1. Microbial Diseases of the Nervous System

2. Lesson objectives
List the anatomical features and the defenses of the nervous system.
List the methods of entry of microorganisms into the nervous system.
Discuss the important agents of bacterial meningitis; the symptoms, diagnosis, prevention and treatment.
Briefly discuss neonatal meningitis.
Discuss the epidemiology and prevention of tetanus and botulism.
List the important viral diseases of the nervous system.

3. Human Central Nervous system: Brain and Spinal Cord
Basic layout: Brain and spinal cord are composed of cells called neurons. The structures are surrounded by three protective tissues called meninges: From outside to inside: 1) Dura mater: Thick and leathery layer.
Subarachnoid space: This is the area bathed by cerebrospinal fluid (csf). This is the specimen most often collected to diagnose infections of the nervous system.
Pia mater: Thinner layer right next to the brain.

4. Blood/brain barrier
Capillaries that feed the central nervous system are selectively permeable to certain substances. Under normal circumstances, the meninges (csf) only receive essential substances from the blood (e.g. O2, water, sugars, amino acids). Larger materials (e.g. antibodies, cells, many drugs) do not cross.
The CNS is “immunologically privileged.” This means, only certain types of cells carry out immune functions. There is minimal phagocytosis, and normally, little to no inflammation.

5. Why doesn’t the Central Nervous System mount an aggressive response to non-self?

6. Normal microbes found in the Central Nervous System
Any organisms (bacteria, fungi, protozoa, or viruses) found in nerve tissue or cerebrospinal fluid is considered a pathological condition.

7. Meningitis—a life threatening contagious disease
-itis: inflammation, so meningitis is an inflammation of the meninges.
Meningitis can be immediately life threatening because it represents increased intracranial pressure. The function of csf is to cushion the brain and spinal cord, so edema in the meninges can damage specific brain functions.

8. Symptoms of (bacterial) meningitis
Sudden onset
Severe headache
Very stiff neck
High fever
Nausea/vomiting
Disorientation/confusion/seizures

9. Diagnosis of meningitis
Time is crucial, so the doctor collects a sample of csf. Bacterial meningitis has certain diagnostic characteristics that can be detected immediately.
Indicator
Reference value—normal csf
Bacterial meningitis
Color and appearance
Transparent, colorless
Cloudy, yellow or beige
csf pressure
mm Hg
Greater than 180 mm
Protein level
20-50 mg/100 ml
Elevated (sometimes >1000)
Glucose level
40-70 mg/100 ml
decreased
Cells
Few, all monocytes
Abundant neutrophils, lymphocytes, etc.

10. Explanations of abnormal findings
Appearance: cloudiness may be due to increased cells or organisms.
Color may be red (intracranial hemorrhage or traumatic puncture), or yellow (jaundice).
Protein: elevation due to inflammation, presence of antibodies, or bacterial products.
Glucose: decrease due to increased metabolism or use of glucose reserves by pathogens.

11. Risk factors for meningitis
Extreme age: neonates and elderly.
Immunocompromised persons (chemotherapy, AIDS)
Severe alcohol/drug abuse
Recent cranial surgery

12. Causative agents for meningitis:
Most common: Neisseria meningitidis: Gram negative cocci, usually in pairs, intracellular and extracellular. Forms capsules, which prevent phagocytosis. In addition to other meningitis symptoms, causes petechiae: small patches of localized bleeding which appear as red blotches. Can be prevented with a vaccine. Recommended for persons living in close quarters (military, dorm residents)

13. Streptococcus pneumoniae: Gram positive cocci in pairs.
Mostly seen with elderly or immuno-compromised patients.
Similar symptoms as seen with N. meningitidis but no petechiae.
Also avoids host defenses by producing capsules. Preventable with vaccine

14. There are many other causes of meningitis
There are many other causes of meningitis. The more common ones can be classified by population:
Population
Most common pathogens causing meningitis
Newborns (age 0-4 weeks)
E. coli, Streptococcus agalactiae (Group B strep), Listeria monocytogenes
Small children
Hemophilus influenzae (rare since vaccine developed in 1988). Streptococcus pneumoniae
Children-young adults
Neisseria meningitidis
Over 50 years old
Streptococcus pneumoniae, Listeria monocytogenes
Immunocompromised
All of the above, plus fungi: Cryptococcus neoformans (yeast), Mycobacterium species
Recent neurosurgery or head trauma
Staphylococcus aureus, coagulase negative staph, skin microbes

15. How do these populations contract meningitis?
How did they get infected with agents of meningitis?
Newborns (age 0-4 weeks)
Children-young adults
Recent neurosurgery or head trauma

16. Encephalitis—inflammation of the brain
Usually viral. Includes West Nile Virus.
Often spread by arthropods (mosquitoes)
Slower onset than meningitis. Symptoms include flu-like symptoms, which may resolve on their own.
Severe symptoms include nausea, confusion, seizures, personality changes, hallucinations.
No known treatment. Diagnosed by detecting antibodies or detecting viral antigens in csf.
Prevention is aimed at controlling mosquito populations.

17. Rabies
Viral brain infection acquired from mammals. Infection occurs from animal bites. The virus is shed in the animal’s saliva and enters through the bloodstream.
Rabies has a 3-12 week incubation period. During this time, the victim may be infectious, but symptoms have not appeared.
Symptoms: flu-like at first, followed by “twitching,” impaired brain function, extreme thirst compounded with difficulty swallowing (hydrophobia), and death.
Vaccines for animals—each year. Humans treated with gamma globulin (IgG) immediately, followed by four doses of vaccine given over 2 weeks.

18. Bacterial neurotoxins
Clostridium tetani tetanus Clostridium botulinum botulism Both organisms are Gram positive rods, form endospores, and are obligate anaerobes. Tetanus: infection occurs through puncture wounds containing endospores.

19. Risk factors: Anyone exposed to a puncture wound where animal droppings may be (farms, horse trails, even if animals have not been around recently).
Symptoms: toxin causes rigid paralysis. Death occurs from suffocation (“lockjaw” prevents mouth from opening).
Vaccine—tetanus toxoid. Given every 10 years and after exposure.

20. Botulism
Infection can occur through a wound (like tetanus). More often, disease occurs through ingestion of toxin (botulin).
Causes: improperly canned foods (especially non-acidic vegetables), infused oils (especially root vegetables).
Symptoms: flaccid paralysis: weakness, double vision, impaired gait, slurred speech.

21. Paralysis eventually leads to impaired breathing (ventilator required).
Toxin is extremely virulent. Most toxic substance produced by a living organism (to humans).
Prevention: vaccine (for workers), culinary education on how to prepare/preserve food.