Multiple Sclerosis and Parkinson's Disease

Multiple Sclerosis (MS)

• Primarily an autoimmune disorder
• The immune system mistakenly attacks the central nervous system (CNS), especially the myelin sheaths around axons

Pathophysiological Processes of MS

• Immune Activation: Th1 and Th17 CD4+ T cells, CD8+ cytotoxic T cells, macrophages & plasma cells attack oligodendrocytes, which are responsible for myelinating CNS axons
• Cytokine Damage: Th1 cells release IFN-γ, and Th17 cells release IL-17, causing inflammation and damage to myelin and axons
• Cytotoxic T cells release cytotoxins (e.g., perforin) and cytokines that further exacerbate damage
• Microglial and Macrophage Activation: These cells secrete reactive oxygen species and proinflammatory cytokines, worsening axonal damage
• Consequences: Demyelination disrupts action potential conduction, leading to neurological impairments such as motor dysfunction, sensory deficits, and cognitive issues

Parkinson's Disease (PD)

• Primarily a neurodegenerative disorder
• Primarily caused by the loss of dopaminergic neurons in the substantia nigra pars compacta

Pathophysiological Processes of PD

• Loss of Dopaminergic Neurons: Death of dopamine-producing neurons leads to reduced dopamine levels, impairing the initiation and regulation of voluntary movement
• Lewy Body Formation: Intracellular aggregates of α-synuclein protein form Lewy bodies, which disrupt neuronal function and contribute to cell death
• Mitochondrial Dysfunction: Mitochondria in affected regions generate excessive reactive oxygen species, causing oxidative damage to lipids, proteins, and DNA, promoting neurodegeneration
• Excitotoxicity: Decreased energy production and increased oxidative stress can lead to abnormal neuronal excitability and further damage

Myasthenia Gravis (MG)

• Primarily an autoimmune disorder
• Affects the neuromuscular junction, where autoantibodies target acetylcholine receptors (AChRs) on the postsynaptic membrane

Pathophysiological Processes of MG

• Autoantibody Production: Most commonly, autoantibodies block, alter, or destroy AChRs, reducing the effectiveness of synaptic transmission
• Complement-Mediated Damage: Binding of autoantibodies activates the complement system, leading to inflammation and structural damage to the postsynaptic membrane
• Reduced Signal Transmission: Reduction in functional AChRs causes impaired signal transmission from nerves to muscles, leading to muscle weakness and fatigue
• Fluctuating Weakness: Muscle weakness typically worsens with activity and improves with rest

Multiple Sclerosis (MS) Details

• Nature: Autoimmune disorder characterized by progressive demyelination of axons in the central nervous system (CNS)

Multiple Sclerosis (MS) Symptoms

• Sensory and motor deficits: Patients may experience numbness, tingling, muscle weakness, and spasticity
• Fatigue: One of the more common and debilitating symptoms
• Visual disturbances: Optic neuritis leading to blurred or double vision is a hallmark
• Cognitive impairments: Memory loss, difficulty concentrating, impaired problem-solving
• Mood disorders: Depression and mood swings
• Gait abnormalities: Walking difficulty, poor coordination, balance issues
• Pain and bladder dysfunction: Neuropathic pain and urinary incontinence are frequent

Parkinson's Disease (PD) Details

• Nature: A neurodegenerative disorder
• Involves the basal ganglia
• Characterized by the loss of dopaminergic neurons in the substantia nigra

Parkinson's Disease (PD) Symptoms

• Motor symptoms
  • Resting tremor: Often begins asymmetrically and typically affects the hands
  • Bradykinesia: Slowness of movement and difficulty initiating movements
  • Muscle rigidity: Increased resistance to passive limb movement
  • Postural instability: Impaired balance, leading to falls
  • Shuffling gait: Short, hesitant steps, a "stooped posture"
• Non-motor symptoms
  • Autonomic dysfunction: Sweating, urinary retention, constipation
  • Cognitive decline: Dementia can develop later
  • Psychiatric symptoms: Depression, anxiety, and hallucinations

Myasthenia Gravis (MG) Details

• Nature: Chronic autoimmune disorder characterized by fluctuating muscle weakness
• Caused by autoantibodies targeting acetylcholine receptors at the neuromuscular junction

Myasthenia Gravis (MG) Symptoms

• Muscle weakness: Typically worsens with activity and improves with rest
• Ocular involvement: Ptosis (drooping eyelid) and diplopia (double vision) are common
• Bulbar symptoms: Difficulty swallowing, speaking (dysarthria), and chewing
• Respiratory involvement: Respiratory muscles may weaken, leading to a life-threatening crisis
• Proximal muscle weakness: Difficulty with tasks like climbing stairs or lifting objects

This lesson covers the pathophysiology of Multiple Sclerosis (MS) and Parkinson's Disease (PD). MS is an autoimmune disorder where the immune system attacks the central nervous system, leading to demyelination and neurological impairments. Key processes include immune activation, cytokine damage, and microglial activation.