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BMJ Open Jun 2024This planned scoping review aims to provide insight into current literature regarding perceived quality of life (QoL), functioning and participation of patients with...
Quality of life, functioning and participation of adult patients with an amputation following complex regional pain syndrome I or brachial plexus injury: a scoping review protocol.
INTRODUCTION
This planned scoping review aims to provide insight into current literature regarding perceived quality of life (QoL), functioning and participation of patients with upper limb amputations (ULA) because of therapy-resistant debilitating complex regional pain syndrome type I (CRPS-I) or brachial plexus injury (BPI). It is important to gain insight into these outcomes, so we can properly inform and select patients eligible for amputation.
METHODS AND ANALYSIS
Joanna Briggs Institute methodology for scoping reviews, Systematic Reviews and Meta-Analyses Scoping Reviews guidelines and Arksey and O'Malley's framework will be used. Studies regarding adult patients with either BPI or CRPS-I who underwent ULA will be considered for inclusion. Studies should include one or more of the following topics: QoL, functioning or participation and should be written in English, German or Dutch. Searches will be conducted in the Cochrane database, PubMed, EMBASE and Google Scholar. Search strings will be provided by a licenced librarian. All relevant literatures will be considered for inclusion, regardless of published date, in order to give a full scope of available literature. Studies will be selected first by title, then abstract and finally by full article by two reviewers who will discuss after every round. A third reviewer will make final decisions to reach consensus if needed. Data will be presented as brief summaries and in tables using a modified data extraction table.
ETHICS AND DISSEMINATION
No ethical approval is required since no original data will be collected. Results will be disseminated through publication in a peer-reviewed journal and presentations at (inter)national conferences.
Topics: Humans; Quality of Life; Amputation, Surgical; Brachial Plexus; Adult; Research Design; Reflex Sympathetic Dystrophy; Upper Extremity
PubMed: 38839383
DOI: 10.1136/bmjopen-2023-079393 -
Neurobiology of Disease Aug 2024Multiple system atrophy (MSA) is characterized by glial cytoplasmic inclusions (GCIs) containing aggregated α-synuclein (α-syn) in oligodendrocytes. The origin of...
Multiple system atrophy (MSA) is characterized by glial cytoplasmic inclusions (GCIs) containing aggregated α-synuclein (α-syn) in oligodendrocytes. The origin of α-syn accumulation in GCIs is unclear, in particular whether abnormal α-syn aggregates result from the abnormal elevation of endogenous α-syn expression in MSA or ingested from the neuronal source. Tubulin polymerization promoting protein (TPPP) has been reported to play a crucial role in developing GCI pathology. Here, the total cell body, nucleus, and cytoplasmic area density of SNCA and TPPP transcripts in neurons and oligodendrocytes with and without various α-syn pathologies in the pontine base in autopsy cases of MSA (n = 4) and controls (n = 2) were evaluated using RNAscope with immunofluorescence. Single-nucleus RNA-sequencing data for TPPP was evaluated using control frontal cortex (n = 3). SNCA and TPPP transcripts were present in the nucleus and cytoplasm of oligodendrocytes in both controls and diseased, with higher area density in GCIs and glial nuclear inclusions in MSA. Area densities of SNCA and TPPP transcripts were lower in neurons showing cytoplasmic inclusions in MSA. Indeed, TPPP transcripts were unexpectedly found in neurons, while the anti-TPPP antibody failed to detect immunoreactivity. Single-nucleus RNA-sequencing revealed significant TPPP transcript expression predominantly in oligodendrocytes, but also in excitatory and inhibitory neurons. This study addressed the unclear origin of accumulated α-syn in GCIs, proposing that the elevation of SNCA transcripts may supply templates for misfolded α-syn. In addition, the parallel behavior of TPPP and SNCA transcripts in GCI development highlights their potential synergistic contribution to inclusion formation. In conclusion, this study advances our understanding of MSA pathogenesis, offers insights into the dynamics of SNCA and TPPP transcripts in inclusion formation, and proposes regulating their transcripts for future molecular therapy to MSA.
