2/8/2017 Disclosures • I have no disclosures. NEUROINFECTIOUS DISEASES : PRACTICAL TIPS FOR COMMON DISORDERS Felicia Chow, MD, MAS Assistant Professor of Neurology and Medicine (ID) February 8, 2017 Learning objectives Neurosyphilis • Recognize the clinical presentation of common neuroinfectious diseases • Identify pitfalls of diagnostic testing frequently obtained in the evaluation and management of common neuroinfectious diseases • Be familiar with the approach to the treatment of common neuroinfectious diseases Camarero-Temino Nephrology 2013 1
2/8/2017 Stages of syphilis Question: My patient has neurosyphilis. Does that automatically mean they have late, or like later, or latent syphilis? Camarero-Temino Nephrology 2013 Lafond et al. Clin Microbiol Rev 2006 Question: I have a patient whose MRI demonstrated a small acute infarct in the internal capsule. He has hypertension and Reply: Neurosyphilis can occur at any uncontrolled diabetes, and urine tox screen was stage of infection. positive for cocaine. His RPR was 1:64 and was negative 6 months ago. Since strokes in syphilis usually occur as a late presentation and he has many other vascular risk factors, I don’t have to LP him, do I? 2
2/8/2017 Think meninges, CSF and blood vessels in early syphilis and parenchymal disease in late syphilis Reply: I would recommend an LP for any patient with a newly positive RPR (or positive RPR of unknown duration) and clinical/radiologic evidence of strokes. Ghanem CNS Neurosci Ther 2010 Which syphilis patients need an LP? Question: My clinic patient has uveitis • Any stage of syphilis + neurological symptoms and an RPR of 1:128. Ophtho sent him to • Any stage of syphilis + ocular or otologic disease clinic for neurological evaluation, but he • HIV-infected patients PLUS: has no neurological symptoms. I don’t • Late latent syphilis have to LP him, do I? • Syphilis of unknown duration • Inappropriate serologic response after treatment • Consider for any HIV-infected patient with CD4 <350 cells/mm 3 and/or RPR ≥ 1:32 Ghanem Clin Infect Dis 2009 3
2/8/2017 Beware the ongoing ocular syphilis epidemic Reply: I would recommend an LP for all • Can occur at any stage of syphilis � most cases now present in early syphilis patients with ocular syphilis. • Can involve ANY ocular structure • Anterior uveitis (iris, ciliary body) • Posterior uveitis (chorioretinitis) • Retinitis, retinal detachment • Optic neuritis • ~50% of patients with ocular syphilis will have evidence of meningitis in the CSF • Treatment is the same as neurosyphilis even if CSF is non-inflammatory • May have residual vision loss despite treatment Woolston et al. MMWR 2015 Syphilis diagnostic testing Question: My HIV+ patient, intermittently Test characteristics Notes non-adherent to his ARVs, presented to SERUM Sensitivity: *Titers correspond to disease 1° : 78-86% activity clinic with headaches that are more RPR (non- 2° : Near 100% treponemal 3° /Latent: Varies, ~85% *Used to assess treatment severe than his usual migraines. tests) response � 4-fold decline False positives 1-2%, usually titer < 1:8 considered to be clinically (autoimmune disease, IVDU, TB, significant pregnancy, endocarditis) Serum RPR was 1:64. CSF had 20 WBC False negatives in HIV, prozone effect and a mildly elevated protein, but CSF SERUM False positives with other spirochetal *Titers do not correspond to infections, malaria, leprosy disease activity Treponemal *Most positive for life despite VDRL was negative. Could this still be tests False negative in HIV treatment (TPPA, *15-25% treated in primary stage neurosyphilis? FTA-Abs) revert to seronegativity CSF VDRL CSF VDRL Sensitivity : 30-80%, *+CSF VDRL at any titer = and FTA- Specificity 99% neurosyphilis Abs FTA-abs high sensitivity but low specificity 4
2/8/2017 HSV-1 encephalitis Reply: Yes, CSF VDRL can be insensitive for neurosyphilis. This absolutely could still be neurosyphilis, and based on the clinical data, I would recommend treating him for neurosyphilis with 2 weeks of Penicillin G (4 million units IV q4 hours). Question: We have an inpatient who presented HSV encephalitis with 2 days of fever, headache and confusion. CSF with 11 WBC (85%L), protein 75 and glucose 53. • HSV is the most frequently identified viral etiology of sporadic encephalitis in the US • Occurs any time of year • Bimodal distribution: 1/3 cases <20 y, 2/3 >40 y • Case fatality rate >70% if untreated; 1/3 of patients may be significantly disabled despite treatment • CSF: 5-500 WBC/mm 3 , normal to moderately elevated protein, glucose typically normal • DWI may be most sensitive sequence early in the CSF HSV 1 PCR negative. Could this still be course of infection HSV encephalitis? 5
