Anti-IgLON5 disease

Anti-IgLON5 disease is a neurodegenerative autoimmune disease. It is marked by parasomnias and chorea - an involuntary movement disorder.[1][2][3][4][5]

Anti-IgLON5 disease
SpecialtyImmunology

Pathophysiology

The IgLON proteins are a family of five cell-adhesion molecules IgLON 1, 2, 3, 4 & 5, which assist in neuronal growth and connections among nerve cells.[6] and help in brain evolution and maturation to maintain integrity of the blood brain barrier.[7]

Abnormal pTau deposits seen in several brains, brain stems and upper cervical cords shown by neuro-immuno-histochemistry studies of brain tissue from these regions without inflammatory cells differentiate this entity from other autoimmune encephalitis.[8][2]

IgLON5 refers to a cell surface protein involved in promoting connections among nerve cells.[9] Prevalence of the HLA-DRB1*10:01 allele was greatly increased in people with anti-IgLON5 disease.[1] The sleep problems seen in this disorder are insomnia, sleep related abnormal movements called parasomnias which may be seen in both REM and NREM sleep and poor efficiency of sleep. Respiratory problems related to sleep disorder such as obstructive sleep apnea (OSA) and jerky stertorous breathing were noted in more than half the cases.[10]

Diagnosis

Serum studies show IgLON5 antibodies in almost all patients while the presence of CSF antibodies is more sporadic, occurring in ~50% of cases. Additional findings may be Oligoclonal bands(OCB), a few leukocytes and a slight rise in proteins, with otherwise normal CSF examination in more than half the cases.[11]

If tau, p-tau or beta-amyloid are found then they indicate the neuropathology of the disorder, thereby distinguishing it from other autoimmune encephalitis.

Brain Imaging

MRI scans of the brain show brain stem atrophy in half the cases and changes in brain regions having tau-pathy in one fifths, FDG Positron emission scans-(FDG - PET)show hyper-metabolism in region of tau-pathy in half the cases correlating well with the clinical features.

Treatment

Anti-IgLON5 disease is mainly treated with immunosuppressants (80%), mostly cycles of IV corticosteroids (58%) in combination with IV immunoglobulins (IVIg−36%) and/or TPE (27%). Alternative successfully used, second-line treatments are Rituximab (22%) and Cyclophosphamide (12%), Azathioprine and Mycophenolat Mofetil.[12][13][14]

Sudden death is the most common outcome in nearly 34% of patients, irrespective of partial response to therapy. While complications from aspiration were the other common cause of death.[15][16][17]

Symptomatic treatment with CPAP in patients with OSA helps improve respiratory symptoms, while parasomnias and movement disorders (myoclonus, parkinsonism, and dystonia) did not respond when antiepileptic, dopaminergic, and anti-hyperkinetic drugs were administered.[12][17][18]

