The disease of Heine-Medin is an acute infectious disorder produced by several neurotropic viruses attacking especially the anterior horns of the medulla, affecting children, adolescents, and rarely adults, causing paralysis in diverse regions of the organism.
Although this disease existed since 3700 BC (Marque), its clinical description dates of 1840, in which Heine did the first publication separating it from the other diseases of the nervous system. Prevost (1865) described the lesions of the anterior horns of the medulla. Medin, studying the epidemics of Stockholm of 1887, 1895 and 1899, established the contagiousness of the disease, affirming its infectious character. In 1909, Landsteiner and Popper were able to reproduce, anatomically and pathologically, the clinical disease in the monkey, by peritoneal inoculation of a marrow fragment from a boy dead from poliomyelitis.
ETIOLOGY AND PATHOGENY
A. — Virus. — The agents producing the Heine-Medin disease are filterable viruses measuring from 10 to 15 nanometers and whose existence was demonstrated for the first time by Landsteiner and Popper who, as we were saying, have inoculated great apes, with marrow fragments extracted from a boy dead from poliomyelitis. The disease was reproduced with its paralysis and in the autopsy the typical lesions in the anterior horns were discovered.
The agents producing the disease of Heine-Medin are filterable viruses very sensible to heat, because they die in twenty minutes at 60°C; however, at 0°C and in glycerin they conserve their virulence for years. They resist cold, desiccation, and also chlorine in the proportion used to disinfect the water of swimming pools. They are destroyed by menthol and permanganate of potassium at one percent and by hydrogen peroxide at one percent.
These viruses are neurotropic, meaning they have a special affinity for the nervous system, found especially in the medulla and the bulb, although it is also possible to find them in other parts of the nervous system, as well as in the tonsils and nasopharyngeal secretions of the diseased subjects and healthy people in contact with them (germ carriers). The viruses pass in the pharyngeal and pituitary mucosa, where they conserve their virulence for several months. They are also eliminated in fecal matter as much by diseased subjects as by some healthy carriers.
Inoculation in the animal is obtained intracerebrally, but also it has been possible to be obtained intraperitoneally, subcutaneously, intravenously, pharyngeally and nasally. Also, it has been possible to infect monkeys via the digestive tract, by way of water and contaminated foods (King, Levaditi and Lépine).
The virus propagates via the nervous system along the axons. Flexner and Clark demonstrated that 48 hours after intranasal inoculation, the disease could be transmitted through the olfactory bulb. Schultz and Bebhard demonstrated experimentally that the virus inoculated nasally arrives at the central nervous system by the filaments of the abdominal sympathetic nerve. Then we see that the way followed by the virus is through the nerves; meaning that the disease of Heine-Medin is a septineuritis by analogy with septicemia.
The virus of the disease of Heine-Medin is neutralized by the blood of a monkey cured of poliomyelitis and by the serum of convalescence. Leaning on this principle, Netter and Levaditi established the reaction of neutralization of the virus, allowing to make exact diagnosis of the disease even after several years. The treatment of this affection by serotherapy (serum of convalescent or animals) is also based on this principle, although no good results have ever been obtained.
Ninety percent of normal adults have neutralizing antibodies in their serum, just like suckling babies before the age of six months. In adults it is accepted that this immunity must be acquired from undetected infections in the course of life, whereas in the suckling baby immunity is due to transmission of antibodies from the mother (passive immunity) and would disappear after six months.
B. — FORMS of CONTAGION. — The disease of Heine-Medin is contagious; this concept, although disputed by some authors, is nowadays accepted anywhere in the world. The epidemiologist report of the Hygiene Section of the Society of Nations, presented in December 1935, accepts the fundamental cause of the nasopharyngeal mucosa as being a likely origin of entry of the infection. The virus-loaded salivary particles, coming from poliomyelitis patients or healthy carrier subjects, arrive to the nervous centers by the nasopharyngeal mucosa and through the olfactory nerve.
