Send Correspondence to journal:
Re: Seizures during stroke thrombolysis heralding dramatic neurologic recovery

We read with interest the article by Rodan et al who report three patients with a severe acute stroke who experienced a generalized tonic-clonic seizure during thrombolysis with tissue plasminogen activator (tPA). [1] All patients had a dramatic neurological recovery.

The authors postulate that the seizures were a consequence of acute reperfusion and therefore should be considered a marker of good outcome provided that imaging can exclude secondary hemorrhage. The acute NIH Stroke Scale (NIHSS) is a valid predictor of long-term outcome and immediate quasi-complete recovery from a high initial NIHSS score is unusual, although it might be more frequent with tPA treatment. [2] We would like to initiate further discussion on the acute occurrence of seizures during or before tPA treatment and its influence on the diagnosis and prognosis. First, the seizure itself could not only be a marker but a key player in the good recovery. In two of the patients, GTCS and the associated increase of arterial and intracranial pressure might have contributed to the thrombolytic process. This could have helped the reperfusion further, by improving the access of tPA to the clot or dislodging it with the pressure surge.

A rapid increase of unknown metabolic factors triggered by the seizures, a protective role of post-ictal inhibitory cellular mechanisms, or a direct mechanical thrombolytic role of the convulsions may also be speculated. Second, it should not be forgotten that a clinical or subclinical epileptogenic activity could lead to an overestimation of the initial NIHSS, which is why the occurrence of convulsive seizures has long represented an absolute contra-indication to thrombolysis.

Focal seizures preceding the observed seizures might not have been recognized because of subtle clinical presentation or purely negative motor symptoms. Such atonic seizure can precisely occur in parietal lobe seizure, which was the site of the reperfusion in patient three. [3] Seizures in the post-acute phase may have direct negative effects on the brain tissue. The focal hypermetabolic demand associated with epileptogenic activity makes the hypoperfused cortex more at risk for cellular death. The occurrence of seizures in patients with established vascular lesions can permanently worsen the neurological outcome [4] and requires anti-epileptic treatment (AET).

In this situation, AET such as sodium valproate with its neuroprotective properties, in animal studies [5] as well as action on platelets, could have more than just an antiepileptogenic effect. This reported dramatic recovery in patients with acute seizures during tPA should motivate further studies on the role of seizures in stroke recovery.

References

1. Rodan LH, Aviv RI, Sahlas DJ et al. Seizures during stroke thrombolysis heralding dramatic neurologic recovery. Neurology. 2006;67:2048-2049.

2. Felberg RA, Okon NJ, El-Mitwalli A et al. Early dramatic recovery during intravenous tissue plasminogen activator infusion: clinical pattern and outcome in acute middle cerebral artery stroke. Stroke. 2002;33:1301- 1307.

3. Satow T, Ikeda A, Yamamoto J et al. Partial epilepsy manifesting atonic seizure: report of two cases. Epilepsia. 2002;43:1425-1431.

4. Bogousslavsky J, Martin R, Regli F et al. Persistent worsening of stroke sequelae after delayed seizures. Arch Neurol. 1992;49:385-388.

5. Costa C, Martella G, Picconi B et al. Multiple mechanisms underlying the neuroprotective effects of antiepileptic drugs against in vitro ischemia. Stroke. 2006;37:1319-1326.