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Journal of Clinical Medicine Jan 2023Horner’s syndrome (HS), caused by lesions of the 3-neuron oculosympathetic nerve pathway (ONP), includes the triad: blepharoptosis, miosis and anhidrosis (ipsilateral... (Review)
Review
Horner’s syndrome (HS), caused by lesions of the 3-neuron oculosympathetic nerve pathway (ONP), includes the triad: blepharoptosis, miosis and anhidrosis (ipsilateral with ONP damage). Thyroid−related HS represents an unusual entity underling thyroid nodules/goiter/cancer−HS (T-HS), and post-thyroidectomy HS (Tx-HS). We aim to overview Tx-HS. This is a narrative review. We revised PubMed published, full-length, English papers from inception to November 2022. Additionally, we introduced data on post-thyroidectomy lymphocele/chylous leakage (Tx-L), and introduced a new pediatric case with both Tx-HS and Tx-L. Tx-HS: the level of statistical evidence varies from isolated case reports, studies analyzing the large panel of post-thyroidectomy complications reporting HS among the rarest side effects (as opposite to hypocalcemia), or different series of patients with HS due to various disorders, including T-HS/Tx-HS. Tx-HS is related to benign or malignant thyroid conditions, regardless the type of surgery. A pre-operatory rate of T-HS of 0.14%; a post-operatory rate of Tx-HS between 0.03% and 5% (mostly, 0.2%) are identified; a possible higher risk on endoscopic rather than open procedure is described. Incomplete HS forms, and pediatric onset are identified, too; the earliest identification is after 2 h since intervention. A progressive remission is expected in most cases within the first 2−6 months to one year. The management is mostly conservative; some used glucocorticoids and neurotrophic agents. One major pitfall is an additional contributor factor like a local compression due to post-operatory collections (hematoma, cysts, fistula, Tx-L) and their correction improves the outcome. The prognostic probably depends on the severity of cervical sympathetic chain (CSC) lesions: indirect, mild injury due to local compressive masses, intra-operatory damage of CSC like ischemia and stretching of CSC by the retractor associate HS recovery, while CSC section is irreversible. Other iatrogenic contributors to HS are: intra-operatory manipulation of parathyroid glands, thyroid microwave/radiofrequency ablation, and high-intensity focused ultrasound, and percutaneous ethanol injection into thyroid nodules. Tx-L, rarely reported (mostly <0.5%, except for a ratio of 8.3% in one study), correlates with extended surgery, especially lateral/central neck dissection, and the presence of congenitally—aberrant lymphatic duct; it is, also, described after endoscopic procedures and chest-breast approach; it starts within days after surgery. Typically low-fat diet (even fasting and parental nutrition) and tube drainage are useful (as part of conservative management); some used octreotide, local sealing solutions like hypertonic glucose, Viscum album extract, n-Butyl-2-cyanoacrylate. Re-intervention is required in severe cases due to the risk of lymphorrhoea and chylothorax. Early identification of Tx-HS and Tx-L improves the outcome. Some iatrogenic complications are inevitable and a multifactorial model of prediction is still required, also taking into consideration standardized operatory procedures, skillful intra-operatory manipulation, and close post-operatory follow-up of the patients, especially during modern era when thyroid surgery registered a massive progress allowing an early discharge of the patients.
PubMed: 36675400
DOI: 10.3390/jcm12020474 -
Genes Jan 2023X-linked hypohidrotic ectodermal dysplasia (XLHED) is a rare genetic disorder characte-rised by abnormal development of the skin and its appendages, such as hair and...
Protocol for the Phase 2 EDELIFE Trial Investigating the Efficacy and Safety of Intra-Amniotic ER004 Administration to Male Subjects with X-Linked Hypohidrotic Ectodermal Dysplasia.
