Data_Sheet_1_Risk assessment of arrhythmias related to three antiseizure medications: a systematic review and single-arm meta-analysis.DOCX

ObjectiveAntiseizure medications (ASMs) are first line therapy for seizure disorders. Their effects on arrhythmias, especially the risk of arrhythmias associated with lacosamide (LCM), levetiracetam (LEV), and perampanel (PER), have been intensely investigated.MethodsWe searched four databases (PubMed, EMBASE, Cochrane Library, and Web of Science) until August 6, 2023. We used a common effects model and reported data as pooled incidence with 95% CIs. Meta-analyses were conducted to elucidate the risk of arrhythmias with different drugs, and Egger’s regression was performed to detect publication bias analysis.ResultsWe included 11 clinical trials with 1,031 participants. The pooled incidence of arrhythmias in the LEV group was 0.005 (95% CI: 0.001-0.013), while it was 0.014 in the LCM group (95% CI: 0.003-0.030). Publication bias analyses indicated no significant bias in the LEV group (t = 0.02, df = 4, p-value = 0.9852) but a significant bias in the LCM group (t = 5.94, df = 3, p-value = 0.0095). We corrected for this bias in the LCM group using the trim-and-fill method, which yielded a similar pooled incidence of 0.0137 (95% CI: 0.0036-0.0280), indicating good reliability. Due to insufficient studies, we could not conduct a meta-analysis for PER, and we analyzed them in our systematic review.ConclusionThe use of LCM significantly elevated the risk of arrhythmias, while LEV had non-significant arrhythmogenic effects. As for the arrhythmogenic effects of PER, more clinical trials are needed in the future.</p

Table_1_Risk assessment of arrhythmias related to three antiseizure medications: a systematic review and single-arm meta-analysis.XLSX

ObjectiveAntiseizure medications (ASMs) are first line therapy for seizure disorders. Their effects on arrhythmias, especially the risk of arrhythmias associated with lacosamide (LCM), levetiracetam (LEV), and perampanel (PER), have been intensely investigated.MethodsWe searched four databases (PubMed, EMBASE, Cochrane Library, and Web of Science) until August 6, 2023. We used a common effects model and reported data as pooled incidence with 95% CIs. Meta-analyses were conducted to elucidate the risk of arrhythmias with different drugs, and Egger’s regression was performed to detect publication bias analysis.ResultsWe included 11 clinical trials with 1,031 participants. The pooled incidence of arrhythmias in the LEV group was 0.005 (95% CI: 0.001-0.013), while it was 0.014 in the LCM group (95% CI: 0.003-0.030). Publication bias analyses indicated no significant bias in the LEV group (t = 0.02, df = 4, p-value = 0.9852) but a significant bias in the LCM group (t = 5.94, df = 3, p-value = 0.0095). We corrected for this bias in the LCM group using the trim-and-fill method, which yielded a similar pooled incidence of 0.0137 (95% CI: 0.0036-0.0280), indicating good reliability. Due to insufficient studies, we could not conduct a meta-analysis for PER, and we analyzed them in our systematic review.ConclusionThe use of LCM significantly elevated the risk of arrhythmias, while LEV had non-significant arrhythmogenic effects. As for the arrhythmogenic effects of PER, more clinical trials are needed in the future.</p

Data_Sheet_3_Risk assessment of arrhythmias related to three antiseizure medications: a systematic review and single-arm meta-analysis.PDF

ObjectiveAntiseizure medications (ASMs) are first line therapy for seizure disorders. Their effects on arrhythmias, especially the risk of arrhythmias associated with lacosamide (LCM), levetiracetam (LEV), and perampanel (PER), have been intensely investigated.MethodsWe searched four databases (PubMed, EMBASE, Cochrane Library, and Web of Science) until August 6, 2023. We used a common effects model and reported data as pooled incidence with 95% CIs. Meta-analyses were conducted to elucidate the risk of arrhythmias with different drugs, and Egger’s regression was performed to detect publication bias analysis.ResultsWe included 11 clinical trials with 1,031 participants. The pooled incidence of arrhythmias in the LEV group was 0.005 (95% CI: 0.001-0.013), while it was 0.014 in the LCM group (95% CI: 0.003-0.030). Publication bias analyses indicated no significant bias in the LEV group (t = 0.02, df = 4, p-value = 0.9852) but a significant bias in the LCM group (t = 5.94, df = 3, p-value = 0.0095). We corrected for this bias in the LCM group using the trim-and-fill method, which yielded a similar pooled incidence of 0.0137 (95% CI: 0.0036-0.0280), indicating good reliability. Due to insufficient studies, we could not conduct a meta-analysis for PER, and we analyzed them in our systematic review.ConclusionThe use of LCM significantly elevated the risk of arrhythmias, while LEV had non-significant arrhythmogenic effects. As for the arrhythmogenic effects of PER, more clinical trials are needed in the future.</p

