Volume 95 Number 3
Editorial correspondence
Reply To the Editor: Preston's letter has properly called attention to the implications for infant nutrition raised by the recognition that Clostridium botulinum can produce its toxin in vivo in the infant gut, in some cases so rapidly that typical crib death results. M y colleagues and I have had under active investigation several factors that may govern such intestinal colonization and toxin production, including the possible differential availability of iron to C. botulinum from either formula, breast milk, or other dietary sources such as cereal. We are presently analyzing the data collected from our first 50 hospitized patients and their controls and plan to publish the results in the near future. Stephen S. Arnon, M.D. Infectious Disease Section California Department of Health Services Berkeley, CA 94704
495
of her anemia, and abatement of the chipping lead-ladened paint in her house. The abnormal liver enzymes were confusing initially, but the CSF protein concentration is usually normal in Reye syndrome and was elevated in this lead-burdened child. Peter D. Magnus, M.D., F.A.A.P., M.P.H. 17260 Kohfield Road Bend, OR 97701 Richard J. Powers, M.D. Albin Leong, M.D. CHLA 4560 Sunset Bird Los Angeles, CA 90054 REFERENCE
!.
Fox DW, Hart MC, Bergeson PS, Jarrett PB, Stillman AE, and Huxtable RJ: Pyrrolizidine (Senecio) intoxication mimicking Reye syndrome, J PEDIATR 93:980, 1978.
Reply Pb encephalopathy mimicking Reye syndrome To the Editor: We have an addition to make to the "discussion" of the article entitled "Pyrrolizidine (Senecio) intoxication mimicking Reye syndrome."' The authors state that "several diseases produce encephalopathy, elevation of serum transaminase values, and other signs of liver dysfunction." In addition to those cited, we would like to add lead encephalopathy. A recent example was a 21-month-old black girl admitted to Children's Hospital of Los Angeles with a four-day history of vomiting, anorexia, and lethargy. She was anemic (Hgb 7.8 gm/dl; MCV 62 /~3), and mildly dehydrated. CSF showed a normal pressure, 5 leukocytes/mm 3, and a protein concentration of 173 mg/dl (normal CSF and blood glucose concentration). Serum enzymes were SGOT 152 IU and SGPT 124 IU; serum ammonia level was 242 #g/dl. The initial impressions were iron deficiency anemia with Reye snydrome, toxic encephalopathy, 'acute gastroenteritis, gastrointestinal obstruction, or hepatitis. Approximately 12 hours after admission, after being "rehydrated," the patient had a grand mal seizure lasting 10 minutes, and eventually needed ventilatory assistance for several hours. Several hours after the medical management of her seizures and cerebral edema, however, "lead flecks" were noted on the admission flat plate, and long bone films revealed "lead lines." The patient was chelated immediately (dimercaprol and versenate) for seven days, and later for five days more; she has received two more out-patient series of chelations with CaNaEDTA alone. Her pre-chelation blood lead concentration was 231 /~g/dl, and her first erythrocyte protoporphyrin obtained 13 days after the first chelation (when her blood lead had diminished to 46 btg/dl), was still markedly elevated at 829/Lg/dl. Fortunately, this patient has made a successful recovery after chelation therapy, correction
To the Editor: The differentiation of Reye syndrome from lead poisoning encephalopathy has previously been commented upon? However, Drs. Magnus, Powers, and Leong are to be congratulated on their astute differentiation of this case. They once again emphasize the importance of a good history and physical, and also of knowing the disease entities prevalent in your community. Donald W. Fox, D.O. Perinatal Services Welborn Baptist Hospital 401 S.E. Sixth St Evansville, I N 47713 Paul S. Bergeson, M.D. Good Samaritan Hospital Phoenix, A Z 85072 REFERENCE
