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Current Pain and Headache Reports Sep 2023This review presents the most current information about the epidemiology of complex regional pain syndrome (CRPS), classification and diagnostic criteria, childhood... (Review)
Review
PURPOSE OF REVIEW
This review presents the most current information about the epidemiology of complex regional pain syndrome (CRPS), classification and diagnostic criteria, childhood CRPS, subtypes, pathophysiology, conventional and less conventional treatments, and preventive strategies.
RECENT FINDINGS
CRPS is a painful disorder with multifactorial pathophysiology. The data describe sensitization of the central and peripheral nervous systems, inflammation, possible genetic factors, sympatho-afferent coupling, autoimmunity, and mental health factors as contributors to the syndrome. In addition to conventional subtypes (type I and type II), cluster analyses have uncovered other proposed subtypes. Prevalence of CRPS is approximately 1.2%, female gender is consistently associated with a higher risk of development, and substantial physical, emotional, and financial costs can result from the syndrome. Children with CRPS seem to benefit from multifaceted physical therapy leading to a high percentage of symptom-free patients. The best available evidence along with standard clinical practice supports pharmacological agents, physical and occupational therapy, sympathetic blocks for engaging physical restoration, steroids for acute CRPS, neuromodulation, ketamine, and intrathecal baclofen as therapeutic approaches. There are many emerging treatments that can be considered as a part of individualized, patient-centered care. Vitamin C may be preventive. CRPS can lead to progressively painful sensory and vascular changes, edema, limb weakness, and trophic disturbances, all of which substantially erode healthy living. Despite some progress in research, more comprehensive basic science investigation is needed to clarify the molecular mechanisms of the disease so that targeted treatments can be developed for better outcomes. Incorporating a variety of standard therapies with different modes of action may offer the most effective analgesia. Introducing less conventional approaches may also be helpful when traditional treatments fail to provide sufficient improvement.
Topics: Child; Humans; Female; Male; Complex Regional Pain Syndromes; Pain Management; Ketamine; Peripheral Nervous System; Pain Measurement
PubMed: 37421541
DOI: 10.1007/s11916-023-01130-5 -
Acta Neuropathologica Sep 2023Dysautonomia has substantially impacted acute COVID-19 severity as well as symptom burden after recovery from COVID-19 (long COVID), yet the underlying causes remain...
Dysautonomia has substantially impacted acute COVID-19 severity as well as symptom burden after recovery from COVID-19 (long COVID), yet the underlying causes remain unknown. Here, we hypothesized that vagus nerves are affected in COVID-19 which might contribute to autonomic dysfunction. We performed a histopathological characterization of postmortem vagus nerves from COVID-19 patients and controls, and detected SARS-CoV-2 RNA together with inflammatory cell infiltration composed primarily of monocytes. Furthermore, we performed RNA sequencing which revealed a strong inflammatory response of neurons, endothelial cells, and Schwann cells which correlated with SARS-CoV-2 RNA load. Lastly, we screened a clinical cohort of 323 patients to detect a clinical phenotype of vagus nerve affection and found a decreased respiratory rate in non-survivors of critical COVID-19. Our data suggest that SARS-CoV-2 induces vagus nerve inflammation followed by autonomic dysfunction which contributes to critical disease courses and might contribute to dysautonomia observed in long COVID.
Topics: Humans; COVID-19; SARS-CoV-2; Post-Acute COVID-19 Syndrome; RNA, Viral; Endothelial Cells; Inflammation; Primary Dysautonomias; Vagus Nerve
PubMed: 37452829
DOI: 10.1007/s00401-023-02612-x -
JAMA Oct 2023There are ongoing concerns about the benefits of intensive vs standard blood pressure (BP) treatment among adults with orthostatic hypotension or standing hypotension. (Comparative Study)
Comparative Study Meta-Analysis
IMPORTANCE
There are ongoing concerns about the benefits of intensive vs standard blood pressure (BP) treatment among adults with orthostatic hypotension or standing hypotension.
OBJECTIVE
To determine the effect of a lower BP treatment goal or active therapy vs a standard BP treatment goal or placebo on cardiovascular disease (CVD) or all-cause mortality in strata of baseline orthostatic hypotension or baseline standing hypotension.
DATA SOURCES
Individual participant data meta-analysis based on a systematic review of MEDLINE, EMBASE, and CENTRAL databases through May 13, 2022.
STUDY SELECTION
Randomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) with orthostatic hypotension assessments.
