Somatic Neuropathy Research Articles

Peripheral neuropathy in patients with gout, beyond focal nerve compression: a cross-sectional study.

Neuropathies secondary to tophus compression in gout patients are well known; however, limited data exist on other types of peripheral neuropathies (PN). Our aim was to describe PN frequency, characteristics, distribution, patterns, and associated factors in gout patients through clinical evaluation, a PN questionnaire, and nerve conduction studies (NCS). This cross-sectional descriptive study included consecutive gout patients (ACR/EULAR 2015 criteria) from our clinic. All underwent evaluation by Rheumatology and Rehabilitation departments, with IRB approval. Based on NCS, patients were categorized as PN + (presence) or PN- (absence). PN + patients were further classified as local peripheral neuropathy (LPN) or generalized somatic peripheral neuropathy (GPN). We enrolled 162 patients, 98% male (72% tophaceous gout). Mean age (SD): 49.4 (12) years; mean BMI: 27.9 (6.0) kg/m2. Comorbidities included dyslipidemia (53%), hypertension (28%), and obesity (23.5%). Abnormal NCS: 65% (n = 106); 52% LPN, 48% GPN. PN + patients were older, had lower education, and severe tophaceous gout. GPN patients were older, had lower education, and higher DN4 scores compared to LPN or PN- groups (p = 0.05); other risk factors were not significant. Over half of gout patients experienced neuropathy, with 48% having multiplex mononeuropathy or polyneuropathy. This was associated with joint damage and functional impairment. Mechanisms and risk factors remain unclear. Early recognition and management are crucial for optimizing clinical outcomes and quality of life in these patients. Key Points Peripheral neuropathies in gout patients had been scarcely reported and studied. This paper report that: • PN in gout is more frequent and more diverse than previously reported. • Mononeuropathies are frequent, median but also ulnar, peroneal and tibial nerves could be injured. • Unexpected, generalized neuropathies (polyneuropathy and multiplex mononeuropathy) are frequent and associated to severe gout. • The direct role of hyperuricemia /or gout in peripheral nerves require further studies.

Prevalence of somatic small fiber neuropathy in elderly: a review

Somatic small fiber neuropathy (SSFN) is a neuromuscular disease that affects peripheral nerves and leads to structural and functional changes involving small myelinated (Aδ) and unmyelinated (C) fibers, and whose pathophysiological mechanisms are not well elucidated, but depend on the underlying etiology. Due to the lack of studies on this pathology, it is likely to be underdiagnosed, which is a problem, since this disease in elderly people can lead to multiple negative effects on daily life due to neuropathic pain, paresthesia, and dysautonomia of various systems. The clinical diagnosis of this pathology is based on data from the clinical history and physical examination, as well as some complementary examinations and tests, such as the quantitative sudomotor axon reflex test (QSART). Moreover, the treatment of the disease is still limited and most approaches focus on the control of symptoms, such as neuropathic pain. The present study consists of a narrative review of the literature conducted in Medline databases from 2010 to 2022 on small-fiber neuropathy, the elderly, and neuralgia, using the terminology indicated by the Health Sciences Descriptor System (DeCS), and aims to highlight the relevance of the association of senile comorbidities and the aging process with somatic small-fiber neuropathy. Thus, future studies investigating the pathophysiological mechanisms of SSFN are of utmost importance, as well as studies aimed at developing more effective diagnostic methods.

Peripheral Neuropathy in Diabetes Mellitus: Pathogenetic Mechanisms and Diagnostic Options.

Diabetic neuropathy (DN) is one of the main microvascular complications of both type 1 and type 2 diabetes mellitus. Sometimes, this could already be present at the time of diagnosis for type 2 diabetes mellitus (T2DM), while it appears in subjects with type 1 diabetes mellitus (T1DM) almost 10 years after the onset of the disease. The impairment can involve both somatic fibers of the peripheral nervous system, with sensory-motor manifestations, as well as the autonomic system, with neurovegetative multiorgan manifestations through an impairment of sympathetic/parasympathetic conduction. It seems that, both indirectly and directly, the hyperglycemic state and oxygen delivery reduction through the vasa nervorum can determine inflammatory damage, which in turn is responsible for the alteration of the activity of the nerves. The symptoms and signs are therefore various, although symmetrical painful somatic neuropathy at the level of the lower limbs seems the most frequent manifestation. The pathophysiological aspects underlying the onset and progression of DN are not entirely clear. The purpose of this review is to shed light on the most recent discoveries in the pathophysiological and diagnostic fields concerning this complex and frequent complication of diabetes mellitus.

