We report the case of a young man who presented with bilateral third nerve palsies without pupillary involvement. Brain MRI demonstrated lesions in the region of the oculomotor nerves, and further evaluation led to the diagnosis of multiple sclerosis. Our case documents a rare initial clinical presentation of this demyelinating disease.
Department of Ophthalmology (LSS, JCE, JAL), Mayo Foundation, Mayo Clinic, Rochester, Minnesota; and Department of Neurology (EH), University of Minnesota, Minneapolis, Minnesota.
Supported in part by an unrestricted grant from the Research to Prevent Blindness, New York, NY, the Robert R. Waller Career Development Award, and the Mayo Foundation, Rochester, MN.
The authors report no financial conflicts of interest related to this article.
Address correspondence to Jacqueline A. Leavitt, MD, Mayo Clinic, 200 First Street SW, Rochester, MN 55905; E-mail: firstname.lastname@example.org.
A 30-year-old white man reported a 3-week history of blurred vision and difficulty tracking objects. In the days preceding presentation, he noted inability to look down and slight ptosis of the left eyelid. On review of systems, he mentioned an unintentional 5-pound weight loss over a week, fatigue, nausea, vomiting (exaggerated with motion), and increased sensitivity of the skin over his chest. Fatigue and eye symptoms were worse at the end of the day. Medical history was significant for alcohol abuse, and he was taking no medications. His family history was significant for a 27-year-old sister diagnosed with multiple sclerosis (MS) at age 24. He also had a great-great aunt with MS.
On ophthalmologic examination, the patient's visual acuity was 20/20 in both eyes. Pupils were 4 mm, round, briskly reactive with no relative afferent pupillary defect. Visual fields by confrontation, Ishihara color vision testing, and funduscopic appearance were normal bilaterally. Bilateral ptosis was noted with palpebral fissures of 9 mm, right eye, and 7mm, left eye. Extraocular movements were limited (Fig. 1). He had a right hypertropia of 2 prism diopters (PD) and an exotropia of 2 PD in primary position.
Neurological examination revealed mildly decreased deep tendon reflexes in the right arm. He was unable to stand on the left foot alone or hop on that foot. He also had mild difficulty with tandem gait.
A tensilon test was performed and was negative. MRI of the brain showed multiple periventricular foci of increased intensity consistent with a demyelinating process. There were bilateral areas of hyperintensity in the ventral midbrain, including the periaqueductal region, which did not enhance following intravenous contrast (Fig. 2). Cerebrospinal fluid (CSF) analysis showed 11 oligoclonal bands (normal, <4), IgG of 6.67 mg/dL (normal: 0-8.1 mg/dL), and total protein of 59 mg/dL (normal: 15-45 mg/dL). Neuromyelitis optica antibodies and venereal disease research laboratory results were negative in the CSF. Acetylcholinesterase receptor binding antibody and striated muscle antibody were negative.
The patient was treated with methylprednisolone 1 g/day intravenously for 3 days. He became orthophoric in primary position, his ptosis resolved, and extraocular movements gradually improved and were documented to be full at a 21-month follow-up examination. The patient noted an increased energy and strength, and he was subsequently started on interferon therapy.
Third nerve palsy as the presenting sign of MS is rare (1). In a retrospective study by Rush and Younge (2), 2.75% of third nerve palsies were due to MS. There are 7 published reports documenting third nerve palsy as the presenting sign of MS. In 4 (3-6), the deficit was unilateral. In 1 case (7), in addition to a right third nerve palsy, there was bilateral optic nerve involvement, while in another (8), a unilateral third nerve palsy was associated with bilateral internuclear ophthalmoplegia. In 1 case (9), details of third nerve involvement were not given. In these 7 cases, the pupil was involved in 3, spared in 3, and in 1 case, examination of the pupils was not described. Our case appears unique documenting bilateral pupil-sparing third nerve palsies as the presenting sign of MS. With resolution of the cranial neuropathies, the MRI abnormalities present on the initial study resolved as well.
MRI with FLAIR demonstrated midbrain lesions of the fascicular portion of each third nerve. Yet, the most rostral regions of the midbrain were not involved, consistent with sparing of the Edinger-Westphal nuclei. It is remarkable that our patient had profound loss of bilateral inferior rectus function, while sparing the pupils. Based on the model of third nerve fascicular arrangement proposed by Ksiazek et al (10), the parasympathetic pupillary fibers and inferior rectus motor fibers are adjacent to one another. However, there are several cases in the literature that report normal pupils but impaired infraduction including patients with MS (5,11).
1. Cerovski B,
Vidovic T, Petricek I, Popovic-Suic S, Kordic R, Bojic L, Cerovski J, Kovacevic S. Multiple sclerosis and neuro-ophthalmologic manifestations. Coll Antropol. 2005;29 (suppl 1):153-158.
2. Rush JA,
Younge BR. Paralysis of cranial nerves III, IV, and VI. Cause and prognosis in 1,000 cases. Arch Ophthalmol. 1981;99:76-79.
3. Uitti RJ,
Rajput AH. Multiple sclerosis presenting as isolated oculomotor nerve palsy. Can J Neurol Sci. 1986;13:270-272.
4. Galer BS,
Lipton RB, Weinstein S, Bello L, Solomon S. Apoplectic headache and oculomotor nerve palsy: an unusual presentation of multiple sclerosis. Neurology. 1990;40:1465-1466.
5. Newman NJ,
Lessell S. Isolated pupil-sparing third-nerve palsy as the presenting sign of multiple sclerosis. Arch Neurol. 1990;47:817-818.
6. Lee AG,
Tang RA, Wong GG, Schiffman JS, Singh S. Isolated inferior rectus muscle palsy resulting from a nuclear third nerve lesion as the initial manifestation of multiple sclerosis. J Neuroophthalmol. 2000;20:246-247.
7. Desai HB,
MacFadyen DJ. Multiple sclerosis presenting as third nerve palsy. Can J Neurol Sci. 1987;14:178-179.
8. Gnanaraj L,
Rao VJ. Partial unilateral third nerve palsy and bilateral internuclear ophthalmoplegia: an unusual presentation of multiple sclerosis. Eye. 2000;14:673-675.
9. Thoemke F,
Lensch E, Ringel K, Hopf HC. Isolated cranial nerve palsies in multiple sclerosis. J Neurol Neurosurg Psychiatry. 1997;63:682-685.
10. Ksiazek SM,
Slamovits TL, Rosen CE, Burde RM, Parisi F. Fascicular arrangement in partial oculomotor paresis. Am J Ophthalmol. 1994;118:97-103.
11. Saeki N,
Yamaura A, Sunami K. Bilateral ptosis with pupil sparing because of a discrete midbrain lesion: magnetic resonance imaging evidence of topographic arrangement within the oculomotor nerve. J Neuroophthalmol. 2000;20:130-134.