An ongoing problem: Rhesus hemolytic disease of the newborn - A decade of experience in a single centre.

BACKGROUND: The objectives were to evaluate the descriptive features of newborns with a diagnosis of Rhesus (Rh) hemolytic disease, to determine the morbidity and mortality rates, to evaluate the treatment methods and the factors affecting treatment requirements and clinical outcomes during a ten-year period at a tertiary center. METHODS: Newborn infants who had a positive direct Coombs test and/or had a history of intrauterine transfusion (IUT) due to Rh hemolytic disease were included. The data regarding the prenatal, natal and postnatal periods were collected from hospital records. RESULTS: A total of 260 neonates were included of which 51.2% were female. The mean ± standard deviation gestational age was 36.9 ± 2.7 weeks. The rate of preterm birth was 41.2%. Of 257 mothers whose obstetric medical history could be accessed, 87.2% were multigravida, whereas 76.3% were multiparous. Among mothers who had a reliable history of anti-D immunoglobulin prophylaxis (n=191), 51.3% had not received anti-D immunoglobulin prophylaxis in their previous pregnancies. The antenatal transfusion rate was 31.7% and the frequency of hydrops fetalis was 8.8%. While combined exchange transfusion (ET) and phototherapy (PT) was performed in 15.4% of the babies, the majority either needed phototherapy only (51.1%) or no treatment (33.5%). The mortality rate was 3.8 % (n = 10), and nine babies out of these 10 were those with severe hydrops fetalis. CONCLUSION: This study showed that Rh hemolytic disease is still a major problem in developing countries. Multiple comorbidities may occur in addition to life threatening complications, including hydrops fetalis, anemia and severe hyperbilirubinemia. High rates of multiparity and low rates of anti-D immunoglobulin prophylaxis are potential barriers for the eradication of the disease. It should be remembered that Rh hemolytic disease is a preventable disease in the presence of appropriate antenatal follow-up and care facilities.

Evaluation of Congenital Cytomegalovirus Infection in Pregnant Women Admitted to a University Hospital in Istanbul.

Cytomegalovirus (CMV) can cause serious complications in immunocompromised individuals and fetuses with congenital infections. These can include neurodevelopmental impairments and congenital abnormalities in newborns. This paper emphasizes the importance of concurrently evaluating ultrasonography findings and laboratory parameters in diagnosing congenital CMV infection. To examine the prenatal characteristics of CMV DNA-positive patients, we assessed serum and amniotic fluid from 141 pregnant women aged 19-45 years, each with fetal anomalies. ELISA and PCR tests, conducted in response to these amniocentesis findings, were performed at an average gestational age of 25 weeks. Serological tests revealed that all 141 women were CMV IgG-positive, and 2 (1.41%) had low-avidity CMV IgG, suggesting a recent infection. CMV DNA was detected in 17 (12.05%) amniotic fluid samples using quantitative PCR. Of these, 82% exhibited central nervous system abnormalities. Given that most infections in pregnant women are undetectable and indicators non-specific, diagnosing primary CMV in pregnant women using clinical findings alone is challenging. We contend that serological tests should not be the sole means of diagnosing congenital CMV infection during pregnancy.

Association of antenatal evaluations with postmortem and genetic findings in the series of fetal osteogenesis imperfecta.

INTRODUCTION: Counseling Osteogenesis Imperfecta (OI) pregnancies is challenging due to the wide range of onsets and clinical severities, from perinatal lethality to milder forms detected later in life. METHODS: Thirty-eight individuals from 36 families were diagnosed with OI through prenatal ultrasonography and/or postmortem clinical and radiographic findings. Genetic analysis was conducted on 26 genes associated with OI in these subjects that emerged over the past 20 years, while some genes were examined progressively, all 26 genes were examined in the group where no pathogenic variations were detected. RESULTS: Prenatal and postnatal observations both consistently showed short limbs in 97%, followed by bowing of the long bones in 89%. Among 32 evaluated cases, all exhibited cranial hypomineralization. Fractures were found in 29 (76%) cases, with multiple bones involved in 18 of them. Genetic associations were disclosed in 27 families with 22 (81%) autosomal dominant and five (19%) autosomal recessive forms, revealing 25 variants in six genes (COL1A1, COL1A2, CREB3L1, P3H1, FKBP10, and IFITM5), including nine novels. Postmortem radiological examination showed variability in intra-family expression of CREBL3 and P3H1-related OI. CONCLUSION: Prenatal diagnosis for distinguishing OI and its subtypes relies on factors such as family history, timing, ultrasound, genetic and postmortem evaluation.

