Central Nervous System

Infections
 INTRODUCTION

* Central nervous system infections are usually:

1- Blood-borne invasion; most common

(e.g. polioviruses or Neisseria meningitidis)

2- Invasion via peripheral nerves; less common

(e.g. herpes simplex, varicella-zoster, rabies)

 INTRODUCTION
1- Blood-borne invasion takes place across:
- blood-brain barrier (encephalitis)
- blood-cerebrospinal fluid (CSF) barrier (meningitis).
* Microbes can traverse these barriers by:
- Infecting the cells that comprise barrier.
 INTRODUCTION
2-Invasion via peripheral nerves:

* Herpes simplex virus (HSV) and varicella-zoster virus

(VZV) present in skin or mucosal lesions travel up
axons to reach the dorsal root ganglia.

* Rabies virus, introduced into muscle tissues by:

- bite of a rabid animal.

- It enters peripheral nerves and travels to CNS,

to reach the neurons.
Pathologic consequences of CNS infection
* In CNS; viruses infect neural cells, sometimes
showing a marked preference.

* Polio and rabies viruses invade neurons. CJD virus

invades oligodendrocytes.

* Spread of infection is direct from cell to cell along

established nervous pathways.

* Bacteria and protozoa induce brain abscesses.

Meningitis
 Introduction
* Meningitis is one of the
most terrifying disease.

* It can be fatal in hours.

* Early symptoms resemble

self-limiting conditions
(flu and colds).
 Definition of Meningitis

* A general name for inflammation of:

a) Meninges:
Sheaths that cover brain and spinal cord

b) Cerebrospinal fluid:
Fluid that circulates in the spaces
in and around brain and spinal cord

* Meningitis can be caused by:

infectious or non-infectious agents

* Infectious agents include:

bacteria, viruses, fungi, protozoa
and rickettsia.
 Causes of Meningitis
 Bacterial Infections

 Viral Infections

 Fungal Infection

 Mycobacterium tuberculosis

 Trauma to head or spine

 Causes of Meningitis (cont.)

Most common causes of meningitis are:

a) Bacterial infections (Septic meningitis)

may result in death or brain damage.

b) Viral infections (Aseptic meningitis)

usually resolve without treatment.
 Bacterial Meningitis (Septic Meningitis)

- Pneumococcal, Streptococcus pneumoniae (38%)

- Meningococcal, Neisseria meningitidis (14%)

- Haemophilus influenzae (4%)

- Staphylococcal, Staphylococcus aureus (5%)

- Tuberculous, Mycobacterium tuberculosis

 Symptoms of meningitis
Adults and children

Babies
Neonates and the elderly often present atypically
 Neisseria Meningitidis
(Meningococci)
*Meningococcus: The causative organism of epidemic
cerebrospinal meningitis.

* Aerobic gram-negative diplococci.

*13 serogroups based on polysaccharide capsule.

*Most invasive disease caused by:

serogroups A, B, C, Y, and W-135.
 Pathogenesis Of Meningococcal
Meningitis
* Organism colonizes membranes of nasopharynx.

* Organism may reach blood stream producing

meningococcemia, the symptoms may be like
upper respiratory tract infection.

* Meningococcemia may occur with or without

meningitis.

* Meningitis is the most common complication of

meningococcemia.
 Clinical Features Of Meningococcal
Meningitis
* Transmission: respiratory droplets

* Incubation period: 3-4 days

* Clinical Features
- Fever

- Vomiting

- Headache

- Stiff neck

- Hypotension, and rash

 Meningococcal Disease Laboratory Diagnosis

Specimen:

- Cerebrospinal fluid (CSF)

. Fluid usually collected from
arachnoid space.
. A sterile needle is
inserted between 4th and 5th

lumbar vertebrae and the CSF

is allowed to drip into a dry

sterile container

- Blood
 CSF
Appearance Cells (WBC’s) Protein Glucose
Normal CSF Clear colorless Below 5x106/l 15-40mg% 45-72mg%

