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Cerebral allergic edema
CEREBRAL
ALLERGIC R.
WILLIAM
CROWE,
ATLANTA,
EDEMA
M.D. GA.
V
ARIED symptom complexes due to cerebral edema caused by allergic phenomena have been recorded. In 1927 Vaughan1 definitely connected food allergy with Galen’s hemicrania. That an allergic edema of the internal ear can produce vertigo has been proved by Criep2 and Clark.3 Certain types of epilepsy have been given an allergic basis.* Further comprehensive work of headaches of allergic origin has been furnished by Thomas and Johnston.” Choreiform movements, marked personality changes, and mental backwardness in the allergic person with improvement following proper desensitization have been seen.6 This case of probable cerebral edema is of interest because it reveals the importance of considering cerebral allergy in differential diagnosis of diseases of the central nervous system and at the same time offers an explanation of the unusual behavior and personality found in the patient. CASE
REPORT
W. R. S., Jr., a white male, aged 16 years, was first seen at the Good Samaritan He was undersized and had not grown Clinic in 1933, when he was 9 years old. during the four preceding years. Dull in school, he was then making the fourth annual attempt to pass the first grade. This mental inaptitude was explained by an almost diurnal sleepiness, accompanied by an occasional dull, boring pain between the eyes, since its onset in 1930. He was very nervous, was never still, had a poor appetite, and awoke every morning feeling very cold. At birth, which had been normal in every way, he weighed 8 pounds. His ,earliest development was uneventful until the beginning of the headaches in January, 1930. He had had an uncomplicated diphtheria treated with antitoxin at 2 years, measles at 7 years, and an occasional epist,axis without any rheumatic involvement. His mother and two maternal uncles had asthma. Examination
revealed normal height and weight for his chronological age and of his mental age with an I.&. (Sanford-Binet) of 71, low normal being 90. Other findings included dry, coarse skin and hair, infected tonsils, enlarged epitrochlears, and a palpable thyroid gland. The testes, although descended, were smaller than normal. The basal metabolic rate was minus 12 per cent. The Schilling differential count disclosed an eosinophilia of 12 per cent. The blood Wassermann test was negative.
a retardation
Treatment for hypothyroidism and 1933, a tonsillectomy was performed. thyroid extract and orchic substance. telligence improved only slightly. All From
the
Good
Samaritan
Clinic,
hypogonadism was instigated. In December, For the next six years the patient received His height increased 9.5 inches, but the inmedication was stopped on July 5, 1938. In btlanta.
173
174
THE
JOURNAL
OF
ALLERGY
the interim, he had passed the fourth grade requirements, although the sleepy spells had increased in frequency, with as many as three to twenty a day, lasting from five to sixty minutes. He was advised to quit school and take up a trade. In March, 1940, I saw the patient for the first time. His father, as informant, stated that, for the past seven years, his son had complained of severe, one-sided frontal headaches, which were occasionally heralded by a swelling of the lips and beneath one eye. These headaches, without aura or other prodromata, were always associated with drowsiness and sometimes with nausea and vomiting. First, the facial swelling appeared, soon to be followed by headache; then, in about an hour came increasing drowsiness. If permit,ted, the patient would sleep but could be aroused by vigorous shaking. The lethargy usually cleared in ten or twelve hours, but the swelling required two 01 three additional hours for its disappearance. The attacks had no seasonal variation, began at any time of the day, and occurred from one to three times a month. Neither patient nor informant had discovered any precipitating factors. Reexamination revealed a. well-developed but mentally sluggish l&year-old male with moderate edema of the lips. The pulse rate was 78 per minute; the blood pressure, 115/70 mm. in both arms. The hair and skin were dry. The thyroid was of normal size and consistency. The genitals were normally tleveloped. A 4 per cent eosinophilia was found in the blood. The rest of the blood count, the blood chemistry, urinalysis, phenolsulphonephthalein test of kidney function, and the feces were all normal. The blood Kahn was negative. X-ray examination of the head showed no pathology. The basal metabolic rate was minus 21 per cent with a, pulse rate of 68 per minute. Because of the familial history of allergy and the migrainous-like headaches with facial edema associated with drowsiness, cerebral angioneurotic edema with possible hypothalamic involvement was strongly suspected. Dr. Clarence Laws made both scratch and intradermal skin tests, which showed sensitization to the following foods : corn, rice, wheat, spinach, beans, peas, apple, pear, orange, grapefruit, lemon, and all seasonings. Neurological examination by Dr. Richard Wilson revealed occasional spasmo.dic contractions of the head and limbs. At times, only one limb was involved, but No objective evidence of organic occasionally all were abducted to a slight degree. disease of the central nervous system was found. Dr. Wilson could explain his findings only on the basis of a cerebral angioneurotic edema which probably involved predominantly the hypothalamus. Mr. Robert Brush, a psychologist, using the Weehsler-Bellevue intelligence test, rated the patient’s total I.