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Pain Reports Sep 2023Previous clinical observations raised the possibility that COVID-19 vaccination might trigger a small-fibre neuropathy.
INTRODUCTION
Previous clinical observations raised the possibility that COVID-19 vaccination might trigger a small-fibre neuropathy.
OBJECTIVES
In this uncontrolled observational study, we aimed to identify small fibre damage in patients complaining of generalized sensory symptoms and pain after COVID-19 vaccination.
METHODS
We collected clinical data, including a questionnaire for assessing autonomic symptoms (Composite Autonomic Symptom Score-31), and investigated quantitative sensory testing (QST) and skin biopsy in 15 prospectively enrolled patients with generalized sensory symptoms and pain after COVID-19 vaccination. Nine patients complaining of orthostatic intolerance also underwent cardiovascular autonomic tests.
RESULTS
We found that all patients experienced widespread pain, and most of them (11 of 15) had a fibromyalgia syndrome. All patients had normal skin biopsy findings, and in the 9 patients with orthostatic intolerance, cardiovascular autonomic tests showed normal findings. Nevertheless, 5 patients had cold and warm detection abnormalities at the QST investigation.
CONCLUSIONS
In our study, most patients complaining of generalized sensory symptoms and pain after COVID-19 vaccination had clinical and diagnostic test findings compatible with a fibromyalgia syndrome. Although the abnormal QST findings we found in 5 patients might be compatible with a small-fibre neuropathy, they should be cautiously interpreted given the psychophysical characteristics of this diagnostic test. Further larger controlled studies are needed to define precisely the association between small fibre damage and COVID-19 vaccination.
PubMed: 38225959
DOI: 10.1097/PR9.0000000000001089 -
Neurology(R) Neuroimmunology &... Mar 2024Immune-mediated small fiber neuropathy (SFN) is increasingly recognized. Acute-onset SFN (AOSFN) remains poorly described. Herein, we report a series of AOSFN cases in...
BACKGROUND AND OBJECTIVES
Immune-mediated small fiber neuropathy (SFN) is increasingly recognized. Acute-onset SFN (AOSFN) remains poorly described. Herein, we report a series of AOSFN cases in which immune origins are debatable.
METHODS
We included consecutive patients with probable or definite AOSFN. Diagnosis of SFN was based on the NEURODIAB criteria. Acute onset was considered when the maximum intensity and extension of both symptoms and signs were reached within 28 days. We performed the following investigations: clinical examination, neurophysiologic assessment encompassing a nerve conduction study to rule out large fiber neuropathy, laser-evoked potentials (LEPs), warm detection thresholds (WDTs), electrochemical skin conductance (ESC), epidermal nerve fiber density (ENF), and patient serum reactivity against mouse sciatic nerve teased fibers, mouse dorsal root ganglion (DRG) sections, and cultured DRG. The serum reactivity of healthy subjects (n = 10) and diseased controls (n = 12) was also analyzed. Data on baseline characteristics, biological investigations, and disease course were collected.
RESULTS
Twenty patients presenting AOSFN were identified (60% women; median age: 44.2 years [interquartile range: 35.7-56.2]). SFN was definite in 18 patients (90%) and probable in 2 patients. A precipitating event was present in 16 patients (80%). The median duration of the progression phase was 14 days [5-28]. Pain was present in 17 patients (85%). Twelve patients (60%) reported autonomic involvement. The clinical pattern was predominantly non-length-dependent (85%). Diagnosis was confirmed by abnormal LEPs (60%), ENF (55%), WDT (39%), or ESC (31%). CSF analysis was normal in 5 of 5 patients. Antifibroblast growth factor 3 antibodies were positive in 4 of 18 patients (22%) and anticontactin-associated protein-2 antibodies in one patient. In vitro studies showed IgG immunoreactivity against nerve tissue in 14 patients (70%), but not in healthy subjects or diseased controls. Patient serum antibodies bound to unmyelinated fibers, Schwann cells, juxtaparanodes, paranodes, or DRG. Patients' condition improved after a short course of oral corticosteroids (3/3). Thirteen patients (65%) showed partial or complete recovery. Others displayed relapses or a chronic course.
DISCUSSION
AOSFN primarily presents as an acute, non-length-dependent, symmetric painful neuropathy with a variable disease course. An immune-mediated origin has been suggested based on in vitro immunohistochemical studies.
