-
Muscle & Nerve Feb 2021Idiopathic small fiber neuropathy (iSFN) lacks broadly accepted diagnostic criteria, which hinders its timely diagnosis and treatment. A systematic literature review was...
Idiopathic small fiber neuropathy (iSFN) lacks broadly accepted diagnostic criteria, which hinders its timely diagnosis and treatment. A systematic literature review was performed to assess the published screening and diagnostic criteria for iSFN, excluding studies where SFN was of well-established etiology. Eighty-four clinical studies and seven guideline/review publications were included in this systematic review. Substantial heterogeneity existed in iSFN diagnostic criteria. The most common set of criteria to diagnose iSFN [presence of any symptoms of iSFN, absence of large fiber involvement, and reduced intraepidermal nerve fiber density (IENFD)] was used in only 14% of studies. Mandatory individual criteria to confirm iSFN included any sensory symptoms (60% of studies), pain (19% of studies), small fiber signs (20% of studies), absence of large fiber signs (62% of studies), reduced IENFD (38% of studies), and autonomic symptoms (1% of studies). This review highlights a clear need for standardized, evidence-based guidelines for diagnosing iSFN.
Topics: Autonomic Nervous System; Electrodiagnosis; Epidermis; Galvanic Skin Response; Humans; Hyperalgesia; Hypesthesia; Nerve Fibers; Neural Conduction; Neuralgia; Paresthesia; Pruritus; Small Fiber Neuropathy; Vasomotor System
PubMed: 32989823
DOI: 10.1002/mus.27070 -
Current Therapeutic Research, Clinical... 2020The World Health Organization estimates that diabetes is the seventh leading cause of death. Uncontrolled diabetes may cause severe consequences such as cardiovascular... (Review)
Review
BACKGROUND
The World Health Organization estimates that diabetes is the seventh leading cause of death. Uncontrolled diabetes may cause severe consequences such as cardiovascular (CV) events (myocardial infarction, stroke, or CV mortality), lower-extremity amputations, and end-stage renal disease. Microvascular complications include retinopathy, autonomic and peripheral neuropathy, nephropathy, and diabetic ulcers. Major CV outcomes trials that were by the Food and Drug Administration for all new antihyperglycemia medications for patients at high risk for CV events were recently completed for all 4 US-marketed dipeptidyl peptidase-4 (DPP-4) inhibitors.
OBJECTIVE
To present a comprehensive review of the clinical trials that evaluate macrovascular and microvascular complications reported with DPP-4 inhibitors in patients with type 2 diabetes mellitus.
METHODS
In this review, we analyzed published articles in PubMed and Ovid databases between January 2008 and September 2019 that evaluated the effect of DPP-4 inhibitors on macrovascular and microvascular complications in patients with type 2 diabetes mellitus.
RESULTS
A total of 18 studies, which included randomized controlled trials and meta-analyses were assessed. Current evidence demonstrates that the addition of DPP-4 inhibitors to standard antihyperglycemic and CV risk reduction treatment has not shown CV benefit relative to placebo in contrast to recently published studies for other medications within the glucagon-like peptide 1 agonist and sodium-glucose co-transporter 2 inhibitor classes. Notably, the potential risk for heart failure hospitalizations may exist for saxagliptin, and this effect is not extrapolated as a class effect. Based on our review, DPP-4 inhibitors may not influence microvascular complications in patients with diabetes. However, some studies have shown that saxagliptin and linagliptin may slow down the progression of albuminuria in patients with type 2 diabetes mellitus. The overall quality of the studies included in this review was high due to the inclusion of randomized controlled trials and meta-analyses.
CONCLUSIONS
DPP-4 inhibitors were found to have a neutral effect on macrovascular and microvascular complications, with the exception of saxagliptin, which may increase the risk for heart failure hospitalizations.
