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Myasthenia gravis
 

Myasthenia gravis

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    Myasthenia gravis Myasthenia gravis Presentation Transcript

    •  INTRODUCTION GROSS ANATOMY OF ARM HISTO-ANATOMY OF ARM PHYSIO OF SKELETAL MUSCLE SIGNS & SYMPTOMS PATHOPHYSIOLOGY OF MG DIAGNOSIS MANAGEMENT PROGNOSIS REFERENCES
    •  The word MYASTHENIA GRAVIS is derived from Greek & Latin  Greek: myasthenia: muscle weakness  Latin:gravis: serious
    •  Mg is an autoimmune neuromuscular disease, leading to fluctuating muscle weakness & fatigue
    •  In MG weakness is caused by circulating antibodies that block acetylcholine receptors at the postsynaptic neuromuscular junction, inhibiting the excitatory effects of the neurotransmitter acetylcholine on nicotinic receptors throughout neuromuscular junctions.
    •  Myasthenia gravis: It affects people of any age, it's more common in women younger than 40 and in men older than 60  The disease incidence is 3–30 cases per million per year and rising as a result of increased awareness.
    •  NEONATAL MYASTHENIA: If a woman with myasthenia gravis gives birth, the baby may have some temporary, and potentially life-threatening, muscle weakness (neonatal myasthenia) because of antibodies that have transferred from the mother's bloodstream.
    •  Typically, during the baby's first weeks of life, the antibodies are cleared from the baby's circulation and the baby develops normal muscle tone and strength.
    •  Biceps Brachii  Triceps Brachii  Brachialis  Anconeus  Brachiorradialis  Coracobrachialis
    • Origin • • short head: coracoid process of the scapula long head: supraglenoid tubercle of the scapula Insertion • tuberosity of the radius Action  flexes the forearm, flexes arm (long head), supinates
    • anatomy.uams.edu/anatomyhtml/gross_a tlas.htm
    • Origin • anterior surface of the lower one-half of the humerus and the associated intermuscular septa Insertion • coronoid process of the ulna Action  flexes the elbow, assists in pronation & supination
    • anatomy.uams.edu/anatomyhtml/gross_a tlas.htm
    • Coracobrachialis Origin  Coracoid process of the scapula Insertion  medial side of the humerus at mid-shaft Action  flexes and adducts the arm
    • Triceps Brachii Origin •long head: infraglenoid tubercle of the scapula •lateral head: posterolateral humerus & lateral intermuscular septum •medial head: posteromedial surface of the inferior 1/2 of the humerus Insertion •olecranon process of the ulna Action extends the forearm, the long head extends and adducts arm
    • anatomy.uams.edu/anatomyhtml/gross_a tlas.htm
    • Anconeus Origin •lateral epicondyle of the humerus Insertion •lateral side of the olecranon and the upper one-fourth of the ulna Action •extends the forearm
    • anatomy.uams.edu/anatomyhtml/gross_a tlas.htm
    •  Nerves that supply the arm are branches of the brachial plexus.  There are five main nerves from the brachial plexus, these nerves are;  Axillary  Ulnar  Median  Musculocutaneous  Radial
    •    However, there are two main nerves that supply the Arm. These nerves are; Musculocutaneous nerve Radial Nerve
    • It’s a mixed nerve , it has both sensory and motor function.  Its root value is C5,C6,C7  It arises from the lateral cord  The musculocutaneous nerve leaves the brachial plexus sheath high in the axilla at the level of the lower border of the teres major muscle and passes into the coracobrachialis muscle.  It innervates the muscles in the flexor compartment of the arm and carries sensation from the lateral (radial) side of the forearm  Its responsible for the biceps jerk (C5,C6) (Stephen et al, 2013) 
    • http://emedicine.medscape.com/article/1877731overview#showall
    •  It is derived from the posterior cord  Its root value is C5,C6,C7,C8,C9,T1  The nerve passes out of the axilla posteriorly and supplies branches to the long and medial heads of the triceps brachii.  It has both sensory and motor function
    •  Sensory; Innervates most of the skin of the posterior side of forearm, and the dorsal surface of the lateral side of the palm, and lateral three and a half digits  Motor; Innervates the triceps brachii, responsible for extension at the elbow.  Innervates the majority of the extensor muscles in the forearm, responsible for extension of wrist and fingers and supination of the forearm (Oliver, 2013)
