A Diabetic Male with AMS, Fever, and Hallucinations

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A Diabetic Male with AMS, Fever, and
Hallucinations
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Edward P. Sloan, MD, MPHAssociate
ProfessorDepartment of Emergency
MedicineUniversity of Illinois College of
MedicineChicago, IL
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Attending PhysicianEmergency
MedicineUniversity of Illinois HospitalOur
Lady of the Resurrection HospitalChicago, IL
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EMS Presentation

• 51 year old 0028 CFD EMS call for AMS
• Per family, high temp, flu-like symptoms
• Fever and hallucinations
• Hot, flushed, diaphoretic, O x 1
• VS 140/P, HR 120, RR 30
• Glucose 300
• Hx DM, HTN
• Recent viral illness

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ED Presentation

• August 2002, Illinois, 101 AM
• ED Presentation non-verbal, moaning
• Temp 102.2
• Viral Sx, N/V/D for 2 days
• Taking NSAIDs, refused PMD admit
• Responds to verbal, moans Help me.

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ED History

• ED Presentation non-verbal, moaning
• Temp 102.2
• Viral Sx, N/V/D for 2 days
• Taking NSAIDs, refused PMD admit
• Responds to verbal, moans Help me.
• No drugs or EtOH history
• Hx psoriasis

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ED Physical Exam

• Agitated, confused, combative, diaphoretic
• Pupils 2-3 mm, non-reactive airway OK
• Neck supple, no thyromegaly
• Cardiopulmonary tachycardia, tachypnea
• Abdomen non-tender
• Neuro CN grossly normal, no motor weakness,
  tremor, intermittent nystagmus on central gaze
• Skin old psoriasis, no new rash

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Clinical Questions

• What are the differential diagnoses?
• What are the etiologies?
• What tests must be performed?
• What therapies must be provided?
• What consultations are required?
• What outcome is likely?

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Lumbar Puncture

• Are there settings in which a lumbar puncture is
  NOT to be performed?
• Why?
• What are they?

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Meningitis Rx

• What is the optimal initial treatment strategy
  for the management of presumed meningitis?
• Why?
• What microbes are we treating?

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Encephalitis Rx

• What is the optimal initial treatment strategy
  for the management of presumed encephalitis?
• When should we empirically give acyclovir?
• What clinical or lumbar puncture findings suggest
  the need for acyclovir?

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ED Management

• DDx Viral Sx, AMS
• R/o encephalitis, meningitis, sepsis
• Need to R/o West Nile Virus (Illinois)
• 115 Haldol, ativan
• 125 RSI with etomidate, pavulon, sux
• 440 Ceftriaxone 2 gr IV
• 455 Acyclovir 1 gr IV over 1 hour

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ED Diagnostics

• WBC 11,900 Hb 16.1
• Glu 313, Bicarb 25, chem ok
• 7.33 / 39 / 79 / 22 / 97
• CXR no clear infiltrate
• EKG sinus tach
• UA no UTI
• CT no lesions
• LP Unable x 2

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Consultations

• Neuro consult LP under fluoro, EEG
• ID consult
• R/o septic shock, resp failure
• R/o staph, given psoriasis
• R/o pneumococcal pneumonia
• R/o meningitis
• R/o toxic or metabolic encephalopathy
• Add vancomycin, obtain 2-D echo

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Hospital Course

• LP by neurosurgery
• 20 WBC, 20 RBC, glu 137, protein 32
• ID viral synd, R/o aseptic meningitis
• Day 3 Possible sub-endocardial AMI
• Day 3 Seizure, rx with fosphenytoin
• Rocephin changed to cefipime, levaquin
• Day 9 More responsive, temp to 102.6
• Day 10 Maculopapular rash

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Hospital Course

• EEG Non-specific diffuse slowing
• ECHO LV dysfunction
• Blood cultures negative
• Repeat CT maxillary sinus fluid
• PCR negative for herpes simplex virus
• Tests for systemic vasculitides negative
• Ab for myeloperoxidase
• Ab for proteinase-3

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Hospital Course

• Legionella Ag in urine negative
• Mycoplasm antibody titre negatvie
• Chlamydia pneumoniae IgG, IgA positive
• HIV Ab negative
• Day 11 West Nile Arbovirus (CSF)

