Disclosures I have no disclosures. CNS INFECTIONS: PEARLS AND - PDF document

3/12/2019 Disclosures • I have no disclosures. CNS INFECTIONS: PEARLS AND PERILS Felicia Chow, MD, MAS Assistant Professor University of California, San Francisco March 28, 2019 https://www.intechopen.com/books/novel-aspects-on-cysticercosis-and- neurocysticercosis/epilepsy-and-neurocysticercosis-in-sub-saharan-africa Learning objectives • Recognize the clinical presentation of common neuroinfectious diseases • Identify pitfalls of diagnostic testing in the evaluation and management of common neuroinfectious diseases • Be familiar with treatment strategies for common Photo credit: succeedonline.asu.edu neuroinfectious diseases BREAD AND BUTTER 1

3/12/2019 Case One Case One • 52 year-old woman presents with 2 days of fever, headache and confusion; her daughter who is home for winter break brings her to the ED • Exam: T 39.2 C, decreased level of arousal and poor attention • CSF with 11 WBC (65%L, 15%M), 680 RBC, protein 85 and glucose 53; gram stain negative, bacterial culture negative • HSV 1/2, VZV and enterovirus PCR negative How sensitive is the CSF HSV PCR for HSV- HSV-1 encephalitis 1 encephalitis? A. Sensitive enough that I would feel comfortable discontinuing IV acyclovir based on the negative result. B. Pretty sensitive, but in this situation I would continue IV acyclovir, repeat a lumbar puncture and resend the PCR in a few days. A. Not at all sensitive. I do not use the HSV PCR to guide decisions in terms of stopping or starting IV acyclovir. 2

3/12/2019 How reliable is HSV-1 PCR from the CSF ? HSV encephalitis • HSV is the most frequently identified viral etiology of sporadic encephalitis in the US • 54 patients with biopsy- • Bimodal distribution: 1/3 cases <20 y, 2/3 >40 y proven HSE underwent • Case fatality rate >70% if untreated; 1/3 of patients may be significantly disabled despite treatment HSV-1 PCR from CSF • CSF: 5-500 WBC/mm 3 , normal to moderately elevated protein, glucose typically normal • Sensitivity 98% • Specificity 94% • Involvement on imaging of the medial temporal lobes, insula, and/or inferolateral frontal lobes • Diffusion weighted sequence (DWI) most sensitive early in disease course Lakeman et al J Infect Dis 1995 Sensitivity of CSF HSV- Treatment of HSV-1 encephalitis: Time is brain 1 PCR is lower early in the course of HSV • Earlier initiation of acyclovir associated with improved mortality encephalitis • Acyclovir 10 mg/kg every 8 hours x 14 to 21 d • No data for use of corticosteroids as adjunctive therapy • No role for oral antivirals after completion of IV therapy *In patients with a compatible clinical syndrome for HSV encephalitis and/or temporal lobe abnormalities on neuroimaging, consider repeat CSF HSV PCR in 3 to 7 days. Weil et al. Clin Infect Dis 2002 Tunkel et al Clin Infect Dis 2008 3

3/12/2019 Case Two • 42-year-old man presents to clinic with new diffuse headache and light sensitivity for 1 week • Exam is notable for a generalized macular rash and unilateral optic disc hyperemia with blurred disc margins THE BIG THREE https://bpac.org.nz/BT/2012/June/06_syphilis.aspx Case Two Neurosyphilis • RPR 1:128 • Brain MRI with a small acute infarct in right corona radiata • LP results • Normal opening pressure • WBC 23 (83% lymphocytes) • 0 RBC • Protein 95 • Glucose normal • CSF VDRL non-reactive Camarero-Temino Nephrology 2013; https://en.wikipedia.org/wiki/Neurosyphilis#/media File:Skull_damage_from_neurosyphilis.jpg https://openi.nlm.nih.gov/detailedresult.php?img=PMC3095916_SRT2011-726573.008&req=4 4

