INFECTIONS OF THE CENTRAL NERVOUS

SYSTEM
Meningitis and encephalitis are neurologic emergencies.

Infections of the central nervous system either a primary event or part of systemic infection

Infection of the nervous system is different from neurological manifestations of systemic

infection by the invasion, establishment and growth of the organism in the affected part of
the nervous system.

An infection of the central nervous system may primarily

affect:

 The meninges , called meningitis.

 The brain parenchyma, called encephalitis.

 The spinal cord, called myelitis.

A patient may have more than one affected area.

The nervous system may also suffer from localized pockets of

infection.
 Within the brain tissue, there may be an abscess or cerebritis
 Outside them there may be an epidural abscess or subdural empyema.
 Localized to the venous system. There may be infected dural venous sinus
thrombosis or infectious thrombophlebitis.

The clinical presentation of central nervous system Infection

depends on:
1. Temporal profile: acute, subacute or chronic.
2. The location of infection:
Which part of the nervous system is involved?

3. The causative organism: virus or bacteria or other species (fungus, syphilis,

brucella, malaria, schistosomiasis).

Anatomical involvement and the temporal profile usually imply the

causative organism.
Page1

Page 1 of 18
 The possibility of meningitis or encephalitis should be suspected in any
severely ill patient presenting with alteration in consciousness, with or without
focal neurologic signs.

Approach to the patient with central nervous

system Infection
Step by step clinical methodology can recover the nature of the
infection and the probable organism. This can be achieved by
answering the following questions:

 What is the lesion?

Define the symptoms (the constitutional and neurological)

Determine the temporal profile.

1. Mode of onset and time course.

2. Chronologic evolution (which symptoms came first and order in which follow).
 Where is the lesion?

The anatomical site(s) involved, and is it focal, multifocal, diffuse or systemic.

This includes the primary insult and its complications.

 What are the predisposing factors?

With a patient who may have acquired an infection of the nervous system while
traveling: through which country or countries, did the patient travel? And what would
a doctor from the country or travel consider in the differential diagnosis?

Pyogenic bacterial meningitis

Bacterial meningitis is an acute purulent infection within the subarachnoid space. It is
associated with a central nervous system inflammatory reaction. The meninges, the
subarachnoid space, and the brain parenchyma are all involved in the inflammatory
reaction; as such, meningoencephalitis is the more accurate descriptive term.
The condition either occurs as a primary event or as part of systemic infection.

Predisposing factors
1. Systemic (especially upper and lower respiratory tract) and parameningeal
Page1

infection.
Page 2 of 18
 2. Mechanical defect of the meninges to the subarachnoid space.
3. Suppressed immunity.

Epidemiology
The annual incidence bacterial meningitis is between 3-5/100000 overall population. The
highest attack rate of all bacterial species is in children under 1 year of age and falls
off rapidly with increasing age.

Meningococcal meningitis may occur in epidemics.

Aetiological agents:
The agents causing bacterial meningitis vary with the age of the patient, the route by which
infection is acquired, and the presence of associated or predisposing conditions.

Many bacteria can cause meningitis but some do so more frequently

than other.

Meningitis in neonates and infants up to 3 months old is usually caused by:

1. Group B streptococci.
2. Escherichia coli.

3. Listeria monocytogenes.

Spontaneous community-acquired meningitis in pre-school children is usually caused by

1. Haemophilus influenzae.
2. Neisseria meningitides.(Meningococcus)

3. Streptococcus Pneumoniae.

In older children and adults<50 years, spontaneous community-acquired meningitis is

caused by

1. Neisseria meningitides.(Meningococcus)
2. Streptococcus pneumoniae.

In adults, greater than 50 years.

1. Streptococcus Pneumoniae.
2. Listeria monocytogenes.

Post-traumatic meningitis and neurosurgical patients.Bacteria can gain access to the

Page1

subarachnoid space.

Page 3 of 18
 1. staphylococci.
2. Escherichia coli.

3. Pseudomonas aeruginosa.

4. Streptococcus Pneumoniae.

Chronic depleting diseases and pregnency

1. Streptococcus Pneumoniae.
2. Listeria monocytogenes.

3. Pseudomonas aeruginosa.

4. Escherichia coli.

Pathology and Pathogenesis

The incubation period is only a few days.

