Case 1-2022: A 67-Year-Old Man With Motor Neuron Disease and Odd Behaviors During Sleep

The n e w e ng l a n d j o u r na l of m e dic i n e
Case Records of the Massachusetts General Hospital
Founded by Richard C. Cabot

Eric S. Rosenberg, M.D., Editor
David M. Dudzinski, M.D., Meridale V. Baggett, M.D., Kathy M. Tran, M.D.,
Dennis C. Sgroi, M.D., Jo‑Anne O. Shepard, M.D., Associate Editors
Emily K. McDonald, Tara Corpuz, Production Editors
Case 1-2022: A 67-Year-Old Man with Motor

Neuron Disease and Odd Behaviors during Sleep
Aleksandar Videnovic, M.D., Suma Babu, M.B., B.S., M.P.H., Brian Zhao, M.D.,
Haatem M. Reda, M.D., and Jenny J. Linnoila, M.D., Ph.D.
Pr e sen tat ion of C a se
Dr. Suma Babu: A 67-year-old man was evaluated in the sleep clinic at this hospital From the Departments of Neurology
because of odd behaviors during sleep, daytime sleepiness, and apnea detected on (A.V., S.B., H.M.R., J.J.L.) and Radiology
(B.Z.), Massachusetts General Hospital,
a home sleep study. and the Departments of Neurology (A.V.,
Three years before the current evaluation, the patient’s wife noticed that the S.B., H.M.R., J.J.L.) and Radiology (B.Z.),
patient had vocalizations, including talking and yelling, while sleeping. He also Harvard Medical School — both in Boston.
had thrashing movements while sleeping; he fell out of bed more than once and N Engl J Med 2022;386:173-80.
inadvertently hit his wife during these movements. DOI: 10.1056/NEJMcpc2115844
Copyright © 2022 Massachusetts Medical Society.
Two years before the current evaluation, the patient’s wife noticed that the
patient had prolonged episodes of daytime sleepiness. During the episodes, he CME
appeared to fall asleep while sitting up and was unresponsive to shaking and loud at NEJM.org
voices; several hours later, he returned to normal interaction without any interven-
tion. The daytime sleepiness was intermittent and fluctuated in severity.
Four months before the current evaluation, the patient fell asleep while washing
dishes. This resulted in a fall and unstable C1 spinal fracture, which required
urgent surgical repair. After the surgical repair, melatonin and trazodone were
prescribed for insomnia, and abnormal movements during sleep abated. However,
vocalizations during sleep — including singing, talking, and expression of fear
and anger in the context of upsetting dreams — continued and were most prom-
inent in the early morning hours.
The patient also had a motor neurologic syndrome that had started before the
onset of sleep symptoms, approximately 3.5 years before the current evaluation.
Symptoms included progressive gait imbalance with falls, hand clumsiness, hoarse
voice, and dysphagia. Serial neurologic examinations, performed over a 3-year
period by multiple neuromuscular specialists, revealed slow progression of gener-
alized fasciculations and the development of bulbar hyperreflexia, postural insta-
bility, and hypophonia, although strength in the arms and legs remained intact.
Serial electromyography revealed progressive and widespread involvement of
muscles showing chronic reinnervation changes, including eventual involvement
of craniobulbar muscles (tongue and masseter muscles).
n engl j med 386;2 nejm.org January 13, 2022 173

The New England Journal of Medicine
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A B C
D E F
Figure 1. MRI of the Head.

