Etiology and pathophysiology
First described in 1979, DPHL is rare, posing diagnostic challenges for clinical providers.6 Although the exact incidence of DPHL is unknown, the precipitating event typically involves cerebral anoxia, which can occur through carbon monoxide (CO) poisoning, strangulation, cardiac arrest, respiratory failure, and overdose from sedatives and narcotics (Table 2).7 DPHL was first observed in a small percentage (2.75%) of patients suffering from CO poisoning.8,9 Progression of the disease generally includes a period of unconsciousness, then a lucid interval that can last 2 to 40 days, followed by the abrupt onset of neuropsychiatric symptoms.10 The specific pathophysiologic mechanism is unknown, but has been hypothesized to involve inferior compensatory response to decreased oxygenation in the white matter.
Diagnosis and clinical features
DPHL can be divided into 2 clinical variations: parkinsonism and akinetic mutism. The former consists of conventional parkinsonian features along with agitation, apathy, hallucinations, dystonic posturing, and odd behaviors. The latter variant presents with apathy, minimal response to pain, functional bowel and bladder incontinence, mutism, and, at times, inappropriate laughter or tearfulness.5 Both variants share similar features with hypokinetic forms of catatonia.
DPHL is a diagnosis of exclusion. A careful history is critical to establish the possibility of a recent anoxic event. MRI findings, including hyperintensities in the cerebral white matter on T2-based sequencing, are suggestive of the disease. A choline peak on magnetic resonance spectroscopy also might be present in patients with DPHL, although it is not specific to the diagnosis.
Early reports of DPHL suggested an associated deficiency of arylsulfatase A, an enzyme required in the modulation of myelin; however, more recent case reports are conflicting.11 Familial mutations in the gene for arylsulfatase A also result in metachromatic leukodystrophy, and adult onset can present with psychiatric symptoms, including delusions and hallucinations.12
Treatment and prognosis
The treatment of DPHL consists primarily of supportive care and rehabilitation with physical, occupational, and speech therapy.11 With these measures, most patients improve after 3 to 6 months; however, a large percentage sustain some long-term cognitive deficit, the most prevalent symptom being frontal executive dysfunction.5
OUTCOME Supportive care
A second MRI shows diffuse hyperintensities in the white matter that spare the cerebellum and brainstem (Figure). This finding is pathognomonic for DPHL.
ECT is discontinued because there is no evidence to support ECT-associated improvement in DPHL. Moreover, ECT might worsen the clinical course through increased stress and metabolic demand on the brain.13
Because the primary treatment of DPHL is early rehabilitation, we consider that Ms. M would benefit most from increased supportive care and therapy. She is discharged to a brain injury rehabilitation facility, where metoprolol is prescribed for mild tachycardia, along with thiamine and vitamins B12 and D. Physical, occupational, and speech therapy are continued.
Approximately 3 weeks after admission to the rehabilitation program, Ms. M is discharged home. Although she improves in overall activities of daily living, she continues to experience moderate communication deficits and occasional external distractibility.
Bottom Line
Although delayed post-hypoxic leukoencephalopathy is considered rare, consider it in the differential diagnosis when a patient has a recent history of an anoxic event followed by the abrupt onset of neuropsychiatric symptoms. Keep in mind that the condition can be missed if an MRI is obtained too early, and the clinical signs can mimic hypokinetic catatonia.
Related Resources
• Meyer MA. Delayed post-hypoxic leukoencephalopathy: case report with a review of disease pathophysiology. Neurol Int. 2013;5(3):e13. doi: 10.4081/ni.2013.e13.
• Aljarallah S, Al-Hussain F. Acute fatal posthypoxic leukoencephalopathy following benzodiazepine overdose: a case report and review of the literature. BMC Neurol. 2015;15:69.
Drug Brand Names
Gabapentin • Neurontin
Lorazepam • Ativan
Metoprolol • Lopressor
Paroxetine • Paxil
Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of com