# Acute Poliomyelitis (Heine-Medins disease)/Chapter 1

Acute Poliomyelitis
HEINE-MEDIN'S DISEASE
CHAPTER I
Introduction
Historical Review.—Acute poliomyelitis, for many years known as infantile paralysis, has so often of late appeared in epidemic form that our knowledge of it has been considerably amplified. We have learned that acute poliomyelitis is much more protean in its manifestations than was formerly taught. So variable has it shown itself, that even clinicians of wide experience doubt the identity of epidemic infantile paralysis with the classical malady in which only sporadic cases appeared.
Wickman has suggested that all forms of disease arising from the same virus as acute poliomyelitis should be grouped under the one term—Heine-Medin's Disease. This nomenclature has been adopted, especially in Germany and Austria, by many with considerable experience in the recent epidemics.
Infantile paralysis was mentioned first by Underwood at the end of the eighteenth century. The credit of differentiating the disease from more or less similar conditions of cerebral origin belongs to Heine, who in 1840 published his masterly article on this disease. Duchenne, later, demonstrated the behavior of the affected muscles to faradic, and Erb, to galvanic stimulation. Surprisingly little further progress in our clinical knowledge was made until Medin published his celebrated observations on the Stockholm epidemic of 1887. Medin recognized, in addition to the already familiar spinal form, a bulbar, a polyneuritic, an ataxic and an encephalitic type. The last, from theoretical considerations, had previously been foreshadowed by Strümpell and Pierre Marie. The clinical significance of Medin's work ​remained almost unappreciated until the accumulated evidence from the recent epidemics emphasized its enormous value.
The first of these great epidemics appeared in 1905 almost simultaneously in Norway and Sweden. Wickman fully reported the Swedish epidemic. He distinguished several new types,—a meningitic, an abortive, and a form resembling Landry's paralysis. The basis of Landry's paralysis he found sometimes to be an acute poliomyelitis; but he further noted—what until then had not been recognized—that most fatal cases run a course closely resembling that of a Landry's paralysis. His observations showed that the disease was a general infection with specific localization in the nervous system. Wickman's work was followed by that of Leegaard (1909), upon the Norwegian epidemic of 1905; by that of Zappert and others (1909), upon the Austrian epidemic of 1908; by the report of the American School (1910), upon the New York epidemic of 1907; and by a particularly valuable contribution from Ed. Müller (1910), upon the Hesse-Nassau epidemic of 1909.
Although Prévost and Vulpian, in 1865, had described atrophy of the anterior horn and of the motor ganglion cells in a case of infantile paralysis in which the acute stage of the disease was long passed; and Roger and Damaschino. in 1871, had reported the changes in the stage of recovery; Rissler, in 1885, was the first to give a comprehensive description of the pathologic-anatomical processes of the acute stage. He demonstrated the inflammatory reaction in the blood vessels and also the degeneration in the ganglion cells. Later, isolated cases were reported by Dauber, Goldscheider, Siemerling, Redlich, and others. Wickman, in 1905, published the first work comprising a large series of recent cases. By his, and by the subsequent investigations of Forssner, Sjovall, Harbitz and Scheel, Marburg, Beneke, Strauss and others, the pathological anatomy of the acute stage was conclusively demonstrated to be an acute meningoencephalopoliomyelitis.
Thanks, not only to the researches above mentioned, but also to those of Charcot and Joffroy, Roth, Fr. Schultze, and others, the changes in the chronic stage, however, had then long been known.
The first attempt to explain the morbid process was made by Charcot. He conceived it to be a primary degeneration of the ganglion cells with secondary involvement of the vessels. This was a simple and apparently adequate conception and it conformed ​to the clinical picture presented by the malady. Most observers of recent cases—which were just beginning to be recognized—believed the process to be a true inflammation. Some regarded the degeneration of the ganglion cells as a sequel to the inflammation, while others looked upon the degeneration and the inflammation as simultaneous processes. Following the lead of Pierre Marie, most considered that the anterior horns were always affected because of implication of the arteria centralis. Wickman, on the other hand, maintained the lymphatic spread of the disease, and the latest experimental researches confirm the correctness of his opinion.
Very inexact ideas were prevalent concerning the nature of the disease until Strümpell and Pierre Marie, from its general character and its onset with fever, recognized it to be an infection. Their opinion was supported by the fact that infantile paralysis sometimes appeared in epidemics.
