2. When to suspect Demyelinating
Disease
• Demyelination should be considered in any patient
with unexplained neurologic deficits.
Primary demyelinating disorders are suggested by the
following:
• Diffuse or multifocal deficits
• Sudden or subacute onset, particularly in young adults
• Onset within weeks of an infection or vaccination
• Deficits that wax and wane
• Symptoms suggesting a specific demyelinating disorder
(eg, unexplained optic neuritis or internuclear
ophthalmoplegia suggesting multiple sclerosis)
3. • Demyelinating diseases of the CNS:
• acquired conditions characterized by preferential damage to previously
normal myelin
• commonly result from immune-mediated injury
• also viral infection of oligodendrocytes as in progressive multifocal
leukoencephalopathy, drugs and other toxic agents.
• Dysmyelinating diseases of the CNS
(leukodystrophy.) :
• myelin is not formed properly or has abnormal turnover kinetics
• associated with mutations affecting the
• proteins required for formation of normal myelin or
• in mutations that affect the synthesis or degradation of myelin lipids
7. Demylinating Disorders
• Immune mediated attack on white matter
including brain, optic nerve or spinal chord
• characterized clinically by
• localization of neurologic deficits (i.e., single site, such as spinal
cord [transverse myelitis], optic nerves [optic neuritis] or brainstem,
vs polyregional demyelination);
• the presence vs absence of encephalopathy; and
• disease course (i.e., monophasic vs repeated attacks involving
either the same or new CNS regions).
8. CIS
• first monofocal or multifocal CNS demyelinating
event
• 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
9. Acute Disseminated Encephalomyelitis
ADEM
• • Acute monophasic course
• • Immune-mediated inflammatory disorder, triggered by
inflammatory response to viral infections and vaccination
• • Affects children more commonly than adults
• • Best viewed as a “syndrome” rather than a specific
disorder
• Clinical presentation
• • Headaches, vomiting, drowsiness, fever, lethargy
(uncommon MS)
• • Self-limiting, good outcome
10. Proposed 2012 IPMSSG criteria
Pediatric ADEM
• • First polyfocal, clinical CNS event (presumend
inflammatory demyelinating)
• • Encephalopathy (cannot be explained by fever)
• • No new clinical and MRI findings ≥ 3 months after onset
• • Brain MRI abnormal in acute phase (3 months) Typical
MRI
• • Diffuse, poorly demarcated, large (>1-2 cm) lesions
(cerebral WM)
• • T1 hipointense lesions rare
• • Deep GM lesions can be present
11. Recurrent ADEM
• Defined previously as a new event of ADEM
with recurrence of initial symptoms and sign
• 3 or more months after the first ADEM
• Without involvement of new clinical history,
examination or imaging
• Now substituted under multiphasic ADEM
12. Multiphasic Demyelinating
encephalomyelitis
• ADEM F/b new clinical event also meeting
criteria for ADEM
• But involving new anatomic areas of CNS as
confirmed by history, Neurologic examination
and neuroimaging.
• Event must develop within 3 months of initial
event.
13. MS
• Any of the following:
• Two or more nonencephalopathic CNS clinical
events separated by more than 30 days, involving
more than1 area of the CNS
• Single clinical event and MRI features rely on 2017
Revised McDonald criteria for DIS and DIT (but
criteria relative for DIT for a single attack and
single MRI only apply to children ages 2-12 yr and
only apply to cases without an ADEM onset)
15. RED Flags for possibility of alternate
diagnosis than MS
(1) family history of neurological disease,
(2) a well-demarcated spinal level in the absence of
disease above the foramen magnum,
(3) prominent back pain that persists,.
(4) symptoms and signs that can be attributed to
one anatomical site,
(5) patients who are older than age 60 or younger
than age 15 at onset,
(6) progressive disease
e Miller et al., 2008
16. ADEM vs MS
Age
Gender
Prior flu
Encephalopathy
Symptoms
Attacks
CSF white blood cell count
>50
CSF oligoclonal bands
10 years (rare in adults)
male=female
very frequent
required
multifocal
fluctuate over 3 months
frequent
variable
>10 years
male<female
variable
rare
monofocal
separated by >1 month
very rare
frequent
ADEM MS
18. MS Diagnostic Criteria After ADEM
• 3 requirements for 2nd clinical event
• • Nonencephalopathic
• • ≥ 3 months after incident neurologic illness
• •Associated with new MRI findings
(disseminated in space)
20. ADEM
MS if ≥ 2
• 2 or more PV lesions
• Black holes
• Absence of diffuse bilateral lesions
MS
ADEM
21. ADEM
SC involvement in ~30%
Large and tumefactive lesions
Variable enhancement
8 years old boy
22. Acute Haemorragic
leukoencephalitis(Hurst disease)
• Considered as hyperacute or fulminanat form of
ADEM
• Seen in young age group
• Charectorized by fever, neckstiffness, progressive
neurologic deficit, coma and death within few
days.
