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Treatment of acquired epileptic aphasia
Volume 90 Number 6
Brief clinical and laboratory observations
nary artery embolism in a h u m a n fetus spontaneously aborted at five months; there was no adhesion of the embolus to the arterial wall. Examination of several other fetuses failed to show similar findings. In a series of 28 instances of coronary embolism in 856 autopsied infants and children, O p p e n h e i m e r and Esterly ~ demonstrated the emboli to arise from either mural thrombi, vegetations associated with bacterial endocarditis, or venous thromboses with passage of clots across either the atrial or ventricular septum. In only two patients, both 11 years o f age, was there evidence of coronary sclerosis and in neither could a source for the emboli be identified. In another series of 29 cases, Bor ~ reported essentially similar findings. The histologic sections in our patient indicate that the inflammatory condition of the coronary arterial wall was of relatively recent onset and the fact that the infant was delivered live at term tends to support that contention. SUMMARY A unique occurrence o f antenatal thrombosis of the left main coronary artery in a term infant is presented. The clinical features are indistinguishable from those of
Treatment of acquired epileptic aphasia Ruthmary K. Deuel, M.D.,* Chicago, IlL, and Nicholas J. Lenn, M.D., Davis, Calif.
L o N G - LA S T I N G acquired receptive and expressive aphasia associated with continuous severe electroencephalographic abnormalities and infrequent seizures has only been reported in childhood, is o f unknown and probably diverse etiology, and frequently has a devastating effect on the subsequent life course of the patient. 1-' The present report presents the first such case in which alleviation of aphasia was clearly and rapidly accomplished by treat-
Supported in part by grant No. PHS 2P01 HD04583, Department of Pediatrics, the Joseph P. Kennedy Mental Research Center, University of Chicago. Presented to the Child Neurology Society Annual Meeting, October, 1974. *Reprint address: Department of Pediatrics, St. Louis Children's Hospital, 500 Kingshighway Blvd., St Louis, Mo. 63110.
959
several other forms of congenital heart disease. The etiology o f the thrombosis is unknown.
REFERENCES 1. Oppenheimer EH, and Esterley JR: Some aspects of cardiac pathology in infancy and childhood. III. coronary embolism, John Hopkins Med J 120:317, 1967. 2. James TN, Froggat P, and Marshall TK: De subitaneis mortibus. II. Coronary embolism in the fetus, Circulation 48:890, 1973. 3. Favara BE, Franeiosu RA, and Butterfield L J: Disseminated intravascular and cardiac thrombosis of the neonate, Am J Dis Child 127:197, 1974. 4. Askenazi J, and Nadas AS: Anomalous left coronary artery originating from the pulmonary artery. Report on 15 cases, Circulation 51:976, 1975. 5. Behrendt DM, Aberdeen E, Waterson D J, and Bonham Carter RD: Total anomalous pulmonary venous drainage in infants. I. Clinical and hemodynamic findings, methods and results of operation in 37 cases, Circulation 46:347, 1972. 6. Chesler E, Joffie HS, Vecht R, Beck W, Schrire V: Ultrasound cardiography in single ventricle and the hypoplastic left and right heart syndromes, Circulation 42:123, 1970. 7. Bor I: Myocardial infarction and ischemic heart disease in infants and children. Analyses of 29 cases and review of the literature, Arch Dis Child 44:268, 1969.
