CHAPTER XVIII

BERIBERI

DEFINITION AND SYNONYMS

=Definition.=—Beriberi is a food deficiency disease due to the absence from the dietary of a neuritis-preventing vitamine. It is

## particularly important among the people of the Orient whose diet

is preponderatingly one of rice. In milling the grain the outer vitamine-containing layers are rubbed off and this polished rice, when the chief constituent of a dietary, is capable of causing, after a period of two or three months, a peripheral neuritis.

This neuritis not only involves the nerves of the extremities but, as well, the pneumogastric, and it is the manifestation of cardiac disturbances which best differentiate this form of neuritis from those due to alcohol or arsenic.

The disease is usually described under two types: (1) a wet or dropsical beriberi, in which the vasomotor nerves are affected with resultant general oedema and (2) a dry atrophic or paraplegic type, in which muscular palsies and atrophies are the leading features. Pathologically, we have a Wallerian degeneration of the peripheral nerves with possibly axonal degeneration of the cells of the neuron involved.

=Synonyms.=—Neuritis Multiplex Endemica, Polyneuritis Endemica, Hydrops Asthmaticus. Japanese: Kakke.

HISTORY AND GEOGRAPHICAL DISTRIBUTION

=History.=—While modern knowledge of beriberi may be said to date from the writings of Bontius, in 1642, yet the disease is distinctly described by Chinese writers of the seventh century and treated in writings of the second century and possibly referred to in writings as ancient as B. C. 2697. It is probable that the disease described by Strabo as occurring in a Roman army while invading Arabia, in 24 B. C., was beriberi. While mention of the disease may be found in Japanese writings of the ninth century it is thought by Scheube that this relates to the disease in China and that beriberi first appeared in Japan about the eighteenth century. Bontius described the atrophic form of the disease, Rogers, in 1808, the serous effusions, and Marshall, in 1812, noted two types, barbiers, when the paralysis predominated, and beriberi, when the dyspnoea and oedema were leading features.

In 1835 Malcolmson noted that cases of beriberi assumed the type of barbiers and vice versa, from this time the view has obtained that the two affections belong to one disease.

The disease seems to have first made its appearance in Brazil in 1866.

[Illustration: FIG. 82.—Geographical distribution of Beriberi.]

=Geographical Distribution.=—Reference to the chart will show 3 markedly endemic centers for beriberi, one embracing Japan, a second the Dutch East Indies (Java, Borneo, Sumatra), and a third, involving the Eastern coast of Brazil. In somewhat less degree the disease prevails in India, Indo-China, Malay Peninsula, Eastern China, and the Philippine Islands. It is also found in the regions of the East and West Coasts of Africa, and was devastating to the laborers on the Congo railway. It has been reported from many parts of the world among coolies from Asiatic countries. A disease of similar nature has been noted in asylums in England and America. Beriberi occurred among the British soldiers in Mesopotamia during the recent war—more than 300 cases in 1915. It is interesting to note that scurvy, and not beriberi, occurred among the Indian troops in Mesopotamia at this time. There was no scurvy in the British troops.

ETIOLOGY AND EPIDEMIOLOGY

=Etiology.=—There is probably no disease about which there exist so many views as to etiology as with beriberi. Many of those formerly advanced are so negatived by recent investigations that it would seem hardly worth while to mention them. While the cause is still unsolved attention is at present almost exclusively directed to some deficiency of a neuritis-preventing substance in the dietary and such studies have in large part centered about the question of such deficiencies in certain kinds of rice.

Reserving until the last the discussion of the rice theories we may briefly dismiss such views as those assigning bacterial or protozoal causes with the exception of those of Manson and Hamilton Wright.

_Manson’s Theory._—Under conditions of overcrowding, filth, warmth, moisture and lack of ventilation, as would obtain in the forecastle of a ship carrying a native crew, the development of a hypothetical germ is favored. This germ in its growth gives off emanations which like alcohol act as toxins upon the peripheral nerves. The germ itself does not infect the patient.

_Wright’s Theory._—According to this view a bacillus which was given off in the faeces was ingested and locating in the duodenal mucosa gave off a toxin similar to that of the diphtheria bacillus. Instead of developing its soluble toxin in the membrane of the region of the throat this action took place in the upper part of the small intestines.

Of the bacterial causes may be mentioned: (1) The coccus of Pekelharing and Winckler. This organism was supposed to be short lived in the body and repeated infections were necessary to produce the disease.

(2) Dangerfield held views somewhat similar to those of Pekelharing and thought a coccus in the alimentary canal the cause.

(3) Isuzuki regarded a coccus isolated from the urine as the cause.

(4) Okata and Kokubo thought a coccus obtained from the blood to be the infecting agent.

Various bacilli, other than that incriminated by Wright, have been brought forward as pathogenic agents but it may be stated without further discussion that the claims of the advocates of bacterial causes have not been verified and are solely of historical interest. The same statement will hold for the plasmodium-like protozoon of Glogner which was found in the splenic blood.

_Of the chemical theories_ may be mentioned; (1) Arsenic poisoning. In an outbreak of arsenical neuritis in England, from arsenic contained in the glucose used in making beer, Ross diagnosed the illness as beriberi. Subsequently, arsenic was found in the hair of certain patients with beriberi, hence the theory which has never been substantiated. It may be stated that a careful study of this epidemic by Reynolds and Bury indicated that the alcoholic factor was also operative as persons taking an equal amount of arsenic but without alcohol, did not develop neuritis.

(2) Treutlein’s oxalate theory.—This was based on the fact that polyneuritis gallinarum could be produced in fowls by feeding them oxalic acid.

_Of the food deficiency theories_, the most prominent is (1) that of Takaki, generally designated the _nitrogen deficiency_ theory. As the result of increasing the proteid constituents of the ration of the Japanese Navy from 109 to 196 grams, the disease was largely eliminated (from about 32% incidence to less than 0.5%).

In the old ration the ratio of N to C was as 1 to 17—32, in the new ration, 1—16. In looking over the constituents of the new ration the addition of about 100 grams of beans is noted. These are rich in vitamines.

(2) According to Fales the hypothetical germ of beriberi can only live in body fluids deficient in potassium carbonate. The high content of potash in potatoes made him greatly increase the amount of this vegetable in the dietary he recommended. Fales noted scurvy as well as beriberi in the Bilibid prisoners on a diet deficient in potash.

