Delayed-onset seizure after dantrolene-treated malignant hyperthermia in a patient with traumatic brain injury and a pathogenic RYR1 variant: a multiple-hit model

Malignant hyperthermia (MH) is a life-threatening pharmacogenetic disorder primarily affecting skeletal muscle via ryanodine receptor 1 (RYR1) hyperactivation. Central nervous system (CNS) complications following MH are rarely reported, and the role of dantrolene in preventing or treating such sequelae remains unclear. Patients with concurrent traumatic brain injury (TBI) present a particularly complex scenario where multiple etiologies for neurological complications may converge. We report a 53-year-old male with a confirmed pathogenic RYR1 variant (c.7108_7109delinsAAGCC, p.Gly2370delinsLysPro) who developed fulminant MH during emergency intracranial hematoma evacuation following traumatic brain injury with extensive cerebral contusions. Clinical data were collected prospectively during the ICU course, including continuous EEG monitoring, serial neuroimaging, and detailed documentation of seizure characteristics and treatment responses. The relationship between MH, TBI, and delayed seizure was analyzed through a multifactorial etiological framework. In patients with MH and concomitant TBI, delayed seizures may arise primarily from the structural brain injury (cerebral contusions and/or the surgical manipulation of hematoma evacuation), although acute systemic insult (MH) and potential genetic susceptibility (RYR1 variant) could represent additional, unconfirmed contributing factors.Dantrolene should not be relied upon for CNS complications, as its limited CNS penetration and RyR1 selectivity render it ineffective for seizure control.This case suggests that CNS sequelae deserve consideration in MH patients with overlapping risk factors, while recognizing that traumatic brain injury remains the most likely primary cause of seizure in this setting.