Functional MRI of neuronal activation in epilepsy patients with malformations of cortical development
Introduction
Approximately 30% of patients with focal epilepsy do not respond to drug treatment (Liu, 2000). These patients experience a greatly reduced quality of life, as they are prone to frequent uncontrolled seizures. Surgical treatment is a reasonable option for those suffering from focal intractable epilepsy provided the seizure focus is localized and safe to resect (Mathern, 2009). Epileptic seizures, derived from uncontrolled electrical discharges predominantly in the cortex, are increasingly associated with malformations of cortical development (MCD) (Kuzniecky and Barkovich, 1996, Kuzniecky and Barkovich, 2001, Barkovich and Raybaud, 2004, Kuzniecky, 2006, Gungor et al., 2007a, Gungor et al., 2007b, Leventer et al., 2008). MCDs are disturbances in brain formation resulting from abnormalities that affect the processes of cortical development (Kuzniecky and Barkovich, 2001). Approximately 25–40% of intractable childhood epilepsy is associated with MCDs and 75% of patients with MCDs will develop epilepsy (Kuzniecky and Barkovich, 2001). Prior to surgical intervention the epileptogenic and eloquent cortical zones of the patient's brain must be mapped. In patients with central and rolandic MCDs this task can be quite challenging due to the fact that those zones generally lack anatomical definition. Functional MRI allows the non-invasive visualization and mapping of human brain function (Friston et al., 1999, Francis et al., 2000, Jancke et al., 2000, Rodrigo et al., 2008, Muller et al., 2009). Functional MRI infers brain activity by detecting changes in cerebral blood flow linked to neuronal activation. Increased neuronal activity in functioning areas of the brain reduces local oxygen concentration that leads to increased blood flow. Functional MRI is becoming the diagnostic method of choice for the evaluation of brain performance for critical functions such as movement, sensation, thought, and speech (Zhuang et al., 2005, Rodrigo et al., 2008, Etzel et al., 2009, Muller et al., 2009, Cheng et al., 2012). It has been used to monitor growth and function and to identify cortical reorganization in patients suffering from brain tumors, strokes, trauma and degenerative diseases (Gao et al., 2001, Araujo et al., 2006, Rodrigo et al., 2008, Cheng et al., 2012).
Functional MRI is also becoming an effective tool in the detection of cortical reorganization in patients suffering from temporal lobe epilepsy (Carpentier et al., 2001, Gao et al., 2001, Baciu et al., 2003, Szaflarski et al., 2008). Most of these studies address the dissociation in language regions in epileptic patients and stress the importance of language center reorganization in those patients prior to consideration for surgical resection (Carpentier et al., 2001, Araujo et al., 2006, Cheung et al., 2006, Rodrigo et al., 2008, Szaflarski et al., 2008). Vitali et al. (2008) have also shown functional activation in dysplastic neural tissue in patients suffering from MCD (Vitali et al., 2008).
The aim of the current study was to determine whether functional reorganization occurs in patients with epileptogenic malformations of cortical development and to evaluate the use of fMRI as a tool for the assessment of brain reorganization. Such information would be beneficial for the surgical planning and treatment of these patients.
Section snippets
Patient recruitment
Eleven patients (four male, seven female), with medically intractable focal epilepsy due to MCDs, with a mean age of 36 years (range 18–55 years) and a mean age at epilepsy onset of 23 years (range 3–55 years) were recruited for this study and were required to provide informed consent prior to participation. The study was approved by Western University Health Sciences Research Ethics Board. All patients underwent pre-surgical evaluation within the Epilepsy program in the University Hospital.
Results
The mean age of patients was 36 years (range 18–55 years), while the mean age at epilepsy onset was 23 years (range 3–55 years). Table 1 summarizes the demographic and clinical characteristics of all patients that participated in the study. Of the 11 patients with malformations of cortical development two had polymicrogyria (PM), three had heterotopia (HT), and four had cortical dysplasia (CD). Patient 1 (P1) presented with left PM and bilateral perisylvian CD with a small focal band of HT
Discussion
All controls recruited for this study had very consistent reproducible fMRI activation. Activations were well defined and confined to the rolandic cortex in comparison with the MCD patients and were indicative of properly organized motor cortex. Average control activation was calculated using a second level 1 sample t-test analysis in SPM. In contrast, the activity in the patient population was highly variable and consequently, patients’ results were presented individually. When presenting
Conclusion
This study showed evidence of functional reorganization of sensory and motor cortices in patients with malformations of cortical development. Patients with polymicrogyria did not present with significant functional reorganization and patients with heterotopias and coexisting polymicrogyria and/or cortical dysplasia had variable patterns of activation. Such information should be carefully considered in surgical planning and treatment of patients with malformations of cortical development. These
Conflicts of interest
None of the authors has any conflicts of interest to disclose.
Funding
Funding for this project was provided by the Ontario Brain Institute EpLink Discovery Project.
Acknowledgements
The authors would like to thank the research study coordinator Suzan Brown for her diligent work on patient recruitment and pre-screening.
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