Disclosures I have no disclosures. NEUROINFECTIOUS DISEASES EVERY - PowerPoint PPT Presentation

2/14/2019 Disclosures • I have no disclosures. NEUROINFECTIOUS DISEASES EVERY CLINICIAN SHOULD KNOW Felicia Chow, MD, MAS Assistant Professor University of California, San Francisco Department of Neurology and Division of Infectious Diseases February 14, 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

2/14/2019 Case One Case One • 50-year-old woman with type 2 diabetes presents to the ED with 3 days of fever, headache, and nausea/vomiting followed by confusion. • Exam: Febrile to 103 degrees F. Somnolent, disoriented and agitated. Neck is stiff but remainder of neurologic exam unremarkable with negative Kernig’s and Brudzinski’s signs. What is the most likely diagnosis? Acute bacterial meningitis A. Bacterial meningitis B. Viral meningitis C. TB meningitis D. Fungal meningitis Photo credit: http://neuropathology-web.org/chapter5/chapter5aSuppurative.html 2

2/14/2019 Diagnostic accuracy of Kernig’s and Brudzinski’s Clinical presentation of bacterial meningitis signs for meningitis • Among 297 adults with 1. Fever (77-95%) 44-66%: Triad suspected meningitis, 100%: 1 or 2 or 3 2. Nuchal rigidity (83-88%) sensitivity of Kernig’s and 95%: at least 2 of 3. Mental status changes (69-78%) Brudzinski’s signs 5%, 4 sensitivity of nuchal rigidity 4. Headache (87%) 30% 5. Rash (11-26%) 6. Seizures (5-23%) • For those with severe 7. Focal neurological findings (28-33%) meningeal inflammation 8. Papilledema (3-4%) (WBC≥ 1000), sensitivity of Kernig’s and Brudzinski’s still poor (0 and 25%) but *Absence of fever, nuchal rigidity and altered mental status makes nuchal rigidity sensitivity acute bacterial meningitis extremely unlikely 100% Durand N Engl J Med 1993, Attia JAMA 1999, Van de Beek N Engl J Med 2004 Thomas et al. Clin Infect Dis 2002; Pictured credit https://i.pinimg.com/originals/da/4c/37/da4c37ad4ab794cce9b9c32bc2d963d0.png Differences in CSF profile in viral vs. bacterial meningitis Case One Viral Bacterial Opening pressure Normal or mildly elevated Often elevated • Lumbar puncture Color “Gin” clear Cloudy • Normal opening pressure Cells/mm 3 Mild to moderately elevated High to extremely high • Cloudy appearance (10-500 cells/mm 3 ) (100-5000+ cells/mm 3 ) • WBC 6250 cells/μL (95% polys) Differential Lymphocytes Neutrophils • Glucose 15 mg/dL • Total protein 405 mg/dL CSF:plasma glucose ratio Normal Low • Gram stain and bacterial culture pending, although LP performed Protein (mg/dL) Normal to mildly elevated Elevated (>100) 24 hours after empiric antibiotics initiated (45-100) Many exceptions to the rule! *Can see lymphocyte predominant pleocytosis in partially treated bacterial meningitis or with certain organisms (e.g., Listeria ) *Can see neutrophils early in course of many infections, including viral, TB, and fungal meningitis *Low CSF glucose is not specific to bacterial meningitis  also seen in some viral processes (e.g., herpesviruses), along with TB/fungal/parasitic infections, malignancy, sarcoid, SAH Solomon Pract Neurol 2007 3

