Acute Hemorrhagic Leukoencephalitis

Primary Category

Neuroimmunology

P-Category

Secondary Category

S-Category

Authors:

Sharmi Biswas MBBS,
Junaid Kalia MD

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

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

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 neurology, 11, 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.