Search Results (599)

Background: In Parkinson’s disease (PD), a higher prevalence of polyneuropathy (PNP) is increasingly recognized, although the causal association is still under debate. In contrast, PNP in atypical parkinsonian syndromes (APS) has been insufficiently addressed, despite preliminary evidence suggesting elevated prevalence. Methods: Nerve conduction studies were performed on 13 patients with multiple system atrophy (MSA) and 9 patients with progressive supranuclear palsy (PSP) at baseline. PNP was diagnosed according to standard electrophysiological criteria after exclusion of common secondary causes. Comprehensive clinical evaluation included motor and non-motor assessments over two years of follow-up. Results: At baseline, PNP was present in 53.8% of MSA patients and 66.7% of PSP patients. MSA patients with PNP showed greater motor symptom severity (UPDRS III score; p = 0.046) and worse cognitive performance (MoCA; p = 0.044) compared to those without PNP. Over two years, a significant reduction in the tibial nerve amplitude was observed exclusively in MSA patients (p = 0.039), paralleling disease progression. Conclusions: This study provides the first longitudinal evaluation of clinical and electrophysiological PNP progression in MSA and PSP. A high comorbidity of PNP in patients with APS could contribute to motor and sensory impairments in these patients. Our findings indicate that PNP progression may reflect disease progression in MSA. Given the limited sample size, larger-scale longitudinal studies are needed to further investigate biomarker potential of PNP in APS and to clarify differences in peripheral nerve involvement between synucleinopathies and tauopathies. Full article

Background: Melioidosis, caused by Burkholderia pseudomallei, is a severe and often underdiagnosed infection endemic to South Asia, Southeast Asia, and northern Australia. While pneumonia and sepsis are the classical presentations, the disease is increasingly recognized for its diverse and atypical clinical manifestations. Objective: The objective is to improve diagnostic accuracy and increase clinical awareness in both endemic and non-endemic settings by reviewing and classifying atypical presentations of melioidosis that have been documented in the literature. Methods: A narrative, case-based review was conducted using 238 published case reports and series from endemic and transitional regions during the period from 2000 to 2025. Cases with non-respiratory presentations or anatomical locations not commonly linked to melioidosis were classified as atypical. Clinical syndromes were used to classify the extracted cases, and common patterns in presentation, diagnosis, and outcome were examined. Results: One hundred and sixty published articles were included after a full text review. The most frequent atypical presentations included neurological involvement (e.g., brain abscess, encephalomyelitis), musculoskeletal infections (osteomyelitis, myositis), thyroid abscess, tubo-ovarian abscess, and dermatologic manifestations such as erythema nodosum. Imported and pediatric cases were also found. Numerous cases were misidentified as cancer, fungal infections, or tuberculosis. Among risk factors, diabetes mellitus was the most prevalent. Non-specific symptoms, a lack of laboratory capacity, and incorrect pathogen identification frequently resulted in delays in diagnosis. Conclusions: In endemic areas, melioidosis should be taken into account when making a differential diagnosis of a variety of clinical syndromes, especially in patients who have diabetes or have had relevant environmental exposure. Poor outcomes and diagnostic delays are greatly exacerbated by atypical presentations. Improving diagnostic capabilities and raising awareness are crucial to lessening the worldwide burden of this often ignored but potentially deadly infection. Full article

Background: Aortic dissection (AoD) is a life-threatening medical emergency characterized by the separation of the layers of the aortic wall. The typical clinical presentation of AoD includes intense thoracic pain in the anterior chest or interscapular region, often described as migratory and tearing in nature. However, in rare cases, AoD can present without classic signs but with neurological symptoms, including seizures. Case Presentation: A 60-year-old patient experienced a sudden loss of consciousness followed by a tonic–clonic seizure and subsequently developed right-sided weakness. He had a medical history of hypertension and smoking. Although the symptoms quickly resolved, the brain imaging revealed signs of an acute ischemic stroke located in the left hemisphere. The seizures resumed, blood D-dimer levels were found to be highly elevated, and subsequent thoracic and abdominal computed tomography angiography revealed the presence of AoD, which originated at the proximal part of the ascending aorta. The patient received symptomatic treatment to alleviate his symptoms and prevent complications and was quickly transferred for surgical intervention, resulting in a favorable outcome. Conclusions: This case demonstrates that a tonic–clonic seizure can be the first clinical manifestation of AoD. Such atypical symptoms highlight the diverse and misleading nature of AoD presentations, underscoring the challenges in the diagnostic process. This emphasizes the need for increased clinical vigilance when treating a patient experiencing their first seizure episode. Full article

