A fetopathological and clinical study of the Dandy-Walker malformation and a literature review

Introduction

The Dandy-Walker malformation (DWM) is a congenital abnormality of the central nervous system (CNS), which includes an agenesis or hypoplasia and an upward displacement of the cerebellar vermis, a cystic dilatation of the fourth ventricle and its communication with cisterna magna, an enlargement of the posterior cranial fossa and an upward displacement of tentorium cerebelli and torcular herophili. DWM often leads to developmental disorders and severe disability, but they are largely related to the presence of associated anomalies of CNS and other organs and systems, which need to be thoroughly searched and evaluated. The malformation needs to be differentiated from the so called DW variant which is a ciliopathy associated with the sign of the molar tooth, and also from the Blake pouch cyst which is the rudimental fourth ventricular tela choroidea caused by a failed perforation of the Magendie foramen [1]. The evaluation of the cytogenetic status is also important, as DWM is often seen in the context of various chromosomal disorders [2]. Many parents prefer to interrupt the pregnancy after an ultrasound diagnosis of DWM, even without explicit imaging or cytogenetic data for other abnormalities, due to the potential for neurological and cognitive deficits.

The aim of this study is to compare two cases of an isolated DWM – one by autopsy after abortion due to medical indications during the 25^th gestational week and a one-year-old boy, and to compare the results with those in the literature.

Materials and methods

The data from the macroscopic, fetopathological and microscopic examination of the fetus from the aborted for medical reasons pregnancy after an ultrasound diagnosis of DWM at the Clinic of Embryo and Fetopathology, Center for Maternity and Neonatology, Tunis, Tunisia, as well as clinical and neuroimaging studies, operational findings, and the postoperative result in a 1-year-old infant diagnosed at the Clinic of Neurosurgery, Medical University Plovdiv, Plovdiv, Bulgaria. All research was performed after written authorization for an autopsy and histological study and in accordance to the local ethics committee guidelines.

Case Description

Case 1

A female fetus obtained after abortion due to medical indications during the 25^th gestational week after the prenatal diagnosis of DWM. The mother is a 23-year-old from Tunis of blood type A(+). This was her first pregnancy, and there is information on first degree incest. The macroscopic study of the fetus showed macrocrania, hypertelorism, malformed and attached low to the head ear shells, microretrognathia, single transverse palmar crease and curved feet – pes varus (Figure 1A). The fetopathological study found hypoplasia and incorrect lobulation of the lungs, an abnormal mesentery, cerebellar hypoplasia and hydrocephalus. Regardless of the hypoplasia of the cerebellum, the histological study found that the cortex seems normal for the age of the fetus with a four-ply organization, including an external granular layer, a molecular layer with migrating granule cells, a layer of Purkinje cells which is normally immature at the 25^th gestational week and an internal granular layer (Figure 1B). The ultrasound diagnosis of DWM was proven by the fetopathological autopsy.

Figure 1:

(A) Macroscopic image of the fetus. (B) The four-layered cerebellar cortex including the external granular cell layer, the molecular layer with many migrating granular cells, the Purkinje cell layer and a thin internal granular cell layer.

Case 2

A 1-year-old boy from the third pregnancy of a 27-year-old mother with three healthy children from two previous pregnancies. They live in an area without known hazards. The mother denies having harmful habits, chronic diseases, and infectious conditions, as well as taking medications during the pregnancy, having sick family members and a consanguineous relationship with her husband. The latter is a smoker of 29 years, without chronic diseases. During the normal development and ending on term pregnancy, several ultrasound studies were conducted, all of which did not detect any abnormalities. A couple of days before the admission of the child to the clinic, he had begun to stumble and fall, was drowsy and vomited repeatedly. Two days before his hospitalization, he had a seizure and fell into a state of opisthotonus. For this reason, a computed tomography (CT) study of his head was performed, and he was directed to the clinic. At his admission to the clinic, the child was somnolent, and his somatic status was only represented by a poor general condition and an unclosed, tense fontanelle. The neurological status showed a pronounced intracranial hypertensional and meningoradical syndrome (opisthotonus) and bilateral pyramidal symptoms with hypertonia of the four limbs, more pronounced in the legs. The papillae were bilaterally outlined on the level of the retina in the fundoscopy study. Also, the blood vessels showed no harsh changes. The blood markers were in the normal ranges for the child’s age and the CT scan established an expressed hydrocephalus (IIIth ventricle 19 mm), as well as data for DWM (Figure 2A and B). Due to the urgency of the child’s status, an external drainage was preformed immediately, and a few days later, a ventricluloperitoneal shunt was placed (CODMAN HAKIM programmable valve, DePuy Synthes Spine, Raynham, MA, USA).

Figure 2:

Computed tomography (CT).

(A) Axial plane – a wide communication of the IV^th ventricle with cisterna magna and hypoplasia of the vermis and the two cerebellar hemispheres. (B) Sagittal plane – an elevation of vermis cerebelli, tentorium cerebelli and torcular herophili.

After the surgical treatment, the child’s condition rapidly improved, and only the discoordinational syndrome persisted. His psychomotor status was deemed normal for his age. The postoperative magnetic resonance imaging (MRI) showed a reduction of the hydrocephalus and a confirmation of the presence of DWM – an expansion of the IVth ventricle, widely communicating with cisterna magna, hypoplasia of the vermis with aplasia of its lower part and hypoplasia of the left cerebellar hemisphere. Supratentorially, there was no data for other CNS anomalies (Figure 3A, B and C).

Figure 3:

Postoperative magnetic resonance imaging (MRI).

