Volume 93 Number 5
Clinical notes
tissues in neurofibromatosis may be a reflection of a more generalized growth abnormality shared by multiple cell lines.
James S. Roloff, M.D. Fellow, Pediatric Hematology-Oncology Jennifer L. Najjar, M.D. lntern, Department of Pediatrics John N. Lukens, M.D. Professor, Department of Pediatrics Children's Hospital Vanderbilt University Medical Center Nashville, TN 37232 REFERENCES 1. Reich SE, and Wiernik PH: Von Recklinghausen neurofibromatosis and acute leukemia, Am J Dis Child 130:888, 1976. 2. Cockington RA: Leukaemic infiltration of the gastrointestinal tract. An unusual cause of protein-losing enteropathy, Med J Aust 1:103, 1975. 3. Stokes DC, Mulvihill JJ, and Zinkham WH: Neurofibromatosis and leukemia, Am J Dis Child 132:321, 1978. 4. Fiennian NL, and Yakovac WC: Neurofibromatosis in childhood, J PEDIATR76:336, 1970. 5. Stay EJ, and Vawter G: The relationship between nephroblastoma and neurofibromatosis (yon Recklinghausen's disease), Cancer 39:2550, 1977.
character and number did not change during the course of therapy for CML. Patient W. W. was seen at the age of 21 to determine whether there were any late sequelae of the earlier neoplasm or treatment. Multiple nevi were most prominent over the chest but a few were present on the back and extremities as well. An osteochondroma had been removed from his tenth rib three years earlier and, two years later, a neurofibroma of the rectum was excised. The osteochrondroma as well as the neurofibrosarcoma, which developed in the left retroperitoneal space, appeared to have arisen in the field of radiation for the Wilms tumor. Neither patient had any stigmata of neurofibromatosis or of congenital anomalies associated with Wilms tumor. The histories of both were negative for unusual exposures, neurofibromatosis, and excessive cancer in family members. Both patients died of their second cancers.
Pigmented nevi, Wilms tumor, and second malignant neoplasms The interesting clinical note by Simon et aP prompts this report of two long-term Wilms tumor survivors seen at our institution with numerous pigmented nevi, both of whom developed second malignant neoplasms. One patient (M. A.) has been reported previously.2.3
See related article, p. 888. DISCUSSION The nevi seen in the patient reported by Simon et aP decreased in size and pigmentation after removal of the tumor, and the authors suggest that their growth may have been enhanced by tumor-related, melanin-stimulating hormones. The findings in our patients suggest an alternative explanation for the association between the neoplasm and the skin lesions. Both tumor and nevi may be manifestations of a constitutional predisposition to cancer such as occurs in neurofibromatosis, a condition in which pigmentation is also associated with tumors of both neural and nonneural tissues, particularly Wilms tumor and leukemia.'. 5 Multiple tumors, whether occurring in the same or in different tissues, have been found in patients with genetically determined susceptibility to cancer.~ Such patients, too, may be particularly sensitive to the oncogenic effects of X-irradiation and hence should be observed more carefully following the treatment and cure of a childhood neoplasm? In addition, when such patients are seen, skin fibroblasts should be obtained for in vitro studies of radiation sensitivity and stored for future studies as new research procedures are developed which bear on the increased susceptibility of some individuals to radiation-associated tumors.
Anna T. Meadows, M.D. Patricia Jarrett Division of Oncology The Children's Hospital of Philadelphia Philadelphia, PA 19104
CASE R E P O R T S The Table summarizes the clinical histories of Patients M. A. and W. W. Patient M. A. was initially examined at the diagnosis of Ph. chromosome positive chronic myelogenous leukemia (CML). Multiple nevi were present in large numbers on her back. Their Table. Patients with p i g m e n t e d nevi, Wilms tumor, and second malignant neoplasms
Wilms tumor Patient
Sex
Age at Ox (yr)
M.A.
F
4½
W.W.
M
3
Treatment
Second neoplasm Age at Ox (yr)
2,400 r to left flank
14
X-irradiation to left flank
25
0022-3476/78/110889+02500.20/0 © 1978 The C. V. Mosby Co.
