Search Results (131)

Background: Hantavirus pulmonary syndrome (HPS), also designated hantavirus cardiopulmonary syndrome, is caused by New World hantaviruses, principally Sin Nombre virus in North America and Andes virus in South America. The syndrome is characterized by rapidly progressive noncardiogenic pulmonary edema and myocardial depression, with case fatality rates of 25% to 40%. A 2026 outbreak aboard an expedition cruise ship in the South Atlantic, comprising 13 cases and three deaths, confirmed that Andes virus can be transmitted between humans in a confined setting remote from the rodent reservoir. Methods: Virological, pathophysiological, clinical, and therapeutic aspects of HPS were reviewed, with particular emphasis on cardiopulmonary mechanisms. Sources were identified through PubMed, Scopus, and Google Scholar, with priority given to original research articles, clinical series, and controlled trials published through 2025. Literature published in English and Spanish was included. Results: Pathogenic hantaviruses enter endothelial cells and platelets via αvβ3 integrins, disrupting the VEGF-VEGFR2 signaling axis and rendering endothelial cells hypersensitive to physiological VEGF concentrations. Expansion of CD8+ T cells and activated macrophages releases TNF-alpha, IFN-gamma, and nitric oxide, amplifying microvascular permeability and contributing to myocardial depression. Autopsy studies demonstrate direct hantaviral myocarditis with viral antigen in cardiac endothelium and interstitial macrophages. Transpulmonary thermodilution confirms simultaneous hypovolemia, reduced global ejection fraction, and elevated extravascular lung water. Because the incubation period is long and the cardiopulmonary phase is substantially immune-mediated, seroconversion precedes rather than follows clinical deterioration, which preserves the diagnostic utility of IgM serology in a disease that can kill within 48 h. VA-ECMO initiated at the first signs of cardiopulmonary decompensation has reported survival rates approaching 80% in selected experienced centers. No antiviral has demonstrated efficacy in controlled trials during the cardiopulmonary phase, and no licensed vaccine exists. Conclusions: HPS produces a mixed shock state through increased microvascular permeability, T cell-mediated immunopathology, and direct myocarditis. Management follows a stepwise algorithm: suspected HPS triggers immediate complete blood count with peripheral blood smear and concurrent hantavirus IgM serology and RT-PCR, followed by ICU admission, conservative fluid resuscitation guided by transpulmonary thermodilution, and early contact with an ECMO-capable center at the first sign of rising lactate, falling cardiac index, refractory shock, arrhythmia, or rapid oxygenation failure. Full article

Anthracycline cardiotoxicity involves early oxidative–inflammatory injury to the myocardium and vasculature. Repurposing anti-inflammatory agents may offer pragmatic cardioprotection. The purpose of this study is to evaluate whether sulfasalazine (SSZ) mitigates doxorubicin (DOX)-induced myocardial and aortic injury in rats. Twenty-eight male Wistar albino rats were randomized to: Control (vehicle, n = 8), DOX (20 mg/kg i.p., single dose; n = 10), and SSZ + DOX (SSZ 300 mg/kg i.p. once daily for 3 days, then DOX 20 mg/kg i.p.; n = 10). At 24 h post-DOX, ECG and invasive blood pressure (BP) were recorded. The heart and thoracic aorta were harvested for histopathology and oxidative stress assays (MDA, SOD, GSH, CAT; composite indices where applicable). Compared with SSZ + DOX, the DOX group exhibited higher BP and greater arrhythmic burden. In the aorta, DOX elevated MDA and reduced SOD, GSH, and CAT versus the control, whereas SSZ + DOX shifted these toward control values. In the myocardium, DOX decreased SOD and increased oxidative index; SSZ + DOX attenuated histological injury (edema, hemorrhage, cardiomyocyte degeneration) and restored aortic intima–media thickness toward control. Heart rate was lower in SSZ + DOX than other groups. Short-course SSZ pretreatment alleviated early DOX-induced oxidative stress and structural damage in myocardial and aortic tissues, with concurrent improvement in hemodynamic and ECG profiles. These data support further dose–timing optimization and longer-term functional studies to define SSZ’s translational potential as an adjunct cardioprotective strategy during anthracycline exposure. Full article