&. at 50, which suggested .definite mental deficiency. His isolated vocabulary rating was 72. Since March, 1940, when the offending foods were omitted from the diet, the patient has remained free of attacks of drowsiness and facial edema. In May, 1940, the patient was given purposely a piece of wheat bread. Forty-five minutes after ingestion, periorbital edema of the right eye occurred. One hour later: the patient became very lethargic. Adrenalin chloride (1 :l,OOO solution), 0.2 c.c., was given every ten minutes for four doses; the edema and drowsiness almost cleared within the next hour. There have been no recurrences since this experimentally induced one. The patient has now shown greater aptitude in carrying out his present job as a mechanic, than at, any previous time. DISCUSSION
The cerebral pathology involved can best be understood by reviewing the dog experiments of Davidoff and Kopeloff.7 They sensitized a previously injured left cerebral motor area with horse serum and two to four weeks later administered horse serum, intravenously, to these
CROWE
:
CEREBRAL
ALLERGIC
EDEMA
175
dogs. A transient right-sided hemiparesis ensued. While injecting the brains of the animals, they accidentally sensitized the overlying scalp, which reacted along with the cerebral tissue and, in so doing, served as a visual reaCtion indicator. This is quite analogous to the periorbital and cerebral edema observed in the present case. The cerebral edema, with foods as the excitant allergens, is best explained by local vasodilatation and increased capillary permeability.” That the hypothalamus was a most vulnerable area in this case is very suggestive. Smprovement in personality on subsidence of frontal lobe edema is a likely possibility. Kennedy and his associates8 considered vasomotor changes in cerebral vessels as an important mechanism in epilepsy, arterial hypertension, carotid sinus syncope, migraine, and angioneurotic edema Migraine was associated with vasodilatation, a beginning rise in a fallen blood pressure, and an increased amplitude of intracranial pulsations when the headache was severest. Kennedy observed the exposed cortex of an epileptic person undergoing operation with local anesthesia. He described a primary cortical blanching followed by marked venous engorgement and brain protrusion, at the onset of the attack. Carotid sinus syncope was explained on the basis of a momentary constriction and then marked dilatation of the pial vessels. Sudden cerebral anoxemia. produced in this way was held as a likely explanation of the va,gal a.nd depressor carotid sinus response. Goltman’9 observations on allergic migraine in a young woman were greatly sustained by a postoperative opening in the left frontal area of the skull. He concluded that the mechanism of migraine consisted of a primary vasomotor spasm, a secondary vascular dilatation with resulting edema of the brain. A subsequent state of hypersecretion along with a simultaneous hyperabsorption of the cerebrospinal fluid brought an eventual equalization of pressure in the subarachnoid space. This was successfully controlled by avoidance of the causative irritants, which were both foods and inhalants. Cerebral allergy can simulate a countless number of diseases. There are, on record, cases where it has effected marked personality and mental changes.6 With improvement in our diagnost,ic apparatus, along with continued detailed study of each case, we may be able to recognize the underlying altered physiology in these unfortunate people and thereby establish them as useful citizens in their community. SUMMBRP
1. A case of food allergy causing cerebral edema in a patient with familial allergy is presented. 2. The symptoms were controlled or aggravated at will, by elimination or introduction of the offending allergen. 3. Improvement in personality, but not of the intelligence quotient, followed cessation of the cerebral edema.
176
THE
JOURNAL
OF
ALLERGY
REFERENCES 1. Vaughan, W. T.: Allergic Migraine, J. A. M. A. 88: 1383, 1927. 2. Criep, L. H.: Allergic Vertigo, Pennsylvania M. J. 43: 258, 1939. 3. Clark, T. W.: Allergic Manifestations m the Central Nervous System, New York State J. Med. 39: 1498, 1939. Protein Sensitization as a Possible Cause of Epilepsy and Cancer, 4. Ward, J. F.: New York M. J. 115: 592, 1922. Heatlaches of Allergic Origin, M. Clin. 5. Thomas, J. W., and Johnston, C. R. K.: North America 24: 285, 1940. 6. Vaughan, W. T.: Practice of Allergy, ed. 1, St. Louis, 1939, The C. V. Mosby Co., p, 1024. 7. Davidoff, L. M., and Kopeloff, N.: Local Cerebral Anaphylaxis in the Dog, Proc. Sot. Exper. Biol. & Med. 31: 980, 19.74. 8. Kennedy, F., Wortis, S. B., and Wortis, H.: Clinical Evidence for Cerebral Vasomotor Changes, New York State J. Med. 38: 1441, 1938. 9. Goltman, A. M.: The Mechanism of Migraine, J. ALLERGY 7: 351, 1936.
