2. 2 forms of encephalitis.
Acute post infections measles encephalitis
0.1 % of immunocompetent pt.
20 % mortality rate
Measles virus induced pathological immune
mediated "post-infectious" encephalitis
Not by direct invasion
3. Measles virus in immunocompetent patients
causes SSPE
In immunocompromized patients it causes
Measles Inclusion Body Encephalitis
4. Viral etiology proposed by Dawson in 1933
and 1934-Subacute inclusion body
encephalitis
Subacute sclerosing leukoencephalitis –Van
Bogaert, 1945
SSPE was coined by Greenfield in 1950
Very high titers of anti- measles antibodies in
the blood and CSF of all patients-Connolly et
al. in 1967
5. Annual incidence of 21 per million population
in India
History of primary measles infection at an
early age (<2 years)
Latent period of 6–8 years
Measles under age of 1 year carry a risk of 16
times greater than those at age 5 years or
later
Male/female ratio 3:1
6. Higher among rural children, with two or
more siblings, with mental retardation
More common in children with lower birth
order, overcrowded environments
7. RNA virus belongs to marbillivirus subgroup
of paramyxoviruses
Measles virus infection of brain occurs soon
after the acute infection
Virus reaches through infection of cerebral
endothelial cells or by circulating
inflammatory cells
Type II transmembrane protein H mediates
virus cell attachment by binding to the cell
surface protein CD46
8. Exact factors and influences that allow
measles infection to persist are unclear
Addition of antibodies against measles virus
may alter pattern of viral gene expression
Apoptosis of various cell types either as a
direct effect of viral infection or of cytokine
mediated responses
Results in oligodendroglial and neuronal cell
death in SSPE
9. Early stages-mild inflammation of meninges and
brain parenchyma involving cortical and
subcortical grey matter as well as white matter
Later stages-gross examination reveals mild to
moderate atrophy of cerebral cortex
Parieto-occipital region-most severely affected
Subsequently pathological involvement spreads
to the anterior portions of cerebral hemispheres,
subcortical structures, brainstem, and spinal cord
10. Focal or diffuse perivascular infiltrates of
lymphocytes, plasma cells, and phagocytes in
meninges and brain parenchyma
Inclusion bodies seen within both nucleus
and cytoplasm of neurons and glial cells.
Cowdry type-A eosinophilic inclusion bodies
seen in neurons and oligodendroglia
Another Cowdry type-B inclusion bodies
almost always present in the brainstem
These nuclear inclusions correspond to viral
particles and contain viral antigens
11. Neurofibrillary tangles may be seen within
neurons and oligodendrocytes
Cells containing tangles often contain the
viral genome
Inflammatory cell infiltrate in brain tissue in
perivascular cells are predominantly CD4+ T
cells, with B cells seen more frequently in
parenchymal inflammatory infiltrate
12. Initial symptoms noted between 8-11 years
of age, 6-7 years after measles infection
Initial symptoms subtle, mild intellectual
deterioration and behavioural changes
Progressive deterioration in scholastic
performance
13. Periodic stereotyped myoclonic jerks
Initially involve head and subsequently trunk and
limbs
Muscular contraction followed by 1–2 seconds of
relaxation associated with decrease in muscle
action potential or complete electrical silence
Do not interfere with consciousness
Exaggerated by excitement
May disappear during sleep
Difficulty in gait, periodic dropping of the head,
and falling
14. Pyramidal and extrapyramidal signs
Ataxia, dystonia, and dyskinesia
Generalised tonic-clonic seizures and partial
seizures
Catatonia
Depression
16. Advanced stages patients become
quadriparetic, spasticity increases, and
myoclonus may decrease or disappear.
Autonomic failure with loss of
thermoregulation
Progressive deterioration of sensorium to a
comatose state ->vegetative.
Decerebrate and decorticate rigidity
Breathing->noisy and irregular.
Death due to hyperpyrexia, cardiovascular
collapse, or hypothalamic disturbances
17. Above 18 years of age
Uncommon, between 1– 1.75% and 2.6%
Measles exposure usually either earlier (younger
than 3 years old) or later (after 9 years)
Unusually long measles to SSPE intervals from 14
to 22 years.
Presents with either cognitive or behavioral
changes and/or ophthalmic symptoms
Myoclonus may be absent
Progressive and fatal in majority
Higher rate of spontaneous remission as
compared with childhood-onset SSPE
18. Rapidly progress during pregnancy
Due to immunological and hormonal
alterations of pregnancy
Associated with death of child in utero, or in
the immediate peripartum period
Cortical blindness reported as most common
presenting manifestation
Characteristic myoclonus may not be
apparent
Clinical picture resembles that of eclampsia
19. Most of survive for 1–3 years after diagnosis,
with a mean survival of about 18 months.
