Sistem Neuromuskular

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-or-
none" 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 Tanda-tanda
kelumpuhan UMN : kelumpuhan LMN :
Hiperrefleksia Arefleksia (hilangnya
Terdapat refleks refleks tendo)
patologis Tidak ada refleks
Tonus otot meninggi patologis
atau hipertonia Hilangnya tonus otot
Terdapat Klonus (flacid)
Tidak terdapat atrofi Tidak terdapat klonus
otot yang lumpuh Terdapat atrofi pada
Refleks automatisme otot yang lumpuh
spinal (-)
 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 Inherited
Drugs, alcohol,
HMSN and HLPP
organophosphates
Amyloid
Inflammatory/Immune
GBS, CIDP Metabolic
Vasculitis Diabetes
Infective Vitamins: B12, B1, E
Leprosy, Lyme, HIV, Dialysis, Liver failure
Diphtheria
Paraneoplastic
Traumatic
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 radiculopathy
Plexus plexopathy
Single nerve mononeuropathy
Several nerves multiple mononeuropathy,
mononeuritis multiplex
All nerves, polyneuropathy
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 GBS

1- 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
Polyradiculo-
neuropathy 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 receptor blockade:
Myasthenia gravis (antibodies to ACh
receptor)
 Myasthenia Gravis
Kelemahan yang berfluktuasi
Mata: ptosis, diplopia
Bulbar weakness: dysarthria,
dysphagia
Kelemahan otot proksimal
Kelemahan respirasi
Penyakit autoimun pada transmisi
Normal reflexes neuromuskular junction yang
Normal sensation diakibatkan oleh antibodi yang
menyerang reseptor asetilkolin atau
Berkaitan dg thymoma melawan muscle spesific receptor
tyrosine kinase
Berkaitan dg penyakit
autoimun
 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
autoimmune
toxic (drugs...)
Inflammatory myopathies
Polymyositis
isolated
with collagen vascular
disease
Dermatomyositis
childhood
adult: association with
cancer
others
 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