Curriculum

Vitae
• Nama Lengkap : Dwi Putro Widodo
• Pendidikan : Dokter Umum, FK Univ. Indonesia, tahun 1983
Dokter Spesialis Anak, FK Univ. Indonesia, tahun 1992
Dokter Spesialis Konsultan Neurologi Anak tahun 1998
Doktor Ilmu Kesehatan Anak FKUI, September 2012
• Pendidikan tambahan : Master of Medicine in Clinical Neuro science.
Univ. Melbourne, 1996 -1998
Course on Clinical Neurophysiology in Royal Children
Hospital, Melbourne, 1998
• Jabatan : Kepala Divisi Neurologi
Departemen Ilmu Kesehatan Anak 2011-2017
• Jabatan lain : Delegasi Indonesia untuk Asean Oceanian Child Neurologi
Assotiation (AOCNA) tahun 2010 – 2016
• Institusi : Divisi Neurologi
Dept. Ilmu Kesehatan Anak
FK. Univ. Indonesia – RS. Dr. Cipto Mangunkusumo
 GBS vs Transverse Myelitis

Motor neuron

Brain

Spinal cord
 Autoimmune disease affecting the
peripheral nervous system

Usually triggered by an acute infectious

process or vaccination

Characterized by weakness and numbness or a

tingling sensation in the leg
• GBS has three stages:
– Progression phase: several days to several weeks
– Plateau phase: similar duration
– Recovery phase: over weeks to months

• The neuropathy usually progress over 2-4 weeks

• Progressive neuropathy > 8 weeks à chronic inflammatory

demyelinating polyneuropathy (CIDP)

• CIDP à chronic variant of GBS that recur intermittently or do

not improve for a period of months or years

Seneviratne U. Postgrad Med J 2000;76:774-82

Amato AA. Rev Mex Neuroci 2005;6:455-69
 AIDP = Acute Inflammatory Demyelinating
Polyneuropathy

• Develops over ~2 weeks

• reflexes lost early
• Intubate if severe weakness
• Autonomic instability, arrhythmia
• Most have good long-term recovery
GBS is usually easy to diagnose once weakness develops.
Strongly suspected if there is the triad of weakness,
abnormal sensation, and absent reflexes
Gareth J, et al. AAN’2007

5
Clinical Characteristics of 56 children with GBS

• Antecedent infection 70%

• Distal weakness predominantly 44%
• Cranial nerve weakness 43%
• Paresthesia and pain 43%
• Full recovery or mild impairment 77%
• Autonomic dysfunction 13%
• Mortality 4%

6
 Spectrum
GBS

AMAN EUR

varian
AIDP AMSAN MFS USA

t
AMAN JAP
AIDP AMSAN MFS variant

• Acute inflammatory demyelinating

• Acute motor (and sensory)
• Miler Fisher syndrome
• Cervico-brachial variant
 Guillian-Barre Syndromes
Acute Acute Fisher
Inflammatory Motor axonal syndrome
Demyelinating Neuropathy
polyneuropathy (AMAN)

Increasing
Severity
Of the immune
attack AIDP with Acute motor-
Secondary Sensory axonal
Axonal Neuropathy
degeneration (AMSAN)

Fig. 22-3. Proposed interrelationships of the forms of GBS. (Reprinted with permission
From Griffin et al., Pathology of the motor-sensory axonal Guillian-Barre syndrome,
Ann Neurol 39:17 – 28, 1996 [41].)
8
Paraparetic form of GBS
Van den Berg at al, 2014

At hospital admission:
40(8%) of 494 patients weakness of legs only
§ 87% unable to walk
§ 15% cranial nerve involvement
§ 50% sensory nerve involvement
§ 39% absent reflexes arms

During follow-up
§ 28% weakness of arms
§ 89% abnormal EMG of arms

Conclusion:
§ Most have other signs of damaged nerves in arms
 Workup

• Serologies, especially for treatable causes

• EMG helps localize and characterize lesions of PNS
• Imaging for some focal lesions, or to exclude CNS
mimics (such as cord lesion or stroke)
• CSF analysis in demyelinating neuropathies, or
polyradiculopathy
• Nerve biopsy

