Hydranencephaly: Symptoms, Types, Causes and Treatment

Hydranencephaly is a rare and devastating neurological disorder, marked by the extensive loss of cerebral hemispheres and their replacement with fluid-filled sacs. Despite its severity, advances in neuroimaging and management have expanded what we know about this condition, its variations, and how affected individuals can be supported. This comprehensive article explores the symptoms, types, causes, and treatment options for hydranencephaly, drawing on the latest scientific findings.

Symptoms of Hydranencephaly

Hydranencephaly often presents with a striking set of symptoms, but the variability and subtlety of early signs can make diagnosis challenging. Understanding its clinical features is essential for prompt recognition and intervention.

Symptom	Onset	Key Features	Sources
Macrocephaly	Early infancy	Enlarged head circumference	3 10 12
Developmental Delay	Infancy	Delayed milestones, poor responsiveness	10 12
Seizures	Infancy/childhood	Convulsions, abnormal movements	10 12
Endocrine Issues	Throughout childhood	CDI, hypothyroidism, panhypopituitarism	10
Neurological Impairment	Infancy	Spasticity, poor voluntary movement	1 10 12
Visual Impairment	Infancy	Blindness or poor vision	1 3

Table 1: Key Symptoms

Macrocephaly

One of the most prominent features of hydranencephaly is macrocephaly, or an abnormally large head. While infants may have a normal head size at birth, rapid head growth typically begins within a few weeks as cerebrospinal fluid accumulates in the cranial cavity, replacing the missing brain tissue 3 12. This progressive enlargement is often the first physical sign that draws medical attention.

Developmental Delay and Neurological Impairment

Children with hydranencephaly universally experience profound developmental delays. These may include failure to achieve motor milestones, such as rolling, sitting, or crawling. Voluntary movement is severely limited, and spasticity (increased muscle tone) is common 1 10 12. Responsiveness to stimuli is often reduced, and affected infants may seem unusually quiet or lethargic.

Seizures

Seizures are frequently reported in hydranencephaly. These may range from subtle twitching to overt convulsive episodes, sometimes triggered by fever or other stressors 10 12. Seizure management can be complicated by the underlying brain abnormalities.

Endocrine and Associated Issues

A notable but less commonly recognized complication is central diabetes insipidus (CDI), a condition characterized by excessive thirst and urination due to a deficiency of antidiuretic hormone. Other endocrine disturbances seen in hydranencephaly include hypothyroidism and panhypopituitarism (deficiency of multiple pituitary hormones) 10. Visual impairment, including blindness, is also frequent due to the loss of cortical processing centers 1 3.

Variability in Clinical Presentation

It's important to note the considerable variability in symptoms. Some rare cases, particularly of hemi-hydranencephaly, exhibit milder neurological issues, with individuals maintaining a degree of functional independence 2. More commonly, however, the condition results in severe, lifelong disability.

Types of Hydranencephaly

Hydranencephaly is not a uniform condition. Several distinct types and variants exist, each with unique features and implications for prognosis.

Type	Hemisphere(s) Involved	Distinguishing Features	Sources
Classic Hydranencephaly	Both	Nearly complete absence of cerebral hemispheres, replaced by fluid	3 5
Hemi-hydranencephaly	One (unilateral)	Loss of one hemisphere, other remains functional	2
Hydranencephaly with Lissencephaly	Both	Also features smooth (lissencephalic) cortex	1
Hydranencephaly/Porencephaly	Both/partial	Spectrum disorder, overlap with porencephalic cysts	4

Table 2: Types of Hydranencephaly

Classic (Bilateral) Hydranencephaly

This is the most frequently observed form, characterized by the near-total absence of both cerebral hemispheres. The cranial cavity is largely filled with cerebrospinal fluid, while the meninges and skull remain intact 3 5. Remnants of brain tissue may persist, particularly in the basal ganglia, brainstem, and thalamus 1.

Hemi-hydranencephaly

An exceedingly rare variant, hemi-hydranencephaly involves the loss of only one cerebral hemisphere. Remarkably, some individuals with this form have demonstrated near-normal cognitive and motor functions, likely due to functional compensation by the remaining hemisphere 2. This highlights the brain’s remarkable plasticity, especially during early development.

Hydranencephaly with Lissencephaly

Some forms of hydranencephaly are associated with additional cortical malformations such as lissencephaly, where the brain surface is unusually smooth due to absent or incomplete development of gyri and sulci 1. This combination can further exacerbate neurological impairment.

Hydranencephaly/Porencephaly Spectrum

Hydranencephaly may overlap with porencephaly, a related condition where cystic cavities form within the cerebral hemispheres. The distinction is often one of degree; in hydranencephaly, the destruction is more complete, while in porencephaly, some cortical tissue remains 4. Both are believed to share common pathogenic mechanisms.

Causes of Hydranencephaly

While the symptoms and types of hydranencephaly are striking, understanding why and how this condition develops is critical. Multiple factors—genetic, vascular, and infectious—can converge to disrupt normal brain formation.

