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Journal of Internal Medicine Nov 2023A significant proportion of COVID-19 patients experience debilitating symptoms for months after the acute infection. According to recent estimates, approximately 1 out... (Review)
Review
A significant proportion of COVID-19 patients experience debilitating symptoms for months after the acute infection. According to recent estimates, approximately 1 out of 10 COVID-19 convalescents reports persistent health issues more than 3 months after initial recovery. This 'post-COVID-19 condition' may include a large variety of symptoms from almost all domains and organs, and for some patients it may mean prolonged sick-leave, homestay and strongly limited activities of daily life. In this narrative review, we focus on the symptoms and signs of post-COVID-19 condition in adults - particularly those associated with cardiovascular and respiratory systems, such as postural orthostatic tachycardia syndrome or airway disorders - and explore the evidence for chronic autonomic dysfunction as a potential underlying mechanism. The most plausible hypotheses regarding cellular and molecular mechanisms behind the wide spectrum of observed symptoms - such as lingering viruses, persistent inflammation, impairment in oxygen sensing systems and circulating antibodies directed to blood pressure regulatory components - are discussed. In addition, an overview of currently available pharmacological and non-pharmacological treatment options is presented.
Topics: Adult; Humans; COVID-19; Primary Dysautonomias; Antibodies; Blood Pressure; Postural Orthostatic Tachycardia Syndrome
PubMed: 37183186
DOI: 10.1111/joim.13652 -
Handbook of Clinical Neurology 2024A number of the well-recognized autoimmune and paraneoplastic neurologic syndromes commonly involve the autonomic nervous system. In some cases, the autonomic nerves or... (Review)
Review
A number of the well-recognized autoimmune and paraneoplastic neurologic syndromes commonly involve the autonomic nervous system. In some cases, the autonomic nerves or ganglia are primary targets of neurologic autoimmunity, as in immune-mediated autonomic ganglionopathies. In other disorders such as encephalitis, autonomic centers in the brain may be affected. The presence of autonomic dysfunction (especially gastrointestinal dysmotility) is sometimes overlooked even though this may contribute significantly to the symptom burden in these paraneoplastic disorders. Additionally, recognition of autonomic features as part of the clinical syndrome can help point the diagnostic evaluation toward autoimmune and paraneoplastic etiologies. As with other paraneoplastic disorders, the clinical syndrome and the presence and type of neurologic autoantibodies help to secure the diagnosis and direct the most appropriate investigation for malignancy. Optimal management for these conditions typically includes aggressive treatment of the neoplasm, immunomodulatory therapy, and symptomatic treatments for orthostatic hypotension and gastrointestinal dysmotility.
Topics: Humans; Autoantibodies; Nervous System Diseases; Autonomic Nervous System Diseases; Paraneoplastic Syndromes, Nervous System; Neoplasms; Autonomic Nervous System
PubMed: 38494282
DOI: 10.1016/B978-0-12-823912-4.00005-0 -
Translational Neurodegeneration Jul 2023Multiple system atrophy (MSA) is a fatal progressive neurodegenerative disease. Biomarkers are urgently required for MSA to improve the diagnostic and prognostic... (Review)
Review
Multiple system atrophy (MSA) is a fatal progressive neurodegenerative disease. Biomarkers are urgently required for MSA to improve the diagnostic and prognostic accuracy in clinic and facilitate the development and monitoring of disease-modifying therapies. In recent years, significant research efforts have been made in exploring multidimensional biomarkers for MSA. However, currently few biomarkers are available in clinic. In this review, we systematically summarize the latest advances in multidimensional biomarkers for MSA, including biomarkers in fluids, tissues and gut microbiota as well as imaging biomarkers. Future directions for exploration of novel biomarkers and promotion of implementation in clinic are also discussed.
Topics: Humans; Multiple System Atrophy; Biomarkers
PubMed: 37501056
DOI: 10.1186/s40035-023-00370-0 -
Scientific Reports Sep 2023Autonomic symptoms (AS) are critical in Parkinson's disease (PD). We aimed to determine the relative significance of clinical factors allowing predictions about...
