Sistem Neuromuskular

Iwan Setiawan
Bagian Ilmu Penyakit Saraf
Fakultas Kedokteran UMS

Sistem Neuromuskular
Tiga komponen utama Neuromuskular
Nerve
Neuromuscular junction
Muscle

Upper Motor Neuron

Semua

neuron yang menyalurkan impuls

motorik secara langsung ke LMN atau
melalui interneuronnya, tergolong dalam
kelompok UMN. Neuron-neuron tersebut
banyak terdapat di girus presentralis
dinamakan juga korteks motorik. Melalui
aksonnya neuron korteks motorik
menghubungi motoneuron di kornu
anterior medulla spinalis.

Area Motorik

Upper motorneuron

Lower motorneuron

Lower Motor Neuron

Merupakan

neuron-neuron yang
menyelurkan impuls motorik pada bagian
perjalanan terakhir (kornu anterior medula
spinalis) ke sel-sel otot skeletal.

Motor end Plate

Pada

ujungnya setiap akson akan

bercabang-cabang dan setiap cabang
menghubungi membrane serabut otot.
Serabut-serabut otot setiap unit motorik
berkisar antara 10-500 serabut otot. Tiap
serabut otot memilki satu motor end
plate.

 Ujung-ujung

terminal dari akson

mengandung mitokondria dan ezim cholin
acertyltransferase, yang diperlukan untuk
sintesis neurotransmitter yang
dinamakan acetylcholine.

Pelepasan Acetilkolin
Nerves

releasing Achetylcholine at the

neuromuscular junction (=end plate)
cause the contraction of skeletal muscle.
The functional unit of a muscle organ is
the muscle fiber (=muscle cell).

 The

muscle fiber contracts in an "all-ornone" fashion when stimulated by an

action potential. The action potential first
causes intracellular Ca++ release from the
sarcoplasmic reticulum and the Ca ++
activates a cascade of events which
results in the movement of actin over
myosin (=sliding filament theory).

Tanda-tanda
kelumpuhan UMN :
Hiperrefleksia
Terdapat refleks
patologis
Tonus otot meninggi
atau hipertonia
Terdapat Klonus
Tidak terdapat atrofi
otot yang lumpuh
Refleks automatisme
spinal (-)

Tanda-tanda
kelumpuhan LMN :
Arefleksia (hilangnya
refleks tendo)
Tidak ada refleks
patologis
Hilangnya tonus otot
(flacid)
Tidak terdapat klonus
Terdapat atrofi pada
otot yang lumpuh

Gangguan yang menyebabkan kelemahan

gerak (paralysis)
Kelainan pada otot

Periodik Paralysis
Inflamatory miopathy
Miopati karena steroid
Rabdomyolisis

Neuromuscular junction

Miastenia Gravis
Botulism
Tick paralysis
Lambert Eaton Myastenic Syndrome

Gangguan yang menyebabkan kelemahan

gerak (paralysis)
Neuropati akut

Paraneoplastik
Vaskulitis (lupus, poliarteritis)
Neuropati motorik multifokal

Poliradikulopati akut

Guillain-Barre syndrome
Lime Disease
Sindrome Cauda Equina

Penyakit Motor neuron

Poliomyelitis
Amyotropic Lateral Sclerosis (ALS)

Gangguan yang menyebabkan kelemahan

gerak (paralysis)
Medula Spinalis

Inflamasi (mielitis transversus)

Mielopati (spondilosis, hematom, infark)

Otak (Cerebrum, cerebellum)

Lesi di Pons
Lesi fokal/multifokal (infark, hematom)

Jenis Gangguan Saraf

Polyneuropathy:

motor, sensory,
sensorimotor

Radiculopathy
Polyradiculopathy
Plexopathy
Mononeuropathy:

isolated
multiplex

Klasifikasi kausa

Toxic

GBS, CIDP
Vasculitis

Infective

Drugs, alcohol,
organophosphates

Inflammatory/Immune

Leprosy, Lyme, HIV,

Diphtheria

Traumatic

Inherited
HMSN and HLPP
Amyloid
Metabolic
Diabetes
Vitamins: B12, B1, E
Dialysis, Liver failure
Paraneoplastic
sensory (anti-Hu)

Klasifikasi tipe kerusakan

Demyelinating
Axonal
Small

fibre
Large fibre
Autonomic

Physical findings
Nerve

NMJ

Muscle

Reflexes

Usually decr.