Outcomes of Surgical Treatment for Sural Nerve Pain

Category: Ankle; Hindfoot Introduction/Purpose: Somatic neuropathy is a common complication following foot and ankle surgery, trauma, or compression due to entrapment. Symptoms can be intense and debilitating. The Sural nerve is commonly affected and is at risk due to the location and proximity to frequently used surgical approaches. The purpose of this study is to investigate the outcomes of sural nerve neurolysis and neurectomy with intramuscular burial for sural neuritis. Methods: IRB approval was obtained, and patients were identified who underwent operative treatment by two foot and ankle specialists for sural nerve related pain. Exclusion criteria included patients under the age of 18, prisoners, those who underwent concomitant osseous procedures, and less than 6-week follow-up. Demographics and preoperative outcomes including FFI, SF-36, FAAM, and VAS were recorded. Final follow-up questionnaires using PROMIS measures and FAAM were administered using REDCap. Results: The 25 patients meeting inclusion criteria for this study had a median age of 47 (interquartile range [IQR], 43 to 49) and had median follow-up of 33.7 months (IQR, 4.5 -73.2). Median FAAM ADL improved from 40.8 (IQR 38.1-51.3) preoperatively to 59.5 (IQR 47.6-76.2) postoperatively, p=0.032. FAAM Sports scores improved from 15.6 (IQR 9.4-21.9) to 31.3 (IQR 25.0-56.3) postoperatively, p=0.002. VAS scores improved from a median of 9.0 (IQR 7.0-9.0) to 4.5 (3.0-6.0), p<0.0001. At final follow-up patients reported PROMIS lower extremity function score median of 46.7 (IQR 36.7-51.2), PROMIS neuropathic pain quality score of 51.5 (IQR 45.5-60.2), and PROMIS pain interference of 55.7 (IQR 41.1-63.7). Patients with current or recent nicotine use, depression, anxiety, and complex regional pain syndrome (CRPS) prior to surgery reported poorer outcomes. Conclusion: Neurectomy with burial or neurolysis can significantly improve symptoms for sural neuritis secondary to neuroma or nerve entrapment. Tobacco use, depression and anxiety are associated with poorer outcomes following surgery. Further research is needed to More clearly identify patients at risk for worse outcomes and perioperative factors that could allow interventions to optimize patient outcomes.

A Study of Cardiovascular Autonomic Neuropathy in Adult Patients with Diabetes Mellitus at Levy Mwanawasa University Teaching Hospital

Cardiac autonomic neuropathy (CAN) is the diminished capacity of autonomic regulation of the cardiovascular system occurring in the presence of diabetes mellitus (DM) and in the absence of other aetiologies. Diabetes mellitus is a well- known cause of peripheral neuropathy. However, in comparison to somatic neuropathy, autonomic neuropathy is an under-diagnosed and under-treated chronic complication of diabetes mellitus despite its serious and significant contribution to morbidity and mortality in the diabetes mellitus population. A variety of tests, based on evaluation of the cardiovascular reflexes triggered by performing specific provocative manoeuvres, have been proposed to measure autonomic function. This study used four cardiovascular reflex tests to estimate appropriate autonomic function by examining heart rate, heart rate variation and the baroreceptor reflex. The aim of this study was to determine the presence of cardiovascular autonomic neuropathy in adult patients with diabetes mellitus at Levy Mwanawasa University Teaching Hospital in Lusaka, Zambia. Adult patients with diabetes mellitus, aged between 21 and 70 years, participated in this cross-sectional study. Four, non-invasive, cardiac autonomic reflex tests to assess for cardiac autonomic neuropathy were employed according to Ewing’s method. The parasympathetic function was analysed based on the heart rate response to paced deep breathing and to Valsalva manoeuvring. The sympathetic function was assessed by measuring heart rate and blood pressure response to postural change. Ewing`s criteria was used for the categorisation of cardiac autonomic neuropathy. Data were analysed using SPSS version 20. Continuous data were presented as means and standard deviation. Categorical data were analysed using a Fishers’ Exact Test (χ2) and a logistic regression was performed to verify the effects of diabetes mellitus’ duration, sex and age on the probability that the participants have cardiac autonomic neuropathy. A total of 52 patients participated in the study. The prevalence of Cardiac autonomic neuropathy was 48.1%. Out of 52 patients, 42.3% had definite cardiac autonomic neuropathy and 5.8% had severe cardiac autonomic neuropathy. Early cardiac autonomic neuropathy was observed in 34.6% of patients while 17.3% had no signs of cardiac autonomic neuropathy. The mean age of patients with cardiac autonomic neuropathy was 54.44 ± 10.90 years and the mean duration of diabetes mellitus from diagnosis was 5.36 ± 6.78 years. The probability of developing cardiac autonomic neuropathy increased with increasing age and hypertensive participants were more likely develop cardiac autonomic neuropathy (ѵ = 5.82, p = .001). In conclusion, cardiac autonomic neuropathy was present in a significant proportion of adult patients with diabetes mellitus at Levy Mwanawasa University Teaching Hospital, reflecting the increased morbidity encountered by this population. In order to improve patient quality of life and reduce disease burden, screening for cardiac autonomic neuropathy should be implemented using cardiovascular autonomic reflex tests which are relatively simple, safe and affordable.

