Encephalitis lethargica

What is Encephalitis Lethargica?

Encephalitis lethargica (EL), also known as “sleepy sickness,” is a rare and severe form of encephalitis that leads to inflammation of the brain, causing a range of neurological and psychiatric symptoms. While the disease was most famously seen during an epidemic in the early 20th century, sporadic cases still occur today. EL can result in long-term disability or death, and its cause remains unknown, making diagnosis and treatment challenging.

Symptoms of Encephalitis Lethargica

Encephalitis lethargica is known for its wide variety of symptoms, which can often make diagnosis difficult. The disease was historically called “sleepy sickness” due to the profound sleep disturbances it causes. However, the condition presents a much broader range of symptoms, including:

• Hypersomnolence (excessive sleepiness): Patients may experience extreme tiredness, often falling asleep or freezing during routine activities.
• Psychiatric changes: Unusual behaviour, irritability, mood changes, and confusion are common. Patients may seem detached or unresponsive.
• Ophthalmoplegia: Paralysis of the muscles that control eye movement, leading to difficulties in focusing and other visual issues.
• Movement disorders: Symptoms resembling Parkinson’s disease, such as tremors, stiffness, and slow movements, may appear.
• Flu-like symptoms: Fever, headaches, and muscle aches are often early signs.

EL is notoriously difficult to diagnose because the symptoms can resemble other conditions such as epilepsy, hysteria, drug intoxication, or psychiatric disorders. Patients are often referred to psychiatrists initially before the neurological cause is recognised.

Causes of Encephalitis Lethargica

The exact cause of encephalitis lethargica remains unknown, which complicates diagnosis and treatment. Several theories have been suggested, but no single explanation has been confirmed:

• Influenza link: One prominent theory connects EL with the 1918 influenza pandemic, suggesting that EL might be a viral or post-viral syndrome. However, no direct link to a virus has been established.
• Streptococcal infection: More recent research points to a potential connection with streptococcal bacteria, which could trigger an autoimmune response leading to brain inflammation. This theory has garnered support, though it remains unproven.
• Autoimmune causes: Some modern cases of EL are suspected to be forms of autoimmune encephalitis, such as NMDA-receptor encephalitis, which presents with similar symptoms. Therefore, doctors must test for other autoimmune conditions when diagnosing EL.

Despite these theories, the root cause of EL remains a mystery. This makes it challenging to estimate how many cases have occurred in recent years.

Diagnosis and Treatment

Diagnosis

Diagnosing encephalitis lethargica is challenging because there is no specific test for it. Instead, doctors rely on a process of elimination, ruling out other causes of encephalitis. To confirm a diagnosis of EL, the following criteria are often used:

• Acute or subacute onset of symptoms, typically over days or weeks.
• Exclusion of other causes of encephalitis, such as infections, toxins, or autoimmune disorders.
• Presence of key symptoms, such as hypersomnolence, ophthalmoplegia, and psychiatric changes.

Because the symptoms can mimic other neurological or psychiatric conditions, misdiagnosis is common. Doctors may conduct tests like brain imaging (MRI) and spinal fluid analysis to help rule out other possible causes, though these tests may not show definitive results for EL.

Treatment

There is currently no cure for encephalitis lethargica, and treatment focuses on managing symptoms and providing supportive care. Historically, various treatments have been attempted, with varying degrees of success.

Common Treatments:

• Steroids: Anti-inflammatory medications like corticosteroids can help reduce brain inflammation, especially in the early stages of the disease.
• Anti-Parkinson’s drugs: Medications used to treat Parkinson’s disease, such as levodopa, can help manage parkinsonism-like symptoms such as tremors and muscle stiffness.
• Electroconvulsive therapy (ECT): In some cases, ECT has been used to manage severe psychiatric symptoms or movement disorders, though it is not commonly used.

Supportive Care:

In the acute phase of the illness, patients may require intensive care to maintain vital functions like breathing and feeding. As the condition stabilises, rehabilitative therapies are critical to help patients regain strength and functionality. These therapies include:

• Physiotherapy: To improve muscle strength and coordination.
• Speech therapy: To help those who have difficulty speaking or swallowing.
• Occupational therapy: To support daily living activities and regain independence.

Emotional and psychological support is equally important, as the disease can have a profound impact on both the patient and their family.

Prognosis and Future Outlook

The long-term prognosis for encephalitis lethargica varies widely. Some patients recover fully, while others suffer long-term neurological damage or, in severe cases, die. One of the most debilitating outcomes of EL is post-encephalitic parkinsonism, a condition that causes:

• Tremors
• Muscle stiffness
• Difficulty initiating movement

This form of parkinsonism can last for decades, leaving patients in a nearly frozen state, though their minds remain intact. As von Economo, who first described the disease, noted: “To look at these patients, one would suppose them to be in a state of profound secondary dementia. Emotions are scarcely noticeable in the face, but they are mentally intact.”

Because of the variability in symptoms and outcomes, some patients may make significant improvements with treatment, while others may remain severely affected.

History of Encephalitis Lethargica

Since the late 16th century, epidemic outbreaks of disease that appear to have been like EL have been reported in various European countries. The name encephalitis lethargica itself was given by the neurologist Constantin Von Economo in 1916 at an early stage of the epidemic that happened during and after the First World War.

Difficulty of diagnosis and the lack of statistical records in many countries mean that estimates of the number of cases have varied greatly. Most cases are at the younger end of the age spectrum (up to 30/40 years old). There was little confirmed data around race and ethnicity although some reports suggested mortality was lower among black people.

For many years EL was regarded as a phenomenon of the past. In recent years there has been a recurrence of interest in the disease, concerning its cause and links with post-encephalitic Parkinsonism. The neurologist Oliver Sacks described the ‘awakenings’ of past cases, but recent papers have described contemporary cases and defined the disease in modern terms.

Modern reports suggest that perhaps half a million to a million or more people were affected, of whom about one-third died. Patients who survived EL often developed a form of parkinsonism called post-encephalitic parkinsonism, which results in serious neurological disability.

Some information contained in this factsheet is courtesy of The Sophie Cameron Trust (www.thesophiecamerontrust.org.uk

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By Dr Ava Easton, Encephalitis International and reviewed by Dean Walton, Core Medical Trainee 2 (CMT2), Whiston Hospital, UK and Dr Jonathan P Rogers, Clinical Lecturer in Psychiatry, University College London

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