedehnte subcorticale Erweichungsherde in den Großhirnhemisphären, perivenöse Entmarkungsherdchen in deren Umgebung und auch verstreut im Marklager und eine akute Vasculitis mit fibrinoiden Exsudaten in den veränderten und nichtveränderten Arealen. Perivenöse rund- und spindelzellige Infiltrationen fallen in den Markherden auf. Die Laboratorium- und Postmortemuntersuchungen ergeben einige Merkmale der Kollagenkrankheiten wie systemischer Lupus erythematosus, z.B. eine markante Vermehrung von γ-Globulin, besonders IgG, von CRP, RA und ANA im Serum, mäßige Verdickung der glomerulären Basalmembranen in der Niere, zwiebelschalenartige periarterioläre Fibrose in der Milz, fibröse Pericarditis und periadventielle Fibrose der myocardialen Arterien. Es findet sich auch eine bilaterale Degeneration der Hinterstränge und Hinterwurzeln im Rückenmark. Ein möglicher Zusammenhang zwischen den modifizierten Bildern im vorliegenden Fall der Entmarkungsencephalomyelitis und abnormen Immunmechanismen als Grundlage wird diskutiert.

The influence of age on infection in experimental herpes simplex encephalo-myelo-neuritis of mice as demonstrated by fluorescent antibody method

SummaryThe modification of infection pattern in the nervous system and viscera of one hundred and eight mice, which were administered intraperitoneally with herpes simplex virus at various stages of growth ranging from newborn to 30 days old, was investigated with fluorescent antibody method. DD strain mouse was proved to be far more susceptible than C57BL strain mouse.The lung and liver became less affected in parallel with advance of age, particularly complete absence of infection occurred in the latter organ of even one week old. The gastrointestinal tracts retained high sensitivity through the experiment.The nervous system displayed a fair susceptibility in all periods of growth. The regions showing definite change of infection were the cerebrum and cerebellum, in which marked but transient increase of infection rate was demonstrated at one week of age. The elevation of infectability in the cerebrum was accompanied by certain topistic vulnerability as seen in the temporal cortex and hippocampus. Peripheries of sympathetic and spinal nerves tended to be more extensively involved after two weeks of age. The spinal cord was representative of lesions with high incidence and stable pattern of infection. No essential change occurred in the range of host cells of the nervous system through the course of aging. The perivascular cellular cuffing took place in the parenchymal lesions of the central nervous system in three weeks old mice. There was no precise accumulation of virus antigen lining the cuffs.The role and significance of virus pathways, viremia and tissue susceptibility as possible factors taking part in the pattern modification in central nervous system infection were discussed in connection with aging of animals.ZusammenfassungDie Modifikation des Infektionsmusters im Zentralnervensystem und in den Körperorganen von 108 Mäusen, die zu verschiedenen Zeiten, vom Neugeborenen bis 30 Tage alt, mit Herpes simplex-Virus intraperitoneal inoculiert worden waren, wurde mit der Fluorescenz-Antikörpermethode untersucht. Der DD-Stamm von Mäusen war viel empfänglicher gegen Herpes simplex-Virus als der C57BL-Stamm.Die Stärke der Affektion in der Lunge und Leber nimmt parallel mit dem Alter ab. Keine Läsion wurde in der Leber der über 7tägigen Mäuse verursacht. Während der Dauer des Experiments war eine hohe Sensitivität im Gastrointestinaltrakt bemerkbar.Das Nervensystem zeigte eine mäßig starke Empfänglichkeit in allen Zeiten der Entwicklung. Die Regionen, in denen Veränderungen des Infektionsmusters bestanden, waren Groß- und Kleinhirn, dabei war eine markante, doch vorübergehende Steigerung der Infektionsrate bei 7 tägigen Mäusen auffällig. Die Zunahme der Ansprechbarkeit im Großhirn fiel mit einer topistischen Vulnerabilität des Temporallappens und Hippocampus zusammen. Peripherien der sympathischen und spinalen Nerven tendierten zu stärkerem Befall bei einem Alter über 14 Tage. Im Rückenmark war die Läsion am häufigsten und von stabilem Muster. Durch den Verlauf des Alters gab es keine wesentliche Veränderung der Wirtzellen des ZNS. Die perivasculäre Zellinfiltration fand sich in den parenchymatösen Läsionen des ZNS bei 21 Tage alten Mäusen. Es gab keine deutliche Ansammlung der Virus-Antigene in der direkten Umgebung der Zellinfiltration.Rolle und Bedeutung gewisser Faktoren, wie der Weg für Viruswanderung, Virämie und Empfänglichkeit des Gewebes, die die Modifikation des Infektionsmusters im ZNS möglicherweise beeinflussen, werden in Beziehung zur Alterung der Tiere erörtert.