Clinical and molecular characteristics of 26 fetuses with lethal multiple congenital contractures.

Multiple congenital contractures (MCC) due to fetal akinesia manifest across a broad spectrum of diseases, ranging from mild distal arthrogryposis to lethal fetal akinesia deformation sequence. We hereby present a series of 26 fetuses displaying severe MCC phenotypes from 18 families and describe detailed prenatal ultrasound findings, postmortem clinical evaluations, and genetic investigations. Most common prenatal findings were abnormal facial profile (65%), central nervous system abnormalities (62%), polyhydramnios (50%), increased nuchal translucency (50%), and fetal hydrops (35%). Postmortem examinations unveiled additional anomalies including facial dysmorphisms, dysplastic skeletal changes, ichthyosis, multiple pterygia, and myopathy, allowing preliminary diagnosis of particular Mendelian disorders in multiple patients. Evaluation of the parents revealed maternal grip myotonia in one family. By exome sequencing and targeted testing, we identified causative variants in ACTC1, CHST14, COG6, DMPK, DOK7, HSPG2, KLHL7, KLHL40, KIAA1109, NEB, PSAT1, RAPSN, USP14, and WASHC5 in 15 families, and one patient with a plausible diagnosis associated with biallelic NEB variants. Three patients received a dual diagnosis. Pathogenic alterations in newly discovered genes or in previously known genes recently linked to new MCC phenotypes were observed in 44% of the cohort. Our results provide new insights into the clinical and molecular landscape of lethal MCC phenotypes.

The correlation between pregnancy, disease activity and adverse pregnancy outcomes in patients with systemic lupus erythematosus.

OBJECTIVE: In this study, our pregnant systemic lupus erythematosus (SLE) cohort, which was under medical surveillance of both our Rheumatology and Obstetrics departments, was analyzed. We intended to determine the effects of pregnancy on disease activity and the correlation between disease flares and adverse pregnancy outcomes. METHODS: One hundred sixty eight pregnancy data involving 136 patients with SLE were examined. Cumulative clinical, laboratory, and serological parameters were described. Disease activity and flares were calculated using the systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) in the pre/postpartum periods and the SLEPDAI in the three trimesters of pregnancy. Patients with a SLEDAI-2K or SLEPDAI ≥ 4 were classified as "active." Patients with lupus low disease activity state (LLDAS) during each of these periods were identified.Fetal/neonatal death, premature birth due to pre-eclampsia, eclampsia or hemolysis, elevated Liver enzymes (HELLP) syndrome, and neonates small for gestational age were determined as adverse pregnancy outcomes (APO). RESULTS: Out of 168 pregnancies, there were 60 (35.7%) pregnancies with flares covering the pregnancy and 6 months of postpartum period. The mean SLEDAI in the 6 months postpartum period was significantly higher compared to mean disease activity during pregnancy (p < .05). Of all pregnancies, 132 (78.6%) were in LLDAS during pregnancy. Comparison of the frequency of severe postpartum flares in patients who were in LLDAS during pregnancy revealed a lower percentage of flares compared to those who were not in the LLDAS group (11 vs 29%, p < .05). APO was observed in 33.9% of 168 pregnancies. The mean SLEPDAI score was significantly higher in APO+ pregnancies than in APO- pregnancies (4.9 ± 6.1 vs 2.8 ± 4.9, p = .002). Comparison of SLICC damage score between APO - and + pregnancies revealed a significantly higher score in APO+ pregnancies (1.8 ± 2.1 vs 0.8 ± 1.3, p = .001). CONCLUSION: Postpartum six-month period appears to have the highest risk for disease flares during SLE pregnancies. Disease activity during pregnancy increases the risk of APO. In order to achieve a positive pregnancy outcome and lower maternal morbidity, regular follow-up of patients is necessary.

Fibular Agenesis and Ball-Like Toes Mimicking Preaxial Polydactyly: Prenatal Presentation of Du Pan Syndrome.