Topics: alpha-Synuclein; Multiple System Atrophy; Humans; Oligodendroglia; Inclusion Bodies; Aged; Female; Male; Middle Aged; Nerve Tissue Proteins; Neurons; Aged, 80 and over
PubMed: 38839023
DOI: 10.1016/j.nbd.2024.106551 -
Tidsskrift For Den Norske Laegeforening... Jun 2024
Topics: Humans; Headache; Autonomic Nervous System Diseases
PubMed: 38832616
DOI: 10.4045/tidsskr.24.0184 -
Neuropsychopharmacology Reports Jun 2024Neuroleptic malignant syndrome (NMS) is a rare and potentially life-threatening condition that may arise at any point during treatment and is often associated with...
BACKGROUND
Neuroleptic malignant syndrome (NMS) is a rare and potentially life-threatening condition that may arise at any point during treatment and is often associated with adverse reactions to dopamine-blocking agents. This syndrome is normally characterized by features such as muscle rigidity, alteration in consciousness, autonomic instability, and leukocytosis.
AIM
The aim of this study is to investigate a borderline intellectual functioning (BIF) case in which NMS with insidious disease progression and long prodromal symptoms was developed.
CASE PRESENTATION
The investigated patient was a 38-year-old female diagnosed with bipolar disorder and a variety of corresponding disorders. The patient exhibited gastrointestinal symptoms and restlessness in the weeks leading up to the study, subsequent to the administration of elevated doses of haloperidol, risperidone, and lithium. In addition, she was hospitalized for restlessness and aggressiveness in the summer of 2023. Furthermore, due to her chief complaint, she received parenteral haloperidol twice in the emergency room, subsequently experiencing fever, altered consciousness, generalized rigidity, and dysphagia. Moreover, the patient's initial creatine phosphokinase (CPK) level was 2550 IU/L, and she was hospitalized in an intensive care unit with the diagnosis of NMS for 8 days.
CONCLUSIONS
This case study highlights the necessity of being attentive about prodromal symptoms of NMS and emergent interventions.
PubMed: 38832410
DOI: 10.1002/npr2.12454 -
Scientific Reports Jun 2024Lumbar sympathetic ganglion neurolysis (LSGN) has been used for long-term pain relief in patients with complex regional pain syndrome (CRPS). However, the actual effect... (Observational Study)
Observational Study
Lumbar sympathetic ganglion neurolysis (LSGN) has been used for long-term pain relief in patients with complex regional pain syndrome (CRPS). However, the actual effect duration of LSGN has not been accurately measured. This prospective observational study measured the effect duration of LSGN in CRPS patients and investigated the relationship between temperature change and pain relief. After performing LSGN, the skin temperatures of both the maximum pain site and the plantar area in the affected and unaffected limbs were measured by infrared thermography, and pain intensity was assessed before and at 2 weeks, 1 month, and 3 months. The median time to return to baseline temperature was calculated using survival analysis. The skin temperature increased significantly at all-time points relative to baseline in both regions (maximum pain site: 1.4 °C ± 1.0 °C, plantar region: 1.28 °C ± 0.8 °C, all P < 0.001). The median time to return to baseline temperature was 12 weeks (95% confidence interval [CI] 7.7-16.3) at the maximum pain site and 12 weeks (95% CI 9.4-14.6) at the plantar area. Pain intensity decreased significantly relative to baseline, at all-time points after LSGN. In conclusion, the median duration of the LSGN is estimated to be 12 weeks.
Topics: Humans; Complex Regional Pain Syndromes; Female; Male; Middle Aged; Prospective Studies; Skin Temperature; Adult; Ganglia, Sympathetic; Pain Measurement; Thermography; Autonomic Nerve Block; Treatment Outcome; Aged; Time Factors; Lumbosacral Region
PubMed: 38830944
DOI: 10.1038/s41598-024-63732-2 -
Neurobiology of Disease Aug 2024Multiple system atrophy (MSA) and Parkinson's disease (PD) are neurodegenerative disorders characterized by α-synuclein pathology, disrupted iron homeostasis and...
BACKGROUND
Multiple system atrophy (MSA) and Parkinson's disease (PD) are neurodegenerative disorders characterized by α-synuclein pathology, disrupted iron homeostasis and impaired neurochemical transmission. Considering the critical role of iron in neurotransmitter synthesis and transport, our study aims to identify distinct patterns of whole-brain iron accumulation in MSA and PD, and to elucidate the corresponding neurochemical substrates.
