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Facial palsy, an unusual presenting feature of childhood leukemia
Facial Palsy, an Unusual Presenting Feature of Childhood Leukemia
Bell’s palsy in young children and infants, however, are not available. This report describes two infants and one child of 6 years of age who presented with facial paresis as their first manifestation of leukemia. The purpose of this report is to draw attention to this uncommon presenting manifestation of leukemia. Case Reports Patient 1
Shedthikere N. Krishnamurthy, MD*, Arie L. Weinstock, MD*, Sharon H. Smith, MD†, and Patricia K. Duffner, MD* Facial paralysis is not a well-recognized presenting feature of leukemia in children. We present two infants and one older child in whom the initial manifestation of their leukemia was lower motor neuron facial paresis. Initial diagnosis in all the patients was Bell’s palsy. The presence of Bell’s palsy in young children requires a complete evaluation, including consideration of leptomeningeal disease. Leukemic children presenting with cranial neuropathy require intensive central nervous system therapy. © 2002 by Elsevier Science Inc. All rights reserved. Krishnamurthy SN, Weinstock AL, Smith SH, Duffner PK. Facial palsy, an unusual presenting feature of childhood leukemia. Pediatr Neurol 2002;27:68-70.
An 11-month-old white male presented with an acute onset of left facial palsy. A diagnosis of Bell’s palsy was made because the child did not have any additional findings. No treatment was administered. The child was brought back to the pediatrician 5 days later with bilateral facial palsy. This prompted a referral for a neurological consultation. The child did not have petechiae, bruising, bleeding of the mucosa, or fever. There was no lymphadenopathy or hepatosplenomegaly. He had bilateral peripheral facial palsy, but no other neurologic deficit was present. The hemoglobin was 10 gm/dL, platelets 90,000/dL, and white blood cell count (leukocytes) was 18,000/dL. He had 50% lymphoblasts in the peripheral blood smear. Bone marrow biopsy confirmed acute lymphoblastic leukemia. A magnetic resonance imaging scan of the brain did not reveal either meningeal enhancement or enhancement of the facial nerve. There was, however, evidence of bilateral mastoiditis. He had bilateral tympanocentesis, and antibiotics were administered for presumed mastoiditis. Cerebrospinal fluid analysis was normal without leukemic cells, increased protein, or hypoglycorrhachia. He was treated as a high-risk leukemic with a four-drug induction with daunomycin, vincristine, l-asparaginase, steroids, and intrathecal methotrexate. Antimetabolitebased consolidation and maintenance were administered. His facial paresis had improved at 6-month follow-up. The leukemia responded to chemotherapy, and the child remained in remission for 2 years after the diagnosis.
Patient 2
Introduction Facial paralysis is a known complication of central nervous system leukemia, but facial palsy as the presenting symptom of childhood leukemia is not well recognized. Indeed the standard textbooks in neurology, pediatrics, and oncology do not even mention facial palsy as one of the presenting features of leukemia [1-4]. Idiopathic facial paralysis (Bell’s palsy) is the most common facial palsy in adults with an incidence rate of 35/100,000 patients [5]. In adults and older children, 85% of peripheral facial palsy is idiopathic [6]. Incidence figures of
From the *Department of Neurology; State University of New York at Buffalo; Children’s Hospital of Buffalo; Buffalo, New York; and the † Department of Pediatric Hematology/Oncology; St. Vincent Hospital; Children’s Center for Cancer and Blood Diseases; Indianapolis, Indiana 46260.
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An 11-month-old white male was observed to have right facial droop when he awakened in the morning. The child was taken to the pediatrician, and a diagnosis of Bell’s palsy was made. Prednisolone was prescribed. Five days later the child’s facial palsy had not improved, and he developed truncal ataxia and was referred for neurologic evaluation. On close questioning, the mother reported that the child had been unusually irritable for 3 weeks before developing the facial palsy. On examination, he had hepatosplenomegaly and peripheral facial palsy. His leukocyte count was 149,000/dL, hemoglobin 10 gm/dL, and platelets 100,000/dL. Peripheral blood smear demonstrated 45% myeloblasts. Cerebrospinal fluid analysis was normal with no leukemic cells. A polymerase chain reaction study for herpes simplex virus was negative in the cerebrospinal fluid. Bone marrow biopsy confirmed acute myeloblastic leukemia. Magnetic resonance imaging of the brain was normal, with no evidence of facial nerve or meningeal enhancement. He was treated with both arabinoside-C intrathecally and intravenously and daunorubi-
Communications should be addressed to: Dr. Duffner; Professor of Neurology and Pediatrics; Children’s Hospital of Buffalo; 219 Bryant Street; Buffalo, NY 14222. Received October 9, 2001; accepted February 4, 2002.