    • http://emedicine.medscape.com/a rticle/1877731-overview#showall
    • A skeletal muscle consists of muscle fibres held together by connective tissue (collagenous fibres).(Hill,2013) Skeletal muscle constitutes the muscle that is attached to the skeleton and controls motor movements and posture. There are a few instances where this type of muscle is restricted to soft tissues: the tongue, pharynx, diaphragm and upper part of the esophagus 
    • LONGITUDINAL SECTION TRANSVERS SECTION
    •  Skeletal muscle fibres (cells) are actually a multinucleated syncytium formed by the fusion of individual small muscle cells(myoblasts), during development. They’re filled with longitudinally arrayed subunits(myofibrils). The myofibrils are made up of the myofilaments myosin (thick filaments) and actin (thin filaments).  The striations reflect the arrangement of actin and myosin filaments and support structures. The individual contractile units are called sarcomeres.  A myofibril consists of many sarcomeres arranged end to end. The entire muscle exhibits cross-striations because sarcomeres in adjacent myofibrils and muscle fibers are in register
    • . The most obvious feature in longitudinal sections of skeletal muscle is the alternating pattern of dark and light bands, A (anisotropic) and I (isotropic) band.  The I band is bisected by a dense zone called the Z line, to which the thin filaments of the I band are attached. The nuclei are located peripherally, immediately under the plasma membrane (sarcolemma),(mark,2013)
    • . Individual muscle fibres are surrounded by a delicate layer of reticular fibres(endomysium). Groups of fibres are bundled into fascicles by a thicker CT layer(perimysium). The collection of fascicles that constitutes one muscle is surrounded by a sheath of dense CT(epimysium) which continues into the tendon. Blood vessels and nerves are found in the CT associated with muscle. The endomysium contains only capillaries and the finest neuronal branches.(mark,2013)
    • Extremely elongated Unbranched cylindrical cells Each muscle cell is called muscle fibre Numerous flattened nuclei located just beneath the sarcolemma Shows regular striations .(Hill,2013) Sarcolemma – plasma membrane of muscle cell Sarcoplasm (cytoplasm of muscle cell) myofibrils,mitochondria, T-tubules, sarcoplasmic ( smooth endoplasmic) reticulum.(HILL,2013) Sarcosomes – mitochondria of muscles
    • The structural subunit of the muscle fibre is the myofibril. Myofilaments are individual filamentous polymers of myosin ( thick filaments) and actin ( thin filaments ) and its associated proteins.(Hill,2013) Thin filaments – composed primarily of the protein actin . each thin filament of fibrous actin ( Factin) is a polymer formed from globular actin molecules ( G- actin) Tropomyosin , troponin also present. Thick filaments – composed of protein myosin.(Hill,2013) Myoglobin – is oxygen- binding protein. Numerous in red muscle.)
    • UNDER MICROSCOPIC I-BAND ABAND Z-LINE
    • Dark bands / A bands – anisotropic i.e. birefringent in polarised light. Light band / I bands – isotropic i.e. do not alter the plane of light. (Hill,2013) The functional subunit of the myofibril is the sarcomere , the segment of the myofibril b/w Light I band is bisected by a dense line Z line / Z disk. Dark A band is bisected by a light region called H band. Bisecting the light H band is a narrow dense line called M line(Hill,2013)
    • N C S
    •  Autoimmune disease Extreme muscle weakness(Leite et.al, 2008) In this disease , Ach receptors on sarcolemma are blocked by antibodies to the receptor protein.(Leite et.al,2008) No. of receptor sites are reduced – weakening of muscle fiber response to nerve stimuli
    •  Under voluntary control.  Each skeletal muscle is innervated by a branch of motorneurons.  Action potentials are propogated along motorneurons, leading to release of Ach at the nuromuscular junction,depolarisation of the motor end plate and initiation of action potential in the muscle fiber.  Events occuring between action potential and contraction in muscle fiber are called excitationcontraction coupling(mechanism that translates the muscle action potentialinto the production of tension).
    • Step 1 A nerve impulse travels down an axon and causes the release of acetylcholinein the neuro muscular junction. Acetylecholine causes the impulse to spread across the surface of the sarcolemma.
