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HOME > J Mov Disord > Volume 18(4); 2025 > Article
Letter to the editor
 Anti-IgLON5-Related Movement Disorders: A Series of Three Cases from a Tertiary Centre in India
Shivani Rathorcid, Puthiyarambath Arjun Chandrashekarorcid, Aravind Gunasekaranorcid, Vikram Venkappayya Hollaorcid, Nitish Kambleorcid, Pramod Kumar Palorcid, Ravi Yadavcorresp_iconorcid
Journal of Movement Disorders 2025;18(4):385-388.
DOI: https://doi.org/10.14802/jmd.25121
Published online: August 11, 2025

Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India

Corresponding author: Ravi Yadav, MD, DM Department of Neurology, National Institute of Mental Health and Neurosciences, Hosur Road, Bengaluru 560029, Karnataka, India / Tel: +91-80-26995149 / E-mail: docravi20@yahoo.com
• Received: May 3, 2025   • Revised: July 29, 2025   • Accepted: August 11, 2025

Copyright © 2025 The Korean Movement Disorder Society

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Dear Editor,
Anti-immunoglobulin-like cell adhesion molecule-5 (IgLON5) disease is an autoimmune disorder in which antibodies target the IgLON5 cell adhesion molecule and affect the nervous system [1]. This disease presents a broad clinical spectrum and complex pathogenesis involving autoimmune antibodies and neurodegeneration. Unlike damage caused by other autoimmune encephalitis-related antibodies, IgLON5 antibody-induced neuronal damage is irreversible, suggesting a link between autoimmunity and neurodegeneration [1,2].
The clinical features of anti-IgLON5 disease span the neurological spectrum, ranging from cognitive issues to movement disorders, sleep abnormalities, and neuromuscular symptoms [1]. Sleep issues involve parasomnias and sleep-disordered breathing, such as stridor and apnea [3]. Movement disorders include parkinsonism, chorea, dystonia, myoclonus, ataxia, and myorhythmia [1,4]. Cognitive dysfunctions include executive dysfunction, attention impairment, and memory issues. Neuromuscular symptoms include tongue and peripheral muscle fasciculations, bulbar palsy, limb weakness, and muscle atrophy [1]. The overall presentation may mimic atypical parkinsonism and/or motor neuron disease presentations, complicating prompt diagnosis.
We report the cases of three patients with anti-IgLON5 disease presenting with complex movement disorders, sleep issues, and myoclonus (Table 1).
Patient 1 was a 70-year-old man with hypertension and type 2 diabetes who presented with a 20-month history of speech and swallowing difficulties, followed by abnormal gait, slowness in activities, excessive daytime sleepiness, memory impairment and behavioral disturbances in the form of irritability and outbursts of anger. Over time, involuntary movements in sleep, sleep apnea, and stridor were also noted. Later, autonomic dysfunctions such as postural dizziness, constipation, urinary urgency, and incontinence appeared. Examination (Supplementary Video 1 in the online-only Data Supplement) revealed excessive sleepiness during conversations, impaired cognition, and spastic-ataxic dysarthria. The patient had hypometric saccades, mild upgaze restriction, reduced facial expression, decreased palatal movements, lower limb hypotonia, mild weakness, tongue and shoulder fasciculations, and brisk deep tendon reflexes. In addition, he had asterixis, stimulation-sensitive myoclonus in the fingers, knee-heel-shin test impairment, and generalized bradykinesia. He could walk with the support of another person. He had normal routine blood results, cerebrospinal fluid (CSF) pleocytosis (22 cells/μL, 50% lymphocytes), and normal CSF protein and sugar levels. The results of magnetic resonance imaging (MRI) of the brain and fluorodeoxyglucose positron emission tomography (FDG-PET) of the whole body were also normal. The serum antinuclear antibody profile, antineutrophil cytoplasmic antibody and paraneoplastic (anti-Hu, anti-Ri, anti-Yo, anti-Tr, anti-CV2/CRMP5, anti-Ma2, anti-Amphiphysin, anti-SOX1, anti-Zic4, anti-Titin, anti-Recoverin, anti-DPPX, and anti-GAD65) panels and serum CSF autoimmune (anti-NMDA, anti-CASPR-2, anti-LGI-1, anti-GABABR, and anti-AMPA1/2) test results were negative. His serum and CSF anti-IgLON5 antibody test results were strongly positive. The patient received 30 g/day of intravenous immunoglobulin (IV-IG) along with 1 g/day of intravenous methyl prednisolone (IV-MP) over 5 days, followed by two doses of 1 g of intravenous rituximab (IV-RTx) 5 days apart, which led to mild improvement at the time of discharge. At the 3-month follow-up, sleep symptoms, memory, and gait improved moderately.
Patient 2 was a 58-year-old man with hypertension who presented with a 1-year history of illness involving urinary frequency, urgency, and incontinence, sleep disturbances, jerky abdominal movements, and slowness in activities. Jerky movements occurred mostly when the patient lay supine and decreased when he was sitting, prompting him to sleep upright. There were no other relevant symptoms. Examination (Table 1) revealed pedal edema, normal cognition, mild upgaze restriction, truncal predominant generalized synchronous, rhythmic myoclonus, which was more apparent in the supine position and extended from the neck to the abdominal muscles, along with anterocollis, camptocormia, mild rigidity, and bradykinesia (Supplementary Video 2 in the online-only Data Supplement). Routine tests and serological markers were normal. MRI of the brain revealed mild cerebral atrophy and cervical disc changes. CSF analysis was normal, and serum and CSF anti-IgLON5 antibody test results were strongly positive. The whole-body FDG-PET MRI result was normal. The patient received five alternate-day cycles of large-volume plasmapheresis (LVPP) along with 1 g/day of IV-MP for 5 days, followed by two doses of 1 g IV-RTx 15 days apart. The patient had moderate improvement at the 3-month follow-up and had recovered completely at the 6-month follow-up.