Background: Neuroimaging protocols for neurotologic disease are often developed without consideration of patient-specific factors such as biological differences, clinical presentation variability, and comorbidities. This lack of tailored design contributes to insufficient detection, delayed diagnosis, and inappropriate treatment. Objectives: To critically examine the literature on diagnostic limitations of neuroimaging for neurotologic lesions and identify gaps in protocol validation, accuracy, and clinical translation. Methods: A systematic review of PubMed and Google Scholar was conducted, focusing on studies published between 2015 and 2025 that evaluated diagnostic imaging outcomes in patients with neurotologic lesions. Eligible studies included prospective cohorts, retrospective analyses, and consensus statements. Outcomes of interest included the sensitivity and specificity of imaging modalities, prevalence of misdiagnosis, and the influence of biological, anatomical, and clinical variability on diagnostic performance. Results: The literature demonstrates that neurotologic disorders are frequently associated with diagnostic challenges, including atypical clinical presentations, overlapping symptoms, and stroke mimics, which complicate image interpretation. Standard magnetic resonance imaging (MRI) protocols often miss subtle or early ischemic changes, resulting in delayed intervention. Few studies stratify outcomes by patient characteristics, and most protocols were developed in generalized populations without comprehensive validation. Evidence on advanced imaging modalities (positron emission tomography (PET), single-photon emission computed tomography (SPECT), high-resolution MRI) remains limited, and large-scale prospective studies addressing diagnostic accuracy gaps are lacking. In summary, a total of 27 studies met inclusion criteria. Conclusions: Current neuroimaging methods are insufficiently validated across diverse patient populations, contributing to the underdiagnosis and mismanagement of neurotologic disease. Improved diagnostic accuracy will require large-scale, prospective research, standardized outcome reporting, and imaging protocols designed to account for patient-specific variability. Full article

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation tool for investigating the neurophysiology of different neurological and neuropsychiatric disorders, including Parkinson’s disease (PD) and other parkinsonian syndromes and movement disorders. Briefly, TMS enables targeted stimulation of specific cortical regions through externally applied magnetic pulses, avoiding surgical intervention (as it occurs in deep brain stimulation) and making it a safe, repeatable, and well-tolerated approach. Over the past two decades, extensive research has explored the clinical utility of TMS in PD, with particular emphasis on motor cortex excitability, synaptic plasticity, and functional connectivity, which are central contributors to both motor and non-motor symptoms in PD patients. In addition, repetitive TMS and related stimulation paradigms have been shown to positively modulate cortical plasticity, i.e., the brain’s capacity to reorganize neural circuits, suggesting potential benefits for longer-term non-pharmacological management and rehabilitation protocols. More recently, studies have also investigated the role of TMS in atypical and secondary parkinsonisms, indicating that it may help characterize distinct neurophysiological abnormalities and provide symptomatic improvement in selected patients. This narrative expert review provides a comprehensive summary of TMS applications across the wide spectrum of parkinsonian syndromes, highlighting not only clinical potential, but also methodological limitations and future research directions. Full article