NL or decr.

NL or decr.

Atrophy

Can be severe

Minimal

Variable

Fascic.

Sometimes

None

None

Sensory loss Sometimes

None

None

The Motor Unit

Myopathies

Motor Neurone
Disorders

Peripheral Neuropathy

Myasthenia etc

Gangguan pada saraf:

Variasi:
Cell body, axon & myelin
Fiber size: large, small
Motor, sensory, autonomic
Distribution: focal, multifocal, generalized
Course: acute, subacute, chronic, lifelong
Etiology: genetic, toxic, metabolic,
autoimmune, traumatic, vascular, infectious

Gangguan pada Saraf:

berdasarkan Lokasi
Radix
Plexus
Single

nerve
Several nerves
All

radiculopathy
plexopathy
mononeuropathy
multiple mononeuropathy,
mononeuritis multiplex
polyneuropathy

nerves,
length-dependent
All nerves,
polyradiculoneuropathy
not length-dependent

Radix
Segmental

loss of

motor
atrophy
weakness

reflexes
sensation

Signs

usually minimal; symptoms can be

severe (pain);
Usually only one limb.

Plexus
Pain
Weakness,

atrophy, variable, but

usually more severe than radiculopathy
Usually restricted to one limb
Etiology:
Brachial:

trauma, neoplasm, idiopathic

Lumbosacral: diabetes, neoplasm

Single nerve (mononeuropathy)

Restricted

distribution
Pain, numbness or tingling,
atrophy, weakness
Etiology:
entrapment
trauma

Carpal tunnel syndrome

N.Medianus
Pain

in hand,
forearm, arm
Numbness in
median distribution
Symptoms
aggravated by wrist
flexion

Ulnar neuropathy
Numbness
Atrophy

of first dorsal
interosseous
Weakness
Compression at elbow
Entrapment in cubital
tunnel
Distal injury

Radial nerve: Saturday night palsy

Weakness

of wrist &
finger extensors,
brachioradialis
Pressure palsy
Trauma (humerus
fracture)

Peroneal palsy
Crossing

legs
Weight loss
Hospitalization
Surgery

Several nerves (mononeuritis multiplex)

Often

painful at onset
Often sudden
Deficits in the distribution of several
peripheral nerves (one at a time)
Etiology: vasculitis

All nerves: Length-dependent

(polyneuropathy)
Lower

before upper extremity

Distal first (feet)
Atrophy of intrinsic foot muscles
Decreased ankle jerks
Stocking, then glove sensory loss
Distal motor and sensory findings always
much more severe than proximal

Polyneuropathy (contd)

Polyneuropathy (contd)
Most

common kind of neuropathy

Etiology
metabolic

(diabetes, renal failure)

nutritional (thiamine, B12 deficiency)
toxic (heavy metals, organic solvents,
some drugs)
familial (Charcot-Marie-Tooth)

All nerves, not length-dependent

(polyradiculoneuropathy)
Both

proximal and distal weakness

Variable sensory symptoms
Autonomic symptoms (pulse, blood
pressure, urination...)
Can affect respiration, swallowing
Autoimmune

Guillain-Barr Syndrome (GBS)

Merupakan penyakit Autoimmun

Definisi GBS :
Penyakit demyelinasi akut, yang terutama
mengenai susunan saraf tepi. Penyakit
inflamasi pada sistim saraf tepi mempunyai
karakteristik adanya infiltrasi limfosit dan
makrofag dengan destruksi myelin
Derajad dan lokasi kerusakan tergantung
saraf yang bermyelin: Motorik

Guillain-Barre syndrome
Progresses

over days to <4 weeks

Typically ascending weakness
Reflexes lost early
Motor symptoms predominate, but can
affect sensation and autonomic function
Respiratory failure requires support

Guillain-Barre syndrome (contd)

Penyebab : autoimmun
Target Antigen

biasanya tidak diketahui

Pada beberapa kasus: Target serangan imun
gangliosida (GM1, GQ1b)

Faktor presipitasi:

Infeksi virus (HIV, CMV, varicella zoster)

Infeksi bakteri (campylobacter jenjuni, typhoid,
paratyphoid)
Immunisasi
Sistemik (Hodgkins disease, leukemia, hipertiroidisme,
sarkoidosis)
Transplantasi organ, operasi, kehamilan

