Villacieros-lvarez, L. or several concurrent movement disorders. At the time of anti-IgLON5 diagnosis, 63 (87%) patients had at least 1 movement disorder with a median of 3 per patient. The most frequent abnormal movements were gait and balance disturbances (52 patients [72%]), chorea (24 [33%]), bradykinesia (20 [28%]), dystonia (19 [26%]), abnormal body postures or rigidity (18 [25%]), and tremor (15 [21%]). Other hyperkinetic movements SR-13668 (myoclonus, akathisia, myorhythmia, myokymia, or abdominal dyskinesias) occurred in 26 (36%) patients. The craniofacial region was one of the most frequently affected by multiple concurrent movement disorders (23 patients [32%]) including dystonia (13), myorhythmia (6), chorea (4), or myokymia (4). Considering any body region, the most frequent combination of multiple movement disorders consisted of gait instability or ataxia associated with craniofacial dyskinesias or generalized chorea observed in 31 (43%) patients. In addition to abnormal movements, 87% of patients had sleep alterations, 74% bulbar SR-13668 dysfunction, and 53% cognitive impairment. Fifty-five (76%) patients were treated with immunotherapy, resulting in important and sustained improvement of the movement disorders in only 7 (13%) cases. == Discussion == Movement disorders are a frequent and leading cause of initial neurologic consultation in patients with anti-IgLON5 disease. Although multiple types of abnormal movements can occur, the most prevalent are disorders of gait, generalized SR-13668 chorea, and dystonia and other dyskinesias that frequently affect craniofacial muscles. Overall, anti-IgLON5 disease should be considered in patients with multiple movement disorders, particularly if they occur in association with sleep alterations, bulbar dysfunction, or cognitive impairment. Anti-IgLON5 disease is usually a neurologic disorder associated with antibodies against IgLON5, a neuronal cell adhesion protein of unknown function.1Most patients Mouse monoclonal to MPS1 develop a combination of sleep alterations (non-REM and REM sleep parasomnias with stridor and obstructive sleep apnea), bulbar dysfunction (dysarthria, dysphagia, vocal cord palsy, or episodes of respiratory failure), and gait difficulties.2Initial autopsy studies showed deposits of phosphorylated tau protein predominantly involving neurons of the tegmentum of the brainstem, suggesting a primary neurodegenerative disease.1However, there is a strong association SR-13668 with the human leukocyte antigen (HLA) haplotype DRB1*10:01-DQB1*05:01, which is present in 60% of patients (compared to 2% in the general population)3and recent autopsy studies demonstrated absence of abnormal deposits of tau.4,5Cultures of live neurons treated with IgLON5 antibodies showed an irreversible loss of surface IgLON5 SR-13668 clusters accompanied by changes in the cytoskeleton such as dystrophic neurites and axonal swellings.6,7Taken together, these studies suggest that an antibody-mediated disruption of IgLON5 function leads to cytoskeletal alterations that could potentially result in tau accumulation. Several reviews have addressed the movement disorders of different types of autoimmune encephalitis8,9but for anti-IgLON5 disease the associated abnormal movements are less known or only partially described due to its more recent discovery. Although the sleep manifestations contributed to the identification of anti-IgLON5 disease,1many patients develop movement disorders that precede the sleep dysfunction or are the reason for initial consultation, often suspecting initial symptoms of progressive supranuclear palsy (PSP).10-13We describe the frequency, spectrum, and phenomenology of movement disorders in patients with anti-IgLON5 disease and provide clinical clues that may help in its diagnosis. == Methods == == Patients and Clinical Evaluation == We retrospectively reviewed the clinical information of all patients with IgLON5 antibodies consecutively identified at the Neuroimmunology Laboratory of the Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Hospital Clinic (Barcelona, Spain), from January 2014 to August 2020. The sleep dysfunction and general clinical features of 31 patients have been reported,1,2,5,10,11,14-22but the abnormal movements were previously described in detail in only 3 of them.11,16,22 == Initial Clinical Evaluation == Demographic and clinical data of the patients were provided by the referring physicians through a structured written questionnaire obtained by the time of IgLON5 antibody detection.2Patients were classified into 1 of 5 clinical phenotypes according to the most predominant symptoms2,23-25: (1) sleep disorder; (2) bulbar syndrome; (3) movement disorders; (4) cognitive impairment; and (5) neuromuscular manifestations with muscle weakness, atrophy, or fasciculations. == Assessment of the Movement Disorders == The presence and types of movement disorders at the time of diagnosis were specifically assessed in all patients with a second standardized questionnaire. In this questionnaire (eQuestionnaire available in Dryad [doi.org/10.5061/dryad.000000040]), the referring neurologists were asked to provide a complete description of the movement disorders and, if available, video recordings of the patients. Eighteen (40%) of 45 referring neurologists were movement.