Myasthenia Gravis by Ananya Singha final year

basics of myasthenia gravis

1. BURDWAN INSTITUTE OF MEDICAL AND LIFE SCIENCES Topic: myasthenia gravis Demo class presentation given by Ananya Singha BPT final year

2. Myasthenia gravis is a disorder of neuromuscular transmission characterized by Weakness and fatigue of some or all muscle groups. Weakness worsening on sustained or repeated exertion, or towards the end of the day, relieved by rest. This condition is a consequence of an autoimmune destruction of the nicotinic postsynaptic receptors for acetylcholine. The counter disease is Lambert-Eaton myasthenic syndrome (LEMS). Introduction

3. History of MG Several students of medical history affirm that Willis, in 1672, gave an account of a disease that could be none other than myasthenia gravis. Others give credit to Wilks (1877) for the first description and for having noted that the medulla was free of disease, in distinction to other types of bulbar paralysis. The first reasonably complete accounts were those of Erb (1878), who characterized the disease as a bulbar palsy without an anatomic lesion, and of Goldflam (1893); for many years thereafter, the disorder was referred to as the Erb-Goldflam syndrome. Jolly (1895) was the first to use the name myasthenia gravis, to which he added the term pseudoparalytica to indicate the lack of structural changes at autopsy. Also it was Jolly who demonstrated that myasthenic weakness could be reproduced in affected patients by repeated faradic stimulation of the relevant motor nerve and that the “fatigued” muscle would still respond to direct galvanic stimulation of its membrane. Interestingly, he suggested the use of physostigmine as a form of treatment, but there the matter rested until Reman, in 1932, and Walker, in 1934, demonstrated the therapeutic value of the drug. Campbell and Bramwell (1900) and Oppenheim (1901) each analyzed over 60 cases and crystallized the clinical concept of the disease. The relationship between myasthenia gravis and tumors of the thymus gland was first noted by Laquer and Weigert in 1901, and in 1949 Castleman and Norris gave the first detailed account of the pathologic changes in the gland. In 1905 Buzzard published a careful clinicopathologic analysis of the disease, commenting on both the thymic abnormalities and the infiltrations of lymphocytes (called lymphorrhages ) in muscle. He postulated that an “ autotoxic agent” caused the muscle weakness, the lymphorrhages , and the thymic lesions. He also commented on the close relation of myasthenia gravis to Graves disease and Addison disease, which are all now considered to have an autoimmune basis. In 1960, Simpson and, independently, Nastuk and coworkers theorized that an autoimmune mechanism must be operative in myasthenia gravis. Finally, in 1973 and subsequently, the autoimmune nature of myasthenia gravis was established through a series of investigations by Patrick and Lindstrom, Fambrough , Lennon, and A. G. Engel and their colleagues (see further on, under “Etiology and Pathogenesis”). These and other references to the early historical features of the disease are to be found in the reviews by Viets and by Kakulas and Adams; A. G. Engel’s monograph (1999) is an excellent modern reference .

4. Epidemiology Myasthenia gravis is rare, with a prevalence of 5 per 1,00,000. The increased incidence of autoimmune disorders in patients and first degree relatives and the association of the disease with certain histocompatibility antigens (HLA) – B7, B8, and DR2 – suggests an immunological basis. Interestingly myasthenia gravis effects men and women at different ages. Typical patients are either women under the age of 40 or a man over the age of 40. There is a strong link between thymoma and myasthenia gravis . 10-20% of patients with a thymoma develops myasthenia gravis.

5. Aetiopathogenesis In around 85% of patients with myasthenia gravis, acetylcholine receptor antibodies are produced by immune system. These bind to the post synaptic neuromuscular junction receptors. This blocks the receptor and prevents the acetylcholine from being able to stimulate the receptor and trigger muscle contraction. As the receptors are used more during muscle activity, more of them become blocked up. This leads to less effective stimulation of the muscle with increased activity (fatiguability). This improved with rest as more receptors are freed up for use again. These antibodies also activate the complement system within the neuromuscular junction, leading to damage to cells at post synaptic membrane, this further worsens the symptoms. There are 2 other antibodies that cause the other 15% of cases of myasthenia gravis. These are against muscle specific kinase ( MuSK ) and antibodies against low density lipoprotein receptor related protein 4 (LRP4). MuSK and LRP4 are important proteins for the creation and organisation of acetylcholine receptors. Destruction of these proteins by antibodies leads to inadequate acetylcholine receptors. This causes symptoms of myasthenia gravis.

6. Classification

7. Clinical features

8. Clinical grading Class I: any ocular muscle weakness, possible ptosis, no other evidence of muscle weakness elsewhere. Class II: eye muscle weakness of any severity, mild weakness of other muscles. Class IIa : Predominantly limb or axial muscles. Class IIb: predominantly bulbar or respiratory muscles. Class III: eye muscle weakness of any severity, moderate weakness of other muscles. Class IIIa: Predominantly limb or axial muscles. Class IIIb : predominantly bulbar or respiratory muscles. Class IV: eye muscle weakness of any severity, severe weakness of other muscles. Class IVa : Predominantly limb or axial muscles. Class IVb : predominantly bulbar or respiratory muscles (can also include feeding tube w/o intubation). Class V: intubation needed to maintain airways.

9. Examinations Looking upward and sideward for 30 secs – ptosis and diplopia. Looking at the feet while lying on the back for 60 secs. Keeping the arms stretched forward for 60 secs. 10 deep knee bends. Walking 30 steps on both the toes and heels. 5 sit ups. Lying down and sitting up completely. Peek sign: after complete initial apposition of the lid margins, they quickly ( within 30 secs) start to separate and the sclera starts to show drying response.

10. Investigations Chest X-ray will show large mediastinal mass but will not exclude a small thymoma. CT of chest should be performed in all newly diagnosed cases

11. Complications MYASTHENIC CRISES: Definition : A myasthenic crisis occurs when there is a sudden exacerbation of muscle weakness, leading to respiratory failure and other severe symptoms. It is considered a medical emergency requiring immediate intervention and hospitalization Management: – Identify and treat the precipitating cause, e.g. infection, drug interaction or overdose. – Sit patient at 45°, clear airway, give nasal O2 and if overt respiratory failure. – intubate and ventilate for as long as required.

12. Complications CHOLINERGIC CRISES: Definition : Cholinergic crisis is characterized by excessive cholinergic activity resulting from overstimulation at the neuromuscular junction. It typically occurs as a result of overmedication with cholinesterase inhibitors, such as pyridostigmine, which are commonly used to manage MG. Management: Immediate withdrawal of cholinesterase inhibitors. Airway management: Intubation and mechanical ventilation if respiratory compromise is severe. Atropine: A competitive antagonist of acetylcholine, it counteracts excessive cholinergic stimulation. Supportive care: Intravenous fluids, electrolyte correction, and monitoring for complications.

13. Treatment

14. Physiotherapy management