Dataset Information

Correcting for physiological ripples improves epileptic focus identification and outcome prediction.

ABSTRACT:

Objective

The integration of high-frequency oscillations (HFOs; ripples [80-250 Hz], fast ripples [250-500 Hz]) in epilepsy evaluation is hampered by physiological HFOs, which cannot be reliably differentiated from pathological HFOs. We evaluated whether defining abnormal HFO rates by statistical comparison to region-specific physiological HFO rates observed in the healthy brain improves identification of the epileptic focus and surgical outcome prediction.

Methods

We detected HFOs in 151 consecutive patients who underwent stereo-electroencephalography and subsequent resective epilepsy surgery at two tertiary epilepsy centers. We compared how HFOs identified the resection cavity and predicted seizure-free outcome using two thresholds from the literature (HFO rate > 1/min; 50% of the total number of a patient's HFOs) and three thresholds based on normative rates from the Montreal Neurological Institute Open iEEG Atlas (https://mni-open-ieegatlas.

Research

mcgill.ca/): global Atlas threshold, regional Atlas threshold, and regional + 10% threshold after regional Atlas correction.

Results

Using ripples, the regional + 10% threshold performed best for focus identification (77.3% accuracy, 27% sensitivity, 97.1% specificity, 80.6% positive predictive value [PPV], 78.2% negative predictive value [NPV]) and outcome prediction (69.5% accuracy, 58.6% sensitivity, 76.3% specificity, 60.7% PPV, 74.7% NPV). This was an improvement for focus identification (+1.1% accuracy, +17.0% PPV; p < .001) and outcome prediction (+12.0% sensitivity, +1.0% PPV; p = .05) compared to the 50% threshold. The improvement was particularly marked for foci in cortex, where physiological ripples are frequent (outcome: +35.3% sensitivity, +5.3% PPV; p = .014). In these cases, the regional + 10% threshold outperformed fast ripple rate > 1/min (+3.6% accuracy, +26.5% sensitivity, +21.6% PPV; p < .001) and seizure onset zone (+13.5% accuracy, +29.4% sensitivity, +17.0% PPV; p < .05-.01) for outcome prediction. Normalization did not improve the performance of fast ripples.

Significance

Defining abnormal HFO rates by statistical comparison to rates in healthy tissue overcomes an important weakness in the clinical use of ripples. It improves focus identification and outcome prediction compared to standard HFO measures, increasing their clinical applicability.

SUBMITTER: Zweiphenning WJEM

PROVIDER: S-EPMC9300035 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:RationaleHigh frequency oscillations (HFO; ripples = 80-200, fast ripples 200-500 Hz) are promising epileptic biomarkers in patients with epilepsy. However, especially in temporal epilepsies differentiation of epileptic and physiological HFO activity still remains a challenge. Physiological sleep-spindle-ripple formations are known to play a role in slow-wave-sleep memory consolidation. This study aimed to find out if higher rates of mesial-temporal spindle-ripples correlate with good memory performance in epilepsy patients and if surgical removal of spindle-ripple-generating brain tissue correlates with a decline in memory performance. In contrast, we hypothesized that higher rates of overall ripples or ripples associated with interictal epileptic spikes correlate with poor memory performance.MethodsPatients with epilepsy implanted with electrodes in mesial-temporal structures, neuropsychological memory testing and subsequent epilepsy surgery were included. Ripples and epileptic spikes were automatically detected in intracranial EEG and sleep-spindles in scalp EEG. The coupling of ripples to spindles was automatically analyzed. Mesial-temporal spindle-ripple rates in the speech-dominant-hemisphere (left in all patients) were correlated with verbal memory test results, whereas ripple rates in the non-speech-dominant hemisphere were correlated with non-verbal memory test performance, using Spearman correlation).ResultsIntracranial EEG and memory test results from 25 patients could be included. All ripple rates were significantly higher in seizure onset zone channels (p < 0.001). Patients with pre-surgical verbal memory impairment had significantly higher overall ripple rates in left mesial-temporal channels than patients with intact verbal memory (Mann-Whitney-U-Test: p = 0.039). Spearman correlations showed highly significant negative correlations of the pre-surgical verbal memory performance with left mesial-temporal spike associated ripples (rs = -0.458; p = 0.007) and overall ripples (rs = -0.475; p = 0.006). All three ripple types in right-sided mesial-temporal channels did not correlate with pre-surgical nonverbal memory. No correlation for the difference between post- and pre-surgical memory and pre-surgical spindle-ripple rates was seen in patients with left-sided temporal or mesial-temporal surgery.DiscussionThis study fails to establish a clear link between memory performance and spindle ripples. This highly suggests that spindle-ripples are only a small portion of physiological ripples contributing to memory performance. More importantly, this study indicates that spindle-ripples do not necessarily compromise the predictive value of ripples in patients with temporal epilepsy. The majority of ripples were clearly linked to areas with poor memory function.

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