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Diagnosis and Treatment of Polyneuritis
Medical Clinics of North America May, 1938. Boston Number
CLINIC OF DR. MADELAINE R. BROWN FROM THE NEUROLOGICAL UNIT, BOSTON CITY HOSPITAL DIAGNOSIS AND TREATMENT OF POLYNEURITIS* TODAY there are only 2 types of polyneuritis which the physicians of North America need seriously consider. Endemic beriberi has practically disappeared from this continent and the majority of physicians may practice a lifetime without being called on to treat those forms due to chemical agents, pregnancy, diabetes, and conditioned deficiency states. Therefore, the greater portion of this discussion will be devoted to the diagnosis and treatment of 2 types of polyneuritis only. These 2 are alcoholic and acute infectious polyneuritis, and the more common of these is alcoholic polyneuritis. Perhaps it is not coincidence that paralysis among alcoholics was well described by John Lettsom 1 and James Jackson2 as early as 1787 and 1822 respectively, and that ChomeP by 1828 had given a vivid picture of an epidemic of polyneuritis in Paris. These 3 observers had no conception with what they were dealing. Graves/ who had been in Paris at the time of the epidemic and knowing that the pathologists had found no changes in the central nervous system, fifteen years later suggested disease of the peripheral nerves. ALCOHOLIC POLYNEURITIS
The diagnosis of alcoholic polyneuritis is not usually difficult for the cause of the patient's indisposition is all too evident. Out of the past of one hundred and fifty years ago comes a description on which it would be difficult to improve: "The first appearance of indisposition very much resembles the gout; and the fuel is heaped upon the fire until the at-
* No contraindication for the use of the word "neuritis" has been found since "itis" is merely the Greek feminine adjectival termination and the word disease is understood. Neuritis therefore means disease of the nerve and not necessarily inflammation.
MADELAlNE R. BROWN
tachment to the use of spiritous drinks becomes so predominant that neither threats nor persuasions are powerful enough to overcome it. Frequently the appetite for food vanishes but sometimes continues voracious; and at the same time, whilst the body is costive, and no vomiting ensues, the lower extremities grow more and more emaciated; the legs become smooth as polished ivory and the soles of the feet even glassy and shining and at the same time so tender that the weight of the finger excites shrieks and moaning. The legs and the whole lower extremities lose all power of action. The arms and hands acquire the same paralysis and render the patients incapable of feeding themselves. "Mostly before they die they take less food; sometimes a diarrhea succeeds, sometimes a vomiting of black matter, but most generally they gradually sink from the accumulation of pain and debility. There is rarely any fever. They do not fall into dropsies but usually become paralytic." If we cannot add to the graphic language of Dr. Lettsom's description perhaps we can add a few facts relevant to the history and physical examination. Neuritis in chronic alcoholics may have a gradual or an acute onset. The first symptoms are numbness and weakness of the feet followed by severe pain and tenderness of the calf muscles. Foot drop and then wrist drop appear and the reflexes are abolished, especially those of the knee and ankle. The sensory loss is most marked in the distal portions of the extremities yet there may be extreme hypersensitivity to pressure over the soles of the feet. Atrophy of the involved muscles soon appears and occasionally edema of the legs and arms. Coarse tremors of the mouth and tongue are almost always present but paralysis of a cranial nerve is rare. Sphincter difficulties are not present. . At times a psychosis occurs. If diarrhea is present over a long period dermatitis follows and determines the diagnosis of alcoholic pellagra, if not, the dementia is termed Korsakov's psychosIs. Typical of both mental disorders are confabulation, confusion, memory loss and disorientation. Acute excitement and depression and delirium accompanied by hallucinosis are more typical of the psychosis with endemic rather than with alcoholic pellagra.
