Grand Rounds at the New England Eye Center

Young woman presents with intermittent diplopia and nausea

She had limited abduction of the left eye and displayed high-frequency, low-amplitude nystagmus that increased in lateral gaze.

An 18-year-old woman presented to Lahey Medical Center with 2 weeks of intermittent diplopia, nausea and headache.

Two weeks earlier, she had experienced acute onset binocular diplopia with horizontal and vertical double images. The episode was accompanied by severe nausea, headache, dizziness and photophobia. After 30 minutes, she experienced complete resolution of all symptoms. One week later, she had a similar episode that lasted for 10 minutes before resolving. Her third episode occurred 2 days before presentation and prompted a visit to the emergency department at an outside hospital. She was evaluated with CT imaging and MRI and MRA of the head and neck with and without contrast. Each of the imaging studies was read as normal (Figure 1), and she was discharged to follow up with neuro-ophthalmology in the outpatient setting.

Brain MRI T2 axial FLAIR sequence performed before patient’s presentation
Figure 1. Brain MRI T2 axial FLAIR sequence performed before patient’s presentation, showing no lesions.

Source: Jarod Santoro, MD, and Geetha Athappilly, MD

The patient’s review of systems was negative for intracranial noises, weight change, new medication or transient visual obscuration. She denied any additional neurologic symptoms including weakness or paresthesia. She had no history of trauma. The patient’s medical history was significant for irritable bowel syndrome, anemia, migraine and peptic ulcer disease. Her surgical and social history was unremarkable. Her family history was noncontributory. Her prescribed medications included ferrous sulfate.

Examination

On examination, the patient’s best corrected visual acuity was 20/20 in each eye. Her pupils were symmetric, and she had no afferent pupillary defect. IOP was within normal limits. Her color vision was fully intact.

On motility examination, the patient had limited abduction of the left eye, consistent with a left sixth cranial nerve palsy. She also displayed high-frequency, low-amplitude nystagmus that increased in lateral gaze. Slit lamp and dilated fundus examinations were unremarkable in each eye.

Workup and management

The patient underwent additional in-office testing including OCT of each optic nerve and macula, which showed normal retinal nerve fiber layer and ganglion cell complex in each eye. She was also sent for 30-2 automated Humphrey visual field testing, which was unremarkable. The initial MRI brain was reviewed in collaboration with a neuroradiologist and was found to be within normal limits.

What is your diagnosis?

See answer on next page.

Diplopia, nausea

The primary diagnostic considerations for this young woman presenting with diplopia, headache, nausea and photophobia were idiopathic intracranial hypertension (IIH), cerebral venous sinus thrombosis (CVST) and meningitis.

Typically, IIH is seen in young females with a history of headache, nausea and diplopia, as in our patient. Bilateral disc edema is commonly found on examination but may be absent in 5.7% of patients with elevated intracranial pressure (ICP) from IIH. Sixth cranial nerve involvement is reported in 12% of adults with IIH. Patients with increased intracranial pressure from cerebral venous sinus thrombosis typically present with headache, an altered level of consciousness or a focal neurologic deficit. These patients rarely have sixth cranial nerve deficits. Bilateral disc edema is reported in 28% to 67.5% of patients with elevated ICP from CVST, so suspicion should remain high despite the absence of disc edema in this patient. Meningitis may also present with headaches and photophobia, and abducens nerve palsy has been reported in 16.5% of patients with bacterial meningitis. Given the presence of nystagmus on examination, additional diagnostic considerations for this patient included demyelinating disease, malignancy, ischemia and toxic exposure.

Additional workup

At the time of evaluation, the patient continued to endorse severe nausea, dizziness and photophobia, and was unable to participate further in the examination. She was sent to the emergency room for evaluation and workup. She underwent additional testing including a lumbar puncture with cerebrospinal fluid analysis. She also had a repeat MRI as well as an MRV. The repeat MRI showed a new enhancing lesion in the left middle cerebellar peduncle consistent with an area of acute demyelination (Figure 2). She subsequently underwent MRI of the cervical and thoracic spine, which revealed an old focus of demyelination in the cervical spine. The findings were believed to be consistent with a diagnosis of multiple sclerosis (MS).

Brain MRI T2 axial FLAIR sequence showing enhancing lesion
Figure 2. Brain MRI T2 axial FLAIR sequence showing enhancing lesion in the left middle cerebellar peduncle consistent with an area of acute demyelination.

Discussion

Multiple sclerosis is a demyelinating disease of the central nervous system and a leading cause of disability in young adults. The diagnosis of MS requires the presence of multiple lesions disseminated in time and space, as was seen in our patient. Optic neuritis is a frequent ocular finding that affects nearly half of MS patients. However, efferent pathway deficits involving the brainstem and cerebellum are also common. Findings may include internuclear ophthalmoplegia, saccadic dysmetria and nystagmus. In addition, nausea and vertigo can be seen with middle cerebellar peduncle lesions.

Isolated cranial nerve palsies are rare in MS, affecting about 10% of patients. When present, cranial nerve deficits typically present at the time of disease onset. Trigeminal and facial nerve defects are most frequently observed. Abducens nerve palsies occur in only 1% of MS patients.

Although our patient had undergone CT imaging and MRI only a few days before presentation with no apparent findings, it is important to consider additional imaging when clinical findings persist and localize to a specific region in the brain.

Treatment of acute MS exacerbation is often accomplished with corticosteroids.

Disease-modifying therapy is usually necessary for long-term treatment of MS. Numerous immunosuppressive treatments are available and should be selected based on patient comorbidities and disease activity.

Clinical course

The patient was admitted to the neurology service for treatment with 3 days of intravenous steroids. During the course of her admission, she experienced significant improvement of her diplopia, nystagmus and nausea. She was discharged home with outpatient referral to neurology for consideration of disease-modifying therapy.