Evaluation of peripheral amyloid neuropathy

Symptoms of peripheral nervous system (PNS) damage are common clinical manifestations of systemic amyloidosis. Peripheral amyloid neuropathy is characterized by a progressive course, leading to the disability of patients; however, the current possibilities of pathogenetic therapy make the early diagnosis of amyloid neuropathy particularly urgent.Objective: to evaluate the informative value of laser confocal microscopy (LCM) of the cornea in diagnosing small fiber neuropathy of peripheral nerves in patients with systemic amyloidosis.Patients and methods. The study included nine patients (three men and six women) with morphologically confirmed primary amyloidosis (ALamyloidosis) and 12 patients (three men and nine women) with hereditary transthyretin amyloidosis (TTR-amyloidosis) verified by genetic and morphological methods. At baseline, the mean age of patients with AL-amyloidosis was 60.6±10.7 years, with hereditary TTR-amyloidosis – 57.1±13.1 years. According to the history of the disease in AL-amyloidosis, the mean duration of clinical symptoms was 2.7±1.4 years, with TTR-amyloidosis – 5.5±3.6 years. 20 age- and sex-adjusted healthy volunteers were included in the control group. All patients underwent a clinical neurological examination with an assessment of the severity of neuropathy according to the Neuropathy Impairment Score (NIS); 21 patients with systemic amyloidosis and all volunteers of the control group underwent LCM of the corneal nerve fibers (CNF). The coefficients of anisotropy (КΔL) and orientation symmetry (Ksym) of the CNF were calculated to assess the severity of damage to the corneal nerves.Results and discussion. Clinical neurological examination in patients with AL-amyloidosis revealed polyneuropathic syndrome (45%), tunnel syndrome (22%), their combination (22%), and autonomic dysfunction in the form of orthostatic hypotension and impaired motility of the gastrointestinal tract (GI tract; 56%). Symptoms in patients with TTR-amyloidosis were characterized by a combination of tunnel neuropathy and sensory-motor polyneuropathy (50%), distal symmetric polyneuropathy (42%). Frequent symptoms of PNS damage in systemic amyloidosis include autonomic neuropathy (56% – in AL-amyloidosis, 92% – in TTR-amyloidosis) presenting with orthostatic hypotension, impaired gastrointestinal motility, hypohidrosis, and dysuria. The mean NIS score, which characterizes the severity of somatic neuropathy, was significantly higher in patients with TTR-amyloidosis than AL-amyloidosis (p<0.02). LCM of the cornea showed disturbances in the course and structure of the corneal nerve fibers in all examined patients with systemic amyloidosis. The mean anisotropy coefficient values were lower in patients with systemic amyloidosis than in the control group. There were no significant differences in the AL- and TTR-amyloidosis groups. An inverse correlation of average strength between the values of the anisotropy coefficient and NIS was revealed (r=-0.6; p=0.04) in the group of patients with TTR-amyloidosis.Conclusion. Clinical polymorphism of peripheral somatic and autonomic nervous systems lesions is typical for patients with systemic amyloidosis. LCM of the cornea is informative in the diagnosis of small fibers neuropathy of peripheral nerves in systemic amyloidosis; however, it cannot establish the nosology of neuropathy.