ALLERGIC R.
WILLIAM
CROWE,
ATLANTA,
EDEMA
M.D. GA.
V
ARIED symptom complexes due to cerebral edema caused by allergic phenomena have been recorded. In 1927 Vaughan1 definitely connected food allergy with Galen’s hemicrania. That an allergic edema of the internal ear can produce vertigo has been proved by Criep2 and Clark.3 Certain types of epilepsy have been given an allergic basis.* Further comprehensive work of headaches of allergic origin has been furnished by Thomas and Johnston.” Choreiform movements, marked personality changes, and mental backwardness in the allergic person with improvement following proper desensitization have been seen.6 This case of probable cerebral edema is of interest because it reveals the importance of considering cerebral allergy in differential diagnosis of diseases of the central nervous system and at the same time offers an explanation of the unusual behavior and personality found in the patient. CASE
REPORT
W. R. S., Jr., a white male, aged 16 years, was first seen at the Good Samaritan He was undersized and had not grown Clinic in 1933, when he was 9 years old. during the four preceding years. Dull in school, he was then making the fourth annual attempt to pass the first grade. This mental inaptitude was explained by an almost diurnal sleepiness, accompanied by an occasional dull, boring pain between the eyes, since its onset in 1930. He was very nervous, was never still, had a poor appetite, and awoke every morning feeling very cold. At birth, which had been normal in every way, he weighed 8 pounds. His ,earliest development was uneventful until the beginning of the headaches in January, 1930. He had had an uncomplicated diphtheria treated with antitoxin at 2 years, measles at 7 years, and an occasional epist,axis without any rheumatic involvement. His mother and two maternal uncles had asthma. Examination
revealed normal height and weight for his chronological age and of his mental age with an I.&. (Sanford-Binet) of 71, low normal being 90. Other findings included dry, coarse skin and hair, infected tonsils, enlarged epitrochlears, and a palpable thyroid gland. The testes, although descended, were smaller than normal. The basal metabolic rate was minus 12 per cent. The Schilling differential count disclosed an eosinophilia of 12 per cent. The blood Wassermann test was negative.
a retardation
Treatment for hypothyroidism and 1933, a tonsillectomy was performed. thyroid extract and orchic substance. telligence improved only slightly. All From
the
Good
Samaritan
Clinic,
hypogonadism was instigated. In December, For the next six years the patient received His height increased 9.5 inches, but the inmedication was stopped on July 5, 1938. In btlanta.
173
174
THE
JOURNAL
OF
ALLERGY
the interim, he had passed the fourth grade requirements, although the sleepy spells had increased in frequency, with as many as three to twenty a day, lasting from five to sixty minutes. He was advised to quit school and take up a trade. In March, 1940, I saw the patient for the first time. His father, as informant, stated that, for the past seven years, his son had complained of severe, one-sided frontal headaches, which were occasionally heralded by a swelling of the lips and beneath one eye. These headaches, without aura or other prodromata, were always associated with drowsiness and sometimes with nausea and vomiting. First, the facial swelling appeared, soon to be followed by headache; then, in about an hour came increasing drowsiness. If permit,ted, the patient would sleep but could be aroused by vigorous shaking. The lethargy usually cleared in ten or twelve hours, but the swelling required two 01 three additional hours for its disappearance. The attacks had no seasonal variation, began at any time of the day, and occurred from one to three times a month. Neither patient nor informant had discovered any precipitating factors. Reexamination revealed a. well-developed but mentally sluggish l&year-old male with moderate edema of the lips. The pulse rate was 78 per minute; the blood pressure, 115/70 mm. in both arms. The hair and skin were dry. The thyroid was of normal size and consistency. The genitals were normally tleveloped. A 4 per cent eosinophilia was found in the blood. The rest of the blood count, the blood chemistry, urinalysis, phenolsulphonephthalein test of kidney function, and the feces were all normal. The blood Kahn was negative. X-ray examination of the head showed no pathology. The basal metabolic rate was minus 21 per cent with a, pulse rate of 68 per minute. Because of the familial history of allergy and the migrainous-like headaches with facial edema associated with drowsiness, cerebral angioneurotic edema with possible hypothalamic involvement was strongly suspected. Dr. Clarence Laws made both scratch and intradermal skin tests, which showed sensitization to the following foods : corn, rice, wheat, spinach, beans, peas, apple, pear, orange, grapefruit, lemon, and all seasonings. Neurological examination by Dr. Richard Wilson revealed occasional spasmo.dic contractions of the head and limbs. At times, only one limb was involved, but No objective evidence of organic occasionally all were abducted to a slight degree. disease of the central nervous system was found. Dr. Wilson could explain his findings only on the basis of a cerebral angioneurotic edema which probably involved predominantly the hypothalamus. Mr. Robert Brush, a psychologist, using the Weehsler-Bellevue intelligence test, rated the patient’s total I.