Patient 3 was a 48-year-old man with diabetes who presented with a 1-year history of swallowing difficulty, neck pain, sleep disturbances, and slowness in daily activities. Dysphagia had progressed from solids to liquids. Occipital burning pain caused fragmented sleep, frequent awakenings, and a reduced sleep duration of 3–4 hours/night without dream enactment. There were no other relevant symptoms. Examinations revealed normal cognition, hypokinetic speech, mild upgaze restriction, saccadic intrusions, tongue/lip tremors, mild rigidity, and bradykinesia. The patient had rhythmic, synchronous, slow myoclonic jerks involving the tongue, uvula, palate, and throat (Supplementary Video 3 in the online-only Data Supplement). Routine blood test and CSF analysis results were normal. His serum and CSF anti-IgLON5 and anti-GABABR antibody test results were strongly positive. However, no anti-GABABR-related symptoms were present. MRI of the brain, contrast-enhanced chest and abdominal computerized tomography, and whole-body PET scans were normal. The patient was started on five alternate-day cycles of LVPP along with 1 g/day IV-MP for 5 days. However, the patient developed an anaphylactic reaction to fresh-frozen plasma post-LVPP; hence, the treatment was stopped after two cycles. After the completion of 5 days of IV-MP, the patient received two doses of 1 g of IV-RTx 15 days apart. The patient experienced a 50% improvement in sleep and swallowing symptoms at the 3-month follow-up and an approximately 90% improvement at the 6-month follow-up. However, myoclonus still persisted on examination.
All three patients involved subacute onset progressive complex movement disorders with both hypokinetic and hyperkinetic phenomenologies and other neurological findings. All patients had mild axial predominance, symmetrical mild parkinsonism, sleep disturbances, and myoclonus. In addition, cognitive impairment (patient 1), neuromuscular involvement (patient 1), bulbar symptoms (patient 1 and patient 2), and autonomic dysfunction (patient 1 and patient 2) occurred. Myoclonus/jerky movements were noted in all three patients. However, patient 1 had distal arrhythmic myoclonic jerks in the hands, which were stimulus sensitive, along with negative myoclonus/asterixis, suggesting cortical localization. In contrast, patients 2 and 3 had predominantly axial (truncal in patient 2 and craniobulbar in patient 3), rhythmic, and synchronous jerks, which were also slower than those of patient 1 and more akin to myorhythmia than myoclonus. Craniofacial/abdominal myorhythmia is being increasingly recognized and, in a given clinical setting, should raise suspicion of anti-IgLON5 disease [1,4]. However, myoclonus and asterixis/negative myoclonus are not frequently reported. Pierro et al [5]. reported a patient with anti-IgLON5 disease who had slow, rhythmic, left periorbital–perioral–lingual–palatal myorhythmia along with bilateral upper limb negative myoclonus. Jeyakumar et al [6]. reported the only case of anti-IgLON5 disease with bilateral postural and orthostatic myoclonus of the legs.
Another interesting observation was the dual antibody positivity seen in patient 3, which has been reported in the literature, but the anti-GABABR antibody was seen only in serum in the previously reported case [7]. Despite the presence of anti-GABABR antibodies in both the serum and CSF in our patient, there were no symptoms pertaining to the antibody, and the malignancy screen result was also negative. In light of these findings, the contribution of anti-GABABR antibodies to the clinical features of patient 3 is uncertain. Anti-GABABR antibody encephalitis accounts for 5% of autoimmune encephalitis cases, is often tumor-associated, and almost always presents as seizures, cognitive impairment, and/or personality changes.
Owing to the atypical parkinsonism and motor neuron disease-like presentation, anti-IgLON5 disease should be considered in the differential diagnosis of Parkinson-plus syndrome and amyotrophic lateral sclerosis, especially when sleep disturbance is present [1,3]. Sleep symptoms are frequent and include insomnia, reduced nocturnal sleep, excessive daytime sleepiness, poor sleep efficiency, parasomnias in both rapid eye movement (REM) and non-REM (NREM), undifferentiated NREM sleep, stridor or snoring with obstructive sleep apnea and central hypoventilation.
The disease progresses chronically in more than 70% of patients, with fewer than 40% of patients responding to immunotherapy [2]. There is a genetic predisposition, with the HLA-DRB110:01 and HLA-DQB105:01 alleles increasing the risk and modifying the clinical presentation [1,4]. All our patients received immunotherapy in the form of IV-IG (patient 1) or LVPP (patients 2 and 3) with IV-MP (all patients), followed by long-term immunomodulation in the form of IV-RTx (all 3 patients). Improvement was noted in all patients but to a variable extent.
This report emphasizes the complex neurological presentation of anti-IgLON5 disease and the treatable nature of the disease with prompt management. However, the short follow-up, lack of objective scale-based assessments at follow-up, and case-based reporting could not rule out the possibility of subjective transient improvement and the possibility of spontaneous improvement in these patients. Additionally, polysomnographic evaluation was not performed for these patients and should be considered to better characterize and manage the heterogeneous sleep symptoms observed in patients with anti-IgLON5 disease.
The online-only Data Supplement is available with this article at https://doi.org/10.14802/jmd.25121.
Video 1.
Video of patient 1 demonstrates spastic-ataxic dysarthria, excessive sleepiness, mild up-gaze restriction, stimulus-sensitive myoclonus, asterixis, mild parkinsonism, postural instability, and finalistic movements. In addition (not shown in the video), the patient had cognitive impairment, hypometric saccades, tongue and shoulder fasciculation, lower limb hypotonia, mild weakness and brisk deep tendon reflexes, and an impaired knee-heelshin test.
Video 2.
Video of patient 2 demonstrates axial rhythmic myoclonus involving predominantly trunk, abdominal, and neck muscles, antecollis, mild bradykinesia, slow gait with forward bending, and no postural instability. In addition (not shown in the video), the patient had hypophonic speech, mild up-gaze restriction, and mild pedal oedema. The video also demonstrates mild improvement in the severity of the jerks at the time of discharge after completing the immunomodulation therapy.
Video 3.
Video of patient 3 demonstrates dysarthria, oro-lingual-palatal rhythmic myoclonus or myorhythmia, and electrophysiological evidence of the rhythmic myoclonus/myorhythmia. In addition (not shown in the video), the patient had hypophonic speech, mild up-gaze restriction, saccadic intrusions, and mild parkinsonism.

