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Cureus Jun 2024This study investigated the pathogenesis and pathophysiology of chronic epipharyngitis, which presents a variety of symptoms, with a focus on autonomic neuropathy... (Review)
Review
This study investigated the pathogenesis and pathophysiology of chronic epipharyngitis, which presents a variety of symptoms, with a focus on autonomic neuropathy symptoms, and also investigated the literature for information on EAT, which is useful as a treatment method. The mechanism of action of EAT has recently been clarified in terms of its immune system-stimulating and endocrine system-stimulating effects. However, the autonomic nerve-stimulating effects of EAT are still largely unexplained. This study was conducted to collect and integrate previous studies and papers focusing on the autonomic nerve-stimulating effects of EAT and to provide insight into the still not fully elucidated autonomic nerve-stimulating effects of EAT on chronic epipharyngitis. The local stimulating effects of zinc chloride and the bleeding and pain effects of EAT are also summarized, suggesting that EAT exerts its therapeutic effects through the interaction of the immune system, the endocrine system, and the autonomic nervous system. It is important to determine which mechanism is predominantly involved in each case of chronic epipharyngitis and to utilize it in treatment. Elucidating the effects of EAT on the autonomic nervous system will be an important guideline in determining the treatment strategy for chronic epipharyngitis.
PubMed: 38933344
DOI: 10.7759/cureus.63182 -
Acta Endocrinologica (Bucharest,... 2023This study aims to determine the prevalence of neuropathy in the prediabetic period.
OBJECTIVE
This study aims to determine the prevalence of neuropathy in the prediabetic period.
DESIGN SUBJECTS AND METHOD
Informed consent was attained from the patients who volunteered to participate in the study after ethics committee approval was obtained. Patients under the age of 18, having vitamin B12 or folic acid deficiency, history of collagen tissue-rheumatological disease, chronic kidney failure, cirrhosis, ethylism, thyroid disease, autoimmune disease, malignancy, tuberculosis, type 1 or 2 diabetes mellitus and pregnant women were excluded from the study. Patients diagnosed with prediabetes were evaluated by the DN4 neuropathy complaint questionnaire. Neuropathy was diagnosed in patients having a score of four or more. For the statistical analyses Student t-test, Pearson chi-square test, and Fisher's exact test were performed using the NCSS program.
RESULTS
A total of 224 volunteers, 167 women and 57 men, were included in the study. The mean age of the participants was 51 and the mean level of hemoglobin A1C was 5.9. Neuropathy was detected in 45% of the cases. Especially in women, there was a significant increase in the frequency of neuropathy compared to men. The most common complaints found in our study were burning sensation and numbness in the extremities.
CONCLUSIONS
Similar to diabetic patients, prediabetic patients also have a high rate of neuropathy. For the early diagnosis of neuropathy and to be treated promptly, screening tests such as DN4 should be performed for all prediabetic patients. According to the test results, advanced examinations such as EMG or biopsy should be performed earlier.
PubMed: 38933248
DOI: 10.4183/aeb.2023.497 -
Journal of Personalized Medicine May 2024Pain perception, far from being a pathological mechanism, is a crucial protective stimulus to prevent additional injuries. Any disturbance in this complex system poses... (Review)
Review
INTRODUCTION
Pain perception, far from being a pathological mechanism, is a crucial protective stimulus to prevent additional injuries. Any disturbance in this complex system poses significant risks to individuals, affecting their quality of life and even their survival.
OBJECTIVE
This review aims to explore congenital insensitivity to pain, an extremely rare genetic disorder with an autosomal recessive pattern that results in the inability to perceive pain. We will focus on the well-known subtype, congenital insensitivity to pain with anhidrosis (CIPA). Our research seeks to update existing knowledge through a comprehensive literature review.
METHODOLOGY
The review employs a systematic literature review, analyzing various sources and scientific documents, primarily emphasizing CIPA. The review follows the PROSPERO protocol, registered under CRD42023394489. The literature search was performed on the Scopus, PubMed, and Cinahl databases.
RESULTS
Our review reveals secondary complications associated with CIPA, such as recurrent bone fractures, temperature insensitivity, self-mutilation, and, occasionally, intellectual disabilities. The limited available information underscores the need for expanding our knowledge.
CONCLUSIONS
In summary, CIPA, particularly, presents a significant medical challenge with adverse impacts on quality of life. Early diagnosis, education for families and healthcare professionals, and appropriate nursing care are essential for effective management. This review highlights the necessity of further research and awareness to enhance support for those affected.