    • Depolarisation of sarcolemma-influx of Na+ and efflux of k+. The nerve impulse enters the T Tubules and Sarcoplasmic Reticulum, stimulating the release of calcium ions.
    • Release of Ca ions into actin filaments. Calcium ions combine with Troponin, shifting troponin and exposing the myosin binding sites on the actin.
    • Head of myosin binds with ATP and makes way for forming cross- bridges to actin filament.In this process ATP breaks down to ADP + Pi. The released energy activates the myosin cross bridges and results in the sliding of thin actin myofilament past the thick myosin myofilaments.
    • The sliding of the myofilaments draws the Z lines towards each other, the sarcomere shortens, the muscle fibers contract and therefore muscle contracts.
    • ACh is inactivated by Acetylcholinesterase, inhibit the nerve impulse conduction across the sarcolemma. Nerve impulse is inhibited, calcium ions are actively transported back into the Sarcoplasmic Reticulum, using the energy from the earlier ATP breakdown. The low calcium concentration causes the myosin cross bridges to separate from the thin actin myofilaments and the actin myofilaments return to their relaxed position.
    •  MUSCLE WEAKNESS Facial Neck Limb Respiratory ocular  PTOSIS  DIPLOPLIA  FACE AND THROAT MUSCLES Altered speaking. (DYSARTHRIA) Difficulty swallowing. (DYSPHAGIA) Problems chewing.
    •  Myasthenia gravis is caused by a problem with the transmission of nerve signals to the muscles.  It is an autoimmune condition, which means the body's immune system attacks its own tissues.
    •  Genetic factors also may be associated with myasthenia gravis.  Rarely, mothers with myasthenia gravis have children who are born with myasthenia gravis (neonatal myasthenia gravis). If treated promptly, children generally recover within two months after birth.
    • Diagnosis MG can be a difficult diagnosis, as the symptoms can be subtle and hard to distinguish from both normal variants and other neurological disorders A thorough physical examination can reveal easy fatigability A good response to medication can also be considered a sign of autoimmune pathology.
    • Physical examination Muscle fatigability can be tested for many muscles. A thorough investigation includes: •looking upward and sidewards for 30 seconds: ptosis (DROOPING OF EYELIDS) and diplopia(DOUBLE VISION) •looking at the feet while lying on the back for 60 seconds •keeping the arms stretched forward for 60 seconds •ten deep knee bends •walking 30 steps on both the toes and the heels
    • •five sit-ups, lying down and sitting up completely •"Peek sign": after complete initial apposition of the lid margins, they quickly (within 30 seconds) start to separate and the sclera starts to show
    • Blood test If the diagnosis is suspected, serology can be performed in a blood test to identify certain antibodies: •One test is for antibodies against the acetylcholine receptor]The test has a reasonable sensitivity of 80–96%, but in MG limited to the eye muscles (ocular myasthenia) the sensitivity falls to 50% (negative in up to 50% who have MG). •A proportion of the patients without antibodies against the acetylcholine receptor have antibodies against the Muscle protein.
    • •In specific situations (decreased reflexes which increase on facilitation, coexisting autonomic features, suspected presence of neoplasm, especially of the lung, presence of increment or facilitation on repetitive EMG (electromyography) testing) testing is performed for •Lambert-Eaton syndrome, in which other antibodies (against a voltage-gated calcium channel) can be found.
    • Electrodiagnostics Muscle fibers of patients with MG are easily fatigued, and thus do not respond as well as muscles in healthy individuals to repeated stimulation. By stimulating a nerve-muscle motor unit with short sequences of rapid, regular electrical impulses, before and after exercising the motor unit, the fatiguability of the muscle can be measured. This is called the repetitive nerve stimulation test. In single fiber electromyography (SFEMG), which is considered to be the most sensitive (although not the most specific) test for MG,
    • Ice test Applying ice to weak muscle groups characteristically leads to improvement in strength of those muscles. Applying ice for 5 minutes to the muscles reportedly has a sensitivity and specificity of 76.9% and 98.3%, respectively, for the identification of MG. It is thought that acetylcholinesterase is inhibited at the lower temperature and that this is the basis for this diagnostic test.
