Home Table of contents About the author Acknowledgements Contact 

(III-1) Classical Clinical Observations

In commenting on the neurology of his “peculiar diseased state”, whose lesion illustration provided the earliest unequivocal specification of multiple sclerosis, Carswell freely stated, “I could not ascertain that there was anything in the character of the paralysis or the history of the cases calculated to throw any light on the nature of the lesion" (24).

Cruveilhier, 1841: First Clinical Account of Multiple Sclerosis
Nothing is known concerning the clinical history of Cruveilhier's first specimen of multiple sclerosis, pictured in 1839, and only in his second case report were neurological data given in some detail.
A year and a half before the patient’s death, the affection had first made itself felt with creeping or prickling sensations beginning in the soles of her feet and rising up to the calves. Soon afterwards, a trembling of the arms and a clumsiness of the hands supervened, so that grasped objects often slipped from the patient's hand.
Half a year later fitful incapacitations of the upper limbs forced the woman to give up her job as a chambermaid. In the three months before her death, she was further handicapped by stumbling, dragging of the legs, and occasional collapses of the knees. The left and then also right hands could no longer be relied upon.
During the last two weeks of her life, the patient lost almost all sense of feeling in both legs, although feeling in the arms was less impaired. The arms, more than the legs, especially on the right side, could still only be moved awkwardly.
The patient’s suffering during her last ten days was aggravated by a feeling of constriction around her waist, urinary retention and complicating infections of the lungs and left shoulder. The patient died, aged thirty-eight, of suffocation (34).

Conclusion: There is no evidence of any distinctive neurological features of the disease. As against Carswell's "peculiar diseased state", however, this condition culminated not in a plain paralysis but in an almost complete loss of sensation in the lower, rather than upper, limbs, and in disturbed motor control. This last finding might be attributed to the presence of damages not only to the spinal cord’s sides but also to its back.

Clinical Manifestation of Charcot's Specific Lateral Cord Lesion
Charcot's neurological observations on his earliest case of multiple sclerosis describe the capricious development of a progressively severe central nervous affection lasting between the patient's fourteenth year and her death at sixty.
For the first six years of its forty-six year course, the disease manifested itself with recurring feelings of strangulation, followed at monthly intervals by convulsive attacks with loss of consciousness, lasting for up to three hours. The attacks were generally preceded, for two or three days, by "girdling" pains around the lower chest and, in the beginning, also by giddiness, heart flutterings and choking. The episodes during her twenties were limited to feelings of strangulation, shortly preceding and then persisting during menses.
The first actual neurological phenomena were observed in the woman’s thirty-fifth year. Having experienced, for a few days, crawling sensations and a feeling of numbness in her left shoulder, she suddenly noticed a cramping of her left arm and leg and then lost consciousness. She was awakened by a painful contracture of the left half of her body, including the neck, which slowly subsided only after two weeks. The left arm, however, never regained its former mobility.
One year later the woman again suffered a severe nervous attack. This became a generalized tremor and weakening which gradually worsened so that, after a month, the patient could no longer leave her bed. There followed painful contractures of, at first the limbs on the left and, after three weeks, also on the right side, including body and neck.
The condition worsened for more than a year and to such a degree that the patient could no longer make use of her limbs. In addition, she suffered from a continuous feeling of strangulation and a hypesthesia extending over the (already severely cramped) left arm and leg, back and chest. All of these symptoms lasted for two years.
At the age of forty-seven the patient’s condition gradually improved, over three months, to such an extent that, despite an enduring weakness of her lower limbs and a certain degree of cramping of the upper limbs, she could even walk and keep house.
At the age of fifty the woman awoke from a last fit of unconsciousness, with contractures of all four limbs. She then remained bedridden and became fully incontinent and incapacitated by a cramped fixation of her limbs, finally succumbing to an erysipelas, a skin infection spreading from her left leg over her trunk to most of her back. Up to the end her thinking, speech, and facial expressions seemed unimpaired, and she also retained a certain motility of the head and neck (26).

The significance of this observation: Charcot categorized the condition in three different ways:
  1. as an instance of unequivocal hysterical attacks;
  2. as a case of multiple sclerosis directly corresponding to Carswell’s and Cruveilhier’s classic pictorial lesion specifications (the Bibliothèque Charcot at Paris has crude sketches of Charcot’s which impressively document this analogy); and
  3. from 1874 onwards, as the first standard example of amyotrophic lateral sclerosis, a primary motor neuron disease whose existence was postulated by Charcot himself.
This last categorization was made
  • although Charcot’s own description of a boat-shaped scarring of the spinal cord’s flanks clearly contradicted the idea of a corresponding lateral spinal tract degeneration;
  • despite the fact that no amyotrophy, i.e. dwindling of the muscles, had been observed in the patient’s lower extremities; and
  • although Charcot had noted diverse massive sensory deprivations on the patient’s part (26,29).