References
  1. Gaig C, Graus F, Compta Y, Högl B, Bataller L, Brüggemann N, et al. (May 2017). "Clinical manifestations of the anti-IgLON5 disease". Neurology. 88 (18): 1736–1743. doi:10.1212/WNL.0000000000003887. PMC 5409845. PMID 28381508.
  2. Sabater L, Gaig C, Gelpi E, Bataller L, Lewerenz J, Torres-Vega E, et al. (June 2014). "A novel non-rapid-eye movement and rapid-eye-movement parasomnia with sleep breathing disorder associated with antibodies to IgLON5: a case series, characterisation of the antigen, and post-mortem study". The Lancet. Neurology. 13 (6): 575–86. doi:10.1016/S1474-4422(14)70051-1. PMC 4104022. PMID 24703753.
  3. Honorat JA, Komorowski L, Josephs KA, Fechner K, St Louis EK, Hinson SR, et al. (September 2017). "IgLON5 antibody: Neurological accompaniments and outcomes in 20 patients". Neurology. 4 (5): e385. doi:10.1212/NXI.0000000000000385. PMC 5515599. PMID 28761904.
  4. Graus F, Santamaría J (September 2017). "Understanding anti-IgLON5 disease". Neurology. 4 (5): e393. doi:10.1212/NXI.0000000000000393. PMC 5570673. PMID 28852690.
  5. "NEJM Journal Watch: Summaries of and commentary on original medical and scientific articles from key medical journals". www.jwatch.org. Retrieved 16 June 2018.
  6. Ranaivoson FM, Turk LS, Ozgul S, Kakehi S, von Daake S, Lopez N, et al. (June 2019). "A Proteomic Screen of Neuronal Cell-Surface Molecules Reveals IgLONs as Structurally Conserved Interaction Modules at the Synapse". Structure. 27 (6): 893–906.e9. doi:10.1016/j.str.2019.03.004. PMC 6609445. PMID 30956130.
  7. Kubick N, Brösamle D, Mickael ME (January 2018). "Molecular Evolution and Functional Divergence of the IgLON Family". Evolutionary Bioinformatics Online. 14: 1176934318775081. doi:10.1177/1176934318775081. PMC 5967153. PMID 29844654.
  8. Gelpi E, Höftberger R, Graus F, Ling H, Holton JL, Dawson T, et al. (October 2016). "Neuropathological criteria of anti-IgLON5-related tauopathy". Acta Neuropathologica. 132 (4): 531–43. doi:10.1007/s00401-016-1591-8. PMC 5023728. PMID 27358064.
  9. Database, GeneCards Human Gene. "IGLON5 Gene - GeneCards | IGLO5 Protein | IGLO5 Antibody". www.genecards.org. Retrieved 16 June 2018.
  10. Nissen, Mette Scheller; Blaabjerg, Morten (2019). "Anti-IgLON5 Disease: A Case With 11-Year Clinical Course and Review of the Literature". Frontiers in Neurology. 10: 1056. doi:10.3389/fneur.2019.01056. PMC 6783555. PMID 31632341.
  11. Solnes, Lilja B (2017). "Diagnostic Value of 18F-FDG PET/CT Versus MRI in the Setting of Antibody-Specific Autoimmune Encephalitis". Journal of Nuclear Medicine. 58 (8): 1307–1313. doi:10.2967/jnumed.116.184333. PMC 6944181. PMID 28209905.
  12. Haitao R, Yingmai Y, Yan H, Fei H, Xia L, Honglin H, et al. (November 2016). "Chorea and parkinsonism associated with autoantibodies to IgLON5 and responsive to immunotherapy". Journal of Neuroimmunology. 300: 9–10. doi:10.1016/j.jneuroim.2016.09.012. PMID 27806876. S2CID 206278688.
  13. Montagna M, Amir R, De Volder I, Lammens M, Huyskens J, Willekens B (2018-05-17). "IgLON5-Associated Encephalitis With Atypical Brain Magnetic Resonance Imaging and Cerebrospinal Fluid Changes". Frontiers in Neurology. 9: 329. doi:10.3389/fneur.2018.00329. PMC 5966542. PMID 29867738.
  14. Schöberl F, Levin J, Remi J, Goldschagg N, Eren O, Okamura N, et al. (July 2018). "IgLON5: A case with predominant cerebellar tau deposits and leptomeningeal inflammation". Neurology. 91 (4): 180–182. doi:10.1212/WNL.0000000000005859. PMID 29970401. S2CID 49680135.
  15. Schröder JB, Melzer N, Ruck T, Heidbreder A, Kleffner I, Dittrich R, et al. (January 2017). "Isolated dysphagia as initial sign of anti-IgLON5 syndrome". Neurology. 4 (1): e302. doi:10.1212/NXI.0000000000000302. PMC 5120591. PMID 27900347.
  16. Wenninger S (2017-11-21). "Expanding the Clinical Spectrum of IgLON5-Syndrome". Journal of Neuromuscular Diseases. 4 (4): 337–339. doi:10.3233/JND-170259. PMID 29103046.
  17. Bahtz R, Teegen B, Borowski K, Probst C, Blöcker IM, Fechner K, et al. (October 2014). "Autoantibodies against IgLON5: Two new cases". Journal of Neuroimmunology. 275 (1–2): 8. doi:10.1016/j.jneuroim.2014.08.027. S2CID 53172498.
  18. Brüggemann N, Wandinger KP, Gaig C, Sprenger A, Junghanns K, Helmchen C, Münchau A (May 2016). "Dystonia, lower limb stiffness, and upward gaze palsy in a patient with IgLON5 antibodies". Movement Disorders. 31 (5): 762–4. doi:10.1002/mds.26608. PMID 27030137. S2CID 3443301.
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