• Occurs after viral respiratory tract infection,
sepsis, ulcerative colitis
• CSF: elevation of IgG and polymorphonucleated
cell pleocytosis (in contrast to lymphocytic
pleocytosis in the CSF noted in typical ADEM)
23. MRI findings in acute disseminated encephalomyelitis. Multiple scattered T2 hyperintensities
are appreciated on fluid-attenuatedinversion recovery images (A) with evidence of
hemorrhage on susceptibility-weighted images (B), contrast enhancement on T1
postgadolinium
images (C), and without diffusion restriction on diffusion-weighted imaging (D).
24. AQP4 Channelopathy AB Disease’
NMO •
Aquaporin 4
• most abundant CNS water channel
• concentrated in astrocytic foot processes
Antibodies to AQP4 → astrocytopathy
25. AQP4 Channelopathy
• Female > 80%
• Non-Caucasian predominance
• Relapsing if untreated
• Severe disability and high mortality
• Associated with other auto-immunity
• Onset with both ON + TM uncommon
26.
27. NMO-IgG Seronegative’
Some NMO patients remain seronegative for NMO-IgG (12-24%)
• Male predominance
• Younger patients
• Milder clinical presentation:
• lower relapse rate, lower disability, lower number of severe attacks
• Simultaneous occurrence of ON and transverse myelitis (33% vs 6%)
• No differences in brain MRI
• Shorter SC lesions
• Spinal cord confinement
• Some NMOneg could suffer either atypical ADEM or MS
• Hyun et al. Mukt Scler J 2014; Bernard-Valnet et al. Eur J Neurol 201
40. Myelin Oligodendrocyte Glycoprotein
(MOG)-AB Disease
• Female : Male equal
• No non-caucasian
predominance
• ~ 50% monophasic
• Better outcome than AQP4-Ab
disease
• Not associated with other
auto-immunity
• Onset with both ON + TM
common
• Overlap with ADEM
(monophasic & relapsing)
45. Relapsing Demylinating disease
ADEM
Polyfocal with
encephalopathy
with no new
areas
Polyfocal with
encephalopathy
new areas
invoved
Recurrent
ADEM
Multiphasic
ADEM
Dissemination
in space and
time
MS
Restricted to
spinal chord and
Optic Nerve
Relapsing NMO
48. Case
• A 34-year-old man presented with 3 days of gradual worsening,
paresthesia starting at his right chest and ending at his toes on his right
side. He had no additional history of medical problems or prior neurologic
symptoms. Neurologic examination revealed diminished pinprick from the
T4 dermatome and below on the right side and mild diminished vibration
in the right first toe. General and neurologic examinations were otherwise
unremarkable. MRI of his thoracic spinal cord demonstrated a T2-
hyperintense contrast-enhancing lesion at the T4 vertebral disk level
visualized on both sagittal and axial images. Brain MRI demonstrated six
T2-hyperintense lesions, including one ovoid periventricular lesion, with
the remainder located in the subcortical or deep white matter. None
demonstrated contrast enhancement. Cervical spinal cord MRI was
normal. Serum evaluation for inflammatory, metabolic, and infectious
diagnoses other than MS was nonrevealing. CSF evaluation demonstrated
four oligoclonal bands restricted to the CSF, a white blood cell count of 3
cells/mm3 with lymphocytic predominance, and protein elevation to 65;
the CSF was otherwise normal.
Editor's Notes
patient presented with objective evidence of a single attack of myelitis MRI dissemination in space and dissemination in time according to 2017 McDonald criteria, because the symptomatic thoracic spinal cord lesion can count toward both MRI demonstration of dissemination in space and dissemination in time the periventricular and spinal cord lesions demonstrated MRI dissemination in space, and the presence of contrast-enhancing and nonenhancing lesions demonstrated dissemination in time