Subscribe to RSS
DOI: 10.1055/s-0030-1255216
Central Nervous System Infections in Cancer Patients
Publication History
Publication Date:
24 June 2010 (online)
ABSTRACT
With improved treatments, patients with many types of cancer survive longer. However, both the acute adverse effects of more intensive therapies and the risks of chronic immunosuppression have led to a diverse and evolving spectrum of central nervous system (CNS) infections. The presentation and course of CNS infections in cancer patients may be different from those in patients without cancer, complicating and delaying accurate diagnosis. New syndromes related both to the underlying malignancies and to their treatment continue to emerge. Noninfectious disorders such as adverse drug effects, vascular lesions, and radiation effects can mimic CNS infections. The two major clinical presentations of CNS infections are meningoencephalitic syndromes and focal deficits due to mass lesions. The range of pathogens can be narrowed by considering the type of immune deficit present, local nosocomial trends, and the specific vulnerabilities created by the underlying disease and treatment regimen. Patients undergoing neurosurgical procedures and those receiving hematopoietic cell transplants (HCT) account for the majority of cancer patients with CNS infections. Significant recent changes reviewed here include evolving patterns of bacterial meningitis, current treatment recommendations for fungal infections, special infectious risks associated with immunomodulatory therapies, and neuroimaging techniques to distinguish infection from other intracranial processes.
KEYWORDS
Opportunistic infections - encephalitis - meningitis - brain abscess - fungal infections
REFERENCES
- 1 Tan K, Patel S, Gandhi N, Chow F, Rumbaugh J, Nath A. Burden of neuroinfectious diseases on the neurology service in a tertiary care center. Neurology. 2008; 71(15) 1160-1166
- 2 Safdieh J E, Mead P A, Sepkowitz K A, Kiehn T E, Abrey L E. Bacterial and fungal meningitis in patients with cancer. Neurology. 2008; 70(12) 943-947
- 3 Carson K R, Focosi D, Major E O et al.. Monoclonal antibody-associated progressive multifocal leucoencephalopathy in patients treated with rituximab, natalizumab and efalizumab: A review from the Research on Adverse Drug Events and Reports (RADAR) Project. Lancet Oncol. 2009; 10 816-824
- 4 Maschmeyer G, Patterson T F. New immunosuppressive agents and risk for invasive fungal infections. Curr Infect Dis Rep. 2009; 11(6) 435-438
- 5 Pruitt A A. Nervous system infections in patients with cancer. Neurol Clin. 2003; 21 193-219
- 6 Denier C, Bourhis J H, Lacroix C et al.. Spectrum and prognosis of neurologic complications after hematopoietic transplantation. Neurology. 2006; 67(11) 1990-1997
- 7 Taal W, Brandsma D, de Bruin H G et al.. Incidence of early pseudo-progression in a cohort of malignant glioma patients treated with chemoirradiation with temozolomide. Cancer. 2008; 113(2) 405-410
- 8 Olin J L, Gugliotta J L. Possible valacyclovir-related neurotoxicity and aseptic meningitis. Ann Pharmacother. 2003; 37(12) 1814-1817
- 9 Sekul E A, Cupler E J, Dalakas M C. Aseptic meningitis associated with high-dose intravenous immunoglobulin therapy: frequency and risk factors. Ann Intern Med. 1994; 121(4) 259-262
- 10 Creel G B, Hurtt M. Cephalosporin-induced recurrent aseptic meningitis. Ann Neurol. 1995; 37(6) 815-817
- 11 Quan D, Hackney D B, Pruitt A A, Lenkinski R E, Cecil K M. Transient MRI enhancement in a patient with seizures and previously resected glioma: use of MRS. Neurology. 1999; 53(1) 211-213