PubMed: 38929791
DOI: 10.3390/jpm14060570 -
Genes May 2024Hereditary sensory and autonomic neuropathy type 1 is an autosomal dominant neuropathy caused by the or variants. These variants modify the preferred substrate of...
Hereditary sensory and autonomic neuropathy type 1 is an autosomal dominant neuropathy caused by the or variants. These variants modify the preferred substrate of serine palmitoyl transferase, responsible for the first step of sphingolipids synthesis, leading to accumulation of cytotoxic deoxysphingolipids. Diagnosis of HSAN1 is based on clinical symptoms, mainly progressive loss of distal sensory keep, and genetic analysis. Identifying new or "" variants raises the question as to their pathogenicity. This work focused on characterizing six new variants using in silico prediction tools, new meta-scores, 3D modeling, and functional testing to establish their pathogenicity. Variants from six patients with HSAN1 were studied. , CADD and REVEL scores and the 3D modeling software MITZLI were used to characterize the pathogenic effect of the variants. Functional tests based on plasma sphingolipids quantification (total deoxysphinganine, ceramides, and dihydroceramides) were performed by tandem mass spectrometry. In silico predictors did not provide very contrasting results when functional tests discriminated the different variants according to their impact on deoxysphinganine level or canonical sphingolipids synthesis. Two variants were newly described as pathogenic: NM_006415.4:c.998A>G and NM_006415.4:c.1015G>A. The combination of the different tools provides arguments to establish the pathogenicity of these new variants. When available, functional testing remains the best option to establish the in vivo impact of a variant. Moreover, the comprehension of metabolic dysregulation offers opportunities to develop new therapeutic strategies for these genetic disorders.
Topics: Humans; Serine C-Palmitoyltransferase; Hereditary Sensory and Autonomic Neuropathies; Mutation, Missense; Male; Female; Sphingolipids; Adult; Middle Aged
PubMed: 38927628
DOI: 10.3390/genes15060692 -
BMC Pediatrics Jun 2024Guillain‒Barre syndrome (GBS) is an acute inflammatory peripheral neuropathy caused by autoimmunity. Gangliosides and sulfatides are important components of peripheral...
BACKGROUND
Guillain‒Barre syndrome (GBS) is an acute inflammatory peripheral neuropathy caused by autoimmunity. Gangliosides and sulfatides are important components of peripheral nerves. Anti-sulfatide antibody-mediated complement is associated with acute sensorimotor peripheral neuropathy in GBS, which is characterized by pain and paresthesias.
CASE PRESENTATION
The child was a 7-year-old girl with headache and abdominal pain, followed by limb numbness and pain. Cranial imaging showed ventricular dilatation, peripheral nerve function conduction examination showed polyradiculopathy, and cerebrospinal fluid tests showed normal cell counts but elevated protein levels, all of which led to the diagnosis of GBS. After treatment with intravenous immunoglobulin (400 mg/kg × 5 days), the symptoms did not improve, and muscle strength progressively worsened, accompanied by paroxysmal complexion flushing, heart rate fluctuation, hyperhidrosis, and a progressive increase in cerebrospinal fluid protein (up to 3780.1 mg/L). On the basis of these findings combined with serum anti-sulfatide IgM positivity, anti-sulfatide antibody-related GBS was considered, and treatment with low-dose prednisolone (1 mg/kg/d) led to symptom improvement.
CONCLUSIONS
Anti-sulfatide antibody-associated GBS is associated with small fiber peripheral neuropathy. The main manifestations are pain, paresthesias and autonomic dysfunction. In addition to the dysfunction of spinal nerve root absorption caused by increased cerebrospinal fluid protein, autonomic dysfunction may be involved in pain. When the therapeutic effect of immunoglobulin is not satisfactory, a low dose and short course of corticosteroids can be considered, and the prognosis is good.
