Meckel-Gruber Syndrome: Clinical and Molecular Genetic Profiles in Two Fetuses and Review of the Current Literature

Background: Meckel-Gruber syndrome (MKS; OMIM No. 249000) is a rare, in utero lethal disease characterized by occipital encephalocele, polycystic kidneys, and polydactyly. Methodology and Results: In this study, two fetuses diagnosed as having MKS in the prenatal period were evaluated on the basis of ultrasonographic findings, postmortem autopsy findings, and molecular genetic analyses. Using exome sequencing analyses a novel homozygous frameshift variant (NM_015631: c.530delA, p.Lys177Argfs*47) was detected at exon 4 of TCTN3 gene in case 1, and a novel homozygous synonymous variant (NM_025114: c.180G>A, p Lys60Lys) was detected at exon 3 of CEP290 gene in case 2. Case 1 is the first reported case in the literature, which showed the typical MKS clinical feature with a novel frameshift variation in the TCTN3 gene. The variant in case 2 is the first reported synonymous variant of CEP290 gene in the literature, which has been shown to affect splicing in a functional study at the RNA level. Conclusion: TCTN3 gene variants that were rarely associated with the typical MKS phenotype and all cases with these variations have been discussed in the context of genotype-phenotype. The detection of the first synonymous variant of CEP290 gene and the demonstration of its effect on splicing by a functional study are likely to contribute to the molecular etiology of MKS

Atrial Fibrillation Management in Acute Stroke Patients in Türkiye: Real-life Data from the NöroTek Study

Objective: Atrial fibrillation (AF) is the most common directly preventable cause of ischemic stroke. There is no dependable neurology-based data on the spectrum of stroke caused by AF in Turkiye. Within the scope of NoroTek-Turkiye (TR), hospital-based data on acute stroke patients with AF were collected to contribute to the creation of acute-stroke algorithms.Materials and Methods: On May 10, 2018 (World Stroke Awareness Day), 1,790 patients hospitalized at 87 neurology units in 30 health regions were prospectively evaluated. A total of 929 patients [859 acute ischemic stroke, 70 transient ischemic attack (TIA)] from this study were included in this analysis.Results: The rate of AF in patients hospitalized for ischemic stroke/TIA was 29.8%, of which 65% were known before stroke, 5% were paroxysmal, and 30% were diagnosed after hospital admission. The proportion of patients with AF who received "effective" treatment [international normalization ratio >= 2.0 warfarin or non-vitamin K antagonist oral anticoagulants (NOACs) at a guideline dose] was 25.3%, and, either no medication or only antiplatelet was used in 42.5% of the cases. The low dose rate was 50% in 42 patients who had a stroke while taking NOACs. Anticoagulant was prescribed to the patient at discharge at a rate of 94.6%; low molecular weight or unfractionated heparin was prescribed in 28.1%, warfarin in 32.5%, and NOACs in 31%. The dose was in the low category in 22% of the cases discharged with NOACs, and half of the cases, who received NOACs at admission, were discharged with the same drug.Conclusion: NoroTekTR revealed the high but expected frequency of AF in acute stroke in Turkiye, as well as the aspects that could be improved in the management of secondary prophylaxis. AF is found in approximately one-third of hospitalized acute stroke cases in Turkiye. Effective anticoagulant therapy was not used in three-quarters of acute stroke cases with known AF. In AF, heparin, warfarin, and NOACs are planned at a similar frequency (one-third) within the scope of stroke secondary prophylaxis, and the prescribed NOAC dose is subtherapeutic in a quarter of the cases. Non-medical and medical education appears necessary to prevent stroke caused by AF

Gastrostomy in hospitalized patients with acute stroke: "NoroTek" Turkey point prevalence study subgroup analysis

