Prenatal diagnosis of arachnoid cysts: a case series and systematic review.

INTRODUCTION: Primary cysts are believed to arise from the splitting of the arachnoid membrane during prenatal development and can be diagnosed in utero. Prenatal diagnosis is uncommon; therefore, the evidence base for counselling expectant mothers is limited. The purpose of this article is to present a case series and review the current literature on prenatally diagnosed arachnoid cysts. METHOD: A keyword search of hospital electronic records was performed for all patients with a prenatally diagnosed arachnoid cyst at a tertiary neurosurgical centre. Case notes were reviewed for all patients diagnosed between 2005 and 2017. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to structure a systematic review of all English language articles published up to May 2018. RESULTS: A total of eight eligible patients were identified from our own records and 123 from the literature. Sixty-eight per cent of patients had a normal outcome. Sixty-three per cent of patients underwent surgical intervention which was not associated with abnormal outcome. The diagnosis of syndromic/genetic diagnosis (p < 0.001) and the presence of other intra-cranial anatomical abnormalities (p = 0.05) were significant predictors of abnormal outcome. CONCLUSION: The pathogenesis and prognosis of a prenatal arachnoid cyst diagnosis remain unclear. These results suggest favourable outcomes from simple cysts without associated abnormalities and expectant mothers should be counselled accordingly. A wider prospective review is required to better established evidence-based practice.

Which Dopamine Polymorphisms Are Functional? Systematic Review and Meta-analysis of COMT, DAT, DBH, DDC, DRD1-5, MAOA, MAOB, TH, VMAT1, and VMAT2.

BACKGROUND: Many polymorphisms in dopamine genes are reported to affect cognitive, imaging, or clinical phenotypes. It is often inferred or assumed that such associations are causal, mediated by a direct effect of the polymorphism on the gene product itself. However, the supporting evidence is not always clear. METHODS: We conducted systematic reviews and meta-analyses to assess the empirical evidence for functional polymorphisms in genes encoding dopaminergic enzymes (COMT, DBH, DDC, MAOA, MAOB, and TH), dopamine receptors (DRD1, DRD2, DRD3, DRD4, and DRD5), the dopamine transporter (DAT), and vesicular transporters (VMAT1 and VMAT2). We defined functionality as an effect of the polymorphism on the expression, abundance, activity, or affinity of the gene product. RESULTS: We screened 22,728 articles and identified 255 eligible studies. We found robust and medium to large effects for polymorphisms in 4 genes. For catechol-O-methyltransferase (COMT), the Val158Met polymorphism (rs4680) markedly affected enzyme activity, protein abundance, and protein stability. Dopamine ß-hydroxylase (DBH) activity was associated with rs1611115, rs2519152, and the DBH-STR polymorphism. Monoamine oxidase A (MAOA) activity was associated with a 5' VNTR polymorphism. Dopamine D2 receptor (DRD2) binding was influenced by the Taq1A (rs1800497) polymorphism, and rs1076560 affected DRD2 splicing. CONCLUSIONS: Some widely studied dopaminergic polymorphisms clearly and substantially affect the abundance or activity of the encoded gene product. However, for other polymorphisms, evidence of such an association is negative, inconclusive, or lacking. These findings are relevant when selecting polymorphisms as "markers" of dopamine function, and for interpreting the biological plausibility of associations between these polymorphisms and aspects of brain function or dysfunction.