3/12/2019 No one test has high sensitivity/specificity for neurosyphilis Which syphilis patients need an LP? Test characteristics Notes SERUM Sensitivity: *Titers correspond to disease A. Any stage of syphilis + neurological signs/symptoms, 1°: 78-86% activity RPR (non- 2° : Near 100% ocular or otologic disease treponemal 3°/Latent: Varies, ~85% *Used to assess treatment tests) response  4-fold decline False positives 1-2%, usually titer <1:8 considered to be clinically A. Inappropriate serologic response (4-fold decline in RPR (autoimmune disease, IVDU, TB, significant titer) after treatment for syphilis pregnancy, endocarditis); false negatives in HIV, prozone effect SERUM Sensitive and specific for past or current *Titers do not correspond to T. pallidum infection disease activity B. Any person living with HIV with a newly positive RPR Treponemal and CD4 <350 cells/mm 3 False positives with other spirochetal *Most positive for life despite tests infections, EBV, malaria, leprosy; false treatment (TPPA, negative in HIV FTA-Abs) C. A & B CSF VDRL CSF VDRL Sensitivity : 30-80%, *CSF VDRL considered “gold (non-trep) Specificity 99% standard” for neurosyphilis D. A, B, & C *Positive CSF VDRL at any titer = CSF FTA-Abs/TPPA generally more sensitive neurosyphilis treponemal than VDRL *Negative CSF FTA-Ab essentially tests rules out neurosyphilis Ghanem Clin Infect Dis 2009 Which syphilis patients need an LP? Which syphilis patients need an LP? • Any stage of syphilis + neurological signs/symptoms • Any stage of syphilis + neurological signs/symptoms • Any stage of syphilis + ocular or otologic disease • Any stage of syphilis + ocular or otologic disease • Tertiary syphilis w/ or w/o neurological signs/symptoms • Tertiary syphilis w/ or w/o neurological signs/symptoms • Inappropriate serologic response after treatment • Inappropriate serologic response after treatment • HIV-infected patients PLUS: • HIV-infected patients PLUS: • Consider for HIV-infected patients with CD4 <350 cells/mm 3 and/or • Consider for HIV-infected patients with CD4 <350 cells/mm 3 and/or RPR ≥ 1:32 RPR ≥ 1:32  Thorough neurologic history and exam Ghanem Clin Infect Dis 2009 Ghanem Clin Infect Dis 2009 5

3/12/2019 Treatment of neurosyphilis Case Three • 34-year-old previously healthy man from Mexico, • Aqueous crystalline penicillin G 18–24 million units per has lived in the US for 10 years, works as a chef day, administered as 3–4 million units IV every 4 hours or continuous infusion, for 10-14 days in a restaurant, non-smoker, develops sudden onset left hand and face “twisting” followed by • Alternative treatment: Procaine penicillin 2.4 million units loss of consciousness IM once daily PLUS Probenecid 500 mg orally four times a day, both for 10-14 days • ROS negative, including no fever/chills, night sweats, or weight loss • Possible alternative treatment??? Ceftriaxone 2 g IV daily for 10-14 days (data are limited) • General and neurologic exam unremarkable Marra et al. Clin Infect Dis 2000 Case Three What is the most likely diagnosis? A. Pyogenic brain abscess B. Neurocysticercosis C. Tuberculoma D. Toxoplasmosis E. Brain metastasis 6

3/12/2019 Case Four Case Four • 28-year-old man, originally from Mexico but has lived in the US for over 15 years, with a history of a generalized seizure 5 years ago treated with divalproex, presents with headache, blurred vision, and nausea/vomiting for 1 month • ROS negative for fever/chills, night sweats, or weight loss; denies weakness or other neurologic symptoms • Afebrile on exam. Somnolent. Incomplete abduction bilaterally. Mild left-sided weakness in pyramidal pattern with associated hyperreflexia and left upgoing toe. Neurocysticercosis What is the most likely diagnosis? • Infection of the nervous A. Pyogenic brain abscess system with larval stage of the helminth, Taenia B. Neurocysticercosis solium C. Tuberculoma • 50+ million people affected worldwide D. Toxoplasmosis • One of the most E. Brain metastasis common causes of acquired epilepsy in developing world 7

3/12/2019 Stage of Number cysts Location of cysts of cysts Natural history, clinical presentation, diagnostic testing, and management of NCC https://www.who.int/news-room/fact-sheets/detail/taeniasis-cysticercosis Stages of neurocysticercosis Stages of NCC Viable cyst Degenerating cyst Dead cyst Garcia et al. Curr Opin Infect Dis 2003;16:411-419. Garcia et al. NEJM 2004 Courtesy of HH Garcia 8

3/12/2019 How good is serology for the diagnosis of NCC? Location, location, location • ELISA • Intraparenchymal (70%) • Sensitivity and specificity range from 50-80% • Cortical (>90%), deep gray matter • Sensitivity lower in patients w/ single lesions (5%), brainstem/infratentorial or calcifications (30-60%) (uncommon) • Performs better in CSF than serum • Most commonly present with seizures • Enzyme-linked immunotransfer blot (EITB) • Extraparenchymal (30%) • Sensitivity near 100% for multiple • Sylvian fissure, basal cisterns, parenchymal, ventricular, or subarachnoid intraventricular, spinal (usually cysts; specificity 100% extramedullary) • Sensitivity lower in patients w/ single lesions • Most commonly present with or calcifications (33-80%) hydrocephalus and increased • Performs as well (or better) in serum as CSF intracranial pressure • Often much more difficult to treat • Test of choice per IDSA guidelines with worse prognosis • Neither can be used to distinguish prior from • Mixed (10-30% of cases) active infection Tsang VC et al. J Infect Dis 1989, Rodriguez et al. J Infect Dis 2009, White et al. Clin Infect Dis 2018 Treatment summary Treatment summary CALCIFIED VIABLE DEGENERATING SUBARACHNOID CALCIFIED VIABLE DEGENERATING SUBARACHNOID VENTRICULAR VENTRICULAR CYSTS CYSTS CYSTS CYSTS CYSTS CYSTS CYSTS CYSTS CYSTS CYSTS No antiparasitic therapy indicated White et al. Clin Infect Dis 2018 White et al. Clin Infect Dis 2018 9