Genetic Associations with Polycystic Ovary Syndrome: The Role of The Mitochondrial Genome; A Systematic Review and Meta-analysis

BACKGROUND: Polycystic Ovary Syndrome (PCOS) remains the most common female reproductive endocrine disorder. Genetic studies have predominantly focused on the role of the nuclear genome, whilst the contribution of mitochondrial genetics in PCOS remains largely unknown. AIM: This study aims to systematically evaluate the literature regarding the associations between the mitochondrial genome and PCOS. METHODS: A literature search focused on PCOS and mitochondrial genetics was conducted on (1) MEDLINE (2) EMBASE and (3) The Cochrane Library (CENTRAL and Cochrane Reviews). Search results were screened for eligibility, and data involving genetic variants of mitochondrial DNA (mtDNA) was extracted. Quantitative data was presented in forest plots, and where this was not possible, data was analysed in a qualitative manner. Quality of studies was assessed using the Q-Genie tool. RESULTS: Of the 13,812 identified studies, 15 studies were eligible for inclusion, with 8 studies suitable for meta-analysis. Women with PCOS showed higher frequencies of a 9-bp deletion, and aberrant SNPs in the ND5, A6, and 7 tRNA-encoding genes. They also showed lower frequencies of two SNPs in the D-Loop of the genome. Women with PCOS also exhibited significantly lowered mtDNA copy number. CONCLUSION: Women with PCOS harbour genetic variants in coding and non-coding regions of the mitochondrial genome. This may disrupt the electron transport chain and lead to oxidative stress, causing apoptosis of cells and further genetic damage. However, further studies of higher quality are required to confirm these associations

Extent of piriform cortex resection in children with temporal lobe epilepsy

OBJECTIVE: A greater extent of resection of the temporal portion of the piriform cortex (PC) has been shown to be associated with higher likelihood of seizure freedom in adults undergoing anterior temporal lobe resection (ATLR) for drug-resistant temporal lobe epilepsy (TLE). There have been no such studies in children, therefore this study aimed to investigate this association in a pediatric cohort. METHODS: A retrospective, neuroimaging cohort study of children with TLE who underwent ATLR between 2012 and 2021 was undertaken. The PC, hippocampal and amygdala volumes were measured on the preoperative and postoperative T1-weighted MRI. Using these volumes, the extent of resection per region was compared between the seizure-free and not seizure-free groups. RESULTS: In 50 children (median age 9.5 years) there was no significant difference between the extent of resection of the temporal PC in the seizure-free (median = 50%, n = 33/50) versus not seizure-free (median = 40%, n = 17/50) groups (p = 0.26). In a sub-group of 19 with ipsilateral hippocampal atrophy (quantitatively defined by ipsilateral-to-contralateral asymmetry), the median extent of temporal PC resection was greater in children who were seizure-free (53%) versus those not seizure-free (19%) (p = 0.009). INTERPRETATION: This is the first study demonstrating that, in children with TLE and hippocampal atrophy, more extensive temporal PC resection is associated with a greater chance of seizure freedom-compatible with an adult series in which 85% of patients had hippocampal sclerosis. In a combined group of children with and without hippocampal atrophy, the extent of PC resection was not associated with seizure outcome, suggesting different epileptogenic networks within this cohort

Extent of piriform cortex resection in children with temporal lobe epilepsy

Abstract Objective A greater extent of resection of the temporal portion of the piriform cortex (PC) has been shown to be associated with higher likelihood of seizure freedom in adults undergoing anterior temporal lobe resection (ATLR) for drug‐resistant temporal lobe epilepsy (TLE). There have been no such studies in children, therefore this study aimed to investigate this association in a pediatric cohort. Methods A retrospective, neuroimaging cohort study of children with TLE who underwent ATLR between 2012 and 2021 was undertaken. The PC, hippocampal and amygdala volumes were measured on the preoperative and postoperative T1‐weighted MRI. Using these volumes, the extent of resection per region was compared between the seizure‐free and not seizure‐free groups. Results In 50 children (median age 9.5 years) there was no significant difference between the extent of resection of the temporal PC in the seizure‐free (median = 50%, n = 33/50) versus not seizure‐free (median = 40%, n = 17/50) groups (p = 0.26). In a sub‐group of 19 with ipsilateral hippocampal atrophy (quantitatively defined by ipsilateral‐to‐contralateral asymmetry), the median extent of temporal PC resection was greater in children who were seizure‐free (53%) versus those not seizure‐free (19%) (p = 0.009). Interpretation This is the first study demonstrating that, in children with TLE and hippocampal atrophy, more extensive temporal PC resection is associated with a greater chance of seizure freedom—compatible with an adult series in which 85% of patients had hippocampal sclerosis. In a combined group of children with and without hippocampal atrophy, the extent of PC resection was not associated with seizure outcome, suggesting different epileptogenic networks within this cohort