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Archives of Iranian Medicine Apr 2024Hereditary sensory autonomic neuropathy type VIII (HSAN-VIII) is a rare genetic disease that occurs due to mutations in the gene. Here, we describe a novel homozygous...
Hereditary sensory autonomic neuropathy type VIII (HSAN-VIII) is a rare genetic disease that occurs due to mutations in the gene. Here, we describe a novel homozygous mutation c.826_840dupTGCAACCGCCGCTTC (p.Cys276_Phe280dup) on exon 5 in the gene identified by WES and confirmed using Sanger sequencing method.
Topics: Female; Humans; Infant; Carrier Proteins; DNA-Binding Proteins; Exons; Hereditary Sensory and Autonomic Neuropathies; Homozygote; Mutation; Nerve Tissue Proteins; Pedigree; Transcription Factors; Male
PubMed: 38685849
DOI: 10.34172/aim.2024.32 -
Cureus Mar 2024Antineutrophil cytoplasmic antibody-related vasculitis (AAV), is a group of diseases marked by systemic symptoms and severe small vessel inflammation. The three subtypes...
Antineutrophil cytoplasmic antibody-related vasculitis (AAV), is a group of diseases marked by systemic symptoms and severe small vessel inflammation. The three subtypes of AAV are eosinophilic GPA (EGPA), Microscopic Polyangiitis (MPA), and Granulomatosis with Polyangiitis (GPA). The organs that get involved in the disease process are the kidneys and the upper and lower respiratory tracts, with a spectrum of neurological manifestations. Here, we present a case report of a 68-year-old man who came with complaints of tingling and numbness over bilateral lower limbs for two months accompanied by difficulty in walking and bilateral foot drop without any respiratory complaints or involvement of sensory or autonomic system who was diagnosed with AAV (c-ANCA +) on further workup. A sural Nerve biopsy was done for confirmation which was suggestive of chronic, asymmetrical axonal neuropathy with perivascular inflammation, suggestive of vasculitic neuropathy. The patient had no other organ involvement. The patient was started on glucocorticoids and cyclophosphamide therapy for 6 cycles after which his symptoms and quality of life improved drastically.
PubMed: 38681477
DOI: 10.7759/cureus.57046 -
Journal of Personalized Medicine Apr 2024Orthostatic intolerance is a broad term that represents a spectrum of dysautonomic disorders, including postural orthostatic tachycardia syndrome (POTS) and orthostatic... (Review)
Review
Orthostatic intolerance is a broad term that represents a spectrum of dysautonomic disorders, including postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH), as manifestations of severe autonomic failure. While the etiology of orthostatic intolerance has not yet fully been uncovered, it has been associated with multiple underlying pathological processes, including peripheral neuropathy, altered renin-aldosterone levels, hypovolemia, and autoimmune processes. Studies have implicated adrenergic, cholinergic, and angiotensin II type I autoantibodies in the pathogenesis of orthostatic intolerance. Several case series have demonstrated that immunomodulation therapy resulted in favorable outcomes, improving autonomic symptoms in POTS and OH. In this review, we highlight the contemporary literature detailing the association of autoimmunity with POTS and OH.
PubMed: 38673062
DOI: 10.3390/jpm14040435 -
Biomedicines Mar 2024Many anti-cancer drugs, such as taxanes, platinum compounds, vinca alkaloids, and proteasome inhibitors, can cause chemotherapy-induced peripheral neuropathy (CIPN).... (Review)
Review
Many anti-cancer drugs, such as taxanes, platinum compounds, vinca alkaloids, and proteasome inhibitors, can cause chemotherapy-induced peripheral neuropathy (CIPN). CIPN is a frequent and harmful side effect that affects the sensory, motor, and autonomic nerves, leading to pain, numbness, tingling, weakness, and reduced quality of life. The causes of CIPN are not fully known, but they involve direct nerve damage, oxidative stress, inflammation, DNA damage, microtubule dysfunction, and altered ion channel activity. CIPN is also affected by genetic, epigenetic, and environmental factors that modulate the risk and intensity of nerve damage. Currently, there are no effective treatments or prevention methods for CIPN, and symptom management is mostly symptomatic and palliative. Therefore, there is a high demand for better understanding of the cellular and molecular mechanisms involved in CIPN, as well as the development of new biomarkers and therapeutic targets. This review gives an overview of the current knowledge and challenges in the field of CIPN, focusing on the biological and molecular mechanisms underlying this disorder.
PubMed: 38672107
DOI: 10.3390/biomedicines12040751 -
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