Background: Cardiac involvement in cryoglobulinemia (CG) is rare but potentially fatal, and its clinical spectrum remains poorly characterized. Methods: This retrospective study enrolled 11 patients with cardiac involvement among 885 patients with CG at Peking Union Medical College Hospital between January 2015 and March 2026. We analyzed its clinical characteristics, radiological features and management. Results: Among 885 CG patients, 11 (1.2%; 4 type I, 7 type II) had cardiac involvement. Cardiac symptoms included dyspnea (n = 6), chest tightness (n = 4), edema (n = 3), and orthopnea (n = 1). All patients had elevated N-terminal pro-B-type natriuretic peptide (median 29,799 pg/mL). Echocardiography, performed in all 11 patients, revealed left heart enlargement (n = 9), reduced left ventricular ejection fraction (n = 7), myocardial disease (n = 6), pericardial effusion (n = 4), and pulmonary hypertension (n = 3). Cardiac magnetic resonance in 5 of 11 patients showed non-ischemic late gadolinium enhancement in two cases. For first-line therapy, 6 of 11 patients received rituximab-based regimens, 3 of 11 received bortezomib-based regimens, and 1 of 11 received antiviral therapy with corticosteroids; 1 patient declined treatment. All 10 treated patients achieved initial cardiac improvement, with 5 relapsing and 2 dying during a median follow-up of 57 months (range 9–130 months). The estimated 4-year overall and progression-free survival rates were 77.9% (95% CI: 0.546–1.000) and 50.0% (95% CI: 0.269–0.929), respectively. Conclusions: Cardiac involvement in CG is rare and associated with diverse structural and functional abnormalities. Cardiac involvement should be considered in CG patients presenting with unexplained cardiac manifestations after excluding alternative causes. B-cell-targeted therapy induced an initial response, but relapse is common. Early intervention is essential given the substantial relapse burden and potential for severe morbidity. Full article

Introduction: Otorrhagia is an uncommon finding in forensic practice and is classically associated with skull base fractures, temporal bone trauma, or barotraumatic events. However, the literature suggests that ear bleeding may also rarely occur in deaths due to neck compression, including strangulation and hanging. Case Presentation: We report the case of a man died by hanging. External examination revealed an oblique ligature mark on the neck, conjunctival petechiae, and bilateral otorrhagia. At autopsy, no fractures of the skull vault or skull base were identified. Otoscopic examination showed bilateral tympanic membrane laceration. Internal examination of the neck disclosed small hemorrhagic infiltrates in the perithyroid muscles and prevertebral soft tissues, as well as bilateral carotid intimal tears consistent with Amussat’s sign. Moreover, a unilateral lesion involving the petrous portion of the temporal bone was observed. The distinctive feature of this case is the association of bilateral otorrhagia, bilateral tympanic membrane laceration, and unilateral petrous bone erosion in the absence of skull base fracture. Histology showed visceral congestion, pulmonary overdistension with rupture of interalveolar septa, cerebral edema, myocardial fiber fragmentation and trabecular remodeling and areas of necrosis of the bone fragment sampled from the right petrous temporal bone. Death was attributed to mechanical asphyxia due to hanging. Conclusions: This case suggests that bilateral otorrhagia in hanging may result from the combined effects of impaired cervico-cephalic venous drainage and pressure changes transmitted to the middle ear during forceful respiratory efforts. The pre-existing unilateral petrous bone lesion may have acted as a local predisposing factor, although its etiology and actual contribution cannot be established with certainty. Otoscopic examination should therefore be regarded as a potentially useful adjunct in selected cases, particularly for documenting auricular findings and supporting differential diagnosis. Full article