Cause	Mechanism	Key Evidence	Sources
Vascular Insult	Bilateral carotid artery occlusion, ischemia	Most common, especially in early gestation	1 4 5
Genetic Factors	Mutations (e.g., CEP55)	Rare familial cases, syndromic presentations	7
Infections	Viral (e.g., Bluetongue Virus)	Destruction of neural tissue in utero	6
Monozygotic Twinning	Vascular disruption via shared placenta	Seen in twins, especially with deceased co-twin	4

Table 3: Causes of Hydranencephaly

Vascular Insult: The Leading Cause

The most widely accepted cause of hydranencephaly is a massive, bilateral vascular insult—typically an occlusion or disruption of the internal carotid arteries supplying the developing brain. This catastrophic event usually occurs between the 8th and 12th week of gestation, leading to extensive ischemic destruction of the cerebral hemispheres 1 4 5. In some cases, the timing of the insult can be later, even up to the second year of life, but earlier insults tend to cause more severe phenotypes 1.

Genetic Factors

Rarely, hydranencephaly can be part of a genetic syndrome. Mutations in the CEP55 gene, for example, have been linked to a syndrome known as MARCH (Multinucleated neurons, Anhydramnios, Renal dysplasia, Cerebellar hypoplasia, and Hydranencephaly), demonstrating the role of impaired neuronal mitosis in its pathogenesis 7. These cases often present with other congenital anomalies.

Infectious Etiologies

Congenital infections may also lead to hydranencephaly. In animals, certain viruses such as Bluetongue virus (BTV) can cross the placenta and destroy developing brain tissue 6. While direct parallels in humans are less established, intrauterine infections remain a recognized risk factor.

Monozygotic Twinning and Placental Factors

Hydranencephaly has a unique association with monozygotic (identical) twins. Vascular disruptions can occur via the shared monochorionic placenta, especially when a co-twin dies in utero. Embolic phenomena or the transfer of thromboplastin material may trigger the destructive process in the surviving twin 4.

Treatment of Hydranencephaly

While there is no cure for hydranencephaly, treatment focuses on supportive care, symptom management, and addressing complications. Advances in surgical interventions have improved quality of life and, in some cases, extended survival.

Treatment	Approach	Main Goals	Sources
Supportive Care	Multidisciplinary, symptom-focused	Comfort, nutrition, prevent complications	10 12
Ventriculoperitoneal Shunt (VPS)	Surgical	Control hydrocephalus, relieve pressure	8 9 12
Endoscopic Choroid Plexus Cauterization (ECPC)	Minimally invasive	Reduce CSF production, avoid shunt	8 9 11 12
Hormone Replacement	Medical	Treat endocrine dysfunctions	10
Seizure Management	Antiepileptics	Control convulsions	10 12

Table 4: Treatment Options

Supportive and Multidisciplinary Care

The mainstay of treatment remains supportive, tailored to the individual’s needs. This includes nutritional support (often via feeding tubes), physical therapy to prevent contractures, and regular monitoring for complications such as respiratory infections or pressure sores. Multidisciplinary teams involving neurologists, pediatricians, physical therapists, and palliative care specialists are essential 10 12.

Surgical Interventions: VPS and ECPC

Ventriculoperitoneal Shunt (VPS):
Historically, the insertion of a VPS has been used to manage hydrocephalus, relieving increased intracranial pressure by diverting excess cerebrospinal fluid from the brain to the abdominal cavity. However, shunt-related complications—such as infection, blockage, and the need for revision—are common 12.

Endoscopic Choroid Plexus Cauterization (ECPC):
ECPC is a less invasive alternative, involving endoscopic cauterization of the choroid plexus (the tissue producing CSF) to reduce fluid accumulation. Studies report success rates of 70–88%, with advantages including fewer complications and the potential to avoid lifelong shunt dependency 8 9 11. ECPC can be a definitive intervention in many cases, though rare complications like arachnoid collapse have been described 11.

Management of Endocrine and Neurological Complications

Endocrine abnormalities such as CDI and hypopituitarism require specific treatments, including desmopressin for CDI and hormone replacement for other deficiencies 10. Seizures are managed with antiepileptic medications, tailored to the individual’s response and tolerance 10 12.

Prolonged Survival and Quality of Life

While hydranencephaly was once considered universally fatal in infancy, improved supportive care and modern interventions have allowed some children to survive for years, albeit with profound disabilities. Quality of life depends on the prevention and prompt management of complications and the provision of adequate support for families 12.

Conclusion

Hydranencephaly is a complex, multifaceted disorder that profoundly impacts affected individuals and their families. Scientific research has shed light on its diverse symptoms, underlying mechanisms, and evolving treatment strategies. While there is no cure, compassionate, multidisciplinary care and advances in surgical management have improved the outlook for many patients.

Key takeaways from this article:

• Symptoms: Macrocephaly, developmental delay, seizures, endocrine problems, and profound neurological impairment are hallmark features 1 3 10 12.
• Types: Includes classic (bilateral), hemi-hydranencephaly, lissencephalic variants, and overlaps with porencephaly 1 2 3 4 5.
• Causes: Most commonly due to prenatal vascular insults, but can also result from genetic mutations, infections, or complications of monozygotic twinning 1 4 5 6 7.
• Treatment: Supportive care is central; surgical options (VPS, ECPC) can improve symptoms and quality of life. Hormonal and seizure management are important for associated complications 8 9 10 11 12.

Ongoing research and advances in care continue to shape the management of this challenging condition, offering hope for better outcomes and improved quality of life for affected children and their families.