Search Results (27)

A key limitation in contemporary HF management is the marked heterogeneity of the syndrome, driven by diverse pathophysiological mechanisms that are not fully captured by traditional classifications based on left ventricular ejection fraction. Precision medicine has emerged as a promising approach to address this heterogeneity by integrating clinical characteristics, circulating biomarkers, advanced imaging, and computational phenotyping strategies. However, current frameworks predominantly emphasize myocardial dysfunction, while the contribution of vascular abnormalities remains underrepresented. The interaction between the left ventricle and the arterial system plays a fundamental role in cardiovascular performance. Arterial stiffness, commonly assessed by pulse wave velocity (PWV), represents a key determinant of vascular aging and a robust predictor of cardiovascular risk. Increasing evidence suggests that vascular dysfunction contributes significantly to the pathophysiology and clinical expression of HF, particularly in phenotypes characterized by preserved ejection fraction. This review synthesizes current evidence on precision medicine in HF and highlights the emerging role of arterial stiffness and PWV in multidimensional patient phenotyping. We propose that integrating vascular parameters into existing phenotyping frameworks may enhance risk stratification, improve mechanistic understanding, and support the development of more personalized therapeutic strategies in heart failure. Unlike previous reviews that have addressed arterial stiffness or heart failure phenotyping separately, this work uniquely integrates ventricular–vascular interaction and pulse wave velocity into a comprehensive precision medicine framework for heart failure. By bridging vascular physiology with data-driven phenotyping strategies, this review provides a novel conceptual model for incorporating arterial stiffness into multidimensional patient characterization across the full spectrum of heart failure phenotypes. Full article

Stiff person syndrome (SPS) is an autoimmune disorder with muscle stiffness and spasms, for which current therapies provide incomplete relief. Botulinum neurotoxin (BoNT) has been explored as an adjunctive symptomatic treatment. The aim of this review was to critically evaluate the clinical evidence for BoNT therapy in SPS. Using Medline, Scopus and Google Scholar, we identified nine reports that were published up to 1 January 2026. English articles and articles with information on study type, type/dose of BoNT and treatment results were included. One study was double-blind and placebo-controlled, one was retrospective and seven were single-case reports, comprising 46 patients. Open-label trials used botulinumtoxin-A (Botox, Dysport or Xeomin), while the blind study applied abobotulinumA (Dysport). All but one study (a case report) demonstrated motor improvement and a reduction in painful spasms associated with patient satisfaction. Reported doses ranged from 300 to 800 units for onabotulinumtoxinA and incobotulinumtoxinA and from 700 to 1000 units for abobotulinumtoxinA. The literature highlights the need for randomized clinical trials in larger cohorts, with careful selection of dose, injection sites, and adjunct physiotherapy, as well as an evaluation of early BoNT therapy in SPS. The novelty of this review lies in its critical synthesis of reported data and inclusion of most recent reports. Full article

Background: Heart failure (HF) is a systemic syndrome characterized by venous congestion, which critically involves the splanchnic circulation. Conventional assessment methods often lack sensitivity for early or regional congestion. Methods: We conducted a systematic review of studies utilizing contrast-enhanced ultrasound (CEUS) and shear wave elastography (SWE) to evaluate congestion in adult HF patients, synthesizing evidence up to July 2025. Results: The integrated evidence demonstrates that CEUS and SWE provide distinct, complementary quantitative data. CEUS acts as a functional pillar, detecting microvascular congestion through parameters like prolonged hepatic vein transit time. SWE serves as a structural pillar, quantifying tissue stiffness that correlates with central venous pressure, tracks decongestion, and independently predicts adverse outcomes. Together, they differentiate reversible hemodynamic congestion from irreversible fibrotic remodeling across the liver, spleen, kidneys, and heart. Conclusions: Integrating CEUS and SWE into a multi-parametric ultrasound framework provides a comprehensive, bedside assessment of systemic congestion in HF. This approach enhances early detection, improves risk stratification, and offers a potential tool for guiding and monitoring personalized decongestive therapy, representing a significant advancement in holistic HF management. Full article

