| OCR Text |
Show Journal of Clinical Neuro-ophthalmology 13(1); 18-23, 1993. Parainfectious Optic Neuritis and Encephalomyelitis A Report of Two Cases with Thalamic Involvement Latif M. Hamed, M.D., Jonathan Silbiger, M.D., John Guy, M.D., J. Parker Mickle, M.D., Patrick Sibony, M.D., Alfred Cossari, M.D., and Mary Andriola, M.D. © 1993 Raven Press, Ltd., New York Two children developed mental status alteration and bilateral profound visual loss secondary to optic neuritis. The clinical picture was consistent with parainfectious encephalomyelitis. Magnetic resonance imaging showed bilateral involvement of the thalamus in both cases. In one case the thalamic involvement was solitary and was suspected initially to represent a primary thalamic neoplasm. This was ruled out by a stereotactic biopsy of the thalamus, which showed perivascular inflammation consistent with parainfectious encephalomyelitis. The clinical and neuroimaging findings improved significantly following corticosteroid administration. Several relapses occurred upon initial attempts at corticosteroid cessation. Key Words: Encephalitis---Thalamus---NeuroimagingCorticosteroid therapy. From the Departments of Ophthalmology (L.M.H., }.S., J.G.), Neurology (J.G.), and Neurosurgery (J.P.M.), University of Florida College of Medicine, Gainesville, Florida, and the Departments of Ophthalmology (P.S., A.c., M.A.) and Neurology (P.S.), State University of New York at Stony Brook, Stony Brook, New York, U.S.A. This work was supported in part by an unrestricted grant from Research to Prevent Blindness, Inc., New York, New York. Address correspondence and reprint requests to Dr. Latif M. Hamed, Department of Ophthalmology, University of Florida College of Medicine, Box 100284, JHMHSC, Gainesville, FL 32610-0284, U.S.A. 18 Optic neuritis is uncommon in children and differs from that in adults in that it is frequently bilateral (1). Optic neuritis in children has been associated with many systemic diseases including mononucleosis, measles, mumps, chickenpox, pertussis, and viral encephalitis (2). Immunizations have also been temporally associated with initial as well as recurrent episodes of optic neuritis (3). Two children developed bilateral severe optic neuritis with thalamic lesions. Both cases were preceded by a viral prodrome, and one case was temporally associated with diphtheria-tetanuspertussis (DTP) and oral polio vaccination. Both patients favorably responded clinically and radiographically to intravenous corticosteroid therapy, although the first case required long-term immunosuppression. CASE 1 A 5-year-old girl was referred to Shands Teaching Hospital at the University of Florida for evaluation of a thalamic mass. The patient was in her usual state of good health until 2 weeks prior to admission, when she developed a sore throat, mild fever, and nausea. On the day of admission to another hospital she acutely developed eye pain, gait instability, lethargy, and disorientation. The patient had received her scheduled DTP and oral polio immunizations 3 weeks prior to admission, and had been exposed to a child with viral encephalitis 2 weeks prior to admission. No other significant past medical history was present. On admission to the outside hospital the patient OPTIC NEURITIS AND ENCEPHALOMYELITIS 19 was obtunded but showed no localizing neurological signs. A lumbar puncture revealed a normal opening pressure, WBC = 39, RBC = 5, protein = 29, glucose = 60, and negative latex agglutination, bacterial, and fungal cultures. There was an elevated white blood cell count of 19.5 (74% polymorphonuclear cells) and normal hematocrit, electrolytes, and urinalysis. A magnetic resonance scan demonstrated bilateral thalamic lesions, which showed increased signal on T2-weighted images, but no signs of mass effect (Fig. 1). The patient was treated with ceftriaxone for 2 days with little change in her clinical status. She was transferred to Shands Teaching Hospital for further evaluation. The patient's clinical examination was essentially unchanged on arrival at our hospital. The patient was begun on intravenous dexamethasone (2 mg every 6 hours). Ceftriaxone (800 mg every 12 hours) was continued. The patient underwent a stereotactic biopsy of the right thalamic lesion. Histopathologic examination revealed chronic perivascular inflammation with microglial activation and microglial nodule formation. Tumor, intranuclear inclusions, and myelin destruction were absent. Stains for herpes viral antigens were negative. Additional studies including erythrocyte sedimentation rate, liver profile, antinuclear antibody, immunoglobulin, complement, C-reactive protein, rheumatoid factor, and meningoencephalitis antibodies (herpes simplex virus, Dengue fever, eastern equine encephalomyelitis, St. Louis