Child Neurology - part 6 pot

871. Dickson DW, et al. Central nervous system pathology in pediatric AIDS: an autopsy study. APMIS 1989; 8[Suppl]:40–57. 872. Donaldson YK, Bell JE, Ironside JW. Redistribution of HIV outside the lymphoid system with onset of AIDS. Lancet 1994;343:382–385. 873. Falloon J, et al. Human immunodeficiency virus infection in children. J Pediatr 1989;114:1–30. 874. Spencer DC, Price RW. Human immunodeficiency virus and the central nervous system. Annu Rev Microbiol 1992;46:655–693. 875. Petito CK. What causes brain atrophy in human immunodeficiency virus infection? Ann Neurol 1993; 34:128–129. 876. Kure K, et al. Morphology and distribution of HIV-1 gp41-positive microglia in subacute AIDS encephalitis. Pattern of involvement resembling a multisystem degeneration. Acta Neuropathol 1990;80:393–400. 877. Giangaspero F, et al. Massive neuronal destruction in human immunodeficiency virus (HIV) encephalitis. A clinico-pathological study of a pediatric case. Acta Neuropathol 1989;78:662–665. 878. Evans BK, Donley DK, Whitaker JN. Neurological manifestations of infection with the human immunodeficiency viruses. In: Scheld WM, Whitley RJ, Durack DT, eds. Infections of the central nervous system. New York: Raven Press, 1991:201–232. 879. Gray F, et al. Neuropathology of early HIV-1 infection. Brain Pathology 1996;6:1–15. 880. Adamson DC, et al. Immunologic NO synthase: elevation in severe AIDS dementia and induction by HIV-1 gp41. Science 1996;274:1917–1921. 881. Markham RB, et al. Maternal IgG1 and IgA antibody to the V3 loop consensus sequence and maternal-infant HIV-1 transmission. Lancet 1994;343:390–391. 882. Blanche S, et al. Relation of the course of HIV infection in children to the severity of the disease in their mothers at delivery. N Engl J Med 1994;330:308–312. 883. Sperling RS, et al. Maternal viral load, zidovudine treatment, and the risk of transmission of human immunodeficiency virus type 1 from mother to infant. N Engl J Med 1996;335:1621–1629. 884. Landesman SH, et al. Obstetrical factors and the transmission of human immunodeficiency virus type 1 from mother to child. N Engl J Med 1996;334: 1617–1623. 885. Newell M-L. Mechanisms and timing of mother-to-child transmission of HIV-1. AIDS 1998;12:831–837. 886. Pantaleo G, Graziosi C, Demarest JF. HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature 1993;362: 355–358. 887. Fauci AS. Multifactorial nature of human immunodeficiency virus disease: implications for therapy. Science 1993;262:1011–1018. 888. Civitello LA. Neurologic complications of HIV infection of children. Pediatr Neurosurg 1991;17:104–112. 889. Belman AL, et al. Pediatric acquired immunodeficiency syndrome: neurologic syndromes. Am J Dis Child 1988;142:29–35. 890. Roy S, et al. Neurological findings in HIV-infected children: a review of 49 cases. Can J Neurol Sci 1992;19:453–457. 890a. Cooper ER, et al. Encephalopathy and progression of human immunodeficiency virus disease in a cohort of children with perinatally acquired human immunodeficiency virus infection. Women and Infants transmission study group. J Pediatr 1998;132:808–812. 891. Kahn JO, Walker BD. Acute human immunodeficiency virus type 1 infection. N Engl J Med 1998;339:33–39. 891a. Morriss MC, et al. Progressive multifocal leukoencephalopathy in an HIV-infected child. Neuroradiology 1997;39:142–144. 892. Bale JF Jr, et al. Neurologic history and examination results and their relationship to human immunodeficiency virus type 1 serostatus in hemophilia subjects: results from the hemophilia growth and development study. Pediatrics 1993;91:736–741. 893. Mitchell WG, et al. Longitudinal follow-up of a group of HIV-seropositive and HIV-seronegative hemophiliacs: results from the hemophilia growth and development study. Pediatrics 1997;100:817–824. 893a. DeCarli C, et al. The prevalence of computerized tomographic abnormalities of the cerebrum in 100 consecutive children symptomatic with the human immunodeficiency virus. Ann Neurol 1993;34:198–205. 894. Post MJ, et al. CT, MR, and pathology in HIV encephalitis and meningitis. Am J Roentgenol 1988; 151:373–380. 895. Scarmato V, et al. Central brain atrophy in childhood AIDS encephalopathy. AIDS 1996;10:1227–1231. 896. States LJ, Zimmerman RA, Rutstein RM. Imaging of pediatric central nervous system HIV infection. Neuroimaging Clin N Am 1997;7:321–339. 897. Pavlakis SG, et al. Brain lactate and N-acetylaspartate in pediatric AIDS encephalopathy. Am J Neuroradiol 1998;19:383–385. 898. Salvan AM, et al. Localized proton magnetic resonance spectroscopy of the brain in children infected with human immunodeficiency virus with and without encephalopathy. Pediatr Res 1998;44:755–762. 899. Miles SA, et al. Rapid serologic testing with immune-complex-dissociated HIV p24 antigen for early detection of HIV infection in neonates. N Engl J Med 1993;328:297–302. 899a. Dunn DT, et al. The sensitivity of HIV-1 DNA polymerase chain reaction in the neonatal period and the relative contributions of intra-uterine and intra-partum transmission. AIDS 1995;9:7–11. 899b. McIntosh K, et al. Blood culture in the first 6 months of life for diagnosis of vertically transmitted human immunodeficiency virus infection. The woman and infant study group. J Infect Dis 1994; 170:996–1000. 899c. Public Health Service Task Recommendations. Guidelines for the use of antiretroviral agents in pediatric HIV infection. MMWR Morb Mortal Wkly Rep 1998;47(RR-4):1–34. 899d. Burgard M, et al. The use of viral culture and p24 antigen testing to diagnose human immunodeficiency virus infection in neonates. N Engl J Med 1992;327: 1192–1197. 899e. Sei S, et al. Evaluation of human immunodeficiency virus (HIV) type 1 RNA levels in cerebrospinal fluid and viral resistance to zidovudine in children with HIV encephalopathy. J Infect Dis 1996;174: 1200–1206. 900. McFarlin DE. Neurological disorders related to HTLV-I and HTLV-II. J Acquir Immune Defic Syndr 1993;6: 640–644. 901. Gessain A, Gout O. Chronic myelopathy associated with human T-lymphotropic virus type I (HTLV-I). Ann Intern Med 1992;117:933–946. 902. Harrington WJ Jr, et al. Spastic ataxia associated with human T-cell lymphotropic virus type II infection. Ann Neurol 1993;33:411414. 903. Sheremata, WA, et al. Association of '(tropical) ataxic neuropathy' with HTLV-II. Virus Res 1993;29:71–77. 904. Levin MC, et al. Immunologic analysis of a spinal cord biopsy specimen from a patient with human T-cell lymphotropic virus type I-associated neurologic disease. N Engl J Med 1997;336:839–845. 905. Moritoyo T, et al. Human T-lymphotrophic virus type I myelopathy and tax gene expression in CD4+ T lymphocytes. Ann Neurol 1996;40:84–86. 906. Leon-Monzon M, Illa I, Dalakas MC. Polymyositis in patients infected with human T-cell leukemia virus type I: the role of virus in the cause of the disease. Ann Neurol 1994:36;643–649. 907. Izumo S, et al. Interferon-alpha is effective in HTLV-I-associated myelopathy: a multicenter, randomized, double-blind, controlled trial. Neurology 1996;46: 1016–1021. 908. Gibbs CJ Jr, et al. Clinical and pathological features and laboratory confirmation of a Creutzfeldt-Jakob disease in a recipient of pituitary-derived human growth hormone. N Engl J Med 1985;313:734–738. 909. Rappaport EB, Graham DJ. Pituitary growth hormone from human cadavers: neurologic disease in ten recipients. Neurology 1987;37:1211–1213. 910. Brown P, et al. Human spongiform encephalopathy: the National Institutes of Health series of 300 cases of experimentally transmitted disease. Ann Neurol 1994;35:513–529. 911. Monreal J, et al. Creutzfeldt-Jakob disease in an adolescent. J Neurol Sci 1981;52:341–350. 912. Brown P, et al. Iatrogenic Creutzfeldt-Jakob disease: an example of the interplay between ancient genes and modern medicine. Neurology 1994;44:291–293. 913. Deslys J-P, Lasmizas C, Dormont D. Selection of specific strains in iatrogenic Creutzfeldt-Jakob disease. Lancet 1994;343:848–849. 914. Hayashi R, et al. Serial computed tomographic and electroencephalographic studies in Creutzfeldt-Jakob disease. Acta Neurol Scand 1992;85:161–165. 915. Zerr I, et al. Diagnosis of Creutzfeldt-Jakob disease by two-dimensional gel electrophoresis of cerebrospinal fluid. Lancet 1996;348:846–849. 916. Hsich G, et al. The 14-3-3 Protein in cerebrospinal fluid as a marker for transmissible spongiform encephalopathies. N Engl J Med 1996;335:924–930. 917. Berndt RM. Reaction to contact in the eastern highlands of New Guinea. Oceania 1954;24:206. 918. Gajdusek DC. Unconventional viruses and the origin and disappearance of Kuru. Science 1977;197: 943–960. 919. Gajdusek DC, Zigas V. Kuru. Am J Med 1959;26: 442–469. 920. Gajdusek DC, Gibbs CJ Jr. Transmission of Kuru from man to Rhesus monkey (Macaca mulatta) eight and one-half years after inoculation. Nature 1972; 240:351. 921. Grabow JD, et al. A transmissible subacute spongiform encephalopathy in a visitor to the eastern highlands of New Guinea. Brain 1976;99:637–658. 922. Gajdusek DC, Zigas V. Degenerative disease of the central nervous system in New Guinea: the endemic occurrence of “Kuru” in the native population. N Engl J Med 1957;257:974–978. 923. Hilton DA, et al. Prion immunoreactivity in appendix before clinical onset of variant Creutzfeldt-Jakob disease. Lancet 1998;352:703–704. 924. Aguzzi A. Neuro-immune connection in spread of prions in the body? Lancet 1997;349:742–743. 925. Zeidler M, et al. New variant Creutzfeldt-Jakob disease: neurological features and diagnostic tests. Lancet 1997;350:903–907. 926. Zeidler M, et al. New variant Creutzfeldt-Jakob disease: psychiatric features. Lancet 1997;350:908–910. 927. Collee JG, Bradley R. BSE: a decade on—part 1 and 2. Lancet 1997;349:636–641, 715–721. 928. Medori R, et al. Fatal familial insomnia, a prion disease with a mutation at codon 178 of the prion protein gene. N Engl J Med 1992;326:444–449. 929. Dawson JR Jr. Cellular inclusions in cerebral lesions of epidemic encephalitis. Arch Neurol Psychiatr 1934;31: 685–700. 930. Bergamini F, Defanti CA, Ferrante P. Subacute sclerosing panencephalitis: a reappraisal. New York: Elsevier Science Publishers, 1986:440. 931. Case 15-1998 Case records of the Massachusetts General Hospital. N Engl J Med 1998;338:1448–1456. 932. Herndon RM, Rubinstein LJ. Light and electron microscopy observation on the development of viral particles in the inclusions of Dawson's encephalitis (subacute sclerosing panencephalitis). Neurology 1968;18:8–20. 933. Ohya T, et al. Subacute sclerosing panencephalitis: correlation of clinical, neurophysiologic and neuropathologic findings. Neurology 1974;24:211–218. 934. Shapshak P, et al. Subacute sclerosing panencephalitis: measles virus matrix protein nucleic acid sequences detected by in situ hybridization. Neurology 1985;35: 1605–1609. 935. Hirano A, et al. The matrix proteins of neurovirulent subacute sclerosing panencephalitis virus and its acute measles progenitor are functionally different. Proc Natl Acad Sci U S A 1992;89:8745–8749. 936. Schmid A, et al. Subacute sclerosing panencephalitis is typically characterized by alterations in the fusion protein cytoplasmic domain of the persisting measles virus. Virology 1992;188:910–915. 937. Hirano A, et al. Functional analysis of matrix proteins expressed from cloned genes of measles virus variants that cause subacute sclerosing panencephalitis reveals a common defect in nucleocapside binding. J Virol 1993;67:1848–1853. 938. Mehta PD, Thormar H, Wisniewski HM. Oligoclonal IgG bands with and without measles antibody activity in sera of patients with subacute sclerosing panencephalitis (SSPE). J Immunol 1982;129: 1983–1985. 939. Mehta PD, et al. Increased levels of b 2 -microglobulin, soluble interleukin-2 receptor, and soluble CD8 in patients with subacute sclerosing panencephalitis. Clin Immunol Immunopathol 1992;65: 53–59. 940. Miller C, Farrington CP, Harbert K. The epidemiology of subacute sclerosing panencephalitis in England and Wales 1970–1989. Int J Epidemiol 1992;21: 998–1006. 941. Kornberg AJ, Harvey AS, Shield LK. Subacute sclerosing panencephalitis presenting as simple partial seizures. J Child Neurol 1991;6:146–149. 942. Robb RM, Watters GV. Ophthalmic manifestations of sub-acute sclerosing panencephalitis. Arch Ophthalmol 1970;83:426–435. 943. Jabbour JT, et al. Subacute sclerosing panencephalitis: a multidisciplinary study of eight cases. JAMA 1969;207:2248–2254. 944. Cochereau-Massin I, et al. Changes in the fundus in subacute sclerosing panencephalitis. Apropos of 23 cases. J Fr Ophthalmol 1992;15:255–261. 945. Freeman JM. The clinical spectrum and early diagnosis of Dawson's encephalitis. J Pediatr 1969;75: 590–603. 946. Grünewald T, et al. A 35-year-old bricklayer with myoclonic jerks. Lancet 1998;351:1926. 947. PeBenito R, et al. Fulminating subacute sclerosing panencephalitis: case report and literature review. Clin Pediatr 1997;36:149–154. 948. Huber M, et al. Changing patterns of glucose metabolism during the course of subacute sclerosing panencephalitis as measured with 18 FDG-positron-emission tomography. J Neurol 1992;293: 157–161. 949. Pedersen H, Wulff CH. Computed tomographic findings in early subacute sclerosing panencephalitis. Neuroradiology 1982;23:31–32. 950. Winer JB, et al. Resolving MRI abnormalities with progression of subacute sclerosing panencephalitis. Neuroradiology 1991;33:178–180. 951. Anlar B, et al. MRI findings in subacute sclerosing panencephalitis. Neurology 1996;47:1278–1283. 952. Brismar J, et al. Subacute sclerosing panencephalitis: evaluation with CT and MR. AJNR Am J Neuroradiol 1996;17:761–772. 953. Wulff CH. Subacute sclerosing panencephalitis: serial electroencephalographic studies. J Neurol Neurosurg Psychiatry 1982;45:418–421. 