Approach to different Demyelinating disorders in the Paediatric age-group. Namely- acute disseminated encephalomyelitis, paediatric multiple sclerosis, neuromyelitis optica. Approach, MRI features, differences, clinical features

1. Approach to
Demyelinating disorders
presentation by
Dr.Aheed Khan

2. Demyelinating Disorders
• immune mediated attacks on white matter including brain,
optic nerve or spinal cord
• Characterised clinically by
• localisation of neurological deficits
• Presence v/s Absence of Encephalopathy
• monophasic v/s polyphasic or repeated attacks in CNS

3. effects of demyelination
.

4. types
• Inflammatory/Immune-MS, ADEM, Optic Neuritis,SLE
• Infectious- HIV,PML,Lyme’s disease
• Granulomatous-Sarcoidosis, Wegeners
• Myelin-Metachromatic Leukodystrophy,
Adrenoleukodystrophy, Canavan disease,Alexander
disease
• Toxic/Metabolic-B12 deficiency,Cerebral pontine-
myelinolysis,radiation, PRES

5. Paediatric -MC
• Acute disseminated Encephalomyelitis
• Multiple Sclerosis
• CIS-Clinically Isolated Syndrome
• Neuromyelitis Optica spectrum syndrome

6. Acute Disseminated
Encephalomyelitis
• immune mediated self-limiting, inflammatory and
demyelinating disease of CNS
• mostly affects white matter of brain and spinal cord
• acute-onset encephalopathy with neurological deficits,
typically monophasic,
• preceded by viral/bacterial infection or post-vaccination

7. Pediatric Multiple Sclerosis
• immune system dysregulation-T-and-B-cell mediated
Axonal demyelination
• relapsing-remitting course- episodes divided by space and
time
• C/F of hemi-or-paraparesis, focal sensory loss, ataxia,
bladder-bowel involvement
• unilateral painful loss of vision
• Encephalopathy-less common

8. Neuromyelitis Optica
• monophasic or polyphasic demyelinating episodes with optic neuritis and/or
transverse myelitis
• range of onset-1 to 54 years, more common in females
• antibodies to Aquaporin-4 channel causing complement activation—>
oligodendrocyte and neuron damage
• C/F- optic neuritis or transverse myelitis with brainstem features-intractable
vomiting, hiccups, diplopia, facial weakness or dysphagia
• optic myelitis and transverse myelitis maybe simultaneous or separated by weeks
or years
• Optic neuritis is usually b/l than in MS where its unilateral
• Residual disease-visual and spinal cord function

9. Clinically Isolated Syndrome
• first monodical or multifocal CNS demyelinating event s/o
MS
• encephalopathy absent, unless caused by fever
• episode should last for at least 24 h and should occur in
the absence of fever or infection and with no clinical
features of encephalopathy
• involve the optic nerve, brainstem, cerebellum, spinal cord,
or cerebral hemisphere

10. .
Epidemiology
• ADEM > MS
• NMO and MS-adults; ADEM-pre-pubertal children
• ADEM-0.07-0.4 per 100’00 per year in
paediatric population
• MS- 2-5% of MS patients experience symptoms before 18 years
• NMO-range of onset 1-54 years, common in females
• ADEM-self-limiting; full recovery- 57-92% patients, residual
disease in NMO, relapses in MS

11. Neurological Symptoms
• Encephalopathy-hallmark of ADEM, absent in MS
• Long tract pyramidal signs like acute hemiparesis
• focal sensory deficits/post column signs suggests MS
• cerebellar ataxia
• cranial neuropathies, including optic neuritis-seen b/l in
NMO and U/l in MS
• spinal cord dysfunction (transverse myelitis)