Topics: Adult; Animals; Female; Humans; Male; Mice; Antibodies; Axons; Nerve Fibers; Pain; Peripheral Nervous System Diseases; Small Fiber Neuropathy; Middle Aged
PubMed: 38170952
DOI: 10.1212/NXI.0000000000200195 -
Psychology Research and Behavior... 2023To explore the relationship between long-term glycemic variability and anxiety and depression in patients with type 2 diabetes.
PURPOSE
To explore the relationship between long-term glycemic variability and anxiety and depression in patients with type 2 diabetes.
PARTICIPANTS AND METHODS
A cohort comprising 214 individuals diagnosed with type 2 diabetes participated in this study. Comprehensive demographic and laboratory information was gathered for them. The evaluation of anxiety relied on the 7-item Generalized Anxiety Disorder Scale (GAD-7), while depression was assessed utilizing the 9-item Health Questionnaire (PHQ-9). Based on the presence or absence of anxiety and depression, participants were categorized into either the mood disorder or control groups. Subsequently, univariate and stepwise multiple binary logistic regression analyses were conducted to investigate the potential correlations between factors and the presence of anxiety and depression.
RESULTS
The prevalence of anxiety disorders is 23%, and depression is 32%. The prevalence of smoking, diabetic autonomic neuropathy, stroke, and osteoporosis in the mood disorder group was significantly higher than that in the control group (P < 0.05), the glycated hemoglobin A1c variability score (HVS), mean hemoglobin A1c value, total cholesterol, urinary albumin/creatinine and systemic immune-inflammatory index (SII) were significantly higher in the control group (P < 0.05). The level of high-density lipoprotein in the mood disorder group was significantly lower than the control group (P < 0.05). In stepwise multiple binary logistic regression analyses, the main factors associated with anxiety were depression (P < 0.001, OR=117.581) and gender (P < 0.001, OR=9.466), and the main factors related to depression included anxiety (P < 0.001, OR=49.424), smoking (P=0.042, OR=2.728), HVS (P=0.004, OR=8.664), and SII (P=0.014, OR=1.002).
CONCLUSION
Persistent fluctuations in blood glucose levels have been linked to anxiety and depression. Consequently, maintaining an optimal level of glycemic control and minimizing fluctuations becomes imperative in the comprehensive management of diabetes.
PubMed: 38144235
DOI: 10.2147/PRBM.S441058 -
Medicine Dec 2023Diabetic neuropathy, including autonomic neuropathy is a serious complication related to type 2 diabetes mellitus (T2D). The vagus nerve (VN) is the longest nerve in the...
Diabetic neuropathy, including autonomic neuropathy is a serious complication related to type 2 diabetes mellitus (T2D). The vagus nerve (VN) is the longest nerve in the autonomic nervous system, and since diabetic neuropathy manifests first in longer nerves, the VN is commonly affected in early diabetic autonomic neuropathy. The use of high-resolution ultrasound for peripheral and cranial nerve imaging has significantly increased over the past 2 decades. The aim of the study is to compare the cross-sectional area of the VN in patients with T2D to that of a control cohort without T2D. A total of 52 VN cross-sectional areas were recorded from patients with T2D. A total of 56 VN cross-sectional areas were also recorded from asymptomatic subjects without T2D. In each subject, high-resolution ultrasound imaging of the bilateral VNs was performed in the short-axis between the common carotid artery and the internal jugular vein. The VN cross-sectional areas were recorded and compared. In the patients with T2D, HbA1c and fasting blood glucose levels were obtained as well as the duration of T2D in years and correlated with the cross-sectional areas. The bilateral VN cross-sectional areas were similar in both cohorts. Additionally, no correlation was seen between the VN cross-sectional areas, demographics, or clinical data of T2D. Our study demonstrated normal VN cross-sectional areas in patients with T2D without any significant relation with the patients' demographic or clinical data.
Topics: Humans; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Vagus Nerve; Autonomic Nervous System; Ultrasonography
PubMed: 38134052
DOI: 10.1097/MD.0000000000036768 -
Tomography (Ann Arbor, Mich.) Dec 2023Hereditary sensory and autonomic neuropathy type 4 (HSAN4), also known as congenital insensitivity to pain with anhidrosis (CIPA), is a rare genetic disorder caused by...
