Search Results (20)

Purpose: Dirofilariasis is a zoonotic infectious disease caused by a species belonging to the Dirofilaria genus. Human dirofilariasis cases have increased in Europe in the last few decades. Dogs and wild canids represent the definitive hosts and principal reservoirs of Dirofilaria repens, while mosquito species are biological vectors. Humans act as accidental hosts, and clinical manifestations depend on the location of the worm in the organs or tissues. We described the first case of ocular dirofilariasis in the Aosta Valley region (Italy). Case description: a 62-year-old Italian woman complained of recurrent ocular redness, pain and discomfort, accompanied by itching and foreign body sensation in the right eye. The slit lamp biomicroscopic examination revealed conjunctival congestion on the temporal region of bulbar conjunctiva, and a long whitish vermiform mobile mass was detected under the conjunctiva. The anterior chamber showed no flare or cells in either eye, and the dilated fundus examination was normal. The worm was immediately surgically removed to prevent further migration, and was diagnosed morphologically and molecularly as D. repens. Following surgical removal, the symptoms resolved completely and rapidly, with no recurrence of ocular symptoms recorded during 12-month follow-up visits. Conclusions: Ocular dirofilariasis can lead to misdiagnosis due to its rare ocular manifestations, and it is considered an emergent zoonosis in European countries. Accurate diagnosis and control of ocular dirofilariasis by D. repens require a multidisciplinary approach under the One Health framework to effectively address this emergent zoonosis. Full article

Background/Objectives: Urethral stricture disease, characterized by narrowing of the urethra due to scar tissue, affects urinary and sexual health. While urethroplasty is the standard treatment, its impact on erectile function is less understood. This study examines changes in International Index of Erectile Function (IIEF) scores post-urethroplasty across various stricture etiologies, identifies predictors of erectile function outcomes, and explores recovery trajectories following surgery. Methods: This multicenter retrospective study included 103 patients who underwent urethroplasty between 2017 and 2023. Preoperative and postoperative IIEF scores at 3 and 6 or 12 months were analyzed. Stricture etiologies included pelvic fracture urethral injury, transurethral resection, catheterization, idiopathic, and hypospadias. The Wilcoxon signed-rank test and multivariate regression models were used to assess changes in IIEF scores and identify significant predictors. Results: Preoperative erectile function and patient age were significant predictors of postoperative outcomes. Younger patients and those with higher baseline IIEF scores experienced better erectile function post-surgery. Long-term outcomes (6 to 12 months) were significantly worse for strictures involving both penile and bulbar regions. Multivariate analysis showed higher pre-surgery IIEF scores and younger age were associated with better outcomes both short-term (R² = 0.562) and long-term (R² = 0.507). Diabetes was associated with worse erectile function outcomes at 3 months post-surgery. Conclusions: Younger patients and those with higher baseline IIEF scores have better erectile function outcomes following urethroplasty. Complex strictures involving both penile and bulbar regions adversely affect long-term outcomes. Additionally, the presence of diabetes is correlated with diminished erectile function in the short-term postoperative period. Full article

N, N-Dimethylaniline is an important chemical intermediate and an important metabolite of the pesticide Fenaminosulf. It is widely used in chemical production, but there is an extreme paucity of environmental risk assessments for N, N-dimethylaniline.: In this study, the cardiotoxicity of continuous exposure to N, N-dimethylaniline (20, 40, and 80 μg/mL) for 72 h was evaluated using zebrafish embryos.: The study found that N, N-dimethylaniline not only exhibits developmental toxicity to zebrafish embryos, leading to abnormalities such as pericardial edema, yolk sac edema, and spinal curvature, but also induces oxidative stress, lipid accumulation, and apoptosis, particularly affecting the heart region. Cardiac function indicators such as pericardial area, sinus venosus (SV) and bulbar artery (BA) distance, heart rate, and red blood cell (RBC) rate were all significantly altered due to exposure to N, N-dimethylaniline, with impaired cardiac morphology and structure and the downregulation of gene expression related to heart development and function (myl7, vmhc, myh6, bmp4, tbx2b, and has2).: The research findings suggest that the heart may be the potential target organ for the toxic effects of N, N-dimethylaniline, providing a scientific basis for the rational use of this compound and environmental protection. Furthermore, it enhances public awareness of the safety of substances that may degrade to produce N, N-dimethylaniline during their use. Full article