954. Yagi S, et al. The origin of myoclonus and periodic synchronous discharges in subacute sclerosing panencephalitis. Acta Paediatr Jpn 1992;34:310–315. 955. Giminez-Roldan S, et al. Preclinical EEG abnormalities in subacute sclerosing panencephalitis. Neurology 1981;31:763–767. 956. Johnson RT. Subacute measles encephalitis with immunosuppression. In: Johnson RT, ed. Viral infections of the nervous system. New York: Raven Press, 1982:247. 957. Kim TM, et al. Delayed acute measles body encephalitis in a 9-year-old girl: ultrastructural, immunohistochemical, and in situ hybridization studies. Mod Pathol 1992;5:348–352. 958. Baczko K, et al. Restriction of measles virus gene expression in measles inclusion body encephalitis. J Infect Dis 1988;158:144–150. 959. DuRant RH, Dyken PR. The effect of inosiplex on the survival of subacute sclerosing panencephalitis. Neurology 1983;33:1053–1055. 960. Anlar B, et al. Long-term follow-up of patients with subacute sclerosing panencephalitis treated with intraventricular gamma-interferon. Neurology 1997; 48:526–528. 961. Yoshioka H, et al. Administration of human leukocyte interferon to patients with subacute sclerosing panencephalitis. Brain Dev 1989;11:302–307. 962. Hayashi T, et al. Carbamazepine and myoclonus in SSPE subacute sclerosing panencephalitis. Pediatr Neurol 1996;346:346. 963. Weil ML, et al. Chronic progressive panencephalitis due to rubella virus simulating subacute sclerosing panencephalitis. N Engl J Med 1975;292:994–998. 964. Wolinsky J. Subacute sclerosing panencephalitis, progressive rubella panencephalitis, and multifocal leukoencephalopathy. Res Publ Assoc Res Nerv Ment Dis 1990;68:259–268. 965. Townsend JJ, et al. Neuropathology of progressive rubella panencephalitis after childhood rubella. Neurology 1982;32:185–190. 966. Vandvik B, et al. Progressive rubella panencephalitis: synthesis of oligoclonal virus-specific antibodies and free light chains in the central nervous system. Acta Neurol Scand 1978;57:53–64. 967. Wolinsky JS, Berg BO, Maitland CJ. Progressive rubella panencephalitis. Arch Neurol 1976;33:722–723. 968. Weil ML, et al. Chronic progressive panencephalitis due to rubella virus. Arch Neurol 1975;32:501. 969. Wolinsky JS, et al. Progressive rubella panencephalitis: immunovirological studies and results of isoprinosine therapy. Clin Exp Immunol 1979;35: 397–404. 970. Noorden SK, Lopez-Bravo L, Sundaresan TK. Estimated number of leprosy cases in the world. Bull World Health Organ 1992;70:7–10. 971. Smith WCS. The epidemiology of disability in leprosy including risk factors. Lep Rev 1992;63[Suppl]:23–30. 972. Centers for Disease Control. Public health service. Veterinary public health notes. Mosquitoes carry Hansen's disease. US Dept HEW 1975;90:183. 973. Jacobson RR, Krahenbuhl JL. Leprosy. Lancet 1969; 353:655–660. 974. Pfaltzgraff RE, Bryceson A. Clinical leprosy. In: Hastings RC, ed. Leprosy. Edinburgh: Churchill Livingstone, 1985:134–176. 975. Yamamura M, Uyemura K, Deans RJ. Defining protective responses to pathogens: cytokine profiles in leprosy lesions. Science 1991;254:277–279. 976. van Voorhis WC, et al. The cutaneous infiltrates of leprosy. Cellular characteristics and the predominant T-cell phenotypes. N Engl J Med 1982;307:1593–1597. 977. Wallach D, Cottenot F, Bach M. Imbalance in T cell subpopulations in lepromatous leprosy. Int J Lepr 1982;50:282–290. 978. Job CK, Desikan KV. Pathological changes and their distribution in peripheral nerves in lepromatous leprosy. Int J Lepr 1968;36:257–270. 979. Miko TL, Maitre CL, Kinfu Y. Damages and regeneration of peripheral nerves in advanced treated leprosy. Lancet 1993;3442:521–525. 980. Bullock WE. Mycobacterium leprae. In: Mandel CL, Douglas RG, Bennett JE, eds. Principles and practice of infectious diseases, 3rd ed. New York: Churchill Livingstone, 1990:1906–1914. 981. Wall JR, Wright D.M. Antibodies against testicular germinal cells in lepromatous leprosy. Clin Exp Immunol 1974;17:51–54. 982. Bullock WE. Studies of immune mechanisms in leprosy. Depression of delayed allergic responses to skin test antigens. N Engl J Med 1968;278:298–301. 983. Flaguel B, Wallach D, Vignon-Pennamer M. Late onset reversal reaction in borderline leprosy. J Am Acad Dermatol 1989;20:857–860. 984. Pearson JMH, Ross WX. Nerve involvement in leprosy: pathology, differential diagnosis and principles of management. Lepr Rev 1975;46:199–207. 985. Crawford CL. Neurological lesions in leprosy. Lepr Rev 1968;39:9–13. 986. Monrad-Krohn GH. The neurological aspect of leprosy. Chicago: Chicago Medical Book Co, 1923. 987. Browne SG. Some less common neurological findings in leprosy. J Neurol Sci 1965;2:253–261. 988. Dash MS. A study of the mechanisms of cutaneous sensory loss in leprosy. Brain 1968;91:379–392. 989. Job CK, et al. Leprous myositis—a histopathological and electron microscopic study. Lepr Rev 1969; 40:9–16. 990. Editorial. Ocular complications of leprosy. Lancet 1992;340:642–643. 991. Nations SP, et al. Leprous neuropathy: an American perspective. Semin Neurol 1998;18:113–124. 992. Willcox ML. The impact of multiple drug therapy on leprosy disabilities. Lepr Rev 1997;68:350–366. 993. Hubbert WT, Humphrey GL. Epidemiology of leptospirosis in California: a cause of aseptic meningitis. Calif Med 1968;108:113–117. 994. Lecour H, et al. Human leptospirosis: a review of 50 cases. Infection 1989;17:10–14. 995. Edwards GA, Domm BM. Human leptospirosis. Medicine 1960;39:117–156. 996. Watt G, Manaloto C, Hayes CG. Central nervous system leptospirosis in the Philippines. Southeast Asian J Trop Med Public Health 1989;20:265–269. 997. American Academy of Pediatrics. Leptospirosis. In: Peter G, ed. 1997 Red Book: report of the Committee on Infectious Diseases, 24th ed. Elk Grove Village, IL: American Academy of Pediatrics, 1997:326–327. 998. Merritt HH, Adams RD, Solomon HC. Neurosyphilis. New York: Oxford University Press, 1946. 999. Marcus JC. Congenital neurosyphilis: a re-appraisal. Neuropediatrics 1982;13:195–199. 1000. Hallgren B, Hollström E. Congenital syphilis: a follow-up study with reference to mental abnormalities. Acta Psychiatr Neurol Scand 1954;93[Suppl]:1–81. 1001. Sanchez PJ, et al. Evaluation of molecular methodologies and rabbit infectivity testing for the diagnosis of congenital syphilis and neonatal central nervous system invasion by Treponema pallidum. J Infect Dis 1993;167:148–157. 1002. Jordan KG. Modern neurosyphilis—a critical analysis. West J Med 1988;149:47–157. 1003. Davis LE, Sperry S. The CSF-FTA test and the significance of blood contamination. Ann Neurol 1979;6: 68–69. 1004. Davis LE, Schmitt JW. Clinical significance of cerebrospinal fluid tests for neurosyphilis. Ann Neurol 1989;25:50–55. 1005. Burstain JM, et al. Sensitive detection of Treponema pallidum by using the polymerase chain reaction. J Clin Microbiol 1991;29:62–69. 1006. Rosen EU, Richardson NJ. A reappraisal of the value of the IgM fluorescent treponemal antibody absorption test in the diagnosis of congenital syphilis. J Pediatr 1975;87:38–42. 1007. American Academy of Pediatrics. Syphilis. In: Peter G, ed. 1997 Red Book: report of the Committee on Infectious Diseases, 24th ed. Elk Grove Village, IL: American Academy of Pediatrics, 1997:504–514. 1008. Pfister H-W, Wilske B, Weber K. Lyme borreliosis: basic science and clinical aspects. Lancet 1994;343: 1013–1016. 1009. Steere AC, et al. The spirochetal etiology of Lyme disease. N Engl J Med 1983;308:733–740. 1010. Spach DH, et al. Tick-borne diseases in the United States. N Engl J Med 1993;329: 936–947. 1011. Reik L, Burgdorfer W, Donaldson JO. Neurological abnormalities in Lyme disease without erythema chronicum migrans. Am J Med 1986;81:73–78. 1012. Christen H-J, et al. Epidemiology and clinical manifestations of Lyme borreliosis in childhood. A prospective multicentre study with special regard to Neuroborreliosis. Acta Paediatr 1993;386[Suppl]:176. 1013. Oksi J, et al. Inflammatory brain changes in Lyme borreliosis: a report of three patients and review of literature. Brain 1996;119:2143–2154. 1014. Sigal LH, Tatum AH. Lyme disease patients' serum contains IgM antibodies to Borrelia burgdorferi that cross-react with neuronal antigens. Neurology 1988;38:1439–1442. 1015. Szer IS, Taylor E, Steere AC. The long-term course of Lyme arthritis in children. N Engl J Med 1991; 325:159–163. 1016. Glasscock ME III, et al. Lyme disease. A cause of bilateral facial paralysis. Arch Otolaryngol 1985; 111:47–49. 1017. Darras BT, Annunziato D, Leggiadro RJ. Lyme disease with neurologic abnormalities. Ped Infect Dis 1983;2:47–49. 1018. Krejcova H, et al. Otoneurological symptomatology in Lyme disease. Adv Otorhinolaryngol 1988;42:210–212. 1019. Belman AL, et al. Neurologic manifestations in children with North American Lyme disease. Neurology 1993;43:2609–2614. 1020. Jörbeck HJ, et al. Tick-borne Borrelia-meningitis in children. An outbreak in the Kolmar area during the summer of 1984. Acta Paediatr Scand 1987;76: 228–233. 1021. Hansen K, Lebech AM. The clinical and epidemiological profile of Lyme neuroborreliosis in Denmark 1985–90. A prospective study of 187 patients with Borrelia burgdorferi specific intrathecal antibody production. Brain 1992;115:399–423. 1022. Sterman AB, Nelson S, Barclay P. Demyelinating neuropathy accompanying Lyme disease. Neurology 1982;32:1302–1305. 1023. Kan L, Sood SK, Maytal J. Pseudotumor cerebri in Lyme disease: a case report and review of the literature. Pediatr Neurol 1998;18:439–441. 1024. Ryberg B, et al. Antibodies to Lyme-disease spirochaete in European lymphocytic meningoencephalitis (Bannwarth's syndrome) [Letter]. Lancet 1983;2:519. 1025. Feder HM, Zalneraitis EL, Reik L Jr. Lyme disease: acute focal meningoencephalitis in a child. Pediatrics 1988;82:931–934. 1026. Pfister H-W, et al. Catatonic syndrome in acute severe encephalitis due to Borrelia burgdorferi infection. Neurology 1993;43:433–435. 1026a. Eppes SC, et al. Characterization of Lyme meningitis and comparison with viral meningitis in children. Pediatrics 1999;103:957–960. 1027. Ackermann R, et al. Chronic neurologic manifestations of erythema migrans borreliosis. Ann NY Acad Sci 1988;539:16–23. 1028. Bensch J, Olcen P, Hagberg L. Destructive chronic Borrelia meningoencephalitis in a child untreated for 15 years. Scand J Infect Dis 1987;19:697–700. 1029. Halperin JJ, Volkman DJ, Wu P. Central nervous system abnormalities in Lyme neuroborreliosis. Neurology 1991;41:1571–1582. 1030. Martin R, et al. Persistent intrathecal secretion of oligoclonal, Borrelia burgdorferi–specific IgG in chronic meningoradiculomyelitis. J Neurol 1988; 235:229–233. 1031. Halperin JJ, et al. Lyme neuroborreliosis: central nervous system manifestations. Neurology 1989;39: 753–759. 1032. Hirai K, et al. Borrelia burgdorferi and Shulman syndrome [Letter]. Lancet 1992;340:1472. 1033. Hansen K, Lebech A-M. The clinical and epidemiological profile of Lyme neuroborreliosis in Denmark 1985–1990. A prospective study of 187 patients with Borrelia burgdorferi specific intrathecal antibody. Brain 1992;115:399–423. 1034. Albisetti M, et al. Diagnostic value of cerebrospinal fluid examination in children with peripheral facial palsy and suspected Lyme borreliosis. Neurology 1997;49:817–824. 1035. Belman AL, et al. MRI findings in children infected by Borrelia burgdorferi. Pediatr Neurol 1992;8:428–431. 1036. Dattwyler RJ, et al. Seronegative Lyme disease. Dissociation of specific T- and B-lymphocyte responses to Borrelia burgdorferi. N Engl J Med 1988;319: 1441–1446. 1037. Tumani H, Nölker G, Reiber H. Relevance of cerebrospinal fluid variables for early diagnosis of neuroborreliosis. Neurology 1995;45:1663–1670. 1038. Rose CD, et al. Use of Western blot and enzyme-linked immunosorbent assay in the diagnosis of Lyme disease. Pediatrics 1991;88:465–470. 1039. Halperin JJ, Heyes MP. Neuroactive kynurenines in Lyme borreliosis. Neurology 1992;42:43–45. 1040. Karlssen M, et al. Comparison of intravenous penicillin G and oral doxycycline for treatment of Lyme neuroborreliosis. Neurology 1994;44:1203–1207. 1041. American Academy of Pediatrics. Lyme disease. In: Peter G, ed. 1997 Red Book: report of the Committee on Infectious Diseases, 24th ed. Elk Grove Village, IL: American Academy of Pediatrics, 1997:329–333. 1042. Weber K, Pfister H-W. Clinical management of Lyme borreliosis. Lancet 1994;343:1016–1017. 1043. Salazar JC, Gerber MA, Goff CW. Long-term outcome of Lyme disease in children given early treatment. J Pediatr 1993;122:591–593. 1044. Crisp D, Ashby P. Lyme radiculoneuritis treated with intravenous immunoglobulin. Neurology 1996;46: 1174–1175. 1045. Benke T, et al. Lyme encephalopathy: long-term neuropsychological deficits years after neuroborreliosis. Acta Neurol Scand 1995;91:353–357. 1046. Southern PM Jr, Sanford JP. Relapsing fever: a clinical and microbiological review. Medicine 1969;48: 129–149. 1047. Lehtokoski-Lehtiniemi E, Koskiniemi ML. Mycoplasma pneumoniae encephalitis: a severe entity in children. Pediatr Inf Dis J 1989;8:651–653. 1048. Pellegrini M, et al. Mycoplasma pneumoniae infection associated with an acute brainstem syndrome. Acta Neurol Scand 1996;93:203–206. 1049. Cherry JD, Hurwitz ES, Welliver RC. Mycoplasma pneumoniae infections and exanthems. J Pediatr 1975;87:369–373. 1050. Lerer RJ, Kalavsky SM. Central nervous system disease associated with Mycoplasma pneumoniae infection: report of five cases and review of literature. Pediatrics 1973;52:658–668. 1051. Al-Mateen M, et al. Encephalitis lethargica-like illness in a girl with mycoplasma infection. Neurology 1988;38:1155–1158. 