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Expert Review of Neurotherapeutics Feb 2024Complex regional pain syndrome (CRPS) is a rare and painful condition that has a wide range of triggering factors, often traumatic, and can present various clinical... (Review)
Review
INTRODUCTION
Complex regional pain syndrome (CRPS) is a rare and painful condition that has a wide range of triggering factors, often traumatic, and can present various clinical manifestations. The lack of knowledge about the underlying mechanisms has led to numerous treatment approaches, both conservative and surgical, which work through different mechanisms of action.
AREAS COVERED
In this review, the authors explore the key aspects of CRPS, including definition, diagnostic criteria, pitfalls, pathogenic hypotheses, and treatment strategies with a focus on pharmacotherapy. The review was based on a comprehensive search of the literature using PubMed, while also considering international guidelines for managing CRPS.
EXPERT OPINION
Based on the available evidence, pharmacological interventions appear to be effective in treating CRPS, especially when they target peripheral mechanisms, specifically nociceptive inflammatory pain, and when administered early in the course of the disease. However, there is still a lack of reliable evidence regarding the effects of drugs on central mechanisms of chronic pain in CRPS. In our expert opinion, drug therapy should be initiated as soon as possible, particularly in warm CRPS patient clusters, to prevent significant functional limitations, psychological distress, and negative impacts on individuals' social and economic well-being.
Topics: Humans; Complex Regional Pain Syndromes; Chronic Pain
PubMed: 38241139
DOI: 10.1080/14737175.2024.2307490 -
Annals of Allergy, Asthma & Immunology... Apr 2024Mast cells (MC) are ubiquitous in the body, and they are critical for not only in allergic diseases but also in immunity and inflammation, including having potential... (Review)
Review
Mast cells (MC) are ubiquitous in the body, and they are critical for not only in allergic diseases but also in immunity and inflammation, including having potential involvement in the pathophysiology of dysautonomias and neuroinflammatory disorders. MC are located perivascularly close to nerve endings and sites such as the carotid bodies, heart, hypothalamus, the pineal gland, and the adrenal gland that would allow them not only to regulate but also to be affected by the autonomic nervous system (ANS). MC are stimulated not only by allergens but also many other triggers including some from the ANS that can affect MC release of neurosensitizing, proinflammatory, and vasoactive mediators. Hence, MC may be able to regulate homeostatic functions that seem to be dysfunctional in many conditions, such as postural orthostatic tachycardia syndrome, autism spectrum disorder, myalgic encephalomyelitis/chronic fatigue syndrome, and Long-COVID syndrome. The evidence indicates that there is a possible association between these conditions and diseases associated with MC activation. There is no effective treatment for any form of these conditions other than minimizing symptoms. Given the many ways MC could be activated and the numerous mediators released, it would be important to develop ways to inhibit stimulation of MC and the release of ANS-relevant mediators.
Topics: Humans; Mast Cells; Neuroinflammatory Diseases; Autism Spectrum Disorder; Post-Acute COVID-19 Syndrome; Autonomic Nervous System; Postural Orthostatic Tachycardia Syndrome
PubMed: 37951572
DOI: 10.1016/j.anai.2023.10.032 -
Journal of Neurology, Neurosurgery, and... Aug 2023GGC repeat expansions have been associated with various neurogenerative disorders, including neuronal intranuclear inclusion disease and inherited peripheral...
BACKGROUND
GGC repeat expansions have been associated with various neurogenerative disorders, including neuronal intranuclear inclusion disease and inherited peripheral neuropathies (IPNs). However, only a few -related disease studies in IPN have been reported, and the clinical and genetic spectra remain unclear. Thus, this study aimed to describe the clinical and genetic manifestations of -related IPNs.
METHOD
Among 2692 Japanese patients clinically diagnosed with IPN/Charcot-Marie-Tooth disease (CMT), we analysed repeat expansion in 1783 unrelated patients without a genetic diagnosis. Screening and repeat size determination of repeat expansion were performed using repeat-primed PCR and fluorescence amplicon length analysis-PCR.
RESULTS
repeat expansions were identified in 26 cases of IPN/CMT from 22 unrelated families. The mean median motor nerve conduction velocity was 41 m/s (range, 30.8-59.4), and 18 cases (69%) were classified as intermediate CMT. The mean age of onset was 32.7 (range, 7-61) years. In addition to motor sensory neuropathy symptoms, dysautonomia and involuntary movements were common (44% and 29%). Furthermore, the correlation between the age of onset or clinical symptoms and the repeat size remains unclear.
