Longitudinal magnetic resonance findings in delayed posthypoxic leukoencephalopathy

Abstract

Delayed posthypoxic leukoencephalopathy is a rare condition that can occur following prolonged cerebral hypo-oxygenation and manifests as acute onset of neuropsychiatric symptoms after a period of apparent recovery. We describe a case of a 76-year-old man who presented after an unwitnessed fall of unknown duration with initial recovery followed by progressive neurocognitive decline resulting in dementia, dysphasia, and gait apraxia. Initial brain magnetic resonance imaging was unremarkable but repeated brain imaging revealed progressive leukoencephalopathy, which started as small foci of abnormal diffusion restriction in bilateral frontal lobes and gradually evolved over the next 3 weeks to diffuse signal changes in the white matter.

Delayed posthypoxic leukoencephalopathy (DPHL) is a rare demyelinating syndrome characterized by acute neurologic deterioration occurring 2 to 4 weeks following initial recovery from a prolonged hypoxic event. ^1–4 DPHL typically presents with impaired cognition, parkinsonism (muscle rigidity, gait shuffling, and facial masking), and akinetic mutism (nearly absent speech and bodily movement). ^{2 , 3} Early supportive care and rehabilitation are the mainstay of treatment, and no known treatment completely reverses the course of disease. Recovery may be gradually achieved over a period of 3 to 12 months; however, some cases have resulted in permanent neurocognitive damage. ²

CASE DESCRIPTION

A 76-year-old man with a history of hypertension, hyperlipidemia, type 2 diabetes mellitus, and coronary artery disease was in his usual state of health until he was found on the ground at his cabin during a deer hunting trip. The patient was awake but disoriented to place, time, and situation when found. He was taken to an outside hospital where he was reported to have an unremarkable neurologic exam (apart from mild difficulties with short-term memory and balance), laboratory workup, and brain magnetic resonance imaging (MRI). The patient initially showed improvement in mental status upon discharge, but subsequently experienced progressive confusion, dysphasia, and shuffling gait over the next 2 weeks and was brought to our hospital for further evaluation.

Laboratory workup was unremarkable, including complete blood count, comprehensive metabolic panel, urine drug screen, basic rheumatologic antibodies, and Mayo Clinic serum encephalopathy autoantibody panel. Cerebrospinal fluid studies were also within normal limits, including the real-time quaking-induced conversion test and Mayo Clinic cerebrospinal fluid encephalopathy panel.

On imaging, brain MRI obtained at 24 days of his last known well (LKW) was notable for small foci of abnormal diffusion restriction in bilateral frontal lobes (Figure 1a), demonstrating the possibility of a small cerebrovascular accident contributing to the initial presentation. Subsequent MRI conducted at 28 days of LKW showed subtle diffusion restriction throughout cerebral white matter, most prominent in the frontal lobes (Figure 1b). Repeat MRI at 32 days of LKW (Figure 1c) and then at 43 days (Figure 1d) continued to reveal increasingly demarcated foci of diffusion restriction throughout cerebral white matter consistent with diffuse hypoxic-ischemic injury.

Figure 1.

Longitudinal axial diffusion-weighted MRI. (a) Brain MRI obtained at 24 days of last known well (LKW). (b) MRI taken at 28 days of LKW. (c) MRI taken at 32 days of LKW. (d) Final MRI taken at 43 days of LKW.

The patient’s neurologic status continued to deteriorate, ultimately resulting in severe aphasia and complete loss of ambulation. Empiric treatment with methylprednisone 1000 mg intravenous daily for 5 days did not result in any noticeable change in mental status, and his family decided to pursue palliative and hospice care.

DISCUSSION

DPHL is an uncommon demyelinating syndrome characterized by neurologic decline after initial recovery from a relatively prolonged hypoxic or global ischemic brain injury. ^1–4 The occurrence of DPHL has been reported in various settings such as carbon monoxide intoxication, drug overdose, cardiac arrest, and seizures. ³ Although the exact mechanism behind the delayed presentation is not completely understood, theories include delayed apoptosis of oligodendrocytes, myelin-sheath damage, and dysfunction of arylsulfatase A enzymes. ^{2 , 4} MRI findings reveal diffuse hyperintensity of cerebral white matter on T2-weighted sequences, located predominantly in the centrum semiovale and periventricular regions; conversely, cerebellar white matter is characteristically spared. ² Diagnosis of DPHL requires a high degree of clinical suspicion and should remain high on the differential in the presence of neurologic decline following apparent recovery from hypoxic injury.