Search Results (798)

We present a family of five siblings who came to our attention with a clinical and radiological diagnosis of familial hypomyelinating leukodystrophy. Despite brain white matter abnormalities being present in all siblings, the clinical phenotype was variable: the three brothers presented with a clear-cut late-onset spastic paraplegia, whereas the two sisters displayed only mild pyramidal signs. Molecular analysis revealed a single relevant variant shared by all affected siblings, namely the likely pathogenic variant c.659C>T (p.Ser220Phe) in the GJA1 gene. Variants in this gene are generally associated with oculodentodigital dysplasia (ODDD), an autosomal dominant condition characterized by distinctive facial features and anomalies of the eyes, teeth, and digits. Neurological features are reported in about 30% of cases. In this family, ODDD manifested as a predominantly neurological phenotype. Although a clear explanation for this uncommon presentation is lacking, shared genetic modifiers, the effect of the specific variant, and a possible patient-population bias may have contributed. This case highlights the wide phenotypic spectrum of CX43-related disorders and suggests the importance of testing the GJA1 gene in individuals with atypical presentations, including predominant or isolated neurological phenotypes such as late-onset spastic paraplegia. MRI findings may also provide a useful diagnostic clue when ODDD is suspected. Full article

Background: Juvenile-onset Huntington disease (JoHD) is a rare form of Huntington disease characterized by symptom onset at or before 20 years of age. Early manifestations are often non-choreic and may be attributed to developmental, psychiatric, movement, metabolic, or epileptic disorders. We described three molecularly confirmed cases and examined early manifestations, diagnostic pathways, and epilepsy. Methods: We conducted a retrospective case series and a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 systematic review of PubMed, Scopus, and Web of Science Core Collection through 5 July 2026. The strict patient-level synthesis required attributable onset at or before 20 years, patient-specific molecular confirmation of a pathogenic HTT repeat expansion, and extractable clinical data. Complementary aggregate or linked reports using closely aligned JoHD criteria were retained for context but excluded from patient-level calculations. Results: The cases included childhood-onset JoHD with drug-resistant epilepsy, adolescent-onset JoHD with progressive motor-cognitive decline and epilepsy in a known Huntington disease pedigree, and childhood-onset JoHD without available family history, in whom status epilepticus prompted renewed diagnostic evaluation. Ninety-three reports were included; of these, 81 contributed 228 unique patients and 12 provided complementary data. Early manifestations were heterogeneous and broadly consistent with previously described childhood-onset JoHD phenotypes. Diagnostic delay was extractable in 180/228 patients; among 172 with point estimates, the median was 4.0 years. Definite epilepsy was reported in 60/145 patients with ascertainable seizure status and was descriptively more frequent in childhood-onset (<10 years) than adolescent-onset (10–20 years) JoHD (49/84 [58.3%] vs. 11/57 [19.3%]). Conclusions: JoHD should be considered in children and adolescents with progressive multisystem neurological involvement, particularly when epilepsy occurs with developmental regression, gait or speech deterioration, pyramidal or extrapyramidal signs, basal-ganglia abnormalities, or a compatible family history. Full article

Raccoon dog and fox amdoparvovirus (RFAV) has been reported in raccoon dogs and foxes, but natural infection in domestic dogs has not previously been documented. During March–April 2026, samples from four affected Dobermann dogs from a kennel near Novi Sad, Serbia, were submitted for laboratory investigation. After negative testing for canine adenovirus, canine coronavirus, herpesvirus, parvovirus, distemper virus, influenza A virus, and leptospirosis, metagenomic sequencing was performed on selected tissues, followed by bioinformatic analysis and targeted RFAV PCR screening of additional outbreak-associated samples. Affected dogs had prolonged illness characterized by conjunctivitis with ocular and nasal discharge, occasional blue eye appearance, progressive weight loss, poor coat quality, jaundice and biochemical evidence of hepatic injury, and neurologic signs including paraplegia in advanced cases. Sequencing generated 434,220 reads and identified multiple RFAV hits; pooled assembly produced a 4799 bp consensus genome with approximately 97% similarity to known RFAV strains and genome organization consistent with the genus Amdoparvovirus. RFAV DNA was subsequently detected by virus-specific PCR in an epidemiologically linked dog and across diverse specimen types including blood, urine, kidney, spleen, brain, lung, testicle, ileocecal lymph node, and throat swabs, whereas clinically healthy unrelated dogs were PCR-negative. Full article