encephalitis) showed normal results. The patient's mental status returned to normal while on corticosteroid therapy, which was tapered as an outpatient. The patient did extremely well for 2 months with normalization of vision. However, 6 days after corticosteroid cessation she developed bilateral eye pain and decreased vision. Visual acuity was 20/400 in the right eye and count fingers in the left eye. There was a left afferent pupillary defect. The left optic nerve head was edematous. Neurological examination was otherwise normal. Magnetic resonance imaging (MRI) of the brain showed encephalomalacia at the site of the biopsy in the right thalamus but was otherwise normal. After 3 days of intravenous methylprednisolone (10 mg/kg) therapy, visual acuity improved to 201 30 in the right eye and 20/50 in the left eye. The left afferent pupillary defect and optic disc edema persisted but were improved. The patient was again discharged on a tapering regimen of oral corticosteroids. The patient suffered several subsequent recur-rences of optic neuritis and altered mental status upon tapering the corticosteroid regimen below 20 mg/day. Imuran was then added to the therapeutic regimen. Six months later, visual acuity was 20/15 in each eye. The afferent pupillary defect and left disc edema had resolved. CASE 2 A 4-year-old girl was examined after admission to University Hospital at State University of New York at Stony Brook for evaluation of papilledema. The patient was in her usual state of good health until 2 months prior to admission when she developed a bifrontal headache, mild fever, vomiting, and diarrhea. This episode resolved spontaneously after 5 days. One week prior to admission the patient complained of headache and ear pain, and was diagnosed with pharyngitis and otitis media. She was treated with oral amoxicillin. Two days prior to admission the mother noted decreased vision, frequent blinking, and clumsiness in the child. The patient had been exposed to chickenpox 9 days prior to admission but never developed a rash. Visual acuity upon admission was hand motion vision OU. The pupils were sluggishly reactive to light and without a relative afferent defect. There was bilateral disc edema. The general examination revealed erythematous tympanic membranes but was otherwise normal. The patient was awake and alert. Cranial nerves III-XII were intact. She had normal motor and sensory findings and intact reflexes. A lumbar puncture showed a normal opening pressure, WBC = 16 (83% mononuclear cells), RBC = 8, protein = 26, glucose = 69 (serum glucose = 122). Spinal fluid viral, bacterial, and fungal cultures as well as cytological studies were negative. Other laboratory tests revealed Hct = 35, WBC = 16.4, ESR = 29, C3 = 121, C4 = 28.3, ASO = 200 to 400, RPR negative, rheumatoid factor negative, Lyme titer negative, and negative blood cultures. MRI with multiple sagittal and axial sections of the brain were obtained using multiplanar spinecho pulse sequences including Tl-, proton density, and T2-weighted images. The study revealed an abnormal signal in the left pulvinar of the thalamus measuring over 1 cm with surrounding edema (Fig. 2). There was also increased signal intensity on the T2-weighted images in the gray matter in the posterior parietal regions and left corona radiata (probably representing edema). Re- I Clin Neuro-ophthalmol, Vol. 13, No. I, 1993 20 c L. M. HAMED ET AL. B FIG. 1. Case 1. (A) T2-weighted MR scan upon initial presentation shows a bilateral thalamic lesion with high signal intensity. (B) T1- and (C) T2-weighted MR scans obtained following treatment with intravenous corticosteroids show total resolution of thalamic lesions; focal encephalomalacia of right thalamus at the site of previous stereotactic biopsy was present. No white matter lesions in the subcortical white matter were seen in this case. peat MRI 3 days later with gadolinium EDTA and additional views of the orbits showed minimal thickening of the optic nerves and nodular, patchy gadolinium enhancement in the prechiasmal seg- I Gin Neuro-ophthalmol, Vol. 13, No.1, 1993 ments, The thalamic lesion showed minimal enhancement with gadolinium, The patient was treated with intravenous SoluMedrol40 mg every day, acyclovir 250 mglkg/day, A c OPTIC NEURITIS AND ENCEPHALOMYELITIS FIG. 2. Case 2. (A) T1-weighted MR scan shows low-signal intensity lesion in left thalamus with two small foci of gadolinium enhancement in the right subcortical white matter. (B) Proton density and (C) T2-weighted MR scans show increased signal intensity of left thalamic lesions as well as several high-signal lesions bilaterally in the subcortical white matter of the parietal and occipital areas. B 21 and ampicillin 100 mglkg/day. During the hospitalization the patient's vision, pupillary