DIAGNOSIS AND TREATMENT OF POLYNEURITIS
629
Laboratory studies are usually negative with the exception of gastric acidity. About 50 per cent show diminished or absent free HCI. The prognosis of a single attack of alcoholic neuritis without psychosis is goodlmt the ultimate prognosis is poor. Treatment.-Bed rest is essential whatever the severity of the signs and symptoms of polyneuritis. Analgesics and a cradle to keep the bedclothes off the feet may be necessary if pain and tenderness are severe. If the patient is restless or psychotic, paraldehyde is a useful drug. Sand bags and later . splints should be used to prevent contractions. When the patient has recovered sufficiently, physiotherapy should be undertaken. Within the last few years a great deal of stress has been laid on the use of a high vitamin diet in this type of polyneuritis. Since the symptoms bear a resemblance to beriI beri and pellagra vitamins Bl and B2 have been employed extensively. The results of this therapy are extremely difficult to evaluate. In the fi.rst place one is dealing with degenerated and degenerating nerve fibers which cannot be hurried in their recovery process. A large number of alcoholic polyneuritides are admitted to this clinic yearly and it is our impression that neither parenteral liver extract, brewer's yeast, nor vitamin Bl speeds up to any great extent the process of healing in the presence of a severe foot and wrist drop. As an example of the extremely slow rate of recovery in the presence of high vitamin therapy, a patient had a severe alcoholic polyneuritis in 1931 with return of knee jerks within a year. The ankle jerks did not return until January, 1937, though the foot drop had disappeared four years before. If pellagra is present nicotinic acid should be given. These patients should have a high caloric, high vitamin and easily digestible diet. Concentrated vitamin Bl therapy should be utilized, especially on incipient instances of alcoholic polyneuritis. ACUTE INFECTIOUS POLYNEURITIS
For fifty years the greatest of confusion has existed with regard to infectious polyneuritis. The textbooks mention any number of acute infections which may be complicated by a symmetrical multiple neuritis and pay but scant attention to the disease entity, acute infectious polyneuritis. In spite of
MADELAINE R. BROWN
this fact let it be said that the former type is extremely rare while the latter is next in frequency of occurrence to the alcoholic type. As early as the 1860's the syndrome of facial diplegia and weakness of the Jegs had been described by several authors. Twenty years later it was realized that the clinical picture was that of a polyneuritis, possibly of an infectious nature. In 1908 Laurans" collected 18 instances of this syndrome and during the World War Holmes 6 and Bradford et al. 7 observed 12 and 30 examples respectively of this disease among the British soldiers in France. By 1916 Guillain8 had observed the characteristic spinal fluid finding, that is, a high total protein without increase of cells. Taylor and McDonald9 performed both a lumbar and cistern puncture on one patient and found that with a protein of 206 mg. in the lumbar fluid, that of the cisternal fluid was 49mg.
The etiology is unknown, though Bashford believed he had transmitted the disease to monkeys. He used an emulsion of cord obtained at postmortem. The pathological anatomy is not spectacular and consists of degeneration of myelin of peripheral nerves with axonal changes in their cells of origin. Diagnosis.-The onset is usually afebrile with weakness of the legs followed by weakness of the arms and paresthesia of the extremities. The thighs and upper arms are more affected than the feet and hands. Involvement of the trunk muscles is common but the facial diplegia is the most characteristic feature of the disease, though cranial nerves such as the third and sixth may be involved. The deep reflexes are lost. In comparison to the great motor weakness the sensory loss is extremely slight and often amounts to paresthesia only. There are no mental symptoms. The spinal fluid is of great assistance in diagnosis due to the high protein unaccompanied by pleocytosis. The initial spinal fluid pressure may be raised, accounting for the headache in these instances. Treatment.-The treatment is largely symptomatic. Complete bed rest is essential. If necessary, contractions should be prevented by splints. A respirator, if one is available, should be held in readiness. If the cerebrospinal fluid pressure
DIAGNOSIS AND TREATMENT OF POLYNEURITIS
631
is raised frequent lumbar punctures add to the comfort of the patient. This measure also removes the excess protein and gives valuable information as to the progress of the disease. Prognosis is usually favorable. ACRODYNIA
A rare form of infectious polyneuritis in children is acrodynia or pink disease. The name acrodynia was first used to describe the symptoms in the 1828 Paris epidemic of polyneuritis, and possibly it was the same disease in adults. There is a widespread involvement of the peripheral autonomic nervous system with some degeneration of the peripheral somatic nerves. The symptoms referable to the autonomic nervous system are sweating, lacrimation, tachycardia, hypertension, photophobia, abdominal cramps, anorexia and pain and erythema of the extremities. The child presents a vivid clinical picture which, once seen, is not easily forgotten. It lies with the face buried in the pillow in the knee-chest position, constantly rubbing together its reddened desquamating hands. The symptoms referable to the central nervous system are apathy, muscular pain and weakness. In 7 out of 17 lumbar punctures Blackfan and McKhann10 found the spinal fluid protein raised (in one patient as high as 250 mm.) . Inasmuch as all 17 of these patients were seen late in the course of the disease it is likely that a much higher percentage would have shown a high protein had they been examined earlier. Since the etiology is probably some unknown type of infection, treatment is wholly symptomatic. Most important of all is the nutrition of the child and secondly the use of sedatives such as the barbiturates. POLYNEURITIS IN PREGNANCY, ACUTE INFECTIOUS DISEASES AND BERIBERI
