Publicaties van Gabriel Steiner over Multiple Sclerose (MS)

[Martijn]

Environmental studies in multiple sclerosis.
by Gabriel Steiner, M.D.
Neurology, Vol. 2, May-June:260-262. 1952.

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“A particular environmental extrahuman reservoir of the disease agent is highly probable.”
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Environmental studies in multiple sclerosis have been very much neglected. Recent mortality and morbidity statistics (1,2) show that there is a definite geographic difference in the occurrence of this disease.

The present environmental studies are limited to the state of Michigan. Five hundred cases were collected. ...Only cases with well established diagnoses were accepted. ...The fact that this material of 500 cases comes from two sources, one group examined and evaluated clinically in the Multiple Sclerosis Center and the other group obtained from questionnaire surveys of medical sources is of importance. The results are the same in both groups. ...

1. A difference was found in various regions of the state. ...

2. Intrafamilial cases. In places where multiple sclerosis is more common, there are often more cases in one household. ...These figures show that in these households females are more exposed to the outside source of the disease than males and that in families, combinations of multiple sclerosis among siblings are two and one-half times more common than paternal-filial combinations. Apparently sisters and/or brothers are more exposed to the outside source of multiple sclerosis than parents and their sons or daughters.

It seems worthwhile to note that all of the familial cases shared the same household. In one case of two brothers and one case of two sisters the patients shared the same beds for some time before the onset of the disease. Of interest also is the presence of pet animals, dogs and cats, in the same household. Relatively often, these animals were infested with fleas. As to the occupations of the fathers, there seem to be some preferences: farming, gardening and greenhouse work, five times; building industry (lumberman, carpenter, contractor), five times; maintenance of estates (supervisor, janitor), three times; and teaching, three times. In one of the familial cases (father and daughter) the father had a work shop in the basement of his home.

3. If there is an environmental extrahuman source in our material, other non-familial contact cases should be found also. Of special interest is the case of a girl with multiple sclerosis of two months' duration which was verified by necropsy. In the home of this girl there was a boarder, a female nurse who took care of a chronic female case of multiple sclerosis in another part of the city. The girl was very fond of cats. At the time of death of this patient the cat was no longer available because it had to be removed from the home and sacrificed, the reason given was that the cat was flea-ridden.

4. If there is an environmental factor, the occupations of cases may be of interest. In 500 cases of multiple sclerosis collected up to the present, 34 teachers with multiple sclerosis were found. Twenty-five of these teachers were born and teaching in Michigan before the onset of their disease. It is interesting to note that the disease was found among elementary school and kindergarten teachers 24 times and among high school teachers only seven times. Also interesting is the high frequency of pet animals belonging to teachers. Cases of multiple sclerosis among non-teaching personnel in schools were found only three times...


There are some of the statistical facts. What are the conclusions?

1. There is no man to man transfer. There is no transovarian passage.

2. A particular environmental extrahuman reservoir of the disease agent is highly probable.

3. This extrahuman reservoir and its accumulation in the environment of certain groups is responsible for the higher incidence in household groups (families) and among teachers, especially kindergarten and elementary school teachers, and moreso in rural areas.

4. In the same household siblings are more exposed to the extrahuman source than in the paternal-filial combination.

5. Dogs or cats may be suspected as reservoirs of the agent. However, the popularity of dogs as pets in the general population renders a statistical evaluation of this factor extremely difficult. Other investigations have been inaugurated.

6. Insect vectors as links in the chain of transmission may be significant or not; the chronicity of the disease and damaged memories in the later stages of the disease make the evaluation of this factor very difficult.

[Martijn]

Acute plaques in multiple sclerosis, their pathogenic significance and the role of spirochaetes as etiological factor.
by Gabriel Steiner, M.D.
Journal of Neuropathology, 11:343-72. 1952.

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“In this respect the discovered spirochetes were totally different from the treponema-type and resembled the borrelia-type of spirochetes.”
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In the chronic form [of multiple sclerosis] the findings at the time of death represent a terminal cross section of the course of the disease; previous inflammatory reactions may have disappeared partially or entirely. In many other chronic inflammatory disease entities of the central nervous system and other organs of the human body, acute phases and chronic forms of the same disease entity are of common occurrence.

