• Bladder / bowel urgency and incontinence • Cognitive deficits
Blurred vision
Diagnostic approaches
• CSF: non specific in cellular profile
– CSF IgG Index – Oligoclonal bands
ancestry • Vitamin D3 • Genetic Influences
Prodromal and potential causal pathway for MS
Ramagopalan S et al. Lancet Neurol 2010; 9: 727–39
PATHOPHYSIOLOGY OF MS
• MS is a clinical diagnosis
Epidemiology of MS
• Age onset 20 – 50 years old • Women are 2 times more likely to develop MS • 500,000 cases in US • Over 2.5 million people around the world • More prevalent in whites of northern European
• Reference value < 0.85
• ~70% patients show higher value
• Electrophysiology
– VEP (visual evoked potentials ): 75% abnormal – BAEP(brainstem auditory evoked response)—30%
abnormal – SSER (somatosensory evoked response)
Multiple Sclerosis
Definition of Multiple Sclerosis
• An inflammatory demyelinating disease of the CNS where there is:
– Dissemination in space (DIS) – Dissemination in time (DIT) – No alternative neurologic disease
– Myelin basic protein (MBP) – Myelin oligodendrocyte glycoprotein (MOG) – Proteolipid protein (PLP) – Myelin associated glycoprotein (MAG)
PATHOPHYSIOLOGY OF MS
• Cells
– CD4 TH1, CD4 TH2 and CD8 T cells – Macrophages and microglial cells – Mast cells – B cells
• Cytokines, chemokines and adhesion molecules
– Inerleukin family (IL-4, 10,12) – IFN-gamma – ALCAM (Activated leukocyte cell adhesion molecule) – Tumour necrosis factor receptor superfamily
– Relapsing-remitting (85% at onset) – Primary progressive (10%) – Secondary Progressive (transitional form) – Progressive Relapsing (5%)
Multiple Sclerosis Subtypes
• Sensory changes
– Heat intolerance – Paraesthesia, neuralgia – Lhermitte’s sign (dorsal column sign) induced by head flexion
• Cerebellum
– Ataxia, nystagmus-tremor-dysarthria(Charcot triads)
• Destruction of
– Myelin, oligodendrocytes, nerve axons
• Hypothesis of molecular mimicry: infected virus share with myelin molecules common antigens
• Targeted antigens mimicked by virus
The immunopathogenesis of MS
Gole R et al. Acta Neurol Scand 2011: 124: 75–84
Multiple Sclerosis Subtypes
(Lublin F, et Biblioteka l Neurology 1996)
• Asymptomatic • Symptomatic
SYMPTOMS OF MS
• Visual disturbances
– Blurred vision, diplopia, intranuclear ophthalmoplegia – Marcus Gunn pupil
• Fatigue • Motor
– Spasticity, paresis, dysarthria, spasms, muscle weakness
• Imaging: MRI is used routinely, most effective
CSF IgG INDEX
• CSF IgG to CSF albumin ratio compared to serum IgG to serum albumin ratio CSF IgG / CSF albumin serum IgG / serum albumin