(3) Deficient fat. (4) Deficient phosphorus.—It was Schaumann’s idea that the phosphorus contained in the outer layers of the rice grain was essential in the prevention of beriberi. While it is now known that the beriberi-preventing substance does not contain phosphorus, yet the idea has proven of practical value as giving an index of beriberi-producing power of rice.

_P_{2}O_{5} Index of Beriberi-producing Rice._—If a rice contain under 0.4% of phosphorus pentoxide it is liable to produce beriberi.

Schaumann now considers that the antineuritic substance in rice polishings acts as an activator in the metabolism of phosphorus.

_Vitamine Deficiency._—Grijns was the first to insist that beriberi was due to the absence in the diet of some substance essential to proper metabolism of the peripheral nerves. His views were along the line of our present _vitamine deficiency ones_. There are undoubtedly many different vitamines, varying as to nature of protective power, temperature at which destroyed, solubility, etc. McCollum emphasizes the importance of a fat soluble A and a water and alcohol soluble substance B for proper metabolism. This latter, usually designated “Water soluble B,” is generally considered the same as the anti-neuritis vitamine but there is recent evidence that this may not be the case. The antiscorbutic vitamine is water soluble C.

_Food Poisoning as Cause._—There are other theories as to intestinal parasites causing the disease and in particular views as to relation of fish eating to the disease, which are (1) that it is caused by the ingestion of raw fish, or again (2) from the eating of certain poisonous fish.

Miura, who is the great advocate of a fish intoxication, believes that this comes about from eating fish belonging to the Scomberidae family. As proving this, he cites the absence of beriberi in prisons in Japan, where no fish is allowed. He does not recognize that it is the diet of barley 6 to rice 4 parts which is the prophylactic factor. Barley is rich in vitamines.

RICE AND BERIBERI

There are a few points in connection with rice which should be understood. The larger part of the rice grain is starch and covering this central starch core we have the rather thin aleurone layer containing the proteid and fat constituents of the grain. Externally there is an adherent layer, the pericarp, which varies in color from red to white according to the kind of rice. The pericarp contains the salts. The grain is covered by the husk which is always removed to render the rice suitable for food. Unhusked rice is called _padi_ in India and _palay_ in the Philippines. In the process of removing the husk (milling) the pericarp and more or less of the aleurone layer may be rubbed off the grain. When the milling process is carried to the extent that but little remains except the starch the rice is termed _polished_, _highly milled_, or _white_ rice. A process of parboiling causes the husk to be more easily detached and the pericarp to adhere more firmly to the grain and when milled there is less loss of the anti-neuritis principle, which is contained in the outer layers. Such rice is called _cured_ rice. The embryo also contains the anti-neuritis vitamine as well as the fat soluble A one. It is also lost in milling. The scale-like dust is termed _rice polishings_ and has curative value for those who have developed beriberi under a diet of polished rice. When the milling process is less complete the rice so treated is called _undermilled_ rice or _red_ rice. Polished, highly milled or white rice contains as a rule less than 0.4% of phosphorus pentoxide while the beriberi-preventing rices contain more than 0.4% of this compound for which reason legislation has required rice to have more than 0.4% phosphorus pentoxide.

Siam rice is a polished white rice which contains about 0.25% phosphorus pentoxide and has more often been associated with severe outbreaks of beriberi than Rangoon rice, which has about 0.32%, this latter, however, being a well-recognized beriberi-producing rice. Unpolished rice contains about 0.55% of phosphorus pentoxide. Natives generally prefer the polished rice because it is clean and free from weevils, while the undermilled kind is dirty. Parboiled rice has a disagreeable odor.

Voegtlin has recommended a P_{2}O_{5} requirement of 0.5% for corn products and 1% for wheat ones. Thus whole wheat contained 1.12% while highly milled flour had only 0.114%. Fowls fed on this flour developed polyneuritis in twenty to thirty-two days.

Whole corn contains 0.76% P_{2}O_{5}, while highly milled corn grits has approximately 0.2%, and highly milled corn meal about 0.3%. These highly milled corn products produced polyneuritis within from thirty to thirty-five days.

With rock ground corn meal, containing 0.7% P_{2}O_{5} the fowls remained well.

_Experiment of Fraser and Stanton._—While there have been numerous instances reported to show the connection between polished rice and beriberi, when such rice was the predominating article of diet, it will suffice to refer to the experiments of Fraser and Stanton and of Strong.

In 1909, Fraser and Stanton experimented with 493 Javanese coolies who were employed in building a road far removed from any village which might introduce the factor of bacterial etiology into the problem. They noted that the Javanese prefer white rice, and reference is made to the fact that many cases of beriberi occurred among these laborers in 1906, which outbreak ceased upon requiring them to eat parboiled rice at the suggestion of Doctor Braddon. They state that they informed the coolies of the danger of white rice but, notwithstanding, they all expressed a preference for the white rice over parboiled rice. For the purpose of comparison, only one-half were allowed the white rice diet. The two parties were quartered in virgin jungle and were isolated from each other by an interval of 7 miles. Of 220 individuals on white rice there were 20 cases of beriberi recorded while among 273, who lived on parboiled rice, no cases occurred.

_Prolonged Continuation of Faulty Diet Necessary._—It appeared that a considerable period of continuance of white rice diet was necessary before the appearance of the disease (eighty-seven days). As against the infectious nature of the disease they note that contact of persons on a parboiled rice diet with the beriberi cases was without result. Substitution of parboiled rice for white rice brought about a cessation of the outbreak.

The Philippine scouts, numbering about 5000 natives, gave 618 cases of beriberi in 1908 and 550 cases in 1909. In 1910 undermilled rice was substituted for polished rice and they were required to eat 1-6 oz. beans daily. No other change in their mode of living was made. By 1913 beriberi had disappeared among them, although the disease still prevailed among the native population in contact with them.

_Experiment of Strong and Crowell._—Strong and Crowell stated that the object of their study was to determine whether beriberi, as it occurs in the Philippines, is an infectious disease or whether it is one which has its origin in disturbances of metabolism, due chiefly to the prolonged use of polished rice as a staple article of diet.

The experiments were carried out in Bilibid prison. Prisoners, who had been condemned to death, were informed of the nature of the experiment and were told of the diet on which it was proposed to place them. They were also told that they might contract beriberi. Twenty-nine volunteered and each signed a statement in his own dialect that he undertook the experiment voluntarily.

In general, the groups were fed for the greater part of the time occupied by the experiments as follows: Group (1) “White rice and extract of rice polishings and special diet.” Group (2) “White rice and special diet.” Group (3) “Red rice and special diet.” Group (4) “White rice and special diet.”