MRI of the head was performed 4 months before the current evaluation. Diffusion‑weighted images (Panels A and B) and a fluid‑attenu‑
ated inversion recovery (FLAIR) image (Panel C) show a punctate subacute infarct in the left posterior centrum semiovale (arrows). FLAIR
images (Panels C and D) show nonspecific moderate‑to‑severe background white‑matter changes. T2‑weighted images (Panels E and F)
show chronic infarcts in the left middle frontal gyrus and right cerebellar hemisphere (arrows).
Dr. Brian Zhao: One year before the current diagnosis of slowly progressive motor neuron
evaluation, magnetic resonance imaging (MRI) disease was made, and therapy with riluzole was
of the cervical spine revealed moderate neural begun. A videofluoroscopic swallowing study
foraminal narrowing at the level of C3–C4 bilat- revealed severe oropharyngeal dysphagia with
erally and no central canal stenosis. Four months laryngeal penetration and silent aspiration; a
before the current evaluation, MRI of the head gastrostomy tube was placed, and tube feeding
revealed a punctate subacute infarct in the left was initiated.
posterior centrum semiovale, chronic infarcts in The patient underwent a home sleep-apnea
the left middle frontal gyrus and right cerebel- test, which showed sleep-disordered breathing
lum, and nonspecific moderate-to-severe white- with an apnea–hypopnea index of 20 events per
matter changes (Fig. 1). hour; hypoxemia was present at rest while he
Dr. Babu: Blood tests for paraneoplastic, nutri- was breathing ambient air. Severe oxygen de-
tional, and paraproteinemic causes of the pa- saturation occurred with frequent respiratory
tient’s neurologic syndrome were unrevealing. A events while he was asleep in the supine position.
174 n engl j med 386;2 nejm.org January 13, 2022

Case Records of the Massachuset ts Gener al Hospital
The patient was then referred to the sleep clinic Deep-tendon reflexes were brisk in the arms,
for an initial evaluation. with mild spasticity in the legs. Plantar responses
On evaluation in the sleep clinic, the patient were normal. Vibratory sensation in the legs was
reported that obstructive sleep apnea had been mildly diminished. Results of finger-to-nose and
diagnosed on the basis of a home sleep study heel-to-shin testing were normal. There were
performed 1 year earlier. Multiple attempts at mild myoclonic movements in both hands. Alter-
treatment with continuous positive airway pres- nating movements were mildly clumsy. Tone was
sure (CPAP) had been unsuccessful; there had slightly increased in the legs. The gait was on a
been difficulty in finding a mask that fit com- narrow base and was unsteady; the patient was
fortably. unable to walk with a tandem gait. The Rom-
In addition to the sleep and motor neurologic berg test showed truncal titubation.
syndrome described previously, the patient’s A sleep study to determine the appropriate
symptoms included snoring, difficulty with sleep positive airway pressure (PAP) therapy was per-
initiation, forgetfulness, poor judgment regard- formed. In CPAP mode, there was good control
ing his ability to safely complete physical tasks, of respiratory events. Electromyographic signals
urinary urgency and frequency, and night sweats. revealed elevated muscle tone during rapid-eye-
He had a history of type 2 diabetes mellitus, movement (REM) sleep, but there were no ab-
which was well controlled with insulin and had normal behaviors.
been complicated by mild, stable, length-depen- Two weeks later, during a follow-up visit in
dent sensory polyneuropathy; other history includ the neuromuscular clinic, the patient became
ed hyperlipidemia, a heterozygous factor V Leiden unresponsive to sternal rub; the vital signs and
mutation, depression, orthostatic hypotension, blood glucose level were normal. He was trans-
and gastroesophageal reflux disease. Medications ported to the emergency department, where he
included alprazolam, bupropion, fenofibrate, in- returned to a normal level of consciousness
sulin, melatonin, metformin, riluzole, sertraline, without intervention. Electroencephalography
and trazodone; there were no known drug aller- (EEG) revealed frequent intermittent diffuse
gies. The patient lived in New England with his polymorphic delta slowing of the background,
wife. He was a retired engineer. He drank two often with bifrontal predominance, but showed
alcoholic beverages per day. He did not smoke no epileptiform abnormalities. The patient was
tobacco or use illicit drugs. His mother had died fitted with a mask for CPAP, and treatment was
from an unknown cause at an elderly age; his initiated. Several weeks after the initiation of
father had died from trauma. One of his brothers treatment, download of CPAP data revealed good
had cerebrovascular disease, and another had effectiveness and adherence.
schizophrenia. However, episodes of unresponsiveness in-
On examination, the temperature was 36.6°C, creased in frequency and lasted up to 3 hours at
the blood pressure 112/60 mm Hg, the pulse 83 a time. During the episodes, the patient’s wife
beats per minute, the respiratory rate 18 breaths was unable to arouse him despite performing a
per minute, and the oxygen saturation 96% while sternal rub. Modafinil was prescribed, but the
the patient was breathing ambient air. The body- episodes did not abate. The patient was admitted
mass index (the weight in kilograms divided by to the epilepsy monitoring unit for long-term
the square of the height in meters) was 24.2. The monitoring and EEG. During the admission, two
patient was awake, alert, and oriented, although episodes of unresponsiveness occurred, during
his attention was somewhat diminished. He which the patient had a normal blood pressure,
could recall two words out of three. Naming and heart rate, and glucose level and EEG revealed
repetition were intact. The pupils were equally findings consistent with sleep.
reactive to light and accommodation. Extraocular A diagnostic test was performed.
movements were intact, and visual fields were
full. Facial sensation and strength were normal. Differ en t i a l Di agnosis
Speech was hypophonic and mildly slurred. Eleva-
tion of the palate was symmetric, and movement Dr. Aleksandar Videnovic: I evaluated this patient
of the tongue was normal. Shoulder shrug was when he was referred to the sleep clinic, and I
symmetric. Strength was 5/5 in all muscle groups. am aware of the final diagnosis in this case.