Transdermal Delivery of Capsaicin Nanoemulgel: Optimization, Skin Permeation and In Vivo Activity against Diabetic Neuropathy.

Purpose: Diabetic somatic neuropathy is one of the most prevalent complications in type 1 diabetes mellitus (T1D). Many treatments were investigated to alleviate the pain associated with this condition. Capsaicin is a naturally occurring lipophilic alkaloid that proved to be an effective and safe treatment of chronic painful disorders. Despite the known therapeutic benefits of capsaicin, the conventional topical formulations have limited bioavailability. Therefore, the current study aims to develop capsaicin nanoemulgel to increase skin permeation and enhance its activity against neuropathic pain. Methods: Low-energy emulsification method was used to prepare nanoemulsions, using eucalyptus oil as the oily phase, Tween 80 as a surfactant, propylene glycol, ethanol and isopropyl alcohol as co-surfactants. Pseudo-ternary phase diagrams were constructed to investigate and optimize the formulation. Subsequently, the optimum formulation was formulated as a nanoemulgel and investigated for, skin permeation using Franz diffusion cell, and diabetic neuropathy (DN) management using alloxan-induced diabetic mice. Results: The selected nanoemulsion containing 0.05% capsaicin is composed of 8 % oil, 24 % S mix (Tween 80: isopropyl alcohol 2:1 w/w) and 68 % water. It is characterized by nanosized globules (28.15 ± 0.24 nm) with a relatively low polydispersity index (0.27 ± 0.05). The nanoemulgel revealed circa 4-fold increase in capsaicin cumulative permeation when compared to the conventional gel, and an improvement in its antinociceptive properties was observed in the treated diabetic mice (P < 0.05). Conclusion: The selected capsaicin nanoemulgel would be a promising transdermal formulation that may alleviate diabetic neuropathy in T1D patients.

Expert opinion on monitoring symptomatic hereditary transthyretin-mediated amyloidosis and assessment of disease progression

BackgroundHereditary transthyretin-mediated amyloidosis, also known as ATTRv amyloidosis (v for variant), is a rare, autosomal dominant, fatal disease, in which systemic amyloid progressively impairs multiple organs, leading to disability and death. The recent approval of disease-modifying therapies offers the hope of stabilization or eventual reversal of disease progression, and yet highlights a lack of disease-management guidance. A multidisciplinary panel of expert clinicians from France and the US came to consensus on monitoring the disease and identifying progression through a clinical opinion questionnaire, a roundtable meeting, and multiple rounds of feedback.Monitoring disease and progressionA multidisciplinary team should monitor ATTRv amyloidosis disease course by assessing potential target organs at baseline and during follow-up for signs and symptoms of somatic and autonomic neuropathy, cardiac dysfunction and restrictive cardiomyopathy, and other manifestations. Variability in penetrance, symptoms, and course of ATTRv amyloidosis requires that all patients, regardless of variant status, undergo regular and standardized assessment in all these categories. Progression in ATTRv amyloidosis may be indicated by: worsening of several existing quantifiable symptoms or signs; the appearance of a new symptom; or the worsening of a single symptom that results in a meaningful functional impairment.ConclusionsWe suggest that a multisystem approach to monitoring the signs and symptoms of ATTRv amyloidosis best captures the course of the disease. We hope this work will help form the basis of further, consensus-based guidance for the treatment of ATTRv amyloidosis.

Lipids and peripheral neuropathy.

