Sistem Neuromuskular

Sistem Neuromuskular
Tiga komponen utama Neuromuskular
Nerve

Neuromuscular
Muscle

junction

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

Miastenia Gravis Botulism Tick paralysis Lambert Eaton Myastenic Syndrome

Neuromuscular junction

Gangguan yang menyebabkan kelemahan gerak (paralysis) Neuropati akut

Paraneoplastik Vaskulitis (lupus, poliarteritis) Neuropati motorik multifokal

Guillain-Barre syndrome Lime Disease Sindrome Cauda Equina Poliomyelitis Amyotropic Lateral Sclerosis (ALS)

Poliradikulopati akut

Penyakit Motor neuron

Gangguan yang menyebabkan kelemahan gerak (paralysis) Medula Spinalis

Inflamasi (mielitis transversus) Mielopati (spondilosis, hematom, infark)

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

Otak (Cerebrum, cerebellum)

Jenis Gangguan Saraf

Polyneuropathy: motor, sensory, sensorimotor Radiculopathy Polyradiculopathy Plexopathy Mononeuropathy: isolated multiplex

Klasifikasi kausa

Toxic

Drugs, alcohol, organophosphates GBS, CIDP Vasculitis Leprosy, Lyme, HIV, Diphtheria

Inflammatory/Immune

Infective

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 Reflexes
Usually decr.

NMJ
NL or decr.

Muscle
NL or decr.

Atrophy
Fascic.

Can be severe
Sometimes

Minimal
None None

Variable
None None

Sensory loss Sometimes

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

radiculopathy plexopathy mononeuropathy multiple mononeuropathy, mononeuritis multiplex polyneuropathy

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 Program rehabilitasi, bladder training, perbaikan ADL (activity daily living)

Setelah fese akut

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 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 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 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