Neurological Data on Frommann's Observations
Frommann’s classic histological account on a case of spinal multiple sclerosis was complemented by a clinical history put down by Leyden (65): The patient’s disease probably first became manifest fifteen and a half years before death when, especially while carrying heavy loads, he suffered from intense twinges in his back.
One day, about two and a half years later, the patient suddenly collapsed, feeling that his right leg had been "punched through". He then noticed that he could not bend his right knee, nor was there any feeling in his right side. For about six months he was unable to walk, and thereafter continued dragging his right leg. The initial bladder incontinence turned into urinary retention. Moreover, the patient soon complained of racking pains of unspecified localization, and later about pains in the left leg, as well as numbness in the lower back. During the following ten years both legs became increasingly paralysed so that, in the end, he was only capable of changing his position supported by two crutches, and dragging his legs. The patient further perceived, from time to time, a creeping sensation in the lower limbs and eventually also a frequent trembling of his right arm. In his last week of life the man was unable to move or feel his legs, except for slight perceptions in his knees. His right arm was now weakened as well. The patient died, 42 years old, of a sepsis ensuing eight days after being scalded in an overheated bath – which the patient could not feel, owing to a loss of sensation in the lower half of his body (50).

Conclusion: In comparison to Charcot's previous observations (26), Frommann's patient, despite an apparently more extensive spinal cord involvement, was subject to far less severe and extensive nervous incapacitations. In both cases, moreover, it is futile to attempt to trace any direct correlations between functional clinical and gross morphological post-mortem findings, as a comparison of the findings’ laterality makes evident. Nothing in the character of this disease can be considered indicative of the underlying lesion specificity.

Charcot's Prime Clinical Example of Cerebrospinal Multiple Sclerosis
By the age of twenty-five, this patient had already suffered much from headaches, as well as frequent cramps in her lower limbs. Neurological troubles arose the following year, in the form of a weakening of the legs more than the arms, particularly on the left side. The legs also felt numb and cold. Three years later, her vision became dimmed, and perceived objects seemed to sway and turn. After another three year period, recurrent girdling pains set in and, at the same time, the patient lost her ability to walk, which she regained in the following year, though only for a month.
About a year and a half before her death, both legs became immotile, apart from slight toe movements on the right foot. The arms, especially the left one, were considerably weakened. In addition, a mainly left-sided impairment of sight, a severe nystagmus, i.e. spontaneous oscillation of the eyes, a trembling on exertion, pains around the trunk, and alternations of urinary retention and incontinence supervened.
Nearly one year previous to death, the patient suffered from painful leg spasms for about one month. After another month the woman's legs, particularly her right one, could again be brought into different positions, despite their spasticity, and also the distortion of her handwriting diminished. Bladder control was shortly regained.
During the last months of her life, all exertions of hands, neck, or body provoked a trembling of the respective parts. Both legs, especially the right one, went into spastic extension, leaving only a weak, one-sided, residual motility of foot and toes. The one arm achieved only poorly coordinated movements. The patient herself looked apathic and dull. Two months after having slightly recovered for the last time Charcot’s patient succumbed, at the age of thirty-six, to a vast decubital ulcer (93).

Conclusion: In referring primarily to the progressive weakening and eventual contracture of the patient’s four limbs, Charcot was particularly interested in the trembling of the arms during exertion. Yet his classical observation of cerebral and spinal multiple sclerosis presented no data which actually defined the disease in clinical terms, nor did it offer any clues as to its specific macropathology.

Lauenstein's Myelitis
In this case, a man suddenly began to feel exhausted, giddy, and so stiff that he could hardly climb stairs, and this all during a work pause, thirteen days before his death. Subsequently he began suffering from an obstinate constipation and increasing upper back pains, radiating especially towards the nape of the neck.
Ten days later he was admitted to the hospital. The following day, all of a sudden, costal breathing, limb motility, as well as sensation from the toes up to the third rib and in the arms, except the arms' proximal inner side, suddenly ceased. A total urinary retention and fluctuating body temperatures set in.
During his last two days, the man could neither expectorate to alleviate breathing difficulties, nor was his speech any longer comprehensible. During the last night before death from suffocation, pains in the back and nape of the neck further intensified. Lauenstein’s patient died, forty-six years old, of a relentlessly worsening breathing insufficiency (64).
Conclusion: This patient’s history demonstrates that multiple sclerosis can lead to death even during the first attack. However, neither the symptoms and signs themselves, nor the course of the disease, can be considered as indicative of a specific injurious process.