It is the purpose of this paper to contribute some observations to the study of subacute cases of multiple sclerosis, to discuss some of the pathogenetic features of acute plaques in multiple sclerosis and to establish a relationship between spirochetes and tissue reactions in multiple sclerosis.

...Acute plaques in multiple sclerosis occur, significantly, not only in subacute cases of several months' duration but also in older cases in acute clinical relapse. Equally and especially important is the presence of older plaques in subacute cases, indicating morphological manifestations dating back to clinically latent initial stages of the disease at its earliest onset. With these findings in mind, separation of multiple sclerosis into two distinct and different entities seems not justified. [some of Steiner's peers had argued that there were two disease entities -- one an acute disease, the other a purely degenerative chronic disease]

The search for the causative agent in the diseased tissues promises more success when earliest stages of tissue alteration are available for such investigation. Significant pathogenetic information is furnished by the following case of subacute multiple sclerosis.

CASE REPORT

History: A Negro, aged 30 years, was in good health until May of 1948. At that time he noticed weakness of the left leg. This gradually progressed so that he was forced to drag his left leg, and to remain home from work. The paralysis then extended to the left arm and the left side of the face. His condition grew rapidly worse. Finally he was unable to walk or talk and was admitted to Receiving Hospital on August 7, 1948. ...Course: The patient improved slightly with supportive therapy until August 20, 1948, when his temperature rose to 102 F. Five days later he developed hyperthermia and fell into a deep coma, without recovery. He expired the following day.

...Post Mortem Findings... Central Nervous System: The entire brain and two small pieces of the spinal cord were obtained...There were multiple demyelinated plaques in the right parietal region, mostly in the white matter...In the left hemisphere there were a few scattered plaques also...In sections of the spinal cord no definite plaques were found but some whitish discolorations in wedge shape with the base at the periphery.

Microscopic Observations: In myelin sheath preparations, numerous demyelinated plaques were seen (fig. 1). In these plaques the myelin sheaths were either completely lost or a few islands of preserved myelin sheaths were seen, but the complete loss prevailed. The demyelinated plaques were of varying dimensions. In fat stains these demyelinated areas showed equal distribution of the fatty products; in older plaques, however, these fatty products were lacking or remained in larger quantities only in adventitial spaces of blood vessels. ... The nerve cells in plaques were well preserved (Nissl stain). ...When grey and white matter participated in one single demyelinated plaque the demyelination took place in grey and white matter alike without respect to the border-line between grey and white matter. ...

The Special Silver Salt Reduction Technique to Demonstrate Granular Bodies and Spirochetes:
[a detailed description is provided].

Extracellular Granular Bodies: These granules were of varying sizes and shapes. Round, ovoid, or irregularly contoured shapes were common. ...Two or more granules in close proximity were also seen. The dimensions of these extracellular granules varied from the size of a mast cell granule to one of the size of a red blood corpuscle or even of a small glial nucleus. Often the extracellular granules and astrocytes containing intracellular granules were accumulated around blood vessels in perivascular parenchyma. They were seen abundantly also in the parenchyma without any relationship to blood vessels and less frequently in vessel walls themselves. The photomicrographs (fig. 4) show better than any detailed description the shapes, sizes and locations of these extracellular granular bodies.
[a series of photographs of spirochetes and spirochetal granules found in the autopsied tissues is provided]

Intracellular Granular Bodies: ...The granules differed in shape and size from the extracellular granules. They were more massive, and of a very irregular shape. Nevertheless, they were of the same black, shiny color. ...The intracellular granules were demonstrable by the silver techniques I and II.

Spirochetes: In their fully developed, not yet disintegrating forms, the spirochetes appeared as screw-like organisms. ...Crests and roots were always rounded, never pointed. The minimal thread angle was 60°, its maximum 130°, the average being 97°. In this respect the discovered spirochetes were totally different from the treponema-type and resembled the borrelia-type of spirochetes. ...

