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Orphanet Journal of Rare Diseases Mar 2008Hereditary sensory neuropathy type I (HSN I) is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic... (Review)
Review
Hereditary sensory neuropathy type I (HSN I) is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances) are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7) identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN), especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra neuropathy, or decaying skin tumours like amelanotic melanoma. Management of HSN I follows the guidelines given for diabetic foot care (removal of pressure to the ulcer and eradication of infection, followed by the use of specific protective footwear) and starts with early and accurate counselling of patients about risk factors for developing foot ulcerations. The disorder is slowly progressive and does not influence life expectancy but is often severely disabling after a long duration of the disease.
Topics: Foot Diseases; Genetic Linkage; Hereditary Sensory and Autonomic Neuropathies; Humans; Mutation
PubMed: 18348718
DOI: 10.1186/1750-1172-3-7 -
Diabetes Therapy : Research, Treatment... Dec 2021Pentoxifylline (Px) has protean effects that can be utilized in the therapy of diabetes and its complications. There have been well-documented but often inconclusive... (Review)
Review
Pentoxifylline (Px) has protean effects that can be utilized in the therapy of diabetes and its complications. There have been well-documented but often inconclusive improvements in peripheral arterial disease, foot ulcers, peripheral neuropathy, nephropathy, retinopathy, ischemic heart disease and cerebrovascular disease. In addition, non-alcoholic steatosis and steatohepatitis, which are closely associated with insulin resistance and type 2 diabetes, have been shown to improve with pentoxifylline. Surprisingly, pentoxifylline modestly improves insulin resistance through improvements in capillary blood flow as well as beta cell function and decreased hepatic glucose production. The therapeutic effects of pentoxifylline are complementary to the effects of drugs such as blockers of the renin-angiotensin-aldosterone system when utilized in the therapy of diabetic nephropathy.
PubMed: 34647189
DOI: 10.1007/s13300-021-01168-x -
PloS One 2022Cirrhosis causes alterations in the cardiovascular and autonomic nervous systems and leads to cirrhotic cardiomyopathy (CCM). CCM is defined as cardiac dysfunction...
BACKGROUND
Cirrhosis causes alterations in the cardiovascular and autonomic nervous systems and leads to cirrhotic cardiomyopathy (CCM). CCM is defined as cardiac dysfunction characterized by an impaired systolic responsiveness to stress or exercise, and/or impaired diastolic function, as well as electrophysiological abnormalities, including chronotropic incompetence (CI), in the absence of other known cardiac disease. CI is a common feature of autonomic neuropathy in cirrhosis. The aim of the study is to assess the role of cardiac exercise stress test in the diagnosis of CCM.
METHODS
The analysis included 160 end-stage liver disease (ESLD) patients who underwent a cardiac exercise stress test prior to the orthotopic liver transplantation. CI was defined as the inability to achieve the heart rate reserve (HRR). Pertaining to the therapy with beta-blockers: 80% of HRR was achieved in patients not taking beta-blockers and 62% in patients taking beta-blockers.
RESULTS
In the analyzed population, 68.8% of patients met the criteria for CI. CI was more frequent in the more severe ESLD (with a higher MELD score and in a higher Child-Pugh class). In comparison to the viral hepatitis and other etiologies of ESLD, patients with alcoholic cirrhosis had a significantly lower rest heart rate (HR), lower maximal HR, lower median achieved percentage of maximal predicted HR (MPHR), a smaller percentage of patients achieved ≥ 85% of MPHR and a lower heart rate reserve. No significant relationship between the survival of OLT recipients and presence of chronotropic incompetence regarding to class of Child-Pugh scale, MELD score and etiology of ESLD were found.
CONCLUSIONS
The prevalence of CI is higher among liver transplant candidates than previously described. The altered chronotropic response may differ in regard to the severity of liver disease correlating with both the Child-Pugh and MELD scores, however CI does not seem to influence the long-term survival post OLT. Exercise stress test is a reliable, safe and useful tool for the diagnosis of CCM in liver transplant candidates and should be included in the standard cardiovascular assessment prior to OLT.