CONCLUSIONS
These findings of this study help us understand the clinical heterogeneity of -related disease, such as non-length-dependent motor dominant phenotype and prominent autonomic involvement. This study also emphasise the importance of genetic screening, regardless of the age of onset and type of CMT, particularly in patients of Asian origin, presenting with intermediate conduction velocities and dysautonomia.
Topics: Humans; Charcot-Marie-Tooth Disease; Intranuclear Inclusion Bodies; Japan; Phenotype; Primary Dysautonomias
PubMed: 36948577
DOI: 10.1136/jnnp-2022-330769 -
Heart Rhythm Jan 2024There is an association between coronavirus disease 2019 (COVID-19) mRNA vaccination and the incidence or exacerbation of postural orthostatic tachycardia syndrome...
BACKGROUND
There is an association between coronavirus disease 2019 (COVID-19) mRNA vaccination and the incidence or exacerbation of postural orthostatic tachycardia syndrome (POTS).
OBJECTIVE
The purpose of this study was to characterize patients reporting new or exacerbated POTS after receiving the mRNA COVID-19 vaccine.
METHODS
We prospectively collected data from sequential patients in a POTS clinic between July 2021 and June 2022 reporting new or exacerbated POTS symptoms after COVID-19 vaccination. Heart rate variability (HRV) and skin sympathetic nerve activity (SKNA) were compared against those of 24 healthy controls.
RESULTS
Ten patients (6 women and 4 men; age 41.5 ± 7.9 years) met inclusion criteria. Four patients had standing norepinephrine levels > 600 pg/mL. All patients had conditions that could raise POTS risk, including previous COVID-19 infection (N = 4), hypermobile Ehlers-Danlos syndrome (N = 6), mast cell activation syndrome (N = 6), and autoimmune (N = 7), cardiac (N = 7), neurological (N = 6), or gastrointestinal conditions (N = 4). HRV analysis indicated a lower ambulatory root mean square of successive differences (46.19 ±24 ms; P = .042) vs control (72.49 ± 40.8 ms). SKNA showed a reduced mean amplitude (0.97 ± 0.052 μV; P = .011) vs control (1.2 ± 0.31 μV) and burst amplitude (1.67 ± 0.16 μV; P = .018) vs control (4. 3 ± 4.3 μV). After 417.2 ± 131.4 days of follow-up, all patients reported improvement with the usual POTS care, although 2 with COVID-19 reinfection and 1 with small fiber neuropathy did have relapses of POTS symptoms.
CONCLUSION
All patients with postvaccination POTS had pre-existing conditions. There was no evidence of myocardial injuries or echocardiographic abnormalities. The decreased HRV suggests a sympathetic dominant state. Although all patients improved with guideline-directed care, there is a risk of relapse.
Topics: Adult; Female; Humans; Male; Middle Aged; COVID-19; COVID-19 Vaccines; Postural Orthostatic Tachycardia Syndrome; Vaccination; mRNA Vaccines
PubMed: 38176772
DOI: 10.1016/j.hrthm.2023.09.012 -
Expert Opinion on Pharmacotherapy Feb 2024Postural tachycardia syndrome (POTS) is a disorder characterized by a constellation of symptoms including lightheadedness, fatigue, and palpitations when upright,... (Review)
Review
INTRODUCTION
Postural tachycardia syndrome (POTS) is a disorder characterized by a constellation of symptoms including lightheadedness, fatigue, and palpitations when upright, associated with an increase in the heart rate (HR) of > 30 beats per minute when changing from a lying down to standing position or head-up tilt position and not associated with orthostatic hypotension. The causes as well as the management of POTS are not quite fully understood.
AREAS COVERED
We performed a literature review on the diagnosis and management of POTS, and this article includes an overview of novel pharmacotherapeutic options for the treatment of (POTS), although an effective treatment has not been established.
EXPERT OPINION
POTS is a clinical syndrome characterized by a constellation of symptoms that are nonspecific. No single etiology or unified hypothesis could be identified. In fact, multiple pathophysiological mechanisms have been proposed, and none of the suggested medications have been approved by the FDA for this indication. Further understanding of the autonomic nervous system and its adjustment to standing position is needed to provide better management strategies.