Clinical History of Dawson's Standard of Comparison
Both a clinical history and the entire pathology of one particular instance of multiple sclerosis were comprehensively detailed side by side for the last time, by Dawson in 1916. His report deserves particular attention.
Two years and three months before her death, a woman one morning found her legs swollen and tender. Pains shot down her right leg, and she had great trouble in getting out of bed. Returning to work a fortnight later, she no longer felt able to walk as quickly as before, her right knee having become stiff.
Sixteen months later, the woman was forced to give up her job, mainly owing to a progressive stiffening of both legs, unpredictable bouts of arm trembling and periods of incontinence. Her speech had slowed down, and she had difficulties in pronouncing words.
All of these symptoms gradually worsened. On admission to the hospital a slight nystagmus, a minor right-sided mal-coordination in the finger-nose test, and leg reflexes pointing to a bilateral damaging of the cerebrospinal tracts were noted. During her first seven weeks in hospital, five months before death, the patient made one last hopeful recovery.
At intervals of a few days, in the fourth month before death, the following symptoms were recorded: a numbness in the right arm, followed by near-complete deafness with a dull buzzing sound in the right ear, right-sided facial paralysis preventing the closing of the eye and, finally, double vision to the right, protrusion of the tongue to the left, and difficulties in speech and swallowing.
A distinctly progressive weakening and spasticity of the legs, severe vomiting, a dimming of vision which gradually turned into complete blindness, a rapid wasting away of the muscles of especially the legs, diarrhea, and urinary retention were observed in the month preceding death. Inspite of short periods with slight improvements, in the end the woman passed away rapidly, aged twenty-eight, with a distinctly septicemic appearance.
Conclusion: For all of its thoroughly registered complexity, the history of Dawson's exceptionally well documented case of multiple sclerosis again did not provide neurological observations proving the condition's clinical peculiarity, nor did it provide for reliable in vivo identification of comparable illnesses.

Reflections on Classical Clinical Observations
As to nature and course, all of the nervous troubles by which the pathologically specific instances of multiple sclerosis became clinically manifest proved utterly variable, paralleling one another merely in non-distinctive respects. A comparison of the preceding accounts on multiple sclerosis also discloses remarkable inconsistencies among clinical and pathological findings. Thus the specific spinal cord involvement is most extensive in Frommann's case, followed by Charcot's and then Lauenstein's. With regard to the nervous afflictions, however, Lauenstein's patient appears most and Frommann's least severely affected. The extent of the nervous tissue involvement traced at post mortem therefore by no means correlates with the severity of the nervous deficits registered in vivo. With respect to the clinical data on Frommann's total cross-sectional scarring of the thoracic spinal cord and Lauenstein's narrowly localized lateral cord destructions, it must be assumed that completely but very slowly demyelinated areas can remain more or less functional, while peracute functional nerve tract interruptions need not be autoptically traceable.
We must also be aware of the fact that no neurological screening can achieve the "spatial resolution" which would be necessary for a reliable in vivo identification of the distinctive lesion patterns of either spinal or cerebral multiple sclerosis: A particular neurological dysfunction in principle simply indicates that the corresponding nerve tract has been affected somewhere. As a consequence, in involvements of longer functional pathways, it can sometimes not even be determined whether the trouble is cerebral or spinal in origin. But in spatially indiscriminate, lump-sum assessments a neurological dysfunction can never be expected to disclose exact position(s), number(s) and length(s) to which a definite nervous pathway has been affected.
It should not be surprising, therefore, that no individual multiple sclerosis patient has ever been observed to show clinical phenomena betraying the specific nature of the underlying post-mortem findings: There is simply no possibility of identifying the distinctive patterns of spinal or cerebral multiple sclerosis by evaluating a patient’s clinical history, as well as physical and, in particular, neurological findings.
In clinical medicine, as in any other natural science, any criterion adduced for some condition's specific qualification must be shown to be both consistent, i.e. to occur in each and every patient suffering from the given disease, and exclusive, i.e. never to occur in a patient affected by a condition of different nature. For lack of any evidence that multiple sclerosis is characterized by distinctive neurological features, it is important to find out how it has come to be defined primarily in clinical terms, and why it is understood as a disease identifiable by the nature or course of its symptoms.

(III-2) CDMS: Chronically Delusive Misidentification Syndrome
The ways in which the highly cherished idea of a "clinically definite multiple sclerosis" evolved have as yet never been subjected to a sober logical analysis and critique. In order to properly evaluate this type of disease conception we need to find its origins and to delve into the maelstrom of diagnostic speculations which have established multiple sclerosis as a neurological entity, without any connection whatsoever to the specific post mortem evidence referred to by the same name.

(III-2-a) The First Clinical Cases
Friedrich Theodor Frerichs, professor of "pathology and therapy" in Breslau, is commonly credited with having made the first in vivo diagnosis of multiple sclerosis. The principles which guided Frerichs are of considerable interest. As it turned out, he entrusted the publication of his diagnostic results to a young pupil of his, Wilhelm Valentiner, and it is the latter's work which will gain our attention here. In order to fully understand and judge Valentiner's lines of reasoning, it is indispensable to first acquaint ourselves with Frerichs' concept of "cerebral sclerosis".