© 2002 by Elsevier Science Inc. All rights reserved. PII S0887-8994(02)00394-6 ● 0887-8994/02/$—see front matter
cin. He also received radiation to the base of the skull with opposing lateral fields delivering a total dose of 600 cGy in 200-cGy daily fractions. Two months later the leukemia was in complete remission, although the facial palsy had not improved.
Patient 3 A 6-year-old Native American male presented with a 2-week history of intermittent fever and leg pain. He was evaluated by his pediatrician and was diagnosed as having a viral illness. His initial hemoglobin was 12 gm/dL, leukocytes of 16,000/dL, with lymphocytosis, and platelets of 150,000/dL. The day before referral he developed a left facial paralysis. Neurologic examination revealed a peripheral left facial palsy. His repeat leukocyte count was 18,800/dL, hemoglobin was 9.4 g/dL, and platelets were 93,000/dL. He had 8% lymphoblasts in the peripheral blood smear. Bone marrow biopsy confirmed acute lymphoblastic leukemia of L-3 morphology (Burkitt’s leukemia). Magnetic resonance imaging of the brain with contrast revealed enhancement of the left facial nerve in the facial canal. The cerebrospinal fluid was normal without any leukemic cells. The child’s course was complicated by renal failure as a result of tumor lysis syndrome requiring hemodialysis, hypocalcemia causing carpopedal spasms, Staphylococcus epidermidis sepsis treated with ceftazidime and vancomycin, and intractable vomiting requiring intravenous hyperalimentation. He was treated with methotrexate with leucovorin rescue, arabinoside-C, prednisolone, cyclophosphamide, Adriamycin, and intrathecal methotrexate. Radiation therapy was not administered. The child ultimately recovered, and he was discharged after 5 weeks of hospitalization. Six months later his facial palsy had improved. There was no relapse of leukemia for 2 years.
Discussion In all the cases presented, facial palsy was the initial clinical presentation of their leukemia. Both of the younger children (Patients 1 and 2) were diagnosed initially as having a Bell’s palsy. In the first patient, appearance of bilateral facial paralysis prompted neurologic referral. In the second patient, the child developed truncal ataxia, which resulted in the neurologic referral. It is important to note that facial paresis was the presenting symptom in all the patients for which primary care physicians were consulted. In infants and young children, symptomatic facial nerve palsy can be misdiagnosed as Bell’s palsy because of the difficulty of examining a fretful child in a busy pediatric practice. Subtle evidence of leukemia, such as splenomegaly, bone tenderness, mild bruising, irritability, and gait difficulties, can be overlooked as in the cases illustrated in this report. Idiopathic facial palsy is less common in infants and young children compared with older children and adults; other causes of facial palsy, such as traumatic, neoplastic, infective, inflammatory, metabolic, congenital, and vascular etiologies, should always be considered and excluded by diligent clinical examination and appropriate investigations (Table 1). Cranial neuropathies, especially of the seventh nerve, are well known to occur in children with central nervous system leukemia caused by leukemic infiltration; however, they are not typically the presenting sign of the disease [2]. Indeed, in our research of the literature, we did not come across any report of facial palsy as the presenting mani-
Table 1.