Introduction: GDF5-BMPR1B signaling pathway-associated chondrodysplasias are a genetically heterogeneous group of conditions with significant phenotypic and genotypic overlap, consisting of Hunter-Thompson-type acromesomelic dysplasia, Grebe dysplasia, and Du Pan syndrome. Constituting a spectrum of clinical severity, these disorders are characterized by disproportionate short stature mainly involving middle and distal segments of the extremities. Du Pan syndrome represents the mildest end of this spectrum with less marked shortened limbs, fibular agenesis or hypoplasia, absence of frequent joint dislocations, and carpotarsal fusions with deformed phalangeal bones. Case Presentation: Here, we report the first prenatal diagnosis of Du Pan syndrome based on the sonographic findings of bilateral fibular agenesis and ball-shaped toes mimicking preaxial polydactyly accompanying subtle brachydactyly in the family. GDF5 (NM_000557.5) sequencing identified a homozygous pathogenic variant c.1322T>C, p.(Leu441Pro) in the fetus and confirmed the carrier status in the mother. Discussion: We suggest that the presence of bilateral fibular agenesis and the apparent image of preaxial polydactyly of the feet on prenatal ultrasound should alert suspicion to Du Pan syndrome, with the latter possibly being a sonographic pitfall. Alongside the fetal imaging, a detailed clinical examination of the expectant parents is also of great importance in establishing a preliminary diagnosis of Du Pan syndrome, as well as the other GDF5-BMPR1B-associated chondrodysplasias.

FREM2-related Fraser syndrome with popliteal pterygium and structural central nervous system anomalies.

Fraser syndrome (FS) is a rare multiple malformation disorder characterized by cryptophthalmos, characteristic craniofacial dysmorphism, cutaneous syndactyly, malformations of the respiratory and urinary tract, and anogenital anomalies. Although the characteristic presentation of FS can be detected prenatally, oligohydramnios often challenges the clinical diagnosis. Here we report on the atypical prenatal and postmortem findings of a fetus with FS caused by a novel homozygous frameshift variant in FREM2. Our study highlights the variable manifestations of the FS and expands the clinical spectrum to include popliteal pterygium and structural central nervous system anomalies.

Fetal skeletal dysplasia cohort of a single tertiary referral center in Istanbul, Turkey.

We report on 314 fetal cases from 297 unrelated families with skeletal dysplasia evaluated in the postmortem period from 2000 to 2017 at a single clinical genetics center in Istanbul, Turkey. The definite diagnostic yield was 40% during the prenatal period, while it reached 74.5% when combined with postmortem clinical and radiological evaluation. Molecular analyses were performed in 25.5% (n: 76) of families, and 21 novel variants were identified. Classification according to International Skeletal Dysplasia Society-2019 revision revealed limb hypoplasia-reduction defects group (39) as the leading one, 24.5%, then followed by FGFR3 chondrodysplasias, osteogenesis imperfecta, and decreased mineralization and polydactyly-syndactyly-triphalangism groups 13.6, 11.1, and 8.9%, respectively. The inheritance pattern was autosomal recessive in 54% and autosomal dominant in 42.6% of index cases. The overall consanguinity rate of the cohort was 33%. The high prevalence of ultrarare diseases along with two or more unrelated autosomal recessive entities running in the same family was noteworthy. This study highlights the pivotal role of postmortem evaluation by an experienced clinical geneticist to achieve a high diagnostic yield in fetal skeletal dysplasia cohorts. The cohort is not only a representation of the spectrum of skeletal dysplasias in a population with a high consanguinity rate but also provides an ideal research group to work on to identify the unknowns of early fetal life.

Clinical, Cytogenetic and Molecular Cytogenetic Outcomes of Cell-Free DNA Testing for Rare Chromosomal Anomalies.