2/8/2017 What is the utility of HSV-1 PCR in the CSF? Sensitivity of CSF HSV-1 PCR is lower early in the course of HSV encephalitis • 54 patients with biopsy- proven HSE underwent HSV-1 PCR from CSF • Sensitivity 98% • Specificity 94% Lakeman J Infect Dis 1995 Weil Clin Infect Dis 2002 Reply: Yes, this could definitely still be Question: The repeat CSF HSV-1 PCR HSV-1 encephalitis. I recommend you was positive. She received 3 weeks of IV repeat the lumbar puncture, resend an acyclovir but is still quite impaired, far from HSV-1 PCR from the CSF and start IV her baseline. Should we discharge her on acyclovir 10-15 mg/kg every 8 hours as oral antiviral therapy? you await the results. 6
2/8/2017 No significant cognitive benefit of oral therapy after IV acyclovir Reply: No, unfortunately there is no • 87 HSE patients evidence that a longer course of oral randomized to valacyclovir 2 g TID versus placebo x antiviral therapy after completing IV 90 days acyclovir is beneficial, and I do not • Excluded individuals with recommend she be discharged on oral life expectancy <90 d and those who couldn’t take therapy. PO • Primary outcome was survival with no/mild impairment at 12 months Gnann Clin Infect Dis 2015 Relapsing symptoms after HSV encephalitis • ~15-25% of patients have early relapsing symptoms after Question: Our HSV-1 encephalitis patient completing acyclovir was readmitted from rehab 4 weeks after • More common in children � chorea, dystonia, fever, AMS, behavioral changes, seizures she was discharged with worsening confusion. Could this be recurrent HSV • Adults � movement symptoms less common infection? • CSF pleocytosis and elevated protein; contrast enhancement on MRI • Immune-mediated hypothesis supported by recent discovery of NMDAR and other antibodies patients with relapsing symptoms Armangue Neurology 2015 7
2/8/2017 Diagnostic approach to relapsing symptoms in HSV RELAPSING NEUROLOGICAL SYMPTOMS Reply: I would repeat a lumbar (e.g., CHOREOATHETOSIS, CONFUSION, AGGRESSION, AGITATION, SEIZURES ) puncture and resend the CSF HSV-1 PCR. If the HSV-1 PCR is negative, I would NOT restart IV acyclovir and CSF HSV-1 PCR PCR + CSF/SERUM FOR ANTIBODIES TO ACYCLOVIR would consider serum/CSF evaluation NMDAR, OTHERS for NMDAR antibodies if there is no PCR - identified cause for a persistent decline. NEGATIVE CONSIDER ANTIBODY RESULTS IMMUNOTHERAPY POSITIVE IMMUNOTHERAPY Titulaer Mov Disorder 2014 Toxoplasmosis Question: Our patient with newly diagnosed HIV infection (CD4 count 90 cells/mm 3 , viral load 75K) presented with progressive right sided weakness and confusion. https://www.urmc.rochester.edu/libraries/courses/neuroslides/lab3b/slide137.cfm 8
2/8/2017 CNS toxoplasmosis I know the serum • Most common focal brain toxoplasma lesion in HIV+ w/ CD4 < 200 in US antibody status of an HIV+ patient • Presentation usually evolves with focal brain over weeks to months lesions is key. The patient’s serum • TMP/SMX prophylaxis toxo IgM ELISA is reduces risk of negative, so does toxoplasmosis this rule out toxoplasmosis? • Ddx: CNS lymphoma, pyogenic abscess, tuberculoma, cryptococcoma Tan et al. Lancet Neurology 2012, Laing et al. Int J STD AIDS 1996 Utility of toxoplasma serology • Toxoplasmosis seropositivity in general population in the Reply: The serum toxoplasma IgG is US is estimated to be 10-40% typically more informative in an HIV • Toxoplasmosis in HIV is typically reactivation of prior patient in whom you are worried about infection (i.e., IgM antibodies unhelpful) toxoplasmosis. Send the IgG and, if safe, do a lumbar puncture and send the CSF • Serum IgG is positive in most HIV patients with CNS toxoplasmosis for toxoplasma IgG and/or toxo PCR. • CSF toxo IgG (>1:64) and PCR are very specific but sensitivity varies Laing Int J STD AIDS 1996, Correira Trans R Soc Trop Med Hyg 2010, Vidal J Clin Microbiol 2004, Sakamoto Parasitol Int 2014 9
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