Knobs at one end were not unusual (figs. 8d, e, and 9c). There were also loops in the center of the longitudinal axis or more toward the end. The spirochetes were completely detached from any tissue elements. ... The spirochetes were found in marginal areas of acute plaques and in perifocal location in areas close to the periphery of acute plaques, often in histologically seemingly intact tissues. They were always found in locations where abundant extracellular and intracellular granular bodies were present. This close spatial relationship between the spirochetes and the granular bodies is of the greatest practical importance in finding intact and well preserved spirochetes. When masses of extracellular and intracellular granular bodies are found, spirochetes should be looked for at the peripheral areas of an acute plaque containing granular masses close to and in the normal tissues of the central nervous system. One should not expect, however, to find such enormous masses of well preserved spirochetes, as for example, treponemas are seen in the organs of congenital syphilis... The highest number of individual spirochetes in brain and spinal cord of this polysclerotic case were 8 in a high power oil immersion microscopic field. ...

The not disintegrated spirochetes [8 were found] apparently represent stragglers left behind by an enormous army of regularly coiled individual spirochetes. If the granular bodies seen in abundant masses are remnants of disintegrated spirochetes these microorganisms must have been present in enormous numbers and apparently their individual life-span must have been short, in inverse ratio to the speed of reproduction. Excessive reproductive activity of spirochetes, that is speed of multiplication on one hand and very short life-span of the individual spirochetes on the other, are conclusions to be made from the histological appearances.


Significance of Granular Bodies: The very abundant accumulation of granular bodies in close regional relationship to polysclerotic plaques of acute or subacute order can easily be detected. Thus, the granular bodies were seen by many observers (Austregesilo (son) (11), Steinger (12), Guirand (13a, b), Rogers (14), Austregesilo (father) and Fortes (15), Scheinker (16a,b), Marburg (17). These granular bodies were interpreted differently by the various observers, but all agreed that they represented products of disintegration either of tissue elements (Marburg (17)) or of microorganisms. Only Giraud (13a,b) claims that the bodies are the microorganisms themselves. ...

The Relationship of Granular Bodies and Spirochetes: There are all intermediate stages between well preserved regularly coiled spirochetes and granular bodies. There are terminal granules with adherent spirochetal threads (fig. 9c); there are granules already freed from the still persisting spirochetal thread, but at a very short distance from it, so that the breaking off of the granule from the spirochetal thread seems very probable. ...There are spirochetes...still showing the structural continuity between the granule and the spirochete. The knobs and loops represent probably the earliest transitional phases from the spirochetal form to granule formation. There is no doubt that the granular bodies, the haptocytes and the spirochetes are in intimate pathogenetic relationship. ...

The biological significance of these bodies in multiple sclerosis is still obscure. One aspect, however, is certain: These granular bodies are definitely related to the presence of well preserved spirochetes and their disintegrating forms.

Granular bodies in general may represent 1) involutional forms (a) with possibility of redevelopment into typical spirochetal forms, (b) representing beginning disintegration and final death of the spirochetes, (c) possibility of (a) and (b), that is, redevelopment into spirochetal forms as well as irreversible disintegration; 2) specific evolutional forms in the life-cycle of the spirochete. At present no decision between 1) or 2) is possible. ...Experimentally we can produce the granular bodies in cultures of well known spirochetes by exposure to a temperature to 56° centigrade. ...

In the case of multiple sclerosis it is certainly premature to speculate about the significance of the granular bodies in the life cycle of the specific spirochetes. Nevertheless, the value of the granular bodies as indicators of spirochetal presence in the tissues cannot be underestimated.

In Table I a short review of positive findings [of spirochetes or granules in cases of multiple sclerosis] has been compiled. ...Until 1936, among 48 examined cases of multiple sclerosis, 12 were spirochete-positive (25 per cent). Two of these 12 cases (Brack and Kocheise) showed numerous spirochetes. Silver cells were found in over 90 per cent of the examined cases and haptocytes in 25 per cent. ...

