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Neurology(R) Neuroimmunology &... May 2024To report a case-control study of new-onset small fiber neuropathy (SFN) after COVID-19 with invasive cardiopulmonary exercise testing (iCPET). SFN is a critical...
OBJECTIVES
To report a case-control study of new-onset small fiber neuropathy (SFN) after COVID-19 with invasive cardiopulmonary exercise testing (iCPET). SFN is a critical objective finding in long COVID and amenable to treatment.
METHODS
A retrospective chart review was conducted on patients seen in the NeuroCOVID Clinic at Yale who developed new-onset SFN after a documented COVID-19 illness. We collected demographics, symptoms, skin biopsy, iCPET testing, treatments, and clinical response to treatment or no intervention.
RESULTS
Sixteen patients were diagnosed with SFN on skin biopsy (median age 47, 75% female, 75% White). 92% of patients reported postexertional malaise characteristic of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and 7 patients underwent iCPET, which demonstrated neurovascular dysregulation and dysautonomia consistent with ME/CFS. Nine patients underwent treatment with IVIG, and 7 were not treated with IVIG. The IVIG group experienced significant clinical response in their neuropathic symptoms (9/9) compared with those who did not receive IVIG (3/7; = 0.02).
DISCUSSION
Here, we present preliminary evidence that after COVID-19, SFN is responsive to treatment with IVIG and linked with neurovascular dysregulation and dysautonomia on iCPET. A larger clinical trial is indicated to further demonstrate the clinical utility of IVIG in treating postinfectious SFN.
CLASSIFICATION OF EVIDENCE
This study provides Class III evidence. It is a retrospective cohort study.
Topics: Humans; Female; Middle Aged; Male; Small Fiber Neuropathy; Case-Control Studies; Retrospective Studies; Fatigue Syndrome, Chronic; Post-Acute COVID-19 Syndrome; Immunoglobulins, Intravenous; COVID-19; Autonomic Nervous System Diseases
PubMed: 38630952
DOI: 10.1212/NXI.0000000000200244 -
International Journal of Molecular... Mar 2024Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. The neurofilament light chain (NfL), a neuron-specific biomarker, is... (Review)
Review
Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. The neurofilament light chain (NfL), a neuron-specific biomarker, is released into the blood and cerebrospinal fluid after neuronal damage. There is a need for an early and sensitive blood biomarker for polyneuropathy, and this systematic review provides an overview on the value of NfL in the early detection of neuropathy, central nervous system involvement, the monitoring of neuropathy progression, and treatment effects in systemic amyloidosis. A literature search in PubMed, Embase, and Web of Science was performed on 14 February 2024 for studies investigating NfL levels in patients with systemic amyloidosis and transthyretin gene-variant (v) carriers. Only studies containing original data were included. Included were thirteen full-text articles and five abstracts describing 1604 participants: 298 controls and 1306 v carriers or patients with or without polyneuropathy. Patients with polyneuropathy demonstrated higher NfL levels compared to healthy controls and asymptomatic carriers. Disease onset was marked by rising NfL levels. Following the initiation of transthyretin gene-silencer treatment, NfL levels decreased and remained stable over an extended period. NfL is not an outcome biomarker, but an early and sensitive disease-process biomarker for neuropathy in systemic amyloidosis. Therefore, NfL has the potential to be used for the early detection of neuropathy, monitoring treatment effects, and monitoring disease progression in patients with systemic amyloidosis.
Topics: Humans; Prealbumin; Intermediate Filaments; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Polyneuropathies; Biomarkers
PubMed: 38612579
DOI: 10.3390/ijms25073770 -
Cureus Mar 2024Multiple sclerosis (MS) is an autoimmune demyelinating neurological disorder primarily manifesting with a range of neurological symptoms, with cardiovascular autonomic...
Multiple sclerosis (MS) is an autoimmune demyelinating neurological disorder primarily manifesting with a range of neurological symptoms, with cardiovascular autonomic involvement being a rare occurrence. We report a case where a patient initially presented with Bell's palsy, without other notable symptoms or signs, and subsequently developed atrial fibrillation, hypertension, and hemiparesis. Magnetic resonance imaging (MRI) revealed extensive demyelination in the cerebral hemispheres, brainstem, and notably, the area postrema. The anatomy of the area postrema and its connections, in relation to neurogenic hypertension, are discussed. The demyelination in the area postrema was thought to be the cause of our patient's arrhythmias and acute hypertension. Furthermore, we discuss the cerebral origins of cardiac arrhythmias, with a focus on MS and other neurological conditions. This case underscores the rarity of isolated cranial neuropathies, such as Bell's palsy, as an initial sign of MS, marking the onset of a relapse.
PubMed: 38595879
DOI: 10.7759/cureus.55860 -
World Journal of Diabetes Mar 2024While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus (DM) is a well-known precursor to complications such as diabetic retinopathy, neuropathy...