After I was asked to see this 67-year-old man Parasomnias

with progressive motor neuron disease, my ini- Parasomnias are divided into non-REM (NREM)
tial thoughts were centered around the detection and REM forms, depending on whether the be-
of sleep-disordered breathing on a home sleep- haviors emanate from NREM or REM sleep.2,3
apnea test, along with his previous diagnosis of Certain clinical characteristics can help to differ-
sleep apnea in the context of motor neuron dis- entiate between these two forms. For example,
ease and his history of unsuccessful treatment NREM parasomnias — such as sleepwalking,
with CPAP. sleep terrors, and confusional arousals — often
occur in younger patients, mainly happen during
Sleep-Disordered Breathing the first half of the night, and are associated
This patient’s symptoms of snoring, breathing with a lack of clear dream recall. During NREM
pauses during sleep, and daytime sleepiness are parasomnias, the patient is often difficult to
supportive of the diagnosis of sleep-disordered arouse, and the associated movements have a
breathing. The findings on an initial home sleep- rather normal appearance. In this patient, the
apnea test had led to the diagnosis of obstructive abnormal behaviors mainly happened during the
sleep apnea. The timely diagnosis and adequate second half of the night and were characterized
treatment of sleep-disordered breathing are very by vocalizations and movements that indicated
important for overall health and quality of life. emotions of fear and anger in the context of
The standard treatment is PAP, with CPAP being upsetting dreams. These episodes suggested that
used most frequently. However, patients with the patient was acting out his dreams, which is
neuromuscular disorders may have clinically sig- a hallmark feature of a REM parasomnia known
nificant hypoventilation at night, in addition to as REM sleep behavior disorder.
apnea or hypopnea, and may receive bilevel PAP
treatment.1 REM Sleep Behavior Disorder
Therefore, during the initial evaluation, my The loss of muscle atonia that accompanies nor-
first question was whether the unsuccessful treat- mal REM sleep is the neurophysiologic signature
ment with CPAP was related to coexisting cen- of REM sleep behavior disorder. Therefore, a sleep
tral sleep apnea that had not been detected on study is needed to establish the diagnosis; this
the initial home sleep-apnea test or to a need for was another reason to perform the sleep study
bilevel PAP, which would enable oxygenation in this patient.
overnight. I recommended that the patient un- It is important to emphasize that not every-
dergo a study in our sleep laboratory to deter- thing that looks and sounds like REM sleep be-
mine the appropriate treatment for his sleep- havior disorder is indeed that condition.4 The dif-
disordered breathing. The complete sleep study ferential diagnosis includes nightmares, seizures,
also allowed us to gather information about EEG psychogenic disorders, malingering, and sleep-
activity during sleep, sleep stages, arousals from disordered breathing. Nightmares are character-
sleep, muscle activity, and unusual behaviors ized by unpleasant dream imagery during REM
during sleep; a home sleep-apnea test cannot sleep. Dream recall is usually very detailed, sleep
provide such a detailed characterization of sleep. may not be interrupted, and vocal and motor
behaviors are absent. Seizures, specifically those
Abnormal Behaviors during Sleep originating from the frontal or temporal lobes,
The patient had additional sleep-related symp- can be differentiated from REM sleep behavior
toms, specifically difficulty with sleep initiation disorder on the basis of the presence of stereo-
and abnormal behaviors while asleep. Difficulty typic tonic and dystonic posturing. Video poly-
with sleep initiation may be due to sleep-onset somnography with an extended EEG montage
insomnia, which has many causes. The patient’s should be performed when epileptic seizures are
abnormal behaviors during sleep included vocal- suspected.
izations and movements, along with episodes of Psychogenic disorders occur on a background of
falling out of bed during sleep. These behaviors overnight wakefulness. Psychological testing may
are suggestive of parasomnias, a group of sleep be helpful in distinguishing these disorders from
disorders characterized by abnormal behaviors REM sleep behavior disorder. Malingering can
during sleep. manifest with a variety of unusual behaviors at

