1. Rachel Coombes PSY4170 MULTIPLE SCLEROSIS (MS)

2. Contents 1.What is MS? 2.Presenting symptoms 3.Types of MS 4.Diagnostic criteria and known neuropathology 5.Neuroimaging, neurological and neuropsychological tests used to diagnose and understand MS 6.How MS is distinguished from similar conditions 7.Challenges and controversies of diagnosis 8.References

3. What is Multiple Sclerosis (MS)? Chronic inflammatory disease of the central nervous system (CNS) interferes with nerve impulses in the brain, spinal cord and optic nerves. Occurs due to the breakdown of myelin sheath covering nerve axons which leads to the breakdown of axons. Sclerosis – Greek word meaning ‘hardened tissue or scars’ (MS Australia)

4. Presenting Symptoms Most common Sensory problems Weakness Difficulty walking Monocular decreased vision Poor coordination Ataxia Other symptoms Diplopia Vertigo Bladder problems Gait disturbance Lhermitte’s sign Pain Fatigue Headache Bowel problems Sexual dysfunction Cognitive difficulties (Joy & Johnston, 2001; Samkoff & Goodman, 2014 )

5. The nerve fibre in multiple sclerosis This image illustrates what the nerves look like in an individual suffering from MS compared with someone without. (Joy & Johnston, 2001)

6. Diagnostic Criteria – McDonald 2010 revised Clinical PresentationParaclinical Tests Needed SpaceTime 2 attacks 2 locationsNo 2 attacks 1 location MRI abnormal or 2 MRINo lesions + CSF 1 attack 2 locations NoMRI criteria or 2 nd attack 1 attack 1 location (CIS) MRI abnormal or 2 MRI MRI criteria or 2 nd attack lesions + CSF PP-MS (progression for 1 year) Need 2 of the following: 9 MRI brain lesions or 4-8 brain lesions + VEP 2 MRI cord lesions Positive CSF (Weiner W. J., 2010; Polman, et al., 2011; Samkoff & Goodman, 2014 )

7. Known Neuropathology Plaques Perivascular inflammation Demyelination, in particular fibers near ventricles Myelin disruption Abnormalities in spinal fluid Oligodendrocyte damage (Roncaroli, 2005; Gazzaniga, Ivry, & Mangun, 2013)

8. Tests Used to Diagnose MS – Neurological Major areas of the examination include: Mental status testing Cranial Nerves Muscle strength, tone and bulk Reflexes Coordination Sensory Function Gait Strengths Provides a means to access further testing Weaknesses Can lead to incorrect diagnosis Not a conclusive test (Goldberg, 2008)

9. Tests Used to Diagnose MS – Neuroimaging Magnetic resonance imaging (MRI) 5-10 times more sensitive to ongoing inflammatory demyelination than clinical assessment Visible neuropathology Lesions Brain atrophy Strengths Most sensitive technique available to detect brain lesions Weaknesses Can be misleading if not interpreted correctly Conventional MRI measures do not provide all the information needed (Weiner & Stankiewicz, 2012)

10. Tests Used to Diagnose MS - Neuropsychological Areas of testing: Attention, processing speed, mood, verbal and visual learning and memory, language, verbal and visual-spatial reasoning and judgment Strengths Necessary to reveal the extent of cognitive dysfunction Sensitive to short term changes in cognitive function Weaknesses Time Consuming – takes 6-8 hours to administer a full battery Costly Can be misleading Need for disease specific neuropsychological tests (Joy & Johnston, 2001; Olek, 2005; Brassington & Marsh, 1998)

11. Differential Diagnosis EtiologyDisease InflammatoryNeurosarcoidosis Systemic lupus erythrmatosis Granulomatous angiitis Antiphospholipid syndrome Optic neuritis Behçet disease Sjögren syndrome Polyarteritis nodosa Neuromyelitis optica InfectiousHIV Lyme disease Neurosyphilis Whipple disease PML Cat scratch disease HTLV-1 and HTLV-2 NeoplasticLymphomaParaneoplastic disorders VascularLeukoaraiosis CNS vasculitis Spinal dural AV malformation Susac syndrome Stroke (Samkoff & Goodman, 2014; Olek, 2005; Weiner & Stankiewicz, 2012)