The scope of cell-free DNA (cfDNA) testing was expanded to the genome, which allowed screening for rare chromosome anomalies (RCAs). Since the efficiency of the test for RCAs remains below the common aneuploidies, there is a debate on the usage of expanded tests. This study focuses on the confirmatory and follow-up data of cases with positive cfDNA testing for RCAs and cases with screen-negative results in a series of 912 consecutive cases that underwent invasive testing following cfDNA testing. Chorion villus sampling (CVS), amniocentesis (AS), fetal blood sampling, and term placenta samples were investigated using classical cytogenetic and molecular cytogenetic techniques. Out of 593 screen-positive results, 504 (85%) were for common aneuploidies, 40 (6.7%) for rare autosomal trisomies (RATs), and 49 (8.3%) for structural chromosome anomalies (SAs). Of the screen-positives for RATs, 20 cases were evaluated only in fetal tissue, and confined placental mosaicism (CPM) could not be excluded. Among cases with definitive results (n = 20), the rates of true positives, placental mosaics, and false positives were 35%, 45%, and 10%, respectively. Among screen-positives for SAs, 32.7% were true positives. The confirmation rate was higher for duplications than deletions (58.3% vs. 29.4%). The rate of chromosomal abnormality was 10.9% in the group of 256 screen-negatives with pathological ultrasound findings. This study provides further data to assess the efficiency of expanded cfDNA testing for RATs and SAs. The test efficiency for cfDNA seems to be higher for duplications than for deletions, which is evidence of the role of expert ultrasound in identifying pregnancies at increased risk for chromosome anomalies, even in pregnancies with screen-negatives. Furthermore, we discussed the efficiency of CVS vs. AC in screen-positives for RATs.

Prenatal ultrasonographic features in Blomstrand osteochondrodysplasia: Antenatal case series confirmed by postmortem radiology and molecular diagnosis.

OBJECTIVE: Blomstrand osteochondrodysplasia (BOCD, MIM #215045) is an ultrarare lethal skeletal dysplasia (LSD) perinatally, characterized by extremely advanced bone maturation, generalized osteosclerosis, and severe tetramicromelia caused by biallelic loss-of-function mutations in the parathyroid hormone receptor-1 gene (PTHR1). We aim to describe prenatal ultrasonographic features in a retrospective fetal case series of BOCD and emphasize the importance of multidisciplinary antenatal evaluation of LSDs to improve the differential diagnosis. METHOD: Prenatal ultrasound findings of five fetal cases diagnosed with BOCD between 2000 and 2019 in the Prenatal Diagnosis Unit and Medical Genetics were reviewed, along with postmortem examination results and confirmatory molecular results. RESULTS: All fetuses presented with severe sonographic findings of LSDs comprising tetramicromelia, thoracic hypoplasia, and retro-micrognathia. Marked cervical hyperextension was present in three fetuses. Flared metaphyses were prenatally identified in only one fetus. X-rays of four fetuses evaluated postmortem showed advanced bone maturation, generalized osteosclerosis, and dumbbell-like appearance of long bones due to metaphyseal enlargement. CONCLUSION: The presence of retro-micrognathia along with a protruding tongue and severe metaphyseal flaring can suggest a diagnosis of BOCD, when prenatal ultrasound findings are indicative for LSD. The diagnosis can be ascertained through postmortem clinical and radiological evaluation and/or molecular testing.

The effects of early or late multifetal reduction procedure on perinatal outcomes in multiple pregnancies reduced to twins or singletons: A single tertiary center experience.

OBJECTIVE: The aim of the study was to compare the effect of early or late fetal reduction (FR) procedures on perinatal outcomes in multiple pregnancies reduced to twins or singletons. STUDY DESIGN: This retrospective cohort study consisted of data from a single tertiary center between January 2013 and December 2020 and included 103 women with multiple pregnancies between 8 and 14 gestational weeks and who underwent FR by transabdominal approach. Late FR was defined as 11-13 6/7 gestational weeks (Group L) and early FR was defined as 8-10 6/7 gestational weeks (Group E) in the study. All pregnancies with FR were named Group S (Single) if reduced to singletons and Group T (Twin) if reduced to twin pregnancies. RESULTS: Thirty four percent (n = 35) were reduced to single pregnancy, the remaining 66% of these cases (n = 68) were reduced to twin pregnancy. The overall survival rate was 90%.When the cases were examined in terms of pregnancy complications, it was observed that the PPROM rate and preterm labor rate in the Group T were statistically significantly higher than the Group S (p = 0.015 and p < 0.001, respectively). When comparing the overall survival results between Group S and Group T, it was found that the overall survival of Group S was statistically significantly better (p < 0.001). When Group E and Group L were compared in terms of their pregnancy course and neonatal outcomes, no statistically significant difference was found between them. No statistically significant difference was found between the complication rates in the first week after the procedure (p < 0.05). Neonatal intensive care need was found at a rate of 31% in those with Group E, while this rate was found as 39% in Group L, and this difference was also not statistically significant (p = 0.480). When the preterm labor rate was compared between these two groups, there was no statistically significant difference in all three subgroups (<32nd, <34th, and <37th gestational weeks). CONCLUSION: When FR to singleton is required for fetal or maternal reasons, it should be discussed with the parents that the risk of fetal loss is similar to FR to twins, but the effect on perinatal survival is more favorable than expected.