Takotsubo syndrome (TTS) is an acute disorder characterized by transient left ventricular dysfunction with typical regional wall motion abnormalities, most commonly apical ballooning. It accounts for 1–3% of all suspected acute coronary syndromes and up to 5–6% in women presenting with ST-segment elevation myocardial infarction requiring coronary angiography to exclude obstructive coronary artery disease. The pathophysiology of TTS is complex and not fully elucidated, with sympathetic hyperactivation playing a central role through calcium dysregulation, oxidative stress, and metabolic alterations. Both clinical and experimental data demonstrate the importance of inflammation, with cell infiltration and persistent immune activation exceeding the acute phase. Increasing evidence highlights the impact of coronary microvascular disfunction (CMVD) as a secondary phenomenon, with some findings that support its role as a causative substrate. Beyond well-known predisposing conditions such as female sex, postmenopausal age, and neurological and psychiatric disorders with the trigger of a physical or psychological event, numerous case reports associate the syndrome with chronic autoimmune diseases, even if clear experimental evidence remains poor and worthy of further study. Echocardiography and advanced imaging techniques, including cardiac magnetic resonance and positron emission tomography, have provided insights into transient CMVD, reversible myocardial edema, and metabolic impairment, strengthening our knowledge of the syndrome as a dynamic process. It is also of growing interest to perform invasive hemodynamic assessment to explain the increase in microvascular resistance. This review offers a comprehensive and up-to-date overview of these techniques in the context of TTS. Since clinically, TTS may be associated with significant morbidity and mortality, with some unexplained cases of long-term myocardial disfunction or even recurrence, a deeper understanding of the interplay between catecholamines, inflammation, immune substrate, and CMVD may improve risk stratification and lead to the development of targeted therapeutic strategies. Full article

Cardiomyopathies are traditionally classified by structural and genetic phenotypes, but emerging evidence highlights chronic myocardial inflammation as a pivotal driver of disease progression across different etiologies. This review synthesizes the current literature on the cellular and molecular inflammatory mechanisms underlying hypertrophic cardiomyopathy, Anderson–Fabry disease, cardiac amyloidosis, arrhythmogenic cardiomyopathy, and dilated cardiomyopathy. Across these distinct conditions, endogenous triggers such as metabolic substrates, misfolded amyloid fibrils, mechanical stress, or viral genomes act as damage-associated molecular patterns. These stimuli activate innate and adaptive immune cascades, notably the Toll-like receptors, the NF-κB pathway, and the NLRP3 inflammasome. This immune activation establishes a pro-inflammatory microenvironment that promotes fibroblast reprogramming, myocardial edema, and progressive fibrotic or fibro-fatty remodeling. Inflammation is an active, core pathophysiological mechanism rather than a passive secondary bystander in cardiomyopathies. Recognizing these shared immune pathways provides a framework for improved risk stratification and highlights the potential for targeted immunomodulatory therapies to alter disease trajectories. Full article

Myocardial scar and edema segmentation from multi-sequence cardiac magnetic resonance (MS-CMR) is important for myocardial infarction assessment, but remains challenging due to heterogeneous modal characteristics, severe class imbalance, and the small, ambiguous nature of pathological regions. To address these issues, a dynamic synergistic segmentation network (DSS-Net) is proposed for myocardial pathology segmentation. The framework adopts a coarse-to-fine strategy, in which a coarse stage first segments the myocardium to provide anatomical priors and region constraints, and a fine stage then delineates scar and edema within the myocardium-aware space. In addition, a Modality Dynamic Fusion Module (MDFM) is designed to adaptively emphasize pathology-relevant modal information, and a Stage Feature Aggregation Module (SFAM) is introduced to enhance cross-stage feature interactions and fine-grained lesion representation. Experiments on the MyoPS 2020 and MyoPS 2024 datasets demonstrate that DSS-Net achieves competitive and balanced performance, reaching Dice scores of 0.706 for scar and 0.753 for edema on MyoPS 2020. Additionally, compared with SOTA methods in the MyoPS 2020 Challenge, the proposed method attains comparable scar segmentation performance while maintaining a more balanced trade-off between sensitivity and specificity. These findings suggest that combining anatomical guidance with pathology-aware multi-modal learning is a promising strategy for robust myocardial pathology segmentation in MS-CMR images. Full article