1. Schubert W, Bobo RC, Partin JC, et al: Reye's syndrome, Disease-A-Month December, 1975.
Cerebral blood flow re intracranial hemorrhage To the Editor: We read the recent paper by Lou et aP with great interest. Impaired autoregulation of cerebral blood flow (CBF) in asphyxiated infants is noteworthy and, as they postulate, may have an etiologic implication to neonatal intracranial hemorrhage (ICH). We wish to draw your attention to some of our recent observations in this regard. To evaluate various factors which may contribute to ICH, 40 variables were analyzed in 198 consecutive infants requiring
496
Editorial correspondence
assisted ventilation in our N1CU during a 24-month period (1976-1978). Sixty-two infants with ICH (Group I) and 136 infants without ICH (Group II) were compared. The diagnosis of ICH was documented at autopsy in all 57 who died. In Group II no ICH was noted at autopsy in 23 of the infants who died, and the rest had no clinical evidence of a major ICH. In addition, there were no differences in the incidence of hyperglycemia, administration of sodium bicarbonate, and other perinatal factors between the groups. Group I infants were more immature, asphyxiated, hypothermic, and hypotensive than Group II at birth. In an attempt to correct severe hypotension in asphyxiated infants, a rapid volume expansion was carried out, shown by a larger volume of fluid administered to Group I infants during the first two days of life. ~ Lou et al 1 postulate that impaired autoregulation of CBF in asphyxiated infants may predispose to ICH by causing already maximally dilated vessels to rupture when the blood pressure returns to normal. We have noted several times that some infants with severe asphyxia and hypotension respond to the administration of volume expanders, and within the next few hours seemed to develop ICH. The mean age of ICH was 42 _+ 6.5 hours, with 50% of the infants developing ICH within the first 24 hours. Thus, it seems appropriate to speculate that rapid volume expansion in these infants may play a role in the occurrence of intracranial hemorrhage. Age of death varied depending upon the response to ' treatment (10 _+ 3.5 days); 25 of 47 (23%) infants died within two days.
T.N.K. Raju, M.D. Assistant Professor of Pediatrics George Cybulski J. Ramirez-Lavin, M.D. D. Vidyasagar, M.D. Professor of Pediatrics Director of Neonatology University of Illinois Hospital 840 South Wood St. Chicago, 'IL 60612 REFERENCES 1.
2.
Lou HC, Lassen NA, Friis-Hansen B: Impaired autoregulation of cerebral blood flow in the distressed newborn infant, J PEDIATR 94:118, 1979. Cybulski GR, Raju TNK, Ramirez-Lavin J, and Vidyasagar D: Clinical and biochemical factors related to neonatal intracranial hemorrhage (1CH) in the neonate: Abstract to the Midwest Society for Pediatric Research, November, 1978.
To the Editor: Drs. Lou, Lassen, and Friis-Hansen have described very low values for cerebral blood flow (CBF) in distressed newborn infants, and conclude that autoregulation of CBF in these infants is impaired? These findings are at variance with our own data obtained using jugular venous occlusion plethysmography ~- (a noninvasive method) in a similar group of 13 premature infants with respiratory distress? Cerebral blood flow was invariably increased, the increase being greatest in the sickest infants.
The Journal of Pediatrics September 1979
Multivariate analysis showed that the most significant correlation of CBF was with arterial Pc% levels. Systolic blood pressure, when measured, ranged from 36 to 45 mm Hg, which we considered to be low normal values for infants of low gestation on the first day of life. We feel that the explanation of the discrepancy may lie in the method used by Lou et al. Calculation of the value for CBF from xenon studies of the type used assumes that no recirculation of the tracer occurs. In older subjects without lung disease, this is a reasonable assumption as xenon is rapidly cleared through normal lungs, mostly in one circulation. In the healthy newborn infant however, a degree of right-to-left shunting occurs during the first 24 hours of life. If the infant is premature, has a history of asphyxia, or has respiratory disease, this R-L shunt can be very large.'. ~ If such a shunt were present in the infants examined, as would seem likely, recirculation would have occurred, reducing the value of CBF obtained. Without further evidence that recirculation is not occurring, we do not feel that the results obtained can be held to demonstrate that the rather mild birth asphyxia and degree of hypotension reported impairs autoregulation in the newborn infant. Neither can they be considered to be"of immediate relevance to the management of the individual patient," thus obviating the need for informed parental consent for research procedures involving radioactive isotopes.