This study analyzed 2102 conjunctival lesions excised between 1981 and 2003 at a single tertiary center in Serbia, with the aim of evaluating their histopathological characteristics, anatomical localization, and demographic distribution. Of the total cases recorded, 55.1% were male, indicating a slight male predominance. The bulbar conjunctiva was the most commonly affected site (34.5%), with 39.3% of tumors extended to multiple regions of the conjunctiva, including areas such as the plica and caruncula. The most common benign lesion was compound conjunctival nevus (16.7%), while squamous cell carcinoma (SCC) (11.4%) and melanoma (11.3%) were the most prevalent malignant tumors. Tumor incidence peaked in the 61–70 and 51–60 year age groups, with malignant tumors such as SCC being more frequent in males. Comparisons with similar global studies reveal that our findings align with worldwide trends, such as the predominance of SCC, which has been linked to UV exposure, and the frequency of melanoma in fair-skinned populations. However, the lower prevalence of fibrodegenerative lesions like pterygia and pinguecula in our cohort likely reflects Serbia’s cooler climate compared to regions with higher UV exposure. These findings underscore the diverse nature of conjunctival tumors, the critical role of histopathological examination for diagnosis, and the influence of environmental factors. This study provides valuable insights into the epidemiology of conjunctival tumors, contributing to global understanding and guiding future diagnostic and therapeutic approaches. Full article

Antisense oligonucleotides (ASOs) are short oligodeoxynucleotides designed to bind to specific regions of target mRNA. ASOs can modulate pre-mRNA splicing, increase levels of functional proteins, and decrease levels of toxic proteins. ASOs are being developed for the treatment of motor neuron diseases (MNDs), including spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and spinal and bulbar muscular atrophy (SBMA). The biggest success has been the ASO known as nusinersen, the first effective therapy for SMA, able to improve symptoms and slow disease progression. Another success is tofersen, an ASO designed to treat ALS patients with SOD1 gene mutations. Both ASOs have been approved by the FDA and EMA. On the other hand, ASO treatment in ALS patients with the C9orf72 gene mutation did not show any improvement in disease progression. The aim of this review is to provide an up-to-date overview of ASO research in MNDs, from preclinical studies to clinical trials and, where available, regulatory approval. We highlight the successes and failures, underline the strengths and limitations of the current ASO research, and suggest possible approaches that could lead to more effective treatments. Full article

Approximately 80–96% of people with amyotrophic lateral sclerosis (ALS) become unable to speak during the disease progression. Assessing upper and lower motor neuron impairment in bulbar regions of ALS patients remains challenging, particularly in distinguishing spastic and flaccid dysarthria. This study aimed to evaluate acoustic voice parameters as useful biomarkers to discriminate ALS clinical phenotypes. Triangular vowel space area (tVSA), alternating motion rates (AMRs), and sequential motion rates (SMRs) were analyzed in 36 ALS patients and 20 sex/age-matched healthy controls (HCs). tVSA, AMR, and SMR values significantly differed between ALS and HCs, and between ALS with prevalent upper (pUMN) and lower motor neuron (pLMN) impairment. tVSA showed higher accuracy in discriminating pUMN from pLMN patients. AMR and SMR were significantly lower in patients with bulbar onset than those with spinal onset, both with and without bulbar symptoms. Furthermore, these values were also lower in patients with spinal onset associated with bulbar symptoms than in those with spinal onset alone. Additionally, AMR and SMR values correlated with the degree of dysphagia. Acoustic voice analysis may be considered a useful prognostic tool to differentiate spastic and flaccid dysarthria and to assess the degree of bulbar involvement in ALS. Full article