night. Video polysomnography is critical in docu- Because the episodes of unresponsiveness were
menting whether the events are occurring dur- increasing in frequency, the patient was admit-
ing wake time and in confirming the absence of ted to the neurology unit of this hospital for
characteristic findings of REM sleep behavior dis- long-term monitoring. During the admission, two
order. Complex behaviors that resemble events episodes occurred. Corresponding EEG monitor-
of REM sleep behavior disorder can occur during ing revealed findings consistent with sleep,
arousal caused by respiratory events in the context mostly stage 2 (N2) and stage 3 (N3) NREM
of sleep apnea. These pseudo-events of REM sleep sleep, without evidence of epileptiform activity.
behavior disorder resolve with the use of CPAP. In summary, this patient’s sleep–wake pheno-
The patient underwent a sleep study in CPAP type consisted of sleep-disordered breathing that
mode, and the sleep-disordered breathing abated. was responsive to CPAP treatment, behaviors of
He was subsequently fitted with a mask for REM sleep behavior disorder that were respon-
CPAP, and treatment was initiated. The sleep sive to melatonin treatment, and excessive sleep-
study also revealed increased muscle activity dur- iness with prolonged episodes of unresponsive-
ing REM sleep, a finding that confirms the diag- ness (sleep) that did not abate after modafinil
nosis of REM sleep behavior disorder. He was treatment.
treated with melatonin, one of a few medica-
tions used to treat this condition, which resulted Other Symptoms
in decreased dream enactment. As I learned more about the patient’s sleep–wake
phenotype, I tried to integrate his symptoms of
Excessive Sleepiness poor sleep and poor alertness with his other
The patient had fallen asleep while washing symptoms, specifically the motor neuron pheno-
dishes. He had several episodes of unresponsive- type (predominantly bulbar features with dysar-
ness, which were preceded by sleepiness. During thria and dysphagia), the autonomic dysfunc-
these episodes, his wife was unable to arouse tion, and the decline in balance. Sleep-disordered
him. He would eventually, sometimes after many breathing is commonly associated with motor
hours, wake up and be back to normal. There neuron disease, but REM sleep behavior disorder
was no mention of involuntary movements, in- and autonomic symptoms are not. In addition,
continence, or signs of cardiorespiratory distress his imbalance was unlikely to be related to his
during the episodes. motor neuron disease, given that he had normal
Despite treatment with CPAP, the patient con- strength in his arms and legs.
tinued to have excessive sleepiness. Because this
residual sleepiness could have been due to poor Neurodegenerative Disorders
adherence to CPAP or poor effectiveness of REM sleep behavior disorder has been linked to
CPAP, we checked his CPAP data, which were neurodegenerative disorders and is now recog-
satisfactory. For the residual sleepiness, he was nized as a prodromal stage of three evolving
treated with modafinil, but he did not have a synucleinopathies: Parkinson’s disease, demen-
clinically significant increase in alertness. tia with Lewy bodies, and multiple-system atro-
The differential diagnosis of these episodes phy.5 REM sleep behavior disorder is exceedingly
of unresponsiveness includes seizure disorder, rare in patients with other neurodegenerative
syncope, arrhythmia, a cerebrovascular event, disorders. The combination of this patient’s signs
and substance use. Seizures were unlikely to and symptoms did not fit well with any of the
explain these episodes because there was no mo- three neurodegenerative disorders associated with
tor activity and no confusion on arousal. Syncope REM sleep behavior disorder. Parkinsonism is a
would not be associated with prolonged unre- hallmark of these disorders and was not a fea-
sponsiveness. There was no history of findings ture of this patient’s presentation. Although bal-
suggestive of cardiac or cerebrovascular abnor- ance can be affected in any of these disorders, a
malities. Although sleepiness is the defining balance abnormality is unlikely to be present in
phenotype of narcolepsy, there were no other the early stages and to be rapidly progressive,
clinical features suggestive of narcolepsy, and except in patients with multiple-system atrophy
such prolonged episodes of unresponsiveness of the cerebellar type. Patients with this condi-
would be atypical. tion have an ataxic gait, which was not present

