Microbial Diseases of the Nervous System

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.

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.

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.

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

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.

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.

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

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 90-180 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.

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.

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

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)

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

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

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

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.

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.

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.

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.

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.

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.