Ethics Statement

Institute Ethics Committee approval waiver was obtained for this publication (NIMHANS/13/53rd IEC [BS & NS DIV.]/2025) and informed consent was obtained from the patients for video recording and publishing.

Conflicts of Interest

The authors have no financial conflicts of interest.

Funding Statement

None

Acknowledgments

None

Author Contributions

Conceptualization: Shivani Rath, Puthiyarambath Arjun Chandrashekar, Vikram Venkappayya Holla, Ravi Yadav. Data curation: Shivani Rath, Puthiyarambath Arjun Chandrashekar, Aravind Gunasekaran. Formal analysis: Shivani Rath, Puthiyarambath Arjun Chandrashekar. Investigation: all authors. Methodology: all authors. Resources: Shivani Rath, Puthiyarambath Arjun Chandrashekar, Aravind Gunasekaran, Vikram Venkappayya Holla, Ravi Yadav. Supervision: Ravi Yadav. Validation: Nitish Kamble, Pramod Kumar Pal, Ravi Yadav. Visualization: Ravi Yadav. Writing—original draft: Shivani Rath. Writing—review & editing: Puthiyarambath Arjun Chandrashekar, Aravind Gunasekaran, Vikram Venkappayya Holla, Nitish Kamble, Pramod Kumar Pal, Ravi Yadav.

