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Childhood leukemia: Implications of EEG findings at time of diagnosis
Volume 98 Number 3
breathing during sleep has been shown to cause pulmonary hypertension in both adults and children with a wide variety of diseases, ranging from the sleep apnea syndrome to chronic obstructive pulmonary disease? -7 (2) These nocturnal events are often unrecognized, especially in children whose daytime symptoms are subtle and somewhat atypical? (3) We suggest that certain of the stigmata of Down syndrome may predispose to sleepinduced upper airway obstruction. Quantitative studies of such patients have demonstrated a generalized midfacial hypoplasia and micrognathia? This relative crowding of the midfacial structures, coupled with the recognized muscular hypotonia characteristic of Down syndrome, 1' may predispose to upper airway collapse during sleep, especially if enlargement of the tonsils and adenoids and/or nasal congestion is also present. Recently Clark et al 1I reported three adults with Down syndrome and the sleep apnea syndrome. However, all of these patients were obese and two had massive enlargement of tonsils and adenoids, both well-established factors in producing sleep apnea. Additional studies of this population are needed to clarify the nature of the association between Down syndrome and airway obstruction during sleep, and to investigate the possible causes arm consequences. The authors gratefully acknowledge the contributions of Dr. Nicholas Cassisi for referring two of the patients, of Dr. Alvin Felman for performing and interpreting the cinefluroscopies,and of Mr. Christopher Thiessen for his editorial assistance.
Brief clinical and laboratory observations
437
REFERENCES 1. Greenwood RD, and Nadas AS: The clinical course of cardiac disease in Down's syndrome, Pediatrics 58:893, 1976. 2. Soudon P, Stijns M, Tremouroux-Wattiez M, and Vliers A: Precocity of pulmonary vascular obstruction in Down's syndrome, Eur J Cardiol 21:473, 1975. 3. Borowiecki B, Pollak CP, Weitzman ED, Rakoff S, and Imperator J: Fiberoptic study of pharyngeal airway during sleep in patients with the hypersomnia sleep apnea syndrome, Laryngoscope 88:1310, 1978. 4. Felman AH, Loughlin GM, Leftridge CA, and Cassisi NJ: Upper airway obstruction during sleep in children, Am J Roentgenol 133:213, 1979. 5. BoysenPG, Block AJ, Wynne JW, Hunt LA, and Flick MR: Nocturnal pulmonary hypertension in patients with chronic obstructive pulmonary disease, Chest 76:536, 1979. 6. Tilkian AG, Guilleminault C, Schroeder JS, Lehrman KL, Simmons FB, and Dement WC: Hemodynamics in sleepinduced apnea, Ann Intern Med 85:714, 1976. 7. Lugaresi E, Coccagna G, Mantovani M, and Brignani F: Effects of tracheostomy in two cases of hypersomnia with periodic breathing, J Neurol Neurosurg Psychiatry 36:15, 1973. 8. Guilleminauh C, Eldridge FL, Simmons FB, and Dement WC: Sleep apnea in eight children, Pediatrics 58:23, 1976. 9. Fink GB, Madaus WR, and Walker GF: A quantitative study of the face in Down's syndrome, Am J Orthod 67:540, 1975. 10. Smith DW: Recognizable patterns of human malformations, Philadelphia, 1976, WB Saunders Company, pp 6-8. 11. Clark RW, Schmidt HS, and Schuller DE: Sleep-induced ventilatory dysfunction in Down's syndrome, Arch Intern Med 140:45, 1980.
Childhood leukemia: Implications of EEG findings at time of diagnosis Donald H. Mahoney, Jr., M.D.,* Charles W. Britt, M.D., Peter Kellaway, Ph.D., and Donald J. Fernbach, M.D., Houston, Texas
ELECTROENCEPHALOGRAPHIC EXAMINATIONS of children at various stages of acute lymphoblastic leukemia have re~ealed a variety of alterations? -~ However, the From the Department of Pediatrics and the Neurophysiology Section of the Department of Neurology, Baylor College of Medicine. Supported in part by research grant CA-03161 and education grant CA-24268 from the National Cancer Institute. *Reprint address: Research Hematology Laboratory, Texas Children's Hospital, 6621 Fannin St., Houston, TX 77030.
0022-3476/81/030437+04500.40/00 198I The C. V. Mosby Co.