Causes of facial paresis in children
Congenital/Structural Chiari malformation, absence of depressor anguli oris muscle (cardiofacial syndrome), inner ear and/or facial nerve malformations, Mo¨ bius syndrome, syringobulbia. Genetic Facioscapulohumeral dystrophy, familial cranial neuropathy (recurrent), Fazio-Londe disease, myasthenia gravis, myotonic dystrophy, nemaline myopathy. Idiopathic Bell’s palsy Infectious-inflammatory Basilar meningitis, Epstein-Barr infection (infectious mononucleosis), Guillain-Barre´ syndrome, Miller-Fisher syndrome, Mycoplasma pneumoniae infection, Lyme disease (borreliosis), otitis media and mastoiditis, parotitis, poliomyelitis, Ramsay Hunt syndrome (herpes zoster), sarcoidosis, trichinosis, tuberculosis. Trauma-nerve compression Forceps pressure during delivery, cleidocrainal dysostosis, histiocytosis X, hyperostosis cranialis interna, increased intracranial pressure, petrous bone fracture, pressure from maternal sacrum. Metabolic conditions Hyperparathyroidism, hypothyroidism, idiopathic infantile hypocalcemia, osteopetrosis, diabetes. Neoplasms Brainstem glioma, parotid gland tumors, leukemias. Vascular Arterial hypertension, vascular syndromes of the cranial nerves. Other Idiopathic cranial neuropathy, Melkersson-Rosenthal syndrome, multiple sclerosis, myasthenia gravis (immune mediated), myasthenia gravis (transient neonatal).
festation of leukemia in children, although there was one patient in whom it was the first sign of relapse [7]. However, there have been isolated reports of facial palsy as the presenting symptom of leukemia in adults [8]. Facial paralysis in children with leukemia is caused by infiltration of the nerve with leukemic cells [9]. It is of interest that only one patient (Patient 3) had enhancement of the seventh cranial nerve on magnetic resonance imaging, and none of the patients had had positive cytology. Meningeal infiltration in the early stages, however, may not result in an abnormality either on magnetic resonance imaging or cerebrospinal fluid analysis [7]. The absence of positive magnetic resonance imaging in Patients 1 and 2 may reflect the fact that thin slicing of the facial canal was not performed. Current magnetic resonance imaging techniques are able to demonstrate facial nerve enhancement more readily [10]. We conclude that facial palsy can occasionally be the presenting symptom of childhood leukemia and may be misdiagnosed as Bell’s palsy by the unwary. The presence of facial palsy suggests meningeal disease and hence requires intensive central nervous system therapy even in the absence of positive cytology or enhancement of the nerve on magnetic resonance imaging. References [1] Crist WM, Smith WA. The leukemias. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson textbook of pediatrics, 16th ed. Philadelphia: WB Saunders, 2000:1543-4.
Krisnamurthy et al: Childhood Leukemia and Facial Palsy 69
[2] Cohen ME, Duffner PK. Tumors of the brain and spinal cord including leukemic involvement. In: Swaiman KF, ed. Pediatric neurology: Principles and practice, 2nd ed. St. Louis: Mosby, 1994;2:931-4. [3] Rohatiner A, Lister TA. The general management of patient with leukemia. In: Henderson ES, Lister A, Greaves MF, eds. Leukemia, 6th ed. Philadelphia: WB Saunders, 1995:247-55. [4] Pui C-H. Acute lymphoblastic leukemia. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, Seligsohn U, eds. Williams’s hematology, 6th ed. New York: McGraw Hill, 2000:1141-61. [5] Adur KK, Byl FM, Hilsinger Jr RL, Khan ZM, Sheldonet MI. The true nature of Bells palsy: Analysis of 1000 consecutive patients. Laryngoscope 1978;5:787-801. [6] Hauser WA, Karnes WE, Annis J, Kurland LT. Incidence, and
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prognosis of Bell’s palsy in the population of Rochester, Minnesota. Mayo Clin Proc 1971;4:258-64. [7] Juhn YJ, Inoue S. Facial nerve palsy as an early manifestation of relapse in T-cell acute lymphoblastic leukemia. Ear Nose Throat J 1996;75:157-60. [8] Sawada H, Matsui M, Udaka F, Nishimura M, Fujita M, Kameyama K. Adult T-cell leukemia initially manifesting as facial diplegia. Am J Hematol 1989;32:61-5. [9] Zechner G, Altman F. The temporal bone in leukemia. Histological studies. Ann Otol Rhinol Laryngol 1969;78:375-87. [10] Navarrete ML, Rovira A, Quesada P, Garcia M. Gadoliniumenhanced magnetic resonance imaging in Bell’s palsy. Eur Arch Otorhinolaryngol 1994;S356-7.
