CNS INFECTIONS, VIRAL HEPATITIS
CNS INFECTIONS
GENERAL OVERVIEW
SYMPTOMS
The CNS infections are life-threatening problems associated with high mortality and morbidity. The
presentation may be acute, subacute, or chronic. In case of an acute CNS infection, it is required to
promptly recognise the patient with an acute CNS infection
syndrome, to rapidly initiate appropriate empiric therapy, to
identify the aetiological agent, adjusting therapies, and to optimise
management of complicating features rapidly and specifically.
At the beginning the typical symptoms are:
• Fever.
• Headache.
• Altered mental status: lethargy to come.
• Meningismus, neck stiffness.
• Increased intracranial pressure: it is associated with other
symptoms, which are:
Papilledema.
Nausea/vomiting.
Abducens palsies.
Bulging fontanelles: it is observed in infants.
EXAMINATION
The exams that should be addressed in case of suspected CNS infection are:
• Mental status assessment.
• Cranial nerve and fundoscopic exam.
• Meningeal signs assessment: it is evaluated through
different exams, which are:
Nuchal rigidity: it may be present as resistance
to passive flexion of the neck.
Kerning’s sign: it is elicited by flexing the thigh
and knee while the patient is supine; in case of
meningitis there is resistance to extension of
the leg and knee.
Brudzinski’s sign: it is positive when passive
flexion of the neck causes the flexion of the
hips and knees.
• General exams (e. g. rashes, lymphadenopathy).
• Labs: blood culture and CSF analysis.
• Radiology: CT with contrast in case of masses, no contrast medium if no focal signs.
CSF ANALYSIS
LUMBAR PUNCTURE (LP)
The lumbar puncture (LP) is the most important test that should be performed in case of CNS
infection. It is contraindicated in case of the presence of a mass or if epidural spinal abscess is
suspected. It is performed with the patient positioned in the left lateral decubitus or in a sitting
position. Then, the area that will be perforated is sterilised. The needle is inserted between the L3-L4
or L4-L5 interspace.
,The lumbar puncture, however, may be a cause infection, and even of superinfection. It is a rare
condition (1:50,000). For that reason, it is suggested to give patient antibiotic prophylaxis after lumbar
puncture, typically ceftriaxone.
The cerebrospinal fluid that is
collected from LP is inserted
within four vials, which are:
• Tube 1: it is used to
measure glucose and
protein.
• Tube 2: it is used to
measure cell count and
differential cell count.
• Tube 3: it is used to
perform microbiological examination, which are Gram stain, routine culture, Cryptococcal
antigen search, stain, and culture, VDRL, and PCR; FilmArray is available for most common
bacteria, viruses, and fungi causing CNS infection.
• Tube 4: it is collected in case of negativity in the tube 3; this is stored in the lab, and it will be
used only in case of negativity of tube 3.
BIOCHEMICAL EXAMINATION
The CSF characteristics varies depending on the type of pathogen that is causing the CSF infection.
Four main possibilities can arise, which are:
• Bacterial infections: they are characterised by:
Opening pressures: elevated.
Glucose: low due to consumption.
Protein: very high.
RBC: absent.
WBC: >200mm3.
Differential cell count: PMNs.
• Viral infections: they are characterised by:
Opening pressures: slightly elevated.
Glucose: normal.
Protein: normal.
RBC: none.
WBC: <200mm3.
Differential blood count: lymphocytes and monocytes.
• Fungal infections: they are characterised by:
Opening pressures: normal to high.
Glucose: low due to consumption.
Protein: high.
RBC: absent.
WBC: <50mm3.
Differential cell count: lymphocytes and monocytes.
• TB infections: they are characterised by:
Opening pressures: usually high.
Glucose: low due to consumption.
Protein: high.
RBC: absent.
WBC: 20-30mm3.
Differential cell count: lymphocytes and monocytes.
,Therefore, the biochemical components help to differentiate the types of CNS infection, and it
provides a possible diagnosis before the culture results arrive.
