Synonyms: Hydrocephalic anencephaly, hydroencephalodysplasia, hydromercencephaly, cystencephaly.

Prevalence: 1-2.5:10,000 births²

Definition: Absence of the cerebral hemispheres with an incomplete or absent falx and a sac-like structure containing cerebral spinal fluid surrounding the brainstem and basal ganglia.

Etiology: Five theories have been proposed: 1) bilateral occlusion of the supraclinoid segment of the internal carotid arteries or of the middle cerebral arteries⁶, 2) an extreme form of leukomalacia formed by confluence of multiple cystic cavities, 3) diffuse hypoxic-ischemic brain necrosis⁷, 4) infection - necrotizing vasculitis^8,9,10,11,

5) thromboplastic material from a deceased co-twin¹.

Pathogenesis: Liquefaction of the brain tissue in the area involved (usually the hemispheres), with replacement of the neural tissue by cerebrospinal fluid and preservation of the membranes.

Associated anomalies: Spacticity, renal aplastic dysplasia, polyvalvular developmental heart defect¹² and trisomy 13.

Differential diagnosis: Extreme hydrocephalus, alobar holoprosencephaly, porencephaly.

Prognosis: Fatal.

Recurrence risk: Not known to be increased.

Management: As for disorders with fatal outcome.

MESH Hydranencephaly-diagnosis BDE 0480 ICD9 742.3 CDC 742.320

* Address correspondence to Thomas C. Wheeler, MD Department of Obstetrics & Gynecology, Vanderbilt University Medical Center, 21^st and Garland, Nashville, TN 37232-2519. Phone: (615) 322-2308 Fax (615) 343-8881, §Dept. of Pathology, Nashville General Hospital, ¶ Dept of Radiology, Vanderbilt.

Introduction

Recent reports describe the antenatal diagnosis of hydranencephaly based upon sonographic recognition of characteristic intracranial anomalies. We present two cases in which the initial evaluation demonstrated normal anatomic development, while the follow-up evaluations, revealed complete absence of the cerebral cortex and findings consistent with hydranencephaly.

Case reports

Case #1

A 30-year-old G₅P ₀₃₁ white female presented to the emergency room with fever, pyuria, and a positive pregnancy test. She was admitted to the medicine service with a presumptive diagnosis of pyelo­nephritis. Her past medical history was significant for chronic hypertension, intravenous drug abuse, and 3 previous spontaneous abortions. An ultrasound examination revealed a normal singleton fetus at 15 weeks (fig. 1).

Fig. 1: Case #1: Normal cranial structures at 13 weeks.

The patient was lost to follow-up until she presented at 26 weeks with vaginal bleeding and pelvic pain. The second ultrasound revealed markedly abnormal intracranial structures (fig. 2).

Fig. 2: Case #1: Liquefaction of the brain at 26 weeks with persistence of midline structures

The cerebral anatomy was reduced to fluid surrounding a dense midline echo. These findings were interpreted as either hydranencephaly or severe alobar holoprosencephaly. The patient was again lost to follow up and later delivered at 30 weeks, a 960g female infant who was unresponsive and expired after 1 hour.

The autopsy revealed a premature infant with a head circumference of 24cm. The bones of the skull were thin and elastic with open fontanelles. The cranial cavity, when opened, was filled with bloody fluid and remnants of the falx were noted in the midline. The cerebellum was of normal size and shape. The medulla and spinal cord were grossly intact. Multiple microscopic sections from the CNS were taken. The cerebral hemispheres were reduced to a thin layer of glial tissue with foci of calcification. No neurons were identified within the glial tissue. The choroid plexuses were well developed within the ventricular spaces. Maternal serology for Cytomegalovirus, Toxoplasmosis, and Rubella were negative. No culture for Herpes Simplex Virus was obtained. The karyotype was that of a normal female.

Fig. 3: Case #1: Sagittal section of the central nervous system. The cerebral cortex is reduced to a thin layer of glial tissue covered with meninges (arrows). The thalamus (black arrowhead) and, immediately above it, the choroid plexus, are present. The pons and cerebellum are of normal size.