Background: Heart failure patients are frequently prescribed SGLT2 inhibitors, but the incremental real-world benefit of adding GLP-1 receptor agonists is uncertain. Methods: A retrospective propensity-matched cohort study was conducted using the TriNetX Global Collaborative Network (171 healthcare organizations). Adults aged ≥18 years with incident heart failure who initiated either dual SGLT2 inhibitor and GLP-1 receptor agonist therapy or SGLT2 inhibitor monotherapy within 1 month of the first heart failure diagnosis were compared. Outcomes over 365 days included all-cause mortality, all-cause hospitalization, acute myocardial infarction, atrial fibrillation/flutter, acute kidney failure, pulmonary edema, new-onset diuretic use, urinary tract infection, retinopathy, and laboratory hypoglycemia (glucose ≤ 70 mg/dL). Cox proportional hazards models were used; the proportional hazards assumption was formally tested. Bonferroni and Benjamini–Hochberg adjustments were applied for multiple comparisons. E-values quantified robustness to unmeasured confounding. Appendicitis was used as a negative control outcome. Results: After 1:1 propensity score matching, 3421 patients were included in each cohort. Cohorts were well-balanced (all standardized mean differences < 0.10). Over 365 days of follow-up, no significant differences were observed between dual therapy and monotherapy in all-cause mortality (HR 0.92, 95% CI 0.77–1.09), all-cause hospitalization (HR 1.16, 95% CI 0.96–1.40), acute myocardial infarction (HR 1.20, 95% CI 0.92–1.55), atrial fibrillation/flutter (HR 1.05, 95% CI 0.85–1.30), acute kidney failure (HR 1.05, 95% CI 0.89–1.26), new-onset diuretic use (HR 0.92, 95% CI 0.78–1.09), or urinary tract infection (HR 1.16, 95% CI 0.90–1.48). Dual therapy was associated with a significant increase in retinopathy (HR 2.66, 95% CI 1.81–3.93; Bonferroni p = 0.001; E-value 4.77, lower CI bound 3.01), and a modest increase in laboratory hypoglycemia (HR 1.22, 95% CI 1.04–1.44) and pulmonary edema (HR 1.35, 95% CI 1.06–1.70), both of which survived FDR but not Bonferroni adjustment. Prespecified subgroup analyses showed lower mortality with dual therapy in patients aged 18–64 (HR 0.64, 95% CI 0.43–0.93) and in women (HR 0.60, 95% CI 0.45–0.81). The negative control outcome (appendicitis) was non-significant. Conclusions: In a propensity-matched real-world cohort with a conservative cohort definition, dual SGLT2 inhibitor and GLP-1 receptor agonist therapy was not associated with significant differences in mortality or major cardiovascular outcomes compared with SGLT2 inhibitor monotherapy. Subgroup signals favoring dual therapy in younger and female patients, alongside safety signals for retinopathy and laboratory hypoglycemia, are hypothesis-generating and should be confirmed in prospective trials. Full article

