B117 Infections of the nervous system, Meningitis, Encephalitis

Question 1

What are the routes of infection to the CNS?

Answer 1

Hematogenous

• arterial spread is the most common
• retrograde venous spread throug the veins of the face and skull into the dural sinuses

Implantation - post tramatic, or in iatrogenic from lumbar puntures.

Local extenstion

• from infection of the sinuses, especially mastoid or frontal
• Infected teeth
• Crainal or vertebral osteomyelitis
• infected meningomyelocele

Peripheral nerve infections - especially for viruses that affect these nerves.

• HSV infections
• Rabies Rhabdovirus

Question 2

Bacterial meningitis, major agents

Answer 2

Neonates: E coli, S. agalactiae,

Adolescents: Neisseria meningitidis, H. influenzae

Elderly: S. pneumoniae, L. monocytogenes

Question 3

Aseptic meningitis, agents

Answer 3

~70% are enteroviruses of the picornaviridae

HSV2 is also a cause

Question 4

Describe meningitis caused by Tuberculosis

Answer 4

Tuberculous Meningitis
a. Usually presents with generalized symptoms of headache, malaise,
mental confusion, and vomiting.
b. There is only a moderate increase of WBC in the CSF made up by
mononuclear cells, or a mix of mononuclear cells and granulocytes, the
protein elevated and the glucose normal or slightly reduced.
c. Infection with M. tuberculosis may also result in a well‐circumscribed
intraparenchymal mass (tuberculoma).
d. Chronic tuberculous meningitis is a cause of arachnoid fibrosis, which
may produce hydrocephalus.

Question 5

Meningitis caused by T pallidum

Answer 5

3. Neurosyphilis
   a. Neurosyphilis is a tertiary stage of syphilis and occurs in only ~ 10% of
   individuals with untreated infection.
   b. Neurosyphilis is caused by invasion of the brain by Treponema pallidum.
   c. As with other chronic infections it may affect the brain parenchyma.
   d. Affected patients may have asymptomatic infection, acute syphilitic
   meningitis, or meningovascular syphilis; direct parenchymal invasion of
   the brain is much less common.

Question 6

Meningitis caused by Borrelia

Answer 6

Neuroborreliosis
a. Characterized by involvement of the nervous system by the spirochete
Borrelia burgdorferi, the pathogen of Lyme disease.
b. Neurologic symptoms are highly variable and include aseptic meningitis,
facial nerve palsies, mild encephalopathy, and polyneuropathies.

Question 7

Symptoms and diagnosis of acute pyogenic meningitis

Answer 7

Systemic infection signs; leukocytosis, fever

Specific signs

• Stiff neck
• headache
• photophobia
• neurologic impairment, confusion
• can easily be fatal without treatment, but most are treatable
• The infection and high neutrophil infiltration to the meningeal veins/dural sinuses can cause venous phlebitis and thrombosis.

Lumbar puncture:

• Increased CSF pressure
• Neutrophils in CNS - in the brain there is massive neutrophil infiltration to the subarachnoid space of affected areas
• elevated protein
• reduced glucose (infection consuming and and immune cells)

gross morpholgy:

• purulent exudate covering the meninges of the brain.
• dilated meningeal vessels
• infection may spread into the ventricles, ventriculitis
• focal infection areas of the brain, focal cerebritis,

Question 9

Signs and symptoms of acute viral meningitis

Answer 9

aka septic meningitis

symptoms are the same, but less severe than pyogentic meningitis, and most often self limiting. treatment is generally supportive.

Lumbar puncture:

• Increased lymphocytes
• mild protein elveation
• glucose is normal

Macroscopically, the brain looks normal or is mildly swollen/edematous.