ment with anticonvulsant medication, thus allowing the patient to continue her normal school and social life. C A S E REPORT
Patient K. H., a right-handed female born after a normal pregnancy, had normal developmental milestones. She used words at 12 months and talked in sentences by two years. At age four brief episodes of staring and loss of consciousness began to occur several times a day. A complete neurologic examination, including speech, was normal; an EEG, however, showed gener-
Abbreviation used EEG: electroencephalogram
]
alized spike and wave discharges at a rate of 1 1/2 to 2 cycles per second. Treatment with ethosuximide, 250 mg three times a day, and phenobarbital, 30 mg three times a day, was prescribed and seizures stopped. At age 6 4/12, inasmuch as her teachers noted that she responded slowly to verbal commands, a normal pure tone audiogram was obtained. The dose of phenobarbital was decreased with improvement. Six months later over a period of one week, the patient's speech comprehension and expression deteriorated and became even worse when the dose of ethosuximide was reduced. Social interaction, even with her parents, was impossible. She was hospitalized and was found to have marked receptive and expressive aphasia, with an otherwise normal
960
Brief cfinicaI and laboratory observations
K,H, 8"11"72 Eyesr [t.E~
PLACEId(NT
The Journal of Pediatrics June 1977
F3-AI
~_~,~
F4 -AZ C3 -AI
mint
C4 - A2 ~
~
T3-AI T4 -A2 o,.,,
50~vL - lUC
Fig. 1. EEG taken at the height of the first aphasic episode. Spike discharges were continuous throughout this record. Most were bilaterally synchronous, but occasionally independent right temporal discharges were seen. Such a pattern, of almost continuous bilateral spike discharges with left or right temporal predominance, is typical of acquired epileptic aphasia; .~ neurologic examination. Results of skull roentgenograms, brain scan, pneumoencephalogram, and a pure tone audiogram were all normal. Spinal fluid examination was normal, including colloidal gold curve. An EEG was abnormal with frequent bilaterally synchronous spikes and single spike-wave complexes (Fig. 1). Despite the absence of clinical seizures, the dose of ethosuximide was increased to 750 mg/day. An EEG taken seven days later was improved but speech was no better. Over the next week, however, the patient made rapid, progressive improvement to normal speech and understanding. She returned to her regular school class. Five months later dense aphasia developed for a second time, but lasted tess than one month; recovery was complete within 10 days after the dose of phenobarbital was increased to 180 mg/day. Ten months later, inasmuch as the patient was reported to be hyperkinetic, the dose of phenobarbital was decreased to 120 mg daily. Within seven days aphasia was again so severe she had no useful communication. The higher dose of phenobarbital was reinstituted and for the third time speech became normal, this time within four days of the increase in dosage of phenobarbital. Two days later phenobarbital therapy was stopped due to misunderstanding. Dense aphasia was present by two days after the last dose. During this fourth aphasic interval intravenous diazepam led to suppression of spike discharges on the EEG, but no improvement in speech, which was tested during the period of spike suppression. Primidone therapy was then started and within five days the patient's speech had regained normal fluency. On examination at age 11 1/2 her social life was normal, and her progress was good in a class for children with learning disabilities. The neurologic examination, including speech, was normal. No seizures have occurred since age 5 4/12 years. DISCUSSION The cardinal symptoms of this syndrome are acquired receptive and expressive aphasia, severe continuous bitemporal electroencephalographic abnormalities (Fig. 1), and occasional seizures of several clinical types.
Behavior disturbances arc common. Whereas the seizure disorder is benign in this syndrome, the communication disorder constitutes a severe handicap. Recovery of the ability for adequate communication may require years of special schooling? Patients may appear to be mentally retarded or psychotic and thus may never receive treatment directed specifically toward re-establishing speech, especially when seizures are absent. Our patient's E E G and clinical response to manipulation of anticonvulsant drugs suggest that the aphasic symptoms were on the basis o f a b n o r m a l cerebral electrical events, i.e., she was experiencing an "epileptic" aphasia. This interpretation was also made by Shoumaker and associates ~on the basis of the relationship between the degree of EEG abnormality and speech quality in their patients. Treatment of patients with this syndrome has often included anticonvulsant drugs, but the usefulness of the medications for treating the aphasia per se has not been previously documented. Perhaps this is because elimination of clinical convulsions, the usual goal of anticonvulsant treatment, is easily achieved in patients with this syndrome. Also, as illustrated by Patient K.H. and other cases? . . . . there is a variable delay between administration of the anticonvulsant drug and changes in EEG and speech. The interval between onset of the aphasia and the start of anticonvulsant treatment may also be important, with improvement more likely in promptly treated cases. The syndrome of acquired asphasia in conjunction with EEG abnormalities and seizures appears to be an epileptic phenomenon. Any child presenting with acquired aphasia in the absence of a demonstrable lesion, if the EEG supports a diagnosis of epileptic aphasia, should be started early on anticonvulsant treatment, with relief of aphasia as the ultimate goal.