METHODS
A total of 122 PD patients, 58 MSA patients and 78 age-, sex-matched health controls underwent multi-echo gradient echo sequences and neurological evaluations. We conducted voxel-wise and regional analyses using quantitative susceptibility mapping to explore MSA or PD-specific alterations in cortical and subcortical iron concentrations. Spatial correlation approaches were employed to examine the topographical alignment of cortical iron accumulation patterns with normative atlases of neurotransmitter receptor and transporter densities. Furthermore, we assessed the associations between the colocalization strength of neurochemical systems and disease severity.
RESULTS
MSA patients exhibited increased susceptibility in the striatal, midbrain, cerebellar nuclei, as well as the frontal, temporal, occipital lobes, and anterior cingulate gyrus. In contrast, PD patients displayed elevated iron levels in the left inferior occipital gyrus, precentral gyrus, and substantia nigra. The excessive iron accumulation in MSA or PD correlated with the spatial distribution of cholinergic, noradrenaline, glutamate, serotonin, cannabinoids, and opioid neurotransmitters, and the degree of this alignment was related to motor deficits.
CONCLUSIONS
Our findings provide evidence of the interaction between iron accumulation and non-dopamine neurotransmitters in the pathogenesis of MSA and PD, which inspires research on potential targets for pharmacotherapy.
Topics: Humans; Multiple System Atrophy; Parkinson Disease; Male; Female; Middle Aged; Aged; Brain; Magnetic Resonance Imaging; Iron; Neurotransmitter Agents; Brain Mapping
PubMed: 38830476
DOI: 10.1016/j.nbd.2024.106549 -
PloS One 2024Familial Dysautonomia (FD) is a rare disease caused by ELP1 exon 20 skipping. Here we clarify the role of RNA Polymerase II (RNAPII) and chromatin on this splicing...
Familial Dysautonomia (FD) is a rare disease caused by ELP1 exon 20 skipping. Here we clarify the role of RNA Polymerase II (RNAPII) and chromatin on this splicing event. A slow RNAPII mutant and chromatin-modifying chemicals that reduce the rate of RNAPII elongation induce exon skipping whereas chemicals that create a more relaxed chromatin exon inclusion. In the brain of a mouse transgenic for the human FD-ELP1 we observed on this gene an age-dependent decrease in the RNAPII density profile that was most pronounced on the alternative exon, a robust increase in the repressive marks H3K27me3 and H3K9me3 and a decrease of H3K27Ac, together with a progressive reduction in ELP1 exon 20 inclusion level. In HEK 293T cells, selective drug-induced demethylation of H3K27 increased RNAPII elongation on ELP1 and SMN2, promoted the inclusion of the corresponding alternative exons, and, by RNA-sequencing analysis, induced changes in several alternative splicing events. These data suggest a co-transcriptional model of splicing regulation in which age-dependent changes in H3K27me3/Ac modify the rate of RNAPII elongation and affect processing of ELP1 alternative exon 20.
Topics: RNA Polymerase II; Dysautonomia, Familial; Humans; Exons; Animals; Chromatin; Mice; Alternative Splicing; HEK293 Cells; Histones; Mice, Transgenic; Transcriptional Elongation Factors; Kinetics; RNA Splicing; Nerve Tissue Proteins
PubMed: 38829854
DOI: 10.1371/journal.pone.0298965 -
Frontiers in Pain Research (Lausanne,... 2024Complex Regional Pain Syndrome (CRPS) is a chronic pain disorder characterized by a diverse array of symptoms, including pain that is disproportionate to the initial... (Review)
Review
Complex Regional Pain Syndrome (CRPS) is a chronic pain disorder characterized by a diverse array of symptoms, including pain that is disproportionate to the initial triggering event, accompanied by autonomic, sensory, motor, and sudomotor disturbances. The primary pathology of both types of CRPS (Type I, also known as reflex sympathetic dystrophy, RSD; Type II, also known as causalgia) is featured by allodynia, edema, changes in skin color and temperature, and dystrophy, predominantly affecting extremities. Recent studies started to unravel the complex pathogenic mechanisms of CRPS, particularly from an autoimmune and neuroimmune interaction perspective. CRPS is now recognized as a systemic disease that stems from a complex interplay of inflammatory, immunologic, neurogenic, genetic, and psychologic factors. The relative contributions of these factors may vary among patients and even within a single patient over time. Key mechanisms underlying clinical manifestations include peripheral and central sensitization, sympathetic dysregulation, and alterations in somatosensory processing. Enhanced understanding of the mechanisms of CRPS is crucial for the development of effective therapeutic interventions. While our mechanistic understanding of CRPS remains incomplete, this article updates recent research advancements and sheds light on the etiology, pathogenesis, and molecular underpinnings of CRPS.