Hereditary sensory and autonomic neuropathy type 4 (HSAN4), also known as congenital insensitivity to pain with anhidrosis (CIPA), is a rare genetic disorder caused by NTRK1 gene mutations, affecting nerve growth factor signaling. This study investigates the central nervous system's (CNS) involvement and its relation to pain insensitivity in HSAN4. We present a 15-year-old girl with HSAN4, displaying clinical signs suggestive of CNS impact, including spasticity and a positive Babinski's sign. Using Technetium-99m ethyl cysteinate dimer single-photon emission computed tomography (Tc-99m ECD SPECT) imaging, we discovered perfusion deficits in key brain regions, notably the cerebellum, thalamus, and postcentral gyrus. These regions process pain signals, providing insights into HSAN4's pain insensitivity. This study represents the first visualization of CNS perfusion abnormality in an HSAN4 patient. It highlights the intricate relationship between the peripheral and central nervous systems in HSAN4. The complexity of HSAN4 diagnosis, involving potential unidentified genes, underscores the need for continued research to refine diagnostic approaches and develop comprehensive treatments.
Topics: Female; Humans; Adolescent; Organotechnetium Compounds; Tomography, Emission-Computed, Single-Photon; Hereditary Sensory and Autonomic Neuropathies; Pain
PubMed: 38133079
DOI: 10.3390/tomography9060175 -
Ugeskrift For Laeger Dec 2023In this case report, a 55-year-old man presented with back pain, urinary retention, sensory disturbances, erectile dysfunction, leg paresis and orthostatism. Spinal MRI...
In this case report, a 55-year-old man presented with back pain, urinary retention, sensory disturbances, erectile dysfunction, leg paresis and orthostatism. Spinal MRI showed longitudinal extensive myelitis. Lymph node biopsy was compatible with sarcoidosis and a diagnosis of probable neurosarcoidosis (NS) was made. The patient benefited from prednisolone but relapsed during withdrawal. Infliximab resulted in almost complete remission. In conclusion, relapse is often seen when phasing out prednisolone, whereas infliximab appears to have a lasting effect and should be considered in the early stages of severe NS.
Topics: Male; Humans; Middle Aged; Infliximab; Central Nervous System Diseases; Sarcoidosis; Myelitis; Prednisolone; Magnetic Resonance Imaging
PubMed: 38078475
DOI: No ID Found -
Annals of Dermatology Nov 2023Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare disease characterized by insensitivity to pain, anhidrosis, and intellectual disability....
Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare disease characterized by insensitivity to pain, anhidrosis, and intellectual disability. CIPA is caused by a genetic mutation in the neurotrophic tyrosine receptor kinase 1 () gene on chromosome 1. The anhidrosis leads to cutaneous changes such as skin dryness, lichenification, and impetiginization. Moreover, patients with CIPA may experience repeated trauma and recalcitrant eczema due to excessive scratching of wounds on their skin, because they do not feel any pain. Severe whole-body eczema in a patient with CIPA may be overlooked, leading these patients to be frequently diagnosed with atopic dermatitis and common eczema. Indeed, in patients with treatment-resistant or atypically distributed eczema and underlying anhidrosis, CIPA should be considered as a potential causative disease. Increased awareness of CIPA among dermatologists is necessary to ensure that patients receive an appropriate diagnosis. Herein, we report a rare case of generalized xerotic eczema in a patient with CIPA.
PubMed: 38061701
DOI: 10.5021/ad.21.082 -
Endocrinology, Diabetes & Metabolism Jan 2024The mechanisms behind the diminished incretin effect in type 2 diabetes are uncertain, but impaired vagal transmission has been suggested. We aimed to investigate the...
OBJECTIVE
The mechanisms behind the diminished incretin effect in type 2 diabetes are uncertain, but impaired vagal transmission has been suggested. We aimed to investigate the association between the incretin effect and autonomic neuropathy, and the degree of dysglycaemia and duration of diabetes.
DESIGN AND METHODS
For a cross-sectional study, we included participants with either longstanding type 2 diabetes, recent onset, untreated diabetes and controls without diabetes matched for age, sex and body mass index. Autonomic nerve function was assessed with cardiovascular reflex tests, heart rate variability and sudomotor function. Visceral afferent nerves in the gut were tested performing rapid rectal balloon distention. An oral glucose tolerance test and an intravenous isoglycaemic glucose infusion were performed to calculate the incretin effect and gastrointestinal-mediated glucose disposal (GIGD).
