Diseases of the Nervous System Notes

Diseases of the Nervous System

Clostridium tetani

• Appears as "Drumstick Appearance" under a microscope.

Tetanus ("Lockjaw")

• Causative agent: Clostridium tetani
• Signs/symptoms:
  • Muscle spasms (arching of the back)
  • "Lock-jaw" (first sign)
  • Death due to suffocation
• Pathogenesis:
  • Exotoxin – tetanospasmin
  • Blocks inhibitory neurons à tetany

Reservoir of Infection

• Mouth
• Esophagus
• Liver
• Gallbladder
• Stomach
• Pancreas
• Small intestine
• Large intestine
• Rectum
• Salivary glands

Transmission of Tetanus

• Contaminated puncture wounds, burns, or frostbite (indirect contact).
• Contaminated severed umbilical cord (indirect).

High-Risk Groups for Tetanus

• Elderly population (those over the age of 50 years)
• Heroin users
• Patients with puncture wounds and lacerations
• Underdeveloped countries = neonatal tetanus (poor birthing conditions)
• Neonatal tetanus is almost always fatal (signs: forced grin/raised eyebrows)

Tetanospasmin Toxin

• A/B neurotoxin
• Neurotoxin can enter the bloodstream after being injected into skeletal muscle and affect several motor neurons.
• Binds to terminal axons of inhibitory interneurons inside the spinal cord (CNS); which communicate with motor neurons.
• Mechanism of action: blocks inhibitory neurotransmitters (GABA, glycine) release by interneuron.
• Result?

Tetanus Treatment

• After wounds: Tetanus Immune Globulin (TIG) (anti-sera) + vaccine booster + muscle relaxants

Tetanus Prevention

• DTaP (7 years and younger)
  • Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed

DTaP: Combination Vaccine

• Diphtheria: Corynebacterium diphtheriae; Cause of upper respiratory infection or skin infection
  • Life-threatening complication: The formation of a greenish/gray film in the pharynx; cause of asphyxiation
• Tetanus: Clostridium tetani (toxin)
• Pertussis: Bordetella pertussis
  • Cause of an acute respiratory syndrome called “whooping cough”
  • Diphtheria “Bull’s Neck”

Botulism

• Causative agent: Clostridium botulinum
• Signs/symptoms: Dizziness, blurred vision or drooping eyelids, abdominal pain, vomiting, slurred speech
• Flaccid paralysis; Death due to respiratory
• Pathogenesis: Neurotoxin can be produced in the body after spores enter or in contaminated food.

Epidemiology of Botulism

• Foodborne botulism: Ingestion of spores in contaminated food (home-canned food at risk) 18-36 hours after ingestion
• Wound botulism: drug users at risk

Infant Botulism Epidemiology:

• Most common in children 2 weeks - 6 months
• Currently the most common type of botulism in the U.S.!
• Exact food source is not known; honey can be a source

Pathogenesis of Botulism

• Bacteria grow in the body
• Neurotoxin- Botulinum toxin is secreted
• Effect: Blocks secretion of acetylcholine (stimulatory) neurotransmitter from neuron to skeletal muscle

Treatment/Prevention of Botulism

• Treatment: Botulism Immune Globulin (BIG) to neutralize toxin (helps slow progression IF given in time)
• Prevention: Improve food preservation; don’t feed honey to infants; do NOT eat foods that spurt liquid OR foam.

Botox

• 1989: Botox first approved for cross-eyes & uncontrollable blinking
• 2002: FDA approved using Botox for cosmetic removal of lines/wrinkles and excessive underarm sweating
• Botox is manufactured by Allergan (in Irvine)

Review Question

• A medication designed to INCREASE GABA/Glycine production in the CNS would be most helpful for what disease?
• A medication designed to INCREASE acetylcholine production in the CNS would be most helpful for what disease?

