426
Brief clinical and laboratory observations
patterns o f occurrence o f second m a l i g n a n t n e o p l a s m s in children m a y also change. REFERENCES
1. Li FP: Second malignant tumors after cancer in childhood, Cancer 40:1800, 1977. 2. D'Angio GJ, Clatworthy HW, Evans AE, Newton WA, and Tefft M: Is the risk of morbidity and rare mortality worth the cure? Cancer 41:377, 1978. 3. Castro EB, Rosen PP, and Quan SHQ: Carcinoma of the large intestine in patients irradiated for carcinoma of cervix and uterus, Cancer 21:45, 1973.
The Journal of Pediatrics September 1979
4.
Upton AC: Radiation carcinogenesis, Front Radiat Ther Oncol 6:470, 1972. 5. Meadows AT, D'Angio GJ, Mike V, Banff A, Harris C, Jenkin RTD, and Schwartz A: Patterns of second malignant neoplasms in children, Cancer 40:1903, 1977. 6. Harris C: The carcinogenicity of anticar/cer drugs--a hazard in man, Cancer 37:(Suppl):1014, 1976. 7. D'Angio GJ, Evans AE, Breslow N, Beckwith B, Bishop H, Feigl P, Goodwin W, Leape LL, Sinks LF, Sutow W, Tefft M, and Wolff J: The treatment of Wilms' tumor--results of the National Wilms' Tumor Study, Cancer 38:633, 1976.
Orbital apex syndrome secondary to sickle cell anemia Rashid A. AI-RaShid, M.D., Omaha, Neb.
includes a spectrum o f disorders o f varying etiologies involving the apex o f the orbit a n d leading to alterations in ocular a n d extraocular f u n c t i o n s ? -4 Its association with sickle cell disease has n o t b e e n r e p o r t e d previously. This b r i e f report describes a n adolescent with sickle cell a n e m i a who, experienced several episodes o f o r b i t a l apex syndrome. F u r t h e r episodes were a p p a r e n t l y p r e v e n t e d by prophylactic transfusional therapy. THE
ORBITAL
APEX
SYNDROME
CASE REPORT
A 15-year-old black boy was diagnosed as having sickle cell anemia at about 2 years of age. His hemoglobin electrophoresis then showed an S-S pattern with 10% hemoglobin F. He was also found to have glucose-6-phosphate dehydrogenase deficiency, with a level of 3.5 IU/gm hemoglobin. Since that time he has had numerous hospitalizations as a result of vaso-occlusive crises. In May, 1976, he began to experience nausea associated with vomiting and mild diarrhea. Two days later he complained of pain in the right eye which became progressively more severe. He also began to experience diplopia and difficulty in opening his right eye; vision in that eye became blurred. A day prior to admission his vomiting subsided but the pain in his'0rbital region continued. He had had no fever, upper respiratory tract infection, or trauma to the eye. The patient was admitted to the University of Nebraska Medical Center for further evaluation. Physical examination revealed a thin, small for age male who appeared to have right-sided exophthalmos with ptosis of the right upper lid. He was slightly dehydrated. His temperature was
From the Department of Pediatric Hematology/Oncology, University of Nebraska Medical Center. Reprint address: Department of Pediatrics, University of Nebraska Medical Center, 42nd & Dewey Ave., Omaha, NE 68105.
