Environmental Studies, Multiple Sclerosis and Lyme Disease
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...
There are some of the statistical facts. What are the conclusions?
by Gabriel Steiner, M.D.
Acute plaques in multiple sclerosis, their pathogenic significance and the role of spirochetes as etiological factor.
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.
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:
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 show better than any detailed description the shapes, sizes and locations of these extracellular granular bodies.
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 very 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). The various observers interpreted these granular bodies differently, 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
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
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.by Gabriel Steiner, M.D.
Journal of Neuropathology, 11:343-72. 1952.
Morphology of spirocheta myelophthora in multiple sclerosis.
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.
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...
by Gabriel Steiner, M.D.
Gabriel Steiner was a German physician/scientist, who had studied syphilis for years in the early 1900's.
Steiner knew his spirochetes ... he had noticed that "granules" were always present in spirochetal infections, although he did not know what they were. He 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 now we know that spirochetal infections which are missed for years are not "easily cured" with antibiotics.
Here are references for Steiner's publications from 1950 to 1965. Of particular interest are the "Acute Plaques" and "Morphology" papers (1952/54)
For his earlier works, please check the Bibliography file posted at 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.
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.
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.
Dr. Schaller neither supports or nor opposes this information