BACKGROUND: Anti-IgLON5 disease is a rare but potentially reversible cause of cognitive impairment, sleep disturbances, dysautonomia, and movement disorders. It is an autoimmune encephalitis which, due to its insidious onset, could mimic neurodegenerative disorders, and multiple symptoms overlap with those seen in dementia with Lewy bodies (DLB). We hypothesized that the symptomatology and findings in patients with anti-IgLON5 disease overlapped with that of DLB.
OBJECTIVE: To assess the commonality of features in anti-IgLON5 disease and DLB and identify potential red flags for anti-IgLON5 disease in patients undergoing diagnostic evaluation for DLB.
METHODS: We searched in MEDLINE, Web of Science, and Embase from inception on December the 8th, 2022 with the search term \"IgLON5\". We performed a systematic review of case reports and case series of anti-IgLON5 disease, and two reviewers independently extracted data on symptoms and findings. Frequencies of symptoms were compared with consensus criteria for DLB.
RESULTS: We included 57 studies with 127 individual case reports of anti-IgLON5 disease (mean age 63 years at diagnosis, median symptom duration 2 years). Cognitive dysfunction was reported in 45% of cases, REM-sleep behavioral disorder in 15%, and 14% had parkinsonism. Respiratory insufficiency was reported in 37%, and bulbar symptoms in 67%.
CONCLUSIONS: We found a significant overlap between anti-IgLON5 disease and DLB. We propose that anti-IgLON5 disease should be considered in young patients with DLB with chorea, gaze palsy, early dysphagia, or prominent respiratory symptoms. Our study contributes to the emerging knowledge on symptoms and biomarkers in anti-IgLON5 disease.

UNASSIGNED: Anti-IgLON5 disease is an uncommon neurological disorder characterized by diverse clinical manifestations. Although many relevant cases have been reported, our understanding of this disorder is still quite restricted. We present a rare case of anti-IgLON5 disease and performed a comprehensive systematic review of all published cases to expand the clinical spectrum of this disorder.
UNASSIGNED: We report a 61-year-old woman with an atypical presentation of epileptic seizures with abnormal signals in her right hippocampus on brain magnetic resonance imaging (MRI). A systematic review was performed of electronic databases, including PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), WanFang and VIP China Science.
UNASSIGNED: We identified 161 cases from 65 publications. With heterogeneous clinical manifestations, we found that bulbar dysfunction, sleep apnea, gait instability and neurocognitive and behavioral symptoms are the most common symptoms of anti-IgLON5 disease. Anti-IgLON5 antibodies presented a higher positive rate and titer in the serum than in the cerebrospinal fluid (CSF). Haplotype DRB1*10:01-DQB1*05:01 is highly correlated with anti-IgLON5 disease. Only 38 patients have presented distinctive MRI alterations (26.2%). Approximately half of the cases are responsive to immunosuppressive or immunomodulatory treatment.
UNASSIGNED: Anti-IgLON5 disease is characterized by various clinical manifestations and laboratory findings. Immunotherapy may be effective in treating anti-IgLON5 disease, but the results are far from satisfactory. Studies with larger sample sizes are required to improve the current understanding of this disorder.

Anti-IgLON5 disease is a rare neurodegenerative tauopathy that displays heterogeneity in clinical spectrum, disease course, cerebrospinal fluid (CSF) findings, and variable response to immunotherapy. Sleep disorders, bulbar dysfunction, and gait abnormalities are common presenting symptoms, and conventional brain MRI scanning is often unrevealing.
To provide a comprehensive overview of the literature and to assess the frequency of symptoms, MRI findings, and treatment response in patients with IgLON5 autoimmunity in the serum and CSF or restricted to serum.
We examined a 65-year-old woman with bulbar-onset IgLON5 disease with serum-restricted antibodies, and we also performed a systematic review of all confirmed cases reported in the English literature.
We identified 93 patients, included our case. Clinical data were obtained in 58 subjects, in whom the most frequent symptoms were sleep-disordered breathing, dysphagia, parasomnias, dysarthria, limb or gait ataxia, stridor or vocal cord paresis, movement disorders, and postural instability. Distinct MRI alterations were identified in 12.5% of cases, as opposed to unspecific or unremarkable changes in the remaining patients. T2-hyperintense non-enhancing signal alterations involving the hypothalamus and the brainstem tegmentum were observed only in the present case. Inflammatory CSF was found in half of the cases and serum-restricted antibodies in 4 patients. Treatment with immunosuppressant or immunomodulatory drugs led to sustained clinical response in 19/52 patients.
Anti-IgLON5 autoimmunity should be considered in patients with sleep disorders, bulbar syndrome, autonomic involvement, and movement disorders, and high-field brain MRI can be of diagnostic help.

Anti-IgLON5 disease is a rare disorder characterized by a heterogeneous myriad of symptoms that may include sleep disorders, bulbar dysfunction, gait problems, movement disorders, cognitive impairment, oculomotor abnormalities, and nervous system hyperexcitability. Its physiopathology remains unknown, with a combination of both autoimmune and neurodegenerative findings.
We describe clinical, cerebrospinal fluid (CSF), and ioflupane single-photon emission computed tomography (SPECT) findings of a positive case of anti-IgLON5 disease mimicking probable progressive supranuclear palsy (PSP). We performed a literature review of previous publications reporting on anti-IgLON5 disease and ioflupane SPECT.
We report the case of a 66-year-old male who met clinical criteria for probable PSP, in whom ioflupane SPECT showed an alteration of the left presynaptic dopaminergic pathway. However, the presence of atypical neurological symptoms for PSP led to further complementary tests, and IgLON5 antibodies were detected in CSF. According to our literature review, ioflupane SPECT findings have been previously described in only three other patients with anti-IgLON5 disease, with a reduced uptake in the striatum in two of them.
Ioflupane SPECT abnormalities, though scarcely described, are not uncommon in anti-IgLON5 disease. They could be related to nigrostriatal dopaminergic degeneration in the context of the tauopathy component of the disease, but further case descriptions are necessary.

The aim of this study was to evaluate the frequency of response to immunotherapy in patients with anti-IgLON5 disease through a systematic review of the literature. MEDLINE and Embase databases were searched for studies that included patients with anti-IgLON5 disease who received immunotherapy (IT). Review inclusion criteria were met by 18 studies. The main study variable was response to IT, defined as the frequency of patients with an improvement greater than mild in at least one of the main symptoms defined by the clinical phenotype. Data were also gathered on the rate of response to last follow-up, the line(s) of IT received, the administration of monotherapy or combination therapy, and clinical and analytical characteristics. Selected studies included a total of 46 patients. A response to IT was observed in 20 (43.4%) and the presence of response to last follow-up in 15 (32.6%). Response was achieved more frequently with combination therapy vs monotherapy (14/21 [66.6%] vs 7/22 [31.8%]) and second-line therapy vs first-line therapy (7/13 [53.8%] vs 15/46 [32.6%]). The response rate by drug was 34.2% (12/35) for steroids, 42.8% (9/21) for IVIg, 46% (7/15) for PLEX, 100% (5/5) for AZA and 75% (3/4) for MMF. Factors associated with a response to IT included the cognitive impairment and non-classical phenotypes, presence of HLA-DQB1*05:01 without HLA-DRB1*10:01 and cerebral spinal fluid inflammation. Patients with anti-IgLON5 disease respond to IT, and this response is associated with certain clinical and analytical characteristics of the patients. Also rate of response seems higher with second-line and combination treatment. However, the quality of available studies is inadequate to allow definitive conclusions to be drawn.