Case #2

 A 28-year-old G₃P₀₀₂₀ white female was referred to the high-risk obstetric clinic at 17 weeks gestation after a routine ultrasound screen for anomalies revealed abnormal intracranial anatomy. The patient"s prenatal course had been complicated by multiple episodes of first trimester bleeding. Her obstetric history was significant for 2 previous spontaneous abortions. There was no familial history of congenital anomalies and no history of Herpes Simplex exposure. An ultrasound at 13 weeks gestation revealed appropriate biometry and anatomic development. During the follow-up exam at 17 weeks, however, the cerebral hemispheres could not be identified but structures in the posterior fossa appeared normal.

Fig. 4: Case #2: Layering of the necrotic brain tissue is evident when the mother is placed in different position (left: supine, right: left lateral decubitus).

A left- sided pleural effusion and contracted limb posturing was noted as well. After counseling, she elected to undergo termination of this pregnancy. She delivered a 148g male fetus without gross internal or external abnormalities. The sagittal suture was incised and 30cc of sanguineous fluid was drained, and there was no visible gray or white matter. No Herpes culture was obtained. The karyotype was that of a normal male.

Discussion

Hydranencephaly is a congenital malformation of the brain characterized by the absence of the cerebral hemispheres, an incomplete or absent falx and a saclike structure containing cerebral spinal fluid surrounding the brainstem and basal ganglia⁵. Approximately 1 percent of infants thought to have hydrocephalus by clinical examination are later found to have hydranencephaly³. Hydranencephaly is found in 0.2% of infant autopsies⁴.

Etiology

Five etiologies have been described. They include:

1) Bilateral occlusion of the supraclinoid segment of the internal carotid arteries or of the middle cerebral arteries⁶. Myers described the surgical ligation of the common carotid arteries and jugular veins of a rhesus monkey fetus of 84-86 days of gestational age. On subsequent post mortem examination, the fetal head was fully developed and of normal conformation. The cerebral hemispheres, however, were thin membranous sacs filled with cerebrospinal fluid. The brainstem and cerebellum were unremarkable on gross examination. Similar procedures performed at later gestational ages typically demonstrated less severe cerebral dysgenesis. Thus, it was reasoned that the magnitude of cerebral dysgenesis appears to be a function of the gestational age of the fetus at the time of the vascular accident.

2) An extreme form of leuko­malacia formed by confluence of multiple cystic cavities¹.

3) Diffuse hypoxic-ischemic brain necrosis. Fetal hypoxia due to maternal exposure to carbon monoxide or butane gas may result in massive tissue necrosis. Subsequent cavitation and resorption of necrotized tissue creates the characteristic findings⁷.

4) Infection - necrotizing vasculitis or local destruction of the brain tissue: congenital toxoplasmosis, cytomegalovirus, and Herpes simplex infections (HSV) have been associated with multiple cases of hydrancephaly.^8,10 There is an increased incidence of spontaneous abortion following a maternal Herpes infection in early gestation. Fetal infectins with HSV and toxoplasmosis are frequently associated with central nervous system and occular anomalies later in gestation^8,9,10,11.

5) Thromboplastic material from a deceased co-twin: monochorionic twins have presented with a variety of cerebral lesions. Lesions in the recipient twin result from emboli or thromboplastic material originating from the macerated co-twin¹. Coincident blood pressure instability and episodes of severe hypotension may lead to brain and visceral lesions in the recipient twin.

Pathogenesis

In its classical form, the cerebral hemispheres are reduced to a thin layer of tissue made of pia-arachnoid membrane, a molecular layer, and abundant cerebrospinal fluid.¹ The falx cerebri is absent or hypoplastic and the lateral ventricles are represented by a single cavity surrounding the paired basal ganglia. The basal portion of the frontal, temporal, and occipital lobes may be preserved depending on the variations in collateral blood supply. The thalamus, basal ganglia, brainstem, and cerebellum are preserved due to flow from the basilar artery.