DATA EXTRACTION AND SYNTHESIS
Individual participant data meta-analysis extracted following PRISMA guidelines. Effects were determined using Cox proportional hazard models using a single-stage approach.
MAIN OUTCOMES AND MEASURES
Main outcomes were CVD or all-cause mortality. Orthostatic hypotension was defined as a decrease in systolic BP of at least 20 mm Hg and/or diastolic BP of at least 10 mm Hg after changing position from sitting to standing. Standing hypotension was defined as a standing systolic BP of 110 mm Hg or less or standing diastolic BP of 60 mm Hg or less.
RESULTS
The 9 trials included 29 235 participants followed up for a median of 4 years (mean age, 69.0 [SD, 10.9] years; 48% women). There were 9% with orthostatic hypotension and 5% with standing hypotension at baseline. More intensive BP treatment or active therapy lowered risk of CVD or all-cause mortality among those without baseline orthostatic hypotension (hazard ratio [HR], 0.81; 95% CI, 0.76-0.86) similarly to those with baseline orthostatic hypotension (HR, 0.83; 95% CI, 0.70-1.00; P = .68 for interaction of treatment with baseline orthostatic hypotension). More intensive BP treatment or active therapy lowered risk of CVD or all-cause mortality among those without baseline standing hypotension (HR, 0.80; 95% CI, 0.75-0.85), and nonsignificantly among those with baseline standing hypotension (HR, 0.94; 95% CI, 0.75-1.18). Effects did not differ by baseline standing hypotension (P = .16 for interaction of treatment with baseline standing hypotension).
CONCLUSIONS AND RELEVANCE
In this population of hypertension trial participants, intensive therapy reduced risk of CVD or all-cause mortality regardless of orthostatic hypotension without evidence for different effects among those with standing hypotension.
Topics: Aged; Female; Humans; Male; Blood Pressure; Blood Pressure Determination; Cardiovascular Diseases; Hypertension; Hypotension, Orthostatic; Middle Aged
PubMed: 37847274
DOI: 10.1001/jama.2023.18497 -
JAMA Apr 2024Finding a reliable diagnostic biomarker for the disorders collectively known as synucleinopathies (Parkinson disease [PD], dementia with Lewy bodies [DLB], multiple...
IMPORTANCE
Finding a reliable diagnostic biomarker for the disorders collectively known as synucleinopathies (Parkinson disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA], and pure autonomic failure [PAF]) is an urgent unmet need. Immunohistochemical detection of cutaneous phosphorylated α-synuclein may be a sensitive and specific clinical test for the diagnosis of synucleinopathies.
OBJECTIVE
To evaluate the positivity rate of cutaneous α-synuclein deposition in patients with PD, DLB, MSA, and PAF.
DESIGN, SETTING, AND PARTICIPANTS
This blinded, 30-site, cross-sectional study of academic and community-based neurology practices conducted from February 2021 through March 2023 included patients aged 40 to 99 years with a clinical diagnosis of PD, DLB, MSA, or PAF based on clinical consensus criteria and confirmed by an expert review panel and control participants aged 40 to 99 years with no history of examination findings or symptoms suggestive of a synucleinopathy or neurodegenerative disease. All participants completed detailed neurologic examinations and disease-specific questionnaires and underwent skin biopsy for detection of phosphorylated α-synuclein. An expert review panel blinded to pathologic data determined the final participant diagnosis.
EXPOSURE
Skin biopsy for detection of phosphorylated α-synuclein.
MAIN OUTCOMES
Rates of detection of cutaneous α-synuclein in patients with PD, MSA, DLB, and PAF and controls without synucleinopathy.
RESULTS
Of 428 enrolled participants, 343 were included in the primary analysis (mean [SD] age, 69.5 [9.1] years; 175 [51.0%] male); 223 met the consensus criteria for a synucleinopathy and 120 met criteria as controls after expert panel review. The proportions of individuals with cutaneous phosphorylated α-synuclein detected by skin biopsy were 92.7% (89 of 96) with PD, 98.2% (54 of 55) with MSA, 96.0% (48 of 50) with DLB, and 100% (22 of 22) with PAF; 3.3% (4 of 120) of controls had cutaneous phosphorylated α-synuclein detected.
CONCLUSIONS AND RELEVANCE
In this cross-sectional study, a high proportion of individuals meeting clinical consensus criteria for PD, DLB, MSA, and PAF had phosphorylated α-synuclein detected by skin biopsy. Further research is needed in unselected clinical populations to externally validate the findings and fully characterize the potential role of skin biopsy detection of phosphorylated α-synuclein in clinical care.