12. Pathophysiology
• HPE-ADEM-perivenular round cell inflammation
• HPE-MS- plaques with mononuclear lymphocytic infiltrate
• NMO-perivascular foamy macrophages with eosoniphils
• patchy demyelination with preservation of axon cylinders
and the prominence of microglial cells in the inflammatory
exudate
• ADEM-T-helper cell mediated Molecular mimicry to auto-Ag
• MS-T-cell inflammation to CNS self-ag
• NMO-Antibodies to Aquaporin-4 channel-astrocyte foot
processed in optic nerve, spinal cord and periventricular
regions
• Serum IgG to Myelin Oligodendrocyte-
glycoprotein[MGO]- 40%- a/w favourable outcome*
perivenular round
cell inflammation
*Van Haren, K., Tomooka, B. H., Kidd, B. A., Banwell, B., Bar-Or, A., Chitnis, T., … Robinson, W. H. (2013). Serum autoantibodies to myelin peptides distinguish a
NMO

13. Diagnosis
• Careful history and examination
• Neuroimaging
• Lab studies

14. Neuroimaging
• MRI
Brain>>CT
Scan
• T2/Flair
Images for
diagnosing
demyelinati
ng
diseases
Potential location for lesions in acquired demyelination

15. MRI Features-ADEM
• small punctate to tumefactive
lesions-multifocal areas of
hyperintensity on MRI
• supratentorial or infratentorial
white matter
• bilateral, asymmetrical
7 year old ADEM MRI

16. ADEM Features
• centrifugal at the junction of the deep cortical gray and subcortical
white matter
ADEM

17. ADEM Features
• additional lesions-deeper white matter-basal ganglia,cerebellum, spinal
cord
ADEM
FLAIR Image of ADEM
showing lesions
spinal cord lesions

18. Paediatric
MS-MRI features
• poorly defined large
hyperintense areas in deep
white matter on T2 and flair
• Presence of 2 of the 3:
• 5 or more T2 bright foci
• 2 or more periventricular t2
bright foci
• 1 or more T2 bright areas in
the brainstem
T2 lesions
Deep periventricular lesions

19. NMO-MRI features
• peri-aqueductal pr
periventricular hyper
intensities
• optic nerve lesions
• spinal cord lesions
extending from 2 to 3
segments
Cervical segment
hyperintensities in
NMO
optic neuritis

20. International Paediatric Multiple Sclerosis Study Group
in 2012 Definitions:
• CIS=Clinically Isolated syndrome: A first monofocal or multifocal CNS
Demyelinating event
• Monophasic ADEM:
• first polyfocal CNS event
• Encephalopathy-not explained by fever
• MRI- large,poor margins, >1-2 lesions involving Cerebral white matter
• no new symptoms or signs after 3 months
• Multiphasic ADEM: new episode after 3 months or more from 1st
episode with new or re-emergence or prior findings

21. International Paediatric Multiple Sclerosis Study Group
in 2012 Definitions:
• Multiple Sclerosis: any of the following:
• 2 or more non-encephalopathic CNS events separated by >30 days, involving >1 CNS area
• single clinical event with MRI features with 2010 McDonald Criteria
• NMO: All are required:
• Optic Neuritis
• Acute Myelitis
• At least 2 of the 3 supporting criteria:
• contiguous three spinal cord MRI lesions
• Brain MRI not meeting diagnostic criteria for MS
• Antibody to Aquaporin-4
• ADEM followed 3 mo later by a non-encephalopathic clinical event with new lesions on brain MRI
consistent with MS

22. Approach

23. For MS

24. .

25. .

27. Treatment
• Pediatric MS- methylprednisolone[20-30mg/kg/day-max
1g/day] for 3-5 days for relapses, with or without taper;
and for decreasing relapse frequency- Interferon
alpha/beta or injectable DMA-natalizumab
• NMO- Initial episodes and relapses -methylprednisolone
for 3-5 days f/b tapering. Rituximab is effective in relapses
• ADEM-high dose i/v steroids for 5 days, with oral
prednisone taper of 1 month for relapses. Follow up at 3
months for checking signs of demyelination.