Bacterial meningitis is usually secondary to a bacteremic illness, although infection may

result from direct spread from an adjacent focus of infection in the ear, skull fracture, or
sinus. Organisms causing spontaneous meningitis are acquired by person-to-person
spread. Colonization is followed by invasion. The nasopharynx is the probable site of
systemic invasion resulting in bacteraemic spread to the cerebrospinal fluid. The decrease
in susceptibility to infection with increasing age results from the achievement of protective
immunity, mainly through nasopharyngeal carriage.

Once in the subarachnoid space; bacteria multiply in the cerebrospinal fluid. A critical
event in the pathogenesis of bacterial meningitis is the inflammatory reaction induced by
the invading bacteria. Many of the neurologic manifestations and complications of bacterial
meningitis result from the immune response to the invading pathogen rather than from
direct bacteria-induced tissue injury. The lysis of bacteria with the subsequent release of
cell-wall components into the subarachnoid space is the initial step in the induction of the
inflammatory response and the formation of a purulent exudate in the subarachnoid space.

Cerebral oedema does occur.

Vessels may become obstructed either by encroachment by purulent exudates or by

vasculitis, both may affect mainly the large vessels traversing the subarachnoid space.
The inflammation in the subarachnoid space can extend along the Virchow- Robin spaces
surrounding the blood vessels deep into the brain parenchyma. This perivascular
inflammation can cause thrombosis in both the arterial and venous circulation.
Page1

Page 4 of 18
 Clinical features

When meningitis is secondary to infection elsewhere, such as pneumococcal pneumonia

or H. influenzae, the presenting symptoms may be those of the original infection. Otitis
media, sinusitis, mastoiditis, and nasopharyngeal and other possible sites of sepsis must
be excluded.

Meningitis can present as either an acute fulminant illness that progress rapidly in a few
hours that the patient becomes comatose within a few hours of the first symptoms or
progressively worsens over several days.

The classic clinical triad of meningitis is fever, headache, and meningism.

Nausea, vomiting, and photophobia are also common complaints.
As symptoms advance, cognitive dysfunction includes confusion, delerium, progressing to
stupor and coma.

Neck stiffness is the pathognomonic sign of meningeal irritation and is present when the
neck resists passive flexion. Kernig's sign (with the hip joint flexed to a 90°angle, extension
at the knee causes spasm in the hamstring muscles and inability to allow full knee
extension) and Brudzinski's sign (passive flexion of the neck causes flexion of the thighs
and knees) are also classic signs of meningeal irritation. Meningism seen in about 80% of
the cases,but are often absent in the two extremes of life and in comatose patients.
In awake patients, a more sensitive test is to ask patients to put their chin on their chest
with the mouth closed.

Focal neulogical signs may occur due to cerebral infarct.

Seizures occur as part of the initial presentation of bacterial meningitis or during the
course of the illness.

Raised intracranial pressure is an expected complication of bacterial meningitis and is the

major cause of disturbance of level of consciousness in this disease. Signs of increased
intracranial pressure include a deteriorating of consciousness, papilledema, sixth nerve
palsies, decerebrate posturing, and the Cushing reflex (bradycardia, hypertension, and
irregular respirations). The most disastrous complication of increased intracranial pressure
is cerebral herniation.

The most common rash of meningococcal meningitis is a very transient, maculopapular

rash that appears early in the course of the disease.
The petechial, often appearing first on the shins or the forearms. it is most likely to appear
in dependent areas (such as the back of a patient lying down) and in areas of pressure,
such as under the elastic band of underwear or stockings. The brownish or reddish,
vasculitic rash of fulminant meningococcaemia is unmistakable. with thrombocytopenia,
which can very rapidly progress to purpura, ecchymosis, and disseminated intravascular
Page1

Page 5 of 18
 coagulation. There is associated profound hypotension, shock with peripheral cyanosis,
gangrene of the extremities, and spontaneous systemic bleeding.
The petechial rash is evident in 60% of adults and up to 90% of children

Herpes labialis is associated with all forms of bacterial meningitis.

Atypical Presentations of Meningitis: In neonates, bacterial meningitis may present with

tachypnea, apneic spells, changes in heart rate, atypical seizures, or simply vague decline.
Individuals, who are immunocompromised may not develop fever.

