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Journal of Neurology Aug 2023Multiple sclerosis (MS) is a chronic progressive demyelinating disease of the central nervous system (CNS), which also affects the autonomic nervous system (ANS).... (Review)
Review
Multiple sclerosis (MS) is a chronic progressive demyelinating disease of the central nervous system (CNS), which also affects the autonomic nervous system (ANS). Manifestations of MS in the ANS include urological, sexual, gastrointestinal, cardiovascular, and thermoregulatory disorders as well as increased fatigue. These problems are common yet are often underestimated due to the non-specificity of the symptoms and the limited evaluation of the ANS in the usual clinical practice. Most of these symptoms seem to be related to localized lesions in the CNS. However, the mechanisms by which these disorders are caused in MS have not been fully investigated, thus preventing any focused etiological treatment. The most common disorders of the ANS in MS represent a challenge for clinicians due to the variability of the clinical picture and our minimal data on their diagnosis and treatment. Early diagnosis and initiation of individualized treatment regimens, often in need of multiple approaches, seem to yield the best results in managing ANS dysfunction in MS patients.
Topics: Humans; Multiple Sclerosis; Autonomic Nervous System Diseases; Autonomic Nervous System; Central Nervous System
PubMed: 37084150
DOI: 10.1007/s00415-023-11725-y -
Seminars in Arthritis and Rheumatism Dec 2023Over the years several lines of evidence have implied a pathological involvement of autonomic nervous system (ANS) in systemic sclerosis (SSc). However, the relationship... (Review)
Review
INTRODUCTION
Over the years several lines of evidence have implied a pathological involvement of autonomic nervous system (ANS) in systemic sclerosis (SSc). However, the relationship between autonomic dysfunction and SSc is not yet fully understood. The aims of this scoping review were to map the research done in this field and inform future research to investigate pathogenic hypotheses of ANS involvement.
METHODS
We performed a scoping review of publications collected through a literature search of MEDLINE and Web of Science databases, looking for dysautonomia in SSc. We included original data from papers that addressed ANS involvement in SSc regarding pathogenesis, clinical presentation and diagnostic tools.
RESULTS
467 papers were identified, 109 studies were selected to be included in the present review, reporting data from a total of 2742 SSc patients. Cardiovascular system was the most extensively investigated, assessing heart rate variability with 24 h HolterECG or Ewing's autonomic tests. Important signs of dysautonomia were also found in digital vasculopathy, gastrointestinal system and SSc skin, assessed both with non-invasive techniques and histologically. Research hypotheses mainly regarding the relationship between sympathetic system - ischemia and the role of neurotrophins were then developed and discussed.
CONCLUSION
We described the currently available evidence on pathogenesis, clinical presentation and diagnostic assessment of dysautonomia in SSc patients. A strong influence of ANS deregulation on SSc clearly emerges from the literature. Future research is warranted to clarify the mechanisms and timing of autonomic dysfunction in SSc.
Topics: Humans; Autonomic Nervous System Diseases; Autonomic Nervous System; Heart Rate; Scleroderma, Systemic; Gastrointestinal Tract
PubMed: 37776665
DOI: 10.1016/j.semarthrit.2023.152268 -
Anesthesiology Apr 2024Pain that accompanies deafferentation is one of the most mysterious and misunderstood medical conditions. Prevalence rates for the assorted conditions vary considerably...
