The document discusses demyelinating diseases, highlighting the clinical features and diagnostic criteria for conditions such as multiple sclerosis and acute disseminated encephalomyelitis (ADEM). Key indicators for suspecting demyelination include unexplained neurologic deficits, acute onset, and characteristic symptoms associated with specific demyelinating disorders. It also covers the evolution of different demyelinating conditions, their causes, and includes a case study illustrating the diagnostic approach to a patient with a possible demyelinating disease.

1. Approach to Demyelinating
Diseases
Dr Shobhit Gupta

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

4. Demyelinating Disease of PNS
• Guillain–Barré syndrome
• Chronic inflammatory demyelinating
polyneuropathy
• Anti-MAG peripheral neuropathy
• Charcot–Marie–Tooth disease
• Progressive inflammatory neuropathy

5. Causes of Demylination

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)

14. Revised McDonald MRI criteria

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

17. ADEM vs MS 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)

19. ADEM vs MS
Evolution
MS
ADEM

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

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

28. NMO
• SC lesions
• • Extent > 3 segments
• • Central grey matter
• • Swelling
• • Partial enhancement
• • Atrophy & cavity formation

29. • Devic Neuromyelitis optica
Multiple sclerosis

30. Spinal cord MRI in NMO
• Central necrosis: pseudosyringomyelia

31. Neuromyelitis optica
Multiple sclerosis

32. NMO
• Specific brain lesions
• •Medullary periaqueductal grey
• •Bilat hypothalamus

33. NMO
• Brain lesions
• •Present 60%
• •Location PV ( AQP4 expression)
• •Extensive
• •Multiple, patchy, enhancing (cloud-like
enhancement) in 90% of pat with CE
• •CC Splenium; diffuse; oedematous,
heterogenous

34. Cloud-like enhancement
NMO 90%
MS 8%

35. Cortical lesions
NMO 0
MS 67%

36. Central Vein Sign
Class III evidence
CVS accurately
distinguishes
MS vs sero+ve NMOSD

37. NMO: 2015 diagnostic criteria
MR requirements (AQP4-IgG -ve/unknown
Acute optic neuritis
Brain Normal / unspecific
Optic nerve >1/2 ON length or optic chiasm

38. NMO: 2015 diagnostic criteria
MR requirements (AQP4-IgG -ve/unknown)
Acute myelitis
Intramedullary lesions ≥ 3 contiguos segments
(LETM) ≥ 3 contiguous segments SC atrophy
(history of myelitis

39. NMO: 2015 diagnostic criteria
MR requirements (AQP4-IgG -ve/unknown)
Acute brainstem syndrom
Periependymal brainstem lesions

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)

41. MOG-AB Disease

42. AQP4-ab vs MOG-ab
De Seze Brain 2017

44. Multiple CNS
site affected
With
encehalopathy
ADEM
Without
encephalop
athy
Polyfocal CIS
Optic Neuritis
and Transverse
Myelitis
NMO
Single CNS
site affected
Monofocal
CIS
Transversemyelitis
Optic Neuritis
others
First episode of demylination

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

47. Diagnostic Algorithm

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.