- 12 De Marcaida J A, Reik Jr L. Disorders that mimic central nervous system infections. Neurol Clin. 1999; 17(4) 901-941
- 13 Nettis E, Calogiuri G, Colanardi M C, Ferrannini A, Tursi A. Drug-induced aseptic meningitis. Curr Drug Targets Immune Endocr Metabol Disord. 2003; 3(2) 143-149
- 14 Nadal Desbarats L, Herlidou S, de Marco G et al.. Differential MRI diagnosis between brain abscesses and necrotic or cystic brain tumors using the apparent diffusion coefficient and normalized diffusion-weighted images. Magn Reson Imaging. 2003; 21(6) 645-650
- 15 Omuro A M, Leite C C, Mokhtari K, Delattre J Y. Pitfalls in the diagnosis of brain tumours. Lancet Neurol. 2006; 5(11) 937-948
- 16 Camacho D L, Smith J K, Castillo M I. Differentiation of toxoplasmosis and lymphoma in AIDS patients by using apparent diffusion coefficients. AJNR Am J Neuroradiol. 2003; 24(4) 633-637
- 17 Schroeder P C, Post M J, Oschatz E et al.. Analysis of the utility of diffusion-weighted MRI and ADC values in distinguishing central nervous system toxoplasmosis from lymphoma. Neuroradiology. 2006; 48 715-720
- 18 Hong J T, Son B C, Sung J H et al.. Significance of diffusion-weighted imaging and apparent diffusion coefficient maps for the evaluation of pyogenic ventriculitis. Clin Neurol Neurosurg. 2008; 110(2) 137-144
- 19 Gaviani P, Schwartz R B, Hedley-Whyte E T et al.. Diffusion-weighted imaging of fungal cerebral infection. AJNR Am J Neuroradiol. 2005; 26(5) 1115-1121
- 20 Charlot M, Pialat J B, Obadia N et al.. Diffusion-weighted imaging in brain aspergillosis. Eur J Neurol. 2007; 14(8) 912-916
- 21 Morais L T, Zanardi VdeA, Faria A V. Magnetic resonance spectroscopy in the diagnosis and etiological definition of brain bacterial abscesses. Arq Neuropsiquiatr. 2007; 65(4B, 4-B) 1144-1148
- 22 Carrera E, Claassen J, Oddo M, Emerson R G, Mayer S A, Hirsch L J. Continuous electroencephalographic monitoring in critically ill patients with central nervous system infections. Arch Neurol. 2008; 65(12) 1612-1618
- 23 Sommers L M, Hawkins D S. Meningitis in pediatric cancer patients: a review of forty cases from a single institution. Pediatr Infect Dis J. 1999; 18(10) 902-907
- 24 van de Beek D, de Gans J, Tunkel A R, Wijdicks E FM. Community-acquired bacterial meningitis in adults. N Engl J Med. 2006; 354(1) 44-53
- 25 Kranick S M, Vinnard C, Kolson D L. Propionibacterium acnes brain abscess appearing 10 years after neurosurgery. Arch Neurol. 2009; 66(6) 793-795
- 26 Korinek A M, Baugnon T, Golmard J L, van Effenterre R, Coriat P, Puybasset L. Risk factors for adult nosocomial meningitis after craniotomy: role of antibiotic prophylaxis. Neurosurgery. 2006; 59(1) 126-133 discussion 126-133
- 27 van de Beek D, Drake J M, Tunkel A R. Nosocomial bacterial meningitis. N Engl J Med. 2010; 362(2) 146-154
- 28 Conen A, Walti L N, Merlo A, Fluckiger U, Battegay M, Trampuz A. Characteristics and treatment outcome of cerebrospinal fluid shunt-associated infections in adults: a retrospective analysis over an 11-year period. Clin Infect Dis. 2008; 47(1) 73-82
- 29 Muttaiyah S, Ritchie S, Upton A, Roberts S. Clinical parameters do not predict infection in patients with external ventricular drains: a retrospective observational study of daily cerebrospinal fluid analysis. J Med Microbiol. 2008; 57(Pt 2) 207-209
- 30 Zarrouk V, Vassor I, Bert F et al.. Evaluation of the management of postoperative aseptic meningitis. Clin Infect Dis. 2007; 44(12) 1555-1559