Diagnosis
Early diagnosis and treatment reduces mortality and the incidence of complications.
The diagnosis depends on:
1. Suspicious clinical symptoms and signs.
2. CT of head to rule out abscess or other space-occupying lesion, if it can be done
quickly. CT scanning can reveal skull fractures, or parameningeal septic foci.
3. Lumbar puncture.

Examination of cerebrospinal fluid is crucial for the diagnosis of meningitis. The main risk
of lumbar puncture is fatal pressure coning; this is rare in spontaneous meningitis. If there
is any suggestion of raised intracranial pressure and/or focal neurological signs, newly
onset seizure, immunocompromized patient or disturbance level of consciousness, CT
scanning is indicated.

Other contraindications to lumbar puncture include:

1. Local skin sepsis at the site of puncture.

2. clinical suspicion of spinal-cord compression

3. A bleeding diathesis.

4. Shock and respiratory insufficiency

The classic CSF abnormalities in bacterial meningitis are:

(1) polymorphonuclear leukocytosis (100 -10000 cells per microliter)
(2) decreased glucose concentration (<40 mg/dL) and/or CSF/serum glucose ratio of less
than 40%
(3) increased protein concentration (100-500 mg/dL).
(4) increased opening pressure.
(5) Turbid in appearance.
(6) CSF should be sent for Gram stain, culture, and PCR
Specific diagnosis of the causative organism of bacterial meningitis and determination of
antibiotic sensitivity require bacterial culture. CSF bacterial cultures are positive in 70-80%
of patients, and CSF Gram's stain demonstrates organisms in >60% ( it is specific but not
Page1

very sensitive ). CSF bacterial antigen assay is positive in 50-95 %. CSF bacterial PCRs
are increasingly available.
Page 6 of 18
 Other tests
1. Blood cultures should be taken. The causative organisms of bacterial meningitis can
often be detected in blood cultures.
2. Petechial skin lesions, if present, should be biopsied. The rash of meningococcemia
results from the dermal seeding of organisms with vascular endothelial damage, and
biopsy may reveal the organism on Gram's stain.
3. Blood count. May reveal polymorphnuclear leukocytosis related to systemic infection or
leucopenia reflecting immunosuppression.
4. Chest and skull (sinus) radiography to identify the primary source of infection.
5. Serum C-reactive protein and procalcitonin levels can aid in the differentiation of
bacterial from viral meningitis. These inflammatory markers are more elevated in
bacterial infection.

Differential diagnosis

1. Subarachnoid haemorrhage presents with sudden headache.

2. Chemical meningitides resulting from the introduction of irritants into the
subarachnoid space (contrast media, antimicrobial agents, and contaminants of
lumbar puncture and spinal anaesthesia).

3. Aseptic meningitis.

Complications

1. Hydrocephalus.
2. Subdural empyema. This is a collection of pus in the subdural space.

3. Cerebral infarction.

4. Cerebral oedema and raised intracranial pressure.

5. Inappropriate antidiuretic hormone secretion.

6. Septic shock.

Management
Unlike most other diseases, the management of patients with suspected meningitis or
encephalitis begins with empiric therapy. The etiologic organism cannot always be
identified. The goal is to identify those that are treatable, provide supportive care for those
that are not, and, when possible, prevent the neurologic complications of these infections.

Antibiotic treatment must be started immediately the diagnosis is suspected clinically; this
is especially important in meningococcal meningitis/septicaemia. Antimicrobial treatment
should then be started, based on clinical assessment, before the results of the
examination of cerebrospinal fluid are known. Empirical treatment is dictated by the clinical
Page1

circumstances, the likely causative agents, and their antibiotic susceptibilities

Page 7 of 18
 Empirical therapy of community-acquired bacterial meningitis in children and adults should
include a third-generation cephalosporin (ceftriaxone).

Vancomycin may add because of the high prevalence of penicillin-resistant S.

pneumoniae.

Ampicillin should be added to the empirical regimen for coverage of L. monocytogenes in

individuals less than three months of age

Meropenem is a carbapenem antibiotic has been demonstrated to be effective in cases of

meningitis caused by Pseudomonas and penicillin-resistant S. pneumoniae.