EEG findings have not previously been well described and attempts to correlate EEG abnormalities noted at diagnosis with subsequent clinical events have not been successful. Consequently, a review of EEG and clinical findings at diagnosis in a group of children with ALL was Abbreviations used ALL: acute lymphoblastic leukemia EEG: electroencephalogram CSF: cerebrospinal fluid CNS: central nervous system
43 8
Brief clinical and laboratory observations
F MALE
AGs
3
The Journal of Pediatrics March 1981
-
IIoo~v
_
_
MALE
AGE 5 Y R ,
5MO
CT~ T4
I sec
l'vvF
v
Figure. A, EEG of a 3-year-old girl with ALL. The alpha rhythm of 5 Hz (normal for age is 8 Hz) is slow and is intermixed with much irregular, high-vohage, 2-3 Hz activity (underlined), B, EEG of a 5ryear-old boy with ALL. The activity m all areas is moderately slow, with prominent, irregular, 2-3 Hz wave forms in the occipital regions (underlined), more marked on the left side. Myogenic artifact is present in the lower four channels.
undertaken. The purposes of this study were to determine the incidence and nature of alterations of EEG findings at diagnosis and their relationship, if any, to current clinical events and laboratory findings; and to assess the prognostic value of EEG examinations for subsequent neurologic complications. METHODS
AND MATERIALS
During the period January, 1974, to July, 1979, 116 children with ALL, having no clinical or CSF findings of
leukemic infiltration of the CNS, had EEG examinations prior to the initiation of chemotherapy. After induction of remission, all patients received CNS therapy according to Southwest Oncology Group protocols. These protocols include intrathecal adminislration of methotrexate (with or without hydrocortisone and cytosine arabinoside), with or without cranial irradiation. The EEGs were recorded on 8- or 16-channel machines, utilizing both referential and scalp-to-scalp derivations. Early, transient neurotoxicity resulting from CNS therapy
Volume98 Number3 was defined by the presence of lethargy, headache, fever, nausea, and vomiting, or meningismus appearing either acutely during the course of therapy or within five to seven weeks after completion of therapy, as characterized by the post-irradiation somnolence syndrome? -8 RESULTS The patients were divided into three groups: Group I comprised 46 patients with normal EEGs; Group II comprised 53 patients with mild-to-moderate abnormalities; and Group III comprised 17 patients with marked abnormalities. The prevailing abnormality in Group II was the presence of moderate-to-high-voltage random and rhythmic activity of theta (4-7 Hz) or, more often, delta (--< 3 Hz) frequency in the occipital regions (Figure, A). In some patients in this group, the alpha rhythm and anterior rhythmic activity were slightly slow. In Group III, the prevailing abnormality consisted of moderate-tomarked slowing of activity in all areas, often with prominent delta activity in the occipital regions (Figure, B). In addition to background slowing, bursts of generalized, high-voltage, rhythmic delta activity were present in many of these recordings; a spike focus was present in several; and a slow-wave focus was seen in one. Several clinical and laboratory features were examined for correlation with the EEG findings. Subjective neurologic complaints of lethargy, headache, and/or irritability were noted at the time of the initial examination in 11% of Group I, 17% of Group II, and 37% of Group III patients. General neurologic assessments including cranial nerve, motor, and sensory examinations prior to EEG were otherwise unremarkable. No definite correlation between concurrent neurologic complaints and specific EEG patterns could be established. Abnormalities of the EEG were more prevalent in girls than in boys (75 vs 50%). No association was observed between EEG abnormalities at diagnosis and the following: age, thrombocytopenia, hemorrhage, white blood cell count, intercurrent infection, metabolic disturbance, or CSF protein concentration. Of greater importance, the presence of abnormal EEGs at diagnosis was not predictive for subsequent occurrence of isolated leukemic infiltration of the CNS. Of th~ 116 children, 37 (32%) had early, transient neurotoxicity, as previously described. Twenty-seven (73%) of these 37 children had received 2,400 rads cranial irradiation plus intrathecal methotrexate therapy. Overall, trapsient neurologic side effects were seen more frequently in the group of children receiving cranial irradiation with intrathecal methotrexate (44%) as compared to children receiving intrathecal therapy alone (17%). In retrospect, those children who developed early, transient neurotoxicity after CNS therapy had a greater
Brief clinical and laboratory observations
439
Table. EEG findings at diagnosis and CNS therapyrelated neurotoxicity
