Controversies in Neurological Infectious Diseases

ABSTRACT

The past several years have seen major advances in our understanding of neurological infectious diseases, their diagnosis, and their treatment. Along with these advances, however, new information about infectious agents and new therapeutic options have also introduced both uncertainty and controversy in the approach and management of patients with diseases of the central nervous system. Here, we discuss six such areas: the long-term efficacy of HAART therapy in treatment of HIV infection; the role of viral infection in chronic fatigue syndrome; Rasmussen's encephalitis as an infectious or autoimmune disease; the spectrum of neurological diseases caused by rickettsial infection; the role of Mycoplasma pneumoniae in human central nervous system disease; and the possible association of Chlamydia pneumoniae and human herpesvirus 6 with multiple sclerosis.

KEYWORD

Rasmussen's encephalitis - chronic fatigue syndrome - rickettsial infection - mycoplasma pneumoniae - multiple sclerosis - controversies in neurology

REFERENCES

• 1 Hanna G J, Hirsch M S. Antiretroviral therapy of human immunodeficiency virus infection. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 5th ed Philadelphia: Churchill-Livingstone; 2000;0:1479-1500
• 2 Palella F J, Delaney K M, Moorman A C. Declining morbidity and mortality among patients with advanced immunodeficiency virus infection.  N Engl J Med . 1998;  338 853-860
• 3 Hogg R S, Heath K V, Yip B. Improved survival of HIV infected individuals following initiation of antiretroviral therapy.  JAMA . 1998;  279 450-454
• 4 Gendelman H E, Zheng J, Coulter C L. Suppression of inflammatory neurotoxins by highly active antiretroviral therapy in human immunodeficiency virus-associated dementia.  J Infect Dis . 1998;  178 1000-1007
• 5 Sepkowitz K A. Effect of HAART on natural history of AIDS-related opportunistic disorders.  Lancet . 1998;  351 228-230
• 6 Carr A, Marriott D, Field A, Vasak E, Cooper D A. Treatment of HIV-1 associated microsporidiosis and cryptosporidiosis with combination antiretroviral therapy.  Lancet . 1998;  351 256-261
• 7 Aboulafia D M. Regression of acquired immunodeficiency syndrome-related pulmonary Kaposi's sarcoma after highly active antiretroviral therapy.  Mayo Clin Proc . 1998;  73 439-443
• 8 Calista D, Boschini A, Landi G. Resolution of disseminated molluscum contagiosum with highly active anti-retroviral therapy (HAART) in patients with AIDS.  Eur J Dermatol . 1999;  9 211-213
• 9 Anders H J, Goebel F D. Neurological manifestations of cytomegalovirus infection in the acquired immunodeficiency syndrome.  Int J STD AIDS . 1999;  10 151-159
• 10 Rauz S, Murray P I. Changing patterns of HIV related ocular disease.  Sex Transm Infect . 1999;  75 18-20
• 11 Albrecht H, Hoffmann C, Degen O. Highly active antiretroviral therapy significantly improves the prognosis of patients with HIV-associated progressive multifocal leukoencephalopathy.  AIDS . 1998;  12 1149-115
• 12 Clifford D B, Yiannoutsos C, Glicksman M. HAART improves prognosis in HIV-associated progressive multifocal leukoencephalopathy [see comments].  Neurology . 1999;  52 623-625
• 13 Miralles P, Berenguer J, Garcia de Viedma D. Treatment of AIDS-associated progressive multifocal leukoencephalopathy with highly active antiretroviral therapy.  AIDS . 1998;  12 2467-2472
• 14 Ho D D, Neumann A U, Perelson A S. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection.  Nature . 1995;  373 123-126
• 15 Wong J K, Hezareh M, Gunthard H F. Recovery of replication-competent HIV despite prolonged suppression of plasma viremia.  Science . 1997;  278 1291-1295