889
[
Type Chronic myleogenous leukemia Neurofibrosarcoma
Age at death (yr) 20
26
890
Clinical notes
REFERENCES
I. Simon FA, Drutz JE, and Corriere JN: Wilms tumor and pigmented nevi, J PEDIA'rR90:840, 1977 (Letter). 2. Meadows AT, D'Angio GJ, Mike V, et al: Patterns of second malignant neoplasms in children, Cancer 40:1903, 1977. 3. Schwartz AD, Lee H, and Baum ES: Leukemia in childi'en with Wilms' tumor, J PEDIA'rR87:374, 1975. 4. Stay EJ, and Vawter G: The relationship between nephroblastoma and neurofibromatosis (von Recklinghausen'.s disease), Cancer 39:2550, 1977. 5. Bader JL, and Miller RW: Neurofibromatosis and childhood leukemia, J PEDIATR92:925, 1978. 6. Strong L: Theories of pathogenesis: Mutation and cancer in Mulvihill JJ, Miller RW, and Fraumeni JF Jr, Editors: Genetics of human cancer, New York, 1977, Raven Press, pp 401-414.
Cortical blindness as a complication of hemodialysis One of the most serious complications following hemodialysis is the disequilibrium syndrome, manifested by headache, nausea, muscle cramps, irritability, disorientation, seizures, and cardiac irregularities. The estimated frequency of this complication in adult patients is 8%,' and in children is thought to be higher. Cortical blindness has never been reported as a manifestation of the disequilibrium syndrome, though visual disturbances related to uremia, per se, have been known for a long time. ~ We recently observed the occurrence of cortical blindness in a child after hemodialysis. CASE REPORT
A 5-year-old white boy was transferred to State University Hospital because of acute renal failure secondary to the hemolytic uremic syndrome. On admission he was conscious but pale and listless. He weighed 22.1 k g - a 2 kg increase in three days. His blood pressure was 110/80 mm Hg and funduscopic examination was normal. The abdomen was markedly distended and diffusely tender; the bowel sounds were absent. Hematocrit was 21.5% and the platelet count was 50,000/mm~; the peripheral blood smear revealed anisocytosis, polychromasia, and fragmented burr ceils. Blood chemistry values were sodium 126 mEq/l, potassium 5.1 mEq/1, CO2 9 mM/1, pH 7.28, BUN 94 mg/dl, and serum creatinine 6.3 mg/dl. During the first 24 hours the patient remained anuric and acidosis was not correctable despite administration of large doses of sodium bicarbonate. Hemodialysis was performed because it was felt that peritoneal dialysis would be difficult in a child with a distended, silent abdomen. A two-hour dialysis, performed after both femoral veins were catheterized, was relatively inefficient, reducing the BUN from 105 to 86 mg/dl. Two days later a second dialysis was performed using a single needle technique, which
0022-3476/78/110890+02500.20/0 © 1978 The C. V. Mosby Co.
