Central Nervous System (CNS) Infections

Bacterial infections

Acute bacterial meningitis Chronic meningitis Tubercular meningitis Cryptococcosis Fungal meningitis Syphilitic meningitis

Amoebic meningitis

     

Acute Bacterial meningitis

• The cerebrum, cerebellum, brain stem, spinal cord and their covering membrane (meninges) constitute The central Nervous System (CNS)

• One specialized defense mechanism of the CNS is the blood-brain barrier (BBB).

• BBB serve to minimize passage of infectious agents and toxic metabolites into the cerebrospinal fluid ( CSF) and tissues

• BBB also regulate the rate of transport of plasma proteins, glucose and electrolytes.

• When CNS infection develops, the BBB poses difficulties in control                                                                                             

Overview

CSF Flow

• Within the brain are ventricles, which are cavities in which CSF is actively produced

• CSF is produced by choroid plexuses, the CSF fills the lateral ventricles in each half of the brain

• CSF circulates into the third ventricle, and then through cerebral aqueduct and to the 4th ventricles and then to the subarachnoid space (SAS) over the entire CNS including the spinal cord

• It is reabsorbed by venous system in the meninges

Bacterial meningitis in patients with disributed BBB

Routes of infection• The disease usually begins as an infection by normal body flora, of:

1. The ear (otitis media) - Haemophilus influenzae

2. The lung (lobar pneumoniae) - Streptococcus pneumoniae

3. The upper respiratory tract (rhinopharyngitis) - Neisseria meningitidis, Haemophilus influenzae, Streptococcus, Group B

4. The skin and subcutaneous tissue (furunculosis) S. aureus

5. The bone (osteomyelitis) - S. aureus

6. The intestine - E. coli

• This localized infection develops into a bacteremia with a metastatic infection in the leptomeninges (arachnoid and pia mater),

• Traumatic surgical, or congenital lesions may give direct access

• Males are affected twice as often as females

Neonates (0-2 weeks)         Escherichia coli         Streptococcus, Group B         Staphylococcus aureus         Listeria monocytogenes         Streptococcus, Group A

Infants (½ - 3 months)         Streptococcus, Group B         Listeria monocytogenes         Escherichia coli

"Normal" Adults (6-21 years)  Neisseria meningitidis ( A, B, C, Y, and W-135)        Streptococcus pneumoniae

Etiology

Clinical symptoms

1. Infection, manifestations         a. Chills         b. Fever         c. Malaise         d. Headache         e. Myalgia

The manifestations of acute bacterial meningitis are independent of the etiological agent: They result from:    

2. Increased intracranial pressure, manifestations of which are:         a. Headache         b. Vomiting         c. Eye effects         d. Papilledema (late)         e. Full fontanelle         f. Enlarged cranium

3. Meningeal irritation        a. Stiff neck         b. Spasms of muscles         c. Nuchal rigidity         d. Opisthotonos

5. Eye effects         a. Photophobia         b. Venous congestion of ocular fundi         c. Unequal pupils         d. Pupil dilation         e. Sluggish reaction to light         f. Squint         g. Diplopia         I. Papilledema

       

       6. Mental status         a. Drowsiness         b. Delirium         c. Coma

4. Hemorrhage         a. Petechia         b. Purpura         c. Ecchymosis

Lab Diagnosis

• Examination CSF is the key to the definitive diagnosis of acute bacterial meningitis. The CSF should be examined in every patient in whom the clinical findings are consistent with even the possibility of meningitis,

Examine the CSF for: 1. Pressure 2. Clarity 3. Presence of microorganisms 4. Presence of leukocytes 5. Concentration of glucose 6. Concentration of protein    

Therapy

1. Correction of fluid and electrolyte deficits. 2. Provision for adequate oxygenation. 3. Monitoring of cardiovascular function: a. Pulse b. Arterial blood pressure c. Central venous pressure 4. Monitoring intracranial pressure -

administer urea or mannitol to reduce cerebral edema.

5. Administration of antibiotics -

Prevention

Purified polysaccharide vaccines are available for the prevention of infection by:

• Neisseria meningitidis - each dose of the multivalent vaccine provides A, C, Y and W-135 capsular polysaccharides. Effective in children over 3 months of age.

• Streptococcus pneumoniae, each dose of the multivalent vaccine provides 23 types of capsular polysaccharide covering the majority of strains causing meningitis. Recommended for children over 2 years of age.

