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JCEM Case Reports Jun 2024Rapid onset obesity with hypoventilation, hypothalamic, and autonomic dysregulation (ROHHAD) syndrome in childhood is characterized by abrupt onset weight gain and...
Rapid onset obesity with hypoventilation, hypothalamic, and autonomic dysregulation (ROHHAD) syndrome in childhood is characterized by abrupt onset weight gain and dysautonomia with variable neuroendocrine involvement. In the absence of definitive disease-modifying therapies, the primary management strategy remains symptom control. This case report describes the first successful correction of obesity, dysautonomia, and metabolic derangement in a patient with ROHHAD following Roux-en-Y gastric bypass. Anthropometrics, metabolic profiling, and stool microbiome composition were assessed in a longitudinal fashion. In the 48-month period following surgery, the patient body mass index (BMI) reduced by 9.5 kg/m and metabolic status improved, evidenced in weaning of insulin, and improved glycated hemoglobin, lipid profile, and hepatic enzymes. Chronic diarrhea resolved after surgery and prior to significant weight loss. Evaluation of stool bacterial composition and biomass demonstrated shifts in absolute abundance and taxonomic composition in longitudinal samples following surgery. This case demonstrates the potential efficacy of bariatric surgery in correcting the metabolic disruption of ROHHAD syndrome, producing long-term changes in gut microbiome composition and biomass.
PubMed: 38832003
DOI: 10.1210/jcemcr/luae091 -
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 Neurology 2024Prior investigations into post-COVID dysautonomia often lacked control groups or compared affected individuals solely to healthy volunteers. In addition, no data on the...
INTRODUCTION
Prior investigations into post-COVID dysautonomia often lacked control groups or compared affected individuals solely to healthy volunteers. In addition, no data on the follow-up of patients with SARS-CoV-2-related autonomic imbalance are available.
METHODS
In this study, we conducted a comprehensive clinical and functional follow-up on healthcare workers (HCWs) with former mild COVID-19 (group 1, n = 67), to delineate the trajectory of post-acute autonomic imbalance, we previously detected in a case-control study. Additionally, we assessed HCWs for which a test before SARS-CoV-2 infection was available (group 2, n = 29), who later contracted SARS-CoV-2, aiming to validate findings from our prior case-control investigation. We evaluated autonomic nervous system heart modulation by means of time and frequency domain heart rate variability analysis (HRV) in HCWs during health surveillance visits. Short-term electrocardiogram (ECG) recordings, were obtained at about 6, 13 months and both at 6 and 13 months from the negative SARS-CoV-2 naso-pharyngeal swab (NPS) for group 1 and at about 1-month from the negative NPS for group 2. HCWs who used drugs, had comorbidities that affected HRV, or were hospitalized with severe COVID-19 were excluded.
RESULTS
Group 1 was split into three subgroups clinically and functionally followed at, about 6 months (subgroup-A, = 17), 13 months (subgroup-B, = 37) and both at 6 and 13 months (subgroup-C, = 13) from the negative SARS-CoV-2 NPS. In subgroup-A, at 6-month follow-up compared with baseline, the spectral components in the frequency domain HRV parameters, showed an increase in normalized high frequency power (nHF) ( = 2.99, = 0.009), a decrease in the normalized low frequency power (nLF) ( = 2.98, = 0.009) and in the LF/HF ratio ( = 3.13, p = 0.006). In subgroup B, the comparison of the spectral components in the frequency domain HRV parameters, at 13-month follow-up compared with baseline, showed an increase in nHF ( = 2.54, = 0.02); a decrease in nLF ( = 2.62, = 0.01) and in the LF/HF ratio ( = 4.00, = 0.0003). In subgroup-C, at both 6 and 13-month follow-ups, the spectral components in the frequency domain HRV parameters were higher than baseline in nHF ( = 2.64, p = 0.02 and ( = 2.13, = 0.05, respectively); lower in nLF ( = 2.64, p = 0.02 and ( = 2.13, p = 0.05, respectively), and in LF/HF ( = 1.92, p = 0.08 and ( = 2.43, = 0.03, respectively). A significant proportion of HCWs reported persistent COVID-19 symptoms at both the 6 and 13-month follow-ups, seemingly unrelated to cardiac autonomic balance. In group 2 HCWs, at 1-month follow-up compared with baseline, the spectral components in the frequency domain HRV parameters, showed a decrease in nHF ( = 2.19, = 0.04); an increase in nLF ( = 2.15, = 0.04) and in LF/HF ( = 3.49, = 0.002).
CONCLUSION
These results are consistent with epidemiological data suggesting a higher risk of acute cardiovascular complications during the first 30 days after COVID-19. The SARS-CoV-2 associated autonomic imbalance in the post-acute phase after recovery of mild COVID-19 resolved 6 months after the first negative SARS-CoV-2 NPS. However, a significant proportion of HCWs reported long-term COVID-19 symptoms, which dot not seems to be related to cardiac autonomic balance. Future research should certainly further test whether autonomic imbalance has a role in the mechanisms of long-COVID syndrome.