Frerichs' (Cryptic) Cerebral Sclerosis
In 1848 Frerichs, at the University of Göttingen, undertook a classification of the solidifications of brain substance: He differentiated between consolidations of the brain as a whole, attributable to consumptive processes and aging, and localized cerebral hardenings, produced by neoplasms, tuberculosis and exudative inflammations. This was some time before the actual nature of the last three pathological processes really became understood.
Urging that the changes in the consistency of cerebral tissue be clearly discriminated as to their causes, Frerichs went on to compile data on “the unexplained form” of brain sclerosis. It was said to be sharply circumscribed, to usually start in the white matter above the lateral ventricles, and to have a texture somehow differing from that of pathologic growths and scars of chronic inflammations, as well as from that of general cerebral consolidations in advanced age, and in systemic diseases.
This cryptic sort of cerebral sclerosis was exemplified by four specimens which, in retrospect, can be said to have shown lesions of three essentially different kinds. Frerichs' second and third examples represented, to all appearances, malignant gliomas of the cerebrum (butterfly type) and brain stem (infiltrative form) respectively. The fourth specimen, secured from a victim of tuberculosis, had been adduced by Cruveilhier as illustrating grey degeneration (Plate II , fig. 4).
The first specimen, which stemmed from a boy who died of incessant convulsions at the age of six, had been observed by Frerichs himself. The epileptic fits had started with nodding spasms in the child’s sixth month and had continually grown worse. Frerichs' drawing and description of the boy's brain showed a massive, overall Y-shaped scar involving cerebral cortex and subjacent white matter, conformable to the vascular territory of the two terminal branches of the middle cerebral artery (69).
While its origins remained undetermined, Frerichs' brain sclerosis presented the following physical features:
  1. An unusually textured, scarred appearance of part(s) of the brain.
  2. A lack of any specific parallel to Carswell's "peculiar diseased state".

First Clinical Diagnosis of Cerebrospinal Sclerosis
In 1856 Frerichs' student, Wilhelm Valentiner, presented a series of papers entitled "On the Sclerosis of Brain and Spinal Cord" (147). These expositions began with a detailed history of the nervous illness for which the first in vivo diagnosis of Frerichs' cryptic sclerosis had been made: Tactile and motor functions had failed first on the left and soon also on the right side of a patient suffering from muscular twitchings and pains. The subsequent excessive fluctuations in the patient’s moods were eventually superseded by stuporous indifference. Special attention was paid to the severe trembling interfering with all of the patient’s voluntary activities, including speech.
This symptomatology already sufficed to convince Frerichs of the actual presence of his pathological entity, "cryptic cerebral sclerosis". Frerichs’ long-winded, confusing clinical argumentations as to why any other form of pathological process could be excluded from this case will not be recapitulated here.
Valentiner also detailed this patient's later troubles: Unsteadiness of the eyes, a fitfully aggravated paresis, increasing tremors, episodes of urinary retention, varying pains in head and neck, and a mental decline, until death ensued from an intestinal infection, two and a half years after the onset of the disease.
At post mortem, the circumference of the brain stem as well as basal and inner parts of the cerebrum proved invaded by sclerosed areas. If properly illustrated and explained, Valentiner’s findings of a dense scarring of outer wall and roof of the lateral ventricles, forming the basis of a radiation of both sclerosed and softened lesion-expansions into the cerebral hemispheres, might have anticipated and complemented Charcot's and Dawson's specifications of cerebral multiple sclerosis. The affection of the spinal cord remained undescribed, but it is quite obvious that, while supposedly of the same cryptic origin, Valentiner's case of cerebrospinal sclerosis and Frerichs' diverse instances of brain sclerosis did not show any distinctive morphological features in common.
In an attempt to clinically characterize (cryptic) cerebrospinal sclerosis, Valentiner additionally evaluated the case histories of one personally observed and nine reported instances of unexplained cerebral, bulbar and spinal sclerosis. There were three clear instances of continuous degeneration of the posterior columns of the spinal cord (Plate II, fig. 3); one observation of genuine multiple sclerosis (Plate II , figg. 1, 1'); and seven rather vaguely characterized pathological conditions. Each and every case of this highly heterogeneous mix-up of different neuropathological observations was deemed useful for determining the clinical picture of Frerichs’ cerebrospinal sclerosis.
Clinical criteria derived from, and supposedly indicating, all of these equally enigmatic, but otherwise scarcely comparable disease processes obviously had to be very broad. And, like the histological feature of "sclerosis", so also all clinical and neurological phenomena appearing common to the diverse pathological processes subsumed under Frerichs’ and Valentiner's notion of cerebrospinal sclerosis merely constituted non-specific findings.
Valentiner seems to have sensed some of these inconsistencies. He asked for the reader's forbearance in case conclusions arrived at in the course of his studies might not be diagnostically valid. He also voiced some concern about his own indiscriminate inclusion, in his clinical study on cerebrospinal sclerosis, of instances of a systematic degeneration of the posterior columns of the spinal cord. All the substantial differences between the various specimens of Frerichs' and Valentiner’s cerebrospinal sclerosis appeared negligible when considering the fact that Cruveilhier himself had depicted the particular lesions side by side, labeling them with the same term.
Valentiner's diagnostic criteria or hints about how to identify future cases of cerebrospinal sclerosis will be cited insofar as they, or their modifications, came to form part of later clinical definitions of multiple sclerosis. Such criteria were:
  1. Relentless progression, yet interrupted by frequent remissions;
  2. Occurrence of all possible kinds of nervous incapacitations;
  3. Earlier and more severe involvement of the lower as against the upper limbs;
  4. Affection of motor functions in general more than sensory ones; and
  5. Primarily non-consumptive character of the illness (147).
There can be no denying the fact that Valentiner's criteria for the clinical diagnosis of the cryptic form of cerebrospinal sclerosis were not derived from a study of patients suffering from one and the same disease. But no criticisms of the flaws of Valentiner's expositions seem ever to have surfaced. Instead, his paper became an integral part of the standard literature on the subject of multiple sclerosis.

