Clinical Utility of Non-invasive Imaging in MRI-negative Focal Epilepsy

Academic Background

Epilepsy surgery is a crucial treatment modality for drug-resistant epilepsy. However, the likelihood of achieving good outcomes postoperatively is significantly diminished when Magnetic Resonance Imaging (MRI) fails to detect lesions. Previous studies indicate that only 30%-50% of MRI-negative epilepsy patients achieve favorable outcomes of ILAE (International League Against Epilepsy) grade I-II after surgery. The success of surgery in such patients primarily depends on various non-invasive imaging techniques, such as Positron Emission Tomography (PET), Subtraction Ictal SPECT co-registered to MRI (SISCOM), Electrical Source Imaging (ESI), and Morphological MRI Analysis (MAP). This study focuses on identifying the optimal combination of imaging techniques to improve postoperative outcomes in MRI-negative focal epilepsy patients.

Study Provenance

This study was authored by Christian Czarnetzki, Laurent Spinelli, Hans-Jürgen Huppertz, Karl Schaller, Shahan Momjian, Johannes Lobrinus, Maria-Isabel Vargas, Valentina Garibotto, Serge Vulliemoz, and Margitta Seeck, from institutions such as the Clinical Neurosciences Department and Medical School of Geneva University Hospital, Switzerland, and Lengg Clinic, Zurich, Switzerland. The study was received on June 5, 2023, revised on September 2, 2023, accepted on September 4, 2023, and published online in the Journal of Neurology on November 1, 2023.

Research Methods

Case Selection

The study screened drug-resistant epilepsy patients evaluated at Geneva University Hospital between 2000 and 2018. Inclusion criteria were: single focal epilepsy (indicated by EEG and symptomatology), MRI-negative findings, underwent resective surgery and had at least 2 years of follow-up. Exclusion criteria included: diffuse or multifocal epilepsy, palliative surgery, follow-up less than 2 years, or epilepsy due to genetic or autoimmune reasons.

Imaging Techniques

Resting-state PET Scan: Used 2-[18F]Fluoro-2-deoxy-D-glucose (FDG) for resting-state PET scans. Each patient received 200-250 MBq injection and was scanned after resting in a quiet, dim room for 30 minutes, with EEG monitoring to exclude potential subclinical seizures.

Ictal SPECT Scan: Incorporated 99mTc-labelled stabilised-Hexamethylpropyleneamine oxime (HMPAO) or Ethyl Cysteinate Dimer (ECD) for SPECT scanning, with scans collected 30-120 minutes post-injection. Subtraction techniques (SISCOM) were used to identify areas of maximum hyperperfusion.

Electrical Source Imaging (ESI): Reconstructed brain activity based on scalp electrode recordings, using high-density electrodes for recording up to 12 hours.

Morphological MRI Analysis (MAP): Utilized SPM12 software for morphological analysis of 3D MRI images to detect MRI features of focal cortical dysplasia.

Data Statistics

Accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were used to evaluate the effectiveness of each imaging technique. Diagnostic odds ratios (OR) were calculated by comparing imaging results between patients with complete seizure control (ILAE I-II) and poor postoperative outcomes (ILAE III-VI).

Research Results

Patient and Imaging Results

Out of 930 epilepsy patients, 168 were MRI-negative. Among them, 33 patients met the inclusion criteria, underwent surgery, and had follow-up. Of these 33 patients, 23 (69.7%) were seizure-free postoperatively, classified as ILAE I-II.

Among individual imaging techniques, only Electrical Source Imaging (ESI) had an odds ratio (OR) over 1.5, at 3.2, when considering patients with interictal epileptiform discharges (IEDs). In pairs, the combination of SISCOM and ESI was most effective, with an OR of 6. MAP showed 75% sensitivity in detecting indistinguishable focal cortical dysplasia. A combination of PET, ESI, and SISCOM results corresponded to the highest likelihood of seizure control postoperatively (OR=11).

Data Support

The study results indicate that in MRI-negative cases, combining and stringently applying multiple non-invasive imaging tools can yield success rates comparable to those in lesional epilepsy surgeries.

Conclusion

The study highlights the importance of coordinated use of multiple non-invasive imaging techniques in MRI-negative epilepsy cases. If these techniques are implemented rigorously and their results accurately co-registered, postoperative outcomes can be significantly improved, which has crucial implications for clinical practice.

Study Highlights

1. Synergistic Effect of Imaging Techniques: The study demonstrates that single imaging techniques are limited in their effectiveness, whereas combinations of multiple imaging techniques significantly improve diagnostic and surgical success rates.
2. Importance of Non-invasive Imaging Techniques: Techniques such as PET, SISCOM, and ESI provide critical information in low-signal and no-signal MRI cases, offering clinicians more diagnostic tools and decision-making basis.
3. Value of Morphological MRI Analysis (MAP): Although its target analysis is limited, MAP excels in detecting hard-to-distinguish focal cortical dysplasia.

Limitations and Future Directions

The study’s limitations include its retrospective nature and relatively small sample size. Despite this, the research clearly underscores the importance of using multiple non-invasive imaging techniques in MRI-negative focal epilepsy. Future studies should further validate the broad applicability of these techniques and explore ways to enhance their diagnostic accuracy and surgical success rates. The study also suggests incorporating a combination of non-invasive imaging methods in clinical practice to optimize surgical outcomes for patients.