Question 10

Classifications of encephalitis

Answer 10

Are based on the infecting agents:

Bacterial

Viral

Fungal

Question 11

Major agents for the different types of encephalitis

Answer 11

Bacterial encephalitis

• mainly T. pallidum in tertiary syphillis, as well as the other causes of meningitis

Viral encephalitis:

• almost always occurs as meningoencephalitis
• rabies
• poliomyelitis
• HSV
• SSPE after mumps, measles
• Bunyaviruses
• Arboviruses -California encephalitis. Japanese encephalitis. St. Louis ecephalitis. Tick‐borne encephalitis. West Nile fever

Fungal encephalitis

• Mucor
• Aspergillus fumigatus
• Cryptococcus Neoformans
• Candida albicans

Parasitic encephalitis

• Toxoplasmosis
• Naegleria
• Tenia solium, cystercicosis
• Echinococcus granulosus, hydatid cysts

Question 12

General differences between bacterial/fungal/viral/parasitic encephalitis and parenchymal brain infection

Answer 12

Viruses generally cause diffuse involvment

Bacteria and fungi produce more focal/localized regions of infections.

Parasites are generally distinct to their species

Question 13

describe HSV-1 encephalitis

Answer 13

Occurs in any age, common in children and young adults

Not always preceeded by oral herpes

Temporal lobe encphalitis -

• mood, memory, behavioral changes are major presenting symptoms
• can progress to hemorrhagic, necrotic inflammation of the limbic system

Question 16

VZV encephalitis

Answer 16

VZV causes a latent lifelong infection.

In immunocompromised it can re-emerge and cause encephalitis, along with lymphomonocytic inflammation in the DRGs where it is infecting.

Question 17

CMV encephalitis

Answer 17

Encephalitis in the fetus and immunosuppressed

in fetus:

• periventricular necrosis and significatn brain destruction
• periventricular calcification
• microcephaly

AIDS:

• opportunistic infection, generalized encephalitis

Question 18

Rabies encephalitis

Answer 18

2. The virus enters the CNS by ascending along the peripheral nerves from the
   wound site, so the incubation period depends on the distance between the wound
   and the brain, usually taking a few months.
3. First symptoms of rabies are non‐specific and flu‐like such including malaise,
   headache, and fever.
4. As the infection advances, the patient shows extraordinary CNS excitability; the
   slightest touch is painful, with violent motor responses progressing to
   convulsions.
5. Periods of alternating mania and stupor progress to coma and death from
   respiratory center failure.

Question 19

HIV meningitis

Answer 19

HIV-associated neurocognitive disorder (HAND) is a common occurence in HIV, even with HAART therapy.

HIV infects microglial cells in the brain, and activation of innate immune response, inducing general neuronal injuiry.

a. Aseptic HIV‐1 meningitis
i. Occurring within 1 ‐ 2 weeks in about 10% of patients.

b. HIV‐1 meningoencephalitis
i. Causes AIDS‐dementia complex.
ii. This dementia begins insidiously with mental slowing, memory
loss, and mood disturbances, such as apathy and depression.
iii. Brains of individuals with HIV‐1 encephalitis show chronic
inflammation with infiltrates of microglial nodules containing
macrophage‐derived multinucleated giant cells

c. Vacuolar myelopathy
i. Affects the spinal cord tracts.
ii. The pathogenesis of the lesion is unknown; it does not appear to
be caused directly by HIV‐1, and virus is not present within the
lesions.

Question 20

Discuss the differnt patterns of encephalitis in

Candida

Mucor

Aspergillus

Cryptococcus

Answer 20

Candida albicans
a. Candida usually produces multiple microabscesses, with or without
granuloma formation.

Mucor
a. Mucor causes tissue destruction of all kinds invading the brain directly through the cribriform plate most commonly in diabetics with ketoacidosis.

Aspergillus fumigatus
a. Aspergillus tends to cause a distinctive pattern of widespread septic
hemorrhagicinfarctionsbecause of its markedpredilection for invasion
of blood vessel walls and subsequent thrombosis.

Cryptococcus neoformans
a. Cryptococcal meningitis and meningoencephalitis is observed often in
association with AIDS. It can be fulminant and fatal in as little as 2
weeks, orindolent, or it can evolve over months or years.