title: Spinal Arachnoiditis as a Complication of Cryptococcal Meningoencephalitis in Non-HIV Previously Healthy Adults.
abstract: BACKGROUND
  Cryptococcus can cause meningoencephalitis (CM) among previously healthy non-HIV adults. Spinal arachnoiditis is under-recognized, since diagnosis is difficult with concomitant central nervous system (CNS) pathology.
  
  
  METHODS
  We describe 6 cases of spinal arachnoiditis among 26 consecutively recruited CM patients with normal CD4 counts who achieved microbiologic control. We performed detailed neurological exams, cerebrospinal fluid (CSF) immunophenotyping and biomarker analysis before and after adjunctive immunomodulatory intervention with high dose pulse corticosteroids, affording causal inference into pathophysiology.
  
  
  RESULTS
  All 6 exhibited severe lower motor neuron involvement in addition to cognitive changes and gait disturbances from meningoencephalitis. Spinal involvement was associated with asymmetric weakness and urinary retention. Diagnostic specificity was improved by MRI imaging which demonstrated lumbar spinal nerve root enhancement and clumping or lesions. Despite negative fungal cultures, CSF inflammatory biomarkers, sCD27 and sCD21, as well as the neuronal damage biomarker, neurofilament light chain (NFL), were elevated compared to healthy donor (HD) controls. Elevations in these biomarkers were associated with clinical symptoms and showed improvement with adjunctive high dose pulse corticosteroids.
  
  
  CONCLUSIONS
  These data suggest that a post-infectious spinal arachnoiditis is an important complication of CM in previously healthy individuals, requiring heightened clinician awareness. Despite microbiological control, this syndrome causes significant pathology likely due to increased inflammation and may be amenable to suppressive therapeutics.
authors.affiliation: Laboratory of Clinical Infectious Diseases (LCID), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda,Maryland; anil.panackal@nih.gov.|Division of Infectious Diseases, Department of Medicine, F. Hebert School of Medicine, Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland.
authors.forename: Anil A
authors.initials: AA
authors.lastname: Panackal
authors.affiliation: Neuroimmunological Diseases Unit, Neuroimmunology Branch, National Institute of Neurological Diseases and Stroke (NINDS), NIH, Bethesda, Maryland.
authors.forename: Mika
authors.initials: M
authors.lastname: Komori
authors.affiliation: Neuroimmunological Diseases Unit, Neuroimmunology Branch, National Institute of Neurological Diseases and Stroke (NINDS), NIH, Bethesda, Maryland.
authors.forename: Peter
authors.initials: P
authors.lastname: Kosa
authors.affiliation: Neurology Consult Service, NINDS, NIH, Bethesda, Maryland.
authors.forename: Omar
authors.initials: O
authors.lastname: Khan
authors.affiliation: Center for Infectious Disease Imaging, Radiology and Imaging Sciences, NIH Clinical Center, Bethesda, Maryland.
authors.forename: Dima A
authors.initials: DA
authors.lastname: Hammoud
authors.affiliation: Laboratory of Clinical Infectious Diseases (LCID), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda,Maryland.
authors.forename: Lindsey B
authors.initials: LB
authors.lastname: Rosen
authors.affiliation: Laboratory of Clinical Infectious Diseases (LCID), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda,Maryland.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Browne
authors.affiliation: Neuroimmunological Diseases Unit, Neuroimmunology Branch, National Institute of Neurological Diseases and Stroke (NINDS), NIH, Bethesda, Maryland.
authors.forename: Yen-Chih
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Neuroimmunological Diseases Unit, Neuroimmunology Branch, National Institute of Neurological Diseases and Stroke (NINDS), NIH, Bethesda, Maryland.
authors.forename: Elena
authors.initials: E
authors.lastname: Romm
authors.affiliation: Infectious Diseases, Kaiser San Jose Medical Center, San Jose, California.
authors.forename: Charu
authors.initials: C
authors.lastname: Ramaprasad
authors.affiliation: Division of Infectious Diseases, Stony Brook University, Stony Brook, New York.
authors.forename: Bettina C
authors.initials: BC
authors.lastname: Fries
authors.affiliation: Laboratory of Clinical Infectious Diseases (LCID), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda,Maryland.|Division of Infectious Diseases, Department of Medicine, F. Hebert School of Medicine, Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland.
authors.forename: John E
authors.initials: JE
authors.lastname: Bennett
authors.affiliation: Neuroimmunological Diseases Unit, Neuroimmunology Branch, National Institute of Neurological Diseases and Stroke (NINDS), NIH, Bethesda, Maryland.
authors.forename: Bibiana
authors.initials: B
authors.lastname: Bielekova
authors.affiliation: Laboratory of Clinical Infectious Diseases (LCID), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda,Maryland.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Williamson
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001100:Arachnoiditis / Q000151:congenital* / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016516:CD4-CD8 Ratio; D003454:Cryptococcus; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000069544:Infectious Encephalitis / Q000134:cerebrospinal fluid / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D018810:Magnetic Resonance Angiography; D008297:Male; D016919:Meningitis, Cryptococcal / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D008590:Meningoencephalitis / Q000134:cerebrospinal fluid / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D008727:Methotrexate / Q000627:therapeutic use; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D009460:Neurologic Examination; D020551:Pulse Therapy, Drug; D016559:Tacrolimus / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D007166:Immunosuppressive Agents; D016559:Tacrolimus; D008775:Methylprednisolone; D008727:Methotrexate
keywords: 
  Cryptococcus
  ; cauda equina/conus syndromes; meningoencephalitis; pulse corticosteroids.; spinal arachnoiditis