Novel therapies in CIDP.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a heterogeneous but clinically well-described disease within circumscribed parameters. It is immunologically mediated through several poorly understood mechanisms. First-line therapies with steroids, intravenous immunoglobulin (IVIG) or plasma exchange are each effective in about two-thirds of patients. These treatments are seldom associated with complete resolution or cure, and often pose considerable practical, financial and medical implications.Our understanding of many of the key pathological processes in autoimmune diseases is expanding, and novel targeted therapeutics are being developed with promise in several autoimmune neurological disorders.This narrative review looks first at detailing key pathogenic mechanisms of disease in CIDP, followed by an in-depth description of potential novel therapies and the current evidence of their application in clinical practice.

Evaluation of an ambulatory care pathway for patients with nitrous oxide-induced myeloneuropathy.

Introduction: Cases of nitrous oxide (N2O)-induced myeloneuropathy are increasing at UK hospitals. At our centre, a dedicated ambulatory care pathway, endorsed nationally, was established to treat and monitor patients with N2O-myeloneuropathy in 2021 and refined through three audit cycles. We analysed the outcomes of patients on this pathway to better understand factors associated with non-engagement. Alongside, a novel approach using WhatsApp for questionnaire delivery was trialled in an attempt to improve engagement with treatment. Methods: Patients on the N2O ambulatory care pathway were identified from MDT meeting lists from 9 September 2022 to 25 April 2023. Clinical data were collected via electronic clinical records, including the most recent neurological examination and reason for discharge from the pathway. Patients identified from MDT lists from 27 January 2023 to 14 March 2023 were approached to participate in weekly 12-item surveys, delivered via WhatsApp. This was approved as a service development project with approval for WhatsApp use given by the chief clinical information officer. Results: 35/56 (62.5%) patients were discharged from ambulatory care due to non-attendance and 17/56 (30.4%) completed their treatment course. The median time from initial presentation to discharge was 49 days. 24/40 (60.0%) of patients with a final neurological examination documented had a residual deficit, with objective sensory deficits most common. 12 patients were approached to receive weekly questionnaires via WhatsApp. 5/8 who expressed interest returned a consent form. All participants were withdrawn due to non-response or participant choice. 1/5 returned more than two surveys. Conclusion: Despite poor participation in surveys delivered via WhatsApp, novel approaches are needed to improve engagement with patients on the N2O ambulatory care pathway.

Recreational nitrous oxide and thrombotic events: a case series.

Background: The study aimed to elucidate the prevalence of nitrous oxide (N2O) usage in patients with unexplained venous thromboembolism (VTE), highlighting the potential association with hyperhomocysteinaemia (HHcy). Methods: We conducted a retrospective study at the Royal London Hospital, examining cases of N2O-related VTE from March to August 2023. Among 50 patients identified, four (8%) had recent unprovoked VTE. Patient data were collected based on N2O ambulatory emergency care pathway admissions. Results: Among the 50 patients identified, four (8%) had recent or concurrent VTE. Three were male (75%), with an ethnic distribution of 50% Asian or Asian British and 50% Black or Black British. Patients were distributed across quintiles of the index of multiple deprivation. All had actual or functional vitamin B12 deficiency. Discussion: The association between N2O use and VTE requires further investigation, though a plausible mechanism involving HHcy has been proposed. Clinicians should be vigilant for VTE in N2O users, especially those presenting with unexplained symptoms. VTE prophylaxis may be worth considering, particularly if continued exposure to nitrous oxide is anticipated. Conclusion: N2O misuse may increase the risk of VTE, warranting attention from healthcare providers. Further research is needed to elucidate this association and inform preventive strategies. Public awareness about the risks of N2O remains essential.

Effectiveness of interactive workshops to raise awareness of the neurological harms associated with nitrous oxide use: a cross-sectional study.

BACKGROUND: The Royal London Hospital, East London, receives a case of nitrous oxide (N2O) myeloneuropathy roughly every 9 days. No formal education programme is widely available to warn young people of the risks of recreational N2O use. Our aim was to develop and evaluate the effectiveness of workshops focusing on the neurological risks of N2O, with the primary outcome to increase awareness of these risks among young people. METHODS: For this cross-sectional study, the workshop content was piloted with over 200 people at a community event, received input from a person with lived experience, and then piloted with a youth group, all in east London, UK. Between Oct 10, 2022, and April 11, 2023, 32 workshops were delivered to 984 young people in schools and youth groups in east London. The workshop included three interactive activities exploring how and why N2O causes neurological damage. An online anonymous questionnaire including free text and 5-point Likert scale answers was provided after each workshop. The HRA ethical toolkit and NIHR INVOLVE guidance were consulted, and NHS ethics approval was not required. FINDINGS: 396 (40%) of 984 workshop participants completed the questionnaire. The median age bracket of attendees was 13-15 years. 38 (10%) of 396 respondents reported past use of N2O, while 24 (6%) did not divulge use or non-use. Self-perceived likelihood of use was reduced after the workshop, with 261 (66%) very unlikely to use N2O before the session compared with 290 (73%) after the session. 238 (60%) respondents reported an increase in self-perceived knowledge of the risks after the session. When asked about their understanding of the risks of N2O, 206 (52%) relayed something related to N2O causing neurological damage. 327 (83%) respondents found the workshop useful. INTERPRETATION: This work highlights the feasibility of raising awareness among young people of N2O-myeloneuropathy in this workshop format. Limitations included difficulties involving many participants with lived experience in design, an absence of pre-existing interventions to compare against these workshops, and that data collection from young people required pragmatic, short questions. Overall, this work supports larger-scale preventive approaches to N2O-myeloneuropathy, such as a national education programme. FUNDING: Queen Mary Centre for Public Engagement Small Grant Fund.

Nitrous oxide-induced myeloneuropathy: a case series.

BACKGROUND: Nitrous oxide (N2O) is the second most common recreational drug used by 16- to 24-year-olds in the UK. Neurological symptoms can occur in some people that use N2O recreationally, but most information comes from small case series. METHODS: We describe 119 patients with N2O-myeloneuropathy seen at NHS teaching hospitals in three of the UK's largest cities: London, Birmingham and Manchester. This work summarises the clinical and investigative findings in the largest case series to date. RESULTS: Paraesthesia was the presenting complaint in 85% of cases, with the lower limbs more commonly affected than the upper limbs. Gait ataxia was common, and bladder and bowel disturbance were frequent additional symptoms. The mid-cervical region of the spinal cord (C3-C5) was most often affected on MRI T2-weighted imaging. The number of N2O canisters consumed per week correlated with methylmalonic acid levels in the blood as a measure of functional B12 deficiency (rho (ρ)=0.44, p=0.04). CONCLUSIONS: Preventable neurological harm from N2O abuse is increasingly seen worldwide. Ease of access to canisters and larger cylinders of N2O has led to an apparent rise in cases of N2O-myeloneuropathy in several areas of the UK. Our results highlight the range of clinical manifestations in a large group of patients to improve awareness of risk, aid early recognition, and promote timely treatment.