Iniencephaly: radiologic and pathomorphologic perinatal observation

Abstract

Iniencephaly (IE) is a rare neural tube malformation involving severe head retroflexion and deformity of the spine. IE is typically accompanied with other congenital abnormalities and carrying a poor fetal prognosis. This report presents radiological findings in a rare case of IE associated with multiple malformations of the skull, spine, face, heart, and body. A 44-year-old pregnant female underwent an obstetric ultrasound examination on the 26th week of gestation followed by fetal magnetic resonance imaging on the 36th week. Imaging revealed complex developmental anomalies, which led to the diagnosis of IE with a large cervical meningocele, occipital bone defect, spina bifida of the cervical vertebrae, multiple malformed vertebra, deformed face, coarctation of the aortic arch, and hypoplastic lungs. Based on these findings, a decision to terminate pregnancy was made. Pathological examination of the fetus showed close agreement with imaging. The presented case underscores the importance of multimodal imaging for clinical decision making in the management of complex neural tube malformations.

Introduction

Iniencephaly (IE) is a rare neural tube defect [1,2] involving dysmorphic spine and abnormal fusion of the portion of the occipital skull with the back. It results in extreme fixed head retroflexion. This condition accounts for approximately 1% of all fetal malformations and has been described in scattered case reports [2], [4], [5], [6], [7], [8]. We present a case of the iniencephaly apertus variant (characterized by the presence of cervical encephalocele) accompanied with numerous additional neural axis and body malformations.

Case report

A 44-year-old woman (gravida 2, para 1) living in a rural area of the mountain Altay region of Siberia appeared at the first obstetric appointment on the 25th week of pregnancy. No obvious risk factors were noticed. The mother was on iron and folic acid supplementation during the second trimester due to mild anemia.

Ultrasonography and magnetic resonance imaging

The routine ultrasonogram performed at 26 weeks of pregnancy revealed a live single female fetus with multiple congenital anomalies including cervical meningocele, neck hyperextension, and abnormally short and deformed spine (Fig. 1a and b). In addition, a congenital heart defect, coarctation of the aortic arch with a transposition of the great vessels was detected.

Fig. 1.

Transabdominal ultrasound images at 26 weeks of pregnancy. (a) Excessive thickening of the fetal neck with subcutaneous craniothoracic lipoma (arrow). (b) Cystic lesion in the neck.

Fetal 3 T magnetic resonance imaging (MRI) was performed on the 36th week of pregnancy. The delay was due to limited availability of advanced care at the patient's place of residence. MRI revealed complex developmental anomalies, which led to the diagnosis of iniencephaly apertus variant (with cervical encephalocele) accompanied with face and body malformations (Fig. 2a and b). An exramidline exophytic cystic lesion filled with cerebrospinal fluid with the size of 7.7 × 7.1 × 3.1 cm and overlying skin was identified in the occipital neck region. The finding was impressive of a closed cervical meningocele (Figs. 2b, and 3a). A small soft tissue component was present within the proximal part of the cyst (Fig. 2a). The occipital bone defect, spina bifida of the cervical vertebrae, enlarged foramen magnum, and herniation of the brainstem and cerebellum beyond the cervicomedullary junction were also seen (Figs. 2a, and 3d). The spinal canal in this region was widened (Fig. 2a). The malformed cervicothoracic spine appeared thin and curved due to hyperextension and shortening of the spinal column. The supratentorial brain parenchyma was normal. The lateral and third ventricles were normal in size and shape, except for mild colpocephaly (Fig. 3a–d). The fourth ventricle and cisterna magna were moderately compressed (Fig. 3а and d). T1- and T2*-weighted images demonstrated no signs of cerebral hemorrhage. On the screening fetal body MRI, the small round trunk was seen (Figs. 1a, and 3b, d). Lungs were hypoplastic and dehydrated with a reduced thoracic volume (Fig. 3a and b). In the coronal plane, flexion of the large arms and clenched fists were observed (Fig. 3b). Face was stigmatic with frontal hyperostosis, hypotelorism, face-neck lipoma, and malformed ears (Figs. 2 a, and 3c). The lack of movement was observed on fetal cine-MRI.

Fig. 2.

T2-weighted MRI of the fetal head at 36 weeks of pregnancy . Axial (a) and sagittal (b) images show meningocele with a small soft tissue component in the proximal part (arrow), low-set and malformed ears, posterior fossa defect with the cerebellum herniation, polyhydramnios, neck hyperextension, and fusion of fatty tissue at the neck level.

Fig. 3.

