MRI Imaging of Neuromyelitis Neuromyelitis Optica

MRI Imaging of MRI Imaging of NeuromyelitisNeuromyelitis OpticaOptica

Jenna Nolan, Harvard Medical School Year IIIJenna Nolan, Harvard Medical School Year IIIGillian Lieberman, MDGillian Lieberman, MD

July 2009

Our Patient: Initial PresentationOur Patient: Initial Presentation

J.H. is a 29 yearJ.H. is a 29 year--old woman who presents with acute vision old woman who presents with acute vision loss and pain in the right eye.loss and pain in the right eye. Monocular central vision loss and Monocular central vision loss and fuzzinessfuzziness in the right eye.in the right eye. Colors are Colors are less brightless bright through the right eye.through the right eye. Pain in the right eye with movement in all directions. Pain in the right eye with movement in all directions.

Past medical history: uncomplicated vaginal delivery one Past medical history: uncomplicated vaginal delivery one month prior to presentation; no other significant medical, month prior to presentation; no other significant medical, neurological or surgical history.neurological or surgical history.

Neurologic exam: Neurologic exam:

Visual acuity OD 20/400, OS 20/20.Visual acuity OD 20/400, OS 20/20.

Visual field testing: right eye central scotoma. Visual field testing: right eye central scotoma.

Right eye red desaturation.Right eye red desaturation.

Causes of Optic NeuropathyCauses of Optic Neuropathy1.1. Optic Neuritis: Optic Neuritis:

inflammatory, demyelinating condition of the optic nerveinflammatory, demyelinating condition of the optic nerve most common in younger adults (ages 18most common in younger adults (ages 18--40)40)

2.2. Ischemic Optic Neuropathy: Ischemic Optic Neuropathy: ischemic insult to the optic nerve headischemic insult to the optic nerve head most common in patients over the age of 50most common in patients over the age of 50

3.3. Infectious/PostInfectious/Post--infectiousinfectious viral, Bartonella, Toxoplasmosis, Lyme, Syphilisviral, Bartonella, Toxoplasmosis, Lyme, Syphilis

4.4. Inflammatory Optic Neuropathy: Inflammatory Optic Neuropathy: manifestation of Sarcoidosis, Systemic lupus erythematosus (SLE)manifestation of Sarcoidosis, Systemic lupus erythematosus (SLE), Sjogren, Sjogrens syndrome, s syndrome,

WegenerWegeners granulomatosiss granulomatosis

5.5. CompressiveCompressive Neoplasm (optic glioma, meningioma, lymphoma), carotidNeoplasm (optic glioma, meningioma, lymphoma), carotid--ophthalmic artery aneurysmophthalmic artery aneurysm

6.6. Genetic Genetic LeberLebers hereditary optic neuropathy, Kjer type autosomal dominant optis hereditary optic neuropathy, Kjer type autosomal dominant optic atrophyc atrophy

7.7. ToxicToxic Drugs, toxins, radiationDrugs, toxins, radiation

8.8. TraumaTrauma closed head trauma causing contusion or hemorrhageclosed head trauma causing contusion or hemorrhage

Anatomy of the OrbitAnatomy of the Orbit

Axial T2-weighted MRI

PACS, BIDMC

Lens Medial Rectus Muscle

Lateral Rectus MuscleOptic Nerve

Orbital Fat

Vitreous Body

Menu of Tests:Menu of Tests: Imaging the Optic NerveImaging the Optic Nerve

MRI MRI Primary modality for imaging the optic nerve and orbital soft Primary modality for imaging the optic nerve and orbital soft

tissuestissues Useful in the evaluation of: Useful in the evaluation of:

compressive lesionscompressive lesions

inflammatory and demyelinating lesions inflammatory and demyelinating lesions

infarction and ischemia infarction and ischemia

infectioninfection

CTCT Able to detect bony detail, calcifying lesions (e.g. meningiomasAble to detect bony detail, calcifying lesions (e.g. meningiomas), ),

early hemorrhageearly hemorrhage Useful in the evaluation of acute trauma for orbital fractures aUseful in the evaluation of acute trauma for orbital fractures and nd

hemorrhagehemorrhage

Imaging the Optic Nerve: MRIImaging the Optic Nerve: MRI

Imaging the optic nerve presents many challenges:Imaging the optic nerve presents many challenges: Small size requires high spatial resolutionSmall size requires high spatial resolution Surrounding fat, CSF, and bone can produce artifactsSurrounding fat, CSF, and bone can produce artifacts Eye movements can cause motion artifactEye movements can cause motion artifact

