Nervous System = peripheral nerves + central nervous system (CNS)
I. Generalities:
A. Structure of
B. Protection of
C. How do microbes get to the central nervous system (CNS)?
**1. from the bloodstream - cross the Blood-Brain-Barrier (ex. bacterial meningitis, polio)
*2. from the peripheral nerves (ex. herpes, VZV, rabies)
3. invasion from:
bone
sinuses
middle ear
4. trauma
II. Clinical Syndromes
A. meningitis - of meninges
Characterized by high fever, headache, stiff neck (classic triad)
Pathology due to acute inflammation:
Vascular permeability  ↑WBC, ↑fluids
Fluids  swelling
Swelling  ↑pressure  headache
Inflammation affects muscles  stiff neck
Inflammation  fever
Causes:
clogging of blood vessels (DIC)  necrosis of tissue
↓ CSF flow
impaired CNS function
In bacterial meningitis, death occurs from shock & other serious complications within
hours as a result of release of peptidoglycan + endotoxins (GN) or teichoic acid (GP)
B. encephalitis - of the brain
Characterized by acute febrile illness + changes in mental state, consciousness,
behavior
C. myelitis - of spinal cord
Symptoms vary depending on where damage to cord occurs
III. Infections of the Meninges
A. Bacterial meningitis
Acute - nearly always fatal
Strong correlation of microbe with age of patient – influences the top R/O:
Neonates – E. coli, Group B streptococci
1 month to 5 yrs - Haemophilus influenzae type B (Hib)
5 to 40 - Neisseria meningitidis
30 and over - Streptococcus pneumoniae
Pathogenesis
1. colonization and invasion of nasopharynx
2. nasopharynx  bloodstream  BBB to subarachnoid
3. replicate and induce inflammation in subarachnoid space  increased
permeability of BBB, cerebral edema, increased intracranial pressure, decreased
cerebral blood flow.
Pathology
Subarachnoid space purulent exudates, vein distension, focal necrosis
Diagnosis
CSF examination – elevated opening pressure, very ↑neutrophils, very ↑ protein, ↓glucose
Prognosis
Serious to grave
Mortality rates
Hib
N. meningitides
S. pneumoniae
without txt = near 100%
without txt = near 100%
without txt = near 100%
All can be present in humans in an asymptomatic carrier state
with txt = 5%
with txt = 7-10%
with txt = 20-30%
1. Haemophilus influenzae type B (Hib) (1 month – 5) 2,895U.S./ 24 MI
GNR
Normal upper RT microbiota
Inactivate IgA using IgA protease
Colonize the nasopharynx using common pili
Penetrate submucosa (invasive) bloodstream (capsule to avoid phagocytosis)
Incubation - 5-6 days
Symptoms develop over 1-2 days
Endotoxin:
1. inflammation
2. DIC
Complications – hearing loss, delayed language development, mental retardation
Prevention – Vaccination
2. Neisseria meningitidis (5-40) 887 U.S./ 20 MI
GNdC
Person-person in respiratory droplets; 20% carriers (as high as 60-80%)
Inactivate IgA using IgA protease
Colonize the nasopharynx using pili  sore throat
Endocytized  bloodstream (capsule to avoid phagocytosis)
Incubation 1-3 days
Symptoms develop over 6-24 hours
Endotoxin:
1. affects blood vessel permeability  cross BBB (attach to dura mater w/ pili)
2. drop in blood pressure  shock
3. clotting of blood  hemorrhage (rash = petichiae and purpura), also DIC
Complications – amputations, permanent hearing loss
Prevention - Vaccination
3. Streptococcus pneumoniae (30+) 4,591 U.S./ 98 MI
GPC
Normal upper RT microbiota
sinuses or middle ear  brain
or
pneumonia in lungs  bloodstream  brain
Capsule
Teichoic acid  inflammation
Prevention - Vaccination
B. Viral meningitis = aseptic meningitis
Most common
Self-limiting, non-fatal
Many different viruses:
1. Enteroviruses - 40% (primarily Coxsackievirus and Echovirus)
2. Arboviruses
3. HIV
4. HSV-2
Several considerations affect differential:
Summer, fall + geographic clustering  Arboviruses
Late fall, winter + history of exposure to mice  LCMV
Late winter, early spring + male  mumps virus
With genital lesions  HSV-2
With atypical lymphocytes  EBV
With chickenpox or shingles  VZV
Diagnosis
CSF examination – ↑ lymphocytes, moderately ↑ protein, normal glucose
Prognosis - In adults, excellent
C. Fungal meningitis
Chronic presentation – symptoms develop over days to weeks
1. Coccidioides immitis – 12,729 U.S./ 19 MI cases of coccidiodomycoses
2. Cryptococcus neoformans - AIDS
IV. Infection of the Brain (Encephalon) – involvement of brain parenchyma
A. Viral encephalitis
Same viruses as for aseptic meningitis but relative frequency varies
1. Arboviruses (Arthropod-borne)
Ex. Equine encephalitis, (West Nile virus) neuroinvasive – 361 U.S./ 0 MI
Bird
Mosquito
Mosquito
Bird
Horse
(human)
Epidemics, geographic clustering
2. HSV-1
no insect
sporadic, not epidemic
3. Enteroviruses, mumps – 982 U.S.
4.Rabies - Rhabodovirus – in animals 3,581 U.S./ 66 MI
Bite
Multiplies at site
Travels to local nerves
Peripheral nerves  spinal cord  brain
Long incubation
Prodromal phase - flulike symptoms, tingling, burning, depression
Excitation phase - muscle function, speech, vision, anxiety, hydrophobia
Paralytic phase - muscles weaken, consciousness fades, death
Mortality - 100% with best treatment
Post exposure prophylaxis (PEP) - has never failed in US
B. Protozoan encephalitis
1. Primary amebic encephalitis - Naegleria fowleri
Mortality = 100%
2. African Sleeping Sickness - Trypanosoma
Misc.
1. Tetanus – 14 U.S.
Clostridium tetani – exotoxin tetanospasmin (mimics strychnine poisoning)
2. Botulism – foodborne - 12; infant - 57; wound – 23 U.S.
Clostridium botulinum
Genes for toxin are carried on a bacteriophage
Exotoxin botulinum prevents release of acetylcholine
Produces a limp, flaccid, paralysis
Eyes  blurry, double vision
Throat  slurring speech, difficulty swallowing
Difficulty breathing
Cardiac problems