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Encephalitis and other brain infection final (autosaved)
1. Encephalitis and other brain infection final
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Encephalitis.
Introduction and definition
īˇ The term âencephalitisâ implies inflammatory change affecting brain parenchyma.
By common usage the name refers to inflammation of the brain caused by infection.
īˇ The onset and evolution of the disease
1. is most commonly acute encephalitic features
appearing within hours or at most a day or so, and usually following a non-specific prodrome
which has evolved over a few days at the most.
2. Chronic encephalitis
has similar clinical features and the picture evolves over weeks or even months
it may reach a plateau or it may relapse and remit to a degree.
īˇ Most cases of encephalitis are caused by
1. viruses
2. protozoa such as malaria and toxoplasma
3. bacteria such as spirochaetes and rickettsiae
īˇ viral encephalitis can be grouped into three distinct categories:
1. Acute viral encephalitis
īŧ is due to direct invasion of the brain by virus
īŧ The signs and symptoms result from this invasion and from the inflammatory change
which it induces in the brain parenchyma.
2. Post-infectious encephalitis
īŧ is characterized pathologically by perivenous demyelination caused by allergic or immune
mechanisms relating to viral infection.
3. Prion diseases.
īŧ The third group includes those encephalitides with a prolonged clinical evolution, known heretofore
as the âslow virus infectionsâ and now as âprion diseasesâ. (small proteinaceous infective particles)
The main virus groups are listed in Table 34.1.
Table 34.1. Viruses associated with neurological disease
DNA viruses
Herpes virus Herpes simplex 1 and 2
Varicellaâzoster
Cytomegalovirus
EpsteinâBarr
Papovavirus JC virus-progressive multifocal leucoencephalopathy
RNA viruses
Retroviruses HTLV-1âHAM-TSP
HIVâAIDS
Picornovirus
Enteroviruses Poliomyelitisâpolio
C
o
x
sakie
â aseptic meningitis
E
c
h
O virus
Arenavirus Lymphocytic choriomeningitis
Paramyxovirus Influenza
Mumps
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Morbillivirus Measles
Rhabdovirus
Lyssavirus Rabies
Bunyavirus California and LaCrosse encephalitis
Rift Valley fever
CongoâCrimean haemorrhagic fever
Retrovirus
Orbivirus Colorado tick fever
Togavirus
Alphavirus Western, Eastern, and Venezuelan equine encephalitis
Flavivirus Japanese, Murray Valley, and St Louis encephalitis
Central European and Russian springâsummer
encephalitis
Louping ill
Rubivirus Rubella
The diagnosis of viral infection of the nervous system
īˇ Careful attention to historical details
īˇ meticulous clinical examination
Confirmation that a clinical syndrome difficulties
1. demonstration of the presence of the
virus or viral antigen in body tissue or
fluids
1. the presence of a virus may be due to a co-existing and
unrelated infection
2. or a specific antibody response to its
presence
2. âantibody levels may be persistently raised from a
previous infection
3. or the rise may represent an anamnestic generalized
immune response to infection
4. There may also be difficulties with inadequate sensitivity
of the tests employed
5. problems with cross-reactions that impair specificity
6. and timing the taking of specimens against the
progression of the disease
Viral identification
īˇ Virus culture
īŧ has not been greatly successful in the diagnosis of CNS infections, in large part due to the
difficulty of obtaining specimens of neural tissue.
īŧ It may be possible to cultivate virus from other sources but this is seldom fruitful.
īˇ Traditionally, the demonstration of a fourfold rise in antibody titre
īŧ between an acute phase and a convalescent serum sample to a specific virus has been
sufficient to confirm the diagnosis.
īˇ Numerous techniques that employ immunofluorescence and ELISA
īŧ have greatly increased the sensitivity of diagnosis and the development of monoclonal
antibodies has permitted the detection of viral antigen using these techniques.
1. IgM capture ELISA
Rapid results can now be obtained
2. Western blotting
in which electrophoretic gels use specific antibodies to trap antigen, is very sensitive.
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Viral nucleic acid can be detected and characterized by sensitive molecular techniques such as
Southern blot hybridization and in situ hybridization.
3. The polymerase chain reaction (PCR)
īŧ is an exquisitely sensitive method to detect nucleic acid, capable of picking out a single viral
genome in specimens that contain thousands of cells
Clinical features and differential diagnosis of encephalitis
īˇ However, encephalitis is an unusual consequence of common viral infections, and only a small
minority of patients with systemic viral infections develop clinical disease of the CNS.
īˇ A list of the virus groups that cause encephalitis is found in Table 34.2.
īˇ Encephalitis may be sporadic or epidemic.
Table 34.2. Viral causes of encephalitis
Herpes simplex
Varicellaâzoster
Cytomegalovirus â
EpsteinâBarr virus
Human herpes virus 6 -B herpes virus
Mumps-Measlesââby immunization
Rabies
HIV
Arboviruses-JC virus
Clinical features
I-Common features to all varieties.
1. prodrome of several days non-specific illness with
fever, malaise, fatigue, and myalgia.
2. With the onset of encephalitis
the patient usually has signs of meningitis
as wellâheadache, fever, and neck stiffness.
