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Introduction: Disease susceptibility of chronic axonal polyneuropathy is not fully explained by clinical risk factors. Therefore, we determined the contribution of common genetic variants in chronic axonal polyneuropathy in the general population. Methods: This study was performed in two population-based studies. Polyneuropathy diagnosis was based on screening in the Rotterdam Study and on ICD-10 codes in the UK Biobank. We determined the heritability of the sural nerve amplitude and performed genome-wide association studies of chronic axonal polyneuropathy and sural sensory nerve amplitude. Furthermore, we zoomed in on variants in and surrounding 100 autosomal genes known to cause polyneuropathy based on literature and expert knowledge (candidate genes), and we performed a gene-based analysis. Analyses were adjusted for age, sex and population stratification. Results: Chronic axonal polyneuropathy was present in 2,357 of the 458,567 participants and 54.3% of the total population was female. Heritability of sural nerve amplitude was 0.49 (p = 0.067) (N = 1,153). No variants (p < 5.0×10-8) or genes (p < 2.7×10-6) reached genome-wide significance for its association with polyneuropathy. Focusing on variants in and surrounding the candidate genes in the GWAS (p < 3.9×10-6) and on these genes in the gene-based analysis (p < 5.0×10-4) neither yielded significant results. Discussion: We did not find common variants associated with chronic axonal polyneuropathy in the general population. Larger studies are needed to determine if genetic susceptibility based on both common and rare genetic variants affect the risk for chronic axonal polyneuropathy in the general population. [ABSTRACT FROM AUTHOR]

Pedigree analysis showed that a large proportion of Leber hereditary optic neuropathy (LHON) family members who carry a mitochondrial risk variant never lose vision. Mitochondrial haplotype appears to be a major factor influencing the risk of vision loss from LHON. Mitochondrial variants, including m.14484T>C and m.11778G>A, have been added to gene arrays, and thus many patients and research participants are tested for LHON mutations. Analysis of the UK Biobank and Australian cohort studies found more than 1 in 1,000 people in the general population carry either the m.14484T>C or the m.11778G>A LHON variant. None of the subset of carriers examined had visual acuity at 20/200 or worse, suggesting a very low penetrance of LHON. Haplogroup analysis of m.14484T>C carriers showed a high rate of haplogroup U subclades, previously shown to have low penetrance in pedigrees. Penetrance calculations of the general population are lower than pedigree calculations, most likely because of modifier genetic factors. This Matters Arising Response paper addresses the Watson et al. (2022) Matters Arising paper, published concurrently in The American Journal of Human Genetics. [ABSTRACT FROM AUTHOR]

After extensive evaluation, one-third of patients affected by polyneuropathy remain undiagnosed and are labelled as having chronic idiopathic axonal polyneuropathy, which refers to a sensory or sensory-motor, axonal, slowly progressive neuropathy of unknown origin. Since a sensory neuropathy/neuronopathy is identified in all patients with genetically confirmed RFC1 cerebellar ataxia, neuropathy, vestibular areflexia syndrome, we speculated that RFC1 expansions could underlie a fraction of idiopathic sensory neuropathies also diagnosed as chronic idiopathic axonal polyneuropathy. We retrospectively identified 225 patients diagnosed with chronic idiopathic axonal polyneuropathy (125 sensory neuropathy, 100 sensory-motor neuropathy) from our general neuropathy clinics in Italy and the UK. All patients underwent full neurological evaluation and a blood sample was collected for RFC1 testing. Biallelic RFC1 expansions were identified in 43 patients (34%) with sensory neuropathy and in none with sensory-motor neuropathy. Forty-two per cent of RFC1-positive patients had isolated sensory neuropathy or sensory neuropathy with chronic cough, while vestibular and/or cerebellar involvement, often subclinical, were identified at examination in 58%. Although the sensory ganglia are the primary pathological target of the disease, the sensory impairment was typically worse distally and symmetric, while gait and limb ataxia were absent in two-thirds of the cases. Sensory amplitudes were either globally absent (26%) or reduced in a length-dependent (30%) or non-length dependent pattern (44%). A quarter of RFC1-positive patients had previously received an alternative diagnosis, including Sjögren's syndrome, sensory chronic inflammatory demyelinating polyneuropathy and paraneoplastic neuropathy, while three cases had been treated with immune therapies. [ABSTRACT FROM AUTHOR]