During both pregnancy and fever the metabolism is raised and often the intake of food diminishes. Therefore a deficiency state such as beriberi may follow. The polyneuritis following hyperemesis gravidarum and that which used to follow a variety of acute infections in the days of "starve a fever" was probably on this basis. Landry's acute ascending paralysis also appears to belong in this group since the poly-
MADELAINE R. BROWN
neuritis followed after extreme dietary deficiency and pneumonia.l1 Gestational polyneuritis usually follows hyperemesis gravidarum and is thought to be the manifestation of a deficiency state. Clinically it resembles the infectious type of polyneuritis with the exception of the facial diplegia. The motor symptoms are much more marked than the sensory and the proximal musculature may be more involved than the distal. Tachycardia and a psychosis of the Korsakov type occurs frequently. The spinal fluid is negative. Prognosis is poor but if the patient survives the first two weeks recovery usually takes place. Treatment according to Plass and Mengert 12 is none too successful (8 of the 12 cases died), but they believe parenteral vitamin Bl should be used. If all else fails the statement that a therapeutic abortion is going to be performed may be successful in terminating the vomiting. Here again, since death is usually due to respiratory failure, a respirator should be in readiness if possible. When recovery is under way preventive methods directed toward the skin, joints and muscles, as previously described, should be instituted. DIABETIC NEURITIS
Polyneuritis or tabes as a complication of diabetes is so rare that Jordan13 reports 120 only out of the thousands of patients attending J oslin's clinic during a three-year period. In fact the so-called "diabetic neuritis" is usually not a neuritis at all but a diabetic tabes with loss of reflexes and position sense in the legs. However, a certain percentage do show the typical picture of an acute polyneuritis of the extremities. There are 4 possibilities suggested as to etiology. First, that the nerve degeneration is due to vitamin deficiency, either dietary or conditioned by lack of gastric secretion. Secondly, that fat metabolism is altered. Thirdly, changes are due to arteriosclerosis and poor nutrition of the nerves. Fourth, that the changes in the nerves are due to an infection. Without giving the many negative reasons against these various mechanisms let the one positive, constant finding be stated. The spinal fluid protein is high, 37 out of 40/3 the more severe the neuritis or posterior column involvement, the higher the protein. In 6 fluids from bed-ridden patients ex-
DIAGNOSIS AND TREATMENT OF POLYNEURITIS
633
amined at the Massachusetts General Hospital and the Boston City Hospital, the protein has ranged from 95 to 399 mg. per 100 cc. Three cistern fluids had 36 to 47 mg., showing that the protein arose in the spinal canal. This finding alone removes the disorder from the deficiency and arteriosclerosis groups. Even in diabetic coma the protein is normal. As far as known only tumors, myxedema, and infections give such !"Iroteins without pleocytosis. Since there is no question of tumor or myxedema and since the resistance to acute infections is lowered in diabetes, the neuritis or radiculitis may be due to an actual infection. The prognosis for the patients with acute diabetic neuritis is good. In our experience the instances of chronic diabetic tabes have not improved. It goes without saying that the first rule of treatment is to treat the diabetes first, last and always. Since pernicious anemia and diabetes may occur in the same patient, perhaps because both are due to glandular deficiency states, the gastric juice should be examined in patients with diabetic neuritis. A certain percentage, 30.4 per cene 3 will have no free acid in the gastric juice, although the number is no greater than in diabetics in general, and these should be treated intensively with parenteral liver extract. The others should at least be tried on liver by mouth and a high vitamin diet, though Jordan did not feel that this group improved any more rapidly on this therapy. Trophic ulcers of the feet are common in this disorder since both an arterial and nerve lesion is usually present. Cleanliness and absence of any friction from shoe or stocking should be stressed to the patient. If an ulcer is present the problem becomes surgical. POLYNEURITIS IN CONDITIONED DEFICIENCY STATES
Following interference with digestion or absorption of food, a polyneuritis on a deficiency basis may occur. Any chronic diarrhea due to dysentery, chronic ulcerative colitis, gastrostomy, or surgical accidental short-circuiting of the intestine may be followed by a polyneuritis. It is probable that this type is closely related to beriberi, pellagra, and combined systemic disease. In conditioned deficiency states the clinical picture, of necessity, is not clear cut. When a chronic diarrhea is present