While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus (DM) is a well-known precursor to complications such as diabetic retinopathy, neuropathy (including autonomic neuropathy), and nephropathy, a paradoxical intensification of these complications can rarely occur with aggressive glycemic management resulting in a rapid reduction of glycated haemoglobin. Although, acute onset or worsening of retinopathy and treatment induced neuropathy of diabetes are more common among these complications, rarely other problems such as albuminuria, diabetic kidney disease, Charcot's neuroarthropathy, gastroparesis, and urinary bladder dysfunction are also encountered. The recently published a rare case of all these complications, occurring in a young type 1 diabetic female intensely managed during pregnancy, as a case report by Huret . It is essential to have a comprehensive understanding of the pathobiology, prevalence, predisposing factors, and management strategies for acute onset, or worsening of microvascular complications when rapid glycemic control is achieved, which serves to alleviate patient morbidity, enhance disease management compliance, and possibly to avoid medico-legal issues around this rare clinical problem. This editorial delves into the dynamics surrounding the acute exacerbation of microvascular complications in poorly controlled DM during rapid glycaemic control.
PubMed: 38591086
DOI: 10.4239/wjd.v15.i3.311 -
Molecular Genetics & Genomic Medicine Apr 2024Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder caused by loss-of-function mutations of the NTRK1 gene,... (Review)
Review
BACKGROUND
Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder caused by loss-of-function mutations of the NTRK1 gene, affecting the autonomic and sensory nervous system. Clinical manifestation is varied and includes recurrent fever, pain insensitivity, anhidrosis, self-mutilating behavior, and intellectual disability.
METHODS
Clinical and genetic features were assessed in two males and one female with genetically confirmed CIPA using exome or genome sequencing.
RESULTS
CIPA symptoms including recurrent fever, pain insensitivity, and anhidrosis manifested at the age of 1 year (age range: 0.3-8 years). Two patients exhibited self-mutilation tendencies, intellectual disability, and developmental delay. Four NTRK1 (NM_002529.3) mutations, c.851-33T>A (p.?), c.2020G>T (p.Asp674Tyr), c.2303C>T (p.Pro768Leu), and c.574-156_850+1113del (exons 5-7 del) were identified. Two patients exhibited early onset and severe phenotype, being homozygous for c.851-33T>A (p.?) mutations and compound heterozygous for c.851-33T>A (p.?) and c.2020G>T (p.Asp674Tyr) mutation of NTRK1. The third patient with compound heterozygous mutations of c.2303C>T (p.Pro768Leu) and c.574-156_850+1113del (exons 5-7 del) displayed a late onset and milder clinical manifestation.
CONCLUSION
All three patients exhibited variable phenotypes and disease severity. This research enriches our understanding of clinical and genetic aspects of CIPA, highlighting variable phenotypes and disease severity.
Topics: Child; Child, Preschool; Female; Humans; Infant; Male; Channelopathies; Hereditary Sensory and Autonomic Neuropathies; Hypohidrosis; Indoles; Intellectual Disability; Pain; Pain Insensitivity, Congenital; Propionates
PubMed: 38581121
DOI: 10.1002/mgg3.2430 -
BMC Pediatrics Apr 2024Cardiovascular autonomic neuropathy (CAN) is a serious complication of diabetes, impacting the autonomic nerves that regulate the heart and blood vessels. Timely...
BACKGROUND
Cardiovascular autonomic neuropathy (CAN) is a serious complication of diabetes, impacting the autonomic nerves that regulate the heart and blood vessels. Timely recognition and treatment of CAN are crucial in averting the onset of cardiovascular complications. Both clinically apparent autonomic neuropathy and subclinical autonomic neuropathy, particularly CAN pose a significant risk of morbidity and mortality in children with type 1 diabetes mellitus (T1DM). Notably, CAN can progress silently before manifesting clinically. In our study, we assessed patients with poor metabolic control, without symptoms, following the ISPAD 2022 guideline. The objective is is to determine which parameters we can use to diagnose CAN in the subclinical period.
METHODS
Our study is a cross-sectional case-control study that includes 30 children diagnosed with T1DM exhibiting poor metabolic control (average HbA1c > 8.5% for at least 1 year) according to the ISPAD 2022 Consensus Guide. These patients, who are under the care of the pediatric diabetes clinic, underwent evaluation through four noninvasive autonomic tests: echocardiography, 24-h Holter ECG for heart rate variability (HRV), cardiopulmonary exercise test, and tilt table test.
RESULTS
The average age of the patients was 13.73 ± 1.96 years, the average diabetes duration was 8 ± 3.66 years, and the 1-year average HbA1c value was 11.34 ± 21%. In our asymptomatic and poorly metabolically controlled patient group, we found a decrease in HRV values, the presence of postural hypotension with the tilt table test, and a decrease in ventricular diastolic functions that are consistent with the presence of CAN. Despite CAN, the systolic functions of the ventricles were preserved, and the dimensions of the cardiac chambers and cardiopulmonary exercise test were normal.