Table 1.
Summary of the clinical features of anti-IgLON5 cases in our cohort
Variables Patient 1 Patient 2 Patient 3
Age/gender/duration 70 years/male/20 months 58 years/male/12 months 48 years/male/12 months
Presenting symptoms Speech and swallowing difficulty, walking difficulty, excessive sleepiness, memory and behavioural disturbance, slowness in daily activities, abnormal movements in sleep, sleep apnoea, stridor, and autonomic dysfunction Urinary disturbance, jerky abdominal movements, slowness of activities of daily living, and excessive sleepiness Swallowing difficulty, fragmented and reduced night sleep, and slowness of activities of daily living
Cognitive dysfunction MMSE: 22/30 MMSE: 27/30 MMSE: 28/30
ACE-III: 77/100
EOM abnormality Hypometric saccades, mild up-gaze restriction Mild up-gaze restriction Mild up-gaze restriction, saccadic intrusions
Dysphagia To liquid and later solid Absent To solid only
Speech disturbances Spastic ataxic Hypokinetic speech Hypokinetic speech
Movement disorders Mild parkinsonism, stimulus-sensitive myoclonus, asterixis, impaired kneeheel-shin test Parkinsonism, axial predominant, generalized synchronous, slow, rhythmic myoclonus, antecollis, stooped posture Mild parkinsonism, synchronous, slow, rhythmic, oral, lingual, and palatal myoclonus
Neuromuscular involvement Fasciculations in the tongue and shoulder regions; hypotonia and proximal weakness in lower limbs with brisk deep tendon reflexes Occasional fasciculations in the shoulder region None
Autonomic dysfunction Orthostatic hypotension, constipation, urinary disturbances Urinary disturbance None
Sleep disturbances Lack of nocturnal sleep, excessive daytime sleepiness, sleep apnoea, stridor, and involuntary movements in sleep Lack of nocturnal sleep, daytime sleepiness, sleep talking, OSA, and sleeping in the sitting position Fragmented and decreased nocturnal sleep, frequent awakenings
Others Gnawing pain in the low back None Burning pain in the occipital area
Serum and CSF anti-IgLON5 antibody Strongly positive Strongly positive Strongly positive
Treatment
 LVPP - + + (2 cycles)
 Pulse steroids + + +
 IV-IG + - -
 Rituximab + + +
 Improvement At 3-month follow-up, sleep symptoms, memory, and gait showed moderate improvement The patient had moderate improvement at 3-month follow-up and had recovered completely at 6-month follow-up The patient had around 90% improvement at the 6-month follow-up. However, myoclonus was still persisting on examination

MMSE, Mini-Mental Status Examination; ACE-III, Addenbrooke’s Cognitive Examination-III; EOM, extra-ocular movements; OSA, obstructive sleep apnoea; CSF, cerebrospinal fluid; IgLON5, immunoglobulin-like cell adhesion molecule-5; LVPP, large volume plasmapheresis; IV-IG, intravenous immunoglobulin.

  • 1. Graus F, Sabater L, Gaig C, Gelpi E, Iranzo A, Dalmau JO, et al. Anti- IgLON5 disease 10 years later: what we know and what we do not know. Neurol Neuroimmunol Neuroinflamm 2025;12:e200353.PubMed
  • 2. Grüter T, Möllers FE, Tietz A, Dargvainiene J, Melzer N, Heidbreder A, et al. Clinical, serological and genetic predictors of response to immunotherapy in anti-IgLON5 disease. Brain 2023;146:600–611.PubMed
  • 3. Gaig C, Iranzo A, Cajochen C, Vilaseca I, Embid C, Dalmau J, et al. Characterization of the sleep disorder of anti-IgLON5 disease. Sleep 2019;42:zsz133.ArticlePubMedPDF
  • 4. Gaig C, Compta Y, Heidbreder A, Marti MJ, Titulaer MJ, Crijnen Y, et al. Frequency and characterization of movement disorders in anti-IgLON5 disease. Neurology 2021;97:e1367–e1381.PubMedPMC
  • 5. Pierro S, Verde F, Maranzano A, De Gobbi A, Colombo E, Doretti A, et al. Further insights into anti-IgLON5 disease: a case with complex clinical presentation. BMC Neurol 2024;24:334.ArticlePubMedPMCPDF
  • 6. Jeyakumar N, Garcia MC, Qiu J, Kim S, Mahant N, Morales-Briceño H. Clinical and neurophysiological features of orthostatic myoclonus in a patient with IgLON5-disease: a novel presentation. Mov Disord Clin Pract 2023;10:1687–1690.PubMedPMC
  • 7. Chung HY, Wickel J, Voss A, Ceanga M, Sell J, Witte OW, et al. Autoimmune encephalitis with anti-IgLON5 and anti-GABAB-receptor antibodies: A case report. Medicine (Baltimore) 2019;98:e15706.PubMedPMC