Isolated cortical vein thrombosis is a rare subtype of cerebral venous thrombosis with highly variable clinical and radiologic manifestations that frequently delay diagnosis. Bilateral thrombosis of the veins of Trolard is exceptionally uncommon, with only a few cases reported in the literature. We report a 64-year-old right-handed man who presented after being found unresponsive with suspected seizure. Although his neurological examination was normal at evaluation (NIHSS 0), noncontrast CT demonstrated subtle bilateral cortical vein hyperdensities (cord sign). Subsequent MRI and MR venography confirmed bilateral thrombosis of the veins of Trolard with associated venous congestion and a small sulcal subarachnoid hemorrhage. The patient was treated with therapeutic anticoagulation and levetiracetam. The patient achieved an excellent functional outcome (modified Rankin Scale score of 0). At 3-month follow-up, he remained neurologically intact without recurrent seizures. Follow-up MRI demonstrated improvement of the cortical FLAIR abnormality, and MR venography showed significant interval improvement in the bilateral vein of Trolard thromboses with residual short-segment nonocclusive filling defects, consistent with partial venous recanalization. This case expands the recognized clinical spectrum of the bilateral vein of Trolard thrombosis by demonstrating that extensive bilateral cortical venous involvement may present predominantly with seizure despite a normal neurological examination (NIHSS 0). Early recognition of subtle CT findings, confirmation with dedicated venous imaging, and prompt anticoagulation can result in excellent clinical recovery and favorable radiographic evolution. Full article

Clinical Rationale and Objectives: Refractory out-of-hospital cardiac arrest (OHCA) is associated with very poor outcomes when treated with conventional cardiopulmonary resuscitation alone, particularly when low-flow time is prolonged. Prehospital extracorporeal cardiopulmonary resuscitation (ECPR) may shorten the interval to extracorporeal perfusion, but its implementation requires a highly standardized operational framework to ensure appropriate patient selection, procedural safety, and efficient use of specialized resources. This manuscript describes the PrehospECPR-GOKVI operational framework, a standardized prehospital ECPR protocol developed by the Gottsegen National Cardiovascular Center in cooperation with the Hungarian National Ambulance Service and the Hungarian Air Ambulance. ECPR Pathway: The programme is based on a dedicated two-person ECPR team, consisting of an experienced physician and a paramedic, deployed with mobile ECPR-specific equipment, including point-of-care ultrasound, a pre-primed VA-ECMO circuit, an ECMO console, and a mobile oxygenator/gas blender. The protocol defines strict inclusion and exclusion criteria, emphasizing witnessed OHCA, age below or apparently below 50 years, initial shockable rhythm or selected pulseless electrical activity with suspected pulmonary embolism, refractory cardiac arrest lasting at least 15 min, no-flow time below 5 min or signs of life, and the feasibility of establishing ECMO flow within 60 min from collapse or emergency call. Two mandatory sonographic STOP criteria are incorporated before cannulation: relevant pericardial effusion or suspected aortic dissection, and inability to safely visualize the femoral artery, femoral vein, and bifurcation. The operational workflow further specifies dispatch activation, ALS continuation, equipment layout, ultrasound-guided femoro-femoral cannulation, failed-access management, air-free circuit connection, post-flow stabilization, receiving-centre notification, and transport to GOKVI. A target interval of no more than 15 min from initiation of ECPR-specific steps to ECMO flow is mandated. Conclusions: The PrehospECPR-GOKVI framework describes a locally developed, standardized operational pathway intended to support early identification, safe procedural preparation, and structured delivery of prehospital ECPR for selected patients with refractory OHCA. The protocol is designed to reduce avoidable delays, standardize ALS–ECPR coordination, and incorporate predefined sonographic safety checkpoints before cannulation. As no patient-level data are reported in this manuscript, feasibility, safety, complication rates, survival, neurological outcomes, resource utilization, and transferability remain to be evaluated prospectively after programme launch. Full article