Background: This study used quantitative and qualitative research methods to analyze how acute hepatic porphyria (AHP) affects patients with varying annualized porphyria attack rates. The overall impact of AHP on patients and caregivers, including their quality of life, was explored. The nature and treatment of acute attacks, experiences of long-term heme arginate treatment and access to other appropriate treatment, and the extent of and treatment for chronic symptoms were also investigated within this study.Methods: Patient and caregiver data were collected via an online survey of members of the British Porphyria Association, followed by an optional 1-h telephone interview.Results: Thirty-eight patients and 10 caregivers responded to the survey. Of those, 10 patients and three caregivers completed follow-up interviews. Overall, 19 patients (50%) had experienced an acute attack within the previous 2 years, and the severity and types of symptoms experienced during or between acute attacks varied considerably. There were no clear definitions among patients for 'mild' or 'severe' attacks. Treatments and treatment settings used to manage attacks also varied. Following unsatisfactory care experiences at hospitals, some patients reported avoiding further hospital services for later attacks. Therefore, using settings of care as a measure of attack severity should be avoided. Ninety-four percent of patients also experienced chronic symptoms, which were as varied as acute attacks. Pain was the predominant chronic symptom and was managed with opioids in severe cases. Regardless of AAR, porphyria heavily impacted the daily lives of patients and caregivers. Although patients experiencing frequent attacks generally endured a greater impact on their daily life, patients with less frequent attacks also experienced impacts on all domains (social, leisure activities, relationship with family, relationships, psychological wellbeing, finances, employment, and study). Caregivers were most affected in the finance, relationships with family, and employment domains, and just over half of the caregivers reported a moderate impact on their psychological wellbeing.Conclusions/implications: The burden of illness with AHP is high across all patients, regardless of frequency of attacks, and AHP negatively affects patients and caregivers alike. [ABSTRACT FROM AUTHOR]

• Chronic pain is common in patients with mitochondrial disease. • Pain due to mitochondrial disease is primarily of neuropathic nature. • Distribution, intensity and type of pain are genetically determined. In the absence of cure, the main objectives in the management of patients with mitochondrial disease are symptom control and prevention of complications. While pain is a complicating symptom in many chronic diseases and is known to have a clear impact on quality of life, its prevalence and severity in people with mitochondrial disease is unknown. We conducted a survey of pain symptoms in patients with genetically confirmed mitochondrial disease from two UK mitochondrial disease specialist centres. The majority (66.7%) of patients had chronic pain which was primarily of neuropathic nature. Presence of pain did not significantly impact overall quality of life. The m.3243A>G MTTL1 mutation was associated with higher pain severity and increased the likelihood of neuropathic pain compared to other causative nuclear and mitochondrial gene mutations. Although previously not considered a core symptom in people with mitochondrial disease, pain is a common clinical manifestation, frequently of neuropathic nature, and influenced by genotype. Therefore, pain-related symptoms should be carefully characterised and actively managed in this patient population. [ABSTRACT FROM AUTHOR]

Foot ulceration in people with diabetes is a global problem (Boulton, 2004). The human and financial costs within the UK are significant and increasing with a calculation of £900m for the year 2014-15 (Kerr, 2019). On average, an episode of ulceration costs the NHS £14,600 to treat (Kerr, 2017). Ulcerations increase 5-year morbidity by almost 2.5 times (Walsh, 2016). The presence of callus and neuropathy occur commonly and are a recognised high predicator of foot ulceration (International Working Group on the Diabetic Foot, 2019; NICE, 2019). National and international guidelines recommend the use of emollients and the reduction of callus as important preventative actions. Most people with diabetes are likely to have their first interaction with professional advice on ulcer prevention within the community in a primary care setting. Patients with callus and neuropathy are most likely to be prescribed non-keratolytic emollients or, on rare occasions, low-concentration urea creams by their GP to treat callus. This paper assesses the effectiveness of these creams in treating callus in patients referred to diabetic foot clinics, and compares their efficacy to that of a high-concentration keratolytic (25% urea) cream prescribed or recommended by podiatrists. [ABSTRACT FROM AUTHOR]

Background: Low-density lipoprotein cholesterol (LDL-C) is causally associated with a high risk of coronary artery disease. Whether this also holds for a spectrum of peripheral vascular diseases is unknown.Objectives: The purpose of this study was to determine whether high LDL-C causally relates to risk of retinopathy, neuropathy, chronic kidney disease (CKD), and peripheral arterial disease (PAD) in the general population.Methods: One-sample Mendelian randomization (MR) of 116,419 Danish individuals, 2-sample MR on summary-level data from the Global Lipid Genetics Consortium (GLGC) (n = 94,595) and the UK Biobank (n = 408,455), and meta-analysis of randomized statin trials (n = 64,134) were performed.Results: Observationally, high LDL-C did not associate with high risk of retinopathy or neuropathy. There were stepwise increases in risk of CKD and PAD with higher LDL-C (both p for trend <0.001), with hazard ratios of 1.05 (95% confidence interval [CI]: 0.97 to 1.13) for CKD, and 1.41 (95% CI: 1.23 to 1.62) for PAD in individuals with LDL-C above the 95th percentile versus below the 50th percentile. In genetic, causal analyses in the Copenhagen studies, the risk ratio of disease for a 1 mmol/l higher LDL-C was 1.06 (95% CI: 0.24 to 4.58) for retinopathy, 1.05 (95% CI: 0.64 to 1.72) for neuropathy, 3.83 (95% CI: 2.00 to 7.34) for CKD, and 2.09 (95% CI: 1.30 to 2.38) for PAD. Summary-level data from the GLGC and the UK Biobank for retinopathy, neuropathy, and PAD gave similar results. For CKD, a 1-mmol/l lower LDL-C conferred a higher eGFR of 1.95 ml/min/1.73 m2 (95% CI: 1.88 to 2.02 ml/min/1.73 m2) observationally, 5.92 ml/min/1.73 m2 (95% CI: 4.97 to 6.86 ml/min/1.73 m2) genetically, and 2.69 ml/min/1.73 m2 (95% CI: 1.48 to 3.94 ml/min/1.73 m2) through statin therapy.Conclusions: High LDL-C was not causally associated with risk of retinopathy and neuropathy; however, high LDL-C was observationally and genetically associated with high risks of PAD and CKD, suggesting that LDL-C is causally involved in the pathogenesis of these diseases. [ABSTRACT FROM AUTHOR]