Polio virus

Epidemiology of Polio

• Family: Picornaviridae
  • All members are small RNA viruses
• Genus: Enterovirus
• Transmission: Fecal-oral route (contaminated hands, shellfish, contaminated H2O) or mucous droplets-less common!
• Capsids: Resistant! (salt water, detergent, mild sewage treatment)
• Shellfish: A common culprit
• Reservoir: Humans
• Eradicated from U.S.

Pathogenesis of Polio

• Virus enters via the mouth
• Virus multiplies in the pharynx & GI tract
• Initial Symptoms: Fever, vomiting, stiffness of neck, pain in limbs
• Some patients-virus leaves GI & enters blood, then CNS
• Less than 1% develop bulbar polio- virus may enter motor neurons & brain stem (cause IRREVERSIBLE paralysis of limbs, can affect respiration & swallowing)
• 40% of survivors: “Post-Polio Syndrome” due to deterioration of motor neurons (muscle weakness, pain)

Prevention: Polio Vaccine

Jonas Salk Vaccine (1955)

• Contains: inactivated polio virus (treated with formalin)
• Injectable form
• Advantage: safe
• Recommended in U.S.!
• Disadvantage: Cannot be given by volunteers; is expensive

Albert Sabin Vaccine (1963)

• live, attenuated vaccine
• Oral form (sugar cubes)
• Advantage: longer-lasting immunity; can be transmitted to non-vaccinated children on accident!
• Disadvantage: can mutate & cause paralysis (1/2.5 million cases)
• Used abroad in other countries (8 cents per dose!)

Rabies

Zoonotic Disease

Rabies Background

• Rabies Virus:
  • Enveloped, RNA virus
  • Virus has a distinct “bullet shape”
  • Family: Rhabdoviridae
  • Genus: Lyssavirus
• Rabies = Endemic in Africa, Asia, Central America
• Travelers- high risk
• All mammals are susceptible.
• 55,000 people die/yr. worldwide
• Many are $\$15$ yrs. & younger
• Main Reservoir: skunks, bats, raccoons.

Transmission of Rabies

• Usually direct contact (direct bite)
• Indirect contact (aerosol transmission)

Pathogenesis of Rabies

• Humans get infected via bite (saliva contains virus)
• Virus enters peripheral nerves
• Virus is eventually transported to CNS; travels via sensory or motor neurons (length of time varies)
• Virus replicates in the brain & causes encephalitis
• Average incubation = 1-2 months
• First symptoms:
  • Sensory nerve infection: “prickly feeling”, burning
  • Motor neuron infection: weakness, muscle paralysis or ‘twitches/jerks’, fever
• Terminal Rabies: either of these outcomes
  • A) “Furious” rabies & hydrophobia (muscle spasms in throat) can develop; agitation.= cardiovascular arrest
  • B) After brain infection, EVERY peripheral nerve is infected. “dumb phase” (paralysis & disoriented); death due to respiratory failure/heart stoppage; hypersalivation

Treatment of Rabies

Ideal Regimen (Post-exposure prophylaxis Treatment; PEP)

1. Wound cleansing: Clean wounds w/ soap. If possible use iodine to cleanse wound and kill the virus at the site.
2. RIG: 1 shot @ the site of the wound + 1 shot IM administration of RIG for systemic dissemination.
3. HDCV: Administer IM & follow dosing schedule (see next slide).

Prevention: Post Exposure Prophylaxis

• Human Diploid Cell Vaccine (HDCV)
  • Contains inactivated rabies virus
  • Administered IM
  • Administered to veterinary employees & travelers
  • NOT the same as the older version of the vaccine (required 21 shots in the abdomen)

Rabies Prevention

• Oral Vaccine for Raccoons: Coated in fish meal
• Vaccine drops have proved to be very successful!

Miracle Survivor!

• Read article on the first survivor of Rabies!
• Jeanna Giese, Milwaukee
• “Milwaukee Protocol”
• Difficulty with repeating

Diagnosis of Rabies

• Humans: saliva & skin biopsy (before death) can be tested for rabies = DNA amplification technique called PCR (Polymerase Chain Reaction)
• Brain biopsy of animal: test for rabies antigen present in the brain.