自己免疫性運動異常症の症候学

Phenomenology of Autoimmune Movement Disorders Recognizing Treatable Disorders Through Movement Phenomenology Takayoshi Shimohata, MD, PhD, FAAN Department of Neurology Gifu University Graduate School of Medicine, Japan COI; I have nothing to disclose.

Why Does Phenomenology Still Matter? • Autoimmune movement disorders are treatable. • However, antibody results take time. Patients cannot wait. • Phenomenology can guide early diagnosis and treatment.

Three Questions at the Bedside Whenever I encounter an unusual movement, I try to avoid making an immediate diagnosis. Instead, I ask myself three simple questions.

When Should We Suspect an Autoimmune Movement Disorder? Acute or subacute onset Rapid progression Mixed movement phenomenology Seizures Encephalopathy Dysautonomia The more red flags present, the stronger the suspicion.

What Do You See? Lancet. 2014;383(9933):2018 • It is extremely brief (usually <3 s), stereotyped, frequent, and unilateral. • Dystonic posturing of the face and arm Phenomenology: faciobrachial dystonic seizures (FBDS) Diagnosis: LGI1 antibodyassociated encephalitis

FBDS is not always restricted to one side. Mov Disord Clin Pract. 2020; 7: 228–9. Patient 1. Unilateral 2. Bilateral The attacks may alternate between sides. In addition, this patient had mildly impaired awareness.

FBDS may also involve the leg: Facio-brachio-crural dystonic seizures. The attack occurred when he tried to stand up. This can cause sudden falls, so fall prevention is important. Neurol Clin Pract. 2024;14(3):e200301. Lancet. 2026;407(10542):1968-83

What Do You See? Lancet. 2026;407:1968-83 There are continuous, variable orofacial and limb dyskinesias. Phenomenology: Orofacial and limb dyskinesias Diagnosis: Anti-NMDAR encephalitis

What Do You See? Mov Disord. 2013;28:543-7. repetitive and stereotyped movement of the left upper limb. Phenomenology: Stereotypy Diagnosis: Anti-NMDAR encephalitis

Stereotypies can aid in the diagnosis of anti-NMDAR encephalitis. Mov Disord. 2014;29:1539-42. • Vigorous stereotyped movements involve the upper limbs, trunk, and lower limbs. • Complex mixed hyperkinetic movements are common in anti-NMDAR encephalitis.

What Do You See? Mov Disord. 2014;29:1539-42. • The right arm remains in a sustained posture. Phenomenology: Tonic perseveration It is another characteristic movement in anti-NMDAR encephalitis.

What Do You See? Case Rep Neurol 2022;14:494–500 • This patient has a rhythmic “yes–yes” head movement. Phenomenology: Head titubation and cerebellar ataxia Diagnosis: mGluR1 antibodyassociated cerebellitis

The patient improved markedly after immunotherapy (IVIg). Case Rep Neurol 2022;14:494–500 This illustrates the importance of early recognition and treatment.

Head titubation in mGluR1 antibody-associated cerebellitis Neurology. 2018;90(16):746-747 Following apathy and catatonia, the patient developed head titubation that persisted for more than one month. Severe ataxia emerged several weeks later.

Head titubation may occur with other antibodies. • 27-year-old woman • Headache, gait disturbance, and limb tremor • Seizures and mild cognitive impairment • This patient had GluK2 antibody-associated encephalitis with cerebellar ataxia and limbic encephalitis. Ann Neurol. 2023;93:635-636

Cerebellar Microglial Activation on 18F-DPA-714 PET/MRI in GluK2 Antibody-Associated Encephalitis Ann Neurol. 2023;93:635-636 • Imagings showed limbic abnormalities and cerebellar microglial activation. • These findings were consistent with the clinical manifestations.

What Do You See? Mov Disord Clin Pract. 2021;8:1260-2 • There are rhythmic, continuous abdominal movements. • The movement resembled belly dancing, raising the possibility of diaphragmatic involvement. Phenomenology: Abdominal segmental myoclonus Diagnosis: CASPR2 antibody-associated encephalomyelitis

Differential Diagnosis of Abdominal Segmental Myoclonus • Trauma, including surgery • Drug (e.g., salbutamol, levodopa, and galantamine) • Neurodegenerative diseases (e.g., PSP) • Functional neurological disorders • Autoimmune encephalitis Consider CASPR2 antibody testing, particularly in patients with coexisting other autoimmune diseases or thymoma.

What Do You See? Neurology. 2021;97(14):e1367-e1381. • Slow, rhythmic tongue movements at a frequency of 1–4 Hz • These movements were continuous at rest and persistent during wakefulness Phenomenology: Lingual myorhythmia Diagnosis: IgLON5 disease

Synchronous Lingual and Abdominal Myorhythmia associated with IgLON5 Disease has been reported. Mov Disord Clin Pract. 2026 https://doi.org/10.1002/mdc3.70594 The movements occurred at a frequency of 1-4 Hz and became more prominent in the supine position.