The same report does not deny the possibility of infection through the intestinal tract, whether from drinking water or contaminated foods, but it is considered rare. On the other hand, in publication number 90 of the Third Pan-American conference of National Directors of Health held in Washington, DC in April 1936, it is accepted that transmission takes place by direct contagion from an infected person, including virus carriers and indirectly by contact with articles just contaminated with secretions from the throat or nose, or defecations of such people. Also one says that proof of the propagation by milk exists; but this way of transmission is unusual. Levaditi, who has done so much for the progress of the bacteriological study of this disease, also accepts that the commonest entry is via the nasopharyngeal tract. Our epidemiologists have adhered to this opinion.
In these last years, the theory of the intestinal tract has again received all the attention. Then water contamination would also have a great importance, as for typhoid fever. The infection would occur from water ingested, inhaled during swimming, from vegetables washed with well-water, water mixed with milk, etc., also insects would be main factors (transport of contaminated matter), especially flies, and particularly the Regina Phormia. The champion of this doctrine is Kling (of Stockholm).
But this theory, which until recently was almost accepted, has been demolished by clinical facts and quite demonstrative experiments: In full acute phase, when acute symptoms are ending and paralysis begins, the patient still lying in bed — the phase accepted as being the most contagious— the patient’s siblings and friends exchanging treats or foods from mouth to mouth, without any cases having been infected by this direct means of transmission. In Vietnam and many Asian countries, where there is no sewer service, excrements and other waste products discharged by man are handled by hand. In those places, where there are clouds of flies year around, there are very rare cases of Infantile Paralysis. They were only observed during the last war with soldiers landing ashore. And in spite of having carried this disease to those places favorable for all types of infections, to date, there has been no news of some epidemic worthy to be taken into account. However, in a city like Stockholm, the cleanest in the world, where at no time flies can be seen, periodically, each spring and autumn, this disease appears in epidemic form.
We must once again call attention to the report of apparently healthy carriers and also of aborted cases, that is to say, of those constituted of momentary febrile acute episodes without signs of invasion of the nervous system (seen as clinical forms). Most of the cases of contagion taking place are due to these types. Collier has maintained that all infections are caused by healthy carriers and affirms that when the disease is developed in a person, she stops being able to transmit it to another subject. Nevertheless, it is also accepted that patients can propagate the virus.
It has been observed that the frequency of the disease among close friends of a patient is small. The report of the Third Pan-American Conference says that this is due to the fact that only a very small proportion of those exposed to the infected patients contracts the disease.
As far as the period of contagiousness is concerned, that is to say, the time during which a healthy or ill carrier can infect, is debatable. Although it is possible that the infection can still occur months after an attack of poliomyelitis (Lucas and Osgood), the contagious period includes the incubation phase and the first week of the disease (Publication No. 9, of the Third Pan-American Conference). Many investigators have found in almost all patients that polio viruses are in the throat of patients already paralyzed, and for this reason, repeating myself frequently, one of the surest forms of contagion is by products of the throat or the nose. As a contradiction to this form of contracting the disease is the fact that during the epidemic of this year in the City of Mexico, in three families several children from a single family, were taking foods with the same spoon, and others were licking the same popcicle [ice cream on a stick] ruin the theory so often repeated that the secretions of the mouth and throat are the most effective vehicle of contagion.
C. — PREVAILING CAUSES. — In the first place we must take age into consideration. Infantile Paralysis is a childhood disease. The highest frequency is from 1 to 9 years (87% of all cases, according to Wilson, statistics of 14,000 cases). In Mexico, from 1 to 2 years of age. Later it gets more infrequent with increasing age, although cases in adults have been observed everywhere in the world. We have already said that 90% of normal adults have neutralizing antibodies in their serum. We must also consider the influence of the seasons. The epidemic break-outs of the disease are almost always observed in the summer and fall.
It was said that the disease attacks weak subjects, and that a chill and “surmenage” [stress], could be prevailing causes. Nothing of this is acceptable, and we see that quite often the disease attacks very well constituted and healthy children, without being able to discover the smallest predisposing cause. It is somewhat more frequent in the male than in the female (Wickman). And in the epidemiology of the infection, racial factors do not seem to intervene. Nevertheless, the white race presents more cases.
