Encephalitis lethargica (EL) is a rare form of encephalitis that garnered attention during an epidemic of the disease between 1917 and 1926. The cause of EL is still not known [1]. It is sometimes referred to as the sleepy sickness or sleeping sickness.

The illness was mainly characterized by lethargy and somnolence, although there were significant variations in presentation. Some patients presented with insomnia, mania, psychosis, or even coma. Patients with EL suffered for years. It was estimated that the disease affected over a million people [2] [3].

Common clinical features included movement disorders which in the acute phase of the illness included muscular rigidity, tremor, and abnormal eye movements. Other associated manifestations were fever, visual disturbances, myalgias, weakness, and slow physical and cognitive functioning. In patients that survived the disease, one of the most prominent sequelae was postencephalitic parkinsonism (PEP). PEP could be distinguished from Parkinson's disease (PD) based on an early age of onset and because the associated tremor was not the typical pill-rolling tremor seen in PD. PEP also caused pyramidal signs and respiratory distress.

Since the aforementioned epidemic, there have been a few sporadic cases recorded [2]. Speculations about the etiology of EL have mostly revolved around a possible link with the Spanish influenza virus that caused a pandemic around the same time as EL. Some atypical enteroviruses have also been suspected. EL is diagnosed clinically, although there are brain changes that can be visualized by magnetic resonance imaging (MRI). There were as many as 28 proposed types of the disease, based on clinical presentation and symptomatology [4].

• Fatigue

  Persistence of enterovirus RNA in muscle biopsy samples suggests that some cases of chronic fatigue syndrome result from a previous, inflammatory viral myopathy. [ncbi.nlm.nih.gov]

  Ward, On doing nothing: Descriptions of sleep, fatigue, and motivation in encephalitis lethargica, Movement Disorders, 26, 4, (599-604), (2011). David J. Burn, Commentary on the postencephalitic cases of Dr. [dx.doi.org]

• Pupillary Abnormality

  abnormalities (7), headache (6), and seizures (3). [pediatricneurologybriefs.com]

  Cranial nerve palsies were also a common feature, particularly affecting nerves III, IV and VI, resulting in ophthalmoplegia and pupillary abnormalities. [academic.oup.com]

• Headache

  Definition Encephalitis lethargica is a disease characterized by high fever, headache, double vision, delayed physical and mental response, and lethargy. In acute cases, patients may enter coma. [ninds.nih.gov]

  […] noun A form of encephalitis caused by a virus and characterized by headache and drowsiness leading to coma. ‘As a young man Milne had suffered from encephalitis lethargica.’ [en.oxforddictionaries.com]

  […] noun mass noun A form of encephalitis caused by a virus and characterized by headache and drowsiness leading to coma. [oxforddictionaries.com]

  Summary of Case A 31 year-old female presented at our centre with headache and fever. She had suffered from a headache for about 3 weeks, and 2 weeks previously, her symptoms were aggravated by nausea and vomiting. [esciencecentral.org]

  Synonyms: epidemic encephalitis, lethargic encephalitis, sleeping sickness, sleepy sickness Type of: cephalitis, encephalitis, phrenitis inflammation of the brain usually caused by a virus; symptoms include headache and neck pain and drowsiness and nausea [vocabulary.com]

Although the diagnosis is clinical, there are measurable and observable changes in the nervous system. About half of patients with encephalitis lethargica have lymphocytes in their cerebrospinal fluid (CSF), as well as elevated proteins [5]. Autoantibodies against the basal ganglia cells are found in EL. Often there is evident grey matter inflammation on magnetic resonance imaging (MRI). Nuclear medicine has also been utilized for diagnostic purposes.

EL can be initially diagnosed as a psychiatric or neurological condition such as substance intoxication or epilepsy. Consequently, many patients with EL were regarded as having a psychiatric disorder before the diagnosis of EL became clear.

Literature has proposed certain criteria for the diagnosis of EL and these include acute or subacute encephalitis, flu-like symptoms, hypersomnia, ophthalmoplegia, and psychiatric symptoms. These features should be present with no other illness that could explain their existence.