Pain that accompanies deafferentation is one of the most mysterious and misunderstood medical conditions. Prevalence rates for the assorted conditions vary considerably but the most reliable estimates are greater than 50% for strokes involving the somatosensory system, brachial plexus avulsions, spinal cord injury, and limb amputation, with controversy surrounding the mechanistic contributions of deafferentation to ensuing neuropathic pain syndromes. Deafferentation pain has also been described for loss of other body parts (e.g., eyes and breasts) and may contribute to between 10% and upwards of 30% of neuropathic symptoms in peripheral neuropathies. There is no pathognomonic test or sign to identify deafferentation pain, and part of the controversy surrounding it stems from the prodigious challenges in differentiating cause and effect. For example, it is unknown whether cortical reorganization causes pain or is a byproduct of pathoanatomical changes accompanying injury, including pain. Similarly, ascertaining whether deafferentation contributes to neuropathic pain, or whether concomitant injury to nerve fibers transmitting pain and touch sensation leads to a deafferentation-like phenotype can be clinically difficult, although a detailed neurologic examination, functional imaging, and psychophysical tests may provide clues. Due in part to the concurrent morbidities, the physical, psychologic, and by extension socioeconomic costs of disorders associated with deafferentation are higher than for other chronic pain conditions. Treatment is symptom-based, with evidence supporting first-line antineuropathic medications such as gabapentinoids and antidepressants. Studies examining noninvasive neuromodulation and virtual reality have yielded mixed results.
Topics: Humans; Causalgia; Neuralgia; Brachial Plexus; Spinal Cord Injuries
PubMed: 38470115
DOI: 10.1097/ALN.0000000000004881 -
Continuum (Minneapolis, Minn.) Feb 2024This article discusses the effects of myelopathy on multiple organ systems and reviews the treatment and management of some of these effects.
OBJECTIVE
This article discusses the effects of myelopathy on multiple organ systems and reviews the treatment and management of some of these effects.
LATEST DEVELOPMENTS
Recent advances in functional electrical stimulation, epidural spinal cord stimulation, robotics, and surgical techniques such as nerve transfer show promise in improving function in patients with myelopathy. Ongoing research in stem cell therapy and neurotherapeutic drugs may provide further therapeutic avenues in the future.
ESSENTIAL POINTS
Treatment for symptoms of spinal cord injury should be targeted toward patient goals. If nerve transfer for upper extremity function is considered, the patient should be evaluated at around 6 months from injury to assess for lower motor neuron involvement and possible time limitations of surgery. A patient with injury at or above the T6 level is at risk for autonomic dysreflexia, a life-threatening condition that presents with elevated blood pressure and can lead to emergent hypertensive crisis. Baclofen withdrawal due to baclofen pump failure or programming errors may also be life-threatening. Proper management of symptoms may help avoid complications such as autonomic dysreflexia, renal failure, heterotopic ossification, and fractures.
Topics: Humans; Autonomic Dysreflexia; Baclofen; Spinal Cord Injuries; Autonomic Nervous System Diseases; Hypertension
PubMed: 38330480
DOI: 10.1212/CON.0000000000001383 -
The Journal of Clinical Endocrinology... Sep 2023Hyperglycemia and autonomic dysfunction are bidirectionally related.
CONTEXT
Hyperglycemia and autonomic dysfunction are bidirectionally related.
OBJECTIVE
We investigated the association of longitudinal evolution of heart rate variability (HRV) with incident type 2 diabetes (T2D) among the general population.
METHODS
We included 7630 participants (mean age 63.7 years, 58% women) from the population-based Rotterdam Study who had no history of T2D and atrial fibrillation at baseline and had repeated HRV assessments at baseline and during follow-up. We used joint models to assess the association between longitudinal evolution of heart rate and different HRV metrics (including the heart rate-corrected SD of the normal-to-normal RR intervals [SDNNc], and root mean square of successive RR-interval differences [RMSSDc]) with incident T2D. Models were adjusted for cardiovascular risk factors. Bidirectional Mendelian randomization (MR) using summary-level data was also performed.
RESULTS
During a median follow-up of 8.6 years, 871 individuals developed incident T2D. One SD increase in heart rate (hazard ratio [HR] 1.20; 95% CI, 1.09-1.33), and log(RMSSDc) (HR 1.16; 95% CI, 1.01-1.33) were independently associated with incident T2D. The HRs were 1.54 (95% CI, 1.08-2.06) for participants younger than 62 years and 1.15 (95% CI, 1.01-1.31) for those older than 62 years for heart rate (P for interaction <.001). Results from bidirectional MR analyses suggested that HRV and T2D were not significantly related to each other.