It has been observed that physical fatigue, and particularly pregnancy, and all the causes that increase the customary yield of the organism, produce in the nerve cells a weakness predisposing to contract the disease. The customary thing is that during the pre-paralytic period, absolute rest is imposed on the presumed victim. As a demonstration of this comes to mind the 1947 epidemic in England: out of 100 patients, 38 remained paralyzed; these had not exercised in the first days; 30 were with slight paralysis, which improved considerably with time; 6 had very moderate paralysis, and only 2 were in serious condition. On the other hand, of 29 patients who had followed a normal life routine in the beginning, only 2 escaped with a slight paralysis remaining, 12 with moderate paralysis and 15 in serious condition.
Recent statistics seem to demonstrate that a recent tonsillectomy constitutes a first class predisposing factor, especially in those with the bulbar form of the disease (27% of bulbar paralysis were children who had a previous tonsillectomy, versus 4% who were not operated).
It is now customary to abstain from practicing tonsillectomies during spring and fall; subsequent more careful observations will or not justify this new custom.
D. — EPIDEMIOLOGY. — Cases of Poliomyelitis exist in sporadic form at any time, but most of the time they appear in epidemic form.
Epidemics of this disease have been registered in every country of the world. Just to mention the most serious and the worst, in the United States, in 1916, with 29,000 cases and 2,400 deaths; in 1949, with 42,375 cases, and a higher average in comparison with the period from 1942 to 1948; in this same period, all the European countries experienced a rapid increase.
Before 1946, between 22 to 47 cases of polio were recorded annually in the whole Republic [Mexico]. But as of this year, the count abruptly jumped to 274 cases, and with fluctuations, has increased, to such degree that in 1951 nearly 2,000 cases have been recorded. And if we took into account that there is a large number of victims who are not being reported, this number would increases considerably. Of course, in the northern states of the country, and in the large population areas, this is where the greatest percentage is seen; the southern states of the republic have been less affected. From the epidemiological point of view it would be interesting to know where the beginning is, although so far we do not know what the factors are.
The sensitivity to the virus is small, because, as we were saying, only a small number of subjects exposed to the infection become ill; in an epidemic there is no more than one case per thousand inhabitants.
As to the geographic distribution, it is well defined; it abounds more in the temperate zones and it is less frequent in warm climates, the least, corresponding to the tropical areas. Perhaps this is why it is observed more frequently among the white race. A special characteristic of this disease is its clinical distribution; in general, the years of epidemic in a given zone are separated by a few years of lower morbidity.
As to the mortality of epidemics, it is variable, arriving in some cases, as the one of the United States in 1916, at 25% of the victims. The average for the 38 epidemics studied by the Third Pan-American conference was 20.8%. In our country [Mexico], in the cases studied on the epidemic from January 1st. to April 20th.,1946, it was 16.21%. But sifting through the statistics one reached the conclusion that the real percentage of mortality should be 5.73%. As we can see, this is not a very high number.
The most important lesions of the Heine-Medin disease sit in the anterior horns of the medulla, where the name Acute Anterior Poliomyelitis came from. Subsequent works of Wickman, Thomas and Harbitz, Scheeil, Strauss, Spielmeyer, etc., have demonstrated that the disease invades, in addition to the white substance of the medulla, the meninges, the spinal ganglia, the bulb, the pons, peduncles, cerebellum, gray central nucleus, cerebral cortex, and peripheral nerves. We see, then, that no part of the nervous system is respected.
Microscopically, it is observed that the spinal Pia Mater is hyperemic and tumefied, and in the cross section of the medulla their vascularized anterior horns are seen, congested and edematous. The peripheral nerves are also tumefied and congested, and lesions of the same type are observed in other parts of the central nervous system. Additionally, hypertrophy of the spleen, and subpericardial and subpleural hemorrhages are seen (Hanbaud).
Microscopically, the meningeal lesions, in the form of lymphocyte infiltration of the Pia Mater, are observed. And additionally, punctate hemorrhages and edema occur.
In the anterior horn of the medulla (just as in other zones of the central nervous system) one later sees an infiltration of the nervous fabric and accidental infiltration of the vessels by cellular elements that are polynuclear in the beginning, and then lymphocytes and histiocytes. The nervous cells, especially the anterior horn motor cells, present degenerative lesions: chromatolysis, vasculitis, displacement of the nucleus, then cellular destruction. The cellular exudates overflow the gray matter and they are also noticed in the white matter.
