05-06 Brain Infections

Question 1

Four cardinal manifestations of brain inflammation

Answer 1

1. fever
2. headache
3. altered mental status
4. focal neuro signs

Question 2

Where does meningitis occur anatomically?

Answer 2

Inflammation of the membranes of the brain or spinal cord; infection involving the subarachnoid and Virchow-Robin spaces over the surface of the brain

Question 3

Where does encephalitis occur anatomically?

Answer 3

Brain parenchyma

Question 4

Where does myelitis occur anatomically?

Answer 4

Inflammation of the spinal cord

Question 5

Define encephalopathy

Answer 5

Disorders/diseases of the brain that include non-infectious causes

Question 6

Review: in what space is the CSF located?

Answer 6

CSF is in the sub-arachnoid space

Question 7

Give example 1) cause(s) and 2) Major distinguishing sx at presentation for:

• Meningitis: Acute
• Meningitis: Subacute or chronic
• Encephalitis: Acute a) Hematogenous
• Encephalitis: Acute b) Neuronal
• Encephalitis: Chronic
• “Space-occupying lesions”
• Toxin-mediated syndromes

Answer 7

Question 8

What are the encephalitis viruses we worry most about?

Answer 8

Most concerning viral encephalidites:

• Arboviruses: 1-50% cases are fatal
• Herpes simplex viruses: > 70% untreated cases are fatal; 6-11% of treated cases are fatal.
• Rabies: >99% cases are fatal without early post-exposure prophylaxis.

Question 9

Clinical features of encephalitis

Answer 9

Acute febrile illness with h/a, AMS, focal neuro signs +/-:

• a.Change in level of consciousness, disorientation, behavior change
• b.Problems with speech
• c.Seizures
• d.Motor weakness
• e.Hyper-reflexia and extensor plantar responses
• f.Abnormal movements or tremor
• g.Pituitary involvement: hypothermia, poikilothermy, diabetes insipidus, SIADH
• h.Spinal cord involvement (myelitis): Flaccid paralysis, loss DTR’s, bladder and bowel dysfunction
• i.Raised ICP (?papilledema)

Question 10

Pathophysiology of Viral Encephalitis

Answer 10

1. True encephalitis: Direct tissue destruction, vascular damage, and edema
   
   • a. Hematog.: e.g. Arboviruses (e.g. EEE, WEE, WNV StLE Cali-E)
   • b. Neuronal transmission: e.g. HSV, Rabies
2. Post-infx encephalomyelitis: Autoimm demyelination

Question 11

Host and vector for North American arboviruses?

Answer 11

North American arboviruses have an enzoonotic life cycle between the host (birds) and the vector (mosquitoes). Hu- mans and horses are accidental hosts.

Question 12

West Nile

• Presentation
• Diagnosis
• Treatment
• Prevention

Answer 12

Presentation

• Ill 3-14 days after infected mosquito bite
• West Nile fever (most viremic patients): Fatigue, fever, headache, muscle weakness; rash (50%)
• Neuroinvasive disease (rare):
  
  • Encephalitis – (most common neuroinvasive form)
  • Meningitis
  • Flaccid paralysis
  • Other

Diagnosis

• Serology; PCR in blood banking
• CSF: Lymphocytic pleocytosis/↑ prot; CSF Abs
• Imaging: Often normal
• EEG: Generalized slowing (frontal or temporal)

Treatment—supportive

Prevention—mosquito control/insect repellants

Question 13

HSV Encephalitis

• Presentation
• Routes of Infection
• Where does HSV-1 cause dz? HSV-2?
• Diagnosis
• Treatment

Answer 13

Presentation

• F (89%), h/a (78%), AMS (96%), personality ∆ (61%), szs (38%), aphasia, hemiparesis

Routes of Infection—3 Routes

1. 1/3 1° infx (usually via oropharynx) with CNS invasion via the trigeminal nerve or olfactory tract. Most patients with primary infection are <18 y.o.
2. 1/3 CNS invasion after an episode of recurrent HSV-1 infection, likely viral reactivation with subsequent spread.
3. 1/3 CNS infection without clinically obvious primary or recurrent HSV-1 infection, presumed reactivation of latent HSV in situ within the CNS.

​HSV-1 vs. HSV-2

• HSV-1: Localized inflammation in medial-temporal, orbital-frontal lobes, limbic structures.
• HSV-2: Can be more generalized encephalitis.

Diagnosis

• 1. CSF: High opening pressure, lymphocytic pleocytosis (0-1000 cells) + many RBC’s, raised protein; nl glucose
• 2. HSV PCR: Sensitivity 75-98%; Specificity100% (compared to biopsy)
     * Expanded range of clinical presentations now documented using this sensitive test.
• 3. EEG
• 4. MRI
• 5. Biopsy

Treatment—IV acyclovir – high dose

Question 14

Rabies

• Pathophys
• Clinical Course
• Clinical Presentation
• Management
• Prevention

Answer 14

Pathophysiology

Replicates in muscles cells, taken up by unmyelinated periph nerve terminals and transported to CNS by retrograde axoplasmic flow at 8-20 mm a day.

• Serum Ab develops in 10 days (but intraneural virus replicates undeterred).
• After generalized CNS replication, centrifugal spread via peripheral nerves.

Clinical Course

The incubation from exposure to clinical rabies disease depends on the inoculation distance from CNS (average 20-60 days and range from 11 months to 6 yrs.)

• Sx onset occurs when virus reaches the spinal cord.

​Clinical Presentation

• nonspecific prodrome that may include localized pain (?in the region of bite), parathesias, and myoedema.
• most common presentation is “furious “(encephalitic) rabies = 80% cases
  
  • agitation
  • hydrophobia
  • excessive salivation (+ other autonom insuff.)
  • arrhythmias
  • coma, seizures, and death
• “Paralytic” (dumb) rabies occurs in 20%
  
  • ascending paralysis
  • weakness
  • meningeal signs

Management is supportive.

Preventive measures include:

• contact isolation precautions.
• animal vaccination
• management of human bite exposures (basic wound care)
• human rabies vaccination (pre-exposure prophylaxis for vets and longterm travelers to high-endemicity areas) or post-exposure prophylaxis with rabies vaccine and rabies immunoglobulin

Question 15

ADEM

• Stands for? What is it?
• Typical Course?
• Diagnosis
• Incidence

Answer 15

Acute demyelinating encephalomyelitis (ADEM)

A.K.A. post-infectious encephalomyelitis

Autoimmune demyel. dz, mimics acute viral encephalitis.

Typical Course

Often h/o fever, rash, nonspecific respiratory, or GI illness in the days to weeks preceding illness.

• Rarely, it follows vaccination or an atypical bacterial infection.

Diagnosis

• The CSF is normal or nonspecific.
• MRI scanning shows enhancing multifocal white matter disease c/w demyelination

Incidence

Uncommon, but kids > adults

• incidence has been reduced dramatically by routine vaccination for childhood illnesses