Tick-borne co-infections are an increasingly recognized and clinically important aspect of Lyme borreliosis, particularly in regions where Ixodes ticks transmit a wide range of bacterial, protozoan, and viral pathogens. In addition to Borrelia burgdorferi sensu lato, these ticks frequently harbor microorganisms such as Babesia spp., Anaplasma phagocytophilum, Ehrlichia spp., Borrelia miyamotoi, Bartonella spp., and several tick-borne viruses. Co-infections may increase disease severity, prolong symptom duration, and contribute to atypical or overlapping clinical presentations, thereby complicating diagnosis and management. Growing evidence from epidemiological studies, clinical case series, and experimental in vivo and in vitro models indicates that pathogen–pathogen and pathogen–host interactions can modulate immune responses and influence disease progression. Diagnostic challenges arise from non-specific clinical features and limitations of current laboratory methods. From a therapeutic perspective, although standard antibiotic regimens for Lyme disease are effective against some bacterial co-infections, they do not provide coverage for protozoan or viral agents, necessitating pathogen-specific and, in some cases, combination treatment strategies. This review synthesizes current knowledge on the epidemiology, clinical impact, diagnostic limitations, and treatment approaches for tick-borne co-infections associated with Lyme disease, and highlights critical evidence gaps and future research directions to improve patient outcomes. Full article

Background and Objectives: Celiac disease (CD) is a major global public health problem that can occur at any age. Pediatric CD can be typical, atypical, or even asymptomatic. Early diagnosis and early initiation of treatment are essential for improving patients’ quality of life and preventing serious complications later in life. However, it is impossible to identify asymptomatic children and adolescents without screening. In this systematic review, we attempted to identify different mass screening programs that have been reported for CD in apparently healthy children and adolescents across the world, to highlight the advantages and disadvantages of such strategies, and to collect and synthesize data from these studies reporting the prevalence of CD. In addition, where data were available, we also attempted to evaluate the diagnostic accuracy of the tests used, their cost-effectiveness, the reported clinical benefits, and follow-up data from individuals identified through screening. Materials and Methods: Electronic databases, including PubMed and Scopus, were systematically searched. Initially, a total of 316 studies were retrieved. Finally, 55 studies met all inclusion criteria and were included in this review. The included studies were published between 1996 and 2023. Results: The reported age of participants ranged from 6 months to 23 years. Confirmation of CD by biopsy was reported in all but six studies. According to the studies that provided data, the (tTG IgA) seroprevalence of CD in apparently healthy children and adolescents, detected through different mass screening methods around the world, ranged from 0.20% (Turkey) to 3.11% (Italy). In addition, the prevalence of biopsy-confirmed CD ranged from 0.036% (Vietnam) to 3% (Sweden and Spain). Studies from 17 countries reported mass screening strategies based on finger-prick rapid tests. All rapid tests detected CD antibodies, except two, which detected HLA DQ2/DQ8 haplotypes. Rapid tests appeared to be no less sensitive and specific than other screening tests for CD and were probably less expensive, but further studies are needed for more reliable conclusions. Of the 55 studies in the review, only 10 reported follow-up data. After 3 months of a gluten-free diet, the general condition of the patients improved; after 6 months, tTG IgA and EMA IgA levels decreased and hemoglobin values increased; while after 1 year, tTG IgG levels also decreased, symptoms subsided, the children’s weight and height increased, school performance improved, episodes of upper respiratory tract infections decreased, and thyreoperoxidase antibodies that were positive at screening became negative. Conclusions: Mass screening for CD in asymptomatic children and adolescents is a challenge. Future research should provide more answers regarding the most appropriate target age, the frequency of screening, the optimal screening method, the cost-effectiveness, the clinical utility, and the long-term impact of mass screening on patients’ quality of life. Full article