Objective: Nutritional status assessment, dysphagia evaluation and enteral feeding decision are important determinants of prognosis in acute neurovascular diseases. Materials and Methods: NöroTek is a point prevalence study conducted with the participation of 87 hospitals spread across all health sub regions of Turkey conducted on 10-May-2018 (World Stroke Awareness Day). A total of 972 hospitalized neurovascular patients [female: 53%, age: 69±14; acute ischemic stroke in 845; intracerebral hematoma (ICH) in 119 and post-resuscitation encephalopathy (PRE) in 8] with complete data were included in this sub-study. Results: Gastrostomy was inserted in 10.7% of the patients with ischemic stroke, 10.1% of the patients with ICH and in 50% of the patients with PRE. Independent predictors of percutaneous endoscopic gastrostomy (PEG) administration were The National Institutes of Health Stroke Scale score at admission [exp (β): 1.09 95% confidence interval (CI): 1.05-1.14, per point] in ischemic stroke; and mechanical ventilation in ischemic [exp (β): 6.18 (95% CI: 3.16-12.09)] and hemorrhagic strokes [exp (β): 26.48 (95% CI: 1.36-515.8)]. PEG was found to be a significant negative indicator of favorable (modified Rankin’s scale score 0-2) functional outcome [exp (β): 0.032 (95% CI: 0.004-0.251)] but not of in-hospital mortality [exp (β): 1.731 (95% CI: 0.785-3.829)]. Nutritional and swallowing assessments were performed in approximately two-thirds of patients. Of the nutritional assessments 69% and 76% of dysphagia assessments were completed within the first 2 days. Tube feeding was performed in 39% of the patients. In 83.5% of them, tube was inserted in the first 2 days; 28% of the patients with feeding tube had PEG later. Conclusion: The NöroTek study provided the first reliable and large-scale data on key quality metrics of nutrition practice in acute stroke in Turkey. In terms of being economical and accurate it makes sense to use the point prevalence method.Amaç: Akut nörovasküler hastalıklarda nütrisyonel durum ve disfaji değerlendirmesi ve enteral beslenme kararı önemli prognoz belirleyicilerindendir. Gereç ve Yöntem: NöroTek, 10 Mayıs 2018’de (Dünya İnme Farkındalık Günü) Türkiye’nin tüm sağlık alt bölgelerine yayılmış 87 hastanenin katılımıyla gerçekleştirilen bir nokta prevalans çalışmasıdır. Hastanede yatan ve bu alt çalışma için toplanan verisi tam olan toplam 972 nörovasküler hasta (kadın: %53, yaş: 69±14 yıl; 845’i akut iskemik inme; 119’u intraserebral hematom ve 8’i post-resüsitasyon ensefalopatisi) analiz edildi. Bulgular: Gastrostomi iskemik inmeli hastaların %10,7, intraserebral kanamalıların %10,1 ve post-resusitasyon ensefalopatisi olanların %50’sine uygulanmıştır. Perkütan endoskopik gastrostomi (PEG) gereksiniminin bağımsız belirleyicileri, iskemik inme grubunda kabul NIHSS [exp (β): 1,09, %95 güven aralığı (GA): 1,05-1,14, puan başına] ile hem iskemik hem de hemorajik inmelerde mekanik ventilasyon uygulanmış olmasıdır [iskemik için: exp (β): 6,18, %95 GA: 3,16- 12,09] ve hemorajik inme için: [exp (β): 26,48, 95% GA: 1,36-515,8]. İnme olgularında PEG uygulaması hastane içi mortalite için bağımsız belirleyici değildi [exp (β): 1,731, 95% GA: 0,785-3,829]. Ancak, PEG uygulanmış olması taburculuk esnasında iyi prognoza (modifiye Rankin skoru 0-2) sahip olabilme için anlamlı bir negatif etmen olarak bulundu [exp (β): 0,032, %95 GA: 0,004-0,251]. Hastanede yatan nörovasküler hastaların yaklaşık üçte ikisinde malnütrisyon ve yutma bozukluğu açısından değerlendirme yapılmıştı. Nutrisyonel status değerlendirmesinin %69’u ve disfaji değerlendirmesinin %76’sı ilk 48 saat içinde gerçekleştirilmişti. Tüple enteral nütrisyon uygulama oranı %39’du. Beslenme tüplerinin %83,5’i ilk 2 gün içinde yerleştirilirken beslenme tüpü olan hastaların %28’ine daha sonra PEG açılmıştı. Sonuç: NöroTek çalışması ile Türkiye’de hastanede yatan akut inme hastalarında nutrisyonel uygulamaların temel kalite ölçütlerine ilişkin ilk güvenilir ve büyük ölçekli veri sağlanmıştır. Ekonomik olması ve doğruluğu açısından nokta yaygınlık yönteminin bu tip verilerin temini için daha fazla kullanılması mantıklıdır