Cancer therapies have significantly improved survival but are frequently limited by cancer therapy-related cardiovascular toxicity (CTR-CVT). Cardiovascular imaging plays a central role in baseline risk stratification, surveillance during therapy and long-term follow-up. Transthoracic echocardiography (TTE) remains the first-line imaging modality; however, conventional parameters such as left ventricular ejection fraction (LVEF) often fail to detect early myocardial injury. Myocardial deformation imaging, particularly global longitudinal strain (GLS), has emerged as a sensitive marker of subclinical dysfunction across multiple cardiotoxic phenotypes. Cardiac magnetic resonance (CMR) further enhances diagnostic accuracy through tissue characterization techniques, enabling the detection of myocardial edema, inflammation, and fibrosis before overt functional decline. Different anticancer therapies induce distinct pathophysiological mechanisms of injury, each associated with characteristic imaging patterns. Emerging imaging biomarkers and multimodality approaches may improve early detection, the spatial characterization of myocardial injury and individualized surveillance strategies. Pediatric patients represent a uniquely vulnerable population due to their myocardial immaturity, altered pharmacokinetics and prolonged post-treatment life expectancy, resulting in a higher cumulative lifetime cardiovascular risk. In conclusion, a mechanism-based multimodality imaging approach integrating echocardiography, CMR and emerging data-driven technologies is essential to optimize early detection, risk stratification and long-term cardiovascular outcomes in both adult and pediatric cardio-oncology populations. Full article

Ezrin, expressed by the EZR gene, is a member of the ERM protein family that connects the plasma membrane to the actin cytoskeleton, participating in processes such as cell adhesion, migration, and signaling. However, its role in cardiac morphogenesis remains incompletely understood. In zebrafish (Danio rerio), two ezrin homologs, ezra and ezrb, are present. CRISPR/Cas9 gene editing technology was used to generate ezra knockout lines, and the simultaneous knockdown of ezra and ezrb was induced via morpholino oligonucleotides (MOs). To investigate the molecular mechanisms, transcriptome sequencing and bioinformatic analysis were conducted on 48 h post-fertilization (hpf) ezrin–MO embryos, with subsequent validation using a real-time quantitative polymerase chain reaction (RT-qPCR) and whole-mount in situ hybridization (WISH) experiment. The results showed that ezra^−/− exhibited a compensatory upregulation of ezrb without overt developmental defects, whereas ezrin–MO embryos presented with pericardial edema, reduced cardiac chamber size, and atrioventricular valve malformations at 48 hpf. RNA-seq revealed that myocardial contraction-related genes were significantly dysregulated and apoptotic signaling pathways were activated in ezrin–MO embryos. These findings demonstrate that ezra and ezrb are functionally redundant in cardiac development and that the loss of ezrin function may lead to cardiac developmental defects and impaired myocardial contractility via the activation of apoptotic signaling pathways. Full article

Background: Autoimmune rheumatic diseases (ARDs) often present diagnostic challenges, particularly in undifferentiated disease or overlap syndromes. Autoantibodies (AABs) serve as early biomarkers, but their relationship with cardiac involvement during the prodromal phase remains unclear. We hypothesized that cardiac involvement is an early, unifying feature in AAB-seropositive patients with suspected ARD/overlap syndromes but an as-of-yet unclear diagnosis. Methods: We prospectively recruited 18 treatment-naïve patients (mean age 52 ± 17 years, 94.4% women) with suspected undifferentiated ARD/overlap syndromes who were seropositive for myositis-specific (MSAs), myositis-associated (MAAs), or scleroderma-specific autoantibodies (SScSAs). All underwent comprehensive rheumatologic, pulmonologic, and cardiac evaluations, including multiparametric cardiovascular magnetic resonance (CMR) to assess myocardial inflammation, edema, and fibrosis. Results: Despite normal echocardiograms, electrocardiograms, and inflammatory biomarkers, all patients exhibited CMR evidence of cardiac involvement. Active myocardial inflammation (revised Lake Louise criteria) was confirmed in 66.7%, while subepicardial fibrosis was universal (median 5.0% of LV mass). During the 12-month follow-up, all patients with evidence of inflammation received immunosuppressive and cardioprotective therapy, leading to symptomatic improvement in all and reduced inflammation in 75% of repeat CMRs (3/4 patients). A definitive rheumatologic diagnosis was established in all cases, with 50% classified as overlap syndromes. Conclusions: Cardiac involvement is a highly prevalent disease manifestation in AAB-seropositive patients with suspected ARD/overlap syndromes and can be detected by CMR during the prodromal phase, even before diagnostic criteria are met. These findings support early CMR integration in the workup of such patients to guide timely immunosuppressive and cardioprotective interventions. Full article

