Second-impact syndrome (SIS) is a rare but potentially fatal condition that occurs when an individual experiences a second head injury before complete recovery from an initial head injury. The second impact does not have to be strong to trigger SIS, and even a minor blow to the head, chest, or back that snaps the head enough to cause the brain to move inside the skull can trigger the usually lethal damage. SIS disproportionately affects teenagers, and all documented cases occurred in people younger than 20 except in boxing. Young athletes have been found to be both more susceptible to concussions and more likely to get SIS than their older counterparts.

The brain swells rapidly and catastrophically after a person has a second concussion before symptoms from an earlier one have subsided, leading to severe swelling of the brain and possible herniation of the brain. Death or lifelong disability occurs because the brain suddenly loses its ability to regulate cerebral spinal fluid pressure. The impact of the second event may start with the athlete appearing stunned with no loss of consciousness, and the athlete may be able to get up and stay on their feet long enough to walk off the field, then within seconds to minutes will collapse into a semi-comatose state during which rapid dilation of the pupils may occur and possible respiratory failure. Other signs and symptoms may include seizures, vomiting, and headache.

Although SIS is a relatively rare condition, clinicians should be aware of it and educate patients who have experienced or are at risk of experiencing a head injury, as the syndrome is often deadly. Whenever there is suspicion of a serious brain injury or SIS, the patient must immediately go to the nearest emergency center to have a CT scan of the head that will evaluate for swelling and/or bleeding in the brain.