Structure and Function of the Nervous System

Central and Peripheral Nervous Systems

The nervous system is divided into two main components: the central nervous system (CNS) and the peripheral nervous system (PNS). These structures are essential for sensory input, integration, and motor output.

• Central nervous system (CNS): Consists of the brain and spinal cord. Responsible for processing and integrating information.

• Peripheral nervous system (PNS): Composed of nerves that branch from the CNS, connecting it to limbs and organs.

Meninges and Cerebrospinal Fluid

The CNS is protected by three layers of connective tissue called meninges, and by cerebrospinal fluid (CSF) which cushions neural tissue.

• Meninges: Three layers—dura mater (outer), arachnoid mater (middle), pia mater (innermost).

• Subarachnoid space: Located between arachnoid and pia mater; contains CSF.

• Cerebrospinal fluid (CSF): Provides mechanical protection and nutrient transport.

Blood-Brain Barrier

The blood-brain barrier is a selective permeability barrier that protects the brain from pathogens and toxins in the bloodstream.

• Function: Restricts passage of substances from blood to CNS, allowing only essential nutrients.

• Clinical relevance: Limits effectiveness of many antimicrobial drugs in treating CNS infections.

Definitions: Meningitis and Encephalitis

Inflammatory diseases of the CNS are classified based on the affected tissue.

• Meningitis: Inflammation of the meninges.

• Encephalitis: Inflammation of the brain (whole brain = encephalon).

• Meningoencephalitis: Inflammation of both meninges and brain tissue.

Bacterial Diseases of the Nervous System

Bacterial Meningitis

Bacterial meningitis is a severe infection of the meninges, often leading to life-threatening complications.

• Symptoms: Fever, headache, stiff neck, nausea, vomiting, convulsions, coma.

• Pathogenesis: Death may result from shock and inflammation due to endotoxin and cell wall release.

• Viral meningitis: More common and generally milder than bacterial forms.

Major Bacterial Pathogens Causing Meningitis

Diagnosis and Treatment of Bacterial Meningitis

Rapid diagnosis and treatment are critical for patient survival.

• Diagnosis: CSF sampling via spinal tap/lumbar puncture; pathogens in CSF are sensitive to storage/temperature changes.

• Latex agglutination tests: Used for rapid identification of pathogens.

• Treatment: Chemotherapy with broad-spectrum third-generation cephalosporins, often initiated before diagnosis is confirmed.

Listeriosis

Listeria monocytogenes is a foodborne pathogen causing meningitis, especially in immunocompromised individuals and pregnant women.

• Characteristics: Gram-positive facultative anaerobic rod; reproduces in phagocytes and spreads cell-to-cell.

• Transmission: Usually foodborne; can cross placenta causing stillbirth.

• Pathogenesis: Invades bloodstream, causes sepsis; spreads phagocyte-to-phagocyte.

Tetanus

Tetanus is caused by Clostridium tetani, which produces a potent neurotoxin.

• Characteristics: Gram-positive, endospore-forming, obligate anaerobe.

• Toxin: Tetanospasmin (TeNT) blocks muscle relaxation, causing spasms and "lockjaw"; death from respiratory muscle spasms.

• Prevention: DTaP vaccine (tetanus toxoid); booster every 10 years.

• Treatment: Tetanus immune globulin (TIG); debridement of infected tissue.

Botulism

Botulism is a neuroparalytic disease caused by Clostridium botulinum toxin.

• Characteristics: Gram-positive, endospore-forming, obligate anaerobe.

• Toxin: Botulinal exotoxin blocks acetylcholine release, causing flaccid paralysis; most potent toxin known (1 ng/kg lethal dose).

• Death: Usually from respiratory or cardiac failure.

Types and Treatment of Botulism

• Treatment: Respiratory assistance and antitoxins (BIG).

• Prevention: Proper canning and use of nitrites in foods.

Leprosy (Hansen's Disease)

Leprosy is a chronic infection caused by Mycobacterium leprae, affecting skin and peripheral nerves.

