anti-Iglon5 disease - information and support

KEY INFORMATION

What is anti-IgLON5 disease?

How can anti-IgLON5 disease be diagnosed?

Anti-IgLON5 disease appears to have been first identified in 2014.

It is difficult, as a lay person, to find an authoritative definition of anti-IgLON5 disease. It is not yet included in the World Health Organisation’s International Statistical Classification of Diseases and Related Health Problems (ICD), on the NHS website, or in NICE guidelines.

However, from a review of a textbook plus various articles and case studies available online [1], it seems that (i) anti-IgLON5 disease can be (currently) defined/ understood as a rare disorder whose core presentation consists of sleep disorder, bulbar symptoms and abnormal gait, although other symptoms such as cognitive impairment and muscle fasciculation and cramps can also be present, (ii) the clinical course of the majority (more than 75%) of patients is slowly progressive, over months or years, although 24% had a subacute evolution reaching the nadir of the neurological dysfunction in less than 4 months and (iii) it is currently unclear whether the disease is a primary neurodegenerative disorder or a primary ongoing autoimmune disorder. Dalmau and Graus, Autoimmune Encephalitis and Related Disorders of the Nervous System, 2022, chapter 15 Anti-IgLON5 Disease, state that although the possibility of a primary neurodegenerative process cannot be definitively ruled out as the cause of anti-IgLON5 disease, the absence of tauopathy in the brain of patients with typical clinical and immunological features of the disease, the robust association with a rare HLA haplotype (HLA DRB1*10:01 and DQB1*05:01) and the effects of IgLON5 antibodies in vitro strongly suggest a primary immune-mediated disorder.

[1] Dalmau and Graus, Autoimmune Encephalitis and Related Disorders of the Nervous System, 2022, chapter 15 Anti-IgLON5 Disease; Gaig C, Graus F, Compta Y, Hogl B, Bataller L, Bruggemann N, et al, Clinical manifestations of the anti-IgLON5 disease, Neurology, 2 May 2017; Bonello, Jacob, Ellul, Barker, Parker, Jefferson, and Alusi, IgLON5 disease responsive to immunotherapy, 7 August 2017, National Library of Medicine; Nissen and Blaabjerg, Anti-IgLON5 Disease: A Case With 11-Year Clinical Course and Review of the Literature, 2 October 2019; Werner, MD, Jelcic, MD, Schwarz, MD, Probst-Muller, MD, PhD, Nilsson, MD, PhD, Schwizer, MD, Bloch, MD, Lutterotti, MD, Jung, MD, Schreiner, MD, Anti-IgLON5 Disease, A New Bulbar-Onset Motor Neuron Mimic Syndrome, 2 February 2021; Madetko, Marzec, Kowalska, Przewodowska, Alster, Koziorowski, Anti-IgLON5 Disease -The Current State of Knowledge and Further Perspectives, 1 March 2022; Li, Landis, Karazanashvili and Diaz, Anti-IgLON5 disease exacerbated by asymptomatic SARS-COV-2 infection, 5 February 2023, Elsevier Neuroimmunology Reports. For ease of reference, copies of articles or case studies referred to in this footnote are included on this website where permission has been given by the author to include a copy of the article/casenote on this website.

How can anti-IgLON5 disease be diagnosed?

Anti-IgLON5 disease can be diagnosed by a particular blood test.

The blood test is inexpensive as compared to other diagnostic tests (the blood test cost to the NHS is understood to be about £50).

However, because anti-IgLON5 disease is such a rare disease that some doctors may not be aware of, and because the symptoms can also be suggestive of other conditions (i) anti-IgLON5 disease may not be considered by doctors as a possible diagnosis for some time or at all and/or (ii) patients with anti-IgLON5 disease can be misdiagnosed with different conditions depending on the clinical profile at presentation [1].

It may be that there are other ways to diagnose the condition. However, blood test, plus clinical evaluation, is the method that was used in the case of our family member.

Articles available online suggest that early diagnosis is important in order to maximise treatment options.

[1] Dalmau and Graus, Autoimmune Encephalitis and Related Disorders of the Nervous System, 2022, chapter 15 Anti-IgLON5 Disease.

How many people have been diagnosed with anti-IgLON5 disease in Great Britain or worldwide?

It is very difficult to find an authoritative source of how many people have been diagnosed with anti-IgLON5 disease since it was first identified in 2014, whether in Great Britain, or worldwide.

An article in 2021 by Werner MD and others (Werner, MD, Jelcic, MD, Schwarz, MD, Probst-Muller, MD, PhD, Nilsson, MD, PhD, Schwizer, MD, Bloch, MD, Lutterotti, MD, Jung, MD, Schreiner, MD, Anti-IgLON5 Disease, A New Bulbar-Onset Motor Neuron Mimic Syndrome, 2 February 2021) stated that by 2021 more than 60 cases had been reported.