Background: Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of upper (UMN) and lower motor neurons (LMN) in four different body regions (bulbar, cervical, thoracic, and lumbosacral). Over the past decades, several clinical scoring systems have been developed to assess the UMN and LMN burden in ALS. However, concerning the bulbar LMN burden, the available scoring systems solely assess the presence/absence of bulbar LMN signs without providing a degree of impairment. Therefore, in this study, we proposed a novel scale to stratify subjects with ALS according to the bulbar LMN involvement and assessed its prognostic value. Methods: We developed a four-item scale based on the LMN signs according to the El Escorial criteria. Ten raters, specializing in ALS or neurocognitive disorders, retrospectively applied the scale to the first evaluation of 195 patients with ALS. Cohen’s kappa (Cohen’s k) and an intra-class correlation coefficient (ICC) were used to assess the inter-rater reliability. The Kaplan–Mayer estimator was used to estimate survival distribution according to the bulbar scale scores. Results: The raters showed a substantial to excellent agreement with Cohen’s k, ranging from 0.834 to 0.975, with an overall ICC of 0.922 (95% CI = 0.906–0.936). The survival distribution was statistically different across the three bulbar scale scores (χ²₍₂₎ = 9.50, p < 0.01). Conclusions: Our bulbar LMN scale represents a reliable measure of the bulbar LMN signs in ALS. This easy-to-administer clinical scale could provide unique information in phenotyping and predicting survival in ALS. Full article

The lowland tapir is one of four species belonging to the Tapiridae family of the Ceratomorpha suborder, similar to Rhinocerotidae. This study describes anatomy with morphometry, histology (hematoxylin and eosin, Masson-Goldner trichrome, Movat pentachrome, mucicarmine, picro-Mallory trichrome) and histochemistry (PAS, AB pH 1.0, AB pH 2.5; AB pH2.5/PAS and HDI) of the upper and lower eyelids, and superficial gland of the third eyelid with the third eyelid, deep gland of the third eyelid, and lacrimal gland. The aim of the work is to show the features of the above-mentioned structures typical only for Tapiridae, as well as to show the presence of similarities and differences between the families forming the order Perissodactyla. The eyelashes on the upper eyelid were long, while those of the lower eyelid were short and much less prominent. In the upper and lower eyelid sebaceous glands, a characteristic simple alveolar gland producing a mucus-like secretion and poorly developed tarsal glands were observed. The marginal zone of the posterior surface of the eyelids was covered by stratified columnar epithelium with 18–21 layers of nucleated cells, while the bulbar zone of these surfaces was covered by cubic multilayer epithelium with 6–11 non-keratinized layers of cells and with sparse goblet cells. In only lower eyelids, numerous lymphoid nodules, diffuse lymphocytes and high endothelial venules were observed. The superficial gland was an acinar complex which secreted mucous and contained plasma cells within the interlobular and interlobular connective tissue. The upper and lower branches of the third eyelid were the shape of a bent “caudal fin” and were composed of hyaline cartilage, and they contained conjunctiva associated lymphoid tissue (CALT). The deep gland was also an acinar complex producing a serous character and having numerous diffuse lymphocytes. The lacrimal gland was an acinar complex producing seromucous secretions and had numerous plasma cells located in the glandular interstitium. The results of our research indicate that the features of the anatomy of the eyelids and orbital region in the lowland tapir are also typical of the family Tapiridae, but also have features common to the families Equidae and Rhinocerotidae. We confirm the presence of poorly developed tarsal glands in both eyelids as well as presence of a palpebral part of the lacrimal gland in the upper eyelid, which is typical only to Tapirus terrestris. Full article

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that progressively affects bulbar and limb function. Despite increasing recognition of the disease as a multinetwork disorder characterized by aberrant structural and functional connectivity, its integrity agreement and its predictive value for disease diagnosis remain to be fully elucidated. In this study, we recruited 37 ALS patients and 25 healthy controls (HCs). High-resolution 3D T1-weighted imaging and resting-state functional magnetic resonance imaging were, respectively, applied to construct multimodal connectomes. Following strict neuroimaging selection criteria, 18 ALS and 25 HC patients were included. Network-based statistic (NBS) and the coupling of grey matter structural–functional connectivity (SC–FC coupling) were performed. Finally, the support vector machine (SVM) method was used to distinguish the ALS patients from HCs. Results showed that, compared with HCs, ALS individuals exhibited a significantly increased functional network, predominantly encompassing the connections between the default mode network (DMN) and the frontoparietal network (FPN). The increased structural connections predominantly involved the inter-regional connections between the limbic network (LN) and the DMN, the salience/ventral attention network (SVAN) and FPN, while the decreased structural connections mainly involved connections between the LN and the subcortical network (SN). We also found increased SC–FC coupling in DMN-related brain regions and decoupling in LN-related brain regions in ALS, which could differentiate ALS from HCs with promising capacity based on SVM. Our findings highlight that DMN and LN may play a vital role in the pathophysiological mechanism of ALS. Additionally, SC–FC coupling could be regarded as a promising neuroimaging biomarker for ALS and shows important clinical potential for early recognition of ALS individuals. Full article