Background/Objectives: Lumbar puncture (LP) is an essential diagnostic and therapeutic procedure in neurological practice. Despite its clinical value, misconceptions and fear may influence its acceptance among the public. This study aimed to assess knowledge, attitudes, and misconceptions regarding LP among adults in Saudi Arabia and to examine associated sociodemographic factors. Methods: A cross-sectional study was conducted between June 2025 and January 2026 using a structured, self-administered online questionnaire adapted from a previously validated instrument. Adults aged ≥18 years residing in Saudi Arabia were recruited via convenience sampling through open social media channels, so the sample is self-selected rather than population-representative. Knowledge and attitude scores were categorized into defined levels, and multivariable regression analyses were performed to identify independent predictors. Results: A total of 1267 participants were included. Knowledge of LP was limited (mean 6.1 ± 3.9 of 18), with 905 (71%) scoring poor and only 362 (29%) demonstrating good knowledge; misconceptions about complications such as urinary incontinence and erectile dysfunction were common. Attitudes appeared favorable, with 1182 (93%) reaching the pre-specified 50% threshold, but this cut-off is lenient because an entirely neutral respondent scores 60% on a summed five-point scale, and only 692 (55%) agreed they would sign consent if their physician recommended LP. Knowledge and attitude were weakly but significantly related (r = 0.21, 95% CI 0.16 to 0.26; adjusted β = 0.25 per additional correct item, p < 0.001). Higher education, student status, healthcare occupation, and higher income predicted better knowledge, and male sex predicted lower knowledge (all p < 0.05), whereas sociodemographic factors were weakly associated with attitude. Conclusions: Among self-selected online respondents in Saudi Arabia, knowledge of lumbar puncture was limited while attitudes were comparatively favorable, and the two were weakly but positively related. Targeted educational interventions are warranted to address misconceptions, enhance public awareness, and support informed decision-making within the healthcare system. Full article

Background: Temporomandibular disorders (TMD), bruxism, and occlusal dysfunction have traditionally been managed as localized orofacial conditions. Emerging evidence suggests, however, that the stomatognathic system may interact with broader neuromusculoskeletal and central pain-processing networks, with potential systemic and neurological implications. Methods: A structured narrative literature search was conducted using PubMed, Google Scholar, and Web of Science, with the final targeted search performed in June 2026. Original research articles, systematic reviews, meta-analyses, and relevant pilot studies were considered. No formal risk-of-bias or certainty-of-evidence assessment was performed. Results: The reviewed literature indicates that TMD and bruxism are associated with musculoskeletal pain beyond the orofacial region, cervical musculoskeletal dysfunction, and headache comorbidity, with relatively stronger evidence derived from systematic reviews and meta-analyses. Emerging neuroimaging evidence suggests alterations in central pain-modulatory networks, including the default mode network, which may be relevant to central sensitization, although this evidence remains preliminary. Clinically accessible parafunctional signs may prompt further orofacial assessment, and individualized intraoral splint therapy has been investigated for effects beyond local symptom relief, although the evidence remains heterogeneous across domains. Conclusions: TMD and occlusal dysfunction may be better understood within a broader neuromusculoskeletal framework. Multidisciplinary assessment and management may warrant consideration in selected patients. Future research should incorporate standardized TMD diagnostic criteria and, where relevant, neuroimaging and posturographic outcomes. Full article

