1. Palmetto Health Richland August 2008
35 yo AAF presents with confusion, agnosia, apraxia, right-sided lower extremity paresis
Symptoms first noticed 2 hours ago
CT scan- no blood
MRI- single hyperintense lesion in the left periventricular white matter
Started IV steroids, ran a panel of CSF & blood studies
3 days later- Symptoms resolved
Diagnosed with Multiple Sclerosis

2. Jessica Floyd, M4
The Imaging of Multiple Sclerosis * Utility of MRI * Differential of White Matter Lesions * Future direction of neuroradiology

3. What is Multiple Sclerosis?
Chronic Inflammatory demyelinating disease of the CNS
2nd-3rd decade of life (“belongs to the climax of life”)
2:1 Female predominance
,000 people with MS in the US
Cyclical inflammatory reactions followed by remission of symptoms and variable recovery
Relapsing-Remitting- 80%
Primary Progressive- 20%; closer incidence M:F
Secondary Progressive
There is a whole host of interesting topics to discuss with MS but since this is focused mainly on the imaging of MS, we will save that for another time.

4. Charcot’s description
First described by Charcot in 1835
Patient history, physical exam, autopsy
Salpetriere (1865)  to the United States
Blood vessel at the center of each lesion
Preserved axis cyllinder
Atrophy of the medullary sheath
Types:
Cephalic
Spinal
Mixed: cerebrospinal

5. Broad Symptom Complex Sensory disturbances Unilateral optic neuritis
Diplopia- Internuclear opthalmoplegia
Nystagmus
Lhermitte’s sign
Limb weakness
Clumsiness
Gait ataxia
Neurogenic bladder
Bowel symptoms

6. Symptoms Fatigue Post Partum worsening of Symptoms ~ 4wk
Worse in the afternoon
Physiologic increases in temperature
Post Partum worsening of Symptoms ~ 4wk
Uhthoff’s symptom- hot shower, hot bath
Pseudoexacerbations with fever

7. Symptoms Highly suggestive of MS: Less common:
Paroxysmal pain, paresthesias
Trigeminal neuralgia
Episodic clumsiness, nysarthria
Tonic limb posturing
Less common:
Prominent cortical signs
Aphasia, apraxia, recurrent seizures, visual field loss, early dementia
Extrapyramidal phenomena
Chorea, rigidity

8. WHAT DOES IT LOOK LIKE?

9. Brain Lesions Most sensitive modality is MRI
Sensitive to inflammation
Sensitive to demyelination
CT is a poor tool unless very severe destruction
Callosal atrophy
Whole brain atrophy

10. T2 Lesions
Inflammation (water) & Demyelination (loss of fat)  Hyperintensities on T2 weighted images
Confirm with FLAIR images
Round, Ovoid
Vary in size. Few mm Few cm
Periventricular region, corpus callosum
Perivascular distribution, penetrating venules
Dawson’s fingers
Juxtacortical Lesions, U-fibers

11. T2 Lesions Temporal Lobe Brainstem- peripherally
Deep Gray Matter- BG, Thalamus (LC)
Cerebellum
Spinal Cord
Recurrent Lesions in Same Area CONFLUENT lesions
MC anterior & posterior to lateral ventricle
Vasogenic edema = “fuzzy extension” of T2 signal
LARGE DIFFERENTIAL FOR T2 Hyperintensities
These will help with differentiating from vascular pathology

12. T2 Lesions- FLAIR Red arrow- involvement of the temporal lobe
Green arrow- juxtacortical lesions, touching the cortex
Blue arrow- involvement of the corpus callosum
Periventricular lesions- touching the ventricles

13. Dawson’s Fingers- Sagital FLAIR

14. T1 Holes SEVERE Tissue Injury  T1 dark signals
Rarely seen in the spinal cord or post fossa
Stronger correlation with demyelination & axonal loss than T2 hyperintensities
Evolution of enhancing lesions  T1 Holes associated with more progressive disease

15. T2 lesions & T1 Holes
Fig 3 = Typical ovoid periventricular lesions of ms in 31 yo man with 10 yr h/o RR neurologic Sx
A : First echo T2 MR sequence showing several ovoid lesions with T2 prolongation, with long axes perpendicular to ventricular walls
B: T1-weighted MRI shows that T1 is also prolonged within lesions

16. Gadolinium-Enhancing Lesions
Indicates breakdown of the blood-brain barrier
Very active inflammation
Pattern of enhancement
Homogenous
Ring reactivation of an old lesion
Heterogeneous
Enhancement duration varies- days, weeks
5% pts have >3 months of single lesion enhancement