    • Edrophonium test The "edrophonium test" is infrequently performed to identify MG; its application is limited to those situations in which other investigations have failed to yield a conclusive diagnosis. This test requires the intravenous administration of edrophonium chloride (Tensilon, Reversol) or neostigmine (Prostigmin), drugs that block the breakdown of acetylcholine by cholinesterase (acetylcholinesterase inhibitors) and temporarily increases the levels of acetylcholine at the neuromuscular junction. In people with myasthenia gravis involving the eye muscles, edrophonium chloride will briefly relieve weakness.
    • Edrophonium test Photograph of a patient showing right partial ptosis (left picture), Right picture: after an edrophonium test, note the improvement in ptosis.
    • Imaging A chest X-ray is frequently performed; it may point towards alternative diagnoses (e.g., Lambert-Eaton syndrome due to a lung tumor) and comorbidity. It may also identify widening of the mediastinum suggestive of thymoma, but computed tomography (CT) or magnetic resonance imaging (MRI) are more sensitive ways to identify thymomas and are generally done for this reason. MRI of the cranium and orbits may also be performed to exclude compressive and inflammatory lesions of the cranial nerves and ocular muscles.
    • A chest CT-scan showing a thymoma (red circle)
    • Pulmonary function test Spirometry (lung function testing) may be performed to assess respiratory function if there are concerns about breathing adequacy. The forced vital capacity may be monitored at intervals to detect increasing muscular weakness. Acutely, negative inspiratory force may be used to determine adequacy of ventilation. Severe myasthenia may cause respiratory failure due to exhaustion of the respiratory muscles.
    • Pathological finding Muscle biopsy is only performed if the diagnosis remains in doubt and clinical suspicion of MG persists. Immunofluorescence shows IgG antibodies on the neuromuscular junction. (The antibody which causes myasthenia gravis does not fluoresce, but rather a secondary antibody directed against it.) Muscle electron microscopy shows receptor infolding and loss of the tips of the folds, together with widening of the synaptic clefts. Both these techniques are currently used for research rather than diagnostically.
    •  Specific treatment to age, overall health, and medical history and extent of the condition  No cure for MG, but the symptoms can be controlled.  MG is a life-long medical condition and the key to medically managing MG is early detection.  The goal of treatment is to prevent respiratory problems and provide adequate nutritional care to the child since the swallowing and breathing muscles are affected by this condition.
    • TREATMENT OF MYASTHENIA GRAVIS SHORT TERM ANTICHOLESTERASE S eg : Neostigmine Pyridostigmine EPHEDRINE PLASMAPHERESIS LONG TERM IMMUNOSUPPRESSIVE AGENTS Eg : PREDNISONE AZATHIOPRINE CYCLOPHOSPHAMIDE CYCLOSPORINS IMMUNOGLOBULIN G
    • Cholinesterase inhibitors  neostigmine and pyridostigmine can improve muscle function by slowing the natural enzyme cholinesterase that degrades acetylcholine in the motor end plate.  the neurotransmitter is therefore around longer to stimulate its receptor  Side effects, such as perspiration and diarrhea, can be countered by adding atropine  Pyridostigmine is a short-lived drug, with a halflife of about four hours.
    • CORTICOSTEROIDS  Produce rapid improvement in many  Produce total remission / marked improvement in > 75 % of patients  Used as initial definite therapy  Used as secondary treatment in who do not respond to thymectomy / immunosuppressive therapy  Initial dose prednisone 15 – 25 mg/day increased until maximal improvement is seen or upto 50 – 60 mg/day
    • Immunosuppressants  eg:prednisone, cyclosporin, mycophenolate and azathioprine  Patients are commonly treated with a combination of these drugs with an acetylcholinesterase inhibitor.  Treatments with some immunosuppressives take weeks to months before effects are noticed.  Other immunomodulating substances, such as drugs that prevent acetylcholine receptor modulation by the immune system, are currently being researched. 
    • Plasmapheresis  This procedure is done in serious case of myasthenia gravis  This procedure uses a filtering process similar to dialysis.  Blood is routed through a machine that removes the antibodies that are blocking transmission of signals from nerve endings to muscles' receptor sites.  However, the beneficial effects usually last only a few weeks .