1052. Pongsakdi V, Chiemchanya S, Sirinavin S. Internal carotid artery occlusion associated with Mycoplasma pneumoniae infection. Pediat Neurol 1992;8: 237–239. 1053. Siber GR, et al. Neonatal central nervous system infection due to Mycoplasma hominis. J Pediatr 1977;90:625–627. 1054. McDonald JC, Moore DL. Mycoplasma hominis meningitis in a premature infant. Pediatr Infect Dis J 1988;7:795–798. 1055. Gilbert GL, et al. Chronic Mycoplasma hominis infection complicating severe intraventricular hemorrhage, in a premature neonate. Pediatr Infect Dis J 1988; 7:817–818. 1056. Hulihan JF, Bebin EM, Westmoreland BF. Bilateral periodic lateralized epileptiform discharges in Mycoplasma encephalitis. Pediatr Neurol 1992;8: 292–294. 1057. MacFarlane PI, Miller V. Transverse myelitis associated with Mycoplasma pneumoniae. Arch Dis Child 1984;59:80–82. 1058. Francis DA, et al. MRI appearances of the CNS manifestations of Mycoplasma pneumoniae: a report of two cases. J Neurol 1988;235:441–443. 1059. Maida E, Kristoferitsch W. Cerebrospinal fluid findings in Mycoplasma pneumoniae infections with neurological complications. Acta Neurol Scand 1982;65: 524–538. 1060. Murray HW, et al. The protean manifestations of Mycoplasma pneumoniae infection in adults. Am J Med 1975;58:229–242. 1061. Vikerfors T, et al. Detection of specific IgM antibodies for the diagnosis of Mycoplasma pneumoniae infections: a clinical evaluation. Scand J Infec Dis 1988;20: 601–610. 1062. Narita M, et al. DNA diagnosis of central nervous system infection by Mycoplasma pneumoniae. Pediatrics 1992;90:250–253. 1063. Fetter BF, Klintworth GK, Hendry WS. Mycoses of the central nervous system. Baltimore: Williams & Wilkins, 1967. 1064. Kozinn PJ, et al. Candida meningitis successfully treated with amphotericin B. N Engl J Med 1963;268: 881–884. 1065. Chesney PJ, et al. Successful treatment of Candida meningitis with amphotericin B and 5-fluorocytosine in combination. J Pediatr 1976;89:1017–1019. 1066. Kourtopoulos H, Holm SE. Treatment of Candida ventriculitis and septicemia with 5-fluoro-cytosine. Combined peroral and intraventricular administration. Neuropaediatrie 1976;7:356–361. 1067. Roessmann U, Friede RL. Candidal infection of the brain. Arch Pathol 1967;84:495–498. 1068. Chesney PJ, Justman RA, Bogdanowicz WM. Candida meningitis in newborn infants: a review and report of combined amphotericin B-flucytosine therapy. Johns Hopkins Med J 1978;142:155–160. 1069. Como JA, Dismukes WE. Oral azole drugs as systemic antifungal therapy. N Engl J Med 1993;330: 263–272. 1070. Conant NF. Medical mycology. In: Dubos RJ, Hirsch JG, eds. Bacterial and mycotic infections of man. Philadelphia: JB Lippincott, 1965:825–885. 1071. Caudill RG, Smith CE, Reinarz JA. Coccidioidal meningitis. A diagnostic challenge. Am J Med 1970;49:360–365. 1072. McCullough DC, Harbert JC. Isotope demonstration of CSF pathways. Guide to antifungal therapy in coccidioidal meningitis. JAMA 1969;209:558–560. 1073. Wrobel CJ, et al. MR findings in acute and chronic coccidioidomycosis meningitis. Am J Neuroradiol 1992; 13:1241–1245. 1074. Reeves DL. Chronic coccidioidal meningitis. Report of two cases. J Neurosurg 1968;28:383–386. 1075. American 63 of Pediatrics. Systemic treatment with amphotericin B. In: Peter G, ed. 1997 Red Book: report of the Committee on Infectious Diseases, 24th ed. Elk Grove Village, IL: American Academy of Pediatrics, 1997:630–631. 1076. Galgiani JN, et al. Fluconazole therapy for coccidioidal meningitis. The NIAID-mycosis study group. Ann Int Med 1993;119:28–35. 1077. Kauffman CA. Role of azoles in antifungal therapy. Clin Infect Dis 1996;22[Suppl 2]:S148–S153. 1078. Patel R. Antifungal agents. Part I. Amphotericin B preparations and flucytosine. Mayo Clin Proc 1998; 73:1205–1225. 1079. Tucker RM, et al. Itraconazole therapy for chronic coccidiodal meningitis. Ann Intern Med 1990;112: 108–112. 1080. Cooper RA Jr, Goldstein E. Histoplasmosis of the central nervous system. Report of two cases and review of the literature. Am J Med 1963;35:45–57. 1081. Couch JR, Abdou NI, Sagawa A. Histoplasma meningitis with hyperactive suppressor T cells in cerebrospinal fluid. Neurology 1978;28:119–123. 1082. Wheat LJ, Batteiger BE, Sathapatayavongs B. Histoplasma capsulatum infections of the central nervous system. A clinical review. Medicine 1990;69: 244–260. 1083. Rivera IV, et al. Chronic progressive CNS histoplasmosis presenting in childhood: response to fluconazole therapy. Pediatr Neurol 1992;8:151–153. 1084. Gonzalez-Amaro R, et al. Natural killer cell-mediated cytotoxicity in cryptococcal meningitis. Rev Invest Clin 1991;43:133–138. 1085. Woodall WC III, et al. Spinal arachnoiditis with Cryptococcus neoformans in a nonimmunocompromised child. Pediatr Neurol 1990;6:206–208. 1086. Gordon MA, Vedder DK. Serologic tests in diagnosis and prognosis of cryptococcosis. JAMA 1966;197:961–967. 1087. McIntyre HB. Cryptococcal meningitis. A case successfully treated by cisternal administration of amphotericin B with a review of the recent literature. Bull Los Angeles Neurol Soc 1967;32: 213–219. 1088. Sarosi GA, Parker JD, Doto IL. Amphotericin B in cryptococcal meningitis: long-term results of treatment. Ann Intern Med 1969;71:1079–1087. 1089. Goodman JS, Kaufman L, Koenig MG. Diagnosis of cryptococcal meningitis. Value of immunologic detection of cryptococcal antigen. N Engl J Med 1971; 285:434–436. 1090. Dismukes WE, et al. Treatment of cryptococcal meningitis with combination amphotericin B and flucytosine for four as compared with six weeks. N Engl J Med 1987;317:334–341. 1091. American Academy of Pediatrics. 1997 Red Book: report of the Committee on Infectious Diseases, 24th ed. Elk Grove Village, IL: American Academy of Pediatrics, 1997:184–185. 1092. Leake HA, Appleyard MN, Hartley JP. Successful treatment of resistant cryptococcal meningitis with amphotericin B lipid emulsion after neurotoxicity with conventional intravenous amphotericin B. J Infect 1994;28:319–322. 1093. Laing RB, et al. Anaphylactic reactions to liposomal amphotericin [Letter]. Lancet 1994;344:682. 1094. Saag MS, et al. Comparison of amphotericin B with fluconazole in the treatment of acute AIDS-associated cryptococcal meningitis. N Engl J Med 1992;326: 83–89. 1095. Barter AP, Falconer MA. Actinomycosis of the brain. Guy Hosp Rep 1955;104:135–145. 1096. Iyer S, Dodge PR, Adams RD. Two cases of Aspergillus infection of the central nervous system. J Neurol Neurosurg Psychiatry 1952;15:152–163. 1097. Mukoyama M, Gimple AB, Poser CM. Aspergillosis of the central nervous system. Report of a brain abscess due to A. fumigatus and a review of the literature. Neurology 1969;19:967–974. 1098. Koh S, et al. Myelopathy resulting from invasive Aspergillosis. Pediatr Neurol 1998;19:135–138. 1099. Gonyea EF. The spectrum of primary blastomycotic meningitis: a review of central nervous system blastomycosis. Ann Neurol 1978;3:26–39. 1100. Papadatos C, Pavlatou M, Alexiou D. Cephalosporium meningitis. Pediatrics 1969;44:749–751. 1101. Landau JW, Newcomer VD. Acute cerebral phycomycosis (mucormycosis). Report of a pediatric patient successfully treated with amphotericin B and cycloheximide and review of the pertinent literature. J Pediatr 1962;61:363–385. 1102. Blodi FC, Hannah FT, Wadsworth JA. Lethal orbitocerebral phycomycosis in otherwise healthy children. Am J Ophthalmol 1969;67:698–705. 1103. Smego RA Jr, Moeller MB, Gallis HA. Trimethoprimsulfamethoxazole therapy for Nocardia infections. Arch Intern Med 1983;143:711–718. 1104. Ballenger CN Jr, Goldring D. Nocardiosis in childhood. J Pediatr 1957;50:145–169. 1105. Lope ES, Gutierrez DC. Nocardia asteroides primary cerebral abscess and secondary meningitis. Acta Neurochir 1977;37:139–145. 1106. Spach DH, et al. Tick-borne diseases in the United States. N Engl J Med 1993;329:936–947. 1107. Miller JQ, Price TR. The nervous system in Rocky Mountain fever. Neurology 1972;22:561–566. 1108. Horney LF, Walker DH. Meningoencephalitis as a major manifestation of Rocky Mountain spotted fever. South Med J 1988;81:915–918. 1109. Bell WE, Lascari AD. Rocky Mountain spotted fever. Neurological symptoms in the acute phase. Neurology 1970;20:841–847. 1110. Hornaday CA, Kernodle DS, Curry WA. Neurogenic bladder in Rocky Mountain spotted fever. Arch Intern Med 1983;143:365. 1111. Miller JQ, Price TR. Involvement of the brain in Rocky Mountain spotted fever. South Med J 1972;65:437–439. 1112. Raab EL, Leopold IH, Hodes HL. Retinopathy in Rocky Mountain spotted fever. Am J Ophthalmol 1969; 68:42–46. 1113. Rosenblum MJ, Masland RL, Harrell GT. Residual effects of rickettsial disease on the central nervous system. Results of neurologic examinations and electroencephalograms following Rocky Mountain spotted fever. Arch Intern Med 1952;90:444–455. 1114. Wright L. Intellectual sequelae of Rocky Mountain spotted fever. J Abnormal Psychol 1972;80:315–316. 1115. Haynes RE, Sanders DY, Cramblett HG. Rocky Mountain spotted fever in children. J Pediatr 1970;76: 685–693. 1116. American Academy of Pediatrics. Rocky mountain spotted fever. In: 1997 Red Book: report of the Committee on Infectious Diseases, 24th ed. Elk Grove Village, IL: American Academy of Pediatrics. 1997: 452–454. 1117. Noad KB, Haymaker W. Neurological features of tsutsugamushi fever with special reference to deafness. Brain 1953;76:113–131. 1118. Herman E. Neurological syndromes in typhus fever. J Nerv Ment Dis 1949;109:25–36. 1119. Watt G, et al. Scrub typhus infections poorly responsive to antibiotics in northern Thailand. Lancet 1996;348: 86–89. 1120. Case records of the Massachusetts General Hospital. Case 38-1996. N Engl J Med 1996;335:1829–1834. 1121. Most H. Treatment of common parasitic infections of man encountered in the United States. N Engl J Med 1972;287:495–498, 698–702. 1122. Brown WJ. Cysticercosis. In: Brown WJ, Voge M, eds. Neuropathology of parasitic infections. New York: Oxford University Press, 1982:108. 1123. Kramer LD, et al. Cerebral cysticercosis: documentation of natural history with CT. Radiology 1989; 171:459–462. 1124. Virmani V, Roy S, Kamala G. Periodic lateralised epileptiform discharges in a case of diffuse cerebral cysticercosis. Neuropädiatrie 1977;8:196–203. 1125. Kalra V, Sethi A. Childhood neurocysticercosis—epidemiology, diagnosis and course. Acta Paediatr Jpn 1992;34:365–370. 1126. Lopez-Hernandez A, Garaizar C. Childhood cerebral cysticercosis: clinical features and computed tomographic findings in 89 Mexican children. Can J Neurol Sci 1982;9:401–407. 1127. Thompson AJG. Neurocysticercosis: experience at the teaching hospitals of the University of Cape Town. S Afr Med J 1993;83:332–334. 1128. Garg RS. Neurocysticercosis. Postgrad Med J 1998;74:321–326. 1129. Liu LX, Weller PF. Antiparasitic drugs. N Engl J Med 1996;334:1178–1184. 1130. Mitchell WG, Crawford TO. Intraparenchymal cerebral cysticercosis in children: diagnosis and treatment. Pediatrics 1988;82:76–82. 1131. Rajshekhar V. Albendazole therapy for persistent, solitary cysticercosis granulomas in patients with seizures. Neurology 1993;43:1238–1240. 1132. Dalessio DJ, Wolff HG. Trichinella spiralis infection of the central nervous system. Report of a case and review of the literature. Arch Neurol 1961;4: 407–417. 1133. Tatatuto AL, Venturiello SM. Trichinosis. Brain Pathology 1997;7:663–672. 1134. Kramer MD, Aita JF. Trichinosis with central nervous system involvement. A case report and review of the literature. Neurology 1972;22:485–491. 1135. Lopez-Lozano JJ, Garcia-Merino JA, Liano H. Bilateral facial paralysis secondary to trichinosis. Acta Neurol Scand 1988;78:194–197. 1136. Evans RW, Pattern BM. Trichinosis associated with superior sagittal sinus thrombosis. Ann Neurol 1982;11:216–217. 1137. Gay T, et al. Fatal CNS trichinosis. JAMA 1982;127: 1024–1025. 1138. American Academy of Pediatrics. Trichinosis (Trichinella spiralis). In: Peter G, ed. 1997 Red Book: report of the Committee on Infectious Diseases, 24th ed. Elk Grove Village, IL: American Academy of Pediatrics, 1997:535–536. 1139. Zucker JR, Campbell CC. Malaria: principles of prevention and treatment. Infect Dis Clin North Am 1993;7:547–567. 1140. Phillips RE, Solomon T. Cerebral malaria in children. Lancet 1990;336:1355–1360. 1141. Warrell DA. Cerebral malaria. QJM 1989;71:369–371. 1142. Brewster DR, Kwiatkowski D, White NJ. Neurological sequelae of cerebral malaria in children. Lancet 1990;336:1039–1043. 1143. van Hensbroek MB, et al. Residual neurologic sequelae after childhood cerebral malaria. J Pediatr 1997;131:125–129. 1144. Turner G. Cerebral malaria. Brain Pathol 1997;7: 569–582. 1145. MacPherson GG, et al. Human cerebral malaria. A quantitative ultrastructural analysis of parasitized erythrocyte sequestration. Am J Pathol 1985;119: 385–401. 1146. Aikawa M, et al. The pathology of human malaria. Am J Trop Hyg 1990;43:30–37. 1147. Nakamura K, et al. Plasmodium falciparum-infected erythrocyte receptor(s) for CD36 and thrombospondin are restricted to knobs on the erythrocyte surface. J Histochem Cytochem 1992;40: 1419–1422. 1148. Newbold C, et al. Receptor-specific adhesion and clinical disease in Plasmodium falciparum. Am J Trop Med Hyg 1997;57:389–398. 1149. Fernandez-Reyes D, et al. A high frequency African coding polymorphism, in the N-terminal domain of ICAM-1 predisposing to cerebral malaria in Kenya. Hum Mol Genet 1997;6:1357–1360. 1149a. Urban BC, et al. Plasmodium falciparum—Infected erythrocytes modulate the maturation of dendritic cells. Nature 1999;400:73–77. 1150. Johnson JK, et al. Cytoadherence of Plasmodium falciparum-infected erythrocytes to microvascular endothelium is regulatable by cytokines and phorbol ester. J Infect Dis 1993;167:698–703. 