A Rare Case of Abdominal Myorhythmia in Anti‐ IgLON 5 Disease

Anti-IgLON5 disease, identified in 2014,1 is a distinct autoimmune disorder targeting the neuronal cell-adhesion molecule IgLON5, essential for synaptogenesis and neuronal maturation.2 It is characterized by relentless progression, profound disability, and therapeutic resistance.3 Its expanding phenotype encompasses progressive supranuclear palsy-like features, gait instability, movement disorders, bulbar and oculomotor deficits, cognitive impairment, and Amyotrophic lateral sclerosis (ALS) mimics.4-6 Herein, we describe a rare case presenting with prominent tongue and abdominal myorhythmia. A 73-year-old man presented with a 3-month history of excessive daytime sleepiness and disrupted sleep–wake cycles, followed by 2 months of involuntary abdominal and tongue movements, and 1 month of rapid cognitive decline. He exhibited rhythmic movements affecting the tongue and abdomen (worsened by recumbency, relieved by sitting), along with action tremor in upper limbs, infrequent hiccups, and snoring. Symptoms began with misplacing objects and repetitive questioning, followed by loss of interest in previously pleasurable activities such as watching television and reading newspapers. Relatives noted difficulty recalling names and recent conversations. Over time, he became socially withdrawn, mute, and required prompting for activities of daily living. By admission, he was bedridden and had bladder and bowel incontinence, yet moved all limbs spontaneously and obeyed simple commands. No seizures, hallucinations, disinhibition, or autonomic features were noted. The neurological examination revealed prominent frontal lobe dysfunction with severe impairment of speech initiation and expressive language, resulting in absent spontaneous verbal output. Receptive language was relatively preserved, as evidenced by correct execution of single-step commands. Executive dysfunction was noted on bedside frontal lobe testing, with impaired motor sequencing and reduced inhibitory control. Visuoconstructive abilities were largely preserved, with intact copying of simple figures. Formal cognitive screening using standard tests was not considered valid due to profound expressive language deficits and inattention. He had supranuclear vertical gaze palsy with slow saccades, axial-appendicular rigidity, and rhythmic, low-frequency (1–4 Hz) myorhythmia affecting the tongue and abdomen (Video 1). Localization implicated the hypothalamus, brainstem, basal ganglia, and frontal subcortical circuits. MRI of the brain and spine with contrast was normal. CSF showed mild pleocytosis (2 lymphocytes/100 cells), elevated protein (72 mg/dL), normal glucose (101 mg/dL), negative malignant cytology, IgG index, and oligoclonal bands. EEG displayed generalized delta activity without periodic complexes. Serum onconeural antibodies (Ma2, Tr, CV2/CRMP5, Hu, Yo, Zic4, Amphiphysin) and tumor markers (serum alpha-fetoprotein, prostate specific antigen, Carcinoembryonic Antigen, Lactate Dehydrogenase, Carbohydrate Antigen 19–9 and Beta Human Chorionic Gonadotropin) were negative; CT thorax/ abdomen and testicular ultrasound did not show any neoplasms. Serum and CSF Autoimmune panel (NMDAR, GABA, LGI-1, CASPR-2, AMPA, mGluR5, GAD) was negative. Serum (1:10 dilution) and CSF (undiluted) IgLON5 antibodies were strongly positive via cell-based assay (Euroimmun, Lubeck, Germany) (Fig. 1A,B), with HLA-DRB110:01 and HLA-DQB105:01 positivity confirming the diagnosis of anti-IgLON5 disease. He received IV methylprednisolone (1 g for 5 days), IVIG (2 g/kg over 5 days), and Rituximab (1 g × 2, 15 days apart), yielding minimal improvement only. At discharge, the patient was more alert with improved reaction time compared to baseline. However, there was no significant improvement in cognitive status or the involuntary movements. Although cranioskeletal myorhythmia has been reported in IgLON5-related disorders, this case expands its spectrum by featuring rare abdominal myorhythmia, which has seldom been previously described.7 Myorhythmia is defined as rhythmic, repetitive, slow (1–4 Hz) movements predominantly affecting cranial and limb muscles, typically arising from autoimmune, infectious, or vascular lesions in brainstem or diencephalic structures, with presumed subcortical-supraspinal origin. Limb involvement often appears oscillatory and jerky. Oculo-masticatory-myorhythmia—classically linked to Whipple's disease features slow, repetitive, often asymmetric facial and ocular motions.8 Notably, ocular muscles are spared in IgLON5 antibody-related cranial myorhythmia. When involving multiple body regions, movements may be synchronous (implying a shared pacemaker) or asynchronous (suggesting distinct supraspinal pacemakers). Points favoring abdominal myorhythmia over myoclonus in our patient include the slow, rhythmic nature, occurring at nearly the same frequency as tongue movements, with frequent synchronization. Beyond cranial muscles and limbs, myorhythmia can occur in the axial musculature, as evidenced by a steroid-responsive case in the right pectoralis muscle associated with anti-Tr antibody disease.9 Anti-IgLON5 disease is mediated predominantly by IgG4 antibodies and less commonly by IgG1 subclasses. This patient received Rituximab due to its efficacy in targeting pathogenic IgG4 production; however, the response was suboptimal.10 Sustained responses to immunotherapy in anti-IgLON5 disease remain rare, reported in only a few cases, particularly those receiving early and aggressive treatment, further underscoring the critical need for prompt identification of this syndrome.3 (1) Research project: A. Conception, B. Organization, C. Execution; (2) Data Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the first draft B. Review and Critique. A.V.: 1A, 1B, 1C, 2A, 2B, 2C, 3A. D.K.P: 1A, 1B, 3B. S.S.: 1A, 1B, 3B. D.N.: 2B, 2C. S.K.: 1A, 1B, 1C, 2A, 3B. The Authors are grateful to Miss Gayathri M S's contributions to editing the patient's video. Ethical Compliance Statement: Written informed consent was taken from the patient. The authors confirm that the approval of the institutional review board was not required for this work. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Funding Sources and Conflicts of Interest: No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work. Financial Disclosures for Previous 12 Months: The authors declare that there are no additional disclosures to report. Author disclosures are available in the Supporting Information. The data that support the findings of this study are available from the corresponding author upon reasonable request. Data S1. COI merged. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.