Genetic Testing Contributes to Diagnosis in Cerebral Palsy: Aicardi-Goutières Syndrome as an Example.

Cerebral palsy (CP) is a non-progressive neurodevelopmental disorder characterized by motor impairments, often accompanied by co-morbidities such as intellectual disability, epilepsy, visual and hearing impairment and speech and language deficits. Despite the established role of hypoxic-ischemic injury in some CP cases, several studies suggest that birth asphyxia is actually an uncommon cause, accounting for <10% of CP cases. For children with CP in the absence of traditional risk factors, a genetic basis to their condition is increasingly suspected. Several recent studies indeed confirm copy number variants and single gene mutations with large genetic heterogeneity as an etiology in children with CP. Here, we report three patients with spastic cerebral palsy and a genetically confirmed diagnosis of Aicardi-Goutières syndrome (AGS), with highly variable phenotypes ranging from clinically suggestive to non-specific symptomatology. Our findings suggest that AGS may be a rather common cause of CP, that frequently remains undiagnosed without additional genetic testing, as in only one case a clinical suspicion of AGS was raised. Our data show that a diagnosis of AGS must be considered in cases with spastic CP, even in the absence of characteristic brain abnormalities. Importantly, a genetic diagnosis of AGS may have significant therapeutic consequences, as targeted therapies are being developed for type 1 interferonopathies, the group of diseases to which AGS belongs. Our findings demonstrate the importance of next generation sequencing in CP patients without an identifiable cause, since targeted diagnostic testing is hampered by the often non-specific presentation.

Are neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and/or mean platelet volume (MPV) clinically useful as predictive parameters for preeclampsia?

OBJECTIVE: Preeclampsia (PE) is a severe pregnancy complication with significant maternal and neonatal morbi-mortality resulting in high health care costs. Prevention, mainly based on the administration of acetylsalicylic acid, is only possible if timely identification of high-risk patients can be realized in an easy, nonexpensive, and widely available method. This paper explores the clinical usability of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and/or mean platelet volume (MPV) in discriminating between women that will and those that will not develop PE. STUDY DESIGN: Demographic data and laboratory results were retrospectively collected and compared in 2050 pregnant women (164 PE and 1886 controls) between 1 January 2014 and 31 January 2016. RESULTS: In the PE group, gravidity, parity, gestational age, and birth weight were significantly lower compared to the control group. Before the 20th pregnancy week, MPV was significantly elevated in the PE group compared to the controls (p = .006), hence analysis revealed an optimal cut-off point of 8.15 (sensitivity 66.7%, specificity 56.3%) for predicting PE. At the end of pregnancy, NLR and MPV appeared to be higher and PLR lower in the PE group compared to the controls, which strengthens the current knowledge on the pathogenesis of PE. CONCLUSIONS: MPV is significantly elevated in the first half of pregnancy in women who later develop PE and might therefore be implemented in combination with other parameters in a PE prediction model.