Of 6 men on the Group 1 diet, 2 developed beriberi. The symptoms however, were not marked, being chiefly loss of weight, tachycardia, slight oedema of legs and tenderness of muscles of calves. Four of the 6 men of Group 2 developed beriberi and 6 out of 11, in Group 4, showed symptoms of beriberi. In Group 3, only 2 in 6 developed symptoms and these consisted in case No. 13 only in tenderness of epigastrium, paraesthesia, cardiac disturbance and marked diminution of knee jerk. In case No. 18 there was noted only slight cardiac disturbance and epigastric pulsation. In none of the cases was the complete picture of beriberi obtained except in those in which the white polished rice formed the staple article of diet, but in one case, fed on red rice, the diagnosis of beriberi was almost definite.

The results of their experiments with the addition of rice polishings to the diet would indicate that whatever may be the results obtained with extracts from this material in preventing polyneuritis of fowls or in curing it after it has developed it is not as efficient in man as the cheaper and more readily obtainable mongo or katjangidjo bean or yeast.

Evidently symptoms of beriberi may also sometimes occur in individuals fed on red rice as a staple article of diet when the diet is very monotonous, comprising few articles and continued for long periods of time. From the experiments it is evident that beriberi may be produced by the prolonged consumption of white rice as a staple diet. Of 17 individuals fed on such diet 8 developed beriberi, all with distinct loss of knee jerk, as well as with other marked symptoms of the disease. Symptoms appeared within 61 to 75 days after the commencement of the diet.

Vedder thinks that the red rice used in these experiments may not have been sufficiently undermilled, as it was found most difficult to obtain such a beriberi-preventing rice for the Philippine scouts. As regards the lack of success with extract of rice polishings the same author considers that a sufficient amount of alcohol for the extraction of the vitamines was not used in the above experiments, as he found it necessary to use 30 litres of alcohol to 5 kilos of rice polishings. Strong and Crowell used only 14 litres of 95% alcohol to 5 kilos of polishings.

_Braddon’s views._—Prior to the investigations of Fraser and Stanton the importance of the rice factor in the etiology of beriberi was insisted upon by Braddon who thought that a poison was elaborated by some organism which poison was contained in the beriberi-producing rice. This development was thought to occur in rice stored in damp places, but Vedder has shown that storing undermilled rice in a damp place for a year does not cause it to lose its anti-beriberi-producing properties.

_Endocrine Gland Disturbances and Beriberi._—We owe in particular to the researches of McCarrison our appreciation of the important rôle of the endocrine glands in deficiency diseases. With dietaries deficient in vitamines he noted in birds and other animals hypertrophy of the adrenals, atrophy of the thyroid, thymus, testicles and ovary. The pituitary was unaffected. Vitamine deficiency seems to impair the activity of the thyroid and to thus favor the action of products of intestinal bacteria. It is now accepted as important this secondary factor of bacterial infection in all types of food deficiency pathology. Dietaries rich in fats and proteins with sufficiency of vitamines bring about thyroid hyperplasia. In a diet too rich in carbohydrates and deficient in vitamines marked endocrine disturbances are noted.

The adrenals show hypertrophy on a vitamine-deficient diet and this hypertrophy is associated with increase of the adrenalin content of the glands. Oedema seems to be associated with adrenal hypertrophy. McCarrison believes the oedema to be associated with increased intracapillary pressure from the effect of adrenalin but others dispute the explanation. The adrenalin content of the enlarged adrenals varies; it is in excess with a diet rich in carbohydrates and deficient in proteins and vitamines, but is below normal when the diet is scurvy-producing. Butter, probably from its fat soluble A content, seems to protect against oedema.

_Polyneuritis gallinarum._—The work of Eijkman in showing that polyneuritis could be produced in fowls by feeding them on polished rice and prevented when a diet of rice polishings was added to the neuritis-producing rice opened the way for a vast amount of experimental work. As regards the nature of the neuritis-preventing substance in the rice polishings it was soon found that it had no relation to the phosphorus content. Funk has isolated a substance he calls _vitamine_, a pyramidine base precipitated by phosphotungstic acid, which is present in rice polishings and seems to possess extraordinary curative properties in polyneuritis gallinarum. Heart muscle, egg yolk and yeast are rich in this anti-neuritis substance, which is also present in lentils and barley.

_Various Vitamines._—The anti-neuritis vitamine is soluble in water and alcohol and is comparatively thermostable (destroyed by a temperature of 120°C. in two hours). It is affected by alkaline reaction but is stable in acid solution. The water soluble B vitamine does not seem to be destroyed by a temperature of 120°C. for two hours, hence it may be different from the anti-neuritis one. The antiscorbutic vitamines differ in being thermolabile, these factors in certain foods being destroyed by a temperature of 60°C. Another vitamine, fat soluble A, found particularly in butter, seed embryos and leaves of plants, is a food essential. Its absence from a diet causes xerophthalmia. Cod-liver oil and glandular organs of animals contain it.

Schaumann considers malt as richer in the anti-neuritis vitamine than any other article of diet, rice bran coming next. Many think that vitamines have not as yet been separated but that they are intimately combined with some mother substance in the food.

There is, in all probability, a large number of vitamines present in various animal and vegetable foods, the deficiency of which in a diet may lead to vague disorders or to well-recognized diseases, such as scurvy, ship beriberi, beriberi or pellagra.

Schaumann considers the curative principle to be of the nature of an activator. An increase in the ingestion of carbohydrates and necessarily in the vitamine as well seems to produce neuritis more rapidly than where a smaller amount is given, this indicating the importance of these vitamines in carbohydrate metabolism.

There are those who deny this carbohydrate metabolism function of vitamines and it is a fact that polyneuritis of fowls will develop on a diet from which carbohydrates are excluded.

In epidemics of beriberi it has been observed that those who eat most rice are more often attacked, thus men more frequently than women. A temperature of 120°C. destroys the vitamine. Owing to the absence of rice as a constituent of other than slightest importance in the dietary of Brazilian cases of beriberi, as well as from numerous reports of the occurrence of the disease in nonrice-eating persons, the view that is now entertained is that not only polished rice, but any predominating carbohydrate article of diet, which is deficient in the neuritis-preventing substance, can produce beriberi. Wellman and Bass have shown that such articles of diet as sago, boiled white potatoes, corn grits and macaroni practically parallel polished rice in the production of polyneuritis in fowls.

=Predisposing Causes.=—There does not seem to be any racial predisposition other than that associated with the more varied and the more neuritis-preventing diet of the white race. For the same reason beriberi is more prevalent among the poor than among the prosperous classes of countries where the disease exists extensively.

