Degenerative Disorders: Parkinson’s Disease, Multiple Sclerosis & Myasthenia Gravis

Parkinson’s Disease

• Characterized by degeneration of cells in the substantia nigra (dopamine-producing cells in the midbrain).
• Etiology is unknown; commonly affects people in their 6th or 7th decade of life; family history is a risk factor.
• Degeneration leads to decreased dopamine production, affecting the basal ganglia's function in fine motor movement and coordination.
• Imbalance between excitatory (acetylcholine) and inhibitory (dopamine) neurotransmitters leads to movement disorders.
• Cardinal signs: pin-rolling tremors, rigidity, and bradykinesia.
• Early signs may be unilateral; diagnosis is made when symptoms become bilateral and severe.
• No definitive diagnostic tests; diagnosis based on thorough history and physical examination.
• Other signs and symptoms: loss of postural reflexes, shuffling gait, loss of finger dexterity, micrographia.
• Nursing diagnoses may include impaired mobility, risk for falls/injury/aspiration.
• Provide safe environment, regular exercise, and prevent aspiration by positioning the client with upper back elevated during feeds and serving small meals with thick consistency.
• Supportive management includes good nutrition, rest, and prevention of complications like constipation and urinary tract infection.
• Drug therapy aims to balance neurotransmitters by replacing dopamine and blocking acetylcholine.
• Dopaminergic agents replace or enhance dopamine action and includes:
  • Dopamine Precursor.
  • Amantadine.
  • Bromocriptine – Increase the effect of Dopamine at the receptor sites by increasing the levels of dopamine in the substantia nigra or directly stimulating the receptors.
• Levodopa, a precursor of dopamine, crosses the BBB and is converted into dopamine.
• Carbidopa inhibits dopa decarboxylase, preventing the breakdown of levodopa before it crosses the BBB; often combined with levodopa (Sinemet).
• Anticholinergic drugs help normalize the dopamine-acetylcholine imbalance in the basal ganglia; however, they block some receptors at the autonomic nervous system.

Multiple Sclerosis (MS)

• Chronic, degenerative, progressive disease of the central nervous system (CNS) characterized by demyelination in the brain and spinal cord.
• Demyelination impairs nerve impulse transmission.
• Cause is unknown, but a defective immune response likely plays a major role.
• Sensitized T cells inhabit the CNS, leading to inflammation and destruction of myelin and oligodendroglia cells.
• Plaques of sclerotic tissue appear on demyelinated axons, further interrupting impulse transmission.
• Typically manifests in young adults between 20 and 40 years; affects women more frequently than men.
• Various courses: benign, relapsing-remitting (most common), primary progressive, and progressive-relapsing.
• Signs and symptoms vary and reflect the location of the lesion.
• Primary symptoms: fatigue, depression, weakness, numbness, difficulty in coordination, loss of balance, and pain.
• Visual disturbances: blurred vision, diplopia, patchy blindness, and total blindness.
• Spastic weakness of the extremities, ataxia, tremor, cognitive and psychosocial problems, and bladder/bowel/sexual problems are possible.
• Diagnosis: MRI (primary tool) to visualize small plaques and electrophoresis study of the CSF.
• Treatment goals: delay progression, manage chronic symptoms, and treat acute exacerbations.
• Pharmacologic Therapy:
  • Interferon beta-1a (Rebif) and interferon beta-1b (Betaseron) are administered subcutaneously.
  • Glatiramer acetate (Copaxone) to reduce the rate of relapse in the RR course of MS; administered subcutaneously daily.
  • IV methylprednisolone to treat acute relapse in the relapsing remitting course.
  • Mitoxantrone (Novantrone) is administered via IV infusion every 3 months for patients with secondary-progressive or worsening relapsing-remitting MS.
  • Baclofen (Lioresal) is the medication of choice for treating spasticity;
  • amantadine (Symmetrel), pemoline (Cylert), or fluoxetine (Prozac) to treat fatigue.
  • Beta-adrenergic blockers (Inderal), antiseizure agents (Neurontin), and benzodiazepines (Klonopin) to treat ataxia.

Myasthenia Gravis (MG)

• Autoimmune disorder affecting the myoneural junction.
• Antibodies directed at acetylcholine receptor sites impair impulse transmission.
• Fewer receptors are available for stimulation, leading to voluntary muscle weakness that escalates with continued activity.
• Women are affected more frequently than men; they tend to develop the disease at an earlier age.
• MG is purely a motor disorder with no effect on sensation or coordination.
• Initial manifestation involves ocular muscles (diplopia and ptosis).
• Weakness of the face and throat muscles, generalized weakness, laryngeal involvement (dysphonia), and decreased vital capacity.
• Diagnosis: Injection of edrophonium (Tensilon) is used to confirm the diagnosis and MRI may demonstrate an enlarged thymus gland.
• Complications: Myasthenic crisis (severe muscle weakness and respiratory failure) and cholinergic crisis (overmedication with cholinesterase inhibitors).
• Management: Improve function and reduce circulating antibodies; includes anticholinesterase medications, immunosuppressive therapy, plasmapheresis, and thymectomy.
• Pharmacologic Therapy: Pyridostigmine bromide (Mestinon) is the first line of therapy.
• Ensure patient understands the actions of the medications and emphasize the importance of taking them on schedule and the consequences of delaying medication; stress the signs and symptoms of myasthenic and cholinergic crises.
  • Other Therapy:
    • Plasma exchange (plasmapheresis) produces a temporary reduction in the titer of circulating antibodies.
    • Thymectomy (surgical removal of the thymus) produces substantial remission, especially in patients with tumor or hyperplasia of the thymus gland.