Few studies have focused on elderly (>80 years) amyotrophic lateral sclerosis (ALS) patients, who represent a fragile subgroup generally not included in clinical trials and often neglected because they are more difficult to diagnose and manage. We analyzed the clinical and genetic features of very late-onset ALS patients through a prospective, population-based study in the Emilia Romagna Region of Italy. From 2009 to 2019, 222 (13.76%) out of 1613 patients in incident cases were over 80 years old at diagnosis, with a female predominance (F:M = 1.18). Elderly ALS patients represented 12.02% of patients before 2015 and 15.91% from 2015 onwards (p = 0.024). This group presented with bulbar onset in 38.29% of cases and had worse clinical conditions at diagnosis compared to younger patients, with a lower average BMI (23.12 vs. 24.57 Kg/m²), a higher progression rate (1.43 vs. 0.95 points/month), and a shorter length of survival (a median of 20.77 vs. 36 months). For this subgroup, genetic analyses have seldom been carried out (25% vs. 39.11%) and are generally negative. Finally, elderly patients underwent less frequent nutritional- and respiratory-supporting procedures, and multidisciplinary teams were less involved at follow-up, except for specialist palliative care. The genotypic and phenotypic features of elderly ALS patients could help identify the different environmental and genetic risk factors that determine the age at which disease onset occurs. Since multidisciplinary management can improve a patient’s prognosis, it should be more extensively applied to this fragile group of patients. Full article

The olfactory bulb (OB) is one of two regions of the mammalian brain which undergo continuous neuronal replacement during adulthood. A significant fraction of the cells added in adulthood to the bulbar circuitry is constituted by dopaminergic (DA) neurons. We took advantage of a peculiar property of dopaminergic neurons in transgenic mice expressing eGFP under the tyrosine hydroxylase (TH) promoter: while DA neurons located in the glomerular layer (GL) display full electrophysiological maturation, eGFP+ cells in the mitral layer (ML) show characteristics of immature cells. In addition, they also display a lower fluorescence intensity, possibly reflecting different degrees of maturation. To investigate whether this difference in maturation might be confirmed at the gene expression level, we used a fluorescence-activated cell sorting technique on enzymatically dissociated cells of the OB. The cells were divided into two groups based on their level of fluorescence, possibly corresponding to immature ML cells and fully mature DA neurons from the GL. Semiquantitative real-time PCR was performed to detect the level of expression of genes linked to the degree of maturation of DA neurons. We showed that indeed the cells expressing low eGFP fluorescence are immature neurons. Our method can be further used to explore the differences between these two groups of DA neurons. Full article

It is generally believed that eye movements are completely spared in amyotrophic lateral sclerosis (ALS). Although a series of eye movement abnormalities has been recognized in recent years, the findings are highly controversial, and bulbar disabilities should be considered in relation to eye movement abnormalities. The present study aimed to determine whether eye movement abnormalities are present in ALS and, if so, to investigate their characteristics and their association with bulbar disability in ALS patients. A total of 60 patients and 30 controls were recruited and underwent the standardized evaluations of the oculomotor system using videonystagmography. Square-wave jerks (OR: 16.20, 95% CI: 3.50–74.95, p < 0.001) and abnormal cogwheeling during smooth pursuit (OR: 14.04, 95% CI: 3.00–65.75, p = 0.001) were more frequently observed in ALS patients than in the control subjects. In subgroup analyses, square-wave jerks (OR: 26.51, 95% CI: 2.83–248.05, p = 0.004) and abnormal cogwheeling during smooth pursuit (OR: 6.56, 95% CI: 1.19–36.16, p = 0.031) were found to be more common in ALS patients with bulbar involvement (n = 44) than in those without bulbar involvement (n = 16). There were no significant differences in the investigated eye movement parameters between bulbar-onset (n = 12) and spinal-onset patients (n = 48). ALS patients showed a range of eye movement abnormalities, affecting mainly the ocular fixation and smooth pursuit systems. Our pioneering study indicates that the region of involvement could better indicate the pathophysiological essence of the abnormalities than the type of onset pattern in ALS. Eye movement abnormalities may be potential clinical markers for objectively evaluating upper brainstem or supratentorial cerebral lesion neurodegeneration in ALS. Full article