Latar belakang GBS

Epidemiologi
1-

GBS

4 kasus/100.000
Paling banyak pada pria
Meningkat sesuai usia
Insidennya bervariasi sesuai musim

Gambaran klinis GBS

-

Gangguan Motorik:
paralisis yang progressif, simetris pada extremitas
bawah dan atas, bersifat asendern
dimulai dari distal ke proksimal

Gangguan sensibilitas: Stocking, dan glove

sensory loss (dysesthesia)

Gangguan otonom:
penyebab kematian

Clinical Picture of Polyneuropahty

(Valenstein, 2000)

Gambaran klinis GBS

Atypical

presentations

Miller-Fisher

Syndrome

Areflexia
Ophthalmoplegia
Ataxia

diagnosis GBS
Riwayat

penyakit sebelumnya atau vaksinasi

Dari pemeriksaan fisik (Physical Exam)
Laboratoratorium:
Peningkatan

kadar protein pada pemeriksaan LCS dan

rendahnya jumlah sel di LCS (disosiasi sitoalbumin)

Electromyography

adanya blok konduksi saraf

KRITERIA GBS MENURUT GILROY DAN MEYER (1979)

1. Paralisis flasid simetris, difus

2. Gejala sensoris subyektif
3. Penyembuhan sempurna dalam 6 bulan
4. Disosiasi citoalbumin
5. Tanpa atau sedikit demam saat muncul paralysis
6. AL normal atau lymphositosis dengan sedikit atau
tanpa kenaikan KED.
Harus memenuhi 5 kriteria dari 6 kriteria

Pengobatan GBS
Fase akut
Supportive

care : monitoring fungsi vital (perawatn

ICU)
Pemberian IV imunoglobulin (ivIg) 400 mg/kg
selama 5 hari, plasmapheresis 40-50 ml/kg plasma
exchange diberikan 4 kali seminggu
Kortikosteroid
Artificial ventilation (if necessary) paralysis
diafragma

Setelah fese akut

Program

rehabilitasi, bladder training, perbaikan

ADL (activity daily living)

Summary of nerve disorders

Root

Disk, Herpes zoster

Plexus
Autoimmune, trauma, neoplasm
Mononeuropathy
Trauma, entrapment
Multiple
mononeuropathy
Vasculitis...
Polyneuropathy Toxic, metabolic, nutritional
Polyradiculoneuropathy
Autoimmune

Neuromuscular junction

Disorders of the neuromusuclar

junction
Release

of acetyl choline:

Botulism

(toxin = endopeptidase targeting

various proteins mediating exocytosis)
Lambert-Eaton myasthenic syndrome
(antibodies to voltage-gated calcium channel)
Acetylcholine
Myasthenia

receptor)

receptor blockade:

gravis (antibodies to ACh

Myasthenia Gravis

Kelemahan yang berfluktuasi

Mata: ptosis, diplopia
Bulbar weakness: dysarthria,
dysphagia
Kelemahan otot proksimal
Kelemahan respirasi
Normal reflexes
Normal sensation
Berkaitan dg thymoma
Berkaitan dg penyakit
autoimun

Penyakit autoimun pada transmisi

neuromuskular junction yang
diakibatkan oleh antibodi yang
menyerang reseptor asetilkolin atau
melawan muscle spesific receptor
tyrosine kinase

Myasthenia gravis is a neuromuscular disease leading

to fluctuating muscle weakness and fatiguability.
It is an autoimmune disorder, in which weakness is
caused by circulating antibodies that block acetylcholine
receptors at the post-synaptic neuromuscular junction,
inhibiting the stimulative effect of the neurotransmitter
acetylcholine.
Myasthenia is treated medically with cholinesterase
inhibitors or immunosuppressants, and, in selected
cases, thymectomy.
At 200400 cases per million it is one of the less
common autoimmune disorders.