The CSF analysis requires enough volume of this fluid, otherwise tests may result negative. Beware of
diabetic patients in which glucose level is 2/3 of the serum glucose. Moreover, a high CSF protein levels
make CSF yellow (i. e. xanthochromic).
Together with CSF even blood culture should be performed. There are some bacteria that can be
isolated from blood but not from CSF. This should be carried out always before beginning the empiric
therapy.
EXAM BACTERIAL VIRAL FUNGAL TB
Opening
Elevated Low Normal to high Usually high
pressures
Glucose Low Normal Low Low
Protein Very high Normal High High
RBC Few None None None
WBC >200mm3 <200mm3 <50mm3 20-30mm3
Lymphocytes and Lymphocytes and Lymphocytes and
Differential PMNs
monocytes monocytes monocytes
BACTERIAL MENINGITIS
TYPES AND AETIOLOGY
The most common bacterial pathogens causing meningitis are:
• Streptococcus pneumoniae.
• Haemophilus influenzae: it is common in
developing countries in which vaccine is
not available.
• Listeria monocytogenes: it affects mainly
young children (in-utero infection) and
immunocompromised elderly patients.
• Group B streptococcus.
• Neisseria meningitidis.
The chronic meningitis from
immunocompromised host is caused by other
pathogens, which are:
• Cryptococcus neoformans.
• HIV.
• M. tuberculosis.
• M. avium.
• Carcinomatous meningitis: it is caused by brain metastasis (e. g. lung cancer, breast cancer).
The acute meningitis occurs in case of bacterial meningitis, meningoencephalitis, brain abscess,
subdural empyema, epidural abscess, and septic venous sinus thrombophlebitis.
ROUTES OF CONTAMINATION
The methods of contamination of CNS infection can be of three types, which are:
• Haematogenic route: it can be either arterial or venous; the arterial route is the most
common route of CNS contamination, while the venous route is rarer (observed in
schistosomiasis and thrombophlebitis).
, • Damage via contiguity: it is the second most common route of CNS contamination; it may
come from infection of the face (e. g. sinusitis), of the petrous bone (e. g. otitis), which causes
a transosseous infection,
leading to either an
intracerebral abscess or a
pericelebral collection; the
source of the lesion is mainly
frontal or temporal.
• Neuronal route: it is less
common, and it is responsible
for some types of
encephalitis, such as herpes
simplex, varicella, and rabies
encephalitis; it also explained
damages of cranial nerve
nuclei in listeriosis.
The direct contamination is an even rarer condition, which may occur in case of cranial or vertebral
wound, or after intracranial surgery. Unknown contamination accounts 20% of cases.
DIAGNOSIS
APPROACH TO SUSPECTED MENINGITIS
The approach to the patient with suspected meningitis is based on an immediate lumbar puncture.
Since CNS infections are life-threatening decision-making must be done within 30 minutes, as well as
the clinical assessment. After the LP, CSF analysis should be up
after 1-2h (usually 3h), while cultures require longer time (24-
48h).
The presentation of CNS infection can be classified as acute
(symptoms duration <24h), subacute (<7 days), and chronic (>4
weeks).
During the evaluation of the patient’s clinical status, the physician
may notice a rash, which is a sign of meningococcal infection. In
this condition, prophylactic measures should be performed,
which should be isolation of the patient and of individuals that
enter in contacted with him, antibiotic prophylaxis, and meningococcal vaccination for individuals
entered in contact.
CSF STUDIES AND CULTURE
The CSF studies, as said before, are based on colour-clarity, cell count, chemistry (protein, glucose),
stains, culture, and antigen screen/PCR. The Gram staining is positive in 60%-90% of patients with
untreated bacterial meningitis.
With a prior antibiotic therapy,
the positivity is decreased to 40%-
60%, and therefore antibiotic
therapy should be started after
CSF collection. Note that positive
Gram staining is associated with
heavy organism burden and
worse prognosis.
The CSF profile helps clinicians in making a diagnosis before the culture results. Indeed, based on the
glucose, protein levels, and cell count it is possible to differentiate bacterial, viral, fungal, and TB
infections.