Volume 90 Number 6
Brief clinical and laboratory observations
REFERENCES 1. Landau WM, Kleffner FR: Syndrome of acquired aphasia with convulsive disorder in children, Neurology 7:523, 1957. 2. Worster-Drought C: An unusual form of acquired aphasia in children, Dev Med Child Neurol 13:563, 1971. 3. Gascon G, Victor D, Lombroso CT, and Goodglass H: Language disorder, convulsive disorder, and electroencephalographic abnormalities, Arch Neurol 28:156, 1973.
Dominant
polysyndactyly: A report of two families Carol E. Anderson, M.D.,* Paul M. Fernhoff, M.D., Atlanta, Ga, and Linda Quan, M.D., Seattle, Wash.
POLYDACTYLY of the hands and feet is a common minor malformation. When it is preaxial, affecting the thumbs or big toes, and is seen in conjunction with syndactyly, another common trait, it is classified as preaxial polydactyly IV or polysyndactyly?-' This uncommon malformation :' demonstrates an autosomal dominant mode of inheritance and varies in its expression. We report two families who illustrate these points (Fig. l). FAMILY A The only affected members are a 31-year-old woman and her 7-year-old daughter. The mother was the fourth of eight children; her father was 38 years old at her birth. She had broad and bifid thumbs, bilateral soft tissue webs between the third and fourth digits, and bilateral accessory digits originating from the proximal phalanx of the fifth fingers. She also had bilateral accessory and preaxial toes, proximally placed fifth toes, and soft tissue webs between all toes. The 7-year-old daughter had similar findings, except that she had no significant webbing of her hands, and she had syndactyly between her first and From the Cancer and Birth Defects Division, Bureau of Epidemiology, and the Pathology Division, Bureau of Laboratories, Center for Disease Control, Public Health Service, United States Department of Health, Education and Welfare, and the University of Washington, Department of Pediatrics, School of Medicine. *Reprint address: Centerfor Disease Control, Attn: Carol E. Anderson, M.D., Cancer and Birth Defects Division, Bureau of Epidemiology, Building 1, Room 5115, Atlanta, GA 30333.
96 1
4. Shoumaker R, Bennett D, Bray P, and Curless R: Clinical and EEG manifestations of an unusual aphasic syndrome in children, Neurology 24:10, 1974. 5. McKinney W, and McGreal DA: An aphasic syndrome in children, Can Med Assoc J 110:637, 1974. 6. Watters G: The syndrome of acquired aphasia and convulsive disorder in children, Can Med Assoc J 110:611, 1974.
second toes and normal fifth digits on both feet. Mother and daughter have each had the accessory digits removed; the daughter has had plastic surgical repair of her thumbs. FAMILY B In this family, one individual is affected in each of four generations in direct descent. The first person affected (1-3) is now 70 years old. He was born, the eighth of 11 children, when his father was > 70 years. He has duplication of the thumb (one thumb with two nails) and soft tissue webs at the base of the second, third, and fourth digits. His son has bilateral abnormal thumbs (no roentgenograms available) with soft tissue webs in the same locations as his father. The third affected member had abnormal thumbs (no roentgenograms available) with more extensive webbing between the second, third, and fourth fingers. Her child (IV-l) has bilateral duplication of thumbs (one thumb with two nails) (Fig. 2) and extensive syndactyly of the fingers like her mother, but she is the first and only family member to have syndactyly of the fourth and fifth toes. Each of the women has undergone plastic surgery. DISCUSSION Family B better illustrates an autosomal dominant mode of inheritance, with half or all the members of three consecutive generations affected. Advanced paternal age has not been studied in the other eight families described with polysyndactyly,~-~ but has been associated with other autosomal dominant gene mutations '~and may be a factor in these two families. Although the two affected members of Family A have functional heart murmurs, there are no associated defects in either family. Other defects have been described in association with one case of polysyndactyly (cleft palate, pectus excavatum, high-arched palate, and hypertelorism)? Hands and feet have not been symmetric. Findings varied between our families as in the previous reports '-8 (Table I). In particular, although syndactyly of the feet has been the most consistent feature previously described, it was not present in Family B until the fourth generation.