Ordenstein's Prototypal Clinical Reports
When multiple sclerosis was diagnosed in vivo for the first time, the decisive findings were not proudly announced, but expressed in a rather roundabout way.
Introducing multiple sclerosis as a distinct form of cerebrospinal lesion, Ordenstein at first declared as absurd the search for a direct parallel between the given pathological findings and some neurological disease specification. Notwithstanding this explicit caveat, in his review of the literature on the subject of multiple sclerosis he cited Valentiner's paper prominently. And, in thus repeating Valentiner’s mistake, Ordenstein once more indiscriminately presented the case histories relating to several profoundly differing forms of Cruveilhier's “grey degeneration” (cf. Plate II , figg. 2-4) as the earliest clinical evidence on multiple sclerosis.
Before beginning his long, drawn-out account on the symptomatology of multiple sclerosis, Ordenstein attempted to give a definition of the condition's anatomical pathology. He maintained that multiple sclerosis was characterized by an asymmetrical dissemination of lesion nuclei or wedges at the most varied places of the spinal cord and brain – areas of grey degeneration appearing everywhere. This lesion definition of multiple sclerosis was similar to that in a paper presented by Vulpian in 1866, which Ordenstein's thesis hailed as the standard French work on this pathology. Vulpian had posited that multiple sclerosis was specified by an orderless spread of one or more plaques into brain and/or spinal cord (152).
Ordenstein's exposition reached its climax in statements concerning the disease's clinical traits. The main message was that the manifestions of multiple sclerosis in the living appeared explicit enough to permit the condition's reliable (clinical) identification. The following symptoms were considered diagnostic:
  1. Motoric disturbances, primarily of the legs;
  2. A progressive advancement, with occasional remissions;
  3. A pathognomonic trembling, emerging during physical efforts and ceasing during periods of rest;
  4. Nystagmus, i.e. spontanous oscillations of the eyes; and
  5. Scanning speech, i.e. monotonous drawling utterances.
Despite his initial admonition that there could be no clinical diagnosis of an anatomically defined condition, Ordenstein later stated his belief in the reliability of these diagnostic criteria, even affirming the presence of multiple sclerosis in two in vivo cases. His presentations of two "clinically identified instances" made multiple sclerosis appear as an authentic clinical entity (93), and these two putative in vivo diagnoses were later "legitimized" by confirming the presence of multiple sclerosis at post mortem.
At least in one case, the description of a predominance of large plaques in the ventricular walls actually was reminiscent of the lesion arrangement of cerebral multiple sclerosis (17). In principle, however, Ordenstein's (and his teacher and supervisor Charcot's) in vivo specification of multiple sclerosis harbored the same fundamental flaws as Valentiner and Frerichs' clinical characterization of cerebrospinal sclerosis: Ordenstein’s attempts at defining more precise criteria for the disease's in vivo diagnosis were founded simply on a more extended co-evaluation of causally enigmatic instances of a (frequent but only postulated) cerebrospinal grey degeneration or multilocular scarring process -- many instances of which were merely concretized by the mysterious epithet "unpublished observation".
All this, together with Ordenstein's adoption of Vulpian's utterly vague lesion specification, betray the fact that Ordenstein's newly established "clinically diagnosed multiple sclerosis" and Carswell's, respectively Charcot's, pictorially specified multiple sclerosis, though bearing the same name, were certainly not the same entities.

