| Identifier |
920-1 |
| Title |
Unilateral Ptosis |
| Creator |
Shirley H. Wray, MD, PhD, FRCP |
| Contributors |
Steve Smith, Videographer |
| Affiliation |
(SHW) Professor of Neurology, Harvard Medical School; Director, Unit for Neurovisual Disorders, Massachusetts General Hospital, Boston, Massachusetts |
| Subject |
Unilateral Ptosis; Positive Tensilon Test; Ocular Myasthenia Gravis; Unilateral Myasthenia Gravis; Ptosis - Myasthenic |
| History |
This patient is a 46 year old man who carried a diagnosis of late onset diabetes mellitus and hypertension. In October 1985, five weeks prior to admission, he developed vertical diplopia while playing golf. Drooping of the left upper lid (ptosis) developed a few days later and closed the eye. The ptosis completely recovered during sleep, but he noted, immediately on waking in the morning double vision and within one hour drooping of the left eyelid which persisted and closed the eye for the rest of the day. He consulted his ophthalmologist and was referred to a neurologist. A tensilon test was positive. Diagnosis: Ocular myasthenia gravis (OMG). Treatment was started with pyridostigmine (mestinon) 60 mg t.i.d., p.o., with no recovery of ptosis. He was then referred for a second opinion to rule out a pupil sparing third nerve palsy. Symptomatic inquiry: Negative for fatigue, transient weakness, ptosis of the right eye, or difficulty in swallowing or breathing. Past History: Positive for a transient period of diplopia at the age of 13 attributed to a lazy eye. Treated with prism glasses for approximately 2 months. Hypertension for 18 years. Late onset diabetes treated with oral medication for one year. Family History: Grandfather, a French Canadian, had droopy eyelids attributed to his age. He died at the age of 85. Father died laryngeal CA. Neuro-ophthalmological examination: Visual acuity 20/20 OD, 20/25 OS Visual fields and fundi no abnormality Pupils 4 mm OU constricting to 2 mm to light and to near Palpebral fissure OD 12 mm in primary gaze OS complete ptosis. OD lid retraction with overaction of the frontalis OD eyelid returned to normal position on primary gaze when the left eyelid was manually held open. No ptosis OD on sustained upgaze Impaired ability to bury his eyelashes fully on eye closure Ocular movements full OU Right hyperphoria 20 diopters in primary gaze Convergence normal No nystagmus Neurological examination: Bulbar muscles normal No lower facial weakness Neck strength good No motor weakness Sensory system intact Symmetrical 1+ reflexes Hematological studies: CBC, electrolytes, liver function test, BUN and creatinine all normal. Sedimentation rate 10 mm/hr. Antibody studies: Serum anti-acetylcholine receptor antibody (AChR) titer < 0.40 nmol/L (normal <0.50 nmol/L). This test measured binding antibodies only. Thyroid studies: Thyroid stimulating hormone (TSH), normal level and T4 and T3 levels normal. Electrocardiogram: Normal sinus rhythm, non-specific T segment and T wave changes. Chest CT: No evidence of thymic enlargement Normal study Tensilon Test: An intravenous tensilon (edrophonium chloride, 10 mg in l cc.) test was performed 36 hours after stopping mestinon. The patient had had no adverse side effects following a previous tensilon test and he had no known drug allergies or cardiac disease. The tensilon test was performed as follows: 1. A pediatric intravenous needle was inserted and two 1- mL syringes attached to a 3-way stopcock. One syringe contained 10 mg of tensilon and the second normal saline. 2. A test dose and 0.2mL tensilon was flushed in with saline and blood pressure and pulse rate monitored. 3. In the absence of side effects (excess sweating, salivation, bradycardia and hypotension) after 1 ½ minutes a further dose of 0.3 mL tensilon was flushed in with saline. 4. With no recovery of ptosis over 2 minutes, a further dose of 0.3 mL tensilon was given. 5. A positive response resulted. The left eyelid elevated completely and the positive tensilon response persisted over 5 minutes before the left upper lid slowly drooped again and completely shut the eye. Patient received a total dose of 8 mg tensilon and the test was stopped. The only side effect experienced was excess tearing. Electrophysiologic testing: Repetitive nerve stimulation In generalized myasthenia gravis (MG) the strength of muscular contractions progressively declines in response to a train of stimuli. Right ulnar nerve - abductor digiti minimi muscle normal. Right facial nerve - orbicularis oculi muscle normal. A decrement > 10% represents a positive test for MG. Stimulated single-fiber EMG (SF-EMG) is the more sensitive electrophysiological method for the diagnosis of myasthenia. This is a special technique for the recording of single-muscle- fiber action potentials and is used to measure fiber density and so-called jitter. Jitter is the variability of the interpotential interval of successive discharges of two single-muscle-fibers belonging to the same motor unit. This phenomenon is due largely to the very slight variability of delay at the branch points in the distal axon and by synaptic delay at the neuromuscular