SEARCH RESULTS FOR: Neuroleptic-Malignant-Syndrome

Neuroleptic Malignant Syndrome

Neuroleptic Malignant Syndrome (NMS): Pathogenesis and clinical findings Initiation or ↑ dose of dopamine receptor (D2) antagonist medication (typical antipsychotics more common than atypical; antiemetics eg. metoclopramide) Medication blocks dopamine D2 receptors in the central nervous system Genetic risk factors including DRD2 A1 allele (TaqI A1 polymorphisms) & CYP2D6 deficiency Sudden ↓ in central dopamine activity Rapid withdrawal of dopaminergic medications (eg. Levodopa) Abrupt withdrawal of D2 receptor stimulation in the central nervous system Depolarization blockade of the nigrostriatal pathway & basal ganglia (mechanism not fully understood) Disinhibition of striatal indirect pathway Hyperactive subthalamic nuclei drives excitation of globus pallidus internus (GPi) Overactive GPi strongly inhibits thalamus & ↓ cortical motor output ↓ Cortical motor output produces sustained muscle contraction ↑Peripheral calcium release from myocyte sarcoplasmic reticulum Continuous depolarization & sustained contraction ↑ Metabolic demand & heat production Dopamine depletion in mesolimbic & neocortical pathways (mechanism not fully understood) Altered mental status (e.g. delirium) Hypothalamic dysregulation & autonomic instability (mechanism not fully understood) Disinhibition of posterior hypothalamus sympathetic premotor neurons Dysregulated thermogenesis & impaired cooling mechanisms in the anterior pre-optic area Strong neuronal excitation in the paraventricular nucleus amplifies signals along descending autonomic tracts Persistent sympathetic tone & suppressed parasympathetic tone Diaphoresis Tachycardia Fluctuating blood pressure Severe “lead-pipe” muscle rigidity ↑ Serum creatine kinase Myoglobinuria Hyperthermia (fever ≥40◦C) Acute renal failure Prolonged illness promotes skeletal muscle damage & breakdown, immobilization, & dehydration Rhabdomyolysis Author: Amena Thraya Reviewers: Emily J. Doucette, Rupang Pandya* * MD at time of publication Legend: Pathophysiology Mechanism Published Feb 24, 2026 on www.thecalgaryguide.com Sign/Symptom/Lab Finding Complications