Ein Autopsie-Fall von hypoglykämischem Koma bei einer jungen Diabetikerin mit verzögerter Geistes-und Körperentwicklung

SummaryThe autopsy findings of a 27-year-old diabetic woman who had a mental and somatic retardation since childhood (Prader-Labhart-Willi syndrome) and expired of hypoglycemic coma due to the insulin administration 13 days later are reported. The most remarkable changes in the CNS were prominent vascular reaction in the involved areas and fresh necrotic foci in the corpus callosum, optic chiasm, midbrain, pons and other areas, indicating recent disturbances of blood-brain-barrier. Some metabolic-humoral dysfunctions which cosisted in the background of Prader-Labhart-Willi syndrome could play a significant role for the development of the above mentioned fresh changes. Generalized hypoplasia of the endocrine organs, fibrosis of the pituitary posterior lobe, phenomena of the precocious senility in the CNS and an advanced focus of the optic tract, on the other hand, were possibly related to this longstanding syndrome of the present example.

Aktuelle mitteilungen · News items · renseignements actuels

The First Symposium on Neurotexicology is concerned with adverse reactions and toxic effects of tranquilizers and sedatives, antidepressives and stimulants (including hallucinogens), narcotics and opiates, alkylating and immunosuppressors, trace metals and lithium, and some insecticides and pesticides. Original contributions and reviews of the literature will consider the clinical, biochemical-pharmacological, toxicological and with special emphasis on the ncuropathological aspects. The latter will include histopathological, histechemical and electron microscope techniques as well as tissue culture and subcellular fractions methodologies. I t is believed that this exchange of multidisciplinary ideas may: a) shed some additional light upon the biochemical properties, b) give a clearer view of the mode of action and c) offer a better understanding of the possible pathogenic mechanisms of the chemical agents under discussion. I t is hoped that this more comprehensive knowledge may stimulate further research directed toward the development of antidotes and preventive measures to safeguard the patient and the society from iatrogenic disease processes. Organizing Committee: Prof. Leon Roizin, Chairman, U.S.A., Hirotsugu Shiraki, CoChairman, Japan, Nenad Grcevic, Secretary, Yugoslavia.

THE ACTUAL STATUS OF NEUROPATHOLOGY OF DEMYELINATING ENCEPHALOMYELITIDES OF UNKNOWN ORIGIN IN THE JAPANESE

One of the reasons why the studies on demyelinating encephalomyelitides in the Japanese have attracted the general attentions of the Western scientists in this particular field can be attributed to the traditional conception in which those diseases in oriental countries including Japan have been absent or exceedingly rare as compared with the high incidence of the illnesses in Caucasians. In fact, according to the recent clinico-pathospidemiologic studies by OKINAKA et all), the prevalence rate of the diseases to 100,000 populations of the Japanese in both Kumamoto and Sapporo cities was exceedingly low, i.e., 2 in each, while those in different cities of USA and Canada*) ranged from 16 (New Orleans) to 60 (New York). The definite diagnostic criteria for multiple sclerosis and allied disorders from a clinical viewpoint, on the other hand, have never been established up to date, except for the followings: Over two different clinical impairments according to invasion of lesions to different areas of the central nervous system do occur at different time intervals, while a clinical fluctuation, such as relapses and remissions, can develop. Thow clinicodiagnostic criteria of a polyphasic character, however, are essentially not pathognomonic for the diseases, and may possibly occur in other types of the central nervous system diseases, for examples, cerebrovascular, hepatocerebral and others. In this regard, it can be well understood that the pathomorphological examinations on those clinical cases are absolutely necessary. The 25 verified autopsied cases of demyelinating encephalomyelitides of unknown origin from different laboratories in Japan comprized; 9 of neuromyelitis optica, 1 of demyelinating myelitis, 1 of demyelinating optic neuritis, 3 of acute multiple sclerosis and allied disorders, 2 of transitional sclerosis and allied diseases, 6 of Schilder’s disease and 3 of subacute to chronic disseminated encephalomyelitis, brain stem type (SHIRAKI). The kernels of the pathomorphologic features of classic type of mu2tiple sclerosis as frequently encountered in Caucasians can be summarized as follows