Encephalitis and other brain infection final (autosaved)

Encephalitis and other brain infection final
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Encephalitis.
Introduction and definition
 The term ‘encephalitis’ implies inflammatory change affecting brain parenchyma.
By common usage the name refers to inflammation of the brain caused by infection.
 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.
 Most cases of encephalitis are caused by
1. viruses
2. protozoa such as malaria and toxoplasma
3. bacteria such as spirochaetes and rickettsiae
 viral encephalitis can be grouped into three distinct categories:
1. Acute viral encephalitis
 is due to direct invasion of the brain by virus
 The signs and symptoms result from this invasion and from the inflammatory change
which it induces in the brain parenchyma.
2. Post-infectious encephalitis
 is characterized pathologically by perivenous demyelination caused by allergic or immune
mechanisms relating to viral infection.
3. Prion diseases.
 The third group includes those encephalitides with a prolonged clinical evolution, known heretofore
as the ‘slow virus infections’ and now as ‘prion diseases’. (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
Varicella–zoster
Cytomegalovirus
Epstein–Barr
Papovavirus JC virus-progressive multifocal leucoencephalopathy
RNA viruses
Retroviruses HTLV-1—HAM-TSP
HIV—AIDS
Picornovirus
Enteroviruses Poliomyelitis—polio
C
o
x
sakie
— 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
Congo–Crimean 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 spring–summer
encephalitis
Louping ill
Rubivirus Rubella
The diagnosis of viral infection of the nervous system
 Careful attention to historical details
 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. ↑antibody 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
 Virus culture
 has not been greatly successful in the diagnosis of CNS infections, in large part due to the
difficulty of obtaining specimens of neural tissue.
 It may be possible to cultivate virus from other sources but this is seldom fruitful.
 Traditionally, the demonstration of a fourfold rise in antibody titre
 between an acute phase and a convalescent serum sample to a specific virus has been
sufficient to confirm the diagnosis.
 Numerous techniques that employ immunofluorescence and ELISA
 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)
 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
 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.
 A list of the virus groups that cause encephalitis is found in Table 34.2.
 Encephalitis may be sporadic or epidemic.
Table 34.2. Viral causes of encephalitis
Herpes simplex
Varicella–zoster
Cytomegalovirus –
Epstein–Barr virus
Human herpes virus 6 -B herpes virus
Mumps-Measles→↓by 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 well—headache, 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 focal→common
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
 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
 ADAM
 more explosive varieties of MS may have an encephalitic onset
3-Brain tumours
 Intracranial suppuration

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 advanced primary or metastatic brain tumours
 ↑ICP from whatever cause may lead to coma and to neck stiffness from cerebellar tonsillar
herniation.
4-Vascular
 Intracranial haemorrhage can cause a similar picture, including pyrexia.
 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
 e.g kidney and liver failure
often occur in the context of generalized infection and may be particularly difficult to diagnose
 Rare encephalopathies such as Wilson's disease must not be forgotten.
The history may reveal
 a characteristic epidemiological pattern
 the time of year and the disease known to occur in a particular community.
 Has there been a bite from or exposure to known insect vectors of disease?
 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
↑↑↑
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
 The EEG is useful in demonstrating and following up epileptic activity
Findings
 diffuse slow wave activity that becomes slower with increasing severity.
 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
 Abnormal EEG activity is commonly seen from one temporal lobe and this may spread to the other
side as the disease progresses.
 This may be followed by spike and slow wave activity and PLEDs arising from a temporal lobe
 This is not pathognomonic.
Creutzfeldt–Jakob 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
 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.
 It is necessary for them to lie still for about 30 min within a tube
 This is not possible for patients who are ill or confused.
 Any movement degrades the image →quite long.
 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
 areas of necrosis, granulomas
 abscesses, neoplasm
 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
 if the Glasgow Coma Scale falls to 8 or below
 if there is radiological evidence of significant brain swelling
 or if there is mass effect.
→Hyperventilation and the administration of mannitol
→There 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
 herpes simplex encephalitis
 and childhood bacterial meningitis
In practice, dexamethasone is given to patients
 who have raised ICP