T1: used to evaluate anatomyT1: used to evaluate anatomy Fat tends to be brightFat tends to be bright CSF is darkCSF is dark

T2: used to evaluate edema resulting from pathologic processesT2: used to evaluate edema resulting from pathologic processes CSF is brightCSF is bright Fat tends to be darkFat tends to be dark

Fat Saturation:Fat Saturation: Short Tau inversion Recovery (STIR): suppresses the fat signal aShort Tau inversion Recovery (STIR): suppresses the fat signal allowing for llowing for

better detection of optic nerve lesionsbetter detection of optic nerve lesions T1 postT1 post--contrast with Fat Sat contrast with Fat Sat suppresses fat signal allowing for better suppresses fat signal allowing for better

visualization of contrast uptake visualization of contrast uptake

Because our patient presented with monocular vision loss, dyschromatopsia, and eye pain, an MRI was performed to evaluate the optic nerve.

Our Patient: Coronal STIR ImagesOur Patient: Coronal STIR Images

PACS, Mt. Auburn Hospital

Sequential STIR images show:Abnormal T2 hyperintensity within the right optic nerveEnlarged right optic nerve

Coronal STIR images

Our Patient: Axial T1 FSE with ContrastOur Patient: Axial T1 FSE with Contrast

Following contrast Following contrast administration, there is administration, there is enhancement of the right optic enhancement of the right optic nerve.nerve.

Diagnosis:Diagnosis:The clinical presentation and The clinical presentation and MRI findings are compatible MRI findings are compatible with the diagnosis of right with the diagnosis of right acute optic neuritisacute optic neuritis..


Axial T1 FSE with Contrast

Optic Neuritis: The BasicsOptic Neuritis: The Basics

Acute inflammatory demyelinating disorder of the optic Acute inflammatory demyelinating disorder of the optic nerve.nerve.

Typically presents with monocular vision loss, Typically presents with monocular vision loss, dyschromatopsia (loss of color vision), and eye pain.dyschromatopsia (loss of color vision), and eye pain.

More common in women (twoMore common in women (two--thirds) and typically thirds) and typically affects younger patients between the ages of 20 and 40.affects younger patients between the ages of 20 and 40.

Diagnosis can usually be made based on clinical features Diagnosis can usually be made based on clinical features but MRI of the orbits (STIR, gadolinium contrastbut MRI of the orbits (STIR, gadolinium contrast-- enhanced) provides confirmation.enhanced) provides confirmation.

Optic Neuritis: Prognosis Optic Neuritis: Prognosis

Vision typically improves spontaneously over a period of Vision typically improves spontaneously over a period of weeks to months and 90% of patients have at least weeks to months and 90% of patients have at least 20/40 vision after one year.20/40 vision after one year.

Longer lesions in the optic nerve are associated with Longer lesions in the optic nerve are associated with poorer visual recovery.poorer visual recovery.

The Optic Neuritis Treatment Trial (ONTT) found that The Optic Neuritis Treatment Trial (ONTT) found that there was recurrence in 35% of patients at 10 years and there was recurrence in 35% of patients at 10 years and that patients with recurrent optic neuritis had a greater that patients with recurrent optic neuritis had a greater risk of developing MS.risk of developing MS. Optic neuritis is the presenting symptom in 15Optic neuritis is the presenting symptom in 15--20% of patients 20% of patients

diagnosed with MSdiagnosed with MS Optic neuritis occurs in 50% of patients with MS during the Optic neuritis occurs in 50% of patients with MS during the

course of their illness course of their illness

The Optic Neuritis Study Group. Multiple Sclerosis Risk After Optic Neuritis: Final Optic Neuritis Treatment Trial Follow-up. Arch Neurol 2008;65:727-732.