Data_Sheet_2_Risk assessment of arrhythmias related to three antiseizure medications: a systematic review and single-arm meta-analysis.DOCX

ObjectiveAntiseizure medications (ASMs) are first line therapy for seizure disorders. Their effects on arrhythmias, especially the risk of arrhythmias associated with lacosamide (LCM), levetiracetam (LEV), and perampanel (PER), have been intensely investigated.MethodsWe searched four databases (PubMed, EMBASE, Cochrane Library, and Web of Science) until August 6, 2023. We used a common effects model and reported data as pooled incidence with 95% CIs. Meta-analyses were conducted to elucidate the risk of arrhythmias with different drugs, and Egger’s regression was performed to detect publication bias analysis.ResultsWe included 11 clinical trials with 1,031 participants. The pooled incidence of arrhythmias in the LEV group was 0.005 (95% CI: 0.001-0.013), while it was 0.014 in the LCM group (95% CI: 0.003-0.030). Publication bias analyses indicated no significant bias in the LEV group (t = 0.02, df = 4, p-value = 0.9852) but a significant bias in the LCM group (t = 5.94, df = 3, p-value = 0.0095). We corrected for this bias in the LCM group using the trim-and-fill method, which yielded a similar pooled incidence of 0.0137 (95% CI: 0.0036-0.0280), indicating good reliability. Due to insufficient studies, we could not conduct a meta-analysis for PER, and we analyzed them in our systematic review.ConclusionThe use of LCM significantly elevated the risk of arrhythmias, while LEV had non-significant arrhythmogenic effects. As for the arrhythmogenic effects of PER, more clinical trials are needed in the future.</p

HP ¹²⁹Xe distribution in the rat brain.

<p>(<b>3a</b>) HP ¹²⁹Xe CSI image acquired with a 2D CSI pulse sequence from rat head under normal breathing conditions (slice thickness 10 mm). (<b>3b</b>) same image with false color applied. Warmer colors indicate increased HP ¹²⁹Xe signal intensity. (<b>3c</b>) Proton MRI of a rat head showing a 1 mm coronal slice through the brain acquired with a RARE pulse sequence. (<b>3d</b>) Proton image shown with overlay of HP ¹²⁹Xe MRI, in which only HP ¹²⁹Xe signal with an SNR above 2 are shown. FOV was 25 mm.</p

HP ¹²⁹Xe spectrum obtained from rat brain <i>in vivo</i> after the administration of HP ¹²⁹Xe gas.

<p>The spectrum was acquired from 50 averages using an RF pulse with a flip angle of 90°, and a frequency of 55.477 MHz. At least four separate peaks are discernable, the largest of which occurs at 194.7 ppm downfield from the HP ¹²⁹Xe gas peak at 0 ppm. The SNR of the largest peak is 476.</p

HP ¹²⁹Xe fMRI data from three animals.

<p>The HP ¹²⁹Xe signal is shown as a false colour overlay on the corresponding 1 mm thick coronal proton reference image taken from the same animal. The left panel shows HP ¹²⁹Xe signal intensity during baseline and the right panel shows HP ¹²⁹Xe signal intensity after injection of capsaicin 20 ul (3 mg/ml) into the right forepaw. Colour scale represents SNR and only signal with SNR above 2 are shown. Superimposition of a rat brain atlas (18) demarcates specific areas of the brain: cingulate cortex (Cg), motor cortex (M), primary somatosensory cortex and SS1 forelimb region (SS1 and SS1 fl), secondary samatosensory cortex (SS2), and striatum (CPu).</p

Percent HP ¹²⁹Xe signal change in four brain regions^*.

<p>*Measured from regions of interest (ROIs) in hemisphere contralateral to pain stimulus.</p

Superimposition of a rat brain atlas [<b>18</b>] showing four regions of interest (ROIs) analyzed for changes in HP ¹²⁹Xe signal following forepaw stimulation, including cingulate cortex (Cg), primary somatosensory cortex and SS1 forelimb region (SS1 and SS1 fl), and secondary samatosensory cortex (SS2).

<p>Superimposition of a rat brain atlas <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0021607#pone.0021607-Paxinos1" target="_blank">[<b>18</b>]</a> showing four regions of interest (ROIs) analyzed for changes in HP ¹²⁹Xe signal following forepaw stimulation, including cingulate cortex (Cg), primary somatosensory cortex and SS1 forelimb region (SS1 and SS1 fl), and secondary samatosensory cortex (SS2).</p

Vital Signs Data (N = 3).

<p>Vital Signs Data (N = 3).</p