Hyperlipidaemia is associated with the development of neuropathy. Indeed, a mechanistic link between altered lipid metabolism and peripheral nerve dysfunction has been demonstrated in a number of experimental and clinical studies. Furthermore, post hoc analyses of clinical trials of cholesterol and triglyceride-lowering pharmacotherapy have shown reduced rates of progression of diabetic neuropathy. Given, there are currently no FDA approved disease-modifying therapies for diabetic neuropathy, modulation of lipids may represent a key therapeutic target for the treatment of diabetic nerve damage. This review summarizes the current evidence base on the role of hyperlipidaemia and lipid lowering therapy on the development and progression of peripheral neuropathy. A body of literature supports a detrimental effect of dyslipidaemia on nerve fibres resulting in somatic and autonomic neuropathy. The case for an important modulating role of hypertriglyceridemia is stronger than for low-density lipoprotein cholesterol (LDL-C) in relation to peripheral neuropathy. This is reflected in the outcomes of clinical trials with the different therapeutic agents targeting hyperlipidaemia reporting beneficial or neutral effects with statins and fibrates. The potential concern with the association between proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor therapy and cognitive decline raised the possibility that extreme LDL-C lowering may result in neurodegeneration. However, studies in murine models and data from small observational studies indicate an association between increased circulating PCSK9 levels and small nerve fibre damage with a protective effect of PCSK9i therapy against small fibre neuropathy. Additionally, weight loss with bariatric surgery leads to an improvement in peripheral neuropathy and regeneration of small nerve fibres measured with corneal confocal microscopy in people with obesity with or without type 2 diabetes. These improvements correlate inversely with changes in triglyceride levels. Hyperlipidaemia, particularly hypertriglyceridemia, is associated with the development and progression of neuropathy. Lipid modifying agents may represent a potential therapeutic option for peripheral neuropathy. Post hoc analyses indicate that lipid-lowering therapies may halt the progression of neuropathy or even lead to regeneration of nerve fibres. Well designed randomized controlled trials are needed to establish if intensive targeted lipid lowering therapy as a part of holistic metabolic control leads to nerve fibre regeneration and improvement in neuropathy symptoms.

Ethoxyquin is neuroprotective and partially prevents somatic and autonomic neuropathy in db/db mouse model of type 2 diabetes

Ethoxyquin (EQ), a quinolone-based antioxidant, has demonstrated neuroprotective properties against several neurotoxic drugs in a phenotypic screening and is shown to protect axons in animal models of chemotherapy-induced peripheral neuropathy. We assessed the effects of EQ on peripheral nerve function in the db/db mouse model of type II diabetes. After a 7 week treatment period, 12-week-old db/db-vehicle, db/+ -vehicle and db/db-EQ treated animals were evaluated by nerve conduction, paw withdrawal against a hotplate, and fiber density in hindlimb footpads. We found that the EQ group had shorter paw withdrawal latency compared to vehicle db/db group. The EQ group scored higher in nerve conduction studies, compared to vehicle-treated db/db group. Morphology studies yielded similar results. To investigate the potential role of mitochondrial DNA (mtDNA) deletions in the observed effects of EQ, we measured total mtDNA deletion burden in the distal sciatic nerve. We observed an increase in total mtDNA deletion burden in vehicle-treated db/db mice compared to db/+ mice that was partially prevented in db/db-EQ treated animals. These results suggest that EQ treatment may exert a neuroprotective effect in diabetic neuropathy. The prevention of diabetes-induced mtDNA deletions may be a potential mechanism of the neuroprotective effects of EQ in diabetic neuropathy.

Dual diagnosis of Ochoa syndrome and Niemann-Pick disease type B in a consanguineous family

Ochoa syndrome (UFS1; Urofacial syndrome-1) is a very rare autosomal recessive disorder caused by mutations in the HPSE2 gene that results bladder voiding dysfunction and somatic motor neuropathy affecting the VIIth cranial nerve. Niemann-Pick disease is a rare autosomal recessive lysosomal storage disorder with systemic involvement resulting from sphingomyelinase deficiency and generally occurs via mutation in the sphingomyelin phosphodiesterase-1 gene (SMPD1). Here, we report a 6-year-old girl with symptoms such as urinary incontinence, recurrent urinary tract infections, peculiar facial expression, mainly when smiling, hypertelorism, constipation, incomplete closure of eyelids during sleep and splenomegaly. Homozygote mutations in two different genes responsible for two distinct syndromes were detected in the patient. Homozygous NM_000543.5:c.502G>A (p.Gly168Arg) mutation was found in the SMPD1 gene causing Niemann-Pick disease. In addition, some of the clinical features were due to a novel homozygous mutation identified in the HPSE2 gene, NM_021828.5:c.755delA (p.Lys252SerfsTer23). Here, we discuss about the importance of considering dual diagnosis in societies where consanguineous marriages are common. Accurate diagnosis of the patient is very important for the management of the diseases and prevention of complications.

Hereditary Transthyretin Amyloidosis- Clinical and Genetic Characteristics of a Multiracial South-East Asian Cohort in Singapore.

