Myasthenia Gravis (Guest Lecture)

The patient is a 46 year old woman who presented in July 1977 with horizontal double vision lasting two weeks. Three weeks later the left upper eyelid started to droop and by the end of the day the eye was closed. She had no ptosis of the right eye and no generalized fatigue. She consulted an internist: a glucose tolerance test was normal. She was referred to a neurosurgeon, who noted weakness of the medial rectus muscle - third nerve palsy. CT brain scan: normal. She was referred to the Neurovisual Clinic, Massachusetts General Hospital. Past History: Negative for previous attacks of diplopia, ptosis or fatigue. Neuro-ophthalmological examination: Visual acuity: 20/30, J1 OU. Visual fields, pupils and fundus examination normal Eyelids: •Partial ptosis left eye (OS) •Lid retraction right (OD) •Bilateral overaction of the frontalis muscle •Myasthenic lid twitch OS •Slight increase in ptosis OS on fatigue •No recovery of ptosis on gentle eye closure •Impaired ability to bury her eyelashes fully Ocular motility: •Mild weakness of the medial rectus muscle bilaterally, left > right •Poor convergence •Vertical gaze normal Intravenous Tensilon Test (edrophonium chloride): The test dose of 0.2 ml was adequate to produce a positive response with elevation of the ptotic left eyelid and correction of lid retraction OD. (Figures 1-3) The response lasted 30 seconds and then the left eyelid drooped. A further 0.3 ml of tensilon again resulted in correction of ptosis OS. The full 1 ml (10 mg) dose of tensilon was not given. Diagnosis: Ocular myasthenia gravis. Hematological tests: Thyroid studies normal Anti-skeletal muscle antibodies positive (The presence of antibodies to striatal muscle suggests that the patient harbors a thymoma) Tests for antibodies to the nicotinic acetylcholine receptor (AChR) were not available at that time. Chest x-ray PA and Lateral: A large anterior mediastinal mass was found consistent with an enlarged thymus gland. (Figures 4 and 5) CT of the chest: Multiple transverse sections through the mid-thorax showed the presence of a softly demarcated rounded mass in the anterior mediastinum directly contiguous and anterior to the inferior portion of the transverse aortic arch. The mass measured approximately 4 cm. and was surrounded by fat, and had diminished attenuation in the center indicating the presence of a moderate amount of fat or liquid within the tumor. (Figures 4 & 5) Tomograms revealed the mediastinal mass to be homogeneous without evidence of calcification or lobulation. There was no hilar adenopathy. Diagnosis: Thymoma Thymectomy: On August 8, 1977 a thymectomy was performed and encapsulated tumor completely excised. Pathology: The specimen contained a partially cystic mass and a solid portion which comprised approximately one half of the tumor. The cystic mass was 5 x 4 x 1 cm. and the overall dimensions of the tumor 11 x 5 x 1 cm, weighing 45 grams. Diagnosis: Thymolipoma Post operative status: On day one she complained of diplopia in mid-afternoon and marked drooping of her eyelids. At that time she had: •Bilateral asymmetrical ptosis, OS > OD •Palpebral fissure OD 9, OS 7. •Increased ptosis bilaterally on prolonged upgaze •Full horizontal and vertical gaze •No facial weakness •Bulbar muscles normal •Neck flexion 3/4 mild weakness •Proximal strength in the limbs good •Ventilatory capacity normal. Patient made an excellent recovery and was discharged home without any medication. Second Admission: In September 1977, six weeks post-op, she was readmitted with increasing ptosis, diplopia and generalized fatigue. At the end of the day she had fatigue chewing and weakness of the jaw and neck. Importantly, she had no difficulty swallowing or breathing and no change in the quality of her voice. She had become depressed and anxious. Ocular motility: •Bilateral symmetrical ptosis with weakness of the orbicularis oculi, and an inability to bury her eyelashes •Increased ptosis on fatigue •Myasthenic lid twitch OS •Fatigue of horizontal saccades after rapid gaze right and left, to the point where the eyes came to a standstill Neurological examination: •A mild bulbar palsy •Bilateral facial weakness with difficulty pursing her lips •Inability to sustain the arms elevated for long periods •Normal vital capacity Electrophysiological studies: Repetitive stimulation The technique for repetitive stimulation studies is similar to motor nerve conduction studies. Rather than a single supramaximal stimulus trains of repetitive stimuli are delivered at a rate of 3 stimuli per second, with 6 to 10 stimuli in a train. The compound muscle action potential of the first response is compared with the fifth response and the percentage decrement measured. A decrement of greater than 10% represents a positive test for myasthenia gravis (MG). In this patient the study revealed decrements in the right deltoid, right biceps, and inferior orbicularis oculi muscle confirming a diagnosis of generalized myasthenia gravis. Stimulated Single-fiber EMG (SF-EMG) was performed in the right digitorum communis. Seven pairs were recorded. Jitter was abnormal in one pair. MCD ranged from 15.7 to 134.8 ųsec. Blocking was present. 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 singe-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. Diagnosis: Myasthenia Gravis Treatment: Mestinon (pyridostigmine bromide) 60 mg q.3 hours Prednisone 40 mg daily. Hospital Course: Twenty-four hours after starting medication there was striking improvement. By day four, she had fully recovered. In July 1980 she was admitted for the third time with acute difficulty swallowing, shortness of breath, ptosis, diplopia, and limb weakness. Her relapse was due to her starting to taper her own prednisone dose down from 5 mg/day to 2.5 mg/day because she was mildly cushionoid. In the ER she had on examination: •A mild bulbar palsy •Moderate weakness of proximal muscles •Bilateral ptosis •Easy fatigue of her eye movements •Vital capacity normal Medication: Prednisone was increased to 10 mg b.i.d. Mestinon 60 mg 4x/day She rapidly recovered back to her normal baseline and was discharged home. In May 1998 she was admitted as an emergency with occlusion of the right dorsalis pedis and anterior tibialis arteries. A thrombectomy was performed. Hematological studies revealed a hypercoagulable state. Prothrombin time 15.6 Partial thromboplastin time 24.1. CEA level of 120 Hematocrit 26.7. The presence of a hypercoagulable state and elevated CEA level led to a workup for an occult malignancy. Colonoscopy revealed a sigmoid mass approximately 2 x 2 cm obstructing the colon. A left colectomy and colorectal anastomosis was performed. Observations during surgery revealed metastatic spread with 4 nodules located in the right lobe of the liver. Pathology: Adenocarcinoma of the colon with 18/18 positive mesenteric lymph nodes. Patient died in 1999. See also: http://content.lib.utah.edu/cdm/ref/collection/ehsl-shw/id/263