Pyogenic Purulent/cloudy usually many High very low

Bacterial pus cells
Meningitis

Viral Clear/slightly Raised Normal or usually

Meningitis turbid lymphocytes increased

Tuberculosis Clear/slightly Raised High reduced

Meningitis turbid lymphocytes
 Meningococcal Disease
Laboratory Diagnosis
 Bacterial culture
on chocolate agar in 5-10% CO2

 Gram stain:
Gm –ve diplococci intracellular in pus

 Blood culture: give positive results

 Detection of meningococcal polysaccharide

antigens in CSF

 PCR test for detection of meningococcal DNA in

blood or serum
Neisseria Meningitidis Management

* Penicillin G is drug of choice for patients

* Chloramphenicol and cephalosporins for:

- persons allergic to penicillin or

- strain is resistant to penicillin

* Chemoprophylaxis for contacts:

- Rifampicin, orally twice daily for 2 days
- Ciprofloxacin as a single oral dose
 Vaccination For Meningitis
- A polyvalent vaccine from the capsular
polysaccharide of groups A, C, Y and
W-135 strains.

- The vaccine does not include group B

polysaccharide.
 Viral Meningitis (Aseptic meningitis)
 Etiological Agents:
 Enteroviruses, most common (Coxsackie and Echovirus)
 Adenovirus
 Arbovirus
 Measles virus
 Herpes Simplex virus
 Varicella Zoster virus

 Modes of transmission:
 Primarily from person to person
 Arthopod vectors for Arboviruses

 Incubation Period:
 Enteroviruses 3-6 days
 Arboviruses 2-15 days

Most patients recover completely on their own

Tetanus
 Introduction
* Tetanus (Greek Word) Tetanos means to contract

* Tetanus is an acute, often fatal, disease caused by:

An exotoxin produced by Clostridium tetani

* Toxins are produced with growth of bacteria.

* Tetanospasmin toxin:
- Estimated human lethal dose (2.5 ng/kg).
 Clostridium tetani
* Clostridium tetani:
- Anaerobic gram-positive bacilli
- Spore-forming bacteria
* It is characterized by:
. Generalized rigidity
. Convulsive spasms of skeletal muscles
. Muscle stiffness of jaw and neck
(lockjaw)

* It is prevented by immunization with

tetanus toxoid
 Reservoir Of Cl. Tetani
* Spores of Cl. tetani are found in soils and animal
feces.

* Spores are very resistant to: - heat

- radiation
- chemicals
- drying

* Spores can survive for a long time in environment

(months or years)
 Mode Of Transmission
Transmission by: contaminated wounds

- Surgical wounds

- Deep puncture wounds

- Crush wounds

- Burns

- Dental infection

- Animal bites

- Delivery or abortion
 Pathogenesis Of Tetanus

At wound, blood supply to tissues decreases.

Cl. tetani spores germinate into active vegetative

cell that grows and produces

Tetanospasmin toxin
 Pathogenesis (cont’d)
* Tetanospasmin is a lethal neurotoxin.

* It Induces spastic paralysis by:

inhibiting release of inhibitory neurotransmitters

which lead to uncontrolled muscle contractions

(spastic paralysis)
 Clinical Picture of Tetanus
* Lock jaw:
Convulsive muscle contractions of the jaw

* Opisthotonos:
Extension of lower extremities, flexion of
upper extremities and arching of the back.

* Neck rigidity

* Death
Heart or respiratory failure
 Diagnosis of Tetanus
* Tetanus is suspected upon exposure to a bite or a
wound.

* Diagnosis depends on:

Clinical findings and history.

* Because Cl. tetani exhibits such sensitivity to O2

it is very difficult to recover and/or grow from clinical

specimens.
 Treatment of Tetanus

* Antitoxin is administered

* Muscle relaxants

* Supportive therapy (ventilator)

* Cleansing of the wound

 Prevention of Tetanus
* A highly effective vaccine is available.

* Tetanus immunity is achieved using:

- A formalized tetanus toxoid.
- Toxoid is administered as part of DTP vaccine

* Boosters every 10 yrs.

