Systematic Reviews
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Oct 16, 2024; 12(29): 6285-6301
Published online Oct 16, 2024. doi: 10.12998/wjcc.v12.i29.6285
Spectrum of delayed post-hypoxic leukoencephalopathy syndrome: A systematic review
Bahadar S Srichawla, Maria A Garcia-Dominguez
Bahadar S Srichawla, Maria A Garcia-Dominguez, Department of Neurology, University of Massachusetts Chan Medical School, Worcester, MA 01655, United States
Author contributions: Srichawla BS was responsible for data curation, writing, editing, and supervision; Garcia-Dominguez MA was responsible for data curation and editing; all authors have read and approved the final manuscript.
Conflict-of-interest statement: The authors declare no conflict of interest.
PRISMA 2009 Checklist statement: This systematic review was completed in concordance with the PRISMA 2009 checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Bahadar S Srichawla, DO, MS, Staff Physician, Department of Neurology, University of Massachusetts Chan Medical School, 55 Lake Ave N, Worcester, MA 01655, United States. bahadar.srichawla@umassmemorial.org
Received: July 8, 2024
Revised: July 31, 2024
Accepted: August 14, 2024
Published online: October 16, 2024
Processing time: 51 Days and 6.9 Hours
Abstract
BACKGROUND

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.

AIM

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

Keywords: Delayed post hypoxic leukoencephalopathy syndrome; Anoxic encephalopathy; Delayed post hypoxic leukoencephalopathy; Hypoxic-ischemic brain injury; Grinker's myelinopathy; Toxic leukoencephalopathy; Toxic leukoencephalopathy; Delayed postanoxic encephalopathy; Carbon monoxide poisoning

Core Tip: Delayed post hypoxic leukoencephalopathy syndrome (DPHLS) manifests days to weeks after a hypoxic event, presenting with neurological and cognitive deficits. This systematic review consolidates current knowledge on DPHLS, highlighting the complexity of its pathophysiology and the challenges in diagnosis and treatment. Common causes include benzodiazepine and opioid overdose, and carbon monoxide (CO) poisoning. Neuroimaging typically shows diffuse T2 hyperintensities in cerebral white matter sometimes involving subcortical structures such as the basal ganglia and thalamus. Early recognition and supportive management are crucial. Hyperbaric oxygen therapy may be beneficial in CO poisoning.