It is customary to consider as predisposing causes bad hygienic surroundings, such as occur in jails, camps, etc., as well as the influence of warmth and dampness of the atmosphere. Beriberi is more common among men than women and affects most commonly individuals between 15 and 30 years of age. Physical exhaustion, excessive grief, digestive derangements, abuse of alcohol and tobacco are considered to have a bearing in the production of the beriberi symptoms. Surgical operations may be followed by manifestations of the disease.

=Epidemiology.=—Inasmuch as the experiments of Strong force us to the conclusion that the disease is not infectious, the study of the prevention of the disease would appear to rest almost exclusively in the question of a neuritis-preventing dietary.

In this connection Heiser, in the Philippines, has reported that with a diet in which polished rice was contained the monthly death rate at the leper colony at Culion was approximately 100, the majority of these deaths being from beriberi. As a result of the substitution of unpolished rice, about 1909, the monthly death rate fell to less than 20 and of these none were from beriberi.

Toward the close of 1911 there was a great shortage of the rice crop and the Philippine government bought quantities of rice in order to protect the people from extortionate dealers. Much of this rice was polished rice. The use of this polished rice was commenced at Culion in November, 1911. In January, 1912, there were 35 deaths, of which 2 were from beriberi. In February 86 deaths with 36 from beriberi and in March 82 deaths with 60 from beriberi. In February the use of polished rice was discontinued and unpolished rice substituted. In April the deaths had fallen to 25 with 3 from beriberi and, subsequent to that month, deaths from beriberi cases developing at Culion ceased to be reported.

As regards the length of time necessary for the production of the symptom-complex, Strong’s experiments show that beriberi was produced in from sixty-one to seventy-five days. In Fraser and Stanton’s work no case developed under eighty-seven days and many of the cases did not develop for 120 to 160 days. Hamilton Wright considered that the incubation period for his toxin-producing bacillus was ten to thirty days.

PATHOLOGY AND MORBID ANATOMY

In polyneuritis gallinarum, Vedder and Clark are of the opinion that there may be two vitamines involved, the absence of one from the dietary causing the neuritis, while that of the other leads to general prostration and cardiac degeneration, so that there may be other factors in the production of beriberi than the degeneration of the peripheral nerves and involvement of the vasomotors.

Furthermore, extract of rice polishings rapidly cures the cardiac condition as well as the dropsy, but not the paresis; while Funk’s vitamine base, which will cure the paralysis, will not affect the cardiac disorder.

The blood of beriberics in the acute stage, has been shown to contain a substance capable of profoundly influencing the vasomotor functions, causing venous engorgement and a fall of blood pressure.

In deaths from wet beriberi the tissues are very moist so that incisions tend to fill with fluid. There are generally present pleural and in particular pericardial effusions. Serous fluid in the abdominal cavity may also be present. The lower end of the stomach and the upper portion of the small intestines, in

## particular the duodenum, show marked congestion with more or less

abundant haemorrhagic extravasations. Some authorities do not admit the existence of this duodenal congestion so insisted upon by Wright.

The oesophagus is usually congested as may be also the pharynx and the larynx.

Next to the peripheral nerve degenerations, to be later considered, the most important lesions are found in connection with the heart. All chambers of the heart show a dilatation with hypertrophy as well as dilatation of the right ventricle in cases that have lasted for some time. The heart muscle has the faded-leaf appearance indicative of fatty degeneration. Microscopically there are segmentation and vacuolation of the fibres. The lungs show congestion and at times present the characteristics of pulmonary oedema. The kidneys are congested but show only exceptionally parenchymatous or interstitial changes. As would be expected, the back pressure in the right heart gives a dilatation of the central vein of the liver lobules which at times is productive of atrophy of the adjacent liver cells. The muscles supplied by the affected peripheral nerves show more or less atrophy according to the duration of the disease.

Microscopically, the affected fibres show a loss of striation with a colloid degeneration. These changes are more marked in beriberic residual paralysis. The key to the disease is in the changes present in the peripheral nerves. While these may appear normal yet histological examination shows varying nerve degenerations from slight medullary degeneration in a few fibres to complete destruction of the nerve, giving a Wallerian degeneration (vacuolation and formation of myelin droplets in the medullary sheath with fragmentation of the axis-cylinder).

While it is usually stated that the central nervous system (brain and cord), remains uninvolved yet we note axonal degeneration in the cells of the nuclear centres of the affected peripheral nerves as shown by convexity of the cell sides, dislocation of the nucleus and disappearance of the tigroid substance. The striking feature of the pathology of beriberi is the involvement of the vagus nerve and there is evidence of degenerative changes in the cells of the vagal origin in the floor of the fourth ventricle.

Various investigators have shown that in fowls marked peripheral neuritis can exist long before clinical manifestations appear and that typical cases of beriberi may show striking improvement following vitamine administration, notwithstanding the continued existence of peripheral nerve degeneration. For such reasons Vedder thinks the more important changes to probably belong to cells of cord and brain.

McCarrison has noted striking changes in the endocrine glands in avian polyneuritis, particularly hypertrophy of the adrenals and atrophy of the other glands of internal secretion. He attributes the oedema to increase in adrenalin content. Shimbo has reported adrenal hypertrophy in 14 human cases of beriberi.

SYMPTOMATOLOGY

It is well to remember that beriberi is but a form of multiple neuritis which in many cases shows only motor and sensory disturbances of the lower portions of the upper and lower extremities.

In fact an extensive epidemic of arsenical neuritis, or, to be more exact, a neuritis in which both alcoholic and arsenical factors were operative, was regarded by eminent authorities as beriberi.

The key to beriberi, however, is the peculiar and striking selection of the vagus nerve in the degenerative processes as well as those of the peripheral nerves of the extremities. It is vagal involvement, giving disturbances of heart particularly and lungs in less degree, which chiefly differentiates beriberi from other forms of multiple neuritis.

Another peculiarity of beriberi is the tendency to vasomotor involvement as shown in the patchy areas of oedema.

_Epidemic Dropsy._—Beriberi is typically a nonfebrile disease. There is, however, a disease with fever, called epidemic dropsy, which seems to have a similar etiology to beriberi. It also shows the symptoms of a peripheral neuritis plus cardiac disturbances. In fact Pearse has maintained the identity of the two diseases. Greig considers epidemic dropsy as resembling ship beriberi.

