We report on a patient with delayed post-hypoxic leukoencephalopathy (DPHL) who showed akinetic mutism and gait disturbance, neural injuries that were demonstrated on diffusion tensor tractography (DTT). A patient was exposed to carbon monoxide (CO) and rapidly recovered; however, two weeks after onset, he began to show cognitive impairment and gait disturbance. At six weeks after CO exposure, he showed akinetic mutism and gait inability. DTT at 6-weeks post-exposure showed discontinuations in neural connectivities of the caudate nucleus to the medial prefrontal and orbitofrontal cortex in both hemispheres. In addition, the corticoreticulospinal tract revealed severe thinning in both hemispheres.

This is the case of a 26-year-old male who developed Anton Babinski syndrome (ABS), quadriplegia, and delayed post-hypoxic leukoencephalopathy (DPHL) after an opioid overdose. He exhibited cortical blindness, visual anosognosia, and confabulation upon awakening. Several days later, he experienced acute psychosis and agitation. T2-FSE MRI revealed extensive supratentorial leukoencephalopathy involving both cerebral hemispheres, extending to the posterior corpus callosum due to cerebral anoxia. This case report will discuss different types of encephalopathy from opioid abuse, ABS, visual anosognosia, and confabulation\'s pathogenic mechanisms. It underscores the necessity of researching substance-induced neuropsychiatric disorders and their pathogenic mechanisms for effective treatments.

Delayed post-hypoxic leukoencephalopathy (DPHL) is a poorly recognized syndrome characterized by neuropsychiatric symptoms following recovery from an acute hypoxic episode. Although most cases are related to carbon monoxide poisoning, some have been linked to excessive opioid use. Opioid intoxication has recently become known for manifesting the characteristic imaging findings involving cerebellar, hippocampal, and basal nuclei transient edema with restricted diffusion (CHANTER) syndrome. Herein, we present a patient with severe disturbances in consciousness who was initially diagnosed with CO poisoning but was later found to have taken excessive tramadol. Magnetic resonance imaging (MRI) in the acute phase revealed abnormal intensities in the bilateral globus pallidus and the cerebellum, indicative of CHANTER syndrome. After intensive care, his level of consciousness was restored. However, around the 3rd week after hospitalization, his consciousness gradually deteriorated and he developed severe neurological symptoms. Another MRI on day 25 revealed a new diffuse white matter abnormality; DPHL was suspected. Cerebrospinal fluid collected on day 28 revealed significantly elevated myelin basic protein levels. Although it was challenging to decide on a treatment plan, hyperbaric oxygen (HBO) therapy trials were initiated on day 58; the patient\'s condition improved after a series of HBO sessions. MRI revealed gradual shrinkage of the white matter abnormality. A total of 63 consecutive HBO sessions were performed, leading to the successful resolution of the serious neurological symptoms. While the effectiveness of HBO therapy for DPHL remains inconclusive, especially in opioid-related cases, this patient made a remarkable recovery, likely due to the therapeutic effect of improved cerebral blood flow and oxygenation.

Background: Delayed Post-Hypoxic Leukoencephalopathy (DPHL), or Grinker\'s myelinopathy, is a syndrome in which extensive changes are seen in the white matter of the cerebral hemispheres with MRI weeks or months after a hypoxic episode. T2-weighted spin echo (T2-wSE) and/or T2-Fluid Attenuated Inversion Recovery (T2-FLAIR) images classically show diffuse hyperintensities in white matter which are thought to be near pathognomonic of the condition. The clinical features include Parkinsonism and akinetic mutism. DPHL is generally regarded as a rare condition. Methods and Results: Two cases of DPHL imaged with MRI nine months and two years after probable hypoxic episodes are described. No abnormalities were seen on the T2-FLAIR images with MRI, but very extensive changes were seen in the white matter of the cerebral and cerebellar hemisphere on divided Subtraction Inversion Recovery (dSIR) images. dSIR sequences may produce ten times the contrast of conventional inversion recovery (IR) sequences from small changes in T1. The clinical findings in both cases were of cognitive impairment without Parkinsonism or akinetic mutism. Conclusion: The classic features of DPHL may only represent the severe end of a spectrum of diseases in white matter following global hypoxic injury to the brain. The condition may be much more common than is generally thought but may not be recognized using conventional clinical and MRI criteria for diagnosis. Reappraisal of the syndrome of DPHL to include clinically less severe cases and to encompass recent advances in MRI is advocated.

Objective: We report a neuropsychological evaluation for a 39-year-old, right-handed, white female who 8 years ago developed delayed post-hypoxic leukoencephalopathy (DPHL), a rare demyelinating syndrome, two-weeks following an anoxic brain injury due to an overdose from benzodiazepines. Methods: An extensive record review documenting her medical timeline and treatment over the last 8 years was conducted using the available EMR system, which also included both EEG and neuroimaging data. Eight years post injury, a comprehensive neuropsychological battery was administered with corrected normative data for age, race, education, and other demographic factors when available. Collected data was compared with other case reports of DPHL. Results: The neuropsychological profile indicated difficulties across multiple cognitive domains that appeared driven by executive dysfunction, likely related to fronto-subcorto-striatal dysfunction. Conclusion: As a rare disease, the process by which DPHL occurs is not fully understood. Our results revealed similar findings in the literature for learning and memory, attention, processing speed, and executive functions. This is discussed in the context of available neuroimaging while highlighting the value of comprehensive neuropsychological assessment in DPHL even years post-injury.

