mk pen slide pediatrics neuromuscular disorders

7/24/2019 Mk Pen Slide Pediatrics Neuromuscular Disorders

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sor ers o e ower mo or neuron ana omca approac

AnteriorHorn CellHereditary

Spinal Muscular AtrophyAcquired

Poliomyelitis

Nerve FibreNeuropathies

a) Demyelinating eg GBS.

b) Axonal, eg lead.

2

Neuromuscular JunctionMyasthenia gravis

MuscleHereditary

1. Muscular Dystrophy

2. Congenital MyopathiesAcquired1. Dermatomyositis.2. Endocrine myopathies.


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Symptoms of Neuromuscular Disease

1. Abnormal gait

a. Steppageb. Toe-walking

c. Waddle

2. Easy fatigability

3

3. Frequent falls4. Slow motor development

5. Specific disability

a. Arm elevation

b. Climbing stairs

c. Hand grip

d. Rising from floor


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Signs of Neuromuscular Disease

Observation1. Atrophy and hypertrophy

2. Fasciculations3. Functional ability

Pal ation

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1. Muscle texture2. Tenderness

Examination1. Joint contractures2. Myotonia

3. Strength

4. Tendon reflexes


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Parental Concern not Weakness

5


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NMD in Dept of Childhealth Cipto-Mangunkusumo tHospial

()

()

()

()

()

6


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Differentiation between upper motor and lower motor unit disease

Upper motor unit Lower motor unit

Tone Hypotonia (infants)or spasticity Hypotonia

(infants and older children)

Strength Weakness (normal or minimal) Weakness (usually profound)

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Reflexes Increased tendon reflexes Decreased or absent tendon reflexesPersistance of infantile reflexes

Babinskis sign No Babinskis sign

Ankle or knee clonus No clonus

Muscle mass Usually no atrophy Atrophy (usually not detectable in

infants)Fasciculations (usually not detectable

in infants except in tongue)


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A Nerveterminal

Axon

Mitochondria

Vesicle

Acetylcholine

ReleaseSite

10

receptor

Acetylcholinesterase

Basal lamina

Muscle

(end-plate)


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B

11


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Postsynaptic Alterations in MG

1. Reduction of AChR number2. Destruction and simplification of junctional fold

3. Attachment of antibody to AChR and blocking of

its function

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4. Increase the gap between nerve terminal andpostsynaptic

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

Junction. B, Neuromuscular junction of a patient with myasthenia

gravis


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Clinical classification

G :

G : G B:

G :

G B: G :

G B:

13


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Bedside clinical clues in the diagnosis of MG *

History

Onset of fluctuating ptosis or diplopia that worsens with repeated use

and improves with restOnset of fluctuating dysarthria, dysphagia, dysphonia with or without

ocular symptoms or generalized weakness that worsens with repeated

use and improves with rest

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Physical examination

Weakness referable to ocular, bulbar, or limb muscle

Limb Weakness prominent in proximal flexor groups

Normal muscle tone and bulkNormal reflexes and sensation

Induction of muscle weakness with exercise when weakness is subtle

* For otherwise healthy persons


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Clinical feature

(53%)

25% , 25% , 3 % B 16%

6% , 5% , 4% ,

1%

40% , 35% , 15% G

56% 6

78%

85%

92%

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Symtomps and Signs in 35 Patients With

Juvenile Myasthenia Gravis

Symptom or Sign Number of patients

Ptosis 32Diplopia 30

Facial weakness 29

D s honia 29

16

Weakness of arms 29Weakness of legs 29

Chewing weakness 22

External opthalmoplegia 18

Respiratory difficulties 12

After Millichap and Dodge (69)


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TABLE 3. Diagnostic tests *

Studies to demonstrate neuromuscular transmission defectsPharmacologic

Edrophonium (Tensilon)Neostigmine (Prostigmin)

Electrophysiologic

Repetitive nerve stimulation

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Single-fiber electromyography

Studies to demonstrate an abnormal immune respons against the endplate

and muscleAcetylcholine receptor antibodies

Anti-strational muscle antibodies

* Diagnostic test that are currently used in practice


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Clinical test for MG

E () ()

F 0,2 / ( 10 ). A 1/10

0,020,04 / , 4

0,08 /

0,5 1,5

0,01 /

18


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TABLE . Therapeutic steps in ocular myasthenia gravis

1. Begin by optimizing the response to pyridostigmine2. If a satisfactory response is obtained, continue pyridostigmine

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3. If the response to pyridostigmine is unsatisfactory, consideralternate-day low-dose prednisone or immunosuppressive drug


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

Drug Available Dose Dosage Frequency

Endro honium chloride Tensilon 10 m /ml 0.2 m /k iv

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Neostigmine bromide (Prostigmin) 15-mg tablet 7.5-15 mg/dose po 3-4 hoursNeostigmine 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


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TABLE 7. Therapeutic options in myasthenia gravis

Symptomatic therapy

Short-acting cholinesterase inhibitors

Pyridostigmine bromide (Mestinon)

Longer-acting cholinesterase inhibitorsNeostigmine (Prostigmin)

Mestinon Timespan

Lon -term immunosu ressive dru thera

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CorticosteroidsImmunosuppressive drugs

Azathioprine (Imuran)

Long-term surgical Immunosuppression

Thymectomy

Short-term Immunosuppression

Plasma exchange

Intravenous administration of immune globulin


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22


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Duchenne muscular dystrophy

30 100,000

(30%)

(). 8 11

23


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Duchenne muscular dystrophy .