in this patient. Autonomic dysfunction is com- syndrome. Because the diagnosis of anti-IgLON5
mon in patients with multiple-system atrophy, disease is usually delayed, the symptoms are
but bulbar symptoms are not. Profound lapses in often quite prominent at the time of diagnosis.
consciousness from falling asleep are not char- Death occurs within 3 years after diagnosis in
acteristic of any of the three disorders. The ques- more than 50% of patients.
tion remained of whether we could fit the pa- Current knowledge about treatment effective-
tient’s sleep and alertness problems and other ness is limited. Most patients are treated with
neurologic manifestations into a unifying diag- immunotherapy including glucocorticoids, immu-
nosis. noglobulins, plasma exchange, rituximab, cyclo-
phosphamide, azathioprine, mycophenolate
Anti-IgLON5 Disease mofetil, or a combination of these therapies.10
As I considered this question, a disorder that had The reported response rate to immunotherapy
been described relatively recently came to mind: ranges from 10 to 70%. Combination therapy
anti-IgLON5 disease. This disorder is associated seems to be more effective than monotherapy.
with autoantibodies to IgLON5, a neural cell This patient had many of the typical sleep
adhesion molecule of unknown function.6 The symptoms reported in patients with anti-IgLON5
disorder affects men and women equally and disease, as well as a combination of neurologic
usually develops at 50 to 60 years of age. symptoms reported in patients with clinical
Anti-IgLON5 disease is characterized by a subtypes of the disease. To establish this diag-
distinctive sleep phenotype and a wide range of nosis, testing for IgLON5 autoantibodies was
associated neurologic symptoms. Sleep pheno- performed.
types of the disorder encompass poorly consoli-
dated sleep, NREM parasomnia with undifferen- Dr . A l ek s a nda r V idenov ic’s
tiated or poorly differentiated NREM sleep early Di agnosis
in the sleep episode with vocalizations and move-
ments, sleep-disordered breathing, REM sleep Anti-IgLON5 disease.
behavior disorder, and stridor.7 Daytime sleepi-
ness may be present. Other symptoms include Di agnos t ic Te s t ing
dysarthria, dysphagia, gait instability, chorea,
eye movement abnormalities, cognitive changes, Dr. Jenny J. Linnoila: Initially, serum paraneoplas-
fasciculations, and myoclonus. Several clinical tic antibody panel testing was performed in a
phenotypes of anti-IgLON5 disease have been neuroimmunology reference laboratory. The test-
recognized: a predominantly sleep-related disor- ing was negative; at that time, tests for IgLON5
der, a bulbar syndrome with or without chronic autoantibodies were not commercially available.
reinnervation changes in arm and leg muscles Since then, tests for IgLON5 autoantibodies
on electromyography, a progressive supranuclear have become commercially available. These tests
palsy–like syndrome, a cognitive syndrome, and have equal sensitivity when performed on serum
hyperexcitability with cramps, myoclonus, and and on cerebrospinal fluid (CSF).8 This is not the
fasciculations.7-9 case with tests for all neural autoantibodies. For
The clinical heterogeneity of anti-IgLON5 dis- example, testing for anti–N-methyl-d-aspartate
ease, the rarity of the disease, and the slow receptor antibodies, which are associated with
progression over a period of months or years are the most common form of autoimmune encepha-
factors that frequently contribute to a delay in litis, is more sensitive with CSF than with serum,11
diagnosis. The median time from symptom on- whereas testing for anti–leucine-rich, glioma-
set to diagnosis is 2.5 years. The clinical hetero- inactivated 1 antibodies, which are associated
geneity can also lead to misdiagnosis with one with the second most common form of autoim-
of several conditions, such as isolated sleep- mune encephalitis, is more sensitive with serum
disordered breathing, REM sleep behavior disor- than with CSF.12
der, motor neuron disease, myasthenia gravis, In general, when an autoimmune neurologic
progressive supranuclear palsy, multiple-system condition is suspected, good practice involves
atrophy, Huntington’s disease, or stiff-person testing of both serum and CSF with autoanti-

