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 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 Inherited HMSN and HLPP Amyloid Drugs, alcohol, organophosphates Inflammatory/Immune GBS, CIDP Vasculitis Infective 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 Myasthenia etc Peripheral Neuropathy

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 (cont’d)

Polyneuropathy (cont’d) 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-Barré 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 (cont’d) 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) Paralisis flasid simetris, difus Gejala sensoris subyektif Penyembuhan sempurna dalam 6 bulan Disosiasi citoalbumin Tanpa atau sedikit demam saat muncul paralysis AL normal atau lymphositosis dengan sedikit atau tanpa kenaikan KED. Harus memenuhi 5 kriteria dari 6 kriteria

Pengobatan GBS Fase akut Setelah fese 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 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 200–400 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 (cont’d) Inherited Acquired 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 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

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