18. Spinal Cord Lesions Round, Ovoid on T2
Limited to 1-2 spinal cord segments
80% involve half of cord cross sectional area
Ddx- ITM, Devic’s Dz
Typically unilateral
Inflammatory edema temporary cord expansion
Ddx- Tumor (bx)
Gadolinum enhancment with active BBBB
Post mortem path studies show greater demyelination than assumed with conventional t2 imaging
But can be central or bilateral
Not the case with Brain demyelination- not seen outside of T2 lesion

19. 35 yo female- acute onset Quadriparesis
Figure 5 = MS involving upper spinal cord in 35 yo woman with acute onset of quadriparesis.
T2 weighted MRI shows a large area of demyelination in upper cervical spinal cord and cervicomedullary junction

20. Spinal Lesions- Gad-enhancement
Sagittal (A) T2 weighted and (B) post-gad T1 weightedimages froma pt with MS showing a discrete enhancing T2 lesion; and a nonenhancing lesion seen in the medulla (arrow)

21. Brain Atrophy Significant Clinical Implications
Correlates with clinical disability
Predictive of later progressive disability
Many standard therapies slow progression of atrophy over time

22. Callosal Atrophy
Figure 4 = Callosal involvement with MS in 48 yo woman with clinically definite MS for 20 years.
A: T1 weighted midline sagittal MRI shows diffuse callosal atrophy
B: Inner Callosal hyperintensity, and multiple confluent periventricular lesions, are shown on first echo of T2-weighted series

23. Diagnosis
Ensuring MS is of high suspicion, consider prevalence and a priori probability

25. How suspicious are you?
Imaging is only one part of the story, clinical picture
Incidental Finding versus Manifesting Clinically
Normal Aging or Virchow Robin Spaces
Vascular disease
Infarction
Multi-infarct Dementia
Hypertensive encephalopathy
Sarcoidosis- ACE level, pulmonary Sx, CXR
SLE- discoid/malar rash, other organ involvment
Lyme Disease- CN7 palsy, rash, influenza-like illness
HIV- test, immunocompromised
Progressive Multifocal Leukoencephalopathy- immunocompromised
Largest differential concerns Vascular versus MS

26. Normal Aging & Fazeka’s
Can have caps and bands around the ventricles
I: small punctate lesions in the deep white matter- considered normal in aging
II: larger WMLs that are beginning to become confluent- abnormal in pts <75 yo
III: abnormal in any age group; probably due to microangiopathy and seen more frequently in patients with vascular risk factors.

27. Virchow Robin Spaces
CSF spaces around penetrating leptomeningeal vessels
Typically located in the BG, anterior commissure and in the middle of the brainstem; they follow the signal intensity of CSF; enlarge with age and HTN secondary to atrophy of surrounding structures

28. Vascular vs Multiple Sclerosis

29. Vascular disease vs Multiple Sclerosis
66 yo Male
T2 Hyperintensities
None being Ovoid
Few Periventricular Lesions
No Juxtacortical lesions
Figure 6 = Multiple Ischemic WM Lesions in 66 yo man with Sx of cerebellar infarction. First echo of T2 weighted MR sequence shows hyperintensities similar to those of demyelinating dz, but none are ovoid and few periventricular lesions are present

30. Vascular vs. Multiple Sclerosis
Juxtacortical lesions- specific for MS
This is not subcortical.
In Small vessel dz, these juxtacortical U-fibers are not involved, there will be a dark band between the WML and the cortex which is also bright

31. Criteria for Diagnosis of MS
Since MRI revolutionized the diagnosis of MS, needed specific criteria
Crux of the Dx is demonstrating attacks of neurologic dysfunction are separated in space and time
Clinical criteria* pt hx, PE findings,
Laboratory Criteria* oligoclonal bands, IgG index
MRI * 2001 McDonald Criteria, 2005 revised

34. Diagnostic Criteria
Fig 1 = typical cerebral lesions of MS in 64 yo woman with sudden onset of diplopia & ataxia; Multiple periventricular lesions of MS, with lumpy-bumpy contour, on first echo of T2 weighted MR sequence
Fig 2 = MS lesions in brainstem of 38 yo man with bilateral weakness & sensory Sx in LE. T2 weighted MRI shows lesion of MS in R cerebral peduncle

35. Dissemination in TIME- 3 months
Re-examined 3 months after the first clinical attack.
Multiple Enhancing lesions, many touch the cortex & must be located in the U-fibers
These enhanced lesions are all new lesions, since Gad enhancement is only visible for about 1 month, so this finding is proof of dissemination in time