Phosphate is emerging as an active mediator of oxidative stress and vascular injury in chronic kidney disease (CKD). This emerging pathophysiological framework, referred to as “Phosphatopathy”, describes the systemic syndrome driven by chronic phosphate overload and characterized by oxidative stress, inflammation, endothelial dysfunction, vascular calcification, cellular senescence, and metabolic imbalance. Beyond being a biochemical marker, phosphate overload triggers NOX-derived reactive oxygen species (ROS), activates Wnt/β-catenin and TGF-β signaling, and disrupts the FGF23–Klotho axis, promoting endothelial dysfunction, vascular calcification, and left ventricular hypertrophy (LVH). These pathways converge with systemic inflammation and energy imbalance, contributing to the malnutrition–inflammation–atherosclerosis (MIA) syndrome. Experimental and clinical data reveal that the phosphate/urinary urea nitrogen (P/UUN) ratio is a sensitive biomarker of inorganic phosphate load, while emerging regulators such as microRNA-125b and calciprotein particles integrate phosphate-driven oxidative and inflammatory responses. Therapeutic strategies targeting phosphate burden—rather than serum phosphate alone—include dietary restriction of inorganic phosphate, non-calcium binders, magnesium and zinc supplementation, and activation of important pathways related to the activation of antioxidant defense such as AMP-activated protein kinase (AMPK) and SIRT1. This integrative framework redefines phosphate as a modifiable upstream trigger of oxidative and metabolic stress in CKD. Controlling phosphate load and redox imbalance emerges as a convergent strategy to prevent vascular calcification, improve arterial stiffness, and reduce cardiovascular risk through personalized, mechanism-based interventions. Full article

Background: Antibodies to glutamic acid decarboxylase (anti-GAD) can give rise to stiff person syndrome (SPS), an infrequent autoimmune condition of the central nervous system marked by fluctuating muscular rigidity and stimulus-evoked spasms. Disturbances in eye-movement control are rarely identified yet may provide insight into underlying neural involvement. Methods: Two individuals with anti-GAD-related SPS showing distinctive ocular-motor abnormalities were examined with quantitative videonystagmography, supplemented by representative video documentation. Results: Recordings demonstrated varied patterns of ocular-motor disturbance, including reduced smooth-pursuit accuracy, delayed saccadic initiation, dysmetria, intrusive saccades, and several nystagmus types. Partial improvement occurred after immunomodulatory therapy. Conclusions: These findings extend current understanding of the anti-GAD SPS phenotype and indicate that quantitative analysis of eye movements may offer a sensitive, non-invasive marker of disease activity. Larger, prospective studies are needed to clarify prevalence and responsiveness to treatment. Full article

Hypermobile Ehlers–Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) are increasingly recognized as complex, multisystem connective tissue disorders characterized by joint hypermobility and instability, chronic pain, autonomic dysfunction, immune dysregulation, and structural fragility. Despite their clinical impact and prevalence, the underlying pathophysiology remains poorly understood, and diagnosis is frequently delayed or missed altogether. Emerging research highlights the fascia as a central player in the pathogenesis of these conditions. This narrative review synthesizes current molecular, histological, and biomechanical findings to propose a fascia-centered framework for understanding hEDS and HSD. Evidence from transcriptomic and imaging studies reveals consistent abnormalities in fascial thickness, interfascial gliding, myofibroblast activation, tendon elongation, and tissue stiffness—findings that mirror the functional impairments reported in clinical populations. We explore fascia as a dynamic tissue network and consider how dysregulation in these processes may contribute to the widespread symptoms seen in hypermobility disorders. By reframing hEDS and HSD as disorders of pathological fascial remodeling, this review offers an integrated model that connects molecular mechanisms with clinical expression. It underscores the urgent need for multidisciplinary research to define diagnostic biomarkers, clarify therapeutic targets, and support the development of more effective, personalized interventions. Full article

SPS is characterized by progressive spasmodic muscular rigidity. SPS is thought to be an autoimmune disease with a prominent feature of antibodies against glutamic acid decarboxylase (GAD). GAD is responsible for the enzymatic conversion of glutamic acid (glutamate) into the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Reduced GABA activity leads to increased excitability in the central nervous system, resulting in muscle rigidity and spasms characteristic of SPS. While SPS is rare, anti-GAD antibodies seen in SPS are also seen in the much more common autoimmune disease, type 1 diabetes (T1D). There is evolving research showing that the anti-GAD antibodies of T1D are produced in response to the presence of mycobacterial heat shock protein 65 (mHSP65), and the mHSP65 is produced in response to an occult infection by a bacterium, Mycobacterium avium subspecies Paratuberculosis (MAP). Humans are broadly exposed to MAP in food, water, and air. There are linear and conformational similarities between the epitopes of GAD and mHSP65. This article proposes that MAP is also an infectious trigger for SPS. Dehydroepiandrosterone (DHEA) is a principal component of the steroid metabolome; it plateaus in young adults and then steadily declines. Bromo-epi-androsterone (BEA) is a potent synthetic analog of DHEA; unlike DHEA, it is non-androgenic, non-anabolic, and an effective modulator of immune dysregulation. BEA is also an anti-infective agent and has been shown to benefit mycobacterial infections, including tuberculosis and leprosy. With the immune stabilizing capacity of BEA as well as its anti-mycobacterial properties, there is reason to believe that a randomized clinical trial with BEA may be beneficial for SPS. Full article