• Characteristics: Acid-fast rod; grows best at 30°C; survives in macrophages and invades myelin sheath.

• Transmission: Prolonged contact or inhalation of secretions.

• Diagnosis: Skin biopsy or smear.

• Treatment: Antibiotics (Dapsone inhibits folic acid synthesis; Rifampin inhibits RNA polymerase) for 6–24 months.

Forms of Leprosy

Viral Diseases of the Nervous System

Poliomyelitis

Poliomyelitis is caused by the poliovirus, a naked ssRNA virus, and can result in paralysis.

• Transmission: Ingestion of water contaminated with feces.

• Symptoms: Sore throat, nausea; viremia may lead to CNS entry and paralysis (1% of cases).

• Postpolio syndrome: Muscle weakness decades after infection.

Polio Vaccines

• Global impact: Polio cases fell 99% from 1988 to 2000; reservoirs remain in Pakistan, Afghanistan, Nigeria.

Rabies

Rabies is a fatal encephalitic disease caused by the rabies virus (genus Lyssavirus).

• Characteristics: Enveloped ssRNA virus; bullet-shaped.

• Transmission: Saliva of animal bite; can cross mucous membranes.

• Reservoirs: In the U.S., bats, skunks, foxes, raccoons, domestic animals.

• Symptoms: Muscle spasms, hydrophobia, encephalitis; incubation 30–50 days.

• Forms: Furious (excitable) and paralytic (minimally excitable).

Diagnosis and Treatment of Rabies

• Diagnosis: Direct fluorescent-antibody (DFA) test on bodily fluids.

• Pre-exposure: 3 doses of killed virus (HDCV).

• Post-exposure prophylaxis (PEP): 4 doses of killed virus plus immune globulin (RIG).

Rabies Epidemiology

• Human cases: 1–6 per year in the U.S.; most worldwide cases from dog bites.

Fungal Diseases of the Nervous System

Cryptococcus neoformans Meningitis (Cryptococcosis)

This fungal disease primarily affects immunocompromised individuals.

• Agent: Cryptococcus neoformans, a soil fungus associated with pigeon and chicken droppings.

• Transmission: Respiratory route via dried contaminated droppings.

• Pathogenesis: Spreads through blood to CNS; up to 30% mortality.

• Treatment: Amphotericin B and flucytosine.

Protozoan Diseases of the Nervous System

African Trypanosomiasis

African sleeping sickness is caused by Trypanosoma brucei species and transmitted by tsetse flies.

• Reservoirs: Humans (T.b. gambiense), livestock/wild animals (T.b. rhodesiense).

• Symptoms: Early mild symptoms, then fever, headache, CNS deterioration.

• Immune evasion: Antigenic variation complicates vaccine development.

• Treatment: Eflornithine (crosses blood-brain barrier, blocks essential enzyme).

• Prevention: Elimination of tsetse fly vectors.

Amebic Meningoencephalitis

• Naegleria fowleri: Causes primary amebic meningoencephalitis (PAM); infects nasal mucosa from swimming water, penetrates brain, feeds on tissue; nearly 100% fatal.

• Acanthamoeba: Causes granulomatous amebic encephalitis (GAE); granulomas form around infection sites, causing multiple brain lesions.

Nervous System Diseases Caused by Prions

Prion Diseases

Prion diseases are chronic, fatal neurodegenerative disorders caused by abnormally folded proteins.

• Mechanism: Prions induce normal brain proteins to misfold, leading to spongiform degeneration.

• Transmissible spongiform encephalopathies (TSE): Includes chronic wasting disease (deer/elk), Creutzfeldt-Jakob disease (CJD, humans), Kuru (humans, cannibalism), bovine spongiform encephalopathy (BSE, cattle), sheep scrapie.

• Variant CJD (vCJD): Occurs in younger individuals; some forms are inherited.

• Prion resistance: Difficult to destroy; requires NaOH and extended autoclaving at 134°C for sterilization.