Charcot: Multiple Sclerosis – A Kind of Lesion, Yet Clinically Defined
The seventh of Charcot's famous lectures dealing with the clinical diagnosis of multiple sclerosis was introduced with the statement: "Nothing is simpler ... than to diagnose the affection in question at the bedside of the patient" (29, 31). Not fully agreeing with Ordenstein's thesis, Charcot posited the following criteria for differentiating multiple sclerosis from similar illnesses:
  1. An absence of sensory disorders in general and, in particular, the absence of girdling pains, i.e. pains around the waist.
    -- As to this point, the clinical observations in both of Charcot's, in the second of Cruveilhier’s, in Frommann's, Lauenstein's and Dawson's specific instances offer a large body of conflicting evidence.
  2. Intentional tremor, i.e. trembling only under exertion, increasing in direct proportion to the extent of the movements executed. As opposed to Ordenstein's thesis, this symptom was now considered not to be pathognomonic, even inconstant or present only in late stages of the disease.
    -- Remarkably, episodes of trembling or shaking of the limbs were made mention of in most of the histories of specific instances of multiple sclerosis, but Charcot and Ordenstein alone described this trembling as characteristic of multiple sclerosis.
  3. Remissions to an extent not found in other chronic diseases of the spinal cord. This was, however, immediately conceded to be an unreliable criterion.
    -- In this respect, also the degree beyond which a remission had to go to indicate multiple sclerosis was anything but clear.
  4. Paresis of the lower limbs, a symptom which should have put physicians on the right track! Charcot admitted, nevertheless, that corresponding observations were common to a large number of different diseases.
    -- Whether this criterion be fulfilled depends not on the injurious agent’s nature but on whether it affects the pathways of the leg's motoric innervation.
  5. "Trembling of the extremities, impeded articulation, giddiness, unsteadiness of the eyes, etc. ... symptoms belonging to multilocular sclerosis alone". Of all these troubles none was yet considered a constant feature of the disease.
    -- This bold assertion apparently resulted in the establishment of "Charcot's diagnostic triad" (omitting the giddiness) or Charcot's four clinical marks of multiple sclerosis. But it applied originally to a comparison of multiple sclerosis with "progressive locomotor ataxia", a clinical syndrome typically associated with sclerosis of the spinal cord's posterior nerve tracts (29, 31).
All in all, Charcot's contributions to the subject of multiple sclerosis thus prove highly contradictory. With his superb drawings on specific spinal and cerebral findings (Plates IV, V ) and his precise and comprehensive early documentation on spinal multiple sclerosis (26), he provided clear evidence of the unique pathological features of multiple sclerosis. In addition, he often stressed that the condition was to be defined by its pathological anatomy alone. And yet, his statement that nothing is simpler than to diagnose the disease at the patient's bedside, and his role in the propagation of the first supposedly diagnostic clinical multiple sclerosis syndrome appears widely responsible for the fact that multiple sclerosis has come to be considered primarily as a clinical disease entity. Charcot has rightly been praised, but unfortunately for the wrong achievements.

(III-2-b) Mutations of the Multiple Sclerosis Syndrome
However ill-founded, Charcot's "diagnostic triad", was enthusiastically greeted. Not only were its handy criteria for diagnosing multiple sclerosis in the living patient everywhere uncritically embraced, but famed neurological scholars began to cast about for other methods of identifying the mysterious condition in vivo. The ensuing conceptual odyssey lead mainstream research far away from evaluating the multiple sclerosis-specific post mortem evidence, establishing instead a blunt clinical neurological understanding of the disease.

Wilson's Audacious Attack
In 1876, Edward T. Wilson recommended replacing the term "disseminated insular sclerosis", used as a synonym for multiple sclerosis, with the expression "rhythmic or oscillating ataxia", referring to the disease's allegedly diagnostic tremor. Wilson obviously held that the condition was distinguishable rather by its symptoms than by any other abnormality. Unfortunately there seems to have been no reaction to his doubts about multiple sclerosis-specific post mortem findings (161).

Wernicke's Ambivalent Stance
Carl Wernicke (1883) behaved inconsistently: While questioning the value of Charcot's diagnostic criteria and decrying as futile any attempt at defining multiple sclerosis by its neurological manifestations, he himself worked out yet another clinical definition of the disease. The essential features of multiple sclerosis, according to Wernicke, were
  1. the overall relentless progression;
  2. the apparent sparing of the organism as a whole;
  3. the involvement of the nervous system in at least two sites;
  4. cerebral symptoms "revealing the nature of the disease by themselves" (158).
Rather Controversial: Balint
Rudolph Balint's reasoning was no less contradictory. In an 1899 article, he defined multiple sclerosis as a clinical syndrome, to be identified by its "four characteristic symptoms" – an understanding traceable to Charcot -- and then exemplified the affection in the following case-report:
A woman's nervous illness had arisen in four episodes, each provoked by an otherwise uncomplicated parturition. The first episode was marked by weakness of the left leg, the next of the right hand, the third of both legs, and the fourth of all limbs. Finally, the patient became incontinent, her legs insensitive to pain, and, after the emergence of left-sided facial paresis, she succumbed to pneumonia.
Of Charcot's four clinical multiple sclerosis criteria, none had been noted here. And the post mortem was ultimately said to have disclosed the well-known lesion development and image of multiple sclerosis. After first characterizing multiple sclerosis as a clinical syndrome, Balint had thus ultimately proceeded to identify the condition on the basis of its (unfortunately not specified) macropathology (7).