Topics: Humans; Postural Orthostatic Tachycardia Syndrome; Hypotension, Orthostatic; Heart Rate; Fatigue; Dizziness
PubMed: 38465412
DOI: 10.1080/14656566.2024.2319224 -
PM & R : the Journal of Injury,... Dec 2023Autonomic dysreflexia (AD) is a frequent complication of spinal cord injury (SCI), though current clinical practice patterns for medication management of this condition...
BACKGROUND
Autonomic dysreflexia (AD) is a frequent complication of spinal cord injury (SCI), though current clinical practice patterns for medication management of this condition are unknown. Correspondingly, it is unclear if national differences in practice patterns exist.
OBJECTIVE
To determine trends in current pharmacologic management of AD throughout the Americas.
DESIGN
International survey of current physician practice patterns.
SETTING
Academic medical center.
PARTICIPANTS
Sixty physicians managing patients with SCI and prescribing medications to manage AD.
INTERVENTIONS
Not applicable.
MAIN OUTCOME MEASURES
Presence of a formal pharmacologic AD management protocol, first- and second-line medications, patient characteristics influencing pharmacologic management.
RESULTS
The majority of physicians (69%) had a formal AD management protocol for inpatient care, with nitroglycerin ointment (82%) being the most common first-line medication. Strong national differences existed regarding the use of nitroglycerin ointment, with 98% of U.S.-based physicians using this as first-line medication and 0% of physicians in Canada or Latin America using this due to recent lack of medication availability. Only 67% of physicians had a preferred second-line medication, with preferences split between hydralazine (48%) and nifedipine (28%). A systolic blood pressure threshold for pharmacologic management was used by 56% of physicians, wheres 26% considered neurological level of injury in decisions to use medications for AD. Heart rate was used by only 5% of physicians in their decision to manage AD with medications.
CONCLUSIONS
As of 2023, U.S.-based physicians caring for individuals with SCI largely have formal inpatient protocols in place for medication management of AD, with nearly all relying on nitroglycerin ointment as their first-line medication. In areas outside of the United States where nitroglycerin ointment is unavailable, pharmacologic practice patterns significantly differ.
Topics: Humans; Autonomic Dysreflexia; Nitroglycerin; Ointments; Spinal Cord Injuries; Blood Pressure
PubMed: 37545115
DOI: 10.1002/pmrj.13051 -
Database : the Journal of Biological... Aug 2023Polyglutamine (polyQ) diseases are neurodegenerative disorders caused by abnormally expanded Cytosine, Adenine, Guanine (CAG) triplet repeat sequences in the coding...
Polyglutamine (polyQ) diseases are neurodegenerative disorders caused by abnormally expanded Cytosine, Adenine, Guanine (CAG) triplet repeat sequences in the coding region of otherwise unrelated genes. Until now, nine different polyQ diseases have been described: Huntington's disease, dentatorubral-pallidoluysian atrophy, spinal and bulbar muscular atrophy and six types of spinocerebellar ataxias-1, 2, 3, 6, 7 and 17. The pathogenic expansion translates into an aberrant tract of glutamines in the encoded proteins, compromising several cellular functions and biological processes. There is currently no cure available for the progressive neurodegenerative disorders caused by the ensuing cytotoxic alterations. Although each disease is considered rare, polyQ diseases constitute the largest group of monogenic neurodegenerative disorders. Information about these disorders is scattered among several books, articles and general databases, hindering exploration by students and researchers, but also by patients and their families. Therefore, we aimed to develop a free online database to fill this gap, by centralizing relevant available information. The PolyQ Database is a platform that focuses on all nine polyQ diseases and offers information about topics that are pertinent for scientists, clinicians and the general public, including epidemiology, the characteristics of the causative genes and the codified proteins, the pathophysiology of the diseases and the main clinical manifestations. The database is available at https://polyq.pt/, and it is the first of its kind, focusing exclusively on this group of rare diseases. The database was conceived to be continuously updated and allow incorporation and dissemination of the latest information on polyQ diseases.
Topics: Humans; Peptides; Cytosine; Databases, Factual; Olivopontocerebellar Atrophies
PubMed: 37599593
DOI: 10.1093/database/baad060 -
Scientific Reports Jul 2023Occurrence of amyloid-β (Aβ) aggregation in brain begins before the clinical onset of Alzheimer's disease (AD), as preclinical AD. Studies have reported that sleep...