Disease rapidly evolves leading to death within
three months
Approximately 10% of patients had fulminant
course.
Various stages of disease cannot be recognised.
Several factors such as exposure to measles at an
early age, viral virulence, impaired host defence
mechanisms, and concurrent infections with
other viruses
20. i. Personality changes accompanied by school
failure and bizarre behavior
ii. Axial (Especially characteristic rapid neck
flexion) massive myoclonus causing frequent
and violent falls
iii. Generalized rigidity with extrapyramidal
features and progressive unresponsiveness
iv. Minimal conscious state progressing to
akinetic mutism with severe progressive
autonomic failure
21.
22. 1)Cerebrospinal fluid
Usually normal
Acellular with normal or a mildly raised
protein concentration
Markedly raised gammaglobulin level greater
than 20% of total cerebrospinal fluid protein
CSF IgG concentration ranges from 10–54
μg/dl (5–10 μg/dl in normal)
Oligoclonal band
23. Raised antimeasles antibody titres >1:256 in
serum, and >1:4 in CSF -diagnostic of SSPE
CSF to serum titre -1:4 to 1:128 (below 200)
normal ratio (1:200–1:500).
ELISA highly sensitive for measles virus
specific IgG as well as IgM
Measles virus RNA can be detected by reverse
transcription polymerase chain reaction
24. Early-normal or show only moderate, non-
specific generalised slowing
Periodic complexes consisting of bilaterally
symmetrical, synchronous, high voltage (200–
500 mv) bursts of polyphasic, stereotyped delta
waves
Identical in any given lead
Repeat at fairly regular 4–10 second intervals and
have 1:1 relationship with myoclonic jerks
Shortening of interval between periodic
complexes with progression of disease
25. In early stages Periodic complex seen in sleep
Can be brought out in awake if diazepam is
administered intravenously
Later course EEG may become increasingly
disorganised, show high amplitudes and
random dysrhythmic slowing.
Terminal stages-amplitude of waveforms may
fall.
26. Type II abnormalities-periodic giant delta waves
intermixed with rapid spikes as fast activity.
EEG background is usually slow.
Type III periodic complexes-long spike-wave
discharges interrupted by giant delta waves
Video-split EEG monitoring-more sensitive
technique for early diagnosis and detection of
atonia or Myoclonus
Type III periodic complexes- associated with the
worst outcome
Type II periodic complexes- best outcome
27.
28. Computed tomography
Normal in early stages
Later stages-small ventricles and obliteration of
hemispheric sulci and interhemispheric fissure
due to diffuse cerebral oedema.
Generalised or focal cerebral atrophy and ex
vacuo ventricular dilatation seen after a very
prolonged course.
Low attenuation areas in cortex and basal
ganglion observed
CT normal as late as five years after onset
29. More sensitive
Early-ill defined high signal intensity areas on T2-
weighted images
More commonly seen in occipital subcortical white
matter than frontal region
Grey matter is spared even in advanced clinical and
MRI stages.
Tuncay et al -Early asymetrical lesions were
dominantly involving grey matter and subcortical
white matter in posterior parts of cerebral
hemispheres
Parenchymal lesions correlated with duration of
disease.
Mass effect and contrast enhancement unusual
30.
31. Stage 0-no atrophy or white matter changes
Stage I(+) white matter changes or atrophy
Stage II(+) white matter changes and atrophy
Stage III(++) white matter changes, 0 to +
atrophy or vice versa
Stage IV(++) white matter changes and atrophy
Stage V(+++) white matter changes, 0 to ++
atrophy or vice versa
Stage VI(+++) white matter changes and
atrophy
32. MR spectroscopy (MRS)
Diagnostic modality for early diagnosis
Findings suggestive of inflammation in stage
II
Findings of demyelination, gliosis, cellular
necrosis, and anaerobic metabolism in stage
III
18F-FDG PET
Metabolic impairments early when MRI
findings show no obvious abnormalities
33. Seldom required
Acute phase-inflammatory,consist of classical
cortical and subcortical "perivascular cuffing",
spongiosis and demyelination, sparing the
cerebellum
Cowdry type-A inclusions
Cowdry type-B inclusions
Neurofibrillary tangles
Very difficult to isolate even a small amount of
infectious virus from brain while viral antigens
can be easily identified.
34.
35.
36. No curative treatment
General nursing care
Anticonvulsants-sodium valproate,
clonazepam,Lam otrigine
Myoclonus responds atleast partially
Antispasmodics-baclofen may be used
Primary prevention by immunization
37.