Loss-of-function (LoF) variants in the PRPS1 gene, encoding the phosphoribosyl pyrophosphate (PRPP) synthetase 1 enzyme, cause rare neurometabolic disorders historically viewed as discrete entities: nonsyndromic deafness (DFNX1), Charcot–Marie–Tooth disease type X5 (CMTX5), and Arts syndrome. A major clinical challenge is the temporal dissociation between early auditory failure and subsequent neurodegeneration, causing fragmented diagnostics. We systematically quantified this diagnostic latency and reconceptualized the disease spectrum through a molecular lens. A PRISMA-compliant systematic review identified 19 patients with genetically confirmed PRPS1 LoF variants, including our index case (c.362C>G) presenting a 15-year diagnostic delay. Kaplan–Meier analysis revealed sensorineural hearing loss manifested acutely (median 0 years; 95% CI: 0–1). In contrast, neurological deficits demonstrated a prolonged latency (median 3 years; 95% CI: 1–8), followed by ophthalmological signs (median 11.5 years). The median symptomatic delay was 3 years (range up to 19). We posit that this temporal dissociation reflects differential tissue vulnerability to intracellular ATP/GTP and NAD+ depletion caused by the primary enzymatic defect. Ultimately, DFNX1, CMTX5, and Arts syndrome represent a continuous PRPS1-related neurometabolic spectrum. Because targeted metabolic interventions (such as S-adenosylmethionine or nicotinamide riboside) have limited efficacy on advanced structural nerve damage, recognizing this early diagnostic window to initiate biochemical rescue prior to irreversible axonal degeneration is critical. Full article

Background/Objectives: Sciatica and hip osteoarthritis (OA) are common causes of lower extremity pain and functional impairment. Because both conditions may produce overlapping symptoms, distinguishing them can be challenging. Misdiagnosis may lead to inappropriate treatment, delayed intervention and unnecessary procedures. In addition, the frequent coexistence of hip and lumbar degenerative pathology, commonly referred to as hip–spine syndrome, further complicates diagnostic evaluation. This review aims to examine current diagnostic strategies used to differentiate lumbar radiculopathy from hip OA and to introduce the Athena Sign, which is presented as a preliminary, hypothesis-generating clinical observation requiring prospective validation. Methods: A narrative review of the literature was performed focusing on the pathophysiology, clinical presentation, differential diagnosis, physical examination and imaging evaluation of sciatica and hip OA. Particular emphasis was placed on clinical examination techniques and diagnostic injections used to identify the primary pain generator. Results: Both conditions share overlapping symptom patterns and inflammatory mechanisms, which may obscure the source of pain. Careful assessment of gait, hip range of motion, neurological findings and provocative maneuvers remains essential for accurate diagnosis. Imaging findings should be interpreted in conjunction with clinical examination due to the high prevalence of asymptomatic degenerative changes. The Athena Sign, observed with internal and external rotation of the hips in a prone position with the knee flexed, is associated with anterior intra-articular hip pathology and may provide an additional diagnostic indicator in patients with ambiguous hip–spine presentations. Conclusions: A systematic diagnostic approach integrating clinical examination, imaging and targeted diagnostic injections is essential for distinguishing between lumbar radiculopathy and hip OA. Recognition of dynamic clinical findings such as the Athena Sign may further improve diagnostic accuracy and guide appropriate management in patients presenting with overlapping hip and lumbar symptoms. Full article

Neurological disorders drive demand for prolonged upper-limb rehabilitation, yet specialist access is uneven and assessment stays subjective. Marker-based and inertial measurement unit (IMU) systems are accurate but costly and impractical at home, while pose estimation pipelines mostly stop at keypoints, and many process video server-side, raising privacy concerns. We present a markerless pipeline that analyzes monocular RGB video entirely on-device in the browser, so it never leaves the machine. From 33 BlazePose keypoints, it derives five geometric metrics designed to limit body-size dependence—incomplete elbow extension, inter-limb asymmetry, shoulder girdle elevation, lateral trunk lean, and head tilt—compared against empirically calibrated, preliminary thresholds; a finite-state machine segments repetitions, and the flags are pooled into an unvalidated, exploratory quality score. Against an IMU reference over the 0–${62}^{\circ }$ range that the recordings cover, the image-plane angle showed a mean absolute error of ${2.18}^{\circ }$, below the pre-specified $5^{\circ }$ tolerance, a trajectory-averaged bias within $\pm 2^{\circ }$, and Lin’s concordance correlation coefficient of $0.956$; the difference is, however, proportional to the angle—about $4\%$ of the measured value—so the accuracy should not be extrapolated to larger elevations, and because that comparison was made offline, it does not include the timing error of the causal real-time path. On a single seated frontal-plane abduction task, with 18 healthy volunteers simulating the compensations and annotated by two independent clinicians blind to the instructed condition, compensation detection reached a macro-averaged $F_1$ of $0.75$ and $0.72$ against the individual raters. The five signs differ in maturity: near-expert for trunk lean and head tilt, moderate for incomplete elbow extension and inter-limb asymmetry, and weakest for shoulder elevation, which a single frontal view cannot fully disentangle from the abduction motion. Running at 22–30 frames per second on consumer laptops without relying on a discrete GPU, it offers an accessible, privacy-preserving proof-of-concept foundation for home telerehabilitation; generalization beyond this one exercise and effectiveness on genuine post-stroke compensations remain to be established. Full article