37.6 ~ pulse 84/minute, respiration 20/minute, and blood pressure 120/70. The ophthalmologic examination showed ptosis of the right lid with l-ram proptosis of the right eye. The visual acuity of the right eye was limited to finger counting. There was marked reduction in movement of the right eye in all directions, especially medial gaze, with total third and fourth nerve paralysis and partial sixth nerve paralysis. There was no conjunctival or scleral injection. The fundoscopic examination showed increased venous tortuosity; no papilledema or hemorrhage was evident. Laboratory data showed hemoglobin 6.8 gm/dl, hematocrit 20%, WBC count 8,600/mm ~, with 34% polys, 6% bands, 34% lymphocytes, 24% monocytes, and 2% eosinophils. Platelet count was 602,000/mm, erythrocyte sedimentation rate 3 mm/hour, prothrombin time 13 seconds with a control of 12 seconds, and partial thromboplastin time 30 seconds with a control of 28 seconds. Serum electrolyte values were normal; the BUN was 15 mg/dl. Four blood cultures showed no growth; urine cultures were negative. Roentgenograms of the sinuses showed left mucous retention cyst; orbital views revealed prominent frontal sinuses with no evidence of, bony destruction, and the optic canal appeared normal. Radaonuchde encephalogram and cerebral flow studies were normal. Electroencephalogram showed a mild focal slow abnormality in the right hemisphere. During the hospitalization period, the patient was transfused to a hemoglobin level of 14 gm/dl and maintained on intravenous fluids and sedation. He developed a questionable episode of seizure activity. Over a three-week period of time his orbital pain became less, intense and there was noticeable improvement in his vision and eye movement. On discharge, the proptosis had almost receded and the patient no longer complained of pain. Three months later, he was seen because of recurrence of similar symptoms. He was again transfused and maintained on intravenous fluids and sedation, with complete recovery. A third episode, but milder than the previous ones, occurred two months later. It was then decided to maintain a hemoglobin level above 10 gm/dl by repeated transfusions. With this regimen, hemoglo-
0022-3476/79/090426 + 02500.20/0 9 1979 The C. V. Mosby Co.
Volume 95 Number 3
bin S level ranged from 25 to 50%. Since initiation of prophylactic transfusion therapy, no further episodes have developed. A recent computed tomography scan showed no evidence of retro-orbital mass, A peripheral area of low density was seen in the left occipital region, which did not enhance with contrast, considered to be an old infarction. DISCUSSION The orbital apex syndrome is a clinical entity characterized by marked restriction of mobility of the globe associated with proptosis, lid edema, reduction of vision, and pain in the orbital region and forehead? This syndrome is caused by several unrelated disorders, including infection, trauma, vascular and malignant lesions, as well as other inflammatory processes. 2-4 Earlier studies described the syndrome in association with syphilis and tuberculosis, but subsequent reports pointed to its occurrence with sinusitis, fungal infections such as aspergillosis, and herpes zoster ophthalmicus. The syndrome was initially described in 1896 by Rochon-DuVigneaud as sphenoid fissure syndrome? It has been emphasized by Walsh 1 and others that the manifestations of the orbital apex syndrome are usually incomplete. The syndrome ranges from complete involvement of all the nerves i n the orbit to partial involvement of the third cranial nerve. The major complications are optic neuritis and atrophy, which 9 result in permanent blindness. The diagnosis must be reached in a short period of time and appropriate treatment undertaken. In addition to the usual evaluation for orbital cellulitis, computed tomography has proved to be helpful and accurate in the initial evaluation of suspected intracranial lesions, and can be of considerable value in determining the etiology of Orbital disease. 6 The ophthalmic veins are very tortuous, large vessels with abundant collaterals. When obstruction to flow occurs and the anastomotic collaterals are insufficient, edema of the orbital tissue forms and, if unchecked, predisposes to orbital inflammation. Since the orbit is essentially a nonexpansible closed cavity, any increase in its contents will lead to displacement of the globe anteriorly. The edematous orbital structures lead to proptosis, decrease in mobility of the globe, and pain. Impairment of vision occurs as a result of pressure on the optic nerve, which compromises its circulation and leads to the development of papilledema and optic atrophy. Partial or complete ophthalmoplegia results, depending on the extent of the lesion. Sickle cell anemia has been known to be associated with ocular manifestations, but a recent review of this subject did not mention the orbital apex syndrome. ~It is generally considered that infarction in sickle cell disease is a result