Topics: Humans; Female; Child; Guillain-Barre Syndrome; Abdominal Pain; Headache; Sulfoglycosphingolipids; Autoantibodies; Prednisolone
PubMed: 38926645
DOI: 10.1186/s12887-023-04287-5 -
Annals of Neurology Jun 2024Amyloid neuropathy is caused by deposition of insoluble β-pleated amyloid sheets in the peripheral nervous system. It is most common in: (1) light-chain amyloidosis, a... (Review)
Review
Amyloid neuropathy is caused by deposition of insoluble β-pleated amyloid sheets in the peripheral nervous system. It is most common in: (1) light-chain amyloidosis, a clonal non-proliferative plasma cell disorder in which fragments of immunoglobulin, light or heavy chain, deposit in tissues, and (2) hereditary transthyretin (ATTRv) amyloidosis, a disorder caused by autosomal dominant mutations in the TTR gene resulting in mutated protein that has a higher tendency to misfold. Amyloid fibrils deposit in the endoneurium of peripheral nerves, often extensive in the dorsal root ganglia and sympathetic ganglia, leading to atrophy of Schwann cells in proximity to amyloid fibrils and blood-nerve barrier disruption. Clinically, amyloid neuropathy is manifested as a length-dependent sensory predominant neuropathy associated with generalized autonomic failure. Small unmyelinated nerves are involved early and prominently in early-onset Val30Met ATTRv, whereas other ATTRv and light-chain amyloidosis often present with large- and small-fiber involvement. Nerve conduction studies, quantitative sudomotor axon testing, and intraepidermal nerve fiber density are useful tools to evaluate denervation. Amyloid deposition can be demonstrated by tissue biopsy of the affected organ or surrogate site, as well as bone-avid radiotracer cardiac imaging. Treatment of light-chain amyloidosis has been revolutionized by monoclonal antibodies and stem cell transplantation with improved 5-year survival up to 77%. Novel gene therapy and transthyretin stabilizers have revolutionized treatment of ATTRv, improving the course of neuropathy (less change in the modified Neuropathy Impairment Score + 7 from baseline) and quality of life. With great progress in amyloidosis therapies, early diagnosis and presymptomatic testing for ATTRv family members has become paramount. ANN NEUROL 2024.
PubMed: 38923548
DOI: 10.1002/ana.26965 -
Healthcare (Basel, Switzerland) Jun 2024Diabetic autonomic neuropathy is a common complication of type 2 diabetes mellitus (T2DM), especially in patients with long-term, poorly controlled diabetes. This study... (Review)
Review
BACKGROUND
Diabetic autonomic neuropathy is a common complication of type 2 diabetes mellitus (T2DM), especially in patients with long-term, poorly controlled diabetes. This study investigates the effects of exercise on autonomic nervous system activity in T2DM patients over time.
METHODS
A literature review using MEDLINE, Embase, Cochrane Library, Scopus, and PubMed identified studies assessed via heart rate variability. Papers were categorized into three groups: immediate effects (within 60 min), short-term effects (2-3 months), and long-term effects (over 4 months).
RESULTS
Nine articles with 161 T2DM patients were included in the meta-analysis. RMSSD changes after exercise were -4.3 ( = 0.227), 8.14 ( < 0.001), and 4.17 ( = 0.002) for the immediate, short-term, and long-term groups, respectively. LF/HF ratio changes were 0.21 ( = 0.264), -3.04 ( = 0.102), and -0.05 ( = 0.006) for the respective groups. Meta-regression indicated age, male gender, and exercise duration were associated with increased RMSSD, with coefficients of 2.36 ( = 0.001), 13.76 ( = 0.008), and 1.50 ( = 0.007), respectively. Age positively correlated with the LF/HF ratio, with a coefficient of 0.049 ( = 0.048).
CONCLUSIONS
Regular exercise (≥3 times per week) for over 2 months increases parasympathetic activity in T2DM patients, while sympathetic activity decreases significantly after 4 months. Further study is needed to validate these findings.
PubMed: 38921350
DOI: 10.3390/healthcare12121236 -
Journal of Neurology Jun 2024Biallelic pathogenic repeat expansions in RFC1 were recently identified as molecular origin of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) as...
Biallelic pathogenic repeat expansions in RFC1 were recently identified as molecular origin of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) as well as of one of the most common causes of adult-onset ataxia. In the meantime, the phenotypic spectrum has expanded massively and now includes mimics of multiple system atrophy or parkinsonism. After identifying a patient with a clinical diagnosis of amyotrophic lateral sclerosis (ALS) as a carrier of biallelic pathogenic repeat expansions in RFC1, we studied a cohort of 106 additional patients with a clinical main phenotype of motor neuron disease (MND) to analyze whether such repeat expansions are more common in MND patients. Indeed, two additional MND patients (one also with ALS and one with primary lateral sclerosis/PLS) have been identified as carrier of biallelic pathogenic repeat expansions in RFC1 in the absence of another genetic alteration explaining the phenotype, suggesting motor neuron disease as another extreme phenotype of RFC1 spectrum disorder. Therefore, MND might belong to the expanding phenotypic spectrum of pathogenic RFC1 repeat expansions, particularly in those MND patients with additional features such as sensory and/or autonomic neuropathy, vestibular deficits, or cerebellar signs. By systematically analyzing the RFC1 repeat array using Oxford nanopore technology long-read sequencing, our study highlights the high intra- and interallelic heterogeneity of this locus and allows the identification of the novel repeat motif 'ACAAG'.
