21.1 Neurodegenerative & Demyelinating Disease and Antiparkinsonian Pharmacology
Key Takeaways
- Levodopa has a 1-3 hour half-life; continue it through the morning of surgery and resume immediately, because abrupt withdrawal causes severe rigidity and a neuroleptic malignant-like syndrome.
- Central dopamine antagonists (metoclopramide, droperidol, haloperidol, promethazine, prochlorperazine) are contraindicated in Parkinson disease; ondansetron and dexamethasone are safe antiemetics.
- In multiple sclerosis a core temperature rise of only 1 degree Celsius can trigger a relapse; succinylcholine is avoided with significant paresis and spinal anesthesia is relatively contraindicated.
- Succinylcholine is contraindicated in ALS and Guillain-Barre syndrome because of extrajunctional acetylcholine receptor upregulation and hyperkalemia.
- Home cholinesterase inhibitors for Alzheimer disease (donepezil, rivastigmine) prolong succinylcholine and antagonize nondepolarizing blockade.
Why This Topic Matters on the NCE
Domain I of the NCE content outline lists neurodegenerative diseases, myelin diseases, and neuropathies as separate pathophysiology sub-topics, and Domain I.C.12.c lists antiparkinsonian drugs as their own pharmacologic class. These patients arrive for routine surgery constantly, and almost every question about them hinges on one of three decisions: which neuromuscular blocking agent is safe, which antiemetic is safe, and what happens if the home drug is withheld.
1. Parkinson Disease: Dopamine Depletion and the Drugs That Make It Worse
Parkinson disease (PD) is degeneration of dopaminergic neurons in the substantia nigra pars compacta, depleting dopamine in the striatum. Symptoms appear once roughly 80% of dopaminergic neurons are lost. The loss of dopaminergic inhibition leaves unopposed cholinergic activity in the basal ganglia, producing the classic tetrad: resting ("pill-rolling") tremor, cogwheel rigidity, bradykinesia, and postural instability.
Perioperative implications beyond the movement disorder
| System | Finding | Anesthetic consequence |
|---|---|---|
| Airway/pulmonary | Pharyngeal and laryngeal muscle dysfunction, sialorrhea, weak cough | Silent aspiration; consider full-stomach precautions |
| Respiratory | Chest-wall rigidity, restrictive ventilatory defect, upper-airway obstruction on flow-volume loop | Postoperative respiratory failure risk |
| Autonomic | Orthostatic hypotension, blunted baroreflex, dysrhythmias | Exaggerated hypotension on induction and positioning |
| CNS | Depression, dementia (~30%), hallucinations | Higher postoperative delirium risk |
| GI | Delayed gastric emptying, constipation | Erratic absorption of oral levodopa |
Levodopa pharmacology and the withdrawal trap
Levodopa is the dopamine precursor that crosses the blood-brain barrier; carbidopa is a peripheral decarboxylase inhibitor that prevents systemic conversion (reducing nausea and allowing lower levodopa doses). The critical NCE fact is that levodopa has an elimination half-life of only 1 to 3 hours.
- Continue levodopa/carbidopa up to and including the morning of surgery, and restart it as early as possible postoperatively — through an orogastric or nasogastric tube if the case is long.
- Abrupt withdrawal produces severe rigidity, worsened ventilation, and can precipitate a neuroleptic malignant-like syndrome (hyperthermia, rigidity, rhabdomyolysis, altered mental status) that is clinically confusable with malignant hyperthermia but is not triggered by volatiles and is not treated primarily with dantrolene.
Drugs that are contraindicated or hazardous
- Central dopamine (D2) antagonists worsen parkinsonism and must be avoided: metoclopramide, droperidol, haloperidol, promethazine, prochlorperazine.
- Safe antiemetic choices: ondansetron (5-HT3 antagonist), dexamethasone, and domperidone where available (does not cross the blood-brain barrier).
- Selegiline and rasagiline are MAO-B inhibitors. Combining them with meperidine risks serotonin syndrome; meperidine is contraindicated. Indirect-acting sympathomimetics (ephedrine) may produce exaggerated pressor responses — prefer titrated phenylephrine.
- Deep brain stimulators are increasingly present: use bipolar electrocautery, place the grounding pad far from the generator, and turn the device off before cautery.
