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ID Case Conference October 31, 2007

ID Case Conference October 31, 2007. Meredith Niess MS3 UNC-SOM. HPI. CC – “right-sided weakness” 50 y/o right-handed man c/o of approximately 6 week history of right leg, hand, and facial weakness. Reports numbness of right palm, 4 th , and 5 th digits

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ID Case Conference October 31, 2007

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  1. ID Case Conference October 31, 2007 Meredith Niess MS3 UNC-SOM

  2. HPI CC – “right-sided weakness” • 50 y/o right-handed man c/o of approximately 6 week history of right leg, hand, and facial weakness. • Reports numbness of right palm, 4th, and 5th digits • Reports difficulty with slower slurred speech • Memory impairment, having lost 2 cell phones in 1 month.

  3. HPI • ED visit 7/28 – around time of onset of symptoms. • c/o Blurred vision, memory deficit, dizziness, unsteady gait. • Normal PE, including neuro exam with nl gait • Glucose finger stick – 178 mg/dL • Symptoms attributed to uncontrolled diabetes • ED visit 8/6 – similar, slightly exacerbated presentation • c/o blurry vision, “shaky”, speech slurring, right- sided weakness, gait difficulties, memory problems. • PE positive for mild aphasia, “sluggish” pupillary exam, and mild cerebellar findings. Otherwise negative. • CBC, BMP and UA all WNL • Head CT done, normal. • Discharged from ED with diagnosis of new onset dementia, referred to neuro.

  4. HPI continued • Patient was seen in neurology, diagnosed with new onset right-sided hemiparesis – ataxic presentation. They were suspicious of lacunar strokes given his diabetic history. • Stroke work-up initiated in Neuro Clinic • Patient presented to ED two days after neuro appointment with persistent symptoms – 6 weeks after initial onset of symptoms.

  5. PMH • Medical: • Diabetes Mellitus type 2 – dx 1999. • d/c medical management 2/2 to cost. • No history of retinopathy or nephropathy • Otherwise unremarkable • Surgical: none reported

  6. PMH • Social hx: • Smoking: 1 pack/week until quit 6 weeks ago • EtOH: 6 drinks/week until quit 3-6 months ago, denies prior problems with addiction. • Drugs: Denies IV or other drug use • Sex: Denies being sexually active for 4-5 years. States previous sexual activity restricted to female only monogomous relationships. No history of STDs. Single. • Occupation: Cook at UNC sorority until 6 weeks previous when symptoms prevented him from working • Residence: Lives with 2 long-term friends • Family: Mom and sister live in Maryland but came in town to help him. • Pets: No pets • Travel: No travel outside east coast.

  7. PMH • Family hx: • Father – deceased at 85: complication related to dementia. • Mother, brother, and sister alive and healthy. • No family history of early onset dementia or other neurologic conditions.

  8. PMH • Allergies: • Keflex causes diarrhea • Medications: • 81 mg Ecotrin • Vitamin C

  9. As mentioned in HPI Vision changes Balance/gait difficulty Right-side facial droop Right-sided weakness Right-sided neuropathy Memory deficit aphasia 20-30 lb weight loss over 2-3 months Excessive fatigue Right knee joint pain Denies CP, SOB, HA, fevers/chills/sweats, LE swelling, n/v/d, or any mood changes. All other systems negative Review of Systems

  10. Gen: well-appearing AA man, NAD, mildly overweight T: 36.4 HR: 70s RR: 20 BP 140/70 Sat 98% RA HEENT: NAT, PERRL, EOM+, MMM Neck: full ROM, no bruits, neg for meningismus, lymphadenopathy, thyromegaly. Pulm: CTAB CV: RRR, nl S1, S2, no m/r/g, pulses 2+ b/l in all extremities Abdomen: obese, soft, NT, +BS, no organomegaly Skin: no rashes/lesion GU: no d/c, no lesions Extremities: no c/c/e, no joint swelling Physical Exam

  11. Mental Status: A&O x 3 Short term memory intact Attention and concentration appropriate Adequate spontaneous speech Intermittent mild slurring of speech Periodic hesitancy with speech Neurologic CN II-XII intact Muscle tone WNL Pronator drift: RUE RLE weak:4/5; RUE weak: 4+/5 Cerebellar abnlities: Dysdiadochokinesis, heel-to-shin abnormality (unable to perform) on RLE, finger-to-nose impaired on RUE Normal gait Romberg Negative Position sense, and vibration intact upper and lower ext. slight difference b/w RLE and LLE on pinprick Neuro Exam

  12. 13.0 292 39.0 Labs – 10/17 Procedures Ordered ESR: 88 Hgb A1C: 5.6 CO2: 25 BUN: 8.0 Creat: 0.8 GFR >60 BUN/Cr: 10 AST: 23 ALT: 29 B12: 412 Folate: 6.2 • MRI • MRA – Circle of Willis • Carotid Duplex • Labs shown plus baseline cholesterol 4.2 MCV: 81 No diff

  13. 12.1 255 36.6 Labs – 10/19 (ED) CSF: TNC:67 RBCs: 11 % PMNs: 2 % Lymphos: 88 Protein: 117 (15-45) Glucose:49 (50-75) BMP – wnl 5.2 Urine tox screen negative Hepatitis panel negative UA and culture wnl

  14. 8/6 ED visit Negative CT D/C with symptoms attributed to dementia

  15. Discussion

  16. “…scattered nonspecific small areas of increased T2/FLAIR signal in the subcortical white matter of the frontal lobes, left centrum semi ovale, and left atria periventricular region. May represent the sequela of chronic small vessel disease. No sequela of acute or remote lacunar stroke is seen.” • MRA wnl • No evidence fluid collections, hemorrhage, or infarct

