Search Results (44)

Background: Post-concussion syndrome (PCS) and Functional Neurological Disorder (FND), including Functional Cognitive Disorder (FCD), are two frequently encountered but diagnostically complex conditions. While PCS is conceptualized as a sequela of mild traumatic brain injury (mTBI), FND/FCD encompasses symptoms incompatible with recognized neurological disease, often arising in the absence of structural brain damage. Yet, both conditions exhibit considerable clinical overlap—particularly in the domains of cognitive dysfunction, emotional dysregulation, and symptom persistence despite negative investigations. Objective: This review critically examines the shared and divergent features of PCS and FND/FCD. We explore their respective epidemiology, diagnostic criteria, and risk factors—including personality traits and trauma exposure—as well as emerging insights from neuroimaging and biomarkers. We propose the “Functional Overlay Model” as a clinical tool for navigating diagnostic ambiguity in patients with persistent post-injury symptoms. Results: PCS and FND/FCD frequently share features such as subjective cognitive complaints, fatigue, anxiety, and heightened somatic vigilance. High neuroticism, maladaptive coping, prior psychiatric history, and trauma exposure emerge as common risk factors. Neuroimaging studies show persistent network dysfunction in both PCS and FND, with overlapping disruption in fronto-limbic and default mode systems. The Functional Overlay Model helps to identify cases where functional symptomatology coexists with or replaces an initial organic insult—particularly in patients with incongruent symptoms and normal objective testing. Conclusions: PCS and FND/FCD should be conceptualized along a continuum of brain dysfunction, shaped by injury, psychology, and contextual factors. Early recognition of functional overlays and stratified psychological interventions may improve outcomes for patients with persistent, medically unexplained symptoms after head trauma. This review introduces the Functional Overlay Model as a novel framework to enhance diagnostic clarity and therapeutic planning in patients presenting with persistent post-injury symptoms. Full article

Background/Objectives: Vague physical complaints with no corresponding organic disease background are called unidentified complaints. The symptoms of patients with unidentified complaints closely resemble medically unexplained or persistent physical symptoms, with the onset sometimes masked by mental disorders. Over the past 50 years, numerous studies have connected unfavorable eating habits to these symptoms; however, no study has systematically examined the association between the symptoms and specific nutrients or food items. Methods: We conducted a cross-sectional study of young Japanese women, using questionnaire surveys, to assess their nutritional intake, quantify unidentified complaints and depression, and identify nutrients/food items primarily associated with the severity of these conditions. Results: Our findings indicate that participants with high scores for unidentified complaints, depression, or both had lower intake levels of eicosapentaenoic acid, docosahexaenoic acid, vitamin D, and vitamin B₁₂ than those with low scores, alongside reduced fish and shellfish consumption. Notably, the median fish and shellfish intake in the group with high scores for both unidentified complaints and depression was less than one-fourth of that in the low-score group. Conclusions: The results align with previous findings, demonstrating a modest inverse association between fish intake and depression risk, and suggesting the involvement of fish and shellfish intake in the occurrence of unidentified complaints. Full article

Background: Somatic symptom disorder (SSD) involves physical symptoms that cannot entirely be explained by an organic medical cause, accompanied by persistent thoughts, feelings and behaviours relating to one’s health. SSD is common yet underdiagnosed in emergency departments (EDs). This study aimed to assess emergency physician (EP) readiness, attitudes and perceptions toward diagnosing SSD and explore demographic trends. Methods: In total, 1339 Canadian EPs were invited to respond to a survey collecting demographic information and assessing attitudes toward SSD in four domains: perceptions of SSD, attitudes toward patients, diagnostic confidence, and physician–patient communication. Data were analyzed using t-tests and ANOVA to determine associations with demographic information. Results: Of the 96 survey respondents, 75 met the eligibility criteria. In total, 44% estimated that emotional stress was the primary cause of symptoms in 11–20% of their patients. Most felt that SSD was underdiagnosed and that effective therapies exist. Concerns included medico-legal implications, managing patients’ emotions, and potential negative reactions to non-organic diagnoses. Most respondents felt prepared and confident broaching the diagnosis. More experienced EPs felt that there was time to broach the topic of SSD, while rural EPs were less concerned about patient offence than urban counterparts. Conclusions: EPs recognize SSD as common and underdiagnosed, acknowledging its diagnosis as part of their role. Challenges identified include managing patients’ emotions, time constraints, and reliance on only diagnosing SSD once an organic etiology is excluded. Training pathway, experience, and practice setting impact perceptions and attitudes around SSD. The findings suggest opportunities for improving SSD care through targeted interventions, communication training, and enhanced diagnostic education. Full article

