Hydrancephaly is a rare brain malformation in which there is near total absence of cerebral hemispheres.

The child may appear normal at birth but usually has a large head. The diagnosis is established by CT or MRI and there is no known treatment. This is a report of two cases of hydrancephaly diagnosed at our hospital. Keywords: hydrancephaly; vascular insult; hydrocephalus. INTRODUCTION Hydrancephaly is a rare congenital malformation of the brain with devastating complications. We report two cases of hydrancephaly diagnosed at our hospital in the last four years. Hydranencephaly - In utero destruction of cerebral parenchyma with intact falx and preservation of posterior fossa structures. Cerebrum replaced with CSF. Caused by in utero occlusion of bilateral supraclinoid internal carotid arteries. Etiology unclear (hereditary thrombophilic states, infection, maternal irradiation/toxin exposure, twin-twin transfusion, intrauterine anoxia). Rarely unilateral Occurs approximately <1:10000 births, greatest incidence in teenage mothers. Clinically, present with macrocephaly, developmental delay, irritability, hyperreflexia, seizures. Often seen with prenatal ultrasound (anechoic cranial vault). On CT and MR (best characterized with MR) – CSF attenuation/signal intensity replacing the supratentorial brain parenchyma with sparing of thalami, brain stem, cerebellum, and choroid plexus. Falx is intact (distinguishes from holoprosencephaly). No thin rim of cerebral parenchyma (distinguishes from severe hydrocephalus). Prognosis is poor – usually death in infancy. Treatment is supportive care, shunting to decrease head growth. 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 8486 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 leuko malacia 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 gestation8,9,10,11. 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. 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 diagnosisThe 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. PrognosisThe 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 e ncephaloclastic 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