Background/Objectives: Hypoxic–ischemic encephalopathy (HIE) remains a leading cause of neonatal death and long-term neurodisability. Cardiovascular dysfunction commonly accompanies HIE and influences neurological recovery, yet it is difficult to recognize because conventional clinical signs correlate poorly with the myocardial function. This review summarizes the current evidence on cardiac dysfunction in neonates with HIE, with particular attention to the diagnostic tools used to evaluate cardiovascular function and the clinical outcomes associated with myocardial injury. Methods: We conducted a narrative review informed by a systematic, reproducible search of four databases (PubMed, Embase, Cochrane Library, and Web of Science) from 2000 to 2026, using a Population–Concept–Context framework to identify studies of term and near-term neonates (≥35 weeks gestation) with HIE or perinatal asphyxia reporting a measure of cardiac dysfunction (electrocardiographic, biomarker, echocardiographic, or clinical hemodynamic). Records were screened and selected using Covidence systematic review software; eligible studies were original, primary-data reports with a minimum sample size of 20 neonates. Findings were synthesized narratively and grouped thematically by diagnostic modality and clinical outcome. Results: Eighty-one studies met the pre-specified eligibility criteria following a systematic multi-database search and structured screening process. As a subset of included studies are secondary analyses or overlapping cohorts, an aggregate patient count is not reported. Reported prevalence of cardiac dysfunction varied widely with the definition applied, reaching 70–90% when multimodal assessment was used. Blood pressure, heart rate, urine output, and lactate were inconsistently reliable indicators of myocardial function, and ejection fraction and fractional shortening often remained normal despite injury. Tissue Doppler imaging and speckle-tracking strain appeared to be more sensitive, with impaired left ventricular global longitudinal strain associated with brain injury. The right ventricle was more commonly and severely affected, with reduced TAPSE, RV fractional area change, and RV strain associated with death or MRI-defined injury. Each additional 24 h of inotropic support was associated with increased odds of adverse short- and long-term outcomes by 14% and 12%, respectively. Conclusions: Cardiac dysfunction is common and prognostically important but remains underrecognized by the routine clinical assessment and cardiovascular monitoring. Multimodal monitoring centered on TnECHO, near infra-red spectroscopy, and specific biomarkers may enable earlier, physiology-based management. Full article

Temporohyoid osteoarthropathy is a disease affecting the temporohyoid joint in equids caused by local inflammation and/or degeneration, leading to neurological deficits ranging from mild signs that affect performance to significant, acute neurological deficits such as facial nerve paralysis or vestibular signs. Multiple surgical treatment options are available, and while treatment has historically been performed unilaterally on the side of the clinical signs, advances in diagnostic imaging have highlighted the occurrence of bilateral disease of the temporohyoid joints, warranting evaluation of bilateral surgical treatment. The objective of this study is to report the findings, surgical complications, and outcomes of both unilateral and bilateral ceratohyoidectomy in 33 equids diagnosed with THO. This study found that there was no significant difference in outcome based on which procedure was performed, but that increased age and longer duration of clinical signs were associated with decreased likelihood of horses returning to work or showing clinical improvement. Overall, this study reports 84% survival to long term; 86% cases showed improvement, with 38% showing complete resolution of signs, 62% returned to the previous level of exercise, and 77% returned to work at the same or lower level. Full article