Studies of hereditary transthyretin amyloidosis (ATTRv amyloidosis) in South-East Asia are underrepresented in the literature. We report the unique phenotypic and genetic characteristics of this disorder in a multiracial South-East Asian cohort. Patients with genetically proven ATTRv amyloidosis were identified over a 13-year period (2007-2020) at the National Neuroscience Institute, Singapore. Clinical, laboratory, genotypic and electrophysiological features were retrospectively reviewed. 29 patients comprising Chinese, Malay, Burmese, Vietnamese and Indonesians with ATTRv amyloidosis were identified. Somatic neuropathy was the most common initial presentation, followed by carpal tunnel syndrome, autonomic dysfunction and cardiac dysfunction. ATTR-A97S (p.Ala117Ser) was the most common variant found in 14 patients, constituting 66.7%of ethnic Chinese patients and 48.3%of the entire cohort. Five patients had early-onset disease (age < 50 years) with the following variants: ATTR-V30M (p.Val50Met), ATTR-G47A (p.Gly67Ala), ATTR-S50I (p.Ser70Ile) and ATTR-A97S (p.Ala117Ser); one patient with ATTR-A97S (p.Ala117Ser) had isolated unilateral carpal tunnel syndrome with amyloid deposits identified on histological examination of the transverse carpal ligament. All early-onset patients had a positive parental history; two patients, with ATTR-S50I (p.Ser70Ile) and ATTR-Ala97Ser (p.Ala117Ser) respectively, demonstrated anticipation with mother-to-daughter inheritance. Amongst the 24 patients with late-onset disease (age≥50 years), two patients had novel variants, ATTR-G66D (p.Glu86Asp) and ATTR-A81V (p.Ala101Val) that were confirmed to be pathogenic based on the histological identification of transthyretin amyloid. Other identified variants included ATTR-V30M (p.Val50Met), ATTR-R34T (p.Arg54Thr), ATTR-S50I (p.Ser70Ile), ATTR-H88R (p.His108Arg) and ATTR-A97S (p.Ala117Ser). Our study further expands the genotypic and phenotypic knowledge regarding ATTRv amyloidosis.

Pearls &amp; Oy-sters: Number, Weaker, and Dizzier Due to Transthyretin Amyloidosis After 2 Liver Transplants

Hereditary transthyretin amyloidosis (hATTR) is an autosomal dominant, rapidly progressive, multisystem disease with substantial clinical heterogeneity, typically marked by lesions in the peripheral nervous system (median neuropathy, sensorimotor polyneuropathy, small-fiber somatic and autonomic neuropathy) and cardiovascular system.

Chronic complications in patients with newly diagnosed type 2 diabetes: prevalence and related metabolic and clinical features: the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 9

IntroductionWe explored the presence of chronic complications in subjects with newly diagnosed type 2 diabetes referred to the Verona Diabetes Clinic. Metabolic (insulin secretion and sensitivity) and clinical features associated...

Prediction of stump healing in lower limb amputation: a narrative review.

Both types of diabetes, as well as different forms of acquired diabetes, are associated with diabetic peripheral neuropathy. Diabetic foot ulcers (DFU) is the condition most commonly related to somatic peripheral neuropathy, often leading to gangrene and limb amputation. Independent from large-vessel disease, sensory loss may result in DFU development and even amputation. The crucial part of any lower limb amputation is the stump healing process, which represents the central goal of postoperative management. Despite the importance attributed to this process, a standard set of guidelines regarding efficient healing methods is yet to be formulated. Health professionals are faced with the challenge of assessing the different risk factors and deciding which has a greater influence on the stump healing rate. There is currently an insufficient number of studies regarding factors effecting lower limb amputation. The main purpose of this review is to discuss the markers that can be helpful in the prediction of stump healing in patients who have undergone lower limb amputation.