In Immunocompromised patients (over age 50, or those with suspected impaired cell-
mediated immunity because of chronic illness, organ transplantation, pregnancy,
malignancies, or immunosuppressive therapy), ampicillin should be added to vancomycin
and ceftazidime combination.

Post-traumatic meningitis and neurosurgical patients empirical therapy should include a

combination of vancomycin and ceftazidime and metronidazole or a combination of
vancomycin and meropenem. ceftazidime is the only cephalosporin with adequate activity
against P. aeruginosa in the central nervous system.

Corticosteroids are used as an adjunct to antibiotics in the treatment of bacterial meningitis

in an attempt to attenuate the intrathecal inflammatory response and thereby reduce
mortality and morbidity. dexamethasone treatment may be associated with a lower
mortality in adults and fewer neurological and auditory sequelae in adults and children, in
particular in adults suffering from pneumococcal meningitis, but no effect could be
demonstrated for N. Meningitidis. Dexamethasone has been shown to reduce hearing loss
in H. influenzae meningitis. Dexamethasone should be given before or with the first dose
of antibiotic, at a dose of 10 mg IV every 6 hours for 4 days for adults.

Once the aetiological agent has been isolated and its susceptibilities determined, the
empirical treatment should be changed, if necessary, to an agent or agents specific for the
isolate.

General management and treatment of complications

Severe headache and pyrexia may require appropriate symptomatic treatment.

In unconscious patients, supportive measures include maintaining the airway and

intravenous or nasogastric feeding.

Septicaemic patients require careful monitoring and treatment of shock. Multiple organ
failures may require intensive medical support, including ventilation and dialysis.
Page1

Page 8 of 18
 Raised intracranial pressure: raising the head of the bed to 30°, administration of mannitol
or dexamethasone, and mechanical hyperventilation may lower intracranial pressure.

Seizures can be rapidly controlled.

Hyponatraemia may develop as a result of the syndrome of inappropriate antidiuretic

hormone secretion. Such cases may require fluid restriction. Hyponatraemia, actually due
to excess of fluid rather than reduce amount of sodium.

Prevention
Household and other closed contacts of patients with Meningococcal infection, prophylaxis
should be given. Two days of oral Rifampicin 600mg/12hours or single dose of
Ciprofloxacin 500mg.

Prognosis
Acute bacterial meningitis carries an untreated mortality of 70 to 100 per cent.
Mortality is 3 to 7% for meningitis caused by H. influenzae, N. meningitidis, or group B
streptococci; 15% for that due to L. monocytogenes; and 20% for S. pneumoniae.
Pneumococcal disease is also more likely to result in long term sequelae. In
meningococcus infection, mortality is doubled if the patient presents with features of
septicaemia rather than meningitis. Recurrent pyogenic meningitis implies an underlying
anatomical or immunological defect.

Factors that worsen prognosis include:

1. Focal neulogical signs.
2. Seizures.
3. Disturbance of consciousness.
4. Complicating illness.
5. Delay in diagnosis and treatment.
6. Extremes of age.
7. Low CSF cell count, low sugar and high protein
8. Shock

Tuberculous central nervous system

infection
Mycobacterium tuberculosis is one of the most common infectious agents in the word.
Mycobacterium tuberculos central nervous system infection affect all ages. The incidence
has increased.
Mycobacterium tuberculosis, an aerobic gram-positive acid-fast pleomorphic bacilli. M.
tuberculosis is an intracellular pathogen that survives within the host macrophages.

Pathology and Pathogenesis

Page1

Page 9 of 18
 Tuberculous central nervous system infection usually results from reactivation of
latent infection with mycobacterium tuberculosis which is an acid-fast bacillus. It is passed
between persons through respiratory droplets. Mycobacteria multiply in alveolar spaces,
and within 2 to 4 weeks hematogenous spread from the primary lesion to extrapulmonary
sites occurs. But it can be as a result of seeding through the bloodstream from a site of
chronic infection. Tuberculous central nervous system infection develops most commonly
shortly after a primary infection in children and adolescents or as part of miliary
tuberculosis. Rather, small, caseous microtubercles develop in the brain, meninges, skull
or vertebrae close to the meninges in the course of primary infection. Here the organism
remains in a dormant state in tubercles. Tuberculous meningitis results from rupture of a
subependymal microtubercle, discharging tuberculoprotein and mycobacteria into the
subarachnoid space. Deeper tubercles enlarge and become tuberculomas.