Background/Objectives: Lower-extremity weakness in older adults is often overlooked, yet it can have reversible or medical causes that contribute to increased falls. Common factors include vision disturbances, impaired balance due to otolith dysfunction, arthritis-related immobility, and lower-extremity neuropathy. This case presents a unique diagnostic challenge in evaluating bilateral lower-extremity weakness and recurrent falls in an older adult, highlighting the complexity of diagnosing conditions with overlapping symptoms. Case Presentation: The patient, a woman with a history of a neuroendocrine tumor, experienced progressive weakness in her lower extremities, along with oculomotor and facial muscle involvement, despite extensive testing. Key clinical findings included elevated protein levels in cerebrospinal fluid, suggesting the possibility of an infectious or autoimmune process. A thorough investigation was conducted, including testing for both common and rare conditions such as Guillain–Barré syndrome, Lyme disease, and tuberculosis. Results: Despite comprehensive diagnostic efforts, no clear etiology was identified. The patient’s condition was eventually considered to be related to carcinomatosis meningoencephalitis, a rare complication from a previous cancer diagnosis. Given the progressive nature of her symptoms and lack of treatment options, she was transitioned to palliative care. Conclusions: This case highlights the importance of a comprehensive differential diagnosis in older patients with unexplained weakness and falls. Rare neurological conditions should not be overlooked, even when more common causes are suspected. Clinicians should remain aware that falls and weakness in older adults may stem from various pathologies, some of which are reversible if identified early, and rare causes must always be considered when standard treatments fail. Full article

Background: Persistent splenomegaly, often an incidental finding, can originate from a number of inherited metabolic disorders (IMDs). Variants of APOE are primarily known as risk factors in terms of cardiovascular disease; however, severe dysfunction of APOE can result in a disease phenotype with considerable overlap with lysosomal storage disorders (LSDs), including splenomegaly and gross elevation of N-palmitoyl-O-phosphocholine-serine (PPCS). Methods: A case study (deep phenotyping, genetic and FACS analysis) and literature study was conducted. Results: The index patient, with a family history of early-onset cardiovascular disease, presented with splenic infarctions in a grossly enlarged spleen. The identified genetic cause was homozygosity for two APOE variants (c.604C>T, p.(Arg202Cys) and c.512G>A, p.(Gly171Asp); ε1/ε1), resulting in a macrophage storage phenotype resembling an LSD that was also present in the brother of the index patient. A FACS analysis of the circulating monocytes showed increased lipid content and the expression of activation markers (CD11b, CCR2, CD36). This activated state enhances lipoprotein intake, which eventually converts these monocytes/macrophages into foam cells, accumulating in tissues (e.g., spleen and vascular wall). A literature search identified seven individuals with splenomegaly caused by APOE variants (deletion of leucine at position 167). The combined data from all patients identified male gender, splenectomy and obesity as potential modifiers determining the severity of the phenotype (i.e., degree of triglyceride increase in plasma and/or spleen size). Symptoms are (partially) reversible by lipid-lowering medication and energy restricted diets and splenectomy is contra-indicated. Conclusions: Inherited dyslipidemic splenomegaly caused by disruptive APOE variants should be included in the differential diagnoses of unexplained splenomegaly with abnormal lipid profiles. A plasma lipid profile consistent with dysbetalipoproteinemia is a diagnostic biomarker for this IMD. Full article