  17. Diagnostic Procedure Performed • RPR+ at 1:>16,384 • HIV ELISA positive • VDRL of CSF was positive at 1:8

  18. Neurosyphilis • CNS infection by spirochete: Treponema pallidum • Occurs at any time after initial infection • Epidemiology: • Usually sexually transmitted • Prior to abx occurred in 25-35% of people with syphilis • 1/3 asymptomatic, 1/3 tabes dorsalis, 10% paresis

  19. Natural History of Neurosyphilis • See UpToDate (on campus only)

  20. Early Neurosyphilis • Affects CSF, meninges, and vasculature • Months to years after infection • asymptomatic – dx based on CSF • symptomatic • Meningitis – usually 1st year • Meningovascular – often presents with ischemic stroke • Late Neurosyphilis • Affects brain and spinal cord parenchyma • 10+ years after infection • General paresis – progressive dementing illness (10-25 years) • Tabes dorsalis

  21. Clinical Features - Symptoms of neurosyphilis • Personality change (including cognitive and/or behavioral impairment) - 33% • Ataxia - 28% • Stroke - 23% • Ophthalmic symptoms (eg, blurred vision, reduced color perception, impaired acuity, visual dimming, photophobia) - 17% • Urinary symptoms (eg, bladder incontinence) - 17% • Lightning pains (larynx, abdomen, various organs) - 10% • Headache - 10% • Dizziness - 10% • Hearing loss - 10% • Seizures - 7% From Timmermans M, Carr J. Neurosyphilis in the modern era. J Neurol Neurosurg Psychiatry. 2004 Dec;75(12):1727-30.

  22. Clinical Features - Signs of Neurosyphilis • Hyporeflexia - 50% • Sensory impairment (eg, decreased proprioception, loss of vibratory sense) - 48% • Pupillary changes (anisocoria, Argyll Robertson pupils) - 43% • Cranial neuropathy - 36% • Dementia, mania, or paranoia - 35% • Romberg sign - 24% • Charcot joint - 13% • Hypotonia - 10% • Optic atrophy 7% From Timmermans M, Carr J. Neurosyphilis in the modern era. J Neurol Neurosurg Psychiatry. 2004 Dec;75(12):1727-30.

  23. Diagnosis • Diagnosis based on clinical suspicion and supportive laboratory values • neurologic signs, +serum RPR • Spinal Fluid Examination is key • LP should be considered in any patient with neurologic or ocular disease and history of syphilis or unknown syphilis history. • Suggestive findings include: • CSF WBC > 5 lymphos/microL • Protein > 45 mg/dL

  24. Who Gets an LP? • Neurologic or ophthalmic signs or symptoms in any stage of syphilis • Evidence of active tertiary syphilis affecting other parts of the body • Treatment failure in any stage of syphilis • HIV with late latent syphilis or syphilis of unknown duration • Some experts recommend LP in all patients with comorbid HIV and syphilis regardless of stage • RPR titer>=1:32

  25. Diagnosis • Positive CSF VDRL is specific for diagnosis of neurosyphilis • Not sensitive – can be false negative in as many as 70% of patients with neurosyphilis • Can be false positive if any blood is present in CSF when sent to lab • Positive CSF FTA-ABS is sensitive but not specific. • Difficult to diagnose if CSF-VDRL is nonreactive

  26. Treatment • Penicillin G 3-4 million units IV q4H for 10-14 days • Note that standard late syphilis treatment is benzathine penicillin 2.4 MU IM once per week for 3 weeks. • Suggested treatment for possibility of coexisting latent infection is 3 additional doses of benzathine penicillin. • Based on pathophysiology of organism and safety of drug. • No clinical trial data available.

  27. Treatment continued • If patients have a severe PCN allergy they should be desensitized • F/U LPs performed 3-6 months after treatment and every 6 months thereafter until CSF WBC is normal and CSF-VDRL is normal. • If these are not met – retreat.

  28. HIV and Syphilis • Risk fx target similar populations • Coinfection results in similar clinical presentation at similar stage of disease when compared to solitary syphilis, however in HIV+ patients: • Primary stage more often has multiple chancres • Secondary stage symptoms more likely to present concurrent with primary chancre(s)

  29. HIV and Neurosyphilis • Recent review of 170 cases of suspected neurosyphilis cases published in MMWR June 29, 2007 • From LA, NY, Chicago, San Diego between Jan 02-June 04. • 67% had symptoms c/w early syphilis • 58% were MSMs • 86% of the MSM (49 patients) were reported to be HIV positive • Of the 49 HIV-positive MSM with symptomatic early neurosyphilis, 53% (26 patients) had no other signs or symptoms of syphilis • 30% had persistent symptoms at 6 months despite documented serologic response. Persistent symptoms were not associated with receipt of HAART, initial CD4, initial viral load, or time from syphilis onset to treatment.

  30. References • UpToDate (on campus access only) • Sparling, F. Late syphilis. • Marra, C. Neurosyphilis. • Rompalo, A. Syphilis and HIV infection. • Timmermans M, Carr J. Neurosyphilis in the modern era. J Neurol Neurosurg Psychiatry. 2004 Dec;75(12):1727-30. • Centers for Disease Control and Prevention (CDC). Symptomatic early neurosyphilis among HIV-positive men who have sex with men--four cities, United States, January 2002-June 2004.MMWR Morb Mortal Wkly Rep. 2007 Jun 29;56(25):625-8.

  31. Search PubMed • Neurosyphilis • Case Reports • Reviews • Differential Diagnosis • Drug Therapy

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