Borst's Counteroffensive with Blanks
In his 1903 survey of the literature on multiple sclerosis, Max Borst emphasized that, without post mortem evidence, it could never be certain whether a nervous disorder was actually multiple sclerosis or not (13). However, he again did not tell which findings would verify the presence of the disease. And, instead of conforming to the archetypes, his instances of multiple sclerosis proved to be a mixture of different imprecisely characterized and not properly understood cerebrospinal lesions. Borst’s multiple sclerosis, although allegedly identified at post mortem, also failed to form a distinct anatomical pathological entity.

(III-2-c) Framing of New Clinical Criteria
Researchers around the turn of the 20th century must have had the impression that neither the in vivo presentation nor the pathology of multiple sclerosis exhibited any truly specific traits. Leading neurologists accordingly felt increasingly called upon to search for more practical ways of identifying the condition. And so, step by step, the conception of a "clinically definite multiple sclerosis" began to emerge.

Marburg's More Accommodating Criteria
In 1906, Otto Marburg frankly conceded that multiple sclerosis could become manifest in nervous disorders of any sort and in any concatenation, no neurological symptom being actually peculiar to it. He therefore suggested substituting the still prevailing "diagnostic triad of Charcot" (co-occurrence, in a particular case, of intentional tremor, scanning speech and nystagmus) by neurological criteria which rather complied with the boundless varieties of the disease's in vivo manifestations. He arrived at the following four clinical diagnostic criteria of his own:
  1. Neurological indications of a multilocular cerebrospinal involvement;
  2. At first insidious, then galloping disease progress -- in certain cases, interrupted by repeated recoveries;
  3. No indications of an affection involving the organism as a whole; this implied, in particular, an absence of fever -- even of neurogenic fever (while Charcot had regarded the latter as a characteristic of peracute multiple sclerosis attacks (29, 31)).
  4. As regards his criteria's specificity, Marburg simply cautioned that also arteriosclerotic lesions could manifest themselves in the specified ways (75).
Multiple Sclerosis Defined by "Multiplicity"
A multiple sclerosis specification which excelled in its simplicity and, moreover, could be applied not only to the affection's clinical presentation but also its organic pathology was presented by C. P. Symonds in 1924. The twin definition was to exert a pervasive and enduring impact on the understanding of the condition. With respect to the diagnosis of multiple sclerosis, Symonds posited: "In clinical practice, the best criterion [for diagnosing] disseminated [= multiple] sclerosis is [neurological evidence for] dissemination of the [not always accountable] lesions both in space, within the central nervous system, and in time." Symonds concluded: "The disease is characterized ... anatomically by the coexistence [at] post mortem of multiple [non-specified] foci in various stages of degeneration" (138).

Pette: Diagnosis by Exclusion and Fulminance of Attacks
Heinrich Pette was the first researcher to freely admit that multiple sclerosis might be clinically diagnosed simply by the exclusion of other nervous diseases (i.e. definite pathological processes known to be capable of causing the observed affections) (100). He emphasized that there were no neurological phenomena peculiar to multiple sclerosis and warned -- as had often been done before and would often be done after him -- that the disease frequently manifested itself with a mask of clinical pictures considered typical of totally different (meaning medically understood) nervous affections. Pette said that the clinical picture of multiple sclerosis appeared primarily characterized by
  1. a fulminant onset, and
  2. exceptionally speedy fluctuations in its development.
But in both respects multiple sclerosis and plain arteriosclerotic or hypertensive cerebrospinal affections were conceded to often be indistinguishable from one another. Pette thought that, in the presence of corresponding affections, it was justifiable to diagnose multiple sclerosis if there was no evidence for risk factors of arterial cerebrovascular affections (100).
Pette placed a heavy reliance on the exclusive procedure of "diagnosing" multiple sclerosis in vivo. Like Marie (82), yet in bold contradiction to any clinical history relating to the specific post mortem observations, he further claimed that multiple sclerosis could spontaneously and fully heal after one single attack. In the end, Pette's argumentation led to the absurd conclusion that any residual defect or history of any cerebrospinal affection(s) of unknown cause could be considered as evidence for the former presence of multiple sclerosis (95, 97, 100).

Need for Definitive "Bedside" Diagnoses
After these and several other quite unconvincing assertions by a number of leading neurologists on identifying multiple sclerosis in the living, the ground appeared well prepared for some official ruling regarding the circumstances under which multiple sclerosis was to be diagnosed. The impulse which proved decisive for laying down standardized criteria for the disease's clinical neurological “identification”, however, originated not in any conceptual endeavors but rather in an interest to obtain statistically comparable patient populations for performing pharmaceutical therapeutic trials.

