Literature
Clinical Pearls & Morning Reports
Published June 23, 2021
What are the most common manifestations of delayed posthypoxic leukoencephalopathy?
Delayed posthypoxic leukoencephalopathy is an uncommon neuropsychiatric disorder characterized by the development of progressive cognitive and neuropsychiatric disturbances after initial recovery from an acute hypoxic episode. Read the NEJM Case Records of the Massachusetts General Hospital here.
Clinical Pearls
Q: What are the most common manifestations of delayed posthypoxic leukoencephalopathy?
A: Delayed posthypoxic leukoencephalopathy most commonly manifests as behavior change, inattention, and executive dysfunction, often with parkinsonism and catatonia-spectrum signs. Symmetric bilateral diffuse subcortical demyelination occurs 1 to 4 weeks after oxygen deprivation in the brain, possibly resulting from hypoxia-induced interruption of myelin turnover.
Q: Diagnosis of delayed posthypoxic leukoencephalopathy requires what two features?
A: Delayed posthypoxic leukoencephalopathy is likely to be underdiagnosed because of the delay between the insult and the onset of symptoms. Although consensus diagnostic criteria are currently not available, diagnosis requires the following two features: a delay in the onset of neurologic or psychiatric symptoms, usually of 3 to 4 weeks (range, 2 to 40 days), and characteristic white-matter abnormalities on MRI.
Morning Report Questions
Q: Describe some of the features of delayed posthypoxic leukoencephalopathy.
A: Two primary clinical forms of delayed posthypoxic leukoencephalopathy have been described, although overlap is common in individual cases. Clinical progression is considered to be fairly stereotypical with the akinetic mutism form and more variable with the parkinsonism form. Although information on prognostic outcomes is limited to case series or individual reports, delayed posthypoxic leukoencephalopathy has been associated with a wide range of neuropsychiatric outcomes; some patients have had a good recovery and others have died. The parkinsonism form appears to be associated with a higher risk of persistent symptoms, but long-term mild-to-moderate dysexecutive cognitive impairment is common with both forms. In most cases, clinical improvement is expected to occur 6 to 18 months after the onset of symptoms. There are currently no available interventions to prevent the development of delayed posthypoxic leukoencephalopathy after hypoxia or to hasten recovery once symptoms occur.
Q: What imaging findings support a diagnosis of delayed posthypoxic leukoencephalopathy?
A: Typical findings on MRI include hyperintense lesions on T2-weighted FLAIR sequences, with extensive symmetric bilateral involvement of subcortical white matter and with preservation of cortical U-fibers. The basal ganglia, thalami, brainstem, and cerebellum are usually not involved. Lesions often show restricted diffusion but do not show contrast enhancement. This pattern makes it possible to differentiate delayed posthypoxic leukoencephalopathy from other acute or subacute disorders affecting white-matter tracts, including medication-induced leukoencephalopathy (e.g., due to methotrexate), posterior reversible encephalopathy syndrome, and acute disseminated encephalomyelitis.