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Journal of Neuromuscular Diseases 2023SELENON(SEPN1)-related myopathy (SELENON-RM) is a rare congenital neuromuscular disease characterized by proximal and axial muscle weakness, spinal rigidity, scoliosis... (Observational Study)
Observational Study
BACKGROUND
SELENON(SEPN1)-related myopathy (SELENON-RM) is a rare congenital neuromuscular disease characterized by proximal and axial muscle weakness, spinal rigidity, scoliosis and respiratory impairment. No curative treatment options exist, but promising preclinical studies are ongoing. Currently, natural history data are lacking, while selection of appropriate clinical and functional outcome measures is needed to reach trial readiness.
OBJECTIVE
We aim to identify all Dutch and Dutch-speaking Belgian SELENON-RM patients, deep clinical phenotyping, trial readiness and optimization of clinical care.
METHODS
This cross-sectional, single-center, observational study comprised neurological examination, functional measurements including Motor Function Measurement 20/32 (MFM-20/32) and accelerometry, questionnaires, muscle ultrasound, respiratory function tests, electro- and echocardiography, and dual-energy X-ray absorptiometry.
RESULTS
Eleven patients with genetically confirmed SELENON-RM were included (20±13 (3-42) years, 73% male). Axial and proximal muscle weakness were most pronounced. The mean MFM-20/32 score was 71.2±15.1%, with domain 1 (standing and transfers) being most severely affected. Accelerometry showed a strong correlation with MFM-20/32. Questionnaires revealed impaired quality of life, pain and problematic fatigue. Muscle ultrasound showed symmetrically increased echogenicity in all muscles. Respiratory function, and particularly diaphragm function, was impaired in all patients, irrespective of the age. Cardiac assessment showed normal left ventricular systolic function in all patients but abnormal left ventricular global longitudinal strain in 43% of patients and QRS fragmentation in 80%. Further, 80% of patients showed decreased bone mineral density on dual-energy X-ray absorptiometry scan and 55% of patients retrospectively experienced fragility long bone fractures.
CONCLUSIONS
We recommend cardiorespiratory follow-up as a part of routine clinical care in all patients. Furthermore, we advise vitamin D supplementation and optimization of calcium intake to improve bone quality. We recommend management interventions to reduce pain and fatigue. For future clinical trials, we propose MFM-20/32, accelerometry and muscle ultrasound to capture disease severity and possibly disease progression.
Topics: Humans; Male; Female; Cross-Sectional Studies; Longevity; Retrospective Studies; Quality of Life; Muscular Diseases; Muscle Weakness; Fatigue
PubMed: 37807786
DOI: 10.3233/JND-221673 -
Journal of Addiction MedicineThis narrative review summarizes literature on pharmaceutical fentanyl's absorption, distribution, metabolism, and excretion patterns to inform research on illicitly... (Review)
Review
OBJECTIVES
This narrative review summarizes literature on pharmaceutical fentanyl's absorption, distribution, metabolism, and excretion patterns to inform research on illicitly manufactured fentanyl (IMF).
RESULTS
Fentanyl is highly lipophilic, lending itself to rapid absorption by highly perfused tissues (including the brain) before redistributing from these tissues to muscle and fat. Fentanyl is eliminated primarily by metabolism and urinary excretion of metabolites (norfentanyl and other minor metabolites). Fentanyl has a long terminal elimination, with a documented secondary peaking phenomenon that can manifest as "fentanyl rebound." Clinical implications in overdose (respiratory depression, muscle rigidity, and "wooden chest syndrome") and opioid use disorder treatment (subjective effects, withdrawal, and buprenorphine-precipitated withdrawal) are discussed. The authors highlight research gaps derived from differences in medicinal fentanyl studies and IMF use patterns, including that medicinal fentanyl studies are largely conducted with persons who were opioid-naive, anesthetized, or had severe chronic pain and that IMF use is characterized by supratherapeutic doses and frequent and sustained administration patterns, as well as adulteration with other substances and/or fentanyl analogs.
CONCLUSIONS
This review reexamines information yielded from decades of medicinal fentanyl research and applies elements of the pharmacokinetic profile to persons with IMF exposure. In persons who use drugs, peripheral accumulation of fentanyl may be leading to prolonged exposure. More focused research on the pharmacology of fentanyl in persons using IMF is warranted.
Topics: Humans; Analgesics, Opioid; Chronic Pain; Clinical Relevance; Drug Overdose; Fentanyl
PubMed: 37788600
DOI: 10.1097/ADM.0000000000001185 -
Anesthesiology Jan 2024Malignant hyperthermia (MH) susceptibility is a heritable musculoskeletal disorder that can present as a potentially fatal hypermetabolic response to triggering...