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Patient Outcome

• PM R Consult Comprehensive rehab
• Pt extubated, improved neurologically
• Pt able to understand plan
• Discharge on day 26
• nursing home/rehab care
• able to speak, ambulate
• beginning to meet needs
• Seen in ED by same EM MD, doing well

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Fever, AMS Differential Dx

• Encephalitis
• Meningitis
• Meningoencephalitis
• Encephalomyelitis
• Sepsis

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Viral Encephalitis Etiologies

• Arboviruses mosquitoes, ticks
• Herpes viruses
• Herpes simplex
• Epstein-Barr
• CMV
• Varicella zoster
• Measles virus

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Encephalitis Pathophysiology

• Brain inflammation
• Usually caused by a viral etiology
• Focal, multi-focal, or diffuse
• Cerebral edema, hemorrhage, neuronal death

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Encephalitis Pathophysiology

• Blood borne CNS infection
• Diffuse encephalitis
• Transmitted thru other tissue
• Focal infection
• DNA or RNA viruses

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Arbovirus Encephalitis

• Mosquitoes or ticks (vectors)
• Vector-transmitted infection
• Mosquitoes
• 10 encephalitis rate if infected
• 150 to 3000 cases per year
• Ticks
• Rocky Mountain spotted fever
• Non-US Russian encephalitis

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Herpes Virus Encephalitis

• Able to lie dormant and reactivate
• HSV causes 10-20 of all cases
• 2 per 1,000,000 persons per year
• Usually HSV-1 from oral herpes
• Children, both HSV-1 and 2
• Only treatable cause of encephalitis

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Varicella Encephalitis

• Bad if related to chicken pox
• Adults and children
• In zoster, less severe unless immunocompromised
• Both types are rare

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Epstein-Barr Encephalitis

• Related to mononucleosis
• Fatigue, sore throat, HA, fever
• 1 encephalitis rate
• Usually mild

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CMV Encephalitis

• 5-10 complication rate
• In HIV patients, 50 complicated
• Significant mortality

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Other Encephalitis Causes

• Rabies
• Severe, fatal
• 16 cases between 1980-91 8 US
• Measles, influenza
• Adenoviruses
• 30 mortality rate if encephalitis
• Symptoms of meningitis, coma
• Parasites raccoons, toxoplasmosis

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What is ADEM?

• Acute disseminated encephalomyelitis
• Non-infectious encephalitis
• 2-3 weeks after a viral illness
• 1/3 of encephalitis cases
• Varicella, URIs are common causes
• Autoimmune reaction, white matter
• Myelin sheath damage, as in MS

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Arbovirus Encephalitis

• Eastern equine
• Western Equine
• St Louis
• California
• Japanese B
• West Nile

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Arbovirus Encephalitis Sx

• St Louis West Nile common in US
• Less than 1 cause CNS symptoms
• Sx 2-14 days post-exposure
• Fever, HA, N/V, lethargy
• West Nile Virus
• Maculopapular rash, morbilliform rash
• Loss of muscle tone and weakness

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Arbovirus Motor Sx

• Motor disorders common
• Severe general weakness
• Ataxia, voluntary motor problems
• Tremor, partial paralysis
• Dysphagia, Brocas aphasia
• Hearing and visual symptoms

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Encephalitis Sx

• Sudden onset
• Meningismus
• Stupor, coma
• Seizures, partial paralysis
• Confusion, psychosis
• Speech, memory symptoms

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Encephalitis Diagnosis

• Find treatable etiologies
• CT no changes early
• MRI early HSV changes detectable
• EEG temporal lobe HSV changes
• LP elevated WBCs and protein
• Labs
• Leukocytosis, LFTs, coags, chem, tox
• Viral cultures

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Encephalitis Serum Ab Tests

• Virus only at 2-4 days (too early)
• Serum Ab titres
• Low early levels
• 4-fold increase in convalescent tires
• Obtained 3-5 weeks after sx onset
• PCR will replicate virus DNA
• Quick results (hours)
• Sensitivity equal to viral culture

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Ruling Out Viral Meningitis

• Self limited
• Headache, photosensitivity
• Stiff neck
• Fever, N/V, fatigue also common
• Confusion, psychosis not seen
• Exclude mycoplasma, legionnella