In old chronic and treated cases of general paresis spirochetes are never found and the same is true for old stationary cases of tabes dorsalis. It is well known to the pathologist that the microscopic search for the agent in chronic infections, such as tuberculosis and syphilis is often troublesome and does not succeed. Why should it be different in multiple sclerosis?

EVIDENCE OF SPIROCHETAL NATURE

1. The specific morphology of the spirochetes could be described, photographed, and measured. The spirochetes were seen in large numbers in 4 cases of multiple sclerosis in identical morphology. Nothing like it was found in numerous control cases.

2. The order of magnitude is that of spirochetal organisms. The spirochetal structures are of varying length, from 4-18 microns. Their cross section is round like in all spirochetes. Length, thickness and shape of the spirochetal structures vary in the same range as in other well-known spirochetes. There are, however, enough specific morphologic peculiarities of these spirochetes which distinguish these organisms from other known spirochetes.

3. The staining reactions were the same as shown by other well known spirochetes contained in tissues. The typical silver affinity of all well known spirochetes which is essential for the demonstration of every type of spirochetes in tissues is a definite quality of the spirochetal structures in cases of multiple sclerosis. The specific argyrophilia of the spirochetal surface is common to bacterial surfaces but not to protozoan surfaces. All these bacterial and spirochetal organisms are without the colloidal protection against the silver mirror formation or at least without the same protection as most tissue elements and protozoa possess. That is the reason why tissue structures stain in yellow tinges while bacteria and spirochetes take the metallic mirror-like black silver coating. There is also a difference between the surface of bacterial rods and cocci, as well as of fungi on the one hand and that of spirochetes on the other, insofar as most bacteria and fungi need less time of exposure to silver salts (silver nitrate) to be reduced to metallic silver. A difference between the surfaces of bacterial and spirochetal organisms seems also to be indicated by the fact that the color reaction in living bacterial cultures by reduction of colorless tetrazolium salts (see article of Smith (39)) is quite common while living leptospira cultures at our disposal did not change their natural color into blue or red.

4. The spirochetal structures are completely detached from any tissue elements at both ends as well as on all sides. They appear as foreign bodies in the tissues. Very often an empty space or microvacuole is surrounding the black, mirror-like structure of the spirochete.

5. The spirochetes are seen in the parenchyma of brain and spinal cord itself, as well as in the vascular walls. This also excludes the possibility that these spirochetal structures may be elements of the parenchyma proper or reticular fibrils of the vascular walls.

To the eye of the experienced microscopist the reported structures cannot be explained otherwise than as specific spirochetes. They differ from any other known type of spirochetes, especially from the treponemas or leptospiras. They resemble the species of the Borrelia group of spirochetes. I named the organisms spirocheta myelophthora, that is, the myelin sheath destroying spirochete.

HOW TO FIND THE SPIROCHETES

The spatial and temporal conditions for a successful search for spirochetes have to be considered first. Not every polysclerotic plaque contains spirochetes. Old plaques with only little inflammatory reactions are unfit for the search. Plaques containing massive amounts of catabolic neutral fat are already too far advanced in the disease process to show spirochetes. ...the normal tissue between two neighboring acute plaques is a good place to look for spirochetes.

The examination for spirochetes in silver preparations is greatly facilitated by the presence of extracellular and intracellular (in astrocytes and microglia cells) granular bodies in masses. Extracellular granules seem to be the first manifestations of spirochetal disintegration. A later phase in intracellular. The finding of extracellular granular bodies is the first step for the search of spirochetes. ...The best preserved spirochetes were found at the margins of an area containing the granular bodies in masses and always at the margins of such a field toward the normal tissues and not toward the inside of a demyelinated plaque.

...Compared to the immense masses of granular bodies, spirochetes are less frequently found. The well preserved remaining spirochetes are to be considered, as already mentioned, as stragglers...

...The search for spirochetes in advanced, non- or slowly progressing cases is too tiresome and time consuming to promise a good chance for finding spirochetes.