Background: Prenatal factors have been implicated in the likelihood of reporting sleep disorders in infants. The influence of prenatal and pregnancy-related factors on the incidence of brief resolved unexplained events (BRUEs) in infants has not been established. Objectives: This study aims to evaluate the prenatal and pregnancy-related factors that may contribute to the development of BRUEs in infants. Methods: A single-center, observational, and cross-sectional cohort study was conducted on mothers of children presenting to the Pediatric Clinic of the University of Insubria’s Center for the Study of Respiratory Sleep Disorders with BRUEs as infants. The mothers of typically developing children were enrolled as a control group consecutively at their respective outpatient clinics. All mothers were administered comprehensive questionnaires including demographics, past medical histories, and pregnancy-related issues (weight gain, Berlin sleep-disordered breathing score, and insomnia severity index), psychological symptoms, medical history, illnesses, and medications. Results: Infants with BRUEs were delivered at an earlier gestational age. Mothers of infants with BRUEs were more likely to snore during pregnancy and have lower extremity edema during the first trimester, uterine contractions and restless legs syndrome symptoms during the second trimester, and muscle aches and aspirin usage during the third trimester. The insomnia severity index composite score was not different between the control and BRUE groups. Mothers of infants with BRUEs were less likely to report leg cramps, pregnancy-related diarrhea, fatigue, and gastroesophageal reflux. Conclusions: Mothers of infants presenting with BRUEs had more symptoms during pregnancy of snoring and uterine contractions but not insomnia and were less likely to report leg cramps, pregnancy-related diarrhea, fatigue, and gastroesophageal reflux. The reporting of this study conforms with the STROBE statement. Full article

Background: Eosinophilic pneumonias denote a rare condition, wherein infiltrating eosinophilic granulocytes accumulate within the lung parenchyma. Although eosinophilic pneumonias may be idiopathic, they are also associated with secondary causes. More than 110 medications have been linked to eosinophilic pneumonia, including several antidepressants. This review presents an analysis of case reports of eosinophilic pneumonia correlated to antidepressants. Objectives: The objectives of this study are to provide a contemporary overview of the literature delineating eosinophilic pneumonia as a potential sequela of antidepressant medication treatment, and to discuss possible pathogenetic mechanisms linking antidepressants to eosinophilic pneumonia. Methods and Data Selection: A literature search was performed in PubMed and Scopus databases from 1963 to October 2024. The search strategy used the terms “eosinophilic pneumonia AND antidepressants”. Sources included in this review were screened for relevance, focusing on references discussing eosinophilic pneumonia associated with any class of antidepressants. Case reports meeting the diagnostic criteria for acute eosinophilic pneumonia (AEP) or chronic eosinophilic pneumonia (CEP) were included in the review. Clinical, epidemiological, laboratory, radiology and bronchoscopy data, implicated antidepressant and dosage, and therapeutic interventions were reported. Results: This study found that various types of antidepressants are associated with AEP and CEP. The clinical presentation ranges from mild symptoms to respiratory failure and intubation. Outcomes were favorable in most cases, with complete remission achieved after discontinuation of the causative drug and, in severe cases, a short course of corticosteroids. Conclusions: Although a rare cause, antidepressants may lead to eosinophilic pneumonia, and should be considered in the differential diagnosis of unexplained pulmonary infiltrates. Clinical suspicion must be aroused, as early recognition would prevent unnecessary work-up and navigation of the diagnosis. Full article