The first epidemic of infantile paralysis to be described was that reported by the Swedish physician, Bergenholtz, in 1881. Subsequently, several others were recorded, but most of them consisted of relatively few cases. The most celebrated were those which occurred in 1887 and 1895, in Stockholm. They were reported by Medin. Neither in these, nor in any other out-break, however, was it possible to ascertain how the disease spread. During the Swedish epidemic of 1905, through the observation of indisputable abortive forms, and through the study of all possible means of communication, Wickman succeeded in proving that Heine-Medin's disease spreads from person to person in exactly the same way as other contagious maladies. This has, in subsequent epidemics, partly been confirmed by Ed. Müller, P. Krause and others.
Although many problems of this malady have been elucidated, many are still unsolved. The cause of the disease is not yet known. Of late years, quite a number of very interesting experimental investigations of poliomyelitis in monkeys have been published and have greatly increased our knowledge of this disease. Landsteiner and Popper were the first successfully to infect monkeys. From the work of Flexner and Lewis, Landsteiner and Prasek, Knöpfelmacher, Leiner and Von Wiesner, Römer, Römer and Joseph, Levaditi and Landsteiner, Netter and Levaditi, and ​others, we must conclude that the cause of acute poliomyelitis does not belong to the class of the common bacteria, but is a filterable virus, and is present in the spinal cord.
Epidemic and Sporadic Acute Poliomyelitis.—It may not be inappropriate to refer here to the relation between epidemic and acute poliomyelitis. Some assert that both conditions are not identical. The following are the principal reasons for this assertion: (a) the clinical picture of Heine-Medin's disease is much more variable than that of the classical infantile paralysis; (b) in a number of cases of the former disease the cranial nerves are specially involved, whereas cranial nerve lesions usually do not occur in infantile paralysis; (c) adults are more liable to be attacked in epidemic poliomyelitis; (d) sporadic poliomyelitis seldom runs a lethal course, whereas the epidemic variety has a considerable mortality; (e) and, finally, the epidemic occurrence itself is a characteristic distinction.
The difference in symptomatology is more apparent than real. Obviously very different opportunities for clinical observation exist when hundreds of cases can be examined together than when only isolated cases are available from year to year. In epidemics, connections can be clearly traced between symptom complexes, which in isolated cases may appear unrelated, and the fact must be emphasized that the spinal type (the classical infantile paralysis) forms the nucleus of Heine-Medin's disease. From the most recent observations as to the localization of the paralysis, it is evident that the extremities—especially the legs—are oftenest affected. No doubt of the complete correspondence of the disease with the ancient infantile paralysis can endure. The changes in the acute and chronic stages have been shown to be absolutely identical in both. Netter and Levaditi have procured further and remarkably interesting evidence. They were able to prove in a case of sporadic acute poliomyelitis in which the acute stage had occurred three years previously, that the serum "in vitro" destroyed the virus of the epidemic poliomyelitis.
I wish, nevertheless, to refer here to certain peculiarities of Heine-Medin's disease, and to some circumstances which may explain why the epidemic and the sporadic forms have been regarded as distinct.
Heine-Medin's disease shows a striking variability which is ​evident not only in the different epidemics; not only in the various foci of the same epidemic; but also even in the different cases within a single focus. Its protean character may be gathered from the reports of different observers. Thus, one observer sees none but the typical; while another, of mature experience, reports a number of atypical cases. I can refer to no better examples than Medin, Nonne and Spieler, who, according to present ideas, had at their disposal very scanty material and yet recorded unusual forms.
Later I shall also show that the prognosis of sporadic acute poliomyelitis and that of epidemic acute poliomyelitis differ relatively less than was formerly alleged; and that the epidemic behavior is in no way distinctive, as was shown by my observations upon the Swedish epidemic, and presents all possible degrees from apparently isolated sporadic to accumulated and more or less pronounced epidemic cases. The map of the distribution of acute poliomyelitis in the Swedish outbreak shows that the disease occurred in foci, within each of which usually a continuity of spread could be demonstrated. Such was the case in those parts of the country in which the disease appeared not in epidemic form but only as isolated sporadic cases. From what I have said there can be little doubt that epidemic and sporadic poliomyelitis are one and the same disease.