The Journal of Pediatrics November 1978
was even less efficient. A third dialysis was performed on the fifth hospital day after an arteriovenous shunt was created in the right forearm. After 2½ hours of dialysis with a C-Dak 0.6 Artificial Kidney (Cordis Dow Corporation, Miami, Fla.), a blood flow of 80 ml/minute, dialysate flow of 500 ml/minute, and a negative pressure of 75 mm Hg, the child had a grand mal seizure lasting only a few seconds, followed by a sudden loss of vision. During the dialysis the vital signs were stable, With blood pressure ranging between 110/80 and 120/90. Blood chemistry values obtained immediately after the incident were sodium 130 mEq/l, potassium 3.7 mEq/l, CO._, 10 mM/1, glucose 145 mg/dl, calcium 11.3 mg/dl, BUN 100 mg/dl (95 mg/dl decrease from predialysis BUN) and creatinine 5.1 mg/dl (4.3 mg/dl decrease from predialysis value). Shortly after the seizure the child appeared moderately drowsy but conscious. Both pupils were equal and reacted briskly to light. Full extraocular movements were present bilaterally and the funduscopic examination was normal. There was complete loss of vision, including the recognition of light and shadow. The blink reflex could not be elicited with either bright illumination or threatening gestures. Neurologic examination was otherwise normal except for bilateral extensor plantar responses, which lasted for several hours. Computerized axial tomographic (CAT) scan, performed four hours after the incident, revealed no evidence of hemorrhage or infarction. The electroencephalogram showed diffuse bilateral slowing which was interpreted as nonspecific bilateral cortical dysfunction. The patient began voiding that evening after seven days of anuria and his urine output improved thereafter; the platelet count began to rise and the hematocrit stabilized at 20%. Vision began to return gradually 48 hours after the seizure. The patient was discharged 20 days after admission. At the time of discharge his BUN was 12 mg/dl, serum creatinine 0.7 mg/dl, hematocrit 20%, platelet count 330,000/mm ~, and reticulocyte count 5.4%. Two months after this transient episode of cortical blindness, the child was examined by an ophthalmologist who found normal visual fields and normal appearing fundi. DISCUSSION Cortical or cerebral blindness is characterized by complete loss of vision with the preservation of pupillary reflexes and a normal appearing fundus. Cortical blindness has been associated with the hemolytic uremic syndrome, due to extensive subarachroid hemorrhage over the visual cortex. A significant cerebral bleed was unlikely in our patient since he had a normal CAT scan and a prompt, complete recovery. Acute blindness has also been described following convulsions. 3 Postictal blindness is most often associated with prolonged, severe convulsions; other neurologic signs, such as aphasia and paresis of hemiplegic distribution, have been observed. Recovery from the postictal blindness usually takes weeks, sometimes months. Uremic amaurosis, cortical blindness associated with renal failure, usually comes on suddenly, may be complete or partial, and is bilateral and commonly transitory? Symptoms disappear rapidly although not always completely when uremia, hypertension, and fluid overload are treated. The mechanism suggested for uremic amaurosis is cerebral edema or ischemia or both,
Clinical notes
tissues in neurofibromatosis may be a reflection of a more generalized growth abnormality shared by multiple cell lines.
James S. Roloff, M.D. Fellow, Pediatric Hematology-Oncology Jennifer L. Najjar, M.D. lntern, Department of Pediatrics John N. Lukens, M.D. Professor, Department of Pediatrics Children's Hospital Vanderbilt University Medical Center Nashville, TN 37232 REFERENCES 1. Reich SE, and Wiernik PH: Von Recklinghausen neurofibromatosis and acute leukemia, Am J Dis Child 130:888, 1976. 2. Cockington RA: Leukaemic infiltration of the gastrointestinal tract. An unusual cause of protein-losing enteropathy, Med J Aust 1:103, 1975. 3. Stokes DC, Mulvihill JJ, and Zinkham WH: Neurofibromatosis and leukemia, Am J Dis Child 132:321, 1978. 4. Fiennian NL, and Yakovac WC: Neurofibromatosis in childhood, J PEDIATR76:336, 1970. 5. Stay EJ, and Vawter G: The relationship between nephroblastoma and neurofibromatosis (yon Recklinghausen's disease), Cancer 39:2550, 1977.
character and number did not change during the course of therapy for CML. Patient W. W. was seen at the age of 21 to determine whether there were any late sequelae of the earlier neoplasm or treatment. Multiple nevi were most prominent over the chest but a few were present on the back and extremities as well. An osteochondroma had been removed from his tenth rib three years earlier and, two years later, a neurofibroma of the rectum was excised. The osteochrondroma as well as the neurofibrosarcoma, which developed in the left retroperitoneal space, appeared to have arisen in the field of radiation for the Wilms tumor. Neither patient had any stigmata of neurofibromatosis or of congenital anomalies associated with Wilms tumor. The histories of both were negative for unusual exposures, neurofibromatosis, and excessive cancer in family members. Both patients died of their second cancers.