PubMed: 32817765
DOI: 10.1016/j.curtheres.2020.100596 -
Autoimmunity Reviews Sep 2020More than one-fourth of all Persian gulf war coalition soldiers remain seriously ill. Several epidemiological studies suggest a link between multiple vaccinations at the...
UNLABELLED
More than one-fourth of all Persian gulf war coalition soldiers remain seriously ill. Several epidemiological studies suggest a link between multiple vaccinations at the time of the military operation and the illness development. Macrophagic Myofasciitis and post-HPV vaccination syndrome are two newer controversial vaccine-related disabling ailments.
OBJECTIVES
1) To systematically review all original articles investigating the association of vaccines with gulf war illness, 2) To discuss gulf war illness, Macrophagic Myofasciitis, and post-HPV vaccination syndrome clinical similarities, 3) To discuss emergent pathogenetic mechanisms proposed for post-HPV vaccination syndrome that may be also relevant to gulf war illness and Macrophagic Myofasciitis.
RESULTS
All original epidemiological studies (n = 11) found a positive association between vaccination and gulf war illness development. Chronic fatigue, widespread pain and cognitive impairment characterize the three syndromes under discussion. Anti-adrenergic receptor antibodies, dysautonomia and small fiber neuropathy have been recently described in patients with post-HPV vaccination syndrome.
CONCLUSION
post-HPV vaccination syndrome, Macrophagic Myofasciitis, and gulf war illness analogy suggests that some vaccines or multiple vaccinations in a very short period of time may induce, in susceptible individuals, chronic pain, fatigue and dyscognition. Vaccine-induced autoimmune dysautonomia is hypothesized as the common pathogenetic mechanism for this symptom cluster. Further research on the presence of small fiber neuropathy, adrenergic receptor antibodies, and abnormal autonomic function tests in the three syndromes under discussion may help to elucidate this hypothesis.
Topics: Fasciitis; Gulf War; Humans; Myositis; Papillomavirus Infections; Primary Dysautonomias; Vaccination; Vaccines
PubMed: 32659478
DOI: 10.1016/j.autrev.2020.102603 -
JAMA Jul 2020Many patients with systemic amyloidosis are underdiagnosed. Overall, 25% of patients with immunoglobulin light chain (AL) amyloidosis die within 6 months of diagnosis...
IMPORTANCE
Many patients with systemic amyloidosis are underdiagnosed. Overall, 25% of patients with immunoglobulin light chain (AL) amyloidosis die within 6 months of diagnosis and 25% of patients with amyloid transthyretin (ATTR) amyloidosis die within 24 months of diagnosis. Effective therapy exists but is ineffective if end-organ damage is severe.
OBJECTIVE
To provide evidence-based recommendations that could allow clinicians to diagnose this rare set of diseases earlier and enable accurate staging and counseling about prognosis.
EVIDENCE REVIEW
A comprehensive literature search was conducted by a reference librarian with publication dates from January 1, 2000, to December 31, 2019. Key search terms included amyloid, amyloidosis, nephrotic syndrome, heart failure preserved ejection fraction, and peripheral neuropathy. Exclusion criteria included case reports, non-English-language text, and case series of fewer than 10 patients. The authors independently selected and appraised relevant literature.
FINDINGS
There was a total of 1769 studies in the final data set. Eighty-one articles were included in this review, of which 12 were randomized clinical trials of therapy that included 3074 patients, 9 were case series, and 3 were cohort studies. The incidence of AL amyloidosis is approximately 12 cases per million persons per year and there is an estimated prevalence of 30 000 to 45 000 cases in the US and European Union. The incidence of variant ATTR amyloidosis is estimated to be 0.3 cases per year per million persons with a prevalence estimate of 5.2 cases per million persons. Wild-type ATTR is estimated to have a prevalence of 155 to 191 cases per million persons. Amyloidosis should be considered in the differential diagnosis of adult nondiabetic nephrotic syndrome; heart failure with preserved ejection fraction, particularly if restrictive features are present; unexplained hepatomegaly without imaging abnormalities; peripheral neuropathy with distal sensory symptoms, such as numbness, paresthesia, and dysesthesias (although the autonomic manifestations occasionally may be the presenting feature); and monoclonal gammopathy of undetermined significance with atypical clinical features. Staging can be performed using blood testing only. Therapeutic decision-making for AL amyloidosis involves choosing between high-dose chemotherapy and stem cell transplant or bortezomib-based chemotherapy. There are 3 therapies approved by the US Food and Drug Administration for managing ATTR amyloidosis, depending on clinical phenotype.