• https://doi.org/10.1002/mdc3.70594

Myorhythmia may also occur in CASPR2 antibody-associated encephalitis Mov Disord Clin Pract. 2025;12:2004-6. This patient had rhythmic movements of the soft palate and tongue, together with cerebellar ataxia.

Differential Diagnosis of Myorhythmia Mov Disord Clin Pract. 2025;12:2004-6. • Autoimmune encephalitis • Anti-NMDAR encephalitis • IgLON5 disease • CASPR2 antibody-associated encephalitis • Tr/DNER antibody-associated encephalitis • Whipple disease • Stroke involving the Guillain–Mollaret triangle • Celiac disease • Drug-induced myorhythmia Therefore, think autoimmune, but keep these alternatives in mind.

Mov Disord Clin Pract. 2022;10(1):135-7. What Do You See? • The patient exhibited repetitive head drops and trunk flexion. • Associated features included insomnia, visual hallucinations, memory impairment, and recurrent falls. Phenomenology: Complex axial involuntary movements Diagnosis: IgLON5 disease

FDG-PET of the patient showed bilateral caudate hypometabolism. Mov Disord Clin Pract. 2022;10(1):135-7. This finding suggests caudate-predominant basal ganglia dysfunction may have contributed to these unusual involuntary movements. 18F‐FDG‐PET

What Do You See? Neurology. 2024;102:e208110. This was an 82-year-old man with a two-year history of limb stiffness and unsteady gait. He also developed widespread fasciculations and muscle cramps. Phenomenology: Widespread fasciculations, muscle cramps, and limb rigidity (neuromuscular hyperexcitability) Diagnosis: IgLON5 disease

IgLON5 disease can involve both central and peripheral nervous systems. Therefore, unexpected combinations, such as rigidity and fasciculations, may occur. 【Clinical Phenotypes of IgLON5 disease】 1. Sleep disorder phenotype 2. Bulbar syndrome phenotype 3. Movement disorder phenotype (PSP-like, CBS, cerebellar syndrome, and MSA-like syndromes) 4. Dementia phenotype with chorea 5. Peripheral nerve hyperexcitability phenotype

What Do You See? Phenomenology: Postural tremor, abdominal wall myoclonus These patients also had cerebellar ataxia and urinary dysfunction. Diagnosis: autoimmune GFAP astrocytopathy Provided by Dr. Yosuke Takeuchi, Kumamoto University and Akio Kimura, Gifu University

Autoimmune GFAP astrocytopathy is associated with a wide variety of movement disorders. Clin Exp Neuroimmunol, 2025；16: 174-187. Brain Sci. 2022;12:462. (1)The major movement disorders are ataxia, tremor, and myoclonus They usually appear relatively early, with approximately half of patients developing within 28 days. Most are mild to moderate in severity. Tremor and myoclonus predominantly affect the upper limbs. (2) Less common but diagnostically important involuntary movements • Dyskinesia • Opsoclonus • Rigidity • Myokymia • Choreoathetosis

What Do You See? Phenomenology: Ocular flutter It consists of rapid horizontal saccadic oscillations. Diagnosis: autoimmune GFAP astrocytopathy SPECT revealed increased blood flow in the cerebellar vermis, including the fastigial nucleus, suggesting hyperactivity in this region may underlie ocular flutter. Clin Neurol Neurosurg. 2022;219:107307.

What Do You See? Neurology. 2019;92:e2298. A 49-year-old man presented with marked weight loss, headache, and memory impairment. These are multidirectional saccades without an intersaccadic interval. Phenomenology: Opsoclonus Diagnosis: DPPX antibodyassociated encephalitis

What Do You See? Neurology. 2022;99(8):356. The patient developed progressive stiffness, predominantly affecting the left leg. Delayed relaxation of the quadriceps was observed after eliciting the patellar reflex. Surface EMG showed continuous motor activity in the left iliopsoas muscle. Phenomenology； fluctuating left leg stiffness with a hung-up reflex Diagnosis: GAD65 antibody-associated stiff-limb syndrome

Anti-GAD65 antibodies can cause treatable cerebellar ataxia, which is not necessarily bilateral. Mov Disord Clin Pract. 2026 Jul 23 :10.1002/mdc3.70741.

Summary 1. Different movement patterns may suggest specific neural antibodies as shown in this Table. LGI1 Facial dyskinesia, Orofacial dyskinesia, Chorea, Athetosis FBDS, FBCDS CASPR2 Myoclonus, Tremor, Ataxia IgLON5 Myorhythmia, Chorea, Parkinsonism GFAP Tremor, Myoclonus, Ataxia mGluR1 Ataxia, Head titubation DPPX Myoclonus, Tremor, Hyperekplexia GAD65 Stiff-person spectrum disorder, Ataxia NMDA receptor The key message is: Recognize movement patterns. Diagnose early ! Treat early !

Summary 2. Consider antibody testing in the following cases: • Subacute onset of involuntary movements progressing over days to weeks • Combination of multiple movement phenomenologies • Associated cognitive impairment, psychiatric symptoms, or seizures Take-home message • The more red flags that coexist, the stronger the indication for neural antibody testing. Thank you for your attention.