1. Ramez Morkous MS4 Medical University Of the Americas April 29, 2016
Internal Medicine
Conference 04/29/16
Encephalitis
Ramez Morkous
MS4 Medical University Of the Americas
April 29, 2016

2. A 57-year-old woman is admitted to the hospital with a 2-day history of fever and confusion. Medical history is significant for hypertension treated with metoprolol.
On physical examination, temperature is 39.0 °C (102.2 °F); other vital signs are normal. The patient is alert but lethargic and answers questions with one-word responses. She is oriented to person only. Passive flexion of the neck elicits mild nuchal rigidity. Remaining physical examination findings are unremarkable.
Lumbar puncture is performed. Opening pressure is 21 mm H2O. The cerebrospinal fluid (CSF) leukocyte count is 147/microliter (147 × 106/L) with 77% lymphocytes. CSF glucose and protein levels are normal. An MRI of the brain is normal.
Treatment with empiric acyclovir, 10 mg/kg intravenously every 8 hours, is initiated. By hospital day 3, the patient's fever has resolved and her mental status has normalized. Results of a CSF herpes simplex virus (HSV) polymerase chain reaction (PCR) performed at admission are negative.

3. Which of the following is the most appropriate management of this patient's acyclovir therapy? A-Change intravenous acyclovir to oral acyclovir to complete a 14-day course B-Continue intravenous acyclovir pending results of repeat HSV PCR C-Continue intravenous acyclovir to complete a 14-day course D-Discontinue intravenous acyclovir
In patients with a low clinical suspicion for herpes simplex encephalitis, empiric acyclovir therapy may be discontinued when herpes simplex virus polymerase chain reaction results are negative.

4. Introduction Meningitis vs. Encephalitis
The clinical distinction between meningitis and encephalitis is based upon the state of brain function and presence of meningeal irritation
Seizures and postictal states can be seen with meningitis alone and should not be construed as definitive evidence of encephalitis

5. Introduction
Encephalitis is an acute inflammatory process affecting the brain
Viral infection is the most common and important cause, with over 100 viruses implicated worldwide
Symptoms
Fever
Headache
Behavioral changes
Altered level of consciousness
Focal neurologic deficits
Seizures
Incidence of per 100,000 persons per year

6. Initial Signs Headache Malaise Anorexia Nausea and Vomiting
Abdominal pain

7. Developing Signs Altered LOC – mild lethargy to deep coma.
AMS – confused, delirious, disoriented.
Mental aberrations:
hallucinations
agitation
personality change
behavioral disorders
occasionally frank psychosis
Focal or general seizures in >50% severe cases.
Severe focused neurologic deficits.

8. Neurologic Signs
Virtually every possible focal neurological disturbance has been reported.
Most Common
Aphasia
Ataxia
Hemiparesis with hyperactive tendon reflexes
Involuntary movements
Cranial nerve deficits (ocular palsies, facial weakness)

9. Differential Diagnosis

10. HSV Encephalitis HSV-1 causes encephalitis in adults
HSV-1 or HSV-2 in neonates
HSV-1 and 2 associated w/Mollaret’s meningitis
Benign recurrent lymphocytic meningitis
Preferentially affects temporal lobe
Can rarely cause recurrent brainstem encephalitis
HSV-2 tends to cause global encephalitis
1/3 cases <20yrs and 1/2 cases >50 yrs
Most common cause of encephalitis at any time of the year
HSV-1 causes more than 95% of cases
age distribution is biphasic: peaks at 5 to 30 and > 50 years of age

11. Pathogenesis Infiltrates CNS via 3 routes
1. Trigeminal nerve or olfactory tract
Typically after primary infection
<18yrs old
2. CNS invasion after recurrent infection
Viral reactivation w/subsequent spread
3. CNS infection w/o primary or recurrent HSV-1
Latent HSV in situ within CNS
Invades and replicates in neurons and glia
Causes necrotizing encephalitis
Widespread hemorrhagic necrosis throughout parenchyma

12. Pathogenesis Necrosis of temporal lobe Immune mediated
Not more common in immunosuppressed
Small studies suggest HSV viral load does not correlate with degree of temporal lobe damage

13. Presentation Fever Altered level of consciousness
Focal cranial nerve deficits
Hemiparesis
Dysphasia/aphasia
Ataxia
Focal seizures
Altered mental status :consequences of temporal lobe damage
Hypomania - elevated mood, excessive animation, decreased need for sleep, inflated self-esteem, and hypersexuality
Kluver-Bucy syndrome (KBS)
Initially seen in Rhesus monkeys
Loss of normal anger and fear responses
Increased sexual activity
Amnesia

14. CSF CSF CSF PCR now diagnostic test of choice
Lymphocytic pleocytosis
Erythrocytosis (84% of patients)
Elevated protein
Low glucose uncommon
CSF PCR now diagnostic test of choice
Quickest, sensitive, and specific
HSV culture out of favor
Brain biopsies previously performed
The most helpful finding on standard tests is CSF red blood cells in the absence of a traumatic lumbar puncture
CSF PCR for viral DNA is highly accurate: 98% sensitive and 100% specific. May be negative in first 72h

15. Imaging Imaging – Temporal lobe injury Usually unilateral
May have mass effect
MRI much more sensitive/specific

16. EEG EEG – focal findings in >80% cases
High amplitude slow waves (delta and theta slowing)
Continuous periodic lateralized epileptiform discharges in the affected region

17. Disease Progression Worsening neurologic symptoms
Vascular collapse and shock
May be due to adrenal insufficiency.
Loss of tissue fluid may be equally important.
Homeostatic failure
Decreased respiratory drive
Untreated, mortality 70%
Survivors with severe neurologic damage
With treatment—mortality ~20%!
Severe disability in 20%
Simplified Acute Physiology Score II >/=27
Delay >2 days b/w admission and acyclovir
GCS <6
Age>30
62% of survivors have neurologic sequelae

18. Treatment

19. Supportive Therapy
Fever, dehydration, electrolyte imbalances, and convulsions require treatment.
For cerebral edema severe enough to produce herniation, controlled hyperventilation, mannitol, and dexamethasone.
Patients with cerebral edema must not be overhydrated.
If these measures are used, monitoring ICP should be considered.
If there is evidence of ventricular enlargement, intracranial pressure may be monitored in conjunction with CSF drainage.
Outcome is usually poor.
For infants with subdural effusion, repeated daily subdural taps through the sutures usually helps.
No more than 20 mL/day of CSF should be removed from one side to prevent sudden shifts in intracranial contents.
If the effusion persists after 3 to 4 weeks of taps, surgical exploration for possible excision of a subdural membrane is indicated.