3. Encephalitis is implied by signs of mental change
disorientation, behavioural and speech disturbance
alteration of consciousness which may range from lethargy and drowsiness to deep coma.
4. Epileptic seizures
generalized or focalâcommon
5. focal neurological signs
hemiparesis, cerebellar upset, sensory loss ,hallucinations
spasticity, speech disturbance
and other signs of parietal dysfunction, and memory upset.
II_Signs may occur in other organ systems
īŧ which may point to causal virus
e.g skin rashes which may be caused by measles
parotitis or orchitis from mumps.
Differential diagnosis
1-CNS infection
Other non-viral forms of encephalitis have identical features.
Meningitis
will affect mentation as it develops into meningo-encephalitis.
2-CNS demyelination
īˇ ADAM
īˇ more explosive varieties of MS may have an encephalitic onset
3-Brain tumours
īˇ Intracranial suppuration
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īˇ advanced primary or metastatic brain tumours
īˇ âICP from whatever cause may lead to coma and to neck stiffness from cerebellar tonsillar
herniation.
4-Vascular
īˇ Intracranial haemorrhage can cause a similar picture, including pyrexia.
īˇ Cerebral vasculitides
a) either primary or secondary to collagen disease, not infrequently present as an
encephalopathy
b) conditions which give rise to cerebral granulomas such as sarcoidosis
may be difficult to differentiate
5-Encephalopathies that complicate metabolic disturbances
īˇ e.g kidney and liver failure
often occur in the context of generalized infection and may be particularly difficult to diagnose
īˇ Rare encephalopathies such as Wilson's disease must not be forgotten.
The history may reveal
īˇ a characteristic epidemiological pattern
īˇ the time of year and the disease known to occur in a particular community.
īˇ Has there been a bite from or exposure to known insect vectors of disease?
īˇ Enquiry must always be made about recent travel abroad and the activities which were undertaken
during that time.
Investigation
1-Virology
2-Cerebrospinal fluid
this must not be done until it is considered safe to do so and after intracranial space occupation has been
excluded by brain imaging
Pressure Cells Protein and Glucose Virology
ICP may be
dangerously
âââ
cerebral oedema
may develop
rapidly
Decision of LP
not simple
a pleocytosis 10 -2000 or more
In the early stages
these may be PMNs but in
general they are lymphocytic
unless there is a necrotizing
component, in which case red
cells are found.
The protein is raised
glucose is normal
bacteria are not
found.
Detetection of virus by
ELISA
DNA probes with
hybridization
or nucleic acid amplification
methods e.g PCR
PCR is the quickest and most
accurate method by which to
diagnose herpes simplex and
other encephalitides
3-Electroencephalography
īˇ The EEG is useful in demonstrating and following up epileptic activity
Findings
īˇ diffuse slow wave activity that becomes slower with increasing severity.
īˇ There may be focal abnormality reflecting greater structural change on one side of the brain and this
seldom has diagnostic significance.
In herpes simplex encephalitis
īˇ Abnormal EEG activity is commonly seen from one temporal lobe and this may spread to the other
side as the disease progresses.
īˇ This may be followed by spike and slow wave activity and PLEDs arising from a temporal lobe
īˇ This is not pathognomonic.
CreutzfeldtâJakob disease (CJD) and subacute sclerosing panencephalitis (
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Have a characteristic appearances
4-Imaging brain infection
some of the abnormalities are subtle, particularly in the early stages.
Advantages of MRI
īˇ For encephalitis, MR is the modality of choice because it is superior to CT in
1. demonstrating changes of cerebral oedema and white matter disturbance
2. infarction and derangement of the BBB and contrast enhancement
3. structures in the posterior fossa
Limitation of MRI
there are some limitations to the use of MR with patients who are ill.
īˇ It is necessary for them to lie still for about 30 min within a tube
īˇ This is not possible for patients who are ill or confused.
īˇ Any movement degrades the image âquite long.
īˇ Not used with patients who are ventilated or has ICP monitoring equipment
For these reasons CT is the more commonly used in emergency situations.
Also CT is superior at interrogating bone
Early changes Later
1. diffuse brain oedema
2. white matter low density changes which may be
diffuse or focal
as in cases of HS encephalitis with predilection
for the temporal lobes
3. sometimes associated with infarction
4. specific changes (not pathognomonic)
1. atrophic changes
2. Imaging will identify
īŧ areas of necrosis, granulomas
īŧ abscesses, neoplasm
īŧ venous thrombosis, and infarction.
NB
In cases of viral encephalitis, no abnormality may be evident for the first few days of the illness
Treatment
General measures
1. similar to the management of any unconscious or confused patient
care being taken to maintain adequate nutrition, hydration, and ventilation.
2. Epileptic seizures
need to be controlled
3. secondary infection
must be prevented or treated vigorously if it occurs.
4. raised ICP
needs to be controlled to ensure adequate brain perfusion to prevent secondary ischaemia and
infarction.
ICP monitoring should be considered
īŧ if the Glasgow Coma Scale falls to 8 or below
īŧ if there is radiological evidence of significant brain swelling
īŧ or if there is mass effect.
âHyperventilation and the administration of mannitol
âThere is no consensus on the use of dexamethasone or other steroids to reduce brain oedema.