Autonomic symptoms (AS) are critical in Parkinson's disease (PD). We aimed to determine the relative significance of clinical factors allowing predictions about incidence of AS, and examine AS profiles among PD patients by motor subtype and its relation to AS. The cross-sectional data of a multicentre sample, including 714 PD patients and 194 healthy controls from Parkinson's Progression Marker Initiative study and Pingchan granule study were analyzed, stratified by PD subtypes [postural instability and gait disturbances (PIGD), tremor dominant (TD), and indeterminate] and domain autonomic dysfunction. Compared with healthy controls, PD patients scored higher in the total Scales for Outcomes in Parkinson's Disease-Autonomic dysfunction score and in several domain scores in particular, and there was a significant overlap in domain AS. Risk factors of individual domain autonomic dysfunction were heterogeneous. PIGD and indeterminate were the predominant subtypes in pupillomotor and thermoregulatory symptoms. TD and indeterminate were more likely to suffer from cardiovascular problem. The odd in sexual dysfunction was significant for PIGD. Gastrointestinal and urinary symptoms seemed not to be associated with a specific subtype. Our study demonstrated that AS were highly heterogeneous and 3 subtypes differed in autonomic performance, providing clues to understand mechanisms underlying AS in PD.
Topics: Humans; Parkinson Disease; Cross-Sectional Studies; Tremor; Primary Dysautonomias; Autonomic Nervous System
PubMed: 37666916
DOI: 10.1038/s41598-023-41662-9 -
Brain and Nerve = Shinkei Kenkyu No... Jul 2023Autoimmune autonomic ganglionopathy (AAG) is a rare acquired immune-mediated neurological disease that causes various autonomic symptoms. AAG is induced by... (Review)
Review
Autoimmune autonomic ganglionopathy (AAG) is a rare acquired immune-mediated neurological disease that causes various autonomic symptoms. AAG is induced by autoantibodies for the α and β subunits of the ganglionic acetylcholine receptor (gAChR). gAChR antibodies mediate synaptic transmission in all autonomic ganglia, resulting in dysautonomia. Recent clinical and basic research topics in AAG include the following: 1)analysis of clinical features; 2)novel methods for gAChR antibody detection; 3)efficacy of combined immunotherapy; 4)novel experimental AAG; 5)COVID-19 and mRNA COVID-19 vaccination and its association with autonomic dysfunction; and 6)dysautonomia as an immune-related adverse event of immune checkpoint inhibitors in cancer therapy. The author and his collaborators have previously established "10 assignments" to understand the basic research and clinical issues of AAG. In this review, the author describes the current status of research on each of the "10 assignments," incorporating research trends over the last five years.
Topics: Humans; COVID-19 Vaccines; COVID-19; Peripheral Nervous System Diseases; Autoimmune Diseases; Primary Dysautonomias; Autoantibodies
PubMed: 37431072
DOI: 10.11477/mf.1416202427 -
Journal of Neural Transmission (Vienna,... Oct 2023Non-motor symptoms (NMS) and Non-motor fluctuations (NMF) in Parkinson's Disease (PD) are common, involving several domains and affecting quality of life. Aim of the...
Non-motor symptoms (NMS) and Non-motor fluctuations (NMF) in Parkinson's Disease (PD) are common, involving several domains and affecting quality of life. Aim of the study is to estimate the burden of NMF in PD patients and to evaluate the possible gender effect. PD patients fulfilling the MDS-PD diagnostic criteria attending the "Parkinson's Disease and Movement Disorders Centre" of the University of Catania were evaluated using the Non-Motor Fluctuations Assessment (NoMoFA) Questionnaire. NoMoFA items were also grouped into the following domains: cognitive, mood, sleep/fatigue, dysautonomia, hallucination/perception and miscellaneous domains were identified. One-hundred and twenty-one patients with PD (67 men, 55.4%; mean age 70.2 ± 8.9 years, disease duration 8.3 ± 4.6 years) were evaluated. All PD patients reported at least one NMS, whereas 87 (71.9%) also reported NMF. "Feel sluggish or had low energy levels" (47.2%) along with "Feel excessively sleepy during the day" (40.0%) were the most common NMF reported in the whole sample. The majority of PD patients reported the presence of NMF during the OFF state (79, 65.3%). At multivariate analysis, NMF were positively associated with the female gender (adjusted OR 3.13; 95%CI 1.21-8.11 p-value 0.01). Women with PD had higher NMF scores especially in depression/anxiety, sleep/fatigue and dysautonomia domains. Our study reported the presence of a gender-related pattern in the frequency of NMS and NMF in PD patients, with female gender associated with a higher risk of developing NMF, highlighting the need for personalized treatment strategies when addressing NMF.