• 16 Zhang L, Ramratnam B, Tenner Racz K. Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy [see comments].  N Engl J Med . 1999;  340 1605-1613
• 17 Ledergerber B, Egger M, Opravil M. Clinical progression and virological failure on highly active antiretroviral therapy in HIV-1 patients: a prospective cohort study. Swiss HIV Cohort Study.  Lancet . 1999;  353 863-868
• 18 Selwyn P A, Arnold R. From fate to tragedy: the changing meanings of life, death, and AIDS.  Ann Intern Med . 1998;  129 899-902
• 19 Michelet C, Arvieux C, Francois C. Opportunistic infections occurring during highly active antiretroviral treatment.  AIDS . 1998;  12 1815-1822
• 20 Cassoux N, Lumbroso L, Bodaghi B, Zazoun L, Katlama C, LeHoang P. Cystoid macular oedema and cytomegalovirus retinitis in patients with HIV disease treated with highly active antiretroviral therapy.  Br J Ophthalmol . 1999;  83 47-49
• 21 Jacobson M A, Zegans M, Pavan P R. Cytomegalovirus retinitis after initiation of highly active antiretroviral therapy [see comments].  Lancet . 1997;  349 1443-1445
• 22 De Luca A, Ammassari A, Cingolani A, Giancola M L, Antinori A. Disease progression and poor survival of AIDS-associated progressive multifocal leukoencephalopathy despite highly active antiretroviral therapy [letter].  AIDS . 1998;  12 1937-1938
• 23 Coffin J M. HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy.  Science . 1995;  267 483-489
• 24 d'Arminio Monforte A, Testa L, Adorni F. Clinical outcome and predictive factors of failure of highly active antiretroviral therapy in antiretroviral-experienced patients in advanced stages of HIV-1 infection.  AIDS . 1998;  12 1631-1637
• 25 Vigouroux C, Gharakhanian S, Salhi Y. Adverse metabolic disorders during highly active antiretroviral treatments (HAART) of HIV disease.  Diabetes Metab . 1999;  25 383-392
• 26 Tobi R, Morag A, Ravid Z. Prolonged atypical illness associated with serological evidence of persistent Epstein-Barr virus infection.  Lancet . 1982;  1 61-64
• 27 DuBois R E, Seeley J K, Brus I. Chronic mononucleosis syndrome.  South Med J . 1984;  77 1376-1382
• 28 Jones J F, Ray C G, Minnich L L. Evidence for active Epstein-Barr virus infection in patients with persistent, unexplained illnesses.  Ann Intern Med . 1985;  105 1-7
• 29 Straus S E, Tosato G, Armstrong G. Persisting illness and fatigue in adults with evidence of Epstein-Barr virus infection.  Ann Intern Med . 1985;  102 7-16
• 30 Holmes G P, Kaplan J E, Gantz N M. Chronic fatigue syndrome: a working case definition.  Ann Intern Med . 1988;  108 387-389
• 31 Fukuda K, Strauss S E, Hickie I. The chronic fatigue syndrome: a comprehensive approach to its definition and study.  Ann Intern Med . 1994;  121 953-959
• 32 Lloyd I, Hickie I, Peterson P K. Chronic fatigue syndrome. In: Richman DD, Whitley RJ, Hayden FG, eds. Clinical virology New York: Churchill Livingstone 1997: 343-355
• 33 Sairenji T, Yamanishi K, Tachibana Y, Bertoni G, Kurata T. Antibody responses to Epstein-Barr virus, human herpesvirus 6 and human herpesvirus 7 in patients with chronic fatigue syndrome.  Intervirology . 1995;  38 269-273
• 34 Levine P H, Jacobson S, Pocinki A G. Clinical, epidemiologic, and virologic studies in four clusters of the chronic fatigue syndrome [see comments].  Arch Intern Med . 1992;  152 1611-1616
• 35 Buchwald D, Ashley R L, Pearlman T, Kith P, Komaroff A L. Viral serologies in patients with chronic fatigue and chronic fatigue syndrome.  J Med Virol . 1996;  50 25-30
• 36 White P D, Thomas J M, Amess J. Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever.  Br J Psychiatry . 1998;  173 475-481