Antenatal diagnostic dilemma in a pseudodominant pedigree with lamin-B receptor (LBR)-related regressive spondylometaphyseal dysplasia.

The lamin-B receptor (LBR) encodes a dual-functioning inner nuclear membrane protein essential for cholesterol biosynthesis and chromatin organization. LBR pathogenic variants cause distinct phenotypes due to the dual function of LBR, including Pelger-Huët anomaly (PHA), PHA with mild skeletal anomalies (PHASK; MIM# 618019), LBR-related regressive type of spondylometaphyseal dysplasia (LBR-R-SMD), Greenberg dysplasia (MIM# 215140). We here report the first case with radiological manifestations of LBR-R-SMD in the fetal period, and milder skeletal findings in the similarly affected father. Direct sequencing of LBR revealed homozygous c.1534C>T (p.Arg512Trp) in exon 12 in both affected individuals. Our report further refines the early phenotype in LBR-R-SMD, and demonstrates that the p.Arg512Trp mutation is associated with PHA. We propose that LBR-R-SMD should be considered as a differential diagnosis in pregnancies with sonographic evidence of short and bowed tubular bones with narrow thorax. Evaluating peripheral blood smears of expectant parents for the presence of PHA may lead to a clinical diagnosis, allowing for comprehensive prenatal genetic counseling.

Prenatal sonographic and cytogenetic/molecular findings of 22q11.2 microdeletion syndrome in 48 confirmed cases in a single tertiary center.

PURPOSE: We aimed to present the fetal ultrasound, cytogenetic/molecular testing and postmortem or postnatal clinical findings of cases with 22q11.2DS diagnosed prenatally. MATERIALS AND METHODS: A retrospective medical record review of 48 prenatal cases diagnosed with 22q11.2DS were evaluated in our institution. Detailed ultrasound examination was performed on all fetuses. Postmortem and postnatal examinations were evaluated. The microdeletions were detected by karyotyping or microarray, then confirmed by FISH. Descriptive statistical analysis was performed. RESULTS: Demographic data of 48 prenatal cases including 46 singletons and 1 dichorionic diamniotic twin pregnancy were evaluated. The most common extracardiac anomaly was skeletal system anomalies (25%), in which PEV was the most frequent one (20.8%). Polyhydramnios rate was detected as 31%, in 6.6% as an isolated finding. Microdeletion has been detected by karyotyping in 13 cases (13/47, 27.7%) (including 2 unbalanced translocations), by FISH in 28 cases (28/48, 58.3%), by microarray/a-CGH testing in 7 cases. Microarray analysis showed that in one case with unbalanced translocation had two consecutive deletions; one was proximal and other one distal to critical region and not encompassing TBX1 gene but CRKL and LZTR1 genes. CONCLUSION: The current study demonstrates the whole spectrum of atypical phenotypic and genotypic variations of 22q11.2DS in the largest prenatal case series reported to date. Therefore, differential diagnosis should be considered not solely in CHD, but also in the presence of isolated clubfeet and polyhydramnios. Establishing the diagnosis in the prenatal period may allow a postnatal multidisciplinary approach, as well as affect the actual prevalence of the disease.

Prenatal Diagnosis and Findings in Ureteropelvic Junction Type Hydronephrosis.