Dynamic digital radiography (DDR) is a recent imaging technique that allows for real-time visualization of thoracic and pulmonary movement in synchronization with the breathing cycle, providing useful clinical information. A 46-year-old male, a former smoker, was evaluated for unexplained dyspnea and reduced exercise tolerance. His medical history included a SARS-CoV-2 infection in 2021. On physical examination, decreased breath sounds were noted at the right-lung base. Spirometry showed results below predicted values. A standard chest radiograph revealed an elevated right hemidiaphragm, a finding not present in a previous CT scan performed during his SARS-CoV-2 infection. To better assess the diaphragmatic function, a posteroanterior DDR study was performed in the standing position with X-ray equipment (AeroDR TX, Konica Minolta Inc., Tokyo, Japan) during forced breath, with the following acquisition parameters: tube voltage, 100 kV; tube current, 50 mA; pulse duration of pulsed X-ray, 1.6 ms; source-to-image distance, 2 m; additional filter, 0.5 mm Al + 0.1 mm Cu. The exposure time was 12 s. The pixel size was 388 × 388 μm, the matrix size was 1024 × 768, and the overall image area was 40 × 30 cm. The dynamic imaging, captured at 15 frames/s, was then assessed on a dedicated workstation (Konica Minolta Inc., Tokyo, Japan). The dynamic acquisition showed a markedly reduced motion of the right diaphragm. The diagnosis of diaphragm dysfunction can be challenging due to its range of symptoms, which can vary from mild to severe dyspnea. The standard chest X-ray is usually the first exam to detect an elevated hemidiaphragm, which may suggest motion impairment or paralysis but fails to predict diaphragm function. Ultrasound (US) allows for the direct visualization of the diaphragm and its motion. Still, its effectiveness depends highly on the operator’s experience and could be limited by gas and abdominal fat. Moreover, ultrasound offers limited information regarding the lung parenchyma. On the other hand, high-resolution CT can be useful in identifying causes of diaphragmatic dysfunction, such as atrophy or eventration. However, it does not allow for the quantitative assessment of diaphragmatic movement and the differentiation between paralysis and dysfunction, especially in bilateral dysfunction, which is often overlooked due to the elevation of both hemidiaphragms. Dynamic Digital Radiography (DDR) has emerged as a valuable and innovative imaging technique due to its unique ability to evaluate diaphragm movement in real time, integrating dynamic functional information with static anatomical data. DDR provides both visual and quantitative analysis of the diaphragm’s motion, including excursion and speed, which leads to a definitive diagnosis. Additionally, DDR offers a range of post-processing techniques that provide information on lung movement and pulmonary ventilation. Based on these findings, the patient was referred to a thoracic surgeon and deemed a candidate for surgical plication of the right diaphragm. Full article

Background: Genetic testing for neurodevelopmental disorders is now considered the standard of care for unexplained epilepsy as well as autism spectrum disorders, intellectual disability, and developmental delays with as many as 50% of individuals identified as having an underlying genetic etiology. Capicua (CIC) is a transcriptional repressor and is widely expressed among human brain tissue. Patients in the literature with pathogenic variants in CIC present with a broad spectrum of phenotypic abnormalities. Common features include epilepsy, developmental delay, intellectual disability, autism spectrum disorder, and MRI abnormalities amongst other neurodevelopmental symptoms. Variant type, age of onset, sex, and severity of manifestation also differ amongst probands. However, the full genotypic and phenotypic spectrum of CIC-related neurodevelopmental disorder has not been elucidated. Methods: Here we review patients reported in the literature with CIC variants and present two additional patients representing a novel genotype and phenotype. Results: Whole exome sequencing (WES) in this proband identified a novel paternally inherited likely pathogenic variant in CIC c.1526del p.(Pro509Hisfs*14). Both proband and father present with isolated epilepsy without other significant neurodevelopmental disorders. A review of the previous literature identified 20 individuals harboring CIC variants; the majority of these individuals present with a combination of neurodevelopmental features. Sixteen distinct variants were identified amongst these 20 patients. Conclusions: This family represents an expansion of the genotypic and phenotypic spectrum of CIC-related neurodevelopmental disorder. This information may lead to clinically actionable management changes for future patients identified with CIC variants considering standard anti-epileptic medication-weaning protocols. Full article