MADELAINE R. BROWN
the patient is losing not only all vitamins but the digestive ferments as well. There may be a degeneration of either or both the posterior and anterior. columns of the cord as well as the peripheral nerves. Keefer 14 has described 2 patients with dysentery and polyneuritis and Urmy et al. 15 mention patients with chronic ulcerative colitis· and accidental surgical shortcircuiting of the intestine complicated by beriberi. The neuritis in conditioned deficiency states is apt to be limited to the legs and often cord involvement is present. The immediate cause of the nerve degeneration is usually apparent and treatment should be directed toward controlling the diarrhea and replacing the vitamins so lost. POLYNEURITIS DUE TO CHEMICAL POISONING
When industrial hazards and poisons in proprietary preparations have been removed another variety crops up in some unexpected spot. Polyneuritis from arsenic and lead has practically disappeared since Fowler's solution is no longer prescribed in large doses over long periods of time and since the majority of paints used by furniture manufacturers no longer contain lead. In 1930, just as the heavy metals were coming under control by public health measures, an epidemic of polyneuritis from ingestion of Jamaica ginger broke out in this country. In Europe the same type of polyneuritis was seen following the use of apiol, a drug used to produce abortion. Both Jamaica ginger and apiol were found to contain triorthocresyl phosphate, a poison affecting the peripheral nerves and cord. After this, thallium acetate, contained in a depilatory paste, was found to be the cause of multiple neuritis. The paralysis due to lead is typically a motor weakness affecting the anterior horn cells of the cervical cord, while that due to arsenic usually affects the sensory portion of all peripheral nerves to the extremities as well as the motor. Clinically it is similar to the alcoholic polyneuritis with extreme sensitivity of the affected parts and the distal musculature more affected than the proximal. An exfoliative dermatitis and a white line,across the nails may be present. The cause of these 4 forms of polyneuritis is determined by chemical tests. At present the spectroscopic test of the blood is the most useful in determining the presence of lead. Stippling of the red cells
DIAGNOSIS AND TREATMENT OF POLYNEURITIS
635
is usually present. A simple qualitative test for arsenic is the Reinsch test on twenty-four-hour urine specimens. The Gutzeit test is used for a quantitative measurement. The treatment of the conditions is largely symptomatic though in lead poisoning calcium and phosphorus are given, and in arsenic poisoning intravenous sodium thiosulfate. SUMMARY
Although it is difficult to distinguish pathologically between the various polyneuritides because secondary degeneration is present in all, a differentiation is more easily accomplished clinically. The types due to arsenic and alcohol involve both the sensory and motor nerves to the distal portions of the extremities. Polyneuritis due to lack, or vomiting of, vitamin Bl or to the acute infectious type, is more widespread and involves the motor to a much greater extent than the sensory nerves. In the latter, however, facial diplegia is usually present. The groups due to conditioned deficiency states, diabetes, and nerve poisons such as lead, triorthocresyl phosphate, and thallium acetate usually show symptoms referable to the spinal cord as well as the peripheral nerves. In North America the two most common forms encountered are acute infectious and alcoholic polyneuritis. BffiLIOGRAPHY 1. Lcttsom, J.
c.: Some Remarks on the Effects of Lignum Quassia
Amarae, Mem. Med. Soc. London, 1: 128, 1779-1787. 2. Jackson, J.: Arthrodynia a Potu. On a Peculiar Disease Resulting from the Use of Ardent Spirits, New Eng. Jour. Med. and Surg., Boston, 2: 351, 1822. : 3. Chomel, A. F.: De l'epidemic actuellement regnante a Paris, J. Hebd. de Med., 1: 333 (Nov. 29), 1828. 4. Graves, R. J.: Clinical Lectures on the Practice of Medicine, Fannin and Co., Dublin, 1848. 5. Laurans, A.: Des diplegies faciales au cours des polyneurites, These de Paris, 1908. 6. Holmes, G.: Acute Febrile Polyneuritis, Brit. Med. Jour., 2: 37,1917. 7. Bradford, J. R., Bashford, E. F., and Wilson, J. A.: Acute Infective Polyneuritis, Quart. Jour. Med., 12: 88, 1918. 8. GuilIain, G., Barre, J. H., and Strohl, A.: Sur un syndrome de radiculoneurite avec hyperalbuminose du liquide cephalo-rachidien sans reaction cellulaire. Bull. et Mem. Soc. Med. d. Hop. de Paris, 40:' 1462, 1916. 9. Taylor, E. W., and McDonald, C. A.: The Syndrome of Polyneuritis with Facial Diplegia, Arch. , Neurol. and Psychiat., 27: 79, 1932.
MADELAiNE R. BROWN 10. BIackfan, K., and McKhann, C. F.: Acrodynia, Oxford Medicine, vol. 4, part 1, page 272. 11. Brown, M. R.: A Note on the Etiology of Landry's Acute Ascending Paralysis. In Press, Arch. Neurol. and Psychiat. 12. Plass, E. D., and Mengert, W. F.: Gestational Polyneuritis, J AMA., 101: 2020, 1933. 13. Jordan, W. R.: Neuritic Manifestations in Diabetes Mellitus, 67: 307, 1936. 14. Keefer, C., Yang, C., and Huang, K.: Anaemia Associated with Chronic Dysentery, Arch. Int. Med., 47: 436, 1931. 15. Urmy, T. V., Ragle, B. H., Alien, G. W., and Jones, C. M.: Beri Beri Secondary to Short Circuited Small Intestine, New Eng. J. Med., 210: 251, 1934.