Background: Feigned restriction of shoulder joint movement for secondary gain is clinically relevant and may misdirect care, distort disability determinations, and inflate system costs. Distinguishing feigning from structural pathology and from functional or psychosocial presentations is difficult because pain is subjective, performance varies, and no single sign or test is definitive. This comprehensive review hypothesizes that the systematic integration of clinical examination, objective biomechanical and neurophysiological testing, and emerging technologies can substantially improve detection accuracy and provide defensible medicolegal documentation. Methods: PubMed and reference lists were searched within a prespecified time frame (primarily 2015–2025, with foundational earlier works included when conceptually essential) using terms related to shoulder movement restriction, malingering/feigning, symptom validity, effort testing, functional assessment, and secondary gain. Evidence was synthesized narratively, emphasizing objective or semi-objective quantification of motion and effort (goniometry, dynamometry, electrodiagnostics, kinematic sensing, and imaging). Results: Detection is best approached as a stepwise, multidimensional evaluation. First-line clinical assessment focuses on reproducible incongruence: non-anatomic patterns, internal inconsistencies, distraction-related improvement, and mismatch between claimed disability and observed function. Repeated examinations and documentation strengthen inference. Instrumented strength testing improves quantification beyond manual testing but remains effort-dependent; repeat-trial variability and atypical agonist–antagonist co-activation can indicate submaximal performance without proving intent. Imaging primarily tests plausibility by confirming lesions or highlighting discordance between claimed limitation and minimal pathology, while recognizing that normal imaging does not exclude pain. Diagnostic anesthetic injections and electrodiagnostics can clarify pain-mediated restriction or exclude neuropathic weakness but require cautious interpretation. Motion capture and inertial sensors can document compensatory strategies and context-dependent normalization, yet validated standalone thresholds are limited. Conclusions: Feigned shoulder impairment cannot be confirmed by any single test. The desirable strategy combines structured assessment of inconsistencies with objective biomechanical and neurophysiologic measurements, interpreted within the whole clinical context and rigorously documented; however, prospective validation is still needed before routine implementation. Full article

Background/Objectives: Atypical femoral fracture (AFF) represents a diagnostic and therapeutic challenge, particularly in autoimmune disease patients receiving long-term bisphosphonate (BP) and glucocorticoid (GC) therapy. Although bilateral AFF is common, the radiographic evolution of asymptomatic incomplete lesions identified at the time of a complete fracture remains insufficiently defined. This study aimed to characterize the natural history and imaging biomarkers associated with progression in this biologically homogeneous high-risk population. Methods: Ten female autoimmune disease patients with complete AFF and asymptomatic incomplete contralateral lesions were retrospectively evaluated over a mean 59 months. Serial radiographs were assessed for cortical beaking, periosteal flaring, and transverse radiolucent lines. All patients discontinued BP therapy postoperatively; teriparatide was administered when tolerated. Results: Six lesions regressed, three remained stable, and one progressed—this progressing case being the only limb with a transverse radiolucent line at baseline. No patient developed symptoms or sustained a complete fracture on the contralateral side. Radiographic remodeling occurred independently of symptoms. BP discontinuation and, when tolerated, teriparatide appeared to contribute to lesion stabilization, although statistical significance was not achieved. Conclusions: In autoimmune patients with severe long-term BP and GC exposure, most asymptomatic incomplete AFF identified at the time of contralateral complete fracture remains stable or improves under conservative management. A transverse radiolucent line is the most decisive imaging biomarker predictive of progression and warrants intensified surveillance or consideration of prophylactic fixation. Larger cohorts are needed to refine risk stratification algorithms and optimize diagnostic and management strategies. Full article

Oropouche virus (OROV) has emerged as a significant arboviral pathogen in South America, responsible for recurrent outbreaks of febrile illness. In the Loreto region of Peru, more than 600 cases were reported in 2024, markedly exceeding expected incidence rates. We conducted a retrospective observational study using clinical–epidemiological records of all RT-qPCR-confirmed cases of Oropouche fever from the Regional Health Directorate of Loreto between October 2024 and March 2025. A total of 100 confirmed cases were identified. The most frequent symptoms were fever (88%), headache (78%), and myalgia (72%). No atypical or neurological presentations were reported. No severe cases or deaths occurred. Eight patients required hospitalization, mainly due to severe abdominal pain, persistent vomiting, arthralgia, and pregnancy. Six pregnant women were identified; three experienced pregnancy complications, though no fetal malformations or miscarriages were observed. This outbreak represents a new OROV epidemic in the region, with fewer cases than in 2024 and predominantly mild clinical courses. Although outcomes were generally favorable, the occurrence of complications in pregnant women underscores the importance of continued molecular surveillance and targeted public health interventions. Full article

