Michael P. Lunn

University College London Hospitals NHS Foundation Trust | uclh · Centre for Neuromuscular Diseases (National Hospital for Neurology and Neurosurgery)

Background Rarer antibodies associated with encephalitis are increasingly requested through specialist laboratories but little is known about the clinical utility and cost effectiveness of these requests. Methods We audited National Hospital of Neurology and Neurosurgery (NHNN) Neuroimmunology laboratory data for serum encephalitis-associated anti...

Introduction Pure autonomic failure (PAF) presents with progressive autonomic failure without other neurological features. A third later develop central neurological features, fulfilling criteria for multiple system atrophy (MSA) and Lewy body diseases (LBD). We hypothesised that multimodal autonomic biomarkers could distinguish between PAF, MSA an...

Background The efficacy of long-term treatment in patients with AAG is still unknown. We evaluated the response to immunotherapy, and the degree of residual autonomic impairment in our cohort. Methods We longitudinally characterised patient response to immunotherapy with a multimodal autonomic biomarker assessment before and after treatment. All r...

Introduction New fatigable weakness following IVIg administration, with improvement after PLEX, in an individual patient with severe, longstanding CIDP was observed on multiple occasions. Her serum displayed AChR antibody titre positivity.Therefore, we considered the possibility that (i) AChR antibodies are transmitted to patients with IVIg and (ii...

Background Intravenous immunoglobulin (IVIG) maintenance therapy in CIDP is effective in 80% of patients but is a costly and limited resource. There is sparse evidence to support mycophenolate as a potential replacement therapy. Aims To assess the efficacy of mycophenolate on IVIg dose, cost and clinical outcome measures in a cohort of CIDP patien...

The immunoglobulin M (IgM)-associated peripheral neuropathies (PN) are a heterogeneous group of disorders representing most paraproteinemic neuropathy cases. They are associated with IgM monoclonal gammopathy of undetermined significance (MGUS) or Waldenström macroglobulinemia. Establishing a causal link between a paraprotein and neuropathy can be...

Polyneuropathy Organomegaly, Endocrinopathy, Monoclonal protein and Skin changes syndrome is a rare multisystem condition with a range of manifestations which are often overlooked as trivial comorbidities, until their whole triggers the possibility of the diagnosis. The diagnosis is typically delayed by 12-16 months, by which time patients can be s...

Aims: To explore associations between plasma neurofilament light chain concentration (pNfL; pg/mL) and disease activity in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and examine the usefulness of pNfL concentrations in determining disease remission. Methods: We examined pNfL concentrations in treatment-naïve C...

Introduction Historically, single tissue vasculitis has been managed with steroid monotherapy. Recent data from large longitudinal databases on systemic vasculitis suggest Non-Systemic Vasculitic Neuropathy (NSVN) has higher rates of relapse, recommending that more aggressive immunotherapy is employed. Aim To investigate the relapse rate in NSVN i...

Background: Regular immunoglobulin treatment maintains strength and prevents disability in CIDP. Discrimination between active disease, with optimum symptom control on treatment, and disease in remission not requiring treatment is essential for therapeutic decision making and clinical trial design. Aims: To compare treatment cessation versus gra...

SARS-CoV-2 is associated with new-onset neurological and psychiatric conditions. Detailed clinical data, including factors associated with recovery, are lacking, hampering prediction modelling and targeted therapeutic interventions. In a UK-wide cross-sectional surveillance study of adult hospitalised patients during the first COVID-19 wave, with m...

Paraproteinaemic neuropathies comprise a heterogeneous group of neuro-haematological conditions with some distinct neurological, haematological and systemic phenotypes. The spectrum of disease varies from mild to severe, indolent to rapidly progressive and from small fibre sensory involvement to dramatic sensorimotor deficits. The haematological as...

Preliminary pathological and biomarker data suggest that SARS-CoV-2 infection can damage the nervous system. To understand what, where and how damage occurs, we collected serum and CSF from patients with COVID-19 and characterised neurological syndromes involving the peripheral and central nervous system (n = 34). We measured biomarkers of neuronal...

Background International guidelines recommend either intravenous immunoglobulin (IVIg) or corticosteroids as first-line treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). IVIg treatment usually leads to rapid improvement and is generally safe, but does not seem to lead to long-term remissions. Corticosteroids act more s...

The heterogeneous disease course of COVID-19 is unpredictable, ranging from mild self-limiting symptoms to cytokine storms, acute respiratory distress syndrome (ARDS), multi-organ failure and death. Identification of high-risk cases will enable appropriate intervention and escalation. This study investigates the routine laboratory tests and cytokin...