CLINIC OF DR. MADELAINE R. BROWN FROM THE NEUROLOGICAL UNIT, BOSTON CITY HOSPITAL DIAGNOSIS AND TREATMENT OF POLYNEURITIS* TODAY there are only 2 types of polyneuritis which the physicians of North America need seriously consider. Endemic beriberi has practically disappeared from this continent and the majority of physicians may practice a lifetime without being called on to treat those forms due to chemical agents, pregnancy, diabetes, and conditioned deficiency states. Therefore, the greater portion of this discussion will be devoted to the diagnosis and treatment of 2 types of polyneuritis only. These 2 are alcoholic and acute infectious polyneuritis, and the more common of these is alcoholic polyneuritis. Perhaps it is not coincidence that paralysis among alcoholics was well described by John Lettsom 1 and James Jackson2 as early as 1787 and 1822 respectively, and that ChomeP by 1828 had given a vivid picture of an epidemic of polyneuritis in Paris. These 3 observers had no conception with what they were dealing. Graves/ who had been in Paris at the time of the epidemic and knowing that the pathologists had found no changes in the central nervous system, fifteen years later suggested disease of the peripheral nerves. ALCOHOLIC POLYNEURITIS
The diagnosis of alcoholic polyneuritis is not usually difficult for the cause of the patient's indisposition is all too evident. Out of the past of one hundred and fifty years ago comes a description on which it would be difficult to improve: "The first appearance of indisposition very much resembles the gout; and the fuel is heaped upon the fire until the at-
* No contraindication for the use of the word "neuritis" has been found since "itis" is merely the Greek feminine adjectival termination and the word disease is understood. Neuritis therefore means disease of the nerve and not necessarily inflammation.
MADELAlNE R. BROWN
tachment to the use of spiritous drinks becomes so predominant that neither threats nor persuasions are powerful enough to overcome it. Frequently the appetite for food vanishes but sometimes continues voracious; and at the same time, whilst the body is costive, and no vomiting ensues, the lower extremities grow more and more emaciated; the legs become smooth as polished ivory and the soles of the feet even glassy and shining and at the same time so tender that the weight of the finger excites shrieks and moaning. The legs and the whole lower extremities lose all power of action. The arms and hands acquire the same paralysis and render the patients incapable of feeding themselves. "Mostly before they die they take less food; sometimes a diarrhea succeeds, sometimes a vomiting of black matter, but most generally they gradually sink from the accumulation of pain and debility. There is rarely any fever. They do not fall into dropsies but usually become paralytic." If we cannot add to the graphic language of Dr. Lettsom's description perhaps we can add a few facts relevant to the history and physical examination. Neuritis in chronic alcoholics may have a gradual or an acute onset. The first symptoms are numbness and weakness of the feet followed by severe pain and tenderness of the calf muscles. Foot drop and then wrist drop appear and the reflexes are abolished, especially those of the knee and ankle. The sensory loss is most marked in the distal portions of the extremities yet there may be extreme hypersensitivity to pressure over the soles of the feet. Atrophy of the involved muscles soon appears and occasionally edema of the legs and arms. Coarse tremors of the mouth and tongue are almost always present but paralysis of a cranial nerve is rare. Sphincter difficulties are not present. . At times a psychosis occurs. If diarrhea is present over a long period dermatitis follows and determines the diagnosis of alcoholic pellagra, if not, the dementia is termed Korsakov's psychosIs. Typical of both mental disorders are confabulation, confusion, memory loss and disorientation. Acute excitement and depression and delirium accompanied by hallucinosis are more typical of the psychosis with endemic rather than with alcoholic pellagra.
