Special considerations for the child with obesity: An Obesity Medicine Association (OMA) clinical practice statement (CPS) 2024.

Background: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) details assessment and management of the child with overweight or obesity. The term "child" is defined as the child between 2 and 12 years of age. Because children are in a continual state of development during this age range, we will specify when our discussion applies to subsets within this age range. For the purposes of this CPS, we will use the following definitions: overweight in the child is a body mass index (BMI) ≥ 85th and <95th percentile, obesity in the child is a BMI ≥95th percentile, and severe obesity is a BMI ≥120% of the 95th percentile. Methods: The information and clinical guidance in this OMA Clinical Practice Statement are based on scientific evidence, supported by medical literature, and derived from the clinical perspectives of the authors. Results: This OMA Clinical Practice Statement provides an overview of prevalence of disease in this population, reviews precocious puberty in the child with obesity, discusses the current and evolving landscape of the use of anti-obesity medications in children in this age range, discusses the child with obesity and special health care needs, and reviews hypothalamic obesity in the child. Conclusions: This OMA Clinical Practice Statement on the child with obesity is an evidence based review of the literature and an overview of current recommendations. This CPS is intended to provide a roadmap to the improvement of the health of children with obesity, especially those with metabolic, physiological, psychological complications and/or special healthcare needs. This CPS addresses treatment recommendations and is designed to help the clinician with clinical decision making.

Validation of a modified-composite autonomic symptom score (COMPASS-31) as an outcome measure for persistent autonomic symptoms post-concussion: an observational pilot study.

OBJECTIVE: Persistent symptoms post-mild traumatic brain injury (mTBI) includes autonomic dysregulation (AD). The composite autonomic symptoms score, (COMPASS-31), was developed to quantify AD symptom severity in the last year, which limits clinical utility. The primary aim was to determine validity of a modified-COMPASS-31 measuring symptoms in the last month compared to the original, secondarily to compare both original and modified versions to the Neurobehavioral Symptom Inventory (NSI), and tertiarily to detect change post-treatment of the modified-COMPASS-31 compared to NSI and headache intensity (HI). PARTICIPANTS: Thirty-three military personnel with persistent headache post-mTBI. MAIN OUTCOME MEASURES: Total and domain scores for COMPASS-31 (original vs. modified) NSI and HI at baseline. Change in modified-COMPASS-31. NSI, and HI. RESULTS: Baseline COMPASS-31 versions were comparable and highly correlated (r = 0.72, p < 0.001), they were moderately correlated at best to the NSI (r < 0.6), which may suggest differences in measurement metrics. The mean change in modified-COMPASS-31 scores (15.4/100, effect size 0.8) was mild to moderately correlated to the change in HI (r = 0.39) score, but not to NSI (r = 0.28). CONCLUSION: The modified-COMPASS-31 appears to be valid, can measure change of AD symptom severity, and is recommended as an outcome measure.

Cold hypersensitivity in the hands and feet is associated with erectile dysfunction in young Taiwanese men.

Cold hypersensitivity in the hands and feet (CHHF) is a protective or predisposing factor for many diseases; however, the relationship between CHHF and erectile dysfunction (ED) remains unclear. We aimed to investigate associations between CHHF and ED among young men of Southeast Asian origin. In this cross-sectional study, sexually active Taiwanese men aged 20-40 years were enrolled via an online questionnaire comprising general demographic information, comorbidities, subjective thermal sensations of their hands and feet in the past 6 months, and their erectile function using the International Index of Erectile Function-5 (IIEF-5). Participants who reported cold sensation of hands and feet were classified to have CHHF; those with IIEF-5 score ≤ 21 were considered to have ED. Total 54.2% and 27.9% of participants had ED and CHHF, respectively. Men with CHHF were significantly younger, had lower body mass index and IIEF-5 scores (p < 0.001), and a lower prevalence of diabetes mellitus (p = 0.033) along with higher prevalence of ED, psychiatric disorders, and insomnia (p < 0.001). After adjusting for predisposing factors of ED, CHHF (odds ratio 1.410, 95% confidence interval 1.159-1.714; p = 0.001) remained an independent predictor of ED. Thus, CHHF is independently associated with ED, affecting more than a quarter of young Taiwanese men. Autonomic dysregulation and subclinical endothelial dysfunction may be common pathophysiologies of CHHF and ED.

