Module 6 - lecture note - Parkinson's Disease and Movement Disorders

Movement Disorders and Parkinson's Disease

• Movement disorders are classified as hypokinetic (decreased movement, e.g., Parkinson's) or hyperkinetic (increased movement).
• Voluntary movement involves the corticospinal tracts, pyramidal tracts, basal ganglia, and cerebellum.
• The extrapyramidal system modulates involuntary actions, reflexes, gross movements, complex movements, and postural control.
• Parkinson's disease is a degenerative disorder with tremor, stiffness, bradykinesia, and rigidity, classified as hypokinetic.
• Parkinson's is caused by degeneration of dopaminergic neurons and accumulation of Lewy bodies (insoluble synuclein aggregates).
• Lewy bodies in the basal ganglia lead to dopamine depletion, impairing movement.
• In Parkinson's, the loss of dopamine leads to an imbalance with overactivity of excitatory acetylcholine within the brain.

Treatment for Parkinson's Disease

• Treatment aims to restore dopaminergic function or affect acetylcholine levels.

Pharmacological Treatment

• Drug classes help restore dopaminergic function, with drugs affecting acetylcholine not targeting the primary cause.

• Levodopa: A dopamine precursor converted to dopamine in the basal ganglia but is largely broken down peripherally.

  • Diet low in methionine may be undesirable

• Carbidopa: Inhibits peripheral dopa decarboxylase, preventing levodopa breakdown before it reaches the CNS.

  • The combination of carbidopa and levodopa is known as Sinemet.
  • Adverse effects include nausea, vomiting, endocrine effects, cardiovascular issues, neuromuscular problems, and psychiatric disturbances like confusion.
  • Parkinsonism Hyperpyrexia Syndrome is a potentially fatal emergency from abrupt levodopa withdrawal and the risk is always present with procedures like Deep Brain Stimulation
  • Drug interactions include dopamine antagonists and MAOIs.

• Dopamine Agonists: Directly bind to dopamine receptors, such as bromocriptine, and can also affect diabetes management.

  • Adverse effects include hallucinations, hypotension, and dyskinesia.

• Amantadine: An antiviral that may increase dopamine release and delay reuptake in the basal ganglia and has anticholinergic properties.

  • Adverse effects include anticholinergic effects, edema, confusion, and psychosis.

• MAO-B Inhibitors: Inhibit dopamine breakdown, such as selegiline and rasagiline.

  • Adverse effects include insomnia, confusion, and hallucinations.

• COMT Inhibitors: Inhibit levodopa breakdown, such as tolcapone and entacapone, increasing its availability to the CNS.

  • Adverse effects include worsened dyskinesias and nausea, rare hepatotoxicity, and rhabdomyolysis.

• Anticholinergics: Block acetylcholine's excitatory effects, such as benztropine and trihexyphenidyl, primarily helping with tremor and salivation, but do not increase dopamine levels.

  • Adverse effects: General anticholinergic side effects.

• Diphenhydramine (Benadryl): Is a histamine-1 antagonist with anticholinergic effects.

Surgical Treatment

• Surgical treatment is considered for patients with disabling symptoms and no dementia.
• Stereotactic Deep Brain Stimulation (DBS): Involves electrode placement to stimulate specific brain areas.
  • Anesthesia considerations include avoiding high blood pressure and careful drug administration, avoiding GABAergic drugs (propofol, benzodiazepines, even dexmedetomidine)
• Lesional Surgery: Involves removing Lewy body deposits, but is less common than DBS.

Anesthetic Considerations for Patients with Parkinson's

• Risk for autonomic dysfunction including orthostatic hypotension.
• Impaired temperature control.
• Excess secretions (salivary).
• Pulmonary dysfunction and aspiration risk.
• Potential for cognitive impairment and post-operative delirium.
• Patients should generally continue anti-Parkinsonian medications preoperatively. Avoid dopamine antagonists (e.g., promethazine, metoclopramide, haloperidol, droperidol), Ondansetron (Zofran) is the preferred antiemetic.
• Patients are at risk for altered mental status, confusion, hallucinations, and involuntary movements postoperatively.
• Assess baseline tremor and rigidity preoperatively.
• For acute extrapyramidal motor symptoms, diphenhydramine (Benadryl) can be administered.

Seizure Disorders and Anti-Epileptic Drugs

• Seizure: An abnormal electrical discharge in the brain that interrupts normal function.
  • Symptoms can include altered awareness, loss of consciousness, abnormal sensations, and convulsions
• Epilepsy: A chronic brain disorder characterized by recurrent seizures greater than 24 hours apart.

Perioperative Considerations for Patients with Seizure Disorders

• Know last seizure date and seizure characteristics, also identify potential contributing factors.
• For acute seizures, anti-seizure medication is needed, with propofol and levetiracetam (Keppra) as options.
• Airway management is a primary concern during seizures. Factors increasing seizure risk in the perioperative period include:
  • Anesthetic drugs, electrolyte abnormalities, withdrawal from anti-seizure medications, extremes of age, and hyperventilation.
• Factors promoting the spread of focal seizures include low serum glucose, tissue hypoxia, electrolyte imbalances, and endocrine changes.
• Patients with low albumin may have increased free concentrations of anti-seizure drugs.
• Many anti-seizure drugs are hepatic enzyme inducers, potentially requiring larger or more frequent doses of anesthetic drugs.
• Non-depolarizing muscle relaxants usually require increased doses.

