What are the symptoms of hypoxic ischemic encephalopathy (HIE)?

Symptoms of Hypoxic Ischemic Encephalopathy

Hypoxic ischemic encephalopathy presents with a wide spectrum of neurological and psychiatric manifestations ranging from subtle cognitive deficits detectable only on specialized testing to profound coma with complete loss of consciousness and motor function. 1, 2

Cognitive and Behavioral Symptoms

Early/Mild Manifestations

• Attention deficits, impaired working memory, slowed psychomotor speed, and visuospatial dysfunction are the earliest cognitive changes, often detectable only through formal neuropsychological testing 1
• Personality changes including apathy, irritability, and disinhibition may be reported by family members before the patient recognizes problems 1
• Excessive daytime sleepiness and disturbances of the sleep-wake cycle are frequent, though complete sleep-wake reversal is less common 1
• Mild cognitive deficits affecting perception, memory, learning, executive functions, and constructive abilities may occur 1, 3

Progressive Cognitive Deterioration

• Disorientation to time and space develops as the condition worsens 1
• Inappropriate behavior and acute confusional states with either agitation or somnolence emerge 1
• Marked confusion with incoherent speech characterizes more severe stages 1
• The spectrum ultimately progresses to stupor and coma in the most severe cases 1

Motor System Abnormalities

Extrapyramidal Signs

• Asterixis (flapping tremor) is a hallmark finding in early to middle stages, elicited by hyperextension of the wrists with separated fingers or rhythmic squeezing of the examiner's fingers 1, 4
• Asterixis can also be observed in feet, legs, arms, tongue, and eyelids, though it is not pathognomonic for HIE and can occur in uremia and other metabolic encephalopathies 1, 4
• Hypomimia, muscular rigidity, bradykinesia, hypokinesia, and monotonous/slow speech resembling parkinsonism are common 1
• Parkinsonian-like tremor and dyskinesia with diminished voluntary movements occur frequently 1
• Involuntary movements similar to tics or chorea occur rarely 1

Pyramidal Signs

• Hypertonia, hyperreflexia, and positive Babinski sign can be observed in noncomatose patients 1
• Deep tendon reflexes may paradoxically diminish and disappear in advanced stages, even while pyramidal signs persist 1
• Transient focal neurological deficits can rarely occur 1

Advanced Motor Dysfunction

• Decorticate or decerebrate posturing develops in comatose patients (Grade IV encephalopathy) 1
• Complete loss of motor responses to painful stimuli represents the most severe stage 1

Seizure Activity

• Seizures are a common manifestation of HIE, occurring as generalized tonic-clonic seizures, myoclonus, or status myoclonus 1, 2, 5
• In neonates, approximately 90% of seizures from HIE occur within the first 2 days after birth 5
• Seizures may be clinically apparent or subclinical (non-convulsive status epilepticus), requiring EEG for detection 1, 2
• Status myoclonus is associated with poor prognosis 2
• Seizures are very rarely reported in adult hepatic encephalopathy but are common in post-cardiac arrest HIE 1, 5

Grading of Encephalopathy Severity

Grade I (Minimal/Mild)

• Changes in behavior with minimal alteration in level of consciousness 1
• Abnormalities detectable primarily through psychometric testing 1
• Slight hypokinesia, psychomotor slowing, and lack of attention that can be easily overlooked 1

Grade II (Moderate)

• Gross disorientation and drowsiness 1
• Asterixis becomes clinically apparent 1, 4
• Inappropriate behavior emerges 1

Grade III (Severe)

• Marked confusion with incoherent speech 1
• Patient sleeps most of the time but remains arousable to vocal stimuli 1
• Asterixis typically disappears as consciousness deteriorates 4

Grade IV (Coma)

• Complete unresponsiveness to pain 1
• Decorticate or decerebrate posturing 1
• Absent pupillary and corneal reflexes indicate very poor prognosis 2

Important Clinical Considerations

Mental and motor signs may not progress in parallel in individual patients, creating difficulties in staging severity 1. Some patients exhibit predominantly cognitive dysfunction while others show more prominent motor abnormalities 1.

The Glasgow Coma Scale provides a robust, operative description for patients with significantly altered consciousness, assessing eye opening, verbal response, and motor response on a standardized scale 1.

Cushing's triad (hypertension, bradycardia, irregular respirations) and pupillary dilatation are late signs of elevated intracranial pressure and should not be relied upon for early detection of cerebral edema 1.

Long-term neurological sequelae in survivors range from mild motor and cognitive deficits to cerebral palsy, severe cognitive impairment, epilepsy, and persistent vegetative states 6, 3, 7.