Autoimmunity in Syndromes of Orthostatic Intolerance: An Updated Review.

Orthostatic intolerance is a broad term that represents a spectrum of dysautonomic disorders, including postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH), as manifestations of severe autonomic failure. While the etiology of orthostatic intolerance has not yet fully been uncovered, it has been associated with multiple underlying pathological processes, including peripheral neuropathy, altered renin-aldosterone levels, hypovolemia, and autoimmune processes. Studies have implicated adrenergic, cholinergic, and angiotensin II type I autoantibodies in the pathogenesis of orthostatic intolerance. Several case series have demonstrated that immunomodulation therapy resulted in favorable outcomes, improving autonomic symptoms in POTS and OH. In this review, we highlight the contemporary literature detailing the association of autoimmunity with POTS and OH.

Anti-ZSCAN1 Autoantibodies Are a Feasible Diagnostic Marker for ROHHAD Syndrome Not Associated with a Tumor.

Recent studies have reported the presence of autoantibodies against zinc finger and SCAN domain-containing protein 1 (ZSCAN1) in the sera of patients with rapid-onset obesity with hypoventilation, hypothalamic and autonomic dysregulation (ROHHAD) syndrome associated with neuroendocrine tumors, suggesting immunologic and paraneoplastic processes as the pathologic underpinnings. Moreover, several hypothalamic regions, including the subfornical organ (SFO), were reported to exhibit antibody reactivity in a patient with ROHHAD syndrome not associated with a tumor. Whether ROHHAD syndrome not associated with a tumor is associated with anti-ZSCAN1 autoantibodies remains unclear. We used a comprehensive protein array analysis to identify candidate molecules in the sera of patients with ROHHAD syndrome and identified ZSCAN1 as a target antigen. We also found that ZSCAN1 was co-expressed at the site of antibody reactivity to the IgG in the patient serum observed in mouse SFOs and an enzyme-linked immunosorbent assay showed that >85% of the patients with ROHHAD syndrome were positive for anti-ZSCAN1 autoantibodies. These results suggest anti-ZSCAN1 autoantibodies as a feasible diagnostic marker in ROHHAD syndrome regardless of the presence of a tumor.

Dysautonomia in 'long COVID': Case report.

Background: The reason for autonomic dysfunction in COVID-19 is yet to get clear, though we tend to notice a few dysautonomia cases during post-COVID-19 manifested most commonly in the form of postural orthostatic tachycardia syndrome (POTS). Case Presentation: A case of autonomic dysregulation is presented in a COVID-19 patient as a post-COVID-19 sequelae. On doing an active stand test and two basic autonomic function tests, dysautonomia was diagnosed in the patient, after going through all routine investigations for six months. Cardiac parasympathetic integrity was assessed by measuring the heart rate response to standing by continuous electrocardiographic tracing. The management of these patients is usually conservative. Conclusion: Family physicians must be aware of such cases in future for early diagnosis and management of the patients.

Interventional Mental Health: A Transdisciplinary Approach to Novel Psychiatric Care Delivery.

Mental health disorders are among the most common health conditions in the United States. Traditional clinical treatments rely on psychiatric counseling and, in many cases, prescription medications. We propose an innovative model, Interventional Mental Health, which employs a combination of modalities through a multifaceted approach to treat conditions that have exhibited limited responsiveness to traditional methods and individuals afflicted with multiple comorbidities simultaneously. We hypothesize that creating a unique treatment algorithm combining current therapeutic modalities such as Stellate Ganglion Blocks (SGB), Transcranial Magnetic Stimulation (TMS) therapy, and ketamine therapy, within a consolidated timeframe, will yield synergistic outcomes among patients presenting with comorbid post-traumatic stress disorder (PTSD), depression, and/or anxiety.

