After he suffered a stroke in 2005, Tony Nicklinson developed locked-in syndrome, a rare condition that left the middle-aged Brit fully paralyzed from the neck down. He lived on, mentally alert but wholly incapable of taking care of himself. He could not walk, feed himself or brush his own teeth. Devastated when a British court refused to allow him to commit assisted suicide, Nicklinson stopped eating or accepting fluids. He developed pneumonia, refused antibiotics, and died this past August 22, 2012.

Although news bulletins focused on his legal efforts to be permitted to commit assisted suicide, Nicklinson’s tragic disability — seven years of what his wife called a “living nightmare” — also bears upon stroke awareness and the availability of the emergency treatment that too few people know about or receive — the clot-busting drug, tissue plasminogen activator (tPA). Locked-in syndrome has something to say to everyone at risk for stroke. So does tPA.

In 2005, Stephan Mayer MD, together with colleagues at the Columbia University College of Physicians and Surgeons, reported on a unique case of heroic treatment to prevent locked-in syndrome in a stroke victim.

tPA and a Case of Locked-In Syndrome

Mayer’s patient, the pastor of a well-known church in Manhattan, suffered from a “stuttering course” of brainstem ischemia that lasted days. He first went to the emergency room some 10 hours after he began to experience facial numbness and right-side weakness. A history of neck pain suggested a vertebral dissection, or tear in the lining of the main artery that supplies blood to the brain. Transferred to the neurointensive care unit (Neuro-ICU), his symptoms were varied and ominous. First the left arm would become weak, afterwards the right; then one side of his face would become paralyzed. To insure he could breathe, he had to be intubated.

“We realized he was in the early stages of an evolving basilar artery syndrome,” recalls Mayer, “the final result of which, in the worst case, you infarct your whole pons and become locked-in.” Patients who end up in a complete locked-in state remain conscious but are completely paralyzed save for the vertical gaze. The condition is widely recognized as a fate worse than death.

Over two days Mayer presided over the patient’s disrupted “low flow state” in the occluded basilar artery of his brainstem. He administered heparin, an anticoagulant, and artificially raised his blood pressure but neither measure had any appreciable effect. An angiogram showed blood seeping into the basilar artery and small fragments of clotted blood. Occlusion of both vertebral arteries shut down the possibility of a mechanical solution such as angioplasty.

Suddenly, on the second day in the ICU, the patient became totally quadriplegic. Efforts to reverse it failed. Mayer went to the patient’s wife.

“I said, ‘We’re losing him. He’s going to develop this locked-in syndrome. We’ve got to try something.” He added: “The one thing I can think of doing is giving tPA.”

Were circumstances less than extraordinary, that meant breaking all the rules. “Forget the three hour [time window for giving tPA]; this ischemic process had been going on for two days.” Mayer was purposely keeping blood pressure high, at around 220 systolic, another contraindication. So was the anticoagulant he administered. Finally, a diagnosis of arterial dissection was not an approved use for tPA, which raised genuine concern for catastrophic hemorrhage.

“Look,” Mayer told the patient’s wife. “It’s high risk. But I don’t know what else to do. It’s a total roll of the dice and probably won’t work. But otherwise you’re going to just stand around and watch this guy become locked-in.”

With her approval, he administered tPA.

“I’ll be damned,” Mayer recalls. “About an hour later, he started to improve. He started to move both sides.” Sensation and movement fully returned. Within days he would walk out of the hospital.

“From a biological point of view, he was thrombosing [developing blood clots],” recalls Mayer. “By giving the tPA, it was just enough to open everything up.”

Mayer and his colleagues went on to write up the case, published in Neurocritical Care. They hoped to illustrate and underscore that, “Sometimes, when you’re facing certain doom, you can roll the dice, break the rules, as long as you have eyes wide open about the risks and benefits.”

The contrast in outcomes between Mayer’s case and that of Tony Nicklinson also points to the importance of stroke awareness and knowing about the use of tPA to treat stroke, now recommended within 3-4.5 hours of symptom onset.

“I’m already dead – don’t mourn for me,” were Tony Nicklinson’s last words before he died after seven years of unmitigated suffering. When Stephan Mayer’s patient, who was about 60 years old at the time of his stroke, left the hospital after beating incipient locked-in syndrome, he took up a new email address. Its username: notdeadyet.

References

Janjua N, Wartenberg KE, Meyers PM, & Mayer SA (2005). Reversal of locked-in syndrome with anticoagulation, induced hypertension, and intravenous t-PA. Neurocritical care, 2 (3), 296-9 PMID: 16159079

Zivin JA, Simmons J. tPA for stroke: the story of a controversial drug. New York: Oxford University Press; 2011.

Image via olly / Shutterstock.