Etiology.—Infantile paralysis has from earliest times been attributed to a variety of causes; e. g., trauma, cold, teething, etc. Infectious diseases, such as scarlet fever, measles, and pneumonia, rarely were alleged to be the cause, and a belief arose that under certain circumstances their toxins could produce infantile paralysis.
In 1887, Strumpell—and later Pierre Marie—stated that infantile paralysis was a disease per se, independent of other infectious maladies. Experimental research and the study of epidemics have since adequately confirmed this statement. Naturally, a specific organism was early sought but as none was found either in cultures or in spinal cord sections, the morbid changes were attributed to the action of a toxin. During the last decade several microorganisms from the spinal fluid in this disease have been announced. Fr. Schultze, Concetti, Looft, Dethloff and others whose examinations were restricted to single cases, and Geirsvold and Potpeschnigg who investigated large series, all reported such ​findings. Usually an organism resembling the Weichselbaum micrococcus was incriminated. Other investigators with similar material have however failed to obtain corroborative evidence of these discoveries. The efforts to demonstrate organisms in sections of affected tissues have likewise proved unsuccessful. Bonhoff by means of the Mann stain demonstrated in the glia cells, bodies which he alleges to be specific. The results of experimental investigation have shown that the bacteria found have absolutely nothing to do with Heine-Medin's disease, and that in those cases in which they arose not from faulty technique, such bacteria must be regarded as having had an accidental and not a causal relation to the malady.
Experimental Poliomyelitis in Monkeys.—Before discussing the recent successful inoculation experiments in monkeys, I shall first refer to earlier experimental researches upon acute poliomyelitis. Roger, Gilbert and Lion, Vincent, Enriquez, and Hallion; Thoinot and Masselin, Crocq fils; Ballet, Charrin, and Claude have produced poliomyelitis with various bacteria. But as I have already mentioned no one has succeeded in reproducing more than a vague semblance of the disease. I, myself, notwithstanding the extensive material employed, could obtain only negative results with streptococcal injections. The time has fully arrived when such experimental investigations should be discarded from the literature of this disease.
Landsteiner and Popper were the first experimentally to reproduce indisputable poliomyelitis. They took a piece of the spinal cord of a boy who had died of acute poliomyelitis and introduced it into the peritoneal cavity of a monkey. They were able to reproduce a disease characterized by paralysis and associated with the pathologic-anatomic changes of acute poliomyelitis. The results of Landsteiner and Popper were extended and corroborated by several observers. Similar investigations by Landsteiner and Prasek, Flexner and Lewis, Knopfelmacher, Leiner and von Wiesner, Romer, Romer and Joseph, Levaditi and Landsteiner, and Netter and Levaditi were carried out about the same time practically independently of each other.
It should be mentioned, in passing, that similar experiments have been made with many other animals, but no constant results have been obtained. Thus, Flexner and Lewis—who have done ​most work in this field—failed in numerous experiments to cause the disease by intracerebral inoculation of guinea pigs, rabbits, horses, calves, goats, pigs, sheep, rats, mice, dogs, and cats. Most observers have found animals other than monkeys to be refractory, But Krause and Meinecke, also Lentz and Huntemuller, have reported as many successful transmissions in rabbits by inoculation through the blood stream, as in monkeys by intraspinal inoculation. Insignificant pathologic-anatomic changes were found in the spinal cord of the rabbits. Meinecke explains most of the negative results of other experimenters on the grounds of variation in the susceptibility of different breeds of rabbits and of insufficiency in the amount of the infective material injected. These features are, however, negligible factors in monkeys in which a minimal dose suffices to produce the disease. It seems to me, with so many contradictory statements about poliomyelitis in rabbits, that until we have further information only monkeys should be used for clinical research purposes, for failure to reproduce the disease by inoculation is in them exceptional.
The clinical picture of monkey poliomyelitis corresponds very closely to that in man. The most important distinctions are the absence in monkeys of the initial fever, and the frequency with which the disease is characterized throughout its course in them by subnormal temperature. Prodromal symptoms sometimes usher in the paralysis but are often absent. The paralytic signs develop in rapid succession. The brunt of the attack falls upon the legs; and a flaccid paralysis develops which is characterized by atrophy and loss of reflexes. The mortality among monkeys is very high. In Flexner and Lewis' experiments the death rate among 81 monkeys was 54.3 per cent. According to these observers the incubation period, from the injection until the onset of paralysis, is 9-10 days; its minimum is 4, and its maximum 33 days.
