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Within the last decade, antibodies targeting the node and paranode of myelinated peripheral nerves have been increasingly identified in patients with acquired immune-mediated neuropathies, commonly termed ‘nodo-paranodopathies’. Crucially, these patients often present with additional clinical features not usually seen with the most common immune-mediated neuropathies, Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy, and respond poorly to conventionally used immunomodulatory therapies. Emerging evidence that these are pathologically distinct diseases has further prompted the use of more targeted treatment, such as the B cell depleting monoclonal antibody rituximab, which has been reported to significantly improve functional outcomes in this subset of patients. We provide an overview of the emerging clinical and serological phenotypes in patients with specific nodal/paranodal antibodies, the practicalities of antibody testing and current evidence supporting the use of non-standard therapies.

BackgroundNitrous 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.MethodsWe 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.ResultsParaesthesia 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 B12deficiency (rho (ρ)=0.44, p=0.04).ConclusionsPreventable 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.

BackgroundPOEMS syndrome is a rare cause of neuropathy misdiagnosed as Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) in 60% of cases. Ineffective CIDP directed therapy is expensive, introduces risk of complications, and often results in disease progression. Vascular endothelial growth factor (VEGF) is a sensitive and specific biomarker in the diagnosis of POEMS syndrome costing approximately £50. Introducing early directed screening with VEGF more accurately distinguishes POEMS syndrome from CIDP than the current standard of care (SOC).Methods100 cases from the UCLH POEMS database were selected. We grouped patients according to diagnostic pathway and compared health outcomes. We conducted a model-based cost-effectiveness analysis to compare diagnostic outcomes and costs of the current SOC with intervention pathways using VEGF screening. We used a study cohort of 1,250 patients with polyneuropathy (UK incidence) and conducted costing from a health-services perspective.ResultsTreatments associated with POEMS misdiagnosis led to a total healthcare expenditure in our cohort of £808,550-£1,111,756 over 20 years, with an average cost-per-POEMS-syndrome-patient misdiagnosed of£14,701-£20,214. Our intervention pathway which introduces VEGF screening into the current SOC results in 4 additional early POEMS diagnoses per year and a cost-saving of almost £40,000 through avoidance of non-POEMS directed therapy and related hospital costs.ConclusionVEGF testing should be routine for patients presenting with an acquired demyelinating neu- ropathy. This will improve early diagnosis of POEMS syndrome, enable effective therapy and reduce cos8ts5.stephen.keddie@nhs.net

BackgroundArterial and venous thrombotic events occur in patients with POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin changes) syndrome with a previously reported rate of 20%. We reviewed the UK POEMS Registry to describe the rate of venous thromboembolism (VTE), arterial events and risk factors.MethodsThe UK POEMS Registry is the largest single-centre cohort in Europe and comprises 100 patients. Data were collected on arterial and venous thrombotic events from 1999 to present day.ResultsOf the 83 assessable patients, median age at presentation was 52 years. Twenty-five patients expe- rienced 35 clinically apparent arterial or venous events. Eleven patients had 14 VTEs including deep vein thrombosis (DVT, 4/14), pulmonary embolism (4/14) and peripherally inserted central catheter-associated DVT occurring during autologous stem cell transplant (4/14). Sixteen patients experienced 21 arterial events: stroke (7/21), peripheral arterial occlusion (6/21), myocardial infarction (4/21) and microvascular disease (2/21), with no discernible relationship with thrombocytosis or polycythaemia. The combined venous and arterial event rate was 42%, over double that previously reported. There were more arterial than venous events, and most occurred during active pre-treated disease indicating a need for a pre- emptive approach to thromboprophylaxis.ConclusionArterial and venous thromboses are more common in POEMS syndrome than previously reported and appear associated with disease pathology and activity. We propose a management strategy for appropriate thromboprophylaxis in POEMS patients throughout the course of disease.stephen.keddie@nhs.net

POEMS syndrome is a rare and disabling autoinflammatory condition characterised by a typical peripheral neuropathy and the presence of a monoclonal plasma cell disorder. The acronym ‘POEMS’ represents the complex and multisystem features of the disease, including polyneuropathy, organomegaly, endocrinopathy, a monoclonal plasma cell disorder and skin disease. The diagnosis of POEMS is a significant challenge because of the heterogeneity of clinical presentations and variation of POEMS features. Patients are often misdiagnosed with another cause of inflammatory neuropathy and receive one or more ineffective immunomodulatory medications, resulting in delayed diagnosis and further clinical deterioration before a diagnosis is made. University College London Hospitals sees one of the largest reported POEMS cohorts in Europe, and runs a multispecialist clinic to assist with diagnosis, treatment and ongoing support. This review draws upon our experience to present the typical features of POEMS syndrome and highlight diagnostic conundrums commonly experienced, supplemented with clinical cases. We provide an investigative guide for clinicians when considering POEMS as the diagnosis, and propose a treatment algorithm that centres on the site and degree of monoclonal cell proliferation.