,

.

.

: 30 200 , , .

24


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Blood creatine kinase 50 300

. 15.000 45.000 / (,


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Dystrophin

.

().

26


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Duchenne Normal

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40 50 60 70 80 90 100 110 120 130 140

IQ

Figure 2-17. Stylized distribution curve of IQ inDuchenne dystrophy showing normal bell-shape but a shift to the left.


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Guillain-Barre syndrome

0.6 1.1 100,000 (


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Guillain-Barre Syndrome

.

.

30


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Guillian-Bare Syndromes

AcuteInflammatoryDemyelinatingpolyneuropathy

AcuteMotor axonalNeuropathy

(AMAN)

Fishersyndrome

IncreasingSeverity

O the i une

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AIDP withSecondaryAxonal

degeneration

Acute motor-Sensory axonal

Neuropathy(AMSAN)

attack

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].)


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Clinical Characteristics of 56children with GBS

A 70%

D 44% C 43%

43%

17%

CF > 45 / 88%

A 9%

F 77% 7%

4%

32


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F :

Features required for diagnosis : Progressive motor weakness of more than one limb

Areflexia or marked hyporeflexia

C

2 4

A

E CF 1

A F

33


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weeks

weeks

ACUTE

MONOPHASIC GBS

ACUTE MONOPHASIC

GBS WITH

LIMITED RELAPSE

RELAPSING ACUTE

MONOPHASIC GBS

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weeks years weeks

weeks Months/years

weeks Months/yearsFigure 10-1.Possible temporal courses following acute GBS

CIDP STARTING

AS GBS

ACUTE GBS

FOLLOWED BY CIDP


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A

:

A

,

A

B

B / G

/G

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Poliomyelitis

, ,

.

37


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Pathophysiology 3 (1,2 3),

C , ,

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Spread of infection Gut

Viremia Along nerves

Virus in spinal cord andBulbar motor neurones

Chronic persistenceIn immunodeficiency

1000 : 1

As m tomatic Symtomatic :

Progressive CNS

Pathology

Clinical

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Acute paralytic

Poliomyelitis

disorder

Recovery withResidual deficits

Post poliomyelitis progressivemuscular atrophy

?? Amyotrophiclateralsclerosis

25 %?

Late effects

Figure 1. Schematic depiction of natural history of poliomyelitis.


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Epidemiology

9095% ; 48% ; 12%

40

DAYS AFTER EXPOSURE


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DAYS AFTER EXPOSURE

01 5 10 15 20

MINOR ILLNESS(NON SPECIFIG)

MAJOR ILLNESS

(CNS INVOLVED)

1-2%

4-8%

FRANK CASES

ABORTIVE

PER

CENTOF

ALLINFECT

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90-95% INAPPARENT

VIRUS PRESENT IN

BLOCO

THROAT

FECES

CNS (FRANK CASES)

MAY PERSIST 12-17 WKS

ANTIBODIES PRESENT

NEUTRALIZING

COUP, FIXING

PERSIST FOR LIFE

PERSIST 1-5 YEARS (?)

01 5 10 15 20

DAYS AFTER EXPOSURE

D


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Table . Distribution of paralysis of acute anterior

poliomyelitis

Location Precentage of cases

Leg 78,6

Arm 41,4

Trunk 27.8

Throat and neck 5.8

Cranial nerves 13.8

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ac a musc es .

Pharyngeal 31.9Ocular 30.1

Palatal 15.8

Glossal 5.6

Masticatory 2,9

Ergebn Inn Med Kinderheilk 1924; 26:248.


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B (

)

B E

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DIAGNOSIS BANDING


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POLIOMIELITIS GUILLAIN - BARRE

1. Akut Subakut-- paralisis perifer ----

(motor neuron) (radix, difus)2. Asimetrik Simatrik

3. Otot terkena Kelumpuhabn naiktak tentu distal proksimal

(ascending)4. Hanya motorik . Sensorik

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.

. Otonom5. Tanda infeksi (+) (-)6. Masa laten (-) (+)7. L.P sel / N < 30/3

Protein / N

9. EMG giantpotensial (> 10 hari) -

KHS N10. Gejala sisa (+) paresis (-) self limiting disease

sembuh 2 mg 4 mg 2 th


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Spinal Muscular Atrophies

A

45


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Classification SMA

A , (

)

A 2, (

A 3,

( )

46


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SMA type I (in utero or 2-3months) ,

F

C 10%

2/3 2 .

47


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SMA type 2 ( 3 to 15 months)

,

F

48


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SMA type 3 ( > 24 months)

: ,

,

.

D

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Age of First Clinical Manifestations in


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Age of First Clinical Manifestations in

Infantile Muscular Atrophy

Age Percent of cases

Newborn 370-1 month 10

1-3 months 12

50

- mon s

6-9 months 129-12 months 9

More than 1 year 8

Modified from Brandt ((15


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51


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Creatine kinase (CK) test

A ()

.

52

2000


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2000

1000

53

Normal range

0 5 10 15 20

70

Age (years)

Figure 2-18. CPK level in early stages ofDuchenne dystrophy and gradual Decline with progression of disease


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Electromyo/neurography(EMG/ENG)

,

, ,

.

.

54


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Muscle and nerve biopsy

55


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Cerebrospinal fluid (CSF)

, 20300 BC/3 , 23

< 200 .

G B D CF

.

56


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GB Protein

57

MG I II III IV

GB SEL < 303

Polio ProteinPolio SEL


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mk pen slide pediatrics neuromuscular disorders

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