A 2-year-old spayed female Bichon Frise presented with progressive neurologic deterioration despite 12 months of medical management for caudal occipital malformation syndrome (CM)-associated syringomyelia (SM) and ventriculomegaly. Repeat magnetic resonance imaging (MRI) performed prior to surgical intervention demonstrated persistent CM-associated structural abnormalities together with multifocal intra-axial lesions involving the bilateral thalami, frontal white matter, and medulla that were considered most compatible with a presumptive inflammatory meningoencephalitic process, with MUO regarded as the leading differential diagnosis. Combined surgical decompression and immunosuppressive therapy using leflunomide and mycophenolate mofetil were subsequently initiated. Progressive clinical improvement followed by long-term neurological stability was observed during the approximately 2-year follow-up period. However, because both interventions were initiated concurrently, the relative contribution of each treatment to the observed clinical outcome could not be determined. No recurrence or progression of neurological signs was observed during the approximately 2-year follow-up period. This case highlights the importance of repeat MRI evaluation in neurologic patients exhibiting progressive deterioration despite previous treatment, even when an established structural diagnosis is present. Recognition of MRI findings suggestive of concurrent inflammatory disease may substantially influence diagnostic interpretation and therapeutic decision-making in selected patients. Full article

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with a high case fatality rate and no specific treatment. Identifying robust clinical predictors of mortality is crucial for improving patient outcomes. This systematic review and meta-analysis aimed to comprehensively evaluate the association of underlying diseases, hemorrhagic symptoms, neurological signs, and complications with fatal outcomes in SFTS patients. We systematically searched PubMed, Web of Science, CNKI, and Wan Fang databases up to 1 March 2026 for observational studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects models. Forty-five studies, encompassing 8078 patients (1729 deaths), were included. Underlying diabetes (OR = 1.77) and hypertension (OR = 2.38) were significant risk factors. Among hemorrhagic symptoms, systemic manifestations (OR = 4.19), melena (OR = 4.26), and petechiae (OR = 3.20) were strong predictors. Neurological symptoms, particularly coma (OR = 55.07), were the most powerful predictors of death. Complications like multiple organ dysfunction syndrome (MODS, OR = 19.77) and disseminated intravascular coagulation (DIC, OR = 12.02) also significantly increased mortality risk. The findings confirm that a range of clinical features, from underlying conditions to severe neurological and organ complications, are strongly associated with SFTS mortality. These predictors can guide clinicians in early risk stratification and intensive monitoring, especially in high-risk patients, to potentially reduce the high case-fatality rate. Full article

Introduction: Adult-onset Alexander disease (AOAD) is a rare astrocytopathy linked to the glial fibrillary acidic protein (GFAP) gene, which is known for its clinical heterogeneity and common misdiagnosis. In adults, it may present with bulbar dysfunction, pyramidal signs, ataxia, dysautonomia, cognitive decline, or parkinsonism, which often mimics atypical parkinsonian syndromes like multiple system atrophy (MSA). The purpose of this case series was to define practical clinical, radiological, and genetic cues for suspecting AOAD in adults with atypical parkinsonism, autonomic dysfunction, or paroxysmal focal symptoms, particularly when genetic findings are inconclusive. Case Presentation: Four patients, aged 40 to 59 years, had progressive and varied neurological symptoms, like gait disturbance, lower limb weakness, dysarthria, dysphagia, autonomic dysfunction, parkinsonism, cognitive decline, and paroxysmal focal deficits. Initial diagnoses were parkinsonian syndrome, stroke, transient ischemic attack (TIA), and MSA. Diagnostic Assessment and Intervention: Brain magnetic resonance imaging (MRI) in all patients showed characteristic lower brainstem abnormalities, particularly atrophy of the medulla oblongata and upper cervical spinal cord, consistent with the “tadpole sign.” GFAP sequencing identified one likely pathogenic variant (p.Arg70Trp) and three variants of uncertain significance: p.Glu122_Arg124del, p.Met415Ile, and p.Glu195Val. Management was mainly symptomatic; one patient showed significant motor improvement after repetitive transcranial magnetic stimulation (rTMS). Conclusions: AOAD should be considered in adults with parkinsonism-plus syndromes or unexplained combinations of bulbar symptoms, pyramidal signs, autonomic dysfunction, and cognitive decline. Recognizing the tadpole sign on MRI may improve diagnostic accuracy, particularly when genetic results are inconclusive. Full article