I EEG Normal Mild to moderately abnormal Markedly abnormal P < 0.001"
Neurotoxicity Absent I Present 35 39
11 14
5
12
*Tested for significanceby chi square. frequency of EEG abnormalities at the time of diagnosis (Table). This observation was most significant in those patients who had marked EEG abnormalities (Group III) at the time of diagnosis (12/17, P < 0.001). However, the occurrence of transient CNS therapy-related neurotoxicity was not associated with an increased incidence of isolated CNS leukemic infiltration later in the course of ALL. DISCUSSION There are few serial studies of EEG findings in children with ALL. Early investigations have dealt with alterations found as a result of presumed or confirmed leukemic infiltration of the CNS. 1, 2 More recent reports present conflicting EEG findings during the course of systemic or intrathecal therapy, or in association with the postirradiation somnolence syndrome. 3-e In brief, there are presently no adequate explanations for EEG abnormalities observed at the time of diagnosis in children with ALL. In this retrospective analysis of 116 children with ALL, 60% had abnormal EEG findings at the time of diagnosis, prior to administration of systemic chemotherapy and local CNS therapy, and in the absence of identifiable leukemic infiltration of the CNS. The EEG abnormalities were categorized into a variety of slow-wave patterns, most frequently involving occipital regions of the brain. Several patients without evidence of CNS infiltration had diffuse, slow-wave EEG abnormalities. The pathophysiology of these EEG findings remains obscure. No single EEG pattern was specific for a clinical presentation o f ALL. The most significant finding in this analysis was the observed association between prior EEG abnormalities and subsequent early, transient neurotoxicity. Whereas neurotoxicity was observed in 23% of the patients in Group I (normal EEGs) and in 27% of the patients in Group II (mildly to moderately abnormal EEGs), it occurred in 71% of the patients in Group III (markedly abnormal EEGs).
440
Brief cfinical and laboratory observations
An increasing number of children with ALL are surviving longer; therefore, therapy for this disease must be designed to minimize iatrogenic neurologic sequelae. The reported frequency of neurologic sequelae is variable and there is no agreement as to how therapy influences CNS toxicity a n d / o r functional impairment2 However, since significant neurologic complications may result from CNS therapy, identification of prognostic indicators and selection of the least toxic yet effective CNS therapy are important objectives currently under investigation. 1~ 11 Our observations tentatively suggest that severe EEG abnormalities present at the time of diagnosis prior to therapy may reflect an ill-defined cerebral disturbance which predisposes the patient to an increased risk of early CNS therapy neurotoxicity. Whether the combination of these findings is also predictive for latent forms of neurotoxicity or the more severe sequelae of progressive leukoencephalopathy remains to be determined. REFERENCES
1. Shaw RK, Moore EW, Freireich EJ, and Thomas LB: Meningeal leukemia, Neurology 10:823, 1960. 2. Iannetti P, Multari G, Del Principe D, Nervi C, and Digilio G: Electroencephalographic findings in patients with acute lymphatic leukemia treated by radiotherapy of the central nervous system, in Metcalf D, Condorelli M, and Peschle C,
The Journal of Pediatrics March 1981
3. 4.
5. 6.
7. 8. 9. 10.
11.
editors: International conference on leukemia and aplastic anemia, Rome, 1974, 11 Pensiero Scientifico, p 598. Onuma A, Uinuma K, and Hayashi T: Electroencephalographic findings in acute childhood leukemias, Jpn J Clin Hematol 19:107, 1978. Butcher DM, Hardisty RM, Lange L, and Pampliglione G: EEG studies in children with leukemia, Electroencephalogr Clin Neurophysiol 28:209, 1970. Moure JMB, and Sullivan M: EEG changes in children with leukaemia during chemotherapy, Electroencephalogr Clin Neurophysiol 38:429, 1975. Garwicz S, Aronson AS, Elmquist D, and Landberg T: Postirradiation syndrome and EEG findings in children with acute lymphoblastic leukaemia, Acta Paediatr Scand 64:399, 1975. Allen JC; The effects of cancer therapy on the nervous system, J P~DIATR93:903, 1978. Pochedly C: Neurotoxicity due to CNS therapy for leukemia, Med Pediatr Oncol 3:101, 1977. Obetz SW, Smithson WA, Groover RV, et al.: Neuropsychologic follow-up study of children with acute lymphoblastic leukemia, Am J Pediatr Hematol/Oncol 1:207, 1979. Nesbit ME, Salther HN, Robison LL, et al: Presymptomatic CNS treatment in childhood acute lymphoblastic leukemia: Comparison between 1800 and 2400 rads, Proc Am Assoc Cancer Res 20:343, 1979 (abstr). Bode U, Otiff A, Bercu BB, et al: Absence of CT brain scan and endocrine abnormalities with less intensive CNS prophylaxis, Am J Pediatr Hematol/Oncol 2:21, 1980.
