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. Joint contractures
2. Myotonia
3. Strength
4. 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
6
SMA type I, severe infantile form (Werdnig-
Hoffmann disease)
SMA type 2, a late infantile form (more
slowly progressive form)
SMA type 3, juvenile form
(Kugelberg-Welander disease)
7
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.

8
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
9
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
11
Age of First Clinical Manifestations in
Infantile Muscular Atrophy
Age Percent of cases
Newborn 37
0-1 month 10
1-3 months 12
3-6 months 6
6-9 months 12
9-12 months 9
More than 1 year 8
Modified from Brandt
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 70%
Distal weakness predominantly 44%
Cranial nerve weakness 43%
Paresthesia and pain 43%
Meningeal irritation 17%
CSF protein > 45 mg/dl 88%
Asymmetry of involvement 9%
Full recovery or mild impairment 77%
Relapses 7%
Mortality 4%

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
Features required for diagnosis :
Progressive motor weakness of more than one limb
Areflexia or marked hyporeflexia
weeks
weeks
weeks years weeks
weeks
Months/years
weeks
Months/years
Figure 10-1.Possible temporal courses following acute GBS
ACUTE
MONOPHASIC GBS
ACUTE MONOPHASIC
GBS WITH
LIMITED RELAPSE
RELAPSING ACUTE
MONOPHASIC GBS
CIDP STARTING
AS GBS
ACUTE GBS
FOLLOWED BY CIDP
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 tend to
prolong the course and possibly
contraindicated
Plasma exchange (plasmapheresis)
Intravenous immune globulin (IVIG)
physioterapi


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


Treatment

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
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 GUILLAIN - BARRE
1. Akut Subakut
-- paralisis perifer ----
(motor neuron) (radix, difus)
2. Asimetrik Simetrik
3. Otot terkena Kelumpuhabn naik
tak tentu distal proksimal
(ascending)
4. Hanya motorik . Sensorik
. Motorik
. Otonom
5. Tanda infeksi (+) (-)
6. Masa laten (-) (+)
7. L.P sel / N < 30/3
Protein / N
9. EMG giant
potensial (> 10 hari) -
KHS N
10. Gejala sisa (+) paresis (-) 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
42
A
Nerve
terminal
Axon
Mitochondria
Vesicle
Acetylcholine
Acetylcholine
receptor
Acetylcholine
sterase
Basal lamina
Muscle
(end-plate)
Release
Site
43
B


44
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
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 I : ocular
Group II : Mild generalized
Group IIB: Mild restricted bulbar
Group III : Moderate generalized
Group IIIB: Moderate restricted bulbar
Group IV : Severe generalized
myastenic crisis
Group IVB: Severe restricted bulbar


46
47
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
48
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
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
50
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
51



Table 2. Commonly Used Drugs in the Treatment of Myasthenic Disorders
Drug Available Dose Dosage Frequency
Endrophonium chloride (Tensilon) 10 mg/ml 0.2 mg/kg iv
Neostigmine bromide (Prostigmin) 15-mg tablet 7.5-15 mg/dose po 3-4 hours
Neostigmine methylsulfate (Prostigmin) 0.25, 0.5, 1.0 mg/ml 0.04 mg/kg im 3-4 hours
0.02 mg/kg iv
Pyridostigmin bromide (Mestinon) 60-mg tablet 30-60 mg/dose po 4-6 hours
Prednisone 1-, 2.5-, 5-, 20-, 2-3 mg/kg/day alternate day
20-, 50-mg tablets
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
Increased turnover of muscle protein
Partial (segmental) necrosis of
Some fibres
Muscle fibre regeneration
Defective regeneration leads to
Loss of muscle fibres
Muscular weakness
Progressive disease
Susceptibility to
Hyaline change
Normal or slightly
Raised serum CK
Hyaline fibres ?
Raised serum CK
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 No. of Patiens
Age (years) 6 8 10
> 8 10 8
> 10 14 3
Clinical features
Weakness in legs 21
Weakness in all limbs 6
Toe Walking 10
Lumbar lordosis 17
Large calves 19
Waddling gait and difficulty with running 15
Gowers maneuver 15
Unable to walk 5
Atrophy 5
Joint contractures 2
Kyphoscoliosis 1
Other clinical features
Thin body 5
Family history 5
Laboratory features
Abnormal EMG 12
High level CK (10 to 300 times) 21
Muscle biopsy 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
Normal range
2000
1000
0 5 10 15 20
70
Age (years)
Figure 2-18. CPK level in early stages of
Duchenne dystrophy and gradual Decline with progression of disease
CPK (iu/1)
40 50 60 70 80 90 100 110 120 130 140
Duchenne
Normal
IQ
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 Moderately Late
1-5 years advanced 10 years
Ambulant 6-10 Years or older
Marked
Weakness
Hyalinized fibres
Fibre necrosis
Phagocytosis
Fibrosis
Rounded fibres
Regenerating
fibres
Fibre splitting
Fibre hypertrophy
Fat replacement
Poor fibre-type
differentiation
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.