Pigmented nevi, Wilms tumor, and second malignant neoplasms The interesting clinical note by Simon et aP prompts this report of two long-term Wilms tumor survivors seen at our institution with numerous pigmented nevi, both of whom developed second malignant neoplasms. One patient (M. A.) has been reported previously.2.3
See related article, p. 888. DISCUSSION The nevi seen in the patient reported by Simon et aP decreased in size and pigmentation after removal of the tumor, and the authors suggest that their growth may have been enhanced by tumor-related, melanin-stimulating hormones. The findings in our patients suggest an alternative explanation for the association between the neoplasm and the skin lesions. Both tumor and nevi may be manifestations of a constitutional predisposition to cancer such as occurs in neurofibromatosis, a condition in which pigmentation is also associated with tumors of both neural and nonneural tissues, particularly Wilms tumor and leukemia.'. 5 Multiple tumors, whether occurring in the same or in different tissues, have been found in patients with genetically determined susceptibility to cancer.~ Such patients, too, may be particularly sensitive to the oncogenic effects of X-irradiation and hence should be observed more carefully following the treatment and cure of a childhood neoplasm? In addition, when such patients are seen, skin fibroblasts should be obtained for in vitro studies of radiation sensitivity and stored for future studies as new research procedures are developed which bear on the increased susceptibility of some individuals to radiation-associated tumors.
Anna T. Meadows, M.D. Patricia Jarrett Division of Oncology The Children's Hospital of Philadelphia Philadelphia, PA 19104
CASE R E P O R T S The Table summarizes the clinical histories of Patients M. A. and W. W. Patient M. A. was initially examined at the diagnosis of Ph. chromosome positive chronic myelogenous leukemia (CML). Multiple nevi were present in large numbers on her back. Their Table. Patients with p i g m e n t e d nevi, Wilms tumor, and second malignant neoplasms
Wilms tumor Patient
Sex
Age at Ox (yr)
M.A.
F
4½
W.W.
M
3
Treatment
Second neoplasm Age at Ox (yr)
2,400 r to left flank
14
X-irradiation to left flank
25
0022-3476/78/110889+02500.20/0 © 1978 The C. V. Mosby Co.
889
[
Type Chronic myleogenous leukemia Neurofibrosarcoma
Age at death (yr) 20
26
890
Clinical notes
REFERENCES
I. Simon FA, Drutz JE, and Corriere JN: Wilms tumor and pigmented nevi, J PEDIA'rR90:840, 1977 (Letter). 2. Meadows AT, D'Angio GJ, Mike V, et al: Patterns of second malignant neoplasms in children, Cancer 40:1903, 1977. 3. Schwartz AD, Lee H, and Baum ES: Leukemia in childi'en with Wilms' tumor, J PEDIA'rR87:374, 1975. 4. Stay EJ, and Vawter G: The relationship between nephroblastoma and neurofibromatosis (von Recklinghausen'.s disease), Cancer 39:2550, 1977. 5. Bader JL, and Miller RW: Neurofibromatosis and childhood leukemia, J PEDIATR92:925, 1978. 6. Strong L: Theories of pathogenesis: Mutation and cancer in Mulvihill JJ, Miller RW, and Fraumeni JF Jr, Editors: Genetics of human cancer, New York, 1977, Raven Press, pp 401-414.