1151. Clark IA, Chaudhri G, Cowden WB. Roles of tumor necrosis factor in the illness and pathology of malaria. Trans R Soc Trop Med Hyg 1989;83: 436–440. 1152. Clark IA, Rockett KA, Cowden WB. Possible central role of nitric oxide in conditions clinically similar to cerebral malaria. Lancet 1992;340:894–896. 1153. Kwiatkowski D, et al. TNF concentration in fatal malaria, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria. Lancet 1990;336: 1201–1204. 1154. Grau GE, et al. Tumor necrosis factor and disease severity in children with falciparum malaria. N Engl J Med 1989;320:1586–1591. 1155. Grau GE, et al. Tumor necrosis factor and other cytokines in cerebral malaria. Experimental and clinical data. Immunol Rev 1989;112:49–70. 1156. Kwiatkowski D, et al. Anti-TNF therapy inhibits fever in cerebral malaria. QJM 1993;86:91–98. 1157. Molyneux ME, et al. Clinical features and prognostic indicators in paediatric cerebral malaria: a study of 131 comatose Malawian children. QJM 1989: 71:441–459. 1158. Jaffar S, et al. Predictors of a fatal outcome following childhood cerebral malaria. Am J Trop Med Hyg 1997;57:20–24. 1159. Taylor TE, Borgstein A, Molyneux ME. Acid-base status in paediatric Plasmodium falciparum malaria. QJM 1993;86:99–109. 1160. Burgner D, et al. Inducible nitric oxide synthase polymorphism and fatal cerebral malaria. Lancet 1998;232:1193–1194. 1161. Looareesuwan S, et al. Magnetic resonance imaging of the brain in patients with cerebral malaria. Clin Infect Dis 1995;21:300–309. 1162. Miller LH, Good MF, Milon G. Malaria pathogenesis. Science 1994;264:1878–1883. 1163. Wright PW, et al. Initial clinical assessment of the comatose patient: cerebral malaria vs. meningitis. Pediatr Infect Dis J 1993;12:37–41. 1164. White NJ, Krishna S, Looareesuwan S. Encephalitis, not cerebral malaria, is likely cause of coma with negative blood smears. J Infect Dis 1992;166: 1195–1196. 1165. Newton CRJC, Warrell DA. Neurological manifestations of falciparum malaria. Ann Neurol 1998;43: 695–702. 1166. Lewallen S, et al. Ocular fundus findings in Malawian children with cerebral malaria. Ophthalmology 1993;100:857–861. 1167. White NJ, et al. Severe hypoglycemia and hyperinsulinemia in falciparum malaria. N Engl J Med 1983; 309: 61–66. 1168. White NJ, et al. Quinine loading dose in cerebral malaria. Am J Trop Med Hyg 1983;332:1–5. 1169. Phillips RE, et al. Intravenous quinidine for the treatment of severe falciparum malaria. Clinical and pharmacokinetic studies. N Engl J Med 1985;312: 1273–1278. 1170. Shwe T, et al. Clinical studies on treatment of cerebral malaria with artemether and mefloquine. Trans R Soc Trop Med Hyg 1989;83:489. 1171. Taylor TE, et al. Rapid coma resolution with artemether in Malawian children with cerebral malaria. Lancet 1993;341:661–662. 1172. Van Hensbroek MB, Onyiorah E, Jaffar S. A trial of artemether or quinine in children with cerebral malaria. N Engl J Med 1996;335:69–75. 1172a. White NJ, et al. Averting a malaria disaster. Lancet 1999;353:1965–1967. 1173. White NJ. The treatment of malaria. N Engl J Med 1996;335:800–806. 1174. Gordeuk V, et al. Effect of iron chelation therapy on recovery from deep coma in children with cerebral malaria. N Engl J Med 1992;327:1473–1477. 1174a. Brandts CH, et al. Effect of paracetamol on parasite clearance time in Plasmodium Falciparum malaria. Lancet 1997;350:704–709. 1175. Mai NTH, et al. Post-malaria neurological syndrome. Lancet 1996;348:917–921. 1176. Lell B, et al. Randomised placebo-controlled study of atovaquone plus proguanil for malaria in children. Lancet 1998;351:709–713. 1177. Power J. Sleeping sickness research and control. TDR News 1989:28:3. 1178. Kuzoe FA. Current knowledge on epidemiology and control of sleeping sickness. Ann Soc Belg Med Trop 1989;69:217–220. 1179. Hajduk SL, Englund PT, Smith DH. African trypanosomiasis. In: Warren KS, Mahmoud AAF, eds. African trypanosomiasis. New York: McGraw-Hill, 1990: 268–281. 1180. Mhlanga JD, Bentivoglio M, Kristensson K. Neurobiology of cerebral malaria and African sleeping sickness. Brain Res Bull 1997;44: 579–589. 1180a. Bentivoglio M, et al. Trypanosoma brucei and the nervous system. Trends Neurosci 1994;17: 325–329. 1181. Poltera AA, Owor R, Cox JN. Pathological aspects of human African trypanosomiasis in Uganda. A postmortem survey of 14 cases. Virchows Arch 1976;373: 249–265. 1182. Adams JH, Hallen L, Boa FY. African trypanosomiasis: a study of 16 fatal cases with some observations on acute reactive arsenical encephalopathy. Neuropathol Appl Neurobiol 1986;12:81–94. 1183. Asongonyi T, Lando G, Ngu JL. Serum antibodies against human brain myelin proteins in Gambian trypanosomiasis. Ann Soc Beg Med Trop 1989;69: 213–221. 1184. Poltera AA. Immunopathological and chemotherapeutic studies in experimental trypanosomiasis with special reference to the heart and brain. Trans R Trop Med Hyg 1980;74:706–715. 1185. Wellde BT, Chumo DA, Hockmeyer WT. Sleeping sickness in the Lambwe Valley in 1978. Ann Trop Med Parasitol 1989;83:21–27. 1186. Lambo TA. Neuropsychiatric syndromes associated with human trypanosomiasis in tropical Africa. Acta Psychiatrica Scand 1966;42:474–484. 1187. Calwell HG. The pathology of the brain in Rhodesian trypanosomiasis. Trans R Soc Trop Med Hyg 1937; 30:611–624. 1188. Van Meirvenne N, Le Ray D. Diagnosis of African and American trypanosomiasis. Br Med Bull 1985;41: 156–161. 1189. Gutteridge WE. Trypanosomiasis: existing chemotherapy and limitations. Br Med Bull 1985;41: 162–168. 1190. Arroz JO. Melarsoprol and reactive encephalopathy in Trypanosoma brucei rhodesiense infection. Trans R Soc Trop Med Hyg 1987;81:192. 1191. McCann PP, Bitoniti AJ, Bacchi CJ. Use of difluoromethylornithine (DFMO, eflornithine) for late stage trypanosomiasis. Trans R Soc Trop Med Hyg 1987; 81:701–702. 1192. Pitella JEH. Brain involvement in the chronic cardiac form of Chagas disease. J Trop Med Hygiene 1985; 88:313–317. 1193. Cegielski JP, Durack DT. Protozoal infections of the central nervous system. In: Scheld WM, Whitley RJ, Durack DT, eds. Infections of the central nervous system. New York: Raven Press, 1991:767–800. 1194. Leiguarda R, Roncoroni A, Taratuto AI. Acute CNS infection by trypanosoma cruzi in immunosuppressed patients. Neurology 1990;40:850–851. 1195. Carrea R, Dowling E Jr, Guevara JA. Surgical treatment of hydatid cysts of the central nervous system in the pediatric age (Dowling's technique). Child's Brain 1975;1:4–21. 1196. Boles DM. Cerebral echinococciasis. Surg Neurol 1981;16:280–282. 1197. Radford AJ. Hydatid disease. In: Weatherall DJ, Ledingham JGG, Warrell DA, eds. Oxford textbook of medicine, 2nd ed. Oxford: Oxford University Press, 1988:561–565. 1198. Banerjee AK, Bhatnagar RK, Bhusnurmath SR. Secondary cerebral amoebiasis. Trop Geogr Med 1993; 35:333–336. 1199. Cegielski JP, Durack DT. Protozoal infections of the central nervous system. In: Scheld WM, Whitley RJ, Durack DT, eds. Infections of the central nervous system. New York: Raven Press, 1991:767–800. 1200. Becker GL, Knep S, Lance KP. Amoebic abscess of the brain. Neurosurgery 1980;6:192–194. 1201. Barnett ND, et al. Primary amoebic meningoencephalitis with Naegleria fowleri: clinical review. Pediatr Neurol 1996;15:230–234. 1202. Visuesuara GS, Callaway CS. Light and electron microscopic observation on the pathogenesis of Naeglaria fowleri in mouse brain and tissue culture. J Protozool 1990;21:239–250. 1203. Thong YH, Ferrante A. Migration patterns of pathogenic and non-pathogenic Naegleria spp. Infect Immun 1986;51:177–180. 1204. Rutherford GS. Amoebic meningo-encephalitis due to free living amoeba. S Afr Med J 1986;69: 52–55. 1205. Kilvington S, Beeching J. Identification and epidemiological typing of Naegleria fowleri with DNA probes. Appl Environ Microbiol 1995;61: 2071–2078. 1206. Brown RL. Successful treatment of primary amoebic meningo-encephalitis. Arch Intern Med 1991;151: 1201–1202. 1207. Slater CA, et al. Brief report: successful treatment of disseminated acanthamoeba infection in an immunocompromised patient. N Engl J Med 1994; 331:85–87. 1208. Koo J, Dien F, Kliks MM. Angiostrongylus eosinophilic meningitis. Rev Infect Dis 1988;10:1155–1162. 1209. Kliks MM, Kroenke K, Handman JM. Eosinophilic radiculomyelo-encephalitis. J Trop Med Hyg 1982; 31:1114–1122. 1210. Lowichik A, Ruff AJ. Parasitic infections of the central nervous system in children. Part II: disseminated infections. J Child Neurol 1995;10:77–87. 1211. Diaz Camacho SP, et al. Clinical manifestations and immunodiagnosis of gnathostomiasis in Culiacan, Mexico. Am J Trop Med Hyg 1998;59:908–915. 1212. Chitanondh H, Rosen L. Fatal eosinophilic encephalomyelitis caused by the nematode Gnathostoma spinigerum. Am J Trop Med Hyg 1967;16: 638–645. 1213. Schmutzhand E, Boorgind P, Veijjava A. Eosinophilic meningitis in Thailand caused by CNS invasion of Gnathostoma spinigerum and Angiostrongylus cantonensis. J Neurol Neurosurg Psych 1988;51:80–87. 1214. Hill IR, Denham DA, Scholtz CL. Toxocara canis larvae in the brain of a British child. Trans R Soc Trop Med Hyg 1985;79:351–354. 1215. Mikhael NZ, Montpetit UJA, Orizaga M. Toxocara canis infestation with encephalitis. Can J Neurol Sci 1974;1:114–120. 1216. Glickman L, et al. Toxocara infection and epilepsy in children. J Pediatr 1979;94:75–78. 1217. Pitella JE. Neuroschistosomiasis. Brain Pathol 1997;7:649–662. 1218. Scrimgeour EM, Gajdusek DC. Involvement of the central nervous system in Schistosoma mansoni and S. haematobium infection. Brain 1985;108:1023–1038. 1219. Anonymous. Acute schistosomiasis with transverse myelitis in American students returning from Kenya. MMWR 1984;33:445–447. 1220. Boyce TG. Acute transverse myelitis in a 6-year-old girl with schistosomiasis. Pediatr Infect Dis J 1990;9: 279–284. 1221. Pitella JE, Lana-Peixoto MA. Brain involvement in hepatosplenic Schistosomiasis mansoni. Brain 1981; 104:621–632. 1222. Bennett G, Provenzale JM. Schistosomal myelitis: finding at MR imaging. Eur J Radiol 1998;27: 268–270. 1223. Ferrari TC, et al. The value of an enzyme-linked immunosorbent assay for the diagnosis of schistosomiasis mansoni myeloradiculopathy. Trans R Soc Trop Med Hyg 1995;89:496–500. 1224. Watt E, et al. Praziquantel in the treatment of cerebral schistosomiasis. Lancet 1986;2:529–532. 1225. Jankovic D, et al. Optimal vaccination against Schistosoma mansoni requires the induction of both B cell- and IFN-gamma-dependent effector mechanisms. J Immunol 1999;162:345–351. 1226. Higashi K, et al. Cerebral paragonimiasis. J Neurosurg 1971;34:515–527. 1227. Oh SJ. Spinal paragonimiasis. J Neurol Sci 1968; 6:125–140. 1228. Oh SJ. Ophthalmological signs in cerebral paragonimiasis. Trop Geogr Med 1968;20:13–20. 1229. Chang KH, Han MH. MRI of CNS parasitic diseases. J Magn Reson Imaging 1998;8:297–307. 1230. Newman LS, Rose CS, Maier LA. Sarcoidosis N. Engl J Med 1997;336:1224–1234. 1231. Johns CJ, Scott PP, Schonfeld SA. Sarcoidosis. Annu Rev Med 1989;40:353–371. 1232. Jefferson M. Sarcoidosis of the nervous system. Brain 1957;80:540–556. 1233. Symonds C. Recurrent multiple cranial nerve palsies. J Neurol Neurosurg Psychiatry 1958;21:95–100. 1234. Heerfordt CF. èber eine, “Febris uveoparotidea sub chronica” an der Glandula parotis und der Uvea des Auges lokalisiert und häufig mit Paresen cerebrospinaler Nerven kompliziert. Arch Ophthalmol (Leipz) 1889;70:254–273. 1235. McGovern JP, Merritt DH. Sarcoidosis in childhood. Adv Pediatr 1956;8:97–135. 1236. Rubinstein I, Hiss J, Baum GL. Intramedullary spinal cord sarcoidosis. Surg Neurol 1984;21:272–274. 1237. Kinnman J, Link H. Intrathecal production of oligoclonal IgM and IgG in CNS sarcoidosis. Acta Neurol Scand 1984;69:97–106. 1238. Borucki SJ, et al. Cerebrospinal fluid immunoglobulin abnormalities in neurosarcoidosis. Arch Neurol 1989;46:270–273. 1238a. Koné-Paut I, et al. The pitfall of silent neurosarcoidosis. Pediatr Neurol 1999;20:215–218. 1239. Miller DH, et al. Magnetic resonance imaging in central nervous system sarcoidosis. Neurology 1988;38: 378–383. 1240. Scott TF. Neurosarcoidosis: progress and clinical aspects. Neurology 1993;43:8–12. 1241. Reye RD, Morgan G, Baral J. Encephalopathy and fatty degeneration of the viscera. A disease entity in childhood. Lancet 1963;2:749–752. 1242. Pollack JD, ed. Reye's syndrome. New York: Grune & Stratton, 1975. 1243. Hardie RM, et al. The changing clinical pattern of Reye's syndrome 1982–1990. Arch Dis Child 1996;74: 400–405. 1244. Jenkins R, Dvorak A, Patrick J. Encephalopathy and fatty degeneration of the viscera associated with chickenpox. Pediatrics 1967;39:769–771. 1245. Powell HC, Rosenberg RN, McKellar B. Reye's syndrome: isolation of parainfluenza virus. Report of three cases. Arch Neurol 1973;29:135–139. 1246. Olson LC, et al. Encephalopathy and fatty degeneration of the viscera in northeastern Thailand. Clinical syndrome and epidemiology. Pediatrics 1971;47:707–716. 1247. Editorial. Reye's syndrome and aspirin. Epidemiological associations and inborn errors of metabolism. Lancet 1987;2:429–431. 1248. Partin JC, Schubert WK, Partin JS. Mitochondrial ultrastructure in Reye's syndrome. N Engl J Med 1971;285:1339–1343. 1249. Lovejoy FH Jr, et al. Clinical staging in Reye's syndrome. Am J Dis Child 1974;128:36–41. 1250. Aoki Y, Lombroso CT. Prognostic value of electroencephalography in Reye's syndrome. Neurology 1973;23:333–343. 1251. Ey JL, Smith SM, Fulginiti VA. Varicella hepatitis without neurologic symptoms or findings. Pediatrics 1981;67:285–287. 1252. Venes JL, Shaywitz BA, Spencer DD. Management of severe cerebral edema in the metabolic encephalopathy of Reye-Johnson syndrome. J Neurosurg 1978;48: 903–915. 1253. Brunner RL, et al. Neuropsychologic consequences of Reye's syndrome. J Pediatr 1979;95:706–711. 