Background and Objectives: Fibromyalgia syndrome (FMS) is defined as a chronic pain syndrome that is characterized by widespread pain, tenderness, and diffuse stiffness. In addition, neuropsychological symptoms such as fatigue, sleep disorders, poor mood, cognitive impairment, and headaches are often reported. Many reports have addressed the coexistence of affective disorders and anxiety with FMS, yet few have focused on its association with obsessive compulsive disorder (OCD). We investigated the occurrence of classical patterns of OCD in participants with FMS and assessed their effect on pain perception and functional impairment. Material and Methods: The research population included 37 patients diagnosed with FMS, treated at the Rheumatology Clinic in the Sheba Medical Center, Tel-Hashomer, Israel. We used validated questionnaires including a demographic questionnaire, a questionnaire on average and maximal pain intensity, the Eysenck Personality Questionnaire-Revised (EPQ-R), the Perceived Stress Scale, the Pain Catastrophizing Scale, the Pain Obsessive questionnaire, and the Yale–Brown Obsessive Compulsive Scale (Y-BOCS). Results: Patients with FMS were found to have intrusive and obsessive thoughts regarding pain for several hours every day, causing a high degree of anxiety and high levels of pain, catastrophizing, and magnification, leading to helplessness and functional impairment. In total, 27% of the patients reported severe malfunction due to pain and pain ideation, and 49% demonstrated mild obsessive compulsive symptoms that were strongly correlated with pain intensity and functional impairment. Conclusions: Obsessive compulsive thinking patterns contribute to pain magnification and to the cognitive aspects of fibromyalgia syndrome. Full article

Introduction: Anti-GAD65 antibodies are associated with several neurological phenotypes. Antibody titers are increasingly recognized as useful in diagnosis and prognosis. Objective: To describe a Portuguese cohort of patients with anti-GAD65-associated neurological syndromes. Methods: Retrospective analysis of all patients with positive anti-GAD65 antibodies and associated neurological syndromes followed in a tertiary referral center. Results: Nineteen anti-GAD65 antibody-positive neurological patients were identified, 62.3% female, with a mean age of onset of 56.0 (SD = 13.3) years. Comorbid autoimmune disorders were present in seven patients. Six patients had limbic encephalitis (31.6%), four had epilepsy (21.1%), four had cerebellar ataxia (21.1%), and three had stiff-person syndrome (15.8%). Two patients presented with isolated cognitive dysfunction (executive and mnesic) in the absence of other neurological symptoms. The mean follow-up time was 24.0 (14.0–42.0) months, at the end of which the mean modified Rankin Scale (mRS) value was 2.0 (1.0–4.0). Screening for malignancies was negative in all patients. Serum quantitative analysis was carried out in 18 patients, 10 of whom showed titers above previously defined cut-off points (>10,000 IU/L for ELISA and >20 mmol/L for RIA). Quantitative CSF analysis was performed in nine patients, with four showing above-threshold titers. There was no association between anti-GAD65 levels and clinical phenotype or the final mRS values. High-dose intravenous methylprednisolone and oral prednisolone were the most common acute and chronic treatment regimens, respectively. Conclusion: Anti-GAD65 antibodies are associated with varied neurological syndromes, and antibody titers alone should not be used to exclude a disease. Full article

Stiff-person syndrome is rare and disabling autoimmune condition that most frequently affects women, with no real predisposition by race. Diagnosis is often arduous, which is why patients concomitantly suffer from anxiety and depression. To date, drug therapy is based on the use of benzodiazepines, barbiturates, and baclofen. Refractory cases are treated with intravenous immunoglobulin, plasmapheresis, B lymphocyte depletion with rituximab, and even the implantation of intrathecal baclofen devices. Botulinum toxin injection is frequently used, even if it still has an unclear role in the literature. Our case report aims to demonstrate the efficacy of a combined treatment of botulinum toxin and therapeutic exercise in a 65-year-old patient with biceps brachii muscle hypertonia and diffuse spasms of the axial musculature, using rating scales such as the Numeric Rating Scale (NRS) and Modified Ashworth Scale (MAS), joint range of motion (ROM) measurement, and muscle dynamic stiffness mensuration, which is performed by using the MyotonPro^®. All the assessments were conducted at the first evaluation (T0), soon after the combined treatment with botulin toxin and therapeutic exercise (T1), three months (T2), six months (T3), and eight months after the botulinum toxin injection (T4). The patient demonstrated benefits for more than 6 months with no side effects. The combined therapy of botulinum toxin and therapeutic exercise had an excellent result in our patient. Full article