- 31 McGovern P C, Lautenbach E, Brennan P J, Lustig R A, Fishman N O. Risk factors for postcraniotomy surgical site infection after 1,3-bis (2-chloroethyl)-1-nitrosourea (Gliadel) wafer placement. Clin Infect Dis. 2003; 36(6) 759-765
- 32 Schaller B, Baumann A. Headache after removal of vestibular schwannoma via the retrosigmoid approach: a long-term follow-up-study. Otolaryngol Head Neck Surg. 2003; 128(3) 387-395
- 33 Riel-Romero R M, Baumann R J. Herpes simplex encephalitis and radiotherapy. Pediatr Neurol. 2003; 29(1) 69-71
- 34 Silvano G, Lazzari G, Resta F, Buccoliero G, Pezzella G, Pisconti S. A herpes simplex virus-1 fatal encephalitis following chemo-radiotherapy, steroids and prophylactic cranial irradiation in a small cell lung cancer patient. Lung Cancer. 2007; 57(2) 243-246
- 35 Kocher M, Kunze S, Eich H T, Semrau R, Müller R P. Efficacy and toxicity of postoperative temozolomide radiochemotherapy in malignant glioma. Strahlenther Onkol. 2005; 181(3) 157-163
- 36 Suzuki H I, Hangaishi A, Hosoya N et al.. Herpes simplex encephalitis and subsequent cytomegalovirus encephalitis after chemoradiotherapy for central nervous system lymphoma: a case report and literature review. Int J Hematol. 2008; 87(5) 538-541
- 37 Klein N C, Go C H, Cunha B A. Infections associated with steroid use. Infect Dis Clin North Am. 2001; 15(2) 423-432, viii
-
38 Kesari S, Paleologos N A, Vick N A.
Corticosteroids in neuro-oncology . In: Schiff D Kesari S Wen PY, et al Cancer Neurology in Clinical Practice. Totowa NJ; Humana Press 2008: 47-56 - 39 Pruitt A A. Treatment of medical complications in patients with brain tumors. Curr Treat Options Neurol. 2005; 7 323-336
- 40 Link K, Orenstein R. Bacterial complications of strongyloidiasis: Streptococcus bovis meningitis. South Med J. 1999; 92(7) 728-731
-
41 Shaz B H.
Transfusion transmitted diseases . In: Hilyer CD, Shza BH, Zimring JG, Abshire TC Transfusion Medicine and Hemostasis: Clinical and Laboratory Aspects. New York; Elsevier 2009: 361-371 - 42 Walker M, Zunt J R. Parasitic central nervous system infections in immunocompromised hosts. Clin Infect Dis. 2005; 40(7) 1005-1015
- 43 Tyler K L. Emerging viral infections of the central nervous system: part 1. Arch Neurol. 2009; 66(8) 939-948, 1065–1074
- 44 Iwamoto M, Jernigan D B, Guasch A M West Nile Virus in Transplant Recipients Investigation Team et al. Transmission of West Nile virus from an organ donor to four transplant recipients. N Engl J Med. 2003; 348(22) 2196-2203
- 45 Fischer S A, Graham M B, Kuehnert M J LCMV in Transplant Recipients Investigation Team et al. Transmission of lymphocytic choriomeningitis virus by organ transplantation. N Engl J Med. 2006; 354(21) 2235-2249
- 46 Burton E C, Burns D K, Opatowsky M J et al.. Rabies encephalomyelitis: clinical, neuroradiological, and pathological findings in 4 transplant recipients. Arch Neurol. 2005; 62(6) 873-882
- 47 García-Suárez J, de Miguel D, Krsnik I, Bañas H, Arribas I, Burgaleta C. Changes in the natural history of progressive multifocal leukoencephalopathy in HIV-negative lymphoproliferative disorders: impact of novel therapies. Am J Hematol. 2005; 80(4) 271-281
- 48 Carson K R, Focosi D, Major E O et al.. Monoclonal antibody-associated progressive multifocal leucoencephalopathy in patients treated with rituximab, natalizumab, and efalizumab: a review from the Research on Adverse Drug Events and Reports (RADAR) Project. Lancet Oncol. 2009; 10 816-824