Aims: To assess the utility of corneal confocal microscopy in identifying small fiber damage in patients with burning mouth syndrome (BMS). Methods: A prospective cross-sectional cohort study was conducted at two United Kingdom dental hospitals between 2014 and 2017. A total of 17 consecutive patients with idiopathic BMS aged between 18 and 85 years and 14 healthy age-matched control subjects were enrolled in this study. Corneal subbasal nerve plexus measures were quantified in images acquired using a laser-scanning in vivo corneal confocal microscope. The main outcome measures were corneal nerve fiber density, nerve branch density, nerve fiber length, and Langerhans cell density. Results: Of the 17 patients with BMS, 15 (88%) were women, and the mean (standard deviation) age of the sample was 61.7 (6.5) years. Of the healthy controls, 7 (50%) were women, and the mean (standard deviation) age was 59.3 (8.68) years. Corneal nerve fiber density (no./mm2) (BMS: 29.27 ± 6.22 vs controls: 36.19 ± 5.9; median difference = 6.71; 95% CI: 1.56 to 11.56; P = .007) and corneal nerve fiber length (mm/mm2) (BMS: 21.06 ± 4.77 vs controls: 25.39 ± 3.91; median difference = 4.5; 95% CI: 1.22 to 6.81; P = .007) were significantly lower in BMS patients compared to controls, and Langerhans cell density (no./mm2) (BMS: 74.04 ± 83.37 vs controls: 29.17 ± 45.14; median difference = -21.27; 95% CI: -65.35 to -2.91; P = .02) was significantly higher. Conclusion: Using a rapid noninvasive ophthalmic imaging technique, this study provides further evidence for small fiber damage in BMS and has potential utility for monitoring disease progression and/or response. Furthermore, this technique shows a hitherto undocumented increased density of immune cells in this group of patients. [ABSTRACT FROM AUTHOR]

Introduction: The increasing prevalence of type 2 diabetes (T2DM) in the UK imposes a significant burden on the National Health Service (NHS). Despite the availability of effective treatments, the loss of glycaemic control over time results in significant comorbidities, including nephropathy, neuropathy and retinopathy. The cost of treating these microvascular complications has not been well documented, and this study aimed to provide an accurate assessment of the healthcare resource utilisation (HCRU) associated with managing T2DM and its complications. Methods: This retrospective cohort study utilised electronic medical records from patients with T2DM from the Heart of England Foundation Trust (HEFT), which captures data from patients using secondary care services. Patients were diagnosed with microvascular complications based on ICD-10 or OPCS codes. HCRU over a 2-year period was based on NHS Tariffs for healthcare services for inpatient, accident and emergency, and dialysis clinic usage. Results: The study cohort comprised 26,629 patients with T2DM who used HEFT services during the study period, 22.6%, 20.8% and 3.1% of whom had comorbid nephropathy, retinopathy or neuropathy, respectively. While the prevalence of diabetes in the overall HEFT population was reported to be 7% in 2012, diabetes and its associated complications accounted for more than 30% of secondary care costs. Furthermore, while patients with diabetes represent only 17% of HEFT inpatients, they account for more than 20% of service usage. The economic burden of microvascular complications increased substantially with the severity of the condition, with the overall cost exceeding £70 million over the 2-year period. Conclusion: This study of patients with T2DM in a typical secondary care provider in the UK showed that avoiding the progression of microvascular complications could provide substantial cost savings through targeted interventions that improve outcomes and lower resource use. Funding: Merck Sharp & Dohme Limited. [ABSTRACT FROM AUTHOR]

Congenital cataracts, facial dysmorphism, and neuropathy (CCFDN) syndrome is a rare autosomal recessive disorder with multisystem involvement. The clinical features include cataracts with other ocular features, mild facial dysmorphism, and peripheral neuropathy with cognitive delay and hypogonadism. Diagnosis is mainly clinical with supportive evidence by electrophysiological studies and can be confirmed by identification of homozygous carboxy terminal domain phosphatase 1 (CTDP1) genemutation. We investigated two siblings of a European Gypsy family where the parents are distant cousins who had a strong family history of cataracts andmotor difficulties. Both siblings had bilateral congenital cataracts, delayed motor development, and subtle dysmorphic features with wasting of calf muscles. The presence of demyelinating neuropathy and homozygous IVS6þ389C>T mutation located in CTDP1 confirmed CCFDN syndrome. To our knowledge, there are no reported cases in the United Kingdom. These two siblings were affected with this rare disorder with different severity. [ABSTRACT FROM AUTHOR]

1-2% of the UK equine population may display headshaking. As such, being called out to investigate these cases is not uncommon, but can be challenging. This article discusses possible causes of headshaking, with an emphasis on headshaking from trigeminally mediated facial dysesthesia. A logical step-by-step approach to investigation is provided. [ABSTRACT FROM AUTHOR]