The first record of epidemic dropsy was during a famine in Southern India in 1877. Outbreaks again occurred in 1902 and 1907. The fact that it is a disease which often shows a house infection has caused the advancing of a theory that the bedbug transmits the disease.

While greatly resembling beriberi clinically the following points of difference are usually noted by those who hold that it is a distinct disease entity.

1. The presence of fever, which rarely exceeds 102°F. and is usually only about 99° to 100°F.

2. An erythematous rash upon the oedematous portions of the extremities.

3. The frequent generalized oedema, which suggested the designation dropsy for the disease, cannot be differentiated from wet beriberi.

4. The neuritis manifestations are slight or absent. There may be formication of the feet but anaesthesia is wanting. The vagal involvement gives cardiac disturbances. There is anaemia.

_Infantile Beriberi._—There is also a condition in nursing infants which would be difficult to recognize if unaware of the existence of this type of beriberi. It is called _infantile beriberi_.

In 1898 Hirota first noted the existence of a condition in infants nourished by beriberi mothers which has more recently been carefully studied by McLaughlin and Andrews and to which the name infantile beriberi is now generally given. In the Philippines it is called “taon.” Clinically there is restlessness, vomiting, altered voice, increased heart action, oedema and cyanosis. After death there is found a marked hypertrophy and dilatation of the right side of the heart with no change of the left side. The peripheral nerves also show the lesions of beriberi of adults but of less intensity.

The disease most often shows itself in an acute form, the child rather suddenly being seized with great pain, crying constantly and soon becoming cyanosed. Death, which may occur in a few minutes or hours, is often thought to be due to meningitis, although there is no fever or true convulsions. There is only rigidity of the body. Less frequently the disease appears in a chronic form in which vomiting and constipation are most marked. There is often a history of the loss by the mother, who herself may have only a rudimentary beriberi, of several children from this disease.

The infants improve rapidly when other infant feeding is substituted for the mother’s milk. An extract of rice polishings gives striking results in these cases.

_Asylum Beriberi._—The beriberi outbreaks which have frequently been reported from European and American camps, prisons and asylums do not differ from the cases one may see in the classical distribution of the disease among the rice-eating populations of the Orient. The cause is the same, a deficiency in beriberi-preventing vitamines, and the symptoms are similar. These vitamines may be deficient in the rice or other cereal or proteid food supplied. Again they may have originally been present in sufficient quantity but later destroyed by too great heat or otherwise.

=Types of Beriberi.=—The ordinary clinical division of beriberi is into (1) _wet or dropsical beriberi_ and (2) _dry or atrophic beriberi_. At the same time, in a typical case, we find such a combination of the vasomotor disturbances which lead to the oedematous or dropsical manifestations of wet beriberi, and likewise of those of peripheral nerve involvement causing more or less development of muscular palsies or atrophies, as seen more strikingly in dry or atrophic beriberi, that it does not seem advisable to employ such a division.

In fact typical cases of wet or dropsical beriberi after a profuse diuresis may change in a short time, as Manson has so aptly stated, from a bloated carcass to little more than skin and bones and assume all the appearance of a case of dry or atrophic beriberi.

Even Vedder, who states that from a theoretical standpoint wet and dry beriberi may be considered separate pathological processes (deficiency in the anti-cardiac degeneration vitamine rather than the anti-neuritis one), is inclined to believe it inadvisable, from a clinical standpoint, to consider the one type apart from the other.

One sees cases which combine the features of dry and wet beriberi which can best be designated _typical beriberi_. Again we see cases where the vagal and vasomotor involvement is so marked that the patient resembles a man with acute nephritis plus all the evidence of extreme cardiac decompensation. Such cases may be designated _fulminating_, _pernicious_ or better _cardiac_.

Again we observe cases which from the start show little if any oedema and very slight cardiac involvement, but with marked motor disturbances as shown by muscular atrophies and palsies. The sensory changes are not so marked as the motor ones. Complete anaesthesia is rarely present, it is rather paraesthesia and blunting of sensation which characterize the sensory phenomena. This is usually designated the _atrophic_ or _paraplegic_ type.

_Rudimentary or Larval Beriberi._—Scheube recognizes a rudimentary type and it must have been the experience of every one in the tropics that these indefinite types of beriberi are quite common.

In such cases there may be nothing more than some weakness of the legs with vague manifestations of blunting of the sensation or variation of the reflexes. At times there may be marked anaesthesia in the region over the shin bones.

Many of these cases show cardiac palpitation on exertion and at times we may note slight evidences of oedema about the lower part of shin bone or dorsum of the foot. It is the frequency of such cases that causes physicians in the tropics to consider almost any affection showing neurological manifestations as of beriberi nature. A careful study of the neurological features of cases in the tropics will show that many of these cases are not beriberi but rather the common cosmopolitan diseases of the nervous system.

=A Typical Case of Beriberi.=—The patient first complains of weakness and heaviness of the legs, particularly after fatiguing work. There is also noted a sense of fullness and tenderness in the epigastric region. The slightest exercise brings about cardiac palpitation and more or less dyspnoea.

As the symptoms of peripheral neuritis become more prominent we have hyperaesthesia of the calf muscles so that squeezing these muscles gives rise to rather marked pain. The thenar muscles or those of the forearm may also be more or less hyperaesthetic. Attention has been called to a circumoral anaesthesia.

An examination at this time will probably show an active patellar reflex, some oedema over the shin and malleoli, possibly extending to the dorsum of the foot, with partial anaesthesia in the oedematous areas. It is a blunting of sensation as though a layer of cotton were interposed between the skin and the examining instrument. Other favorite sites for the oedema are the sacral and sternal regions. Occasionally sharply defined oedematous patches may be observed,

## particularly on the arms.

The exercise attendant upon the physical examination will probably cause a rather marked cardiac palpitation. The pulse is usually rapid and its rate is markedly affected by the slightest exertion. The systolic pressure is low.

The anaesthesia noted in the lower extremities soon tends to show itself about the back of the hands and the finger tips, so that it may be difficult for the patient to button his coat. There is also weakness of the grip. The temperature is normal and the mind is entirely clear. The results from a blood examination are practically negative, although later on there is the blood picture of a secondary anaemia.

In cases where the oedema is more marked and generalized and when pericardial or other effusions are developing we find a diminution in the amount of urine, but with an absence of albuminuria.

Later the case may show a dropsical condition more or less resembling nephritis, but with only slight scrotal oedema. At the same time there will be found a dilatation of the right heart with blowing systolic murmurs and equal spacing of the heart sounds. There may be marked pulsation of the veins of the neck. At this time the patellar reflex may be diminished and the anaesthetic areas more extensive.