Dalmau and Graus, Autoimmune Encephalitis and Related Disorders of the Nervous System, 2022, chapter 15 Anti-IgLON5 Disease, states that as of May 2020 they had identified 80 patients with IgLON5 antibodies and 72 of those had adequate clinical information. The same source states that patients with IgLON5 antibodies identified in the Neuroimmunology Laboratory of the Institute of Biomedical research August Pi i Sunyer Hospital Clinic in Barcelona, Spain represent one of the largest series of cases with anti-IgLON 5 disease.

Whilst there may be bodies or panels which discuss inflammatory conditions or neurological conditions in general, it is understood that there is as yet no panel of doctors convened to discuss (only) anti-IgLON5 disease, and their experiences of diagnosing and treating it, and to share what has worked well and what has worked less well.

Treatment options for anti-IgLON5 disease

How many people have been diagnosed with anti-IgLON5 disease in Great Britain or worldwide?

One of the problems for patients and their families in understanding available treatment options is that there appear to be no NICE guidelines or other published guidelines regarding treatment options. This is presumably because the disease is only recently discovered and poorly understood.

However, we understand that the following treatment options have been used in some cases:

Steroids;
Immunotherapy e.g. intravenous methylprednisolone, intravenous immunoglobulins, rituximab, plasmapheresis, intravenous cyclophosphamide;
Immunosuppressants;
Anti-viral treatment;
Psychiatric treatment e.g. to treat psychosis symptoms;
Rehabilitation e.g. exercise classes, attendance at day centres, aimed at improving cognitive function.

It is difficult, as a lay person, to find information on the availability of treatment options or on the effectiveness of different treatment options. However, there is a textbook plus articles available online which discuss these issues. See, e.g. Dalmau and Graus, Autoimmune Encephalitis and Related Disorders of the Nervous System, 2022, chapter 15 Anti-IgLON5 Disease; Gaig C, Graus F, Compta Y, Hogl B, Bataller L, Bruggemann N, et al.. Clinical manifestations of the anti-IgLON5 disease, Neurology, 2 May 2017; Bonello, Jacob, Ellul, Barker, Parker, Jefferson, and Alusi, IgLON5 disease responsive to immunotherapy, 7 August 2017, National Library of Medicine; Nissen and Blaabjerg, Anti-IgLON5 Disease: A Case With 11-Year Clinical Course and Review of the Literature, 2 October 2019; Werner, MD, Jelcic, MD, Schwarz, MD, Probst-Muller, MD, PhD, Nilsson, MD, PhD, Schwizer, MD, Bloch, MD, Lutterotti, MD, Jung, MD, Schreiner, MD, Anti-IgLON5 Disease, A New Bulbar-Onset Motor Neuron Mimic Syndrome, 2 February 2021; Madetko, Marzec, Kowalska, Przewodowska, Alster, Koziorowski, Anti-IgLON5 Disease -The Current State of Knowledge and Further Perspectives, 1 March 2022; Li, Landis, Karazanashvili and Diaz, Anti-IgLON5 disease exacerbated by asymptomatic SARS-COV-2 infection, 5 February 2023, Elsevier Neuroimmunology Reports.

A disease which crosses medical specialist boundaries

Symptoms of anti-IgLON5 disease can affect multiple different parts of the body as well as the mind and therefore the disease can cross different medical specialisms.

Prior to diagnosis, the patient may therefore be reviewed by multiple consultants with different specialities e.g. neurologist, psychiatrist, urologist, as doctors try to work out what is wrong with the patient. Our experience is that it is essential that there is a joined up approach with the different consultants from their different areas of expertise working together to diagnose and then treat this condition.

A carer's experience

“ "The diagnosis ... is Alzheimer’s disease". This was the opinion of the neurologists after a lengthy stay in hospital involving many tests and questions asked by many doctors... The tests had not come up with any diagnosis. The clinical test for Alzheimer’s had not been carried out at that point. The patient did not experience memory problems.

As anti-Iglon 5 is a rare disease with very few known cases, it is understandably difficult to diagnose. However an open verdict on a condition is preferable to an incorrect diagnosis. This did not seem an acceptable course for the doctors involved. Two members of our family are medics and were convinced the diagnosis was incorrect and were advocates for the diagnosis to be questioned. They were very brave to do this because the one thing that has been very apparent these last months is that, generally, the medical profession do not like being questioned.

Post diagnosis with anti-Iglon5 one enters the world of experimental medicine. This is very scary. Will the person improve with prescribed treatment? Worst case scenario will they survive the treatment? Decisions, decisions what is the best way forward...

These are the downsides. There are some wonderful things. The love, understanding and help from family members that has exceeded all expectations. The real kindness and ongoing support from friends and neighbours. The real practical help from carers and community medical teams. All this helps makes it possible to live a life that has joy in it through the most challenging times."