periictal_pseudoprogression

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.

These radiographic changes are not as well studied in the brain tumor population. Moreover, reversible neuroimaging abnormalities following seizure activity may be misinterpreted for tumor progression and could consequently result in unnecessary tumor-directed treatment.

2016

Dunn-Pirio et al describe two cases of patients with brain tumors who developed peri-ictal pseudoprogression and review the relevant literature 1).

2013

A total of 406 consecutive patients with newly diagnosed HGGs were retrospectively reviewed. The incidence of seizures during the management was investigated. In patients who experienced a seizure, the causality between seizures and disease progression was assessed by pre-ictal, post-ictal (<1 month), and follow-up (<3 months) MRI. After a median follow-up of 17.4 months (range 0.1-88.3), seizures developed in 127 patients (31 %). Of the 127 patients, radiological progression at the post-ictal MRI was found in 83 patients (65 %) and the follow-up MRI confirmed progression in 79 patients (62 %). Four other patients (3 %) were shown to be progression-free. Among those without radiological progression at the post-ictal MRI, the follow-up MRI confirmed progression-free in 31 patients (24 %); however, 13 patients (10 %) revealed eventual progression. In the patients with a seizure, absence of preoperative seizures (p = 0.003), <95 % tumor resection (p = 0.001), and pre-ictal Karnofsky Performance Scale score ≤ 70 (p = 0.025) were significantly associated with disease progression. During the management of HGG, 31 % of patients experienced seizures; of these patients, 72 % harbored progressive disease. The post-ictal MRI is useful for detecting disease progression; however, there are pitfalls. Clinical settings should be considered together for diagnosing disease progression in patients with seizures 2).

2011

Rheims et al 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 3).

2007

Finn et al describe 3 patients with brain tumors and transient postictal MRI changes that mimicked disease progression and infection.

The patients demonstrated fluid-attenuated inversion recovery/T2 hyperintensity and gadolinium enhancement on MRI studies performed shortly after ictal events. These changes were suspicious for tumor progression in 2 cases and for recurrent infection in the third. Control of seizure activity resulted in resolution of these changes on scans obtained 10 to 21 days later.

Imaging shortly after an ictal event can potentially mislead the clinician to interpret changes as tumor or pathologic progression. Unnecessary intervention in these patients with new and suspicious imaging findings should be avoided. We recommend repeat imaging be performed in patients with brain tumors and seizures several weeks after seizure control if clinically feasible. Further research is needed to delineate the time course of seizure-induced MRI changes 4).

2014

A 55-year-old man presented with difficulty in speaking. He had undergone complete resection of right frontal low grade glioma [WHO Grade II oligoastrocytoma] in 2008, followed by 27 fractions of radiotherapy [200cGy/#, total dose of 5400cGy]. Interval magnetic resonance imaging (MRI) scans had shown only focal encephalomalacia in the right frontal region. He was asymptomatic in the interim. Ten days prior to presentation he developed word finding difficulty and severe continuous right sided headache. He was admitted with history of four episodes of vomiting and a generalized seizure. Contrast MRI done outside was normal. Examination revealed global aphasia, left lower facial palsy and a left arm pronator drift. He had five more complex partial seizures in the hospital. Electroencephalograph (EEG) was normal. He was treated with intravenous anticonvulsants, levetiracetam, sodium valproate and phenytoin sodium. Repeat contrast magnetic resonance imaging (MRI) showed new changes of unilateral cortical thickening and gyriform hyperintensity in right frontal lobe, right insular cortex and transverse temporal gyri with borderline reduction in ADC. Patchy gyriform enhancement was seen involving the leptomeninges over the right fronto-temporal region.

Cerebrospinal fluid (CSF) examination was normal. The clinico-radiological picture was suggestive of PIPG and dexamethasone 24 mg/day was added to his regimen. He improved over 10 days and repeat contrast MRI after 2 weeks showed total resolution of contrast enhancement. After 14 days, he had only mild residual anomia 5).


1)
Dunn-Pirio AM, Billakota S, Peters KB. Postictal Magnetic Resonance Imaging Changes Masquerading as Brain Tumor Progression: A Case Series. Case Rep Oncol. 2016 Jun 27;9(2):358-62. doi: 10.1159/000447350. eCollection 2016 May-Aug. PubMed PMID: 27462237.
2)
Kim YH, Park CK, Kim TM, Choi SH, Kim YJ, Choi BS, Han JH, Lee SH, Kim CY, Kim IA, Heo DS, Kim IH, Kim DG, Jung HW. Seizures during the management of high-grade gliomas: clinical relevance to disease progression. J Neurooncol. 2013 May;113(1):101-9. doi: 10.1007/s11060-013-1094-6. Epub 2013 Mar 4. PubMed PMID: 23459994.
3)
Rheims S, Ricard D, van den Bent M, Taillandier L, Bourg V, Désestret V, Cartalat-Carel S, Hermier M, Monjour A, Delattre JY, Sanson M, Honnorat J, Ducray F. Peri-ictal pseudoprogression in patients with brain tumor. Neuro Oncol. 2011 Jul;13(7):775-82. doi: 10.1093/neuonc/nor082. PubMed PMID: 21727213; PubMed Central PMCID: PMC3129278.
4)
Finn MA, Blumenthal DT, Salzman KL, Jensen RL. Transient postictal MRI changes in patients with brain tumors may mimic disease progression. Surg Neurol. 2007 Mar;67(3):246-50; discussion 250. Epub 2006 Nov 3. PubMed PMID: 17320628.
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