Can you explain hydranencephaly, including its causes, clinical presentation, diagnostic methods, prognosis, and management?

Hydranencephaly

Definition and Pathophysiology

Hydranencephaly is a rare, catastrophic congenital brain malformation where the cerebral hemispheres are absent or nearly completely absent and replaced by a cerebrospinal fluid-filled membranous sac, with preservation of posterior fossa structures. 1, 2

• The condition results from bilateral internal carotid artery occlusion occurring between the 8th and 12th gestational weeks, after neurogenesis has begun but before complete cerebral development 3
• The cerebral cortex, thalami, and basal ganglia are typically absent, though rare variants exist where thalami and basal ganglia may be preserved 1
• The posterior fossa structures (cerebellum, brainstem) and midbrain are characteristically preserved, distinguishing this from other severe brain malformations 2, 4
• The falx cerebri is often disrupted or absent 1

Clinical Presentation

Infants with hydranencephaly may initially appear relatively normal at birth but rapidly develop signs of severe neurological dysfunction within the first weeks to months of life. 5, 3

• Macrocephaly with progressive head enlargement due to CSF accumulation 5
• Severe developmental delays and absence of developmental milestones 4
• Seizures are common 5
• Irritability and feeding difficulties 5
• Abnormal neurological examination with hyperreflexia and spasticity 3
• Some infants may demonstrate transillumination of the skull with a bright light 4

Diagnostic Methods

Prenatal or postnatal neuroimaging is essential for diagnosis, with ultrasound being the initial modality and MRI providing definitive anatomical detail. 1, 2

Prenatal Diagnosis

• Obstetric ultrasound can detect hydranencephaly as early as the second trimester, showing absence of cerebral hemispheres with preserved posterior fossa 1
• Early prenatal diagnosis allows for counseling and planning for delivery at a tertiary care center 1

Postnatal Imaging

• Brain ultrasound (through the anterior fontanelle) shows absence of cerebral tissue with a fluid-filled cranial vault and preserved posterior fossa structures 2
• MRI is the gold standard, demonstrating complete or near-complete absence of cerebral hemispheres, preserved brainstem and cerebellum, and absence of the falx 2, 3
• MR angiography confirms bilateral internal carotid artery occlusion or absence above the supraclinoid level 2, 3
• CT scan can confirm the diagnosis but provides less anatomical detail than MRI 1

Critical Differential Diagnoses

• Severe hydrocephalus: Distinguished by the presence of a thin but identifiable cerebral mantle and intact falx 2, 4
• Alobar holoprosencephaly: Shows fusion of cerebral structures rather than absence, with characteristic facial anomalies 2, 4
• Porencephalic cyst: Shows localized rather than global cerebral destruction 4

Prognosis

Hydranencephaly carries an extremely poor prognosis with markedly reduced life expectancy, though survival beyond infancy is possible with modern supportive care. 5, 3

• Historically, most infants died within the first year of life 3
• With modern medical management including CSF shunting, some patients survive for years, though with profound neurological disability 5, 3
• A case series reported 4 patients surviving beyond 5 years, with one patient reaching 32 years of age 5, 3
• Quality of life is severely compromised with complete dependence for all activities of daily living and absence of meaningful cognitive function 4
• No potential for developmental progress or neurological recovery exists given the absence of cerebral tissue 3, 4

Management

Management is primarily supportive and palliative, focused on preventing complications rather than curative treatment, with significant ethical considerations regarding aggressive intervention. 5, 4

Surgical Interventions

• Ventriculoperitoneal shunt (VPS) placement is the most common intervention to control progressive macrocephaly and increased intracranial pressure 5
• All patients in one series required VPS placement and subsequent shunt revisions 5
• Shunt complications are extremely common, with infection occurring in 75% of cases and recurrent malfunction being the norm 5
• Choroid plexus cauterization (CPC) represents an alternative to avoid shunt-related complications, with successful shunt removal reported in one case after CPC 5
• Bloody CSF is frequently encountered (50% of cases), complicating shunt management 5

Supportive Care

• Seizure management with antiepileptic medications 5
• Nutritional support, often requiring gastrostomy tube placement 5
• Prevention and treatment of recurrent infections, particularly pneumonia 5
• Management of spasticity 3

Ethical Considerations

• The decision to pursue aggressive surgical treatment versus comfort care alone requires careful discussion with families regarding the invariably poor prognosis and quality of life 4
• Some argue that CSF shunting may prolong suffering without meaningful benefit given the complete absence of cerebral function 4
• Prenatal diagnosis allows for informed decision-making regarding pregnancy continuation 1

Common Pitfalls

• Misdiagnosing hydranencephaly as severe hydrocephalus leads to inappropriate expectations for neurological recovery 2, 4
• Failing to recognize that preserved posterior fossa structures distinguish hydranencephaly from other severe brain malformations 2
• Underestimating the high rate of shunt complications in this population when counseling families 5
• Not obtaining MR angiography to confirm the vascular etiology 2, 3