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Transcript of Myasthenia Gravis
English Wilson Ricardo Cardoso Myasthenia Gravis What is MG ? Neuromuscular Junction In most cases, the first noticeable symptom is weakness of the eye muscles. (1) Symptoms Who is affected? The symptom of myasthenia gravis is muscle weakness that increases during periods of activity and improves after periods of rest.(1)
Symptoms, which vary in type and severity, may include a drooping of one or both eyelids (ptosis), blurred or double vision (diplopia) due to weakness of the muscles that control eye movements, unstable or waddling gait, a change in facial expression, difficulty in swallowing, shortness of breath, impaired speech (dysarthria), and weakness is the arms, hands, fingers, legs, and neck. (1) MG occurs in all ethnic groups and both genders. It most commonly affects young adult women (under 40) and older men (over 60), but it can occur at any age.(1) Myasthenia gravis is a chronic autoimmune neuromuscular disease characterized by weakness of the visceral skeletal muscles of the body. The name myasthenia gravis literally means "grave muscle weakness,” which is from Latin and Greek origin. (1) http://www.youtube.com/watch?v=vyQWGclkGWQ MG & speaking Who is affected? In neonatal myasthenia, the fetus may acquire immune proteins (antibodies) from a mother affected with myasthenia gravis. Generally, cases of neonatal MG is temporary as the child's symptoms usually disappear within 2-3 months after birth. Myasthenia gravis in juveniles is rare. Elements in MG Acetylcholine (Ach)
Is found in the central and peripheral nervous systems and is the most common neurotransmitter.
Is an enzyme that breaks down the neurotransmitter acetylcholine.
The change in electrical potential associated with the passage of an impulse along the membrane of a muscle cell or nerve cell.
Thymus gland Normal Neuromuscular Junction
Process Neuromuscular Junction Process
in MG Causes There are no known causes to date.
There are some theories that genetics may play a role, another theory speculates that since the thymus does not decrease in size in adulthood, it becomes overactive in producing antibodies. Myasthenia gravis is caused by a defect in the transmission of nerve impulses to muscles. It occurs when normal communication between the nerve and muscle is interrupted at the neuromuscular junction—the place where nerve cells connect with the muscles they control. Normally when impulses travel down the nerve, the nerve endings release a neurotransmitter substance called acetylcholine. ACh travels from the neuromuscular junction and binds to ACh receptors which are activated and generate a muscle contraction. (1) In MG, antibodies block, alter, or destroy the receptors for ACh at the neuromuscular junction, which prevents the muscle contraction from occurring. These antibodies are produced by the body's own immune system. MG is an autoimmune disease because the immune system—which normally protects the body from foreign organisms—mistakenly attacks itself. (1) Diagnosis Physical Examination Tensilon/Edrophonium Test Single fiber electromyography (EMG) Tensilon(edrophonium test) Intravenous administration of edrophonium chloride to very briefly relieve weakness in people with MG. The drug blocks the degradation (breakdown) of ACh and temporarily increases the levels of ACh at the neuromuscular junction. EMG is used detect impaired nerve-to-muscle transmission.
EMG measures the electrical potential of muscle cells when single muscle fibers are stimulated by electrical impulses. Corticosteroids Immunosuppressant Drug Treatments Cholinesterase inhibitors A puridostigimine (Mestinon) enhance communication between nerves and muscles. Doesn’t cure MG, but makes an improvement in muscle contraction and strength. Possible side effects may include gastrointestinal upset, excessive salivation and tearing, and frequent urination. These types of drugs inhibit the immune system, limiting antibody production.
Prolonged use of corticosteroids can lead to serious side effects, such as bone thining, weight gain, diabetes, increased risk of infections. Suppress the production of immunity cells.
Azathioprine (Imuran), cyclosporine (Sand immune, Neoral) are just a few presciptions of immunosuppresants. More Invasive
Longer recovery time
Susceptible to Infection Traditional Thymectomy Side Effects Side Effects Less invasive
Less Recovery Time Non-Invasive Thymectomy Questions??? Bibliography Treatments Surgical Treatment What does MG feel like? "MG breathing weakness is not like an asthma attack, or a coughing fit. It is subtle and truly evil.
To simulate what MG breathing weakness feels like, try this:
Cover your mouth and nose with your hand. Breathe in.
Remove your hand. Exhale.
