Infections of the Central nervous system

Question 1

Homeostasis: CNS

Answer 1

The meninges and CSF: The meninges, whether cranial or spinal, consist of three layers: dura mater, arachnoid mater and pia mater. Between the arachnoid and the pia mater is the subarachnoid space, in which cerebrospinal fluid circulates. The CSF is vulnerable to contamination by microbes carried in the blood that are able to penetrate the blood-brain barrier at the walls of the blood vessels.

Some of the most devastating infectious diseases are those that affect the nervous system, especially the brain and spinal cord. Damage to these areas can lead to deafness, blindness, learning disabilities, paralysis and death.
Because of the crucial importance of the nervous system, it is strongly protected from accident and infection by bone and other structures. Even pathogens that are circulating in the bloodstream cant usually enter the brain and spinal cord because of the blood-brain barrier. Occasionally, some trauma will disrupt these defenses with serious consequences. The CSF is especially vulnerable because it lacks many of the defenses found in the blood. Pathogens capable of causing diseases of the nervous system often have special virulence characteristics that enable them to penetrate these defenses.

Question 2

Key Messages: CNS

Answer 2

Blood brain barrier
CSF is vulnerable
Meningitis = inflammation of the meninges
Encephalitis = is inflammation of the brain

Question 3

Lumbar puncture

Answer 3

Diseases affecting the CNS, such as meningitis, often require a spinal tap for diagnosis. A needle is inserted between two vertebrae in the lower spine. A sample of CSF, which is contained in the subarachnoid space is withdrawn for laboratory examination.

Question 4

CSF Analysis

Answer 4

In meningitis, bacteria use up glucose and excrete protein, therefore you see a decrease in CSF glucose values and an increase in protein levels.
Polymorphonuclear cells are neutrophils which in excess indicate a bacteria infection
Lymphocytes or monocytes = viral or chronic inflammation

Question 5

A Petechial Rash

Answer 5

What is a petechial rash and what was the cause in this case? Petechiae are small (1-2mm) red or purples spots on the skin caused by a minor bleed (from broken capillary blood vessels . In meningococcal disease, Neisseria meningitidis releases endotoxin when it lyses. Endotoxin activates the Hageman factor (clotting factor XII), which causes disseminated intravascular coagulation (DIC). The DIC is what appears as a rash on the affected individual.
The development of this rash indicates widespread dissemination of the organism (meningicoccemia).
What is an easy test to distinguish a petechial rash from other forms of rash?
Glass test

Question 6

Gram stain of CSF

Answer 6

Private Williams was given a lumbar puncture from which his CSF cell count showed
white blood cells (wbc’s) at 500/mm3 ( 80% polymorphonuclear cells), the CSF glucose
was 30mg/dL and protein was 100mg/dL. A gram stain of the CSF revealed small gram-negative diplococci and numerous leukocytes

Elevated wbc count
Decreased glucose
Increased protein

Gram stain consistent with early acute bacterial meningitis caused by N. meningitidis

Question 7

Antibiotic Therapy

Answer 7

Antimicrobial therapy was started immediately with benzylpenicillin pending culture and PCR results. Twenty four hours later, the CSF culture grew N. meningitidis. The benzylpenicllin was discontinued and following 10 days of intravenous ceftriaxone therapy, Pvt Williams recovered completely.

Why was the Benzylpenicillin treatment withdrawn?

It is not the preferred antibiotic for N. meningitidis which is universally sensitive to the penicillin based Ceftriaxone

2. Benzylpenicillin is broad spectrum therefore is also withdrawn to prevent antimicrobial resistance

Question 8

Prophylactic treatment

Answer 8

What preventative treatment would you give to people in contact with the cases?
Rifampicin, Ciprofloxacin or Ceftriaxone +/- vaccine if suitable
Where in their body are the contacts likely to be carrying N. meningitidis?
Nasopharynx

Question 9

Viral meningitis

Answer 9

The CSF contained 76 wbc’s/mm3 (90% lymphocytes), 70 mg/dL of protein and 66mg/dL of glucose. The CSF cultures were negative but the enteroviral PCR returned positive 24 hours after admission. His symptoms resolved without antimicrobial therapy, and he was discharged from the hospital with a diagnosis of aseptic meningitis caused by enterovirus.

How do the CSF findings in Pvt Williams case compare with those in Pvt Jones’s case?
Bacterial meningitis is usually associated with a polymorphonuclear pleocytosis of hundreds to thousands of cells/mm3. Viral meningitis shows a lymphocytic predominance.

The CSF glucose is usually decreased in bacterial meningitis and normal in viral meningitis; the CSF protein is usually increased in bacterial meningitis and normal to mildly increased in viral meningitis.

Question 10

What else can cause meningitis and encephalitis?

Answer 10

Using your text book and your earlier brainstorm as a resource, name the microbes which can cause meningitis or encephalitis in humans? (table 61-1 Schaecter)
Bacteria:
Streptococcus pneumoniae
Neisseria meningitidis
Haemophilus influenza type b (the use of INFANRIX-hexa vaccine has significantly reduced the incidence)
Group B streptococci (babies)
Listeria monocytogenes
Escherichia coli
Mycobacterium tuberculosis
Viruses
Varicella zoster virus, adenovirus, EBV, CMV, Enteroviruses, Herpes simplex virus, Arboviruses, HIV
Fungi
Cryptococcus neoformans, Candida albicans
Parasites
Acanthamoeba from thermal hot pools, Toxoplasma, Cysticercosis