...There remains the problems of who should look for these organisms. Diligence and patience of the examiner and ample time at his disposal are necessary requirements. The investigator should be acquainted with the various silver stains used for demonstration of tissue elements of human body and especially of the nervous system such as neurofibrils, neuroglia cells etc. Some knowledge of the appearance of spirochetes in tissue sections of the central nervous system and other organs of the body prepared with silver techniques will easily be acquired.

POSSIBLE SOURCES OF ERROR

1. Do the spirochete-like structures reported herewith represent pathological or normal tissue elements of the central nervous system and have nothing to do with multiple sclerosis? No structures similar to or identical with the spirochetes have been found in over 250 control cases of diversified diseases other than multiple sclerosis and of normal brains. ...the regularity in form and shape, the limitations at both ends of positive spirochetal findings exclude a mistaken interpretation as argyrophilic senile filaments. ...

2. Artifacts. In one textbook of neurology the spirochetal structures found in multiple sclerosis have been considered as artifacts (Grinker and Bucy (42)).

...Control sections of tissues containing numerous known spirochetes... were used in each batch of staining procedures. These sections serve at the same time as controls for the blackness of the silver-mirror on the spirochetes. Those who regard the spirochetal structures as artifacts are without experience in staining techniques of spirochetes or in the appearance of spirochetes in stained tissue sections. ... To assure a wide range of control of artifacts, numerous pieces of tissue from normal brains or from those affected by diversified diseases were exposed to autolysis, then fixed in formalin, embedded, cut and stained in the same way. No structures like those seen in brains and spinal cords of cases of multiple sclerosis were found. ...

3. The disclosed spirochetes cannot be those of syphilis, post mortem invaders, secondary invaders or contaminants. Spirochetes are found in normal man in the mouth, in the respiratory tract, in human feces and in genital regions. They are, for the most part, harmless non-pathogenic commensals. Spirochetes were never found in the central nervous system of normal man.

...[in] the case presented here and previous cases of multiple sclerosis in which spirochetes were found (Steiner (18, c, d, e), (Rogers (14), Austregesilo and Fortes (15), Scheinker (16)) syphilis could be excluded. Moreover, the disclosed spirochetes do not resemble at all the treponema pallidum; they are specific spirochetes, possibly belonging to the borrelia group

It is known that in the terminal phase of life, the last hours before death and after death central nervous system tissues can be invaded by saprophytic micro-organisms. ...The characteristic and typical finding in such cases is the lack of all inflammatory tissue reactions in spite of the presence of masses of bacteria. On the other hand, in multiple sclerosis there are often massive inflammatory reactions at the borders of recent demyelinated plaques, inside of these and their near extrafocal vicinity. These inflammatory reactions are only indirect evidence of past and present activity of the agent. The immediate proof of its activity is its presence in forms of varying stages of well preserved

to disintegrating forms, from regular spirochetal forms, more or less straight forms to all types of granular spirochetal disintegration, extra- and intracellularly. Particularly, the intracellular astrocytic and microglial ingestion of granular bodies is proof of the intravital activity of the disease process and its agents. Nothing like it is seen in other diseases when secondary post mortem invasion has taken place. ...

4. The possibility that the disclosed spirochetes are harmless intravital saprophytes must be excluded also. The histological reactions are evidence of tissue damage and besides no visible microbial saprophytes have ever been found in brains of normal or diseased human beings. ...

5. Another possibility has to be considered: that is the presence of the spirocheta myelophthora as a microscopically visible and detectable agent together with an ultravisible viral agent. This eventuality cannot be ruled out by our morphological studies with the light microscope. However, such a possibility does not detract anything from the etiological and pathogenetic significance of the findings of spirochetes. In principle, it seems to me very precarious to conclude from our inability to find visible organisms that the agent must be a virus. We know at least one spirochetal infectious disease which was considered due to a virus until Gsell (44) established, beyond doubt, its spirochetal origin (Leptospirosis pomona).