High HDL cholesterol: A risk factor for diabetic retinopathy? Findings from NO BLIND study

AimsTo assess the correlation between diabetic retinopathy (DR) and potential risk factors, as well as the relationship between DR and the other complications of diabetes, in a real-life population of type 2 diabetes patients recruited in several centres in Italy. MethodsThe NO BLIND is a cross-sectional, multicentre, observational study, which involved nine public outpatient clinics in Italy. The patients were assessed for eligibility from November 2016 till November 2017. Those enrolled underwent standard fundus oculi exam. Clinical and laboratory data were also collected. Results2068 T2DM underwent fundus oculi exam. 435 received diagnosis of diabetic retinopathy (21%). Diabetic retinopathy was independently associated with HDL cholesterol (O.R.: 1.042; 95% C.I.: 1.012–1.109; p = 0.004), Albumin Excretion Rate (AER) (O.R.: 1.001; 95% C.I.: 1.000–1.002; p = 0.034) and GFR (O.R.: 1.159; 95% C.I.: 1.039–1.294; p = 0.008). HDL cholesterol values were hence split in two classes according to a potential cut-off (40 mg/dL), as defined by the ROC curve. Following analysis confirmed the association between DR and high HDL values (p = 0.032). Somatic neuropathy and diabetic ulcer were independently related with DR (p < 0.001 and p = 0.012, respectively). ConclusionsA novel relationship between high HDL cholesterol and DR was observed.

An update on the diagnosis and treatment of diabetic somatic and autonomic neuropathy.

Diabetic peripheral neuropathy (DPN) is the most common chronic complication of diabetes. It poses a significant challenge for clinicians as it is often diagnosed late when patients present with advanced consequences such as foot ulceration. Autonomic neuropathy (AN) is also a frequent and under-diagnosed complication unless it is overtly symptomatic. Both somatic and autonomic neuropathy are associated with increased mortality. Multiple clinical trials have failed because of limited efficacy in advanced disease, inadequate trial duration, lack of effective surrogate end-points and a lack of deterioration in the placebo arm in clinical trials of DPN. Multifactorial risk factor reduction, targeting glycaemia, blood pressure and lipids can reduce the progression of DPN and AN. Treatment of painful DPN reduces painful symptoms by about 50% at best, but there is limited efficacy with any single agent. This reflects the complex aetiology of painful DPN and argues for improved clinical phenotyping with the use of targeted therapy, taking into account co-morbid conditions such as anxiety, depression and sleep disturbance.

Broadening the Spectrum of Adulthood X-Linked Adrenoleukodystrophy: A Report of Two Atypical Cases

X-linked adrenoleukodystrophy (x-ALD) is a rare genetic disorder caused by a mutation in the ABCD1 gene, which encodes for a peroxisomal very long chain fatty acid transporter. Clinically, x-ALD can present a wide spectrum of different phenotypes: asymptomatic carriers, Addison only, cerebral x-ALD, and myelopathy with/without evidence of peripheral axonopathy (Adrenomyeloneuropathy). We report on two cases of adult x-ALD, with atypical phenotypes: (Case 1) A 37-years-old male with a 2-years-long history of spastic paraparesis, urinary urgency, and subclinical adrenocortical insufficiency. As an atypical finding, the MRI showed multiple congenital brain development defects. (Case 2) A 63-years-old male with a previous diagnosis of Addison disease, with a 6-years-long history of spastic paraparesis. Two years later, he complained of severe and disabling burning pain in his feet. A nerve conduction study was normal, but a skin biopsy revealed autonomic and somatic small fiber neuropathy. In both cases, genetic testing disclosed hemizygous mutation in ABCD1 associated with x-ALD: c.1394-2A > G and p.(Thr254Met), respectively. While case 1 supports the key role of peroxisome functions in brain development, case 2 points to a possible selective and clinically relevant peripheral small fiber degeneration in x-ALD myelopathy.

Diagnosing and managing diabetic somatic and autonomic neuropathy.

The diagnosis and management of diabetic neuropathy can be a major challenge. Late diagnosis contributes to significant morbidity in the form of painful diabetic neuropathy, foot ulceration, amputation, and increased mortality. Both hyperglycaemia and cardiovascular risk factors are implicated in the development of somatic and autonomic neuropathy and an improvement in these risk factors can reduce their rate of development and progression. There are currently no US Food and Drug Administration (FDA)-approved disease-modifying treatments for either somatic or autonomic neuropathy, as a consequence of multiple failed phase III clinical trials. While this may be partly attributed to premature translation, there are major shortcomings in trial design and outcome measures. There are a limited number of partially effective FDA-approved treatments for the symptomatic relief of painful diabetic neuropathy and autonomic neuropathy.

Diarrhoea and diabetes

Diarrhoea and diabetes