36. One episode, treat or not to treat?
Cannot diagnose MS on MRI alone- need the clinical exam & history
However, MRI can now show us what even a vigorous clinical exam cannot
Revolutionizing treatment treat earlier
Mild cognitive deficits discovered earlier

37. 42 yo woman with MS, no Sx
Figure 7 = Multiple sclerosis in 42 yo woman with clinically definite MS but no acute Sx
A: T1 weighted MRI after administration of gadolinum shows several enhancing ovoid lesions in cerebral white matter bilaterally. Contrast enhancement defines areas of acute inflammation; indicating areas of BBB breakdown
B: First echo of T2 weighted series at same level as A shows many more white matter lesions; primarily periventricular in distribution.

38. Coming in the future… MR Spectroscopy- N-acetyl aspartate, Lactate
Diffusion Tensor Imaging
Able to pick up on lesions not yet detectable on MRI
Ability to give you information on precisely how damaged the lesion is compared to other lesions

39. Diffusion Tensor Imaging
Artist’s depiction of water diffusion. (A) w/in fiber tracts where axons and myelin orient diffusion longitudinally, water diffusion oriented along the fiber tract.
(B) In areas of demyelination and axonal injury, water diffusion is greater in overall amount (increased mean diffusivity), and also less ELONGATED (decreased fractional anisotropy). This indicates the diff vectors.

40. Diffusion Tensor Imaging
3-D water diffusion
Mean Diffusivity- overall diffusion
Fractional anisotropy- amount of elongatedness of diffusion
Colorized primary eigenvector maps- illustrate different directions of the primary fiber tract
RED = L-R
GREEN = Up-Down
BLUE = In-Out of page
Diffusion tensor images from a patient with MS. (A) Mean diffusivity shows the overall amount of diffusion. (B) fractional anisotropy shows the amount of anisotropy, or “elongatedness” of diffusion; and © colorized primary eigenvector maps illustrate different directions of the primary eigenvector, or fiber tract. Red is L-R, Green is Up-Down; Blue is In-Out of the page
Arrows indicate the effect of 2 MS lesions; mean diffusivity is increased (BRIGHT); Fraciational anisotropy is decreased (Dark), and the primary fiber direction is disrupted (DARK)

41. Gad- enhancement T1 & T2 Dawson Fingers:
Ovoid lesions perpendicular to the ventricles
Enhancing lesion on T1 with Gad- indicating active breakdown of BBB
Multiple lesions adjacent to the ventricles
Result of inflammation around penetrating venules
Enhancement is present for about one month after the occurrence of a lesion; simultaneous demonstration of enhancing and non-enhancing lesions in MS is the radiological explanation for clinical dissemination in time and space; The edema will regress and finally only the center will remain as a hyperintense lesion on T2

42. Dawson’s fingers – T1 & T2
Sagittal FLAIR image provide best appreciation of Dawson’s fingers in which lesions extend radially from the ventricular surface into the surrounding white matter (fluid-attentuated inversion recovery)
T1 weighted image from typical MS patient/ periventricular lesions dark on T1 but not all are dark
Axial T2 and Flair

43. FLAIR & T-1 black hole
Axial A FLAIR and B T1 weighted images showing a T1 black hole which is mixed hypo-hyperintense on FLAIR

44. Confluent Lesions & Atrophy
SEMINARS
Figure 3 Axial FLAIR images from a 52-year-old patient with multiple sclerosis. The formerly discrete T2 lesions have now
become confluent (arrows). Also, significant atrophy can be appreciated through loss of brain parenchyma as well as
enlargement of the lateral ventricles, peripheral sulci, and third ventricle (arrowhead). FLAIR, fluid-attenuated inversion recovery.

45. Progressive Multifocal Leukoencephalopathy
MRI of the brain from a patient with PML
Axial T2 weighted (left and middle) and post-contrast T1 weighted (right) images show two lesions in the left hemisphere without mass effect and contrast enhancement. The outer border of the lesion follows exactly the cortical lesion.

46. Sarcoidosis MRI of a patient with sarcoidosis.
Post-contrast T1-weighted coronal image of the brain (left) and axial image of the cord (right) show simultaneous enhancement of multiple white-matter lesions, Virchow-Robin spaces (left), and leptomeninges.

47. Acute Disseminated Encephalomyelitis
Axial FLAIR (left column) and post gad T1 (right) images from pt with ADEM. Most lesions demonstrate gad enhancement suggesting similar age to ongoing inflammatory process