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Seizure at the Onset of an Ischemic Stroke Does Not Predict Poor Prognosis in Patients Receiving IV Thrombolysis

Article In Brief

Those with seizure at the onset of ischemic stroke experienced higher stroke severity and higher levels of dependence than did their counterparts who did not have a seizure. But the seizure at onset of a stroke was not an independent predictor for symptomatic-intracranial hemorrhage, death, or poor functional outcome at three months after the stroke.

It is not necessary to withhold potentially lifesaving intravenous thrombolysis (IVT) for patients who experience seizure at the onset (SaO) of an ischemic stroke, researchers suggested based on an analysis of data on patients with stroke receiving IVT at nine European stroke centers.

The researchers found those with SaO experienced higher stroke severity, more prior stroke, and higher levels of dependence than their counterparts who did not have a seizure. But SaO of a stroke was not an independent predictor for symptomatic-intracranial hemorrhage (sICH), death, or poor functional outcome at three months after the stroke.

“Whether to use or refrain from IVT in SaO patients is controversial, as there is currently hardly any evidence that would allow balancing risks versus benefit of IVT in these patients,” the authors of the study wrote in the paper published online August 21 in Annals of Neurology. “With this study we provide data indicating that in patients treated with IVT for acute ischemic stroke, functional outcome as well as the odds for complications including sICH and mortality are not modified by the presence or absence of SaO.”

Lead researcher Alexandros Polymeris, MD, of University Hospital Basel in Switzerland, told Neurology Today: “We found that SaO is not an independent predictor of poor prognosis among patients treated with IVT for suspected ischemic stroke. Stroke neurologists should not be discouraged from treating with IVT in otherwise eligible patients with seizure at the onset of an acute stroke syndrome, especially when advanced imaging such as MRI, angiography and perfusion studies, further corroborate the diagnosis of an ischemic stroke.”

Study Design, Findings

Dr. Polymeris and colleagues analyzed data from approximately 10,000 patients with suspected acute ischemic stroke who received IVT treatment followed by endovascular treatment at nine European stroke centers that are part of the ThRombolysis in Ischemic Stroke Patients (TRISP) Collaboration.

They found that 146 patients in the sample experienced SaO. These patients had a riskier baseline profile than those without SaO: They had significantly higher NIH Stroke Scale scores (p< 0.001) than those without SaO, more often experienced prior stroke (25.7 percent vs 16.5 percent, p= 0.005), and prior functional dependence (16.4 percent vs 7.6 percent, p< 0.001). More often, they also had a final diagnosis of a stroke mimic (39 percent vs 2.1 percent, p< 0.001) than patients without SaO.

Researchers controlled for multiple confounding factors in patients with SaO such as presence or absence of electrolyte abnormalities, hypoglycemia, chronic ischemic brain lesions, intracranial tumors, brain vascular malformations, meningoencephalitis, dementia or other neurodegenerative disease, multiple sclerosis or other neuroinflammatory disease, and psychiatric or neurodevelopmental disorders.

At three months, and after adjusting for confounders, there were no differences in the odds for developing sICH and for mortality among those who had SaO and those who did not.

Among the 146 patients with SaO, 46 percent received on-the-spot antiepileptic treatment, and half received long-term antiepileptic treatment. The most common potentially confounding factors in SaO patients were chronic ischemic brain lesions in 30 patients (20.5 percent) and prior use of antiepileptic drugs and/or benzodiazepines in 28 patients (19.2 percent).

Some of the study limitations include the fact that the TRISP Collaboration included only IVT-treated patients and there was no comparison group of patients with SaO not treated with IVT, according to the authors. In addition, patients with unwitnessed stroke onset might have had an unobserved seizure and might therefore have been misclassified as non-SaO.

Dr. Polymeris said that in the future, he would like to examine patients that develop a seizure during IVT administration. “In clinical practice this might often lead to discontinuation of the IVT infusion and urgent brain imaging to exclude intracranial bleeding. However, it has been proposed that seizures occurring during IVT might be a sign of treatment success, arising due to reperfusion of the ischemic brain tissue. Obtaining more data on these relatively rare but challenging cases will be of clinical relevance for stroke neurologists,” he said.

Expert Commentary

“The relative contraindication for the use of IV alteplase in patients who had a seizure associated with stroke has been due to the general lack of relevant data from randomized trials. These patients were excluded from the NINDS t-PA trial, in part because treatment of those with a post-ictal Todd's paralysis rather than stroke would dilute the population, making the detection of a treatment effect more difficult,” said Larry B. Goldstein, MD, FAAN, the Ruth L. Works professor and chair of neurology at the University of Kentucky and co-director of the Kentucky Neuroscience Institute.

