Delayed Leukoencephalopathy After Hypoxic-Ischemic Injury

A 53-year-old woman was transferred to our institution from another country for evaluation of mutism, quadriparesis, and incontinence. She had undergone hysterectomy for menorrhagia, complicated by an event characterized to the family as the patient having “died” prior to resuscitation. She was reportedly comatose for 2 days but recovered well and functioned normally for 2 weeks. She then became confused, developed gait difficulty and incontinence, and her condition deteriorated further over 2 weeks prior to transfer.

On neurological examination the patient was mute and did not follow commands. There was a right visual field deficit. Her legs moved purposefully, but her arms were held in a flexed posture. She was spastic and hyperreflexic in all extremities. The results of serum chemistry analyses, lactate and pyruvate level testing, complete blood cell count, coagulation studies, and thyrotropin and vitamin B₁₂ level testing were normal. The cerebrospinal fluid was normal at symptom onset and again 4 weeks later (glucose level, 63 mg/dL; protein, 23 mg/dL; white blood cells, none; red blood cells, 3/mm³; and oligoclonal bands, none). Findings from an electroencephalogram were notable for generalized slowing. Arylsulfatase A activity was normal. Spinal magnetic resonance imaging (MRI) was unremarkable.

Brain MRI 2 weeks and 5 weeks after the initiating event showed extensive, symmetric white matter T2/fluid-attenuated inversion recovery hyperintensities (Figure 1A). Diffusion-weighted imaging at 5 weeks (Figure 1B) revealed restricted diffusion of the white matter, confirmed on apparent diffusion coefficient mapping (Figure 1C). Notably, an MRI performed several years earlier showed none of these lesions, which are consistent with delayed post hypoxic leukoencephalopathy.

Delayed leukoencephalopathy has been associated with carbon monoxide poisoning,¹ heroin inhalation (“chasing the dragon”),² and occult abnormalities in arylsulfatase A activity. Exposure to toxins is not a prerequisite, however, and patients may have no underlying metabolic defect. Previous reports^{3 - 4} describe cases similar to ours, in which neurological decline ensues after a delay of 1 to 2 weeks following a hypoxic-ischemic event. Prognosis is variable, but recovery has been described. Our patient's condition improved over 2 months to the point of speaking and having limited use of her arms, but she remains impaired.

Demyelination has been proposed as a pathophysiological mechanism in these enigmatic cases, accounting for both latency to onset and variable prognosis.⁴ This demyelination might be triggered by selective vulnerability of the white matter to hypoxic injury, resulting from its widely spaced arterioles and lack of anastomoses. The spectroscopic profile in our case (Figure 2) is consistent with a demyelinating process.

Correspondence: Dr Chen-Plotkin, Department of Neurology, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114 (alicechenplotkin@gmail.com).

Author Contributions: Drs Chen-Plotkin and Pau provided clinical care of this patient. Study concept and design: Chen-Plotkin and Schmahmann. Acquisition of data: Chen-Plotkin, Pau. Analysis and interpretation of data: Chen-Plotkin. Drafting of the manuscript: Chen-Plotkin, Pau. Critical revision of the manuscript for important intellectual content: Schmahmann. Statistical analysis: Study supervision: Schmahmann.

Financial Disclosure: None reported.