6. A personal error in interpretation of the findings has also to be excluded. ...The slides containing spirochetes were shown to Drs. Brines, Olsen, Weller, Wohlwill and Zimmerman. In critical appraisal they all acknowledged the shown structures as spirochetes of a type different from treponema pallidum.


As an argument against the spirochetal findings and their significance it has been said that reproduction of the same findings by others is lacking. In fact, it is shown in Table I that among a total of 31 cases examined by various investigators 11 showed spirochetes (over 35 per cent). Thus, the demonstration of specific spirochetes has been possible in more cases of multiple sclerosis and by other investigators. I, myself, was able to find the spirochetes in considerable numbers in 4 cases (once in brain and particularly in spinal cord, once in a case with a second acute relapse after 12 1/2 years remission, once in a case with miliary granulomas, the fourth case is being reported herein). In cases of chronic type the finding of spirochetes is too sporadic to spend much time and effort. Rogers (14), using Marburg's material in Vienna, found the spirochetes in 1 among 11 cases. Blackman (20) found structures resembling spirochetes in 5 of 11 cases of multiple sclerosis. Scheinker (16b) saw spirochetes in 4 out of 8 examined cases. Austregesilo and Fortes reported 1 positive case of a 38 year old woman with a duration of 8 months of disease. ... Spirochetes cannot be expected to be seen in every case of multiple sclerosis. The best chance for finding the spirochetes is in polysymptomatic cases of short duration (3 to 8 months) or older cases in recent relapses. Old burned-out cases do not offer much chance. ...Without the use of adequate silver methods and without a diligent search a reproduction of my findings is impossible. The time applied for the search is proportional to the success of finding spirochetes. ...

A great number of problems are still unsolved:

How do the spirochetes enter the human body? After the entry of the organisms into the body are there systemic reactions or not? How much time elapses from entry into the body until the organisms reach the central nervous system? Where do the spirochetes harbor in the clinically latent initial phase of the disease? And where do they reproduce? What is the stimulus for a new reproductive phase of spirochetes responsible for relapses and acute exacerbations? ... Are there immunological reactions to the presence of spirochetes in the body?

... A special problem arises when we consider the pathogenic role of the spirochetes and the granular bodies, derived from the spirochetes. Is the activity of motion of these corkscrew-like organisms the essential tissue damaging and myelin-sheath destroying factor? In other words, is a micromechanical injury the real tissue damaging effect? Or are substances of the spirochetes or derivatives of these, for example the granular bodies and their substances biochemically noxious myelolytic agents? Or is the defense reaction of the central nervous system itself, especially astrocytic proliferation and haptocyte formation more harmful and injurious to the tissues, particularly to the very sensitive myelin sheaths than the spirochetes themselves and their granular bodies? In multiple sclerosis the detectable tissue damage may be tardy in its development and quite some time behind the appearance of actively motile spirochetes and their granular bodies. These visible tissue reactions may appear some time after the spirochetes and their granular bodies for the most part have already disappeared. This would not be unusual when compared with other chronic infectious diseases. It could explain also the difficulties in detecting the causative agents in the majority of chronic cases and the good chance of finding the spirochetes in subacute cases or in acute relapses of older cases.

With a new discovery a great number of new problems arise and new ways of investigation will lead to new endeavors which may successfully solve the overall important therapeutic problem of multiple sclerosis.

[Martijn]

Morphology of spirochaeta myelophthora in multiple sclerosis.
by Gabriel Steiner, M.D.
Journal of Neuropathology, 13:221-29. 1954.

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“What can be said now, with all reservation, is that the spirocheta myelophthora, taken from its morphological appearance in fixed central nervous system tissues, seems to belong to the genus borrelia of the spirochaetales, family of Treponemataceae.”
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In a recent paper (1) the findings of specific spirochetes in the brain of a newly examine subacute case of multiple sclerosis were reported and evaluated. The purpose of the present paper is to give a detailed description of these spirochetes, their classification, their reproduction, and disintegration. Four cases of multiple sclerosis, including the case to be reported, elicited abundant numbers of specific spirochetes in the central nervous system to warrant the publication of this paper.