As no clear evidence that steroids reduce the oedema of CNS infection
Most data relate to the use of dexamethasone in the treatment of
īŧ herpes simplex encephalitis
īŧ and childhood bacterial meningitis
In practice, dexamethasone is given to patients
īŧ who have raised ICP
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īŧ and who continue to deteriorate.
5. The availability of neuro-intensive care and a multidisciplinary approach
âimprovement in their management.
Antiviral drugs
Specific treatment for viral encephalitis is available for only a minority of infections.
Acyclovir
Related drugs
â valacyclovir and famciclovir
are under investigation.
âmortality rate blow 30 5 in cases of HS encephalitis
It is also useful for the treatment of varicella/zoster encephalitis.
Ganciclovir and foscarnet are of some use in cytomegalovirus infection
antiretroviral combination therapy
incorporating reverse transcriptase
inhibitors
(either nucleoside analogues or non-
nucleoside drugs)
and protease inhibitors
Treatment of AIDS
Superadded and opportunistic infections should be treated
immediately
pyrimethamine and sulphadiazine Toxoplasmosis
antibiotic combinations Mycobacterium avium complex disease
Prognosis
Overall the prognosis for recovery from viral encephalitis is good but this depends greatly on the nature of
the offending pathogen
īŧ rabies is universally fatal once established
īŧ herpes simplex encephalitis can be devastating.
The herpes viruses
Those viruses which cause disease in man are
HSV-1 and -2 varicellaâzoster
Cytomegalovirus EBV
Recently
1. human herpes virus 6 (HHV-6) has been found to produce encephalitis
2. B virus, a herpes virus found in Old World monkeys, has been transmitted to humans by animal bite,
and person to person contact has been documented.
Herpes simplex -Varicellaâzoster
Cytomegalovirus - EpsteinâBarr virus see paper
Human herpes virus 6
âCNS diseases are
1. meningo-encephalitis
2. retinitis,
3. GuillainâBarrÊ polyneuropathy
4. epileptic seizures
on the basis of serological studies and PCR studies of CSF
īˇ causal relationship has not been definitely established found
HHV-6 DNA in CSF of 2.2 % of patients with neurological complications of AIDS.
īˇ Not enough is known to date to make any recommendations about treatment.
Herpes B virus
īˇ human disease has been described in persons bitten by a monkey and is therefore likely to occur only
in laboratory workers.
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īˇ It has also been described following person to person contact.
Clinical picture
īˇ The onset is acute with neurological symptoms within 3â5 days and death has occurred within 2
weeks.
īˇ A localized vesicular eruption
occurs around the area of the bite
īˇ followed by
1. regional lymphadenopathy then malaise, fever, myalgia
2. and neurological signs of myelitis and encephalitis or encephalomyelitis
Other viral encephalitides
Epidemic encephalitis
īˇ This form of encephalitis is caused by one of the arboviruses
īˇ Arbovirus transmitted biologically by haematophagous arthropods such as mosquitoes, ticks,
sandflies, and biting midges (Phlebotomus and Culicoides).
īˇ cause disease in man, such as
dengue and yellow fever, where neurological involvement is of minor importance
or is caused by haemorrhagic or cardiovascular complications.
īˇ There are in excess of 20 arboviruses that cause encephalitis in man (Table 34.3).
īˇ All of them contain RNA and are classified in three families
1. Reoviridae.
2. Bunyaviridae
3. Togaviridae
Reovirus Bunyavirus Togavirus
Colorado tick fever California-
Rift Valley
Canyon
LaCrosse
Jamestown
St Louis-
Japanese
West Nile
Murray Valley
Far Eastern
Kyasanur Forest
Louping ill
Powassan
Eastern equine
Western equine
Venezuelan equine
Togaviridae
īˇ are symmetrical spherical enveloped virions that range in size from 40 to 90 nm in diameter
īˇ subdivided by size into larger flaviviruses and smaller alphaviruses.
īˇ Bunyaviridae are larger and the nucleocapsids have helical symmetry.
īˇ The Reoviridae contain double stranded nucleic acid and have no envelope.
Vectors
īˇ All arboviral encephalitides are maintained by zoonoses with complex life cycles involving a non-
human, vertebrate
īˇ primary hostâusually birds and lower vertebrate
īˇ and a primary arthropod vectorâusually a mosquito or tick.
īˇ Many arboviruses have different vertebrate hosts and more than one vector.
The mechanism of transmission
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īˇ The mosquito or tick bites an infected rodent, primate, or bird, becomes infected, the virus replicates
and spreads to the insect brain and salivary gland and within 2 weeks, the insect is infective.
īˇ It bites a human, injecting virus in the process.
īˇ This replicates in lymph nodes, spleen and vascular endothelium and viraemia develops.
Clinically
Most human infections are
1. asymptomatic
2. or lead to a mild flu-like illness of insidious onset with fever, headache, malaise, and myalgia.
3. In the small number who develop encephalitis
virus enters the brain, probably by infecting vascular endothelial cells and diffusing through
capillaries, spreads rapidly and infects neurones and glia which may die, and an inflammatory
response ensues.
īˇ Humans are infected by accident, and become âdead endâ hosts, because the viraemia which results
is not of sufficient degree to infect a biting mosquito.
