“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”

Babinski’s sign

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“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