Goal of Anti-Seizure Drugs

• To decrease neuronal excitability or enhance inhibition in the brain.

Anti-Epileptic Drug Classes and Mechanisms

• Benzodiazepines: Used for short-term treatment of acute seizures and status epilepticus
• Diazepam is preferred
• Midazolam can effective; IV vial can be squirted in the nose in emergencies
• Clonazepam is often added to other drugs for myoclonic seizures.
• Mechanism of Action: Positive allosteric modulators of GABA receptors, enhancing GABA's inhibitory effects.
• Adverse Effects: Sedation, ataxia, tolerance, withdrawal seizures with abrupt discontinuation. Lorazepam has a slower onset of action compared to diazepam and midazolam.
• Barbiturates (e.g., Phenobarbital): Long-acting anesthetics effective for most seizure types.
  • Mechanism of Action: Increase GABA inhibition and decrease excitation from glutamate.
  • Adverse Effects: Sedation, respiratory depression, generally less favored due to side effects compared to newer agents.
• Gabapentinoids (e.g., Gabapentin, Pregabalin): Mechanism for seizure management not fully understood.
  • Mechanism of Action: Bind to the alpha-2-delta subunit of voltage-gated calcium channels, inhibiting calcium influx and glutamate release.
  • Adverse Effects: Sedation, drowsiness, ataxia, dizziness, vertigo. Usually used as adjunct therapy.
• Levetiracetam (Keppra): Works for a variety of epilepsy and seizure disorders.
  • Perioperative Considerations: Commonly used for seizure prophylaxis in neurosurgery.
  • Adverse Effects: Headache, possible increase in blood pressure, somnolence, and sedation.
• Valproic Acid (Depakene): Used for generalized convulsive epilepsies.
  • Mechanism of Action: May increase GABA levels and inhibits excitatory sodium and calcium channels.
  • Black Box Warning: Fatal hepatotoxicity in very young children.
  • Adverse Effects: Teratogenicity, GI symptoms, increased bleeding time, thrombocytopenia, sedation, enzyme inhibition.
• Phenytoin (Dilantin): Used for partial and generalized seizures.
  • Mechanism of Action: Regulates sodium membrane transport in motor cortex neurons.
  • Therapeutic Range: Plasma level of 10-20 mcg/mL.
  • Black Box Warning: Risk of hypotension and arrhythmias with rapid infusion.
  • Adverse Effects: CNS toxicity, gingival hyperplasia, inhibition of insulin secretion, hepatotoxicity, increases metabolism of non-depolarizing muscle relaxants.
• Carbamazepine (Tegretol): Stabilizes sodium channels in an inactivated state.
  • Adverse Effects: Liver dysfunction, thrombocytopenia, dizziness, vertigo, nausea, vomiting.
  • Black Box Warning: Fatal dermatologic reactions and aplastic anemia.
• Lamotrigine (Lamictal): Inhibits glutamate release and voltage-gated sodium channels.
  • Adverse Effects: Skin disorders/life-threatening rashes, dizziness, vision symptoms, ataxia.
• Ethosuximide (Zarontin): Drug of choice for absence epilepsy.
  • Mechanism of Action: Blocks voltage-gated calcium channels in thalamic neurons.
  • Adverse Effects: GI symptoms, hyponatremia, bone marrow suppression.
• Review of Physiology and Pharmacology:
  • Gabapentinoids inhibit calcium channels via the alpha-2-delta subunit and decrease the release of excitatory neurotransmitters and have no direct effect on the GABA receptor.
  • Anti-epileptic drugs should generally not be held prior to surgery.

Central Nervous System (CNS) Stimulants

• General Mechanism: Stimulate the CNS by blocking inhibition and enhancing excitation.
• Amphetamine and Methylphenidate (Ritalin): Used to treat ADHD, narcolepsy, and obesity.
  • Mechanism of Action: Promote norepinephrine release from nerve terminals, stimulate respiratory centers, increase alertness and muscle strength.
  • Perioperative Considerations: Acute amphetamine intoxication: Increased circulating catecholamines lead to increased blood pressure, tachycardia, bronchodilation, and increased MAC. Chronic amphetamine exposure can lead to catecholamine depletion, resulting in decreased MAC.
  • When treating hypotension, avoid indirect-acting vasopressors (like ephedrine); use direct-acting vasopressors (phenylephrine, epinephrine) or vasopressin.
• Doxapram: Used to treat respiratory depression and hypercapnia.
  • Mechanism of Action: Stimulates medullary respiratory centers, increasing tidal volume and ventilation.
  • Adverse Effects: Sympathetic nervous system outflow effects and CNS stimulation effects.
• Methylxanthines (Caffeine, Theophylline, Aminophylline, Theobromine):
  • Mechanisms of Action: Antagonize adenosine receptors and inhibit phosphodiesterase (PDE).
  • Physiologic Effects: CNS stimulation, diuresis, increased cardiac contractility, and smooth muscle relaxation. Clinical Uses: Apnea of prematurity, bronchospasm, post-dural puncture headache, and promote wakefulness.
• Acidic urine promotes the excretion of basic drugs.