1254. Benjamin PY, et al. Intellectual and emotional sequelae of Reye's syndrome. Crit Care Med 1982;10: 583–587. 1255. Reitman MA, et al. Motor disorders of voice and speech in Reye's syndrome survivors. Am J Dis Child 1984;138:1129–1131. 1256. Levin M, et al. Haemorrhagic shock and encephalopathy: a new syndrome with a high mortality in young children. Lancet 1983;2:64–67. 1257. Whittington LK, Roscelli JD, Parry WH. Hemorrhagic shock and encephalopathy: further description of a new syndrome. J Pediatr 1985;106:599–602. 1258. Jardine DS, Winters WD, Shaw DW. CT scan abnormalities in a series of patients with hemorrhagic shock and encephalopathy syndrome. Pediatr Radiol 1997;27:540–544. 1259. Sofer S, et al. Possible aetiology of haemorrhagic shock and encephalopathy syndrome in the Negev area of Israel. Arch Dis Child 1996;75:332–334. 1260. Behçet H. èber rezidivierende Aphthöse durch ein Virus verursachte Geschwüre am Mund, am Auge, und an den Genitalien. Dermatol Monatsschr 1937;105: 1152–1157. 1261. Devlin T, et al. Neuro-Behçet's disease: factors hampering proper diagnosis. Neurology 1995;45: 1754–1757. 1262. Lewis MA, Priestley BL. Transient neonatal Behcet'sdisease. Arch Dis Child 1986;61:805–806. 1263. Rakover Y, et al. Behçet disease: long-term follow-up of three children and review of the literature. Pediatrics 1989;83:986–992. 1263a. Sakane T, et al. Behcet's disease. N Engl J Med 1999; 341:1284–1291. 1264. Arbesfeld SJ, Kurban AK. Behçet's disease. New perspectives on an enigmatic syndrome. J Am Acad Dermatol 1988;19:767–779. 1265. Allen NB. Miscellaneous vasculitic syndromes including Behcet's disease and central nervous system vasculitis. Curr Opin Rheumatol 1993;5:51–56. 1266. Martinez JM, et al. Anatomo-clinical study of Behcet's syndrome with involvement of the central nervous system. Rev Neurol (Paris) 1988;144:130–135. 1267. Wolf SM, Schotland DL, Phillips LL. Involvement of nervous system in Behçet syndrome. Arch Neurol 1965;12:315–325. 1268. Iseki E, et al. Two necropsy cases of chronic encephalomyelitis: variants of neuro-Behcet's syndrome? J Neurol Neurosurg Psychiatry 1988;51:1084–1087. 1269. Wechsler B, et al. Cerebral venous thrombosis in Behçet's syndrome. A clinical study and long term follow-up of 25 cases. Neurology 1992;42:614–618. 1270. Al-Kawi MZ, Bohlega S, Banna M. MRI findings in neuro-Behçet's disease. Neurology 1991;41:405–408. 1271. Yurdakul S, et al. The prevalence of Behçet's syndrome in a rural area in northern Turkey. J Rheumatol 1988;15:820–822. 1272. Hatzinikolaou P, et al. Adamantiadis–Behçet's syndrome: central nervous system involvement. Acta Neurol Scand 1993;87:290–293. 1273. Feron EJ, et al. Interferon-a-2b for refractory ocular Behçet's disease [Letter]. Lancet 1994;343:14–28. 1274. Riehl JL, Andrews JM. The uveomeningoencephalitic syndrome. Neurology 1966;16:603–609. 1275. Goldberg AC, et al. HLA-DRB1*0405 is the predominant allele in Brazilian patients with Vogt-Koyanagi-Harada disease. Hum Immunol 1998;59:183–188. 1276. Moorthy RS, Inomata H, Rao NA. Vogt-Koyanagi-Harada syndrome. Surv Ophthalmol 1995;39:265–292. 1277. Kimura R, et al. Swollen ciliary processes as an initial symptom in Vogt-Koyanagi-Harada disease. Am J Ophthalmol 1983;95:402–403. 1278. Takeshita T, et al. A patient with long standing melanin laden macrophages in cerebrospinal fluid in Vogt-Koyanagi-Harada syndrome. Br J Ophthalmol 1997;81:11–14. 1279. Ohno C, et al. Vogt-Koyanagi-Harada syndrome. Am J Ophthalmol 1977;83:735–740. 1280. Beniz J, Forster DJ, Lean JS, Smith RE, Rao NA. Variations in clinical features of the Vogt-Koyanagi-Harada syndrome. Retina 1991;11:275–280. 1281. Belfort R Jr, et al. Vogt-Koyanagi-Harada's disease in Brazil. Jpn J Ophthalmol 1988;32:344–347. 1282. Gruich MJ, et al. Vogt-Koyanagi-Harada syndrome in a 4-year-old child. Pediatr Neurol 1995;13:50–51. 1283. Brouzas D, et al. Corneal anesthesia in a case with Vogt-Koyanagi-Harada syndrome. Acta Ophthalmol Scand 1997;75:464–465. 1284. Ikeda M, Tsukagoshi H. Vogt-Koyanagi-Harada disease presenting meningoencephalitis. Report of a case with magnetic resonance imaging. Eur Neurol 1992;32:83–85. 1285. Helveston WR, Gilmore R. Treatment of Vogt-Koyanagi-Harada syndrome with intravenous immunoglobulin. Neurology 1996;46:584–585. 1286. Tabbara KF, Chavis PS, Freeman WR. Vogt-Koyanagi-Harada syndrome in children compared to adults. Acta Ophthalmol Scan 1998;76:723–726. 1287. Picard FJ, et al. Mollaret's meningitis associated with herpes simplex type 2 infection. Neurology 1993;43: 1722–1727. 1288. Achard J-M, Lallement P-Y, Veyssier P. Recurrent aseptic meningitis secondary to intracranial epidermoid cyst and Mollaret's meningitis: two distinct entities or a single disease? A case report and a nosologic discussion. Am J Med 1990;89:807–810. 1289. Mollaret P. La meningite endothelioleucocytaire multiricurrente binigne. Syndrome nouveau ou maladie nouvelle? Documents humoraux et microbiologiques. Ann Inst Pasteur (Paris) 1945;71:1–17. 1290. Cohen BA, Rowley AH, Long CM. Herpes simplex type 2 in a patient with Mollaret's meningitis: demonstration by polymerase chain reaction. Ann Neurol 1994;35:112–116. 1291. Hermans PE, Goldstein NP, Wellman WE. Mollaret's meningitis and differential diagnosis of recurrent meningitis. Report of case, with review of literature. Am J Med 1972;52:128–150. 1292. Haynes BF, Wright R, McCracken JP. Mollaret meningitis—a report of three cases. JAMA 1976;236: 1967–1969. 1293. Iivanainen M. Benign recurrent aseptic meningitis of unknown aetiology (Mollaret's meningitis). Acta Neurol Scand 1973;49:133–138. 1294. Blumenfeld H, Cha J-H, Cudkowicz ME. Trimethoprim and sulfonamide-associated meningoencephalitis with MRI correlates. Neurology 1996;46: 556–558. 1295. Yamamoto LJ, et al. Herpes simplex virus type 1 DNA in the cerebrospinal fluid of a patient with Mollaret's meningitis. N Engl J Med 1991;325:1082–1085. 1296. Pederson E. Epidemic vertigo. Clinical picture, epidemiology and relation to encephalitis. Brain 1959;82:566–580. 1297. Basser LS. Benign paroxysmal vertigo of childhood. (A variety of vestibular neuronitis.) Brain 1964;87: 141–152. 1298. Koenigsberger MR, et al. Benign paroxysmal vertigo of childhood. Neurology 1968;18:301–302. 1299. Eviatar L, Eviatar A. Vertigo in children: differential diagnosis and treatment. Pediatrics 1977;59:833–838. 1300. Morgon A. Vertigo in children. Ann Pediatr (Paris) 1992;39:519–522. 1301. von Economo C. Encephalitis lethargica: its sequelae and treatment. London: Oxford University Press, 1931. 1302. Rail D, Scholtz C, Swash M. Post-encephalitic parkinsonism: current experience. J Neurol Neurosurg Psychiatry 1981;44:670–676. 1303. Association for Research in Nervous and Mental Disease. Acute epidemic encephalitis. New York: Paul B. Hoeber, 1921. 1304. Hohman LB. Post-encephalitic behavior disorders in children. Bull Johns Hopkins Hosp 1922;33:372–375. 1305. Sissons JGP. Superantigens and infectious disease. Lancet 1993;341:1627–1629. 1306. Leung DYM, et al. Toxic shock syndrome toxin-secreting Staphylococcus aureus in Kawasaki disease. Lancet 1993;342:1385–1388. 1307. Nigro G, Zerbini M, Krzysztofiak A. Active or recent parvovirus B19 infection in children with Kawasaki disease. Lancet 1994;343:1260–1261. 1308. Kuijpers TW, et al. A boy with chickenpox whose fingers peeled. Lancet 1998;351:1782. 1309. Yokota S, et al. Presence in Kawasaki disease of antibodies to mycobacterial heat-shock protein HSP65 and autoantibodies to epitopes of human HSP65 cognate antigen. Clin Immunol Immunopathol 1993;67: 163–170. 1310. Gama C, Breeden K, Miller R. Myositis in Kawasaki disease. Pediatr Neurol 1990;6:135–136. 1311. Bushara K, Wilson A, Rust RS. Facial palsy in Kawasaki syndrome. Pediatr Neurol 1997;17:362–364. 1312. Melish ME. Kawasaki syndrome (the mucocutaneous lymph node syndrome). Annu Rev Med 1982;33: 569–585. 1313. Dengler LD, et al. Cerebrospinal fluid profile in patients with acute Kawasaki disease. Pediatr Infect Dis J 1998;17:478–481. 1314. American Academy of Pediatrics. Kawasaki disease. In: Peter G, ed. 1997 Red Book: report of the Committee on Infectious Diseases, 24th ed. Elk Grove Village, IL: American Academy of Pediatrics, 1997: 316–319. 1315. Takei S, Arora YK, Walker SM. Intravenous immunoglobulin contains specific antibodies inhibitory to activation of T cells by staphylococcal toxin superantigens. J Clin Invest 1993;91:603–607. 1316. Newburger JW. Treatment of Kawasaki disease. Lancet 1996;347:11–28. 1317. Takagi, N, et al. Plasma exchange in Kawasaki disease. Lancet 1995;346:1307. 1318. Rasmussen T, Olszewski J, Lloyd-Smith D. Focal seizures due to chronic localized encephalitis. Neurology 1958;8:435–445. 1319. Antel JP, Rasmussen T. Rasmussen's encephalitis and the new hat. Neurology 1996;46:9–11. 1320. Power C, et al. Cytomegalovirus and Rasmussen's encephalitis. Lancet 1990;336:1282–1284. 1321. Andrews JM, et al. Chronic encephalitis, epilepsy and cerebrovascular immune complex deposits. Ann Neurol 1990;28:88–90. 1321a. Whitney KD, Andrews PL, McNamara JO. Immunoglobulin G and complement immunoreactivity in the cerebral cortex of patients with Rasmussen's encephalitis Neurology 1999;53:699–708. 1322. Jay V, et al. Chronic encephalitis and epilepsy (Rasmussen's encephalitis): Detection of cytomegalovirus and herpes simplex virus 1 by the polymerase chain reaction and in situ hybridization. Neurology 1995; 45:108–117. 1323. Rogers SW, et al. Autoantibodies to glutamate receptor GluR3 in Rasmussen's encephalitis. Science 1994;265:648–651. 1324. Aguilar MJ, Rasmussen T. Role of encephalitis in pathogenesis of epilepsy. Arch Neurol 1960;2: 663–676. 1325. Piatt JH Jr, et al. Chronic focal encephalitis (Rasmussen's syndrome): six cases. Epilepsia 1988;29: 268–279. 1326. Hart YM, et al. Chronic encephalitis and epilepsy in adults and adolescents: a variant of Rasmussen's syndrome? Neurology 1997;48:418–424. 1327. Tien RD, et al. Rasmussen's encephalitis: neuroimaging findings in four patients. Am J Roentgenol 1992;158:1329–1332. 1328. Cendes F, et al. Imaging of axonal damage in vivo in Rasmussen's syndrome. Brain 1995;118:753–758. 1329. Vining EP, et al. Why would you remove half a brain? The outcome of 58 children after hemispherectomy—the Johns Hopkins experience. Pediatrics 1997;100: 163–171. 1330. Vining EP, et al. Progressive unilateral encephalopathy of childhood (Rasmussen's syndrome): a reappraisal. Epilepsia 1993;34:639–650. 1331. Krauss GL, et al. Chronic steroid-responsive encephalitis without antibodies to glutamate receptor GluR3. Neurology 1996;46:247–249. 1332. Wise MS, Rutledge SL, Kuzniecky RI. Rasmussen syndrome and long-term response to gamma globulin. Pediatr Neurol 1996;14:149–152. 1333. Andrews PI, et al. Plasmapheresis in Rasmussen's encephalitis. Neurology 1996;46:242–246. 1334. McLachlan RS, Levin S, Blume WT. Treatment of Rasmussen's syndrome with ganciclovir. Neurology 1996;47:925–928. 1335. Ruggenenti P, Remuzzi G. Thrombotic microangiopathies. Crit Rev Oncol Hematol 1991;11:243–265. 1336. Wall RT, Harker LA. The endothelium and thrombosis. Annu Rev Med 1980;31:361–371. 1337. Karmali MA, et al. Sporadic cases of haemolytic-uraemic syndrome associated with faecal cytotoxin and cytotoxin-producing Escherichia coli in stools. Lancet 1983;1:619–620. 1338. Akashi, S, et al. A severe outbreak of haemorrhagic colitis and haemolytic uraemic syndrome associated with Escherichia coli O157:H7 in Japan. Eur J Pediatr 1994;153:650–655. 1339. Rondeau E, Peraldi M-N. Escherichia coli and the hemolytic-uremic syndrome. N Engl J Med 1996;335: 660–662. 1340. Mead PS, Griffin PM. Escherichia coli O157:H7. Lancet 1998;352:1207–1212. 1341. Moake JL. Haemolytic-uremic syndrome: basic science. Lancet 1994;343:393–397. 1342. van de Kar NC, et al. Tumor necrosis factor and interleukin-1 induce expression of the verocytotoxin receptor globotriaosylceramide on human endothelial cells: implications for the pathogenesis of the hemolytic uremic syndrome. Blood 1992;80:2755–2764. 1343. Louise CB, Obrig TG. Shiga toxin-associated hemolytic uremic syndrome: combined cytotoxic effects of shiga toxin and lipopolysaccharide (endotoxin) on human vascular endothelial cells in vitro. Infect Immun 1992;60:1536–1543. 1344. Cimolai N, Morrison BJ, Carter JE. Risk factors for the central nervous system manifestations of gastroenteritis-associated hemolytic-uremic syndrome. Pediatrics 1992;90:616–621. 1345. Moake JL. The role of von Willebrand factor (vWF) in thrombotic thrombocytopenic purpura (TTP) and the hemolytic-uremic syndrome (HUS). Prog Clin Biol Res 1990;337:135–140. 1346. Moake JL. Recent observations on the pathophysiology of thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. Hematol Pathol 1990;4: 197–201. 1347. Remuzzi G. HUS and TTP; variable expression of a single entity. Kidney Int 1987;32:292–308. 1348. Teshima T, Miyoshi T, Ono M. Cyclosporine-related encephalopathy following allogeneic bone marrow transplantation. Int J Hematol 1996;63:161–164. 1349. Siegler RL. Management of hemolytic-uremic syndrome. J Pediatr 1988;112:1014–1020. 1350. Cabrera GR, et al. Hemolytic uremic syndrome associated with invasive Streptococcus pneumoniae infection. Pediatrics 1998;101:699–703. 1351. Kennedy SS, Zacharski LR, Beck JR. Thrombotic thrombocytopenic purpura: analysis of 48 unselected cases. Semin Thromb Hemost 1980;6:341–349. 1352. Fuchs WE, et al. Thrombotic thrombocytopenic purpura. Occurrence two years apart during late pregnancy in two sisters. J Am Med Assoc 1976;235:2126–2127. 1353. Tarr PI, et al. Hemolytic-uremic syndrome in a six-year old girl after a urinary tract infection with shiga-toxin-producing Escherichia coli 0103:H2. N Engl J Med 1996;335:635–638. 