CNS INFECTIONS
GENERAL OVERVIEW
SYMPTOMS
The CNS infections are life-threatening problems associated with high mortality and morbidity. The
presentation may be acute, subacute, or chronic. In case of an acute CNS infection, it is required to
promptly recognise the patient with an acute CNS infection
syndrome, to rapidly initiate appropriate empiric therapy, to
identify the aetiological agent, adjusting therapies, and to optimise
management of complicating features rapidly and specifically.
At the beginning the typical symptoms are:
• Fever.
• Headache.
• Altered mental status: lethargy to come.
• Meningismus, neck stiffness.
• Increased intracranial pressure: it is associated with other
symptoms, which are:
Papilledema.
Nausea/vomiting.
Abducens palsies.
Bulging fontanelles: it is observed in infants.
EXAMINATION
The exams that should be addressed in case of suspected CNS infection are:
• Mental status assessment.
• Cranial nerve and fundoscopic exam.
• Meningeal signs assessment: it is evaluated through
different exams, which are:
Nuchal rigidity: it may be present as resistance
to passive flexion of the neck.
Kerning’s sign: it is elicited by flexing the thigh
and knee while the patient is supine; in case of
meningitis there is resistance to extension of
the leg and knee.
Brudzinski’s sign: it is positive when passive
flexion of the neck causes the flexion of the
hips and knees.
• General exams (e. g. rashes, lymphadenopathy).
• Labs: blood culture and CSF analysis.
• Radiology: CT with contrast in case of masses, no contrast medium if no focal signs.
CSF ANALYSIS
LUMBAR PUNCTURE (LP)
The lumbar puncture (LP) is the most important test that should be performed in case of CNS
infection. It is contraindicated in case of the presence of a mass or if epidural spinal abscess is
suspected. It is performed with the patient positioned in the left lateral decubitus or in a sitting
position. Then, the area that will be perforated is sterilised. The needle is inserted between the L3-L4
or L4-L5 interspace.
,The lumbar puncture, however, may be a cause infection, and even of superinfection. It is a rare
condition (1:50,000). For that reason, it is suggested to give patient antibiotic prophylaxis after lumbar
puncture, typically ceftriaxone.
The cerebrospinal fluid that is
collected from LP is inserted
within four vials, which are:
• Tube 1: it is used to
measure glucose and
protein.
• Tube 2: it is used to
measure cell count and
differential cell count.
• Tube 3: it is used to
perform microbiological examination, which are Gram stain, routine culture, Cryptococcal
antigen search, stain, and culture, VDRL, and PCR; FilmArray is available for most common
bacteria, viruses, and fungi causing CNS infection.
• Tube 4: it is collected in case of negativity in the tube 3; this is stored in the lab, and it will be
used only in case of negativity of tube 3.
BIOCHEMICAL EXAMINATION
The CSF characteristics varies depending on the type of pathogen that is causing the CSF infection.
Four main possibilities can arise, which are:
• Bacterial infections: they are characterised by:
Opening pressures: elevated.
Glucose: low due to consumption.
Protein: very high.
RBC: absent.
WBC: >200mm3.
Differential cell count: PMNs.
• Viral infections: they are characterised by:
Opening pressures: slightly elevated.
Glucose: normal.
Protein: normal.
RBC: none.
WBC: <200mm3.
Differential blood count: lymphocytes and monocytes.
• Fungal infections: they are characterised by:
Opening pressures: normal to high.
Glucose: low due to consumption.
Protein: high.
RBC: absent.
WBC: <50mm3.
Differential cell count: lymphocytes and monocytes.
• TB infections: they are characterised by:
Opening pressures: usually high.
Glucose: low due to consumption.
Protein: high.
RBC: absent.
WBC: 20-30mm3.
Differential cell count: lymphocytes and monocytes.
,Therefore, the biochemical components help to differentiate the types of CNS infection, and it
provides a possible diagnosis before the culture results arrive.