PubMed: 38827576
DOI: 10.3389/fneur.2024.1403551 -
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 -
Neurology India Mar 2024
Topics: Humans; Autonomic Nervous System Diseases; Flushing; Hypohidrosis
PubMed: 38817189
DOI: 10.4103/neurol-india.Neurol-India-D-24-00157 -
Neurology India Mar 2024Morvan's syndrome is a rare, complex autoimmune syndrome comprising peripheral nerve hyperexcitability, dysautonomia, insomnia, and encephalopathy. In this case report,...
Morvan's syndrome is a rare, complex autoimmune syndrome comprising peripheral nerve hyperexcitability, dysautonomia, insomnia, and encephalopathy. In this case report, we highlight the clinical and pathological findings of an elderly gentleman who presented to us with clinical features of Morvan's syndrome associated with anti-contactin-associated protein 2 (CASPR-2) antibodies. Histopathology [Figure 3] revealed cortical atrophy with gliosis and mild microglial proliferation. Microglial activation and gliosis were observed in the hippocampus, hypothalamus, and thalamus. Brainstem showed multifocal inflammation. Mild inflammation was observed in the leptomeninges. Morvan's syndrome is an autoimmune disease with antibodies targeted against CASPR within the voltage-gated potassium channel (VGKC) complex. Early diagnosis and treatment play a key role in the management of patients. Most patients show a good response when treated with plasmapheresis and steroids. This patient presented to us late into the illness and succumbed.
Topics: Humans; Male; Autopsy; Nerve Tissue Proteins; Aged; Syringomyelia; Autoantibodies; Brain; Membrane Proteins
PubMed: 38817173
DOI: 10.4103/ni.ni_692_22 -
Scientific Reports May 2024Despite treatment with levothyroxine, hypothyroidism and autoimmune thyroiditis (AIT) may be associated with reduced quality of life (QoL), an enigmatic condition...
Despite treatment with levothyroxine, hypothyroidism and autoimmune thyroiditis (AIT) may be associated with reduced quality of life (QoL), an enigmatic condition referred to as "syndrome T". Peripheral neuropathy, described in untreated thyroid disease, could be a contributing mechanism. We analysed autonomic and somatosensory function in 29 patients with AIT and treated hypothyroidism and 27 healthy volunteers. They underwent heart rate variability (HRV) analysis and quantitative sensory testing (n = 28), comprising 13 parameters of small and large nerve fibre function and pain thresholds. Autonomic cardiovascular function was assessed in rest, deep respiration and orthostasis. Additionally, biomarkers for autoimmunity and thyroid function were measured. Anxiety, depression and QoL were assessed using validated questionnaires. 36% of the patients showed at least one sign of somatosensory small or large fibre dysfunction. 57% presented with mild hyperalgesia to at least one stimulus. Several markers of autonomic function and some detection thresholds were related to the antibody titres. Anxiety, depression scores and QoL correlated to antibody titres and HRV measures. Autonomic and somatosensory dysfunction indicate that in treated hypothyroidism and AIT a subgroup of patients suffers from neuropathic symptoms leading to impaired QoL. Additionally, mild hyperalgesia as a possible sensitisation phenomenon should be considered a target for symptomatic treatment.
Topics: Humans; Female; Male; Middle Aged; Adult; Autonomic Nervous System; Quality of Life; Thyroiditis, Autoimmune; Heart Rate; Hypothyroidism; Thyroxine; Aged; Somatosensory Disorders; Anxiety
PubMed: 38811750
DOI: 10.1038/s41598-024-63158-w -
BMJ Open May 2024To document current practice and develop consensus recommendations for the assessment and treatment of paroxysmal sympathetic hyperactivity (PSH) during rehabilitation...
OBJECTIVES
To document current practice and develop consensus recommendations for the assessment and treatment of paroxysmal sympathetic hyperactivity (PSH) during rehabilitation after severe acquired brain injury.
DESIGN
Delphi consensus process with three rounds, based on the Guidance on Conducting and REporting DElphi Studies (CREDES) guidelines, led by three convenors (the authors) with an expert panel. Round 1 was exploratory, with consensus defined before round 2 as agreement of at least 75% of the panel.
SETTING
A working group within the Nordic Network for Neurorehabilitation.
PANEL PARTICIPANTS
Twenty specialist physicians, from Sweden (9 participants), Norway (7) and Denmark (4), all working clinically with patients with severe acquired brain injury and with current involvement in clinical decisions regarding PSH.
RESULTS
Consensus was reached for 21 statements on terminology, assessment and principles for pharmacological and non-pharmacological treatment, including some guidance on specific drugs. From these, an algorithm to support clinical decisions at all stages of inpatient rehabilitation was created.
CONCLUSIONS
Considerable consensus exists in the Nordic countries regarding principles for PSH assessment and treatment. An interdisciplinary approach is needed. Improved documentation and collation of data on treatment given during routine clinical practice are needed as a basis for improving care until sufficiently robust research exists to guide treatment choices.
Topics: Humans; Delphi Technique; Brain Injuries; Consensus; Neurological Rehabilitation; Autonomic Nervous System Diseases; Scandinavian and Nordic Countries; Sweden
PubMed: 38806428
DOI: 10.1136/bmjopen-2024-084778