• 37 Read R, Larson E, Harvey J. Clinical and laboratory findings in the Paul-Bunnell negative glandular fever-fatigue syndrome.  J Infect . 1990;  21 157-165
• 38 Smith M S, Mitchell J, Corey L. Chronic fatigue in adolescents [see comments].  Pediatrics . 1991;  88 195-202
• 39 Wallace H L, Natelson B, Gause W, Hay J. Human herpesviruses in chronic fatigue syndrome.  Clin Diagn Lab Immunol . 1999;  6 216-223
• 40 Ablashi D V. Viral studies of chronic fatigue syndrome.  Clin Infect Dis . 1994;  S130-S133 (S130-S133)
• 41 Martin W J, Zeng L C, Ahmed K, Roy M. Cytomegalovirus-related sequence in an atypical cytopathic virus repeatedly isolated from a patient with chronic fatigue syndrome.  Am J Pathol . 1994;  145 440-451
• 42 Martin W J. Simian cytomegalovirus-related stealth virus isolated from the cerebrospinal fluid of a patient with bipolar psychosis and acute encephalopathy.  Pathobiology . 1996;  64 64-66
• 43 Miller G, Carmichael H A, Calder B D. Antibody to Coxsackie B virus in diagnosing postviral fatigue syndrome.  Br Med J . 1988;  302 140-142
• 44 Yousef G E, Bell E J, Mann G F. Chronic enterovirus infection in patients with postviral fatigue syndrome.  Lance . 1988;  1 146-147
• 45 Archard L C, Bowles N E, Behan P O. Postviral fatigue syndrome: Persistence of enterovirus RNA in muscle and elevated creatine kinase.  J R Soc Med . 1988;  81 326-330
• 46 Gow J W, Behan W M, Clements G B, Woodall C, Riding M, Behan P O. Enteroviral RNA sequences detected by polymerase chain reaction in muscle of patients with postviral fatigue syndrome [see comments].  BMJ . 1991;  302 692-696
• 47 Galbraith D N, Nairn C, Clements G B. Evidence for enteroviral persistence in humans.  J Gen Virol . 1997;  78 307-312
• 48 Cunningham L, Bowles N E, Lane R J, Dubowitz V, Archard L C. Persistence of enteroviral RNA in chronic fatigue syndrome is associated with the abnormal production of equal amounts of positive and negative strands of enteroviral RNA.  J Gen Virol . 1990;  71 1399-1402
• 49 Lloyd A R, Hales J P, Gandevia S C. Muscle strength, endurance, and recovery in the post-infection fatigue syndrome.  J Neurol Neurosurg Psychiatry . 1988;  51 1316-1319
• 50 Lloyd A R, Gandevia S C, Hales J P. Muscle endurance, twitch properties, voluntary activation, and perceived exertion in normal subjects and patients with chronic fatigue syndrome.  Brain . 1991;  114 85-93
• 51 Defreitas E, Hilliard B, Cheney P R. Retroviral sequences related to human T-lymphotrophic virus type II in patients with chronic fatigue immune dysfunction syndrome.  Proc Natl Acad Sci U S A . 1991;  88 2922-2925
• 52 Heneine W, Woods T C, Sinha S D. Lack of evidence for infection with known human and animal retroviruses in patients with chronic fatigue syndrome.  Clin Infect Dis . 1994;  S121-S125 (S121-S125)
• 53 Folks T M, Heneine W, Khan A, Woods T, Chapman L, Schonberger L. Investigation of retroviral involvement in chronic fatigue syndrome.  Ciba Found Symp . 1993;  173 160-166
• 54 Gow J W, Simpson K, Schliephake A. Search for retrovirus in the chronic fatigue syndrome.  J Clin Pathol . 1992;  45 1058-1054
• 55 Dale J K, Di Bisceglie A M, Hoofnagle J H, Straus S E. Chronic fatigue syndrome: lack of association with hepatitis C virus infection.  J Med Virol . 1991;  34 119-121
• 56 Nakaya T, Takahashi H, Nakamura Y. Demonstration of Borna disease virus RNA in peripheral blood mononuclear cells derived from Japanese patients with chronic fatigue syndrome.  FEBS Lett . 1996;  378 145-149
• 57 Manningham R. The Symptoms, Nature, and Causes of the Febricula or Little Fever: Commonly Called Nervous or Hysteric Fever; the Fever on the Spirits; Vapors, Hypo or Spleen. 2nd ed. London: J Robinson; 1750 . 
