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“It’s All in Your Mind”Jacksonville Area Microbiology Society
April 6, 2010
Yvette S. McCarter, PhD, D(ABMM)
Professor of Pathology
University of Florida College of Medicine
Director, Clinical Microbiology Laboratory
Shands Jacksonville
“It’s All in Your Mind”
A thirty-nine year old woman presents with
nausea and vomiting
– Progressively more frequent over a six-week
period prior to admission.
Physical exam revealed no abnormalities.
Diagnostic studies…
– Urine pregnancy test – negative
– Endocrine evaluation – normal
– Psychiatric evaluation – normal
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“It’s All in Your Mind”Study Result
Abdominal x-ray Normal
CT of the abdomen Normal
Esophageal gastro-
duodenography (EGD)
Normal
Upper GI series with small
bowel follow through
Normal
Radionuclide biliary scan Normal
Brain MRI Normal
Discharge diagnosis: delayed gastric emptying
(gastroparesis) of unknown origin3
“It’s All in Your Mind”
Patient’s nausea and vomiting persisted for several more weeks. Patient returns to the hospital– Decreased appetite, weight loss, epigastric pain,
weakness and 8-9 episodes of vomiting per day
Repeat EGD
– Significant reflux esophagitis, erosive gastropathy at the level of the fundus, gastritis, bilious gastric fluid and duodenitis
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“It’s All in Your Mind”
Within 3 days of admission she developed
right sided ear pain, difficulty swallowing and
gait imbalance
Episodes of hypoxia and hypotension
necessitated intubation and transfer to MICU
– O2 levels dropping into the low 80%s
Neurologic exam
– Periods of agitation alternating with stupor, ocular
bobbing, difficulty moving both eyes to the left,
absent gag reflex, right sided paralysis and right
Babinski’s sign 5
“It’s All in Your Mind”
Brain CT, electroencephalogram (EEG) and
lumbar puncture performed
– CT
• Normal
– EEG
• “Diffuse brain dysfunction”
• No lateralizing or epileptiform discharges
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“It’s All in Your Mind”
CSF
– 15 WBC (93% lymphs)
– 18 RBC
– Protein 26
– Glucose 75
– Gram stain – No neutrophils, no bacteria
– Routine, fungus, AFB cultures, CSF VDRL -
negative
With worsening symptoms original brain
MRI was reevaluated8
“It’s All in Your Mind”
HSV PCR
positive
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HSV Encephalitis - History
1940
1950 1970
1960 1980
1990
1941 – Intranuclear inclusion bodies first demonstrated in brain of neonate with encephalitis
1941 – HSV first isolated from brain tissue
1944 – First adult case of HSE reported
1960s – Two antigenic types of HSV
1990 – First published detection of HSV in CSF by PCR
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HSV Encephalitis - Epidemiology
Most common cause of acute, sporadic viral encephalitis in US (10-20%)
Age distribution: biphasic (5-30 yrs and > 50 yrs)
HSV-1 causes > 95% of cases
Incidence: 3 per 100,000 persons per year
Atypical presentations reported in 20% of HSE
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HSV Encephalitis - Pathogenesis
Adult – Neuronal spread (access to brain via olfactory or trigeminal nerves)– Caused by primary (1/3) and reactivated (2/3)
infection
• ? Reactivation of virus directly within the CNS
Neonate – Hematogenous spread (virus gains access to neuronal tissue by diffusing through the blood-brain barrier or by infecting the endothelial cells in the blood vessels)
Typical pathology – acute inflammation/ hemorrhage and edema in the temporal lobes
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HSV Encephalitis - Pathogenesis
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HSV Encephalitis – Clinical
Clinical presentation – non specific
Focal encephalopathic process
– Altered mental status/decreased consciousness
with focal neurologic findings
– CSF pleocytosis and proteinosis
– Focal MRI, CT or EEG findings
Cutaneous lesion rare (except neonates)
Mortality without treatment – 70%
~ 20% of patients who survive HSV encephalitis
have severe, debilitating sequelae14
HSV Encephalitis - Diagnostics
CSF – Non-diagnostic– Elevated CSF WBC (average 100 cells/ L)
– Elevated protein (average 100 mg/dL)
– Presence or absence of RBC not diagnostic
– 5-10% of patients have normal CSF
Histology – Low yield
Culture– Brain biopsy – Sensitive and specific
• Morbidity associated with procedure
• Potential for false negatives (sampling)
– CSF – Positive in < 4% of patients (Not useful)15
HSV Encephalitis - Diagnostics
Serology– Serum – not sensitive or specific
– CSF – 4 fold rise in titer may not be seen for 2-3 weeks
PCR – Diagnostic method of choice– Sensitivity 95-100%, specificity 98%
– HSV DNA in 80% of samples after 1 week of therapy
– Small amount of sample
– Rapid TAT
– Can differentiate HSV-1 and HSV-216
HSV Encephalitis - Therapy
IV acyclovir x 14-21 days
– Competes as a substrate for viral DNA
polymerase and halts DNA synthesis
– Most effective when given early in the course
of infection
– Should be initiated when there is clinical
suspicion of encephalitis
Reduction in mortality from >70% to ~
20%
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“It’s All in Your Mind”
Patient treated with IV acyclovir
– Patient became alert, nausea and vomiting
dissipated
Required tracheostomy – airway management
Residual positional imbalance and dysphagia
At the time of hospital discharge
– Several residual neurological deficits –severe
positional imbalance and dysphagia
– Inability to swallow required the placement of a
gastrostomy tube for enteral feeding
– She was discharged to a rehabilitation facility 18
Thank
You