X-linked hypohidrotic ectodermal dysplasia (XLHED) is a rare genetic disorder characte-rised by abnormal development of the skin and its appendages, such as hair and sweat glands, the teeth, and mucous glands of the airways, resulting in serious, sometimes life-threatening complications like hyperthermia or recurrent respiratory infections. It is caused by pathogenic variants of the ectodysplasin A gene (). Most affected males are hemizygous for null mutations that lead to the absence or inactivity of the signalling protein ectodysplasin A1 (EDA1) and, thus, to the full-blown phenotype with inability to perspire and few if any teeth. There are currently no long-term treatment options for XLHED. ER004 represents a first-in-class protein replacement molecule designed for specific, high-affinity binding to the endogenous EDA1 receptor (EDAR). Its proposed mechanism of action is the replacement of missing EDA1 in yet unborn patients with XLHED. Once bound to EDAR, ER004 activates the EDA/NFκB signalling pathway, which triggers the transcription of genes involved in the normal development of multiple tissues. Following preclinical studies, named-patient use cases demonstrated significant potential of ER004 in affected males treated in utero during the late second and third trimesters of pregnancy. In order to confirm these results, we started the EDELIFE trial, a prospective, open-label, genotype-match controlled, multicentre clinical study to investigate the efficacy and safety of intra-amniotic ER004 administration as a prenatal treatment for male subjects with XLHED. This article summarises the rationale, the study protocol, ethical issues of the trial, and potential pitfalls.
Topics: Female; Pregnancy; Male; Humans; Ectodermal Dysplasia 1, Anhidrotic; Prospective Studies; Ectodermal Dysplasia; Ectodysplasins; Skin; Clinical Trials, Phase II as Topic
PubMed: 36672894
DOI: 10.3390/genes14010153 -
Children (Basel, Switzerland) Jan 2023Horner's syndrome (HS) classically consists of the symptom triad of miosis, ptosis, and anhidrosis. It is caused by impairment of a certain pathway in the sympathetic...
BACKGROUND
Horner's syndrome (HS) classically consists of the symptom triad of miosis, ptosis, and anhidrosis. It is caused by impairment of a certain pathway in the sympathetic nervous system. It may also appear as part of the clinical signs of other diseases and syndromes, including Pancoast tumors, intradural and/or epidural tumors, thoracic outlet syndrome, syringomyelia, brachial plexus injury, and aortic dissection. Here, we report a very rare complication of vertebral column resection in children, and we present the clinical findings of a case of Horner's syndrome with a current literature review.
CASE PRESENTATION
A five-year-old child with severe congenital kyphoscoliosis qualified for surgical treatment of the spinal deformity via a posterior approach, with three-column osteotomy and fusion.
RESULTS
After successful surgery, the patient presented with HS due to distraction of the sympathetic nerve trunk and, thus, innervation to the left eye. At the 4-year follow-up, the child had fully recovered.
CONCLUSIONS
Pediatric HS after posterior instrumented scoliosis correction surgery with posterior vertebral column resection of the thoracic spine is very rare. This is the first reported case of HS after posterior vertebral column resection and spinal fusion for congenital kyphoscoliosis without the use of epidural analgesia. Symptom resolution may be variable and, in some cases, delayed.
PubMed: 36670706
DOI: 10.3390/children10010156 -
JIMD Reports Jan 2023Here, we present the first two Swedish cases of Conserved Oligomeric Golgi complex subunit 6-congenital disorders of glycosylation (COG6-CDG). Their clinical symptoms...
Here, we present the first two Swedish cases of Conserved Oligomeric Golgi complex subunit 6-congenital disorders of glycosylation (COG6-CDG). Their clinical symptoms include intellectual disability, Attention Deficit/Hyperactivity Disorder (ADHD), delayed brain myelinization, progressive microcephaly, joint laxity, hyperkeratosis, frequent infections, and enamel hypoplasia. In one family, compound heterozygous variants in were identified, where one (c.785A>G; p.Tyr262Cys) has previously been described in patients of Moroccan descent, whereas the other (c.238G>A; p.Glu80Lys) is undescribed. On the other hand, a previously undescribed homozygous duplication (c.1793_1795dup) was deemed the cause of the disease. To confirm the pathogenicity of the variants, we treated patient and control fibroblasts with the ER-Golgi transport inhibitor Brefeldin-A and show that patient cells manifest a significantly slower anterograde and retrograde ER-Golgi transport.
PubMed: 36636598
DOI: 10.1002/jmd2.12338 -
Skin Appendage Disorders Jan 2023Ectodermal dysplasias (EDs) are a large group of rare and complex genetic disorders, affecting the development of two or more ectodermal structures. Hypohidrotic ED...
INTRODUCTION
Ectodermal dysplasias (EDs) are a large group of rare and complex genetic disorders, affecting the development of two or more ectodermal structures. Hypohidrotic ED (HED) is the most frequent ED's phenotype and is characterized by hypodontia, hypotrichosis, and hypo/anhidrosis, leading to heat intolerance and hyperthermia.