Later, neurologic proliferation invades and replaces the destroyed cells, whereas the perivascular exudates are reabsorbed; it is the healing or regeneration process.
The spinal ganglia show a lymphocyte interstitial infiltration. The cranial motor nuclei are hardly attacked; the vestibular nucleus seems to be a favored site. The thalamus is affected in most cases. In the peripheral nerves a secondary degeneration of motor axons takes place; the corresponding muscles atrophy, while in the bones can be observed osseous atrophy and rarefaction.
From the histopathologic point of view it is difficult to explain the preference of the virus for certain parts of the body. The vascular factor explains the localization, but the lesions do not disperse following the blood vessels . As for the way the infection moves inside the organism, it is not known either. Some authors think that the invasion of the virus occurs by the meningeal route, a hypothesis denied by other authors (Kurst and others). In the report from the International Commission for the Study of Infantile Paralysis, presided over by Park, it is explained that: “Definitive conclusions cannot be reached yet on the route followed by the infection in the organism. Research must continue.”
Some very recent investigations executed by North American doctors have been able to demonstrate that the virus remains in the blood from 8 to 15 days before the appearance of the first symptoms of the acute or pre-paralytic period. If these findings are corroborated, the course of the studies would considerably change towards other avenues that have already been explored.
We will describe here the classic form of the disease of Heine-Medin, studying later the most important clinical forms which are necessary to know, because they have appeared with relative frequency in the last epidemics.
In this classic form we can distinguish, with most of the authors, 5 periods:
A. — INCUBATION PHASE. — During this phase no disorders are observed; its duration is 8 to 15 days, and can last up to 33 (Claude).
B. — INVASION OR PRE-PARALYTIC PHASE. — During this period, diagnosis is fundamental, because an etiologic treatment instituted at this moment is able to stop the disease. Unfortunately such diagnosis is very difficult. In this phase we have a condition of general infection whose symptoms are the following:
2, up to 2,000 per mm2 (Obarrio). In the beginning, the majority are polynuclear, 60 to 80%, and towards the third day, the lymphocytes begin to predominate. The colloidal reactions are positive with deviation to the left; thus the reaction of Lange gives, for example, 1123321000 (Cibilus Aguirre). But these results do not make a diagnosis, and for this reason, the fluid should not be extracted, because most of the time the patient worsens.
C. — PARALYSIS PHASE. — In this phase there are two essential manifestations:
D. — REGRESSION PHASE and LIMITATION of the PARALYSIS, or THERAPEUTIC PHASE. — At the end of the second week, and sometimes the third, the paralysis regresses, and movements begin to appear in certain muscles previously paralyzed. This regression is progressive and sometimes lasts years. Paralysis can sometimes disappear completely. The regression is always more extensive than was expected.
The tendinous reflexes are always lacking, and the atrophy of the muscles that will be definitively paralyzed, begins to assert itself little by little.
In this phase electrodiagnosis acquires a major importance. It must take place 15 days after the beginning of the paralysis. In general terms, it is possible to say that the motor recovery and the prognosis will be much gloomier when the reactions are close to the reaction of complete degeneration, or inexcitability to both currents. In this case, classically, there will be nothing to do. A reaction of partial degeneration allows hope for motor recovery, or at least, partly. Muscles not presenting electrical disorders, or only slight quantitative variations, evolve favorably, healing their paralysis in a short time. The muscle groups, in general, adopt a radical distribution.
The evolution that the paralysis follows will depend on the extent and the type of lesions that the virus leaves in the motor neurons. If there are only congestive disorders around the nerve cells and they do not continue, either because the infection is attacked on time, or because this inflammation yields spontaneously, then we will not observe what we justly call the Residual Paralysis Phase, except that the level of cellular lesions will correspond with the evolution and the symptoms of regression.
If the cellular lesions continue, either because of the gravity of the case, or because an appropriate therapy has not been instituted on time (so far only Cellular Therapy has given manifest curative results), the nervous cells, especially motor neurons, will present degenerative lesions: chromatolysis, vacuolation, etc., already mentioned when speaking about Pathologic Anatomy. It will not be possible to determine in many cases, what kind of lesions, and therefore, what form of paralysis the patient is going to suffer. For these reasons, it is of the utmost importance to perform the treatment as early as possible. According to current observations, in practice, it is possible to say so far that, as in all nervous system diseases causing or producing cellular destruction, these destructions depend on a multitude of extrinsic and intrinsic factors that we cannot determine, much less make an approximate prognosis.
