Focal Cortical Dysplasias and Epilepsy: Characteristics of Histopathology and 7 tesla MRI.

Focal Cortical Dysplasia (FCD) is a developmental brain abnormality and one of
the most common causes of therapy resistant epilepsy. Hallmarks of FCD are
disrupted cortical layering and immature and dysmorphic neurons. Neuronal
function in FCD lesions is disrupted and has a lower seizure threshold than
normal brain tissues or can even produce constant or periodic epileptic
discharges.
Anti-epileptic medication does not effectively control seizure activity in 76%
of patients with FCD. Over the last decennia epilepsy surgery has been quickly
gaining ground as therapy for epilepsy. If possible to identify a circumscript
epileptic focus, resective surgery has a high chance (up to 80%) of achieving
seizure freedom, in case of incomplete resection, i.e. in cases where the
lesion could not be well identified in imaging or where the epileptogenic
lesion is located in or near eloquent regions, this is only around 20%.
Surgery is so far the only curative treatment for epilepsy. Identification of a
resectable lesion in patients with epilepsy remains a challenge, especially
when a focal developmental malformation is suspected. Absence of a lesion on
MRI has been shown to be a predictor of poor surgical outcome and necessitates
additional diagnostic tests. In MRI-negative patients that are operated, Focal
Cortical Dysplasia (FCD) is reported in up to 60%. In 36% of patients FCD MRI
does not show a lesion.
Advances in imaging techniques are expected to improve the detection of
epileptogenic lesions and could consequently increase the portion of epilepsy
patients eligible for surgery and improve the results of surgical intervention.
Advantages of 7 tesla MRI over lower-field systems are the higher
signal-to-noise ratio that allows increased spatial resolution and, and
therefore potentially has a higher sensitivity for subtle structural
abnormalities However, the clinical merit of 7 tesla MRI has not yet been
scientifically proven for patients with epilepsy.

In this study one of the goals is to compare 7 tesla MRI with 3 tesla MRI in
terms of lesion detection in epilepsy patients and depiction of specific
dysplasia-related imaging characteristics. Furthermore, resected tissue will be
scanned ex-vivo at 7 tesla. The extremely high resolution images created will
be compared with histopathological measures of cellular and neuronal density,
myelinisation and inflammation among others. This will provide a better
understanding of the structural and histopathological substrate for specific
MRI characteristics. In turn these data can form the basis for defining
additional identifying characteristics and the development of improvements in
imaging for epileptogenic lesions.

This study is a single center observational study. The duration of the study is
expected to be two years. The study will be performed in the department of
Neurology and Neurosurgery of the UMC Utrecht, in collaboration with de
department of Radiology UMC Utrecht (especially the 7 tesla MR group),
department of pathology UMC Utrecht. Patients will receive the normal work-up
for the epilepsy surgery program with as addition an extra 7 T MRI. Some
patients already had clinically indicated 7T MRI. These scans were carried out
according to scanning protocols that are the same as used in this study. These
patients can be enrolled in the study without the need to repeat the 7T MRI.
If it leads to resective surgery, the tissue will be scanned ex-vivo at 7 tesla
prior to the histopathological examination. On top of the routine
histopathological diagnostics, extra techniques will be used to further
characterize lesions. This has no consequence for the routine clinical
histopathological examination

Epilepsy caused by the developmental abnormalities typically presents at
child-age, consequently minors make up the largest group of potential
candidates for epilepsy surgery. Histopathological diagnoses of developmental
abnormalities - including FCD - are predominantly found in infant and juvenile
patients. Excluding patients of child age would form a study group not
representable for patients with developmental brain abnormalities.
To date no permanent negative health effects of MR imaging have been reported,
after millions of MRI scans, including an appreciable number at field
strengths of 7 tesla and higher. Compared to scanning with 1.5 or 3 T systems
(the current clinical standard) no increase in health risk should be expected
with scanning at 7 Tesla, since it adheres to the same limitations of Specific
Absorption Rate (SAR). Accordingly, in 2003 the FDA concluded that in adults,
children and infants aged>1 month MRI up to field strengths of 8 tesla holds no
significant risk. However, scanning at higher field strength may be experienced
as more unpleasant due to higher noise levels, the longer and narrower bore and
occurrence of potentially unpleasant physical sensations, such as nausea,
vertigo, tingling and twitches. Nonetheless, 7 T MRI is well tolerated, and
scores of discomfort are very close to those of 3 T MRI.
The added burden of participation in the study is solely by the addition of the
7 T MRI in a diagnostic trajectory of several investigations, including 3 T
MRI, EEG, and one or more of the following: PET, MEG, and SPECT. This burden
can be considered acceptable because 7 T MRI is potentially able to visualize
abnormalities which are not, or partially, detected using other diagnostic
tools. This extra information could mean that a better surgical plan can be
made, with more chance of complete resection and thus with a bigger chance of
seizure freedom. Some patients in whom surgery was not considered possible may
even become surgical candidates.