Topics: Adrenergic beta-Antagonists; End Stage Liver Disease; Exercise Test; Heart Rate; Humans; Liver Cirrhosis
PubMed: 35913923
DOI: 10.1371/journal.pone.0270784 -
Vojnosanitetski Pregled May 2012Disulfiram is used in the treatment of chronic alcoholism, because of the unpleasant symptoms produced after ethanol intake. Although it is well tolerated in most...
INTRODUCTION
Disulfiram is used in the treatment of chronic alcoholism, because of the unpleasant symptoms produced after ethanol intake. Although it is well tolerated in most patients, one in 15,000 patients will develop peripheral neuropathy every year, which is frequently misdiagnosed as alcoholic neuropathy.
CASE REPORT
We report clinical, laboratory, electrophysiological and histopathological features in a 19-year-old patient who developed an acute distal sensorymotor neuropathy during the treatment of alcoholism. At the end of 4-month treatment with disulfiram 250 mg/day, the patient complained of weakness in distal segments of the lower limbs associated with burning dysesthesias, numbness and pain in the soles of the feet and the legs below the knees; reduction in foot strength, the absence of ankle jerk tendon reflexes, and tactile stocking pin-pick and vibratory sensory impairment in the lower limbs below the knee. Recovery was successful after treatment cessation.
CONCLUSION
The significance of toxic neuropathy is shown by the fact that the recognition of clinical picture, identifying etiological factors and its elimination may prevent the evolution of polyneuropathy. This allows for more effective treatment of these neuropathies as apposite to idiopathic ones which can be treated only symptomatically. Our case report indicates the possibilities during a period with no serious damage to the axons manifested.
Topics: Alcohol Deterrents; Alcoholism; Disulfiram; Humans; Male; Peripheral Nervous System Diseases; Young Adult
PubMed: 22764551
DOI: 10.2298/vsp1205453v -
Muscle & Nerve Mar 2011Alcohol-related peripheral neuropathy (ALN) is a potentially debilitating complication of alcoholism that results in sensory, motor, and autonomic dysfunction.... (Comparative Study)
Comparative Study Review
Alcohol-related peripheral neuropathy (ALN) is a potentially debilitating complication of alcoholism that results in sensory, motor, and autonomic dysfunction. Unfortunately, ALN is rarely discussed as a specific disease entity in textbooks because it is widely assumed to primarily reflect consequences of nutritional deficiency. This hypothesis is largely based on observations first made over eight decades ago when it was demonstrated that thiamine deficiency (beriberi) neuropathy was clinically similar to ALN. In recent studies, failure of thiamine treatment to reverse ALN, together with new information demonstrating clinical and electrophysiological distinctions between ALN and nutritional deficiency neuropathies, suggests that alcohol itself may significantly predispose and enhance development of neuropathy in the appropriate clinical setting. We reviewed the evidence on both sides and conclude that ALN should be regarded as a toxic rather than nutritional neuropathy.
Topics: Alcoholic Neuropathy; Alcoholism; Animals; Clinical Trials as Topic; Ethanol; Humans; Nutritional Status; Peripheral Nervous System Diseases; Thiamine Deficiency
PubMed: 21321947
DOI: 10.1002/mus.21946 -
Neuroscience Letters Sep 2021Complex Regional Pain Syndrome (CRPS) is a musculoskeletal pain condition that often develops after limb injury and/or immobilization. Although the exact mechanisms...