CONCLUSIONS
CAN is a common complication of T1DM, often associated with the patient's age and poor glycemic control. HRV, active orthostatic tests, and the evaluation of diastolic dysfunctions play significant roles in the comprehensive assessment of CAN. These diagnostic measures are valuable tools in identifying autonomic dysfunction at an early stage, allowing for timely intervention and management to mitigate the impact of cardiovascular complications associated with T1DM.
Topics: Humans; Child; Adolescent; Diabetes Mellitus, Type 1; Cross-Sectional Studies; Case-Control Studies; Glycated Hemoglobin; Diabetic Neuropathies; Autonomic Nervous System Diseases; Heart Rate
PubMed: 38561716
DOI: 10.1186/s12887-024-04644-y -
Cureus Feb 2024SARS-CoV-2 vaccinations can lead to complications, including post-acute COVID-19 vaccination syndrome (PACVS). There has been no report of a patient with PACVS...
SARS-CoV-2 vaccinations can lead to complications, including post-acute COVID-19 vaccination syndrome (PACVS). There has been no report of a patient with PACVS presenting with Guillain-Barre syndrome (GBS), myocarditis/pericarditis, immunodeficiency, or coagulopathy after the second BNT162b2 dose. The patient is a 51-year-old woman with chronic myopericarditis, coagulopathy due to factor-VIII increase and protein-S deficiency, GBS, and a number of other ocular, dermatological, immunological, and central nervous system abnormalities related to the second dose of the BNT172b2 vaccine. GBS manifested with mild, multiple cranial nerve lesions, small fibre neuropathy (SFN) affecting the autonomic system with postural tachycardia syndrome (POTS) and orthostatic hypotension, and sensory disturbances in the upper and lower limbs. PACVS was diagnosed months after onset, but despite the delayed diagnosis, the patient benefited from glucocorticoids, repeated HELP apheresis, and multiple symptomatic treatments. The case shows that SARS-CoV-2 vaccination can be complicated by PACVS manifesting as chronic myopericarditis, coagulopathy, GBS with predominant dysautonomia, and impaired immune competence, and that diagnosis of PACVS can be delayed for months. Delayed diagnosis of PACVS may result in a delay in appropriate treatment and the prolongation of disabling symptoms. Patients and physicians should be made aware of PACVS to improve diagnostic and therapeutic management in terms of patient and healthcare system costs.
PubMed: 38558730
DOI: 10.7759/cureus.55205 -
Frontiers in Endocrinology 2024The pathogenesis of chronic diabetes complications has oxidative stress as one of the major elements, and single-nucleotide polymorphisms (SNPs) in genes belonging to...
AIM
The pathogenesis of chronic diabetes complications has oxidative stress as one of the major elements, and single-nucleotide polymorphisms (SNPs) in genes belonging to antioxidant pathways modulate susceptibility to these complications. Considering that melatonin is a powerful antioxidant compound, our aim was to explore, in a longitudinal cohort study of type 1 diabetes (T1D) individuals, the association of microvascular complications and SNPs in the gene encoding melatonin receptor 1A ().
METHODS
Eight SNPs in were genotyped in 489 T1D individuals. Besides cross-sectional analyses of SNPs with each one of the microvascular complications (distal polyneuropathy, cardiovascular autonomic neuropathy, retinopathy, and diabetic kidney disease), a longitudinal analysis evaluated the associations of SNPs with renal function decline in 411 individuals followed up for a median of 8 years. In a subgroup of participants, the association of complications with urinary 6-sulfatoxymelatonin (aMT6s) concentration was investigated.
RESULTS
The group of individuals with a renal function decline ≥ 5 mL min 1.73 m year presented a higher frequency of the A allele of rs4862705 in comparison with nondecliners, even after adjustment for confounding variables (OR = 1.84, 95% CI = 1.20-2.82; = 0.0046). No other significant associations were found.
CONCLUSIONS
This is the first study showing an association between a variant in a gene belonging to the melatonin system and renal function decline in the diabetic setting.
Topics: Humans; Diabetes Mellitus, Type 1; Antioxidants; Melatonin; Receptors, Melatonin; Cross-Sectional Studies; Longitudinal Studies; Kidney
PubMed: 38549765
DOI: 10.3389/fendo.2024.1331012 -
Diabetologia Jun 2024Diabetic gastroenteropathy frequently causes debilitating gastrointestinal symptoms. Previous uncontrolled studies have shown that transcutaneous vagal nerve stimulation... (Randomized Controlled Trial)
Randomized Controlled Trial
Transcutaneous vagal nerve stimulation for treating gastrointestinal symptoms in individuals with diabetes: a randomised, double-blind, sham-controlled, multicentre trial.
