Search

Toxic neuropathies result from exogenous substances damaging the peripheral nerves. There are numerous causes, including prescribed and recreational drugs, heavy metals, industrial agents and biological toxins. Timely recognition of these neuropathies gives better outcomes, as they usually improve or stabilise once the toxin is removed. Most toxic neuropathies are axonal, length-dependent and sensory predominant, although some have significant motor involvement or can present acutely or subacutely. Here, we outline our clinical approach and discuss the major causes of toxic neuropathy, while emphasising the clinical and neurophysiological features and the neuropathy phenotype. We also include an update on newer medications that can cause neuropathy, including immune checkpoint inhibitors and BRAF/MEK inhibitors.

BackgroundArterial and venous thromboembolic events (TEEs) have been associated with intravenous Ig use, but the risk has been poorly quantified. We aimed to calculate the risk of TEEs associated with exposure to intravenous Ig.MethodsWe included participants from UK Biobank recruited over 3 years, data extracted September 2020.The study endpoints were incidence of myocardial infarction, other acute ischaemic heart disease, stroke, pulmonary embolism and other venous embolism and thrombosis.Predictors included known TEE risk factors: age, sex, hypertension, smoking status, type 2 diabetes mellitus, hypercholesterolaemia, cancer and past history of TEE. Intravenous Ig and six other predictors were added in the sensitivity analysis.Information from participants was collected prospectively, while data from linked resources, including death, cancer, hospital admissions and primary care records were collected retrospectively and prospectively. Findings14 794 of 502 492 individuals had an incident TEE during the study period. The rate of incident events was threefold higher in those with prior history of TEE (8 .7%) than those without previous history of TEE (3.0%).In the prior TEE category, intravenous Ig exposure was independently associated with increased risk of incident TEE (OR=3.69 (95% CI 1.15 to 11.92), p=0.03) on multivariate analysis. The number needed to harm by exposure to intravenous Ig in those with a history of TEE was 5.8 (95% CI 2.3 to 88.3).Intravenous Ig exposure did not increase risk of TEE in those with no previous history of TEE.InterpretationIntravenous Ig is associated with increased risk of further TEE in individuals with prior history of an event with one further TEE for every six people exposed. In practice, this will influence how clinicians consent for and manage overall TEE risk on intravenous Ig exposure.

Background/Aims Haemophagocytic lymphohistiocytosis (HLH) is a devastating condition caused by uncontrolled activation of the immune system. If left untreated, the condition leads to multi-organ failure and death. Even with treatment, recent UK data has shown a mortality rate of 50%. In 2019, a group of clinicians from University College London Hospital (UCLH) came together with the aim of improving outcomes for patients with HLH. The UCLH HLH multi-disciplinary meeting (MDM) has been running since that time and includes representation from rheumatology, haematology, infectious diseases, tropical medicine, virology, neurology, and critical care. Clinicians from any UK trust are invited to join and present patients. As part of a service evaluation project, we aimed to assess the scope of this meeting with regards to the number, demographics and primary diagnoses of patients discussed and the geographical location of the referring clinical team. Methods This is a retrospective descriptive analysis of all patients discussed at the UCLH HLH MDT from 2nd September 2020 to 20th July 2022. Data were obtained from electronic health records and analysed in Prism version 9.4.1. This work has been registered as a service evaluation project within the Division of Medical Specialities at UCLH. Results 93 patients were discussed. 38 were female. 55 were male. The median age was 38 years. Triggers for HLH were haematological malignancy (38.0%), infection (29.3%) rheumatological (14.1%) primary HLH (6.5%) and unknown (7.6%). In 4 patients, HLH was not felt to be the underlying diagnosis. 40 patients were managed as inpatients at UCLH, 37 of whom were transferred from other trusts. Geographical data were obtained on 81 patients. Patients were referred from all 9 regions of England: London (34), North East (1), North West (2), Yorkshire (2), East Midlands (1), West Midlands (3) South East (11), East of England (11), South West (11) as well as Wales (2), Scotland (2) and Ireland (1). Haemophagocytosis was confirmed on bone marrow biopsy in 66.7% of patients. Mortality data showed that 32 (34%) patients died following their diagnosis. Conclusion A multi-disciplinary approach is essential in the management of HLH. Our data show that patients with HLH are young, have a high mortality and broad range of pathology. The UCLH HLH MDT currently serves a wide geographical area across the UK and UCLH acts as a tertiary referral centre for patients with the condition. Disclosure N.S. Shah: None. M. Hutchinson: None. S. Clark: None. E. Sanchez: None. M. Brown: None. N. Stone: None. A.S. Carr: None. B. Carpenter: None. A. Laurence: None. S.H. Gohil: None. R.S. Tattersall: None. J.J. Manson: None. A. Jones: None.