12. EtiologyDisease MetabolicVitamin B12 deficiency Mitochondrial Copper deficiency Central pontine myelinolysis Leber disease Congenital disordersLeukodystrophy Mitochondrial disease Friedriech ataxia Spinocerebellar ataxia CADASIL Arnold-Chiari malformation Nonorganic/psychiatricConverstion disorderSomatization disorders (Samkoff & Goodman, 2014; Olek, 2005; Weiner & Stankiewicz, 2012) Differential Diagnosis

13. Systemic features – Family history, fever/night sweats, weight loss, arthropathy, rash, ulcers, dry mouth and eyes, ocular disease Neurological features – persistent headache, fits, encephalopathy, meningism, movement disorders, stroke-like events, peripheral neuropathy Investigations – raised erythrocyte sedimentation rate and or/C reactive protein, serology, abnormal chest x ray, absent oligoclonal bands or persistent cerebrospinal fluid pleocytosis, normal MRI or pronounced meningeal enhancement (Scolding, 2001) Differential Diagnosis

14. Challenges and Controversies of Diagnosis The biggest challenge in diagnosis of MS is its unpredictability The symptoms can vary from person to person The symptoms can change throughout the lifetime of a patient with MS The lack of understanding of the cause of MS is also a challenge No clear explanation of the cause to help diagnosis Diagnosis is a significant challenge as it requires ruling out all other possible disease or syndromes before the diagnosis of MS can be given Over-diagnosis of MS is controversial Misdiagnoses The process of diagnosis of MS is controversial Due to the difficulty in a clear diagnosis

15. References Brassington, J. C., & Marsh, N. V. (1998). Neuropsychological Aspects of Multiple Sclerosis. Neuropsychology Review, 8 (2), 43-77. Gazzaniga, M., Ivry, R. B., & Mangun, G. R. (2013). Cognitive Neuroscience: The Biology of the Mind (Fourth International Student Edition) (4th ed.). New York, NY: W. W. Norton & Company. Goldberg, C. (2008, August 16). The Neurological Examination. Retrieved August 2, 2015, from University of California, San Diego - A Practical Guide to Clinical Medicine: https://meded.ucsd.edu/clinicalmed/neuro2.htm Joy, J. E., & Johnston, R. B. (Eds.). (2001). Multiple Sclerosis: Current Status and Strategies for the Future. Washington DC: National Academy Press. MS Australia. (n.d.). What is MS? Retrieved August 1, 2015, from MS Australia: http://www.msaustralia.org.au/understanding-ms/what-is-ms Olek, M. J. (Ed.). (2005). Multiple Sclerosis: Etiology, Diagnosis and New Treatment Strategies. Totowa, New Jersey: Humana Press. Polman, C. H., Reingold, S. C., Banwell, B., Clanet, M., Cohen, J. A., Filippi, M., et al. (2011). Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria. Annals of Neurology, 69 (2), 292-302. Roncaroli, F. (2005). Neuropathology of Multiple Sclerosis. ACNR, 5 (2), 16-22. Samkoff, L. M., & Goodman, A. D. (Eds.). (2014). Multiple Sclerosis and CNS Inflammatory Disorders. Chichester, West Sussex, UK: John Wiley & Sons Inc. Scolding, N. (2001). The differential diagnosis of multiple sclerosis. Journal of Neurology, Neurosurgery and Psychiatry, 71 (Issue suppl 2), ii9-ii15. Weiner, H. L., & Stankiewicz, J. M. (Eds.). (2012). Multiple Sclerosis: Diagnosis and Therapy. Hoboken: John Wiley & Sons. Weiner, W. J. (Ed.). (2010). Neurology for the Non-Neurologist (6th ed.). Philadelphia, PA: Lippincott Williams & Wilkins.