junction. For this reason, SF-EMG is particularly useful in the detection of disorders of the neuromuscular junction, especially MG. In this patient the SF-EMG study of the right extensor digitorum communis was normal. Diagnosis: Seronegative ocular myasthenia gravis Comment: Up to 50% of patients with OMG are seronegative for AChR antibodies. In 2001 antibodies to muscle specific kinase (MuSK) were discovered in seronegative patients with generalized MG and subsequently in seronegative patients with OMG. Therapy: Because the patient had failed to respond to oral mestinon tablets, suggesting that this medication had not been fully absorbed, he was started on ambenonium chloride (mytelase), a cholinesterase inhibitor at an equivalent neostigmine (prostigmin) dose of 60 mg q.i.d. at 8 a.m., 12 p.m., 6 p.m. and 10 p.m. q.d. (The equivalent oral dose of 15 mg of prostigmin is 5 mg of mytelase). The patient had an excellent response with recovery of ptosis and improvement in his diplopia. Follow-Up: The patient was seen on an annual basis from 1985 to 2000 and never developed signs of generalized MG. Serial tests for AChR antibodies were negative. In February 2000, his medication was reduced and changed to a mestinon time spansule (180 mg dose) half a spansule (90 mg) at 8 a.m. and 10 p.m. q.d. In 2002, he returned symptom free. He had no ptosis and his diplopia was corrected with prism glasses. To check if he was in remission, a decision was made to stop mestinon. He did extremely well off mestinon until June 2003 when he returned as an emergency stating that his "myasthenia had kicked in again". The sequence of events were as follows: 1. Four weeks prior to his visit he had a sinus infection treated with antibiotics, the names of the drugs he could not recall. 2. Two weeks prior to his visit he cut his right forearm and artery with a very sharp tile and at an outside hospital ER he received an intravenous antibiotic and given keflex (cephalexin) tablets p.o. for a period of one week. 3. A week later, he returned to the hospital to have the forearm tendons repaired under a local regional anesthetic block. 4. Two to three days after this surgery his myasthenia kicked in. The right eyelid drooped a quarter of the way down and he developed horizontal double vision in primary gaze, more marked on looking to the right or to the left. He had no fatigue or generalized symptoms. Exacerbation of MG: Myasthenic weakness due to antibiotics and other drugs: There are over 30 drugs in clinical use (other than anesthetic agents) that may interfere with neuromuscular transmission in normal individuals but especially in myasthenic patients. Eighteen different antibiotics have been reported, but particularly neomycin, kenamycin, cholistin, streptomycin, polymyxine, and certain tetracyclines. These drugs impair transmitter release by interfering with calcium-ion fluxes at nerve terminals. The fluorinated quinolones group, typified by ciprofloxacin affect both pre-and post synaptic activity. A list of these and other drugs that can cause a myasthenic syndrome or worsening of MG are listed in a table in the attached PowerPoint presentation. Neuro-ophthalmological examination: Patient was very anxious. He arrived with a patch over his right eye to prevent diplopia. Partial right ptosis Palpebral fissure 10 OD, OS 14 Increased ptosis on fatigue OD Unable to bury his eyelashes fully OU when asked to close his eyes tightly Mild overaction of the frontalis muscle on the right No lid twitch Ocular movements full OU Esophoria at distance and near Neurological examination: Bulbar muscles normal No lower facial weakness Neck strength good No motor weakness Therapy: He was started back on mestinon 60 mg p.o. at 8 a.m., 12 noon, 4 p.m. and 8 p.m. and half a mestinon time spansule (90 mg) at 10 p.m. q.d. The ocular symptoms fully recovered and he was able to gradually reduce his medication to half a mestinon time spansule (90 mg) b.i.d., p.o. Follow-Up: After his annual visit in 2004, he was lost to follow-up. |
| Anatomy |
Thymic hyperplasia and thyoma are associated with MG. As many as 65 to 70% of all myasthenic patients, particularly younger patients, have thymic hyperplasia, characterized by infiltration of the thymus with lymphocytes and plasma cells and the formation of lymphoid follicles (Germinal centers). Thymoma occurs in 5 to 20% of myasthenic patients. The incidence of this tumor increases with age. Patients with thymoma tend to have more severe disease, higher serum titers of AChR antibodies, and more severe abnormalities on EMG than patients without a thymoma. There is a 23% incidence of associated autoimmune disease in patients with thymoma, although no gender predisposition or HLA antigen has been found. |
| Pathology |
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. 6. In MG, fatigue is limited to muscular fatigue alone and often progresses to frank muscle weakness. |
| Disease/Diagnosis |
Ocular Myasthenia Gravis. |
| Clinical |