DIAGNOSIS AND TREATMENT OF POLYNEURITIS
629
Laboratory studies are usually negative with the exception of gastric acidity. About 50 per cent show diminished or absent free HCI. The prognosis of a single attack of alcoholic neuritis without psychosis is goodlmt the ultimate prognosis is poor. Treatment.-Bed rest is essential whatever the severity of the signs and symptoms of polyneuritis. Analgesics and a cradle to keep the bedclothes off the feet may be necessary if pain and tenderness are severe. If the patient is restless or psychotic, paraldehyde is a useful drug. Sand bags and later . splints should be used to prevent contractions. When the patient has recovered sufficiently, physiotherapy should be undertaken. Within the last few years a great deal of stress has been laid on the use of a high vitamin diet in this type of polyneuritis. Since the symptoms bear a resemblance to beriI beri and pellagra vitamins Bl and B2 have been employed extensively. The results of this therapy are extremely difficult to evaluate. In the fi.rst place one is dealing with degenerated and degenerating nerve fibers which cannot be hurried in their recovery process. A large number of alcoholic polyneuritides are admitted to this clinic yearly and it is our impression that neither parenteral liver extract, brewer's yeast, nor vitamin Bl speeds up to any great extent the process of healing in the presence of a severe foot and wrist drop. As an example of the extremely slow rate of recovery in the presence of high vitamin therapy, a patient had a severe alcoholic polyneuritis in 1931 with return of knee jerks within a year. The ankle jerks did not return until January, 1937, though the foot drop had disappeared four years before. If pellagra is present nicotinic acid should be given. These patients should have a high caloric, high vitamin and easily digestible diet. Concentrated vitamin Bl therapy should be utilized, especially on incipient instances of alcoholic polyneuritis. ACUTE INFECTIOUS POLYNEURITIS
For fifty years the greatest of confusion has existed with regard to infectious polyneuritis. The textbooks mention any number of acute infections which may be complicated by a symmetrical multiple neuritis and pay but scant attention to the disease entity, acute infectious polyneuritis. In spite of
MADELAINE R. BROWN
this fact let it be said that the former type is extremely rare while the latter is next in frequency of occurrence to the alcoholic type. As early as the 1860's the syndrome of facial diplegia and weakness of the Jegs had been described by several authors. Twenty years later it was realized that the clinical picture was that of a polyneuritis, possibly of an infectious nature. In 1908 Laurans" collected 18 instances of this syndrome and during the World War Holmes 6 and Bradford et al. 7 observed 12 and 30 examples respectively of this disease among the British soldiers in France. By 1916 Guillain8 had observed the characteristic spinal fluid finding, that is, a high total protein without increase of cells. Taylor and McDonald9 performed both a lumbar and cistern puncture on one patient and found that with a protein of 206 mg. in the lumbar fluid, that of the cisternal fluid was 49mg.
The etiology is unknown, though Bashford believed he had transmitted the disease to monkeys. He used an emulsion of cord obtained at postmortem. The pathological anatomy is not spectacular and consists of degeneration of myelin of peripheral nerves with axonal changes in their cells of origin. Diagnosis.-The onset is usually afebrile with weakness of the legs followed by weakness of the arms and paresthesia of the extremities. The thighs and upper arms are more affected than the feet and hands. Involvement of the trunk muscles is common but the facial diplegia is the most characteristic feature of the disease, though cranial nerves such as the third and sixth may be involved. The deep reflexes are lost. In comparison to the great motor weakness the sensory loss is extremely slight and often amounts to paresthesia only. There are no mental symptoms. The spinal fluid is of great assistance in diagnosis due to the high protein unaccompanied by pleocytosis. The initial spinal fluid pressure may be raised, accounting for the headache in these instances. Treatment.-The treatment is largely symptomatic. Complete bed rest is essential. If necessary, contractions should be prevented by splints. A respirator, if one is available, should be held in readiness. If the cerebrospinal fluid pressure
DIAGNOSIS AND TREATMENT OF POLYNEURITIS
631
is raised frequent lumbar punctures add to the comfort of the patient. This measure also removes the excess protein and gives valuable information as to the progress of the disease. Prognosis is usually favorable. ACRODYNIA
A rare form of infectious polyneuritis in children is acrodynia or pink disease. The name acrodynia was first used to describe the symptoms in the 1828 Paris epidemic of polyneuritis, and possibly it was the same disease in adults. There is a widespread involvement of the peripheral autonomic nervous system with some degeneration of the peripheral somatic nerves. The symptoms referable to the autonomic nervous system are sweating, lacrimation, tachycardia, hypertension, photophobia, abdominal cramps, anorexia and pain and erythema of the extremities. The child presents a vivid clinical picture which, once seen, is not easily forgotten. It lies with the face buried in the pillow in the knee-chest position, constantly rubbing together its reddened desquamating hands. The symptoms referable to the central nervous system are apathy, muscular pain and weakness. In 7 out of 17 lumbar punctures Blackfan and McKhann10 found the spinal fluid protein raised (in one patient as high as 250 mm.) . Inasmuch as all 17 of these patients were seen late in the course of the disease it is likely that a much higher percentage would have shown a high protein had they been examined earlier. Since the etiology is probably some unknown type of infection, treatment is wholly symptomatic. Most important of all is the nutrition of the child and secondly the use of sedatives such as the barbiturates. POLYNEURITIS IN PREGNANCY, ACUTE INFECTIOUS DISEASES AND BERIBERI
