Isolated sixth nerve palsy: a rare first presentation in multiple sclerosis

Background

The abducens or the sixth cranial nerve is one of the three nerves responsible for extraocular movements of the eye. Of all the cranial nerves, the sixth has the longest intracranial course.1 Demyelinating disease is an uncommon presentation of cranial nerve palsy.

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. This is the most common cause of neurological disability in young adults usually presenting between the ages of 15 years and 45 years.2–4

It presents with episodes of numbness, tingling, muscle weakness, loss of vision, coordination difficulties, altered gait and bladder dysfunction.5 The most common ocular manifestation at initial disease presentation is optic neuritis. Alternative ocular motor deficits that can present initially include internuclear ophthalmoplegia and nystagmus.6

Zadro et al reported that cranial nerve palsy may present as an initial ocular manifestation in MS in 10% of cases.7 Isolated cranial nerve palsies in younger patients should raise suspicion of demyelinating disease. Furthermore, isolated sixth nerve palsy is increasingly considered to be rare as the first presentation of MS.8

In this report, we report the case of a young female who presented with an isolated sixth nerve palsy secondary to MS.

Case presentation

A woman in her 30s presented to the ophthalmology department with new-onset painless visual disturbance. She reported an 8-day history of acute-onset horizontal diplopia on right lateral gaze. There was no further focal neurology reported. There were no red-flag symptoms for raised intracranial pressure suggestive of space-occupying lesion.

She had a known history of sensorineural hearing loss which was investigated as a child, and the cause of it was thought to be hereditary. There are no current medications. Family history revealed that her maternal grandmother experienced symptoms suggestive of rheumatoid arthritis. She does not smoke or drink alcohol.

On examination, her visual acuity was 6/6 in both eyes. She did not have a relative afferent pupillary defect or colour vision deficiency. She had a right head turn with a small right esotropia. There was a large abduction deficit of the right eye on right gaze. There was no evidence of optic nerve swelling or atrophy. A full neurological examination was unremarkable. Limitation of right abduction on dextroversion was suggestive of right lateral rectus underaction.

From the history and examination, a clinical diagnosis of isolated right sixth nerve palsy was made.

Investigations

Blood tests demonstrated normal full blood count, coagulation screen, inflammatory markers and renal function.

Immunology screening tested negative for connective tissue disease and neuromyelitis optica. Immunoglobulin blood test did not demonstrate any positive findings. Atypical infection screen tested negative for Lyme disease. Protein electrophoresis did not demonstrate any monoclonal bands.

MRI of the head in fluid-attenuated inversion-recovery sequences with T2-weighted spin echo sequences demonstrated multiple hyperintense plaques in the following areas: periventricular plaques in the bilateral cerebral hemispheres; and juxtacortical plaques in the bilateral frontal area, left parietal and left anterior temporal areas, and bilateral pons (figure 1). MRI head with T1 sequence showed hyperintense plaques in bilateral pons, splenum of the corpus callosum (figure 2) and left cerebral upper cervical cord. There was no evidence of infarct or haemorrhage. The findings were highly suggestive of demyelinating disease.

Differential diagnosis

Common aetiology of a sixth nerve palsy ranges from stroke, trauma, infection and vascular disease to intracranial lesions.9 10 The presence of the sole ocular manifestation requires a thorough systemic assessment and a wide range of investigations to avoid misdiagnosis and provide timely management.

In a patient of young age presenting with isolated sixth nerve palsy without any additional ocular symptoms, funduscopy and ocular CT are useful investigations to assess the retina and optic nerve. There was no demonstrable papilloedema, which can be seen in raised intracranial pressure in intracranial disease. There was no evidence of retinopathy, which reassured that there was no underlying microvascular diseases such as diabetic or hypertensive retinopathy.

Blood tests including inflammatory markers were requested to screen for infection. Clinically, there were no signs and symptoms of intracranial or systemic infection. Blood tests demonstrated normal inflammatory markers. Atypical immune screen was negative.

Consideration was given to assess for any underlying autoimmune diseases. There was a family history of genetic sensorineural hearing loss, but no other significant autoimmune history was elicited from history and examination findings.

She had no medical history of migraines. There was no prodrome and headache prior to the visual disturbance. Further screen for neurological disease in the history revealed no visual loss, speech disturbances, altered sensation, muscle weakness or coordination difficulties.

The patient had not sustained any head trauma. From history and examination findings, there was no suggestion of acute infarct or haemorrhage. Cross-sectional imaging was requested to assess for acute organic disease. MRI of the head was completed and did not demonstrate evidence of infarct orhaemorrhage but revealed multiple widely disseminated plaques. CT or magnetic resonance angiography would have been necessary if any demonstrable haemorrhage was found on initial scan to exclude any intracranial arteriovenous malformation. MRI of the brain with contrast was not performed as there was no suggestion of skull base tumours or metastasis.

Demyelinating disease must be excluded especially in a young female of European descent who presented with cranial nerve palsy without evidence of ocular pathology. The demonstrable clinical episode coupled with the findings from the MRI of the head would be consistent with a diagnosis of MS.

Treatment

The patient was subsequently started on a 5-day oral course of 500 mg methylprednisolone on the recommendation of the neurology team. Intravenous steroids were not started, given her symptoms were not severe enough requiring admission and intravenous treatment. She was subsequently referred to neurology for further management of MS.

She was referred to orthoptics for cosupportive care of sixth nerve palsy with optical prisms.

Outcome and follow-up

The patient was followed up by the neurology team a week after discharge from ophthalmology. She was commenced on a short course of high-dose oral steroids. Her sixth nerve palsy had resolved after completion of the steroid course.

The neurology team had agreed that the working diagnosis is likely MS. The patient is currently awaiting lumbar puncture and cerebrospinal fluid analysis.