 Muscles

become progressively weaker

during periods of activity and improve after
periods of rest. Muscles that control eye
and eyelid movement,
facial expression, chewing, talking, and
swallowing are especially susceptible. The
muscles that control breathing and neck
and limb movements can also be affected

Myasthenia Gravis
Terapi:

Acetyl cholinesterase inhibitors : pyridostigmin bromida 3x 60

mg
Plasmapharesis : plasma exchange
Imunoglobulin IV
Immunosupresan (kontroversi)
Steroid : mulai 12-50 mg
Azathioprine : 50 mg/hari
Cyclosporine : awal 3-4 mg/kg/hari dalam dosis terbagi
Cyclophosphamide : dosis 1-2 mg/kg/ hari
Thymectomy , indikasi:
Timoma
Generalized myastenia yang tidak terkontrol dengan
antikolinesterase (< 50 th, 6-12 bulan tidak ada remisi spontan)

Krisis Mistenia
Adalah

keadaan eksaserbasi penyakit

Mistenia gravis dimana kelumpuhan
menyebabkan episode akut kegagalan
pernafasan

Terjadi

pada 74% setelah 2 tahun

miastenia gravis

Krisis Mistenia
Faktor pencetus :
Infeksi,

terutama infeksi saluran nafas

Pemakaian obat2an: aminoglikosid,
ciprofloksasin, klindamisin, propanolol, fenitoin
Tidak diketahui (30-40%)

Krisis Mistenia
Terapi :
Kontrol

airways, dan perbaiki ventilasi (jika perlu

menggunakan ventilator)
Terapi antikolinesterase
Kortikosteroid
Plasma axchange atau IV Ig

Penyakit otot (myopathy)

Symmetrical

proximal weakness
Reflexes normal (sometimes depressed)
No sensory loss

Myopathy (contd)
Inherited
Dystrophies
Congenital

myopathies
Channelopathies
Acquired
endocrine
inflammatory, including
toxic

(drugs...)

autoimmune

Inflammatory myopathies
Polymyositis
isolated
with

collagen vascular
disease

Dermatomyositis
childhood
adult:

others

association with cancer

Dystrophy Musculorum
Muscular

dystrophy is a genetic condition

causing muscle weakness

Dermatomyositis - Polymyositis
KRITERIA DIAGNOSIS
Kelemahan otot-otot proksimal simetris
Rash tipikal pada dermatomyositis
Peningkatan enzim otot / plasma muscle enzymes (CK, aldolase, AST),
khususnya creatine kinase
Terdapat korelasi antara beratnya kelemahan dengan peningkatan enzim
Gambaran myopati pada pemeriksaan needle EMG
Gambaran abnormalitas yang khas pada biopsi otot (nekrosis serabut otot
dan degenerasi, dengan infiltrasi sel-sel inflamasi)

Polymyositis
Polymyositis

is a disease of muscle
featuring inflammation of the muscle fibers
The cause of the disease is not known
Polymyositis is slightly more common in
females. It affects all age groups, although
its onset is most common in middle
childhood and in the 20s
Weakness of muscles is the most
common symptom of polymyositis

Amyotrophic lateral sclerosis

Lou

Gehrig's disease
Amyotrophic lateral sclerosis (ALS) is a
nervous system disease that attacks
nerve cells called neurons in your brain
and spinal cord
The cause of ALS is not known

Amyotrophic lateral sclerosis

The

disease belongs to a group of disorders

known as motor neuron diseases, which are
characterized by the gradual degeneration and
death of motor neurons.
In ALS, both the upper motor neurons and the
lower motor neurons degenerate or die, ceasing
to send messages to muscles
At first, this causes mild muscle problems. Some
people notice

Trouble walking or running

Trouble writing
Speech problems

Multiple sclerosis

Multiple sclerosis (MS) is a nervous system disease that

affects your brain and spinal cord. It damages the myelin
sheath
No one knows what causes MS. However, viral and
autoimmune etiologies have been hypothesized. It may
be an autoimmune disease
The symptom can include :

Visual disturbances
Muscle weakness
Trouble with coordination and balance
Sensations such as numbness, prickling, or "pins and needles"
Thinking and memory problems

Key clinical features used to localize a neuromuscular disorder

Myopathy
predilection for neck, limb girdle and proximal muscles
occasional respiratory muscle involvement
possible risk of myoglobulinuria
no sensory loss
normal tendon reflexes (early stage)
Neuromuscular junction
cranial, limb girdle and proximal muscles
may affect respiratory muscles
no sensory loss
autonomic symptoms present if pre-synaptic
fatigueability when post-synaptic, post-exercise increase in strength when pre-synaptic
Neuropathy
weakness and sensory signs
may have associated autonomic signs
may involve cranial nerves
tendon reflexes decreased or absent
Motor neuron
predominantly motor signs
occasional sensory symptoms
often asymmetric
tendon reflexes may be increased if amyotrophic lateral sclerosis