CONCLUSIONS AND RELEVANCE
All forms of amyloidosis are underdiagnosed. All forms now have approved therapies that have been demonstrated to improve either survival or disability and quality of life. The diagnosis should be considered in patients that have a multisystem disorder involving the heart, kidney, liver, or nervous system.
Topics: Algorithms; Benzoxazoles; Dexamethasone; Diagnosis, Differential; Gene Silencing; Heart Failure; Humans; Immunoglobulin Light-chain Amyloidosis; Liver Transplantation; Melphalan; Prognosis; Proteinuria; Stem Cell Transplantation
PubMed: 32633805
DOI: 10.1001/jama.2020.5493 -
Journal of Clinical Medicine Feb 2020Diabetic foot is the most frequent disorder among the chronic complications of diabetes, happening in 25% of patients. Objective clinical outcome measures are tests or... (Review)
Review
Diabetic foot is the most frequent disorder among the chronic complications of diabetes, happening in 25% of patients. Objective clinical outcome measures are tests or clinical instruments that provide objective values for result measurement. The aim of this study was to carry out a systematic review of specific objective clinical outcome measures focused on the assessment and monitoring of diabetic foot disorders. The databases used were PubMed, CINAHL, Scopus, PEDro, Cochrane, SciELO and EMBASE. Search terms used were foot, ankle, diabet*, diabetic foot, assessment, tools, instruments, objective outcome measures, valid*, reliab*. Because of the current published evidence, diabetic neuropathy assessment via sudomotor analysis, cardiovascular autonomic neuropathy and peripheral vascular disease detection by non-invasive electronic devices, wound 3D dimensional measurement, hyperspectral imaging for ulcer prediction and the probe-to-bone test for osteomyelitis diagnosis were highlighted in this study.
PubMed: 32102313
DOI: 10.3390/jcm9020602 -
Diabetes/metabolism Research and Reviews Jul 2020Rigorous glycaemic control-reflected by low HbA1c goals-is of the utmost importance in the prevention and management of complications in patients with type 1 diabetes...
Rigorous glycaemic control-reflected by low HbA1c goals-is of the utmost importance in the prevention and management of complications in patients with type 1 diabetes mellitus (T1DM). However, previous studies suggested that short-term glycaemic variability (GV) is also important to consider as excessive glucose fluctuations may have an additional impact on the development of diabetic complications. The potential relationship between GV and the risk of cardiovascular autonomic neuropathy (CAN), a clinical expression of cardiovascular autonomic dysfunction, is of increasing interest. This systematic review aimed to summarize existing evidence concerning the relationship between GV and cardiovascular autonomic dysfunction in T1DM. An electronic database search of Medline (PubMed), Web of Science and Embase was performed up to October 2019. There were no limits concerning year of publication. Methodological quality was evaluated using the Newcastle Ottawa Scale for observational studies. Six studies (four cross-sectional and two prospective cohorts) were included. Methodological quality of the studies varied from level C to A2. Two studies examined the association between GV and heart rate variability (HRV), and both found significant negative correlations. Regarding cardiovascular autonomic reflex tests (CARTs), two studies did not, while two other studies did find significant associations between GV parameters and CART scores. However, associations were attenuated after adjusting for covariates such as HbA1c, age and disease duration. In conclusion, this systematic review found some preliminary evidence supporting an association between GV and cardiovascular autonomic dysfunction in T1DM. Hence, uncertainty remains whether high GV can independently contribute to the onset or progression of CAN. The heterogeneity in the methodological approach made it difficult to compare different studies. Future studies should therefore use uniformly evaluated continuous glucose monitoring-derived parameters of GV, while standardized assessment of HRV, CARTs and other potential cardiac autonomic function parameters is needed for an unambiguous definition of CAN.
