1. Multiple Sclerosis Jeffrey M. Gelfand, MD
UCSF Multiple Sclerosis Center
SFGH Neuroimmunology Clinic
UCSF and SFGH Departments of Neurology

2. Goals To review the fundamentals of neurological localization
To learn when to suspect multiple sclerosis as the diagnosis in your patient
To discuss ways to optimize care for patients with known multiple sclerosis

3. Case #1 He comes into Urgent Care… What else do you want to know?
26 yo man, previously healthy, woke up with numbness in his feet – a “pins and needles” sensation. He ran on the treadmill to “improve my circulation” but his symptoms persisted. The next day, the numbness was up to knee level, and the day after that, it was up to his abdomen.
PMH/PSH: None
Meds: None
Social History: Lives in SF with girlfriend. Works for car rental agency (on his feet most of the day). Never smoked. Rare ETOH. No drugs. No exposures. Travelled briefly to Mexican resort a few months prior for holiday.
Family History: Unremarkable; Mexican and Eastern European ancestry
Acute or not acute – this is clearly acute. Motor involvement, urinary retention, pain, fever, cancer history, recent vaccines? TURNS OUT 5 MONTHS EARLIER HAD EPISODE OF RIGHT THIGH NUMBNESS LASTING 1 MONTH WHICH RESOLVED
He comes into Urgent Care…
What else do you want to know?

4. Case #1 -- continued Where in the nervous system is his problem?
Over the next few days, the numbness ascended to his lower chest. His legs became heavy. It was harder to walk.
On general exam, vitals were normal. Unremarkable.
Neuro Exam: Normal tone in the arms, increased tone in the legs. Mild weakness in the left hip flexor (ileopsoas). Reflexes brisk in both the arms and legs. Decreased sensation to light touch, temperature and vibration to above the waist line.
Where in the nervous system is his problem?
What do you want to do to evaluate it?

5. Neurological Localization of Weakness
Upper Motor Neuron (CNS)
Lower Motor Neuron (PNS)
Pattern of Weakness
“Pyramidal”
Variable
Tone
Increased (Spasticity)
Decreased (Flaccid)
Reflexes
Increased
Decreased, Absent or Normal
Fine Motor
Slowed Alternating Movements
(Finger tap/Foot Tap)
Functional impairment is primarily due to weakness
Other Findings on Exam
Babinski Sign
Atrophy, Fasciculations
Modified from Ann Poncelet, MD, UCSF Neurology

6. Case #1 -- continued Where in the nervous system is his problem?
Over the next few days, the numbness ascended to his lower chest. His legs became heavy. It was harder to walk.
On general exam, vitals were normal. Unremarkable.
Neuro Exam: Normal tone in the arms, increased tone in the legs. Mild weakness in the left hip flexor (ileopsoas). Reflexes brisk in both the arms and legs. Decreased sensation to light touch, temperature and vibration to T6.
Where in the nervous system is his problem?
What do you want to do to evaluate it?

7. Most Likely Differential Diagnoses:
Case #1 -- Continued
Localization:
Spinal Cord (T6 or above, including C-spine)
Most Likely Differential Diagnoses:
Disc herniation, epidural abscess or hematoma, cord inflammation (myelitis)

8. Clinical Pearls: Spinal Cord MRI
MRI is superior to all other imaging modalities for spinal cord pathology – acute symptoms should be imaged acutely!
The lesion can be at any level at or above the clinical localization – (i.e. cervical cord lesions can spare the arms)
A “Lumbar Spinal” MRI refers to the vertebrae, not the cord level, and MISSES the lower spinal segments.
A thoracic spine MRI is needed to image the lower cord!

9. Case #1 -- Continued T2 Sagittal C-Spine T2 Axial C-Spine
T1 Post-Gadolinium

10. Coronal FLAIR

11. Case #1
LP revealed 3 WBC, 29 RBC, normal glucose and protein. Normal IgG index. Oligoclonal bands were unfortunately not sent.
Rule out labs for other causes of MS mimics were negative, including (Chest CT for sarcoidosis, Lyme, B12, ANA, SSA/B, APLAS antibodies).
Diagnosis: Partial Myelitis from Relapsing-Remitting MS (given episode of thigh numbness in the past)
He initiated treatment with IV pulse steroids then interferon beta-1a. Over the next 2 years, he suffered 2 recurrent episodes of myelitis.