Subacute inflammation, in subarachnoid space especially of the basal meninges, then

develops, a thick exudate forms producing

 Cranial nerves lesions.

 Cerebral arteritis causing infarction.

 Impairment of cerebrospinal fluid absorption, or obstruction to the cerebrospinal

fluid circulation causing hydrocephalus.

Mycobacterial infection may involve the spinal cord either as a spinal arachnoiditis,
producing radiculopathy or myelopathy. Or by extradural compression from a tuberculoma
or vertebral bone infection. Tuberculous spondylitis may result in an epidural abscess.
Usually the thoracic cord is affected. Infarction in the territory of the anterior spinal artery
can be caused by the endarteritis.
Fluid, electrolyte, and acid-base disturbances are common, the result of vomiting,
inadequate fluid intake, and the syndrome of inappropriate secretion of antidiuretic
hormone.
Mycobacterial infection develops when a caseating focus discharges its contents into the
subarachnoid space. Microglial cells are the principal targets of Mycobacterium
tuberculosis. Tumor necrosis factor released from these cells plays a critical role in
containing the infection.
Cerebral vessels may be affected by adjacent meningeal inflammation, producing
vasospasm, constriction, and eventually thrombosis with cerebral infarction. Infarcts are
most often located within the internal capsule, basal ganglia, and thalamus.
The hallmark pathologic feature of tuberculous central nervous system infection is the
presence of a thick exudate most prominent in the basilar meninges. This exudate can
block the flow of CSF and result in hydrocephalus. The entrapment of intracranial vessels
within exudates often produces cerebral infarction. If the basal inflammatory process
affects the brain parenchyma, it can result in encephalopathy.

Clinical features
Page1

Page 10 of 18
 Mycobacterium tuberculous central nervous system infections take a variety of forms
including:
1. Subacute meningitis

Symptoms of meningitis are preceded by 2 weeks of non-specific malaise, irritability,

insomnia, lethargy, anorexia, headache, abdominal pain, vomiting, and behavioural
changes.

Low-grade fever and night sweating is usual.

During the second stage there are meningeal irritation signs.

Focal neurological signs, such as hemiparesis, hemianaesthesia, aphasia, and

hemianopia resulting from cerebral infarction caused by the endarteritis.

Siezures are common in children but rare in adults.

About 10 per cent of patients develop symptoms and signs of spinal arachnoiditis
(radiculopathy: radicular pain, segmental weakness and urinary retention), or (myelopathy:
weakness with sensory loss below the level of the lesion).Tuberculous spondylitis may
result in epidural abscess

The syndrome of inappropriate secretion of antidiuretic hormone is common in patients

with severe tuberculous central nervous system infection .

Untreated, patients become stuporose or comatose and develop signs of brainstem

damage, such as decerebrate rigidity, irregular breathing, and impairment of brainstem
reflexes.

2. Acute fulminant meningoencephalitis.

3. Tuberculoma (a large caseous tubercle): The patient may present with constitutional
symptoms and manifestations of space occupying lesion.

4. Tuberculous encephalopathy: tuberculous infection should be suspected in any patient

with acute or subacute confusional state.

Diagnosis
Because of the variety of presenting forms and the difficulty in diagnosis, high index of
suspicion should be maintained.

Examination of cerebrospinal fluid is crucial:

Its opening pressure is raised in most patients, but may be low in those developing block
from spinal arachnoiditis.
Page1

Page 11 of 18
 The cerebrospinal fluid appears clear or slightly turbid but may form a spider's web clot on
standing. Lymphocytic pleocytosis. The glucose concentration in cerebrospinal fluid is low.
Tubercle bacilli can be detected in cerebrospinal fluid in 10 to 20 per cent of cases and
more in clot. This figure decrease children.

Culture of mycobacteria is successful in 10 to 90 per cent of cases.

The genome of Mycobacterium tuberculosis can be detected in the cerebrospinal fluid by

polymerase chain reaction. A search for evidence of tuberculosis elsewhere in the body is
useful.