PubMed: 38828388
DOI: 10.3389/fpain.2024.1385889 -
Cureus May 2024Guillain-Barre Syndrome (GBS) is an autoimmune condition that causes muscular weakness and can be potentially life-threatening if not identified early. GBS is diagnosed...
Guillain-Barre Syndrome (GBS) is an autoimmune condition that causes muscular weakness and can be potentially life-threatening if not identified early. GBS is diagnosed definitively by cerebrospinal fluid (CSF) analysis and electromyographic (EMG) studies. Identifying illnesses that may have triggered GBS is crucial, as they could affect the course of the disease. Our patient was a 27-year-old woman who developed lower extremity weakness a few days after being treated for a dental abscess. Laboratory and imaging studies ruled out central nervous system (CNS) lesions, myelopathies, and metabolic causes. Diagnosis was difficult due to inconclusive initial investigations, refusal of lumbar puncture, and delayed availability of EMG studies. Additionally, there were no identifiable triggers to support GBS as a diagnosis. During the hospital course, the patient developed tachycardia with new electrocardiogram (EKG) changes. A transthoracic echocardiogram (TTE) showed suspicious vegetation, and a transesophageal echocardiogram (TEE) confirmed severe mitral regurgitation. The new valvular lesions and autonomic dysfunction with worsening lower extremity weakness increased our suspicion of GBS. Intravenous immunoglobulin (IVIG) was administered empirically, but she developed bulbar symptoms, prompting admission to the intensive care unit (ICU). A lumbar puncture performed at this time was negative for albumino-cytological dissociation and CNS infections. Signs of sepsis with valvular lesions raised concerns for infective endocarditis (IE). Due to recent treatment with antibiotics for dental abscess, a negative blood culture was a confounding factor in Duke's criteria, delaying the diagnosis of IE. Infectious disease experts suggested empirical treatment for suspected blood culture-negative infective endocarditis (BCNE) and valvular abscess. She was transferred to a cardiothoracic care facility for valvular surgery evaluation. EMG studies identified the patient's condition as the acute motor sensory axonal neuropathy (AMSAN) variant of GBS. The patient's antibodies tested positive for immunoglobulin G (IgG). Since this indicates a past infection, it is uncertain whether triggered the patient's GBS. However, new valvular vegetation and acute-onset lower extremity weakness make us hypothesize that BCNE may have triggered GBS.
PubMed: 38827011
DOI: 10.7759/cureus.59479 -
Cureus May 2024Lambert-Eaton myasthenic syndrome (LEMS) is a rare neuromuscular junction disorder due to auto-antibodies against presynaptic voltage-gated calcium channels (VGCC). The...
Lambert-Eaton myasthenic syndrome (LEMS) is a rare neuromuscular junction disorder due to auto-antibodies against presynaptic voltage-gated calcium channels (VGCC). The typical manifestation of LEMS is proximal muscle weakness, autonomic dysfunction, and areflexia; however, an atypical manifestation of LEMS is weakness of respiratory muscles, leading to acute respiratory failure. Herein, we describe a case of acute respiratory failure resulting from LEMS. Our patient was a 63-year-old woman with a past medical history of metastatic small cell lung cancer (SCLC) who presented with ambulatory dysfunction, dysarthria, and progressive dyspnea. She was intubated because of hypoxia and developed acute respiratory failure without a clear pulmonary etiology, raising the suspicion of a neuromuscular junction disorder. She was diagnosed with LEMS with a positive paraneoplastic panel for VGCC antibodies, confirmed by electromyography and nerve conduction study (EMG/NCS), and treated with intravenous immunoglobulin (IVIg). The patient's hospital stay was complicated by pneumonia, and comfort care was ultimately pursued. Our case highlights the importance of considering LEMS in patients presenting with isolated respiratory muscle weakness without focal neurological deficits. To our knowledge, this is the first report to review all reported cases of LEMS with resultant respiratory failure. We aim to establish the association of LEMS with respiratory failure so that appropriate treatment is initiated as early as possible.
PubMed: 38826943
DOI: 10.7759/cureus.59516