Background: Arterial 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., Methods: We 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.  FINDINGS: 14 794 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., Interpretation: Intravenous 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., Competing Interests: Competing interests: MK reports Grifols sponsorship for attendance at meeting. ASC reports Grifols sponsorship for attendance at meeting and honorarium from CSL and Lupin for an advisory role. MPL was a Primary Investigator in studies for CSL Behring, UCB Pharma, Novartis, Octapharma. He has also received ad hoc consulting fees from CSL Behring, UCB and an honorarium from Terumo BCT. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To report epidemiologic data on traumatic optic neuropathy (TON) in patients less than 18 years of age in the United Kingdom acquired by prospective population-based active surveillance through the British Ophthalmic Surveillance Unit. Methods: Data were obtained from incident and 6-month follow-up questionnaires sent to reporting ophthalmologists over a period of 2 years. Main outcome measures were demographic data, clinical and visual function at presentation and follow-up, investigations, and treatments used. Results: A total of 26 cases (21 males) were identified; follow-up data were available for 23 (88%). Minimum estimated annual incidence was 0.99 cases per million. Leading causes of TON included 6 sports injuries (23%), 5 falls (19%), and 4 traffic accidents (16%). Presenting best-corrected visual acuity was ≤6/60 in 15 cases (58%), with no light perception in 7 cases (27%). Associated injuries were as follows: nonpenetrating injuries, 8 (31%); adnexal injuries, 3 (11.5%); orbital fractures, 5 (19%); skull fractures, 3 (12%); intracranial bleeding, 1 (4%). Fourteen (54%) received no treatment, and 9 (35%) were treated with steroids. Final visual acuity improved in 7 of 21 patients (33%), with 13 of 23 (56%) achieving final visual acuity ≤6/60, 10 of whom (43%) had no light perception. Baseline visual acuity was associated with last follow-up visual acuity (P = 0.03), but treatment and improvement of visual acuity by at least 3 lines were not associated. Treatment was more common in children with poor presenting vision (P = 0.03). Conclusions: The incidence, natural history, poor presenting visual acuity, and male prevalence of TON in children appear similar to adults in adults in the UK.▪ [ABSTRACT FROM AUTHOR]

The article assesses the value of distal compound muscle action potential duration prolongation in the electrophysiological diagnosis of acute inflammatory demyelinating polyneuropathy in a cohort of 40 patients from Great Britain and France. Fisher exact tests were used to analyze the results. The mean quantity of nerves examined was greater in the control group. Weakness was minimal and involved distal lower limb muscles in those with motor involvement.

OBJECTIVE -- To compare the mortality of patients with an acute Charcot foot with a matched population with uninfected neuropathic foot ulcers (NFUs). RESEARCH DESIGN AND METHODS -- Data were extracted from a specialist departmental database, supplemented by hospital records. The findings were compared with the results of earlier populations with Charcot foot and uninfected NFUs managed from 1980. Finally, the results of all patients with acute Charcot foot and all control subjects managed between 1980 and 2007 were compared with normative mortality data for the U.K. population. RESULTS -- A total of 70 patients presented with an acute Charcot foot (mean age 57.4 ± 12.0 years; 48 male [68.6%]) between 2001 and 2007; there were 66 matched control subjects. By 1 October 2008, 13 (eight male; 18.6%) patients with a Charcot foot had died, after a median of 2.1 years (interquartile range 1.1-3.3). Twenty-two (20 male; 33.3%) control subjects had also died after a median of 1.3 years (0.6-2.5). There was no difference in survival between the two groups (log-rank P > 0.05). Median survival of all 117 patients with acute Charcot foot managed between 1980 and 2007 was 7.88 years (4.0-15.4) and was not significantly different from the control NFU patients (8.43 years [3.4-15.8]). When compared with normative U.K. population data, life expectancy in the two groups was reduced by 14.4 and 13.9 years, respectively. CONCLUSIONS -- These data confirm that the mortality in patients presenting to our unit with either an acute Charcot foot and an uninfected neuropathic ulcer was unexpectedly high. [ABSTRACT FROM AUTHOR]

A decrease in sensory nerve action potentials (SNAP) amplitude has been recently reported in some patients during the course of multifocal motor neuropathy with conduction blocks (MMNCB). It is not known if those patients have different clinical expression and disability when compared with typical MMNCB. Clinical, biological and electrophysiological assessments were performed in 15 patients fitting the diagnosis criteria of MMNCB, including normal SNAP amplitude at initial examination. Patients presenting with nerve entrapment or associated disease causative of sensory neuropathy were excluded. Median time of follow-up was 3 years (1–17 years). At the last examination, four patients had at least one SNAP amplitude below 50% of normal value. None had clinically objective sensory loss. Clinical and electrophysiological data obtained at the last examination were compared between patients with normal SNAP amplitude and patients with decreased SNAP amplitude. No difference between both population in term of age, sex, disease duration, anti-GM1 antibody titers, CSF data and number of conduction blocks was noted. In contrast, patients with decreased SNAP amplitude had worse overall neuropathy limitation scale (ONLS) scores (7 vs. 2; p = 0.02), a higher number of affected nerves (12.5 vs. 4; p = 0.018), a higher number of affected limb regions (6 vs. 2; p = 0.019) and lower median CMAP amplitude (2 mV vs. 6.5 mV; p = 0.04). They were all dependent on higher doses of IVIg (1.4 g/(kg 4 weeks vs. 0.6; p = 0.018). A reduction in SNAP amplitude during the course of MMNCB is associated with a more severe disease and a more prominent axonal loss. This result needs to be confirmed in a larger cohort. [ABSTRACT FROM AUTHOR]