During both pregnancy and fever the metabolism is raised and often the intake of food diminishes. Therefore a deficiency state such as beriberi may follow. The polyneuritis following hyperemesis gravidarum and that which used to follow a variety of acute infections in the days of "starve a fever" was probably on this basis. Landry's acute ascending paralysis also appears to belong in this group since the poly-
MADELAINE R. BROWN
neuritis followed after extreme dietary deficiency and pneumonia.l1 Gestational polyneuritis usually follows hyperemesis gravidarum and is thought to be the manifestation of a deficiency state. Clinically it resembles the infectious type of polyneuritis with the exception of the facial diplegia. The motor symptoms are much more marked than the sensory and the proximal musculature may be more involved than the distal. Tachycardia and a psychosis of the Korsakov type occurs frequently. The spinal fluid is negative. Prognosis is poor but if the patient survives the first two weeks recovery usually takes place. Treatment according to Plass and Mengert 12 is none too successful (8 of the 12 cases died), but they believe parenteral vitamin Bl should be used. If all else fails the statement that a therapeutic abortion is going to be performed may be successful in terminating the vomiting. Here again, since death is usually due to respiratory failure, a respirator should be in readiness if possible. When recovery is under way preventive methods directed toward the skin, joints and muscles, as previously described, should be instituted. DIABETIC NEURITIS
Polyneuritis or tabes as a complication of diabetes is so rare that Jordan13 reports 120 only out of the thousands of patients attending J oslin's clinic during a three-year period. In fact the so-called "diabetic neuritis" is usually not a neuritis at all but a diabetic tabes with loss of reflexes and position sense in the legs. However, a certain percentage do show the typical picture of an acute polyneuritis of the extremities. There are 4 possibilities suggested as to etiology. First, that the nerve degeneration is due to vitamin deficiency, either dietary or conditioned by lack of gastric secretion. Secondly, that fat metabolism is altered. Thirdly, changes are due to arteriosclerosis and poor nutrition of the nerves. Fourth, that the changes in the nerves are due to an infection. Without giving the many negative reasons against these various mechanisms let the one positive, constant finding be stated. The spinal fluid protein is high, 37 out of 40/3 the more severe the neuritis or posterior column involvement, the higher the protein. In 6 fluids from bed-ridden patients ex-
DIAGNOSIS AND TREATMENT OF POLYNEURITIS
633
amined at the Massachusetts General Hospital and the Boston City Hospital, the protein has ranged from 95 to 399 mg. per 100 cc. Three cistern fluids had 36 to 47 mg., showing that the protein arose in the spinal canal. This finding alone removes the disorder from the deficiency and arteriosclerosis groups. Even in diabetic coma the protein is normal. As far as known only tumors, myxedema, and infections give such !"Iroteins without pleocytosis. Since there is no question of tumor or myxedema and since the resistance to acute infections is lowered in diabetes, the neuritis or radiculitis may be due to an actual infection. The prognosis for the patients with acute diabetic neuritis is good. In our experience the instances of chronic diabetic tabes have not improved. It goes without saying that the first rule of treatment is to treat the diabetes first, last and always. Since pernicious anemia and diabetes may occur in the same patient, perhaps because both are due to glandular deficiency states, the gastric juice should be examined in patients with diabetic neuritis. A certain percentage, 30.4 per cene 3 will have no free acid in the gastric juice, although the number is no greater than in diabetics in general, and these should be treated intensively with parenteral liver extract. The others should at least be tried on liver by mouth and a high vitamin diet, though Jordan did not feel that this group improved any more rapidly on this therapy. Trophic ulcers of the feet are common in this disorder since both an arterial and nerve lesion is usually present. Cleanliness and absence of any friction from shoe or stocking should be stressed to the patient. If an ulcer is present the problem becomes surgical. POLYNEURITIS IN CONDITIONED DEFICIENCY STATES
Following interference with digestion or absorption of food, a polyneuritis on a deficiency basis may occur. Any chronic diarrhea due to dysentery, chronic ulcerative colitis, gastrostomy, or surgical accidental short-circuiting of the intestine may be followed by a polyneuritis. It is probable that this type is closely related to beriberi, pellagra, and combined systemic disease. In conditioned deficiency states the clinical picture, of necessity, is not clear cut. When a chronic diarrhea is present