An 18-year-old woman presented to Lahey Medical Center with 2 weeks of intermittent diplopia, nausea and headache.

Two weeks earlier, she had experienced acute onset binocular diplopia with horizontal and vertical double images. The episode was accompanied by severe nausea, headache, dizziness and photophobia. After 30 minutes, she experienced complete resolution of all symptoms. One week later, she had a similar episode that lasted for 10 minutes before resolving. Her third episode occurred 2 days before presentation and prompted a visit to the emergency department at an outside hospital. She was evaluated with CT imaging and MRI and MRA of the head and neck with and without contrast. Each of the imaging studies was read as normal (Figure 1), and she was discharged to follow up with neuro-ophthalmology in the outpatient setting.

Brain MRI T2 axial FLAIR sequence performed before patient’s presentation
Figure 1. Brain MRI T2 axial FLAIR sequence performed before patient’s presentation, showing no lesions.

Source: Jarod Santoro, MD, and Geetha Athappilly, MD

The patient’s review of systems was negative for intracranial noises, weight change, new medication or transient visual obscuration. She denied any additional neurologic symptoms including weakness or paresthesia. She had no history of trauma. The patient’s medical history was significant for irritable bowel syndrome, anemia, migraine and peptic ulcer disease. Her surgical and social history was unremarkable. Her family history was noncontributory. Her prescribed medications included ferrous sulfate.

Examination

On examination, the patient’s best corrected visual acuity was 20/20 in each eye. Her pupils were symmetric, and she had no afferent pupillary defect. IOP was within normal limits. Her color vision was fully intact.

On motility examination, the patient had limited abduction of the left eye, consistent with a left sixth cranial nerve palsy. She also displayed high-frequency, low-amplitude nystagmus that increased in lateral gaze. Slit lamp and dilated fundus examinations were unremarkable in each eye.

Workup and management

The patient underwent additional in-office testing including OCT of each optic nerve and macula, which showed normal retinal nerve fiber layer and ganglion cell complex in each eye. She was also sent for 30-2 automated Humphrey visual field testing, which was unremarkable. The initial MRI brain was reviewed in collaboration with a neuroradiologist and was found to be within normal limits.

What is your diagnosis?

See answer on next page.

PAGE BREAK

Diplopia, nausea

The primary diagnostic considerations for this young woman presenting with diplopia, headache, nausea and photophobia were idiopathic intracranial hypertension (IIH), cerebral venous sinus thrombosis (CVST) and meningitis.

Typically, IIH is seen in young females with a history of headache, nausea and diplopia, as in our patient. Bilateral disc edema is commonly found on examination but may be absent in 5.7% of patients with elevated intracranial pressure (ICP) from IIH. Sixth cranial nerve involvement is reported in 12% of adults with IIH. Patients with increased intracranial pressure from cerebral venous sinus thrombosis typically present with headache, an altered level of consciousness or a focal neurologic deficit. These patients rarely have sixth cranial nerve deficits. Bilateral disc edema is reported in 28% to 67.5% of patients with elevated ICP from CVST, so suspicion should remain high despite the absence of disc edema in this patient. Meningitis may also present with headaches and photophobia, and abducens nerve palsy has been reported in 16.5% of patients with bacterial meningitis. Given the presence of nystagmus on examination, additional diagnostic considerations for this patient included demyelinating disease, malignancy, ischemia and toxic exposure.

Additional workup

At the time of evaluation, the patient continued to endorse severe nausea, dizziness and photophobia, and was unable to participate further in the examination. She was sent to the emergency room for evaluation and workup. She underwent additional testing including a lumbar puncture with cerebrospinal fluid analysis. She also had a repeat MRI as well as an MRV. The repeat MRI showed a new enhancing lesion in the left middle cerebellar peduncle consistent with an area of acute demyelination (Figure 2). She subsequently underwent MRI of the cervical and thoracic spine, which revealed an old focus of demyelination in the cervical spine. The findings were believed to be consistent with a diagnosis of multiple sclerosis (MS).

Brain MRI T2 axial FLAIR sequence showing enhancing lesion
Figure 2. Brain MRI T2 axial FLAIR sequence showing enhancing lesion in the left middle cerebellar peduncle consistent with an area of acute demyelination.

Discussion

Multiple sclerosis is a demyelinating disease of the central nervous system and a leading cause of disability in young adults. The diagnosis of MS requires the presence of multiple lesions disseminated in time and space, as was seen in our patient. Optic neuritis is a frequent ocular finding that affects nearly half of MS patients. However, efferent pathway deficits involving the brainstem and cerebellum are also common. Findings may include internuclear ophthalmoplegia, saccadic dysmetria and nystagmus. In addition, nausea and vertigo can be seen with middle cerebellar peduncle lesions.

Isolated cranial nerve palsies are rare in MS, affecting about 10% of patients. When present, cranial nerve deficits typically present at the time of disease onset. Trigeminal and facial nerve defects are most frequently observed. Abducens nerve palsies occur in only 1% of MS patients.

Although our patient had undergone CT imaging and MRI only a few days before presentation with no apparent findings, it is important to consider additional imaging when clinical findings persist and localize to a specific region in the brain.

Treatment of acute MS exacerbation is often accomplished with corticosteroids.

Disease-modifying therapy is usually necessary for long-term treatment of MS. Numerous immunosuppressive treatments are available and should be selected based on patient comorbidities and disease activity.

Clinical course

The patient was admitted to the neurology service for treatment with 3 days of intravenous steroids. During the course of her admission, she experienced significant improvement of her diplopia, nystagmus and nausea. She was discharged home with outpatient referral to neurology for consideration of disease-modifying therapy.