Topics: Autonomic Nervous System Diseases; Blood Glucose; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus, Type 1; Humans; Hyperglycemia; Prognosis
PubMed: 32073212
DOI: 10.1002/dmrr.3301 -
Immunosuppressive treatment for peripheral neuropathies in Sjogren's syndrome - a systematic review.Romanian Journal of Internal Medicine =... Mar 2020Sjogren's syndrome (SS) is among the most frequent autoimmune diseases and one of its most severe extraglandular manifestations is peripheral neuropathy. There is no...
BACKGROUND
Sjogren's syndrome (SS) is among the most frequent autoimmune diseases and one of its most severe extraglandular manifestations is peripheral neuropathy. There is no consensus about peripheral neuropathy treatment in SS. Our aim is to identify studies proving the efficiency of immunosuppressive treatment on peripheral neuropathies in SS.
METHODS
The search was conducted on the PubMed (MEDLINE) database. Studies with patients diagnosed with SS and peripheral neuropathy were included. Treatment with one of the following was among inclusion criteria: glucocorticoids (GC), rituximab (RTX), azathioprine (AZA), mycophenolic acid (MMF), cyclophosphamide (CP), methotrexate (MTX), plasmapheresis or iv immunoglobulins (IV IG).
RESULTS
A total of 116 results were found and abstracts were examined. 103 papers were excluded, and the remaining 13 papers were analyzed. They were 3 case series and 10 case reports, retrospective, totalizing 62 patients of which 22 (35.5%) received IV IG, 8 (13%) received RTX, 7 (11%) CP, and 5 (8%) received only GC. Drug associations containing corticosteroids were frequent. Of those 22 treated with IV IG, 18 patients improved (82%), and 4 stabilized (18%). IV IG was useful in sensory, motor and sensorimotor neuropathies. CP had good results in mononeuritis multiplex, while autonomic neuropathies responded well to GC or RTX. AZA, RTX, MTX, MMF or plasmapheresis were not used alone. Follow-up periods were heterogenous and the evaluation of the neuropathy was not systematic.
CONCLUSION
There is only low level evidence (retrospective case reports and case series). In most cases, IV IG treatment in patients with peripheral neuropathies and SS resulted in clinical improvement, while other therapies, such as RTX, corticosteroids and CP proved to be useful in a handful of cases.
Topics: Adrenal Cortex Hormones; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Peripheral Nervous System Diseases; Rituximab; Sjogren's Syndrome
PubMed: 31527298
DOI: 10.2478/rjim-2019-0022 -
Clinical Autonomic Research : Official... Sep 2019Autonomic dysfunction is a hallmark feature of hereditary ATTR amyloidosis. The aim of this study was to summarize the characteristics and natural history of autonomic...
BACKGROUND
Autonomic dysfunction is a hallmark feature of hereditary ATTR amyloidosis. The aim of this study was to summarize the characteristics and natural history of autonomic dysfunction in patients with hereditary ATTR amyloidosis.
METHODS
A systematic review of the natural history and clinical trials of patients with ATTR amyloidosis was performed. Alternative surrogate markers of autonomic function were analyzed to understand the prevalence and outcome of autonomic dysfunction.
RESULTS
Patients with early-onset disease displayed autonomic dysfunction more distinctively than those with late-onset disease. The nutritional status and some autonomic items in the quality-of-life questionnaires were used to assess the indirect progression of autonomic dysfunction in most studies. Gastrointestinal symptoms and orthostatic hypotension were resent earlier than urogenital complications. Once symptoms were present, their evolution was equivalent to the progression of the motor and sensory neuropathy impairment.
