Johannes H.

Saing

AnteriorHorn Cell
Hereditary
Spinal Muscular Atrophy
Acquired
Poliomyelitis
Nerve Fibre
Neuropathies
a) Demyelinating eg infectious
polyneuritis ( GBS ), 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

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

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

Anterior Horn 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

 SMA

are degenerative disease of motor

neurons that begin in fetal life and
continue to be progressive in infancy
and childhood

 SMA

type I, severe infantile form (WerdnigHoffmann disease)

SMA type 2, a late infantile form (more
slowly progressive form)
SMA type 3, juvenile form
(Kugelberg-Welander disease)

 Severe

hypotonia, general weakness

The lower limbs are more severely
affected than the upper
Fasciculation and atrophy of the tongue
Intercostal muscles are severely
affected a bell-shaped appearance
Contracture occurs in about 10%
More than 2/3 die by 2 yr of age.

 Never achieves the ability to stand or walk

Symmetrical, proximal muscles are more

affected than the distal

Tendon reflexes are usually depressed or
absent
Fasciculation and atrophy of the tongue
and tremor of the hand are common
The disastrous complication is scoliosis

 Normal

milestones in the first years and

achieves the ability to walk
Muscular dystrophy fashion: waddling gait,
Gowers manouver, walk flat-footed
with eversion of the feet. In contrast to
tendency to inversion in Duchenne
Reflexes may be normal or depressed

10

Age of First Clinical Manifestations in

Infantile Muscular Atrophy
Age

Newborn
0-1 month
1-3 months
3-6 months
6-9 months
9-12 months
More than 1 year

Percent of cases

37
10
12
6
12
9
8

Modified from Brandt

11

 An

enzyme (protein) that is important for

energy production within muscle fibres.
Normally there is only small amount in the
blood

12

 Diagnostic aids in detecting NMD

To determine and to differentiate axonal

or

myelin disorder
Not pathognomonic, when present strongly
suggest the diagnosis
Motor conduction, sensory conduction, F
wave and H wave.
Needle electromyography.

13

 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

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 : ( - )

 Acute

anterior poliomyelitis
Infantile paralysis
Peny Heine Medin
Heine 1840
Medin 1890

 Epidemi:

Selama musim panas

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

 Status imunitas :
Pernah dpt infeksi
Sudah diimunisasi
Neurovirulensi virus :
Parahnya suatu epidemi
Faktor host :
Cellular immunity
Daerah yang terkena

virus polio mel. oropharing

alimentary tract

lympnode

RES

viremia

virus di syaraf

kerusakan

kelumpuhan

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

 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

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 )

Disorders of the lower motor neuron anatomical approach

AnteriorHorn Cell
Hereditary
Spinal Muscular Atrophy
Acquired
Poliomyelitis
Nerve Fibre
Neuropathies
a) Demyelinating eg infectious
polyneuritis ( GBS ), 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

 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

 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)

Antecedent infection
Distal weakness predominantly 44%
Cranial nerve weakness
43%
Paresthesia and pain
Meningeal irritation
CSF protein > 45 mg/dl
Asymmetry of involvement
Full recovery or mild impairment
Relapses
Mortality

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

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

 Transverse

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

 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

 Severity of illness
Mild (able to walk)
Moderate (unable to walk, but lift limbs)
Severe (unable to lift limb)
Corticosteroids are not helpful, they

prolong the course and possibly

contraindicated
Plasma exchange (plasmapheresis)
Intravenous immune globulin (IVIG)
physioterapi

tend to

Treatment

Severity of Illness
Mild

Able to walk
No cardiovascular dysautonomia

Observe : treat with plasma

exchange if still worsening
Active physical therapy
exercises as tolerated

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

Begin plasma exchange/IVIG

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

 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

 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

Disorders of the lower motor neuron anatomical approach

AnteriorHorn Cell
Hereditary
Spinal Muscular Atrophy
Acquired
Poliomyelitis
Nerve Fibre
Neuropathies
a) Demyelinating eg infectious
polyneuritis ( GBS ), 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