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.

In clinical neurology practice, there are few sensitive, specific and responsive serological biomarkers reflecting pathological processes affecting the peripheral nervous system. Instead, we rely on surrogate multimodality biomarkers for diagnosis and management. Correct use and interpretation of the available tests is essential to ensure that appropriate treatments are used and adjusted in a timely fashion. The incorrect application or interpretation of biomarkers can result in misdiagnosis and delays in appropriate treatment. Here, we discuss the uses and limitations of such biomarkers and discuss possible future developments.

Immunoglobulin (Ig) is used to treat chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy with conduction block (MMNCB). Regular infusions may be used for symptom control. Disease activity is monitored with clinical outcome measurements. We examined outcome measure variation during clinically stable periods in Ig-treated CIDP and MMNCB patients. We explored utility of serial outcome measurement in long-term outcome prediction. Retrospective longitudinal analysis of a single neuroscience centre's Ig-treated CIDP and MMNCB patients, 2009-2020, was performed. Mean and percentage change for grip strength, Rasch-built overall disability scales (RODS) and MRC sum scores (MRC-SS) during periods of clinical stability were compared to score-specific minimal clinically important differences (MCID). Latent class mixed modelling (LCMM) was used to identify longitudinal trends and factors influencing long-term outcome. We identified 85 CIDP and 23 MMNCB patients (1423 datapoints; 5635 treatment-months). Group-averaged outcome measures varied little over time. Intra-individual variation exceeded MCID for RODS in 44.2% CIDP and 16.7% MMNCB datapoints, grip strength in 10.6% (CIDP) and 8.8%/27.2% (MMNCB right/left hand) and MRC-SS in 43.5% (CIDP) and 20% (MMNCB). Multivariate LCMM identified subclinical trends towards improvement (32 patients) and deterioration (73 patients) in both cohorts. At baseline, CIDP 'deteriorators' were older than 'improvers' (66.2 vs 57 years, P = .025). No other individual factors predicted categorisation. The best model for 'deteriorator' identification was contiguous sub-MCID decline in more than one outcome measure (CIDP: sensitivity 74%, specificity 59%; MMNCB: sensitivity 73%, specificity 88%). Outcome measure interpretation determines therapeutic decision-making in Ig-dependent neuropathy patients, but intra-individual variation is common, often exceeding MCID. Here we show sub-MCID contiguous changes in more than one outcome measurement are a better predictor of long-term outcome.

Vaccination against viruses has rarely been associated with Guillain-Barré syndrome (GBS), and an association with the COVID-19 vaccine is unknown. We performed a population-based study of National Health Service data in England and a multicentre surveillance study from UK hospitals to investigate the relationship between COVID-19 vaccination and GBS. Firstly, case dates of GBS identified retrospectively in the National Immunoglobulin Database from 8 December 2021 to 8 July 2021 were linked to receipt dates of COVID-19 vaccines using data from the National Immunisation Management System in England. For the linked dataset, GBS cases temporally associated with vaccination within a 6-week risk window of any COVID-19 vaccine were identified. Secondly, we prospectively collected incident UK-wide (four nations) GBS cases from 1 January 2021 to 7 November 2021 in a separate UK multicentre surveillance database. For this multicentre UK-wide surveillance dataset, we explored phenotypes of reported GBS cases to identify features of COVID-19 vaccine-associated GBS. Nine hundred and ninety-six GBS cases were recorded in the National Immunoglobulin Database from January to October 2021. A spike of GBS cases above the 2016–2020 average occurred in March–April 2021. One hundred and ninety-eight GBS cases occurred within 6 weeks of the first-dose COVID-19 vaccination in England [0.618 cases per 100,000 vaccinations; 176 ChAdOx1 nCoV-19 (AstraZeneca), 21 tozinameran (Pfizer) and one mRNA-1273 (Moderna)]. The 6-week excess of GBS (compared to the baseline rate of GBS cases 6–12 weeks after vaccination) occurred with a peak at 24 days post-vaccination; first-doses of ChAdOx1 nCoV-19 accounted for the excess. No excess was seen for second-dose vaccination. The absolute number of excess GBS cases from January–July 2021 was between 98–140 cases for first-dose ChAdOx1 nCoV-19 vaccination. First-dose tozinameran and second-dose of any vaccination showed no excess GBS risk. Detailed clinical data from 121 GBS patients were reported in the separate multicentre surveillance dataset during this timeframe. No phenotypic or demographic differences identified between vaccine-associated and non-vaccinated GBS cases occurring in the same timeframe. Analysis of the linked NID/NIMS dataset suggested that first-dose ChAdOx1 nCoV-19 vaccination is associated with an excess GBS risk of 0.576 (95% confidence interval 0.481–0.691) cases per 100 000 doses. However, examination of a multicentre surveillance dataset suggested that no specific clinical features, including facial weakness, are associated with vaccination-related GBS compared to non-vaccinated cases. The pathogenic cause of the ChAdOx1 nCoV-19 specific first dose link warrants further study.

