Hypothalamic-Bulbar MRI Hyperintensity in Anti-IgLON5 Disease with Serum-Restricted Antibodies: A Case Report and Systematic Review of Literature

Tagliapietra, Matteo; Frasson, Emma; Cardellini, Davide; Mariotto, Sara; Ferrari, Sergio; Zanusso, Gianluigi; Plebani, Mauro; Monaco, Salvatore

doi:10.3233/jad-201105

Cited by 12 publications

(7 citation statements)

References 29 publications

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“…The clinical spectrum of this disorder is still broadening, since the number of reported cases is still low, and cognitive decline as a symptom has been described in 40% of patients, even causing dementia (3). An early treatment with immunosuppressant or immunomodulatory drugs seems to be effective, but even with therapy the greater part of so far described patients suffered from chronic progression or remaining deficits (4,5). Regarding its low prevalence in the general population, only a few articles have addressed symptoms and the course of the anti-IgLON5 disease.…”

Section: Introductionmentioning

confidence: 99%

Case Report: Neuropsychological Findings in IgLON5 Antibody Disorder

et al. 2021

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IgLON5 antibody encephalopathy is a rare but increasingly recognized disorder with a variety of clinical signs. Typical symptoms are sleep disorder, gait disturbances, signs of bulbar dysfunction and a variety of neurological symptoms like oculomotor abnormalities and movement disorders. In addition, cognitive decline can be a prominent symptom. So far, there are only a few studies that have dealt with the course and possible treatment options of IgLON5 antibody encephalopathy. In this study the clinical case of a female patient with IgLON5 antibody disease and the response to treatment is described. Here we report on the case of a 67-year-old female patient who showed cognitive deterioration, gait difficulties, and chronic obstructive sleep disorder. The diagnostic course showed a positive anti-IgLON5 serum and anti-IgLON5 IgG antibodies in cerebrospinal fluid. The patient was subsequently treated with high dosage i.v. methylprednisolone, i.v. immunoglobulins and plasmapheresis. Neuropsychological tests showed cognitive deficits in different domains, including verbal and visual memory. Both, neuropsychological deficits and antibody titer, showed an improvement after plasmapheresis. The presented case shows that IgLON5 disease can present with rapidly progressing cognitive deterioration as the prominent symptom, adding to the variety of clinical signs in this disorder. Testing for IgLON5-antibodies should be considered in patients with progressing cognitive decline, especially if accompanied by sleep disorders or neurological symptoms like oculomotor abnormalities, dysautonomia or bulbar signs.

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Section: Introductionmentioning

confidence: 99%

Case Report: Neuropsychological Findings in IgLON5 Antibody Disorder

et al. 2021

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“…Notably, it has been consistently reported that about 10% of anti-IgLON5 disease patients test negative for anti-IgLON5 IgG in CSF [e.g. (38,39)]. These probably correspond to those with low CSF levels in our cohort when using flow cytometry.…”

Section: Discussionmentioning

confidence: 61%

HLA dependency and possible clinical relevance of intrathecally synthesized anti-IgLON5 IgG4 in anti-IgLON5 disease

Koneczny,

Macher,

Hutterer

et al. 2024

Front. Immunol.

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BackgroundAnti-IgLON5 disease is a rare chronic autoimmune disorder characterized by IgLON5 autoantibodies predominantly of the IgG4 subclass. Distinct pathogenic effects were described for anti-IgLON5 IgG1 and IgG4, however, with uncertain clinical relevance.MethodsIgLON5-specific IgG1-4 levels were measured in 46 sera and 20 cerebrospinal fluid (CSF) samples from 13 HLA-subtyped anti-IgLON5 disease patients (six females, seven males) using flow cytometry. Intervals between two consecutive serum or CSF samplings (31 and 10 intervals, respectively) were categorized with regard to the immunomodulatory treatment active at the end of the interval, changes of anti-IgLON5 IgG1 and IgG4 levels, and disease severity. Intrathecal anti-IgLON5 IgG4 synthesis (IS) was assessed using a quantitative method.ResultsThe median age at onset was 66 years (range: 54–75), disease duration 10 years (range: 15–156 months), and follow-up 25 months (range: 0–83). IgLON5-specific IgG4 predominance was observed in 38 of 46 (83%) serum and 11 of 20 (55%) CSF samples. Anti-IgLON5 IgG4 levels prior clinical improvement in CSF but not serum were significantly lower than in those prior stable/progressive disease. Compared to IgLON5 IgG4 levels in serum, CSF levels in HLA-DRB1*10:01 carriers were significantly higher than in non-carriers. Indeed, IgLON5-specific IgG4 IS was demonstrated not only in four of five HLA-DRB1*10:01 carriers but also in one non-carrier. Immunotherapy was associated with decreased anti-IgGLON5 IgG serum levels. In CSF, lower anti-IgLON5 IgG was associated with immunosuppressive treatments used in combination, that is, corticosteroids and/or azathioprine plus intravenous immunoglobulins or rituximab.ConclusionOur findings might indicate that CSF IgLON5-specific IgG4 is frequently produced intrathecally, especially in HLA-DRB1*10:01 carriers. Intrathecally produced IgG4 may be clinically relevant. While many immunotherapies reduce serum IgLON5 IgG levels, more intense immunotherapies induce clinical improvement and may be able to target intrathecally produced anti-IgLON5 IgG. Further studies need to confirm whether anti-IgLON5 IgG4 IS is a suitable prognostic and predictive biomarker in anti-IgLON5 disease.

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“…Although some patients with IgLON5 antibodies were responsive to immunotherapy, consistent with most other forms of neuronal cell‐surface autoantibody‐mediated diseases, 22,23 patients with improvement in symptoms still require long‐term follow‐up because symptoms may worsen and patients may die suddenly 1,14,24,25 . Grüter et al 26 .…”

Section: Discussionmentioning

confidence: 91%

“…Although some patients with IgLON5 antibodies were responsive to immunotherapy, consistent with most other forms of neuronal cell-surface autoantibody-mediated diseases, 22,23 patients with improvement in symptoms still require long-term follow-up because symptoms may worsen and patients may die suddenly. 1,14,24,25 Grüter et al 26 found that first-line immunotherapy of relapselike acute-to-subacute exacerbation episodes resulted in improvement in 41% of patients and early immunotherapy (before advanced neurodegeneration) was associated with a better long-term clinical outcome. In cultures of hippocampal neurons, antibodies of patients caused a decrease in cell-surface IgLON5 clusters that was not reversed after IgLON5 antibodies were removed from the media, indicating an irreversible antibody-mediated internalization of surface IgLON5 in hippocampal neurons.…”

Section: Discussionmentioning

confidence: 99%