reaction, and optic disc edema improved. The patient was discharged after 5 days on a tapering dose of prednisone. She had a recurrent episode of visual loss with papillitis after tapering off the prednisone, but responded well to a slower tapering schedule. One month after the patient's admission her visual acuity was 20/30 OU. The pupils were normal and the disc edema had resolved. DISCUSSION Optic neuritis is uncommon in childhood and differs from the adult variety in various respects. A study of 41 children with optic neuritis showed a greater tendency for simultaneous bilateral involvement, and a greater frequency of optic nerve edema than in the adult-onset variety (1). Optic neuritis in children is often associated with systemic infections such as measles, mumps, vari- I Clin Neuro-ophthalmol, Vol. 13, No.1. 1993 22 L. M. HAMED ET AL. cella, pertussis, mononucleosis, viral encephalitis, and immunizations (2). Given the high frequency of associated headaches, nausea, vomiting, and spinal fluid lymphocytosis, it may be likely that many cases of childhood optic neuritis are associated with some degree of encephalomyelitis. Even in the absence of these symptoms, some investigators consider many cases of childhood optic neuritis to represent a localized form of encephalomyelitis. Despite the development of optic nerve pallor (88% in one series) the visual prognosis is good in children and the risk of developing multiple sclerosis appears small (4). Various studies have noted an apparent correlation between childhood vaccinations and the subsequent development of encephalitis and optic neuritis. Optic neuritis has been associated with the following immunizations: DTP, polio, vaccinia (3), measles-mumps-rubella (MMR) (5), influenza (6), rabies (7), and hepatitis B (8). Riikonen (3) studied 18 children with optic neuritis and found 56% had a bacterial or viral infection 2 weeks prior to the first symptom of optic neuritis. Various vaccinations preceded (3 days to 1 month) the first attack of optic neuritis in 5 of 18 patients. Three patients had recurrent attacks of optic neuritis when reexposed to the vaccine. Three patients had meningoencephalitis associated with the optic neuritis. While these studies were not controlled and do not prove causation, they show a temporal relationship between viral infections and/or vaccinations and the development of optic neuritis in children. In one of our patients, the onset of symptoms was temporally related to a vaccination with DTP and oral polio virus. Common side effects of childhood immunizations including local tenderness, malaise, irritability, and fever are well known and transient. The association of serious and permanent neurological sequelae with certain immunizations remains debatable, however. Miller et al. (9) studied 1,000 children with serious neurological illnesses and found 3.5% were immunized with DTP vaccine 1 week prior to onset of neurological symptoms. They estimated that in an immunized child the relative risk of developing serious neurological illness was 2.4 times that of an unimmunized child. Many authors disagree with the conclusion that serious clinical problems may be caused by the DTP vaccine. A study of 38,171 children who received DTP vaccines during the first 3 years of life showed no increased risk of seizures as compared to a control population (10). Only two patients in the study developed encephalitis, but its onset was greater than 2 weeks after vaccination JClin Neuro-ophthalmol. Vol. 13, No. 1, 1993 and neither had permanent sequelae (10). A committee of the Child Neurology Society concluded that no controlled studies have proved the association between pertussis vaccine and progressive or chronic neurologic disorders (11). It should be noted that other vaccines have been more clearly associated with serious problems, however. The swine influenza vaccination of 1976 was notorious for a large number of patients developing GuillainBarre syndrome (6). Smallpox and rabies vaccines were associated with considerable neurological morbidity and mortality (11). Viral encephalitis can be divided into four distinctive groups: acute viral encephalitis, parainfectious encephalomyelitis, slow viral infections, and chronic viral infections (12). Parainfectious encephalomyelitis (also known as acute disseminated encephalomyelitis) develops 4 to 14 days after infection or immunization. It has similar symptoms and cerebrospinal fluid (CSF) findings to acute viral encephalitis, but no viral particles can be isolated or cultured. The inflammation is probably due to a hypersensitivity reaction as opposed to direct infection, and results in a perivascular mononuclear cellular infiltration and demyelination. Most commonly, parainfectious encephalomyelitis follows