Pediatrics Neuromuscular

Disorders
Johannes H. Saing

Disorders of the lower motor neuron

anatomical approach

AnteriorHorn Cell
Hereditary
Spinal Muscular Atrophy
Acquired
Poliomyelitis
Nerve Fibre
Neuropathies
a) Demyelinating eg infectious
polyneuritis, peroneal mus
muscular atrophy.
b) Axonal, eg lead, diabetes.
Neuromuscular Junction
Myasthenia gravis
Muscle
Hereditary
1. Muscular Dystrophy
2. Dystrophia Myotonica
3. Congenital Myopathies
Acquired
1. Dermatomyositis / Polymyositis
2. Endocrine myopathies, eg thyrotoxic
3. latrogenic, eg steroid myopathy

Symptoms of Neuromuscular Disease

1. Abnormal gait
a. Steppage
b. Toe-walking
c. Waddle
2. Easy fatigability
3. Frequent falls
4. Slow motor development
5. Specific disability
a. Arm elevation
b. Climbing stairs
c. Hand grip
d. Rising from floor

Signs of Neuromuscular Disease

Observation
1. Atrophy and hypertrophy
2. Fasciculations
3. Functional ability

Palpation
1. Muscle texture
2. Tenderness

Examination
1.
2.
3.
4.

Joint contractures
Myotonia
Strength
Tendon reflexes

Poliomyelitis

Definisi

Infeksi virus akut kerusakan syaraf

berbagai tkt dgn predileksi cornu
anterior dan sel motorik brain stem

Poliomyelitis

Is a generalized viral infection with an

affinity for lower motor neurons
Polios, meaning gray, reflecting the
involvement of the anterior horn gray
matter in the spinal cord.
The paralytic rate also varies with the
virulence of the strain of poliovirus

Etiologi

Virus gol RNA yg 28 m

Resisten thd :
Kloroform, detergent inaktif,
oksidan keras, khlor, formalin, UV
Rusak : pengeringan
Type :
I ( Brunhilde )
II ( Lansing)
III ( Leon )
Cross antibodi : ( - )

Sinonim

Acute anterior poliomyelitis

Infantile paralysis
Peny Heine Medin

Heine 1840
Medin 1890

Epidemiologi

Epidemi:
Selama musim panas
( sekali-sekali musim dingin )
Sporadik :
Musim dingin / musim panas

Faktor Predisposisi

Status imunitas :

Neurovirulensi virus :

Pernah dpt infeksi

Sudah diimunisasi
Parahnya suatu epidemi

Faktor host :

Cellular immunity
Daerah yang terkena

Patogenesis
virus polio mel. oropharing

alimentary tract

lympnode

RES

viremia

virus di syaraf

kerusakan

kelumpuhan

Patologi

Neuropatologi virus polio :

Patognomonik

Kerusakan syaraf ok multiplikasi virus

Tdk semua yg terkena akan mati
Sel neuron yang kena

Nekrosis
Kelumpuhan otot yg disyarafi
Paling sering terkena
Sel cornu anterior
Motor medulla oblongata

Gejala Klinik

Penderita poliomyelitis

10 % < 2 th
70% <10th

Di negara yg imunisasi baik

Jarang

Type infeksi poliomyelitis

Asymptomatic infection
Abortive poliomyelitis
Non paralytic poliomyelitis
Paralytic poliomyelitis

Asymptomatic poliomyelitis

Infeksi polio paling banyak

Virus masuk ke sal pencernaan keluar
dlm feses
Tanpa tanda infeksi nyata
Hanya : panas, anoreksia, mencret, batuk

Abortive poliomyelitis

Diagnosa ditegakkan bila ada wabah polio

Gejala
Panas, malaise, anoreksia, nausea, muntah,
sakit kepala, konstipasi, sakit-perut,
faringitis, batuk, diare
Diagnosa pasti
Isolasi virus polio
Selama wabah
Anak tersangka : istirahat 1 mgg 1 bln
kemudian evaluasi otot

Non paralytic poliomyelitis

Gejala: spt tipe abortive

Terutama :
Sakit kepala
Kekakuan otot :

Belakang leher
Badan
Tungkai

Pencegahan

Jangan masuk daerah epidemi

Jangan melakukan stress yg berat pada
masa epidemi
Aktivitas fisik jangan berlebihan
Imunisasi aktif :

Salk vaccine
Sabin vaccine
Koprowski ( type 1 dan 3 )
Lederle ( type 1,2 dan 3 )

Sindroma Guillain Barre

Guillain-Barre symdrome

Is an acquired desease of the peripheral

nervus system
Acute inflammatory demyelinating
polyradiculoneuropathy; infectious neuronitis;
acute infectious polyneuritis
Is an immune-mediated disease directed
against the peripheral nervous system
The most serious complications are
respiratory failure and autonomic
disturbances

Guillain-Barre syndrome

Commonest cause of acute generalised

paralysis
0.6 1.1 per 100,000 (<15 yrs)
Any time during childhood (4 and 9 yrs)
Core symptom