Life-table analysis of multiple sclerosis (MS) according to the number of lesions on baseline

brain magnetic resonance imaging (MRI)

Optic Neuritis: Risk of MSOptic Neuritis: Risk of MS

In ON, MRI is used to assess In ON, MRI is used to assess the brain for asymptomatic the brain for asymptomatic lesions.lesions.

The risk of developing MS is The risk of developing MS is strongly related to the strongly related to the presence of demyelinating presence of demyelinating lesions on MRI at the time of lesions on MRI at the time of optic neuritis onset.optic neuritis onset.

In the ONTT, the 15In the ONTT, the 15--year risk year risk of developing MS was:of developing MS was: 72% with one ore more lesion 72% with one ore more lesion

presentpresent 25% when no lesions were 25% when no lesions were

presentpresent

MS Lesions on MRIMS Lesions on MRI

MS is an autoimmune inflammatory demyelinating disease MS is an autoimmune inflammatory demyelinating disease of the CNS characterized by attacks and lesions of the CNS characterized by attacks and lesions disseminated in space and time.disseminated in space and time.

MRI is the test of choice for evaluating MS lesions.MRI is the test of choice for evaluating MS lesions. Lesions: typically ovoid in shape and found in the periventriculLesions: typically ovoid in shape and found in the periventricular ar

region, corpus callosum, subcortical white matter, brainstem andregion, corpus callosum, subcortical white matter, brainstem and optic nerves.optic nerves.

T1: T1:

Most lesions are isointense.Most lesions are isointense.

Some are hypointense (Some are hypointense (Black HolesBlack Holes may represent axonal loss and may represent axonal loss and may correlate with disease progression).may correlate with disease progression).

T2 and Proton Density: lesions are hyperintense.T2 and Proton Density: lesions are hyperintense. GadoliniumGadolinium--enhanced: active lesions enhance due to disruption of enhanced: active lesions enhance due to disruption of

the bloodthe blood--brain barrier.brain barrier. Fluid Attenuated Inversion Recovery (FLAIR): suppression of the Fluid Attenuated Inversion Recovery (FLAIR): suppression of the

CSF signal allows for better detection of lesions along the corpCSF signal allows for better detection of lesions along the corpus us callosum.callosum.

Because of the increased risk of MS associated with optic neuritis, our patient underwent an MRI of the brain to look for demyelinating lesions.

Our Patient: Axial FLAIR MRIOur Patient: Axial FLAIR MRI

A series of images show no A series of images show no foci of abnormal signal within foci of abnormal signal within the brain parenchyma. the brain parenchyma.

The corpus callosum appears The corpus callosum appears normal. normal.

Following contrast Following contrast administration, there is no administration, there is no abnormal enhancement.abnormal enhancement.


Axial FLAIR MRI

Our patient had no findings indicative of MS on MRI. The following companion patient illustrates the characteristic appearance of MS lesions on MRI.

Companion Patient #1: MS Companion Patient #1: MS Lesions on Axial T2Lesions on Axial T2--weighted MRIweighted MRI

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There are multiple T2 hyperintensities representing characteristic MS lesions.

Axial T2-weighted MRI

Companion Patient #1: Multiple MS Companion Patient #1: Multiple MS Lesions on Lesions on SagittalSagittal FLAIR MRIFLAIR MRI

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These images illustrate Dawsons Fingers, characteristic MS lesions radiating outward from the corpus callosum.

Sagittal FLAIR MRI

Back to our Patient: Treatment and Follow-up

Recap: J.H. was diagnosed with acute optic neuritis of the right eye based on clinical and radiologic findings. MRI of her brain showed no lesions suggestive of MS.

Must now decide on an appropriate treatment option:1. No treatment: without treatment, vision typically begins to improve over a

period of weeks and continues to improve over a period of months.2. Corticosteroids: according to the ONTT, IV methylprednisolone followed by

oral prednisone accelerates the recovery of visual function but does not impact long-term visual function.

3. Plasma Exchange: for patients with severe ON who are unresponsive to corticosteroid treatment.

4. Chronic Immunomodulatory therapy: in patients with a high risk of developing MS (as evidenced by demyelinating lesions on MRI), treatment with interferon beta may delay the development of clinical MS.

J.H. received two days of IV methylprednisolone but stopped treatment prematurely due to severe flushing. She noted very slight improvement in vision and decreased pain after treatment.