10
 Electrodiagnosis

• Marked slowing of motor conduction velocities, with

prolonged distal latencies in about half
• Delay in F-wave latency is often an early change.
• EMG plays a negligible role in the diagnosis of GBS

Pharmacological reports 2010. 62: 220-232

Current Paediatrics 2005.15 287–291
Lancet Neurol. 2008; 7: 9
 Transverse Myelitis

Motor neuron

Brain

Spinal cord
 Common signs and symptoms
of TM by location

67% . Weakness in the upper and or lower

extremities
. Sensory loss and sensory level
27% . Flaccid or hyper-reflexia
. Difficulty walking
6%
. Muscle cramps
. Bowel/bladder dysfunction
. Fever 50%
. Preceding illness 50%
ANTECEDENT INFECTION

§ Febrile Illness 2
week ago
§ Severe weakness
within 1 day Comparison of the different etiologies of TM
§ Change in behavior
§ Very Sleepy

Ø ADEM 70 - 79 %
Ø GBS 50 - 82 %
Ø Transverse myelitis (idiopathic or infection)
Ø NMO (neuromyelitis optica)
Ø MS increased rate of
respiratory infections
 ACUTE MYELOPATHY – CLINICAL CLUES

MS Acute
ADEM ATM Flacid Ischemic
NMO
myelitis

Onset Hours days Min-hours

Antecedant Ongoing
Previous infections Trauma
Illness febrile Illness

Neurological Decreased Optic neuritis Paraparesis

Consciousness Myelopathy Pure motor
findings Seizures Previous bouts anesthesia

KLINIKUM OF R UNIVERSITAT MUNCHEN OR

VAN HAUNFRCHES KINDERSPITAL
TIME COURSE

Second-minutes Minutes-hours Days Weeks

. Inflammation Tumour
. Trauma Tumour
. Electrolyte Neuro-
. Stroke inflammation degeneration
disorder

KLINIKUM OF R UNIVERSITAT MUNCHEN OR

VAN HAUNFRCHES KINDERSPITAL
 The relationship between time course and aetiology
Aetiology
Inflammatory/infect
Trauma
12 Tumour
Vascular

10

8
Count

0
Seconds Minutes Hours days Weeks Many weeks

Timecourse
Sharpe and Forsyth 2013
 Diagnostic Criteria for Transverse Myelitis*
• Bilateral (not necessarily symmetric) sensorimotor and autonomic spinal
cord dysfunction
• Clearly defined sensory level
• Progression to nadir of clinical deficits between 4 hours and 21 days after
symptom onset
• Demonstration of spinal cord inflammation: cerebrospinal fluid pleocytosis
or elevated IgG index,† or MRI revealing a gadolinium-enhancing cord
lesion
• Exclusion of compressive, post radiation, neoplastic, and vascular causes

* Clinical events that are consistent with transverse myelitis but that are not
associated with cerebrospinal fluid abnormalities or abnormalities detected on
MRI and that have no identifiable underlying cause are categorized as possible
idiopathic transverse myelitis.
Longitudinally extensive transvers myelitis
(LETM)

MOG ab associated
myelitis: longitudinal
extensive

Patients with MOG

antibodies: risk of
relaps

LETM is more
common in children
than adults
Smaller, well
demarcated lesions.

Higher risk of relapse

and MS (multiple
sclerosis)
 Acquired Demyelinating disorders

• 1st episode of CNS demyelination

• Acute disseminated encephalomyelitis
• Clinically Isolated syndrome (transverse myelitis, optic
neuritis, other syndromes)
• Relapsing CNS demyelination
• Multiple sclerosis
• Neuromyelitis optica
• MOG antibody relapsing disease
• Auto-antibodies and their utility
Dale RC, World Congress of Neurology, Dubai, UAE,
2019
 Clinically isolated syndrome (CIS)

• First inflammatory demyelinating event

• May be monofocal (optic neuritis, tranverse myelitis)
• May be multifocal
• Must NOT include encephalopathy
• CIS are thought to be at higher risk of progression of
MS