The pathologic-anatomic picture—apart from the results of Leiner and von Wiesner—corresponds with that which we find in man. The most important results yielded by experimental investigation are, however, those which relate to etiology and pathogenesis. Examination of sections of human and of monkey's tissues and the study of the cerebrospinal fluid, blood, etc., by every conceivable method have given uniformly negative results. ​These failures led many to the belief that poliomyelitis is a toxaemia. Experimental investigation has now proved the incorrectness of this belief. The virus occurs in the spinal cord. By injecting virulent material into the brain the spinal cord is made virulent and we can then reproduce the disease in monkeys by intracerebral inoculation with this virulent spinal cord tissue. The virus has thus been propagated through many generations of monkeys.
The virus shows a special affinity for the spinal cord. Wherever it be injected it will be found mainly localized in that organ. But it has not been demonstrated in the blood, spleen or any other organ of the monkey. Yet it seems to be eliminated by several channels, for after intracerebral injection it has been found in the salivary and mesenteric glands and in the nasal mucous membrane. In the spinal cord its potency is preserved for some time but soon diminishes and finally disappears; at least Levaditi and Landsteiner observed that the spinal cord about six weeks after infection was no longer virulent.
The interesting fact has, moreover, been established that the virus of acute poliomyelitis cannot be classed among the common bacteria, for it passes through bacterial filters such as the Berkfeld. When fluid containing ordinary bacteria is so filtered, the filtrate is sterile: in poliomyelitis the filtrate is infective; hence the virus belongs to that class which we usually designate filtrable. It closely resembles, in many of its characters, the virus of rabies. One property which both enjoy is resistance to the action of glycerin. This resistance distinguishes them from all ordinary bacteria. Römer and Joseph found the virus after almost five months in undiluted glycerin potently infective; but other observers have recorded an attenuation of the virulence under similar conditions.
The poliomyelitis virus is also markedly resistant to other agents. Flexner and Lewis, for example, found the infectivity still preserved after exposure for forty days to a temperature of from -2° to -4° Celsius; and, after fifty days, at -4° C. During the exposure autolysis appeared in the preserved pieces of the cord which were covered with mould, and yet the virus remained unimpaired. Even to drying, the virus is most resistant. The experiments of Leiner and von Wiesner show, however, that ​if the virus be allowed to dry in thin layers of infected tissues, if it be allowed to desiccate therefore under conditions which approximate to actual experience, it rapidly decreases in virulence. The poison is more sensitive to high than to low temperatures. At 55° C. it loses its virulence, and at 45° C. it is perceptibly attenuated.
Much of the experimental research has been directed towards the question of acquired immunity and many interesting facts have been discovered. Flexner and Lewis, Landsteiner and Levaditi, and Römer and Joseph demonstrated that monkeys which recovered from one infection with the virus of poliomyelitis are immune. According to Joseph and Römer this immunity is present even when the first infection produces no clinical symptoms. Moreover, antibodies can be demonstrated in the blood of such immune monkeys. These antibodies can neutralize the action of the virus in vitro (Römer and Joseph, Landsteiner and Levaditi, Flexner and Lewis). Netter and Levaditi, and Flexner and Lewis have further shown that in the serum of children who have recovered from infantile paralysis, antibodies are present; and Netter and Levaditi have also established that these antibodies can be demonstrated in the abortive forms of the disease. Wollenstein, Römer and Joseph, and others failed, however, to demonstrate the presence of amboceptor (komplementbinden Antikorper) in the cerebrospinal fluid or in the blood serum of patients who were suffering from, or who had recovered from poliomyelitis. From similar investigations on monkeys they obtained negative results. Römer and Joseph call attention to the fact that if in highly immunized animals this absence of amboceptor is shown to occur, the analogy already recognized between poliomyelitis and rabies would be reinforced; for amboceptor has not as yet been demonstrated in rabies.
In has already been stated that no culture has been obtained from the spinal cord. Flexner and Lewis and Levaditi have, however, given us an impulse to the further study of the propagation of the virus outside the body for in bouillon prepared from the clear, bacterial-free, virulent spinal cord filtrate they have seen arise a cloudiness which was not due to any contaminating bacteria. With the aid of Borrel's modification of the Löffler method, Levaditi thought that he further observed in the cloudy bouillon ​minute staining bodies oval form. Romer and Joseph have found in examining these nitrates (Berkfeld) by means of the ultramicroscope, extremely small round oval bodies which were not demonstrable in the nitrates from normal spinal cords. Benecke, and Krause and Meinecke have also published similar results which they obtained in working with the blood of infected children. The results of experimental research in pathogenesis and other matters will be dealt with later.
