Are pediatricians missing signs of stroke? Should we intervene? How? Do clot busters work in kids? Clot-retrieval devices?
These were among the questions raised by pediatric neurologist Lori Jordan at a recent Hopkins Children’s grand rounds. The good news is there has been an “explosion of publications” in pediatric stroke research, Jordan said, but the bad news is the information may not be reaching pediatricians. Recent studies show that despite the increase in research pediatricians here and in other countries too often fail to spot the signs and symptoms of stroke in children, resulting in missed or delayed diagnosis.
“Those of us in the pediatric stroke field may be mostly talking to ourselves, reading our own literature and maybe are not disseminating it that well,” Jordan said. “Studies show health-care providers still miss stroke in children.”
Citing a study of 109 children with confirmed stroke at Royal Children’s in Melbourne, Australia – a large tertiary center with well-trained subspecialists – Jordan noted that only one-fourth of the 88 non-neonates in the study had stroke on their initial differential diagnosis list (Pediatrics 2009;124;e227-e234).
“And this was in a group of kids in which more than 80 percent had a focal motor deficit,” said Jordan. “To make matters worse, 60 percent of the patients were inpatients at the time of the stroke.”
The biggest problem in delay of diagnosis, the study found, was physician lack of awareness regarding stroke in children. But the timing and type of imaging can make a difference in detection, too, Jordan said, noting that the time from onset of symptoms to initial imaging ranged from an average of 11.4 hours for inpatients to 9.4 hours for outpatients. Only 8 children had MRI as initial imaging, Jordan added, while 74 children had CT, which, she noted, can miss ischemic stroke, especially when it’s done within the first 12 hours.
“So, a negative CT scan shouldn’t reassure you,” said Jordan. “There are issues of sedation with MRI, and it’s not possible in every case. But this study is a good illustration that often you’re wasting your time with CT.”
When and how should pediatric neurologists intervene? Jordan noted that she most often gets paged from the ED for a stroke consult when the child arrives within three hours of the onset of stroke symptoms. And the first question from the ED, Jordan said, is “Should we give tPA?”
In adults, tPA, or tissue plasminogen activator, and other so-called “clot busters” have proved effective in reducing damage to the brain in ischemic stroke if given within the first few hours after symptoms begin. But pinpointing when symptoms begin, especially in children, is problematic.
“I often say ‘Let’s take a step back.’ The time window for thrombolytics is based upon when the person was last seen normal,” said Jordan. “Just because the mom says he woke up three hours ago and he wasn’t moving his arm doesn’t mean the stroke happened three hours ago. It may have happened when he went to sleep the night before. A lot of people, both adults and children, come to the ED not really meeting the criteria for tPA.”
Even when a patient may meet the criteria, Jordan said, administering thrombolytics is far from a simple decision when the patient is a child. Jordan recalled what an MRI scan with contrast dye showed in the case of an adolescent who suffered stroke symptoms of right hemiparesis, or weakness, and trouble speaking – a perfusion-diffusion mismatch that predicted more damage to the brain without immediate intervention.
“You could see the size of the stroke that’s going to happen if you don’t do anything about it,” said Jordan.
Consulting with the family, Jordan did not recommend tPA or clot retrieval for her adolescent patient. (Corkscrew-like clot-retrieval devices are not recommended for use in children because of their narrow blood vessels.) The patient had been assessed some 12 hours since the onset of symptoms, Jordan explained, and the damage wasn’t significant. Yes, there was a risk of additional injury, imaging showed, but re-perfusing her outside the time window raised her risk of a worse outcome.
“If you have a lot of brain that’s injured and tissue is dying, putting a blood thinner into it may make the blood vessels leaky,” Jordan said. “With a stroke of more than three or six hours, your chances of having a massive hemorrhage are much higher.”
Also, Jordan’s review of the literature on the extent and the nature of the use of thrombolytics in childhood ischemic stroke suggested greater caution before intervening with clot busters. In a large international trial of 687 children with ischemic stroke – part of the International Pediatric Stroke Study (IPSS) of which Hopkins Children’s is a participant – only 15 children received tPA. Compared to published case reports, Jordan concluded, children in the study and receiving tPA were younger, more likely to receive thrombolysis outside the established adult time frame, and tended to show poorer neurological outcomes.
“The range of when people got tPA was from one hour to 54 hours,” Jordan said. “Some kids got tPA in outside EDs by an adult provider, who probably did not ask enough questions about when the child was last seen normal.”
The findings, Jordan noted, stress the need for a safety and dose-finding study for tPA in children. And the take-home message for pediatricians and pediatric neurologists?
“When you’re confronted with a child with a stroke, think about methods to support cerebral perfusion. If you go with tPA, give small, very careful doses right at the clot,” Jordan said. “If you’re not going to use tPA, document why.
Jordan recommends an angiogram to confirm that the child still has a clot in the area needing reperfusion. Other issues include confirmation that the child is not receiving a blood thinner, does not have a coagulation disorder, high blood pressure, or suffer seizures, which may mimic a stroke.
The chances of having a poor outcome – and recurrence – of pediatric stroke, Jordan noted, is also associated with cerebral arteriopathy, according to another recent study (“Cerebral Arteriopathy and Peds Stroke: Increasingly Recognized,” Circulation 2009;119:1417-1423). Noting that researchers found arteriopathy in over 50 percent of pediatric stroke cases, Jordan said, “If you see a kid with stroke, get a good quality MRA, review the case carefully, follow the abnormality, and make a treatment decision that is individualized. And don’t be anxious to anti-coagulate a lot of children.”