Our Patient: Second PresentationOur Patient: Second Presentation

J.H., a 29 yearJ.H., a 29 year--old woman with a history of optic neuritis in the right old woman with a history of optic neuritis in the right eye 2 months ago, now presents with acute vision loss and pain ieye 2 months ago, now presents with acute vision loss and pain in n the left eye.the left eye. Vision loss and Vision loss and fuzzinessfuzziness in the lower half of left eye visual fields.in the lower half of left eye visual fields. Pain in left eye with movement in all directions.Pain in left eye with movement in all directions. Decreased color visionDecreased color vision

J.H. still has visual loss in the right eye but no other new symJ.H. still has visual loss in the right eye but no other new symptoms.ptoms.

Neurologic exam: Neurologic exam: Visual acuity: OD 20/200, OS 20/25 when viewing through left supVisual acuity: OD 20/200, OS 20/25 when viewing through left superior erior

quadrant only.quadrant only. FunduscopicFunduscopic exam: right optic disc pallor and slight obscuration of disc exam: right optic disc pallor and slight obscuration of disc

margins, left optic disc appears normal.margins, left optic disc appears normal. Visual field testing: right central Visual field testing: right central scotomascotoma, left inferior altitudinal , left inferior altitudinal

scotomascotoma.. Relative Afferent Relative Afferent PupillaryPupillary Defect (RAPD) present on the right.Defect (RAPD) present on the right.

Our patient presented a second time with monocular vision loss, dyschromatopsia, and eye pain now in the left eye. An MRI was performed to evaluate the optic nerves.

Our Patient: Coronal STIR ImagesOur Patient: Coronal STIR ImagesFirst Presentation: 3/23/09 Second Presentation: 5/31/09


There is now abnormal increased T2 signal and enlargement of both the right and left optic nerves.

Coronal STIR Images

Our Patient: Coronal T1 FSE with ContrastOur Patient: Coronal T1 FSE with ContrastFirst Presentation: 3/23/09 Second Presentation: 5/31/09


There is enhancement of the right optic nerve, right aspect of the optic chiasm (not seen on this image), and left optic nerve, demonstrating progression from the prior imaging studies.

Findings are compatible with a diagnosis of bilateral optic neuritis.

Coronal T1 FSE with Contrast

Bilateral Optic Neuritis: PrognosisBilateral Optic Neuritis: Prognosis

OpticOptic neuritis may represent an isolated event or neuritis may represent an isolated event or it may precede the onset of a it may precede the onset of a demyelinatingdemyelinating syndrome such as MS or syndrome such as MS or neuromyelitisneuromyelitis opticaoptica (NMO).(NMO).

Bilateral optic neuritis is relatively uncommon but Bilateral optic neuritis is relatively uncommon but occurs more commonly in children younger than occurs more commonly in children younger than 1212--15 years old.15 years old.

Rapid succession of optic neuritis episodes, Rapid succession of optic neuritis episodes, especially in patients with normal brain MRI, is especially in patients with normal brain MRI, is predictive of NMO conversion.predictive of NMO conversion.

Neuromyelitis OpticaNeuromyelitis Optica

NMO is an inflammatory, demyelinating syndrome of the CNS NMO is an inflammatory, demyelinating syndrome of the CNS characterized by severe attacks of optic neuritis and myelitis, characterized by severe attacks of optic neuritis and myelitis, which, which, unlike MS, commonly spare the brain in the early stages.unlike MS, commonly spare the brain in the early stages.

It is up to 9 times more common in women than men.It is up to 9 times more common in women than men.

The median age of onset is 39.The median age of onset is 39.

Diagnostic Criteria:Diagnostic Criteria: Optic neuritisOptic neuritis Acute transverse myelitisAcute transverse myelitis At least 2 out of 3 supportive criteria:At least 2 out of 3 supportive criteria:

Contiguous spinal cord lesion extending over 3 vertebral segmentContiguous spinal cord lesion extending over 3 vertebral segments on MRIs on MRI

Brain MRI findings not satisfying diagnostic criteria for MSBrain MRI findings not satisfying diagnostic criteria for MS

NMONMO--IgG seropositive statusIgG seropositive status

Neuromyelitis Optica on MRINeuromyelitis Optica on MRI

Brain MRI at onset: typically normal or may show nonBrain MRI at onset: typically normal or may show non--specific specific whitewhite--matter lesions that do not meet criteria for MS.matter lesions that do not meet criteria for MS.