Anti-viral vaccination has rarely been associated with Guillain-Barré syndrome(GBS). We performed a population-based study of NHS England data and a UK multicentre surveillance study to investigate the relationship between COVID-19 vaccination and GBS.We linked GBS cases from England’s National Immunoglobulin Database(NID) with COVID-19 vaccina- tion data from December 2020–July 2021. GBS temporally associated within a 6-week risk window of any COVID-19 vaccine was identified.We prospectively collected incident UK GBS cases January–November 2021 regardless of vaccine exposure.The NID recorded 996 English GBS cases January–October 2021. A spike of cases above the 2016-2020 average occurred March–April 2021. 198 cases occurred within 6 weeks of first-dose COVID-19 vaccina- tion (0.618cases/100,000vaccinations: 176 ChAdOx1 nCoV-19, 21 tozinameran, 1 mRNA-1273). First-dose ChAdOx1 nCoV-19 accounted for the excess of 98-140 GBS cases with a peak 24 days post-vaccination. First-dose tozinameran and second-dose any vaccination showed no excess GBS risk. The UK multicen- tre surveillance dataset (121 patients) identified no phenotypic or demographic differences between vaccine-linked and unlinked cases.First-dose ChAdOx1 nCoV-19 vaccination is associated with excess GBS risk 0.576 (95%CI 0.481-0.691) cases/100,000 doses. No specific features are associated with vaccination-related GBS cases. The mechanism of immunogenicity of ChAdOx1 nCoV-19- warrants further study.

Individualized dosing is an established approach in intravenous immunoglobulin (IVIg) treatment for inflammatory neuropathies. There is less experience in effective dosing strategies for subcutaneous (SC) immunoglobulin.We conducted a retrospective cohort study of patients with inflammatory neuropathies transferring from IVIg to SCIg in two UK peripheral nerve services. I-RODS and grip strength were used to measure outcome. Dose and clinical progress were documented at 1 year and at last review.44/56 patients remained on maintenance SCIg beyond 1 year (mean 3.3 years, range 1-9 years) with stable clinical outcomes. Clinical deteriorations were corrected by small increases in SCIg dose in 20 patients at 1 year, a further 9 requiring subsequent further up-titrations. Sixteen tolerated dose reduction. Mean dose change was + 2.4% from baseline. Two patients required IVIg bolus rescue (2 g/kg). Three patients successfully discontinued Ig therapy. Nine patients returned to IVIg due to clinical relapse or patient preference. Overall tolerance was good.Dose titration to clinical response is an effective approach in SCIg maintenance therapy.

ObjectivesIntraneural perineurioma is a rare, benign neoplasm of peripheral nerve. The histopathological features are well defined.DesignWe describe 5 cases of histologically confirmed perineuriomas and 14 cases diagnosed on clinical and radiological characteristics to highlight the features of this rare entity.MethodsWe identified cases from the imaging and histopathology database and conducted a retrospective case note review.ResultsThe subjects include 7 men and 12 women, with mean (standard deviation) age of 17.64 (13) years at onset of symptoms. 14 of the 15 lower limb cases were located in the sciatic nerve or its divisions. 1 each was identified in ulnar, median and radial nerves and 1 case was in a facial nerve. The MRI features were homogenous between the groups. The nerves biopsied included 1 tibial, 1 ulnar, 1 radial, 1 facial and 1 sciatic all showing classic pathology findings. 2 patients, interestingly, had coincidental intracranial meningioma, given the recent discovery of a potential shared pathogenesis (mutations in TRAF7) with intracranial meningiomas. 2 patients had ‘skip lesions’ within the same nerve and 3 patients had foraminal and extraforaminal involvement of lumbosacral nerve roots.ConclusionsOur unit now favours the clinicoradiological features for diagnosing perineuriomas rather than performing a biopsy on all patients. Also, the potential shared pathogenesis with meningiomas raises the clinical issue of screening in patients with perineuriomas but more clinical evidence is required.