2.  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.

3.  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.

4.  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

5.  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.

6.  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

7.  ADEM  Lyme Disease  SLE  Sjogren’s Disease  Spastic paraparesis  Behcet Syndrome  B12 Deficiency  Syphilis  Leukodystrophies  Sarcoidosis  CNS vasculitis  Neuromyelitis Optica  Multiple Sclerosis

8.  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

9.  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%

10.  Immune-mediated inflammatory disease of the CNS  Previously thought to be mainly T-cell mediated (CD-4), now known to involve B- cells, macrophages, cytokines, etc.  May develop in genetically susceptible triggers (many thoughts: viruses, bacteria, etc.)  Results in: demyelination, axonal loss, brain atrophy

12.  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

13.  44% will need an assistive device for walking within 5 years  Relapsing MS leads to progressive MS after 10 years in 50% of cases

14. 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

15.  Neurologic disturbance seen in MS  Subjective report or objective observation  24 hours duration, minimum  Excludes pseudoattacks, paroxsymal events

16.  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.

18.  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

19.  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

20.  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 T- cells and cytokines, Downregulation of MHC class II molecules induced by IFN-g, Reduces antigen presentation to T-cells, Downregulation of adhesion molecules

21.  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

22.  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

23.  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

24.  Diagnose in clinically appropriate patients  Diagnose early  Treat early!!