Complex Regional Pain Syndrome (CRPS) is a musculoskeletal pain condition that often develops after limb injury and/or immobilization. Although the exact mechanisms underlying CRPS are unknown, the syndrome is associated with central and autonomic nervous system dysregulation and peripheral hyperalgesia symptoms. These symptoms also manifest in alcoholic neuropathy, suggesting that the two conditions may be pathophysiologically accretive. Interestingly, people assigned female at birth (AFAB) appear to be more sensitive to both CRPS and alcoholic neuropathy. To better understand the biobehavioral mechanisms underlying these conditions, we investigated a model of combined CRPS and alcoholic neuropathy in female rats. Animals were pair-fed either a Lieber-DeCarli alcohol liquid diet or a control diet for ten weeks. CRPS was modeled via unilateral hind limb cast immobilization for seven days, allowing for the other limb to serve as a within-subject control for hyperalgesia measures. To investigate the role of circulating ovarian hormones on pain-related behaviors, half of the animals underwent ovariectomy (OVX). Using the von Frey procedure to record mechanical paw withdrawal thresholds, we found that cast immobilization and chronic alcohol drinking separately and additively produced mechanical hyperalgesia observed 3 days after cast removal. We then examined neuroadaptations in AMPA GluR1 and NMDA NR1 glutamate channel subunits, extracellular signal-regulated kinase (ERK), and cAMP response element-binding protein (CREB) in bilateral motor and cingulate cortex across all groups. Consistent with increased pain-related behavior, chronic alcohol drinking increased GluR1, NR1, ERK, and CREB phosphorylation in the cingulate cortex. OVX did not alter any of the observed effects. Our results suggest accretive relationships between CRPS and alcoholic neuropathy symptoms and point to novel therapeutic targets for these conditions.
Topics: Alcohol Drinking; Animals; Central Nervous System Stimulants; Cyclic AMP Response Element-Binding Protein; Ethanol; Female; Gyrus Cinguli; Hindlimb Suspension; Hyperalgesia; MAP Kinase Signaling System; Motor Cortex; Nociception; Rats; Rats, Inbred F344; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate
PubMed: 34280506
DOI: 10.1016/j.neulet.2021.136119 -
Journal of Clinical Medicine Feb 2022Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. To date, NAFLD is the most frequent chronic liver disease seen... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. To date, NAFLD is the most frequent chronic liver disease seen day by day in clinical practice across most high-income countries, affecting nearly 25-30% of adults in the general population and up to 70% of patients with T2DM. Over the last few decades, it clearly emerged that NAFLD is a "multisystemic disease" and that the leading cause of death among patients with NAFLD is cardiovascular disease (CVD). Indeed, several observational studies and some meta-analyses have documented that NAFLD, especially its advanced forms, is strongly associated with fatal and non-fatal cardiovascular events, as well as with specific cardiac complications, including sub-clinical myocardial alteration and dysfunction, heart valve diseases and cardiac arrhythmias. Importantly, across various studies, these associations remained significant after adjustment for established cardiovascular risk factors and other confounders. Additionally, several observational studies and some meta-analyses have also reported that NAFLD is independently associated with specific microvascular conditions, such as chronic kidney disease and distal or autonomic neuropathy. Conversely, data regarding a potential association between NAFLD and retinopathy are scarce and often conflicting. This narrative review will describe the current evidence about the association between NAFLD and the risk of macro- and microvascular manifestations of CVD, especially in patients with T2DM. We will also briefly discuss the biological mechanisms underpinning the association between NAFLD and its advanced forms and macro- and microvascular CVD.
PubMed: 35207239
DOI: 10.3390/jcm11040968 -
Experimental Eye Research Jul 2021Peroxisome Proliferator-Activated Receptors (PPARs) are a family of nuclear receptors that play essential roles in modulating cell differentiation, inflammation, and... (Review)
Review
Peroxisome Proliferator-Activated Receptors (PPARs) are a family of nuclear receptors that play essential roles in modulating cell differentiation, inflammation, and metabolism. Three subtypes of PPARs are known: PPAR-alpha (PPARα), PPAR-gamma (PPARγ), and PPAR-beta/delta (PPARβ/δ). PPARα activation reduces lipid levels and regulates energy homeostasis, activation of PPARγ results in regulation of adipogenesis, and PPARβ/δ activation increases fatty acid metabolism and lipolysis. PPARs are linked to various diseases, including but not limited to diabetes, non-alcoholic fatty liver disease, glaucoma and atherosclerosis. In the past decade, numerous studies have assessed the functional properties of PPARs in the eye and key PPAR mechanisms have been discovered, particularly regarding the retina and cornea. PPARγ and PPARα are well established in their functions in ocular homeostasis regarding neuroprotection, neovascularization, and inflammation, whereas PPARβ/δ isoform function remains understudied. Naturally, studies on PPAR agonists and antagonists, associated with ocular pathology, have also gained traction with the development of PPAR synthetic ligands. Studies on PPARs has significantly influenced novel therapeutics for diabetic eye disease, ocular neuropathy, dry eye, and age-related macular degeneration (AMD). In this review, therapeutic potentials and implications will be highlighted, as well as reported adverse effects. Further investigations are necessary before any of the PPARs ligands can be utilized, in the clinics, to treat eye diseases. Future research on the prominent role of PPARs will help unravel the complex mechanisms involved in order to prevent and treat ocular diseases.