The CSF analysis requires enough volume of this fluid, otherwise tests may result negative. Beware of
diabetic patients in which glucose level is 2/3 of the serum glucose. Moreover, a high CSF protein levels
make CSF yellow (i. e. xanthochromic).
Together with CSF even blood culture should be performed. There are some bacteria that can be
isolated from blood but not from CSF. This should be carried out always before beginning the empiric
therapy.
EXAM BACTERIAL VIRAL FUNGAL TB
Opening
Elevated Low Normal to high Usually high
pressures
Glucose Low Normal Low Low
Protein Very high Normal High High
RBC Few None None None
WBC >200mm3 <200mm3 <50mm3 20-30mm3
Lymphocytes and Lymphocytes and Lymphocytes and
Differential PMNs
monocytes monocytes monocytes
BACTERIAL MENINGITIS
TYPES AND AETIOLOGY
The most common bacterial pathogens causing meningitis are:
• Streptococcus pneumoniae.
• Haemophilus influenzae: it is common in
developing countries in which vaccine is
not available.
• Listeria monocytogenes: it affects mainly
young children (in-utero infection) and
immunocompromised elderly patients.
• Group B streptococcus.
• Neisseria meningitidis.
The chronic meningitis from
immunocompromised host is caused by other
pathogens, which are:
• Cryptococcus neoformans.
• HIV.
• M. tuberculosis.
• M. avium.
• Carcinomatous meningitis: it is caused by brain metastasis (e. g. lung cancer, breast cancer).
The acute meningitis occurs in case of bacterial meningitis, meningoencephalitis, brain abscess,
subdural empyema, epidural abscess, and septic venous sinus thrombophlebitis.
ROUTES OF CONTAMINATION
The methods of contamination of CNS infection can be of three types, which are:
• Haematogenic route: it can be either arterial or venous; the arterial route is the most
common route of CNS contamination, while the venous route is rarer (observed in
schistosomiasis and thrombophlebitis).
, • Damage via contiguity: it is the second most common route of CNS contamination; it may
come from infection of the face (e. g. sinusitis), of the petrous bone (e. g. otitis), which causes
a transosseous infection,
leading to either an
intracerebral abscess or a
pericelebral collection; the
source of the lesion is mainly
frontal or temporal.
• Neuronal route: it is less
common, and it is responsible
for some types of
encephalitis, such as herpes
simplex, varicella, and rabies
encephalitis; it also explained
damages of cranial nerve
nuclei in listeriosis.
The direct contamination is an even rarer condition, which may occur in case of cranial or vertebral
wound, or after intracranial surgery. Unknown contamination accounts 20% of cases.
DIAGNOSIS
APPROACH TO SUSPECTED MENINGITIS
The approach to the patient with suspected meningitis is based on an immediate lumbar puncture.
Since CNS infections are life-threatening decision-making must be done within 30 minutes, as well as
the clinical assessment. After the LP, CSF analysis should be up
after 1-2h (usually 3h), while cultures require longer time (24-
48h).
The presentation of CNS infection can be classified as acute
(symptoms duration <24h), subacute (<7 days), and chronic (>4
weeks).
During the evaluation of the patient’s clinical status, the physician
may notice a rash, which is a sign of meningococcal infection. In
this condition, prophylactic measures should be performed,
which should be isolation of the patient and of individuals that
enter in contacted with him, antibiotic prophylaxis, and meningococcal vaccination for individuals
entered in contact.
CSF STUDIES AND CULTURE
The CSF studies, as said before, are based on colour-clarity, cell count, chemistry (protein, glucose),
stains, culture, and antigen screen/PCR. The Gram staining is positive in 60%-90% of patients with
untreated bacterial meningitis.
With a prior antibiotic therapy,
the positivity is decreased to 40%-
60%, and therefore antibiotic
therapy should be started after
CSF collection. Note that positive
Gram staining is associated with
heavy organism burden and
worse prognosis.
The CSF profile helps clinicians in making a diagnosis before the culture results. Indeed, based on the
glucose, protein levels, and cell count it is possible to differentiate bacterial, viral, fungal, and TB
infections.