1. Further Evidence of Spirochetal Nature: It has been said that the reported spirochetes represent only spirochete-like structures of the tissue proper, such as reticulin fibrils, neurofibrils, or axis cylinders. To disprove these objections the following experiments were done: [detailed description given]...This [the results of these experiments] is definite proof that the “spirochete-like structures” are not related in any way to fibrillar reticulin elements, neurofibrils, or axis cylinders. ...

2. Morphology and Polymorphism of Spirochaeta Myelophthora: [detailed description given, as well as photographs for supporting evidence] ...Most characteristic is the corkscrew-like regularly coiled form with 5 to 12 single shallow spirals and with always rounded, never pointed, crests and roots.... the hook at the end shows a round, arc-like bending and is entirely different from the characteristic whip-like ends of the leptospiras. Loops, incomplete, nearly complete or totally complete rings are occasionally seen... The limited polymorphism of micro-organisms is nothing unusual in microbiology. Especially in old cultures or in chemically and antibiotically treated cases micro-organisms very often exhibit bizarre forms.

3. Classification: The classification of spirochaetales is still not very satisfactory. Up to the present time 3 genera are recognized... treponema, borrelia and leptospira... What can be said now, with all reservation, is that the spirocheta myelophthora, taken from its morphological appearance in fixed central nervous system tissues, seems to belong to the genus borrelia of the spirochaetales, family of Treponemataceae.

4. Reproduction: ...In multiple sclerosis, as in other chronic spirochetal infectious diseases, there is no continuous reproductive activity of the organisms. Their propagation may occur at regular or irregular intervals of time.

...the facts concerning the morphological identification must be properly evaluated so that mistakes can be avoided as much as possible. ...The first fact is the presence of enormous masses of extracellular and intracellular argyrophilic granular bodies in recent plaques of multiple sclerosis. This is nothing unusual in comparison with other acute or chronic spirochetal diseases, such as relapsing fever and syphilis... If the granular bodies in multiple sclerosis are developing from broken-up spirochetes, and there is much evidence for it, the possibility of previous presence of countless numbers of actively multiplying spirochetes in the tissues is not far fetched.


...There is not the least evidence for an intracellular reproductive activity of spirochetes in the nerve cells or other cells of the human tissue. The cells are not even used as shelters by the spirochetes. This is in accordance with the behavior of other classified spirochetes. In multiple sclerosis the spirochetes are located only in extracellular regions of the cerebral and spinal cord tissues. The process of individual growth and reproduction does not involve any intracellular phase and is exclusively extracellular.

...The question also arises as to whether or not permanent inactive forms, such as spores, do exist.... no morphological facts favor such as theory. The granular bodies, as in other spirochetal organisms, represent in all probability, remnants of disintegrated spirochetes. Many attempts to establish an evolutional cycle of the granular bodies into spirochetal forms in many other well known spirochetal genera have failed to demonstrate convincing evidence.

5. Disintegration: There is a definite sequence of events in the disintegration of the spirochaeta myelophthora. Breaking-up starts with the appearance of loops, rings (fig. 2d), knobs, (fig. 1r, s, t), partial thickening and the formation of granules of different sizes ....Two chronological sequences may be established: a first phase is the extracellular location of intact, active and probably motile spirochetes, followed by a second phase of extracellular disintegration in granular form. The intracellular ingestion of spirochetal debris seems to be a later phase of the pathological process.
...It should be mentioned here that the disintegration of the spirochaeta myelophthora proceeds in the tissue rather rapidly. In all our cases tissue blocks, containing abundant numbers of spirochetes, were less numerous than blocks containing extracellular and intracellular spirochetal debris without spirochetes. In old plaques, there is no chance to find argyrophilic granules or intact spirochetes.

6. Pathogenesis...: ...The heterophasic nature of the disease process should be, however, emphasized.
It is characterized by the presence of histologically old, more recent and of fresh plaques; the variation of inflammatory reactions in relation to the stage of the plaque and the number of well preserved spirochetes and extracellular spirochetal granular debris in or near acute plaques is impressive.