CONCLUSION
Autonomic dysfunction precedes development of T2D, especially among younger individuals, while MR analysis suggests no causal relationship. More studies are needed to further validate our findings.
Topics: Humans; Female; Middle Aged; Male; Diabetes Mellitus, Type 2; Heart Rate; Atrial Fibrillation; Autonomic Nervous System Diseases; Risk Factors
PubMed: 37022971
DOI: 10.1210/clinem/dgad200 -
Lancet (London, England) Aug 2023
Topics: Humans; Post-Acute COVID-19 Syndrome; COVID-19; Venous Insufficiency; Primary Dysautonomias
PubMed: 37573078
DOI: 10.1016/S0140-6736(23)01461-7 -
Clinical Rheumatology Oct 2023Psoriatic arthritis (PsA) is an inflammatory disease with a high prevalence of cardiovascular (CV) events due to traditional cardiovascular risk factors and increased... (Review)
Review
Psoriatic arthritis (PsA) is an inflammatory disease with a high prevalence of cardiovascular (CV) events due to traditional cardiovascular risk factors and increased systemic inflammation. In this review, our objectives were to (i) evaluate the cardiovascular events and risk factors and (ii) investigate the relationship between autonomic dysfunction and CV diseases in PsA. A systematic review of the literature was done on the Medline/PubMed, Scopus, and the Directory of Open Access Journals databases between January 2017 and July 2022. After screening and exclusions, 73 studies were included for the final review. Patients with PsA have a greater risk of CV diseases and increased traditional CV risk factors, including hypertension, diabetes mellitus, obesity, metabolic syndrome, and dyslipidemia. Although autonomic dysfunction is more common in PsA than in the general population, its relationship with increased CV diseases in these patients is still unclear. Limitations in explaining CV risk in these patient groups complicate patient assessment as cardiovascular risk factors are linked to the morbidity and mortality of PsA, and it is essential to improve an optimal screening and management strategy for CV disease. All CV risk scoring systems cannot fully assess the CV risk in these patients, so in addition to scoring systems, carotid ultrasound evaluation may be a part of the CV evaluation.
Topics: Humans; Arthritis, Psoriatic; Cardiovascular Diseases; Heart Disease Risk Factors; Hypertension; Primary Dysautonomias; Risk Factors
PubMed: 36542174
DOI: 10.1007/s10067-022-06484-6 -
Neurology Dec 2023The second consensus criteria in 2008 have been used in diagnosing multiple system atrophy (MSA). The International Parkinson and Movement Disorder Society (MDS)...
BACKGROUND AND OBJECTIVE
The second consensus criteria in 2008 have been used in diagnosing multiple system atrophy (MSA). The International Parkinson and Movement Disorder Society (MDS) proposed new diagnostic criteria for MSA in 2022. This study aimed to compare the diagnostic accuracy between these 2 criteria and validate the clinical utility of the newly proposed criteria for MSA.
METHODS
We conducted a retrospective autopsy cohort study of consecutive patients with a clinical or pathologic diagnosis of MSA from the Mayo Clinic brain bank between 1998 and 2021. We studied 352 patients (250 pathologically diagnosed MSA and 102 non-MSA); MDS criteria and the second consensus criteria were applied. The sensitivity, specificity, and area under the curve (AUC) of receiver operating characteristic curves were compared between these criteria. Comparison was conducted between clinical subtypes and among clinically challenging cases (those with different clinical diagnoses or those with suspected but undiagnosed MSA before death). We also used machine learning algorithm, eXtreme Gradient Boosting, to identify clinical features contributing diagnostic performance.
