A Woman With Droopy Eyelids and Ophthalmoplegia

A 40-year-old Black woman presented with progressive droopy eyelids and blurred vision for the past 15 years. Her symptoms improved somewhat periodically, but during the past year, she developed intermittent diplopia, and her symptoms were worse in the afternoons.

She denied difficulty swallowing or breathing, limb weakness, or headaches. Previous workup included a normal MRI of the head.

Past medical history included a motor vehicle accident 5 years prior to this evaluation. The accident caused her to have glass fragments in her eyes and blurred vision. Four weeks later, her vision cleared; however, the patient stated that her eyelid droopiness had never been normal since then. She had a history of hypertension.

Family history was negative for neurologic disorders.

Examination revealed ptosis and ophthalmoplegia to all movements, worse on lateral gaze. The ptosis increased somewhat with sustained upward gaze and partially worsened in either eye with the examiner holding the opposite eyelid ( Fig. 89-1 ). Pupils were equal and reactive without evidence of retinopathy. There was mild weakness of the orbicularis oculi. Facial muscles were strong, and other cranial nerves were normal, although neck flexors were mildly weak. She had no weakness of her extremity muscles, either distally or proximally, and there was no muscle fatigue during repetitive contractions. Reflexes, sensation, and coordination were normal. The examination was otherwise unremarkable.

T4 and thyroid-stimulating hormone were normal, erythrocyte sedimentation rate was 35 mm/h (normal, 0–30 mm/h), and acetylcholine receptor antibody titer was normal or less than 0.8 nmol/L. Complete blood count and a comprehensive metabolic profile were normal. Serum lactate was 10 mg/dL (normal, 9–18 mg/dL), and serum creatine kinase (CK) was 97 IU/L (normal, <200 IU/L).

What is the Differential Diagnosis?

In this patient with bilateral ophthalmoplegia and ptosis having normal pupils and without long tract signs, a central nervous system disorder seemed unlikely.

Myasthenia gravis should be considered because of the fluctuation of symptoms, fatigue, and the enhancement of ptosis of either eye while the examiner held the opposite eyelid. A patient like this should be worked up for that disease with edrophonium and repetitive stimulation tests. If the latter is negative, single-fiber electromyography (SFEMG) should be done, and acetylcholine receptor antibodies should be measured. If this test is negative, muscle-specific protein kinase (MuSK) antibody levels should be ordered.

The long-standing symptoms and the symmetry of the ophthalmoplegia, however, are somewhat against myasthenia gravis.

Progressive external ophthalmoplegia (PEO) also occurs in mitochondrial myopathy as the manifestation of a more severe disorder, such as Kearns–Sayre syndrome. The ophthalmoplegia could also be isolated, or patients might have mild proximal limb weakness. Another possibility is oculopharyngeal dystrophy, but this patient did not have a family history or difficulty swallowing to support this diagnosis. Slow channel congenital myasthenic syndrome was a consideration, but she did not have the finger extensor weakness characteristic of this disease; and in this, ptosis and ophthalmoplegia are not prominent. Thyroid eye disease could manifest with ophthalmoplegia and ptosis but is usually accompanied by exophthalmos. This condition could resemble myasthenia gravis or can be associated with myasthenia.

What should be the Workup?

The serum lactate and thyroid function tests in this patient were normal. Acetylcholine receptor antibodies were also normal. An edrophonium test was negative. MuSK antibody test was not available then.

The normal thyroid tests ruled out thyroid disease, and normal serum lactate and CK are somewhat against, but do not rule out, a mitochondrial myopathy. The edrophonium test is a sensitive test for myasthenia; however, it could be negative in some patients. Acetylcholine receptor antibodies could also be negative, particularly when weakness is limited to the eye muscles.

An EMG Test was Performed

Motor Nerve Studies

Nerve and Site	Latency (ms)	Amplitude (mV)	Conduction Velocity (m/s)
Median Nerve L.	Normal ≤ 4.2	Normal ≥ 6	Normal ≥ 50
Wrist	3.7	26	–
Elbow	7.3	25	60

F-Wave Studies

Nerve	Latency (ms)	Normal Latency ≤ (ms)
Median nerve L.	25.5	30

Repetitive Stimulation of Accessory Nerve L.

Potential Number	Amp (mV)	Amp Decrement (%)	Area Decrement (%)
Before Exercise
1	5.28	0	0
2	5.11	3	2
3	5.06	3	1
4	5.05	4	3
5	4.90	8	4
Posttetanic
1	5.58	0	0
2	5.51	1	5
3	5.26	6	10
4	5.26	7	10
5	5.26	7	10
1 min Postexercise
1	5.70	0	0
2	5.52	3	8
3	5.48	4	10
4	5.48	5	10
5	5.48	6	10
2 min Postexercise
1	5.65	0	0
2	5.59	1	3
3	5.47	3	1
4	5.32	6	10
5	5.29	6	10
3 min Postexercise
1	5.76	0	0
2	5.56	3	0
3	5.44	6	2
4	5.45	5	1
5	5.45	5	2

Repetitive Stimulation of Facial Nerve L.—cont’d

Potential Number	Amp (mV)	Amp Decrement (%)	Area Decrement (%)
Before Exercise
1	2.64	0	0
2	2.69	2	3
3	2.59	2	0
4	2.47	6	4
Posttetanic
1	2.75	0	0
2	2.73	1	1
3	2.66	3	3
4	2.64	4	4
1 min Postexercise
1	3.27	0	0
2	3.40	4	1
3	3.24	1	1
4	3.19	2	3
2 min Postexercise
1	3.32	0	0
2	3.36	1	1
3	3.36	1	1
4	3.30	1	0
3 min Postexercise
1	3.10	0	0
2	3.07	5	3
3	3.01	4	1
4	2.96	2	2