Objective. The objective of this study was to evaluate the effect of intravenous immunoglobulin (IVIg) therapy in diabetic lumbosacral radiculoplexus neuropathy (DLRPN) patients who did not respond to analgesic drug therapy and corticosteroids. Background. DLRPN is a rare painful condition that may occur in diabetes mellitus (DM). At the moment, there are limited therapeutic options for DLRPN. Methods. We recruited five patients affected by type 2 DM and DLRPN. They were selected from a cohort of 13 consecutive DLRPN patients. Inclusion criteria were severe pain (visual analog scale [VAS] > 4/10) and no response to pain symptomatic therapy and corticosteroids. Patients were treated with IVIg (0.4 g/kg/day for 5 days). Outcome measures were VAS, time of onset and duration of pain relief, the Medical Research Council (MRC) scale for lower limb muscle strength, and walking distance. Electrophysiology and needle electromyography (EMG) were retested after IVIg. Results. Four of the patients had positive pain response after IVIg. VAS reduction started 5–10 days after IVIg infusion. Two patients underwent additional IVIg infusions due to pain reappearance after 7–18 months, again with positive response. VAS, MRC scale, and walking distance significantly improved at 1 month (Wilcoxon nonparametric test, two-tailed, P < 0.05). Electrodiagnostic testing was unchanged, but needle EMG showed reduction of denervation signs after IVIg. Conclusions. IVIg may rapidly reduce pain and improve motor function in DLRPN despite previous negative response to corticosteroids. IVIg may be repeated in those patients who experience disease relapse. Future double-blind trials are needed to evaluate the role of IVIg in DLRPN. [ABSTRACT FROM AUTHOR]

Peripheral neuropathy is defined as dysfunction of the structure and function of peripheral motor, sensory and autonomic nerves. Although many individual causes of peripheral neuropathy are rare, it is estimated that up to 8% of the population have some degree of peripheral neuropathy or a total of 4.7 million people in the UK alone. There are many different types of peripheral neuropathy but the most common cause is diabetes and up to 60% of diabetic patients have a peripheral neuropathy of some sort. Peripheral neuropathy not only causes problems with everyday functioning but also in many cases causes severe, disabling neuropathic pain. This article aims to provide a simple overview of peripheral neuropathy and its management in primary care. [ABSTRACT FROM PUBLISHER]

OBJECTIVE -- To compare populations with and outcomes of diabetic foot ulcers managed in the U.K., Germany, Tanzania, and Pakistan and to explore the use of a new score of ulcer type in comparing outcomes among different countries. RESEARCH DESIGN AND METHODS -- Data from a series of 449 patients with diabetic foot ulcers managed in the U.K. were used to evaluate the new simplified system of classification and to derive an aggregate score. The use of the score was then explored using data from series managed in Germany (n = 239), Tanzania (n = 479), and Pakistan (n = 173). RESULTS -- A highly significant difference was found in time to healing between ulcers of increasing score in the U.K. series (Kruskal-Wallis test; P = 0). When data from all centers were examined, a step-up in days to healing was noted for those with scores of ≥3 (out of 6). Examination of baseline variables contributing to outcome revealed the following differences among centers: ischemia, ulcer area, and depth contributing to outcome in the U.K.; ischemia, area, depth, and infection in Germany; depth, infection, and neuropathy in Tanzania; and depth alone in Pakistan. CONCLUSIONS -- Any system of classification designed for general implementation must encompass all the variables that contribute to outcome in different communities. Adoption of a simple score based on these variables, the Site, Ischemia, Neuropathy, Bacterial Infection, and Depth (SINBAD) score, may prove useful in predicting ulcer outcome and enabling comparison among different centers. [ABSTRACT FROM AUTHOR]

Aims Different estimates exist regarding the impact of diabetic retinopathy (DR) on health utility. A previously reported prospective observational study has reported much larger decrements in self-reported utility than generic utility data from the UK Prospective Diabetes Study and the Lipids in Diabetes Study. The present study was designed to estimate utility loss using multiple methods. Methods Detailed health state descriptions reflecting declining DR (five different visual acuity levels), neuropathy and nephropathy were validated with patients and used to elicit utility values from people with DR, people with diabetes and members of the UK general public using standard gamble. In addition, a larger sample of people with retinopathy completed different health-related quality of life measures in an interview [EuroQoL (EQ-5D), Health State Utilities Index (HUI)-3, and National Eye Institute Visual Functioning Questionnaire-25]. Results The utility scores from the standard gamble interviews were not significantly different between the three groups. There was a decline in utility from 6/6 vision to counting fingers of −0.244. The utility data derived from the generic measures revealed an equivalent decline of −0.41 on both the EQ-5D single index and the HUI-3. Conclusions This study has re-examined the utility decrements associated with DR and has identified much larger declines in utility than previously reported. The study has also reported the utility values of patients with retinopathy as assessed by standard gamble. We believe that this may be the first study to report utility values for health states associated with vision loss which have been elicited from patients with vision loss. [ABSTRACT FROM AUTHOR]