Background: Many COVID-19 survivors still experience long-term effects of an acute infection, most often characterised by neurological, cognitive and psychiatric sequelae. The treatment of this condition is challenging, and many hypotheses have been proposed. Non-invasive vagus nerve stimulation using slow-paced breathing (SPB) could stimulate both central nervous system areas and parasympathetic autonomic pathways, leading to neuromodulation and a reduction in inflammation. The aim of the present study was to evaluate physical, cognitive, emotional symptoms, executive functions and autonomic cardiac modulation after one month of at-home slow breathing intervention. Methods: 6655 healthcare workers (HCWs) were contacted via a company email in November 2022, of which N = 58 HCWs were enrolled as long COVID (cases) and N = 53 HCWs as controls. A baseline comparison of the two groups was performed. Subsequently each case was instructed on how to perform a resonant SPB using visual heart rate variability (HRV) biofeedback. They were then given a mobile video tutorial breathing protocol and asked to perform it three times a day (morning, early afternoon and before sleep). N = 33 cases completed the FU. At T0 and T1, each subject underwent COVID-related, psychosomatic and dysfunctional breathing questionnaires coupled with heart rate variability and manual dexterity assessments. Results: After one month of home intervention, an overall improvement in long-COVID symptoms was observed: confusion/cognitive impairment, chest pain, asthenia, headache and dizziness decreased significantly, while only a small increase in manual dexterity was found, and no relevant changes in cardiac parasympathetic modulation were observed. Full article

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are chronic syndromes of unknown etiology, accompanied by numerous symptoms affecting neurological and physical conditions. Despite frequent revisions of the diagnostic criteria, clinical practice guidelines are often outdated, leading to underdiagnosis and ineffective treatment. Our aim was to identify microRNA (miRNA) biomarkers implicated in pathological mechanisms underlying these diseases. A comprehensive literature review using publicly accessible databases was conducted. Interesting miRNAs were extracted from relevant publications on ME/CFS and/or FM, and were then linked to pathophysiological processes possibly manifesting these chronic diseases. Dysregulated miRNAs in ME/CFS and FM may serve as promising biomarkers for these diseases. Key identified miRNAs, such as miR-29c, miR-99b, miR-128, miR-374b, and miR-766, were frequently mentioned for their roles in immune response, mitochondrial dysfunction, oxidative stress, and central sensitization, while miR-23a, miR-103, miR-152, and miR-320 were implicated in multiple crucial pathological processes for FM and/or ME/CFS. In summary, both ME/CFS and FM seem to share many dysregulated biological or molecular processes, which may contribute to their commonly shared symptoms. This miRNA-based approach offers new angles for discovering molecular markers urgently needed for early diagnosis or therapeutics to tackle the pathology of these medically unexplained chronic diseases. Full article

The term “Medically Unexplained Symptoms” (MUS) describes chronic symptoms for which medical investigations fail to reveal a specific pathology or biomarker. Even as MUS are among the most prevalent chronic health problems in the global north, patients who experience them reside in a nebulous space. Such nebulousness is heightened for women patients. Moreover, women report MUS at higher rates than men. In this review essay, we analyze the medicalization and feminization processes vis-à-vis MUS by focusing on two particular syndromes: Fibromyalgia (FMS) and Long COVID (LC). FMS and LC present clear parallels that allow us to trace an unhappy marriage of women and MUS. We demonstrate how the medical constructions of these two syndromes as knowledge categories are representations of medical uncertainty vis-a-vis women patients. We then scrutinize the resulting gendered consequences of these categories for the illness experience. We conclude our review by calling for a cultural reorientation in our thinking about MUS that centers a recognition that the origins and manifestations of a great deal of human suffering reside outside of medicine’s ways of knowing. In so doing, we connect to foundational claims in medical anthropology and sociology; namely, that illness is more than disease, and health cannot be achieved primarily via biomedical means. Full article