A condensed table for predicting adult stature Ernest M. Post, M.D.,* and Robert A. Richman, M.D., Syracuse, N.Y.
I ~ 1952 Bayley and Pinneau I published a set of 11 tables for predicting adult height from skeletal age 2 and current height. More recently two other methods 3.' have been developed, but it remains controversal whether they are more accurate?, 6 The Bayley-Pinneau method is the least complicated one and is still widely used. (Science Citation Index: 1978 and 1979). The Table presented here is condensed from their data for simplicity, clarity, and easier clinical application. It shows the decimal fraction of adult height attained at each bone age for boys and girls whose skeletal age is average (within one year), retarded, or advanced compared to chronologic age. The decimal fraction is located in the row for the patient's skeletal age *Reprint address: Department of Pediatrics, State University Hospital, 750 East Adams St., Syracuse, N Y 13210.
(years and months), under the appropriate column. Adult height prediction is calculated by dividing the height by the decimal fraction. For example, a 106/12-year-old boy who is 130.0 cm tall and has a bone age of 86/12years will have a height prediction of present height decimal fraction
m
130.0 0.779
166.9 cm.
This method is equally suitable for height in inches. REFERENCES 1. Bayley N, and Pinneau SR: Tables for predicting adult height from skeletal age: Revised for use with the GreulichPyle hand standards; J P~DIATR50:432, 1952. 2. Greulich WW, and Pyle SI: Radiographic atlas of skeletal development of the hand and wrist, Stanford, Calif. 1959, Stanford University Press, p 190.
0022-3476/81/030440+03500.30/0 9 1981 The C. V. Mosby Co.
breathing during sleep has been shown to cause pulmonary hypertension in both adults and children with a wide variety of diseases, ranging from the sleep apnea syndrome to chronic obstructive pulmonary disease? -7 (2) These nocturnal events are often unrecognized, especially in children whose daytime symptoms are subtle and somewhat atypical? (3) We suggest that certain of the stigmata of Down syndrome may predispose to sleepinduced upper airway obstruction. Quantitative studies of such patients have demonstrated a generalized midfacial hypoplasia and micrognathia? This relative crowding of the midfacial structures, coupled with the recognized muscular hypotonia characteristic of Down syndrome, 1' may predispose to upper airway collapse during sleep, especially if enlargement of the tonsils and adenoids and/or nasal congestion is also present. Recently Clark et al 1I reported three adults with Down syndrome and the sleep apnea syndrome. However, all of these patients were obese and two had massive enlargement of tonsils and adenoids, both well-established factors in producing sleep apnea. Additional studies of this population are needed to clarify the nature of the association between Down syndrome and airway obstruction during sleep, and to investigate the possible causes arm consequences. The authors gratefully acknowledge the contributions of Dr. Nicholas Cassisi for referring two of the patients, of Dr. Alvin Felman for performing and interpreting the cinefluroscopies,and of Mr. Christopher Thiessen for his editorial assistance.