Diabetic foot ulcers are likely to occur in up to 25% of people with diabetes mellitus at some time in their life (Boulton et al, 2005). Without adequate management, there is a high risk of infection, gangrene, amputation and death. Over 50% of major amputations in the UK happen to people with diabetes, and within three years of amputation, 50% of patients will die. Diabetic foot ulcers need specific management, and some of the principles of moist wound healing do not apply. Diabetic patients with foot ulcers benefit from accurate and prompt assessment, diagnosis, treatment, and long-term follow-up in order to conserve the foot (Jeffcoate et al, 2006). Their management cannot be undertaken by one health care professional working in isolation, but should involve a multidisciplinary team to ensure that these complex wounds are treated appropriately. In this first of two articles, wound healing in the diabetic foot and the principles of assessment of the diabetic foot ulcer are discussed. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- To determine 1) foot ulcer rates for European, South-Asian, and African-Caribbean diabetic patients in the U.K. and 2) the contribution of neuropathy and peripheral arterial disease (PAD) differences to altered ulcer risk between the groups. RESEARCH DESIGN AND METHODS -- In this U.K. population-based study, we screened 15,692 type 1 and type 2 diabetic patients in the community health care setting for foot ulcers, foot deformities, neuropathy, and PAD plus other characteristics. In total, 13,409 were European (85.5%), 1,866 were South Asian (11.9%), and 371 were African Caribbean (2.4%). RESULTS -- The age-adjusted prevalence of diabetic foot ulcers (past or present) for Europeans, South Asians, and African Caribbeans was 5.5, 1.8, and 2.7%, respectively (P < 0.0001). Asians and African Caribbeans had less neuropathy, PAD, and foot deformities than Europeans (P = 0.003). The unadjusted risk of ulcer (odds ratio [OR]) for Asians versus Europeans was 0.29 (95% CI 0.20-0.41) (P < 0.0001). PAD, neuropathy, foot deformities, and insulin use attenuated the age-adjusted OR from 0.32 to 0.52 (0.35-0.76) (P < 0.0001). African-Caribbean versus European ulcer risk in males was attenuated from 0.60 to 0.71 by vibration sensation. CONCLUSIONS -- South Asians with diabetes in the U.K. have about one-third the risk of foot ulcers of Europeans. The lower levels of PAD, neuropathy, insulin usage, and foot deformities of the Asians account for approximately half of this reduced foot ulcer risk. Lower neuropathy is the main contributor to the reduced African-Caribbean ulcer rate, particularly in men. The reasons for these ethnic differences warrant further investigation. [ABSTRACT FROM AUTHOR]

Provides information on the nutritional interventions described as a complementary medicine. Overview of the nutritional supplements; Opinion on the safety of unconventional nutritional interventions; Number of neuropaths practicing in Great Britain registered by the General Council and Register Neuropaths.

The article summarizes the recommendations from the National Institute for Health and Clinical Excellence (NICE) of Great Britain on drug management for neuropathic pain in adults in primary and secondary care, exempting specialist pain services, in 2010. It states that the recommendations are taken from systematic reviews of available clinical and cost effectiveness evidence. The key principles of care are enumerated. Also given are first, second and third lines of treatment, other treatment options and definitions of terms that apply to the guidelines. INSET: FURTHER INFORMATION ON THE GUIDANCE.

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. To examine the frequency of biochemically defined and clinically significant episodes of treatment associated haemolysis, neutropenia, thrombocytopenia and acute kidney injury(AKI) in a cohort of patients on maintenance Immunoglobulin(Ig) therapy for inflammatory neuropathy. A retrospective review of routine blood monitoring in patients from two UK specialist peripheral nerve centres. Accepted definitions for clinically and biochemically significant haemolysis, neutropenia, thrombocytopenia and AKI were used. 1919 infusion episodes in 90 patients were analysed. Age(mean(S.D)) = 58.09(14.4)years, 63% male, 72% CIDP(28% MMN), 97% IVIg(3% SCIg). Dose = 1.57(0.79)g/kg/month or 97.1(37.3)g/infusion, frequency:3.9(1.4) weeks. Relative IgA deficiency was noted in 2 individuals (prevalence:2.2%, 95%C.I.:0–5.2) who received a combined total of 38 infusions(3800 g IVIg) without adverse event. No clinically significant episodes of haemolysis, neutropenia, thrombocytopenia or AKI occurred in relation to treatment. An asymptomatic drop>10 g/L haemoglobin(Hb) occurred in 3.5%(95%CI:2.7–4.3) of treatment episodes in 38 individuals, mean reduction:17.7(7.4)g/L; lowest Hb:86 g/L. Lower pre-treatment haemoglobin correlated with risk of recurrent Ig-related drop(p:0.007). Two patients with chronic renal failure(stage 1 and 3) received 28(IV) and 104(SC) infusions respectively(6416 g) without impact on estimated glomerular filtration rate(eGFR). No clinically significant Ig-related episodes of haemolysis or AKI were identified in this representative cohort. This suggests that routine monitoring is not essential in long-term Ig use but should be considered when clinically indicated. • We performed retrospective review of routine blood monitoring for maintenance Ig therapy • No clinically significant Ig-related haemolysis or AKI were identified • We suggest clinically indicated testing in long-term Ig use. [ABSTRACT FROM AUTHOR]