MADELAINE R. BROWN
the patient is losing not only all vitamins but the digestive ferments as well. There may be a degeneration of either or both the posterior and anterior. columns of the cord as well as the peripheral nerves. Keefer 14 has described 2 patients with dysentery and polyneuritis and Urmy et al. 15 mention patients with chronic ulcerative colitis· and accidental surgical shortcircuiting of the intestine complicated by beriberi. The neuritis in conditioned deficiency states is apt to be limited to the legs and often cord involvement is present. The immediate cause of the nerve degeneration is usually apparent and treatment should be directed toward controlling the diarrhea and replacing the vitamins so lost. POLYNEURITIS DUE TO CHEMICAL POISONING
When industrial hazards and poisons in proprietary preparations have been removed another variety crops up in some unexpected spot. Polyneuritis from arsenic and lead has practically disappeared since Fowler's solution is no longer prescribed in large doses over long periods of time and since the majority of paints used by furniture manufacturers no longer contain lead. In 1930, just as the heavy metals were coming under control by public health measures, an epidemic of polyneuritis from ingestion of Jamaica ginger broke out in this country. In Europe the same type of polyneuritis was seen following the use of apiol, a drug used to produce abortion. Both Jamaica ginger and apiol were found to contain triorthocresyl phosphate, a poison affecting the peripheral nerves and cord. After this, thallium acetate, contained in a depilatory paste, was found to be the cause of multiple neuritis. The paralysis due to lead is typically a motor weakness affecting the anterior horn cells of the cervical cord, while that due to arsenic usually affects the sensory portion of all peripheral nerves to the extremities as well as the motor. Clinically it is similar to the alcoholic polyneuritis with extreme sensitivity of the affected parts and the distal musculature more affected than the proximal. An exfoliative dermatitis and a white line,across the nails may be present. The cause of these 4 forms of polyneuritis is determined by chemical tests. At present the spectroscopic test of the blood is the most useful in determining the presence of lead. Stippling of the red cells
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is usually present. A simple qualitative test for arsenic is the Reinsch test on twenty-four-hour urine specimens. The Gutzeit test is used for a quantitative measurement. The treatment of the conditions is largely symptomatic though in lead poisoning calcium and phosphorus are given, and in arsenic poisoning intravenous sodium thiosulfate. SUMMARY
Although it is difficult to distinguish pathologically between the various polyneuritides because secondary degeneration is present in all, a differentiation is more easily accomplished clinically. The types due to arsenic and alcohol involve both the sensory and motor nerves to the distal portions of the extremities. Polyneuritis due to lack, or vomiting of, vitamin Bl or to the acute infectious type, is more widespread and involves the motor to a much greater extent than the sensory nerves. In the latter, however, facial diplegia is usually present. The groups due to conditioned deficiency states, diabetes, and nerve poisons such as lead, triorthocresyl phosphate, and thallium acetate usually show symptoms referable to the spinal cord as well as the peripheral nerves. In North America the two most common forms encountered are acute infectious and alcoholic polyneuritis. BffiLIOGRAPHY 1. Lcttsom, J.
c.: Some Remarks on the Effects of Lignum Quassia
Amarae, Mem. Med. Soc. London, 1: 128, 1779-1787. 2. Jackson, J.: Arthrodynia a Potu. On a Peculiar Disease Resulting from the Use of Ardent Spirits, New Eng. Jour. Med. and Surg., Boston, 2: 351, 1822. : 3. Chomel, A. F.: De l'epidemic actuellement regnante a Paris, J. Hebd. de Med., 1: 333 (Nov. 29), 1828. 4. Graves, R. J.: Clinical Lectures on the Practice of Medicine, Fannin and Co., Dublin, 1848. 5. Laurans, A.: Des diplegies faciales au cours des polyneurites, These de Paris, 1908. 6. Holmes, G.: Acute Febrile Polyneuritis, Brit. Med. Jour., 2: 37,1917. 7. Bradford, J. R., Bashford, E. F., and Wilson, J. A.: Acute Infective Polyneuritis, Quart. Jour. Med., 12: 88, 1918. 8. GuilIain, G., Barre, J. H., and Strohl, A.: Sur un syndrome de radiculoneurite avec hyperalbuminose du liquide cephalo-rachidien sans reaction cellulaire. Bull. et Mem. Soc. Med. d. Hop. de Paris, 40:' 1462, 1916. 9. Taylor, E. W., and McDonald, C. A.: The Syndrome of Polyneuritis with Facial Diplegia, Arch. , Neurol. and Psychiat., 27: 79, 1932.
MADELAiNE R. BROWN 10. BIackfan, K., and McKhann, C. F.: Acrodynia, Oxford Medicine, vol. 4, part 1, page 272. 11. Brown, M. R.: A Note on the Etiology of Landry's Acute Ascending Paralysis. In Press, Arch. Neurol. and Psychiat. 12. Plass, E. D., and Mengert, W. F.: Gestational Polyneuritis, J AMA., 101: 2020, 1933. 13. Jordan, W. R.: Neuritic Manifestations in Diabetes Mellitus, 67: 307, 1936. 14. Keefer, C., Yang, C., and Huang, K.: Anaemia Associated with Chronic Dysentery, Arch. Int. Med., 47: 436, 1931. 15. Urmy, T. V., Ragle, B. H., Alien, G. W., and Jones, C. M.: Beri Beri Secondary to Short Circuited Small Intestine, New Eng. J. Med., 210: 251, 1934.