Brief clinical and laboratory observations
nary artery embolism in a h u m a n fetus spontaneously aborted at five months; there was no adhesion of the embolus to the arterial wall. Examination of several other fetuses failed to show similar findings. In a series of 28 instances of coronary embolism in 856 autopsied infants and children, O p p e n h e i m e r and Esterly ~ demonstrated the emboli to arise from either mural thrombi, vegetations associated with bacterial endocarditis, or venous thromboses with passage of clots across either the atrial or ventricular septum. In only two patients, both 11 years o f age, was there evidence of coronary sclerosis and in neither could a source for the emboli be identified. In another series of 29 cases, Bor ~ reported essentially similar findings. The histologic sections in our patient indicate that the inflammatory condition of the coronary arterial wall was of relatively recent onset and the fact that the infant was delivered live at term tends to support that contention. SUMMARY A unique occurrence o f antenatal thrombosis of the left main coronary artery in a term infant is presented. The clinical features are indistinguishable from those of
Treatment of acquired epileptic aphasia Ruthmary K. Deuel, M.D.,* Chicago, IlL, and Nicholas J. Lenn, M.D., Davis, Calif.
L o N G - LA S T I N G acquired receptive and expressive aphasia associated with continuous severe electroencephalographic abnormalities and infrequent seizures has only been reported in childhood, is o f unknown and probably diverse etiology, and frequently has a devastating effect on the subsequent life course of the patient. 1-' The present report presents the first such case in which alleviation of aphasia was clearly and rapidly accomplished by treat-
Supported in part by grant No. PHS 2P01 HD04583, Department of Pediatrics, the Joseph P. Kennedy Mental Research Center, University of Chicago. Presented to the Child Neurology Society Annual Meeting, October, 1974. *Reprint address: Department of Pediatrics, St. Louis Children's Hospital, 500 Kingshighway Blvd., St Louis, Mo. 63110.
959
several other forms of congenital heart disease. The etiology o f the thrombosis is unknown.
REFERENCES 1. Oppenheimer EH, and Esterley JR: Some aspects of cardiac pathology in infancy and childhood. III. coronary embolism, John Hopkins Med J 120:317, 1967. 2. James TN, Froggat P, and Marshall TK: De subitaneis mortibus. II. Coronary embolism in the fetus, Circulation 48:890, 1973. 3. Favara BE, Franeiosu RA, and Butterfield L J: Disseminated intravascular and cardiac thrombosis of the neonate, Am J Dis Child 127:197, 1974. 4. Askenazi J, and Nadas AS: Anomalous left coronary artery originating from the pulmonary artery. Report on 15 cases, Circulation 51:976, 1975. 5. Behrendt DM, Aberdeen E, Waterson D J, and Bonham Carter RD: Total anomalous pulmonary venous drainage in infants. I. Clinical and hemodynamic findings, methods and results of operation in 37 cases, Circulation 46:347, 1972. 6. Chesler E, Joffie HS, Vecht R, Beck W, Schrire V: Ultrasound cardiography in single ventricle and the hypoplastic left and right heart syndromes, Circulation 42:123, 1970. 7. Bor I: Myocardial infarction and ischemic heart disease in infants and children. Analyses of 29 cases and review of the literature, Arch Dis Child 44:268, 1969.
