Hydranencephaly is a rare congenital post-neurulation disorder that occurs during the second trimester characterized by the destruction of the cerebral hemispheres, which are replaced with a membranous sac filled with cerebrospinal fluid (CSF). The cranial cavity may have remnants of glial tissue and ependyma, especially along the falx and close to the diencephalon. The cranial vault and meninges are intact. It is most commonly caused by a vascular insult involving the anterior circulation. Midbrain structures such as the basal ganglia, brainstem, and posterior fossa structures are present. Patients at birth can appear normal with intact primitive reflexes. With time, they can present with macrocrania due to increased CSF pressure or less commonly with microcephaly. Diagnosis can be made in-utero with ultrasonography. Treatment is usually supportive, although in some cases with hydrocephalus, shunting of the CSF may be considered.
The etiology behind this condition is usually unknown. Different causes have been postulated.
Hydranencephaly is a rare condition and is rarely seen nowadays due to therapeutic abortions. The incidence may vary from 1 in 10,000 to 1 in 5,000 (0.01% - 0.02%) of pregnancies. There is no difference between males and females.
A study performed in the United States with the population of Texas showed an incidence rate of 1.4 to 2.8 per 100,000 live births. A study in a Japanese population found an incidence of 2.1 per 100,000 live births. Another independent study found that 1% of patients with hydrocephalus were diagnosed with hydranencephaly.
Although there is no established model of transmissions between mother and fetus, a few cases have been linked with autosomal recessive inheritance. This mode of transmission occurs in patients with the association of a rare genetic syndrome and/or conditions listed below.
The pathophysiology of hydranencephaly is still controversial, however, most studies suggest that the damage caused to the brain is related to bilateral internal carotid artery occlusion. As such, hydranencephaly is categorized into a group of circulatory developmental encephalopathies. Even though the most probable hypothesis behind the pathophysiology of hydranencephaly is a vascular anomaly, there have been autopsy reports where the internal carotid arteries were intact. An intact internal carotid artery does not exclude it as the key element for the development of hydranencephaly since it has been demonstrated that the internal carotid arteries could revascularize after the damage has already been done. Characteristics that suggest the involvement of the internal carotid artery are:
Two different hypotheses to explain the severe brain damage that occurs in hydranencephaly are suggested.
Although a predisposing molecular/cytogenetic anomaly has not been demonstrated to be linked to hydranencephaly, it cannot be excluded. Molecular dysfunction and cytogenetic anomalies, such as triploidy, could be involved in the development of hydranencephaly in some patients.
The most accepted pathophysiology behind the development of hydranencephaly is a bilateral vascular insult to the internal carotid arteries early during the neurogenic phase. The pathogenesis mechanism itself may start as early as the 8th to 12th weeks of gestation, and the diagnosis of hydranencephaly has been reported as early as the 12th week (1st trimester). Damage to the brain usually is appreciated by diagnostic studies as early as the 13th to the 26th week of pregnancy (2nd trimester) when hemispheres and falx have been formed. Hydranencephaly is a disruption and not a malformation caused by intrauterine ischemia along the areas irrigated by the internal cerebral arteries.
Most patients with hydranencephaly die before birth. During gestation, the mother feels the normal fetal movements, and the abdominal growth is normal. A child born with hydranencephaly may appear completely normal at birth. The head circumference and spontaneous reflexes, such as sucking, swallowing, crying, and moving all extremities spontaneously may be normal at birth. Some patients present with skull and upper facial features that may have a degree of deformity if the intracranial pressure inside the skull was increased. Those with more severe disease may present at birth with evident symptoms such as seizures, myoclonus, and respiratory difficulty.
Patients who appeared normal after birth start developing a few weeks later, more worrisome signs such as hyperirritability, increased or decreased muscle tone (hyper/hypotonia), increase in head circumference, and wide-open anterior fontanelles. These signs become rapidly more pronounced after several more weeks. Months later, patients can develop seizures and hydrocephalus. Hearing is usually preserved, but in rare cases, sensorineural hearing impairment is noted. Visual impairment is noticeable, and most of the children have cortical visual impairment from the absence of visual cortex but with normal eyes.
The majority of patients are diagnosed during pregnancy. Several techniques can be used to make the diagnosis. A regular ultrasound can be used to make a preliminary diagnosis of hydranencephaly. To confirm the diagnosis, a level 2 or higher ultrasound needs to be used. Another study used to diagnose hydranencephaly during pregnancy is a magnetic resonance imaging (MRI), although it is rarely used in pregnant patients. If the diagnosis is not made during the pregnancy, postnatal diagnosis may be delayed from weeks to months, since patients may initially appear and function normally. The gold standard for diagnosis is a brain MRI since it can differentiate between other similar diagnoses, such as severe hydrocephalus and holoprosencephaly.