Occurrence of amyloid-β (Aβ) aggregation in brain begins before the clinical onset of Alzheimer's disease (AD), as preclinical AD. Studies have reported that sleep problems and autonomic dysfunction associate closely with AD. However, whether they, especially the interaction between sleep and autonomic function, play critical roles in preclinical AD are unclear. Therefore, we investigated how sleep patterns and autonomic regulation at different sleep-wake stages changed and whether they were related to cognitive performance in pathogenesis of AD mice. Polysomnographic recordings in freely-moving APP/PS1 and wild-type (WT) littermates were collected to study sleep patterns and autonomic function at 4 (early disease stage) and 8 months of age (advanced disease stage), cognitive tasks including novel object recognition and Morris water maze were performed, and Aβ levels in brain were measured. APP/PS1 mice at early stage of AD pathology with Aβ aggregation but without significant differences in cognitive performance had frequent sleep-wake transitions, lower sleep-related delta power percentage, lower overall autonomic activity, and lower parasympathetic activity mainly during sleep compared with WT mice. The same phenomenon was observed in advanced-stage APP/PS1 mice with significant cognitive deficits. In mice at both disease stages, sleep-related delta power percentage correlated positively with memory performance. At early stage, memory performance correlated positively with sympathetic activity during wakefulness; at advanced stage, memory performance correlated positively with parasympathetic activity during both wakefulness and sleep. In conclusion, sleep quality and distinction between wake- and sleep-related autonomic function may be biomarkers for early AD detection.
Topics: Mice; Animals; Mice, Transgenic; Alzheimer Disease; Primary Dysautonomias; Sleep; Cognition; Amyloid beta-Peptides
PubMed: 37433857
DOI: 10.1038/s41598-023-38214-6 -
Europace : European Pacing,... Mar 2024The term non-cardiac syncope includes all forms of syncope, in which primary intrinsic cardiac mechanism and non-syncopal transient loss of consciousness can be ruled...
The term non-cardiac syncope includes all forms of syncope, in which primary intrinsic cardiac mechanism and non-syncopal transient loss of consciousness can be ruled out. Reflex syncope and orthostatic hypotension are the most frequent aetiologies of non-cardiac syncope. As no specific therapy is effective for all types of non-cardiac syncope, identifying the underlying haemodynamic mechanism is the essential prerequisite for an effective personalized therapy and prevention of syncope recurrences. Indeed, choice of appropriate therapy and its efficacy are largely determined by the syncope mechanism rather than its aetiology and clinical presentation. The two main haemodynamic phenomena leading to non-cardiac syncope include either profound hypotension or extrinsic asystole/pronounced bradycardia, corresponding to two different haemodynamic syncope phenotypes, the hypotensive and bradycardic phenotypes. The choice of therapy-aimed at counteracting hypotension or bradycardia-depends on the given phenotype. Discontinuation of blood pressure-lowering drugs, elastic garments, and blood pressure-elevating agents such as fludrocortisone and midodrine are the most effective therapies in patients with hypotensive phenotype. Cardiac pacing, cardioneuroablation, and drugs preventing bradycardia such as theophylline are the most effective therapies in patients with bradycardic phenotype of extrinsic cause.
Topics: Humans; Bradycardia; Syncope; Syncope, Vasovagal; Hypotension; Hypotension, Orthostatic
PubMed: 38529800
DOI: 10.1093/europace/euae073 -
Unfallchirurgie (Heidelberg, Germany) Oct 2023Traumatic and non traumatic spinal cord injury are rare and an orphan disease in comparison to common diseases. Those affected represent a very special patient... (Review)
Review
Traumatic and non traumatic spinal cord injury are rare and an orphan disease in comparison to common diseases. Those affected represent a very special patient population in the treatment even at the site of the accident and in emergency medicine and require a high level of professional expertise. The rehabilitation with the complexity of a spinal cord injury can only succeed with a multiprofessional team that is less focused on the often similar diagnoses according to the International Classification of Diseases (ICD) but on functional disorders and associated activity impairments. Only then the best possible integration and participation/inclusion in sociocultural and professional life can be achieved. In addition to the importance of classical physiotherapy and occupational therapy, this article highlights important but often missing team players, such as neurourology and electrical stimulation. In addition, the problems of frequent and some less recognized complications, such as autonomic dysfunction and the benefits of airway management are highlighted. For a comprehensive overview of rehabilitation in spinal cord injury, reference textbooks and guidelines are recommended that are cited in the text.
Topics: Humans; Spinal Cord Injuries; Occupational Therapy; Activities of Daily Living; Autonomic Nervous System Diseases; Emergency Medicine
PubMed: 37608182
DOI: 10.1007/s00113-023-01360-7