ment with anticonvulsant medication, thus allowing the patient to continue her normal school and social life. C A S E REPORT
Patient K. H., a right-handed female born after a normal pregnancy, had normal developmental milestones. She used words at 12 months and talked in sentences by two years. At age four brief episodes of staring and loss of consciousness began to occur several times a day. A complete neurologic examination, including speech, was normal; an EEG, however, showed gener-
Abbreviation used EEG: electroencephalogram
]
alized spike and wave discharges at a rate of 1 1/2 to 2 cycles per second. Treatment with ethosuximide, 250 mg three times a day, and phenobarbital, 30 mg three times a day, was prescribed and seizures stopped. At age 6 4/12, inasmuch as her teachers noted that she responded slowly to verbal commands, a normal pure tone audiogram was obtained. The dose of phenobarbital was decreased with improvement. Six months later over a period of one week, the patient's speech comprehension and expression deteriorated and became even worse when the dose of ethosuximide was reduced. Social interaction, even with her parents, was impossible. She was hospitalized and was found to have marked receptive and expressive aphasia, with an otherwise normal
960
Brief cfinicaI and laboratory observations
K,H, 8"11"72 Eyesr [t.E~
PLACEId(NT
The Journal of Pediatrics June 1977
F3-AI
~_~,~
F4 -AZ C3 -AI
mint
C4 - A2 ~
~
T3-AI T4 -A2 o,.,,
50~vL - lUC
Fig. 1. EEG taken at the height of the first aphasic episode. Spike discharges were continuous throughout this record. Most were bilaterally synchronous, but occasionally independent right temporal discharges were seen. Such a pattern, of almost continuous bilateral spike discharges with left or right temporal predominance, is typical of acquired epileptic aphasia; .~ neurologic examination. Results of skull roentgenograms, brain scan, pneumoencephalogram, and a pure tone audiogram were all normal. Spinal fluid examination was normal, including colloidal gold curve. An EEG was abnormal with frequent bilaterally synchronous spikes and single spike-wave complexes (Fig. 1). Despite the absence of clinical seizures, the dose of ethosuximide was increased to 750 mg/day. An EEG taken seven days later was improved but speech was no better. Over the next week, however, the patient made rapid, progressive improvement to normal speech and understanding. She returned to her regular school class. Five months later dense aphasia developed for a second time, but lasted tess than one month; recovery was complete within 10 days after the dose of phenobarbital was increased to 180 mg/day. Ten months later, inasmuch as the patient was reported to be hyperkinetic, the dose of phenobarbital was decreased to 120 mg daily. Within seven days aphasia was again so severe she had no useful communication. The higher dose of phenobarbital was reinstituted and for the third time speech became normal, this time within four days of the increase in dosage of phenobarbital. Two days later phenobarbital therapy was stopped due to misunderstanding. Dense aphasia was present by two days after the last dose. During this fourth aphasic interval intravenous diazepam led to suppression of spike discharges on the EEG, but no improvement in speech, which was tested during the period of spike suppression. Primidone therapy was then started and within five days the patient's speech had regained normal fluency. On examination at age 11 1/2 her social life was normal, and her progress was good in a class for children with learning disabilities. The neurologic examination, including speech, was normal. No seizures have occurred since age 5 4/12 years. DISCUSSION The cardinal symptoms of this syndrome are acquired receptive and expressive aphasia, severe continuous bitemporal electroencephalographic abnormalities (Fig. 1), and occasional seizures of several clinical types.
Behavior disturbances arc common. Whereas the seizure disorder is benign in this syndrome, the communication disorder constitutes a severe handicap. Recovery of the ability for adequate communication may require years of special schooling? Patients may appear to be mentally retarded or psychotic and thus may never receive treatment directed specifically toward re-establishing speech, especially when seizures are absent. Our patient's E E G and clinical response to manipulation of anticonvulsant drugs suggest that the aphasic symptoms were on the basis o f a b n o r m a l cerebral electrical events, i.e., she was experiencing an "epileptic" aphasia. This interpretation was also made by Shoumaker and associates ~on the basis of the relationship between the degree of EEG abnormality and speech quality in their patients. Treatment of patients with this syndrome has often included anticonvulsant drugs, but the usefulness of the medications for treating the aphasia per se has not been previously documented. Perhaps this is because elimination of clinical convulsions, the usual goal of anticonvulsant treatment, is easily achieved in patients with this syndrome. Also, as illustrated by Patient K.H. and other cases? . . . . there is a variable delay between administration of the anticonvulsant drug and changes in EEG and speech. The interval between onset of the aphasia and the start of anticonvulsant treatment may also be important, with improvement more likely in promptly treated cases. The syndrome of acquired asphasia in conjunction with EEG abnormalities and seizures appears to be an epileptic phenomenon. Any child presenting with acquired aphasia in the absence of a demonstrable lesion, if the EEG supports a diagnosis of epileptic aphasia, should be started early on anticonvulsant treatment, with relief of aphasia as the ultimate goal.