RESULTS
The sensitivity and specificity of clinically established and probable MSA by the MDS criteria were 16% and 99% and 64% and 74%, respectively. The sensitivity and specificity of probable MSA and possible MSA by the second consensus criteria were 72% and 52% and 93% and 21%, respectively. The AUC of MDS clinically probable MSA was the highest (0.69). The diagnostic performance did not differ between clinical subtypes. In clinically challenging cases, MDS clinically established MSA maintained high specificity and MDS clinically probable MSA demonstrated the highest AUC (0.62). MRI findings contributed to high specificity. In addition, combining core clinical features with 2 or more from any of the 13 supporting features and the absence of exclusion criteria also yielded high specificity. Among supporting features, rapid progression was most important for predicting MSA pathology.
DISCUSSION
The MDS criteria showed high specificity with clinically established MSA and moderate sensitivity and specificity with clinically probable MSA. The observation that high specificity could be achieved with clinical features alone suggests that MSA diagnosis with high specificity is possible even in areas where MRI is not readily available.
Topics: Humans; Multiple System Atrophy; Cohort Studies; Retrospective Studies; Brain; Sensitivity and Specificity
PubMed: 37816641
DOI: 10.1212/WNL.0000000000207905 -
European Journal of Pain (London,... Aug 2023The aim of this systematic review was to appraise and analyse the knowledge on bone-related biochemical and histological biomarkers in complex regional pain syndrome 1... (Review)
Review
OBJECTIVE
The aim of this systematic review was to appraise and analyse the knowledge on bone-related biochemical and histological biomarkers in complex regional pain syndrome 1 (CRPS 1).
DATABASE
A total of 7 studies were included in the analysis (biochemical analyses n = 3, animal study n = 1, histological examination n = 3).
RESULTS
Two studies were classified as having a low risk of bias and five studies with a moderate risk of bias. Biochemical analysis indicated an increased bone turnover with increased bone resorption (elevated urinary levels of deoxypyridinoline) and bone formation (increased serum levels of calcitonin, osteoprotegerin and alkaline phosphatase). The animal study reported an increased signalling of proinflammatory tumour necrosis factor 4 weeks postfracture, which did, however, not contribute to local bone loss. Histological examination from biopsies revealed thinning and resorption of cortical bone, rarefication and reduction in trabecular bone and vascular modification in the bone marrow in acute CRPS 1, and replacement of the bone marrow by dystrophic vessels in chronic CRPS 1.
CONCLUSION
The limited data reviewed revealed certain potential bone-related biomarkers in CRPS. Biomarkers hold the potential to identify patients who may benefit from treatments that influence bone turnover. Thus, this review identifies important areas for future research in CRPS1 patients.
Topics: Animals; Reflex Sympathetic Dystrophy; Biomarkers; Complex Regional Pain Syndromes
PubMed: 36999437
DOI: 10.1002/ejp.2116 -
Current Neurology and Neuroscience... Apr 2024This review summarizes previous and ongoing neuroprotection trials in multiple system atrophy (MSA), a rare and fatal neurodegenerative disease characterized by... (Review)
Review
PURPOSE OF REVIEW
This review summarizes previous and ongoing neuroprotection trials in multiple system atrophy (MSA), a rare and fatal neurodegenerative disease characterized by parkinsonism, cerebellar, and autonomic dysfunction. It also describes the preclinical therapeutic pipeline and provides some considerations relevant to successfully conducting clinical trials in MSA, i.e., diagnosis, endpoints, and trial design.
RECENT FINDINGS
Over 30 compounds have been tested in clinical trials in MSA. While this illustrates a strong treatment pipeline, only two have reached their primary endpoint. Ongoing clinical trials primarily focus on targeting α-synuclein, the neuropathological hallmark of MSA being α-synuclein-bearing glial cytoplasmic inclusions. The mostly negative trial outcomes highlight the importance of better understanding underlying disease mechanisms and improving preclinical models. Together with efforts to refine clinical measurement tools, innovative statistical methods, and developments in biomarker research, this will enhance the design of future neuroprotection trials in MSA and the likelihood of positive outcomes.
Topics: Humans; Multiple System Atrophy; alpha-Synuclein; Parkinsonian Disorders; Biomarkers; Cerebellum
PubMed: 38416311
DOI: 10.1007/s11910-024-01335-0