• Streptococcus pneumoniae, each dose of the multivalent vaccine provides 7 types of capsular polysaccharide conjugated to a non-toxic diphtheria toxin. Recommended for children at 2, 4, 6 and 12 months of age.

• Haemophilus influenzae - each dose of the monovalent vaccine provides the capsular polysaccharide from serotype b organisms conjugated to a protein. Recommended for children at 2, 4, 6 and 15 months of age.

Chronic Bacterial Meningitis

Has more insidious onset, with progression of

signs and symptoms over a period of weeks

• Tubercular meningitis • Syphilitic meningitis

Clinical Picture

The patient may feel unwell, lose some weight and have no other symptoms

There may be no fever or low fever.

1. Headache - frontal, temporal or retro-orbital. Most common feature and it becomes progressively more frequent and severe.

2. Mental aberrations (from simple irritability to psychosis) 3. Motor abnormalities (altered reflexes to paralyses) 4. Cranial nerve dysfunctions (aphasia, visual disturbances, hearing

loss) 5. Cerebellar signs6. Evidence of increased intracranial pressure 7. Fever in about 1/3 of patients

Diagnosis

Best evidence is from CSF.

1. Increased CSF pressure 2. Protein is elevated 3. Glucose is decreased (45% of blood

glucose) 4. Leukocytosis (40-400/mm3 - mostly

mononuclear cells)

Radiology 

Prognosis: Almost always fatal if it goes untreated (90%

of patients die within one year).  

Treatment:Antimicrobial therapy

Viral Infection of the CNS

Viral meningitis (Aseptic meningitis)

Viral Encephalitis

Etiology of primary acute viral infections of CNS

Agent Major age group affected

Enteroviruses Infants, children

Mumps Children

Herps simplex Type-1 and type-2 Adult

Neonates, young adults

Arboviruses

West virus encephalitis

Adults

Rabies All ages

Measles Infants, children

Varicella-zoster (HSV-3) Infants and children

Lymphocytic chorimeningitis Adults, children

Epstein-Barr virus (HSV-4) Children, young adults

Other, (HIV) All ages

• Penetration of BBB may be accomplished by means of virus-laden phagocytes migrating through blood vessels of the meninges or brain or by passage of virus particles through the choroid plexus

• There is always some involvement of brain tissue so the disease is really a meningoencephalitis.

• Generally milder than bacterial or fungal meningitis and is self limiting.  

Clinical picture

The signs and symptoms of viral meningitis are variable. They may include: 1. Sudden onset 2. Intense frontal or retro-orbital headache 3. Undulating fever that never goes above 40C 4. Skin rash

At the onset of fever or shortly thereafter there is: Malaise , drowsiness Sore throat , myalgia Nausea , vomiting There may also be photophobia , tinnitus (noise in the ears) ,Vertigo , chest and abdominal pain

Nuchal rigidity develops andthere are almost always stiffness of the back and pain on flexion

Lab Diagnosis• CSF is transparent• May be slightly turbid • (<500 leukocytes/mm3),monocytes • glucose is normal • Protein is elevated. • Diagnosis requires virus isolation and serological

techniques

Prognosis • Full recovery with no sequelae

  Therapy • Bed rest, analgesic drugs, repletion and

conservation of fluids and electrolytes.

Prognosis • Full recovery with no sequelae

  Therapy • Bed rest, analgesic drugs, repletion and

conservation of fluids and electrolytes.

Rabies (hydrophobia)

  Overview: • Rabies virus is a bullet-shaped, enveloped, single

stranded RNA virus.• This is primarily a viral infection of non-human

carnivores. • Transmission to man is rare and is usually

effected through a bite. • Clinical evidence of involvement of the CNS

appears after an extremely variable period of incubation.  