Apart from carpal tunnel syndrome, there are no population based studies of the epidemiology of compressive neuropathies. To provide this information, new presentations of compressive neuropathies among patients registered with 253 general practices in the UK General Practice Research Database with 1.83 million patient years at risk in 2000 were analysed. The study revealed that in 2000 the annual age standardised rates per 100 000 of new presentations in primary care were: carpal tunnel syndrome, men 87.8/women 192.8; Morton's metatarsalgia, men 50.2/women 87.5; ulnar neuropathy, men 25.2/women 18.9; meralgia paraesthetica, men 10.7/women 13.2; and radial neuropathy, men 2.97/women 1.42. New presentations were most frequent at ages 55–64 years except for carpal tunnel syndrome, which was most frequent in women aged 45–54 years, and radial nerve palsy, which was most frequent in men aged 75–84 years. In 2000, operative treatment was undertaken for 31% of new presentations of carpal tunnel syndrome, 3% of Morton's metatarsalgia, and 30% of ulnar neuropathy. [ABSTRACT FROM AUTHOR]

Background Juvenile idiopathic arthritis (JIA) is the most common form of inflammatory arthritis in children and has an annual incidence of 33 per 100,000. With the introduction of biologic therapies, the goal of disease remission, both on and off treatment, is becoming increasingly achievable. Etanercept, a TNF-α inhibitor, was the first biologic to be used in JIA and is currently recommended as an add-on therapy in patients with inadequate response to methotrexate alone. While it is generally considered to have a good safety profile, a number of adverse events have been documented, including neuropathy. Methods We present two cases of etanercept related mononeuropathy, which persisted despite intravenous immunoglobulin (IVIG) therapy. Results Case 1: A 12 year-old girl with polyarticular JIA, who had commenced on etanercept 2 years previously, presented with an acute inability to fully flex her right index finger, associated with intermittent paraesthesia over the area. On examination, there was weakness in the deep flexor digit II and she was unable to flex at the distal interphalangeal joint. Deep tendon reflexes and sensation were normal. Nerve conduction studies showed absence of voluntarily recruited motor potentials in the right flexor digitorum profundus median to right digit II. Etanercept was discontinued and following review by a paediatric neurologist, a course of IVIG was commenced. To date, however, there has been no appreciable clinical improvement. Case 2: A 7 year-old girl with oligoarticular JIA, who had commenced on etanercept 3 years prior, presented with a ten week history of selective weakness in her left hand and absent power in her flexor pollicis longus. On examination, there was an apparent weakness in her flexor pollicis longus with 0/5 power. Sensory and deep tendon reflexes were normal. Etanercept was discontinued. EMG and nerve conduction studies definitively outruled a proximal median neuropathy or any median motor problem outside of the anterior interosseous nerve. EMG did not find incontrovertible evidence of motor conduction block however this remains a possible and indeed plausible mechanism. She was referred to paediatric neurology and a course of IVIG was commenced. Conclusion While etanercept remains a widely used medication in the setting of JIA, these case studies highlight the potential neurological adverse events that can occur. To our knowledge are the first reports of persistent isolated motor neuropathy secondary to etanercept use in the paediatric population. Conflicts of Interest The authors declare no conflicts of interest. [ABSTRACT FROM AUTHOR]

Transthyretin amyloidosis (ATTR) is caused by deposition of either wild-type (ATTRwt) or variant (ATTRm) transthyretin. ATTRwt presents with restrictive cardiomyopathy, while ATTRm displays a range of organ involvement. This retrospective analysis includes all patients referred to a single UK center in the last 25 years for clinical and laboratory assessment of known or suspected amyloidosis who underwent TTR gene sequencing. A total of 4459 patients were included in this study; 37% had final diagnosis of ATTR amyloidosis; 27% light chain amyloidosis; 0.7% other types of amyloidosis; 21.3% had no amyloid and 14% had no data. TTR variants were found in 770 (17%) cases; the most prevalent were p.V142I, p.T80A, and p.V50M identified in 42, 25, and 16%, respectively. The median age at referral in each group was: 76 (range 47-93), 66 (40-81), and 45 years (21-86), respectively. Overall 42 rare or novel variants were identified. Forty-two percent patients with ATTRm died at a median age of 73 years (33-89) with a median survival from diagnosis of 50 months. ATTRwt was the final diagnosis in 20% of patients undergoing genetic testing. Our findings of TTR variants in 17% of screened patients highlight the need for routine genetic testing in the evaluation of suspected ATTR amyloidosis., (© 2018 Wiley Periodicals, Inc.)