Nerve
terminal

Axon
Mitochondria
Vesicle
Acetylcholine

Release
Site
Acetylcholine
receptor

Muscle
(end-plate)

Acetylcholine
sterase
Basal lamina

42

43

Postsynaptic Alterations in MG

1. Reduction of AChR number

2. Destruction and simplification of junctional fold
3. Attachment of antibody to AChR and blocking of
its function
4. Increase the gap between nerve terminal and
postsynaptic

FIG.3. Neuromuscular Junction. A, Normal human neuromuscular

Junction. B, Neuromuscular junction of a patient with myasthenia
gravis
44

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

45

 Group
Group
Group
Group
Group
Group

I : ocular
II : Mild generalized
IIB: Mild restricted bulbar
III : Moderate generalized
IIIB: Moderate restricted bulbar
IV : Severe generalized
myastenic crisis
Group IVB: Severe restricted bulbar

46

Bedside clinical clues in the diagnosis of MG *

History
Onset of fluctuating ptosis or diplopia that worsens with repeated use
and improves with rest
Onset of fluctuating dysarthria, dysphagia, dysphonia with or without
ocular symptoms or generalized weakness that worsens with repeated
use and improves with rest

Physical examination
Weakness referable to ocular, bulbar, or limb muscle
Limb Weakness prominent in proximal flexor groups
Normal muscle tone and bulk
Normal reflexes and sensation
Induction of muscle weakness with exercise when weakness is subtle

* For otherwise healthy persons

47

TABLE 3.

Diagnostic tests *

Studies to demonstrate neuromuscular transmission defects

Pharmacologic
Edrophonium (Tensilon)
Neostigmine (Prostigmin)
Electrophysiologic
Repetitive nerve stimulation
Needle electromyography
Single-fiber electromyography
Studies to demonstrate an abnormal immune respons against the endplate
and muscle

Acetylcholine receptor antibodies

Anti-strational muscle antibodies
* Diagnostic test that are currently used in practice
48

Edrophonium chloride (Tensilon) (IV)

Full dose 0,2 mg /kg (maximum dose 10 mg). A

small test 1/10 dose initially is needed

Should not be given to young infant

Neostigmine (IM)
Initial test 0,02-0,04 mg/kg is negative, retested

4 hr later with 0,08 mg/kg

0,5 1,5 mg IM
0,01 mg/kg of atropine before neostigmine

49

TABLE . Therapeutic steps in ocular myasthenia gravis

1. Begin by optimizing the response to pyridostigmine

2. If a satisfactory response is obtained, continue pyridostigmine
with lowest effective dose
3. If the response to pyridostigmine is unsatisfactory, consider
alternate-day low-dose prednisone or immunosuppressive drug

50

Table 2. Commonly Used Drugs in the Treatment of Myasthenic Disorders

Drug

Available Dose

Dosage

Endrophonium chloride (Tensilon)

10 mg/ml
0.2 mg/kg iv
Neostigmine bromide (Prostigmin)
15-mg tablet
7.5-15 mg/dose po
Neostigmine methylsulfate (Prostigmin) 0.25, 0.5, 1.0 mg/ml 0.04 mg/kg im
0.02 mg/kg iv
Pyridostigmin bromide (Mestinon)
60-mg tablet
30-60 mg/dose po
Prednisone
1-, 2.5-, 5-, 20-,
2-3 mg/kg/day
20-, 50-mg tablets

Frequency

3-4 hours
3-4 hours
4-6 hours
alternate day

51

Disorders of the lower motor neuron anatomical approach

AnteriorHorn Cell
Hereditary
Spinal Muscular Atrophy
Acquired
Poliomyelitis
Nerve Fibre
Neuropathies
a) Demyelinating eg infectious
polyneuritis ( GBS ), 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

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

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

 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

Before 5 years of age

Delayed motor development
Gowers sign
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
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

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

 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.

 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

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

 No

effective treatment is available.

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