Cover your mouth and nose again." (3) Physical Therapy & Occupational Therapy Traditional thymectomy
Intravenous immune globin 1)http://www.ninds.nih.gov/disorders/myasthenia_gravis/detail_myasthenia_gravis.htm?utm_source=REFERENCES_R7
9) http://www.mgawpa.org/pdfs/PlasmapheresisLH.pdf Exercises to develop strength and increase motility
Tools for hand therapy
Wii-hab Studies in Respiratory Therapy “A 2005 Spanish study observed the effects of interval-based inspiratory muscle training combined with breathing retaining techniques on 27 patients diagnosed with generalized myasthenia gravis. Researchers placed patients into either a group that participated in interval-based inspiratory muscle training -- with built-in recovery intervals, along with diaphragmatic breathing and pursed-lip breathing, or into a control group. Over an eight-week period, patients completed breathing exercises three times per week: once at the hospital and twice at home -- supervised by a physical therapist. During 45-minute sessions, subjects engaged in 10-minute blocks each of interval-based inspiratory muscle training and the breathing retaining techniques. Patients participating in the breathing exercises exhibited significant improvements in breathing muscle strength, rate and endurance, as well as chest-wall mobility when compared to those in the control group.” (5) Diaphragmatic Breathing Pursed -lip Breathing "Loosen your neck and shoulders, and then inhale slowly with your nose for two seconds. Next pucker your lips and blow out through the lips for four seconds." (6) "To perform diaphragmatic breathing lie on a flat surface with your head supported and your knees bent. Place one hand on your chest and the other on your rib cage. Now breathe in through your nose, this will cause the hand on the rib cage to rise. Last tighten the stomach muscles and exhale, allowing the hand on the ribs to move down. (6) Inspiratory Breath Training Resistive exercises can be done using an inspiratory muscle trainer or having the patient lie down and apply weight to the diaphragm in progressive sessions (6) Wii-Hab Physical examination
EMG Test Anti-body Test How Anti-MuSK Anit-bodies link to MG patients Journals
"The term seronegative myasthenia gravis (SNMG) refers to the generalized disease without detectable anti-acetylcholine receptor (anti-AChR) antibodies. In these patients, IgG antibodies against the muscle-specific kinase (MuSK) have been described, which reduced agrin-induced AChR clustering in vitro. We have assayed anti-MuSK antibodies in 78 patients with SNMG, who have been followed for many years in our Institution. Here we describe the clinical phenotype of the 37 patients whose results were positive on this assay. MG with anti-MuSK antibodies was characterized by a striking prevalence of female patients (eight men and 29 women). Age of onset ranged from 6 to 68 years, with 56.8% of patients presenting under 40 years of age. All these patients shared a similar pattern of muscle weakness, with prevalent involvement of cranial and bulbar muscles and a high frequency of respiratory crises; the involvement of limb muscles was comparatively less severe and inconsistent. Single-fibre-EMG confirmed the most sensitive examination in the EMG diagnosis of MuSK-positive disease, while, owing to weakness topography, repetitive nerve stimulation in limb muscles was diagnostic in 56.8% of cases. The effect of edrophonium (or neostigmine) injection was equivocal or negative in 11 of 37 patients (29.7%), and the response to oral pyridostigmine was even more unsatisfactory, ranging from mild benefit to overt intolerance. In thymectomized patients, thymus was normal for age or atrophied, and no benefit from surgery was noticed. Thirty-five of 37 patients were given immunosuppressive therapy and 22 received plasma-exchange. The course of the disease was often characterized by periodic exacerbation phases requiring hospitalization and even assisted ventilation; plasma-exchange produced marked improvement in these cases. At the end of the observation period, most patients, although improved, were still symptomatic, having developed permanent facial and pharyngeal weakness together with some atrophy of facial muscles. MuSK-negative disease was comparatively more heterogeneous. Most patients were affected with mild to moderate symptoms and responded well to pharmacological treatment; however, a few subjects in this group had severe refractory disease, poorly responsive to both acetylcholinesterase inhibitors and immunosuppressants." (7) References References
1. Warmolts JR, Engel WK, Whitaker JN. Alternate day prednisone in patients with myasthenia gravis. Lancet. 1970;2:1198–1199. [PubMed]
2. Jušić A, Šoštarko M, Majić D, et al. Long-term ACTH and corticosteroid therapy in two siblings with polyneuropathy due to acute intermittent porphyria. Eur Neurol. 1976;5:294–301.