īˇ Most cases of encephalitis occur in the summer, when arthropods are most active.
Climatic factors are importantâa late summer can prolong the period for potential infection.
īŽ St. Louis encephalitis:
īŽ The most common in the USA
īŽ Japanese encephalitis:
īŽ Widely spread in Asia
īŽ The most frequent cause of viral encephalitis in the world
īŽ Eastern Equine encephalitis:
īŽ The most severe with mortality of 50-70%
īŽ Tick born encephalitis:
īŽ Widely spread in Central Europe and former Soviet Union
Clinical features
Features that are common to all, are
īˇ fever headache, , malaise drowsiness
īˇ some neck stiffness, and sometimes epileptic seizures.
īˇ Focal signs may develop less commonly than with other encephalitides.
Diagnosis
The diagnosis of arbovirus encephalitis (A high degree of suspicion)
īˇ if there is a history of exposure to insect bites in a geographical area known to harbour the virus.
īˇ With ease of transcontinental travel
recent movements, recreational and occupational activities
people who hike, camp
or work in forest and scrub exposed to mosquitoes and ticks have a higher exposure to insect bites.
1-Routine blood tests
īˇ are seldom helpful
2- EEG
shows slow wave abnormality in proportion to the degree of impairment of awareness.
3-Imaging with either CT or MR
īˇ is often normal or may show a tight brain.
īˇ In some cases of Japanese and St Louis encephalitis MR and CT have demonstrated abnormality in
basal ganglia, brainstem, and substantia nigra
4-Serum AB
Demonstrating a rise of antibody titre in paired serum samples
5-CSF
Showing viral RNA in CSF by one of the PCR techniques
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or by demonstrating antigen or antibody by ELISA
West Nile Virus
īŽ Seenin Africa, West Asia, Middle East, Eastern Europe and Australia
īŽ Vector: Culex mosquito
Encephalitis or meningioencephalitis
īŽ Diagnostic clues include:
īŽ GIT upset
īŽ Maculopapular rash (up to 5 to 50%)
īŽ Cranial neuropathies (20% of cases):
īŽ Most commonly bilateral peripheral facial palsy
īŽ Optic neuropathy may occur
īŽ Movement abnormalities:
īŽ Postural or kinetic tremor
īŽ Rigidity
īŽ Myoclonus
Lower motor neuron weakness
īŽ May be isolated or associatedwith encephalitis
īŽ Polio like flaccid paralysis affect one limb or any combination of limbs
īŽ Respiratory muscle weakness requiring ventilation may occur
īŽ Bowel and bladder dysfunction in up to 30% of cases
Others
īŽ May be isolated or associatedwith encephalitis
īŽ Polio like flaccid paralysis affect one limb or any combination of limbs
īŽ Respiratory muscle weakness requiring ventilation may occur
īŽ Bowel and bladder dysfunction in up to 30% of cases
Rift Valley Fever
īŽ Disease is found in Egypt, Sudan, east Africa, Mauritania
īŽ Clinical picture:
īŽ Influenza like illness
īŽ Eye manifestations:
īŽ Retro-orbital pain
īŽ Macular retinitis with diminution of vision
īŽ Meningioencephalits
īŽ Hepatitis
īŽ No specific treatment
Equine encephalitis
St Louis and Japanese encephalitis see paper
Tick-borne encephalitis
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Rabies
īŽ Rabies is found enzootic almost all of the world except for Australia, Great Britain, Ireland
and Japan
īŽ Reservoir hosts include:
īŽ Dogs
īŽ Bats
īŽ Transmission:
īŽ Bites
īŽ Aerosoal exposure rarely reported
īŽ Virus enters the peripheral nervous systemat site of bite
īŽ It moves along peripheral nerves to the CNS
īŽ Once inside the CNS it spreads rapidly
īŽ Pathology:
īŽ Little tissue necrosis or cellular loss
īŽ Negri bodies: intra neuronal inclusions
īŽ Changes most prominent in brainstem and limbic system
Clinical picture
īŽ Incubation period:
īŽ Variable from 1-2 months
īŽ Shorter with head and neck bites
īŽ Prodromal phase:
īŽ Headache
īŽ High grade fever
īŽ Pain and paresthesia the site of the bite
īŽ Acute neurological phase:
īŽ Hydrophobia:
īŽ Spasms in pharngeal or nuchal muscles lasting from 1-5 minutes
īŽ Triggered by swallowing attempts or sensory stimuli
īŽ Seizures
īŽ Autonomic hyperactivity
īŽ Behavioral changes:
īŽ Furious rabies:
īŽ Agitation and hallucinations predominate
īŽ May proceede to coma
īŽ Dumb rabies:
īŽ Seenin 20% of cases
īŽ Most commonly associatedwith bat rabies
īŽ PAresthesia and weakness at site of the bite that proceeds to quadriplegia
Investigations
īŽ Virus can be identified by:
īŽ Inoculation of mice with patientâs saliva
īŽ Immune florescence for viral antigens in nuchal biopsy or corneal smears
īŽ PCR from CSF
īŽ Serology:
īŽ Neutralizing antibodies in CSF or serum
īŽ Diagnostic but not highly sensitive
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Prevention
īŽ Pre-exposure prevention:
īŽ Human deploid cell rabies vaccine
īŽ Post exposure prevention:
īŽ Wash wound with soap and water followed by povidone iodine
īŽ Immediate administration of vaccine
īŽ Human rabies immune globulin administered as soon as possible
īŽ Vaccine may cause: GBS,ADEM
Management
īŽ Handling of the animal:
īŽ Animal can be either killed or kept under observation for 10 days
īŽ Treatment can be stopped if animal is healthy after period of observation or its brain is
negative for rabies
īŽ No active treatment available
īŽ Mortality is 100% if patient becomes symptomatic
Encephalitis lethargica
von Economo's encephalitis
īˇ The histological and epidemiological features of the disease have pointed to a viral, infectious
aetiology but no virus has ever been isolated and that the aetiology of these cases is probably
multifactorial.