2/14/2019 Empiric therapy for acute bacterial meningitis is host What is the yield of gram stain and culture after dependent antibiotic therapy in bacterial meningitis? Patient population Pathogens Empiric therapy • Gram stain+ 60-90% before antibiotics 2 to 50 years S. pneumoniae, N. Vancomycin + 3 rd • 90% positive with S. pneumoniae and S. aureus meningitidis generation cephalosporin • 86% positive with H. influenzae (cefotaxime or • 75% positive with N. meningitides ceftriaxone) • 50% positive with gram-negative rods Age >50 years S. pneumoniae, N. Vancomycin + 3 rd • <50% positive with L. monocytogenes meningitidis, L. generation monocytogenes, aerobic cephalosporin • Gram stain+ 40-60% post antibiotics gram-negative bacilli (cefotaxime or ceftriaxone) + ampicillin • Culture+ 70-85% BUT can sterilize quickly after Immunocompromised S. pneumoniae, N. Vancomycin + cefepime administration of antibiotics meningitidis, L. or meropenem + monocytogenes, S. aureus, ampicillin Salmonella spp., aerobic • Blood cultures 50-80% yield before antibiotics, 20% gram-negative bacilli after including P. aeruginosa La Scolea J. Clin Microbiol 1984, Bouwer Lancet 2012 Van de Beek et al. Lancet 2012 Corticosteroids in bacterial meningitis Case One • CSF gram stain with small gram negative coccobacilli • CSF and blood cultures positive for Haemophilus influenzae • Empiric therapy narrowed to IV ceftriaxone • Prolonged course complicated by hydrocephalus, *Adjunctive dexamethasone (0.15 mg/kg q6h x 4 days) recommended for adults with acute bacterial meningitis vasculitis and multifocal infarcts *Initiation before or concurrent with the first dose of antimicrobial therapy De Gans et al. N Engl J Med 2002 4

2/14/2019 Case Two Case Two • 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 What is the most likely diagnosis? HSV-1 encephalitis A. West Nile virus encephalitis B. NMDA encephalitis C. HSV-1 encephalitis D. Neurosyphilis 5

2/14/2019 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 • DWI sequence most sensitive early in disease course Lakeman et al J Infect Dis 1995 Sensitivity of CSF HSV-1 Treatment of HSV-1 encephalitis: Time is brain PCR is lower early in the • Earlier initiation of acyclovir associated with improved course of HSV 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 6

2/14/2019 Case Three What is the most likely diagnosis? • 55-year-old man with no past medical history other than A. CMV “possible meningitis” several years ago presents with 5 days of fever, chills, malaise and headache. B. HSV-2 • One day prior to presentation, developed bilateral hip and buttocks pain and paresthesias along with urinary C. EBV retention D. Enterovirus • Exam: T 101. Neurologic exam notable for decreased sensation in an S3-S5 distribution. • LP with normal opening pressure, 310 WBC (84% L), protein 91 and glucose 40. Is there any benefit of suppressive antiviral therapy to prevent HSV-2 meningitis recurrence? • Lumbosacral myeloradiculitis associated most commonly with HSV-2 reactivation, though HSV-1 increasing in frequency • IF occurs with genital herpes outbreak, onset often 5 to 7 days later • Typically present with lower back/buttocks pain, paresthesias in lumbosacral distribution and bowel/bladder symptoms; s/sx of meningitis often absent • 101 patients with HSV-2 meningitis randomized to valacyclovir • CSF profile consistent with viral meningitis 500 mg BID or placebo for 1 year after completing treatment for • MRI may be normal or may show root/lower spinal cord edema with acute meningitis enlargement, T2/FLAIR hyperintensity and contrast enhancement • Treatment: IV acyclovir 10 mg/kg q8h typically for 14 days Eberhardt et al. Neurology 2004 Aurelius et al. CID 2012 7

2/14/2019 • In Year 1, 14 cases of recurrent meningitis in valacyclovir group (29%) vs. 8 cases in placebo group (16%), p=0.12 • In Year 2, 12 cases in valacyclovir group (24%) vs. 4 in placebo (8%), p=0.03 *No role for suppressive valacyclovir to reduce risk of recurrent HSV-2 meningitis THE BIG THREE Aurelius et al. CID 2012 What is the most likely diagnosis? Case Four • 42-year-old man presents A. Rickettsial infection to clinic with new diffuse headache and light A. VZV meningitis sensitivity for 1 week B. CNS Lyme • Exam is notable for a C. Neurosyphilis generalized macular rash and unilateral optic disc hyperemia with blurred disc margins https://bpac.org.nz/BT/2012/June/06_syphilis.aspx 8