This patient with unilateral ptosis OS as the only sign of OMG shows a strikingly positive response to intravenous tensilon. The tensilon test has long been the gold standard for the diagnosis of MG since its introduction by Osserman and Kaplan in 1952. Tensilon (edrophonium chloride) is a rapidly acting and quickly hydrolyzed anticholinesterase drug supplied in a parenteral formulation at a concentration of 10 mg/mL. Onset of action begins within 30 to 60 seconds after an intravenous injection and the effects resolve within 5 to 10 minutes as the drug is quickly inactivated by hydrolysis. As this patient was free of cardiac disease, the test was performed in the office. Atropine sulfate was available for intravenous use if needed to counteract muscarinic side effects. The tensilon test was performed in steps (as previously described). After 8 mg, there was full recovery of ptosis of the left upper eyelid. The test was stopped at that time. He had no adverse side effects apart from excess tearing. Comment: It is uncertain why ocular muscles are frequently involved in myasthenia and why the disease stays localized to the ocular muscles in 50% of cases. It has been proposed that subtle alterations in the function of extraocular muscles are more likely to produce symptoms than in limb muscles, and that the levator palpebrae under constant activation during eye opening, may be more susceptible to fatigue. Other observations include: • Patients with OMG are more likely to be seronegative for acetylcholine receptor antibodies than patients with generalized MG. • Extraocular muscles (but not the levator palpebrae) are unique in their expression of fetal acetylcholine receptors at the neuromuscular junction; however there is no evidence of specific immunological targeting of this receptor. • The junctional folds of muscle endplates are sparse in the extraocular and levator muscles, perhaps producing a lower safety factor for neuromuscular transmission. • Complement regulatory genes are expressed differentially in extraocular muscles, perhaps producing protective mechanisms to complement-mediated tissue injury. |
| Presenting Symptom |
Drooping of the left eyelid Double vision |
| Ocular Movements |
Unilateral Ptosis: Positive Tensilon Test; Full Eye Movements |
| Neuroimaging |
CT and MRI of the mediastinum are the most sensitive radiologic techniques for detecting a thymoma. CT is superior in screening for thymoma, whereas MRI may offer better resolution in evaluating the extent or spread of a thymoma to the pleural cavity, not withstanding the issue of motion artifact with MRI of the chest. |
| Treatment |
Patients with ocular myasthenia represent a therapeutic challenge, and they are treated very differently in major centers. Initially it is appropriate to start with acetylcholinesterase inhibitors (and prism glasses when appropriate) prior to immunosuppressive therapy with corticosteroids or other medications. |
| Etiology |
Autoimmune disease |
| Supplementary Materials |
Ocular Myasthenia Gravis: Past, Present and Future: https://collections.lib.utah.edu/details?id=2174219 |
| Date |
1985 |
| References |
1. Caress JB, Hunt CH, Batish SD. Anti-MuSK myasthenia gravis presenting with purely ocular findings. Arch Neurol 2005;62-1002-1003. http://www.ncbi.nlm.nih.gov/pubmed/15956173 2. 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 3. Daroff RD. The office tensilon test for ocular myasthenia gravis. Arch Neurol 1986:43:843-844. http://www.ncbi.nlm.nih.gov/pubmed/3729767 4. Elrod RD, Weinberg DA. Ocular myasthenia gravis. Ophthalmol Clin North Am 2004;17:275. http://www.ncbi.nlm.nih.gov/pubmed/15337189 5. Hanisch F, Eger K, Zierz S. MuSK-antibody positive pure ocular myasthenia gravis. J Neurol 2006;253:659-660. http://www.ncbi.nlm.nih.gov/pubmed/16311895 6. Meriggioli MN, Sanders DB. Myasthenia gravis: diagnosis. Semin Neurol 2004;24:31. http://www.ncbi.nlm.nih.gov/pubmed/15229790 7. Seybold ME. The office Tensilon test for ocular myasthenia gravis. Arch Neurol 1986;43-842-843. http://www.ncbi.nlm.nih.gov/pubmed/3729766 8. 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 9. Vincent A, Newsom-Davis J. Acetylcholine receptor antibody as a diagnostic test for myasthenia gravis: results in 153 validated cases and 2967 diagnostic assays. J Neurol Neurosurg Psychiatry 1985;48:1246-1252. http://www.ncbi.nlm.nih.gov/pubmed/4087000 10. Wittbrodt, ET. Drugs and myasthenia gravis an update. Arch Intern Med 1997;157:399-408. http://www.ncbi.nlm.nih.gov/pubmed/9046891 |
| Language |
eng |
| Format |
video/mp4 |
| Type |
Image/MovingImage |
| Source |
3/4" Umatic master videotape |
| Relation is Part of |
163-1, 163-10, 163-11, 166-25, 920-2 |
| Collection |
Neuro-Ophthalmology Virtual Education Library: Shirley H. Wray Collection: https://novel.utah.edu/Wray/ |
| Publisher |
North American Neuro-Ophthalmology Society |
| Holding Institution |
Spencer S. Eccles Health Sciences Library, University of Utah |
| Rights Management |
Copyright 2002. For further information regarding the rights to this collection, please visit: https://NOVEL.utah.edu/about/copyright |
| ARK |
ark:/87278/s6qg1qg6 |
| Setname |
ehsl_novel_shw |
| ID |
188509 |
| Reference URL |
https://collections.lib.utah.edu/ark:/87278/s6qg1qg6 |