• 58 Beard G. Neurasthenia or nervous exhaustion.  Boston Med Surg J (New Ser) . 1869;  3 217-225
• 59 Wheeler E O, White P D, Reed E W, Cohen M E. Neurocirculatory asthenia (anxiety neurosis, effort syndrome, neurasthenia): a twenty year follow-up study of one hundred and seventy three patients.  JAMA . 1950;  142 878-889
• 60 Schrader H, Obelieniene D, Bovim G, Surkiene D, Mickeviciene D, Miseviciene I. Natural evolution of late whiplash outside the medicolegal context.  Lancet . 1996;  347 1207-1211
• 61 Farrell M A, DeRosa M J, Curran J G. Neuropathologic findings in cortical resections (including hemispherectomies) performed for the treatment of intractable childhood epilepsy.  Acta Neuropathol (Berl) . 1992;  83 246-259
• 62 Friedman H, Chi'en L, Parham D. Virus in brain of child with hemiplegia, hemiconvulsions, and epilepsy.  Lancet . 1977;  2 666
• 63 Walter G F, Renella R R. Epstein-Barr virus in brain and Rasmussen's encephalitis [letter].  Lancet . 1989;  1 279-280
• 64 Power C, Poland S D, Blume W T, Girvin J P, Rice G PA. Cytomegalovirus and Rasmussen's encephalitis.  Lancet . 1990;  336 1282-1284
• 65 McLachlan R S, Girvin J P, Blume W T, Reichman H. Rasmussen's chronic encephalitis in adults.  Arch Neurol . 1993;  50 269-274
• 66 Jay V, Becker L E, Blaser S. Pathology of chronic herpes infection associated with seizure disorder: a report of two cases with tissue detection of herpes simplex virus 1 by the polymerase chain reaction.  Pediatr Pathol Lab Med . 1995;  15 131-146
• 67 Jay V, Becker L E, Otsubo H. 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
• 68 Atkins M R, Terrell W, Hulette C M. Rasmussen's syndrome: a study of potential viral etiology.  Clin Neuropathol . 1995;  14 7-12
• 69 Rogers S W, Andrews P I, Gahring L C. Antibodies to glutamate receptor GluR3 in Rasmussen's encephalitis.  Science . 1994;  265 648-653
• 70 Krauss G L, Campbell M L, Roche K W, Huganir R L, Niedermeyer E. Chronic steroid-responsive encephalitis without autoantibodies to glutamate receptor GluR3.  Neurology . 1996;  46 247-249
• 71 Andrews P I, McNamara J O, Lewis D V. Clinical and electroencephalographic correlates in Rasmussen's encephalitis.  Epilepsia . 1997;  38 189-194
• 72 Palmer C A, Geyer J D, Keating J M. Rasmussen's encephalitis with concomitant cortical dysplasia: the role of GluR3.  Epilepsia . 1999;  40 242-247
• 73 He X P, Patel M, Whitney K D, Janumpalli S, Tenner A, McNamara J O. Glutamate receptor GluR3 antibodies and death of cortical cells.  Neuron . 1998;  20 153-163
• 74 Levite M, Hermelin A. Autoimmunity to the glutamate receptor in mice: a model for Rasmussen's encephalitis?.  J Autoimmun . 1999;  13 73-82
• 75 Hart Y M, Cortez M, Andermann F. Medical treatment of Rasmussen's syndrome (chronic encephalitis and epilepsy): effect of high-dose steroids or immunoglobulins in 19 patients.  Neurology . 1994;  44 1030-1036
• 76 Chinchilla D, Dulac O, Robain O. Reappraisal of Rasmussen's syndrome with special emphasis on treatment with high doses of steroids.  J Neurol Neurosurg Psychiatry . 1994;  57 1325-1333
• 77 Andrews P I, Dichter M A, Berkovic S F, Newton M R, McNamara J O. Plasmapheresis in Rasmussen's encephalitis [see comments].  Neurology . 1996;  46 242-246
• 78 Antozzi C, Granata T, Aurisano N. Long-term selective IgG immuno-adsorption improves Rasmussen's encephalitis.  Neurology . 1998;  51 302-305
• 79 Caraballo R, Tenembaum S, Cersosimo R. [Rasmussen syndrome] Sindrome de Rasmussen.  Rev Neurol . 1998;  26 978-983
• 80 Leach J P, Chadwick D W, Miles J B, Hart I K. Improvement in adult-onset Rasmussen's encephalitis with long-term immunomodulatory therapy.  Neurology . 1999;  52 738-742