- 49 Carson K R, Evens A M, Richey E A et al.. Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project. Blood. 2009; 113(20) 4834-4840
- 50 Strangfeld A, Listing J, Herzer P et al.. Risk of herpes zoster in patients with rheumatoid arthritis treated with anti-TNF-alpha agents. JAMA. 2009; 301(7) 737-744
- 51 van der Klooster J M, Bosman R J, Oudemans-van Straaten H M, van der Spoel J I, Wester J P, Zandstra D F. Disseminated tuberculosis, pulmonary aspergillosis and cutaneous herpes simplex infection in a patient with infliximab and methotrexate. Intensive Care Med. 2003; 29(12) 2327-2329
- 52 Peleg A Y, Husain S, Kwak E J et al.. Opportunistic infections in 547 organ transplant recipients receiving alemtuzumab, a humanized monoclonal CD-52 antibody. Clin Infect Dis. 2007; 44(2) 204-212
- 53 Avivi I, Chakrabarti S, Kottaridis P et al.. Neurological complications following alemtuzumab-based reduced-intensity allogeneic transplantation. Bone Marrow Transplant. 2004; 34(2) 137-142
- 54 Safdar N, Smith J, Knasinski V et al.. Infections after the use of alemtuzumab in solid organ transplant recipients: a comparative study. Diagn Microbiol Infect Dis. 2010; 66(1) 7-15
- 55 Safdar A, Papadopoulous E B, Armstrong D. Listeriosis in recipients of allogeneic blood and marrow transplantation: thirteen year review of disease characteristics, treatment outcomes and a new association with human cytomegalovirus infection. Bone Marrow Transplant. 2002; 29(11) 913-916
- 56 Nguyen M T, Virk I Y, Chew L, Villano J L. Extended use dexamethasone-associated posterior reversible encephalopathy syndrome with cisplatin-based chemotherapy. J Clin Neurosci. 2009; 16 1688-1690
- 57 Gocmen R, Ozgen B, Oguz K K. Widening the spectrum of PRES: series from a tertiary care center. Eur J Radiol. 2007; 62(3) 454-459
- 58 Bhatt A, Farooq M U, Majid A, Kassab M. Chemotherapy-related posterior reversible leukoencephalopathy syndrome. Nat Clin Pract Neurol. 2009; 5(3) 163-169
- 59 Kozak O S, Wijdicks E F, Manno E M, Miley J T, Rabinstein A A. Status epilepticus as initial manifestation of posterior reversible encephalopathy syndrome. Neurology. 2007; 69(9) 894-897
- 60 Hefzy H M, Bartynski W S, Boardman J F, Lacomis D. Hemorrhage in posterior reversible encephalopathy syndrome: imaging and clinical features. AJNR Am J Neuroradiol. 2009; 30(7) 1371-1379
- 61 McKinney A M, Short J, Truwit C L et al.. Posterior reversible encephalopathy syndrome: incidence of atypical regions of involvement and imaging findings. AJR Am J Roentgenol. 2007; 189(4) 904-912
- 62 Batts E D, Lazarus H M. Diagnosis and treatment of transplantation-associated thrombotic microangiopathy: real progress or are we still waiting?. Bone Marrow Transplant. 2007; 40(8) 709-719
- 63 Shelburne S A, Visnegarwala F, D' Arcourt J et al.. Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy. AIDS. 2005; 19 399-406
- 64 Makela P, Howe L, Glover S et al.. Recurrent Guillain-Barré syndrome as a complication of immune reconstitution in HIV. J Infect. 2002; 44 47-49
- 65 Airas L, Paivarinta M, Roytta M et al.. Central nervous system immune reconstitution inflammatory syndrome (IRIS) after hematopoietic SCT. Bone Marrow Transplant. 2010; 45(3) 593-596
- 66 Ingram P R, Howman R, Leahy M F, Dyer J R. Cryptococcal immune reconstitution inflammatory syndrome following alemtuzumab therapy. Clin Infect Dis. 2007; 44(12) e115-e117
- 67 Thursky K A, Worth L J, Seymour J F, Miles Prince H, Slavin M A. Spectrum of infection, risk and recommendations for prophylaxis and screening among patients with lymphoproliferative disorders treated with alemtuzumab*. Br J Haematol. 2006; 132(1) 3-12