Topics: Animals; Eye Diseases; Homeostasis; Humans; Ligands; Lipid Metabolism; Peroxisome Proliferator-Activated Receptors
PubMed: 34010603
DOI: 10.1016/j.exer.2021.108617 -
Journal of Diabetes Investigation Mar 2013Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the two primary incretin hormones secreted from the intestine on ingestion of... (Review)
Review
Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the two primary incretin hormones secreted from the intestine on ingestion of various nutrients to stimulate insulin secretion from pancreatic β-cells glucose-dependently. GIP and GLP-1 undergo degradation by dipeptidyl peptidase-4 (DPP-4), and rapidly lose their biological activities. The actions of GIP and GLP-1 are mediated by their specific receptors, the GIP receptor (GIPR) and the GLP-1 receptor (GLP-1R), which are expressed in pancreatic β-cells, as well as in various tissues and organs. A series of investigations using mice lacking GIPR and/or GLP-1R, as well as mice lacking DPP-4, showed involvement of GIP and GLP-1 in divergent biological activities, some of which could have implications for preventing diabetes-related microvascular complications (e.g., retinopathy, nephropathy and neuropathy) and macrovascular complications (e.g., coronary artery disease, peripheral artery disease and cerebrovascular disease), as well as diabetes-related comorbidity (e.g., obesity, non-alcoholic fatty liver disease, bone fracture and cognitive dysfunction). Furthermore, recent studies using incretin-based drugs, such as GLP-1 receptor agonists, which stably activate GLP-1R signaling, and DPP-4 inhibitors, which enhance both GLP-1R and GIPR signaling, showed that GLP-1 and GIP exert effects possibly linked to prevention or treatment of diabetes-related complications and comorbidities independently of hyperglycemia. We review recent findings on the extrapancreatic effects of GIP and GLP-1 on the heart, brain, kidney, eye and nerves, as well as in the liver, fat and several organs from the perspective of diabetes-related complications and comorbidities.
PubMed: 24843641
DOI: 10.1111/jdi.12065 -
Frontiers in Immunology 2018alcohol exposure is emerging as a major risk factor for lifelong aberrant neuroimmune function. Fetal alcohol spectrum disorder encompasses a range of behavioral and... (Review)
Review
alcohol exposure is emerging as a major risk factor for lifelong aberrant neuroimmune function. Fetal alcohol spectrum disorder encompasses a range of behavioral and physiological sequelae that may occur throughout life and includes cognitive developmental disabilities as well as disease susceptibility related to aberrant immune and neuroimmune actions. Emerging data from clinical studies and findings from animal models support that of fetal alcohol exposure may reprogram the developing central nervous system leading to altered neuroimmune and neuroglial signaling during adulthood. In this review, we will focus on the consequences of low to moderate prenatal alcohol exposure (PAE) on neuroimmune interactions during early life and at different stages of adulthood. Data discussed here will include recent studies suggesting that while abnormal immune function is generally minimal under basal conditions, following pathogenic stimuli or trauma, significant alterations in the neuroimmune axis occur. Evidence from published reports will be discussed with a focus on observations that PAE may bias later-life peripheral immune responses toward a proinflammatory phenotype. The propensity for proinflammatory responses to challenges in adulthood may ultimately shape neuron-glial-immune processes suspected to underlie various neuropathological outcomes including chronic pain and cognitive impairment.
Topics: Age Factors; Alcoholic Beverages; Animals; Disease Models, Animal; Disease Susceptibility; Female; Fetal Alcohol Spectrum Disorders; Humans; Maternal Exposure; Neuralgia; Neurogenic Inflammation; Neuroglia; Neuroimmunomodulation; Pregnancy; Prenatal Exposure Delayed Effects; Spinal Cord
PubMed: 29910801
DOI: 10.3389/fimmu.2018.01107