COLUMBUS, OHIO—The dearth of data and the absence of FDA-approved drugs and devices complicate the treatment of children with stroke, according to an overview presented at the 43rd Annual Meeting of the Child Neurology Society. Although stroke requires urgent action, a neurologist may be unsure about how to proceed.
Organizations such as the American Heart Association have provided guidelines that may help neurologists make treatment decisions, however. It can be helpful for a neurologist to discuss a pediatric patient with colleagues and stroke specialists to make sure that all options are considered and no facet of the decision is overlooked.
“Every child neurologist should know how to care for pediatric stroke,” said Catherine Amlie-Lefond, MD, Director of the Pediatric Vascular Neurology Program at Seattle Children’s Hospital. Stroke specialists can prepare their neurology colleagues to treat pediatric stroke, just as these colleagues can help stroke specialists treat disorders such as epilepsy, she added.
Is t-PA Appropriate for Pediatric Stroke?
Several questions about the treatment of pediatric stroke have no clear answer. Perhaps the most common of these questions is whether it is appropriate to administer t-PA to a child with an acute stroke. Although neurologists understand that all eligible adults with stroke should receive t-PA, the drug is not recommended for children because no data about its safety and efficacy in this population are available.
Current knowledge can assist in this decision, however. In adults with stroke, t-PA improves neurologic outcomes, but administering the drug more than 4.5 hours after stroke onset is not likely to be beneficial. Children may share many risk factors (eg, lesion size) that are common among adults, said Dr. Amlie-Lefond.
Other concerns, however, are more acute for pediatric patients. For example, children treated with t-PA are at risk of intracranial hemorrhage and may be more susceptible than adults to the drug’s potential neurotoxicity. In addition, t-PA breaks down the blood–brain barrier, may increase lesion size, and may lead to systemic bleeding.
“We usually will start antiplatelet or antithrombotic medications immediately in children who present with stroke,” said Dr. Amlie-Lefond. “If they have been given t-PA, we like to hold off for 24 hours. We try to avoid extreme hypertension, but in children we are often dealing with collateral arteries, or we are trying to perfuse a partial occlusion, and we really do not know what the optimal blood pressure is for maintaining that perfusion.”
It may be safe and effective to administer t-PA to a child, but this treatment should be given within the safety guidelines established through the Thrombolysis in Pediatric Stroke trial, she added. The drug may pose less risk to older children than to younger children. Neurologists should ensure in advance that they have the infrastructure to administer t-PA and to monitor the children. “I would also make sure that I have an informed consent conversation with the parents,” said Dr. Amlie-Lefond.
Which Type of Neuroimaging Is Necessary?
Another question is which type of neuroimaging, if any, is necessary before administering t-PA. Faced with an acute stroke, a neurologist will want to minimize the time that elapses before treatment is delivered. Approximately one-fifth of children with suspected stroke have a stroke mimic such as migraine, seizures, hemiparesis following a seizure, tumor, infection, or psychogenic diagnoses. Research has established the safety of lytics when they are administered to adult patients with stroke mimics.
“The flipside of the argument is that you need to confirm the stroke,” said Dr. Amlie-Lefond. “You want to confirm that you have a stroke before you use a therapy with potential risk, and you want to prevent diagnostic delay of mimics.” MRI and diffusion-weighted imaging or CT and CT angiogram can confirm stroke if MRI and magnetic resonance angiography (MRA) are not available.
Which Dose of t-PA Is Best for Children?
Neurologists have not established a consensus about whether the appropriate pediatric dose of t-PA is 0.75 mg/kg or 0.9 mg/kg. It is not appropriate to extrapolate the dose from adults to children, and no researchers have studied the pharmacokinetics of t-PA in children.
Children may need the higher dose because they have less t-PA at baseline and more plasminogen activator inhibitor-1. Furthermore, children have a larger volume of distribution and more rapid hepatic clearance than adults. “That said, children will often lyse clots fairly quickly, so we are not sure we really understand the full story of how lysis occurs with or without t-PA in children,” said Dr. Amlie-Lefond.
“I usually use a t-PA dose of 0.9 mg/kg,” she continued. “I do have colleagues that use 0.75 mg/kg, but I prefer to use 0.9 mg/kg. I do not go above the FDA-recommended dose for adults.”