- 68 Singh N, Lortholary O, Alexander B D Cryptococcal Collaborative Transplant Study Group et al. An immune reconstitution syndrome-like illness associated with Cryptococcus neoformans infection in organ transplant recipients. Clin Infect Dis. 2005; 40(12) 1756-1761
- 69 McCombe J A, Auer R N, Maingat F G, Houston S, Gill M J, Power C. Neurologic immune reconstitution inflammatory syndrome in HIV/AIDS: outcome and epidemiology. Neurology. 2009; 72(9) 835-841
- 70 Cesaro S, Boaro M P, Pillon M et al.. Immune reconstitution complicated by CMV retinitis in a pediatric patient who underwent haploidentical CD34 + -selected hematopoietic stem cell transplant for acute lymphoblastic leukemia. Int J Hematol. 2008; 88(2) 145-148
- 71 Otiti-Sengeri J, Meenken C, van den Horn G J, Kempen J H. Ocular immune reconstitution inflammatory syndromes. Curr Opin HIV AIDS. 2008; 3(4) 432-437
- 72 Tan K, Roda R, Ostrow L, McArthur J, Nath A. PML-IRIS in patients with HIV infection: clinical manifestations and treatment with steroids. Neurology. 2009; 72(17) 1458-1464
- 73 Cabellos C, Viladrich P F, Corredoira J, Verdaguer R, Ariza J, Gudiol F. Streptococcal meningitis in adult patients: current epidemiology and clinical spectrum. Clin Infect Dis. 1999; 28(5) 1104-1108
- 74 Gillespie I A, McLauchlin J, Little C L et al.. Disease presentation in relation to infection foci for non-pregnancy-associated human listeriosis in England and Wales, 2001 to 2007. J Clin Microbiol. 2009; 47(10) 3301-3307
- 75 van de Beek D, de Gans J, McIntyre P, Prasad K. Steroids in adults with acute bacterial meningitis: a systematic review. Lancet Infect Dis. 2004; 4(3) 139-143
- 76 Van de Beek D, Farrar J J, de Gans J et al.. Adjunctive dexamethasone in bacterial meningitis: a meta-analysis of individual patient data. Lancet Neurol. 2010; 9(3) 254-263
- 77 McIntyre P. Adjunctive dexamethasone in meningitis: does value depend on clinical setting?. Lancet Neurol. 2010; 9(3) 229-231
- 78 Weathers A L, Lewis S L. Rare and unusual... or are they? Less commonly diagnosed encephalopathies associated with systemic disease. Semin Neurol. 2009; 29(2) 136-153
- 79 Zetola N, Francis J S, Nuermberger E L, Bishai W R. Community-acquired methicillin-resistant Staphylococcus aureus: an emerging threat. Lancet Infect Dis. 2005; 5(5) 275-286
- 80 Kessler A T, Kourtis A P. Treatment of meningitis caused by methicillin-resistant Staphylococcus aureus with linezolid. Infection. 2007; 35(4) 271-274
- 81 Nudelman Y, Tunkel A R. Bacterial meningitis: epidemiology, pathogenesis and management update. Drugs. 2009; 69(18) 2577-2596
- 82 Schut E S, Brouwer M C, de Gans J, Florquin S, Troost D, van de Beek D. Delayed cerebral thrombosis after initial good recovery from pneumococcal meningitis. Neurology. 2009; 73(23) 1988-1995
- 83 Palacio S, Hart R G, Vollmer D G, Kagan-Hallet K. Late-developing cerebral arteropathy after pyogenic meningitis. Arch Neurol. 2003; 60(3) 431-433
- 84 Steiner I. Past as prologue: delayed stroke as a parainfectious process of bacterial meningitis?. Neurology. 2009; 73(23) 1945-1946
- 85 Ko S B, Bae H J, Park S H. Multiple punctate intracerebral hemorrhages in acute leukemia with Escherichia coli sepsis. Arch Neurol. 2008; 65(8) 1128-1129
- 86 Mattiuzzi G, Giles F J. Management of intracranial fungal infections in patients with haematological malignancies. Br J Haematol. 2005; 131(3) 287-300