Refractory Arrhythmias as a Potential Indicator of Underlying Cardiac Amyloidosis: A Case Report.

Primary (AL) amyloidosis is a rare multisystemic disorder that occurs approximately in 9.7-14.0 cases per million per year in the United States. A late diagnosis of amyloidosis can decrease the chance of survival to less than three years. With the intention to diagnose future cases of AL amyloidosis early in clinical presentation, we describe a case of a 64-year-old female who had presented to the hospital for a pre-liver transplant workup for presumed end-stage liver disease secondary to nonalcoholic steatohepatitis (NASH). Pre-transplant electrocardiogram (ECG) findings were significant for atrial fibrillation that was unable to resolve with synchronized cardioversion. Two previous cardioversions attempted in the preceding three years with amiodarone proved unsuccessful. Following her ECG, an endoscopy and colonoscopy were completed that demonstrated a lesion within the gastric mucosa along with two polyps in the transverse colon and ascending colon. Pathology for these lesions revealed amyloidosis in all biopsy sites, which was followed by a bone marrow biopsy also confirming AL amyloidosis and proliferative monoclonal B lymphocytes. A cardiac magnetic resonance imaging (MRI) proceeded to gather more information on the systemic extent of the patient's amyloidosis, which showed signs consistent with cardiac infiltration of amyloid. The patient was discharged with at-home hospice care and later decided to pursue chemotherapy, ultimately expiring from end organ failure. We conclude that failed cardioversion in a patient with persistent atrial fibrillation can be a clinical and diagnostic marker in suspecting a diagnosis of amyloidosis. Thus, we encourage clinicians to consider systemic amyloidosis in the assessment of unsuccessful cardioversion in these patient presentations for the initiation of treatment early on in the disease course.

Rapid-Onset Obesity With Hypothalamic Dysfunction, Hypoventilation, Autonomic Dysregulation, and Neuroendocrine Tumor (ROHHADNET) Syndrome: A Case Report.

Here, we report the case of a rare and complex disorder, rapid-onset obesity with hypothalamic dysfunction, hypoventilation, autonomic dysregulation, and neuroendocrine tumor (ROHHADNET) syndrome, in a three-year-old girl with no significant medical history. This is the first such case reported from the UAE. ROHHADNET is a rare disorder of respiratory control and autonomic nervous system regulation with endocrine abnormalities. It typically presents in children older than 18 months with rapid weight gain. This is a challenging diagnosis as there is no clear diagnostic test, and treatment is essentially supportive. This report describes a case of ROHHADNET syndrome in a previously well child who presented with rapid weight gain followed by ophthalmoplegia, dysphagia, electrolyte disturbance, and other comorbidities. The paper outlines in detail the clinical course, investigations, and management of ROHHADNET syndrome. Cerebrospinal fluid analysis revealed oligoclonal bands, which have been reported in only two other cases of ROHHADNET syndrome. Our goal in reporting this case is to increase awareness of this condition among clinicians to facilitate early diagnosis and timely management.

A narrative review of the mechanisms and consequences of intermittent hypoxia and the role of advanced analytic techniques in pediatric autonomic disorders.

Disorders of autonomic functions are typically characterized by disturbances in multiple organ systems. These disturbances are often comorbidities of common and rare diseases, such as epilepsy, sleep apnea, Rett syndrome, congenital heart disease or mitochondrial diseases. Characteristic of many autonomic disorders is the association with intermittent hypoxia and oxidative stress, which can cause or exaggerate a variety of other autonomic dysfunctions, making the treatment and management of these syndromes very complex. In this review we discuss the cellular mechanisms by which intermittent hypoxia can trigger a cascade of molecular, cellular and network events that result in the dysregulation of multiple organ systems. We also describe the importance of computational approaches, artificial intelligence and the analysis of big data to better characterize and recognize the interconnectedness of the various autonomic and non-autonomic symptoms. These techniques can lead to a better understanding of the progression of autonomic disorders, ultimately resulting in better care and management.