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    Citations

    Citations to this article as recorded by  
    • A Rare Case of Abdominal Myorhythmia in Anti‐IgLON 5 Disease
      Asish Vijayaraghavan, Divya Kalikavil Puthenveedu, Soumya Sundaram, Deepti Narasimhaiah, Syam Krishnan, Sajith Sukumaran
      Movement Disorders Clinical Practice.2026;[Epub]     CrossRef

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    Anti-IgLON5-Related Movement Disorders: A Series of Three Cases from a Tertiary Centre in India
    Anti-IgLON5-Related Movement Disorders: A Series of Three Cases from a Tertiary Centre in India
    Variables Patient 1 Patient 2 Patient 3
    Age/gender/duration 70 years/male/20 months 58 years/male/12 months 48 years/male/12 months
    Presenting symptoms Speech and swallowing difficulty, walking difficulty, excessive sleepiness, memory and behavioural disturbance, slowness in daily activities, abnormal movements in sleep, sleep apnoea, stridor, and autonomic dysfunction Urinary disturbance, jerky abdominal movements, slowness of activities of daily living, and excessive sleepiness Swallowing difficulty, fragmented and reduced night sleep, and slowness of activities of daily living
    Cognitive dysfunction MMSE: 22/30 MMSE: 27/30 MMSE: 28/30
    ACE-III: 77/100
    EOM abnormality Hypometric saccades, mild up-gaze restriction Mild up-gaze restriction Mild up-gaze restriction, saccadic intrusions
    Dysphagia To liquid and later solid Absent To solid only
    Speech disturbances Spastic ataxic Hypokinetic speech Hypokinetic speech
    Movement disorders Mild parkinsonism, stimulus-sensitive myoclonus, asterixis, impaired kneeheel-shin test Parkinsonism, axial predominant, generalized synchronous, slow, rhythmic myoclonus, antecollis, stooped posture Mild parkinsonism, synchronous, slow, rhythmic, oral, lingual, and palatal myoclonus
    Neuromuscular involvement Fasciculations in the tongue and shoulder regions; hypotonia and proximal weakness in lower limbs with brisk deep tendon reflexes Occasional fasciculations in the shoulder region None
    Autonomic dysfunction Orthostatic hypotension, constipation, urinary disturbances Urinary disturbance None
    Sleep disturbances Lack of nocturnal sleep, excessive daytime sleepiness, sleep apnoea, stridor, and involuntary movements in sleep Lack of nocturnal sleep, daytime sleepiness, sleep talking, OSA, and sleeping in the sitting position Fragmented and decreased nocturnal sleep, frequent awakenings
    Others Gnawing pain in the low back None Burning pain in the occipital area
    Serum and CSF anti-IgLON5 antibody Strongly positive Strongly positive Strongly positive
    Treatment
     LVPP - + + (2 cycles)
     Pulse steroids + + +
     IV-IG + - -
     Rituximab + + +
     Improvement At 3-month follow-up, sleep symptoms, memory, and gait showed moderate improvement The patient had moderate improvement at 3-month follow-up and had recovered completely at 6-month follow-up The patient had around 90% improvement at the 6-month follow-up. However, myoclonus was still persisting on examination
    Table 1. Summary of the clinical features of anti-IgLON5 cases in our cohort

    MMSE, Mini-Mental Status Examination; ACE-III, Addenbrooke’s Cognitive Examination-III; EOM, extra-ocular movements; OSA, obstructive sleep apnoea; CSF, cerebrospinal fluid; IgLON5, immunoglobulin-like cell adhesion molecule-5; LVPP, large volume plasmapheresis; IV-IG, intravenous immunoglobulin.

    Table 1.

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