E. — RESIDUAL PHASE or DEFINITIVE PARALYSES of CLAUDE. — In this phase, muscular atrophy is evident, and we notice the loss of size and shape. In these atrophied muscles the functional impotence is absolute, and characteristic deformations appear according to the affected muscles. In the feet, varus equino, valgus, talus, etc., can take place. Deformations in the trunk can also appear. These deformations are aggravated by the tendinous and aponeurotic muscular retractions. These deformations can give origin to other problems as well.
The skin is cyanosed and cold. The bones, in the areas paralyzed due to their deficient irrigation, by lack of muscular mobility, undergo a trophic process that leads sometimes to a decalcification and to a growth stunting, so that the subject can end up with a shortened leg, producing in this case a compensating scoliosis. In this phase, electrodiagnosis shows a reaction of complete degeneration of muscles, definitively beyond repair.
In the whole evolution of the disease, this one does not bring psychological disorders. Neither memory, nor intelligence suffer and thus we see individuals with poliomyelitic lesions reach prominent places in public life.
Following Wickmann, Griffith, and Obarrio, we will describe 8 clinical forms:
1. — Abortive form. — In the report of the International Commission for the study of poliomyelitis, presided over by Park, cases described as abortive are characterized by transient acute febrile episodes from 12 to 72 hours, with or without migraines, vomiting, constipation or diarrhea, angina or phenomenal catarrh, in which signs of invasion of the central nervous system do not exist and in which, therefore, the diagnosis cannot take place with certainty, since they do not present edifying characteristics. Certainty would only be obtained with the reaction of neutralization, or the demonstration of the virus. As we can see, we are talking about cases going through the first and second phase of the disease, and not arriving at the paralytic phase. This form is placed within the forms called nonparalytic, presenting so much importance in the epidemiology of the infection.
2. — Meningeal forms. — Three varieties are described:
3. — Spinal or poliomyelitic form. — This is the most common, and it is the one that we have chosen for typical description; in it, only the muscles of the limbs, trunk, and neck are affected.
4. — Bulbo-pontine form. — After the pre-paralytic phase, paralysis of muscles innerved by the cranial nerves appears: facial nerve, ocular nerves, etc. In addition, respiratory disorders appear (dyspnea) and cardiac (tachycardia not related to temperature). It is a serious form, generally fatal.
5. — Progressive or ascending form. — The Landry syndrome takes place; paralysis begins in the lower limbs and ascends until arriving at the bulb, producing death. One fifth of the cases of precocious mortality belong to this clinical form. Nevertheless, the evolution can be stopped and cure can be attained.
6. — Encephalitic form. — It begins with meningitis and convulsive phenomena, and as a result hemiplegia settles in, that very soon turns into the spasmodic type with exaggeration of the Babinski reflex signs, etc. When this form is combined with spinal type paralysis, it is called the encephalomyelitic form.
7. — Ataxic form. — It is characterized by a staggering walk with frequent falls. There are cases of cerebral localizations, observing the corresponding signs.
8. — Painful form. — It corresponds to the polyneuritic form of Wickmann. The pains in the limbs are very intense, and intensified by the compression of muscular masses and nervous centers. Paralyses do not exist, or are very slight. In some epidemics, like the one of Buenos Aires, in 1935-36, there were many cases of this form.
Park, in the report of the International Commission for the study of Infantile Paralysis, describes 5 clinical forms:
a.— Abortive form.
b.— Non quadriplegic form.
c.— Form with subcortical paralysis.
d.— Encephalic form.
e.— Ataxic form.
Some authors describe the adult form as a special clinical form, which is distinguished solely by its particular gravity and the presence of painful phenomena of great intensity.
A problem to consider is why some subjects get the abortive or non paralytic forms and others get the typical forms.
The epidemiologist report of the Hygiene Section of the League of Nations concludes that at the present time, it cannot say if it is a difference of infectious viruses or of a difference of individual resistance, or both.
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