Richard W. 1. Cooke, M.B., M.R.C.P., D.C.H. Peter Rolfe, B.Sc., Ph.D. Department Paediatric Cardiology Erasmus University Sofia Kinderziekenhuis Gordelweg 160, Rotterdam The Netherlands REFERENCES 1.
Lou HC, Lassen NA, and Friis-Hansen B: Impaired autoregulation of cerebral blood flow in the distressed newborn infant, J PEDIATR 94: 118, 1978. 2. Cooke RWI, and Rolfe P: Cerebral blood flow measurement using venous occlusion plethysmography in the newborn infant, in Rolfe P, editors: Non-invasive physiological measurements, London, 1979, Academic Press, Inc. ,S 3. Cooke RWI, Rolfe P, and Howat P: Apparent cerebral blood flow in neonatal respiratory disease, Dev Med Child Neurol 21:154, 1979. 4. Wallgren G, Hanson JS, Tabakin BS, Raiha N, and Vapaavouri E: Quantitative studies of the human neonatal circulation, Acta Paediatr. Stockh. 56(Supp 179):71, 1967. 5. Strang LB: Neonatal respiration physiological and clinical studies, Oxford, 1977, Blackwell Scientific Publications, pp 207-209.
To the Editor: The recent study by Lou et al' concluded that cerebrovascular ~'autoregulation was impaired in the distressed newborn infant: [cerebral blood flow] CBF was pressure passive and dependent upon the arterial BP [blood pressure]." We wish to offer several alternate interpretations to the investigators' data.
Editorial correspondence
Reply To the Editor: Preston's letter has properly called attention to the implications for infant nutrition raised by the recognition that Clostridium botulinum can produce its toxin in vivo in the infant gut, in some cases so rapidly that typical crib death results. M y colleagues and I have had under active investigation several factors that may govern such intestinal colonization and toxin production, including the possible differential availability of iron to C. botulinum from either formula, breast milk, or other dietary sources such as cereal. We are presently analyzing the data collected from our first 50 hospitized patients and their controls and plan to publish the results in the near future. Stephen S. Arnon, M.D. Infectious Disease Section California Department of Health Services Berkeley, CA 94704
495
of her anemia, and abatement of the chipping lead-ladened paint in her house. The abnormal liver enzymes were confusing initially, but the CSF protein concentration is usually normal in Reye syndrome and was elevated in this lead-burdened child. Peter D. Magnus, M.D., F.A.A.P., M.P.H. 17260 Kohfield Road Bend, OR 97701 Richard J. Powers, M.D. Albin Leong, M.D. CHLA 4560 Sunset Bird Los Angeles, CA 90054 REFERENCE
!.
Fox DW, Hart MC, Bergeson PS, Jarrett PB, Stillman AE, and Huxtable RJ: Pyrrolizidine (Senecio) intoxication mimicking Reye syndrome, J PEDIATR 93:980, 1978.