During the COVID-19 pandemic, SARS-CoV-2 quickly spread all over the world in a pattern of waves. In Mexico, the first wave was from March 2020 to September 2020, and during this time autopsies were forbidden. After that, the postmortem lung samples allowed us to identify histological alterations because of COVID-19. Moreover, SARS-CoV-2 infections are characterized by the manifestation of cytopathic effects like inclusion bodies, and multinucleated cells in alveolar spaces and alveolar walls. Additionally, atypical, enlarged cells, presence of macrophages in alveolar spaces, and congestion of vascular vessels were the other histopathologic alterations of the lung. Our study covered the analysis of nine postmortem lung samples from patients with severe COVID-19 diagnosed by qRT-PCR. The samples were stained with Hematoxylin-Eosin to identify the histological alterations related to lung architecture and cell populations and were subjected to immunohistochemistry for the SARS-CoV-2 Spike and Nucleocapsid proteins. All samples showed alterations associated with diffuse alveolar damage and 1/9 presented no alveolar space, 5/9 presented different levels of pleural fibrosis, and 4/9 presented distention of the small capillaries. Immunohistochemistry results revealed that 4/9 samples showed Spike-positive cytoplasmic inclusion bodies in type I pneumocytes and 2/9 Spike-positive nuclear inclusion bodies in type I pneumocytes. These inclusion bodies were found to be eosinophilic with H&E stains. The H&E results suggest tissue alterations that may contribute to the signs and symptoms of severe COVID-19, as well as the Spike protein expression, as its distribution suggests its participation in pathophysiology. Full article

Background: Aripiprazole is an atypical antipsychotic that acts as a partial agonist on the dopamine receptor D2 while also displaying agonistic activity on the 5-HT1A and antagonistic activity on the 5-HT2A receptors. As a partial agonist, aripiprazole stabilizes the activity of the D2 receptor, preventing overactivation. Case presentation: Within our deprescribing activity, we came across the case of a 30-year-old antipsychotic-naïve patient treated with the depot formulation of aripiprazole for bipolar disorder and acute mania, possibly developing hypersexuality due to an overdose that impacted negatively and heavily on his personal life. Results: The patient developed a peculiar subset of hypersexuality, changing his sexual orientation. Of interest, one month after discontinuing aripiprazole and switching to paliperidone, all the sexual-related symptoms and impulse control disorders resolved. Conclusions: We suggest stronger communication among the clinical teams involved in the patient’s care and screening patients for impulse control disorder prior to the administration of aripiprazole and monitoring them during treatment. Full article

Background: Lung carcinoids—typical and atypical—are rare neuroendocrine tumors (NETs) representing 1–2% of lung cancers. Despite clinicopathological differences, their clinical management often mirrors lung cancer protocols rather than NET-specific recommendations. Objectives: Portray a 12-year real-world experience with lung carcinoids at a Comprehensive Cancer Center, identifying gaps in diagnostic work-up, treatment decision-making, and follow-up. Methods: Retrospective observational cohort study of adult patients with histologically confirmed lung carcinoids diagnosed at IPO Porto between January 2013 and December 2024. Demographic, clinical, imaging, and treatment data were collected from electronic patient records. Analyses were descriptive. Results: Among 179 identified cases, 129 met eligibility criteria. Median age was 62 years (range 18–84); 53.6% were women and 53.5% were non-smokers; 84.5% had ECOG-PS 0–1. The most frequent presentation was respiratory symptoms (34.1%), followed by incidental findings (43.4%, of which ~20% were during staging or surveillance of other cancers). Typical carcinoids accounted for 49.6% and atypical for 43.4%. FDG-PET/CT was requested in 70.9% of cases, including many with typical carcinoid, and SSTR-PET/CT in 64.6% (dual PET in 38.8%). Most patients (65.1%) presented with stage I disease; 17.1% were stage IV. Mean time-to-first treatment was 83 days (range 1–259). Surgery was the first treatment option for 78.3% of patients. Conclusions: This real-world series highlights heterogeneity in diagnostic pathways, excessive FDG-PET use in typical carcinoids, and non-standardized follow-up. Dedicated multidisciplinary lung-NET boards and national reference centers are needed to homogenize and streamline patient management. Full article

