A 46-year-old woman with no previous medical history first visited ophthalmologic department with amaurosis fugax for about 20 min and persistent visual impairment of left eye. The corrective vision examination showed that visual accuracy of the left eye is 0.1 and the right eye is normal 1.0. Pupillary light reflex test showed relative afferent pupillary defect (RAPD) of the left eye. The fundus examination did not find significant abnormalities (Fig. A). The Visual-Evoked Potential (VEP) test demonstrated the prolonged latency and declined amplitude of P100 wave of the left eye (Fig. B), indicating the impairment of left visual pathway. The fundus fluorescein angiography found that the arm-retinal circulation time of left eye was 25 s (Fig. C and Additional file : Video 1), whereas the normal time window is only 10 ~ 15 s. The right eye did not present any abnormality (Fig. C). Accordingly, the CRAO diagnosis was confirmed and ophthalmologic examination indicated that the occlusion might occur in the pathway from aortic arch to ophthalmic artery.\nTherefore, the patient was transferred to neurological department. The MR angiography (MRA) found that bilateral ICAs were absent concurrent with dilated vertebral and basilar arteries. Meanwhile, there were variations in the circle of Willis with opened right posterior communication artery (PCoA) and absence of left PCoA (Fig. A). Moreover, CT angiography (CTA) images (Fig. B, C) illustrated that bilateral hypoplasia of the ICAs from carotid bifurcation with thin remnants and the bilateral bony carotid canals still existed in CT bone window (Fig. D), confirming the diagnosis of bilateral ICAs hypoplasia but not ICAs agenesis. Hereto, we can depict the characteristics of the blood flow of the case: (1) due to bilateral ICAs hypoplasia, vertebrobasilar artery system takes the responsibility to provide blood supply to the whole brain and results in dilated vertebral and basilar arteries; (2) as a result of variation of the circle of Willis, the blood flow first supplies right middle cerebral artery (MCA) and ophthalmic artery via opened right PCoA and then the left MCA and ophthalmic artery via opened anterior communicating artery (ACoA).\nHowever, the amaurosis fugax and lasting visual impairment of left eye cannot be well interpreted. According to the standard of TOAST typing of stroke, the cardiogenic factors were evaluated then. Atrial fibrillation and valve vegetation were not detected by 24-h dynamic electrocardiogram and echocardiograms. Transesophageal echocardiography (TEE) revealed patent foramen ovale (Fig. ) and blood split-flow from right to left atrium when doing Valsalva breath during the Foaming test (Additional file : Video 2). Therefore, the amaurosis fugax and persistent visual impairment of left eye was caused by cardiogenic embolism.\nAspirin 100 mg/day was given to the patient and PFO occlusion surgery was recommended by us. However, the patient refused the surgery and was lost to follow-up.
The patient was a 17-year-old boy on rhGH therapy for 14 years because of a GH deficiency that was diagnosed at the age of 2 years and 3 months. Therapy was stopped 9 months before the beginning of symptoms—fatigue, decreased muscle strength and severe headache. However, the patient had not come for retesting one month after discontinuation of rhGH treatment.\nThe propositus was the first child of non-consanguineous Italian parents. The mother was in treatment for post-partum depression. The maternal grandfather was in treatment for autoimmune hyperthyroidism.\nThe mother’s height was 152 cm and she had menarche at the age of 13; the father’s height was 168 cm and he had a normal development. The target height was 166.0 ± 6.0 cm (−1.70 SDS). All auxological data were normalized for chronological age by conversion to standard deviation scores (SDS) that were calculated according to the following formula: patient value - mean of age-related reference value/standard deviation of the age-related reference value [].\nThe child was born at 40 weeks of gestation with an uncomplicated delivery. The birth weight was 2970 g (−1.15 SDS), length at birth was 50 cm (−0.30 SDS), and his occipito-frontal head circumference (OFC) was 34 cm (−0.61 SDS). He had neonatal jaundice requiring phototherapy. The child’s neuromotor development was normal: he sat at 6 months, walked independently at 12 months, and began to use language at 14 months.\nAt 6 months, the patient exhibited very deficient growth (Fig. ). At 2 years and 3 months, he was admitted to our Paediatric Endocrine Unit for an endocrinological evaluation. His height, evaluated according the growth charts compiled by Cacciari et al. [], was 78.6 cm (−2.79 SDS). His weight was 9.830 kg (−2.78 SDS), and his BMI was 15.91 (−0.28 SDS) (Fig. ). Extensive biochemical, endocrinological and metabolic examinations did not reveal any abnormalities with the exception of plasma concentrations of IGF-I and IGFBP-3 that were low for his age and sex: 27 ng/mL and 1.38 μg/mL, respectively. Thus, GH stimulation tests were performed and showed a reduced response after the clonidine (GH peak of 5.2 ng/mL) and insulin (glucose nadir 2.0 mmol/L at 30 min; GH peak of 3.9 ng/mL) tests. This revealed a GH deficiency (GHD). Bone age was assessed according to the Greulich and Pyle method [], and it was delayed (1 year and 2 months versus a chronological age of 2 years and 3 months). Brain MRI of the hypophyseal region showed the presence of a pituitary hypoplasia (height 1.8 mm and width 2.7 mm). Consequently, hGH therapy (0.22 mg/kg/wk) was started.\nThe child responded very well to rhGH treatment (Fig. ) and at 3 years and 4 months old, his height was 94.5 cm (−1.14 SDS), weight 12.450 kg (−2.10 SDS), height velocity 15.06 cm/yr (5.05 SDS), and BMI 13.94 (−1.75 SDS). At 4 years and 3 months old, his height was 101.9 cm (−0.82 SDS), his weight was 15.300 kg (−1.24 SDS), his height velocity was 8.05 cm/yr (1.12 SDS), and his BMI was 14.73 (−0.82 SDS).\nThe onset of puberty occurred at 12 years old with normal onset, timing, tempo, and magnitude of pubertal changes []. He stopped rhGH treatment at 16 years and 3 months old when he reached the definitive stature []: his height was 170.8 cm (−0.64 SDS) and his weight was 51.800 kg (−1.56 SDS) with a BMI of 17.76 (−1.63 SDS) (Fig. ).\nAt 17 years old, his GH secretion was re-tested by the growth-hormone-releasing hormone (GHRH) + arginine test, which is a reliable test of ITT in retesting patients who had undergone GH treatment in childhood []. The test confirmed a severe GH deficiency (basal GH value of 0.18 ng/mL; GH peak of 2.42 ng/mL).\nMRI angiography was performed because of the severe growth hormone deficiency (GHD) and headache; it confirmed the presence of adenohypophyseal hypoplasia (height 2.5 mm and width 3.5 mm) with a lack of posterior pituitary hyperintensity. The MRI angiography also showed the absence of a normal flow void in the left ICA (Fig. ).\nNo abnormal findings were noted in the electrocardiogram. Chromosomal studies of the peripheral lymphocyte cultures revealed a 46,XY normal male karyotype. An array of CGH analyses on the patient’s DNA was performed with an Agilent 60 K array platform with a resolution of approximately 100 kb. No genomic imbalances were detected. A complete examination was performed with particular attention to neurology, metabolism, and endocrinology (Table ). The only abnormal result was a very low IGF-I value (31 ng/mL). In light of these results, the patient restarted rhGH therapy, and his symptoms at the time of referral disappeared.