Progresive symmetric weakness

Cease by 4 weeks
areflexia

Considerable clinical variability

Untreated mortality 15% (at least)

Clinical Characteristics of 56
children with GBS

Antecedent infection
Distal weakness predominantly
Cranial nerve weakness
Paresthesia and pain
Meningeal irritation
CSF protein > 45 mg/dl
Asymmetry of involvement
Full recovery or mild impairment
Relapses
Mortality

70%
44%
43%
43%
17%
88%
9%
77%
7%
4%

Diagnostic Features of Guillain-Barre Syndrome

Features required for diagnosis :
Progressive motor weakness of more than one limb
Areflexia or marked hyporeflexia
Features strongly supportive of the diagnosis :

Progression over days to a few weeks

Relative symmetry
Mild sensory loss
Onset with extremity pain or discomfort
Cranial nerve involvement
Onset of recovery 2 to 4 weeks after halt of progression
Autonomic dysfunction
Initial absence of fever
Elevated CSF protein level after 1 week of symptoms
Abnormal electrodiagnosis with slowed conduction or prolonged
F Waves

ACUTE
MONOPHASIC GBS

weeks
ACUTE MONOPHASIC
GBS WITH
LIMITED RELAPSE

weeks
RELAPSING ACUTE
MONOPHASIC GBS

weeks

years

weeks
CIDP STARTING
AS GBS

weeks

Months/years
ACUTE GBS
FOLLOWED BY CIDP

weeks

Months/years

Figure 10-1.Possible temporal courses following acute GBS

Differential diagnosis

Transverse myelitis
Acute spinal cord compresion
Botulism
Tick paralysis
Myastenia gravis
Periodic paralysis
Poliomyelitis
Acute inflammatory myopathies

CSF protein content

EMG

Diagnostic aids in detecting GBS

To determine and to differentiate axonal or
myelin disorder
Not pathognomonic, when present strongly
suggest the diagnosis
Present in 50% during the first 2 weeks and
80% the third week
Motor conduction, sensory conduction, F
waves and needle electromyography

Approach to treatment

Severity of illness

Mild (able to walk)

Moderate (unable to walk, but lift limbs)
Severe (unable to lift limb)

Corticosteroids are not helpful, they tend to

prolong the course and possibly
contraindicated
Plasma exchange (plasmapheresis)
Intravenous immune globulin (IVIG)
physioterapi

Table 16-1 SUMMARY OF SURVEY LANCE AND

APPROACH TO TREATMENT IN ACUTE STAGES OF GBS

Treatment

Severity of Illness
Mild

Able to walk
No cardiovascular
dysautonomia

Moderate

Unable to walk, but lifts limbs

from bed or chair
Oropharyngeal weakness but
swallows safety
Severe
Unable to lift limbs
Aspiration risk
Blood pressure fluctuations

Observe : treat with plasma

exchange if still worsening
Active physical therapy
exercises as tolerated
Begin plasma exchange/IVIG
Passive physical therapy

Plasma exchange/IVIG if
hemodynamically stable
Passive physical therapy and
splinting

Case 1

10 yrs old girl had a 3-day history with increasing

difficulty walking. Two weeks earlier, she had
URTI.
On examination. Alert, no facial weakness and no
trouble with chewing/swallowing. Lower
extremities demonstrated flaccid paraplegia. Arm
and hand strength were decreased. Sensory
examination was intact to touch.
EMG findings compatible with moderate -severe
demyelinating polyneuropathy. No lumbal
puncture was performed

Case 1

She had IVIG (400 mg/kgBB/day) for 3

consecutive days. Headache was noted on the first
day of administration.
Improvement were seen after the first dose of
IVIG and much better after the third.
On days 9, she could walk with slight assistance.
On days 16, she walked unsupported

DIAGNOSIS BANDING
POLIOMIELITIS
1. Akut
-- paralisis
(motor neuron)
2. Asimetrik
3. Otot terkena
tak tentu
4. Hanya motorik

5. Tanda infeksi (+)

6. Masa laten (-)
7. L.P
sel
/N
Protein / N
9. EMG giant
potensial (> 10 hari)
KHS
N
10. Gejala sisa (+) paresis

GUILLAIN - BARRE
Subakut
perifer ---(radix, difus)
Simetrik
Kelumpuhabn naik
distal
proksimal
(ascending)
. Sensorik
. Motorik
. Otonom
(-)
(+)
< 30/3

(-) self limiting disease

sembuh 2 mg 4 mg 2 th

Muscular dystrophies

Muscular dystrophies

Dystrophin-related disorder
Duchenne / Becker muscular dystrophy
Non-dystrophin-related disorders
Emery-Dreifuss muscular dystrophy
Facioscapulohumelar dystrophy
Limb-girdle muscular dystrophy
1. Pure congenital muscular dystrophy.
2. Congenital muscular dystrophy (fukuyama type)
3. Walker-warburg syndrome
4. Muscle-eye-brain disease ( Santavouri syndrome)