Bell’s palsy in young children and infants, however, are not available. This report describes two infants and one child of 6 years of age who presented with facial paresis as their first manifestation of leukemia. The purpose of this report is to draw attention to this uncommon presenting manifestation of leukemia. Case Reports Patient 1
Shedthikere N. Krishnamurthy, MD*, Arie L. Weinstock, MD*, Sharon H. Smith, MD†, and Patricia K. Duffner, MD* Facial paralysis is not a well-recognized presenting feature of leukemia in children. We present two infants and one older child in whom the initial manifestation of their leukemia was lower motor neuron facial paresis. Initial diagnosis in all the patients was Bell’s palsy. The presence of Bell’s palsy in young children requires a complete evaluation, including consideration of leptomeningeal disease. Leukemic children presenting with cranial neuropathy require intensive central nervous system therapy. © 2002 by Elsevier Science Inc. All rights reserved. Krishnamurthy SN, Weinstock AL, Smith SH, Duffner PK. Facial palsy, an unusual presenting feature of childhood leukemia. Pediatr Neurol 2002;27:68-70.
An 11-month-old white male presented with an acute onset of left facial palsy. A diagnosis of Bell’s palsy was made because the child did not have any additional findings. No treatment was administered. The child was brought back to the pediatrician 5 days later with bilateral facial palsy. This prompted a referral for a neurological consultation. The child did not have petechiae, bruising, bleeding of the mucosa, or fever. There was no lymphadenopathy or hepatosplenomegaly. He had bilateral peripheral facial palsy, but no other neurologic deficit was present. The hemoglobin was 10 gm/dL, platelets 90,000/dL, and white blood cell count (leukocytes) was 18,000/dL. He had 50% lymphoblasts in the peripheral blood smear. Bone marrow biopsy confirmed acute lymphoblastic leukemia. A magnetic resonance imaging scan of the brain did not reveal either meningeal enhancement or enhancement of the facial nerve. There was, however, evidence of bilateral mastoiditis. He had bilateral tympanocentesis, and antibiotics were administered for presumed mastoiditis. Cerebrospinal fluid analysis was normal without leukemic cells, increased protein, or hypoglycorrhachia. He was treated as a high-risk leukemic with a four-drug induction with daunomycin, vincristine, l-asparaginase, steroids, and intrathecal methotrexate. Antimetabolitebased consolidation and maintenance were administered. His facial paresis had improved at 6-month follow-up. The leukemia responded to chemotherapy, and the child remained in remission for 2 years after the diagnosis.
Patient 2
Introduction Facial paralysis is a known complication of central nervous system leukemia, but facial palsy as the presenting symptom of childhood leukemia is not well recognized. Indeed the standard textbooks in neurology, pediatrics, and oncology do not even mention facial palsy as one of the presenting features of leukemia [1-4]. Idiopathic facial paralysis (Bell’s palsy) is the most common facial palsy in adults with an incidence rate of 35/100,000 patients [5]. In adults and older children, 85% of peripheral facial palsy is idiopathic [6]. Incidence figures of
From the *Department of Neurology; State University of New York at Buffalo; Children’s Hospital of Buffalo; Buffalo, New York; and the † Department of Pediatric Hematology/Oncology; St. Vincent Hospital; Children’s Center for Cancer and Blood Diseases; Indianapolis, Indiana 46260.
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An 11-month-old white male was observed to have right facial droop when he awakened in the morning. The child was taken to the pediatrician, and a diagnosis of Bell’s palsy was made. Prednisolone was prescribed. Five days later the child’s facial palsy had not improved, and he developed truncal ataxia and was referred for neurologic evaluation. On close questioning, the mother reported that the child had been unusually irritable for 3 weeks before developing the facial palsy. On examination, he had hepatosplenomegaly and peripheral facial palsy. His leukocyte count was 149,000/dL, hemoglobin 10 gm/dL, and platelets 100,000/dL. Peripheral blood smear demonstrated 45% myeloblasts. Cerebrospinal fluid analysis was normal with no leukemic cells. A polymerase chain reaction study for herpes simplex virus was negative in the cerebrospinal fluid. Bone marrow biopsy confirmed acute myeloblastic leukemia. Magnetic resonance imaging of the brain was normal, with no evidence of facial nerve or meningeal enhancement. He was treated with both arabinoside-C intrathecally and intravenously and daunorubi-
Communications should be addressed to: Dr. Duffner; Professor of Neurology and Pediatrics; Children’s Hospital of Buffalo; 219 Bryant Street; Buffalo, NY 14222. Received October 9, 2001; accepted February 4, 2002.