12. Multiple Sclerosis
An disorder of the CENTRAL NERVOUS SYSTEM characterized by inflammation, demyelination and secondary nerve loss
Second most common cause of disability in working age adults (the first is trauma)
3x more common in women than men
More common in whites than other racial groups living in the same environment
Complex genetic inheritance of immune-active genes (especially HLA) accounts for about 30% of the variance; environmental factors (sunlight, EBV, smoking, etc.) probably account for the rest

13. Curious Features of MS Epidemiology
-MS prevalence increases with latitude
-MS risk increases with reduced UV exposure
-MS is less common in people born in early winter
Relapses also occur more often in late spring than autumn in the Northern HemisphereAuer DP, et. al. Ann Neurology (2):276-7.
Europeans who migrated to South African before age 15 assumed a lower MS risk (equivalent to that of European South Africans born in South Africa)
Dean, G and Kurtzke, JF. BMJ :
-MS relapses are more frequent in late spring than autumn (in the Northern Hemisphere) 13

14. Whites Blacks Munger, K. L. et al. JAMA 2006
0.57, 0.57, 0.74, and 0.38 (P=.02 for trend across quintiles).
Munger, K. L. et al. JAMA 2006 14

15. Clinical Features of MS
Lesions Disseminated in Space and Time (lasting more than 24 hours, 1 month apart, should have typical MRI changes, must have excluded other causes)
Relapsing-Remitting or Progressive Disease Course
Typical symptoms/syndromes include optic neuritis, myelitis, weakness, numbness, incoordination, double vision, urinary problems, fatigue, concentration/memory problems, depression
Heat-sensitivity and Lhermitte’s symptom are common

16. Classic MRI Features
Sagittal FLAIR
T1 Post-Contrast
Axial FLAIR

17. Classic MRI Features

18. Acute Treatment of Relapses
New neurological symptoms in an MS patient
Evaluate – Is MS relapse the most likely diagnosis? – Not every symptom is due to MS!
Check a Urinalysis/Culture – Is this a Pseudo-Relapse?
Is there functional impairment from this new deficit?
If yes, treat with corticosteroids (usually IV)
If no, then symptomatic management may be appropriate

19. Treatment to Prevent Relapses
Treatment with disease-modifying therapy has been demonstrated in multiple randomized controlled trials to reduce relapse risk and delay disability
Standard FDA-approved options include interferon-beta formulations, glutiramer acetate, natalizumab and fingolimod

20. Comprehensive Care for MS Patients
Disease-Modifying Therapy (monitoring)
2) Symptomatic considerations
-- Depression
-- Pain relief
-- Fatigue
-- Concentration/Attention/Memory
-- Urinary/Bowel/Sexual Dysfunction
-- PT/OT
-- Adaptive Devices
-- Reproductive Issues
-- Social Services/Support

21. What do you recommend as the next step?
Clinical Case #2
51 yo man with MS comes to clinic complaining of worsening gait for the past year, now using a cane.
First MS symptom 10 years prior when he developed leg numbness x 2 months, which remitted. Has had 3 relapses since characterized (respectively) by facial numbness, leg weakness/numbness and visual field cut.
Tried interferon beta-1a but had severe flu-like side effects/depression. Briefly tried glutiramer acetate (daily injection) but severely needle-phobic, not sustainable.
Brain MRIs over the past year showed presence of new lesions, some of which evolved over time and appeared typical of demyelination.
What do you recommend as the next step?

22. Clinical Case #2
Axial FLAIR

23. Clinical Case #2
PEARLS
1) Patients are entitled to as many diagnoses as they please – this is especially true in MS.
2) No MS patient should be allowed to progress to a cane or wheelchair without looking for treatable causes
Degenerative Spondylosis causing multilevel canal stenosis

24. Goals To review the fundamentals of neurological localization
To learn when to suspect multiple sclerosis as the diagnosis in your patient
To discuss how to optimize care for patients with known multiple sclerosis

25. Multiple Sclerosis Jeffrey M. Gelfand, MD
UCSF Multiple Sclerosis Center
SFGH Neuroimmunology Clinic
UCSF and SFGH Departments of Neurology