Brief clinical and laboratory observations
427
of intravascutar sickling and vaso-occlusion, leading to ischemia and necrosis. Recent studies b y Stockman et aP have shown that sickling and vaso-occlusion can occur within the vasa vasorum olr large arteries and lead to changes within the wall of these vessels, with resultant intimal proliferation and repeated episodes of infarction. This additional pathogenic mechanism has been implicated for repeated central nervous system infarctions, and the same mechanism could be responsible for the repeated episodes in our patient. Because of the major complications associated with the mobility as well as function of the eye, we felt that prevention of further episodes in this patient was warranted, similar to that advocated for central nervous system infarction. Prophylactic transfusion therapy has been documented to be effective in preventing repeated central nervous system infarction, and in some patients has resulted in resolution of neurologic deficits) Although the use of chronic transfusion therapy in our patient may seem to constitute over-treatment, the risk of blindness was certainly real if measures had not been taken to prevent further episodes. Since initiation of prophylactic transfusion therapy, this patient has had only one minor attack of orbital pain without other manifestations, at a time when his hemoglobin level was 7 gm/dl. Whether this patient does have a vascular abnormality involving his orbital vessels and predisposing him to develop these localized vaso-occlusive crises remains to be determined. REFERENCES
1. Walsh FB, and Hoyt WF: Clinical neurophthalmology, ed 3, Baltimore, 1969, The Williams & Wilkins Company, pp 2011, 1488. 2. Kronschnabel EF: Orbital apex syndrome due to sinus infection, Laryngoscope, 84:353, 1974. 3. Jones HC, Proctor EH, and Johnson A: Parotid tumors and the orbital apex syndrome, J Natl Med Assoc 65:525, 1973. 4. Hedges TR: Paraseller and orbital apex syndrome caused by aspergillosis, Neurology 26:117, 1976. 5. Rochon-DuVigneaud: Quelques cas de paralysis de tousles nerfs Orbitaires d'origine syphilitique, Arch ophthalmol Tome trezieme, 1893. 6. Goldberg F, Berne AS, and Oski FA: Differentiation of orbital cellulitis from preseptal cellulitis by computed tomography, Pediatrics 62:1000, 1978. 7. Armaly M: Ocular manifestations in sickle cell disease, Arch Intern Med 133:670, 1974. 8. Stockman JA, Nigro M, Misklin M, and Oski FA: Occulsion of large cerebral vessels in sickle cell anemia, N Engl J Med 287:846, 1972. 9. Lusher JM, Haghighat H, and Khalifa AS: A prophylactic transfusion program for children with sickle cell anemia complicated by CNS infarction, Am J Hematol 1:265, 1976.
Brief clinical and laboratory observations
patterns o f occurrence o f second m a l i g n a n t n e o p l a s m s in children m a y also change. REFERENCES
1. Li FP: Second malignant tumors after cancer in childhood, Cancer 40:1800, 1977. 2. D'Angio GJ, Clatworthy HW, Evans AE, Newton WA, and Tefft M: Is the risk of morbidity and rare mortality worth the cure? Cancer 41:377, 1978. 3. Castro EB, Rosen PP, and Quan SHQ: Carcinoma of the large intestine in patients irradiated for carcinoma of cervix and uterus, Cancer 21:45, 1973.
The Journal of Pediatrics September 1979
4.
Upton AC: Radiation carcinogenesis, Front Radiat Ther Oncol 6:470, 1972. 5. Meadows AT, D'Angio GJ, Mike V, Banff A, Harris C, Jenkin RTD, and Schwartz A: Patterns of second malignant neoplasms in children, Cancer 40:1903, 1977. 6. Harris C: The carcinogenicity of anticar/cer drugs--a hazard in man, Cancer 37:(Suppl):1014, 1976. 7. D'Angio GJ, Evans AE, Breslow N, Beckwith B, Bishop H, Feigl P, Goodwin W, Leape LL, Sinks LF, Sutow W, Tefft M, and Wolff J: The treatment of Wilms' tumor--results of the National Wilms' Tumor Study, Cancer 38:633, 1976.
Orbital apex syndrome secondary to sickle cell anemia Rashid A. AI-RaShid, M.D., Omaha, Neb.