Major Depressive Disorder and Chronic Fatigue Syndrome Show Characteristic Heart Rate Variability Profiles Reflecting Autonomic Dysregulations: Differentiation by Linear Discriminant Analysis.

Major depressive disorder (MDD) and chronic fatigue syndrome (CFS) have overlapping symptoms, and differentiation is important to administer the proper treatment. The present study aimed to assess the usefulness of heart rate variability (HRV) indices. Frequency-domain HRV indices, including high-frequency (HF) and low-frequency (LF) components, their sum (LF+HF), and their ratio (LF/HF), were measured in a three-behavioral-state paradigm composed of initial rest (Rest), task load (Task), and post-task rest (After) periods to examine autonomic regulation. It was found that HF was low at Rest in both disorders, but was lower in MDD than in CFS. LF and LF+HF at Rest were low only in MDD. Attenuated responses of LF, HF, LF+HF, and LF/HF to task load and an excessive increase in HF at After were found in both disorders. The results indicate that an overall HRV reduction at Rest may support a diagnosis of MDD. HF reduction was found in CFS, but with a lesser severity. Response disturbances of HRV to Task were observed in both disorders, and would suggest the presence of CFS when the baseline HRV has not been reduced. Linear discriminant analysis using HRV indices was able to differentiate MDD from CFS, with a sensitivity and specificity of 91.8% and 100%, respectively. HRV indices in MDD and CFS show both common and different profiles, and can be useful for the differential diagnosis.

Rapid recovery of poststroke cardiac autonomic dysfunction: Causes to be considered.

BACKGROUND AND PURPOSE: Acute stroke frequently causes cardiovascular-autonomic dysfunction (CAD). Studies of CAD recovery are inconclusive, whereas poststroke arrhythmias may wane within 72 h. We evaluated whether poststroke CAD recovers within 72 h upon stroke onset in association with neurological improvement or increased use of cardiovascular medication. METHODS: In 50 ischemic stroke patients (68 ± 13 years old) who-prior to hospital-admission-had no known diseases nor took medication affecting autonomic modulation, we assessed National Institutes of Health Stroke Scale (NIHSS) scores, RR intervals (RRIs), systolic and diastolic blood pressure (BP), respiration rate, parameters reflecting total autonomic modulation (RRI SD, RRI total powers), sympathetic modulation (RRI low-frequency powers, systolic BP low-frequency powers), and parasympathetic modulation (square root of mean squared differences of successive RRIs [RMSSD], RRI high-frequency powers), and baroreflex sensitivity within 24 h (Assessment 1) and 72 h after stroke onset (Assessment 2) and compared data to those of 31 healthy controls (64 ± 10 years). We correlated delta NIHSS values (Assessment 1 - Assessment 2) with delta values of autonomic parameters (Spearman rank correlation tests; significance: p < 0.05). RESULTS: At Assessment 1, patients were not yet on vasoactive medication and had higher systolic BP, respiration rate, and heart rate, that is, lower RRIs, but lower RRI SD, RRI coefficient of variance, RRI low-frequency powers, RRI high-frequency powers, RRI total powers, RMSSDs, and baroreflex sensitivity. At Assessment 2, patients were on antihypertensives, had higher RRI SD, RRI coefficient of variance, RRI low-frequency powers, RRI high-frequency powers, RRI total powers, RMSSDs, and baroreflex sensitivity but lower systolic blood pressure and NIHSS values than at Assessment 1; values no longer differed between patients and controls except for lower RRIs and higher respiration rate in patients. Delta NIHSS scores correlated inversely with delta values of RRI SD, RRI coefficient of variance, RMSSDs, RRI low-frequency powers, RRI high-frequency powers, RRI total powers, and baroreflex sensitivity. CONCLUSIONS: In our patients, CAD recovery was almost complete within 72 h after stroke onset and correlated with neurological improvement. Most likely, early initiation of cardiovascular medication and probably attenuating stress supported rapid CAD recovery.