body panels. Conditions associated with differ- patient received a diagnosis of anti-IgLON5 IgG–
ent neural autoantibodies can have overlapping associated neurologic disorder, or anti-IgLON5
symptoms, especially early on; with the continu- disease.
ally broadening array of neural autoantibodies
included on panels, it is increasingly difficult to L a bor at or y Di agnosis
predict ahead of time which antibodies could be
detected. Also, it is important to note that many Anti-IgLON5 IgG–associated neurologic disorder.
newly identified neural autoantibodies, such as
IgLON5 autoantibodies, are not included on Fol l ow-up
paraneoplastic panels (which should therefore
be avoided), but they appear on newer autoim- Dr. Haatem M. Reda: After the diagnosis of anti-
mune panels, including panels of autoimmune IgLON5 disease was established, the patient was
encephalitis–associated antibodies. treated with intravenous methylprednisolone
In this patient, because there was a high (1000 mg daily) for 5 days. The patient’s illness
clinical suspicion for anti-IgLON5 disease, testing coincided with the beginning of the coronavirus
for IgLON5 autoantibodies was performed on a disease 2019 pandemic, which delayed further
research basis (given that commercial tests were treatment. He received intravenous immune
not available at the time), with the serum speci- globulin (2 g per kilogram of body weight
men from the initial paraneoplastic antibody monthly) for 2 months, until two induction infu-
panel testing. IgLON5 autoantibodies were first sions of intravenous rituximab (1000 mg 2 weeks
identified on a tissue-based indirect immuno- apart) could be arranged.13
fluorescence assay. In this assay, the patient’s Symptoms of REM sleep behavior disorder
serum sample was applied to a composite of and sleep-disordered breathing abated during
mouse brain, gut, and kidney tissue. Tissue- the first 4 months after treatment was initiated.
binding anti-IgLON5 IgG in the sample was vi- Approximately 1 month before the first mainte-
sualized with the use of a fluorescently labeled nance dose of rituximab, which had been
secondary antibody to human IgG. In the brain, planned for 6 months after the second induction
anti-IgLON5 IgG is known to bind to the cere- dose, was to be administered, the patient’s wife
bellum (to the granular layer more than the reported that the patient had worsening symp-
molecular layer), midbrain, and thalamus and toms of REM sleep behavior disorder. The inter-
binds less strongly to the hippocampus and cor- val between rituximab doses was shortened to
tex.8 It is important to assess the binding pattern 4 months, and the symptoms abated. Episodes
on gut and kidney tissue, as well, because anti- of excessive daytime sleepiness resolved after the
IgLON5 IgG also binds to intestinal smooth initiation of rituximab therapy.
muscle and renal glomeruli. For persistent gait unsteadiness, the patient
Although this tissue-binding pattern is highly has undergone physical therapy and still requires
suggestive of the presence of IgLON5 autoanti- either a walker or the assistance of at least one
bodies, the diagnosis of anti-IgLON5 disease person for stability. Despite precautions, how-
must be confirmed by testing the sample with a ever, he continues to fall approximately once per
cell-based assay specific for IgLON5. In this week at home. He continues to have cognitive
assay, the patient’s serum sample was applied impairment, with abnormalities on the recall
to human embryonic kidney 293 (HEK293) cells and orientation domains of the Montreal Cogni-
expressing the IgLON5 protein. Because IgLON5 tive Assessment screening tool (score, 22; range,
is a cell adhesion molecule, when it is trans- 0 to 30, with lower scores indicating greater
fected into HEK293 cells, it is expressed on the cognitive impairment). Oropharyngeal dysphagia
cell surface. Bound anti-IgLON5 IgG was visual- remains a substantial problem, for which the
ized with the use of a fluorescently labeled sec- patient requires ongoing use of a gastrostomy
ondary antibody to human IgG. Both the tissue- tube; he has had multiple hospitalizations for
based indirect immunofluorescence assay and recurrent complications of aspiration. He contin-
the cell-based assay of the patient’s serum sam- ues to have speech impairment and to undergo
ple were positive for anti-IgLON5 IgG, and the speech therapy. Limited knowledge about the

