Heat stroke is classified as temps >40.6C with neurological dysfunction and is secondary to a failure in ones thermoregulatory system.  It is classically non-exertional and seen in elderly patients during a heat wave or being in a van on a hot day. Can also occur from physical activity like with young football players in hot conditions.

Predisposing factors: anticholinergics, psych meds, sympathomimetics, extremes of age, high temperatures/humidity, lack of acclimatization, dehydration, medical comorbidities

DDX:  NMS, serotonin syndrome, thyrotoxicosis, pheochromocytoma, exertional/seizures,  sympathomimetic/serotonergic toxidromes, sepsis, autonomic dysfunction, anticholinergic toxidrome, CVA, encephalitis, trauma, granulomatous disease, NMS

Treatment:  
Monitor core temperature rectally
Eliminate cause of hyperthermia
Expose and active cooling to < 40 C (cool environment, cold water to skin and fan, ice packs to groin and axilla, cold IV fluids, dialysis)
May require sedation and paralysis to improve shivering reflex
Antipyretics show no improvement
Watch for rhabdo

Outcome: mortality in heat stroke can be >60% with high risk of permanent neuro deficit in survivors.  Those with prolonged courses or higher temps have worse outcomes. High INR is a marker of worse outcome.