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 and who continue to deteriorate.
5. The availability of neuro-intensive care and a multidisciplinary approach
→improvement in their management.
Antiviral drugs
Specific treatment for viral encephalitis is available for only a minority of infections.
Acyclovir
Related drugs
→ valacyclovir and famciclovir
are under investigation.
↓mortality 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
 rabies is universally fatal once established
 herpes simplex encephalitis can be devastating.
The herpes viruses
Those viruses which cause disease in man are
HSV-1 and -2 varicella–zoster
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 -Varicella–zoster
Cytomegalovirus - Epstein–Barr virus see paper
Human herpes virus 6
→CNS diseases are
1. meningo-encephalitis
2. retinitis,
3. Guillain–Barré polyneuropathy
4. epileptic seizures
on the basis of serological studies and PCR studies of CSF
 causal relationship has not been definitely established found
HHV-6 DNA in CSF of 2.2 % of patients with neurological complications of AIDS.
 Not enough is known to date to make any recommendations about treatment.
Herpes B virus
 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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 It has also been described following person to person contact.
Clinical picture
 The onset is acute with neurological symptoms within 3–5 days and death has occurred within 2
weeks.
 A localized vesicular eruption
occurs around the area of the bite
 followed by
1. regional lymphadenopathy then malaise, fever, myalgia
2. and neurological signs of myelitis and encephalitis or encephalomyelitis
Other viral encephalitides
Epidemic encephalitis
 This form of encephalitis is caused by one of the arboviruses
 Arbovirus transmitted biologically by haematophagous arthropods such as mosquitoes, ticks,
sandflies, and biting midges (Phlebotomus and Culicoides).
 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.
 There are in excess of 20 arboviruses that cause encephalitis in man (Table 34.3).
 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
 are symmetrical spherical enveloped virions that range in size from 40 to 90 nm in diameter
 subdivided by size into larger flaviviruses and smaller alphaviruses.
 Bunyaviridae are larger and the nucleocapsids have helical symmetry.
 The Reoviridae contain double stranded nucleic acid and have no envelope.
Vectors
 All arboviral encephalitides are maintained by zoonoses with complex life cycles involving a non-
human, vertebrate
 primary host—usually birds and lower vertebrate
 and a primary arthropod vector—usually a mosquito or tick.
 Many arboviruses have different vertebrate hosts and more than one vector.
The mechanism of transmission

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 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.
 It bites a human, injecting virus in the process.
 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.
 Humans are infected by accident, and become ‘dead end’ hosts, because the viraemia which results
is not of sufficient degree to infect a biting mosquito.
 Most cases of encephalitis occur in the summer, when arthropods are most active.
Climatic factors are important—a late summer can prolong the period for potential infection.
 St. Louis encephalitis:
 The most common in the USA
 Japanese encephalitis:
 Widely spread in Asia
 The most frequent cause of viral encephalitis in the world
 Eastern Equine encephalitis:
 The most severe with mortality of 50-70%
 Tick born encephalitis:
 Widely spread in Central Europe and former Soviet Union
Clinical features
Features that are common to all, are
 fever headache, , malaise drowsiness
 some neck stiffness, and sometimes epileptic seizures.
 Focal signs may develop less commonly than with other encephalitides.
Diagnosis
The diagnosis of arbovirus encephalitis (A high degree of suspicion)
 if there is a history of exposure to insect bites in a geographical area known to harbour the virus.
 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
 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
 is often normal or may show a tight brain.
 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
 Seenin Africa, West Asia, Middle East, Eastern Europe and Australia
 Vector: Culex mosquito
Encephalitis or meningioencephalitis
 Diagnostic clues include:
 GIT upset
 Maculopapular rash (up to 5 to 50%)
 Cranial neuropathies (20% of cases):
 Most commonly bilateral peripheral facial palsy
 Optic neuropathy may occur
 Movement abnormalities:
 Postural or kinetic tremor
 Rigidity
 Myoclonus
Lower motor neuron weakness
 May be isolated or associatedwith encephalitis
 Polio like flaccid paralysis affect one limb or any combination of limbs
 Respiratory muscle weakness requiring ventilation may occur
 Bowel and bladder dysfunction in up to 30% of cases
Others
 May be isolated or associatedwith encephalitis
 Polio like flaccid paralysis affect one limb or any combination of limbs
 Respiratory muscle weakness requiring ventilation may occur
 Bowel and bladder dysfunction in up to 30% of cases
Rift Valley Fever
 Disease is found in Egypt, Sudan, east Africa, Mauritania
 Clinical picture:
 Influenza like illness
 Eye manifestations:
 Retro-orbital pain
 Macular retinitis with diminution of vision
 Meningioencephalits
 Hepatitis
 No specific treatment
Equine encephalitis
St Louis and Japanese encephalitis see paper
Tick-borne encephalitis