Brain MRI (later): 10% of patients have whiteBrain MRI (later): 10% of patients have white--matter lesions matter lesions in the in the periependymalperiependymal regions (enriched in regions (enriched in aquaporinaquaporin 4), 4), including the hypothalamus and including the hypothalamus and periaqueductalperiaqueductal brainstem.brainstem.

Spinal Cord MRI: lesions are longitudinally extensive and span Spinal Cord MRI: lesions are longitudinally extensive and span 3 or more contiguous vertebral segments.3 or more contiguous vertebral segments.

Because of the association between bilateral optic neuritis and NMO, an MRI of the cervical and thoracic spine was performed to look for transverse myelitis.

Our Patient: Our Patient: SagittalSagittal CC--spine Proton spine Proton Density Weighted ImageDensity Weighted Image

There is questionable subtle There is questionable subtle increased signal of the cord at the increased signal of the cord at the level of C5level of C5--C6, though this is not C6, though this is not definite.definite.

Following gadolinium Following gadolinium administration, there is no administration, there is no abnormal enhancement of the abnormal enhancement of the cervical cord. cervical cord.

MRI of the thoracic cord is normal. MRI of the thoracic cord is normal.


Sagittal Proton Density Weighted Image

There was no evidence of transverse myelitis in our patient. The following companion patient with diagnosed NMO illustrates the characteristic appearance of longitudinally extensive transverse myelitis on MRI.

Companion Patient #2: Transverse Companion Patient #2: Transverse MyelitisMyelitis on on SagittalSagittal T2T2--weighted MRIweighted MRI

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Patient with diagnosed NMO presents with a flare.

Abnormal T2 hyperintensity throughout the spinal cord from C1-2 through T12-L1.

Associated spinal cord swelling from C6-T10.

Findings are consistent with an aggressive demyelinating process.

Sagittal T2-weighted MRI

Back to Our Patient: Recap of FindingsBack to Our Patient: Recap of Findings

Presentation: Presentation: J.H. initially presented with acute vision loss and pain with J.H. initially presented with acute vision loss and pain with

movement in the right eye and was diagnosed with optic movement in the right eye and was diagnosed with optic neuritis. neuritis.

Two months later, she presented with similar symptoms in the Two months later, she presented with similar symptoms in the left eye and was diagnosed with bilateral optic neuritis.left eye and was diagnosed with bilateral optic neuritis.

MRI:MRI: Bilateral optic neuritisBilateral optic neuritis No brain lesions suggesting MSNo brain lesions suggesting MS No longitudinally extensive transverse No longitudinally extensive transverse myelitismyelitis

Our Patient: Other Notable Findings Our Patient: Other Notable Findings

Serologic Work Up:Serologic Work Up: NMONMO--IgG Serum: Negative*IgG Serum: Negative*

*Suspicious, but not diagnostic. Recommend follow*Suspicious, but not diagnostic. Recommend follow--up in 6 months if NMO up in 6 months if NMO spectrum disorder is suspected.spectrum disorder is suspected.

76% sensitive and 94% specific for clinical diagnosis of NMO76% sensitive and 94% specific for clinical diagnosis of NMO HSV, HIV, Hep B surface AG, and Lyme: NegativeHSV, HIV, Hep B surface AG, and Lyme: Negative

Rheumatologic Work Up:Rheumatologic Work Up: Positive ANA, Positive AntiPositive ANA, Positive Anti--Ro/SSA, Positive RF, low C4 Ro/SSA, Positive RF, low C4

These lab features can be seen in patients with SLE or SjogrenThese lab features can be seen in patients with SLE or Sjogrens syndromes syndrome

Optic neuritis can be seen in SLE and SjogrenOptic neuritis can be seen in SLE and Sjogrens syndrome s syndrome

The patient has no other manifestations of these diseasesThe patient has no other manifestations of these diseases

CSF Work Up:CSF Work Up: NMONMO--IgG CSF: Negative. IgG CSF: Negative.