Pathogenesis

Inoculation of virus through the epidermis as aresult of an animal bite. Inhalation of heavily Contaminated material, such as bat dropping

Can also cause infection

Replicates initially in muscle and then entersThe peripheral nervous system

Spread to the CNS gray matter, the Pathognomonic lesion the Negri bodies

( eosinophilic cytoplasmic inclusion Bodies)

Virus passes along the Along autonomic nervesTo reach other tissues,

Including the salivary glandsKidneys, and lungs

Diagnosis

• Where there is a history of bite by a known rabid animal and the bitten person shows typical symptoms

• The manifestations of rabies begins in man anywhere from 10-240 days after exposure. However, the incubation period is usually 30-90 days. The length of this incubation period is a function of:

1. The number of sensory nerves ending in the bitten area

2. The dose of virus 3. The severity of the bite wounds 4. The distance from the bite wound from the CNS

• Presents as acute fulminate, fatal encephalitis

• Excess motor activity, hallucination• Muscle spasm, seizures and focal

paralysis, coma

Lab diagbosis

• CSF shows minimal to no abnormalities• Lymphocytic pleocytosis (5-30 cell/mm3)• Detection of rabies antigen by

Immunofluorescent stain of a nape of neck biopsy

• Virus or antigen detected in brain tissue• Negri bodies in 80 % of cases

PROGNOSIS: • Only 4 people have ever recovered from

rabies. CNS sequelae are common.   TREATMENT: 1. Washing the wound with copious amounts of soap and

water. 2. Apply 1% quaternary ammonium compounds after all

traces of soap have been removed. 3. Apply antirabies serum by careful instillation into the wound

and by infiltration around the wound. Administer serum systemically.

4. Postpone suturing the wound. 5. Institute antitetanus procedures 6. Start administration of vaccine pending autopsy of animal

involved in the bite. Stop treatment if animal is normal.

If rabies symptoms ensue give extensive supportive care

a. Tracheostomy to prevent hypoxia  b. Careful tracheal suctioning  c. Use of supplemental oxygen d. Control focal seizures with anticonvulsant

therapy  

Vaccine Available

• Rabies vaccine • Recombinant vaccine - vaccinia virus with

rabies glycoprotein gene. (1 vaccination)

Fungal infections of the CNS

Cryptococcus neoformansCoccidioides immitis

Histoplasma capsulatumCandida speciesAspergillus speciesBlastomyces dermatitidis

Common

Uncommon

Rare

Pseudoallescheria bodiiPenicillum speciesSporothrix schenkii

Other causes of CNS infections

Parasitic infections

Trypanosoma Acanthamoeba species Naegleria fowleri Toxoplasama gondii Trichinella spiralis

Taenia solium (cysticercosis)

Findings of cerebrospinal fluid analysis: Normal versus Infection

clinical situation Leukocytes/mm3 % polymorphonuclears Glucose

% of blood

Protein mg/dl

Children & adultsNormal 0-5 0 ≥ 60 ≤ 30

Viral infection 2-2000 ≤ 50 ≥ 60 30-80

Bacterial infection 5-5000 ≥ 60 ≤ 45 ≥ 60

TB and mycoses 5-2000 ≤ 50 ≤ 45 ≥ 60

Neonates

Normal ( term) 0-32 ≤ 60 ≥ 60 20-170

Normal (preterm) 0-29 ≤ 60 ≥ 60 65-150

Case presentation # 1

A 3-year-old male with recent history of acute otitis media presented to the emergency department. Upon examination, he was febrile to 39.50C and lethargic. No evidence of a rash was present. His vaccination was history was up to date. Laboratory studies included a complete blood count, which showed leukocytosis with a total leukocyte count of 21,000/ml. A lumber puncture produced cloudy CSF with a cell count of 210 leukocytes/mm3 with 85% neutrophils. The CSF glucose was decreased, and the CSF protein was elevated. The child received IV antibiotics, and the CSF sample was sent to the microbiology Laboratory for CSF Gram stain and culture. CSF smear showed moderate intracellular Gram-positive cocci in pairs. Subsequent culture of the CSF grow a mucoid strain of Strep. pneumo

Case presentation # 2

A 2-years unvaccinated child was seen in the emergency room with headache and fever. The spinal fluid was sent to the lab for culture and sensitivity. The Gram stain showed many white blood cells and many Gram-negative rods (small)

Case presentation # 3

A 52 years-old male arrived at an emergency room in a disoriented and poorly responsive state with difficult breathing. The patient’s history included poorly controlled diabetes and chronic obstructive pulmonary disease secondary to cigarette smoking. Current medications included steroids his pulmonary disease. Physical examination showed that the patient was slightly febrile, lethargic, and in respiratory failure. He showed deteriorating mental status, and a diagnosis of meningitis was considered . A lumber tap produced a CSF sample that on direct smear using calcofluor reagent showed encapsulated budding yeast. Despite aggressive therapy with amphotericin B and 5-flucytosine, the patient’s condition failed to improve. The patient died on the third day of hospitalization.