Acute Hemorrhagic Leukoencephalitis - Symptoms, Diagnosis, and Treatment

Introduction:

The central nervous system is regarded as the core processing center. It comprises the brain and spinal cord that are protected by a bony covering and cushioned by certain membranes known as meninges and the cerebrospinal fluid. Thus the central nervous system is well shielded from external or internal detriments. However, infection, inflammation, cysts, and tumors are common diseases of the central nervous system that could result in structural or functional loss. One such rare inflammatory condition affecting the brain is acute hemorrhagic leukoencephalitis.

What Is Acute Hemorrhagic Leukoencephalitis?

Acute hemorrhagic leukoencephalitis (AHLE) is a fatal inflammatory condition affecting the brain and spinal cord. It damages the myelin sheath that primarily protects the nerves in the brain. It is also known as Weston-Hurst syndrome, or Hurst disease, as Weston-Hurst was the first to describe this condition in 1941 in two adults. It is a rare condition as the total number of reported cases from its first description to date is still less than 100. However, this could be due to a lack of appropriate diagnostic criteria and challenging diagnostics that results in underreporting or misdiagnosis.

Acute hemorrhagic leukoencephalitis (AHLE) is a rapidly progressing disease primarily affecting the cerebrum and resulting in neurologic deterioration. It is considered a rare form of acute disseminated encephalomyelitis (ADEM) which is also an inflammatory condition affecting the meninges; however, ADEM is primarily seen in children, unlike AHLE, which affects adults. Some theories also state it to be a variant of tumefactive multiple sclerosis, a rare demyelinating disease characterized by atypical intracranial lesions. Though the exact pathology is unknown, it is usually considered a post-infectious complication of respiratory or other infectious conditions. The overall prognosis is poor, with a mortality rate of around 70 percent. Survivors are mostly found to have neurological deficits.

What Is the Cause of Acute Hemorrhagic Leukoencephalitis?

Though the underlying cause remains debatable, studies have shown a positive correlation between inflammation and infectious diseases. Numerous bacteria and viruses have been associated with acute hemorrhagic leukoencephalitis (AHLE), thus triggering that it could be an autoimmune reaction in response to the bacteria or virus. It is thought that a hyperacute autoimmune cross-reaction between the patient’s neuronal tissues and the antigens from the infectious agent may trigger this disease. It is also associated less often with measles or rabies vaccination. The bacteria and viruses associated with AHLE are

1. Bacterias:

• Mycoplasma pneumonia.

• Borrelia burgdorferi.

• Leptospira.

• Streptococcus.

2. Viruses:

• Influenza virus.

• Enterovirus.

• Measles

• Mumps.

• Rebella.

• Varicella zoster.

• Epstein Barr virus.

• Cytomegalovirus.

• Herpes simplex virus.

• Hepatitis A.

• Respiratory syncytial virus.

• John Cunningham virus.

• Eastern and western equine viruses.

• West Nile.

• California.

• SARS-CoV-2.

What Are the Clinical Features of Acute Hemorrhagic Leukoencephalitis (AHLE)?

Acute hemorrhagic leukoencephalitis (AHLE) is characterized by a sudden or, less often, violent onset. The symptoms manifest between two days and two weeks after a previous infectious condition though the most common associated condition is a viral upper respiratory tract infection. Individuals in hematologic remission due to acute myeloid leukemia or with a pre-existing autoimmune condition may also be vulnerable to this disease. It is increasingly prevalent in males between 20 to 40 years. The disease follows a short course, and death usually occurs in the first week. The general symptoms are

• High fever (106 degrees Fahrenheit).

• Headache.

• Fatigue.

• Vomiting and nausea.

• Stiffness in the neck.

• Photophobia.

• Meningeal irritation.

• Visual disturbances.

• Motor and sensory disturbances.

• Hyperactive reflexes.

• Seizures.

• Papilledema due to high intracranial pressure.

• Lethargy and confusion.

• Progressive, the patients may enter a coma stage.

• Herniation and brain swelling may result in death.

How Is Acute Hemorrhagic Leukoencephalitis Diagnosed?

Diagnosing acute hemorrhagic leukoencephalitis is challenging, considering the presentation and overlapping clinical features with other conditions causing encephalopathy. Neuroimaging is the key diagnostic tool used in diagnosing acute hemorrhagic leukoencephalitis (AHLE). Other laboratory diagnostics, such as blood analysis, histopathology, and cerebrospinal fluid (CSF) analysis, can further support the etiology and diagnosis. The diagnostic workup is as given below:

• Physical Signs and Symptoms: The signs and neurological symptoms presented could lead to the diagnosis of ADEM. Hence clinical history and examination may not be precise enough to reach a conclusive diagnosis of acute hemorrhagic leukoencephalitis (AHLE).

• Laboratory Analysis: Blood analysis reveals neutrophil-predominant leukocytosis, granulocytic pleocytosis, and a drastic increase in protein content. The erythrocyte sedimentation rate (ESR) is elevated.

• Cerebrospinal Fluid (CSF) Analysis: CSF cellularity reveals red blood cells and neutrophils.

• Radiological Examination: Head computed tomography (CT) and magnetic resonance imaging (MRI) are more conclusive diagnostic testing to assess the extent of damage and prognosis. A head CT depicts hypodense areas in the affected gray and white matter. MRI may show hyper-intense lesions. Advanced MRIs such as the fluid-attenuated inversion recovery (FLAIR) sequence offers better visualization and enhanced detection of lesions in the brain.

• Biopsy: A brain biopsy though rarely necessitated, may reveal necrosis, demyelination, fibrin exudation around the vessels, a classic ring-ball sign of hemorrhages, neutrophil, and macrophage infiltration.

How Is Acute Hemorrhagic Leukoencephalitis Treated?

The occurrence of symptoms concurrently makes AHLE difficult to treat. Hence many clinical trials are underway to develop effective and long-term drugs for this condition. The first line of treatment should be aggressive intracranial pressure control. Increased intracranial pressure can be managed with mannitol, phenobarbital, and hyperventilation. Immunomodulation can help deal with the increased inflammation. High-dose corticosteroids, plasmapheresis, cyclophosphamide, and intravenous immunoglobulins are commonly used to treat AHLE.

How Is the Prognosis?

The prognosis is extremely poor as death occurs within the first week due to raised intracranial pressure and brain herniation. Complete recovery is rare; survivors usually present with neurological deficits, psychiatric symptoms, seizures, or psychological decline.

Conclusion:

Acute hemorrhagic leukoencephalitis (AHLE) is a rare fatal neurologic disease associated with a poor prognosis. Considering the need for more literature, there is a significant snag in understanding this condition's course, diagnostics, and management. Since there are no well-defined diagnostic or treatment criteria, acute hemorrhagic leukoencephalitis (AHLE) proves to be a challenging condition. Further research and clinical trials are needed to characterize this disease and deliver more information pertaining to the diagnosis, treatment, and outcome.