Predisposing Factors.— From our experience of conditions in epidemics and from the results of experimental research, we are compelled to regard Heine-Medin's disease as a specific infection. A number of cases have been observed in which the disease has developed during the course of a common infectious malady. It is extremely probable that such cases are merely coincidences, and that the infectious malady is to be regarded in them only as an agent in the production of the favorable moment for the poliomyelitis invasion.
There is practically only one predisposing factor—the age. As is emphasized in the name, infantile paralysis, the disease usually attacks children. In order to show the incidence of the disease at different age periods, I shall quote some figures from various epidemics:—
Leegaard during the two epidemics he reported found the following figures:—
Heine-Medin's disease is therefore principally a disease of childhood. Celebrated writers have even stated that acute poliomyelitis does not occur in adults. But the statistics of Wickman and Leegaard, however, show that adults are by no means immune. Fr. Schultze, Rissler, Taylor, van Gehuchten, Wickman and others had already by pathologic anatomic examinations proved that the disease affects adults. Wickman saw a man of 46 years suffering from a typical attack, while his nine children living in the same house with him remained unaffected. It is possible that conditions change from epidemic to epidemic, so that the frequency of attacks upon adults varies. On the other hand, the great diversity of existing statements upon this point may partly be due to a lack of uniformity in the thoroughness of the reports.
Besides the age, no other predisposing factor is positively known to us. As regards sex, the cases during the various epidemics, of which I have data, occurred as follows:
| | Male | Female | Total |
| Medin (1887) | 22 | 22 | 44 |
| Medin (1895) | 15 | 6 | 21 |
| Leegaard (1899) | 31 | 23 | 54 |
| Wickman (1899) | 33 | 21 | 54 |
| Wickman (1903) | 8 | 10 | 18 |
| Wickman (1905) | 591 | 426 | 1,047 |
| Leegaard (1905) | 472 | 365 | 837 |
| Zapport (1908) | 130 | 97 | 227 |
| Lindner and Mally (1908) | 57 | 37 | 94 |
| Lovett (1907) | 131 | 103 | 234 |
| Lovett (1908) | 39 | 26 | 65 |
| Emerson (1908) | 42 | 47 | 100 |
| Ed Müller (1909) | 53 | 4 | 100 |
These figures show that the male sex is somewhat oftener attacked than the female. But the source of this difference eludes us. Of Byrom Bramwell's cases, 43 per cent, were male; 56 per cent, female.
Dejerine has asserted that a neuropathic disposition is an important etiological factor in the development of acute poliomyelitis. Wickman, Medin and Leegaard, however, could not substantiate this assertion.
Even when I elicited proof of a neurotic tendency in a patient's family, I could not attribute any causal significance to it. Ed. Muller also calls attention to the fact that in his experience the children affected by acute poliomyelitis were free from neuropathic taint, and, as a rule, were physically and mentally normal. Johannessen, however, found various mental diseases among the families in several of his cases.
Occasionally, infantile paralysis has been reported in those whose relatives (uncle and aunt) had previously been affected (Wickman, Furntratt). Leegaard attributes a certain importance to chills and reports strikingly numerous cases which followed exposure to cold and wet. Perhaps, however, we ought rather to consider such exposure as belonging to the general condition under which the people live. It is difficult to determine if over-exertion is a predisposing cause, but I am convinced that at least once the disease has begun, over-exertion has an unfavorable influence upon its further course.
Hochhaus and others have occasionally observed the disease to follow vaccination. This association is most probably accidental.
Finally, an acute atrophic paralysis may rarely arise from a variety of causes other than the virus which produces Heine-Medin's disease. A few cases are recorded of acute poliomyelitis probably due to syphilis; e. g., J. Hoffmann's case. Some may be classed as cases of partial transverse myelitis. Typical Heine-Medin's disease has been observed to develop in a case of an existing luetic infection. Injury may cause a hematomyelia localized to the anterior horns, and thus simulating acute poliomyelitis (Beyer); but the history and onset serve readily to identify this condition.