Hydranencephaly

Hydranencephaly is a rare congenital condition characterized by almost complete replacement of the cerebral hemispheres by fluid content, with exception of the occipital region and the lower brain structures.

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Hydranencephaly is reported in 1 in 5,000 - 10,000 (0.01% - 0.02%) of pregnancies, without difference between the male and female sex and it is usually sporadic.¹

Two different hypotheses have been suggested to explain the condition:

• Destructive theory:  a clastic process occurring during the 2nd trimester after neural migration and causing destruction of the already formed brain and ventricles.
• Disruptive theory: disruption of the organogenesis occurring as early as the 8th to 12th weeks of gestation.

Due to the absent development or destruction of the cerebrum, the intracranial pressure can decrease leading to microcephaly or, alternatively, if large quantities of cerebrospinal fluid (CSF) accumulates, to hydrocephaly.

The most accepted theory is that a vascular insult (bilateral internal carotid artery occlusion) involving the anterior cerebral circulation is responsible.² Infectious causes, along with vascular accidents associated with monochorionicity in twins have also been reported as causal factors. Mutations such as in COL4A1, in PI3K-AKT3-mTOR and chromosomal anomalies such as triploidy, presenting with a massive hydrocephalus-like picture, have also been reported in some cases.³ Hydranencephaly is also part of the rare Fowler syndrome, where a bi‐allelic mutations in FLVCR2 is reported in some families.^4,5

As a consequence of the vascular insult, destruction of the cerebral hemispheres occurs. These are replaced with a membranous sac filled with cerebrospinal fluid. Structures supplied by the posterior circulation (choroid plexus, cerebellum, brain stem, thalamus, basal ganglia) are usually preserved.¹

If the preserved choroid plexuses produce large quantities of CSF macrocrania may be observed. If this is not the case, microcephaly is often seen because of the disruption of hemispheric development.

When the cause is a vascular accident, the condition is sporadic and the recurrence risk extremely low. However, a few cases have been linked with autosomal recessive inheritance. This mode of transmission occurs in patients with the association of a rare genetic autosomal recessive condition known as Fowler syndrome.⁴

Prenatal diagnosis consists in visualization of a mostly non-partitioned fluid filled area replacing the cerebral hemispheres.⁶ The fluid can appear rather homogeneously echo-reflecting. Diagnosis has been reported as early as the 12th week², but it becomes more obvious in the second trimester of pregnancy, when hemispheres and falx have been formed.⁵ When lower cerebral structures such as choroid plexus, thalami and cerebral pedunculi, cerebellum and brain stem are preserved these structures will be visible at US investigation. In case of abnormal accumulation of CSF high pressure hydrocephaly can be present. Although not necessary in prenatal life, (MRI) remains the gold standard for diagnosis after birth.  Typically, placement of a flashlight at the base of the head can also be used as it will be reflected throughout the skull filled with CSF. ¹

Hydranencephaly needs to be differentiated from severe-extreme hydrocephalus, alobar holoprosencephaly and severe open schizencephaly.¹

• Severe hydrocephaly: the cortical mantle, even if extremely thin, is preserved, as well as the third ventricle.
• Alobar holoprosencephaly: there is fusion of the thalami and the falx is missing. Head circumference is usually small and there are mid-facial and other anomalies.
• Severe-open schizencephaly: this neuronal migration disorders is characterized by a cleft lined with abnormal gray matter (polymicrogyria). The cortical mantle is thin, but present.

There is no cure for hydranencephaly and the prognosis is from lethal to very poor. Most patients with hydranencephaly die before birth or will die during the 1st year of life due to post-natal complications. However, some infants born with hydranencephaly may survive due to integrity of the brainstem.³ Head circumference and spontaneous reflexes (sucking, swallowing, crying, and spontaneous movements of the extremities) may be normal at birth. More severe cases may present at birth with seizures, myoclonus, and respiratory difficulty. Symptoms such as spastic diplegia, blindness and severe neurological impairment can become apparent later in life. Sporadic cases may survive up to thirty years.¹

Owing to the severity of the condition therapeutic abortion should be discussed and offered as an option after prenatal diagnosis.

The course of pregnancy may be normal, with the mother feeling normal fetal movements. Serial scans should be performed to check for excessive growth of the fetal head. In case of excessive head growth intra-partum cephalocentesis may be necessary to achieve a vaginal birth. Birth should be planned in a specialized unit.

After birth, symptoms and of associated morbidities and/or complications, may be managed by:

• Placement of a ventriculo-atrial shunt system to reduce the intracranial pressure in case of high pressure hydrocephaly.
• Anti-epileptic drugs to treat seizures.  
• Tracheostomy and/or mechanical ventilation in cases with respiratory failure.

Shunts have to be frequently (25-40% during the first year) revised due to malfunctions and are associated with frequent infections.¹  Endoscopic choroid plexus coagulation (ECPC) is an alternative to treat rapidly enlarging heads in patients with hydranencephaly due to hydrocephalus. ECPC is possible in infants with hydranencephaly because of lack of hemispheric separation, which allows easy access to bilateral choroid plexuses that are the principal producers of CSF. Multiple studies have reported better outcomes in patients treated with ECPC than in those treated with shunts with a success rate of 50 to 80%.⁷ 

There is no primary prevention for hydranencephaly. Early scans in subsequent pregnancies can be offered to exclude the condition.

1. Sandoval JI, De Jesus O. Hydranencephaly. [Updated 2022 Jun 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK558991/

2. Lam, Y.H. and Tang, M.H.Y. (2000), Serial sonographic features of a fetus with hydranencephaly from 11 weeks to term. Ultrasound Obstet Gynecol, 16: 77-79. 

3. Pavone P, Praticò AD, Vitaliti G, Ruggieri M, Rizzo R, Parano E, Pavone L, Pero G, Falsaperla R. Hydranencephaly: cerebral spinal fluid instead of cerebral mantles. Ital J Pediatr. 2014 Oct 18;40:79.

4. Laurichesse‐Delmas H, Beaufrere AM, Martin A, Kaemmerlen AG, Déchelotte P, Lémery D. First‐trimester features of Fowler syndrome (hydrocephaly–hydranencephaly proliferative vasculopathy). Ultrasound Obstet  Gynecol 2002 Dec;20(6):612-5.

5. Radio FC, Di Meglio L, Agolini E, Bellacchio E, Rinelli M, Toscano P, Boldrini R, Novelli A, Di Meglio A, Dallapiccola B. Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome or Fowler syndrome: Report of a family and insight into the disease's mechanism. Mol Genet Genomic Med. 2018 May;6(3):446-451.

6. Sepulveda W, Cortes-Yepes H, Wong AE, Dezerega V, Corral E, Malinger G. Prenatal sonography in hydranencephaly: findings during the early stages of disease. J Ultrasound Med. 2012;31(5):799-804.

7. Ghosh PS, Reid JR, Patno D et-al. Fetal magnetic resonance imaging in hydranencephaly. J Paediatr Child Health. 2013;49 (4): 335-6.

8. Pedrosa HAR, Lemos SP, Vieira C, Amaral LC, Malheiros JA, Oliveira MM, Gomez RS, Giannetti AV. Choroid plexus cauterization on treatment of hydranencephaly and maximal hydrocephalus. Childs Nerv Syst. 2017 Sep;33(9):1509-1516.

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