T2-weighted MRI of the fetus at 36 weeks of pregnancy in the coronal (a, b), axial (c), and sagittal (d) planes. (a) Cervical closed meningocele. (b, c) Subcutaneus craniothoracic lipoma (arrow). (c, d) Facial deformation caused by thickening of the frontal bone, hypotelorizm, hyperextension and fusion of the fat tissue at the neck level, low-set ears. (d) Head retroflexion and posterior fossa defect (arrow), neck thickening.

Pathology

Due to hopeless fetal prognosis, the pregnancy was terminated on the 38th week of gestation by induction of labor upon the mother's informed consent. The fetus was delivered vaginally after induced fetal demise and intrauterine meningocele puncture (Fig. 4a and d). On autopsy, the fetus weighed 2110 g and showed delayed and discordant development according to the anthropometric indicators, which approximately corresponded to 33 weeks of gestation. The retroflexed head (30 cm in circumference) and body were small relative to the enlarged extremities. The abortus had the short and thickened hyper-extended neck covered with hair. The ears were low-set (Fig. 4b and c). Pathologic examination confirmed the diagnosis of IE. The occipital bone had a pronounced defect adjacent to the enlarged foramen magnum (Fig. 5a). Posterior fossa was small. The meningocele was covered from inside with the dura mater, which extended from the cranial cavity. (Fig. 5a). Fixed retroflexion of the head was caused by abnormal fusion between a portion of the occipital skull and hyperlordotic spine. The vertebral column was short with uneven vertebrae. Thoracotomy showed the dysplastic ribs, hypoplastic lungs, and coarctation of the aortic arch (Fig. 5b and c).

Fig. 4.

Photographs of the abortus after delivery. (a-d) Cervical closed meningocele punctured before delivery (arrow). (b, c) Subcutaneus craniothoracic lipoma (arrow). (b-d) Face structures deformation caused by thickening of the frontal bone, hypotelorizm, hyperextension and fusion of the fat tissue at the neck level, low-set ears. (d) Head-neck fusion, short vertebral column and enlarged hands in the abortus.

Fig. 5.

Autopsy view of the fetus. (a) Axial craniotomy shows occipital bone defect (arrow), small posterior and enlarged anterior fosses, frontal bone thickening. (b) Malformed and hypoplastic thorax, ribs. (c) Coarctation of the aortic arch.

Discussion

The embryologic basis of the clinical variations in the neural-tube defects is poorly understood. Different cellular mechanisms and various sites of neural tube closure might underlie clinical manifestations, as they could have different sensitivity to various pathogenic factors, such as the type and time of exposure to teratogenic agents [1]. The advanced maternal age is a known risk factor for neural tube defects [1,2]. A female preponderance (90%) of IE has been noted in the literature [4]. Both these factors were present in our case. Occasionally IE is seen in families with a history of neural tube defects, and the recurrence risk is about 5% [4]. The exact etiology and pathogenesis are not clear, and both genetic and environmental causes have been implicated. Various factors, such as poor socioeconomic status, obesity, certain medications (sulphonamide, tetracycline, antihistamines, and cytostatic agents), and the lack of folic acid supplementation were shown to increase the risk [5]. However, in the present case there were no relevant family history or abovementioned risk factors. The first child in the family has no congenital abnormalities.

From the radiological point of view, we can emphasize that only comprehensive multimodal imaging can prevent the delay in the diagnosis of IE and convince the mother to terminate the pregnancy. Congenital retroflexion of the spine and accompanying heart defects are mainly seen on ultrasound images. Ultrasound findings might be surely confirmed by MRI in most cases, as additional information can be acquired about the precise diagnosis, severity and location of the neural tube anomaly. Thus, further clinical management can be guided with regard to terminating pregnancy or providing adequate postnatal care. IE carries a poor prognosis [3], [4], [5], [8]. There are some cases of long-term survival [6,7], but most neonates die antenatally or soon after birth. Prevention is still problematic due to poorly understood pathogenesis.

In conclusion, accurate MRI diagnosis is required in addition to ultrasonography to demonstrate the inevitability of pregnancy termination in IE to obstetricians and parents. The comparison between imaging and pathological findings in IE revealed the benefits of both ultrasound for the cardiac and great vessel malformation diagnosis and MRI for the detection of the brain and spine abnormalities. Both modalities demonstrated high concordance with pathology and should be complimentary used in evaluation of complex neural tube malformations.

Patient Consent Statement

Written informed consent for publication of this case report was obtained from the patient. All images were anonymized and contain no personally identifiable information.