The widespread use of obstetric ultrasonography has increased the detection rate of antenatal hydronephrosis. Although most cases of antenatal hydronephrosis are transient, one third persists and becomes clinically important. Ultrasound has made differential diagnosis possible to some extent. Ureteropelvic junction type hydronephrosis (UPJHN) is one of the most common cause of persistent fetal hydronephrosis and occurs three times more in male fetuses. It is usually sporadic and unilateral. However, when bilateral kidneys are involved and presents with severe hydronephrosis, the prognosis may be poor. Typical ultrasound findings of UPJHN is hydronephrosis without hydroureter. The size and appearance of the fetal bladder is usually normal without thickening of the bladder wall. Several grading systems are developed and increasingly being used to define the severity of prenatal hydronephrosis and provides much more information about prediction of postnatal renal prognosis. If fetal urinary tract dilation is detected; laterality, severity of hydronephrosis, echogenicity of the kidneys, presence of ureter dilation should be assessed. Bladder volume and emptying, sex of the fetus, amniotic fluid volume, and presence of associated malformations should be evaluated. Particularly the ultrasonographic signs of renal dysplasia, such as increased renal parenchymal echogenicity, thinning of the renal cortex, the presence of cortical cysts, and co-existing oligohydramnios should be noticed. Unfortunately, there is no reliable predictor of renal function in UPJHN cases. Unilateral hydronephrosis cases suggesting UPJHN are mostly followed up conservatively. However, the cases with bilateral involvement are still difficult to manage. Timing of delivery is also controversial.

Utilization of neurosonography for evaluation of the corpus callosum malformations in the era of fetal magnetic resonance imaging.

AIM: We evaluated the ability of fetal neurosonography and magnetic resonance imaging (MRI) to asses callosal anomalies (CA) and associated cranial malformations. We also aimed to determine the long-term prognosis of the cases. METHODS: Thirty-six cases of CA diagnosed combined with neurosonography and MRI between January 2012 and October 2017 were retrospectively reviewed. RESULTS: Seventeen of 36 fetuses were diagnosed complete agenesis of corpus callosum (CACC) (47.2%), 9 had partial agenesis of corpus callosum (PACC) (25%) and 10 was dysgenesis of the corpus callosum (DCC) (27.2%) at ultrasonography (US) examination. Fetal MRI reported 16 of cases as CACC (44.4%), 11 PACC (30.5%) and nine (25%) DCC. The overall consistency between neurosonography and MRI in the definition of CA were 91% of cases. Sulcation anomalies were present in 9 cases in the US (25%) and 11 cases in MRI (30.4%). Seven of cases showed posterior fossa abnormalities in the US (19.4%) and eight cases in MRI (22.1%). Neonatal MRI added new findings to fetal MRI and neurosonography including grade-1 intraventricular hemorrhage and periventricular leukomalacia in two cases (12.5%). Eighteen cases were terminated (50%), 17 cases were followed up and mean follow up interval was 39 ± 5.1 months. The neurologic outcome was abnormal in seven (41.7%) patients. Presence of associated brain anomalies worsened the prognosis. CONCLUSION: Fetal neurosonography has a comparable performance with MRI in the diagnosis of CA and associated anomalies. It should be used in collaboration with MRI to achieve accurate diagnosis which is crucial for counseling.

Evaluation of fetal subarachnoid space using transabdominal ultrasonography and normal values during pregnancy.

OBJECTIVES: To determine the feasibility of evaluating the subarachnoid space by measuring two novel sonographic parameters in axial section using transabdominal ultrasound, in addition to the parameters previously defined in coronal section, and to construct a normal range for the subarachnoid space width in singleton healthy fetuses. METHODS: Healthy pregnant women between 20 and 29 weeks were scanned using transabdominal ultrasound. Four variables were measured for the evaluation of subarachnoid space width; sinocortical width and anterior craniocortical width in coronal plane, and lateral and posterior craniocortical width in axial plane. RESULT: The data of 154 patients were recorded. SCW could be measured in 87.6 % (135) of fetuses, while the same figure was 77.9 % (120), 96.1 % (151) and 98.1 % (148) for anterior, lateral and posterolateral CCW, respectively. The SCW and anterior CCW did not display a significant correlation with gestational age and head circumference. The mean of SCW was 1.55 ± 0.41 mm with a range of 0.85-3.87 mm. The mean anterior CCW was 1.63 ± 0.39 mm with a range of 0.85-2.82 mm. A linear regression line was plotted between gestational age and lateral CCW (r = 0.707; p < 0.0001) and posterolateral CCW (r = 0.437; p < 0.0001), and nomograms for these parameters are constructed. CONCLUSION: This study presents a novel approach for the in utero evaluation of the subarachnoid space with two measurements in axial plane using transabdominal ultrasound. The nomograms will be helpful when there is a suspicion of subarachnoid space dilatation during routine cranial scan.