Peri-ictal pseudoprogression in patients with brain tumor

Abstract

Recent advances in the treatment of malignant gliomas have highlighted the fact that the appearance of new contrast-enhancing lesions on magnetic resonance imaging (MRI) is not always indicative of tumor recurrence. It has been suggested that transient seizure-related MRI changes could mimic disease progression (peri-ictal pseudoprogression [PIPG]). However, the clinical and MRI features associated with this situation have not been well described. Here, we consulted the databases of 6 institutions to identify patients with brain tumor who presented during the follow-up period transient MRI lesions wrongly suggesting tumor progression in a context of epileptic seizures. Ten patients were identified. All patients but 1 were long-term survivors who had initially been treated with radiotherapy. The PIPG episode occurred after a median interval of 11 years after radiotherapy. MRI features were highly similar across patients and consisted of transient focal cortical and/or leptomeningeal enhancing lesions that erroneously suggested tumor progression. All patients improved after adjustment of their antiepileptic drugs and transient oral corticosteroids, and MRI findings were normalized 3 months after the PIPG episode. Two patients demonstrated several seizure relapses with the same clinicoradiological pattern. After a median follow-up period of 3.5 years after the initial PIPG episode, only 1 patient presented with a tumor recurrence. In conclusion, in patients with brain tumor, especially in long-term survivors of radiotherapy, the appearance of new cortical and/or leptomeningeal contrast-enhancing lesions in a context of frequent seizures should raise the suspicion of PIPG. This phenomenon is important to recognize in order to avoid futile therapeutic escalation.

Fig. 1.

Peri-ictal and follow-up T1-weighted imaging after the administration of gadolinium contrast material in patient 10. In October 2006, the patient had 3 generalized seizures, and MRI revealed a right temporal lesion with slight nodular enhancement, initially assumed to be an ischemic lesion. After the introduction of an antiepileptic drug, the control MRI showed a nonenhancing temporal lesion. The patient benefited from near total resection of this lesion in March 2008, and pathological examination of the surgical specimen showed low-grade oligodendroglioma with combined 1p/19q loss. At the most recent follow-up in March 2010, the patient was in complete remission.

Fig. 2.

Peri-ictal and follow-up T1-weighted imaging after administration of gadolinium contrast material in patients 1–9.

Fig. 3.

Examples of peri-ictal pseudoprogression (PIPG) relapse in patients 6 and 9 (T1-weighted imaging after administration of gadolinium contrast material). Patient 6 was treated with surgery, radiotherapy, and adjuvant chemotherapy for a right-side parietal glioblastoma. Eight years after radiotherapy, he presented with a first PIPG episode, which was resolved with oral corticosteroids and an adjustment of his antiepileptic drugs. A second episode of PIPG was observed 5 years later and was treated by antiepileptic drug adjustment only. At the most recent follow-up in October 2010, the patient was in complete remission. Patient 9 was treated with surgery, radiotherapy, and adjuvant chemotherapy for a right fronto-temporal high-grade oligodendroglioma. Three years after radiotherapy, he presented a first episode of PIPG, which resolved with adjustment of antiepileptic drugs and oral corticosteroids. Thereafter, he demonstrated 2 other PIPG episodes, including one related to subclinical epileptic discharges only. At the most recent follow-up visit in October 2010, he was still in complete remission.