Central nervous system infections

Meningitis
Encephalitis
Brain abscess
CNS diseases
 Learning objectives
• NB2.8: Apply knowledge of anatomy, physiology, and biochemistry to understand infections of the
central nervous system and their clinical manifestations, characteristics of causal pathogens,
epidemiological features, pathogenesis, laboratory diagnoses, antimicrobials for treatment, and
preventive measures.
• Given a clinical scenario, students should be able to:
• NB2.8.1 Recognize the normal anatomical, physiological, immunological defenses of the CNS, and
conditions that can compromise or disrupt the defense mechanisms.
• NB2.8.3 Identify the host factors that may increase the risk of CNS infections.
• NB1.4.7. Recognize the structure of the choroid plexus and the arachnoid granulations, and their role
in the formation and reabsorption of cerebral spinal fluid (CSF).
• NB1.4.8. Differentiate communicating and non-communicating hydrocephalus in terms of CSF
circulation
• NB1.4.2. Distinguish the coverings of the brain and the spinal cord—dura mater, arachnoid mater, pia
mater.
• NB1.4.3. Identify the epidural, subdural, and subarachnoid meningeal spaces.
• NB1.3.1. Distinguish the ultrastructure of neurons and their morphological and functional
classifications.
• FO1.30.2. Recognize the molecular components of cell-cell and cell-matrix interactions.
 CNS INFECTIONS
Most infections are acute, life threatening requiring prompt treatment
and diagnosis, sub acute and chronic infections are also seen.

The cerebrum,
cerebellum, Brain enclosed in a tight
brainstem, spinal box, no room for expansion
cord, and their
covering
membranes
Infections of the CNS are
(meninges)
relatively uncommon—
constitute the CNS
several anatomic barriers
prevent the entry of
microorganisms
By Mark D. Shen - Shen MD. Cerebrospinal fluid and the early brain development of autism. J Neurodev Disord.
2018;10(1):39. Published 2018 Dec 13. https://dx.doi.org/10.1186%2Fs11689-018-9256-7, CC BY 4.0,
https://commons.wikimedia.org/w/index.php?curid=79736902
Caption
Ependymal cells are joined with gap
junctions, and CSF communicates relatively
freely with interstitial fluid. Blue fluid
indicates the fluid inside the Brain Barrier.

Caption
Figure 2. blood-cerebrospinal fluid (CSF)
barrier. The choroid plexus has fenestrated
capillaries. Nevertheless, the apical side of
choroid plexus epithelium is tightly
connected with tight junctions, making the
blood-CSF barrier (BCSFB).
 What is the Blood
brain barrier and why
is it important? • Tight junctions of the endothelium
Capillaries of brain
less permeable
and spinal cord
• Limited permeability forms a
differ from those
physiological barrier blood brain
in other regions
barrier

Well developed in adults

99% of adults with

bacteremia do not develop Weak in neonates and infant
meningitis
1/3 of infants with bacteremia
develop meningitis

Blood brain barrier

 Central nervous system infections are categorized depending on where they occur

MENINGITIS: infection of the meninges ENCEPHALITIS: diffuse infection of brain

surrounding the brain and spinal cord and parenchyma
the subarachnoid space

Meningoencephalitis: meninges and parenchyma

MYELITIS: infection of the spinal

cord

PARAMENIGEAL: localized infections besides meninges

•BRAIN ABSCESS: focal infection of the brain parenchyma
•SUBDURAL ABSCESS: beneath duramater; between duramater and arachnoid
•EPIDURAL ABSCESS: immediately outside the duramater
Routes for microbial invasion of the meninges How do microbes reach the CNS ?
Microbes reach meninges/parenchyma via

1 Inhalation – respiratory/olfactory

2 Ingestion - Gastrointestinal

Hematogenous- following systemic infection

3 of the blood- cross the blood brain barrier
(infection of cells/ tissues)

4 Direct traumatic inoculation ( mostly bacteria)

Local extension: from contiguous sites,

5 sinuses, middle ear

6 Peripheral nerves: Rabies, Herpes

 Local extension: from contiguous sites,
5 sinuses, middle ear
 Neuronal damage

6 Peripheral nerves: Rabies, Herpes

Neurotropic viruses may enter the CNS through

retrograde axonal transport.

These pathogens infect the peripheral nerve

that creates a link from the skin and the mucosa
to the sensory, motor, and olfactory neurons.

In neuronal cells, viruses can replicate and infect

adjacent cells.
 Neuronal damage

Pathogens trigger a cascade of

inflammatory responses (increased levels of
cytokines (IL-1,IL-6,IL-8, TNF-alpha, type 1
interferons) for example) that disrupt the
BBB, activate microglia, and lead to a
subsequent clustering around neuronal
cells, resulting in neuronal damage.
 Neuronal damage

Neuronal damage caused by:

• Infection leading to direct injury of
neuronal glia (astrocytes and
oligodendrocytes) by infectious agent

• Indirectly through toxins

• Inflammatory mechanisms
• Immune mediated mechanism
Neuronal damage
 Mechanisms used by pathological agents to cross the BBB

In various neurological diseases, the BBB is damaged, which favors

the entry of pathogens into the brain through the bloodstream.

The transport of pathogens to

Direct crossing - when cells of CNS favored by inflammation, -
Trojan horse
monocyte- typically observed in
macrophage/microglia lineage Paracellular
neurological disorders.
are infected by the pathogens During the inflammation
transcellular
and carry them through the process, inflammatory
BBB, reaching the CNS. molecules are released,
Mechanism called "Trojan triggering the activation of
horse" because the infected leukocytes.
microorganism eludes the The postcapillary venule is
immune system defense by attacked by the infected
using these cells to move from leukocytes, which encircle the
the bloodstream to the brain. endothelial and parenchyma
basement membranes.
Another mechanism used by pathological agents is Next, these cells enter the CNS
to impair the BBB and reach the CNS directly, using by crossing the leaky BBB.
the porous capillaries of the choroid plexus.
 Learning objectives

• NB2.8.2 Recognize infectious diseases of the CNS based on their clinical manifestations and the affected
tissues.

• Additional reading: The Big Picture Medical Microbiology, Neil. R. Chamberlain; Lange; Section 2 Central
Nervous System: Chapters 6,7,8.
• Chapter 28. The Central Nervous system; Section: Infections. Robbins 8th edition
 CNS INFECTIONS

Encephalitis Slow virus

diffuse infection Prion
Meningitis Toxin diseases
of brain Localized disease
infection of the mediated • SSPE
parenchyma infections
meninges and the • Tetanus
Brain abscess
subarachnoid • Botulinum
(bacterial)
space including the
Encephalitic (focal infections of
brain stem and
syndromes the brain
spinal cord
parenchyma
enclosed in a
capsule)

Meningitis syndromes Toxoplasmosis

meningoencephalitis Neurocysticercosis

Brain stem and spinal cord

 Fever
Meningitis

Signs &
symptoms

Classical
triad
Neck stiffness
Headache
Nuchal rigidity
Encephalitis
Fever

Headache

Altered Mental status

Signs &
Focal neurological signs
symptoms Neck
Behavior changes
Classical stiffness
Abnormal reflexes triad
Partial loss of movement
Nuchal
rigidity
Seizures

Papilledema