What are the causes of encephalomalacia?

Causes of Encephalomalacia

Encephalomalacia is brain tissue softening or loss caused by cerebral infarction, ischemia, infection, trauma, or other injury that results in tissue necrosis. 1, 2

Perinatal and Neonatal Causes

Hypoxic-ischemic injury is the most important perinatal cause of encephalomalacia, particularly multicystic encephalomalacia in neonates and infants. 3, 4

• Birth asphyxia represents the single most critical risk factor for brain damage leading to encephalomalacia during delivery 3
• Prematurity and low birth weight increase risk through associated complications including intracranial hemorrhage and hypoglycemia 3
• Placental insufficiency and intrauterine events (eclampsia, premature rupture of membranes) can cause neonatal hypoxic-ischemic encephalopathy 3
• Perinatal infections including toxoplasmosis, syphilis, varicella-zoster, rubella, cytomegalovirus, and herpes can directly damage the developing fetal brain 3

The multicystic form specifically results from perinatal anoxia, creating multiple irregular cysts throughout cerebral white matter and inner cortical layers bilaterally, with characteristic sparing of orbital frontal surfaces, inferior temporal lobes, basal ganglia, and cerebellum. 5

Vascular Causes

Cerebral infarction and ischemia are the predominant causes of encephalomalacia in adults. 3, 1

• Acute ischemic stroke causes encephalomalacia through tissue necrosis in affected vascular territories 3
• Intracranial hemorrhage including intracerebral and subarachnoid hemorrhage leads to tissue destruction and subsequent encephalomalacia 3
• Ruptured intracranial mycotic aneurysms in patients with infective endocarditis can cause hemorrhagic encephalomalacia, particularly in middle cerebral artery distribution 3
• Chronic small vessel disease with multiple lacunar infarcts produces focal areas of encephalomalacia 3
• Hypertensive encephalopathy causes cerebral edema, microscopic hemorrhages, and infarctions that can progress to encephalomalacia if severe 3

Traumatic Causes

Physical head trauma is a well-established but underreported cause of encephalomalacia in adults. 1, 2

• Severe closed head injury can result in delayed encephalomalacia years after the initial trauma, manifesting with progressive neurobehavioral deficits 2
• Penetrating brain injury including iatrogenic trauma (such as during endoscopic sinus surgery) causes direct tissue destruction and subsequent encephalomalacia 1
• Brain trauma with loss of consciousness, near-drowning, and other accidents resulting in cerebral hypoxia can lead to encephalomalacia 3

Infectious Causes

Central nervous system infections cause encephalomalacia through direct tissue destruction and inflammatory damage. 3

• Bacterial meningitis and cerebellitis can progress to permanent brain damage with encephalomalacia 3
• Viral encephalitis (HSV, VZV, CMV, EBV) causes tissue necrosis particularly in immunocompromised patients 3
• Tuberculous meningitis leads to encephalomalacia through vasculitis and infarction 3
• Cerebral abscess results in focal encephalomalacia after resolution 3

Toxic and Metabolic Causes

Substance abuse, toxins, and nutritional deficiencies cause encephalomalacia through direct neurotoxicity or metabolic derangement. 3

• Chronic alcohol abuse produces cerebellar and cortical encephalomalacia 3
• Methanol toxicity causes hemorrhagic necrosis and encephalomalacia 3
• Heroin and opiate abuse can result in cerebellar and cortical infarction with subsequent encephalomalacia 3
• Lead poisoning and other heavy metal toxicity contribute to brain tissue damage 3
• Metronidazole toxicity causes dentate nucleus injury that may progress to encephalomalacia 3
• Vitamin E and thiamine deficiency lead to cerebellar and cortical damage 3

Prenatal Environmental Factors

In utero exposures during critical developmental periods cause encephalomalacia through teratogenic effects. 3

• Fetal alcohol spectrum disorders represent the leading preventable cause of developmental disabilities with associated brain malformations 3
• Maternal malnutrition and vitamin/mineral deficiency affect fetal brain development 3
• Teratogen exposure including drugs and toxins during pregnancy 3
• Maternal illness such as hypothyroidism impacts fetal brain development 3

Neoplastic and Treatment-Related Causes

Brain tumors and their treatments can result in encephalomalacia. 3

• Primary brain tumors cause mass effect and tissue destruction 3
• Surgical resection of tumors or epileptogenic foci leaves areas of encephalomalacia 6
• Radiation therapy to the brain produces delayed radiation necrosis and encephalomalacia 3
• Chemotherapy can contribute to brain tissue damage 3

Key Clinical Pitfall

Do not assume encephalomalacia in adults is always from stroke—obtain detailed trauma history going back years, as physical head injury can cause delayed encephalomalacia with progressive symptoms long after the initial event. 2 Neuroimaging with MRI is essential for identifying the extent and location of encephalomalacia, which directly impacts prognosis and management, particularly in epilepsy surgery candidates where complete resection of encephalomalacia improves seizure outcomes. 6