RESULTS
Sixty-five participants were recruited. Participants with diabetes had rectal hyposensitivity for earliest sensation (3.7 ± 1.1 kPa in longstanding, 4.0 ± 1.3 in early), compared to controls (3.0 ± 0.9 kPa), p = .005. Rectal hyposensitivity for earliest sensation was not associated with the incretin effect (rho = -0.204, p = .106), but an association was found with GIGD (rho -0.341, p = .005). Incretin effect and GIGD were correlated with all glucose values, HbA1c and duration of diabetes.
CONCLUSIONS
Rectal hyposensitivity was uncovered in both longstanding and early type 2 diabetes, and was not associated with the incretin effect, but with GIGD, implying a potential link between visceral neuropathy and gastrointestinal handling of glucose. Both the incretin effect and GIGD were associated with the degree of dysglycaemia and the duration of diabetes.
PREVIOUSLY PUBLISHED
Some of the data have previously been published and presented as a poster on the American Diabetes Association 83rd Scientific Sessions: Meling et al; 1658-P: Rectal Hyposensitivity, a Potential Marker of Enteric Autonomic Nerve Dysfunction, Is Significantly Associated with Gastrointestinally Mediated Glucose Disposal in Persons with Type 2 Diabetes. Diabetes 20 June 2023; 72 (Supplement_1): 1658-P. https://doi.org/10.2337/db23-1658-P.
Topics: Humans; Incretins; Glucose; Glucagon-Like Peptide 1; Diabetes Mellitus, Type 2; Blood Glucose; Cross-Sectional Studies; Insulin
PubMed: 38059537
DOI: 10.1002/edm2.463 -
Cureus Nov 2023Hereditary sensory and autonomic neuropathy type 4 (HSAN4), or congenital insensitivity to pain with anhidrosis (CIPA), is a rare autosomal recessive disorder caused by...
Hereditary sensory and autonomic neuropathy type 4 (HSAN4), or congenital insensitivity to pain with anhidrosis (CIPA), is a rare autosomal recessive disorder caused by mutations in the NTRK1 gene, resulting in pain insensitivity, anhidrosis, and temperature dysregulation. This report focuses on oral manifestations in an 11-year-old girl with CIPA, highlighting the need for early intervention and comprehensive care. The patient had a history of recurrent oral injuries and an unexplained fever, with a confirmed HSAN4 diagnosis through genetic analysis. Clinical features included pain insensitivity, anhidrosis, and intellectual disability. Dental history revealed emergency care, suboptimal oral hygiene, early tooth loss, and infections. Extra-oral examination showed nail-biting and injuries, while intra-oral assessment revealed ulcers and scars. Radiographic evaluation indicated mandibular alveolar bone thinning and periapical lesions in the lower incisors. This case emphasizes the complex challenges of CIPA, including pain insensitivity, recurring fever episodes, and self-inflicted injuries. Early diagnosis and specific dental care are vital to prevent orofacial trauma, necessitating a proactive interdisciplinary approach for comprehensive care.
PubMed: 38058353
DOI: 10.7759/cureus.48294 -
Cellular and Molecular Life Sciences :... Dec 2023MFSD7b belongs to the Major Facilitator Superfamily of transporters that transport small molecules. Two isoforms of MFSD7b have been identified and they are reported to...
MFSD7b belongs to the Major Facilitator Superfamily of transporters that transport small molecules. Two isoforms of MFSD7b have been identified and they are reported to be heme exporters that play a crucial role in maintaining the cytosolic and mitochondrial heme levels, respectively. Mutations of MFSD7b (also known as FLVCR1) have been linked to retinitis pigmentosa, posterior column ataxia, and hereditary sensory and autonomic neuropathy. Although MFSD7b functions have been linked to heme detoxification by exporting excess heme from erythroid cells, it is ubiquitously expressed with a high level in the kidney, gastrointestinal tract, lungs, liver, and brain. Here, we showed that MFSD7b functions as a facilitative choline transporter. Expression of MFSD7b slightly but significantly increased choline import, while its knockdown reduced choline influx in mammalian cells. The influx of choline transported by MFSD7b is dependent on the expression of choline metabolizing enzymes such as choline kinase (CHKA) and intracellular choline levels, but it is independent of gradient of cations. Additionally, we showed that choline transport function of Mfsd7b is conserved from fly to man. Employing our transport assays, we showed that missense mutations of MFSD7b caused reduced choline transport functions. Our results show that MFSD7b functions as a facilitative choline transporter in mammalian cells.
Topics: Animals; Humans; Choline; Heme; Mammals; Mutation, Missense; Membrane Transport Proteins
PubMed: 38055060
DOI: 10.1007/s00018-023-05048-4