2. Demyelinating Disease: Multiple Sclerosis and Guillain-Barre Syndrome
Multiple sclerosis (MS) is demyelination of the central nervous system (brain, spinal cord, optic nerve) — peripheral nerves are spared, which is exactly why the succinylcholine and regional-anesthesia questions differ from those in peripheral neuropathies.
- Temperature is the highest-yield fact: an increase in core temperature of as little as 1 degree Celsius can block conduction in demyelinated axons and precipitate a relapse. Aggressively prevent hyperthermia.
- Relapse is also provoked by surgical stress and infection; many exacerbations after surgery are attributed to anesthesia when the true trigger is fever or stress. Document the neurologic examination before any anesthetic.
- Succinylcholine is avoided where there is significant paresis, because extrajunctional acetylcholine receptor upregulation causes hyperkalemia.
- Response to nondepolarizers is unpredictable — resistance in upregulated muscle, exaggerated sensitivity where muscle mass is lost. Titrate to quantitative train-of-four.
- Spinal anesthesia is relatively contraindicated by long tradition (the cord is exposed to a higher local anesthetic concentration without a protective myelin sheath); epidural and peripheral nerve blocks are considered lower risk, and general anesthesia is not associated with relapse.
- Patients on chronic corticosteroids may need stress-dose coverage.
Guillain-Barre syndrome is an acute inflammatory demyelinating polyradiculoneuropathy causing ascending weakness. Key points: succinylcholine is contraindicated (hyperkalemia), autonomic instability produces wide swings in blood pressure and heart rate with exaggerated responses to indirect vasopressors, and respiratory failure requiring ventilation is common (a vital capacity below 15 mL/kg predicts the need for intubation).
3. Motor Neuron and Cortical Degeneration
| Disease | Core lesion | Anesthetic rules |
|---|---|---|
| Amyotrophic lateral sclerosis (ALS) | Upper and lower motor neuron degeneration | Succinylcholine contraindicated (hyperkalemia); marked sensitivity to nondepolarizers; bulbar weakness = aspiration; very high risk of postoperative ventilatory failure — avoid long-acting agents and plan for possible postoperative ventilation |
| Alzheimer disease / dementia | Cortical cholinergic deficiency | Avoid central anticholinergics (atropine, scopolamine cross the blood-brain barrier); glycopyrrolate is quaternary and does not. Home cholinesterase inhibitors (donepezil, rivastigmine) prolong succinylcholine and antagonize nondepolarizers. High postoperative delirium risk |
| Huntington disease | Autosomal dominant chorea plus dementia | Reduced plasma cholinesterase activity has been reported (prolonged succinylcholine); exaggerated response to thiopental; very high aspiration risk from pharyngeal chorea |
4. Peripheral Neuropathies
Diabetic, chemotherapy-induced, alcoholic, and uremic neuropathies all matter for two reasons on the NCE: (1) a documented preoperative neurologic examination is mandatory before any regional technique so that a preexisting deficit is not later attributed to the block, and (2) demyelinated or already-injured nerves are more vulnerable to a second insult — the double-crush phenomenon. This does not make regional anesthesia forbidden, but it does justify lower local anesthetic concentrations, avoidance of epinephrine adjuvants in some cases, and careful documentation and consent.
Exam Traps
- The most commonly missed item is giving metoclopramide for aspiration prophylaxis to a patient with Parkinson disease. It is contraindicated.
- A patient with Parkinson disease who becomes rigid and hyperthermic 12 hours after surgery has most likely missed levodopa doses, not developed malignant hyperthermia.
- In MS, the danger is hyperthermia, not the anesthetic technique.
A 71-year-old with a 12-year history of Parkinson disease undergoes an open reduction and internal fixation of a hip fracture. Twenty hours postoperatively the patient is febrile to 38.9 C, severely rigid, confused, and has a creatine kinase of 4,200 units/L. The patient has received nothing by mouth since admission. What is the most likely diagnosis and initial management?
A patient with relapsing-remitting multiple sclerosis is scheduled for laparoscopic cholecystectomy. Which intraoperative management priority most directly reduces the risk of a postoperative neurologic exacerbation?
A patient taking donepezil for Alzheimer disease receives succinylcholine 1.5 mg/kg for a rapid sequence induction. What effect should be anticipated?
Which combination of a neuromuscular blocking agent and a neurologic diagnosis is safe?