Schumacher's "Diagnostic Time Schedules"
In 1965 a crucial step towards achieving the rationally impossible was taken by a team of ten neurologists, headed by George A. Schumacher. For the diagnosis "clinically definite multiple sclerosis" they defined six criteria which, by integrating the most fundamental suppositions of the preceding clinical multiple sclerosis definitions, gained general acceptance and official approval. With a view to establishing anatomical pathological specifications, simply one confirming (+) and one excluding criterion (-) were defined:
  • (+) "There must be evidence of involvement of two or more separate parts of the central nervous system"
  • (-) "Simultaneous and symmetric involvement of the lateral and posterior columns of the spinal cord [alone] ... cannot be interpreted as caused by multiple sclerosis" (125).
Concerning the first point, we may ask ourselves whether a counting of unexplained lesions can actually make up for a qualitative lesion specification. This manner of thinking challenges us to ask: Does the finding of a second set of multiple sclerosis-specific "Dawson's fingers" truly enhance the first finding's specificity? Or can the cause of some cryptogenic nervous dysfunction be revealed by its being followed by another no less cryptogenic nervous dysfunction?
The assertion that multiple sclerosis cannot be diagnosed when the spinal cord’s sides and back appear symmetrically affected is particularly strange: It excludes as instances of multiple sclerosis exactly all those observations corresponding specifically to Carswell’s “peculiar diseased state”, i.e. all the classic specimens of spinal multiple sclerosis. The attempt at defining multiple sclerosis in clinical terms thus culminated in an exclusion of in vivo evidence for exactly that lesion pattern by which the disease had first been genuinely identified and consistently specified (cf. Plates I to V, IX and X ; cf. Charcot, 1865)(24,34,93,31,26).
However, regarding the disease's temporal evolution, Schumacher's diagnostic criteria were remarkably strict. As to the efforts devoted to their precise definition, multiple sclerosis might have been taken to reveal its nature mainly by the periods and spans of time within which it made itself felt. A reliable diagnosis of multiple sclerosis thus required:
The individual cryptic cerebrospinal dysfunctions to have evolved either
  1. "… in two or more episodes, separated by a period of one month or more, each episode lasting at least 24 hours", or
  2. "… in a slow or step-wise progression ... over a period of at least six months" (125).
The two time schedules might further have been understood to define two distinct types of disease development, had they not admittedly been arbitrarily chosen. They were in fact devised to lessen the risk of a misdiagnosis of multiple sclerosis in central nervous affections of “essentially different” (i.e. principally known, but at times not traceable) causes, such as in lesions of some "vascular" or "inflammatory" origin.
Little was said about these criteria's reliability, for disease developments which comply with the stipulated time schedules occur not only in multiple sclerosis. Simply two unverified arterial or venous occlusions of some untraced origin are thus, if their clinical manifestations are correspondingly timed, already liable to lead to a mistaken "clinically definite diagnosis of multiple sclerosis".
The responsibility for making a diagnosis of multiple sclerosis was in the end shrewdly shuffled off onto the diagnosing physician: It is he who has to ensure, with all the expertise at his command, that “… the patient's signs and symptoms cannot be explained better [i.e. actually explained] by some other [i.e. known, or even more precariously, curable] disease process” (125).

The Disenchanting Truth
The current understanding of multiple sclerosis, including its interpretation as a demyelinating inflammatory process, and its explanation as a primary autoimmune disease, apparently relies on the conception of clinically identified multiple sclerosis.
However, the evidence in support of also this last notion is extremely meagre, definitions having never been borne out by specific observations. The condition’s true identity has continued to elude researchers completely.
The meretricious nature of the “clinically definite multiple sclerosis” conception is especially revealed by the following:
  • In anatomical-pathological respects, clinically defined multiple sclerosis has, from the start, always reflected a conglomerate of unexplained, and otherwise thoroughly different, pathological conditions.
  • Currently established disease definitions imply that the cause of unexplained neurological dysfunctions (in case such recur) can be directly derived from the times during which the dysfunctions are manifest.
  • The existence of untraced thrombotic or embolic, hypo- or hypertensive, toxic or metabolic, infectious or allergic, as well as of other, more complex and evasive central nervous affections is virtually denied.
  • The conception of clinically defined multiple sclerosis is ultimately based on the logical fallacy of deriving a positive conclusion from blaringly negative premises.
  • Instead of speaking of clinically definite multiple sclerosis, it would be more adequate to speak of cases of unexplained neurological troubles in which the clinicians’ respectively neurologists’ diagnostic repertoire has been exhausted.
As is also highlighted by the lack of any solid identifying features or exemplary case histories, the establishment of the notion of "clinically definite multiple sclerosis" cannot be understood as anything but a soothing stratagem. To make progress in the understanding of the conditions which are at present subsumed under the term "multiple sclerosis", those features must be focused upon which in fact prove peculiar to the specific instances of the disease. Hollow, ultimately speculative diagnostic assertions carrying along in their wake endless series of therapeutic experiments only delay the sound evaluation and explanation, as well as potential cure, of the addressed conditions.

To chapter: Go!

© Dr. F. Alfons Schelling, M.D.