Multiple Sclerosis

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

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Case 1

• 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

He comes into Urgent Care What else do you want
to know?
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Case 1 -- continued

• 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?
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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
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Case 1 -- continued

• 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?
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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)

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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!

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Case 1 -- Continued
T2 Sagittal C-Spine
T2 Axial C-Spine
T1 Post-Gadolinium
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Coronal FLAIR
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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.
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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

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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
-MS relapses are more frequent in late spring
than autumn (in the Northern Hemisphere)
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Whites
Blacks
Munger, K. L. et al. JAMA 2006
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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 Lhermittes symptom are
  common

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

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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

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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?
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Clinical Case 2
Axial FLAIR
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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
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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