nonspecific upper respiratory tract infections (approximately 70%), but may also follow measles, mumps, varicella infections or smallpox and rabies vaccinations (13). The typical MRI findings in parainfectious encephalitis are multifocal brain lesions, often indistinguishable from multiple sclerosis (14). Our patients presented with thalamic masses in addition to the ophthalmologic findings, and the differential diagnosis included the possibility of a primary thalamic tumor. This was particularly considered in Case 1 due to the solitary nature of the thalamic involvement. This concern led to a biopsy in Case 1. Glial tumors make up the majority of thalamic tumors in children. A retrospective study of 60 children with thalamic tumors revealed 35 to be astrocytomas. Approximately half of these were malignant (15). Even though most germinomas occur in the pineal gland or supracellar region, 5 to 10% originate in the thalamus or basal ganglia (16). It is helpful to obtain a histopathological diagnosis of thalamic tumors, because benign and malignant gliomas and germinomas require different therapeutic approaches (17). We described the clinical and neuroradiologic findings in two children who developed severe bilateral optic neuritis and thalamic lesions. One patient underwent stereotactic brain biopsy of the thalamus to rule out a neoplasm; the histopathol- OPTIC NEURITIS AND ENCEPHALOMYELITIS 23 ogy revealed perivascular inflammation. Both patients had an antecedent viral infection and Case 1 was temporally associated with administration of a DTP vaccine. These two cases favorably responded clinically and radiographically to high-dose corticosteroid therapy, and both suffered relapses upon tapering off their corticosteroids. These cases probably represent a clinical variant of parainfectious encephalomyelitis with concurrent papillitis, and point out the need for accurate diagnostic techniques and the need for long-term immunosuppression. Given the striking appearance of the thalamic lesions in Case 1, a decision to treat a similar case conservatively (i.e., with corticosteroids but without obtaining a biopsy) would be a clinical one, and would be difficult to suggest from the neuroimaging alone. However, recognition of this clinical presentation of parainfectious encephalitis may occasionally obviate the performance of a thalamic biopsy. REFERENCES 1. Kennedy C, Carroll F. Optic neuritis in children. Arch Ophthalmol 1960;63:747-75. 2. Farris B, Pickard D. Bilateral postinfectious optic neuritis and intravenous steroid therapy in children. Ophthalmology 1990;97:339-45. 3. Riikonen R. The role of infection and vaccination in the genesis of optic neuritis and multiple sclerosis in children. Acta Neurol Scand 1989;80:425-31. 4. Kriss A, Francis D, Cuendet F, et al. Recovery after optic neuritis in childhood. J Neurol Neurosurg Psychol 1988;51: 1254-8. 5. Kazarian E, Gager W. Optic neuritis complicating measles, mumps, rubella vaccination. Am J Ophthalmol 1978;86: 544--7. 6. Poser C. Neurological complications of swine influenza vaccination. Acta Neurol Scand 1982;66:41~31. 7. Dano P, LeGuyader J. Neurologic complications of vaccinations against rabies, MRI in one case. Rev Neurol Paris 1987;143:55-8. 8. Shaw F, Graham D, Guess H, et al. Postmarketing surveillance for neurological adverse events reported after hepatitis B vaccination, experience after the first three years. Am J EpidemioI1988;127:337-57. 9. Miller DL, Ross EM, Alderslade R, Bellman MH, Rawson NS. Pertussis immunization and serious acute neurological illness in children. Br Med J 1981;282:159~9. 10. Griffin MR, Ray WA, Mortimer EA, Fenichel GM, Schaffner W. Risk of seizures and encephalopathy after immunizations with the diphtheria-tetanus-pertussis vaccine. JAMA 1990;263:1641-5. 11. Ad Hoc Committee for the Child Neurology Society. Pertussis immunization and the central nervous system. Ann Neurol 1991;29:458-60. 12. Johnson R. The pathogenesis of acute viral encephalitis and post infectious encephalomyelitis. J Infect Dis 1987;153:35964. 13. Ho D, Hirsch M. Acute viral encephalitis. Med Clin North Am 1985;69:415-29. 14. Atlas SW, Grossman RI, Goldberg HI. Hackney DB, Bilaniuk LT, Zimmerman RA. MR diagnosis of acute disseminated encephalomyelitis. J Comput Assist Tomogr 1986;10: 798-801. 15. Bernstein M, Hoffman H, Halliday W, et al. Thalamic tumor in children, long-term follow up and treatment guidelines. JNeurosurg 1984;61 :649-56. 16. Soejima T, Takeshita T, Hamamoto H, et al. Computer tomography of germinomas in the basal ganglia and thalamus. Neuroradiology 1987;29:36~70. 17. Ono N, lnove H, Nagamuma H, et al. Diagnosis of germinal neoplasm in the thalamus and basal ganglia. Surg NeuroI1986; 26:24-8. I Clill Neuro-ophthalmol, Vol. 13, No.1, 1993 [VBmeningoencephalitis] |