Cardiogenic shock secondary to acute myocardial infarction complicated by mechanical failure remains associated with high mortality despite advances in cardiac surgery and mechanical circulatory support. We report the case of a 42-year-old patient with posterior papillary muscle rupture leading to severe mitral regurgitation, managed with emergency surgical intervention and extracorporeal membrane oxygenation. The patient, with a history of Type I Bipolar Disorder under long-term lithium therapy and chronic Cannabis use, presented in critical condition with cardiogenic shock (Killip IV), acute pulmonary edema, and ST-segment elevation myocardial infarction in the infero-posterior territory. Coronary angiography revealed right coronary artery occlusion and involvement of an obtuse marginal branch. Emergency mitral valve replacement with a mechanical prosthesis and aortocoronary bypass were performed. Due to failure to wean from cardiopulmonary bypass, central veno-arterial ECMO was initiated. The postoperative course was complicated by hemodynamic instability and recurrent pericardial collections requiring repeated surgical interventions and conversion to peripheral ECMO. Multiorgan dysfunction developed, including hepato-renal failure requiring hemofiltration, neurological injury, respiratory impairment, and neuropsychiatric complications. Despite these challenges, progressive recovery was achieved under intensive multidisciplinary management. This case emphasizes the importance of early surgical correction and tailored ECMO support in managing post-infarction mechanical complications. Full article

Introduction: Hyponatremia is common after nontraumatic intracerebral hemorrhage (ICH) and has been associated with worse outcomes, although prior studies have been limited by smaller sample sizes and heterogeneous exposure definitions. This study evaluated the association between severity-stratified hyponatremia and mortality, survival, and complication rates following nontraumatic ICH. Methods: A retrospective cohort study was performed using the TriNetX database. Patients with nontraumatic ICH were stratified by serum sodium measurements obtained within 7 days of diagnosis. Two separate propensity score-matched analyses were conducted: moderate hyponatremia versus normonatremia (17,547 patients per cohort) and severe hyponatremia versus normonatremia (5010 patients per cohort). The primary outcome was 30-day mortality. Secondary outcomes included seizures, cerebral edema, hydrocephalus, external ventricular drain placement, tracheostomy, percutaneous endoscopic gastrostomy (PEG) placement, pulmonary embolism, deep vein thrombosis, ischemic stroke, and myocardial infarction. Statistical significance was set at p < 0.05. Results: Moderate hyponatremia was associated with increased 30-day mortality (17.5% vs. 13.3%; HR 1.324, 95% CI 1.255–1.398; p < 0.001), while severe hyponatremia demonstrated a greater increase in mortality (18.7% vs. 12.9%; HR 1.473, 95% CI 1.332–1.628; p < 0.001). Both cohorts had higher rates of seizures, cerebral edema, hydrocephalus, tracheostomy, PEG placement, deep vein thrombosis, and myocardial infarction compared with matched normonatremic controls. External ventricular drain placement was also more frequent in both cohorts. Pulmonary embolism increased in moderate hyponatremia but was not significantly different in severe hyponatremia. Ischemic stroke occurred less frequently in both cohorts. Conclusions: Moderate and severe hyponatremia were associated with increased mortality and complications in patients with nontraumatic ICH, with stronger associations observed in severe hyponatremia. These findings support serum sodium as a clinically relevant marker for risk stratification and monitoring during acute ICH care. However, causality cannot be established, and whether correction of hyponatremia improves outcomes requires prospective studies. Full article