Background and Objectives: Patients with Sjögren’s disease (SjD) do not experience any improvement in gastroesophageal reflux disease (GERD) symptoms after SjD treatment, and in some patients, reflux even worsens. It is important to note that GERD manifests itself through typical and atypical symptoms, the latter of which may include eye damage, as evidenced by a growing body of research. When SjD patients were prescribed medication to treat GERD, their condition improved at the same time. Therefore, we aim to investigate whether there is a link between ocular dryness and gastroesophageal reflux disease (GERD) in patients with Sjögren’s disease (SjD). Materials and Methods: Our study included 27 patients with SjD according to the 2016 American College of Rheumatology and the European League Against Rheumatism (ACR/EULAR) Sjögren’s syndrome Classification Criteria, and 28 patients with non-autoimmune sicca syndrome due to GERD (nonautoimmSicca). Results: The study involved 55 participants, 48 (87.3%) women and 7 (12.7%) men. The median age was 54 years (IQR 49–64). A total of 41 subjects (74.5%) had GERD, and 20 subjects (36.4%) tested positive for Helicobacter pylori: 13 (48.1%) and 1 (3.7%) in the SjD group, and 28 (100.0%) and 19 (67.9%) in the nonautoimmSicca group, respectively. A significant difference in asymmetric tear secretion (p < 0.001) was found between the nonautoimmSicca and SjD patients, with values of 5 (3–10) mm/5 min and 1 (0–2) mm/5 min, respectively. A low correlation was detected between sialometry results and tear secretion asymmetry (r = 0.48, p < 0.001). An increase of 1 mm/5 min in the tear secretion asymmetry between the eyes was associated with a 2.04-fold increase in the odds ratio for having GERD (95% CI 1.25–3.32, p = 0.004), and was associated with a 1.9-fold increase in the odds ratio for having GERD (95% CI 1.04–3.49, p = 0.038) in patients with SjD. The presence of Helicobacter pylori is associated with asymmetric tear secretion [95% CI 1.22 (1.05–1.41, p = 0.010)]. Conclusions: Asymmetric tear secretion between the eyes is associated with the odds of having GERD. Patients with non-autoimmune sicca syndrome due to GERD have significantly greater asymmetry in tear secretion compared to those diagnosed with Sjögren’s disease. Full article

Background and Clinical Significance: Annular pancreas is a rare congenital anomaly in which pancreatic tissue partially or completely encircles the duodenum, potentially causing duodenal obstruction. Clinical presentation varies from asymptomatic cases to persistent vomiting, feeding intolerance, and failure to thrive, often leading to delayed diagnosis. Case Presentation: We report a 2-year and 10-month-old girl with a long-standing history of intermittent, recurrent vomiting since the neonatal period, without growth impairment or other alarming symptoms. Initial imaging suggested proximal duodenal dilation, with suspicion for superior mesenteric artery (SMA) syndrome. Endoscopy revealed mechanical obstruction at the second portion of the duodenum. Contrast-enhanced CT confirmed annular pancreas partially encircling the duodenum. The patient underwent duodeno-duodenostomy with an uneventful postoperative course and complete resolution of symptoms. This case illustrates the diagnostic challenges of annular pancreas in older children with atypical presentations. Multimodal imaging is crucial for accurate diagnosis. Surgical bypass remains the definitive treatment, offering excellent long-term outcomes. Conclusions: Persistent or recurrent vomiting in children, even without classic signs such as bilious vomiting or failure to thrive, should prompt consideration of annular pancreas. Early recognition and timely surgical intervention can prevent prolonged morbidity and ensure normal growth and development. Full article