1354. Bale JF Jr, Brasher C, Siegler RL. CNS manifestations of the hemolytic-uremic syndrome: relationship to metabolic alterations and prognosis. Am J Dis Child 1980;134:869–872. 1355. Hahn JS, et al. Neurological complications of hemolytic-uremic syndrome. J Child Neurol 1989;4: 108–113. 1356. Siegler RL. Spectrum of extrarenal involvement in postdiarrheal hemolytic-uremic syndrome. J Pediatr 1994;125:511–518. 1357. Upadhyaya K, et al. The importance of nonrenal involvement in the hemolytic-uremic syndrome. Pediatrics 1980;65:115–120. 1358. Travathan E, Dooling EC. Large thrombotic strokes in hemolytic-uremic syndrome. J Pediatr 1987;111: 863–866. 1359. Gianantonio C, et al. The hemolytic-uremic syndrome. J Pediatr 1964;64:478–491. 1360. Neild GH. Haemolytic-uraemic syndrome in practice. Lancet 1994;343:398–401. 1361. Pascual-Leone A, et al. EEG correlation of improvement in hemolytic-uremic syndrome after plasma infusion. Pediatr Neurol 1990;6:269–271. 1362. Martin DL, et al. The epidemiology and clinical aspects of the hemolytic-uremic syndrome in Minnesota. N Engl J Med 1990;323:1161–1167. 1363. Steele BT, et al. Recovery from prolonged coma in hemolytic-uremic syndrome. J Pediatr 1983;102: 402–404. 1364. Mackenzie JS, et al. Australian encephalitis in Western Australia. Med J Aust 1993;158:591–595. 1365. Richter RW, Shimojyo S. Neurologic sequelae of Japanese B encephalitis. Neurology 1961;11:553–559. 1366. Ishii T, Matsushita M, Hamada S. Characteristic residual neuropathological features of Japanese B encephalitis. Acta Neuropathol (Berl) 1977;38: 181–186. 1367. Burrow JN, et al. Australian encephalitis in the Northern Territory: clinical and epidemiological features, 1987–1996. Aust N Z J Med 1998;28:590–596. 1368. Robertson EG. Murray Valley encephalitis: pathological aspects. M J Australia 1952:1:107–110. 1369. Hloucal L. Tick-borne encephalitis as observed in Czechoslovakia. J Trop Med Hyg 1960;63:293–296. 1370. Gesikova M, Kaluzova M. Biology of tick-borne encephalitis virus. Acta Virol 1997;41:115–124. 1371. Pavri K. Clinical, clinicopathologic, and hematologic features of Kyasanur Forest disease. Rev Infect Dis 1989;11[Suppl 4]:S854–S859. 1372. Kolski H, et al. Etiology of acute childhood encephalitis at The Hospital for Sick Children, Toronto, 1994–1995. Clin Infect Dis 1998;26:398–409. 1373. Silver HK, Meiklejohn G, Kempe CH. Colorado tick fever. Am J Dis Child 1961;101:30–36. 1374. Johnson AJ, Karabatsos N, Lanciotti RS. Detection of Colorado tick fever virus by using reverse transcriptase PCR and application of the technique in laboratory diagnosis. J Clin Microbiol 1997;35: 1203–1208. 1375. Wahlberg P, Saikku P, Brummer-Korvenkontio M. Tick-borne viral encephalitis in Finland. The clinical features of Kumlinge disease during 1959–1987. J Intern Med 1989;225:173–177. 1376. Braito A, et al. Toscana virus infections of the central nervous system in children: a report of 14 cases. J Pediatr 1998;132:144–148. 1377. Davidson MM, Williams H, Macleod JA. Louping ill in man: a forgotten disease. J Infect 1991;23:241–242. Chapter 7 Autoimmune and Postinfectious Diseases Child Neurology Chapter 7 Autoimmune and Postinfectious Diseases Robert Rust and R John H. Menkes Department of Neurology, University of Virginia School of Medicine, Charlottesville, Virginia 22908; and R Departments of Neurology and Pediatrics, University of California, Los Angeles, UCLA School of Medicine, and Department of Pediatric Neurology, Cedars-Sinai Medical Center, Los Angeles, California 90048 Experimental Allergic Encephalomyelitis Primary Demyelinating Diseases of the Central Nervous System Multiple Sclerosis Variants of Multiple Sclerosis Acute Disseminated Encephalomyelitis Historical Aspects Pathology Pathogenesis Clinical Manifestations Diagnosis Treatment Prognosis Optic Neuritis Clinical Manifestations Diagnosis Treatment and Prognosis Acute Transverse Myelitis Pathology and Pathogenesis Clinical Manifestations Diagnosis Treatment and Prognosis Acute Cerebellar Ataxia Pathology and Etiology Clinical Manifestations Diagnosis Treatment Opsoclonus-Myoclonus Syndrome (Myoclonic Encephalopathy) Spasmus Nutans Immunologically Mediated Diseases Affecting Central Nervous System Gray Matter Rheumatic Fever (Sydenham Chorea) Pediatric Autoimmune Neuropsychiatric Diseases Associated with Streptococcal Infection Rasmussen Syndrome Immunologically Mediated Demyelinating Diseases of the Peripheral Nervous System Guillain-Barré Syndrome Bell's Palsy Pathology and Pathogenesis Clinical Manifestations Diagnosis Treatment and Prognosis Postinfectious Abducens Palsy Other Postinfectious Cranial Neuropathies Systemic Vasculitides with Nervous System Manifestations Primary Systemic Vasculitides (Collagen Vascular Diseases, Rheumatic Diseases) General Pathogenetic Mechanisms of Vasculitic Diseases Primary Systemic Vasculitides Secondary Systemic Vasculitides Collagen Vascular Diseases Neurologic Complications of Immunizations Postvaccinal Encephalomyelitis Postrabies Vaccination Encephalopathy Postinfluenza Vaccination Encephalopathy after Pertussis Vaccination Other Immunizations Chapter References This chapter considers several groups of neurologic diseases believed to result from a failure of the normal mechanisms of self-tolerance. One group consists of the primary demyelinating illnesses of the central nervous system (CNS), the second the immunologically mediated diseases affecting CNS gray matter, the third the immunologically mediated demyelinating diseases of the peripheral nervous system, and the last group includes the primary and secondary systemic vasculitides with nervous system manifestations. Myasthenia gravis, another autoimmune condition, is discussed in Chapter 14. The paraneoplastic processes are so uncommon in the pediatric age group that they do not warrant discussion here. EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS Experimental allergic encephalomyelitis (EAE) has served for many years as a useful animal model in the study of the evolution of autoimmune diseases that affect the nervous system. Departing from the postulate that the neuroparalytic accidents observed after the use of a rabies vaccine prepared from neural tissue were allergies, Rivers and Schwentker observed that the repeated injection of cerebral tissue into monkeys produced an inflammatory demyelinating encephalomyelitis ( 1). Similar lesions have been produced consistently in other mammalian species; their appearance is enhanced by the addition of Freund's adjuvant, a commonly used emulsion of water, oil, and killed acid-fast organisms added to the antigenic material. Its mode of action is unknown, but is believed to be a slow release of antigen and the induction of an inflammatory reaction that attracts mononuclear cells. In the original studies of Wolf and associates ( 2), 90% of monkeys developed EAE in 2 to 8 weeks after the first of an average of three weekly subcutaneous inoculations. The characteristic clinical features of this monophasic disease included paresis of the extremities, ataxia, nystagmus, and blindness. The disease was usually fatal, but some animals had mild symptoms that often subsided. A chronic disease and a relapsing disease marked by exacerbations and remissions reminiscent of the clinical picture of multiple sclerosis (MS) were produced subsequently in several animal species, including non-human primates (3,4). Pathologic examination of animals dying from EAE shows multiple focal perivascular areas of demyelination throughout the neuraxis. Microscopically, these lesions show an extensive infiltration by round cells, mainly lymphocytes and microglial cells, small perivascular hemorrhages, and myelin degeneration with preservation of the axon cylinders. The first pathologic alteration observed in experimental lesions is the perivenous appearance of hematogenous cells. These are initially seen in areas where the blood–brain barrier has been damaged or where lack of a barrier allows serum proteins to enter the nervous tissue ( 5). At the same time, primary and secondary (wallerian) demyelination can occur. Electron microscopic examination reveals a focal disruption of the myelin lamellae, and processes of the invading cells extend between the lamellae. Additionally, vesiculation of myelin occurs. In older lesions, the patches of demyelination are well defined and marked by varying degrees of gliosis. It is still unclear how perivascular demyelination develops in EAE. Myelin basic protein (MBP) is the substance in the injected cerebral tissue that initiates the evolution of the demyelinating process ( 6). This encephalitogenic protein has been isolated in relatively pure condition from the brain of a number of species. A component of normal myelin sheath, it contributes approximately 40% of total myelin proteins of adult white matter. In vivo, it is bound to acidic lipids or proteins. The gene coding for it is located on chromosome 18. The complete amino acid sequence has been determined, and the encephalitogenic activity resides in several peptides. As a consequence of the injection of MBP, T cells carrying gene-specified MBP receptors on their surface lose their immunologic tolerance to neural antigens by an unknown mechanism and escape from the host immunoregulatory restraints to develop into clones of cytotoxic cells. These bind to native MBP within the brain of the host, resulting in the deposition of an immune complex. The mechanism by which activated T cells enter the CNS is as yet unknown. Both encepha-litogenic and nonencephalitogenic cells are able to enter the CNS, but only the encephalitogenic cells remain; nonencephalitogenic cells are cleared within a few days ( 7). It is believed that in the course of a systemic immune response, antigen-specific T cells adhere to the brain endothelial cells. Research indicates that EAE is almost exclusively mediated by Th1 cells, which produce interleukin-2 (IL-2) and interferon-g. Multiple other cytokines produced by astrocytes and microglial cells also play major roles in inflammation and tissue destruction. T-cell adherence to endothelial cells is further enhanced by the class II major histocompatibility complex antigens, molecules induced by interferon-g. Other factors, notably endoglycosidases, guide the T cells through the blood–brain barrier. Once within the CNS, these immune complexes can attract hematogenous mononuclear cells and induce the release of chemotactic factors to initiate the ensuing inflammation. Macrophages are believed to play an important role in myelin destruction by their release of myelinolytic proteases ( 8). The passive transfer of EAE can be accomplished by CD4 + T lymphocytes, but not by serum. Other characteristics of EAE are that the disease can be blocked by antibodies against CD4 + T cells, by treatment of susceptible animals with a synthetic peptide, structurally related to the encephalitogenic portion of the MBP, or by irradiation (9,10). The development of EAE also can be suppressed by the administration of corticosteroids, nitrogen mustard, or 6-mercaptopurine. Susceptibility to the induction of the condition depends on a number of host factors. Immature animals are relatively more resistant to EAE than adult animals; diets inadequate in vitamin B 12 , biotin, or folic acid decrease susceptibility. Most important, both highly susceptible and highly resistant genetic lines have been segregated in a number of mammalian species. MBP also is the encephalitogen responsible for the encephalomyelitis after rabies immunization. Antibodies to MBP can be demonstrated in serum and in the cerebrospinal fluid (CSF) at the onset of symptoms, and a T-cell response to CNS myelin can be demonstrated in vaccinated subjects who develop encephalitis ( 11). A T-cell response and circulating antibod-ies to MBP also have been found in postmeasles encephalitis. The role, if any, of MBP in the other autoimmune disorders is not as clear. Whether the antigen responsible for MS is similar to the MBP that induces EAE, or whether the antigen is derived from a virus or viruses remains to be answered. In any case, the sequence of events leading to demyelination in MS appears to be morphologically similar to that observed in EAE (12), and, for the time being, this condition still serves as the best available laboratory model for the pathogenesis of some of the autoimmune and postinfectious disorders. Much work has concentrated on the effects of soluble factors (cytokines) on activated T cells. IL-2 is thought to play a particularly important role in the propagation of the activated T cells that may mediate EAE (12a). Human interferon-g and tumor necrosis factor (TNF) can induce the plasminogen activator of lymphocytes from patients with acute disseminated encephalomyelitis (ADEM) and MS, but not from control subjects, possibly indicating a role for these cytokines in the mediation of demyelination (12b). PRIMARY DEMYELINATING DISEASES OF THE CENTRAL NERVOUS SYSTEM In the northern hemisphere, ADEM, MS, and optic neuritis are the three most frequently encountered primary demyelinating illnesses of the CNS. The first is more common in children younger than age 12 years; the second is more common in adolescents and adults. Difficulty in distinguishing ADEM from the first bout of MS is among the most important reasons for the requirement of a second distinct episode occurring at least 1 month after the first for diagnosis of MS. It remains controversial as to whether “recurrent ADEM” should be distinguished from MS, but it appears likely that this distinction is valuable in