Topics: Male; Humans; Female; Middle Aged; Aged; Parkinson Disease; Quality of Life; Sex Factors; Primary Dysautonomias; Fatigue
PubMed: 37526768
DOI: 10.1007/s00702-023-02679-6 -
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 -
European Heart Journal Jul 2023
Topics: Humans; Syncope, Vasovagal; Nitroglycerin; Isoproterenol; Tilt-Table Test
PubMed: 37317895
DOI: 10.1093/eurheartj/ehad359 -
International Journal of Molecular... Feb 2024Autoimmune autonomic ganglionopathy (AAG) is a disease of autonomic failure caused by ganglionic acetylcholine receptor (gAChR) autoantibodies. Although the detection of... (Review)
Review
Autoimmune autonomic ganglionopathy (AAG) is a disease of autonomic failure caused by ganglionic acetylcholine receptor (gAChR) autoantibodies. Although the detection of autoantibodies is important for distinguishing the disease from other neuropathies that present with autonomic dysfunction, other factors are important for accurate diagnosis. Here, we provide a comprehensive review of the clinical features of AAG, highlighting differences in clinical course, clinical presentation, and laboratory findings from other neuropathies presenting with autonomic symptoms. The first step in diagnosing AAG is careful history taking, which should reveal whether the mode of onset is acute or chronic, followed by an examination of the time course of disease progression, including the presentation of autonomic and extra-autonomic symptoms. AAG is a neuropathy that should be differentiated from other neuropathies when the patient presents with autonomic dysfunction. Immune-mediated neuropathies, such as acute autonomic sensory neuropathy, are sometimes difficult to differentiate, and therefore, differences in clinical and laboratory findings should be well understood. Other non-neuropathic conditions, such as postural orthostatic tachycardia syndrome, chronic fatigue syndrome, and long COVID, also present with symptoms similar to those of AAG. Although often challenging, efforts should be made to differentiate among the disease candidates.
Topics: Humans; Ganglia, Autonomic; Post-Acute COVID-19 Syndrome; Autoimmune Diseases of the Nervous System; Autonomic Nervous System; Autonomic Nervous System Diseases; Autoimmune Diseases; Peripheral Nervous System Diseases; Autoantibodies
PubMed: 38396973
DOI: 10.3390/ijms25042296 -
Journal of Neurology Jun 2024Dysautonomia has been associated with paraneoplastic neurological syndrome (PNS)-related mortality in anti-Hu PNS, but its frequency and spectrum remain ill-defined. We...
BACKGROUND AND OBJECTIVES
Dysautonomia has been associated with paraneoplastic neurological syndrome (PNS)-related mortality in anti-Hu PNS, but its frequency and spectrum remain ill-defined. We describe anti-Hu patients with dysautonomia, estimate its frequency, and compare them to patients without dysautonomia.
METHODS
Patients with anti-Hu antibodies diagnosed in the study centre (1990-2022) were retrospectively reviewed; those with autonomic signs and symptoms were identified.
RESULTS
Among 477 anti-Hu patients, 126 (26%) had dysautonomia (the only PNS manifestation in 7/126, 6%); gastrointestinal (82/126, 65%), cardiovascular (64/126, 51%), urogenital (24/126, 19%), pupillomotor/secretomotor (each, 11/126, 9%), and central hypoventilation (10/126, 8%). Patients with isolated CNS involvement less frequently had gastrointestinal dysautonomia than those with peripheral (alone or combined with CNS) involvement (7/23, 30% vs. 31/44, 70% vs. 37/52, 71%; P = 0.002); while more frequently central hypoventilation (7/23, 30% vs. 1/44, 2.3% vs. 2/52, 4%; P < 0.001) and/or cardiovascular alterations (18/23, 78% vs. 20/44, 45% vs. 26/52, 50%; P = 0.055). Median [95% CI] overall survival was not significantly different between patients with (37 [17; 91] months) or without dysautonomia (28 [22; 39] months; P = 0.78). Cardiovascular dysautonomia (HR: 1.57, 95% CI [1.05; 2.36]; P = 0.030) and central hypoventilation (HR: 3.51, 95% CI [1.54; 8.01]; P = 0.003) were associated with a higher risk of death, and secretomotor dysautonomia a lower risk (HR: 0.28, 95% CI [0.09; 0.89]; P = 0.032). Patients with cardiovascular dysautonomia dying ≤ 1 year from clinical onset had severe CNS (21/27, 78%), frequently brainstem (13/27, 48%), involvement.
DISCUSSION
Anti-Hu PNS dysautonomia is rarely isolated, frequently gastrointestinal, cardiovascular and urogenital. CNS dysfunction, particularly brainstem, associates with lethal cardiovascular alterations and central hypoventilation, while peripheral involvement preferentially associates with gastrointestinal or secretomotor dysautonomia, being the latest more indolent.
Topics: Humans; Male; Female; Middle Aged; Retrospective Studies; Paraneoplastic Syndromes, Nervous System; Primary Dysautonomias; Aged; Adult; ELAV Proteins; Autoantibodies; Young Adult; Aged, 80 and over
PubMed: 38494470
DOI: 10.1007/s00415-024-12278-4