Brief clinical and laboratory observations
437
REFERENCES 1. Greenwood RD, and Nadas AS: The clinical course of cardiac disease in Down's syndrome, Pediatrics 58:893, 1976. 2. Soudon P, Stijns M, Tremouroux-Wattiez M, and Vliers A: Precocity of pulmonary vascular obstruction in Down's syndrome, Eur J Cardiol 21:473, 1975. 3. Borowiecki B, Pollak CP, Weitzman ED, Rakoff S, and Imperator J: Fiberoptic study of pharyngeal airway during sleep in patients with the hypersomnia sleep apnea syndrome, Laryngoscope 88:1310, 1978. 4. Felman AH, Loughlin GM, Leftridge CA, and Cassisi NJ: Upper airway obstruction during sleep in children, Am J Roentgenol 133:213, 1979. 5. BoysenPG, Block AJ, Wynne JW, Hunt LA, and Flick MR: Nocturnal pulmonary hypertension in patients with chronic obstructive pulmonary disease, Chest 76:536, 1979. 6. Tilkian AG, Guilleminault C, Schroeder JS, Lehrman KL, Simmons FB, and Dement WC: Hemodynamics in sleepinduced apnea, Ann Intern Med 85:714, 1976. 7. Lugaresi E, Coccagna G, Mantovani M, and Brignani F: Effects of tracheostomy in two cases of hypersomnia with periodic breathing, J Neurol Neurosurg Psychiatry 36:15, 1973. 8. Guilleminauh C, Eldridge FL, Simmons FB, and Dement WC: Sleep apnea in eight children, Pediatrics 58:23, 1976. 9. Fink GB, Madaus WR, and Walker GF: A quantitative study of the face in Down's syndrome, Am J Orthod 67:540, 1975. 10. Smith DW: Recognizable patterns of human malformations, Philadelphia, 1976, WB Saunders Company, pp 6-8. 11. Clark RW, Schmidt HS, and Schuller DE: Sleep-induced ventilatory dysfunction in Down's syndrome, Arch Intern Med 140:45, 1980.
Childhood leukemia: Implications of EEG findings at time of diagnosis Donald H. Mahoney, Jr., M.D.,* Charles W. Britt, M.D., Peter Kellaway, Ph.D., and Donald J. Fernbach, M.D., Houston, Texas
ELECTROENCEPHALOGRAPHIC EXAMINATIONS of children at various stages of acute lymphoblastic leukemia have re~ealed a variety of alterations? -~ However, the From the Department of Pediatrics and the Neurophysiology Section of the Department of Neurology, Baylor College of Medicine. Supported in part by research grant CA-03161 and education grant CA-24268 from the National Cancer Institute. *Reprint address: Research Hematology Laboratory, Texas Children's Hospital, 6621 Fannin St., Houston, TX 77030.
0022-3476/81/030437+04500.40/00 198I The C. V. Mosby Co.
EEG findings have not previously been well described and attempts to correlate EEG abnormalities noted at diagnosis with subsequent clinical events have not been successful. Consequently, a review of EEG and clinical findings at diagnosis in a group of children with ALL was Abbreviations used ALL: acute lymphoblastic leukemia EEG: electroencephalogram CSF: cerebrospinal fluid CNS: central nervous system
43 8
Brief clinical and laboratory observations
F MALE
AGs
3
The Journal of Pediatrics March 1981
-
IIoo~v
_
_
MALE
AGE 5 Y R ,
5MO
CT~ T4
I sec
l'vvF
v
Figure. A, EEG of a 3-year-old girl with ALL. The alpha rhythm of 5 Hz (normal for age is 8 Hz) is slow and is intermixed with much irregular, high-vohage, 2-3 Hz activity (underlined), B, EEG of a 5ryear-old boy with ALL. The activity m all areas is moderately slow, with prominent, irregular, 2-3 Hz wave forms in the occipital regions (underlined), more marked on the left side. Myogenic artifact is present in the lower four channels.