Weight a minute: The smaller and more immature, the more predictable the autonomic regulation?

AIM: To investigate the relation between autonomic regulation, measured using heart rate variability (HRV), body weight and degree of prematurity in infants. Further to assess utility to include body weight in a machine learning-based sepsis prediction algorithm. METHODS: Longitudinal cohort study including 378 infants hospitalised in two neonatal intensive care units. Continuous vital sign data collection was performed prospectively from the time of NICU admission to discharge. Clinically relevant events were annotated retrospectively. HRV described using sample entropy of inter-beat intervals and assessed for its correlation with body weight measurements and age. Weight values were then added to a machine learning-based algorithm for neonatal sepsis detection. RESULTS: Sample entropy showed a positive correlation with increasing body weight and postconceptual age. Very low birth weight infants exhibited significantly lower HRV compared to infants with a birth weight >1500 g. This persisted when reaching similar weight and at the same postconceptual age. Adding body weight measures improved the algorithm's ability to predict sepsis in the overall population. CONCLUSION: We revealed a positive correlation of HRV with increasing body weight and maturation in infants. Restricted HRV, proven helpful in detecting acute events such as neonatal sepsis, might reflect prolonged impaired development of autonomic control.

Control of Breathing and Central Hypoventilation Syndromes.

Control of breathing in children varies with age and sleep state. There is overlap between central hypoventilation, autonomic dysfunction, and hypothalamic dysfunction in the rare disorders (congenital central hypoventilation syndrome and rapid-onset obesity, hypoventilation, hypothalamic dysfunction, and autonomic dysregulation). Other, more common disorders that typically present in childhood also include central hypoventilation and disordered ventilatory responses.

HIDEA syndrome: A new case report highlighting similarities with ROHHAD syndrome.

Context: ROHHAD syndrome presents a significant resemblance to HIDEA syndrome. The latter is caused by biallelic loss-of-function variants in the P4HTM gene and encompasses hypotonia, intellectual disabilities, eye abnormalities, hypoventilation, and dysautonomia. We report the first patient identified with HIDEA syndrome from our ROHHAD cohort. Clinical case: Our patient was a 21-month-old girl who had a history of severe respiratory infections requiring intensive care, hypotonia, abnormal eye movements, and rapid weight gain. Polysomnography identified severe central hypoventilation. During her follow-up, a significant psychomotor delay and the absence of language were gradually observed. The prolactin levels were initially increased. Hypothermia was reported at 4 years. Exome sequencing identified a new homozygous truncating P4HTM variant. Discussion: Our patient met the diagnosis criteria for ROHHAD, which included rapid weight gain, central hypoventilation appearing after 1.5 years of age, hyperprolactinemia suggesting hypothalamic dysfunction, and autonomic dysfunction manifesting as strabismus and hypothermia. However, she also presented with severe neurodevelopmental delay, which is not a classic feature of ROHHAD syndrome. HIDEA syndrome presents similarities with ROHHAD, including hypoventilation, obesity, and dysautonomia. To date, only 14% of endocrinological disturbances have been reported in HIDEA patients. Better delineation of both syndromes is required to investigate the eventual involvement of P4HTM, a regulator of calcium dynamics and gliotransmission, in ROHHAD patients. Conclusion: In the case of clinical evidence of ROHHAD in a child with abnormal neurological development or eye abnormalities, we suggest that the P4HTM gene be systematically interrogated in addition to the analysis of the PHOX2B gene. A better delineation of the natural history of HIDEA is required to allow further comparisons between features of HIDEA and ROHHAD. The clinical similarities could potentially orient some molecular hypotheses in the field of ROHHAD research.