Dale RC, World Congress of Neurology, Dubai, UAE, 2019

 Comparison of the different actiologies of transverse myelitis

Disease Onset Diagnostic Features Treatment responses

Multiple sclerosis Adolescence Small white matter Improves with steroids
lesions
Idiopathic Any age Single lesion, sometimes Steroids, plasma exchange,
transverse longitudinally extensive cyclophosphamide
myelitis

Demyelination Any age Multiple lesions in spine Improve with steroids

syndrome and brain

Systemic lupus Adolescence Associated systemic lupus Improve with

erythematosus immunosuppression
Infectious disease Any age Fever, CSF pleocytosis Responds to antibiotics,
antiviral drugs
NMO > 7 y of age History of optic neuritis, Steroids, PLEX, and
normal brain MRI, NMO- cyclophosphamide;
IgG positive preventative treatment with
rituximab, mycophenolate, or
azathioprine

CSF, cerebrospinal fluid; IgG, immunoglobulin G; MRI, magnetic resonance imaging; NMO, neuromyelitis optica;
PLEX, plasma exchange.
 Autoantibodies associated CNS demyelination
(define non MS)

• MOG igG
• 20-30% of all CNS demyelination in children
• Strong association with bilateral optic neuritis (also TM and
ADEM)
• Less severe disease, but can result in mortality
• NMO (Aquaporin-4 ) igG
• 1-2 % af all CNS demyelination in children
• Optic neuritis, longitudinally extensive transvers myelitis.
• Severe, disabling and relapsing course
• Others
EPNS Congress Lyon-France ‘2017
 Treatment of acquired acute CNS
demyelination
Methyl-prednisolone 30 mg/kg/day (max 1 g) for 3-7
(oral pred taper if incomplete recovery)

Treatment failure

Intravenous immunoglobulin 2 g/kg over 2-5/7

Steroid medications should not be used in the treatment of GBS
Gareth J, et al. AAN’2007
Treatment failure

Plasmapheresis or IV cyclophosphamide or rituximab

There is increasing evidence of cognitive issue after ADEM, and of cognitive

issues in pediatric MS- so more aggressive treatment is warranted

Dale RC, XXIV World Congress of Neurology, Dubai, UAE, 2019

 Clinical aspect of GBS and Transverse myelitis

Sign and Symptoms GBS TM

• Fever at onset • No • No/yes
• Meningeal irritation • Usually not • No
• Muscle pain • variable • No
• Paralysis • Symmetric ascending • Stationary
• Progression of paralysis • 2 weeks • Few hours
• Paresthesia • frequent • frequent
• Sensation • Maybe diminished • Diminished
• Tendon reflexes • Diminished • Absent
• Spinal fluid at onset • WBC slight increase, • WBC normal,
protein very high high; protein
moderate
WHO: global poliomyelitis eradication by the year 2000
 GBS vs Transvers Myelitis

Guillain Barre Syndrome Transvers Myelitis

• Incidence 1.4/100.000 • 1-4 / 1.000.000
• Progressive bilateral of legs and • A focal inflammatory disorder of
arms the spinal cord
• Sensation and autonomic • Fever 50%
dysfunction • > 50% preceding illness
• CSF; protein increased, cell • Vaccination within 3 weeks
normal (<50/ul) > MRI • > 75% (sensory loss, weakness,
• Progressive phase 4 < weeks loss of urinary control; pain)
• Follow viral infection (70%) or • Nadir in 2-7 days
vaccination • MRI vertebra > CSF
• NCV abnormal • NCV normal
 Conclusion
• TM are syndromes of CNS demyelination that share with GBS
an autoimmune pathogenesis and tendency to develop after a
viral illness or other prodrome.
• There can be considerable overlap in the clinical presentation
of TM and early GBS.
• TM may be associated with marked elevation of the CSF
pleositosis and neuroimaging abnormality. Neurophysiologic
studies are usually normal in TM
• Combined treatment corticosteroid (not GBS) and IVIG or
plasma exchange (occasional cases)