CASE CONFERENCEPaul Odenbach MDJune 19, 2008

Chief Complaint

¨ 79 year old man with headache and confusion

Past Medical History

¨ ASCVD¤ 2002 PTCA and stents

¨ GERD¨ AAA¤ 4.3 cm

¨ Asbestos exposure

History of Present Illness

¨ Malaise and fatigue since tetanus booster one month prior to presentation

¨ Presents to clinic with:¤ New onset right-sided HA¤ Mild confusion¤ Body aches

¨ Head CT normal¨ Sent home without additional intervention

7/8/2006

History of Present Illness

¨ One day later presented to ED¨ Persistent HA, confusion¨ Fever 104¨ Treated with single dose Ceftriaxone and

discharged to home with plan to continue outpatient therapy

7/9/2006

History of Present Illness

¨ Returned to ED with progressive confusion¨ Ongoing HA, fevers¨ Admitted¨ Antibiotics started

¤ Ceftriaxone¤ Doxycycline¤ Levaquin

¨ Blood cultures obtained¨ Serum Lyme IgM/IgG negative¨ Carotid Ultrasound unremarkable¨ Transferred to ANW for further evaluation

7/10/2006

ANW Admission

¨ Alternating agitation and somnolence¨ Spent winter in Arizona, returned to Minnesota

5/2006¨ No significant outdoor exposures¨ No sick contacts

7/11/2006

Medications

¨ Celebrex¨ ASA¨ Lisinopril¨ Simvastatin¨ Lasix¨ Ceftriaxone¨ Levofloxacin¨ Doxycycline

7/11/2006

Additional History

¨ Social History¤Married, retired truck driver¤ Rare EtOH¤ Tobacco: 2 ppd for 20 years, quit 1959

¨ Family History¤ Unremarkable

7/11/2006

Exam

¨ T 100.4 F, P 108, BP 137/76, R 26, SaO2 97% RA¨ Few native teeth, no oral lesions¨ No nuchal rigidity¨ Loud snoring, lungs clear to auscultation¨ Regular tachycardia, 1/6 SEM, no JVD¨ Abd soft¨ No rashes or LAD¨ Eyes open, not responsive to voice. Not following commands.

Groans to pain. Spontaneously moving 4/4 extremities. Normal reflexes.

7/11/2006

Labs

¨ Na 138, K 4.3, Cl 101, CO2 28, BUN 39, Cr 1.4, Ca 8.8, Glucose 132

¨ WBC 13.5 (77% PMN), Hgb 13.9 (MCV 94), Platelets 335

¨ UA: Tr protein, large blood, positive LE, negative nitrite, 49 WBC, 112 RBC

¨ BCx 7/10/2006: NGTD

7/11/2006

Plan

¨ Evaluated by ID and Neurology¨ STAT anti-infectives:

¤ Ceftriaxone¤ Vancomycin¤ Ampicilin¤ Acyclovir

¨ LP¨ MRI¨ Intubate for airway protection

7/11/2006

Hospital Day 1

¨ A fib with hypotension overnight¤ Levophed, heparin¤ TTE EF 65%

¨ Ongoing fevers¨ Intubated, sedated¨ Exam unchanged

7/12/2006

Hospital Day 1

¨ MRI¤ Multiple small foci of signal abnormality throughout cerebral

white matter c/w small vessel ischemic disease

¨ LP¤ WBC 165 (6% PMN, 78% Lymph, 16% Mono)¤ RBC 10¤ Glucose 71¤ Protein 148¤ Viral studies sent

¨ Blood, urine, CSF cultures/stains negative

7/12/2006

Hospital Day 1

¨ Plan¤ Ceftriaxone, Vancomycin, Ampicillin discontinued¤ Await HSV PCR¤ Consider repeat LP

7/12/2006

Hospital Day 3

¨ Exam unchanged¨ Off of pressors¨ WBC 11.0 <-- 13.5¨ TEE normal, patient electrically cardioverted¨ HSV PCR negative

¤ Acyclovir discontinued

¨ West Nile Virus IgM/IgG negative¨ Enterovirus pending¨ Serum Cryptococcal antigen negative¨ Heparin held for repeat LP

7/14/2006

Hospital Day 4

¨ LP¤ WBC 40 (1% PMN, 83% Lymph, 13% Mono)¤ RBC 240¤ Glucose 80¤ Protein 77

¨ CSF Cryptococcal antigen negative¨ CSF AFB and Gram stain negative

7/15/2006

Hospital Day 5

¨ Afebrile for 48 hours¨ Sedation weaned, following commands¨ WBC 5.5¨ All cultures remain negative¨ Extubated

7/16/2006

Hospital Day 6

¨ Drowsy, but oriented¨ Afebrile¨ ID Assessment¤ Resolving viral meningoencephalitis¤ No need for further testing

¨ Neuro Assessment¤ Remarkable improvement¤ Good prognosis for neurologic recovery

7/17/2006

Hospital Days 7-12

¨ Afebrile¨ Recovering strength¨ ID, Neurology sign off¨ Working with PT/OT¨ Discharge planning to SNF

7/18-7/23/2006

Hospital Day 13

¨ New left facial weakness involving forehead¤ Patient unaware of deficit

¨ Mild confusion resurfaces¨ Remainder of Neuro exam unremarkable¨ Afebrile¨ WBC 7.8

7/24/2006

Neurology Evaluation

¨ New 7th nerve palsy¤ Ddx: n Partially treated bacterial infectionn VZVn Coccidioidomycosisn Post infectious: GBS