prepubertal children. Optic neuritis and the combination of optic neuritis and transverse myelitis (Devic disease) usually occur as manifestations of ADEM or MS, but may result from other types of illness. An area of semiologic overlap exists between ADEM and Gullain-Barré syndrome (GBS). This area of overlap includes some or possibly all patients who manifest the clinical findings of Miller-Fisher syndrome. It also includes the minority of ADEM cases that manifest diminished or absent muscle stretch reflexes in combination with weakness and sensory changes referable to peripheral nerve dysfunction. The designation encephalomyeloradiculoneuropathy (EMRN) may be applied to cases exhibiting this overlap of central and peripheral demyelinative manifestations. Other much rarer primary demyelinative conditions that may occur in children and are difficult to accurately classify are acute (Marburg type) MS, Schilder disease, and Balo disease (concentric sclerosis). Infants younger than 2 years of age may experience a single bout of severe demyelination with edema that could be termed acute MS or, perhaps more appropriately, severe ADEM. The etiology and pathogenesis of these various primary demyelinating illnesses are as yet incompletely understood and it is not known whether MS, ADEM, and such related illnesses as optic neuritis, transverse myelitis, and others share exactly the same mechanism. Both MS and ADEM involve autoimmune responses that are directed, at least in part, against myelin antigens, but it is as yet unknown whether this represents a primary or secondary aspect of the inflammatory process of either illness. The onset of MS does not have a clear etiologic relationship to preceding infection and bouts are typically associated with detectable and abnormal production of immunoglobulin within the CNS. ADEM appears in many cases to be provoked by an immediately preceding infectious illness and only a minority of cases exhibit elevated CSF concentrations of immunoglobulin or immunoglobulin oligoclonality. Normal CSF immunoglobulin studies are characteristic of recurrences of ADEM, as compared with a greater than 94% likelihood of abnormality in association with an MS recurrence. A small minority of individuals who have experienced typical cases of ADEM in early childhood ultimately satisfies the clinical criteria for diagnosis of MS during adolescence. It is not known why some individuals experience one or more bouts of postinfectious demyelin-ation but achieve stable remission (ADEM or recurrent ADEM) before adolescence, whereas others satisfy criteria for the diagnosis of MS with either relapsing-remitting or steadily progressive manifestations of primary central demyelination. No completely reliable diagnostic test exists for either illness, and in every case a number of other illnesses must be excluded before assigning either of these labels. It may be particularly difficult to distinguish ADEM and related forms of inflammation from encephalitis. Indeed, some forms of encephalitis (such as those caused by herpes or measles viruses) may manifest pathologic abnormalities of ADEM in combination with those of encephalitis. Multiple Sclerosis Historical Aspects MS is the principal immune-mediated demye-linating illness of humans (13). The pathologic lesions of MS were described by Cruveilhier and Carswell early in the nineteenth century. Frerichs was the first to make a clinical diagnosis of MS in 1849. Charcot's extensive studies of the clinical manifestations and natural history of MS resulted in diagnostic criteria for a coherent clinical entity designated disseminated sclerosis or sclerose en plaques that also is and quite justifiably termed Charcot disease (14). Although the particular prevalence of this illness among young adults was recognized at the outset, subsequent clinical experience and confirmatory pathologic studies have demonstrated that MS may occur in infants and children ( 15,16). Pathogenesis MS occurs more frequently in certain parts of the world, and in regions of greater endemicity, certain subpopulations are at greater risk. Thus, in both Europe and North America, the risk is roughly proportional to the distance from the equator of the latitude in which a given individual has spent the first few decades of life. A particularly significant increase in prevalence exists in North America above the 38th parallel, whereas in Europe this increase occurs above the 46th parallel. Not all populations in these regions of high prevalence (30 to 100 cases per 100,000) partake of this enhanced risk, however. Thus, for example, the risk for Hungarian gypsies is 15- to 25-fold lower than that for the predominantly Magyr population of that country. However, the clear demonstration of regionally determined risk has been one of several lines of evidence advanced in support of the widely held concept that MS is initially provoked by an infectious agent. This line of reasoning has been supported by the development of MS epidemics in certain sheltered populations suddenly exposed to an influx of people from areas of relatively high endemic risk for MS. The appearance of MS on the Faroe Islands when British troops were stationed there during World War II is an important example of this phenomenon. Genetic susceptibility also may have played a role in this epidemic ( 17). Among the most important data supporting a direct etiologic role of infection or some other childhood experience are those obtained in studies of families migrating either from temperate or subarctic regions of the northern hemisphere to Israel or from Israel to these northerly latitudes. These studies demonstrate that the risk for MS is strongly influenced by the latitude, or perhaps even more specifically by the climate in which individuals live during the first two decades of life. This suggests the possibility that MS is caused by infection, incurred early in life, with an agent that is more prevalent in more northern latitudes. It is not known whether any possible directly infectious neurologic dysfunction might chiefly affect oligodendrocytes or myelin. Despite considerable effort and the identification of candidate viruses that are capable of provoking CNS demyelination (visna, JHM virus—a corona virus,—canine distemper, Theiler murine encephalomyelitis virus, measles, herpes simplex virus), a direct etiologic role for viruses or other infectious agents remains unproven ( 18). It remains possible that an intermittently activated MS virus resides undetected in oligodendrocytes. A second hypothesis suggests that infection with a virus or other agent serves indirectly to provoke MS because of the induction of immunodysregulation and autoimmunity. This hypothesis suggests that any of a number of viral or bacterial organisms possess the capacity to produce this unfavorable host response in susceptible individuals. By extension, the increased risk for MS in northern latitudes would be explained by greater prevalence of candidate micro-organisms within the temperate and subarctic ecological niche. The disturbance in immunoregulation might result from (a) abrogation of blood–brain barrier caused by inflammatory injury to blood vessels with secondary exposure of privileged antigens, (b) disturbance of self-tolerance caused by infectious alteration in host antigens, or (c) sensitization to autoantigens because antigens of invading organism happen to closely resemble them. The existence of a limited degree of normal immunosurveillance of the CNS by lymphocytes capable of passing through the intact blood–brain barrier may be permissive of the second and third mechanisms. The third mechanism is termed molecular mimicry. This hypothesis further suggests that the mediation of host autosensitization involves the activity of a trimolecular complex consisting of a cell-surface antigen of an invading organism, phagocytic antigen-presenting cells (macrophages or possibly microglial cells), and T-helper cells. As the result of the interaction between the foreign antigens and these cells, insufficiently specific clonal stimulation of cytotoxic T cells occurs, and inflammatory consequences are experienced by host tissues with similar antigenic determinants. It also is possible that the nonspecific clonal stimulation simply increases the number of activated cells in circulation and that these activated cells incite a poorly regulated inflammatory response directed at epitopes expressed on the surface of endothelial tissues or privileged nervous system tissues that are not similar to those of the foreign organism. The vascular, humoral, and cellular aspects of autoimmunity are discussed in further detail in the following section on ADEM. Support for the notion that MS is provoked indirectly by infection is provided by the characteristic occurrence of pathologically and clinically similar ADEM in the wake of one of a wide variety of febrile infectious illnesses. A novel, and as yet unsubstantiated, third hypothesis suggests attempts to explain the enhancement of MS risk in proportion to distance of early life residence from the equator on the basis of limited cumulative childhood sun exposure and the associated effects on vitamin D metabolism. More than one of these mechanisms or indeed others may contribute to MS or by extension ADEM pathogenesis. It is probable that if any of these mechanisms contribute to MS pathogenesis, the likelihood that such indirect effects will occur is genetically regulated. It is clear that the risk for MS is influenced by the immunologic constitution of the individual, represented in part by the human leukocyte antigen (HLA) genes that control the immune system. Although the HLA genes may play only a minor role in MS pathogenesis (19), the expression of certain HLA haplotypes appears to increase the risk for MS by 10- to 20-fold or more within certain populations. Among these permissive haplotypes are DRw15, DRw2 or DQw6 (North American and northern European whites), DR4 (Italians and Arabs), DR6 (Japanese and Mexicans), and A3, B7, or DR. Diminished rates of expression of the HLA haplotypes A2, B12, and DR7 are found in northern hemisphere whites with MS (20,21 and 22). The genetic aspect of MS risk also is demonstrated by the disparity observed among genetically distinct populations living within the same latitude. Genetic influence on susceptibility for MS is strongly supported by studies of families of patients with MS. Prevalence rates for MS among first-degree relatives of individuals with MS are approximately 20-fold greater than those of other individuals from the same region. Approximately 10% to 15% of patients with MS report another blood relative with this disease. Identical twins have a 25% to 35% concordance rate for MS, as compared with 0.5% for offspring (possibly much higher for daughters of mothers with MS), 0.6% for parents, 1.2% for siblings, and 2% to 4% for dizygotic twins ( 23,24 and 25). Genetic studies have further suggested that T-cell receptor germ-line polymorphisms may participate in the determination of risk for MS, but these data remain inconclusive ( 26,27 and 28). The lack of 100% concordance for identical twins makes it clear that MS is not caused solely by a single gene defect. It has been estimated that as many as 10 to 15 interacting genes may be involved, in addition to environmental factors (29). Pathology The pathognomonic lesion of MS is the plaque. Histopathologically, the typical acute plaques are areas of venulocentric demyelination with relative preservation of axis cylinders. Recent plaques and the margins of “active” plaques contain a mixture of inflammatory cells, primarily lymphocytes, microglia, and macrophages. Older plaques become gliotic and contain astrocytes. Plaques may be found anywhere in brain or spinal cord. They are largely, but not entirely, confined to white matter, with particular abundance in the periventricular zones ( 30) (Fig. 7.1). The histopathology closely resembles that of ADEM and of the experimental system that has been developed as a model for both MS and ADEM, EAE. On the other hand, MS plaques tend to have more discrete margins than those of ADEM. FIG. 7.1. Multiple sclerosis. Disseminated area of demyelination in white and gray matter of cerebral hemispheres. Myelin stain. (From Merritt HH. Textbook of neurology, 5th ed. Philadelphia: Lea & Febiger, 1973. With permission.) Because plaques may be located in almost any portion of the CNS, the clinical manifestations of MS are remarkably diverse. Larger plaques are clearly visible with appropriate brain imaging and may in some instances occupy locations that explain signs or symptoms of disease. However, often no clear clinico-anatomic association exists for any individual plaque. Moreover, clinical improvement may occur before observable resolution of plaques, suggesting that the nervous system dysfunction of MS is caused by more than just demyelination. Immunology An enormous amount of information has accumulated concerning immune system abnormalities found in patients with MS. Much of this information falls beyond the scope of this text. Information particularly relevant to MS is considered in this section, whereas information particularly relevant to the other autoimmune conditions is reviewed in other sections of this chapter. It is clear that patients with MS as a class do not have immune dysfunction such as might result in systemic immunodeficiency or autoimmunity, vasculitis, or susceptibility to malignancy ( 31,32). Systemic antibody responses and delayed-type hypersensitivity are normal. The primary disease is restricted to the CNS, within which no increase in susceptibility