© 2002 by Elsevier Science Inc. All rights reserved. PII S0887-8994(02)00394-6 ● 0887-8994/02/$—see front matter
cin. He also received radiation to the base of the skull with opposing lateral fields delivering a total dose of 600 cGy in 200-cGy daily fractions. Two months later the leukemia was in complete remission, although the facial palsy had not improved.
Patient 3 A 6-year-old Native American male presented with a 2-week history of intermittent fever and leg pain. He was evaluated by his pediatrician and was diagnosed as having a viral illness. His initial hemoglobin was 12 gm/dL, leukocytes of 16,000/dL, with lymphocytosis, and platelets of 150,000/dL. The day before referral he developed a left facial paralysis. Neurologic examination revealed a peripheral left facial palsy. His repeat leukocyte count was 18,800/dL, hemoglobin was 9.4 g/dL, and platelets were 93,000/dL. He had 8% lymphoblasts in the peripheral blood smear. Bone marrow biopsy confirmed acute lymphoblastic leukemia of L-3 morphology (Burkitt’s leukemia). Magnetic resonance imaging of the brain with contrast revealed enhancement of the left facial nerve in the facial canal. The cerebrospinal fluid was normal without any leukemic cells. The child’s course was complicated by renal failure as a result of tumor lysis syndrome requiring hemodialysis, hypocalcemia causing carpopedal spasms, Staphylococcus epidermidis sepsis treated with ceftazidime and vancomycin, and intractable vomiting requiring intravenous hyperalimentation. He was treated with methotrexate with leucovorin rescue, arabinoside-C, prednisolone, cyclophosphamide, Adriamycin, and intrathecal methotrexate. Radiation therapy was not administered. The child ultimately recovered, and he was discharged after 5 weeks of hospitalization. Six months later his facial palsy had improved. There was no relapse of leukemia for 2 years.
Discussion In all the cases presented, facial palsy was the initial clinical presentation of their leukemia. Both of the younger children (Patients 1 and 2) were diagnosed initially as having a Bell’s palsy. In the first patient, appearance of bilateral facial paralysis prompted neurologic referral. In the second patient, the child developed truncal ataxia, which resulted in the neurologic referral. It is important to note that facial paresis was the presenting symptom in all the patients for which primary care physicians were consulted. In infants and young children, symptomatic facial nerve palsy can be misdiagnosed as Bell’s palsy because of the difficulty of examining a fretful child in a busy pediatric practice. Subtle evidence of leukemia, such as splenomegaly, bone tenderness, mild bruising, irritability, and gait difficulties, can be overlooked as in the cases illustrated in this report. Idiopathic facial palsy is less common in infants and young children compared with older children and adults; other causes of facial palsy, such as traumatic, neoplastic, infective, inflammatory, metabolic, congenital, and vascular etiologies, should always be considered and excluded by diligent clinical examination and appropriate investigations (Table 1). Cranial neuropathies, especially of the seventh nerve, are well known to occur in children with central nervous system leukemia caused by leukemic infiltration; however, they are not typically the presenting sign of the disease [2]. Indeed, in our research of the literature, we did not come across any report of facial palsy as the presenting mani-
Table 1.