BACKGROUND
Malignant hyperthermia (MH) susceptibility is a heritable musculoskeletal disorder that can present as a potentially fatal hypermetabolic response to triggering anesthesia agents. Genomic screening for variants in MH-associated genes RYR1 and CACNA1S provides an opportunity to prevent morbidity and mortality. There are limited outcomes data from disclosing variants in RYR1, the most common MH susceptibility gene, in unselected populations. The authors sought to identify the rate of MH features or fulminant episodes after triggering agent exposure in an unselected population undergoing genomic screening including actionable RYR1 variants.
METHODS
The MyCode Community Health Initiative by Geisinger (USA) is an electronic health record-linked biobank that discloses pathogenic and likely pathogenic variants in clinically actionable genes to patient-participants. Available electronic anesthesia and ambulatory records for participants with actionable RYR1 results returned through December 2020 were evaluated for pertinent findings via double-coded chart reviews and reconciliation. Descriptive statistics for observed phenotypes were calculated.
RESULTS
One hundred fifty-two participants had an actionable RYR1 variant disclosed during the study period. None had previous documented genetic testing for MH susceptibility; one had previous contracture testing diagnosing MH susceptibility. Sixty-eight participants (44.7%) had anesthesia records documenting triggering agent exposure during at least one procedure. None received dantrolene treatment or had documented muscle rigidity, myoglobinuria, hyperkalemia, elevated creatine kinase, severe myalgia, or tea-colored urine. Of 120 possibly MH-related findings (postoperative intensive care unit admissions, hyperthermia, arterial blood gas evaluation, hypercapnia, or tachycardia), 112 (93.3%) were deemed unlikely to be MH events; 8 (6.7%) had insufficient records to determine etiology.
CONCLUSIONS
Results demonstrate a low frequency of classic intraanesthetic hypermetabolic phenotypes in an unselected population with actionable RYR1 variants. Further research on the actionability of screening for MH susceptibility in unselected populations, including economic impact, predictors of MH episodes, and expanded clinical phenotypes, is necessary.
Topics: Humans; Genetic Testing; Malignant Hyperthermia; Metagenomics; Mutation; Phenotype; Ryanodine Receptor Calcium Release Channel
PubMed: 37787745
DOI: 10.1097/ALN.0000000000004786 -
Cureus Aug 2023Wooden chest syndrome (WCS) is a rare phenomenon of opioid-induced skeletal muscle rigidity causing respiratory failure and inability to ventilate. The most common...
Wooden chest syndrome (WCS) is a rare phenomenon of opioid-induced skeletal muscle rigidity causing respiratory failure and inability to ventilate. The most common opioid associated with WCS is the synthetic opioid fentanyl. Fentanyl has been called the deadliest drug in America. With the use of fentanyl in critical care units and operation rooms, it is important to better understand fentanyl's side effects and predisposing factors of WCS. The symptoms of WCS are often seen in lower fentanyl doses than what would cause apnea. In this case report, we present a case of WCS with an extremely low dose of fentanyl, i.e., 50 μcg (0.49 μcg/kg), in an 80-year-old patient with a medical history significant for chronic inflammatory demyelinating polyneuropathy (CIDP) and Guillain-Barré syndrome (GBS).
PubMed: 37731415
DOI: 10.7759/cureus.43788 -
Cureus Aug 2023This study presents the clinical features and disease progression of a 39-year-old male patient diagnosed with Huntington's disease (HD). The diagnosis was confirmed by...
This study presents the clinical features and disease progression of a 39-year-old male patient diagnosed with Huntington's disease (HD). The diagnosis was confirmed by direct genetic testing, using DNA obtained from a blood sample that revealed expanded cytosine-adenine-guanine (CAG) repeats in the huntingtin gene (HD gene). The patient exhibited motor symptoms, including chorea, muscle rigidity, coordination difficulties, and speech and swallowing impairments. Cognitive symptoms comprised impaired judgment, planning difficulties, slowed thinking, memory lapses, and attention problems. The patient's progressive deterioration resulted in wheelchair dependency and increased reliance on supportive care. This report highlights the significance of genetic testing in confirming HD diagnosis and emphasizes the need for a multidisciplinary approach to manage the symptoms and improve the patient's quality of life.
PubMed: 37700984
DOI: 10.7759/cureus.43377 -
Case Reports in Pediatrics 2023. Organophosphates are chemicals that lead to the accumulation of acetylcholine, causing muscarinic symptoms such as salivation and nicotinic manifestations like muscle...
. Organophosphates are chemicals that lead to the accumulation of acetylcholine, causing muscarinic symptoms such as salivation and nicotinic manifestations like muscle weakness and hypertension and rarely leading to basal ganglia impairment, manifesting as extrapyramidal symptoms. Literature reported that the use of amantadine, an amine that has both antiviral and dopaminergic activities, improves extrapyramidal manifestations. Most of the studies exploring the effect of amantadine were conducted on adults and there are extremely limited data in regards to this topic in Saudi Arabia. Thus, the purpose of this case study is to report the outcome of treating a child who developed extrapyramidal symptoms due to organophosphates poisoning with amantadine. . A 6-year-old boy was found by his family drowsy and drooling with an insecticide bottle beside him. He was brought to the ER and arrested on arrival, and he was eventually revived after 5 minutes of CPR. Then, he developed features of extrapyramidal involvement such as delirium, hyperactivity, akathisia, aphonia, and tremors. He was started on oral amantadine 50 mg once daily and then increased to twice daily for two weeks while admitted. During admission, his symptoms were assessed daily, and an improvement was noticed by his family and the medical team. Upon discharge, he was able to form sentences; tremors were almost resolved; and there was no rigidity or agitation. He was followed up postdischarge and showed significant improvement. He continued amantadine for almost 3 months until the full resolution of his symptoms. . This case illustrates the promising benefits of using amantadine in treating extrapyramidal manifestations following organophosphate ingestion.