A 59-year-old woman presented with right hemiparesis and was transported from outside hospital. MRI revealed acute infarction and the left middle cerebral artery M2 occlusion. Intravenous infusion of recombinant tissue-type plasminogen activator, and mechanical thrombectomy (MT) were performed. The cause of cerebral infarction was diagnosed as Libman-Sacks endocarditis. She discharged without sequelae. After 10 months later, she presented with mild cognitive decline, and MRI showed new white matter lesion in left deep white matter. In magnetic resonance spectroscopy, the lesion showed an increased rate of choline/creatine, and a decreased rate of N-acetylaspartate/creatine, elevated lactate peak. When new higher brain dysfunction presented after recanalization by MT, it might be related to the delayed white matter lesion.

Acute toxic leukoencephalopathy (ATL) and delayed post-hypoxic leukoencephalopathy (DPHL) are two possible adverse entities related to opioid intoxication (OI), each having a distinct clinical course. While ATL shows a monophasic course with gradual neurological deterioration, DPHL has a distinct biphasic course. We report a case of ATL along with a case of DPHL happening in young male patients with OI, including their clinical courses as well as imaging characteristics with comparable time intervals. Initially, both leukoencephalopathies typically show magnetic resonance imaging findings with confluent and symmetric white matter (WM) abnormalities in the periventricular regions on T2 and fluid-attenuated inversion recovery images along with restricted diffusion on diffusion-weighted imaging. The DPHL patient however also presented with WM cystic substance loss in the deterioration phase, several weeks after hospital admission, which was previously described in a case of DPHL. Interestingly, similar WM changes have recently been observed in virus-associated necrotizing disseminated acute leukoencephalopathy in patients with coronavirus disease 2019 which may suggest a common pathophysiological mechanism. Knowing the distinct imaging features of ATL and DPHL along with their typical clinical courses can provide a faster and more reliable differentiation between these two entities.

Delayed post-hypoxic leukoencephalopathy (DPHL) is a syndrome that may occur as a result of the hypoxic event, including opiate overdose. The pathophysiology of this entity is not fully known. Within a neuropsychiatric context, the diagnosis of this rare disease is important. A 39-year-old man with a history of methadone overdose presented with loss of consciousness and fever. After clinical evaluations, laboratory analysis, including various tests on blood and cerebrospinal fluid and magnetic resonance imaging, the patient was diagnosed with methadone-induced DPHL. Treatment with antioxidants, including vitamins E, C and B complex, produced a favorable outcome. In rare cases, methadone overdose may lead to DPHL. Antioxidants therapy should be considered in the treatment of this rare disorder.

Delayed post-hypoxic leukoencephalopathy (DPHL) is an uncommon, potentially under-recognized, cause of hypoxia induced white matter injury. It characteristically follows a biphasic course: After an initial phase of altered neurologic status a recovery occurs which is then followed by a recurring phase of neurologic deterioration, typically 2-4 weeks after the initial event. At this time white matter changes can be identified on MRI, which are the hallmark of DPHL. The characteristics and the typical MR-imaging signs of DPHL are discussed in this case report.

BACKGROUND: Delayed post-hypoxic leukoencephalopathy (DPHL) is a demyelinating syndrome characterized by neurological relapse after an initial recovery from hypoxic brain injury. We describe a patient with impaired consciousness following DPHL, concurrent with injury of the ascending reticular activating system (ARAS) shown using diffusion tensor tractography (DTT).
METHODS: A 50-year-old male patient was in a drowsy mental state after exposure to carbon monoxide (CO) for about ten hours. About a day after the CO exposure, his mental state recovered to an alert condition. However, his consciousness deteriorated to drowsy 24 days after the exposure and worsened to a semi-coma state at 26 days after onset. When he started rehabilitation six weeks after the CO exposure, he had impaired consciousness, with a Glasgow Coma Scale score of 8 and a Coma Recovery Scale-Revised score of 8. On 6-week DTT, decreased neural connectivity of the upper ARAS between the intralaminar thalamic nucleus and the cerebral cortex was observed in both frontal cortices, basal forebrains, basal ganglia and thalami. The lower dorsal ARAS was not reconstructed on the right side, and was thin on the left side. The lower ventral ARAS was not reconstructed on either side.
CONCLUSIONS: Using DTT, we demonstrated injury of the ARAS in a patient with impaired consciousness following DPHL. Our result suggests that injury of the ARAS is a plausible pathogenetic mechanism of impaired consciousness in patients with DPHL.