Pragmatic guide to peripheral nerve disease and the role of clinical biomarkers

Keh, Ryan; Shah, Sachit; Lilleker, James B; Lavin, Tim; Morrow, Jasper M.; Carr, Aisling; Lunn, Michael P.

doi:10.1136/pn-2022-003438

Cited by 3 publications

(2 citation statements)

References 81 publications

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“…In neuromuscular disease, treatment efficacy or failure is primarily a clinical decision. There are no reliable serological biomarkers of disease activity (other than creatine kinase, which has some relative responsiveness in myositis, and the erythrocyte sedimentation rate or C-reactive protein in some cases of systemic vasculitis) 45. To establish objective evidence of clinical change, we recommend using disease-specific and symptom-specific outcome measurements at pretreatment and post-treatment assessments.…”

Section: Approach To Immunosuppression In Neuromuscular Diseasesmentioning

confidence: 99%

First-line immunosuppression in neuromuscular diseases

2023

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Autoimmune neuromuscular diseases are common and often treatable causes for peripheral nervous system dysfunction. If not optimally managed, they result in meaningful impairments and disability. The treating neurologist should aim to maximise clinical recovery with minimal iatrogenic risk. This requires careful patient and medication selection, appropriate counselling and close monitoring of clinical efficacy and safety. Here, we summarise our consensus departmental approach to first-line immunosuppression in neuromuscular diseases. We combine multispecialty evidence and expertise with a focus on autoimmune neuromuscular diseases to create guidance on starting, dosing and monitoring for toxic effects of the commonly used drugs. These include corticosteroids, steroid-sparing agents and cyclophosphamide. We also provide efficacy monitoring advice, as clinical response informs dosage and drug choice. The principles of this approach could be applied across much of the spectrum of immune-mediated neurological disorders where there is significant therapeutic crossover.

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Section: Approach To Immunosuppression In Neuromuscular Diseasesmentioning

confidence: 99%

First-line immunosuppression in neuromuscular diseases

2023

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“…The application of diagnostic tests or other biomarkers must be performed and interpreted in this context. 11 This becomes increasingly important as we consider the potential pathogenicity of less frequent repeat motifs. 2-6 …”

Section: Introductionmentioning

confidence: 99%

Pathologic RFC1 repeat expansions do not contribute to the development of inflammatory neuropathies

Nagy,

Carr,

Mroczek

et al. 2024

Brain Communications

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Biallelic expansions of the AAGGG repeat in the replication factor C subunit 1 (RFC1) have recently been described to be responsible for the cerebellar ataxia, peripheral neuropathy and vestibular areflexia syndrome. This genetic alteration has also allowed genetic classification in up to one third of cases with idiopathic sensory neuropathy. Here we screened a well characterized cohort of inflammatory neuropathy patients for RFC1 repeat expansions to explore whether RFC1 was increased from background rates and possibly involved in pathogenesis of inflammatory neuropathy. A total of 259 individuals with inflammatory neuropathy and 243 healthy controls were screened for the AAGGG repeat expansion using short-range flanking PCR and repeat-primed PCR. Cases without amplifiable PCR product on flanking PCR and positive repeat-primed PCR were also tested for the mostly non-pathogenic expansions of AAAGG and AAAAG repeat units.None of the patients showed biallelic AAGGG expansion of RFC1, and their carrier frequency for AAGGG was comparable to controls (n = 27 (5,2%) and n = 23 (4,7%), respectively; p > 0.5). Data suggests that pathologic expansions of AAGGG repeats do not contribute to the development of inflammatory neuropathies, nor lead to misdiagnosed cases. Accordingly, routine genetic screening for RFC1 repeat expansion is not indicated in this patient population.

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Ultrasensitive assay technology and fluid biomarkers for the evaluation of peripheral nerve disease

Bellanti,

Keddie,

Lunn

et al. 2023

J Neurol Neurosurg Psychiatry

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The field of biomarker discovery is rapidly expanding. The introduction of ultrasensitive immunoassays and the growing precision of genetic technologies are poised to revolutionise the assessment and monitoring of many diseases. Given the difficulties in imaging and tissue diagnosis, there is mounting interest in serum and cerebrospinal fluid biomarkers of peripheral neuropathy. Realised and potential fluid biomarkers of peripheral nerve disease include neuronal biomarkers of axonal degeneration, glial biomarkers for peripheral demyelinating disorders, immunopathogenic biomarkers (such as the presence and titre of antibodies or the levels of cytokines) and genetic biomarkers. Several are already starting to inform clinical practice, whereas others remain under evaluation as potential indicators of disease activity and treatment response. As more biomarkers become available for clinical use, it has become increasingly difficult for clinicians and researchers to keep up-to-date with the most recent discovery and interpretation. In this review, we aim to inform practising neurologists, neuroscientists and other clinicians about recent advances in fluid biomarker technology, with a focus on single molecule arrays (Simoa), chemiluminescent enzyme immunoassays (CLEIA), electrochemiluminescence (ECL), proximity extension assays (PEA), and microfluidic technology. We discuss established and emerging fluid biomarkers of peripheral neuropathy, their clinical applications, limitations and potential future developments.

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Pragmatic guide to peripheral nerve disease and the role of clinical biomarkers

Cited by 3 publications

References 81 publications

First-line immunosuppression in neuromuscular diseases

First-line immunosuppression in neuromuscular diseases

Pathologic RFC1 repeat expansions do not contribute to the development of inflammatory neuropathies

Ultrasensitive assay technology and fluid biomarkers for the evaluation of peripheral nerve disease

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