Volume 90 Number 6
Brief clinical and laboratory observations
REFERENCES 1. Landau WM, Kleffner FR: Syndrome of acquired aphasia with convulsive disorder in children, Neurology 7:523, 1957. 2. Worster-Drought C: An unusual form of acquired aphasia in children, Dev Med Child Neurol 13:563, 1971. 3. Gascon G, Victor D, Lombroso CT, and Goodglass H: Language disorder, convulsive disorder, and electroencephalographic abnormalities, Arch Neurol 28:156, 1973.
Dominant
polysyndactyly: A report of two families Carol E. Anderson, M.D.,* Paul M. Fernhoff, M.D., Atlanta, Ga, and Linda Quan, M.D., Seattle, Wash.
POLYDACTYLY of the hands and feet is a common minor malformation. When it is preaxial, affecting the thumbs or big toes, and is seen in conjunction with syndactyly, another common trait, it is classified as preaxial polydactyly IV or polysyndactyly?-' This uncommon malformation :' demonstrates an autosomal dominant mode of inheritance and varies in its expression. We report two families who illustrate these points (Fig. l). FAMILY A The only affected members are a 31-year-old woman and her 7-year-old daughter. The mother was the fourth of eight children; her father was 38 years old at her birth. She had broad and bifid thumbs, bilateral soft tissue webs between the third and fourth digits, and bilateral accessory digits originating from the proximal phalanx of the fifth fingers. She also had bilateral accessory and preaxial toes, proximally placed fifth toes, and soft tissue webs between all toes. The 7-year-old daughter had similar findings, except that she had no significant webbing of her hands, and she had syndactyly between her first and From the Cancer and Birth Defects Division, Bureau of Epidemiology, and the Pathology Division, Bureau of Laboratories, Center for Disease Control, Public Health Service, United States Department of Health, Education and Welfare, and the University of Washington, Department of Pediatrics, School of Medicine. *Reprint address: Centerfor Disease Control, Attn: Carol E. Anderson, M.D., Cancer and Birth Defects Division, Bureau of Epidemiology, Building 1, Room 5115, Atlanta, GA 30333.
96 1
4. Shoumaker R, Bennett D, Bray P, and Curless R: Clinical and EEG manifestations of an unusual aphasic syndrome in children, Neurology 24:10, 1974. 5. McKinney W, and McGreal DA: An aphasic syndrome in children, Can Med Assoc J 110:637, 1974. 6. Watters G: The syndrome of acquired aphasia and convulsive disorder in children, Can Med Assoc J 110:611, 1974.
second toes and normal fifth digits on both feet. Mother and daughter have each had the accessory digits removed; the daughter has had plastic surgical repair of her thumbs. FAMILY B In this family, one individual is affected in each of four generations in direct descent. The first person affected (1-3) is now 70 years old. He was born, the eighth of 11 children, when his father was > 70 years. He has duplication of the thumb (one thumb with two nails) and soft tissue webs at the base of the second, third, and fourth digits. His son has bilateral abnormal thumbs (no roentgenograms available) with soft tissue webs in the same locations as his father. The third affected member had abnormal thumbs (no roentgenograms available) with more extensive webbing between the second, third, and fourth fingers. Her child (IV-l) has bilateral duplication of thumbs (one thumb with two nails) (Fig. 2) and extensive syndactyly of the fingers like her mother, but she is the first and only family member to have syndactyly of the fourth and fifth toes. Each of the women has undergone plastic surgery. DISCUSSION Family B better illustrates an autosomal dominant mode of inheritance, with half or all the members of three consecutive generations affected. Advanced paternal age has not been studied in the other eight families described with polysyndactyly,~-~ but has been associated with other autosomal dominant gene mutations '~and may be a factor in these two families. Although the two affected members of Family A have functional heart murmurs, there are no associated defects in either family. Other defects have been described in association with one case of polysyndactyly (cleft palate, pectus excavatum, high-arched palate, and hypertelorism)? Hands and feet have not been symmetric. Findings varied between our families as in the previous reports '-8 (Table I). In particular, although syndactyly of the feet has been the most consistent feature previously described, it was not present in Family B until the fourth generation.