CASE PRESENTATION
We report a case of a 2-year-old girl with hair and teeth abnormalities associated with severe digestive symptoms responsible for failure to thrive. Genetic analysis by mass sequencing in parallel on a 4,867-gene panel was performed in duo (index case and her mother). The girl showed the presence of a new de novo c.100dupG variant in responsible for HED associated with a diagnosis of food protein-induced enterocolitis syndrome (FPIES).
CONCLUSION
We describe a patient with HED and a new variant associated with a diagnosis of FPIES, both implicating increased intestinal permeability. The inclusion of FPIES as a possible digestive symptom of HED can be suggested, although it may occur only in a context of atopy.
PubMed: 36632363
DOI: 10.1159/000526428 -
Journal of Ayub Medical College,... 2022Ectodermal Dysplasia (ED) is a rare genetic condition characterized by the involvement of ectoderm derivatives such as hair, nail, sweat glands, and teeth. It has many...
Ectodermal Dysplasia (ED) is a rare genetic condition characterized by the involvement of ectoderm derivatives such as hair, nail, sweat glands, and teeth. It has many variants, but the two most common ones are hypohidrotic/anhidrotic ectodermal dysplasia and hidrotic ectodermal dysplasia. Herein, we present a case of a 20-year-old female with hypohidrotic ectodermal dysplasia who had anodontia, hypohidrosis, and hypotrichosis, and her condition went unrecognized until she was seen for gastroenteritis at a tertiary care center. This case report will help spread education and awareness regarding such a rare and under-recognized condition. Early diagnosis and intervention help improve the quality of life.
Topics: Humans; Female; Young Adult; Adult; Ectodermal Dysplasia 1, Anhidrotic; Quality of Life; Ectodermal Dysplasia; Anodontia
PubMed: 36566424
DOI: 10.55519/JAMC-04-10890 -
Journal of Pain Research 2022Congenital insensitivity to pain with anhidrosis (CIPA) is a very rare inherited autosomal recessive disease that has multiple clinical manifestations. Since its...
BACKGROUND
Congenital insensitivity to pain with anhidrosis (CIPA) is a very rare inherited autosomal recessive disease that has multiple clinical manifestations. Since its symptoms are related to different systems, this disorder has been investigated on a variety of topics. To better understand publications about CIPA, we conducted a bibliometric study to evaluate research publications on CIPA from 2000 to 2021, and delineate the key contributions in terms of countries, authors and sources.
METHODS
Quantitative analysis of publications on CIPA from 2000 to 2021 was interpreted and graphed through the Science Citation Index Expanded (SCIE) of Web of Science (WOS) Core Collection. The bibliometric package in R 4.1.1, VOSviewer 1.6.18, and GraphPad Prism 8.4 were used to conduct the bibliometric analysis.
RESULTS
From 2000 to 2021, a total of 163 publications were retrieved. China had the largest number of publications (n = 31), while Japan had the highest number of citations (621 citations). Levy J and Indo Y were perhaps the most impactful researchers in the field of CIPA. The co-authorship of authors and institutions indicated little cooperation on CIPA research between different countries. (n=5) and (120 citations) were the most productive and cited journals, respectively, and the top 10 local cited references clarified the theoretical basis of the CIPA research area. Furthermore, the important topics on CIPA mainly include mutations and nerve growth factor (NGF).
CONCLUSION
Based on the bibliometric analysis, we have a comprehensive view of the global status of CIPA research, and the results indicate that CIPA needs more attention and cooperation to facilitate the study of its pathological mechanisms.
PubMed: 36540573
DOI: 10.2147/JPR.S390207 -
Human Molecular Genetics Apr 2023A functional nerve growth factor NGF-Tropomyosin Receptor kinase A (TrkA) system is an essential requisite for the generation and maintenance of long-lasting thermal...