Other ancillary tests performed:
Treatment consists of supportive management for the symptoms and management of associated morbidities and/or complications. The prognosis of the patients with hydranencephaly is poor. Patients affected by this condition usually die in-utero. Those that survive usually die within the first year of life. For these reasons, therapeutic abortion is an option if diagnosed during pregnancy. If the diagnosis is confirmed during pregnancy, discussion in detail with all family members is done. Given the prognosis, to prevent or reduce maternal morbidity (medical, psychological, and economical), the option of medical abortion is discussed and offered. This could be done as late as the third trimester if justified.
Treatment management of associated symptoms and/or complications includes:
Even though shunts are the most commonly used treatment for hydrocephalus, there are many complications associated with them. They have to be frequently revised due to malfunctions and have a high rate of infections, especially in the pediatric population. Approximately 25% to 40% of pediatric patients with a shunt will undergo revision in 1 year, and 81% will require revision in the next 12 years. Additionally, the multiple neurosurgical interventions and costs associated with them are an issue of concern. Other procedures have been proposed to treat and manage hydrocephalus as an alternative to shunts. Endoscopic choroid plexus coagulation (ECPC) is an alternative to treat rapidly enlarging heads in patients with hydranencephaly due to hydrocephalus. 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%. This success rate is high enough to propose that ECPC could be used as the standard of care in the treatment of hydrocephalus or an enlarging head in an infant diagnosed with hydranencephaly.
Nonetheless, it is clearly noted that ECPC can have better results in treating high CSF production only in patients with hydranencephaly and not in other forms of hydrocephalus. This is because patients with hydranencephaly have certain anatomical characteristics that make ECPC possible, such as the lack of septum pellucidum (lack of hemispheric separation), which allows easy access to bilateral choroid plexuses, and the lack of brain parenchyma which makes the choroid plexus the principal production area of CSF. A complication associated with ECPC is arachnoid collapse. It occurs when the dura is opened to pass the endoscope, which liberates the intracranial pressure and leads to arachnoid collapse with the inability to coagulate the choroid plexuses.
Hydranencephaly has some unique findings on imaging and ancillary tests that help to differentiate it from other conditions such as severe-extreme hydrocephalus, holoprosencephaly (especially the alobar holoprosencephaly type), and from severe open schizencephaly.
Unfortunately, there is no cure for hydranencephaly, and treatment is symptomatic and supportive. Most patients with hydranencephaly die in-utero. For those patients that do survive, the prognosis is poor, and the majority of patients die during the 1st year of life due to complications. There are reports of patients that do survive and have reached up to 32 years of age.
The survival of patients with hydranencephaly is dependent on the integrity of the brainstem, which regulates vital aspects such as cardiorespiratory functions and temperature regulation. Those few patients described in the literature that survive past the 1st year of life do not improve after shunt placement. Neurological function remains stable during their lifetime. There is limited use of hands and communication responses; however, some patients can use some words.
Complications associated with hydranencephaly are frequently the cause of death of patients that survive.
It is important to have a wide interprofessional team involved in patient care for a patient with hydranencephaly.
The emotional toll of having a child with hydranencephaly can be profound. There is no prevention of this disease except for those cases with exposure to toxins such as cocaine, smoking, and sodium valproate. Avoidance of these toxins should be encouraged. Counseling and support are necessary for the parents, especially to educate them about the diagnosis and prognosis. Psychologist and psychiatrist interactions may be needed.
It is extremely important to differentiate between hydranencephaly and severe-extreme hydrocephalus. Both disorders can present similarly, but prognosis and management are very different. A patient with severe-extreme hydrocephalus improves significantly clinically and radiographically after treatment, while those with hydranencephaly do not. If treatment is delayed, it can lead to catastrophic outcomes.
While the neonatologist is almost always involved in the care of patients with hydranencephaly, it is important to consult with an interprofessional team of specialists that include an obstetrician, neurologist, physiatrist, neurosurgeon, and social worker. The nurses are also vital members of the interprofessional group as they will assist patients with their daily care, while social workers assist with the education of the family.
The radiologist also plays a vital role in determining the diagnosis. The outcomes of a patient with hydranencephaly depend on its cause and the severity of the disease. To improve outcomes, prompt consultation with an interprofessional group of specialists is recommended.
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