Neuroimaging study is useful in detecting Tuberculoma, cerebral infarction and

hydrocephalus.

Differential diagnosis
1. partially treated bacterial meningitis.
2. neoplastic infiltrations of the meninges (for example, carcinomas, leukaemias,
lymphomas).

A febrile patient with cranial nerve palsies, cerebrospinal fluid (CSF) lymphocytosis and
low CSF glucose is likely to have tuberculosis, whereas an afebrile patient with normal or
mildly reduced CSF glucose is more likely to have malignant meningitis.

3. Fungal infections.

Treatment
Full treatment must be started when the diagnosis is suspected on clinical grounds.
First-line antituberculous medications include rifampicin, isoniazid, pyrazinamide,
ethambutol , and streptomycin.

Isoniazid and pyrazinamide are freely distributed into the cerebrospinal fluid. During this
active phase of meningitis, most antituberculosis drugs achieve therapeutic concentrations
in the cerebrospinal fluid.

second-line antituberculous medications include amikacin, kanamycin, ethionamide,

ofloxacin, and cycloserine.

Antituberculosis treatment is divided into two phases: an intensive (initial) phase

and a continuation phase.
In the intensive phase, therapy includes a combination of four first-line medications:
isoniazid, rifampicin, streptomycin, and pyrazinamide. The intensive phase continues for 2
months. In the continuation phase, the treatment regimen is reduced to two medications
(isoniazid and rifampicin), and the continuation phase is usually extended to a total
treatment period of 12 months.
Page1

Page 12 of 18
 For multidrug resistant tuberculosis the intensive (initiation) phase extended to 4 months
and employs five drugs. the continuation phase extended to 18 months with three drugs.

In adults, daily single doses of 300 mg isoniazid, 600 mg rifampicin, and 1500 mg
pyrazinamide provide adequate concentrations in the serum and cerebrospinal fluid of
patients with active tuberculous central nervous system infection .

Response to antituberculosis chemotherapy is slow. However, some signs of clinical

improvement are usually seen within the first few weeks. Early clinical evidence of
response is an improvement of the headache, sense of general well-being, and a
decrease in the elevated intracranial pressure. It usually takes weeks or months for the
cerebrospinal fluid to return to normal. A rapid return to cerebrospinal fluid of normal
composition within a few days virtually excludes the diagnosis of tuberculous central
nervous system infection , in which case antituberculosis treatment should be stopped.

'Trial' of chemotherapy is justified when there is clinical suspicion of tuberculous central

nervous system infection , particularly when diagnostic facilities are limited.

Tuberculomas usually respond very slowly to antituberculosis drugs and it usually takes at
least 24 months or longer for the lesions to disappear.

corticosteroids used routinely because it is significantly reduced death and disabling

residual neurologic deficits among survivors.

Raised intracranial pressure from hydrocephalus can be treated conservatively with

acetazolamide, with or without frusemide (furosemide), and corticosteroids. Within the first
4 to 6 weeks of treatment, the cerebrospinal fluid pressures of the majority of the patients
return to normal and the oedema disappears. If these measures fail, surgical shunting will
be needed.

Complications
There are permanent complications in 10 to 30 per cent of survivors
 intellectual impairment
 recurrent seizures
 blindness
 deafness
 squints
 residual motor deficit

Prognosis
The untreated mortality of tuberculous central nervous system infection is close to
100 per cent.
Page1

Page 13 of 18
 Complete recovery is the rule if treatment is started before the appearance of focal signs
or stupor.

The overall prognosis remains poor, 10–20% case fatality. Treatment delay, Age <5 or >50
years, and coma at the time of presentation is the most significant predictor of a poor
prognosis.

VIRAL ENCEPHALITIS
Definition In distinction to meningitis, where the infectious process and associated
inflammatory response is limited largely to the meninges, in encephalitis the brain
parenchyma is also involved. Many patients with encephalitis also have evidence of
associated meningitis (meningoencephalitis) and, in some cases, involvement of the
spinal cord or nerve roots (encephalomyelitis, encephalomyeloradiculitis).

