Delayed post hypoxic leukoencephalopathy syndrome (DPHLS), also known as Grinker's myelinopathy, is a rare but significant neurological condition that manifests days to weeks after a hypoxic event. Characterized by delayed onset of neurological and cognitive deficits, DPHLS presents substantial diagnostic and therapeutic challenges.

To consolidate current knowledge on pathophysiology, clinical features, diagnostic approaches, and management strategies for DPHLS, providing a comprehensive overview and highlighting gaps for future research.

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes guidelines, we systematically searched PubMed, ScienceDirect and Hinari databases using terms related to delayed post-hypoxic leukoencephalopathy. Inclusion criteria were original research articles, case reports, and case series involving human subjects with detailed clinical, neuroimaging, or pathological data on DPHLS. Data were extracted on study characteristics, participant demographics, clinical features, neuroimaging findings, pathological findings, treatment, and outcomes. The quality assessment was performed using the Joanna Briggs Institute critical appraisal checklist.

A total of 73 cases were reviewed. Common comorbidities included schizoaffective disorder, bipolar disorder, hypertension, and substance use disorder. The primary causes of hypoxia were benzodiazepine overdose, opioid overdose, polysubstance overdose, and carbon monoxide (CO) poisoning. Symptoms frequently include decreased level of consciousness, psychomotor agitation, cognitive decline, parkinsonism, and encephalopathy. Neuroimaging commonly revealed diffuse T2 hyperintensities in cerebral white matter, sometimes involving the basal ganglia and the globus pallidus. Magnetic resonance spectroscopy often showed decreased N-acetylaspartate, elevated choline, choline-to-creatinine ratio, and normal or elevated lactate. Treatment is often supportive, including amantadine, an antioxidant cocktail, and steroids. Hyperbaric oxygen therapy may be beneficial in those with CO poisoning. Parkinsonism was often treated with levodopa. Most of the patients had substantial recovery over the course of months and many cases had some residual neurocognitive deficits.

DPHLS remains a complex and multifaceted condition with various etiologies and clinical manifestations. Early recognition and appropriate management are crucial to improving patient outcomes. Future research should focus on standardizing diagnostic criteria, using advanced imaging techniques, and exploring therapeutic interventions to improve understanding and treatment of DPHLS. Conducting prospective cohort studies and developing biomarkers for early diagnosis and monitoring will be essential to advance patient care.

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.

Delayed post-hypoxic leukoencephalopathy (DPHL) is characterized by a biphasic clinical course, with complete recovery from coma to a fully conscious state lasting one to four weeks (lucid interval), followed by abrupt neurological deterioration as an indirect consequence of hypoxic events like carbon monoxide poisoning and narcotic drug overdose. To our best knowledge, there are no documented cases in literature of choreoathetosis and dementia following poppy-induced DPHL with 14-3-3 protein in cerebrospinal fluid (CSF).

We report the case of a 70-year-old female who underwent cardiopulmonary resuscitation (CPR) due to overdose of homemade refined opium poppy paste two weeks prior to presentation. She presented a progressive cognitive decline, along with the development of apraxia and choreic movement affecting her tongue and bilateral upper and lower extremities. During the symptomatic phase, brain magnetic resonance imaging (MRI) showed bilateral symmetrical hyperintense signals mostly in central frontal, temporal, and parieto-occipital lobes in the diffusion weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) sequences which are the characteristic findings of DPHL. CSF routine analysis, as well as toxicology screening, autoimmune and paraneoplastic encephalitis panels were negative, but the presence of 14-3-3 protein in the CSF was detected. With steroid therapy, hyperbaric oxygen therapy and symptomatic treatment, she experienced gradual improvement in cognition, motivation, and psychomotor function.

DPHL represents a distinct form of encephalopathy characterized by unique clinical course and imaging features. It is the first report of DPHL with positive 14-3-3 protein in CSF. The potential of 14-3-3 protein as a biomarker for diagnosing DPHL and its ability to predict disease severity and prognosis warrants further research.

Toxic leukoencephalopathy (TLE) is a rare pathology caused by various substances including opioids (notably heroin), immunosuppressants, chemotherapy agents, cocaine, alcohol and carbon monoxide. However, although heroin is metabolised by the body into morphine, there is a striking paucity in cases of primary oral morphine-induced TLE, especially in the adult population. We present the case of a man in his 40s admitted to hospital in respiratory depression with a Glasgow Coma Scale (GCS) score of 6 after taking an overdose of oral morphine sulphate. Following a complete recovery to baseline, he was then readmitted with an acute deterioration in his neurobehavioural condition. Initial investigations returned normal but MRI showed changes characteristic for TLE.In cases of opioid toxicity such as ours, TLE is difficult to differentiate from delayed post-hypoxic leukoencephalopathy, due to their similar clinical presentation, disease progression and radiological manifestation. We explore how clinicians can approach this diagnostic uncertainty.