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BoeEoiATKXmvogGcWqYr1601439144 PDF
BoeEoiATKXmvogGcWqYr1601439144 PDF
• Pendidikan
• Dokter Umum FKUI, 1983
• Dokter Spesialis Anak FKUI, 1992
• Dokter Spesialis Konsultan Neurologi 1998
• Doktor Ilmu kedokteran 2010
• Pendidikan Tambahan
• Master of Medicine in Clinical Neuroscience
Univ. Melbourne, 1996 – 1998
. Course in clinical neurophysiology, RCH-Melbourne 1998
• Pekerjaan
Staff Divisi Neurologi. Dept Ilmu Kesehatan Anak-FKUI
Muscle weakness, relatively common clinical presentation in infants or young children,
result from many different conditions including PNS and CNS
Paralysis in children
Brain
Motor neuron
AHC
muscle
Brainstem
Nerve fiber
Spinal cord
3
Conditions presenting as gait disorder (mimic
weakness)
Non neurologic disorder Neurologic disorder
• Chikungunya • Acute viral myositis
• Arthritis post infectious • Hypotonia
streptococcus • Dopa responsive dystonia
• Henoch-Schonlein purpura • Ataxia cerebellar post
• Toxic transient synovitis infection atau ataxia
(hip) spinocerebellar
• Diskitis (spine) • Conversion disorder -
• Growing pain malingering !
Definition
(Migita R et al. 2019. Etiology and evaluation of the child with weakness)
Central Peripheral
• CNS • NM • MUSCLE
• SPINAL • P Nerve
CORD Junction
• ADEM • DMD
• GBS • LGMD
• MS • Infection • MG
• CIDP • PP
• CP • Tumor • Botulism
• ALS (UMN • Transverse
• CMT • Myotonia
& LMN) myelitis • Erb’s • Myositis
• Bell’s • Myopathy
• Motor
neuron
• SMA
• POLIO
Neuromuscular disorder in pediatric
In CMH ‘2017
179 149
NMJ
NERVE FIBER
UMN
Muscle
AHC
• In patients with SMA, deletion or mutation of the SMN1 gene leads to reduce levels of SMN
protein
• Small amounts of functional SMN protein are still produced by the SMN2 gene
SMA TYPE 2
SMA TYPE 1 Presents between six and 18
The #1 genetic cause of infant months of age 2
mortality, 2 SMA type 1 In natural history studies ,
typically presents within the those affected will never walk
first six months of life and without support 2
those affected :
§ Never sit without support
§ Have poor head control 3
1 IN 10,000 AFFECTED § Have dificulty breathing & MORE THAN
swallowing 2,4
30%
MORE THAN
SMN1 SMN2
DNA 6 7 6 7
Pre-mRNA 6 7 6 7 6 7
FL-SMN ?
Functional SMN Unstable SMN protein Functional SMN
protein rapidly degraded protein
SMA manifestations
M
1a 1b 1c 2a 2b 3a 3b 4
M
Althogh newborn screening is not yet standart practice, time to diagnosis is critical. Based on the natural history of the
disease, earlier diagnosis and intervention may help improve outcomes for children with SMA.3
33 (94) children with Spinal Muscular Atrophy (Biologi
Moleculer Eijkman, Jakarta)
(2004-2018)
Mechanism Increase amount of complete SMN protein production of SMN protein from Increase a mount of
Of action from SMN2 SMN1 complete SMN protein from
SMN2
Dose four loading doses (12 mg each) and one dose of 2.0 vg/kg 5 mg/day or 0.25/kg
maintenance every 4 months
Supportive
§ Progressive phase 4 < weeks
§ CSF; protein increased, cell normal (< 50 /µ)
§ EMG
IVIG Plasma
exchange
Adverse events in
25,5%
Adverse events in
66%
225
CMT1
36
53 CMT2
47 CMT4
CMTX
107
61% CMT1A 910
CMTN
32
HSN
HNPP
287
UNKNOWN
NEUROMUSCULAR
JUNCTION
Motor neuron
Brain
Spinal cord
Clinical feature
• Ocular symptoms (53%)
– 25% ptosis, 25% diplopia, 3 % blurred visio
• Bulbar symptoms 16%
– 6% difficulty swallowing, 5% slurred, 4% difficulty chewing,
1% dyspnea
• Most patients exhibit progession of disease 86%
– 40% purely ocular, 35% generalized, 15% bulbar or ocular-bulbar
• If an ocular MG is going to develop general symptoms
– 56% by 6 months
– 78% by the first years
– 85% by the second years
– 92% by the third years
26
Infantile Botulism
• Background
• Due to consumption of botulinum spores (usually from honey)
– Higher GI tract pH of infants makes them more susceptible
• Most cases occur in <1yr, 90% occur in < 6 m
• Clinical feature
– GI
• Constipation, poor feding
– Lethargy, weak cry, floppy infant
Muscle
NMJ
Peripheral
UMN nerve
Is a degenerative muscle disorder, which Muscle
A retrospective chart review of 20 patients in England found that the mean age at first reported
symtomps was 32.5 months (range 8-72 months).2
§ First contact with a healthcare professional occurred at a mean age of 42.9 months (range
10-90 months).2
§ Diagnosis was confirmed at a mean age of 51.7 months (range 16-90 months).2
§ Total delay from parental concern to diagnosis was 19.2 months (range 4-50 months).2
No dystrophyn
detected
In addition some
laboratories may use RNA
Adapted from references 1,7-9 DMD sequencing to identity
intronic of complex
variants
Medical therapy
Mutation specific treatment
33
EXAMPLE OF A DELETION AMENABLE TO EXON SKIPPING
DELETION
MUTATION
14 15 16 17 18 20 21 22
! EXONS OUT OF
FRAME
20
EXONS 20 15 HIDDEN
14 15 16 17 18 20 21 22
READING FRAME
RESTORED
14 15 16 17 18 21 22 23 24
Exon skipping in development for Duchenne
(eterplirsen)
Exon 53 │
8%
Other exon skips │ ~
Exon 44 │ 30%
6%
Exon 52 │
4%
Exon 50 │
4%
Exon 55 │ Exon 8 │ 2%
2%