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Rabies
 Rabies is found enzootic almost all of the world except for Australia, Great Britain, Ireland
and Japan
 Reservoir hosts include:
 Dogs
 Bats
 Transmission:
 Bites
 Aerosoal exposure rarely reported
 Virus enters the peripheral nervous systemat site of bite
 It moves along peripheral nerves to the CNS
 Once inside the CNS it spreads rapidly
 Pathology:
 Little tissue necrosis or cellular loss
 Negri bodies: intra neuronal inclusions
 Changes most prominent in brainstem and limbic system
Clinical picture
 Incubation period:
 Variable from 1-2 months
 Shorter with head and neck bites
 Prodromal phase:
 Headache
 High grade fever
 Pain and paresthesia the site of the bite
 Acute neurological phase:
 Hydrophobia:
 Spasms in pharngeal or nuchal muscles lasting from 1-5 minutes
 Triggered by swallowing attempts or sensory stimuli
 Seizures
 Autonomic hyperactivity
 Behavioral changes:
 Furious rabies:
 Agitation and hallucinations predominate
 May proceede to coma
 Dumb rabies:
 Seenin 20% of cases
 Most commonly associatedwith bat rabies
 PAresthesia and weakness at site of the bite that proceeds to quadriplegia
Investigations
 Virus can be identified by:
 Inoculation of mice with patient’s saliva
 Immune florescence for viral antigens in nuchal biopsy or corneal smears
 PCR from CSF
 Serology:
 Neutralizing antibodies in CSF or serum
 Diagnostic but not highly sensitive

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Prevention
 Pre-exposure prevention:
 Human deploid cell rabies vaccine
 Post exposure prevention:
 Wash wound with soap and water followed by povidone iodine
 Immediate administration of vaccine
 Human rabies immune globulin administered as soon as possible
 Vaccine may cause: GBS,ADEM
Management
 Handling of the animal:
 Animal can be either killed or kept under observation for 10 days
 Treatment can be stopped if animal is healthy after period of observation or its brain is
negative for rabies
 No active treatment available
 Mortality is 100% if patient becomes symptomatic
Encephalitis lethargica
von Economo's encephalitis
 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.
 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
 No treatment regime has been shown to be beneficial
 steroids have benefited two recent cases
Measles
 A highly contagious respiratory borne disease
 Causes four CNS disorders:

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 Acute encephalitis
 Post viral encephalitis
 Measles inclusion body myositis
 SSPE
Acute encephalitis
 Occurs as a complication of acute measles infection
 Most likely to occur in children under the age of 2
 Other features of acute measles are seen including
 Fever
 Conjunctivits
 Koplik’s spots
 Maculopapular rash
 EEG abnormalites are seen in 50% of patients with acute measles in absence of encephalitis
Post infectious encephomyelitis
 Affects children above the age of 2 with normal immunity
 Pathology (not specific):
 Autoimmune mediated demyelinating disease
 Perivascular demyelination, cuffing and gliosis
 Hemorrhagic changes in severe cases
 Onset: 2 weeks after rash
 Main manifestations:
 Encephalopathy
 Focal pariesis
 Ataxia
 Myoclonus
 Seizure
 Rarely, pure myelitis
 Management:
 Steroids
 Plasma pharesis
 Outcome:
 Mortality is up to 15% untreated
 Residual neurological deficits may occur
Inclusion body encephalitis
 A rapidly progressive dementing illness developing 1 to 6 months after measles infection in
individuals with impaired cell mediated immunity
 Pathology:
 Diffuse inflammatory changes in the brain
 Eosinophilic inclusion bodies within nuclei of neurons
 Virus antigen can be detected in brain tissue
 Clinical picture:
 Behavioral changes
 Myoclonus

