Correspondence

www.thelancet.com/neurology Vol 8 March 2009 225

Perilesional brain oedema and seizure activity: cause or eff ect?

We read the article by Nash and coauthors1 with great interest. In their study, new oedema around calcifi ed lesions occurred in 50% of the participants who had seizures. The authors attributed the oedema to an infl ammatory response to calcifi ed granulomas and proposed that this is an important part of the epileptogenesis seen in patients with calcifi ed lesions. However, further characterisation of the nature of the oedema (ie, whether it was cytotoxic or vasogenic) with other MRI modalities was not done.

There is, indeed, substantial evidence to implicate calcifi ed lesions as seizure-causing foci, but whether the presence of perilesional oedema proves this point is doubtful, because seizures per se can also cause oedema.

Reversible peri-ictal MRI abnormal-ities (RPMA) are well established fi ndings that develop immediately after one or a cluster of seizures and resolve within a few days or weeks of the ictus. RPMA are thought to be a consequence of the epileptic activity, rather than the cause.2–4 When they are confi ned to the region of the epileptiform discharges seen on EEG, RPMA can be local; when the changes are located in areas that are distant from the region of the epileptiform activity, RMPA can be remote.3,4

RMPA can be seen as T2-weighted hyperintensity, T1-weighted hypo-intensity, fl uctuations in the apparent diff usion coeffi cient on diff usion-weighted imaging, vasogenic and cytotoxic oedema, contrast enhance-ment, and evidence of mass eff ect (sulcal eff acement or ventricular compression). Occasionally, the changes might be irreversible.3,4

The precise pathogenesis of RPMA is unknown. Several mechanisms related to excessive activity of focal seizures, such as hyperperfusion,

impaired autoregulation, disruption of the blood–brain barrier, cytotoxic and vasogenic oedema, and excitotoxic cell damage, have been implicated.2,3 These changes can be seen even after just one seizure and in the ictal-onset zone in non-lesional epilepsy.4,5 Moreover, in the study by Nash and coauthors, all the patients who had perilesional oedema after a seizure had MRI within 5 days of the ictus, which is the period during which peri-ictal changes are most likely to develop. RPMA must, therefore, be deemed to be a potential cause of the perilesional oedema, and to regard perilesional oedema as an important cause of neurocysticercosis-associated morbidity might be erroneous.

The occurrence of perilesional oedema in the control group, who did not have seizures, is intriguing, and might indicate an underlying subclinical epileptic focus, with the patient being seizure free when on antiepileptic medication. The EEG data could help to resolve this confl ict.

The puzzling question of why perilesional oedema occurred in some patients but not in others was also discussed by the authors. Similarly, the question of why only some patients develop RPMA is still unanswered.These changes can fi rst appear days or weeks after seizure onset, which suggests that there is a threshold of seizure duration or severity, below which the changes will not occur. This threshold is likely to vary from person to person and might be aff ected by many factors, such as: seizure type and location; seizure duration and the severity of ictal discharge; and the characteristics of the host (eg, age, pre-existing disorders, cardiovascular and metabolic reserve, and pharmacological intervention).3

We have no confl icts of interest.

Abhijit Das, Chandrasekharan Kesavadasabhijit.neuro@gmail.com

Departments of Neurology and Imaging Sciences and Interventional Radiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum 695011, Kerala, India

1 Nash TE, Pretell EJ, Lescano AG, et al, for the Cysticercosis Working Group in Peru. Perilesional brain oedema and seizure activity in patients with calcifi ed neurocysticercosis: a prospective cohort and nested case–control study. Lancet Neurol 2008 ; 7: 1099–105.

2 Briellmann RS, Wellard RM, Jackson GD. Seizure associated abnormalities in epilepsy: evidence from MR imaging. Epilepsia 2005; 46: 760–66.

3 Cole AJ. Status epilepticus and periictal imaging. Epilepsia 2004; 45: 72–77.

4 Raghavendra S, Ashalatha R, Krishnamoorthy T, Kesavadas C, Thomas SV, Radhakrishnan K. Reversible periictal MRI abnormalities: clinical correlates and long-term outcome in 12 patients. Epilepsy Res 2007; 73: 129–36.

5 Oh JB, Lee SK, Kim KK, Song IC, Chang KH. Role of immediate postictal diff usion-weighted MRI in localizing epileptogenic foci of mesial temporal lobe epilepsy and non-lesional neocortical epilepsy. Seizure 2004; 13: 509–16.

Authors’ replyIn our article,1 we prospectively evaluated the incidence of peri-lesional oedema only in patients with neurocysticercosis who had calcifi ed granulomas. Because we found perilesional oedemas in 50% of the patients who had seizures, we made the association between the two. The design and purpose of our study was not to assign cause—the pathophysiology and cause of perilesional oedema are not known—and we reiterated this point in our introduction. In earlier studies,2,3 there were opportunities to discuss the potential causes of perilesional oedema, including seizure activity itself; however, space limitations prevented an expanded discourse on this in our discussion. We do mention that the “most plausible hypothesis is that oedema is an infl ammatory response to the calcifi ed granulomas”; most of the pathophysiology of cysticercosis is caused by the host’s infl ammatory response to the parasite, and this might be a continuation of that process.

Patients with other types of epilepsy or seizures can have reversible oedema.4,5 However, even though oedema has been seen at seizure foci, and some oedema are similar to the perilesional oedema seen in patients with neurocysticercosis, for the most part this oedema is associated with