A Man with Motor Neuron Disease and Odd Behaviors during Sleep

Published
Posted by Carla Rothaus

How would you treat patients with anti-IgLON5 disease? 

Parasomnias are a group of sleep disorders characterized by abnormal behaviors during sleep. Read the NEJM Case Records of the Massachusetts General Hospital here.

Clinical Pearls

Q: What are some of the features of non–rapid-eye-movement (REM) parasomnias?

A: Parasomnias are divided into non-REM (NREM) and REM forms, depending on whether the behaviors emanate from NREM or REM sleep. Certain clinical characteristics can help to differentiate between these two forms. For example, NREM parasomnias — such as sleepwalking, sleep terrors, and confusional arousals — often occur in younger patients, mainly happen during the first half of the night, and are associated with a lack of clear dream recall. During NREM parasomnias, the patient is often difficult to arouse, and the associated movements have a rather normal appearance.

Q: What are some of the features of the REM parasomnia known as REM sleep behavior disorder?

A: REM sleep behavior disorder is characterized by episodes suggesting that an affected person is acting out upsetting dreams, sometimes with vocalizations and movements indicating fear and anger. The loss of muscle atonia that accompanies normal REM sleep is the neurophysiologic signature of REM sleep behavior disorder. REM sleep behavior disorder has been linked to neurodegenerative disorders and is now recognized as a prodromal stage of three evolving synucleinopathies: Parkinson’s disease, dementia with Lewy bodies, and multiple-system atrophy.


Morning Report Questions

Q: Describe some of the symptoms of anti-IgLON5 disease.

A: Anti-IgLON5 disease is a disorder associated with autoantibodies to IgLON5, a neural cell adhesion molecule of unknown function. The disorder affects men and women equally and usually develops at 50 to 60 years of age. Anti-IgLON5 disease is characterized by a distinctive sleep phenotype and a wide range of associated neurologic symptoms. Daytime sleepiness may be present. Other symptoms include dysarthria, dysphagia, gait instability, chorea, eye movement abnormalities, cognitive changes, fasciculations, and myoclonus. The clinical heterogeneity of anti-IgLON5 disease, the rarity of the disease, and the slow progression over a period of months or years are factors that frequently contribute to a delay in diagnosis. The median time from symptom onset to diagnosis is 2.5 years. The clinical heterogeneity can also lead to misdiagnosis with one of several conditions. 

Q: How would you treat patients with anti-IgLON5 disease?

A: Tests for IgLON5 autoantibodies are commercially available, and have equal sensitivity when performed on serum and on cerebrospinal fluid. Because the diagnosis of anti-IgLON5 disease is usually delayed, the symptoms are often quite prominent at the time of diagnosis. Death occurs within 3 years after diagnosis in more than 50% of patients. Current knowledge about treatment effectiveness is limited. Most patients are treated with immunotherapy including glucocorticoids, immunoglobulins, plasma exchange, rituximab, cyclophosphamide, azathioprine, mycophenolate mofetil, or a combination of these therapies. The reported response rate to immunotherapy ranges from 10 to 70%. Combination therapy seems to be more effective than monotherapy.

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