Etiology
Clues that may suggest a specific virus include
1. The time of year
2. Recent travel
3. Contact with insects or other animals
4. Sexual contacts
5. Immunosuppression

The most important viruses causing sporadic cases of encephalitis in immunocompetent

adults are HSV-1, VZV, and, enteroviruses.
Epidemics of encephalitis are caused by arboviruses.
Immunodeficient patients with depressed cell-mediated immunity (Hodgkin's disease) may
develop herpes zoster encephalitis.

Encephalitis has been postulated to follow spread of virus from trigeminal ganglia through
sensory fibers to the meninges overlying temporal lobes and orbitofrontal cortex.
Alternatively, encephalitis could arise following reactivation of a latent virus within the
brain.

Clinical Manifestations
In addition to the acute febrile illness with evidence of meningeal involvement
characteristic of meningitis, the patient with encephalitis commonly has an altered level of
consciousness, seizures and evidence of either focal or diffuse neurologic signs or
symptoms.
The most commonly encountered focal findings are aphasia, ataxia, hemiparesis,
involuntary movements, and cranial nerve deficits.
Features of viraemia include lymphadenopathy and pharyngitis.

Laboratory Diagnosis:
CSF examination should be performed in all patients with suspected viral encephalitis
Page1

unless contraindicated by the presence of severely increased intracranial pressure.

The characteristic CSF profile is consists of:
Page 14 of 18
 1. a lymphocytic pleocytosis.
2. a mildly elevated protein level
3. a normal glucose level.
4. About 20% of patients with encephalitis will have a significant number of red blood
cells in the CSF in a nontraumatic tap.
CSF PCR: PCR amplify DNA from the CSF become the diagnostic procedure of choice
for many types of viral encephalitis.

TREATMENT
Basic management and supportive therapy should include:
1. Careful monitoring of intracranial pressure.
2. Fluid restriction and avoidance of hypotonic intravenous solutions.
3. Suppression of fever.
4. Seizures should be treated with standard anticonvulsant regimens

Herpes Simplex Encephalitis

This is the commonest and gravest form of acute encephalitis. It occurs sporadically
throughout the year and in patients of all ages and in all parts of the world. It is due almost
always to HSV-1, which is also the cause of the common herpetic lesions of the oral
mucosa; rarely, however, do the oral and encephalitic lesions coincide. 2/3 of the cases
over forty years of age. It occurs in 2-5 cases/million adultl/year
The type 2 virus may also cause acute encephalitis, usually in the neonate and in relation
to genital herpetic infection in the mother.

Pathology
The lesions take the form of an intense hemorrhagic necrosis of the inferior and medial
parts of the temporal lobes and the orbital parts of the frontal lobes.
The temporal lobe lesions are usually bilateral but need not be symmetrical. This
distribution of lesions is so characteristic.
In the acute stages of the disease, intranuclear eosinophilic inclusions which are minute
particles are found in neurons and glial cells, in addition to the usual microscopic
abnormalities of acute encephalitis.

Clinical Features
The symptoms, which evolve over several days, are in most cases like those of any other
acute encephalitis namely, fever, headache, seizures, confusion, stupor, and coma.
Other manifestations include olfactory or gustatory hallucinations, anosmia, temporal lobe
seizures, a brief period of personality change, bizarre or psychotic behavior, aphasia, and
hemiparesis.
The CSF is often under increased pressure and almost invariably shows a lymphocytic
pleocytosis. oftenly there are few red cells. The protein content is increased in most cases.
Page1

Rarely, the CSF glucose levels may be reduced to slightly less than 40 mg/dL
Page 15 of 18
 Differential diagnosis
1. Cerebral vasculitis
2. Brain abscess

Diagnosis The diagnosis may be difficult. Acute herpes simplex encephalitis must be
distinguished from other types of viral encephalitis.
The EEG changes, consisting of lateralized periodic slow-wave complexes in the temporal
regions are suggestive though not specific for the disease.
CT and MRI show the affected areas with surrounding oedema and sometimes with
scattered areas of haemorrhage occupying the inferior parts of the frontal and temporal
lobes.
The application of the polymerase chain reaction to amplify DNA from the CSF are proving
to be useful in diagnosis in the first few days of the illness, while the virus is replicating,
and enable one to avoid brain biopsy. The only other absolute way to establish the
diagnosis of acute HSV encephalitis is by fluorescent antibody study and by viral culture of
cerebral tissue obtained by brain biopsy.