Causes of facial paresis in children
Congenital/Structural Chiari malformation, absence of depressor anguli oris muscle (cardiofacial syndrome), inner ear and/or facial nerve malformations, Mo¨ bius syndrome, syringobulbia. Genetic Facioscapulohumeral dystrophy, familial cranial neuropathy (recurrent), Fazio-Londe disease, myasthenia gravis, myotonic dystrophy, nemaline myopathy. Idiopathic Bell’s palsy Infectious-inflammatory Basilar meningitis, Epstein-Barr infection (infectious mononucleosis), Guillain-Barre´ syndrome, Miller-Fisher syndrome, Mycoplasma pneumoniae infection, Lyme disease (borreliosis), otitis media and mastoiditis, parotitis, poliomyelitis, Ramsay Hunt syndrome (herpes zoster), sarcoidosis, trichinosis, tuberculosis. Trauma-nerve compression Forceps pressure during delivery, cleidocrainal dysostosis, histiocytosis X, hyperostosis cranialis interna, increased intracranial pressure, petrous bone fracture, pressure from maternal sacrum. Metabolic conditions Hyperparathyroidism, hypothyroidism, idiopathic infantile hypocalcemia, osteopetrosis, diabetes. Neoplasms Brainstem glioma, parotid gland tumors, leukemias. Vascular Arterial hypertension, vascular syndromes of the cranial nerves. Other Idiopathic cranial neuropathy, Melkersson-Rosenthal syndrome, multiple sclerosis, myasthenia gravis (immune mediated), myasthenia gravis (transient neonatal).
festation of leukemia in children, although there was one patient in whom it was the first sign of relapse [7]. However, there have been isolated reports of facial palsy as the presenting symptom of leukemia in adults [8]. Facial paralysis in children with leukemia is caused by infiltration of the nerve with leukemic cells [9]. It is of interest that only one patient (Patient 3) had enhancement of the seventh cranial nerve on magnetic resonance imaging, and none of the patients had had positive cytology. Meningeal infiltration in the early stages, however, may not result in an abnormality either on magnetic resonance imaging or cerebrospinal fluid analysis [7]. The absence of positive magnetic resonance imaging in Patients 1 and 2 may reflect the fact that thin slicing of the facial canal was not performed. Current magnetic resonance imaging techniques are able to demonstrate facial nerve enhancement more readily [10]. We conclude that facial palsy can occasionally be the presenting symptom of childhood leukemia and may be misdiagnosed as Bell’s palsy by the unwary. The presence of facial palsy suggests meningeal disease and hence requires intensive central nervous system therapy even in the absence of positive cytology or enhancement of the nerve on magnetic resonance imaging. References [1] Crist WM, Smith WA. The leukemias. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson textbook of pediatrics, 16th ed. Philadelphia: WB Saunders, 2000:1543-4.
Krisnamurthy et al: Childhood Leukemia and Facial Palsy 69
[2] Cohen ME, Duffner PK. Tumors of the brain and spinal cord including leukemic involvement. In: Swaiman KF, ed. Pediatric neurology: Principles and practice, 2nd ed. St. Louis: Mosby, 1994;2:931-4. [3] Rohatiner A, Lister TA. The general management of patient with leukemia. In: Henderson ES, Lister A, Greaves MF, eds. Leukemia, 6th ed. Philadelphia: WB Saunders, 1995:247-55. [4] Pui C-H. Acute lymphoblastic leukemia. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, Seligsohn U, eds. Williams’s hematology, 6th ed. New York: McGraw Hill, 2000:1141-61. [5] Adur KK, Byl FM, Hilsinger Jr RL, Khan ZM, Sheldonet MI. The true nature of Bells palsy: Analysis of 1000 consecutive patients. Laryngoscope 1978;5:787-801. [6] Hauser WA, Karnes WE, Annis J, Kurland LT. Incidence, and
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prognosis of Bell’s palsy in the population of Rochester, Minnesota. Mayo Clin Proc 1971;4:258-64. [7] Juhn YJ, Inoue S. Facial nerve palsy as an early manifestation of relapse in T-cell acute lymphoblastic leukemia. Ear Nose Throat J 1996;75:157-60. [8] Sawada H, Matsui M, Udaka F, Nishimura M, Fujita M, Kameyama K. Adult T-cell leukemia initially manifesting as facial diplegia. Am J Hematol 1989;32:61-5. [9] Zechner G, Altman F. The temporal bone in leukemia. Histological studies. Ann Otol Rhinol Laryngol 1969;78:375-87. [10] Navarrete ML, Rovira A, Quesada P, Garcia M. Gadoliniumenhanced magnetic resonance imaging in Bell’s palsy. Eur Arch Otorhinolaryngol 1994;S356-7.