Severe COVID‐19 disease is a hyperinflammatory, pro‐thrombotic state. We undertook plasma exchange (PEX) to determine its effects on organ function and thrombo‐inflammatory markers. Seven critically ill adults with severe COVID‐19 respiratory failure (PaO2:FiO2 ratio < 200 mm Hg) requiring invasive or noninvasive ventilatory support and elevated th...

Background IgM paraprotein-associated peripheral neuropathies (PN) are a heterogenous group of disorders seen in patients with IgM MGUS and Waldenström's Macroglobulinaemia (WM). Anti-myelin associated glycoprotein (MAG) antibodies are causally identified in ~50% of such cases, but other neuropathies with other IgM-targets are described, along with...

Introduction Severe COVID-19 disease is associated with a hyperinflammatory, pro-thrombotic state and a high mortality. A thrombotic phenotype rather than a coagulopathy is suggested and we undertook plasma exchange to determine its effects on organ function and thrombo-inflammatory markers. Methods Plasma exchange was carried out in seven critical...

BACKGROUND Bing-Neel Syndrome (BNS), characterised by the direct infiltration of central nervous system (CNS) with clonal lymphoplasmacytic lymphoma cells, is a rare cause of neurological complications in patients with Waldenström Macroglobulinaemia (WM). The pathophysiology/neurotropism of BNS is not well understood. Various treatments that appear...

Background Prompt diagnosis and early treatment prevents disability in Polyneuropathy Organomegaly Endocrinopathy Monoclonal-protein and Skin Changes (POEMS) syndrome. Delay in diagnosis is common with 55% of patients initially incorrectly diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Patients are often treated wi...

Background: Intravenous immunoglobulin (IVIg) has short and long-term efficacy in both chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy with conduction block (MMNCB). There is potential for under and over-treatment if trial regimens are strictly adhered to in clinical practice where titrating dose to clinica...

The heterogeneous disease course of COVID-19 is unpredictable, ranging from mild self-limiting symptoms to cytokine storms, acute respiratory distress syndrome (ARDS), multi-organ failure and death. Identification of high-risk cases will enable appropriate intervention and escalation. This study investigates the routine laboratory tests and cytokin...

Introduction This series characterises 9 patients with neurohistopathologically proven peripheral nerve neurolymphomatosis. Methods A search of the hospital neuropathology database from 2002‐2019 identified biopsy proven cases. Clinical data, investigation modalities, treatments and outcomes were collated. Results Median age at neuropathy onset w...

Background Reports of Guillain-Barre Syndrome (GBS) have emerged during the Coronavirus Disease 2019 (COVID-19) pandemic. This epidemiological and cohort study sought to investigate any causative association between COVID-19 infection and GBS. Methods The epidemiology of GBS cases reported via the UK National Immunoglobulin Database were studied fr...

Purpose Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a treatable, immune-mediated condition characterised by progressive or relapsing motor and sensory neurological deficits. The diagnosis is based on a combination of clinical, neurophysiological and supportive criteria, but can be challenging. In this study, we quantified th...

Covid-19 Neurological Illness

Objective POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin lesions) is a paraneoplastic disorder resulting in severe neurologic disability. Understanding the clinical, laboratory, neurophysiologic, and histopathologic features as well as treatment responses of POEMS will assist in more accurate and timel...

Arterial and venous thromboses occur in patients with POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein level, and skin changes) syndrome at a previously reported rate of 20%. We reviewed the University College London Hospitals (UCLH) POEMS Registry to determine the rate of venous thromboembolism (VTE), arterial events, and risk factor...

Background: Guillain-Barré syndrome (GBS) is an autoimmune disease that results in demyelination and axonal damage. Five percent of patients die and 20% remain significantly disabled on recovery. Recovery is slow in most cases and eventual disability is difficult to predict, especially early in the disease. Blood or cerebrospinal fluid (CSF) bioma...

Background: There is limited data on cerebrospinal fluid (CSF) biomarkers in sporadic amyloid-β (Aβ) cerebral amyloid angiopathy (CAA). Objective: To determine the profile of biomarkers relevant to neurodegenerative disease in the CSF of patients with CAA. Methods: We performed a detailed comparison of CSF markers, comparing patients with CAA,...

Our objective was to evaluate whether IV immunoglobulin (IVIg) increases the risk of thromboembolic events in neurology outpatients with inflammatory neuropathies, as there is conflicting evidence supporting this hypothesis, mainly from non-neurologic cohorts. We investigated this question over 30 months in our cohort of patients with inflammatory...

