1. Multiple Sclerosis Doug Symptom Presentation and Course
What Causes MS?
Clues from epidemiology
Autoimmune response or idiopathic degeneration?
Neurobehavioral Manifestations
Cognitive profile
The role of fatigue
Psychiatric symptoms

2. Doug 35 y.o. married software engineer
Age 20 – 1st episode unexplained symptoms
Bilateral lower extremity numbness, tingling, weakness, lack of coordination
Resolved spontaneously at 3 mos.
Played hockey senior year of college
Age 26 – 2nd episode
Visual blurring, diagnosed as optic neuritis
MRI showed plaques characteristic of MS
Ages – 3 exacerbations with full recovery
Age 33 – exacerbation followed by persisting BLE weakness, fatigue & cognitive changes

3. Doug Functional limitations Current complaints
severe difficulty concentrating, easily distracted
poor memory for recent events
severe fatigue
Functional limitations
left work 2 years ago
limited multitasking (no complex recipes)
extensive use of lists/cellphone
1-2 household chores/day
sleeps hours/day, fewer with Adderal

4. Multiple Sclerosis
An immune-mediated process in which an abnormal response of the body’s immune system is directed against the central nervous system (brain, spinal cord and optic nerves).
Immune system attacks the myelin and nerve fibers
nerve impulses traveling to and from the brain and spinal cord are distorted or interrupted, producing a wide variety of symptoms.

5. Most Common Presenting Symptoms
Frequency
Sensory disturbance – limbs
30.7
Visual loss
15.9
Motor disturbance (gradual onset)
8.9
Double vision
6.8
Gait disturbance
4.8
Motor disturbance (sudden onset)
4.3
Balance problem
2.9
Sensory disturbance - face
2.8
Bobholz & Gremley, 2011

6. Multiple Sclerosis Diagnostic Criteria
Establish dissemination of 2+ lesions in space and time
Rule out other diagnoses
Polman , 2011

7. Progression of MS Lesions on MRI

8. Signs and Symptoms
Compston, 2008

9. Epidemiology 80-90/100,000 in US ~400,000 in US/ 2.5 million worldwide
Female:Male ratio = 2.6:1
Onset (5% < 18 years)
Slow course

10. Subtypes by Course SYMPTOMS TIME Progressive Relapsing (~5-10%)
Secondary
Progressive ( ~ 65%)
SYMPTOMS
Primary
Progressive ( ~10%)
Relapsing
Remitting( ~15%)
TIME
Bobholz & Gremley, 2011

11. Epidemiology Increased risk with affected family member
linkage to gene for immune molecule
higher latitude of residence in childhood
Ohio = 112.4/100,000
Texas = 42.8/100,000
later infection with Measles, Epstein-Barr virus

12. Compston, 2008

13. Compston, 2008

14. Risk of MS by UV exposure and Gender
Orton, 2011

15. Effect of Month of Birth and Latitude on MS Risk
All Samples
Dobson, 2013

16. Effect of Month of Birth and Latitude on MS Risk
All Samples
Samples Living > 52° Latitude
Dobson, 2012

17. Effect of Month of Birth and Latitude on MS RiskHI LO
Pre-natal
UV Exposure
All Samples
Samples Living > 52° Latitude
Dobson, 2012

18. Effect of Month of Birth and Latitude on MS Risk
Dobson, 2012

19. Pathogenesis of MS
Blood-brain barrier: abnormally activated lymphocytes disrupt BBB
Autoimmune: lymphocytes enter brain, activate local immune response
Inflammation: T- cell attacks on myelin triggers inflammatory processes

20. Waxman, 1998

21. Gray Matter Loss 1 year after 1st MS Episode
Raz, 2010

22. Cognitive Function in MS
Common (40-50%)
Predict vocational status
Affect daily function
Heterogeneous
Emerge early in disease
Deficits in verbal fluency, information processing, working memory, encoding and retrieval

23. adapted from Benedict, 2011

24. Effect of Exertion in MS
Claros-Salinas, 2012

25. Effect of Exertion in MS
Claros-Salinas, 2012

26. Prevalence of Neuropsychiatric Comorbidities
Condition
Prevalence in MS*
Major Depression
25-50%
Anxiety Disorders
36%
Pseudo-bulbar Affect
10%
Euphoria Sclerotica 9%
Bipolar Disorder 2%
Psychosis
2.5-4%
* all elevated compared to control population
Feinstein, 2012; Korostil, 2007;Patten, 2005

27. Doug’s Test Results WAIS-III SS Similarities 11 Premorbid IQ (HART)
Comprehension 13
Trail Making A 8
Matrix Reasoning 15
Trail Making B 1
Symbol Search 6
Phonemic Fluency
Letter-Num Seq.
Category Fluency
Digit Span 5
Grooved Pegboard 10
WMS-III Imm. Memory
Finger Tapping
Delayed Memory
CVLT Initial Learning 7
Intrusions – Cued Recall

28. Self-reported Psychiatric Symptoms
Clinically Significant