(A) Subtentorial axial plane. (B) Sagittal plane – an upward displacement of vermis cerebelli (left marker); tentorium cerebelli is located high (top right marker); torcular herophili is also situated high above protuberantia occipitalis (bottom right marker). (C) Supratentorial axial plane – a significant reduction of the hydrocephalus.

Discussion

The incidence of DWM in live births varies widely from 1:800 to 35,000 depending on the population studied and the methods used [3–5]. In the literature, it is reported that DWM more commonly occurs in females – 1.5:1 to 2:1 [6, 7]. The etiology of the disease is not fully understood, but it is assumed that it is associated with infections (rubella, toxoplasmosis, cytomegalovirus) and alcohol intake during pregnancy as well as genetic and chromosomal disorders [3, 8, 9]. Neither of these risk factors was identified in our cases. The pathogenesis is also unclear, although various theories have been proposed. According to Friede, there is an interruption in the embryonic development of the rhombencephalon and an unsuccessful union of the cerebellum along the midline between the 7^th and 10^th gestational weeks [10]. This leads to the persistence of the front membranous area, which expands and extends between hypoplastic cerebellar vermis and the choroid plexus, causing an upward expansion of the IVth ventricle [10].

Associated abnormalities of the CNS and other systems are found in over 71% of the children with DWM, and the most common is ventriculomegaly – 71%, followed by the agenesis of corpus callosum – 14% [11, 12]. Rarely, holoprosencephaly, micropolygyry, occipital meningocele and meningoencephalocele are seen [13]. Extracranial malformations such as polycystic kidney disease, facial hemangiomas, heart defects, and limb and palate defects are also not uncommon [9]. DWM may be associated not only with polymalformative syndromes such as the Arnold-Chiari malformation, Meckel-Gruber syndrome, Joubert syndrome, Ellis-van Creveld syndrome, but also with recurrent chromosomal abnormalities as the 6p24-25 deletion, 5p and 8p duplications. Hydrocephalus is common in cases of DWM, both prenatally and during the neonatal period, but it is more of a complication rather than a part of DWM [3]. Hydrocephalus is observed in 60–100% of DWM cases with an impaired lobulation of the vermis and postnatally develops in over 80% of cases, mainly during the first few months, most likely due to a primary atresia of the communicative foramina [6, 11]. It is believed that children with DWM represent 1–4% of all cases of hydrocephalus [13].

The improvement of neuroimaging methods increases the diagnosis of malformations of the cerebellum in the prenatal period, as well as after birth [14]. The prenatal diagnosis of DWM is usually achieved by ultrasound, which allows the identification of the characteristics of the disease. Some authors believe that the abilities of the ultrasound prenatal diagnosis of DWM are limited [1, 15–17]. When comparing the prenatal ultrasound and fetopathological findings of brain abnormalities, Carroll et al. find a 77% match, where in the prenatally diagnosed DWM the mismatch was 57% [15]. Similar are the results reported by Isaksen et al. and Sun et al., who found that in three of the eight fetuses the prenatally diagnosed DWM is not supported by the autopsy findings [16, 17].

The prenatal diagnosis of DWM poses an important question to the physician about the prognosis of the disease, based on which the parents have to make a decision. This is often not easy, especially given that there is no consensus in literature. Aletebi et al. believe that all children with DWM develop varying degrees of cognitive impairment, while Eckler et al. and Has et al. found that more than 1/3 of live children with DWS develop normally. [11, 12, 18]

When comparing the IQ of children with DWM with and without normal lobulation of the vermis Boddaert et al. and Klein et al. found that the IQ of the first group is normal in 82%, while none of the children with DWM and without normal lobulation had a normal IQ. Associated anomalies of CNS and other systems are found in children with a normally lobulated vermis but with a lower than normal IQ [6, 19]. Distortions of speech and communication in children with DWM are not well understood, but it is assumed that a neurologic deficit is present in over 50% of cases, and the most common are hypotonia (50%), cerebellar dysfunction (42%) and hemiparesis (5% ) [11, 12, 14].

It is a known fact that in children with DWM which develop normally, the anomaly is isolated, while in cases of associated anomalies of CNS – a developmental delay and epilepsy are observed [6, 14, 19, 20].

In the first of our cases, the prenatal ultrasound diagnosis of DWM led to an abortion due to medical indications. The fetopathologic study confirmed that it was an isolated DWM. In the second case, the prenatal ultrasound study found no abnormalities, but a year after birth in relation to an acute hydrocephalus which caused intracranial hypertension syndrome, the Dandy-Walker complex was diagnosed without evidence of other anomalies. After determining the presence of a sufficient communication between the lateral ventricles and the cyst and that it is not necessary to place a cystoperitoneal shunt, we placed a ventriculoperitoneal shunt. Тhe hydrocephalus was reduced, the child’s condition rapidly improved, and the neuropsychiatric development was assessed as normal for the child’s age.

Conclusion

The prenatal ultrasound findings of cerebellar abnormalities should only serve as an indicator for further detailed studies of the fetus through MRT, amniocentesis for the examination of the fetal karyotype and fetal cardiogram to seek additional malformations of the CNS and beyond, as well as chromosomal disorders. In the absence of such, an abortion due to medical indications should not be offered as the possibility of a favorable outcome of the pregnancy and a normal or near normal neuropsychiatric development is high. A timely and multidisciplinary approach to treatment is necessary because the development of the cerebellum is not completed until the end of the first year after birth [21]. A proper intervention on time can lead to the reorganization of the cerebellar functions and a favorable outcome of the disease, given the high plasticity of the child’s brain [22].