• 81 McLachlan R S, Levin S, Blume W T. Treatment of Rasmussen's syndrome with ganciclovir.  Neurology . 1996;  47 925-928
• 82 DeToledo J C, Smith D B. Partially successful treatment of Rasmussen's encephalitis with zidovudine: symptomatic improvement followed by involvement of the contralateral hemisphere.  Epilepsia . 1994;  35 352-355
• 83 Dabbagh O, Gascon G, Crowell J, Bamoggadam F. Intraventricular interferon-alpha stops seizures in Rasmussen's encephalitis: a case report.  Epilepsia . 1997;  38 1045-1049
• 84 Maria B L, Ringdahl D M, Mickle J P. Intraventricular alpha interferon therapy for Rasmussen's syndrome.  Can J Neurol Sci . 1993;  20 333-336
• 85 Kim J H, Durack D T. Rickettsiae. In: Scheld WM, Durack DT, Whitley RJ, eds. Infections of the Central Nervous System 2nd ed. Philadelphia: Lippincott-Raven 1997: 403-416
• 86 Miller J Q, Price T R. The nervous system in Rocky Mountain spotted fever.  Neurology . 1972;  22 561-566
• 87 Westerman E L. Rocky mountain spotless fever: a dilemma for the clinician.  Arch Intern Med . 1982;  142 1106-1107
• 88 Pai H, Sohn S, Seong Y, Kee S, Chang W H, Choe K W. Central nervous system involvement in patients with scrub typhus.  Clin Infect Dis . 1997;  24 436-440
• 89 Garg P, Blass D A. Rocky Mountain spotted fever manifested by cerebritis and pneumonitis.  Md Med J . 1987;  36 343-345
• 90 Paddock C D, Greer P W, Ferebee T L. Hidden mortality attributable to Rocky Mountain spotted fever: immunohistochemical detection of fatal, serologically unconfirmed disease.  J Infect Dis . 1999;  179 1469-1476
• 91 Wei T Y, Baumann R J. Acute disseminated encephalomyelitis after Rocky Mountain spotted fever.  Pediatr Neurol . 1999;  21 503-505
• 92 Duma R J, Sonenshine D E, Bozeman F M. Epidemic typhus in the United States associated with flying squirrels.  JAMA . 1981;  245 2318-2323
• 93 Ratnasamy N, Everett E D, Roland W E, McDonald G, Caldwell C W. Central nervous system manifestations of human ehrlichiosis.  Clin Infect Dis . 1996;  23 314-319
• 94 Winslow G M, Yager E, Shilo K, Collins D N, Chu F K. Infection of the laboratory mouse with the intracellular pathogen Ehrlichia chaffeensis Infect Immun .  1998;  66 3892-3899
• 95 Grant A C, Hunter S, Partin W C. A case of acute monocytic ehrlichiosis with prominent neurologic signs.  Neurology . 1997;  48 1619-1623
• 96 Dunn B E, Monson T P, Dumler J S. Identification of Ehrlichia chaffeensis morulae in cerebrospinal fluid mononuclear cells.  J Clin Microbiol . 1992;  30 2207-2210
• 97 Carter N, Miller N R. Fourth nerve palsy caused by Ehrlichia chaffeensis J Neuroophthalmol .  1997;  17 47-50
• 98 Carpenter C F, Gandhi T K, Kong L K. The incidence of ehrlichial and rickettsial infection in patients with unexplained fever and recent history of tick bite in central North Carolina.  J Infect Dis . 1999;  180 900-903
• 99 Wenzel R P, Hayden F G, Groschel D H. Acute febrile cerebrovasculitis: a syndrome of unknown, perhaps rickettsial, cause.  Ann Intern Med . 1986;  104 606-615
• 100 Hechemy K E, Fox J A, Groschel D H, Hayden F G, Wenzel R P. Immunoblot studies to analyze antibody to the Rickettsia typhi group antigen in sera from patients with acute febrile cerebrovasculitis.  J Clin Microbiol . 1991;  29 2559-2565
• 101 Linnemann Jr C C, Pretzman C I, Peterson E D. Acute febrile cerebrovasculitis: a non-spotted fever group rickettsial disease.  Arch Intern Med . 1989;  149 1682-1684
• 102 Campbell T A, Strong P S, Grier G S. Primary atypical pneumoniae: two hundred cases at Ft. Eustin, Va.  JAMA . 1943;  122 723-729
• 103 Clyde Jr WA. Mycoplasmal diseases. In: Scheld WM, Durack DT, Whitley RJ, eds. Infections of the Central Nervous System 2nd ed. Philadelphia: Lippincott-Raven 1997: 603-612