Fig. 5: Occlusion of both internal carotid arteries result in infarction of the territories served by the middle and anterior cerebral arteries (black vessels). The vascularization of the posterior fossa (gray vessels) is preserved.

Associated anomalies

Aside from consequential arthrogryposis, hydranencephaly has been associated with syndromes including renal aplastic dysplasia, polyvalvular developmental heart defect¹² and with trisomy 13.

Diagnosis

On ultrasound, hydrancephaly presents as a large cystic mass filling the entire cranial cavity with absence or discontinuity of the cerebral cortex and of the midline echo¹⁴. The appearance of the thalami and brainstem protruding inside a cystic cavity is characteristic. With either extreme hydrocephaly, alobar holoprosencephaly or porencephaly, these structures should still be surrounded by a rim of cortex, and the choroid plexuses should be normally visible. The initial diagnosis of hydrancephaly may be difficult when the infarction and hemorrhage is an evolving process. Recent hemorrhage is typically echogenic while an organizing clot assumes a more transonic texture¹⁵. Layering of this debris may masquerade as cortical tissue. Finally, the clot lyses and becomes an anechoic liquid characteristic of hydrancephaly¹⁵.

The post partum diagnosis of hydrancephaly was historically done by neurologic exam and transillumination of the skull. Today, magnetic resonance imaging (MRI) and evoked potentials can confirm the ultrasound findings. MRI provides excellent resolution of tissue composition and visualization of precise anatomical planes. Computer assisted reconstruction of multiple planes may differentiate hydrancephaly from alobar holoprosencephaly or maximal hydrocephaly resulting in different management strategies¹⁶.

Electroretinograms will demonstrate that the retina is electrically functional. The clinical light reflex suggests an intact optic pathway to the pretectal area. The absence of flash visual evoked potentials, however, implies that the pathway including the lateral geniculate nucleus, optic radiations, and occipital cortex is nonfunctional¹¹. Similar findings have been documented in the auditory pathways¹¹.

Differential diagnosis

The most common diagnostic problem is differentiation among hydranencephaly, extreme hydrocephalus, alobar holoprosencephaly and porencephaly. Some spared cortical mantle should still be seen with porencephaly and alobar holoprosencephaly. Serial sonograms may be necessary to evaluate an evolving intracranial process. Extreme hydrocephalus may be difficult to differentiate form hydranencephaly if a falx remnant is present⁴. The presence of even minimal frontal cerebral cortex, however, indicates extreme hydrocephalus instead of hydranencephaly⁴. At autopsy, differentiation can be made by examining the lining of hte cystic structures. Leptomeninges will be found in hydranencephaly while ependyma lines the ventricular system in hydrocephalus⁴. Magnetic Resonance Imaging may serve as an additional means for confirming the ultrasound diagnosis.

Prognosis

The prognosis is universally poor. Reflex activity is present in infants with hydranencephaly. Irritability, clonus, and hyperreflexia are common. Survival may last several months if an intact hypothalamus permits thermoregulation, but most die in the first year of life¹⁹.

Recurrence risk

A persistant infectious disorder may be a cause for recurrent encephaloclastic damage in the same sibship¹⁷.

Obstetrical management

The distinction between hydranencephaly and maximal hydrocephaly is important for the prognosis¹⁵. Sutton and associates¹⁸ followed 10 neonates with serial computed tomography, electroencephalograms, and developmental evaluations for 4-23 months. Two syndromes were defined. The five infants with hydranencephaly demonstrated neither neurologic nor radiologic improvement beyond 1 month of age despite aggressive surgical management and shunt placement. The five infants with maximal hydrocephalus improved dramatically over time following shunt placement.

It has been suggested that termination of pregnancy as late as the third trimester may be justified when an antenatal diagnosis of hydranencephaly is made. The criteria for termination includes the availability of reliable diagnostic tests that can accurately predict a condition that is either incompatible with post-natal life or characterized by the absence of cognitive function²⁰. If termination of pregnancy is contemplated, chromosomal analysis, serology for CMV, toxoplasmosis, and Herpes cultures should be obtained as these findings may aid in counseling for future pregnancies.

References

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