Multiple_Sclerosis

advertisement

30 yo AAM with past medical history of
asthma, presents to your office with a
complaint of tripping while running. He was
previously able to run 5-10 miles a day. He
ran cross-country in high school and college.
He now can only run a few minutes before he
is tripping. He has almost fallen off the
treadmill.



He denies feeling weak. His upper extremities are
strong. He sometimes has an “electrical shock”
feeling down his back when looking down.
One year ago, he had an episode of blurry vision
with some eye pain. He was diagnosed with
migraines and told to see an ophthomologist. He
never followed up because of his busy class
schedule.
He also noted that sometimes his vision became
blurred when he ran.




Asthma since childhood- controlled with
occasional albuterol
Appendectomy
He worked part-time as a clerk at a
pharmacy. He attended a local college
His father had multiple sclerosis




He had slightly dysarthric speech, but all
other aspects of mental status were intact.
He had an RAPD of the left eye. Visual acuity
in the right eye was 20/20, in the left 20/40.
Optic disc pallor was noted in the left eye.
There was decreased color saturation in the
left eye.
All other cranial nerves were normal.
Normal muscle bulk in all muscles. Increased
tone was noted in the lower extremities.






4/5 right iliopsoas, 4/5 hamstring, 4/5
quadriceps, 4/5 anterior tibialis and gastrocs,
4/5 foot everters. Right foot drop was noted.
Left leg had 4/5 iliopsoas, all others 5/5.
Deep tendon reflexes: 2+ biceps, triceps,
brachioradialis bilaterally. 3+ with crossed
adduction on patellars (left), 3+ patellar on right,
4+ ankle jerk on the left, 3+ ankle on the right
Sensation: Grossly intact
Cerebellar: marked dysmetria left greater than
right
Gait: mild scissoring, foot slapping on the right













ADEM
Lyme Disease
SLE
Sjogren’s Disease
Spastic paraparesis
Behcet Syndrome
B12 Deficiency
Syphilis
Leukodystrophies
Sarcoidosis
CNS vasculitis
Neuromyelitis Optica
Multiple Sclerosis





Most commonly, symptoms appear between
ages 20-40.
Rarely are symptoms seen before age 15 and
after age 60.
Currently there are approximately 250,000 to
350,000 people in the US with MS
2:1 women:men
If move to northern latitudes before age 15,
chance of developing MS over a lifetime
increases




Probably a multi-gene inheritence
Risk of developing MS in US is 1/1000 or
0.1%
Risk of developing MS in first-degree relative
is 1/25 or 4%
Risk of developing MS in identical twins is 1/3
or 30%




Immune-mediated inflammatory disease of
the CNS
Previously thought to be mainly T-cell
mediated (CD-4), now known to involve Bcells, macrophages, cytokines, etc.
May develop in genetically susceptible
triggers (many thoughts: viruses, bacteria,
etc.)
Results in: demyelination, axonal loss, brain
atrophy




















optic neuritis
diplopia
numbness
weakness
gait distubance
ataxia
incoordination
spasticity
tremor
Lhermitte’s sign
Uhtoff
bladder dysfunction
bowel dysfunction
cognitive impairment
sexual dysfunction
speech/swallow deficits
fatigue
depression
delayed processing speed
impaired short term memory


44% will need an assistive device for walking
within 5 years
Relapsing MS leads to progressive MS after 10
years in 50% of cases
Clinical
presentation
Diagnostic criteria needed
•2 or more attacks
•2 or more clinical
lesions
None (additional criteria desirable, but must be
consistent with MS)
•2 or more attacks
•1 objective lesion
Dissemination in space:
•MRI
•+ CSF and 2 lesions
•Further clinical attack involving different site
•1 attack
•2 or more
objective lesions
Dissemination in time:
•MRI
•Or second clinical attack
•1 attack
•Or 1 objective
clinical lesion
Dissemination in space AND time as described by
above
Insidious
neurological
progression
suggestive of MS
(primary
progressive)
•Positive CSF AND
•Dissemination in space demonstrated by:
9 or more T2 lesions
or 2 or more spinal cord lesions
or 4-5 brain and 1 spinal cord lesion
or positive VEP and 4-8 brain lesions
or positive VEP, <4 brain lesions, and 1 sc lesion
AND Dissemination in time demonstrated by
•MRI
•1 year of clinical progression




Neurologic disturbance seen in MS
Subjective report or objective observation
24 hours duration, minimum
Excludes pseudoattacks, paroxsymal events





The first neurological episode that lasts at
least 24 hours
If the MRI is abnormal (1 or more
demyelinating lesion): the chance of
developing MS is 60%
Without an initial abnormal MRI, the chance is
20%.
With an abnormal MRI, several studies
recommend long-term treatment
Without an abnormal MRI, studies
recommend follow up in 3-6 months.



T2 hyperintense lesions represent “footprint”
of prior inflammatory response, representing
demyelination, gliosis, and axonal loss
Gadolinium enhancement is indicative of
acute inflammatory activity within the CNS.
Usually resolves within 4-6 weeks. It leaves
behind a T2 hyperintense lesion.
T1 hypointense lesions (“black holes”)
indicate serious brain injury. Reflect chronic
MS lesion with areas of axonal loss and
gliosis




Treat or remove inciting stimulants
(infections, stress)
Mild: observation, treat symptoms
Moderate: oral prednisone, outpatient PT,
treat symptoms
Severe: IV Solumedrol, intensive PT, treat
symptoms

Interferons
◦ Avonex (Interferon-1a): IM weekly
◦ Betaseron (Interferon-1b): QOD SQ
◦ Rebif (Interferon-1a)
Proposed mechanism of action:
Inhibition of T cell proliferation, Inhibition of
inflammatory cytokines, Activation of regulatory Tcells and cytokines, Downregulation of MHC class II
molecules induced by IFN-g, Reduces antigen
presentation to T-cells, Downregulation of
adhesion molecules




Induction of myelin-specific suppressor cells
Inhibition of proliferation and inflammatory
cytokine production of MBP-specific T cell
lines
Induction of suppressive cytokines and
bystander suppression in the CNS
May provide neurotrophic support to injured
neuronal tissue




Monoclonal antibody that binds to integrins
expressed on surface on all leukocytes except
neutrophils
Inhibits interaction with vascular adhesion
molecules
Prevents migration of leukocytes into CNS
Risk for PML






About 30% reduction in relapes
Delay disease progression by EDSS
Reduction in lesions on MRI
Slow cognitive decline
No significant benefit in secondary
progressive disease without relapses
Benefits seen in monosymptomatic patients



Diagnose in clinically appropriate patients
Diagnose early
Treat early!!
Download