Heart failure (HF) admissions are burdensome, and the mainstay of prevention is the timely detection of impending fluid retention, creating a window for medical treatment intensification. This study evaluated the accuracy and performance of a Triage-HF-guided carepath in real-world ambulatory HF patients in daily clinical practice. In this prospective, observational study, 92 adult HF patients (71 males (78%), with a median age of 69 [IQR 59–75] years) with the Triage-HF algorithm activated in their cardiac implantable electronic devices (CIEDs), were monitored. Following high-risk alerts, an HF nurse contacted patients to identify signs and symptoms of fluid retention. The sensitivity and specificity were 83% and 97%, respectively. The positive predictive value was 89%, and negative predictive value was 94%. The unexplained alert rate was 0.05 alerts/patient year, and the false negative rate was 0.11 alerts/patient year. Ambulatory diuretics were initiated or escalated in 77% of high-risk alert episodes. In 23% (n = 6), admission was ultimately required. The median alert handling time was 2 days. Fifty-eight percent (n = 18) of high-risk alerts were classified as true positives in the first week, followed by 29% in the second–third weeks (n = 9), and 13% (n = 4) in the fourth–sixth weeks. Common sensory triggers included an elevated night ventricular rate (84%), OptiVol (71%), and reduced patient activity (71%). The CIED-based Triage-HF algorithm-driven carepath enables the timely detection of impending fluid retention in a contemporary ambulatory setting, providing an opportunity for clinical action. Full article

(1) Background: Sudden Infant Death Syndrome (SIDS) represents sudden and unexplained deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for a prolonged QTc interval, a marker for Long QT Syndrome (LQTS), should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiograms (ECGs) could identify congenital heart defects (CHDs) early, especially those not detected at birth. Infants with prolonged QTc intervals typically undergo genetic analysis for Long QT Syndrome. (2) Methods: The study involved infants aged 20–40 days, born with no apparent clinical signs of heart disease, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHDs identified immediately after birth, as well as infants who had previously had an ECG or echocardiogram for other medical reasons, were excluded from the study. We used statistical software (SPSS version 22.0) to analyze the data. (3) Results: Of the 42,200 infants involved, 2245 were enrolled, with 39.9% being males. Following this initial screening, 164 children (37.8% males) with prolonged QTc intervals underwent further evaluation. Out of these 164 children, 27 children were confirmed to have LQTS. However, only 18 children were finally investigated for genetic mutations, and mutations were identified in 11 tests. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Treatment options included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%. (4) Conclusions: This screening approach has demonstrated effectiveness in the early identification of LQTS and other cardiac rhythm anomalies, with additional identification of mutations and/or prolonged QTc intervals in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening. Full article

Hybrid machine learning encompasses predefinition of rules and ongoing learning from data. Human organizations can implement hybrid machine learning (HML) to automate some of their operations. Human organizations need to ensure that their HML implementations are aligned with human ethical requirements as defined in laws, regulations, standards, etc. The purpose of the study reported here was to investigate technical opportunities for representing human ethical requirements in HML. The study sought to represent two types of human ethical requirements in HML: locally simple and locally complex. The locally simple case is road traffic regulations. This can be considered to be a relatively simple case because human ethical requirements for road safety, such as stopping at red traffic lights, are defined clearly and have limited scope for personal interpretation. The locally complex case is diagnosis procedures for functional disorders, which can include medically unexplained symptoms. This case can be considered to be locally complex because human ethical requirements for functional disorder healthcare are less well defined and are more subject to personal interpretation. Representations were made in a type of HML called Algebraic Machine Learning. Our findings indicate that there are technical opportunities to represent human ethical requirements in HML because of its combination of human-defined top down rules and bottom up data-driven learning. However, our findings also indicate that there are limitations to representing human ethical requirements: irrespective of what type of machine learning is used. These limitations arise from fundamental challenges in defining complex ethical requirements, and from potential for opposing interpretations of their implementation. Furthermore, locally simple ethical requirements can contribute to wider ethical complexity. Full article