Treatment Acyclovir is given intravenously in a dosage of 30-45 mg/kg per day and
continued for 14 to 21 days in order to prevent relapse. The main problems with acyclovir
are local irritation of the veins used for infusion, mild elevation of hepatic enzymes, or
transient impairment of renal function.

Prognosis: Prognosis is influenced by the patient’s age and level of consciousness at

presentation and by the treatment.

SUBACUTE SCLEROSING PANENCEPHALITIS

It is a chronic nonpermissive infection of brain tissue with measles virus. The frequency
has been estimated at 1 in 100,000–500,000 measles cases. The incidence has declined
dramatically since the introduction of a measles vaccine. Most patients give a history of
primary measles infection at an early age (2 years), which is followed after a latent interval
of 6–8 years by the development of a progressive neurologic disorder. Some 85% of
patients are between 5 and 15 years old at diagnosis.

Clinical manifestation
Initial manifestations include poor school performance and mood and personality changes.
Typical signs of a CNS viral infection, including fever and headache, do not occur. As the
disease progresses, patients develop progressive intellectual deterioration, focal and/or
generalized seizures, myoclonus, cerebellar ataxia, and visual disturbances. In the late
stage of the illness, patients develop disturbance of level of consciousness, and spastic
quadripareses.
Page1

Page 16 of 18
 Diagnostic studies
MRI is often normal early areas develop in the white matter of the brain and brainstem as
disease progresses.
The EEG may initially show only nonspecific slowing, but with disease progression,
patients develop a characteristic periodic pattern with bursts of high-voltage, sharp, slow
waves every 3–8 s, followed by periods of attenuated (“flat”) background.
The CSF is acellular with a normal or mildly elevated protein concentration and a markedly
elevated gamma globulin level (>20% of total CSF protein). CSF antimeasles antibody
levels are invariably elevated, and oligoclonal antimeasles antibodies are often present.
Measles virus can be cultured from brain tissue.
Viral antigen can be identified immunocytochemically, and viral genome can be detected
by in situ hybridization or PCR amplification.

TREATMENT
No definitive therapy for SSPE is available. Treatment with isoprinosine alone or in
combination with intrathecal or intraventricular alpha interferon, has been reported to
prolong survival and produce clinical improvement in some patients.

Fungal meningitis
Fungal meningitis is a rare infection in immunocompetent patients, but it remains a
significant cause of morbidity and mortality in immunocompromised, elderly, and with
cancer. Cryptococcal meningitis is the most common form of fungal meningitis, but there
are dozens of fungi that can cause meningitis. Certain geographic areas have a higher
incidence of certain forms of fungal meningitis based on the relatively higher
concentrations of the organism in those areas.

Epidemiology
Cryptococcal meningitis comprises 4–8% of all forms of meningitis in the elderly or
patients with cancers.

Clinical manifestation
Patients with fungal meningitis often present with subacute course of headache and
meningeal irritation signs with or without fevers. The most important factor in diagnosing
fungal meningitis is suspecting it.

Laboratory Studies
A lumbar puncture helps the clinician to narrow the differential diagnosis, but confirming
fungal meningitis requires specific organism specific testing.
The combination of a lymphocytic predominance on CSF cell counts and normal to mildly
low glucose suggests a nonbacterial and possibly fungal etiology . An India ink stain can
be helpful in identifying cryptococcal meningitis, but it has a low sensitivity. Serum and
CSF antigens and antibodies to specific organisms can confirm a diagnosis if positive, but
Page1

do not rule out fungal meningitis if negative.

Page 17 of 18
 Treatment
Fungi as a class of organisms generally respond well to a few broad-spectrum antifungal
medications. Treatment of fungal meningitis must balance the morbidity from the organism
against the toxicity of the medications.
Fungal infections respond well to amphotericin and/or fluconazole.

Prognosis
There are many factors that affect the prognosis in patients with fungal meningitis.
Because the majority of patients that get fungal meningitis are immunocompromised, the
patient’s underlying comorbidities dramatically affect the patient’s outcome. Certain
factors, such as hydrocephalus, altered mental status, and an elevated CSF pressure,
increase the risk of an unfavorable outcome.
Page1

Page 18 of 18