CONCLUSION
The development of autonomic dysfunction impacts morbidity, disease progression, and mortality in patients with hereditary ATTR amyloidosis.
Topics: Amyloid Neuropathies, Familial; Autonomic Nervous System Diseases; Humans
PubMed: 31473866
DOI: 10.1007/s10286-019-00630-y -
Supportive Care in Cancer : Official... Jan 2020Impaired cardiovascular and autonomic function during treatment and during recovery from leukemia has been indicated. In this context, heart rate variability (HRV) is a...
Is heart rate variability a valuable method to investigate cardiac autonomic dysfunction in subjects with leukemia? A systematic review to evaluate its importance in clinical practice.
Impaired cardiovascular and autonomic function during treatment and during recovery from leukemia has been indicated. In this context, heart rate variability (HRV) is a non-invasive measure that describes the oscillations of the intervals between consecutive heart beats (RR intervals), influenced by the autonomic nervous system. We intend to review literature showing HRV changes in leukemia subjects. The articles selected in the current review were attained up to March 2018, and the search was limited to articles in English language, published in peer-reviewed journals, with both adult and child age samples. The articles were investigated in the five electronic databases: PubMed, Physiotherapy Evidence Database (PEDro), Cochrane Clinical Trials, Scientific Electronic Library Online (SciELO), and Excerpta Medica dataBASE (EMBASE). Towards the end of the research, 9 studies were included. Subjects undergoing treatment for leukemia have reduced HRV, signifying decreased vagal control of heart rate. The subjects that undertook leukemia treatment and their survivors experienced a reduction in HRV with subsequent recovery, but the recovery time is ill defined. HRV is reduced in leukemia subjects who progress to neuropathy secondary to chemotherapy, accompanied by cardiac dysfunction. We advocate the use of HRV to evaluate autonomic function and decide the treatment to prevent autonomic impairment in leukemia subjects.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Autonomic Nervous System Diseases; Child; Electrocardiography; Heart Diseases; Heart Rate; Humans; Leukemia; Practice Patterns, Physicians'
PubMed: 31444641
DOI: 10.1007/s00520-019-05047-x -
Neurology Aug 2019Distal symmetrical axonal polyneuropathy (DSP) is due to injury to peripheral sensory, motor, and autonomic nerve fibers, resulting in distal predominant sensory loss,...
Distal symmetrical axonal polyneuropathy (DSP) is due to injury to peripheral sensory, motor, and autonomic nerve fibers, resulting in distal predominant sensory loss, pain, and gait instability. DSP occurs as a complication of multiple medical conditions including diabetes or HIV, or following exposure to various toxins such as chemotherapy. It affects at least 10% of the United States population. Few treatments for DSP are approved by regulatory agencies. Reliable and responsive outcome measures are integral to developing new DSP treatments. Multiple clinician-rated measures that incorporate neuropathy signs exist, however, it is not clear which of these measures performs best for various DSP phenotypes. This systematic review summarizes the content of 18 published measures of DSP identified using PubMed and from personal archives of the authors. The relative percentage of scoring dedicated to motor, reflex, large and small fiber sensory, and autonomic domains varied considerably among measures. The most common neurologic examination items included in the scales were (1) vibration perception (n = 18, 100%), (2) reflexes (n = 16, 89%), (3) pinprick perception (n = 14, 78%), (4) muscle strength (n = 11, 61%), (5) touch-pressure perception (n = 9, 50%), and (6) joint position perception (n = 8, 44%). This review can be used to inform decisions regarding which of the available clinician-rated sign outcome measures would be most appropriate for use in a particular DSP population, based on the domains most affected by that neuropathy or on the domains most likely to be affected by a particular experimental therapy.
Topics: Clinical Trials as Topic; Drug Development; Humans; Neurologic Examination; Outcome Assessment, Health Care; Polyneuropathies
PubMed: 31320471
DOI: 10.1212/WNL.0000000000007974