īˇ It is probable that the disease has died out, certainly there has been no further epidemic.
Clinically
the clinical syndrome is defined more by the region of the brain which is affected,
Age
Most cases occurred in early adult life, and during spring.
The onset was acute, sometimes fulminant, with
1. headache, malaise, myalgia
2. delirium, and convulsions.
3. pupillary abnormalities
4. and disturbances of ocular movement were common.
Less acute cases
would develop a characteristic sleep disturbance with severe lethargy by day from which they could
be roused, and insomnia by night.
Chronic cases
Extrapyramidal manifestations would supervene, including
1. frank parkinsonism with tremor, rigidity, and oculogyric crises.
2. Some would have chorea or myoclonus.
Treatment
īˇ No treatment regime has been shown to be beneficial
īˇ steroids have benefited two recent cases
Measles
īŽ A highly contagious respiratory borne disease
īŽ Causes four CNS disorders:
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īŽ Acute encephalitis
īŽ Post viral encephalitis
īŽ Measles inclusion body myositis
īŽ SSPE
Acute encephalitis
īŽ Occurs as a complication of acute measles infection
īŽ Most likely to occur in children under the age of 2
īŽ Other features of acute measles are seen including
īŽ Fever
īŽ Conjunctivits
īŽ Koplikâs spots
īŽ Maculopapular rash
īŽ EEG abnormalites are seen in 50% of patients with acute measles in absence of encephalitis
Post infectious encephomyelitis
īŽ Affects children above the age of 2 with normal immunity
īŽ Pathology (not specific):
īŽ Autoimmune mediated demyelinating disease
īŽ Perivascular demyelination, cuffing and gliosis
īŽ Hemorrhagic changes in severe cases
īŽ Onset: 2 weeks after rash
īŽ Main manifestations:
īŽ Encephalopathy
īŽ Focal pariesis
īŽ Ataxia
īŽ Myoclonus
īŽ Seizure
īŽ Rarely, pure myelitis
īŽ Management:
īŽ Steroids
īŽ Plasma pharesis
īŽ Outcome:
īŽ Mortality is up to 15% untreated
īŽ Residual neurological deficits may occur
Inclusion body encephalitis
īŽ A rapidly progressive dementing illness developing 1 to 6 months after measles infection in
individuals with impaired cell mediated immunity
īŽ Pathology:
īŽ Diffuse inflammatory changes in the brain
īŽ Eosinophilic inclusion bodies within nuclei of neurons
īŽ Virus antigen can be detected in brain tissue
īŽ Clinical picture:
īŽ Behavioral changes
īŽ Myoclonus
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īŽ Refractory focal and generalized seizures
īŽ Altered consciousness
īŽ Coma and death in a few months
īŽ Treatment:
īŽ Mainly supportive
īŽ Reverse immune suppression of possible
īŽ Passive immune globulin therapy
N.B Measles virus has been suggested, but not proved to play a role in the pathogenesis of
īŽ Multiple sclerosis
īŽ Autism
īŽ Chronic active hepatitis
īŽ Osteosclerosis
īŽ Crohnâs disease
Subacute sclerosing panencephalitis: see WMD dd
Rubella
Congenital rubella
īŽ 80% have CNS involvement
īŽ Manifestation include
īŽ Mental retardation
īŽ Sensorineural hearing loss
īŽ Motor and posture abnormalities
īŽ Pigmentary retinopathy
Late-onset rubella encephalitis
īŽ An uncommon progressive rubella panencephalitis that may follow congenital rubella or natural
childhood rubella.
īŽ Onset of neurological deterioration during the second decade of life.
īŽ Symptoms include :
īŽ behavioral changes and intellectual decline
īŽ Ataxia
īŽ Spasticity
īŽ Seizures.
īŽ Differs from SSPE in:
īŽ Patients are usually older
īŽ Clinical course is more protracted
īŽ Patients lack generalized myoclonus or periodic burst-suppression EEG patterns.