undertaken. The purposes of this study were to determine the incidence and nature of alterations of EEG findings at diagnosis and their relationship, if any, to current clinical events and laboratory findings; and to assess the prognostic value of EEG examinations for subsequent neurologic complications. METHODS
AND MATERIALS
During the period January, 1974, to July, 1979, 116 children with ALL, having no clinical or CSF findings of
leukemic infiltration of the CNS, had EEG examinations prior to the initiation of chemotherapy. After induction of remission, all patients received CNS therapy according to Southwest Oncology Group protocols. These protocols include intrathecal adminislration of methotrexate (with or without hydrocortisone and cytosine arabinoside), with or without cranial irradiation. The EEGs were recorded on 8- or 16-channel machines, utilizing both referential and scalp-to-scalp derivations. Early, transient neurotoxicity resulting from CNS therapy
Volume98 Number3 was defined by the presence of lethargy, headache, fever, nausea, and vomiting, or meningismus appearing either acutely during the course of therapy or within five to seven weeks after completion of therapy, as characterized by the post-irradiation somnolence syndrome? -8 RESULTS The patients were divided into three groups: Group I comprised 46 patients with normal EEGs; Group II comprised 53 patients with mild-to-moderate abnormalities; and Group III comprised 17 patients with marked abnormalities. The prevailing abnormality in Group II was the presence of moderate-to-high-voltage random and rhythmic activity of theta (4-7 Hz) or, more often, delta (--< 3 Hz) frequency in the occipital regions (Figure, A). In some patients in this group, the alpha rhythm and anterior rhythmic activity were slightly slow. In Group III, the prevailing abnormality consisted of moderate-tomarked slowing of activity in all areas, often with prominent delta activity in the occipital regions (Figure, B). In addition to background slowing, bursts of generalized, high-voltage, rhythmic delta activity were present in many of these recordings; a spike focus was present in several; and a slow-wave focus was seen in one. Several clinical and laboratory features were examined for correlation with the EEG findings. Subjective neurologic complaints of lethargy, headache, and/or irritability were noted at the time of the initial examination in 11% of Group I, 17% of Group II, and 37% of Group III patients. General neurologic assessments including cranial nerve, motor, and sensory examinations prior to EEG were otherwise unremarkable. No definite correlation between concurrent neurologic complaints and specific EEG patterns could be established. Abnormalities of the EEG were more prevalent in girls than in boys (75 vs 50%). No association was observed between EEG abnormalities at diagnosis and the following: age, thrombocytopenia, hemorrhage, white blood cell count, intercurrent infection, metabolic disturbance, or CSF protein concentration. Of greater importance, the presence of abnormal EEGs at diagnosis was not predictive for subsequent occurrence of isolated leukemic infiltration of the CNS. Of th~ 116 children, 37 (32%) had early, transient neurotoxicity, as previously described. Twenty-seven (73%) of these 37 children had received 2,400 rads cranial irradiation plus intrathecal methotrexate therapy. Overall, trapsient neurologic side effects were seen more frequently in the group of children receiving cranial irradiation with intrathecal methotrexate (44%) as compared to children receiving intrathecal therapy alone (17%). In retrospect, those children who developed early, transient neurotoxicity after CNS therapy had a greater
Brief clinical and laboratory observations
439
Table. EEG findings at diagnosis and CNS therapyrelated neurotoxicity
I EEG Normal Mild to moderately abnormal Markedly abnormal P < 0.001"
Neurotoxicity Absent I Present 35 39
11 14
5
12
*Tested for significanceby chi square. frequency of EEG abnormalities at the time of diagnosis (Table). This observation was most significant in those patients who had marked EEG abnormalities (Group III) at the time of diagnosis (12/17, P < 0.001). However, the occurrence of transient CNS therapy-related neurotoxicity was not associated with an increased incidence of isolated CNS leukemic infiltration later in the course of ALL. DISCUSSION There are few serial studies of EEG findings in children with ALL. Early investigations have dealt with alterations found as a result of presumed or confirmed leukemic infiltration of the CNS. 1, 2 More recent reports present conflicting EEG findings during the course of systemic or intrathecal therapy, or in association with the postirradiation somnolence syndrome. 3-e In brief, there are presently no adequate explanations for EEG abnormalities observed at the time of diagnosis in children with ALL. In this retrospective analysis of 116 children with ALL, 60% had abnormal EEG findings at the time of diagnosis, prior to administration of systemic chemotherapy and local CNS therapy, and in the absence of identifiable leukemic infiltration of the CNS. The EEG abnormalities were categorized into a variety of slow-wave patterns, most frequently involving occipital regions of the brain. Several patients without evidence of CNS infiltration had diffuse, slow-wave EEG abnormalities. The pathophysiology of these EEG findings remains obscure. No single EEG pattern was specific for a clinical presentation o f ALL. The most significant finding in this analysis was the observed association between prior EEG abnormalities and subsequent early, transient neurotoxicity. Whereas neurotoxicity was observed in 23% of the patients in Group I (normal EEGs) and in 27% of the patients in Group II (mildly to moderately abnormal EEGs), it occurred in 71% of the patients in Group III (markedly abnormal EEGs).