Treatment Treatment for encephalitis lethargica is symptomatic. Levodopa and other antiparkinson drugs often produce dramatic responses. × Treatment Treatment for encephalitis lethargica is symptomatic. [ninds.nih.gov]

José Fidel Baizabal‐Carvallo, Francisco Cardoso and Joseph Jankovic, Myorhythmia: Phenomenology, etiology, and treatment, Movement Disorders, 30, 2, (171-179), (2014). [dx.doi.org]

The effect of corticosteroid treatment remains controversial in encephalitis; however, some EL syndrome patients exhibit an excellent response to corticosteroid treatment. [ncbi.nlm.nih.gov]

Prognosis The course of encephalitis lethargica varies depending upon complications or accompanying disorders. x Prognosis The course of encephalitis lethargica varies depending upon complications or accompanying disorders. [ninds.nih.gov]

Encephalitis lethargica associated with Parkinsonism in childhood is rare and usually carries a poor prognosis. [ncbi.nlm.nih.gov]

Prognosis The course of encephalitis lethargica varies depending upon complications or accompanying disorders. [brainfacts.org]

What is the Prognosis for Encephalitis Lethargica? Prognosis of encephalitis lethargica varies but complete recovery occurs in just 20% of cases. Mortality rate in case of encephalitis lethargic is around 2% to 12%. [epainassist.com]

The precise etiology of this disorder remains a conundrum. Most investigators suspect a viral etiology. [indiana.pure.elsevier.com]

Cell Biology, Indiana University School of Medicine, Fort Wayne, Indiana 46805, USA. [email protected] Abstract Postencephalitic parkinsonism has been considered unique among disorders with parkinsonian features because it is believed to have a unitary etiology [ncbi.nlm.nih.gov]

Encephalitis lethargica, also known as von Economo encephalitis, is a rare disease of unknown etiology that affects the midbrain and basal ganglia. [radiopaedia.org]

Abstract Since encephalitis lethargica's (EL) prevalence in the 1920s, epidemiologic and clinical debate has persisted over whether EL was caused by, potentiated by, or merely coincident with the Spanish influenza pandemic. [ncbi.nlm.nih.gov]

Clinically, epidemiologically, and morphologically they represent distinct entities, and EL has disappeared. [doi.org]

Theories about the pathophysiology of encephalitis lethargica and postencephalitic Parkinson's disease are offered. [ncbi.nlm.nih.gov]

Giovanni Fabbrini, Giovanni Defazio, Carlo Colosimo, Philip D Thompson and Alfredo Berardelli, Cranial movement disorders: clinical features, pathophysiology, differential diagnosis and treatment, Nature Clinical Practice Neurology, 10.1038/ncpneuro1006 [dx.doi.org]

Prevention of encephalitis lethargica is also possible by prevention of some related infections. [epainassist.com]

MacNalty thought the patients had a new disease, being unaware of von Economo’s publication because war prevented journal circulation. [n.neurology.org]

The NINDS supports research on disorders that affect the brain, such as encephalitis lethargica, with the goal of finding ways to prevent and treat them. (The disease was the subject of the book and film, “Awakenings.”) [neurologycolorado.com]

The patient is unable to prevent herself from falling asleep, even in the middle of performing a nose-touching manoeuvre. My first download was incomplete, thanks to the archivist for fixing the problem. [archive.org]

For secondary prevention, we aim to review whether the use of antiepileptic drugs after a seizure in patients with proven or suspected viral encephalitis is effective in preventing further seizures, improving outcome and reducing the risk of subsequent [doi.org]

1. Dourmashkin RR. What caused the 1918–30 epidemic of encephalitis lethargica? J R Soc Med. 1997;90(9):515–520.
2. National Institute of Neurological Disorders and Stroke. Encephalitis Lethargica Information Page. National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov/Disorders/All-Disorders/Encephalitis-Lethargica-Information-Page. Accessed October 11, 2017.
3. Tappea D, Alquezar-Planas DE. Medical and molecular perspectives into a forgotten epidemic: Encephalitis lethargica, viruses, and high-throughput sequencing. J Clin Virol. 2014;61(2):189-195.
4. Vilensky JA, Goetz CG, Gilman S. Movement disorders associated with encephalitis lethargica: a video compilation. Mov Disord. 2006;21(1):1-8.
5. McCall S, Henry JM, Reid AH, Taubenberger JK. Influenza RNA not detected in archival brain tissues from acute encephalitis lethargica cases or in postencephalitic Parkinson cases. J Clin Neuropathol Exp Neurol. 2001;60(7):696–704.