includes a spectrum o f disorders o f varying etiologies involving the apex o f the orbit a n d leading to alterations in ocular a n d extraocular f u n c t i o n s ? -4 Its association with sickle cell disease has n o t b e e n r e p o r t e d previously. This b r i e f report describes a n adolescent with sickle cell a n e m i a who, experienced several episodes o f o r b i t a l apex syndrome. F u r t h e r episodes were a p p a r e n t l y p r e v e n t e d by prophylactic transfusional therapy. THE
ORBITAL
APEX
SYNDROME
CASE REPORT
A 15-year-old black boy was diagnosed as having sickle cell anemia at about 2 years of age. His hemoglobin electrophoresis then showed an S-S pattern with 10% hemoglobin F. He was also found to have glucose-6-phosphate dehydrogenase deficiency, with a level of 3.5 IU/gm hemoglobin. Since that time he has had numerous hospitalizations as a result of vaso-occlusive crises. In May, 1976, he began to experience nausea associated with vomiting and mild diarrhea. Two days later he complained of pain in the right eye which became progressively more severe. He also began to experience diplopia and difficulty in opening his right eye; vision in that eye became blurred. A day prior to admission his vomiting subsided but the pain in his'0rbital region continued. He had had no fever, upper respiratory tract infection, or trauma to the eye. The patient was admitted to the University of Nebraska Medical Center for further evaluation. Physical examination revealed a thin, small for age male who appeared to have right-sided exophthalmos with ptosis of the right upper lid. He was slightly dehydrated. His temperature was
From the Department of Pediatric Hematology/Oncology, University of Nebraska Medical Center. Reprint address: Department of Pediatrics, University of Nebraska Medical Center, 42nd & Dewey Ave., Omaha, NE 68105.
37.6 ~ pulse 84/minute, respiration 20/minute, and blood pressure 120/70. The ophthalmologic examination showed ptosis of the right lid with l-ram proptosis of the right eye. The visual acuity of the right eye was limited to finger counting. There was marked reduction in movement of the right eye in all directions, especially medial gaze, with total third and fourth nerve paralysis and partial sixth nerve paralysis. There was no conjunctival or scleral injection. The fundoscopic examination showed increased venous tortuosity; no papilledema or hemorrhage was evident. Laboratory data showed hemoglobin 6.8 gm/dl, hematocrit 20%, WBC count 8,600/mm ~, with 34% polys, 6% bands, 34% lymphocytes, 24% monocytes, and 2% eosinophils. Platelet count was 602,000/mm, erythrocyte sedimentation rate 3 mm/hour, prothrombin time 13 seconds with a control of 12 seconds, and partial thromboplastin time 30 seconds with a control of 28 seconds. Serum electrolyte values were normal; the BUN was 15 mg/dl. Four blood cultures showed no growth; urine cultures were negative. Roentgenograms of the sinuses showed left mucous retention cyst; orbital views revealed prominent frontal sinuses with no evidence of, bony destruction, and the optic canal appeared normal. Radaonuchde encephalogram and cerebral flow studies were normal. Electroencephalogram showed a mild focal slow abnormality in the right hemisphere. During the hospitalization period, the patient was transfused to a hemoglobin level of 14 gm/dl and maintained on intravenous fluids and sedation. He developed a questionable episode of seizure activity. Over a three-week period of time his orbital pain became less, intense and there was noticeable improvement in his vision and eye movement. On discharge, the proptosis had almost receded and the patient no longer complained of pain. Three months later, he was seen because of recurrence of similar symptoms. He was again transfused and maintained on intravenous fluids and sedation, with complete recovery. A third episode, but milder than the previous ones, occurred two months later. It was then decided to maintain a hemoglobin level above 10 gm/dl by repeated transfusions. With this regimen, hemoglo-
0022-3476/79/090426 + 02500.20/0 9 1979 The C. V. Mosby Co.