AIMS/HYPOTHESIS
Diabetic gastroenteropathy frequently causes debilitating gastrointestinal symptoms. Previous uncontrolled studies have shown that transcutaneous vagal nerve stimulation (tVNS) may improve gastrointestinal symptoms. To investigate the effect of cervical tVNS in individuals with diabetes suffering from autonomic neuropathy and gastrointestinal symptoms, we conducted a randomised, sham-controlled, double-blind (participants and investigators were blinded to the allocated treatment) study.
METHODS
This study included adults (aged 20-86) with type 1 or 2 diabetes, gastrointestinal symptoms and autonomic neuropathy recruited from three Steno Diabetes Centres in Denmark. Participants were randomly allocated 1:1 to receive active or sham stimulation. Active cervical tVNS or sham stimulation was self-administered over two successive study periods: 1 week of four daily stimulations and 8 weeks of two daily stimulations. The primary outcome measures were gastrointestinal symptom changes as measured using the gastroparesis cardinal symptom index (GCSI) and the gastrointestinal symptom rating scale (GSRS). Secondary outcomes included gastrointestinal transit times and cardiovascular autonomic function.
RESULTS
Sixty-eight participants were randomised to the active group, while 77 were randomised to the sham group. Sixty-three in the active and 68 in the sham group remained for analysis in study period 1, while 62 in each group were analysed in study period 2. In study period 1, active and sham tVNS resulted in similar symptom reductions (GCSI: -0.26 ± 0.64 vs -0.17 ± 0.62, p=0.44; GSRS: -0.35 ± 0.62 vs -0.32 ± 0.59, p=0.77; mean ± SD). In study period 2, active stimulation also caused a mean symptom decrease that was comparable to that observed after sham stimulation (GCSI: -0.47 ± 0.78 vs -0.33 ± 0.75, p=0.34; GSRS: -0.46 ± 0.90 vs -0.35 ± 0.79, p=0.50). Gastric emptying time was increased in the active group compared with sham (23 min vs -19 min, p=0.04). Segmental intestinal transit times and cardiovascular autonomic measurements did not differ between treatment groups (all p>0.05). The tVNS was well-tolerated.
CONCLUSIONS/INTERPRETATION
Cervical tVNS, compared with sham stimulation, does not improve gastrointestinal symptoms among individuals with diabetes and autonomic neuropathy.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04143269 FUNDING: The study was funded by the Novo Nordisk Foundation (grant number NNF180C0052045).
Topics: Humans; Female; Male; Middle Aged; Double-Blind Method; Vagus Nerve Stimulation; Adult; Aged; Transcutaneous Electric Nerve Stimulation; Diabetic Neuropathies; Gastrointestinal Diseases; Diabetes Mellitus, Type 2; Aged, 80 and over; Diabetes Mellitus, Type 1; Treatment Outcome; Young Adult
PubMed: 38546822
DOI: 10.1007/s00125-024-06129-0 -
International Journal of Applied &... 2024Diagnosing diabetic neuropathy is a challenge at times as it is asymptomatic. Diagnosing diabetic neuropathy involves the use of quantitative sensory testing, nerve...
INTRODUCTION
Diagnosing diabetic neuropathy is a challenge at times as it is asymptomatic. Diagnosing diabetic neuropathy involves the use of quantitative sensory testing, nerve conduction study, and autonomic testing. Tempearture threshold testing (TTT) can aid in diagnosing small fiber neuropathy at early stages. This study aimed to assess the small fiber neuropathy using TTT in diabetes mellitus (DM) and correlate with age, duration of diabetes, and lipid profile.
MATERIALS AND METHODS
The study was commenced after obtaining ethics approval from the institute ethics committee. The study participants included 100 patients with type 2 DM of both genders between the ages of 40 and 65 years. The glycemic status and lipid profile were noted along with physical examination. Neuropathy assessment was done using Michigan Neuropathy Screening Instrument (MNSI) and TTT.
RESULTS
The prevalence of small fiber neuropathy based on TTT was 63%. The lipid profile was similar in both the groups. The MNSI B scale had significantly higher scores in the neuropathy group. In the neuropathy group, the thresholds for hot were significantly greater in all four limbs and cold were significantly lower. Age and years of DM were positively correlated with the neuropathy. Hot threshold in the lower limb had shown a strong positive correlation.
CONCLUSION
The age and duration of diabetes are independent risk factors for diabetic peripheral neuropathy. Small fiber neuropathy is a prequel to the motor neuropathy. Hot threshold testing in the lower limb is more sensitive than cold threshold testing for diagnosing small fiber neuropathy.
PubMed: 38504834
DOI: 10.4103/ijabmr.ijabmr_397_23