This condition of wet, dropsical or oedematous beriberi may be fairly rapidly succeeded by a disappearance of the oedema with, as a result, the making more striking of the muscular atrophy incident to the neuritis of the peripheral nerves. In this, the atrophic, dry or paralytic beriberi, the _jongkok test_ is of value. With the hands over the head the patient squats down on the calves of his legs and attempts to rise—something impossible for the beriberic. At this time the patellar reflex probably cannot be elicited and later on there will be found foot and wrist-drop with atrophy of muscles. With complete foot-drop, the reactions of degeneration will be found.

A combination of the dry and wet types of beriberi is often described as the mixed type.

It must always be remembered that the course of the ordinary case of beriberi is essentially chronic, running over months or years.

=Acute Pernicious Beriberi.=—This is the fulminating type of beriberi in which the marked involvement of the vagus overshadows the other but less manifest phenomena of the disease. In some cases the signs of peripheral neuritis may be quite prominent before the fulminating onset of the cardiac manifestations, there being almost a total lack of disturbance of the vasomotor system. Again we may have slight if at all demonstrable motor or sensory disturbances but with marked oedema. It should be borne in mind that this development of cardiac disturbance with its fatal tendency may develop even in a case of rudimentary beriberi. It is a common experience that cases considered as mild types may, in a few hours, show cardiac involvement and terminate fatally with striking suddenness.

There is apt to be marked epigastric tenderness or even distress coming on with the onset of the acute cardiac involvement. It may be so extreme that the patient dreads the slightest palpation of his epigastrium. From a marked palpitation and praecordial distress evidences of the dilatation of the right heart become prominent. Indications of tricuspid insufficiency are seen in the pulsating jugulars and cyanosis. The cardiac dullness is greatly increased to the right and various abnormalities of sounds and rhythm may be observed. There is also dyspnoea and a sensation of constriction of the chest (beriberic corset). These are the cases which give as horrible a picture of death as one ever sees. In the final struggle for breath and praecordial agony of the last stages of decompensation in old heart lesions we have a more gradual course in a more asthenic patient. Acute pernicious beriberi may run its course in a strong, vigorous patient in a few hours. In some cases we have paralysis of the diaphragm.

=Paraplegic and Rudimentary Types.=—The rudimentary type has already been considered and it would be impossible to draw a line between slightly developed paraplegic cases and rudimentary ones. The paraplegic cases show the weakness of feet and hands going on to wrist and foot-drop. There is also marked blunting of sensation of feet and hands which gives one the impression of ataxia when the patient tries to button his coat.

[Illustration: FIG. 83.—_A_, Mixed Beriberi. _B_, Wet Beriberi. _C_, Dry Beriberi. (From Jackson’s Tropical Medicine.)]

There is atrophy of muscles so that the grip of the patient is enfeebled. This partial anaesthesia also accounts for the pseudoataxic gait in which the element of muscular weakness is prominent as opposed to the vigorous heel stamping gait of the ataxic tabetic. The patient drags the toes and leans forward on a cane when walking, thus suggesting the tripod.

It is the typical steppage gait of degeneration of the lower motor neurones. It is a flaccid, atrophic paralysis of the muscles.

There is no involvement of the sphincter.

_Beriberic Residual Paralysis._—Hamilton Wright has used the term beriberic residual paralysis to indicate cases which, in the course of convalescence and favorable regeneration of axis-cylinders and more or less return to a normal condition, become subject to some factor lowering the vital forces and body resistance and experience a return of the beriberi manifestations. To use a common expression the patient has a set-back and the favorable progress to complete recovery is temporarily in abeyance.

Symptoms in Detail

_Nervous Symptoms._—The most common symptoms are those connected with degenerations involving the peripheral nerves of the extremities. The motor nerves are more involved than the sensory ones, there being rarely complete anaesthesia, but rather a blunting of sensation as though a piece of cloth were interposed between the examining instrument and the skin. At first there is weakening of the muscle power as shown by the grip of the hand or weakness of foot muscles. In more advanced cases we may have foot and wrist-drop. Hyperaesthesia of the muscles is prominent, especially that of the calf muscles. The unsteadiness of gait is not true ataxia as the patient does not clearly show the Romberg sign. It is muscular weakness rather than incoördination.

The Argyll-Robertson pupil is absent. The gait is the steppage one of peripheral neuritis, the patient walking as if extracting one foot after the other from clinging mud. Later on, when other muscles than the foot extensors are involved, the gait becomes a shuffling one. The mind is entirely clear. The vasomotor phenomena are often marked as shown by patchy or most extensive development of oedema and serous exudates. The knee-jerk is usually absent. Fibrillary twitchings may be observed in beriberi as well as in progressive muscular atrophy. The extensors of arms and legs are more markedly affected than the flexors. The cardiac symptoms are really connected with vagal involvement.

_The Cardio-respiratory Symptoms._—Owing to involvement of the vagus the inhibitory apparatus is deranged so that we have palpitation and rapid pulse rate both of which are markedly increased by the slightest exertion.

The blood pressure is below normal. Shortness of breath is the earliest feature of respiratory trouble. This may go on to marked thoracic oppression and dyspnoea.

Aphonia may be present in acute pernicious beriberi and probably indicates laryngeal palsies. Such cases are usually fatal.

Pulmonary congestion and oedema always accompany the terminal right side dilatation of the heart which is responsible for the cyanosis, pulsating jugulars and various murmurs. The pulmonic second sound is accentuated and may be reduplicated. The rhythm of the heart sounds is replaced by the equal spacing of embryo-cardia. The diaphragm may be paralyzed as may also happen to the intercostal muscles.

_Digestive and Urinary Symptoms._—Those who considered beriberi as an acute infectious disease were disposed to note frequently evidences of toxaemia as manifested by nausea, vomiting and epigastric distress. As a matter of fact these symptoms only become very prominent in pernicious beriberi and may well be connected with the cardiac decompensation. However caused vomiting is of unfavorable prognostic import.

The amount of urine is markedly decreased when oedema is advancing but is succeeded by a polyuria when this diminishes. If albumin should be present it is not connected with beriberi but some other condition.

_Other Features._—There is nothing characteristic about the blood other than a slowly developing anaemia.

Oedema is the most striking feature of wet beriberi. When slight this oedema may only involve the pretibial-region or sternum. Circumscribed areas of oedema may be present on the upper parts of the body as neck and trunk.

Hydropericardium is the most frequent of the exudates into serous cavities. Fever is almost always absent except in epidemic dropsy.