440
Brief cfinical and laboratory observations
An increasing number of children with ALL are surviving longer; therefore, therapy for this disease must be designed to minimize iatrogenic neurologic sequelae. The reported frequency of neurologic sequelae is variable and there is no agreement as to how therapy influences CNS toxicity a n d / o r functional impairment2 However, since significant neurologic complications may result from CNS therapy, identification of prognostic indicators and selection of the least toxic yet effective CNS therapy are important objectives currently under investigation. 1~ 11 Our observations tentatively suggest that severe EEG abnormalities present at the time of diagnosis prior to therapy may reflect an ill-defined cerebral disturbance which predisposes the patient to an increased risk of early CNS therapy neurotoxicity. Whether the combination of these findings is also predictive for latent forms of neurotoxicity or the more severe sequelae of progressive leukoencephalopathy remains to be determined. REFERENCES
1. Shaw RK, Moore EW, Freireich EJ, and Thomas LB: Meningeal leukemia, Neurology 10:823, 1960. 2. Iannetti P, Multari G, Del Principe D, Nervi C, and Digilio G: Electroencephalographic findings in patients with acute lymphatic leukemia treated by radiotherapy of the central nervous system, in Metcalf D, Condorelli M, and Peschle C,
The Journal of Pediatrics March 1981
3. 4.
5. 6.
7. 8. 9. 10.
11.
editors: International conference on leukemia and aplastic anemia, Rome, 1974, 11 Pensiero Scientifico, p 598. Onuma A, Uinuma K, and Hayashi T: Electroencephalographic findings in acute childhood leukemias, Jpn J Clin Hematol 19:107, 1978. Butcher DM, Hardisty RM, Lange L, and Pampliglione G: EEG studies in children with leukemia, Electroencephalogr Clin Neurophysiol 28:209, 1970. Moure JMB, and Sullivan M: EEG changes in children with leukaemia during chemotherapy, Electroencephalogr Clin Neurophysiol 38:429, 1975. Garwicz S, Aronson AS, Elmquist D, and Landberg T: Postirradiation syndrome and EEG findings in children with acute lymphoblastic leukaemia, Acta Paediatr Scand 64:399, 1975. Allen JC; The effects of cancer therapy on the nervous system, J P~DIATR93:903, 1978. Pochedly C: Neurotoxicity due to CNS therapy for leukemia, Med Pediatr Oncol 3:101, 1977. Obetz SW, Smithson WA, Groover RV, et al.: Neuropsychologic follow-up study of children with acute lymphoblastic leukemia, Am J Pediatr Hematol/Oncol 1:207, 1979. Nesbit ME, Salther HN, Robison LL, et al: Presymptomatic CNS treatment in childhood acute lymphoblastic leukemia: Comparison between 1800 and 2400 rads, Proc Am Assoc Cancer Res 20:343, 1979 (abstr). Bode U, Otiff A, Bercu BB, et al: Absence of CT brain scan and endocrine abnormalities with less intensive CNS prophylaxis, Am J Pediatr Hematol/Oncol 2:21, 1980.
A condensed table for predicting adult stature Ernest M. Post, M.D.,* and Robert A. Richman, M.D., Syracuse, N.Y.
I ~ 1952 Bayley and Pinneau I published a set of 11 tables for predicting adult height from skeletal age 2 and current height. More recently two other methods 3.' have been developed, but it remains controversal whether they are more accurate?, 6 The Bayley-Pinneau method is the least complicated one and is still widely used. (Science Citation Index: 1978 and 1979). The Table presented here is condensed from their data for simplicity, clarity, and easier clinical application. It shows the decimal fraction of adult height attained at each bone age for boys and girls whose skeletal age is average (within one year), retarded, or advanced compared to chronologic age. The decimal fraction is located in the row for the patient's skeletal age *Reprint address: Department of Pediatrics, State University Hospital, 750 East Adams St., Syracuse, N Y 13210.
(years and months), under the appropriate column. Adult height prediction is calculated by dividing the height by the decimal fraction. For example, a 106/12-year-old boy who is 130.0 cm tall and has a bone age of 86/12years will have a height prediction of present height decimal fraction
m
130.0 0.779
166.9 cm.
This method is equally suitable for height in inches. REFERENCES 1. Bayley N, and Pinneau SR: Tables for predicting adult height from skeletal age: Revised for use with the GreulichPyle hand standards; J P~DIATR50:432, 1952. 2. Greulich WW, and Pyle SI: Radiographic atlas of skeletal development of the hand and wrist, Stanford, Calif. 1959, Stanford University Press, p 190.
0022-3476/81/030440+03500.30/0 9 1981 The C. V. Mosby Co.