Introduction Arterial and venous events are known to occur in patients with POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, Skin changes) syndrome which may also include myeloproliferation, with a reported rate in the literature of around 20%. This is higher than in the myeloma cohort where the VTE rate from the UK Myelo...

IgM paraprotein‐associated peripheral neuropathy (PN) in patients without overt evidence of lymphoma is a recognised clinical entity of unknown aetiology. Interrogating the bone marrow B‐cell or plasma cell clones underlying paraproteinemic neuropathies may improve our understanding of both pathogenesis and treatment options. This retrospective obs...

Objective To compare disease course in patients with Guillain-Barré syndrome (GBS) with a poor prognosis who were treated with one or with two intravenous immunoglobulin (IVIg) courses. Methods From the International GBS Outcome Study, we selected patients whose modified Erasmus GBS Outcome Score at week 1 predicted a poor prognosis. We compared t...

Hereditary transthyretin amyloidosis (ATTRm) causes a disabling peripheral neuropathy as part of a multisystem disorder. The recent development of highly effective gene silencing therapies has highlighted the need for effective biomarkers of disease activity to guide the decision of when to start and stop treatment. In this study we measured plasma...

Background: Pre-treatment screening for IgA deficiency and close monitoring of full blood count(FBC) and renal function is recommended with intravenous immunoglobulin(IVIg) therapy in neurological diseases. Aims: To examine the frequency of biochemically defined and clinically significant episodes of treatment associated haemolysis, neutropenia,...

Purpose of review: There is an increasingly recognized association between haematological and neurological disease. This is especially true in the peripheral nervous system in which, to an extent, proof of a link is easier to achieve. The most sensitive low level paraprotein detection methods should always be employed in which a paraprotein is sus...

Introduction Identifying patients who need long-term immunoglobulin (IVIg) treatment in patient with inflammatory neuropathies is essential as recent treatment trials show a remission rate of up to 40%. Aims Compare retrospective data on clinical, investigational and treatment factors in patients who have ceased IVIg with patients who have failed...

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes) is a rare paraneoplastic phenomenon secondary to plasma cell dyscrasia. Treatment is aimed at the underlying plasma cell clone and its survival factors. Autologous stem cell transplantation (ASCT) is selected for patients who have multifocal skeletal...

Background POEMS syndrome is a paraneoplastic phenomenon whose pathogenesis is not fully understood, but an underlying plasmaproliferative process appears to promote cytokine release, including vascular endothelial growth factor (VEGF) which induces capillary leakage and tissue damage. High dose melphalan‐conditioned autologous stem cell transplant...

Objective Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) syndrome is a rare multisystem disease associated with a plasma-cell dyscrasia. Although pachymeningeal involvement has occasionally been described, MRI of the central nervous system (CNS) has not yet been extensively investigated. Methods We retros...

Objectives Intraneural perineurioma is a rare, benign neoplasm of peripheral nerve. The histopathological features are well defined. Design We describe 5 cases of histologically confirmed perineuriomas and 14 cases diagnosed on clinical and radiological characteristics to highlight the features of this rare entity. Methods We identified cases fro...

[This corrects the article DOI: 10.1371/journal.pone.0211184.].

Sepsis-associated encephalopathy (SAE) contributes to mortality and neurocognitive impairment of sepsis patients. Neurofilament (Nf) light (NfL) and heavy (NfH) chain levels as biomarkers for neuroaxonal injury were not evaluated in cerebrospinal fluid (CSF) and plasma of patients with sepsis-associated encephalopathy (SAE) before. We conducted a p...

Systemic amyloidosis can be hereditary or acquired. The autosomal dominant hereditary transthyretin amyloidosis and the acquired light-chain amyloidosis, the result of a plasma cell dyscrasia, are multisystem disorders with cardiovascular, autonomic and peripheral nerve involvement. There are numerous investigational modalities available to diagnos...

The longest contiguous CAG repeat stretch in the SCA17 pathogenic allele size does not influence age at disease onset. Age at disease onset data was available for 21 SCA17 patients that had been both analyzed by fragment sizing and clone sequencing. Cloning and sequencing the SCA17 alleles allows the configuration of the repeat tract to be determin...

Frequency with which each clone sequence was detected for each individual in our cohort. The bold lines indicate the variable penetrance range between 41 and 48 repeats. Domains 1–5 refer to the Domains I–V of the repeat structure as depicted in Figure 1. 467 clones with 61 unique repeat region sequences were analyzed from 30 individuals with varia...

