Multiple Sclerosis Flashcards
(16 cards)
What is Multiple Sclerosis (MS)?
A chronic, inflammatory, demyelinating disease of the central nervous system (CNS) (brain and spinal cord).
- Characterized by CNS lesions (plaques) separated in space and time.
- Autoimmune process: Immune system (white blood cells) attacks myelin sheath around nerve fibers.
- Cause is unknown (likely genetic predisposition + environmental trigger like virus/bacterium).
What is the primary pathological process in MS?
Demyelination: The immune system damages or destroys the myelin sheath insulating nerve axons in the CNS.
- This slows or blocks nerve signal transmission, leading to neurological symptoms.
- Can also involve inflammation and damage to the nerve axons themselves over time.
Describe Relapsing-Remitting MS (RRMS).
- Most common form.
- Characterized by clearly defined relapses (flare-ups, attacks) with new or worsening symptoms.
- Followed by periods of remission where symptoms improve or disappear.
- Little or no disease progression between relapses initially.
Describe Secondary Progressive MS (SPMS).
- Follows an initial RRMS course (often years later).
- Characterized by progressive worsening of symptoms and disability accumulation over time.
- May or may not have occasional relapses superimposed on the progression.
- Remissions become less apparent.
Describe Primary Progressive MS (PPMS).
- Less common (~10-15%).
- Characterized by steady worsening of symptoms and disability from the onset.
- No distinct relapses or remissions.
- May have periods of stability or temporary minor improvements.
List common symptoms experienced by MS patients (can vary widely).
- Sensory: Numbness, tingling, pain (neuropathic)
- Motor: Weakness, spasticity, gait/balance problems, tremor
- Visual: Optic neuritis (pain, vision loss), diplopia (double vision), nystagmus
- Fatigue: Overwhelming tiredness (very common)
- Bowel/Bladder: Incontinence, retention, constipation
- Cognitive: Memory problems, slowed processing speed
- Emotional: Depression, anxiety, pseudobulbar affect
- Uhthoff’s phenomenon (symptoms worsen with heat)
- Lhermitte’s sign (electric shock down spine on neck flexion)
What are the main goals and the three main approaches to MS treatment?
a. Goal: Prevent permanent neurologic damage, minimize disability, manage symptoms, improve Quality of Life (QOL).
b. Three Approaches:
- Treat Acute Relapses: Speed recovery (e.g., corticosteroids).
- Disease-Modifying Therapies (DMTs): Reduce relapse frequency/severity, slow disability progression, limit new - CNS lesions. Target the immune system.
- Symptomatic Treatments: Manage specific MS symptoms (e.g., fatigue, spasticity).
What is the standard treatment for acute MS relapses to speed recovery? Give examples and dosing.
- Methylprednisolone: 500-1000 mg/day IV for 3-7 days.
- Oral Prednisone/Methylprednisolone: Equivalent high doses (e.g., 1250 mg/day) for 3-7 days can be used.
- MOA: Reduce inflammation, inhibit immune cell activation/migration into CNS.
- Common ADRs: GI upset, insomnia, mood changes, hyperglycemia.
What is the purpose of Disease-Modifying Therapies (DMTs) in MS?
DMTs are used long-term to:
- Reduce the frequency and severity of relapses.
- Slow the accumulation of disability.
- Reduce the development of new CNS lesions (seen on MRI).
- They target the underlying autoimmune and inflammatory processes.
List examples of monoclonal antibody DMTs for MS (CD20, CD52) and their general MOA/ADRs.
a. Anti-CD20: (Ocrelizumab, Ofatumumab, Rituximab - off-label)
- MOA: Depletes B cells.
- ADRs: Infusion reactions, infections, risk of PML (Progressive Multifocal Leukoencephalopathy). Ocrelizumab approved for PPMS too.
b. Anti-CD52: (Alemtuzumab)
- MOA: Depletes T and B cells.
- ADRs: Infusion reactions, infections, significant risk of secondary autoimmune disorders (thyroid, kidney). Reserved for highly active disease.
What is the general recommendation for DMT use during pregnancy? Which are strongly contraindicated?
- General: Most DMTs are not recommended during pregnancy due to lack of safety data or known risks. Planning is crucial.
- Contraindicated: Teriflunomide (also for men planning conception with partner), Mitoxantrone.
- Some (e.g., Glatiramer acetate, Interferons) may be considered in specific high-risk situations, but generally stopped pre-conception or upon pregnancy confirmation.
What pharmacological agents might be used for MS-related fatigue?
- Amantadine: (Antiviral with CNS effects) - First-line.
- Methylphenidate: (Stimulant) - Second-line.
- Modafinil/Armodafinil (Wakefulness-promoting agents) - Sometimes used off-label.
(Non-pharm: energy conservation, cooling strategies, exercise, stress management)
List common medications used to treat spasticity in MS.
- Baclofen: (GABA-B agonist) - First-line oral.
- Tizanidine: (Alpha-2 agonist) - Oral.
- Dantrolene: (Muscle relaxant, acts peripherally) - Oral.
- Diazepam: (Benzodiazepine) - Oral, use limited by sedation.
- Intrathecal Baclofen: (Pump) - For severe, refractory spasticity.
- Botulinum Toxin: (Injections) - For focal spasticity.
What medication is specifically approved to improve walking speed in MS patients? What is its MOA and a key contraindication?
- Dalfampridine (Extended-Release):
- MOA: Potassium channel blocker; prolongs action potentials in demyelinated neurons, improving conduction.
- Contraindication: Patients with a history of seizures or moderate/severe renal impairment (increases seizure risk).
What is pseudobulbar affect (PBA) and how is it treated?
- PBA: Characterized by inappropriate, uncontrollable episodes of laughing or crying.
- Treatment: Combination product of Dextromethorphan (NMDA antagonist, sigma-1 agonist) and low-dose Quinidine (inhibits dextromethorphan metabolism, increasing its levels).