Volume 95 Number 3
bin S level ranged from 25 to 50%. Since initiation of prophylactic transfusion therapy, no further episodes have developed. A recent computed tomography scan showed no evidence of retro-orbital mass, A peripheral area of low density was seen in the left occipital region, which did not enhance with contrast, considered to be an old infarction. DISCUSSION The orbital apex syndrome is a clinical entity characterized by marked restriction of mobility of the globe associated with proptosis, lid edema, reduction of vision, and pain in the orbital region and forehead? This syndrome is caused by several unrelated disorders, including infection, trauma, vascular and malignant lesions, as well as other inflammatory processes. 2-4 Earlier studies described the syndrome in association with syphilis and tuberculosis, but subsequent reports pointed to its occurrence with sinusitis, fungal infections such as aspergillosis, and herpes zoster ophthalmicus. The syndrome was initially described in 1896 by Rochon-DuVigneaud as sphenoid fissure syndrome? It has been emphasized by Walsh 1 and others that the manifestations of the orbital apex syndrome are usually incomplete. The syndrome ranges from complete involvement of all the nerves i n the orbit to partial involvement of the third cranial nerve. The major complications are optic neuritis and atrophy, which 9 result in permanent blindness. The diagnosis must be reached in a short period of time and appropriate treatment undertaken. In addition to the usual evaluation for orbital cellulitis, computed tomography has proved to be helpful and accurate in the initial evaluation of suspected intracranial lesions, and can be of considerable value in determining the etiology of Orbital disease. 6 The ophthalmic veins are very tortuous, large vessels with abundant collaterals. When obstruction to flow occurs and the anastomotic collaterals are insufficient, edema of the orbital tissue forms and, if unchecked, predisposes to orbital inflammation. Since the orbit is essentially a nonexpansible closed cavity, any increase in its contents will lead to displacement of the globe anteriorly. The edematous orbital structures lead to proptosis, decrease in mobility of the globe, and pain. Impairment of vision occurs as a result of pressure on the optic nerve, which compromises its circulation and leads to the development of papilledema and optic atrophy. Partial or complete ophthalmoplegia results, depending on the extent of the lesion. Sickle cell anemia has been known to be associated with ocular manifestations, but a recent review of this subject did not mention the orbital apex syndrome. ~It is generally considered that infarction in sickle cell disease is a result
Brief clinical and laboratory observations
427
of intravascutar sickling and vaso-occlusion, leading to ischemia and necrosis. Recent studies b y Stockman et aP have shown that sickling and vaso-occlusion can occur within the vasa vasorum olr large arteries and lead to changes within the wall of these vessels, with resultant intimal proliferation and repeated episodes of infarction. This additional pathogenic mechanism has been implicated for repeated central nervous system infarctions, and the same mechanism could be responsible for the repeated episodes in our patient. Because of the major complications associated with the mobility as well as function of the eye, we felt that prevention of further episodes in this patient was warranted, similar to that advocated for central nervous system infarction. Prophylactic transfusion therapy has been documented to be effective in preventing repeated central nervous system infarction, and in some patients has resulted in resolution of neurologic deficits) Although the use of chronic transfusion therapy in our patient may seem to constitute over-treatment, the risk of blindness was certainly real if measures had not been taken to prevent further episodes. Since initiation of prophylactic transfusion therapy, this patient has had only one minor attack of orbital pain without other manifestations, at a time when his hemoglobin level was 7 gm/dl. Whether this patient does have a vascular abnormality involving his orbital vessels and predisposing him to develop these localized vaso-occlusive crises remains to be determined. REFERENCES
1. Walsh FB, and Hoyt WF: Clinical neurophthalmology, ed 3, Baltimore, 1969, The Williams & Wilkins Company, pp 2011, 1488. 2. Kronschnabel EF: Orbital apex syndrome due to sinus infection, Laryngoscope, 84:353, 1974. 3. Jones HC, Proctor EH, and Johnson A: Parotid tumors and the orbital apex syndrome, J Natl Med Assoc 65:525, 1973. 4. Hedges TR: Paraseller and orbital apex syndrome caused by aspergillosis, Neurology 26:117, 1976. 5. Rochon-DuVigneaud: Quelques cas de paralysis de tousles nerfs Orbitaires d'origine syphilitique, Arch ophthalmol Tome trezieme, 1893. 6. Goldberg F, Berne AS, and Oski FA: Differentiation of orbital cellulitis from preseptal cellulitis by computed tomography, Pediatrics 62:1000, 1978. 7. Armaly M: Ocular manifestations in sickle cell disease, Arch Intern Med 133:670, 1974. 8. Stockman JA, Nigro M, Misklin M, and Oski FA: Occulsion of large cerebral vessels in sickle cell anemia, N Engl J Med 287:846, 1972. 9. Lusher JM, Haghighat H, and Khalifa AS: A prophylactic transfusion program for children with sickle cell anemia complicated by CNS infarction, Am J Hematol 1:265, 1976.