DIAGNOSIS

When the case is one of mixed type with the oedema, cardiac involvement and signs of peripheral neuritis the diagnosis is readily made. A diagnosis of nephritis is often given the wet type of beriberi and locomotor ataxia the dry form, by those who have not in mind the possibility of the disease existing in an oriental crew after a long voyage.

The urine in beriberi is as a rule normal and there are no peripheral nerve disorders in nephritis. Chagas has noted that a quartan form of malaria gives rise to oedema about the ankles and is often mistaken for beriberi by the physicians of the Amazon region.

The cardiac manifestations of beriberi differ from those of valvular disease in that the murmurs are muffled and there does not exist the definite areas for the location of the murmurs of the various valvular lesions. The rapid development of a pericardial effusion is also against valvular heart disease.

The absence of lancinating pains, typical Romberg sign and Argyll-Robertson pupil should differentiate from tabes.

The tripod gait of beriberi takes its name from the wide separation of feet and use, with the hands, of a cane in front. It is a steppage gait instead of the ataxic one of tabes. On account of the lack of power to raise the toes in walking, the beriberic lifts the hip and swings to one side in order to avoid scraping his toes.

In progressive muscular atrophy the palsy attacks the hand first and in a more advanced case showing the main-en-griffe there would also be deltoid involvement. Of course beriberi may show the main-en-griffe characteristic but the greater involvement of the feet with vagal phenomena differentiates.

_Ship Beriberi._—A disease of importance on Scandinavian sailing ships to which the designation “ship beriberi” has been given resembles beriberi in that we have oedema particularly of the lower extremities and at times generalized so that a case would appear to be one of wet beriberi.

More or less dyspnoea and cardiac palpitation are features of the disease as of beriberi. In fact death often is the result of acute cardiac paralysis. The striking point of difference is the generally reported absence of manifestations of neuritis and Nocht in an autopsy of a case failed to find evidence of degeneration of the peripheral nerves.

Another point of distinction is that once the ship arrives in port and a diet of fresh meat and vegetables is substituted for the one of sterilized canned meats and desiccated and preserved vegetables, the patient recovers rapidly so that in one or two weeks there is no sign of the disease remaining. Beriberics improve at once when put on a curative diet but the damage done the peripheral nerves makes complete recovery a matter of weeks or months. Nocht is of the opinion that ship beriberi is closely related to scurvy as he found sore gums and haemorrhages into muscles in some of his cases. He also notes that even in true scurvy there may be cases of dropsy without the spongy gums and haemorrhages. Dropsy plus sore gums is not infrequently noted in the beriberi-like affection of the men of the French fishing fleet off the Newfoundland banks.

Schaumann believes that ship beriberi is due to an acute deficiency in phosphorus, a chronic deficiency causing beriberi. It is probable that this disease is caused by a deficiency in certain vitamines, these being destroyed in the sterilization of canned meats or by drying vegetables.

_Scurvy._—It will be remembered that in scurvy, which is the classic food deficiency disease, we have spongy, swollen gums, loose teeth, oedema about ankles and, in particular, haemorrhages into skin at site of hair follicles and tumor-like haemorrhages into subcutaneous and muscular tissues. Haemorrhages into the mucous membranes are not uncommon. The heart shows marked palpitation and weakness.

The scurvy vitamine is much less stable than the beriberi one. It is contained in fresh foods only, drying destroying it.

In connection with the question of multiplicity of vitamines monkeys fed on rice will develop beriberi while if fed on a bread deficiency diet they develop scurvy.

In Mesopotamia the Indian troops suffered greatly from scurvy but not from beriberi while the British troops had many cases of beriberi. From July to December there were 11,445 cases of scurvy among the Indian forces and 104 cases of beriberi among the British. During this period the British ate white biscuits, tinned meats and horse flesh. This latter protected them from scurvy but the Indian troops would not eat the fresh meat but ate barley flour instead. The antiscorbutic vitamines are sometimes designated as water soluble C vitamines.

_Rand Scurvy._—In investigating the endemic scurvy on the Rand, in South Africa, Darling noted hypertrophy and dilatation of right heart. Such cases often showed vagal degeneration. Pathologically, these cases were closely related to beriberi, but clinically, they showed spongy gums, and haemorrhages elsewhere. The knee-jerks were always exaggerated.

_Infantile Scurvy._—As differing from infantile beriberi, we have in infantile scurvy, which is attributed to the use of sterilized milk instead of fresh milk, a tendency to separation of the epiphyses from the shafts of the bones and extreme sensitiveness to any movement particularly of the legs. A markedly anaemic and asthenic condition is also characteristic. The chief lesion is a subperiosteal blood extravasation.

Milk contains several vitamines some of which, as the growth vitamine, are, destroyed in boiling; others, however, are not destroyed until subjected to a temperature of about 120°C.

_War Oedema._—In those areas of Europe where famine conditions were approached during the great war a condition of weakness and oedema was noted by many observers and to this symptom-complex various designations were applied such as war dropsy, war oedema, etc. The oedema was more marked than would be true in ordinary cases of starvation so that such factors as consumption of large amounts of water and salt in the thin soups so prominent in the dietary, plus hard work, must have been additional causes.

The oedema was most common in the feet and legs, at times extending to the thighs and trunk, and in about one-half the cases involving the face. Marked muscular weakness and alimentary disturbances were common. There was dyspnoea on slight exertion with a slow pulse, but cardiac disturbances were not features of the disease. The urine was pale, of low specific gravity and free of albumin. There was reduction of red cells and a tendency to leukopenia. These cases showed marked emaciation upon the disappearance of the dropsy. As is well known the deficiency in fats was marked in Central Europe so that it was to be expected that ocular manifestations should be frequently noted, deficiency of fat soluble A being the exciting cause of xerophthalmia. The cases tended to recovery under proper diet and hospital care.

Probably the most important conditions to consider in differentiation of beriberi are the peripheral nerve involvements caused by alcohol and arsenic.

In alcoholic neuritis there is the history of alcoholic excesses, long-standing digestive disorders and tremors of hands, lips and tongue. Chiefly characteristic, however, is the mental involvement, such cases almost always showing loss of memory and defective mental concentration.

Mental symptoms and tremors are practically absent in beriberi and we have here the marked feature of vagal involvement plus vasomotor phenomena.

In arsenical neuritis we have an early puffiness under the eyelids and pigmentation of the skin which first shows itself in areas normally pigmented. A dysenteric syndrome may also be present.

