Acute Hemorrhagic Leukoencephalitis

Also known as Weston-Hurst syndrome most commonly affects the cerebrum followed by the cerebellum, brain stem, or spinal cord. As its pathogenesis involves progressive hemorrhagic demyelination of white matter, MRI is considered the diagnostic test of choice to detect any diffuse edema, confluent lesions, or petechial hemorrhage. Failure to provide early treatment will result in a poor prognosis or even death in a few days.

Introduction

  • Inflammatory disease of the brain
  • First described by Weston Hurst in 1941
  • 50-75% of patients have a history of viral or bacterial infections.
  • Most of the patients are children or young adults
  • The most commonly affected site is the cerebrum followed by the cerebellum, brain stem, or spinal cord.
Acute hemorrhagic leukoencephalitis (AHL) is also known as Weston-Hurst syndrome.
A very rare form of demyelinating disease
Occurs sporadically. More common in children and young adults
Considered most severe form of acute disseminated encephalomyelitis (ADEM)

Pathophysiology

  • Acute and rapidly progressive hemorrhagic demyelination of white matter
  • Acute immunological response induced by cross-reaction between human myelin antigens and viral or bacterial antigens, causing demyelination.
  • Injecting the VP2121–130 viral capsid of the Theiler’s murine encephalomyelitis virus in the first murine model of AHLE -induced a strong in vivo activation of CD8+ T cells in C57BL/6 mice leading to the development of hemorrhagic demyelination within 24 hrs.

Clinical Features

  • Headache
  • Seizure
  • Focal neurologic signs
  • Encephalopathy
  • Coma

Differential Diagnosis

  • Optic Neuritis
  • Multiple Sclerosis
  • Transverse Myelitis
  • Neuromyelitis Optica
  • Collagen vascular disease
  • Primary angiitis of the central nervous system
  • Myelin Oligodendrocyte Glycoprotein antibody syndrome

Diagnosis

💡
MRI is the diagnostic test of choice
  • MRI is the diagnostic test of choice - diffuse edema, larger and often confluent lesions, petechial hemorrhage
  • Perivascular demyelination and hemorrhage, inflammatory infiltrate with predominant neutrophil and macrophage, fibrinoid necrosis of vessel wall are the pathologic hallmarks.
  • CSF study shows mild polymorphonuclear leukocytosis or elevated protein or presence of oligoclonal bands
  • In some cases, CSF study showed the presence of anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibodies and anti-aquaporin-4 (anti-AQP4) antibodies
  • Serial MR Imaging Findings of Acute Hemorrhagic Leukoencephalitis can be found here.
 
Figure 1: MRI Finding of Acute Hemorrhagic Leukoencephalitis
notion image
Cerebral MRI presenting the temporal evolution within 3 days (from left to right). First row: axial T2-weighted FLAIR images showing increasing bilateral confluent widespread hyperintensities of the supratentorial white matter predominantly on the left. Second row: axial T2-weighted FLAIR images revealing new hyperintensities of the left cerebellar peduncle. Third row: axial SWI demonstrating subtle and small susceptibility artifacts in the splenium of the corpus callosum. Fourth row: axial pre- and post-contrast T1-weighted MPRAGE showing enhancement of the left parieto-occipital region. FLAIR, Fluid-Attenuated Inversion Recovery; SWI, Susceptibility Weighted Imaging; MPRAGE, Magnetization-Prepared Rapid Acquisition with Gradient Echo
Source: Acute Hemorrhagic Leukoencephalitis: A Case and Systematic Review of the Literature Grzonka P, Scholz MC, De Marchis GM, et al. Acute Hemorrhagic Leukoencephalitis: A Case and Systematic Review of the Literature. Frontiers in Neurology. 2020;11. doi:10.3389/fneur.2020.00899

Treatment

  • No definitive treatment
  • Early treatment is very important
  • Individual or combination immunosuppressive therapy corticosteroids
    • methylprednisolone 2 gram per day for 3 days followed by tapering
    • cyclophosphamide (15 milligrams per kilogram body weight)
    • plasma exchange
  • Control of intracranial pressure with hyper-osmolar therapy (mannitol or hypertonic saline), hyperventilation, and/or therapeutic coma (phenobarbitol)

Prognosis

  • Prognosis is poor
  • It is Fatal disease
  • Death in a few days

Further Reading

  • Wellnitz, K., Sato, Y., & Bonthius, D. J. (2021). Fatal Acute Hemorrhagic Leukoencephalitis Following Immunization Against Human Papillomavirus in a 14-Year-Old Boy. Child neurology open8, 2329048X211016109. https://doi.org/10.1177/2329048X211016109
  • Wang C. X. (2021). Assessment and Management of Acute Disseminated Encephalomyelitis (ADEM) in the Pediatric Patient. Paediatric drugs23(3), 213–221. https://doi.org/10.1007/s40272-021-00441-7

Bibliography

  • Grzonka, P., Scholz, M. C., De Marchis, G. M., Tisljar, K., Rüegg, S., Marsch, S., Fladt, J., & Sutter, R. (2020). Acute Hemorrhagic Leukoencephalitis: A Case and Systematic Review of the Literature. Frontiers in neurology11, 899. https://doi.org/10.3389/fneur.2020.00899
  • Yildiz, Ö., Pul, R., Raab, P. et al. Acute hemorrhagic leukoencephalitis (Weston-Hurst syndrome) in a patient with relapse-remitting multiple sclerosis. J Neuroinflammation 12, 175 (2015). https://doi.org/10.1186/s12974-015-0398-1
  • Fugate JE, Lam EM, Rabinstein AA, Wijdicks EFM. Acute Hemorrhagic Leukoencephalitis and Hypoxic Brain Injury Associated With H1N1 Influenza. Arch Neurol. 2010;67(6):756–758. doi:10.1001/archneurol.2010.122
  • Manzano GS, McEntire CRS, Martinez-Lage M, Mateen FJ, Hutto SK. Acute Disseminated Encephalomyelitis and Acute Hemorrhagic Leukoencephalitis Following COVID-19: Systematic Review and Meta-synthesis. Neurol Neuroimmunol Neuroinflamm. 2021 Aug 27;8(6):e1080. doi: 10.1212/NXI.0000000000001080. PMID: 34452974; PMCID: PMC8404207.
  • Rosman NP, Gottlieb SM, Bernstein CA. Acute hemorrhagic leukoencephalitis: recovery and reversal of magnetic resonance imaging findings in a child. J Child Neurol. 1997 Oct;12(7):448-54. doi: 10.1177/088307389701200707. PMID: 9373802.