PubMed: 37700928
DOI: 10.1155/2023/1632052 -
Medicina (Kaunas, Lithuania) Aug 2023: Whiplash is associated with a wide variety of clinical manifestations, including headache, neck pain, cervical rigidity, shoulder and back pain, paresthesia, vertigo,... (Review)
Review
: Whiplash is associated with a wide variety of clinical manifestations, including headache, neck pain, cervical rigidity, shoulder and back pain, paresthesia, vertigo, and temporomandibular disorders (TMDs). Previous studies reported that TMDs are more common in individuals with chronic whiplash-associated disorders (WAD) than in the general population; however, the pathophysiology and mechanism of this relationship are still not well understood. : A PubMed and Ovid EMBASE review was performed to identify all studies addressing the trauma related cause and effect relationship between WAD and TMDs from January 2003 to March 2023. : After screening for eligibility and inclusion criteria, a total of 16 articles met the selection criteria. The various included studies discussed different aspects of the association between WDA and TMDs, including changes in the coordination and amplitude of jaw opening, the severity of the associated symptoms/signs in cases of WAD, the degree of fatigue and psychological stress, difficulty in feeding, cervical and myofascial pain, changes in the MRI signal at various muscle points, muscle tenderness, and quality of life. : In this review, we summarized the clinical evidence of any trauma related cause and effect relationship between whiplash and TMDs. An accurate screening of the previous literature showed that, in conclusion, the relationship between whiplash and TMDs is still unclear.
Topics: Humans; Quality of Life; Temporomandibular Joint Disorders; Neck; Fatigue; Headache
PubMed: 37629772
DOI: 10.3390/medicina59081482 -
Medicina 2023Stiff-person syndrome is a rare neurological condition characterized by muscular rigidity of the trunk and extremities and muscle spasms triggered by sensory or...
Stiff-person syndrome is a rare neurological condition characterized by muscular rigidity of the trunk and extremities and muscle spasms triggered by sensory or emotional stimuli, which progresses towards prostration. It has a pathophysiogenic mechanism with an immunological basis, in which autoantibodies, such as antiGAD65, play a central role. Likewise, the detection of these antibodies corroborates the diagnosis in a patient with a suggestive clinical picture. Four to 6% of cases have underlying neoplasms. Treatment is based on symptomatic, immunomodulatory, and underlying disease management in paraneoplastic cases. We report a case of classic stiff person syndrome associated with thymoma and review the main characteristics of this entity.
Topics: Humans; Thymoma; Stiff-Person Syndrome; Thymus Neoplasms; Autoantibodies
PubMed: 37582138
DOI: No ID Found -
Digital Health 2023Sleep is vital to many processes involved in the well-being and health of children; however, it is estimated that 80% of children with Rett syndrome suffer from sleep...
Sleep is vital to many processes involved in the well-being and health of children; however, it is estimated that 80% of children with Rett syndrome suffer from sleep disorders. Caregiver reports and questionnaires, which are the current method of studying sleep, are prone to observer bias and missed information. Polysomnography is considered the gold standard for sleep analysis but is labor and cost-intensive and limits the frequency of data collection for sleep disorder studies. Wearable digital health technologies, such as actigraphy devices, have shown potential and feasibility as a method for sleep analysis in Rett syndrome, but have not been validated against polysomnography. Furthermore, the collected accelerometer data has limitations due to the rigidity, periodic limb movement, and involuntary muscle contractions prevalent in Rett syndrome. Heart rate and electrodermal activity, along with other physiological signals, have been linked to sleep stages and can be utilized with machine learning to provide better resistance to noise and false positives than actigraphy. This research aims to address the gap in Rett syndrome sleep analysis by comparing the performance of a machine learning model utilizing both accelerometer data and physiological data features to the gold-standard polysomnography for sleep analysis in Rett syndrome. Our analytical validation pilot study ( = 7) found that using physiological and accelerometer features, our machine learning models can differentiate between awake, non-rapid eye movement sleep, and rapid eye movement sleep in Rett syndrome children with an accuracy of 85.1% when using an individual model. Additionally, this work demonstrates that it is feasible to use digital health technologies in Rett syndrome, even at a young age, without data loss or interference from repetitive movements that are characteristic of Rett syndrome.
PubMed: 37545628
DOI: 10.1177/20552076231191622