A detailed histopathogenetic analysis is still a postulate of the future. The spirochetes appear in complete detachment from any tissue element proper, often surrounded by a small halo. This
micro-halo has been mentioned by several observers concerning the appearance of treponema pallidum in stained sections of the central nervous system. In some of my sections the spirochetes were surrounded by a definite microscopic vacuole in which no tissue elements were found (fig. 1t). This may or may not indicate a tissue-liquefying power of the spirochetes. ...

[Martijn]

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Gabriel Steiner was a genius. He was a German physician/scientist, who had studied syphilis for years in the early 1900's. Came to the U.S. b/c of the war. Later began to study MS.

Steiner knew his spirochetes ... he had noticed that "granules" were always present in spirochetal infections, although he didn't know what they were. Back then they had no DNA testing, so he didn't know they were actually a form of the pathogen itself. But he knew that where there were granules, there had been spirochetes.

He strongly believed that MS was a spirochetal infection, and spent years trying to prove it. Several other research teams actually CONFIRMED his findings of granules in patients with MS.

But they disputed his conclusion that MS was a spirochetal infection, because they didn't usually find spirochetes and b/c MS wasn't easily cured with antibiotics. A viral etiology for MS became the popular explanation (this is years prior to the autoimmune theory of MS).

Well... Steiner knew well that in advanced stages of spirochetal infections, you rarely find spirochetes (true in syphilis as well as Lyme ... b/c the organism is present in other forms). And WE all know that spirochetal infections aren't "easily cured" with antibiotics.

Steiner's colleagues actually accused him of fraud. Having read his papers, I strongly believe he was just ahead of his time ... not a fraud. Some day I hope he will be recognized for his work. Of all the papers I have read, his are among the most ground-breaking and the most brilliant.

Quite a contrast to the papers by certain well-known researchers in the Lyme field, who have fancy labs and fancy equipment, but don't appear to spend much time thinking & observing.

Here are references for Steiner's publications from 1950 to 1965. Of particular interest are the "Acute Plaques" and "Morphology" papers (1952/54) ... I've read them and they are quite interesting in light of what we know today.

For his earlier works, please check the Bibliography file posted at http://www.lymeinfo.net/lymefiles.html -- they are there, along with quotes from the studies. Some of his colleagues' papers (and rebuttals) are also listed there.

1950-1965 publications:

STEINER G. [Causes and treatment of multiple sclerosis.]. [German] Munchener Medizinische Wochenschrift. 101:1321-6, 1959 Jul 31.

STEINER G. Comparison of general paresis and multiple sclerosis in regard to the etiological agent. Journal of Neuropathology & Experimental Neurology. 13(3):492-6, 1954 Jul.

STEINER G. Morphology of Spirochaeta myelophthora in multiple sclerosis. Journal of Neuropathology & Experimental Neurology. 13(1):221-9, 1954 Jan.

STEINER G. Acute plaques in multiple sclerosis, their pathogenetic significance and the role of spirochetes as etiological factor. Journal of Neuropathology & Experimental Neurology. 11(4):343-72, 1952 Oct.

STEINER G. Environmental studies in multiple sclerosis. Neurology. 2(3):260-2, 1952 May-Jun.
Currently received at Scott Library; check Library holdings for details.

STEINER G. Experimental allergic encephalomyelitis, spontaneous demyelinating disease and multiple sclerosis. Gazeta Medica Portuguesa. 4(3):824-34, 1951.

STEINER G. Modified silver stain of microorganisms in tissues. American Journal of Clinical Pathology. 20(5):489-90, 1950 May.

STEINER G. Multiple sclerosis. Journal - Michigan State Medical Society. 49(8 ):938-40, 1950 Aug.

STEINER G. [The study of multiple sclerosis in the U.S.]. [Undetermined] Nervenarzt. 21(11):494-9, 1950 Nov.

Zie ook: Lyme Disease Misdiagnosed as Multiple Sclerosis.