Multiple Sclerosis Flashcards
Multiple sclerosis definition
Chronic autoimmune inflammatory disease of CNS ,progressive, multifocal. Most common demyelinating disease.
Usually : Young adults, 30-40s, 2F>M
Due to genetic (HLA-DR2) and envirronmental factors (Vit-D deficiency)
Viral infactions may be implicated (EBV, HHV-6)
Pathomechanism of multiple sclerosis
T-cells activation in periphery + cross react with myelin in CNS leading to demyeliination and axonal degeneration.
Demyelinated regions are referred as plaques
Characterized by inflammation + demyelination + gliosis (scarring)+ neuronal loss leading to brain atrophy and neurological deficits( delayed)
Course (Types) of multiple sclerosis
Benign= No or minimal neurological disability after 10-15 yrs.
Malignant= Neurological disability requiring assistance after 5 years.
Relapsing MS (RRMS) (85%)= Unpredictable attacks which may nnot leave permanent deficits, followed by periods of remission.Commonly progresses to SPMS
Secondrary Progressive MS( SPMS) : Initially RRMS, suddenly begins to decline without remission or relapses. Has slow progression
Primary progressive MS (PPMS) : Gradual progression/ steady functional decline and no attacks
Progressive/Relapsing MS (PMS) : Steady decline with superimposed attacks.
A) Expanded disability status scale (EDSS) ( measure of neurological impairement) :
Score <3.5= RAMS,walk normally ,generally not disabled.
Score >3.5= Progressive MS, gait impaired, occupationally disabled.
B)Mc Donald criteria :
-Prove that inflammation is chronic and widespread.
-Dissemination in time and space( checked by MRI)
>2 attacks+ >2 lesions= Clinical evidence alone is sufficient
-If 0 attacks then 1 year of disease progression and 2 out of 3 of the following:
demyelination in space in brain
demyelination in space in spinal cord
Positive CSF
Diagnosis of MS
MRI (1st line): T1 axial sccan with gadolinium, T2 Flair axial and sagittal. Typical distribution of demyelinating plaques around ventricles, corpus calossum, brain, spinal cord.
CSF examination: Mild pleocytosis (WBC <50mm3)
Normal routine values : Oligoclonal band (OCB) : High IgG index (oligoclonal gammopathy)
Evoked potentials : VEP, MEP, SEP: Detection of subclinical lesions and predict course of disease.
Serology for DDx : Boreliosis, Treponema e.t.c
*Multifocal white matter lesions (usually >3mm) :
Involves corpus callosum is MS specific
Spinal cord: Lesions is up to 80% of patients=cervical
Dawson Fingers : Periventricular ovoid lesions.
T2 Hyperintense lesions
T1 Hypointense lesions= Black holes= dd plaques, axonal loss, persists for years.
Management of MS
A) Acute attacks:
Corticosteroids( 1st Line) : Accelerate recovery , dont improve long term outcome.
IV Methylprednysolone= 1g/day for 3-5 years
P.os Prednisone = Taper 10-14 days
Plasma Exchange 5-7 exchabges, every other day for 14 days
Disease modifying therapies (DMT) = To reduce biological activity, decrease severity and number of relapses, hospital stays…. Start early and agressive
Most patients with relapsing forms : IFN -B or datiramer acetate+ natalizumab + alemtuzumab ( 1st line)
Off- label : MTZ,AZA,Cyclophosphamide, Rituximab, Mycophenolate Mofetil.
Symptoms of MS
Weakness of limbs
Spontaneous and movement induced muscle spasms
Dysarthria, nystagmus, coordination/balance problems
Optic neuritis
Diplopia
Sensory disturbances such as paresthesias, hyperesthesias, pain, unpleasant sensations.
Bladder dysfunction
Constipation
Sexual dysfunction
Cognitive dysfunction
Depression
Chronic fatigues
Heat insensitivity
Treatment of symptoms
Detrusor hyperreflexia: Solifenacin, tolterodine, oxybutynin
Urinary retention : Bethanecol
Weakness : 4-Aminopyridine (K+ -CH blocker)
Ataxia/Tremor : Clonazepam, Propanolol, Ondasetron
Anticonvulsants: Carbamazepine, Phenytoin, Gabapentin, pregabalin
Antidepressant: Amitryptilline and Venlafaxine