Figure

“Stroke neurologists should not be discouraged from treating with IVT in otherwise eligible patients with seizure at the onset of an acute stroke syndrome, especially when advanced imaging such as MRI, angiography and perfusion studies, further corroborate the diagnosis of an ischemic stroke.”—DR. ALEXANDROS A. POLYMERIS

Figure

“As the authors point out, the reason for including SaO as a contraindication was to prevent stroke mimics from being exposed to the risk of IV tPA. The accumulated data on stroke mimics indicates that they have a low rate of sICH, so fear of treating mimics should not be a contraindication to treatment.”—DR. CAROLYN CRONIN

Dr. Goldstein added that there was no specific reason to believe the patients would be harmed, provided they otherwise met the trial's inclusion and exclusion criteria. “The current American Heart Association guidelines indicate that IV alteplase [tPA] is reasonable in patients with a seizure at the time of onset of acute stroke if evidence suggests that residual impairments are secondary to stroke and not a post-ictal phenomenon. We certainly treat such patients if we believe their deficits are potentially serious and related to stroke rather than the residual effects of a seizure.”

Joseph P. Broderick, MD, FAAN, professor in the department of neurology and rehabilitation medicine and director of the University of Cincinnati Gardner Neuroscience Institute, identified some of the decision-making skills required by clinicians when encountering a patient with SaO.

“The major issue with seizures at onset of a stroke with a persisting neurologic deficit before hospital arrival or before treatment decision for reperfusion therapy with tPA is knowing whether the patient is experiencing post-ictal neurologic deficits from a seizure due to prior brain injury, or having a seizure related to new focal ischemic stroke,” Dr. Broderick said. “If we knew it was for sure the former, we wouldn't give tPA because it wouldn't help patients and carries some small risk. These patients are the stroke mimics, which are much higher in the SaO group.”

Dr. Broderick noted that neurologists normally obtain brain vessel imaging to see if a major artery is blocked to help differentiate between the two groups. “If there is occlusion, there is likely an acute stroke that is the cause of the seizure and we will treat with tPA and endovascular treatment afterward as needed.

“The article is reassuring clinicians that using tPA, even when you are uncertain about whether seizure is due to old stroke, another old brain injury, or new stroke, doesn't worsen outcomes or increase the risk of sICH compared to persons without SaO,” he noted. “That is probably a reasonable conclusion and is consistent with prior research that tPA in stroke mimics has a very low risk of sICH. But if you do know that seizure is due to acutely blocked artery and newly ischemic brain, tPA and endovascular treatment as needed are appropriate treatments.”

“It is my practice to treat stroke patients with IV tPA if seizure at onset is their only potential contraindication,” said Carolyn Cronin, MD, PhD, associate professor of neurology and director of the neurology residency program at the University of Maryland School of Medicine.

Figure

“The article is reassuring clinicians that using tPA, even when you are uncertain about whether seizure is due to old stroke, another old brain injury, or new stroke, doesnt worsen outcomes or increase the risk of sICH compared to persons without SaO. That is probably a reasonable conclusion and is consistent with prior research that tPA in stroke mimics has a very low risk of sICH. But if you do know that seizure is due to acutely blocked artery and newly ischemic brain, tPA and endovascular treatment as needed are appropriate treatments.”—DR. JOSEPH P. BRODERICK

“As the authors point out, the reason for including SaO as a contraindication was to prevent stroke mimics from being exposed to the risk of IV tPA,” Dr. Cronin said. “The accumulated data on stroke mimics indicates that they have a low rate of sICH, so fear of treating mimics should not be a contraindication to treatment.”

“This study provides additional support for removal of SaO from the IV tPA contraindications list in the American Heart Association guidelines,” Dr. Cronin added, “and hopefully will help this change in practice become widely adopted so that patients who may benefit from tPA do not have treatment withheld for unfounded reasons.”

Disclosures

Dr. Polymeris had no disclosures.

Link Up for More Information

• Polymeris AA, Curtze S, Erdur H, et al; for the TRISP Collaborators. Intravenous thrombolysis for suspected ischemic stroke with seizure at onset https://onlinelibrary.wiley.com/doi/full/10.1002/ana.25582. Ann Neurol 2019; Epub 2019 Aug 21.