¨ Plan: repeat LP ¨ FFP to reverse INR

7/24/2006

LP #3

¨ WBC 72 (1% PMN, 98% Lymph, 1% Mono)¨ RBC 119¨ Glucose 69¨ Protein 103¨ Gram Stain negative

7/24/2006

LP #3

¨ WBC 72 (98% L) <-- 40 (83%L) <-- 165 (78% L)¨ RBC 119 <-- 240 <-- 10¨ Glucose 69 <-- 80 <-- 71¨ Protein 103 <-- 77 <-- 148¨ Gram Stain negative

7/24/2006

Plan

¨ Multiple CSF studies sent¨ Empiric treatment for Lyme Disease¤ Ceftriaxone 2g IV daily

7/24/2006

CSF Studies

¨ VDRL nonreactive¨ West Equine Encephalitis PCR negative¨ East Equine Encephalitis PCR negative¨ St. Louis Encephalitis PCR negative¨ Lacrosse Encephalitis PCR negative¨ VZV PCR negative¨ Coccidioides IgM/IgG negative ¨ Bacterial antigens negative

Hospital Days 14-17

¨ Confusion resolves¨ Facial weakness persists¨ Discharged to SNF

¤ Ceftriaxone 2g IV daily for 21 days planned

¨ Pending studies¤ Lyme CSF PCR¤ West Nile CSF serologies (sent to MN Dept of Health)

7/25-7/28/2006

Weeks Later…

¨ CSF West Nile IgM Positive

8/21/2006

WEST NILE VIRUSAugust 22, 2007

Background

¨ Single-stranded RNA virus of the family Flaviviridae, genus Flavivirus

¨ Member of the Japanese encephalitis virus antigenic complex¤ Japanese encephalitis¤ St. Louis encephalitis¤ Murray Valley encephalitis

¨ Serologic cross reactivity possible within this complex

¨ Peak incidence of human disease in North America occurs in late August and early September¤ Cases from April to December have been

reported

Life Cycle

¨ Vector: Culex mosquitos¤ Able to survive in winters by

hibernating 6 months (and perpetuate disease from year to year)

¨ Bird is amplifying host¤ Mostly remain asymptomatic with

high levels of viremia¤ Higher mortality rate in crows and

related species¤ 2002 Midwest outbreak, dead crows

spatially associated with human disease

¤ For unknown reasons, deaths among birds from WNV infection have occurred only in the United States, Israel, Canada, and Mexico

Am J Epidemiol. 2006 Jan 15;163(2):171-80.

www.cdc.gov

Clinical Features

¨ Incubation period 2-14 days¤ Longer incubation in immunocompromised patients

¨ 80% of infected people are asymptomatic¨ 20% develop West Nile Fever ¨ 1 in 150 will develop meningoencephalitis¤ Increased risk in elderly and immunocompromised

West Nile Fever

¨ Classic Clinical Description:¤Mild dengue-like illness of sudden onset¤ Fever, lymphadenopathy, headache, abdominal pain,

vomiting, conjunctivitis, eye pain, anorexia ¤ 50% of patients have maculopapular rash¤ Duration 3 - 6 days¤ Usually self-limited

West Nile Fever

¨ Symptoms of Hospitalized Patients withWest Nile Virus, New York City, 1999

Fever 90%

Weakness 56%

Nausea 53%

Vomiting 51%

Headache 47%

Change in mental status 46%

Diarrhea 27%

Rash 19%

Lymphadenopathy 2%

Neuroinvasive Disease

¨ Can present with encephalitis, meningitis, or flaccid paralysis

¨ Encephalitis more common than meningitis¨ Encephalitis with paralysis is suggestive of WNV¨ Paralysis can occur without associated encephalitis¨ WNV paralysis usually from an anterior horn cell

process ¨ Mortality rate 2-18%¨ Worse prognosis in elderly, immunosuppressed, or

history of diabetes/alcohol abuse

Clinical Features

¨ Less common manifestations¤ Rhabdomyolysis ¤Myocarditisn Found on pathology, unclear clinical significance

¤ Hepatitis and pancreatitis ¤ Central diabetes insipidus ¤ Hemorrhagic feversnOne case of palpable purpura and multi-system organ

failure

Diagnosis

¨ Laboratory Testing¤ IgM ELISA antibodyn Very sensitiven One series of viremic patients, IgM antibody present in 100% of

patients by nine daysn Variable sensitivity in less than nine daysn Can remain positive for up to six monthsn False positives with recent vaccinations (yellow fever) or infection

with other flaviviruses¤ PCR testingn Low sensitivity

n ~50% sensitivity by CSF or serum of patients with west nile fevern 15% in serum of patients with neuroinvasive diseaes

¤ Excellian: n West Nile CSF Inpatient (IgM and PCR)n West Nile Serum Inpatient (IgM and IgG)

CSF Analysis

¨ Series of 334 patients with meningitis/encephalitis¤ PleocytosisnMean of 226 nucleated cells/mm3

n Less than 3% of patients with meningitis and less than 5% of patients with encephalitis had <5 nucleated cells

¤ Elevated Protein¤ Normal Glucose

Treatment

¨ Supportive Cares¨ Interferon alpha (RCT underway)¨ Ribavirin¨ ? IVIG¨ Prevention¤ Avoid mosquitoes

Prognosis

¨ Worse prognosis with advancing age¤ Meningitis 2% fatality¤ Encephalitis 12% fatality

¨ Neuroinvasive Disease¤ One series: 63% had perceived deficits at one yearn Fatiguen memory problemsn weaknessn word-finding difficultyn headaches