• 104 Koskiniemi M. CNS manifestations associated with Mycoplasma pneumoniae infections: summary of cases at the University of Helsinki and review.  Clin Infect Dis . 1993;  S52-S57 (S52-S57)
• 105 Thomas N H, Collins J E, Robb S A, Robinson R O. Mycoplasma pneumoniae infection and neurological disease [see comments].  Arch Dis Child . 1993;  69 573-576
• 106 Kolski H, Ford Jones E L, Richardson S. Etiology of acute childhood encephalitis at The Hospital for Sick Children, Toronto, 1994-1995.  Clin Infect Dis . 1998;  26 398-409
• 107 Heckmann J G, Sommer J B, Druschky A, Erbguth F J, Steck A J, Neundorfer B. Acute motor axonal neuropathy associated with IgM anti-GM1 following Mycoplasma pneumoniae infection.  Eur Neurol . 1999;  41 175-176
• 108 Kusunoki S, Chiba A, Hitoshi S, Takizawa H, Kanazawa I. Anti-Gal-C antibody in autoimmune neuropathies subsequent to mycoplasma infection.  Muscle Nerve . 1995;  18 409-413
• 109 Kasahara I, Otsubo Y, Yanase T, Oshima H, Ichimaru H, Nakamura M. Isolation and characterization of Mycoplasma pneumoniae from cerebrospinal fluid of a patient with pneumonia and meningoencephalitis.  J Infect Dis . 1985;  152 823-825
• 110 Abramovitz P, Schvartzmann P, Harel D, Lis I, Naot Y. Direct invasion of the central nervous system by Mycoplasma pneumoniae: a report of two cases.  J Infect Dis . 1987;  155 482-487
• 111 Cano Sanchez A, Cano Gracia H, Fernandez Pardo J, Artero Galan J M, Gonzalez Sicilia L. Aseptic meningitis caused by Mycoplasma pneumoniae in a 19-year-old woman.  Eur J Clin Microbiol Infect Dis . 1999;  18 228-229
• 112 Ieven M, Demey H, Ursi D, Van Goethem G, Cras P, Goossens H. Fatal encephalitis caused by Mycoplasma pneumoniae diagnosed by the polymerase chain reaction.  Clin Infect Dis . 1998;  27 1552-1553
• 113 Agard C, Hamidou M, Gires C, Grolleau J Y, Raffi F. [Polynuclear neutrophils meningitis disclosing Mycoplasma pneumoniae infection (letter)] Meningite a polynucleaires neutrophiles revelant une infection a Mycoplasma pneumoniae Rev Med Interne .  1996;  17 1043-1044
• 114 Fisher R S, Clark A W, Wolinsky J S, Parhad I M, Moses H, Mardiney M R. Postinfectious leukoencephalitis complicating Mycoplasma pneumoniae infection.  Arch Neurol . 1983;  40 113
• 115 Pellegrini M, O'Brien T J, Hoy J, Sedal L. Mycoplasma pneumoniae infection associated with an acute brainstem syndrome.  Acta Neurol Scand . 1996;  93 203-206
• 116 Nadkarni N, Lisak R P. Guillain-Barré syndrome (GBS) with bilateral optic neuritis and central white matter disease.  Neurology . 1993;  43 842-843.
• 117 Kikuchi M, Tagawa Y, Iwamoto H, Hoshino H, Yuki N. Bickerstaff's brainstem encephalitis associated with IgG anti-GQ1b antibody subsequent to Mycoplasma pneumoniae infection: favorable response to immunoadsorption therapy.  J Child Neurol . 1997;  12 403-405
• 118 Westenfelder G O, Akey D T, Corwin S J, Vick N A. Acute transverse myelitis due to Mycoplasma pneumoniae infection.  Arch Neurol . 1981;  38 317
• 119 Saitoh S, Wada T, Narita M. Mycoplasma pneumoniae infection may cause striatal lesions leading to acute neurologic dysfunction.  Neurology . 1993;  43 2150-2151
• 120 Al-Mateen M, Gibbs M, Dietrich R, Mitchell W G, Menkes J H. Encephalitis lethargica-like illness in a girl with mycoplasma infection.  Neurology . 1988;  38 1155-1158
• 121 Feder H M, Watkin T, Cole S R, Quintiliani R. Severe meningoencephalitis complicating Mycoplasma pneumoniae infection in a child.  Arch Pathol Lab Med . 1981;  105 619-621
• 122 Fernandez C V, Bortolussi R, Gordon K, Lee S H, Gatien J G, Shahdrabadi M S. Mycoplasma pneumoniae infection associated with central nervous system complications.  J Child Neurol . 1993;  8 27-31.
