Familial Myasthenia Gravis

Unilateral Ptosis; External OphthalmoplegiaPowerPoint Presentation: Ocular Myasthenia Gravis: Past, Present and Future: http://library.med.utah.edu/NOVEL/Wray/PPT/Ocular_Myasthenia_Gravis_guest_lecture.ppt Victoria S. Pelak, M.D. University of Colorado Health Sciences CenterDroopy eyelidsIn 1999 Dr. A. G. Engel published a monograph on Myasthenia Gravis and Myasthenic Disorders with a chapter devoted to Congenital Myasthenic Syndromes. Dr. Engel systematically defined and classified hereditary and congenital myasthenic syndromes, delineated on the basis of their electrophysiological and ultra structural features. The congenital myasthenic syndromes are inherited defects in components of the presynaptic, synaptic, or post-synaptic junctional apparatus. It has been estimated that in three quarters of the cases the defect is post-synaptic. Clinically, these disorders are distinguished by: Neonatal onset Fluctuating and sometimes progressive weakness that may be quite severe, Sometimes pronounced muscle hypertrophy and Persistent ptosis and Sero negativity for anti-AChR and anti-MuSK antibodies The interest of the patient presented here is that myasthenia gravis occurred in a father and daughter. The father suffering from generalized ocular myasthenia gravis and the daughter developing ocular manifestations of myasthenia gravis around the age of 9 years. She came to the Massachusetts General Hospital at the age of 12 years in the early 1980's just about the time the autoimmune basis of myasthenia gravis was established and its morphologic and physiological features defined. Details of the full work-up of the father and daughter are unfortunately unknown. Neuro-ophthalmological Examination: Partial ptosis OD Bilateral ptosis with fatigue after prolonged upgaze Cogan's myasthenic lid twitch with overshoot of the left upper eyelid Asymmetrical external ophthalmoplegia Weakness of adduction, downgaze and to a lesser extent upgaze OS Weakness of adduction, elevation and downgaze OD Progression: Within a month of the onset her condition deteriorated. She developed generalized myasthenia gravis with Bilateral ptosis and Bulbar palsy Chest X-Ray: Normal. Her father had generalized myasthenia gravis and ocular signs. When seen with his daughter he was post thymectomy and doing well. He had: No ptosis Impaired upgaze OD > OS Impaired downgaze, fairly symmetric Impaired convergence No lid lag Full horizontal gaze Antibody Studies: These patients were seen in the early 1980's and predated tests for antiacetylcholine receptor antibodies.No neuro-imaging studies are available in this patient.Ptosis: Ptosis is defined as the lid covering more than 2 mm of the cornea. Ptosis is routinely measured by documenting the width of the palpebral fissure in millimeters with the eye in primary gaze and the eyebrow held down. Approximately 50% of patients with ocular myasthenia gravis present with ptosis. More than 90% eventually develop eye movement abnormalities and typical ocular myasthenia. Of those patients who present only with ocular symptoms, half persist with purely ocular myasthenia and half go on to develop generalized myasthenia gravis. Of those who develop generalized myasthenia gravis, most do so within 2 years of the onset of ocular symptoms.Myasthenia gravis (MG) is an autoimmune disease caused by sensitized T-helper cells and an IgG-directed attack on the nicotinic acetylcholine receptor of the neuromuscular junction (NMJ). The mechanism of antibody damage to the receptor and motor endplate probably involves several steps. 1. There is a complement-directed attack with the destruction of acetylcholine receptor and the junctional folds. 2. Binding of the antibody to the receptor can cause receptor blockade. 3. The abnormal and reduced numbers of acetylcholine receptors lead to impaired NMJ transmission. 4. In post synaptic disorders such as MG, the number of quanta of acetylcholine released by each nerve stimulus is normal, but the effect of each quantum on its receptor is reduced. 5. The net result is a lower endplate potential and a reduced safety factor of transmission at the NMJ. Clinically this manifests as pathologic fatigability, that is, progressive muscle weakness with use - the hallmark of MG. Patients typically improve after rest or upon arising in the morning, with worsening as the day passes. In MG, fatigue is limited to muscular fatigue alone and often progresses to frank muscle weakness.Autoimmune diseaseMestinon 60 mg, 1 tab, q.6.h.1. Averbuch-Heller L. Poonyathalang A, von Maydell RD, Remler BF, Hering's law for eyelids: still valid. Neurology 1995;45:1781-1782. http://www.ncbi.nlm.nih.gov/pubmed/7675249 2. Bever CT, Aquino AV, Penn AS, Lovelace RE, Rowland LP, Prognosis of ocular myasthenia. Ann Neurol 1983;14:516-519. http://www.ncbi.nlm.nih.gov/pubmed/6651238 3. Cogan DG. Myasthenia gravis. A review of the disease and a description of lid twitch as a characteristic sign. Arch Ophthalmol 1965;74:217-221. http://www.ncbi.nlm.nih.gov/pubmed/14318498 4. Cogan DG, Yee RD, Gittinger J. Rapid eye movements in myasthenia gravis. 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The Office Tensilon Test for Ocular Myasthenia Gravis. Arch Neurol 1986;43:842-843. http://www.ncbi.nlm.nih.gov/pubmed/3729766 17. Sommer N, Melms A, Weller M, Dichgans J. Ocular myasthenia gravis. A critical review of clinical and pathophysiological aspects. Doc Ophthalmol 1993;84:309-333. http://www.ncbi.nlm.nih.gov/pubmed/8156854 18. Valls-Canals J, Povedano M, Montero J, Pradas J. Stimulated Single-Fiber EMG of the Frontalis and Orbicularis Oculi Muscles in Ocular Myasthenia Gravis . Muscle Nerve 2003;28:501-503. http://www.ncbi.nlm.nih.gov/pubmed/14506723 19. Vincent A, Newsom-Davis J. Anti-acetylcholine receptor antibodies. J Neurol Neurosurg Psychiatry 1980;43:590-600 1980. http://www.ncbi.nlm.nih.gov/pubmed/7400823 20. Wittbrodt ET. Drugs and myasthenia gravis an update. Arch Intern Med 1997:157:399-408. http://www.ncbi.nlm.nih.gov/pubmed/9046891RSmyastheniagravis; EXAMfatigableptosis; NOTE-EXAMMG; NOTE-EXAMfatigableptosi