Cortical blindness as a complication of hemodialysis One of the most serious complications following hemodialysis is the disequilibrium syndrome, manifested by headache, nausea, muscle cramps, irritability, disorientation, seizures, and cardiac irregularities. The estimated frequency of this complication in adult patients is 8%,' and in children is thought to be higher. Cortical blindness has never been reported as a manifestation of the disequilibrium syndrome, though visual disturbances related to uremia, per se, have been known for a long time. ~ We recently observed the occurrence of cortical blindness in a child after hemodialysis. CASE REPORT
A 5-year-old white boy was transferred to State University Hospital because of acute renal failure secondary to the hemolytic uremic syndrome. On admission he was conscious but pale and listless. He weighed 22.1 k g - a 2 kg increase in three days. His blood pressure was 110/80 mm Hg and funduscopic examination was normal. The abdomen was markedly distended and diffusely tender; the bowel sounds were absent. Hematocrit was 21.5% and the platelet count was 50,000/mm~; the peripheral blood smear revealed anisocytosis, polychromasia, and fragmented burr ceils. Blood chemistry values were sodium 126 mEq/l, potassium 5.1 mEq/1, CO2 9 mM/1, pH 7.28, BUN 94 mg/dl, and serum creatinine 6.3 mg/dl. During the first 24 hours the patient remained anuric and acidosis was not correctable despite administration of large doses of sodium bicarbonate. Hemodialysis was performed because it was felt that peritoneal dialysis would be difficult in a child with a distended, silent abdomen. A two-hour dialysis, performed after both femoral veins were catheterized, was relatively inefficient, reducing the BUN from 105 to 86 mg/dl. Two days later a second dialysis was performed using a single needle technique, which
0022-3476/78/110890+02500.20/0 © 1978 The C. V. Mosby Co.
The Journal of Pediatrics November 1978
was even less efficient. A third dialysis was performed on the fifth hospital day after an arteriovenous shunt was created in the right forearm. After 2½ hours of dialysis with a C-Dak 0.6 Artificial Kidney (Cordis Dow Corporation, Miami, Fla.), a blood flow of 80 ml/minute, dialysate flow of 500 ml/minute, and a negative pressure of 75 mm Hg, the child had a grand mal seizure lasting only a few seconds, followed by a sudden loss of vision. During the dialysis the vital signs were stable, With blood pressure ranging between 110/80 and 120/90. Blood chemistry values obtained immediately after the incident were sodium 130 mEq/l, potassium 3.7 mEq/l, CO._, 10 mM/1, glucose 145 mg/dl, calcium 11.3 mg/dl, BUN 100 mg/dl (95 mg/dl decrease from predialysis BUN) and creatinine 5.1 mg/dl (4.3 mg/dl decrease from predialysis value). Shortly after the seizure the child appeared moderately drowsy but conscious. Both pupils were equal and reacted briskly to light. Full extraocular movements were present bilaterally and the funduscopic examination was normal. There was complete loss of vision, including the recognition of light and shadow. The blink reflex could not be elicited with either bright illumination or threatening gestures. Neurologic examination was otherwise normal except for bilateral extensor plantar responses, which lasted for several hours. Computerized axial tomographic (CAT) scan, performed four hours after the incident, revealed no evidence of hemorrhage or infarction. The electroencephalogram showed diffuse bilateral slowing which was interpreted as nonspecific bilateral cortical dysfunction. The patient began voiding that evening after seven days of anuria and his urine output improved thereafter; the platelet count began to rise and the hematocrit stabilized at 20%. Vision began to return gradually 48 hours after the seizure. The patient was discharged 20 days after admission. At the time of discharge his BUN was 12 mg/dl, serum creatinine 0.7 mg/dl, hematocrit 20%, platelet count 330,000/mm ~, and reticulocyte count 5.4%. Two months after this transient episode of cortical blindness, the child was examined by an ophthalmologist who found normal visual fields and normal appearing fundi. DISCUSSION Cortical or cerebral blindness is characterized by complete loss of vision with the preservation of pupillary reflexes and a normal appearing fundus. Cortical blindness has been associated with the hemolytic uremic syndrome, due to extensive subarachroid hemorrhage over the visual cortex. A significant cerebral bleed was unlikely in our patient since he had a normal CAT scan and a prompt, complete recovery. Acute blindness has also been described following convulsions. 3 Postictal blindness is most often associated with prolonged, severe convulsions; other neurologic signs, such as aphasia and paresis of hemiplegic distribution, have been observed. Recovery from the postictal blindness usually takes weeks, sometimes months. Uremic amaurosis, cortical blindness associated with renal failure, usually comes on suddenly, may be complete or partial, and is bilateral and commonly transitory? Symptoms disappear rapidly although not always completely when uremia, hypertension, and fluid overload are treated. The mechanism suggested for uremic amaurosis is cerebral edema or ischemia or both,