There would be less chance of confusing lead palsy as this chiefly involves the upper extremity. Punctate basophilia, lead colic and the blue line on the gums should differentiate.

In diphtheritic palsies the muscles of the soft palate are involved in more than 75% of cases. Ocular palsies are also not infrequent.

In lathyrism we have a history of the eating of the chick-pea (Lathyrus sativus) or other vetches, as may occur in times of famine. Pain in the back, weakness of the legs and symptoms of spastic paraplegia appear. The spasticity differentiates. The heart is not affected.

It may be stated that there is no laboratory diagnosis for beriberi.

PROGNOSIS

There is no disease in which one should be more conservative in making a favorable prognosis than in beriberi. A case which seems to be progressing toward recovery may suddenly develop cardiac disturbances and die in a very short time.

We now know that a change to a beriberi-preventing diet is practically curative.

The mortality rate varies in different countries and in different epidemics, so that we have death rates varying from less than 2 per cent. to those exceeding 50 per cent. In acute pernicious beriberi the prognosis is almost surely fatal.

The epidemic of beriberi which prevailed at Manila in 1882 seems to have been attended by a great mortality, this having been as high as 60% during the early part of the outbreak.

PROPHYLAXIS AND TREATMENT

=Prophylaxis.=—It must be remembered that not only is rice, from which the neuritis-preventing vitamine has been removed by excessive milling, productive of beriberi but that the same applies to other cereals which have been similarly deprived of their vitamines.

The same result may be obtained by the employment of excessive sterilization for canning.

Fresh meat is as valuable as fresh vegetables in prophylaxis but if either kind of food be subjected to excessive heat, as is the case with tinned meats, etc., they not only do not prevent beriberi but in a negative way are beriberi-producing.

While boiled beef is heated throughout, with more or less complete destruction of vitamines, roast beef does not sustain a temperature above 70°C. in its interior, hence the greater portion of the vitamine content is present in such meat.

It is possible that moulds may deprive cereals of their vitamines so that spoiled cereals may be beriberi-producing. There have been many reports both from asylums and prisons which would indicate that the employed and the patients or prisoners lived on the same ration yet the guards or nurses failed to develop beriberi, which disease was prevalent among the inmates. Such statements rarely stand the test of investigation. The same is true of pellagra.

Many of the reported outbreaks of beriberi among those who were enjoying an abundant ration have been found to be connected with the almost exclusive consumption of expensive canned meats and vegetables.

As the beriberi vitamine is apparently important in carbohydrate metabolism, a greater ingestion of carbohydrates demands more vitamine, hence an increase in carbohydrates, without corresponding increase in vitamine-containing foods, may bring on beriberi where, before the increase in carbohydrates, there was an absence of beriberi.

In connection with the development of beriberi it must always be kept in mind that debilitating conditions such as unhygienic quarters and overexertion, as well as disease conditions (malaria, ancylostomiasis, etc.) are factors of importance. In military forces excessive drills should be stopped. The fatigue factor is to be kept in mind in this as in other food deficiency diseases.

A combination of barley, which is rich in vitamines, with the rice is important in oriental countries, thus a diet containing 6 parts barley to 4 parts rice and used in Japanese prisons, on account of its cheapness, not only prevented beriberi but cured the disease in beriberics entering prison.

There is no doubt but that legislation against rice which contains less than 0.4% of P_{2}O_{5} is a valuable measure of prophylaxis. Polished rice has lost in P_{2}O_{5} as well as in vitamines.

Heiser has proposed that an excessive tax be placed on polished rice with free entry for the unpolished article. The following suggestions of Vedder in connection with prophylaxis would seem to be worthy of consideration in pellagra as well as in beriberi.

1. In any institution where bread is the staple article of diet, it should be made from whole wheat flour.

2. When rice is used in any quantity, the brown, undermilled, or so-called _hygienic rice_ should be furnished.

3. Beans, peas, or other legume, known to prevent beriberi, should be served at least once a week. Canned beans or peas should not be used.

4. Some fresh vegetable or fruit should be issued at least once a week and preferably at least twice a week.

5. Barley, a known preventive of beriberi, should be used in all soups.

6. If corn meal is the staple of diet it should be yellow meal or water-ground meal, i.e., made from the whole grain.

7. White potatoes and fresh meat, known preventives of beriberi, should be served at least once a week, and preferably once daily.

8. The too exclusive use of canned food must be carefully avoided.

McCarrison has noted the value of onions even in a diet in which protein and vitamine constituents are sufficient. The onions seem to inhibit the growth of putrefactive bacteria.

=Treatment.=—The most important treatment is that of the substitution of a diet containing the essential vitamines for the beriberi-producing one. In carrying this out regard must be had for the customs and tastes of the race concerned. Thus fresh beef may be excellent for some people but objectionable to others. Eggs, particularly the yolk, are very valuable as is also true of unsterilized milk. Extract of rice polishings has given splendid results in infantile beriberi but does not seem to have been as efficacious in the disease in adults. Yeast has great curative value. An extract of yeast known as _marmite_ has achieved reputation when given in doses of 20 grains daily. Seidell has recently used an autolyzed brewers’ bottom yeast. By treating this material with Lloyds’ reagent he has extracted the vitamines so that instead of having to give 200 cc., a dose of 10 grams of the concentrated product suffices.

Malt extract is very rich in vitamines and liver seems to have a higher content than beef muscle. Fat soluble A vitamine is abundant in glandular organs but scarcely present in the beef of our markets—this is probably true of water soluble B. Heart muscle is about on a par with liver. Germinating wheat and beans seem to have special value in treatment as well as prophylaxis.

In the treatment of a case care must be had not to allow a patient with any cardiac involvement to sit up in bed as this may cause sudden death. Braddon considers atropine hypodermically as of value in cardiac types of cases.

Amyl nitrite inhalations or injections of 1% solution of nitroglycerine are indicated when there is evidence of extreme cardiac dilatation. Venesection is also to be kept in mind. Cardiac tonics are of less value than rest, diet and venesection.

In the feeding of such patients only small amounts should be given at a time to avoid epigastric distress. Again carbohydrates should be restricted as there is evidence that excess of carbohydrates as well as vitamine deficiency may be concerned in the disease. The bowels should be kept open with salines. Mineral oil tends to keep down intestinal putrefaction which is a factor of importance.

Strychnine is usually given as a routine treatment in the less acute cases. With muscular atrophy massage is of prime importance. Electrical stimulation is also usually employed. With the palsies there is great danger of contractures so that even the bed clothing should not rest upon the paralyzed feet. Even splints may be necessitated.

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