3. Dekleva I, Jušić A. Polymyositis subacuta i "HSDAD" kortikosteroidna terapija (Polymyositis Subacuta and "HSDAD" Corticosteroid Therapy). Prvi simpozij o neuromuskularnim bolestima, Zagreb, 1977. Neurologija. 1978;26:153–156. [PubMed]
4. Jušić A, Žagar M. Fluocortolon, Azathioprin i Cyclophosphamid u terapiji miastenije gravis. Drugi simpozij o neuromuskularnim bolestima, Dubrovnik, 1979. Neurologija. 1979;27:167–179. [PubMed]
5. Jušić A, Mikuličić V, Tajić M, et al. Proučavanje utjecaja kortikosteroidne terapije HSDAD tipa na dnevni ritam 11-OHCS sekrecije, metabolite kortizola te kalciuriju u bolesnika s miastenijom gravis, Prvi simpozij o neuromuskularnim bolestima, Zagreb, 1977. Neurologija. 1978;26:63–66. [PubMed]
6. Tepavčević D, Mikuličić V, Tajić M, et al. Endokrinološka kontrola kortikoidne terapije u bolesnika s miastenijom gravis. Drugi simpozij o neuromuskularnim bolestima, Dubrovnik, 1979. Neurologija. 1979;27:181–189. [PubMed]
7. Harmut M, Jušić A. Terapija visokim dozama kortikosteroida (HSDAD) i gama-apsorpciometrijska denzitometrija podlaktice. Drugi simpozij o neuromuskularnim bolestima, Dubrovnik, 1979. Neurologija. 1979;27:191–200. [PubMed]
8. Jušić A, Šoštarko M, Majerić-Kogler V. Fluocortolon long-term therapy of myasthenia gravis and polymyositis. Syllabus / IV jugoslavenski simpozij o neuromuskularnim bolestima. Zagreb. 1990:144–144.
9. Šoštarko M, Jušić A. Fluocortolon in myasthenia gravis therapy, Abstracts of the VII international congress of neuromuscular diseases, Münich, FRG. J Neurolog Sci. 1990;98:416–416. Suppl to Vol.
10. Žagar M, Šoštarko M, Jušić A. Late onset myasthenia gravis. 33th international neuropsychiatric symposium in Pula, 1993; Proceedings 1993; 1993. pp. 53–53.
11. Tanaka J, Matsuzaki K, Arai H, et al. Intermittent methylprednisolone pulse therapy for myasthenia gravis in childhood. No To Hattatsu. 1994;26:14–19. [PubMed]
12. Lindberg C, Andersen O, Lefvert AK. Treatment of myasthenia gravis with methylprednisolone pulse: a double blind study. Acta Neurolo Scand. 1998;97:370–373.
13. Nagane Y, Suzuki S, Suzuki N, et al. Early aggressive treatment strategy against myasthenia gravis. Eur Neurol. 2011;65:16–22. [PubMed]
14. Jušić A, Mitrović Z, Brzović Z, et al. Electromyoneurography, CT and Immunobiochemistry in Neuromyotonia Case Analysis (preliminary report) 5th Congress I.S.E.K. Ljubljana, 82 - Zdrav Vestn. 1982;51:124–126.
15. Baraba R, Jušić A, Sruk A. Progressive Encephalomyelitis with Rigidity: a case report. J Spinal Cord Med. 2010;33:73–76. [PMC free article] [PubMed] Journal on Thymoma & MG One half of cortical thymoma patients develop myasthenia gravis (MG), while 15% of MG patients have thymomas.
Titin and ryanodine receptor (RyR) antibodies are found in 95% of thymoma MG, especially in patient under 60 years
Titin is the largest known protein, with a molecular mass of 3000 kD stretching throughout the sarcomere, providing a direct link between mechanical muscle strain and muscle gene activation
The RyR is the calcium channel of the sarcoplasmic reticulum (SR). Upon opening, the RyR releases Ca2+ into the sarcoplasm resulting in muscle contraction. In vitro, RyR antibodies can inhibit Ca2+ release from the SR .
Thymoma MG may be suspect in Nonlimb symptoms of MG with bulbar, ocular, neck, and respiratory symptoms.(2) Antibodies for Thymoma MG Plasmapheresis Case Study A 30-year-old healthy woman experienced speech disturbance and swallowing difficulty at two months of pregnancy.
Diagnosed with MG with anti-MuSK antibodies
Symptoms at 8 months of pregnancy: bulbar palsy, eye movement disturbance, and muscle weakness
Beginning at week 37, plasma exchange 3x/daily
Infant born w/ anti-MuSK antibodies, weak suckling power
First known case of plasmapheresis during pregnancy (8) Plasmapheresis What is Plasmapheresis?
The selective removal of the patient’s plasma which is then replaced by special intravenous fluids.
What is the process?
Plasma is removed and replaced with a “plasma substitute” sans the antibodies that were causing the problem.
"The procedure itself begins with the insertion of a needle into a vein in each arm. Once the needles wityh connecting tubing are inserted, blood is withdrawn form one arm to flow into the apheresis machine. Once in the machine, the blood is separated into various components allowing for easy removal of the plasma and antibodies. The remainder of the blood components, red cells, white cells and platelets, are then combined with sterile plasma substitutes and returned through the other arm."
The process takes 1-3 hours, it may take 3-5 treatments before symptoms improve, and most MG patients will have this done weekly or bi-weekly. (8)