effects of immunotherapy in patients with anti- Fina l Di agnosis

IgLON5 disease prevents us from making con-
clusions regarding the selective effectiveness of Anti-IgLON5 IgG–associated neurologic disorder.
the treatment that this patient has received. Ir-
This case was presented at Neurology Grand Rounds.
reversible neurodegeneration embedded within Disclosure forms provided by the authors are available with
anti-IgLON5 disease may underlie this limited the full text of this article at NEJM.org.
response to immunotherapy.
References
1. Albdewi MA, Liistro G, El Tahry R. 6. Landa J, Gaig C, Plagumà J, et al. Ef- Estivill Torrús G, Serrano-Castro P. Re-
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with neuromuscular disease. Sleep Breath cytoskeleton: a link between autoimmu- disease: a systematic review. Acta Neurol
2018;22:277-86. nity and neurodegeneration. Ann Neurol Scand 2020;141:263-70.
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and other parasomnias. Clin Geriatr Med KA, et al. IgLON5 antibody: neurological Expanded phenotypes and outcomes
2021;37:483-90. accompaniments and outcomes in 20 pa- among 256 LGI1/CASPR2-IgG-positive pa-
4. Antelmi E, Lippolis M, Biscarini F, tients. Neurol Neuroimmunol Neuroin- tients. Ann Neurol 2017;82:79-92.
Tinazzi M, Plazzi G. REM sleep behavior flamm 2017;4(5):e385. 13. Abboud H, Probasco JC, Irani S, et al.
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The n e w e ng l a n d j o u r na l of m e dic i n e

Case Records of the Massachusetts General Hospital

Founded by Richard C. Cabot

Case 1-2022: A 67-Year-Old Man with Motor

Pr e sen tat ion of C a se

n engl j med 386;2 nejm.org January 13, 2022 173

Figure 1. MRI of the Head.

174 n engl j med 386;2 nejm.org January 13, 2022

The New England Journal of Medicine

n engl j med 386;2 nejm.org January 13, 2022 175

After I was asked to see this 67-year-old man Parasomnias

176 n engl j med 386;2 nejm.org January 13, 2022

The New England Journal of Medicine

n engl j med 386;2 nejm.org January 13, 2022 177

178 n engl j med 386;2 nejm.org January 13, 2022

The New England Journal of Medicine

n engl j med 386;2 nejm.org January 13, 2022 179

effects of immunotherapy in patients with anti- Fina l Di agnosis

180 n engl j med 386;2 nejm.org January 13, 2022

The New England Journal of Medicine

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