- 87 Labbé A C, Su S H, Laverdière M et al.. High incidence of invasive aspergillosis associated with intestinal graft-versus-host disease following nonmyeloablative transplantation. Biol Blood Marrow Transplant. 2007; 13(10) 1192-1200
- 88 Thursky K A, Worth L J, Seymour J F, Miles Prince H, Slavin M A. Spectrum of infection, risk and recommendations for prophylaxis and screening among patients with lymphoproliferative disorders treated with alemtuzumab*. Br J Haematol. 2006; 132(1) 3-12
- 89 Maertens J, Theunissen K, Verhoef G et al.. Galactomannan and computed tomography-based preemptive antifungal therapy in neutropenic patients at high risk for invasive fungal infection: a prospective feasibility study. Clin Infect Dis. 2005; 41(9) 1242-1250
- 90 Odabasi Z, Mattiuzzi G, Estey E et al.. Beta-D-glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome. Clin Infect Dis. 2004; 39(2) 199-205
- 91 Seton M, Pless M, Fishman J A, Caruso P A, Hedley-Whyte E T. Case records of the Massachusetts General Hospital. Case 18-2008. A 68-year-old man with headache and visual changes after liver transplantation. N Engl J Med. 2008; 358(24) 2619-2628
- 92 Schwartz S, Ruhnke M, Ribaud P, Reed E, Troke P, Thiel E. Poor efficacy of amphotericin B-based therapy in CNS aspergillosis. Mycoses. 2007; 50(3) 196-200
- 93 DeLone D R, Goldstein R A, Petermann G et al.. Disseminated aspergillosis involving the brain: distribution and imaging characteristics. AJNR Am J Neuroradiol. 1999; 20(9) 1597-1604
- 94 Rüping M JGT, Vehreschild J J, Cornely O A. Patients at high risk of invasive fungal infections: when and how to treat. Drugs. 2008; 68(14) 1941-1962
- 95 Verduyn Lunel F M, Voss A, Kuijper E J et al.. Detection of the Candida antigen mannan in cerebrospinal fluid specimens from patients suspected of having Candida meningitis. J Clin Microbiol. 2004; 42(2) 867-870
- 96 Rex J H, Larsen R A, Dismukes W E, Cloud G A, Bennett J E. Catastrophic visual loss due to Cryptococcus neoformans meningitis. Medicine (Baltimore). 1993; 72(4) 207-224
- 97 Liu K H, Wu C J, Chou C H et al.. Refractory candidal meningitis in an immunocompromised patient cured by caspofungin. J Clin Microbiol. 2004; 42(12) 5950-5953
- 98 Barchiesi F, Spreghini E, Schimizzi A M et al.. Posaconazole and amphotericin B combination therapy against Cryptococcus neoformans infection. Antimicrob Agents Chemother. 2004; 48(9) 3312-3316
- 99 Schmidt-Hieber M, Zweigner J, Uharek L, Blau I W, Thiel E. Central nervous system infections in immunocompromised patients: update on diagnostics and therapy. Leuk Lymphoma. 2009; 50(1) 24-36
- 100 Pagano L, Offidani M, Fianchi L GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) Infection Program et al. Mucormycosis in hematologic patients. Haematologica. 2004; 89(2) 207-214
- 101 Vickrey E, Allen S, Mehta J, Singhal S. Acyclovir to prevent reactivation of Varicella zoster virus (herpes zoster) in multiple myeloma patients receiving bortezomib therapy. Cancer. 2009; 115(1) 229-232
- 102 Chanan-Khan A, Sonneveld P, Schuster M W et al.. Analysis of herpes zoster events among bortezomib-treated patients in the phase III APEX study. J Clin Oncol. 2008; 26(29) 4784-4790
- 103 Nagel M A, Gilden D H. The protean neurologic manifestations of Varicella-zoster virus infection. Cleve Clin J Med. 2007; 74(7) 489-494 496 498-499 passim
- 104 Nakamoto B K, Dorotheo E U, Biousse V, Tang R A, Schiffman J S, Newman N J. Progressive outer retinal necrosis presenting with isolated optic neuropathy. Neurology. 2004; 63(12) 2423-2425