Reply Pb encephalopathy mimicking Reye syndrome To the Editor: We have an addition to make to the "discussion" of the article entitled "Pyrrolizidine (Senecio) intoxication mimicking Reye syndrome."' The authors state that "several diseases produce encephalopathy, elevation of serum transaminase values, and other signs of liver dysfunction." In addition to those cited, we would like to add lead encephalopathy. A recent example was a 21-month-old black girl admitted to Children's Hospital of Los Angeles with a four-day history of vomiting, anorexia, and lethargy. She was anemic (Hgb 7.8 gm/dl; MCV 62 /~3), and mildly dehydrated. CSF showed a normal pressure, 5 leukocytes/mm 3, and a protein concentration of 173 mg/dl (normal CSF and blood glucose concentration). Serum enzymes were SGOT 152 IU and SGPT 124 IU; serum ammonia level was 242 #g/dl. The initial impressions were iron deficiency anemia with Reye snydrome, toxic encephalopathy, 'acute gastroenteritis, gastrointestinal obstruction, or hepatitis. Approximately 12 hours after admission, after being "rehydrated," the patient had a grand mal seizure lasting 10 minutes, and eventually needed ventilatory assistance for several hours. Several hours after the medical management of her seizures and cerebral edema, however, "lead flecks" were noted on the admission flat plate, and long bone films revealed "lead lines." The patient was chelated immediately (dimercaprol and versenate) for seven days, and later for five days more; she has received two more out-patient series of chelations with CaNaEDTA alone. Her pre-chelation blood lead concentration was 231 /~g/dl, and her first erythrocyte protoporphyrin obtained 13 days after the first chelation (when her blood lead had diminished to 46 btg/dl), was still markedly elevated at 829/Lg/dl. Fortunately, this patient has made a successful recovery after chelation therapy, correction
To the Editor: The differentiation of Reye syndrome from lead poisoning encephalopathy has previously been commented upon? However, Drs. Magnus, Powers, and Leong are to be congratulated on their astute differentiation of this case. They once again emphasize the importance of a good history and physical, and also of knowing the disease entities prevalent in your community. Donald W. Fox, D.O. Perinatal Services Welborn Baptist Hospital 401 S.E. Sixth St Evansville, I N 47713 Paul S. Bergeson, M.D. Good Samaritan Hospital Phoenix, A Z 85072 REFERENCE
1. Schubert W, Bobo RC, Partin JC, et al: Reye's syndrome, Disease-A-Month December, 1975.
Cerebral blood flow re intracranial hemorrhage To the Editor: We read the recent paper by Lou et aP with great interest. Impaired autoregulation of cerebral blood flow (CBF) in asphyxiated infants is noteworthy and, as they postulate, may have an etiologic implication to neonatal intracranial hemorrhage (ICH). We wish to draw your attention to some of our recent observations in this regard. To evaluate various factors which may contribute to ICH, 40 variables were analyzed in 198 consecutive infants requiring
496
Editorial correspondence
assisted ventilation in our N1CU during a 24-month period (1976-1978). Sixty-two infants with ICH (Group I) and 136 infants without ICH (Group II) were compared. The diagnosis of ICH was documented at autopsy in all 57 who died. In Group II no ICH was noted at autopsy in 23 of the infants who died, and the rest had no clinical evidence of a major ICH. In addition, there were no differences in the incidence of hyperglycemia, administration of sodium bicarbonate, and other perinatal factors between the groups. Group I infants were more immature, asphyxiated, hypothermic, and hypotensive than Group II at birth. In an attempt to correct severe hypotension in asphyxiated infants, a rapid volume expansion was carried out, shown by a larger volume of fluid administered to Group I infants during the first two days of life. ~ Lou et al 1 postulate that impaired autoregulation of CBF in asphyxiated infants may predispose to ICH by causing already maximally dilated vessels to rupture when the blood pressure returns to normal. We have noted several times that some infants with severe asphyxia and hypotension respond to the administration of volume expanders, and within the next few hours seemed to develop ICH. The mean age of ICH was 42 _+ 6.5 hours, with 50% of the infants developing ICH within the first 24 hours. Thus, it seems appropriate to speculate that rapid volume expansion in these infants may play a role in the occurrence of intracranial hemorrhage. Age of death varied depending upon the response to ' treatment (10 _+ 3.5 days); 25 of 47 (23%) infants died within two days.