38. 1) Inosine pranobex (Isoprinosine or
Methisoprinol)
Combination of inosine, acetamidobenzoic
acid, and dimethylaminoisopropanol.
Immunomodulatory and antiviral properties,
Inhibits viral RNA and increases mRNA
synthesis in lymphocytes possessing
antiviral properties of interferon alpha and
gamma.
Promotes chemotaxis and phagocytosis by
white blood cells
39. Daily dosage-100mg/kg/day given orally
Duration-possibly lifetime
Side effects-hyperuricemia, dizziness,
stomach pain, digestion problem, itching and
allergic reactions
Leucopenia when combined with ribavarin
Avoided in children under 3years of age
(body weight 15-20 kg)
Contraindication-Gout, Urolithiasis,
Arrhythmia, CRF, Hypersensitivity to the drug
40. 2) Interferon alpha
Obtained from leukocyte fraction of human
blood following induction with Sendai virus.
Given either intrathecally or intravenously.
Six week courses started as 100 000units/m2
of body surface area
Increased to 1 million units/m2 body surface
area per day given for five days a week.
Repeated up to six times, at 2–6 months
intervals
41. End point-eradication of detectable anti-
measles antibodies from CSF
59% showed significant stabilization or
improvement with IFN a with or without
Isoprinosine
Side effects-fever, lethargy, anorexia,
chemical meningitis
IFN alfa induced encephalopathy and upper
and lower motor neuron toxicity
Increase in liver enzyme levels
42. Systemic (subcutaneous) interferon alfa-5
million units with intrathecal interferon
To treat peripheral reservoirs of measles virus
in lymphoid and glandular tissue
43. 3) Ribavirin
Prodrug metabolized to purine RNA
nucleotides and interferes with RNA
metabolism
Side effect-hemolytic anemia, worsening of
preexisting cardiac disease
4) Intravenous Immunoglobulins
Found effective in SSPE when administered
along with prolonged therapy with inosiplex.
Needs further evaluation
44. 5) Cimetidine
H2-receptor antagonist,
Immunomodulatory effect
6) Amantidine
Anti-RNA agent
Retards maturation of viruses by not allowing
them to replicate
7) Flupirtine
Anti apoptotic agent
45. 1)Vitamin A
Reduces measles mortality and morbidity
Role in innate immune response,
particularly in interferon I signalling
pathway
Retinoids directly inhibit MV replication
Vit A levels low in SSPE (<20 mcg/dl)
46. 2) Inhibitors of MV entry
Viral RNA dependent RNA polymerase (AS-
136A)
Targets MV RNA polymerase L protein
catalytic unit
Drawback-MV escape mutants
47. 3)RNA interference
Transiently by short interfering RNA
molecules (siRNA)
Stably by intracellular expression of short
hairpin RNAs (shRNAs)
Inhibit expression of MV Phosphoprotein
gene, involved in viral RNA transcription,
replication, and IFN response
Hemagglutinin gene(H), playing a critical role
in adsorption, cell fusion, assembly and
budding of viral particles inhibited
48. 4)Induction of apoptosis
TNF related apoptosis inducing ligand (TRAIL)
Kills selectively cells where MV resides before
dissemination across brain
49. Invariably progressive with death in 95%
affected
Mean survival-1year 9 months to 3 years
Spontaneous remission between 5 to 6.2%
Factors associated with favourable outcome
1. Age of onset of SSPE less than 12 years
2. Disappearance of periodic complexes
3. Tendency for normalisation of the
background of follow up EEGs
4. Progressive increase in measles antibody
titres in CSF
51. Subacute Sclerosing Panencephalitis Revisited
;V. Sardana, D. Sharma, S.Agrawal; International
Journal of Basic and Applied Medical Sciences;
2013 Vol. 3 (1) January-April, pp.225-241
Subacute Sclerosing Pan-Encephalitis (SSPE)–
Past and Present;Natan
Gadoth:www.intechopen.com: 2013;pg 135-
154
Subacute Sclerosing Panencephalitis and Other
Lethal Encephalitis Caused by Measles Virus
Infection: Pathogenesis and New Approaches to
Treatment: Fernandez-Muñoz R et
al:www.intechopen.com:2013:pg 157-186
52. Subacute sclerosing panencephalitis;R K
Garg; Postgrad Med J 2002;78:63–70
Subacute Sclerosing Panencephalitis;R.K.
Garg,B. Karak,A.M. Sharma:Indian Pediatrics
Volume 35-April 1998
Suabcute sclerosing panencephalitis in The
Netherlands;Beersma M.F et al (1992) Int J
Epidemiol 21, 583-588