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Treating Viral Encephalitis

• Antibiotics for presumed meningitis
• Acyclovir for presumed HSV Dx
• Steroids?
• Supportive therapies
• Seizure Rx
• Sedation
• Airway control
• Pain and fever meds

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Viral Encephalitis Anti-virals

• Acyclovir for presumed HSV, HZ
• Foscarnet (Foscavir)
• When resistant to Acyclovir
• If adverse reaction to Acyclovir
• Foscarnet or gancyclovir in CMV
• Ribavirin (Virazole)

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Encephalitis Pt Outcome

• 25 relapse rate in HSV disease
• ? Due to relapse or new viral illness
• Poorer outcome with
• Age 55
• Immunocompromise
• Pre-existing neurological problem
• Specific virus virulence
• Coma does not bad outcome

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Encephalitis Pt Outcome

• Outcome related to mental status at the time
  anti-viral Rx initiated
• Early use is warranted
• Long-term sequelae can occur
• Motor, speech, cognitive
• Emotional, personality changes
• Sensory problems (vision, hearing)

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Encephalitis Vaccines

• Measles vaccine
• Varicella vaccine
• Rabies vaccine, immunoglobulin
• Japanese encephalitis vaccine
• Experimental West Nile Virus vaccine

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West Nile Virus Encephalitis

• Mosquito-borne, expanding area
• 1/5 mild febrile illness
• 1/150 meningitis, encephalitis
• Advanced age is greatest risk factor
• Clues as to likely WNV infection
• Infected birds or cases identified
• Late summer
• Profound muscle weakness

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West Nile Virus Encephalitis

• IgM Ab testing via Elisa useful
• Test of serum or CSF
• False positives can occur
• Other flaviviral infections (dengue)
• Prior vaccination (yellow fever)
• Rapid reporting is essential

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West Nile Ecology
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West Nile Ecology
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U.S. counties reporting any WNV-infected birds in
1999 (N 28 counties)
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U.S. counties reporting any WNV-infected birds in
2000 (N 136 counties)
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U.S. counties reporting any WNV-infected birds in
2001 (N 328 counties)
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U.S. Counties Reporting WNV-Positive Dead Birds,
2002
15,745 birds 1,888 counties 42 states D.C.
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2003
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June 2004
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West Nile Virus
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WNV Encephalitis Diagnosis

• Leukocytosis, lymphocytopenia
• Hyponatremia
• CSF pleocytosis, lymphocytes
• Elevated CSF protein
• Normal CT
• MR enhanced leptomeninges or periventricular
  areas

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Encephalitis MR Findings

• Inflamed portion of the temporal lobe, involving
  the uncus and adjacent parahippocampal gyrus, in
  brightest white on MR.

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WNV Antibody Diagnosis

• ELISA detection of WNV IgM
• 95 CSF WNV IgM rate
• IgM does note cross BBB
• CSF IgM suggests CNS infection
• 90 remain positive if tested within 8 days on
  symptom onset

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WNV Antibody Diagnosis

• Asymptomatic pts common
• In endemic area, IgM could be high
• Acute, convalescent titres
• Viral culture low yield
• Real-time PCR
• 55 CSF positive, 10 serum

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WNV Encephalitis Pt Outcome

• Overall, 4-14 mortality
• Age 70, 15-29 mortality
• DM, immunosuppression also predict worse outcome

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WNV Encephalitis Prevention

• Reducing the of vector mosquitoes
• Draining standing water sites
• Methoprene spraying (no maturation)
• Adulticides (organophos, pyrethroids)
• Prevent mosquito bites
• 50 DEET, 10 DEET in children
• Permethrin to clothing, fabrics
• Citronella (less effective)

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Key Learning Points

• AMS, fever, weakness encephalitis
• Know clues for West Nile virus
• Early use of ceftriaxone, acyclovir
• Supportive care essential
• Consultation for best diagnostics
• Reportable public health disease
• Prevention is best approach

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Key Learning Points

• No LP if there is a herniation risk
• Abnormal posturing, exam
• Abnormal CT
• Ceftriaxone 2 gr, vancomycin 1 gr
• LP in encephalitis WBCs, lymphocytes, no
  bacteria
• Acyclovir with any encephalitis risk

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Questions?
www.FERNE.org edsloan_at_uic.edu 312 413 7490
destin_ sloan_ams_wnv_2004