Hypoxic ischemic encephalopathy – Neurology anoxic brain injury causes

• pathophysiology:

• anoxia: absence of oxygen in the tissue from pulmonary failure and resulting decrease in partial pressure of oxygen (e.G., pulmonary embolism, neuromuscular respiratory failure, strangulation, status epilepticus), cardiac arrest (inability to circulate oxygenated blood), or anemia and lack of oxygen-carrying capacity (e.G., carbon monoxide inhalation).

• severe hypoglycemia can mimic clinical and pathologic features of hypoxic encephalopathy.

• CNS structures most sensitive to anoxia: cerebellar purkinje cells, dentate nucleus, globus pallidus, hippocampus (CA1 pyramidal cells), cerebral cortex layers III and V.


• clinical manifestations are heterogeneous: usually result of global ischemia preferentially affecting structures most sensitive to anoxia, but focal ischemia may occur from underlying focal cerebrovascular disease. Severity of symptoms: depends on duration of hypoxic event.Anoxic brain injury causes

• syncope: brief episode of hypoxia causing brief loss of consciousness, followed by complete restoration of neurologic function; if episode is long enough, may be associated with clonic movements and, rarely, tonic-clonic seizures.

• more prolonged global hypoxia can cause one or more of following: altered consciousness (obtundation, stupor, coma), neuropsychiatric and behavioral syndrome, predominantly anterograde amnestic syndrome.

• acute mountain sickness: syndrome of headache, nausea, vomiting, and altered consciousness due to diffuse cerebral edema.

• agitation and combativeness may occur as patient awakens from anoxic coma.

• postanoxic amnestic syndrome is believed to be due to selective hippocampal ischemic injury (usually from cardiopulmonary arrest).Anoxic brain injury causes

• movement disorder: stimulus-sensitive and action myoclonus (usually result of cortical damage). Delayed-onset myoclonus may occur days to weeks after cognitive recovery from anoxic coma. Dystonic and akinetic-rigid parkinsonism (usually result of damage to basal ganglia).

• seizures: simple, complex partial, generalized tonic-clonic, or myoclonic seizures. Myoclonus status epilepticus portends extremely poor prognosis; other seizure types have no prognostic value. Myoclonus often involves facial, appendicular, and axial musculature; is often resistant to treatment. Usual electroencephalographic (EEG) pattern of myoclonus status epilepticus: burst suppression. Focal or generalized myoclonus may occur during cardiac resuscitation and needs to be differentiated from myoclonus status epilepticus.Anoxic brain injury causes

• watershed infarcts as result of prolonged arterial hypotension:

• arterial border zones between bilateral acas and mcas (preservation of facial and distal lower limb motor function): bibrachial palsy with relatively less severe lower limb motor involvement (man-in-a-barrel syndrome), transcortical motor aphasia, or more extensive subcortical white matter damage and leukoencephalopathy.

• arterial border zones between bilateral mcas and pcas: balint’s syndrome (asimultanagnosia, optic ataxia, ocular apraxia, and transcortical sensory aphasia.

• anoxic myelopathy often affecting mid-thoracic level

• delayed postanoxic encephalopathy (leukoencephalopathy). Most often reported after carbon monoxide inhalation. Occurs in comatose patients who awaken within 24 to 48 hours after hypoxic insult and resume neurologic function for 4 to 14 days or longer. Subsequently, patients abruptly develop “confusion” and behavioral symptoms (apathy, irritability, agitation, mania) and pyramidal and/or extrapyramidal symptoms (spasticity, rigidity, dystonia, quadraparesis). The syndrome may progress, halt, or, less commonly, the patient may recover partially or completely.Anoxic brain injury causes

• pathology: extensive damage to bilateral subcortical white matter (leukoencephalopathy), ranging from demyelination to hemorrhagic necrosis. Reduction of arylsulfatase A activity (a lysosomal enzyme important for lipid metabolism of myelin) may predispose to leukoencephalopathy.

• cranial nerves: early loss of corneal reflex and ophthalmoplegia are poor prognostic indicators. Dilated, fixed pupils result from asystole. Persistence through resuscitation portends poor prognosis. If resuscitation is successful, pupillary function is usually restored in 6 hours.

• pathology: macroscopic: acute or subacute: diffuse cerebral edema with loss of gray-white matter differentiation. Chronic: watershed infarcts, cortical laminar necrosis, hippocampal sclerosis. Neuronal loss and gliosis of vulnerable areas: CA1 (sommers’ sector) of hippocampus, frontoparietal cortex, basal ganglia, cerebellar purkinje cells, spinal cord (midthoracic segments, particularly anterior horn cells and clarke’s column). Earliest observations in ischemic neurons: pyknotic nuclei and eosinophilic cytoplasm. Later, nuclei become eosinophilic and blend into cytoplasmic background.Anoxic brain injury causes

• diagnostic testing:

• CT: watershed infarcts, loss of gray-white matter differentiation may or may not be seen (usually seen after a few days)

• MRI: widespread increased T2/FLAIR signal may be seen in neocortex, hippocampus, cerebellum, thalamus; watershed infarcts and sulcal edema can also be seen

• EEG patterns: electrocerebral inactivity is usually present for up to an hour after cardiac arrest, but portends a poor prognosis if persistent. Periodic patterns (generally poor prognosis): generalized periodic sharp waves, spikes or spike-and-wave discharges (may be associated with clinical myoclonus); bilateral periodic lateralized epileptiform discharges (pleds); burst-suppression pattern. Invariant monorhythmic patterns: alpha coma pattern portends poor prognosis (most patients die or remain in a persistent vegetative state).Anoxic brain injury causes

• somatosensory evoked potentials (sseps)

• poor prognostic factors:

• no pupillary reaction (admission to day 3)

• no motor response to pain (admission to day 3)

• sustained upward or downward gaze

• myoclonic status eplilepticus

• unwitnessed cardiac arrest

• elderly (75 years old)

• organ failure or other medical comorbidities

• absence of cortical sseps bilaterally in first week

• EEG: alpha coma pattern, burst-suppression pattern, or isoelectric eegs in first week

• treatment: supportive measures. Therapeutic mild hypothermia in adults after cardiac arrest due to ventricular fibrillation may improve neurologic outcome.