Schizophrenia spectrum disorders (SSD) are a group of diseases characterized by one or more abnormal features in perception, thought processing and behavior. Patients suffering from SSD are at risk of developing life-threatening complications. Pharmacogenetic studies have shown promising results on personalized treatment of psychosis. In the current study, 103 patients diagnosed with SSD treated with risperidone as antipsychotic monotherapy were enrolled. Socio-demographics and clinical data were recorded, and laboratory tests and genotyping standard procedure for cytochrome P450 (CYP) 2D6*4 were performed. Patients were evaluated by the Positive and Negative Syndrome Scale (PANSS) on admission and at discharge. Based on the reduction in the PANSS total score, subjects were divided into non-responders, partial responders and full responders. Only 11 subjects had a full response to risperidone (10.67%), 53 subjects (51.45%) had a partial response, and 39 participants (37.86%) were non-responders. Patients at first episode psychosis showed significantly higher levels of blood glucose and prolactin levels, while chronic patients showed significantly higher LDL levels. Adverse drug reactions (ADR) such as tremor and stiffness significantly correlated with genetic phenotypes (p = 0.0145). While CYP2D6 showed no impact on treatment response, ADR were significantly more frequent among poor and intermediate metabolizers. Full article

Antibodies to glutamic acid decarboxylase (GAD) have been predominantly associated with stiff-person syndrome (SPS), which is often accompanied by organ-specific autoimmune diseases, such as late-onset type 1 diabetes. Autoimmune retinal pathology in SPS has recently been suggested to coexist in patients suffering from this disease; however, evidence reporting potential treatment options for the neurological and visual symptoms these patients experience remains scarce. We provide a review of the relevant literature, presenting a rare case of a middle-aged woman with autoimmune retinopathy (AIR) followed by stiff-leg syndrome who responded to intravenous immune globulin treatment (IVIg). Our report adds to previously reported data supporting the efficacy of IVIg in SPS spectrum disorders while also proposing the potential effect of IVIg in treating SPS spectrum patients with coexisting AIR. Full article

Stiff person spectrum disorders (SPSD) are paradigm autoimmune movement disorders characterized by stiffness, spasms and hyperekplexia. Though rare, SPSD represent a not-to-miss diagnosis because of the associated disease burden and treatment implications. After decades as an enigmatic orphan disease, major advances in our understanding of the evolving spectrum of diseases have been made along with the identification of multiple associated autoantibodies. However, the most important recent developments relate to the recognition of a wider affection, beyond the classic core motor symptoms, and to further insights into immunomodulatory and symptomatic therapies. In this review, we summarize the recent literature on the clinical and paraclinical spectrum, current pathophysiological understanding, as well as current and possibly future therapeutic strategies. Full article

Paraneoplastic neurological syndromes (PNS) include any symptomatic and non-metastatic neurological manifestations associated with a neoplasm. PNS associated with antibodies against intracellular antigens, known as “high-risk” antibodies, show frequent association with underlying cancer. PNS associated with antibodies against neural surface antigens, known as “intermediate- or low-risk” antibodies, are less frequently associated with cancer. In this narrative review, we will focus on PNS of the central nervous system (CNS). Clinicians should have a high index of suspicion with acute/subacute encephalopathies to achieve a prompt diagnosis and treatment. PNS of the CNS exhibit a range of overlapping “high-risk” clinical syndromes, including but not limited to latent and overt rapidly progressive cerebellar syndrome, opsoclonus-myoclonus-ataxia syndrome, paraneoplastic (and limbic) encephalitis/encephalomyelitis, and stiff-person spectrum disorders. Some of these phenotypes may also arise from recent anti-cancer treatments, namely immune-checkpoint inhibitors and CAR T-cell therapies, as a consequence of boosting of the immune system against cancer cells. Here, we highlight the clinical features of PNS of the CNS, their associated tumors and antibodies, and the diagnostic and therapeutic strategies. The potential and the advance of this review consists on a broad description on how the field of PNS of the CNS is constantly expanding with newly discovered antibodies and syndromes. Standardized diagnostic criteria and disease biomarkers are fundamental to quickly recognize PNS to allow prompt treatment initiation, thus improving the long-term outcome of these conditions. Full article

Glutamic acid decarboxylase (GAD) antibody-related encephalitis is an autoimmune disease associated with intracellular neuronal antigens. We report on a rare case of GAD antibody-associated encephalitis complicated with focal segmental stiffness-person syndrome (SPS) in a middle-aged woman. The disease course lasted for >10 years, initially presenting with drug-resistant epilepsy, followed by stiffness of the right lower limb, and right upper limb involvement. The patient experienced anxiety and depression symptoms due to long-term illness. During hospitalization, serum and cerebrospinal fluid GAD antibodies were positive and no tumor was found. The symptoms were significantly relieved after corticosteroid therapy and intravenous immunoglobulin immunomodulation therapy. To the best of our knowledge, this case is the first to discuss the early recognition and treatment of chronic epilepsy and focal segmental SPS caused by anti-GAD antibody-related encephalitis. Full article