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 Refractory focal and generalized seizures
 Altered consciousness
 Coma and death in a few months
 Treatment:
 Mainly supportive
 Reverse immune suppression of possible
 Passive immune globulin therapy
N.B Measles virus has been suggested, but not proved to play a role in the pathogenesis of
 Multiple sclerosis
 Autism
 Chronic active hepatitis
 Osteosclerosis
 Crohn’s disease
Subacute sclerosing panencephalitis: see WMD dd
Rubella
Congenital rubella
 80% have CNS involvement
 Manifestation include
 Mental retardation
 Sensorineural hearing loss
 Motor and posture abnormalities
 Pigmentary retinopathy
Late-onset rubella encephalitis
 An uncommon progressive rubella panencephalitis that may follow congenital rubella or natural
childhood rubella.
 Onset of neurological deterioration during the second decade of life.
 Symptoms include :
 behavioral changes and intellectual decline
 Ataxia
 Spasticity
 Seizures.
 Differs from SSPE in:
 Patients are usually older
 Clinical course is more protracted
 Patients lack generalized myoclonus or periodic burst-suppression EEG patterns.
 Serum and CSF anti rubella Abs can be detected
 MRI: diffuse brain atrophy
Mumps
 Incidence markedly declined after introduction of vaccination
 Onset:

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 5 days after onset of parotitis
 In 40-50% meningitis may precede parotitis
 May occur without salivary
 Manifestations:
 Meningeal irritation
 Disturbed conscious level
 Complications:
 Seizures
 Deafness from labyrinth membrane and sensory transducer damage
 Myelitis
 Hydrocephalus following viral replication in choroidal and ependymal cells
Influenza
 Neurological complications include:
 Myositis
 Reye syndrome
 Acute encephalitis:
 High rate of mortlaity
 Post infectious encephalopathy
 Good prognosis
 Encephalitis lethargica
Arena viruses
Lymphocytic choriomeningitis virus
 Aseptic meningitis: the most common
 Encephalitis: (5-34% )
 Ascending or transverse myelitis
 Bulbar syndromes
 Parkinsonism
 Sensorineural hearing loss.
 Hydrocephalus may arise as a sequelae of ependymitis or ventriculitis
 Diagnosis:
 CSF :
 cell counts of 10-500 WBC
 Viral culture and serology
 IgM antibody to LCMV is present in serum and/or CSF during acute meningitic disease
 Treatment: ribavirin
Retroviruses
 The Retroviridae is a large family of viruses including:
 HTLV-bovine leukemia group:

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 Human T-cell lymphotropic virus (HTLV) types I and II.
 Lentivirus group:
 HIV 1 and 2
DNA Viruses
JC virus: PML
Enteroviruses
Poliomyelitis
 Infection is by the oro-fecal route
 95% of infections are asymptomatic or cause non specific Flu like illness
 CNS involvement
 Aseptic meningitis
 Paralytic illness: less than 1 % of all cases
 Incubation Period: 7 -14 days
 Gastroenteritis or flu like symptoms
 Meningeal syndrome:
 Fever
 Headache
 Meningeal irritation
 Disturbed conscious level
 Seizures in infants
 Paralytic Polio:
 Starts within days of meningeal irritation
 Progress over 3-5 days
 Asymmetric acute flaccid paralysis
 Myalgia and severe muscle spasms can occur
 Diaphragm and respiration can be affected
 Cranial nerve involvement
 Bulbar form (brainstem involvement)
 Pure or associatedwith spinal affection
 High mortality (up to 50%) due to
 Vasomotor disturbances (hypo or hypertension)
 Dysphagia
 Dysphonia
 Respiratory failure
 Investigations
 CSF:
 Pleocytosis: PMN→Lymphocytosis
 Proteins: slightly elevated
 Normal glucose
 PCR
 Stool culture:
 Two stool culture for virus isolation in a qualified laboratory
Differential Diagnosis
 Non paralytic polio: Aseptic meningitis