PubMed: 38916676
DOI: 10.1007/s00415-024-12519-6 -
The American Journal of Gastroenterology Jun 2024We examined autoimmunity markers (AIM) and autonomic dysfunction in patients with chronic neurogastroenterological symptoms and their relationship to joint...
Joint Hypermobility, Autonomic Dysfunction, Gastrointestinal Dysfunction and Autoimmune markers (JAG-A): Clinical Associations and Response to Intravenous Immunoglobulin Therapy.
INTRODUCTION
We examined autoimmunity markers (AIM) and autonomic dysfunction in patients with chronic neurogastroenterological symptoms and their relationship to joint hypermobility/hypermobility spectrum disorder (JH/HSD).
METHODS
AIM positivity was defined as a diagnosis of known autoimmune/autoinflammatory disorder (AIDX) with at least one positive seromarker of autoimmunity or at least two positive seromarkers by themselves. Three cohorts were studied: (a) Retrospective (n = 300); (b) Prospective validation cohort (n =133); and (c) Treatment cohort (n=40), administered open-label intravenous immunoglobulin (IVIG).
RESULTS
AIM positivity was found in 40% and 29% of the retrospective and prospective cohorts, the majority of whom (71% and 69%, respectively) had AIDX. Significantly more patients with AIM had elevations of C-reactive protein (31% versus 15%, p<0.001) along with an increased proportion of cardiovascular autonomic dysfunction (48% versus 29%; p<.001), small fiber neuropathy (20% versus 9%; p=.002).8) and HLADQ8 positivity (24% versus 13%, p=.01). JH/HSD patients were more likely to have AIM (43% versus 15%, p=.001) along with more severe autonomic and gastrointestinal symptom scores. IVIG treatment was associated with robust improvement in pain, gastrointestinal and autonomic symptoms but adverse events were experienced by 62% patients.
CONCLUSIONS
Autoimmune markers and autonomic dysfunction are common in patients with unexplained gastrointestinal symptoms, especially in those with JH/HSD. Many patients seem to respond to IVIG treatment but this needs to be confirmed by controlled trials. These results highlight the need for vigilance for autoimmune and autonomic factors and JH/HSD in patients with neurogastroenterological disorders. Clinicaltrials.gov, NCT04859829.
PubMed: 38912927
DOI: 10.14309/ajg.0000000000002910 -
Endocrine Practice : Official Journal... Jun 2024To evaluate the determinants of orthostatic hypotension (OH) in type 2 diabetes (T2D) and the usefulness of ΔHR/ΔSBP, index of cardiac baroreflex function, in...
OBJECTIVES
To evaluate the determinants of orthostatic hypotension (OH) in type 2 diabetes (T2D) and the usefulness of ΔHR/ΔSBP, index of cardiac baroreflex function, in identifying neurogenic OH.
METHODS
In 208 participants with T2D, we performed three heart rate based cardiovascular reflex tests (HR-CARTs) and OH test and assessed clinical history and variables. We defined OH as a systolic blood pressure (BP) fall ≥20 and ≥30 mmHg with supine BP <140 and ≥140 mmHg, respectively, and early and confirmed CAN based on 1 and 2 abnormal HR-CARTs. In participants with OH, we measured ΔHR/ΔSBP, using data from the lying to standing and OH test, and its diagnostic accuracy for neurogenic OH (as OH plus confirmed HR-CAN).
RESULTS
OH was present in 25 participants and associated with lower HR-CARTs (P=0.01), higher HbA1c (P=0.0048), presence of CAN (P=0.0058), retinopathy (P=0.037), and peripheral vascular disease (P=0.0056), absence of hypertension (P=0.0008) and physical activity (P=0.0214), but not with interfering drugs and beta-blockers. In a multiple logistic regression, HR-CAN was the main independent determinant of OH (odds ratio: 4.74) with physical activity and hypertension (odds ratio: 0.16 and 0.23) (R2=0.22). ΔHR/ΔSBP had a good diagnostic accuracy for neurogenic OH (AUC: 0.816±0.087), and at the cut-off of 0.5 bpm/mmHg a sensitivity of 100% and specificity of 63.2%.
CONCLUSION
CAN is still the main determinant of OH in T2D but does not explain all its variance with contribution of comorbidities and physical inactivity. The index ΔHR/ΔSBP might represent a useful clinical tool to identify neurogenic OH.
PubMed: 38908717
DOI: 10.1016/j.eprac.2024.06.008