Frequency with which each clone sequence was detected for each individual in our cohort, corrected for the clone depth sequenced for each patient. The bold lines indicate the variable penetrance range between 41 and 48 repeats. Domains 1–5 refer to the Domains I–V of the repeat structure as depicted in Figure 1. 467 clones with 61 unique repeat reg...

Fragment and sequence analysis of SCA17 alleles in four patients in an Italian cohort. SCA17 alleles were sized by fragment analysis and subsequently sequenced at the Institute of Translational Pharmacology, Rome. Interestingly, two of these patients, G31 and G32, lack the final (CAA/CAG) Domain V interruption which is observed in all clones from t...

Summary of age at disease onset and allele size data for each individual. Data is presented from both fragment sizing and clone sequencing normal and expanded alleles. Age at onset data was available for 21 out of 30 individuals. Patient #8 (highlighted in blue italics) had a genetic diagnosis of ARCA1/SCAR8 (see text), which explains the early age...

Patients with 41 and 42 repeat alleles contribute to improving the correlation between SCA17 pathogenic allele size and age at disease onset. Age at disease onset data was available for 21 SCA17 patients that had been both analyzed by fragment sizing and clone sequencing and this data is plotted in red. If patients with 41 and 42 repeats are exclud...

Short tandem repeat (STR) analysis to confirm identity of individuals #4, 5, 13, and 16. The PowerPlex 16HS System was used to amplify microsatellite markers at 15 STR loci. Numbers represent the alleles (repeat numbers) at that locus. This data confirms that father (#5) and child (#4) are separate samples and yet have the same 51-repeat pathogenic...

Spinocerebellar ataxia type 17 (SCA17) is a rare autosomal dominant neurodegenerative disease caused by a CAG repeat expansion in the TATA-box binding protein gene (TBP). The disease has a varied age at onset and clinical presentation. It is distinct from other SCAs for its association with dementia, psychiatric symptoms, and some patients presenti...

Background Autoimmune Autonomic Ganglionopathy (AAG) is a rare, immune-mediated condition characterised by subacute pandysautonomia. 50% have auto-antibodies to the ganglionic nicotinic acetylcholine receptor (gAChR), affecting synaptic transmission at autonomic ganglia. Methods We describe 13 patients (5 female, median age 47) presenting with wid...

We present the case of a 46 year old man who developed a rapidly progressive sensorimotor neuropathy and skin changes. He was diagnosed with Guillain-Barré Syndrome, and subsequently CIDP, but his condition continued to progress despite IVIG treatment and plasma exchange. On transfer to the National Hospital of Neurology and Neurosurgery, six month...

Background There is currently no accurate way to determine who will need long-term immunoglobulin (IVIg) treatment in chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). Aims Retrospectively compare clinical, investigational and treatment factors in patients who have successfully ceased IVIg with patient...

Context POEMS syndrome is a rare multisystem disorder characterised by polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma-proliferative disorder and skin changes among other features. Objective To describe the prevalence and course of the endocrine dysfunction in the context of POEMS. Design Cohort study with systematic review of the...

Objective: To investigate the sensitivity and the specificity of serum vascular endothelial growth factor (sVEGF) for the diagnosis of polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome in patients with a neuropathy (NP) and to identify confounding causes of raised vascular endothelial growth factor (VEGF) i...

Objectives The treatments of limbic and other autoimmune encephalitis include immunosuppression, symptomatic treatment, and in the case of paraneoplastic syndromes, appropriate therapy for underlying neoplasms. When immunotherapy is considered, intravenous immunoglobulin is one option for treatment, either alone or in combination with corticosteroi...

Purpose of review: To provide an overview of polyneuropathy organomegaly endocrinopathy M-protein and skin changes (POEMS) syndrome, detailing new insights into pathogenesis, prognostic factors, treatments, and outcome scores. Recent findings: With the development of large multicentre national cohorts of patients, POEMS syndrome is evolving into...

Objective To assess the therapeutic potential of bortezomib in treatment refractory NMDA receptor (NMDAR) antibody encephalitis and its potential in other immune mediated, B‐cell driven neurological diseases. Methods Two cases of severe NMDAR‐antibody encephalitis, resistant to first and second line therapy with steroids, IV immunoglobulins, plasm...

Background: Cerebrospinal fluid (CSF) biomarkers are increasingly being used to support a diagnosis of Alzheimer's disease (AD). Their clinical utility for differentiating AD from non-AD neurodegenerative dementias, such as dementia with Lewy bodies (DLB) or frontotemporal dementia (FTD), is less well established. We aimed to determine the diagnos...

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 sk...