īŽ Serum and CSF anti rubella Abs can be detected
īŽ MRI: diffuse brain atrophy
Mumps
īŽ Incidence markedly declined after introduction of vaccination
īŽ Onset:
14. Encephalitis and other brain infection final
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īŽ 5 days after onset of parotitis
īŽ In 40-50% meningitis may precede parotitis
īŽ May occur without salivary
īŽ Manifestations:
īŽ Meningeal irritation
īŽ Disturbed conscious level
īŽ Complications:
īŽ Seizures
īŽ Deafness from labyrinth membrane and sensory transducer damage
īŽ Myelitis
īŽ Hydrocephalus following viral replication in choroidal and ependymal cells
Influenza
īŽ Neurological complications include:
īŽ Myositis
īŽ Reye syndrome
īŽ Acute encephalitis:
īŽ High rate of mortlaity
īŽ Post infectious encephalopathy
īŽ Good prognosis
īŽ Encephalitis lethargica
Arena viruses
Lymphocytic choriomeningitis virus
īŽ Aseptic meningitis: the most common
īŽ Encephalitis: (5-34% )
īŽ Ascending or transverse myelitis
īŽ Bulbar syndromes
īŽ Parkinsonism
īŽ Sensorineural hearing loss.
īŽ Hydrocephalus may arise as a sequelae of ependymitis or ventriculitis
īŽ Diagnosis:
īŽ CSF :
īŽ cell counts of 10-500 WBC
īŽ Viral culture and serology
īŽ IgM antibody to LCMV is present in serum and/or CSF during acute meningitic disease
īŽ Treatment: ribavirin
Retroviruses
īŽ The Retroviridae is a large family of viruses including:
īŽ HTLV-bovine leukemia group:
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īŽ Human T-cell lymphotropic virus (HTLV) types I and II.
īŽ Lentivirus group:
īŽ HIV 1 and 2
DNA Viruses
JC virus: PML
Enteroviruses
Poliomyelitis
īŽ Infection is by the oro-fecal route
īŽ 95% of infections are asymptomatic or cause non specific Flu like illness
īŽ CNS involvement
īŽ Aseptic meningitis
īŽ Paralytic illness: less than 1 % of all cases
īŽ Incubation Period: 7 -14 days
īŽ Gastroenteritis or flu like symptoms
īŽ Meningeal syndrome:
īŽ Fever
īŽ Headache
īŽ Meningeal irritation
īŽ Disturbed conscious level
īŽ Seizures in infants
īŽ Paralytic Polio:
īŽ Starts within days of meningeal irritation
īŽ Progress over 3-5 days
īŽ Asymmetric acute flaccid paralysis
īŽ Myalgia and severe muscle spasms can occur
īŽ Diaphragm and respiration can be affected
īŽ Cranial nerve involvement
īŽ Bulbar form (brainstem involvement)
īŽ Pure or associatedwith spinal affection
īŽ High mortality (up to 50%) due to
īŽ Vasomotor disturbances (hypo or hypertension)
īŽ Dysphagia
īŽ Dysphonia
īŽ Respiratory failure
īŽ Investigations
īŽ CSF:
īŽ Pleocytosis: PMNâLymphocytosis
īŽ Proteins: slightly elevated
īŽ Normal glucose
īŽ PCR
īŽ Stool culture:
īŽ Two stool culture for virus isolation in a qualified laboratory
Differential Diagnosis
īŽ Non paralytic polio: Aseptic meningitis
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īŽ Paralytic polio:
Flaccid paralysis with CSF pleocytosis
īŽ Other viruses:
īŽ Other enteroviruses
īŽ Flavi viruses
īŽ Herpes family myelitis
īŽ Rabies
īŽ Carcinomatous meningitis
īŽ Guillian Barre syndrome
īŽ Antecedent not concurrent fever
īŽ More common facial nerve involvement
īŽ Sensory loss
īŽ Absent reflexes
īŽ CSF protein elevated
Treatment
īŽ Notification
īŽ Mainly supportive with special attention for
īŽ Immobilization in early stages
īŽ Respiratory care
īŽ Pleocarnil used successfully in some cases
īŽ Rehabilitation in Chronic cases
Vaccination
īŽ Sabin:
īŽ Live attenuated oral vaccine
īŽ Advantages: Herd immunity
īŽ Risk of vaccine related paralytic polio in
īŽ Infants with unrecognized immune defeciency
īŽ Immune compromised contacts of vaccinated infants
īŽ Salk:
īŽ Inactivated parentral vaccine
īŽ Used in immune compromised
Post polio Syndrome
īŽ Progressive lower motor neuron weakness 30-40 years after acute polio unrelated to any other
neurological or systemic illness
īŽ Occurs in up to one quarter of cases
īŽ Etiology:
īŽ Not fully understood
īŽ Virus could not be isolated
īŽ Manifests by:
īŽ Atrophy
īŽ Fasciculations
īŽ EMG: evidence of active denervation in involved muscles
īŽ Management:
īŽ Muscle strengthening: avoid fatigue
īŽ Weight Control
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Non-viral encephalitis
Introduction
īŧ Encephalitis which is clinically indistinguishable from the viral form of the disease, can be caused by
other organisms, bacteria, and parasites.
1. Chlamydial diseases
2. Rickettsial infections
3. Mycoplasma infection
4. Malaria
5. Trypanosomiasis
6. Other parasites
7. Whipple's disease
Chlamydial diseases
Bacteriology
Three species of chlamydiae can cause human disease
1. Chlamydia trachomatis
2. Chlamydia pneumonia
3. Chlamydia psittaci.
īŧ Chlamydiae
Human infection results from inhalation of the organism or by ingestion after handling contaminated
plumage.