Table 14.1. Classification of X-linked muscular dystrophie

Duchenne muscular dystrophy

Becker muscullar dystrophy, and other slowly progressive
X-linked myopathies (Mabry et al. 1965; Ringel et al. 1977)
McLeod syndrome
Emery-Dreifuss syndrome
X-linked scapulo-peroneal myopathy
X-linked myotubular myopathy

Duchenne muscular dystrophy

20 % of cases were recognized before the age of

2 yrs and 70% before 4 yrs of ages
Inherited X-linked recessive (transmitted by
females and expressed only in male), but
spontaneus mutation are frequent (30%)
Dystrophin is absent or marginally detectable in
the large majority of patient with DMD
DMD is the commonest serious type of muscular
dystrophy in children

Duchenne muscular dystrophy

The ability to walk is usually lost by the

age of 12 years
60% of patient require wheelchair by the
age of 12 years
Estimated incidens: 1 in 3500 live male
birth (3 : 100.000)
The serum CK is always very elevated
before clinically evidence
Most patients are mildly retarded, and
severe retardation occasionally is found

Basic biochemical lesion

(plasma membrane lesion ?)

Ainflux of calcium ions

Leakage of sarcoplasmic constituents

Normal or slightly
Raised serum CK

Hyaline fibres ?

Increased turnover of muscle protein

Susceptibility to
Hyaline change

Raised serum CK
Partial (segmental) necrosis of
Some fibres
Muscle fibre regeneration

Defective regeneration leads to

Loss of muscle fibres
Muscular weakness

Progressive disease

Normal or slightly
Raised serum CK

Clinical feature

Before 5 years of age

By 6 or 7 years

Harder to walk long distances

Difficulty with running
Walk become more of a waddle and more toe walking
Lordosis
Pseudohypertrophy occurs in 80% of cases

Between 9 and 13 years

Delayed motor development

Gowers sign

No longer able to walk

Kyphoscoliosis with respiratory and cardiac involvement

Aged of 20 years

Chest infection, cardiac failure and arrhythmia, severe contractures

Table 2. Clinical and Laboratory Features of 21 Patients with DMD

Characteristics
68
> 8 10
> 10 14
Clinical features
Weakness in legs
Weakness in all limbs
Toe Walking
Lumbar lordosis
Large calves
Waddling gait and difficulty with running
Gowers maneuver
Unable to walk
Atrophy
Joint contractures
Kyphoscoliosis
Other clinical features
Thin body
Family history
Laboratory features
Abnormal EMG
High level CK (10 to 300 times)
Muscle biopsy
Age (years)

No. of Patiens
10
8
3
21
6
10
17
19
15
15
5
5
2
1
5
5
12
21
5

Blood creatine kinase

The Serum CPK is always elevated to 50 to 300

times normal. Characteristically is 15.000 45.000
IU/L (normal, < 150 IU/L).
Elevations have been demonstrated in placental
blood of affected male fetuses of 16-20 weeks
gestation.
The CK level is decreased in pregnancy by as
much as 30%.
About 70% of genetically definite carriers will
show a raised CPK

Blood creatine kinase

The CK raised at birth, and reaches its peak at 14

to 22 months.
CK at 2 month is greater 2000 IU/L, DMD is
likely. If less 1000 IU/L is unlikely

2000
CPK (iu/1)

1000

70
Normal range
0

10
Age (years)

15

20

Figure 2-18. CPK level in early stages of

Duchenne dystrophy and gradual Decline with progression of disease

Duchenne

40

50

60

70

80

90
IQ

Normal

100

110

120

130

140

Figure 2-17. Stylized distribution curve of IQ in

Duchenne dystrophy showing normal bell-shape but a shift to the left.

EMG

Diagnostic aids in detecting DMD

To determine and to differentiate axonal or
myelin or muscle disorder
Not pathognomonic, when present strongly
suggest the diagnosis
Short duration, low amplitude polyphasic
MUAP
Motor conduction, sensory conduction, F
wave and needle electromyography.

Table 14.2. Sequence of changes in muscle biopsies in Duchenne muscular dystrophy

(from Swash and Schwartz 1984)

Early
1-5 years
Ambulant

Hyalinized fibres
Fibre necrosis
Phagocytosis
Fibrosis
Rounded fibres
Regenerating
fibres
Fibre splitting
Fibre hypertrophy
Fat replacement
Poor fibre-type
differentiation

Moderately
advanced
6-10 Years
Marked
Weakness

Late
10 years
or older

Diagnosis

Symptoms are present before the age of 5 years

Clinical signs comprise progressive symmetrical
muscular weakness; initially only lower limb muscle.
Calf hypertrophy is often present
Loss of unassisted ambulation before the age of 13
There is at least a 10 fold increase of SCK activity
Muscle biopsy: abnormal variation in diameter of
muscle fibres, foci of necrotic, regeneretion fibre,
hyalin fibre and fat tissue.
Muscle biopsy: almost no dystrophin demonstrable
DNA: Duchenne-type mutation within the dystrophin
gene

Management

No effective treatment is available.

Prednisone has shown definite evidence of
improvement of muscle strength and function.