Possible autonomic or cranial nerve symptoms triggered during sustained neck rotation in persistent headache post-concussion: a retrospective observational cross-sectional study.

OBJECTIVES: To examine and categorize symptoms occurring within 60 s of vertebrobasilar-insufficiency (VBI) testing (left- and right-neck rotation) in individuals with persistent post-traumatic headache. BACKGROUND: As part of routine clinical cervical screening in our patients, we found extended VBI testing often triggered additional symptoms. Therefore, we aimed to document the prevalence and precise symptoms occurring during each movement direction of this test and determine any demographic or baseline signs or symptoms associated with a positive test. METHODS: A retrospective medical record review on military personnel receiving treatment for persistent post-traumatic headache was performed. Participants were grouped according to presence of non-headache related symptoms triggered during the tests. Frequency, onset, and symptom characteristics reported were categorized as potentially vascular and/or possible autonomic or cranial nerve in nature. RESULTS: At least one symptom was reported by 81.3% of 123 patients. Of these, 54% reported symptoms in one and 46% in both directions of rotation, yielding 146 abnormal tests. Most reported symptoms were tear disruption (41%), altered ocular-motor-control (25%), and blepharospasm (16%). Enlisted individuals and those with altered baseline facial sensation were more likely to have a positive test. CONCLUSIONS: The majority reported symptoms not typical of VBI within 60 seconds of sustained neck rotation. Further study is needed to better understand the mechanisms and clinical relevance.

Neurocognition as a biomarker in the rare autonomic disorders of CCHS and ROHHAD.

PURPOSE: Congenital central hypoventilation syndrome (CCHS) and rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) are rare disorders of autonomic regulation with risk for disrupted neurocognitive development. Our aim is to summarize research on neurocognitive outcomes in these conditions, advance understanding of how to best support these individuals throughout development, and facilitate future research. METHODS: We conducted a narrative review of literature on neurocognitive outcomes in CCHS and ROHHAD, supplemented with previously unpublished data from patients with CCHS and ROHHAD at our Center for Autonomic Medicine in Pediatrics (CAMP). RESULTS: Individuals with CCHS and ROHHAD experience a wide range of neurocognitive functioning ranging from above average to below average, but are at particular risk for difficulties with working memory, processing speed, perceptual reasoning, and visuographic skills. An assessment framework emphasizing fluid cognition seems especially appropriate for these conditions. Owing to small cohorts and varied methods of data collection, it has been difficult to identify associations between disease factors (including CCHS PHOX2B genotypes) and cognitive outcomes. However, results suggest that early childhood is a period of particular vulnerability, perhaps due to the disruptive impact of recurrent intermittent hypoxic episodes on brain and cognitive development. CONCLUSION: Neurocognitive monitoring is recommended as a component of routine clinical care in CCHS and ROHHAD as a marker of disease status and to ensure that educational support and disability accommodations are provided as early as possible. Collaborative efforts will be essential to obtain samples needed to enhance our understanding of neurocognitive outcomes in CCHS and ROHHAD.

Unilateral corneal arcus and conjunctival vessel alterations in cranial autonomic dysregulation: A case report.

BACKGROUND: Cranial autonomic dysregulation is a common symptom of patients suffering from cluster headache or migraine. The peripheral vascular dysfunction may increase the risk for ischemic or hemorrhagic strokes, myocardial infarction, retinal vasculopathy, cardiovascular mortality, and peripheral artery diseases. Furthermore, it may also manifest with ocular symptoms, e.g., increased lacrimation, conjunctival injection, and facial swelling. CASE PRESENTATION: We here report a case of a patient with migraine and ocular signs of a vascular dysregulation that have led to persisting changes of conjunctival vessels and to a corneal arcus. CONCLUSIONS: Autonomic vascular dysregulation may not only cause headaches but also persisting changes of ocular tissues, e.g., conjunctival vessel alterations and a corneal arcus.