The organism is pathogenic to the lung and infection can range from
ī§ Asymptomatic
ī§ to severe and potentially fatal, atypical pneumonia.
ī§ Liver, spleen, meninges, brain, and heart may also be involved.
Clinically
The incubation period varies from 4 to 15 days and in some, may be as long as a month.
Clinical features
may vary widely.
īˇ mild upper respiratory tract infection which may not be recognized as anything more than a common
cold. In others, there is abrupt onset of fever, rigors, and chills, with
severe headache, myalgia, and a persistent dry cough.
īˇ neurological
A minority develop meningo-encephalitis which may progress to coma.
Rarely, meningo-encephalitis may predominate from the outset
īˇ Other neurological syndromes including
1. transverse myelitis
2. cranial nerve palsies
3. and cerebellar disturbance
Investigations
1. isolation of the organism from respiratory secretions (which is hazardous to laboratory staff)
2. or by the demonstration of antibody rise in acute and convalescent sera.
3. PCR examination of tissue or fluid, and enzyme immunoassays are being developed, but there
have been some problems with cross reactions.
Treatment of chlamydial infection
1. is with tetracycline, erythromycin, or clarythromycin.
2. Some of the newer quinolones are also effective.
For neurological disease
īŧ parenteral administration
īŧ and a prolonged course is often necessary because of the risk of relapse.
Rickettsial infections
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Bacteriology
īŧ On the basis of the clinical syndromes which they produce in humans, and on their antigenicity and
growth characteristics, they are divided into three main groups
1. the spotted fever group
2. the typhus group
3. and the scrub typhus group (Table 34.5).
4. Q fever, due to infection with Coxiella burnetii, is contained in a fourth group that
includes infections caused by Erlichia species, which can rarely cause an acute
meningo-encephalitis.
īŧ Rickettsiae are inoculated into the human body by the bite of the vector insect, or by scratching of
contaminated insect material though skin or mucous membrane.
īŧ Characteristically, they produce a widespread vasculitis which increases vascular permeability,
produces oedema and endothelial cell injury, activates inflammatory and coagulation mechanisms,
and may result in widespread organ damage due to thrombosis, haemorrhage, and shock.
īŧ When this occurs in the brain, meningo-encephalitis results.
īŧ Q fever is probably acquired through inhalation of the organism from infected animal products.
īŧ The incubation period, progression, and clinical features of the different syndromes varies, but all
generally share the features of
1. high pyrexia, skin rash, headache, and myalgia
2. and if neurological features develop, meningo-encephalitis is evident by the second week.
Table 34.5. Human rickettsial diseases
Group Organism Vect
or
Geography Disease
Spotted
fever
R. rickettsii Tick North, Central, South America Rocky Mountain
spotted fever
Typhus R. prowazekii Lous
e
Ubiquitous Epidemic typhus
R. typhi Flea Ubiquitous Murine typhus
Scrub
typhus
R.
tsutsugamushi
Mite
s
Asia, Pacific Australia Scrub typhus
Other C. burnettii Non
e
Ubiquitous Q fever
`
Rocky Mountain Spotted fever
first described from the Rocky Mountain region of the USA and it soon became evident that the same
disease occurred throughout the western hemisphere.
Clinically
IP
is about 1 week and varies in proportion to the bite inoculum.
General
ī§ Most patients can remember and report the insect bite.
ī§ Fever with rigors,
ī§ to be followed by a distinctive rash by the 3rd-5th day of the illness
Neurological
ī§ Headache is invariable
ī§ About 25 %, of patients progress to develop encephalitis followed by stupor and coma if they are not
treated appropriately.
Diagnosis
1. Blood tests
are seldom helpful in the acute stageârise in serum antibody titre is useful but takes time.
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2. Immunofluorescence of skin biopsy
is said to be specific but not very sensitive and is not widely available.
3. PCR of CSF, blood, and skin biopsy specimens is undergoing evaluation.
Treatments
The treatments of choice are
1. tetracycline or doxycycline for 10 days to a fortnight, for adults
2. steroids have been used âmay effective
Mediterranean Spotted fever(Boutonneuse fever)
ī§ This condition is caused by R. conori
ī§ The centre of the papule becomes necrotic and dark coloured, the âtache noireâ,
which is characteristic.
ī§ From there, spread takes place to local lymph nodes then to the general circulation.
ī§ In 7 days or thereby, symptoms similar to those of Rocky Mountain Spotted fever appear
fever, headache, myalgia, arthralgia, lymphadenopathy, and rash.
Meningism and encephalopathic features occur in up to 20 % of cases.
Epidemic and murine typhus
Epidemic and murine typhus are clinically similar.
C/P The incubation period is about 2 weeks.
The clinical syndrome of the two diseases resembles a severe form of RMSF with
ī§ the abrupt onset of fever, headache, myalgia
ī§ and a spreading macular and petechial rash
ī§ delirium, and encephalopathy.
ī§ White spots (typhus nodules) may be evident in the retina on fundoscopy.
Investigations and treatment are similar to those described above
Scrub typhus
ī§ The clinical features
1. are of fever, general lymphadenopathy
2. and an eschar at the site of the bite.