T.N.K. Raju, M.D. Assistant Professor of Pediatrics George Cybulski J. Ramirez-Lavin, M.D. D. Vidyasagar, M.D. Professor of Pediatrics Director of Neonatology University of Illinois Hospital 840 South Wood St. Chicago, 'IL 60612 REFERENCES 1.
2.
Lou HC, Lassen NA, Friis-Hansen B: Impaired autoregulation of cerebral blood flow in the distressed newborn infant, J PEDIATR 94:118, 1979. Cybulski GR, Raju TNK, Ramirez-Lavin J, and Vidyasagar D: Clinical and biochemical factors related to neonatal intracranial hemorrhage (1CH) in the neonate: Abstract to the Midwest Society for Pediatric Research, November, 1978.
To the Editor: Drs. Lou, Lassen, and Friis-Hansen have described very low values for cerebral blood flow (CBF) in distressed newborn infants, and conclude that autoregulation of CBF in these infants is impaired? These findings are at variance with our own data obtained using jugular venous occlusion plethysmography ~- (a noninvasive method) in a similar group of 13 premature infants with respiratory distress? Cerebral blood flow was invariably increased, the increase being greatest in the sickest infants.
The Journal of Pediatrics September 1979
Multivariate analysis showed that the most significant correlation of CBF was with arterial Pc% levels. Systolic blood pressure, when measured, ranged from 36 to 45 mm Hg, which we considered to be low normal values for infants of low gestation on the first day of life. We feel that the explanation of the discrepancy may lie in the method used by Lou et al. Calculation of the value for CBF from xenon studies of the type used assumes that no recirculation of the tracer occurs. In older subjects without lung disease, this is a reasonable assumption as xenon is rapidly cleared through normal lungs, mostly in one circulation. In the healthy newborn infant however, a degree of right-to-left shunting occurs during the first 24 hours of life. If the infant is premature, has a history of asphyxia, or has respiratory disease, this R-L shunt can be very large.'. ~ If such a shunt were present in the infants examined, as would seem likely, recirculation would have occurred, reducing the value of CBF obtained. Without further evidence that recirculation is not occurring, we do not feel that the results obtained can be held to demonstrate that the rather mild birth asphyxia and degree of hypotension reported impairs autoregulation in the newborn infant. Neither can they be considered to be"of immediate relevance to the management of the individual patient," thus obviating the need for informed parental consent for research procedures involving radioactive isotopes.
Richard W. 1. Cooke, M.B., M.R.C.P., D.C.H. Peter Rolfe, B.Sc., Ph.D. Department Paediatric Cardiology Erasmus University Sofia Kinderziekenhuis Gordelweg 160, Rotterdam The Netherlands REFERENCES 1.
Lou HC, Lassen NA, and Friis-Hansen B: Impaired autoregulation of cerebral blood flow in the distressed newborn infant, J PEDIATR 94: 118, 1978. 2. Cooke RWI, and Rolfe P: Cerebral blood flow measurement using venous occlusion plethysmography in the newborn infant, in Rolfe P, editors: Non-invasive physiological measurements, London, 1979, Academic Press, Inc. ,S 3. Cooke RWI, Rolfe P, and Howat P: Apparent cerebral blood flow in neonatal respiratory disease, Dev Med Child Neurol 21:154, 1979. 4. Wallgren G, Hanson JS, Tabakin BS, Raiha N, and Vapaavouri E: Quantitative studies of the human neonatal circulation, Acta Paediatr. Stockh. 56(Supp 179):71, 1967. 5. Strang LB: Neonatal respiration physiological and clinical studies, Oxford, 1977, Blackwell Scientific Publications, pp 207-209.
To the Editor: The recent study by Lou et al' concluded that cerebrovascular ~'autoregulation was impaired in the distressed newborn infant: [cerebral blood flow] CBF was pressure passive and dependent upon the arterial BP [blood pressure]." We wish to offer several alternate interpretations to the investigators' data.