- 105 Gilden D, Cohrs R J, Mahalingam R, Nagel M A. Varicella zoster virus vasculopathies: diverse clinical manifestations, laboratory features, pathogenesis, and treatment. Lancet Neurol. 2009; 8(8) 731-740
- 106 Asahi T, Tsutsui M, Wakasugi M et al.. Valacyclovir neurotoxicity: clinical experience and review of the literature. Eur J Neurol. 2009; 16(4) 457-460
- 107 Quan D, Hammack B N, Kittelson J, Gilden D H. Improvement of postherpetic neuralgia after treatment with intravenous acyclovir followed by oral valacyclovir. Arch Neurol. 2006; 63(7) 940-942
- 108 Tunkel A R, Glaser C A, Bloch K C Infectious Diseases Society of America et al. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2008; 47(3) 303-327
- 109 Koralnik I J, Wüthrich C, Dang X et al.. JC virus granule cell neuronopathy: A novel clinical syndrome distinct from progressive multifocal leukoencephalopathy. Ann Neurol. 2005; 57(4) 576-580
- 110 Wüthrich C, Dang X, Westmoreland S et al.. Fulminant JC virus encephalopathy with productive infection of cortical pyramidal neurons. Ann Neurol. 2009; 65(6) 742-748
- 111 Tan K, Roda R, Ostrow L, McArthur J, Nath A. PML-IRIS in patients with HIV infection: clinical manifestations and treatment with steroids. Neurology. 2009; 72(17) 1458-1464
- 112 Sheikh S I, Stemmer-Rachamimov A, Attar E C. Autopsy diagnosis of progressive multifocal leukoencephalopathy with JC virus-negative CSF after cord blood stem-cell transplantation. J Clin Oncol. 2009; 27(23) e46-e47
- 113 Lima M A, Marzocchetti A, Autissier P et al.. Frequency and phenotype of JC virus-specific CD8 + T lymphocytes in the peripheral blood of patients with progressive multifocal leukoencephalopathy. J Virol. 2007; 81(7) 3361-3368
- 114 Marzocchetti A, Tompkins T, Clifford D B et al.. Determinants of survival in progressive multifocal leukoencephalopathy. Neurology. 2009; 73(19) 1551-1558
- 115 Vendrely A, Bienvenu B, Gasnault J, Thiebault J B, Salmon D, Gray F. Fulminant inflammatory leukoencephalopathy associated with HAART-induced immune restoration in AIDS-related progressive multifocal leukoencephalopathy. Acta Neuropathol. 2005; 109(4) 449-455
- 116 Buckanovich R J, Liu G, Stricker C et al.. Nonmyeloablative allogeneic stem cell transplantation for refractory Hodgkin's lymphoma complicated by interleukin-2 responsive progressive multifocal leukoencephalopathy. Ann Hematol. 2002; 81(7) 410-413
- 117 Przepiorka D, Jaeckle K A, Birdwell R R et al.. Successful treatment of progressive multifocal leukoencephalopathy with low-dose interleukin-2. Bone Marrow Transplant. 1997; 20(11) 983-987
- 118 Aksamit A J. Progressive multifocal leukoencephalopathy. Curr Treat Options Neurol. 2008; 10(3) 178-185
- 119 Brickelmaier M, Lugovskoy A, Kartikeyan R et al.. Identification and characterization of mefloquine efficacy against JC virus in vitro. Antimicrob Agents Chemother. 2009; 53(5) 1840-1849
- 120 Elphick G F, Querbes W, Jordan J A et al.. The human polyomavirus, JCV, uses serotonin receptors to infect cells. Science. 2004; 306(5700) 1380-1383
- 121 Verma S, Cikurel K, Koralnik I J et al.. Mirtazapine in progressive multifocal leukoencephalopathy associated with polycythemia vera. J Infect Dis. 2007; 196(5) 709-711
- 122 Pruitt A A. Central nervous system infections in cancer patients. Semin Neurol. 2004; 24 435-452
Amy A PruittM.D.
Department of Neurology, University of Pennsylvania, 3400 Spruce Street, Philadelphia
PA 10104
Email: pruitt@mail.med.upenn.edu