A 26-year-old man was referred with facial weakness, dysarthria, dysphagia, ophthalmoparesis and severely weak and wasted legs. His symptoms had begun when aged 20 with electric shock pains and paraesthesia in both feet progressing over 6 months to the lower calves. He then developed buttock numbness and occasional faecal incontinence. By age 22, he had diffuse lower limb weakness and wasting, with difficulty standing from a seated position and frequent tripping. He became wheelchair-dependent within 3 years. Over the same time period, he developed progressive facial weakness, bilateral ptosis, slurred speech, difficulty chewing and swallowing and lost 10 kg of weight. He reported hearing difficulty, and an audiogram showed high-frequency hearing loss. Important negatives included absence of upper limb symptoms, autonomic, cardiac, respiratory or cognitive dysfunction. He was from a non-consanguineous, Lithuanian background and the eldest of three siblings. He was born following a normal pregnancy and delivery, and motor development was normal. He had sustained a left corneal abrasion with visual impairment following an accidental chemical injury aged 14. During the initial investigation of his symptoms (age 23), he was found to have a choroid plexus lesion in the fourth ventricle. It was completely resected and histology confirmed benign choroid plexus papilloma WHO grade I. Postoperative neuro-oncology discussion deemed the lesion cured. He had bilateral ptosis, bilateral facial wasting and could not close his mouth against gravity (figure 1A). Visual acuity was reduced to perception of light on the left, 6/9 on the right. There was almost complete, complex ophthalmoplegia (figure 1B) without fatiguability. Trigeminal sensation was reduced. He could not achieve eyelid closure; frontalis, buccinator and orbicularis oris were symmetrically weak. His speech was dysarthric and his tongue was weak. His uvula was central with symmetrical palatal movement, but the gag reflex was reduced. Figure 1 Clinical examination at age 26. …

A 51-year-old right-handed man developed a sensory neuropathy with the sensation of walking on pebbles, and tight cramping pains in the calves requiring amitriptyline. Two months later, he became unsteady with difficulty walking downstairs necessitating a stick, with associated fatigue and weight loss of half a stone. He had a history of haemophilia type A and liver cirrhosis from hepatitis C, contracted through the transfusion of blood products in the 1980s. On examination, there was evidence of a distal symmetrical sensorimotor polyneuropathy with Medical Research Council (MRC) power grade 4+/5 in the intrinsic hand muscles and 0/5 in ankle plantar and dorsiflexion. Supinator, knee and ankle deep tendon reflexes were all absent, with mute plantar responses. He had a loss of pinprick sensation to the knees, vibration loss to the costal margins and temperature perception was altered to the mid-thighs. There was dusky pigmentation of the skin and peripheral oedema in the lower limbs. His history and examination findings are typical of a distal symmetrical neuropathy (see box 1 for the differential diagnosis of a painful large fibre neuropathy). Serological workup for a neuropathy should include full blood count, B12, folate, erythrocyte sedimentation rate (ESR), glucose, thyroid function, a serum protein electrophoresis and immunofixation, and possibly an antinuclear antibody. Note that it is typical for hospital laboratories only to perform serum immunofixation if the serum protein electrophoresis is abnormal. The greater sensitivity of immunofixation may find low-level paraproteins that would be otherwise undetectable, and which may be highly relevant in the context of neuropathy. He also has a history of hepatitis C which is associated with cryoglobulinaemia and cryoglobulinaemic peripheral nerve vasculitis, and therefore an important differential. Constitutional symptoms, including weight loss, are uncommon in isolated peripheral neuropathy, and therefore systemic causes should be considered, including vasculitis, malignancies, metabolic (diabetes), …

Doctors in training are allowed to apply to go ‘Out Of Progamme’ (OOP) to perform research, develop their clinical experience or take a career break. New replacement numbers are not released when a trainee takes an OOP. From 1 January 2016, Locum Appointments for Training (LAT) posts, across all specialties, ended in England. There is now a mismatch between trainee numbers wanting to take time out of programme and those in clinical training programmes. A survey was conducted into OOP preferences of neurology trainees throughout the North London training programme. 48 of 52 trainees responded to the email questionnaire to ascertain the following; 1. What proportion of trainees had already taken time OOP, 2. How many were looking to apply and what year, 3. How many years will trainees apply for OOP, and 4. Do trainees feel taking time OOP is a valuable experience, Neurology is a particularly academic speciality, where time OOP to develop research skills and experience is frequently requested; our survey demonstrates that the majority of trainees in the North London programme will have a research degree by the time they complete training. The survey also demonstrates the considerable benefits that trainees obtain from a period of OOP for research. We postulate that Health Education England should allow ‘mortgaging’ of training numbers in neurology to accommodate demand for OOPs without compromising adequate fill rates in clinical training programmes

Disparity exists between clinical practice and guidelines on discussion of Sudden death in epilepsy (SUDEP) with patients. This study examined how patients were informed about SUDEP; the impact of such discussion, and their views on the discussion.MethodsA quantitative/qualitative questionnaire was given to 50 consenting patients attending epilepsy clinics. Exclusions were patients with intellectual disability, and/or those deemed at risk of negative consequences on completing the study.Results98% of patients were aware of the importance of medication adherence, 78% of driving regulations in epilepsy, and 84% of factors influencing seizure frequency. Only 50% of patients were aware of SUDEP and 38% of status epilepticus.42% of patients preferred SUDEP information at diagnosis and 36% only after three clinic appointments.Negative emotional responses (in 38%), and not behavioural changes, resulted from SUDEP discussions.ConclusionsIn this small in-depth study, only half the patients recalled information about SUDEP. More than one-third of patients reported adverse consequences. There was no improvement in self-management.We suggest a paradigm shift: embedding SUDEP discussion with all potential complications of epilepsy; and emphasising optimal healthcare and self-management. This model has been successfully applied in other areas to empower patients and improve outcome.