• 122a Narita M, Matsuzono Y, Togashi T. DNA diagnosis of central nervous system infection by Mycoplasma pneumoniae.  Pediatrics . 1992;  90 250-253
• 123 Dorff B, Lind K. Two fatal cases of meningoencephalitis associated with Mycoplasma pneumoniae infection.  Scand J Infect Dis . 1976;  8 49-51
• 124 Sriram S, Mitchell W, Stratton C. Multiple sclerosis associated with Chlamydia pneumoniae infection of the CNS.  Neurology . 1998;  50 571-572
• 125 Sriram S, Stratton C, Yao S. Chlamydia pneumoniae infection of the central nervous system in multiple sclerosis.  Ann Neurol . 1999;  46 4-5
• 126 Trieb J, Haass A, Stille W. Multiple sclerosis and Chlamydia pneumoniae Ann Neurol .  2000;  47 408
• 127 Perlmutter L, Darvish M. Possible relationship of Chlamydia pneumoniae to multiple sclerosis.  Med Hypotheses . 1983;  12 95-98
• 128 Le Gac P, Wulffaert F, Arquie E. The psittacosis virus in the etiology of multiple sclerosis.  C R Acad Sci Hebd Seances Acad Sci D . 1966;  22 1793-1795
• 129 Hoption Cann S, van Netten J, van Netten C. Chlamydia, Rickettsia and antibiotic treatment of multiple sclerosis.  Ann Neurol . 2000;  47 408-409
• 130 Sriam S, Stratton C, Yao S. (Reply to letter).  Ann Neurol . 2000;  47 409-411
• 131 Meinl E. Concepts of viral pathogenesis of multiple sclerosis.  Curr Opin Neurol . 1999;  12 303-307
• 132 Dockrell D, Smith T, Paya C. Human herpesvirus 6.  Mayo Clin Proc . 1999;  74 163-170
• 133 Albright A, Lavi E, Black J. The effect of human herpesvirus-6 (HHV-6) on cultured human neural cells: oligodendrocytes and microglia.  J Neurovirol . 1998;  5 486-494
• 134 Soldan S, Leist T, Juhng K. Increased lymphoproliferative response to human herpesvirus type 6A variant in multiple sclerosis patients.  Ann Neurol . 2000;  47 306-313
• 135 Santoro F, Kennedy P, Locatelli G. CD46 is a cellular receptor for human herpesvirus 6.  Cell . 1999;  99 817-827
• 136 Torelli G, Barozzi P, Marasca R. Targeted integration of human herpesvirus 6 in the p arm of chromosome 17 of peripheral blood lymphocytes.  J Med Virol . 1995;  46 178-188
• 137 Sola P, Merelli E, Marasca R. Human herpesvirus-6 and multiple sclerosis: survey of anti-HHV-6 antibodies by immunofluorescence analysis and viral sequences by polymerase chain reaction.  J Neurol Neurosurg Psychiatry . 1993;  56 917-919
• 138 Soldan S, Berti R, Salem N. Association of herpes virus 6 (HHV-6) with multiple sclerosis: increased IgM response to HHV-6 early antigen and detection of serum HHV-6 DNA.  Nat Med . 1997;  12 1394-1397
• 139 Ongradi J, Rajda C, Maordi C. A pilot study on the antibodies to HHV-6 variants and HHV-7 in CSF of MS patients.  J Neurovirol . 1999;  5 529-532
• 140 Wilborn F, Schmidt C, Brinkmann V. A potential role for human herpesvirus type 6 in nervous system disease.  J Neuroimmunol . 1994;  49 213-214
• 141 Ablashi D, Lapps W, Kaplan M. Human herpes virus-6 (HHV-6) infection in multiple sclerosis: preliminary report.  Multiple Sclerosis . 1998;  4 490-496
• 142 Goldberg S, Albright A, Lisak R. Polymerase chain reaction analysis of human herpesvirus-6 sequences in the sera and cerebrospinal fluid of patients with multiple sclerosis.  J Neurovirol . 1995;  5 134-139