to unusual infections or any evidence for vasculitis occurs. Within the CNS and particularly within the demyelinating plaque, there is clear evidence for disturbances of both humoral and cellular immunity ( 26,33). Abnormal modulation of the humoral immune system is a consistent finding in patients with MS. It is represented by the almost universal presence in CSF of (a) electrophoretically detectable oligoclonal immunoglobulin, (b) elevated rates of synthesis and concentration in CSF of intrathecally generated immunoglobulin G (IgG) and IgM with varied or unknown epitopic specificity, and (c) increased levels of immunoglobulin components such as kappa chains ( 26,34,35 and 36). Although IgG 1 subclass elevation is the most common, other classes and subclasses of immunoglobulin also are elevated. As noted, the antigenic specificity of these immunoglobulins is various, including reactivity to a wide variety of viruses or other microbes, but in most cases the specificity is unknown. Abnormalities of cellular immunity include loss of T-suppressor/cytotoxic cells with resulting increases in the circulating CD4 + T-helper/inducer to CD8 + T-suppressor/cytotoxic cell ratio during MS relapses in children and adults ( 31,37,38,39 and 39a). The prominence of lymphocytic infiltration within an active MS plaque suggests the importance of these cells to MS pathogenesis. CD4 + T cells are predominant at the leading edges of active demyelinating lesions, whereas CD8 + T cells are more frequently encountered in less active plaque regions. Most of the T cells found within MS plaques bear the TCR (T-cell receptor) ab chains, although within chronic lesions a number of T cells bear TCRgd chains. It has been speculated that TCRab T cells initiate inflammation, whereas TCRgd T cells downregulate the initial response but perpetuate the inflammatory activity of chronic active lesions ( 33). The considerably diminished cadre of oligodendroglial cells found within chronic active plaques express a particular 65-kD heat shock protein (hsp 65), which is a known stimulus for TCRgd T-cell clones. This suggests some relationship of this protein either to the elimination ( 40) or less likely to the preservation of these oligodendroglia. Enhanced expression of the major histocompatibility antigens also is found within active MS plaques. This expression is found on the surfaces of microglial cells and macrophages and especially involves the class II major histocompatibility complex antigens with which CD4 + T cells characteristically interact (33,41). Astrocytes within plaques are involved to a lesser extent in the expression of major histocompatibility complex antigens, but oligodendroglial cells are not. Data obtained in the EAE experimental model suggest that activated lymphocytes mediate demyelination, because both the monophasic and chronic relapsing forms of EAE can be transferred passively by lymphocytes but not by serum. Moreover, demyelination in the corona-virus–induced experimental demyelination model requires the presence of splenic Thy1+ cells ( 42). In EAE, myelin antigens such as MBP are of considerable importance in cell-mediated demyelination. The particular target antigens of MS are unknown but may include myelin epitopes, viruses, and heat-shock proteins ( 43). Cellular immunity to myelin in MS has not been conclusively proven (33). It is possible that the importance of the MBP sensitization is of greater importance in ADEM than MS. The roles of T-cell activation and T-cell receptor specificity in MS are the subjects of several detailed reviews ( 26,27,33,39a,43,44). Enhanced expression of adhesion molecules and cytokines also is found within MS plaques ( 26,33,43). Among the adhesion molecules of greatest importance are intercellular adhesion molecule-1 (ICAM-1) found on endothelial membranes and leukocyte function-associated antigen-1 (LFA-1) found on lymphocytes. Both appear to facilitate the trafficking of inflammatory cells into MS plaques. Among the proinflammatory cytokines found within MS lesions are IL-2, tumor necrosis factor-a (TNF-a), and interferon-g (IFN-g). Circulating systemic lymphocytes from patients with MS show increased production of these proinflammatory cytokines and subnormal production of such anti-inflammatory cytokines as transforming growth factor-b (TGF-b) ( 45,46). Clinical Manifestations of Multiple Sclerosis in Children and Adolescents MS is primarily a disease of young adults (47). The peak age of onset is 25 to 30 years, and onset before puberty is uncommon. In a series of some 5,000 cases of MS, less than 0.2% presented before 11 years of age. In the same series, only 2.5% of cases presented between 11 and 16 years of age ( 48). In our experience, most adolescent cases present at or after 13 years of age. Thereafter, the prevalence increases with each additional year of age. In the pediatric population, girls are affected 2.2 times as frequently as boys, and whites are at greater risk than blacks ( 48a). The symptoms of the initial attack of MS in childhood are listed in Table 7.1 (48b,48c and 48d). TABLE 7.1. Symptoms during the initial episode of multiple sclerosis in 56 children For reasons as yet unknown, childhood MS is more common in China than in the West. In a series compiled in 1982, 3.5% of Chinese MS patients experienced the onset of their illnesses before age 10 years, and 22% developed it before age 20 years ( 49). This age distribution contrasts with 1.5% and 2.7%, with onset before 10 and 16 years, respectively, for a series compiled in Canada ( 50). In China, MS is characterized by a rapidly progressive course, with lesions most frequently localized to the optic nerve and spinal cord. A similar distribution of lesions, corresponding to what has been designated as neuromyelitis optica (Devic disease), has been observed in Japan (51). Among the most common initial manifestations of MS in adolescents and young adults are such monosymptomatic deficits as pure sensory disturbances, optic neuritis, diplopia, or pure motor paresis. In the series of Duquette and colleagues these symptoms accounted, respectively, for 26%, 14%, 11%, and 11% of initial manifestations (48). In the same series, ataxia, gait abnormalities, visual blurring, and combinations of sensorimotor and visual difficulties accounted for an additional 27% of presentations. Myelitis, sphincter disturbances, vestibular problems, and other manifestations accounted for only 12%. Ataxia and vestibular abnormalities are rather more commonly documented in adult MS than childhood-onset MS (52). Many of the initial manifestations of MS are subtle and transient. They are often unreported or ascribed to some other cause, and their true significance is ascertained only retrospectively. The common paraparetic presentation of young adult MS usually is associated with abnormalities of posterior column sensory dysfunction, which in our experience is often overlooked in adolescent cases because of an inadequate examination. This posterior column dysfunction may be more common in early MS than in ADEM. Prepubertal children may be more likely to manifest unusual clinical features during their first or even during subsequent bouts of MS. Acute encephalopathy, seizures, and prominent pyramidal tract abnormalities are among these unusual presentations. Some young children develop acute MS with rapid and profound psychomotor deterioration (53,54). The clinical signs and symptoms of MS typically progress over hours to days, although some patients have gradual worsening for as long as several months. Transient paroxysmal signs and symptoms may occur in MS, lasting variably from seconds to minutes. These include Lhermitte's and Uhthoff's signs, constricting truncal band sensations, and momentary exacerbation of weakness or sensory disturbance. Lhermitte's sign consists of a sudden, electriclike sensation spreading down the body and into the limbs on sudden flexion of the neck. Uhthoff sign consists of the transient appearance of signs or worsening of existing signs in association with exercise or when exposed to hot ambient temperatures (atmospheric or during bathing). It is thought to be the result of heat-induced impairment of conduction through already demyelinated axons. These various paroxysmal phenomena may occur as patients are improving or between bouts of MS and are not regarded either as evidence for recurrence or progression of illness or as separate bouts. In the experience of Cole and Stuart, only 14% of patients whose symptoms appeared before 16 years of age developed primary progressive MS, whereas the majority of children developed the relapsing-remitting form of MS, with 71% of this group being entirely well between relapses ( 55,56). Diagnosis MS is primarily a clinical diagnosis and one of exclusion. Remission, exacerbation, and CNS multifocality were recognized as key diagnostic features in Charcot's [...]... and optic neuritis [Letter] Neurology1 993;43 :63 2 1 36 137 138 139 140 141 142 143 144 145 1 46 147 148 149 150 151 152 153 154 155 1 56 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 1 76 177 178 179 180 181 182 183 184 185 1 86 187 188 189 190 191 192 193 194 195 1 96 197 198 199 200 201 202 203 204 205 2 06 207 208 209 210 211 212 213 214 215 2 16 217 218 219 220 221 Kapoor... in childhood Neurology 1981;31:555– 560 264 Bell W, Van Allen M, Blackman J Fisher's syndrome in childhood Dev Med Child Neurol 1970;12:758– 766 265 Shuaib A, Becker WJ Variants of Guillain-Barré syndrome: facial diplegia and multiple cranial nerve palsies Can J Neurol Sci 1987;14 :61 1 61 6 266 Landau WM, Glenn C, Dust G MRI in Miller Fisher variant of Guillain-Barré syndrome Neurology1 987;37:14–31 267 ... North Am 1990; 16: 341– 362 Fieschi C, et al Central nervous system vasculitis J Neurol Sci 1998;153:159–171 329a Younger DS, et al Granulomatous angiitis of the brain: an inflammatory reaction of diverse etiology Arch Neurol 1988;45:514–518 330 331 332 333 334 335 3 36 337 338 339 340 341 342 343 344 345 3 46 347 348 349 350 351 352 353 354 355 3 56 357 358 359 360 361 362 363 364 365 366 367 368 369 370 371... in childhood: clinical features of 149 cases Mult Scler 1997;3:4 3-4 6 48b Low NL, Carter S Multiple sclerosis in children Pediatrics 19 56; 18:24–30 48c Isler W Multiple Sklerose im Kindesalter Helv Paediatr Acta 1 961 ; 16: 412–431 48d Gall JC, et al Multiple sclerosis in children: a clinical study of 40 cases with onset in childhood Pediatrics 1958;21:703–709 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 ... for sick children Int Pediatr 1987;2: 163 – 167 Bye AME, Kendall B, Wilson J Multiple sclerosis in childhood: a new look Dev Med Child Neurol 1985; 27:215–222 Shaw CM, Alvord EC, Jr Multiple sclerosis beginning in infancy J Child Neurol 1987;2:252–2 56 Cole GF, Stuart CA A long perspective on childhood multiple sclerosis Dev Med Child Neurol 1995;37: 66 1 66 6 Pinhas-Hamiel O, et al Juvenile multiple sclerosis:... Immunol 1994;152 :60 0 60 10 46 Link J, et al Increased transforming growth factor-beta, interleukin-4, and interferon-gamma in multiple sclerosis Ann Neurol 1994; 36: 379–3 86 47 McFarlin DE, McFarland HF Multiple sclerosis (second of two parts) N Engl J Med 1982;307: 12 46 1251 48 Duquette P, et al Multiple sclerosis in childhood: clinical profile in 125 patients J Pediatr 1987;111: 359– 363 48a Ghezzi A,... immunizations in infants and children Pediatrics1981 ;68 :65 0 66 0 Blumberg DA, et al Severe reactions associated with diphtheria-tetanus-pertussis vaccine: detailed study of children with seizures, hypotonic-hyporesponsive episodes, high fevers, and persistent crying Pediatrics1993;91:1158–1 165 410 Pollock TM, et al Symptoms after primary immunisation with DTP and with DT vaccine Lancet 1984;2:1 46 149 411 Baraff... 1 960 ;63 :747–755 Riikonen R, Donner M, Erkkila H Optic neuritis in children and its relationship to multiple sclerosis: a clinical study of 21 children Dev Med Child Neurol 1988;30:349–359 Meadows SP Retrobulbar and optic neuritis in childhood and adolescence Trans Ophthalmol Soc UK 1 969 ;89 :60 3 63 8 Lucchinetti CF, et al Risk factors for developing multiple sclerosis after childhood optic neuritis Neurology. .. Neurol 1978;3: 565 – 566 Asbury AK, Cornblath DR Assessment of current diagnostic criteria for Guillain-Barré syndrome Ann Neurol 1990;27[Suppl]:S21–S24 Livingstone IR, Cumming WJK Hyperkalemic paralysis resembling Guillain-Barré syndrome Lancet 1979; 963 – 964 Guillain-Barré Syndrome Steroid Trial Group Double-blind trial of intravenous methylprednisolone in Guillain-Barré syndrome Lancet 1993;341:5 86 590 Austin... rheumatic fever J Exp Med 19 76; 144:1094–1110 Figueroa F, et al Anticardiolipin antibodies in acute rheumatic fever J Rheumatol 1992;19:1175–1180 Freeman JM, et al The emotional correlates of Sydenham's chorea Pediatrics 1 965 ;35:42–49 Bird MT, Palkes H, Prensky AL A follow-up study of Sydenham's chorea Neurology 19 76; 26: 601 60 6 Buchanan DN Pathologic changes in chorea Am J Dis Child 1941 ;62 :443–445 Nausieda . Behcet'sdisease. Arch Dis Child 19 86; 61:805–8 06. 1 263 . Rakover Y, et al. Behçet disease: long-term follow-up of three children and review of the literature. Pediatrics 1989;83:9 86 992. 1 263 a. Sakane T,. Treatment of Vogt-Koyanagi-Harada syndrome with intravenous immunoglobulin. Neurology 19 96; 46: 584–585. 12 86. Tabbara KF, Chavis PS, Freeman WR. Vogt-Koyanagi-Harada syndrome in children compared. O157:H7 in Japan. Eur J Pediatr 1994;153 :65 0 65 5. 1339. Rondeau E, Peraldi M-N. Escherichia coli and the hemolytic-uremic syndrome. N Engl J Med 19 96; 335: 66 0 66 2. 1340. Mead PS, Griffin PM. Escherichia