CSF test recommended when NMO is strongly suspected and NMOCSF test recommended when NMO is strongly suspected and NMO--IgG is IgG is negative.negative.

No oligoclonal bands present. No oligoclonal bands present.

Found in 85Found in 85--95% of patients with clinically definite MS95% of patients with clinically definite MS

Our Patient: Treatment and FollowOur Patient: Treatment and Follow--upup

Treatment: Treatment: Completed a 9Completed a 9--day course of IV methylprednisolone with no significant day course of IV methylprednisolone with no significant

improvement of symptoms.improvement of symptoms. After failing to respond to corticosteroids, she completed a 5After failing to respond to corticosteroids, she completed a 5--day course of day course of

plasmapheresis.plasmapheresis.

J.H. was released on oral prednisone and azathioprine.J.H. was released on oral prednisone and azathioprine.

One month followOne month follow--up with outpatient neurologist: up with outpatient neurologist: Neurologic exam was unchanged. J.H. still has bilateral vision Neurologic exam was unchanged. J.H. still has bilateral vision loss and loss and

continues to have pain in the left eye with movement.continues to have pain in the left eye with movement. Assessment: 2 episodes of optic neuritis postAssessment: 2 episodes of optic neuritis post--partum, possibly NMO or SLE.partum, possibly NMO or SLE. Plan: Plan:

1.1. begin tapering prednisone.begin tapering prednisone.2.2. increase azathioprine dose.increase azathioprine dose.3.3. followfollow--up in one month.up in one month.

Key PointsKey Points

Optic Neuritis: an acute inflammatory demyelinating Optic Neuritis: an acute inflammatory demyelinating disorder of the optic nerve that typically presents with disorder of the optic nerve that typically presents with monocular vision loss, dyschromatopsia, and eye pain.monocular vision loss, dyschromatopsia, and eye pain.

MS: an autoimmune inflammatory demyelinating disease MS: an autoimmune inflammatory demyelinating disease of the CNS characterized by attacks and lesions of the CNS characterized by attacks and lesions disseminated in space and time.disseminated in space and time.

NMO: a severe, demyelinating disease of the CNS that NMO: a severe, demyelinating disease of the CNS that preferentially affects the optic nerves and spinal cord.preferentially affects the optic nerves and spinal cord.

MRI is the best imaging modality for detecting lesions MRI is the best imaging modality for detecting lesions associated with these inflammatory, demyelinating associated with these inflammatory, demyelinating conditions.conditions.

AcknowledgmentsAcknowledgments

Dr. Gillian LiebermanDr. Gillian Lieberman

Dr. Gul MoonisDr. Gul Moonis

Dr. Rich Dr. Rich RanaRana

Dr. Iva Dr. Iva PetkovskaPetkovska

Maria Levantakis Maria Levantakis

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MRI Imaging of Neuromyelitis OpticaOur Patient: Initial PresentationCauses of Optic NeuropathyAnatomy of the OrbitMenu of Tests:Imaging the Optic NerveImaging the Optic Nerve: MRISlide Number 7Our Patient: Coronal STIR ImagesOur Patient: Axial T1 FSE with ContrastOptic Neuritis: The BasicsOptic Neuritis: Prognosis Optic Neuritis: Risk of MSMS Lesions on MRISlide Number 14Our Patient: Axial FLAIR MRISlide Number 16Companion Patient #1: MS Lesions on Axial T2-weighted MRICompanion Patient #1: Multiple MS Lesions on Sagittal FLAIR MRIBack to our Patient: Treatment and Follow-upOur Patient: Second PresentationSlide Number 21Our Patient: Coronal STIR ImagesOur Patient: Coronal T1 FSE with ContrastBilateral Optic Neuritis: PrognosisNeuromyelitis OpticaNeuromyelitis Optica on MRISlide Number 27Our Patient: Sagittal C-spine Proton Density Weighted ImageSlide Number 29Companion Patient #2: Transverse Myelitis on Sagittal T2-weighted MRIBack to Our Patient: Recap of FindingsOur Patient: Other Notable Findings Our Patient: Treatment and Follow-upKey PointsAcknowledgmentsReferences

Documents

MRI Imaging of Neuromyelitis Neuromyelitis Optica