Background: Low foot ulcer risk in South Asian, compared with European, people with type 2 diabetes in the UK has been attributed to their lower levels of neuropathy. We have undertaken a detailed study of corneal nerve morphology and neuropathy risk factors, to establish the basis of preserved small nerve fibre function in South Asians versus Europeans., Methods: In a cross-sectional, population-based study, age- and sex-matched South Asians (n = 77) and Europeans (n = 78) with type 2 diabetes underwent neuropathy assessment using corneal confocal microscopy, symptoms, signs, quantitative sensory testing, electrophysiology and autonomic function testing. Multivariable linear regression analyses determined factors accounting for ethnic differences in small fibre damage., Results: Corneal nerve fibre length (22.0 ± 7.9 vs. 19.3 ± 6.3 mm/mm 2 ; P = 0.037), corneal nerve branch density (geometric mean (range): 60.0 (4.7-246.2) vs. 46.0 (3.1-129.2) no./mm 2 ; P = 0.021) and heart rate variability (geometric mean (range): 7.9 (1.4-27.7) vs. 6.5 (1.5-22.0); P = 0.044), were significantly higher in South Asians vs. Europeans. All other neuropathy measures did not differ, except for better sural nerve amplitude in South Asians (geometric mean (range): 10.0 (1.3-43.0) vs. 7.2 (1.0-30.0); P = 0.006). Variables with the greatest impact on attenuating the P value for age- and HbA 1C -adjusted ethnic difference in corneal nerve fibre length (P = 0.032) were pack-years smoked (P = 0.13), BMI (P = 0.062) and triglyceride levels (P = 0.062)., Conclusions: South Asians have better preserved small nerve fibre integrity than equivalent Europeans; furthermore, classic, modifiable risk factors for coronary heart disease are the main contributors to these ethnic differences. We suggest that improved autonomic neurogenic control of cutaneous blood flow in Asians may contribute to their protection against foot ulcers., (© 2018 The Authors. Diabetes/Metabolism Research and Reviews Published by John Wiley & Sons Ltd.)

The article describes the case of a hockey player in Great Britain who suffered from occult peripheral neuropathy. The patient was brought to a physiotherapist after he was unable to walk while doing a training exercise. The therapist found that the patient exhibits a pattern of primary axonal loss that could be caused by the physical demands of hockey.

The article provides an overview on sample case studies and their lessons to be included in the book "The General Practice Book of Golden Rules and Reflective Learning" of the Royal College of General Practitioners (RCGP) in Great Britain. They include a 66-year old man who developed myoclonus and hypereflexia after taking paroxetine for 3 years, an 81-year old female type 2 diabetes patient who had serotonin syndrome after taking sibutramine for weight reduction and 25-year old male with left-sided foot drop and have hereditary pressure palsies.

Analyzes Leber's hereditary optic neuropathy with deficiency of thiosulphate sulphurtransferase in Great Britain. Measurement of thiosulphate sulphurtransferase activity; Hypothesis of an error of cyanide detoxification; Risk of infants in developing the disease.

Examines the incidence of severe peripheral neuropathy after Mandrax overdose in Great Britain. Complications of Mandrax poisoning; Symptoms of peripheral neuropathy; Chemical content of Mandrax.

Examines the effect of analgesic neuropathy on the renal function in Great Britain. Evidence of analgesic intake; Causes of renal damage; Selection of patients for dialysis and transplantation.

In this article the author reflects on cancer survivorship in Great Britain. She discusses her experience as a cancer survivor and comments on the side effects of radiotherapy and chemotherapy. She elaborates the possibility of cancer recurrence after several years of treatment. She reveals the need to support cancer survivors and recognize the long-term effects of cancer on people's lives.

The article discusses a case study on occipital neuropathy, the occurrence of headache in diabetes which is caused by irritation or injury to the greater occipital nerve. According to the British International Headache Society, it is a paroxysmal jabbing pain accompanied by diminished sensation or dyaesthesia in the affected area. Key information on case histories of patients with occipital neuropathy are presented.

Describes a mesothelioma-associated antiphospholipid antibody syndrome presenting with cutaneous infarction and neuropathy in Great Britain. Identification of numerous patches of orange/brown pigmentation; Presence of a lupus anticoagulant; Development of livedo reticularis over the insteps and lower calves; Elevation of plasma viscosity.

Presents views on the developments of medicines as of January 30, 1988 in Great Britain. Campaign for ban of smoking on domestic flights; Clinical features of the trigeminal sensory neuropathy; Implication of cardiopulmonary resuscitation on infants with bradycardia and hypotension.

Presents a case report on the complications of amitriptyline overdose in Great Britain. Efficacy as peripheral neuropathy treatment; Occurrence of severe flaccid tetraplegia; Identification of neuropathy symptoms.

Reports developments of cases related to medical issues in Great Britain as of December 1985. Deposition of amyloid with a foreign body giant cell reaction; Cause of peripheral neuropathy; Recognition of the side effect of metrizamide.

Reports medical developments in Great Britain as of August 1978. Development of neuropathy affecting arms and legs; Assessment of backswings as cause of retinal hemorrhages; Problems in patterns of sexual interaction.

Presents question and answer advisory related to medicine in Great Britain as of September 1975. Treatment of peripheral neuropathy; Causes of neuropathy; Discussion on electrocardiographic changes in patients with hiatus hernia; Description of hiatus hernia.