3. Headache and myalgia are invariable and as many as 10 %develop features of encephalitis.
4. A rash on the trunk, spreading to the limbs, is common.
ī§ Confirmation of the diagnosis is serological and PCR has been developed and is accurate.
ī§ Treatment is with tetracycline.
Q fever
ī§ Q fever is caused by Coxiella burnetii, a cocco-bacillus.
ī§ It infects a large number of animal species, usually asymptomatically, where it localizes to the uterus
and mammary glands.
ī§ Direct or indirect exposure to infected animals may result in clinical disease in humans.
ī§ Infection usually results from aerosol inhalation of infected material.
ī§ This may take several forms which include
1. an acute self-limiting febrile illness
2. pneumonia, endocarditis, hepatitis
3. aseptic meningitis, and encephalitis.
ī§ Neurological complications are in fact quite rare
1. such as hallucinations
2. speech disturbance
3. facial pain in 23 %of patients in one outbreak
ī§ Patients who are immune compromised may be more at risk of developing disease.
ī§ Investigations and treatment are similar to those described above.
Mycoplasma infection
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The two major mycoplasma organisms which are associated with neurological disease are
1. Mycoplasma pneumoniae
2. and Mycoplasma hominis.
The latter is found in the genitourinary tract and may be a cause of neonatal meningitis.
It has been isolated from rare cases of brain abscess.
Mycoplasma pneumoniae
has been associated with several neurological syndromes.
Clinically
ī§ In the majority who become symptomatic
ī§ an influenza-like illness creeps on after 2â3 weeks incubation with
ī§ severe coughing, headache, and myalgia.
Neurological complications
up to 7 % of hospitalized cases and occur from 3 to 30 days after the upper respiratory infection
1. Aseptic meningitis, encephalitis
2. cerebellar syndrome
3. GuillainâBarrÊ polyneuropathy
4. transverse myelitis
5. and cranial nerve palsies
The pathogenic mechanisms
are not always clear
ī§ it seems that direct CNS invasion occurs
ī§ and in others there may be an immune mediated form of post-infectious encephalitis perhaps with
immune complex vasculopathy
Diagnosis
ī§ can be made by the detection of cold haemagglutins in the serum of a patient with neurological
complications after an upper respiratory infection.
Their absence does not exclude the diagnosis as their presence is fairly non-specific.
ī§ Increase in serum antibody titres can be confirmatory.
ī§ PCR of CSF is likely to prove useful
Treatment
1. Erythromycin, doxycycline, or tetracycline for 2 weeks is effective treatment for the acute
respiratory infection
2. the response of neurological disease is variable and probably depends on the pathogenic mechanism.
Prognosis
Perhaps 1/3 of patients have persisting neurological signs
and severe meningo-encephalitis carries a poor prognosis.
Whipple's disease
Tropheryma whippelii
The method of infection and pathogenesis
ī§ are not known.
ī§ Because of the gastrointestinal location of the disease, it is thought to be contracted by ingestion
following which it disseminates through the body via lymph and blood.
ī§ In addition to the gut, the CNS, eyes, heart, lungs, and skin and joints may be involved and the
disease may present in any of these systems.
Clinical features
ī§ Whipple's disease is rare.
ī§ It affects men more than women
ī§ and occurs at any age, most commonly with onset in the 40s.
Clinically
ī§ Usually there is diarrhoea with malabsorption, weight loss
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wasting, pyrexia, sometimes of unknown origin, and lymphadenopathy.
ī§ Onset is insidious and progress is often atypical.
The most frequent CNS manifestations
ī§ 5 and 40 % have neurological manifestations and 5 % the disease may be confined to the CNS
1. Dementia
2. ocular movement disturbance
īŧ Ophthalmoplegia is of supranuclear type and affects vertical rather than horizontal movement.
īŧ Internuclear ophthalmoplegia.
īŧ oculomasticatory myorhythmia and oculo-facial-skeletal myorhythmia are said to be diagnostic
3. movement disorders
particularly myoclonus
4. Ataxia - epilepsy -hypothalamic upset
5. meningitis, and focal cerebral signs.
6. Headache is common.
ī§ Certainly, the triad of
1. Dementia
2. Ophthalmoplegia is highly suggestive of Whipple's disease
3. and myoclonus
Diagnosis
Demonstration of a positive PCR
against T. whippelii in material from affected tissue, including CSF.
CT and MR imaging of the brain
may show atrophy, mass lesions and contrast enhancement, white matter high signal areas, ring
enhancing lesions, and hydrocephalus.
Differential diagnosis
is wide and includes
1. dementias-encephalopathies,
2. CNS vasculitides, demyelination-granulomatous disease
3. chronic CNS infection.
4. If movement disorder is present with dementia CreutzfeldtâJakob disease merits exclusion.
Treatment
1. The regime currently in favour is a combination of
parenteral penicillin and streptomycin for a minimum of 14 days
followed by cotrimoxazole orally for up to 2 years
2. or parenteral ceftriaxone for a month followed by 2 years of oral cefixime.
This length of treatment is necessary because of the high incidence of relapse.
PCR is now recognized to be the best test to monitor progress
and it is necessary to check CSF as well as bowel for negative results before discontinuing treatment