A functional nerve growth factor NGF-Tropomyosin Receptor kinase A (TrkA) system is an essential requisite for the generation and maintenance of long-lasting thermal and mechanical hyperalgesia in adult mammals. Indeed, mutations in the gene encoding for TrkA are responsible for a rare condition, named Hereditary Sensory and Autonomic Neuropathy type IV (HSAN IV), characterized by the loss of response to noxious stimuli, anhidrosis and cognitive impairment. However, to date, there is no available mouse model to properly understand how the NGF-TrkA system can lead to pathological phenotypes that are distinctive of HSAN IV. Here, we report the generation of a knock-in mouse line carrying the HSAN IV TrkAR649W mutation. First, by in vitro biochemical and biophysical analyses, we show that the pathological R649W mutation leads to kinase-inactive TrkA also affecting its membrane dynamics and trafficking. In agreement with the HSAN IV human phenotype, TrkAR649W/m mice display a lower response to thermal and chemical noxious stimuli, correlating with reduced skin innervation, in addition to decreased sweating in comparison to TrkAh/m controls. Moreover, the R649W mutation decreases anxiety-like behavior and compromises cognitive abilities, by impairing spatial-working and social memory. Our results further uncover unexplored roles of TrkA in thermoregulation and sociability. In addition to accurately recapitulating the clinical manifestations of HSAN IV patients, our findings contribute to clarifying the involvement of the NGF-TrkA system in pain sensation.
Topics: Hereditary Sensory and Autonomic Neuropathies; Humans; Animals; Mice; Disease Models, Animal; Mutation; Receptor, trkA; Gene Knock-In Techniques; Nerve Growth Factor; Phosphorylation; Genes, Lethal; Pain; Ganglia, Spinal; Skin; Sympathetic Nervous System; Hypohidrosis; Behavior, Animal
PubMed: 36537577
DOI: 10.1093/hmg/ddac295 -
Cureus Nov 2022Congenital insensitivity to pain with anhidrosis, or hereditary sensory and autonomic neuropathy (HSAN) type IV, is an exceedingly rare neurogenetic disorder. Reported...
Congenital insensitivity to pain with anhidrosis, or hereditary sensory and autonomic neuropathy (HSAN) type IV, is an exceedingly rare neurogenetic disorder. Reported causes are homozygous or compound heterozygous loss-of-function mutations in the neurotrophic tyrosine receptor kinase 1 gene (). Characteristically, patients with this disorder exhibit a complete diminution of pain and temperature sensations over the body disrupted sweat gland functioning, and variable degrees of sensation and cognitive impairments. We hereby present the clinical and neurophysiologic features of a 15-month-old boy with a homozygous frameshift mutation in c.1860_186insT. (p.Pro621Serfs*12) in the gene, consistent with the diagnosis of congenital insensitivity to pain with anhidrosis.
PubMed: 36475157
DOI: 10.7759/cureus.31019 -
BMC Surgery Dec 2022The present research is designed to evaluate the short-term outcome of robot-assisted thoracoscopic surgery (RATS) for the treatment of posterior mediastinal neurogenic...
BACKGROUND
The present research is designed to evaluate the short-term outcome of robot-assisted thoracoscopic surgery (RATS) for the treatment of posterior mediastinal neurogenic tumors.
METHODS
We retrospectively analyzed clinical data on 39 consecutive patients with mediastinal neurogenic tumors after RATS treatment completed by the same operator in the Department of Thoracic Surgery, Gansu Provincial People's Hospital from January 2016 to September 2022. There were 22 males and 17 females with a mean age of (35.1 ± 6.9) years in this analysis report. The tumors of the patients were localized and evaluated preoperatively using magnetic resonance imaging (MRI) or enhanced CT.
RESULTS
All 39 patients successfully underwent the resection of posterior mediastinal neurogenic tumors under RATS, and no conversion to thoracotomy occurred during the operations. The average operative time was (62.1 ± 17.2) min, the average docking time was (10.1 ± 2.5) min, the average intraoperative bleeding was (32.8 ± 19.5) ml, the average 24-h postoperative chest drainage was (67.4 ± 27.9) ml, the average postoperative chest drainage time was (2.2 ± 1.3) days and the average post-operative hospital stay was (3.2 ± 1.3) days. Postoperative complications occurred in 3 patients, including 2 patients with transient Horner's syndrome after surgery and 1 patient with transient anhidrosis of the affected upper limb after surgery.
CONCLUSION
RATS for posterior mediastinal neurogenic tumors is safe, effective, feasible and bring the superiority of robotic surgical system into full play.
Topics: Humans; Retrospective Studies; Neoplasms
PubMed: 36474200
DOI: 10.1186/s12893-022-01855-x