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 Paralytic polio:
Flaccid paralysis with CSF pleocytosis
 Other viruses:
 Other enteroviruses
 Flavi viruses
 Herpes family myelitis
 Rabies
 Carcinomatous meningitis
 Guillian Barre syndrome
 Antecedent not concurrent fever
 More common facial nerve involvement
 Sensory loss
 Absent reflexes
 CSF protein elevated
Treatment
 Notification
 Mainly supportive with special attention for
 Immobilization in early stages
 Respiratory care
 Pleocarnil used successfully in some cases
 Rehabilitation in Chronic cases
Vaccination
 Sabin:
 Live attenuated oral vaccine
 Advantages: Herd immunity
 Risk of vaccine related paralytic polio in
 Infants with unrecognized immune defeciency
 Immune compromised contacts of vaccinated infants
 Salk:
 Inactivated parentral vaccine
 Used in immune compromised
Post polio Syndrome
 Progressive lower motor neuron weakness 30-40 years after acute polio unrelated to any other
neurological or systemic illness
 Occurs in up to one quarter of cases
 Etiology:
 Not fully understood
 Virus could not be isolated
 Manifests by:
 Atrophy
 Fasciculations
 EMG: evidence of active denervation in involved muscles
 Management:
 Muscle strengthening: avoid fatigue
 Weight Control

17
Non-viral encephalitis
Introduction
 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.
 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
 Asymptomatic
 to severe and potentially fatal, atypical pneumonia.
 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.
 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.
 neurological
A minority develop meningo-encephalitis which may progress to coma.
Rarely, meningo-encephalitis may predominate from the outset
 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
 parenteral administration
 and a prolonged course is often necessary because of the risk of relapse.
Rickettsial infections

18
Bacteriology
 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.
 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.
 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.
 When this occurs in the brain, meningo-encephalitis results.
 Q fever is probably acquired through inhalation of the organism from infected animal products.
 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
 Most patients can remember and report the insect bite.
 Fever with rigors,
 to be followed by a distinctive rash by the 3rd-5th day of the illness
Neurological
 Headache is invariable
 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 stage—rise in serum antibody titre is useful but takes time.

19
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 →may effective
Mediterranean Spotted fever(Boutonneuse fever)
 This condition is caused by R. conori
 The centre of the papule becomes necrotic and dark coloured, the ‘tache noire’,
which is characteristic.
 From there, spread takes place to local lymph nodes then to the general circulation.
 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
 the abrupt onset of fever, headache, myalgia
 and a spreading macular and petechial rash
 delirium, and encephalopathy.
 White spots (typhus nodules) may be evident in the retina on fundoscopy.
Investigations and treatment are similar to those described above
Scrub typhus
 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.
 Confirmation of the diagnosis is serological and PCR has been developed and is accurate.
 Treatment is with tetracycline.
Q fever
 Q fever is caused by Coxiella burnetii, a cocco-bacillus.
 It infects a large number of animal species, usually asymptomatically, where it localizes to the uterus
and mammary glands.
 Direct or indirect exposure to infected animals may result in clinical disease in humans.
 Infection usually results from aerosol inhalation of infected material.
 This may take several forms which include
1. an acute self-limiting febrile illness
2. pneumonia, endocarditis, hepatitis
3. aseptic meningitis, and encephalitis.
 Neurological complications are in fact quite rare
1. such as hallucinations
2. speech disturbance
3. facial pain in 23 %of patients in one outbreak
 Patients who are immune compromised may be more at risk of developing disease.
 Investigations and treatment are similar to those described above.
Mycoplasma infection

20
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
 In the majority who become symptomatic
 an influenza-like illness creeps on after 2–3 weeks incubation with
 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. Guillain–Barré polyneuropathy
4. transverse myelitis
5. and cranial nerve palsies
The pathogenic mechanisms
are not always clear
 it seems that direct CNS invasion occurs
 and in others there may be an immune mediated form of post-infectious encephalitis perhaps with
immune complex vasculopathy
Diagnosis
 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.
 Increase in serum antibody titres can be confirmatory.
 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
 are not known.
 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.
 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
 Whipple's disease is rare.
 It affects men more than women
 and occurs at any age, most commonly with onset in the 40s.
Clinically
 Usually there is diarrhoea with malabsorption, weight loss

21
wasting, pyrexia, sometimes of unknown origin, and lymphadenopathy.
 Onset is insidious and progress is often atypical.
The most frequent CNS manifestations
 5 and 40 % have neurological manifestations and 5 % the disease may be confined to the CNS
1. Dementia
2. ocular movement disturbance
 Ophthalmoplegia is of supranuclear type and affects vertical rather than horizontal movement.
 Internuclear ophthalmoplegia.
 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.
 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 Creutzfeldt–Jakob 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

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