Background: Heart failure (HF) has traditionally been interpreted through hemodynamic, neurohormonal, and cardiorenal frameworks. Although these models explain many aspects of clinical decompensation, they do not fully account for persistent tissue congestion, unresolved myocardial edema, chronic sterile inflammation, and progressive fibrosis despite optimized therapy. Objectives: To review the anatomy, physiology, and pathobiological relevance of the cardiac lymphatic system in HF and to evaluate whether cardiac lymphatic dysfunction constitutes a mechanistic bridge linking congestion, inflammation, and adverse remodeling. Methods: This narrative review was based on a structured literature search of PubMed/MEDLINE, supplemented by manual backward reference screening and bibliographic verification through journal webpages. The search covered January 2000 to 15 April 2026, with emphasis on 2018 onward and on seminal mechanistic studies. Search domains included cardiac lymphatics, heart failure, lymphangiogenesis, myocardial edema, congestion, inflammation, myocardial infarction, pressure overload, and HFpEF. Results: Cardiac lymphatics regulate myocardial clearance of interstitial fluid, proteins, cytokines, lipids, and immune cells. Preclinical experimental evidence, mainly derived from myocardial infarction, pressure-overload, and lymphatic-insufficiency models, indicates that impaired lymphatic transport or insufficient lymphangiogenic adaptation promotes myocardial edema, inflammatory persistence, fibroblast activation, collagen deposition, and ventricular dysfunction. Human observational and early translational studies suggest that lymphatic dysregulation may also be relevant in selected HF phenotypes, although direct clinical evidence remains limited. Conversely, lymphangiogenic and lymphatic-restorative strategies, especially through the VEGF-C/VEGFR-3 axis, reduce edema, enhance inflammatory resolution, attenuate fibrosis, and improve ventricular performance in preclinical models. Conclusions: Cardiac lymphatic dysfunction provides a compelling conceptual framework that links congestion and inflammation in HF. Rather than acting as a passive bystander, the cardiac lymphatic circulation appears to be an active determinant of myocardial homeostasis and disease progression. Recognition of lymphatic insufficiency as a pathogenic component of HF may open new diagnostic and therapeutic avenues, including tissue-focused decongestion, lymphatic phenotyping, and targeted lymphatic repair. Full article

Background/Objectives: Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is an autosomal recessive lysosomal storage disorder caused by deficiencies in enzymes required for heparan sulfate degradation. While primarily recognized for its devastating neurodegenerative course, the systemic extent of glycosaminoglycan (GAG) accumulation remains under-characterized. This study aims to provide a detailed multisystemic pathological mapping of MPS III to challenge the traditional “brain-only” disease paradigm and highlight the clinical relevance of extracerebral involvement. Methods: We present a comprehensive clinicopathological analysis of a 15-year-old female patient with a history of profound neuropsychomotor delay, refractory epilepsy, and spastic tetraplegia. Following her death due to terminal bronchopneumonia during palliative care, a complete forensic and pathological autopsy was conducted. Tissue samples from all major organ systems were processed using routine Hematoxylin–Eosin (HE) staining, immunohistochemical staining for CD68, and specialized histochemical stains to identify intracellular storage products. Results: Macroscopic evaluation revealed significant diffuse cerebral atrophy, meningoencephalic edema, cardiac valvulopathy with compensatory myocardial remodeling, and hepatosplenomegaly. Furthermore, erosive gastrointestinal lesions and degenerative renal changes were identified. Histopathological examination confirmed widespread cytoplasmic vacuolization across diverse cell populations, including neurons, hepatocytes, renal tubular cells, and the reticuloendothelial system. These findings demonstrate that GAG deposition is a generalized process affecting nearly every parenchymal structure. Conclusions: Although neurological decline dominates the clinical phenotype, our findings underscore that MPS III is a true systemic storage disorder. Significant involvement of the cardiovascular and visceral systems contributes to the disease’s complexity and mortality. This case reinforces the critical diagnostic value of a comprehensive autopsy in delineating the full morphological spectrum of Sanfilippo syndrome, providing essential insights for multidisciplinary management. Full article