Botulism
 Microbiology
 Clostridium botulinum:
• Large, anaerobic Gram-positive bacilli

• Spore-forming

• Rarely infects humans

• Produces potent neurotoxin

- 7 types (A-G)
- Types A, B, E are the most common
 Botulism
* Cl. botulinum spores widespread in:
- soil
- contaminated vegetables
- meat and fish

* Canned or preserved foods

(without adequate sterilization)
- Spores survive and germinate in
anaerobic environment
- Formation of toxin
 Pathogenesis
 Botulinus toxin is ingested; absorbed from gut
into blood.

 It acts on peripheral nerve synapses by

blocking release of acetylcholine.

 It affects motor and autonomic nervous

system.

 If the organism is ingested by infants, it

multiplies in gut and produce toxin, causing
infant botulism.
 Clinical Features
 Incubation: 12-72 hours

 Classic syndrome
• Acute symmetric cranial nerve palsies
- Blurry vision, ptosis, dysphasia

• Descending flaccid paralysis

 Complete skeletal muscle paralysis

 Respiratory failure

• Autonomic: urinary retention

• Normal mentation
 Diagnosis
* Diagnosis of botulism is mainly clinical

* Laboratory confirmation

• Specimens: Contaminated food

Patient's serum

• ELISA
 Treatment
* Supportive care:
- Mechanical ventilation

* Passive immunization (antitoxin)

- Trivalent antitoxin (Types A, B and E
toxins).
Complications:
- Serum sickness (9 %)
- Anaphylaxis (2 %)
Rabies
 Rabies Virus
 Rabies is an acute infection of
the CNS which is fatal. The main
animals involved are dogs, foxes
and bats.
 Pathogenesis
 It is transmitted by the bite of a rabid
animal, usually a dog.
 Following inoculation, the virus replicates
in the striated or connective tissue at the
site of inoculation and enters the
peripheral nerves through the
neuromuscular junction.
 It then spreads from the peripheral nerves
to the CNS.
 Terminally, there is widespread CNS
involvement but few neurons infected with
the virus show structural abnormalities.
 Laboratory Diagnosis
 Histopathology - Negri bodies are diagnostic of
rabies.
 Rapid virus antigen detection - The Direct
Fluorescent Antibody test (DFA) is commonly
used in which corneal impressions or neck skin
biopsy are taken.
 Virus cultivation - The most definitive means of
diagnosis is by virus cultivation from saliva and
infected tissue.
 Virus cultivation can be done using cell cultures
or more commonly, the specimen is inoculated
intra-cerebrally into infant mice.  
 Serology - circulating antibodies appear slowly
but they are usually present by the time of onset
of clinical symptoms.
Negri Body in neuron cell (left) and
Positive DFA test (right).
Management and Prevention
 Pre-exposure prophylaxis - Inactivated
rabies vaccine is given to persons at
increased risk of rabies e.g. vets, animal
handlers, laboratory workers etc.
 Post-exposure prophylaxis - In cases of
animal bites, dogs and cats in a rabies
endemic area should be held for 10 days
for observation.
 If signs develop, they should be killed and
their tissues examined.
 Post-exposure Prophylaxis
 Wound treatment - surgical debridement should
be carried out.
 Passive immunization - human rabies
immunoglobulin is given around the area of the
wound and an i.m. dose to confer short term
protection.
 Active immunization - The human diploid cell
vaccine is usually administered into the deltoid
region, and 5 doses are usually given.
 Combined treatment with rabies immunoglobulin
and active immunization is much more effective
than active immunization alone.
 Rabies Vaccines
 The vaccines which are available for
humans are inactivated whole virus
vaccines.
• Nervous Tissue Preparation
• Duck Embryo Vaccine
• Human Diploid Cell Vaccine (HDCV)
 Control of Rabies
 Canine rabies accounts for more than
99% of all human rabies. Control
measures against canine rabies
include;
• Stray dog control.
• Vaccination of dogs.
• Quarantine of imported animals.