Reshaping neuroimmunology: diagnosis and treatment in the era of precision medicine

dos Passos, Giordani Rodrigues; Adoni, Tarso; Mendes, Maria Fernanda; Sato, Douglas Kazutoshi

doi:10.1055/s-0043-1777752

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View and Review • Arq. Neuro-Psiquiatr. 81 (12) • Dec 2023 • https://doi.org/10.1055/s-0043-1777752 copy

Reshaping neuroimmunology: diagnosis and treatment in the era of precision medicine

Remodelando a neuroimunologia: diagnóstico e tratamento na era da medicina de precisão

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Precision medicine has revolutionized the field of neuroimmunology, with innovative approaches that characterize diseases based on their biology, deeper understanding of the factors leading to heterogeneity within the same disease, development of targeted therapies, and strategies to tailor therapies to each patient. This review explores the impact of precision medicine on various neuroimmunological conditions, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), optic neuritis, autoimmune encephalitis, and immune-mediated neuropathies. We discuss advances in disease subtyping, recognition of novel entities, promising biomarkers, and the development of more selective monoclonal antibodies and cutting-edge synthetic cell-based immunotherapies in neuroimmunological disorders. In addition, we analyze the challenges related to affordability and equity in the implementation of these emerging technologies, especially in situations with limited resources.

Keywords
Precision Medicine; Autoimmune Diseases of the Nervous System; Multiple Sclerosis; Neuromyelitis Optica; Biomarkers; Immunomodulation; Pharmacogenetics

Conventional approach	Precision medicine approach
An 18-year-old female presents with transverse myelitis extending from T6 to the conus medullaris and recovers well following intravenous steroids. Retrospectively, she reports an episode suggestive of unilateral optic neuritis at age 16, with spontaneous recovery of visual acuity but with residual dyschromatopsia. Testing for AQP4-IgG results negative and a hypothesis of seronegative NMOSD is made, but she fails to meet the diagnostic criteria. Prednisone and azathioprine are started off-label.	Following the two attacks, the same patient is tested for AQP4-IgG and MOG-IgG using live cell-based assays, with the later coming out positive at high titer. A diagnosis of MOG-IgG-associated disease (MOGAD) is made, and the patient is enrolled into one of the ongoing, phase 3 clinical trials testing selective monoclonal antibodies against either the interleukin-6 receptor (satralizumab) or the neonatal Fc receptor (rozanolixizumab). Serial MOG-IgG testing is performed during follow-up.
A 53-year-old male is admitted to the intensive care unit with a four-week history of symmetric ascending weakness and pain, tremor, ataxia, bilateral facial palsy, and eventually respiratory insufficiency. He receives intravenous immunoglobulin due to suspected GBS. Since his condition continues to deteriorate another four weeks later, CIDP is suspected, and indeed he fulfills the EFNS/PNS electrophysiological diagnostic criteria. However, he fails to respond to intravenous methylprednisolone and then to plasma exchange and is discharged home with tracheostomy and unable to walk.	Soon after admission, the presence of tremor and ataxia prompts testing for IgG antibodies against CASPR1/contactin-1 complex, which come out positive, allowing for a diagnosis of paranodopathy instead of CIDP. Following failure of intravenous immunoglobulin, he receives rituximab (instead of intravenous steroids or plasma exchange) and presents good recovery of respiratory and motor function (requires some help for usual activities, but is able to walk unassisted at discharge).
A 38-year-old female, who had been on teriflunomide since age 32 after receiving a diagnosis of relapsing-remitting MS, presented with a two-week complaint of paroxysmal paresthesia on the left side of her body, including the face, superimposed to increasing fatigue over the past six months. Neurological examination remains unchanged and six-monthly 1.5 Tesla MRI scans of the brain have not shown any new lesions since the start of teriflunomide. Her neurologist suggests the paresthesia may represent a pseudorelapse or a non-organic symptom, given the absence of MRI activity, and explains to her there are no grounds to consider a DMT switch.	To further assess the new symptoms, the treating neurologist orders a 3.0 Tesla MRI of the brain, which shows two paramagnetic rim lesions, and measurements of serum neurofilament light chain, which comes out elevated (Z score = 1.65). She explains to the patient these biomarkers are not yet fully validated, but likely suggest the presence of chronic active disease and increased risk for future disease activity. Taking these findings into account, the neurologist ends up considering the paresthesia as a probable true relapse, in spite of no new MRI lesion, and raises the possibility the worsening fatigue may represent smoldering MS. A shared decision is made to switch to a higher efficacy DMT.

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[1] Address for correspondence Douglas Sato (douglas.sato@pucrs.br)