2Lesson objectivesList 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.
3Human 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.
4Blood/brain barrierCapillaries 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.
5Why doesn’t the Central Nervous System mount an aggressive response to non-self?
6Normal 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.
7Meningitis—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.
8Symptoms of (bacterial) meningitis Sudden onsetSevere headacheVery stiff neckHigh feverNausea/vomitingDisorientation/confusion/seizures
9Diagnosis of meningitis Time is crucial, so the doctor collects a sample of csf. Bacterial meningitis has certain diagnostic characteristics that can be detected immediately.IndicatorReference value—normal csfBacterial meningitisColor and appearanceTransparent, colorlessCloudy, yellow or beigecsf pressuremm HgGreater than 180 mmProtein level20-50 mg/100 mlElevated (sometimes >1000)Glucose level40-70 mg/100 mldecreasedCellsFew, all monocytesAbundant neutrophils, lymphocytes, etc.
10Explanations 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.
11Risk factors for meningitis Extreme age: neonates and elderly.Immunocompromised persons (chemotherapy, AIDS)Severe alcohol/drug abuseRecent cranial surgery
12Causative 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)
13Streptococcus 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
14There are many other causes of meningitis There are many other causes of meningitis. The more common ones can be classified by population:PopulationMost common pathogens causing meningitisNewborns (age 0-4 weeks)E. coli, Streptococcus agalactiae (Group B strep), Listeria monocytogenesSmall childrenHemophilus influenzae (rare since vaccine developed in 1988). Streptococcus pneumoniaeChildren-young adultsNeisseria meningitidisOver 50 years oldStreptococcus pneumoniae, Listeria monocytogenesImmunocompromisedAll of the above, plus fungi: Cryptococcus neoformans (yeast), Mycobacterium speciesRecent neurosurgery or head traumaStaphylococcus aureus, coagulase negative staph, skin microbes
15How do these populations contract meningitis? How did they get infected with agents of meningitis?Newborns (age 0-4 weeks)Children-young adultsRecent neurosurgery or head trauma
16Encephalitis—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.
17RabiesViral 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.
18Bacterial 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.
19Risk 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.
20BotulismInfection 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.
21Paralysis 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.