Increased incidence rates of amyotrophic lateral sclerosis (ALS) have been recently reported across various Western countries, although geographic and temporal variations in terms of incidence, clinical features and genetics are not fully elucidated. This study aimed to describe demographic, clinical feature and genotype–phenotype correlations of ALS cases over the last decade in the Emilia Romagna Region (ERR). From 2009 to 2019, our prospective population-based registry of ALS in the ERR of Northern Italy recorded 1613 patients receiving a diagnosis of ALS. The age- and sex-adjusted incidence rate was 3.13/100,000 population (M/F ratio: 1.21). The mean age at onset was 67.01 years; women, bulbar and respiratory phenotypes were associated with an older age, while C9orf72-mutated patients were generally younger. After peaking at 70–75 years, incidence rates, among women only, showed a bimodal distribution with a second slight increase after reaching 90 years of age. Familial cases comprised 12%, of which one quarter could be attributed to an ALS-related mutation. More than 70% of C9orf72-expanded patients had a family history of ALS/fronto-temporal dementia (FTD); 22.58% of patients with FTD at diagnosis had C9orf72 expansion (OR 6.34, p = 0.004). In addition to a high ALS incidence suggesting exhaustiveness of case ascertainment, this study highlights interesting phenotype–genotype correlations in the ALS population of ERR. Full article

Background and Objectives: Knowledge of the internal carotid artery’s (ICA) morphometric features is influential in outlining surgical and minimally invasive procedures in the neurovascular field. Many studies have shown divisive numbers regarding the ICA’s caliber, with the measuring point of the artery sometimes differing. This study presents ICA dimensions based on computed tomography angiography in each of its seven segments as per Bouthillier’s classification, correlating vascular dimensions with anthropometric parameters. Materials and Methods: A thorough CT angiography analysis was performed on 70 patients with internal carotid vessels unaffected by atherosclerotic disease. The extracranial part of the ICA was measured in four locations—carotid bulb, post-bulbar dilation, at its cervical midpoint, and below its entrance into the carotid foramen. Single landmarks were used for measurements in the intracranial segments. ICA length was assessed in the neck region and also in the cranial cavity. Craniometric measurements were performed on sagittal and coronal CT reconstructions. Patient height was taken into consideration. Results: The largest ICA portion is near its origin in the carotid sinus area (7.59 ± 1.00 mm), with a steep decline in caliber following its extracranial course. Distal ICA presented values somewhat similar to its proximal intracranial segment diameters (4.67 ± 0.47 mm). Dimensions of the ICA in the intracranial segments start from a value of 4.53 ± 0.47 mm and decrease by approximately 40% when reaching the origin of the middle cerebral artery (2.71 ± 0.37 mm), showing a marked decrease in caliber after the emergence of the most critical collateral artery, the ophthalmic branch. The length of the ICA varies between genders, with the male ICA being about 10 mm longer in total length than female ICA; this difference is also correlated with patient height and skull dimensions. Conclusions: Both intra- and extracranial ICA have variable dimensions and length related to gender and anthropometric parameters, with no significant differences obtained concerning side or age. Full article

Amyotrophic lateral sclerosis (ALS) is characterised by progressive dysfunction of the upper and lower motor neurons. The disease can evolve over time from focal limb or bulbar onset to involvement of other regions. There is some clinical heterogeneity in ALS with various phenotypes of the disease described, from primary lateral sclerosis, progressive muscular atrophy and flail arm/leg phenotypes. Whilst the majority of ALS patients are sporadic in nature, recent advances have highlighted genetic forms of the disease. Given the close relationship between ALS and frontotemporal dementia, the importance of cortical dysfunction has gained prominence. Transcranial magnetic stimulation (TMS) is a noninvasive neurophysiological tool to explore the function of the motor cortex and thereby cortical excitability. In this review, we highlight the utility of TMS and explore cortical excitability in ALS diagnosis, pathogenesis and insights gained from genetic and variant forms of the disease. Full article