Topics: Aged; Female; Humans; Male; alpha-Synuclein; Biopsy; Cross-Sectional Studies; Lewy Body Disease; Multiple System Atrophy; Parkinson Disease; Synucleinopathies; Phosphorylation; Skin; Pure Autonomic Failure; Reproducibility of Results; Adult; Middle Aged; Aged, 80 and over; Single-Blind Method; Prospective Studies
PubMed: 38506839
DOI: 10.1001/jama.2024.0792 -
Nature Reviews. Cardiology Jun 2024Cardiovascular autonomic dysfunction (CVAD) is a malfunction of the cardiovascular system caused by deranged autonomic control of circulatory homeostasis. CVAD is an... (Review)
Review
Cardiovascular autonomic dysfunction (CVAD) is a malfunction of the cardiovascular system caused by deranged autonomic control of circulatory homeostasis. CVAD is an important component of post-COVID-19 syndrome, also termed long COVID, and might affect one-third of highly symptomatic patients with COVID-19. The effects of CVAD can be seen at both the whole-body level, with impairment of heart rate and blood pressure control, and in specific body regions, typically manifesting as microvascular dysfunction. Many severely affected patients with long COVID meet the diagnostic criteria for two common presentations of CVAD: postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia. CVAD can also manifest as disorders associated with hypotension, such as orthostatic or postprandial hypotension, and recurrent reflex syncope. Advances in research, accelerated by the COVID-19 pandemic, have identified new potential pathophysiological mechanisms, diagnostic methods and therapeutic targets in CVAD. For clinicians who daily see patients with CVAD, knowledge of its symptomatology, detection and appropriate management is more important than ever. In this Review, we define CVAD and its major forms that are encountered in post-COVID-19 syndrome, describe possible CVAD aetiologies, and discuss how CVAD, as a component of post-COVID-19 syndrome, can be diagnosed and managed. Moreover, we outline directions for future research to discover more efficient ways to cope with this prevalent and long-lasting condition.
Topics: Humans; COVID-19; Autonomic Nervous System Diseases; Cardiovascular Diseases; Post-Acute COVID-19 Syndrome; SARS-CoV-2
PubMed: 38163814
DOI: 10.1038/s41569-023-00962-3 -
Nederlands Tijdschrift Voor Geneeskunde Nov 2023In this Clinical Lesson, using two illustrating cases, we explain how to do the initial assessment and treatment of an intoxicated patient. An approach aimed at...
In this Clinical Lesson, using two illustrating cases, we explain how to do the initial assessment and treatment of an intoxicated patient. An approach aimed at toxidromes can serve as a stepping stone. A toxidrome is a combination of symptoms and clinical features that can occur with the use of certain drugs and substances. The most commonly encountered toxidromes are sympathomimetic, serotonergic, anticholinergic, cholinergic, sedative-hypnotic and opioid. All patients need to be approach according to the ABCDE method. The treatment is based on pharmacokinetics by means of the ADME principle (absorption, distribution, metabolism and excretion) and based on pharmacodynamics, aimed at the toxidrome.
Topics: Humans; Analgesics, Opioid; Autonomic Nervous System Diseases; Cholinergic Antagonists; Hypnotics and Sedatives
PubMed: 38175605
DOI: No ID Found -
Practical Neurology Nov 2023Tilt testing can help to diagnose unexplained syncope, by precipitating an episode during cardiac monitoring. The Italian protocol, now most widely used, involves giving...
Tilt testing can help to diagnose unexplained syncope, by precipitating an episode during cardiac monitoring. The Italian protocol, now most widely used, involves giving sublingual nitroglycerine after 15 min, while monitoring beat-to-beat blood pressure (BP) and recording on video. Tilt testing is time-consuming but it is clinically useful and can guide therapy. Complications are rare. Syncope types include vasovagal syncope where BP falls after >3 min of tilt-up and later the heart rate falls; classic orthostatic hypotension where there is an immediate, progressive BP fall with minimal heart rate change; delayed orthostatic hypotension with a late BP fall after a stable phase but little or no heart rate rise; psychogenic pseudosyncope with apparent loss of consciousness, but no BP fall and a moderate heart rate rise; and postural orthostatic tachycardia syndrome where there is a significant heart rate rise but no BP fall.