• 143 Enbom M, Wang F, Fredickson S. Similar humoral and cellular immunological reactivities to human herpesvirus 6 in patients with multiple sclerosis and controls.  Clin Diagn Lab Immunol . 1999;  6 545-549
• 144 Mirandola P, Stefan A, Brambilla E. Absence of human herpesvirus 6 and 7 from spinal fluid and serum of multiple sclerosis patients.  Neurology . 1999;  53 1367-1368
• 145 Mayne M, Kishnan J, Metz L. Infrequent detection of human herpesvirus 6 DNA in peripheral blood mononuclear cells from multiple sclerosis patients.  Ann Neurol . 1998;  44 391-394
• 146 Merille E, Bedin R, Sola P. Human herpes virus 6 and human herpes virus 8 DNA sequences in brains of multiple sclerosis patients, normal adults and children.  J Neurol . 1997;  244 450-454
• 147 Martin C, Enbom M, Soderstrom M. Absence of seven human herpesviruses, including HHV-6, by polymerase chain reaction in CSF and blood from patients with multiple sclerosis and optic neuritis.  Acta Neurol Scand . 1997;  95 280-283
• 148 Nielsen L, Lasen A, Munk M. Human herpesvirus-6 immunoglobulin G antibodies in patients with multiple sclerosis.  Acta Neurol Scand Suppl . 1997;  169 76-78
• 149 Soldan S, Berti R, Secchiero P. Association of human herpes virus 6 (HHV-6) with multiple sclerosis: increased IgM response to HHV-6 early antigen and detection of serum HHV-6 DNA.  Nat Med . 1997;  3 1394-1397
• 150 Challoner P, Smith K, Parker J. Plaque-associated expression of human herpesvirus 6 in multiple sclerosis.  Proc Natl Acad Sci U S A . 1995;  92 7440-7444
• 151 Sanders V J, Felisan S, Waddell A. Detection of herpesviridae in postmortem multiple sclerosis brain tissue and controls by polymerase chain reaction.  J Neurovirol . 1996;  2 249-258
• 152 Mock D, Powers C, Goodman A. Association of human herpesvirus 6 with the demyelinative lesions of progressive multifocal leukoencephalopathy.  J Neurovirol . 1999;  5 363-373
• 153 Merelli E, Sola P, Barozzi P, Torelli G. An encephalitic episode in a multiple sclerosis patient with human herpesvirus 6 latent infection.  J Neurol Sci . 1996;  137 42-46
• 154 Carrigan D, Harrington D, Knox K. Subacute leukoencephalitis caused by CNS infection with human herpesvirus-6 manifesting as acute multiple sclerosis.  Neurology . 1996;  47 145-148
• 155 Novoa L, Nagra R, Nakwatase T. Fulminant demyelinating encephalomyelitis associated with productive HHV-6 infection in an immunocompetent adult.  J Med Virol . 1997;  52 301-308
• 156 Liedke W, Malessa R, Faustmann P. Human herpesvirus 6 polymerase chain reaction findings in human immunodeficiency virus associated neurological disease and multiple sclerosis.  J Neurovirol . 1995;  1 253-258
• 157 Rotola A, Cassai E, Tola M. Human herpesvirus 6 is latent in peripheral blood of patients with relapsing-remitting multiple sclerosis.  J Neurol Neurosurg Psychiatry . 1999;  67 529-531
• 158 Monteyne P, Bureau J, Brahic M. Viruses and multiple sclerosis.  Curr Opin Neurol . 1998;  11 287-291
• 159 Johnson R T. Virology of demyelinating diseases.  Ann Neurol . 1994;  36 S54-S60
• 160 Blumberg B, Mock D, Powers J. The HHV-6 paradox: ubiquitous commensal or insidious pathogen?.  <~>A two step in situ PCR approach. J Clin Virol . 2000;  16 159-178