Several studies have established the two-way relationship between the sporadic and familial forms of Alzheimer's disease (AD) and epilepsy. However, a more robust connection exists between epilepsy and early onset familial AD (EOFAD). Still, the mechanisms underlying the same are not yet fully understood. Aging is also known to be associated with both AD and seizures. Seizures of any type can occur at any stage of AD and are six to 10 times more likely in patients with AD than in controls of a similar age group. Seizures can quicken cognitive decline and increase mortality, amplifying the medical and economic burden. It is, therefore, clinically essential to recognize and treat seizures early in these patients. However, diagnosis of seizures in AD is complicated by the difficulty in identifying non-motor focal seizures in patients with cognitive decline, problems with obtaining histories, low sensitivity of standard scalp electroencephalogram (EEG) methods, nonspecific cerebrospinal fluid (CSF) and radiological findings. This article has reviewed and summarised the existing literature on the association between AD and epilepsy pertaining to epidemiology, pathophysiological links, risk factors, modalities for diagnosis, and treatment strategies.

Purpose: In this study, we aimed to meta-analyze all available data to provide a holistic, well-powered assessment of the effect of PIMSRA on LVOT gradient, LVEF, and anterior and posterior IVS thickness. Methods: PubMed, Cochrane Central, Embase, and Scopus were systematically searched from inception till October 2022 for published clinical trials assessing the efficacy of PIMSRA in patients with HCM using the keywords “PIMSRA” OR “Percutaneous Intramyocardial Septal Radiofrequency Ablation” OR “Liwen procedure.” Studies that reported change in either LVOT gradient, IVS thickness, or LVEF were selected. No time or language restrictions were applied. All case reports were excluded, and only clinical trials were included. The search and data extraction were carried out independently by two reviewers (MP, FT). A third reviewer (IH) was consulted to resolve discrepancies. All statistical analyses were conducted on Open Meta-analyst. Trials were pooled using a continuous random effects model (DL: DerSimonian-Laird), and results were presented with 95% confidence intervals (CIs). P value 75% regarded as substantial heterogeneity. Results: All five studies reported a change in LVOT gradient from the baseline. Integrated analysis showed no significant change from baseline (MD: -69.506; 95% CI: -77.047, -61.966; P = 0.089) (I² = 50.4%). Subgroup analyses based on follow-up revealed that there was no significant difference noted at 6 months according to data from 2 studies (MD: -65.351; 95% CI; -85.253, -45.450; P = 0.181) (I²= 44.1%) however data from 3 studies at one year follow up did reveal a significant difference from baseline (MD: -71.010; 95% CI: -80.262, -61.758; P = 0.047) (I² = 67.2%). Only three studies reported changes in LVEF from the baseline. Integrated analysis Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation showed a significant change from baseline at one-year follow-up in patients who underwent PIMSRA (MD: -1.760; 95% CI: -3.239, -0.282; P = 0.047) (I² = 67.22%). The pooled analysis from four studies that reported anterior IVS thickness showed no significant change from baseline (MD: -9.707; 95% CI: -10.819, -8.595; P = 0.095) (I² = 52.94%). Subgroup analyses based on follow-up revealed that there was no significant difference noted at 6 months (MD: -11.285; 95% CI; -12.825, -9.744; P = 0.933) (I² = 0%) or at one-year follow-up (MD: -9.147; 95% CI: -9.837, -8.456; P = 0.650) (I² = 0%) The combined analysis of the four included studies reporting posterior IVS thickness showed no significant change from baseline (MD: -8.859; 95% CI: -10.073, -7.644; P = 0.119) (I² = 48.73%). Additionally, there was no significant difference noted in the subgroup analysis at 6 months (MD: -10.278; 95% CI; -12.133, -8.423; P = 0.934) (I² = 0%) and at one-year follow-up (MD: -8.335; 95% CI: -9.880, -6.789; P = 0.072) (I² = 69.14%) Conclusion: This single-arm meta-analysis of 284 patients gathered from 5 clinical trials suggested that overall, after PIMSRA, LVOT gradient was reduced, and LVEF was slightly decreased. Additionally, no significant changes were observed in the anterior and posterior IVS thicknesses. Our results had substantial heterogeneity, which could be explained due to differences in the follow-up periods and studies with small sample sizes. It is important to note that even though no significant difference in follow-up was seen from the baseline at 6 months, there was indeed a significant difference noted at one year when assessing the outcomes of LVOT gradient. This could suggest that longer follow-up periods are imperative to truly observe the procedure's efficacy.

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