Topics: Humans; Hypotension, Orthostatic; Tilt-Table Test; Syncope; Syncope, Vasovagal; Heart Rate; Blood Pressure
PubMed: 37726165
DOI: 10.1136/pn-2023-003749 -
Complex regional pain syndrome: advances in epidemiology, pathophysiology, diagnosis, and treatment.The Lancet. Neurology May 2024Complex regional pain syndrome (CRPS) is a rare pain disorder that usually occurs in a limb after trauma. The features of this disorder include severe pain and sensory,... (Review)
Review
Complex regional pain syndrome (CRPS) is a rare pain disorder that usually occurs in a limb after trauma. The features of this disorder include severe pain and sensory, autonomic, motor, and trophic abnormalities. Research from the past decade has offered new insights into CRPS epidemiology, pathophysiology, diagnosis, and treatment. Early identification of individuals at high risk of CRPS is improving, with several risk factors established and some others identified in prospective studies during the past 5 years. Better understanding of the pathophysiological mechanisms of CRPS has led to its classification as a chronic primary pain disorder, and subtypes of CRPS have been updated. Procedures for diagnosis have also been clarified. Although effective treatment of CRPS remains a challenge, evidence-based integrated management approaches provide new opportunities to improve patient care. Further advances in diagnosis and treatment of CRPS will require coordinated, international multicentre initiatives.
Topics: Humans; Prospective Studies; Complex Regional Pain Syndromes; Chronic Pain; Treatment Outcome; Risk Factors
PubMed: 38631768
DOI: 10.1016/S1474-4422(24)00076-0 -
Current Pain and Headache Reports Nov 2023Migraine is prevalent in patients with postural orthostatic tachycardia syndrome (POTS). The purpose of this review is to summarize and interpret studies that examine... (Review)
Review
PURPOSE OF REVIEW
Migraine is prevalent in patients with postural orthostatic tachycardia syndrome (POTS). The purpose of this review is to summarize and interpret studies that examine stress response systems in patients with migraine, focusing on their relevance to the pathologies associated with POTS. Important structural and functional components of the stress response network are also reviewed.
RECENT FINDINGS
In patients with migraine, studies examining the autonomic nervous system have demonstrated interictal sympathetic hypofunction and ictal sympathetic hyperfunction, while those focusing on the hypothalamic-pituitary-adrenal axis have demonstrated elevated responsivity. There is evidence that activation of these stress response systems during a migraine episode may exacerbate vascular dysfunction and play a role in the development of central sensitization. Activation of the stress response systems during an episode of migraine has the potential to exacerbate the pathology of POTS. Treatment approaches for the patient with comorbid episodic migraine and POTS should consider the etiology of POTS.
Topics: Humans; Postural Orthostatic Tachycardia Syndrome; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Autonomic Nervous System; Migraine Disorders
PubMed: 37804458
DOI: 10.1007/s11916-023-01173-8 -
Current Neurology and Neuroscience... Dec 2023Long-COVID is a novel condition emerging from the COVID-19 pandemic. Long-COVID is characterized by symptoms commonly seen in autonomic disorders including fatigue,... (Review)
Review
PURPOSE OF REVIEW
Long-COVID is a novel condition emerging from the COVID-19 pandemic. Long-COVID is characterized by symptoms commonly seen in autonomic disorders including fatigue, brain fog, light-headedness, and palpitations. This article will critically evaluate recent findings and studies on Long-COVID and its physiological autonomic manifestations.
RECENT FINDINGS
Studies have reported on the prevalence of different symptoms and autonomic disorders in Long-COVID cohorts. Autonomic nervous system function, including both the parasympathetic and sympathetic limbs, has been studied using different testing techniques in Long-COVID patients. While numerous mechanisms may contribute to Long-COVID autonomic pathophysiology, it is currently unclear which ones lead to a Long-COVID presentation. To date, studies have not tested treatment options for autonomic disorders in Long-COVID patients. Long-COVID is associated with autonomic abnormalities. There is a high prevalence of clinical autonomic disorders among Long-COVID patients, with limited knowledge of the underlying mechanisms and the effectiveness of treatment options.
Topics: Humans; Post-Acute COVID-19 Syndrome; Pandemics; COVID-19; Autonomic Nervous System Diseases; Autonomic Nervous System; Postural Orthostatic Tachycardia Syndrome
PubMed: 37947962
DOI: 10.1007/s11910-023-01320-z