    • Intravenous immune globulin  This therapy provides body with normal antibodies, which alters immune system response.  It has a lower risk of side effects than do plasmapheresis and immune-suppressing therapy.  But it can take a week or two to start working and the benefits usually last less than a month or two.
    • How antibodies against acetylcholine receptor block impulse conduction in synapse
    • Thymectomy  The surgical removal of the thymus.  Thymectomy is recommended for most young patients.  It improves the disease course and can improve remission.  Thymectomy is thought to remove an antigen source and reduce an anti-AChR antibody source.  Thymectomy is performed when the disease is in control.  But in the presence of myasthenia gravis, thymoma is the most likely diagnosis. Thymectomy may result in cure or great improvement in the myasthenia.
    • Diet Patients may experience difficulty chewing and swallowing due to oropharyngeal weakness • Thickened liquids are preferred, when dysphagia arises to counteract the fear of aspiration. • Asparagus should be taken as it contains steroid-like substance. • Activity • Patients should be as active as possible but should take rest in between. • Yoga exercises to stretch the weakened muscles should be done. • This not only strengthens the muscles but also provides oxygen & removes carbon dioxide from them.
    • Teach patient/family disease process, complications, and treatments  Teach patient about their medications uses dosage etc  Teach medications to use with caution d/t muscle exacerbation    Beta blockers, calcium channel blockers, quinine, quinidine, procainamide, some antibiotics, neuromuscular blocking agents Avoid certain medications  D-penicillinamine, A-interferon, botulinum toxin
    •  In patients with generalized MG, there is some evidence that a partial home program including training in diaphragmatic breathing , pursed lip breathing , and interval based IMT may improve respiratory muscle strength, chest wall mobility, respiratory pattern, and respiratory endurance
    •  Not all patients have adverse effects Streptomycin Ciprofloxacin Levofloxacin Ofloxacin Gatifloxacin Propanol Atenolol Local anaesthetic xylocaine Erythromycin Azithromycin Non depolarizing muscle relaxants – DTC,pancuronium Myasthenic Weakness exaggerated Quininine Magnesium penicilliamine
    • With effective treatment, patients have high possibility of a normal life expectancy, but anexception would be the presence of a malignant thymoma (whose lesser life expectancy is on account of the thymoma itself and is otherwise unrelated to the myasthenia). Quality of life can vary depending on the severity and the cause.
    • Drugs used to control MG either diminish in effectiveness over time (acetylcholinesterase inhibitors) or can possibly cause severe side effects of their own (immunosuppressants).  About 10% of MG patients are found to have tumors in their thymus glands, in which case a thymectomy is a very effective treatment with long-term remission.  However, most patients need treatment for the remainder of their lives, and their abilities vary greatly.   MG is not usually a progressive disease; the symptoms may fluctuate, but do not always get worse as the patient ages. For some, the symptoms decrease after a span of three to five years ( costanzo, 2012).
    • Oliver Jones (2013), The Radial nerve, from; http://teachmeanatomy.info/upperlimb/nerves/the-radial-nerve/ Stephen k, Jeffrey MV, Julia L (2013) The Anatomy of brachial plexus. From; http://emedicine.medscape.com/article/1877731-overview#showall  Hill, M.A. (2013) Skeletal Muscle Histology. Retrieved October 1, 2013, from http://php.med.unsw.edu.au/embryology/index.php?title=Skeleta l_Muscle_Histology Dr Mark Hill 2013, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G  Leite MI, Jacob S, Viegas S, et al. (July 2008). "IgG1 antibodies to acetylcholine receptors in 'seronegative' myasthenia gravis" . Brain 131 (Pt 7): 1940– 52.doi:10.1093/brain/awn092 . PMC 2442426.PMID 18515870
    •  Hill, M.A. (2013) Skeletal Muscle Histology. Retrieved October 1, 2013, from http://php.med.unsw.edu.au/embryology/index.p hp?title=Skeletal_Muscle_Histology  Dr Mark Hill 2013, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G Leite MI, Jacob S, Viegas S, et al. (July 2008). "IgG1 antibodies to acetylcholine receptors in 'seronegative' myasthenia gravis" . Brain 131 (Pt 7): 1940– 52.doi:10.1093/brain/awn092 . PMC 2442426.PMID 1851 5870 