&. at 50, which suggested .definite mental deficiency. His isolated vocabulary rating was 72. Since March, 1940, when the offending foods were omitted from the diet, the patient has remained free of attacks of drowsiness and facial edema. In May, 1940, the patient was given purposely a piece of wheat bread. Forty-five minutes after ingestion, periorbital edema of the right eye occurred. One hour later: the patient became very lethargic. Adrenalin chloride (1 :l,OOO solution), 0.2 c.c., was given every ten minutes for four doses; the edema and drowsiness almost cleared within the next hour. There have been no recurrences since this experimentally induced one. The patient has now shown greater aptitude in carrying out his present job as a mechanic, than at, any previous time. DISCUSSION
The cerebral pathology involved can best be understood by reviewing the dog experiments of Davidoff and Kopeloff.7 They sensitized a previously injured left cerebral motor area with horse serum and two to four weeks later administered horse serum, intravenously, to these
CROWE
:
CEREBRAL
ALLERGIC
EDEMA
175
dogs. A transient right-sided hemiparesis ensued. While injecting the brains of the animals, they accidentally sensitized the overlying scalp, which reacted along with the cerebral tissue and, in so doing, served as a visual reaCtion indicator. This is quite analogous to the periorbital and cerebral edema observed in the present case. The cerebral edema, with foods as the excitant allergens, is best explained by local vasodilatation and increased capillary permeability.” That the hypothalamus was a most vulnerable area in this case is very suggestive. Smprovement in personality on subsidence of frontal lobe edema is a likely possibility. Kennedy and his associates8 considered vasomotor changes in cerebral vessels as an important mechanism in epilepsy, arterial hypertension, carotid sinus syncope, migraine, and angioneurotic edema Migraine was associated with vasodilatation, a beginning rise in a fallen blood pressure, and an increased amplitude of intracranial pulsations when the headache was severest. Kennedy observed the exposed cortex of an epileptic person undergoing operation with local anesthesia. He described a primary cortical blanching followed by marked venous engorgement and brain protrusion, at the onset of the attack. Carotid sinus syncope was explained on the basis of a momentary constriction and then marked dilatation of the pial vessels. Sudden cerebral anoxemia. produced in this way was held as a likely explanation of the va,gal a.nd depressor carotid sinus response. Goltman’9 observations on allergic migraine in a young woman were greatly sustained by a postoperative opening in the left frontal area of the skull. He concluded that the mechanism of migraine consisted of a primary vasomotor spasm, a secondary vascular dilatation with resulting edema of the brain. A subsequent state of hypersecretion along with a simultaneous hyperabsorption of the cerebrospinal fluid brought an eventual equalization of pressure in the subarachnoid space. This was successfully controlled by avoidance of the causative irritants, which were both foods and inhalants. Cerebral allergy can simulate a countless number of diseases. There are, on record, cases where it has effected marked personality and mental changes.6 With improvement in our diagnost,ic apparatus, along with continued detailed study of each case, we may be able to recognize the underlying altered physiology in these unfortunate people and thereby establish them as useful citizens in their community. SUMMBRP
1. A case of food allergy causing cerebral edema in a patient with familial allergy is presented. 2. The symptoms were controlled or aggravated at will, by elimination or introduction of the offending allergen. 3. Improvement in personality, but not of the intelligence quotient, followed cessation of the cerebral edema.
176
THE
JOURNAL
OF
ALLERGY
REFERENCES 1. Vaughan, W. T.: Allergic Migraine, J. A. M. A. 88: 1383, 1927. 2. Criep, L. H.: Allergic Vertigo, Pennsylvania M. J. 43: 258, 1939. 3. Clark, T. W.: Allergic Manifestations m the Central Nervous System, New York State J. Med. 39: 1498, 1939. Protein Sensitization as a Possible Cause of Epilepsy and Cancer, 4. Ward, J. F.: New York M. J. 115: 592, 1922. Heatlaches of Allergic Origin, M. Clin. 5. Thomas, J. W., and Johnston, C. R. K.: North America 24: 285, 1940. 6. Vaughan, W. T.: Practice of Allergy, ed. 1, St. Louis, 1939, The C. V. Mosby Co., p, 1024. 7. Davidoff, L. M., and Kopeloff, N.: Local Cerebral Anaphylaxis in the Dog, Proc. Sot. Exper. Biol. & Med. 31: 980, 19.74. 8. Kennedy, F., Wortis, S. B., and Wortis, H.: Clinical Evidence for Cerebral Vasomotor Changes, New York State J. Med. 38: 1441, 1938. 9. Goltman, A. M.: The Mechanism of Migraine, J. ALLERGY 7: 351, 1936.