Simone Grannò

Background: Posterior fossa arachnoid cysts may cause cranial nerve dysfunction as well as brainstem or vascular compression due to mass effect in a narrow compartment. Optimal surgical management remains debated, particularly regarding the indications to surgery versus conservative management, fenestration or shunting. Methods: We describe a fully anatomical microsurgical fenestration of a posterior fossa arachnoid cyst causing lower cranial nerve compression, performed through a midline suboccipital mini-craniotomy. The technique emphasizes direct visual identification of neurovascular structures and wide cisternal communication. Conclusions: An anatomical suboccipital approach, performed without neuronavigation or intraoperative neuromonitoring, allows safe and effective decompression of posterior fossa arachnoid cysts with lower cranial nerve involvement. Microsurgical fenestration with meticulous dissection guided by direct anatomical landmarks provides durable, low-morbidity symptom relief.

BACKGROUND: Traumatic spinal cord injury is a devastating condition resulting in significant functional impairment. It is known that spinal manipulation therapy, often used as complementary treatment for presumed muscular neck pain, may rarely precipitate spinal cord compression and injury in patients with undiagnosed cervical canal stenosis. OBSERVATIONS: The authors report the case of a 68-year-old woman who presented to the emergency department with right scapular-paravertebral pain and right upper limb paresthesia, initially attributed to muscular causes without imaging. Spinal manipulation therapy was administered in the emergency department, causing sudden bilateral lower limb sensory loss and right lower limb motor deficit. No imaging or neurosurgical consultation was undertaken until she returned the next day with progressive weakness, hypoesthesia, and burning dysesthesia. Subsequently, MRI revealed a large acute C6–7 disc extrusion with underlying chronic multilevel stenosis, requiring anterior fusion and posterior decompression. Postoperatively, she partially improved, but a partial motor deficit, lower limb hypoesthesia, and neuropathic pain persisted. LESSONS: This case highlights the importance of thorough clinical and radiological assessment prior to administering spinal manipulation in the cervical spine, particularly in patients with signs of sensory or motor dysfunction. Torticollis and muscular contractions in the limbs may be presenting signs of cervical stenosis and degenerative cervical myelopathy, thus requiring further neurological investigation before patients are considered for spinal manipulation therapy. https://thejns.org/doi/10.3171/CASE25304

The incidence of early-onset colorectal cancer, defined as colorectal cancer occurring in young adults under the age of 50, is increasing globally. Knowledge of the etiological factors in young adults is far from complete. Questionable eoCRCs’ exogenous factors are represented by processed meat, sugary drinks, alcohol, Western dietary pattern, overweight and obesity, physical inactivity, and smoking, though with heterogeneous results. Therefore, we performed a systematic review to summarize the current evidence on the role of diet and lifestyle as eoCRC risk factors. We systematically searched PubMed, Scopus, and EMBASE up to July 2021, for original studies evaluating diet, alcohol, physical activity, BMI, and smoking in eoCRC and included twenty-six studies. Indeed, the exogenous factors could represent modifiable key factors, whose recognition could establish areas of future interventions through public health strategies for eoCRC primary prevention. Additionally, we discussed the role of additional non-modifiable risk factors, and of epigenetic regulation and microbiota as mediators of the eoCRC triggered by diet and lifestyle.

Over the last decade, a vast YouTube-based ‘market’ of child-produced content involving sexualised behaviour has developed. Children-performers produce videos featuring implicit sexual imagery to satisfy the demands of an adult fan base, and in exchange for a digital reward. We first report the discovery of several YouTube keywords leading to such content, outlining their remarkable interconnectedness via analysis of search trends over the last decade. Following, we investigate audience-child interactions by semantic analysis of n=1398 comments mined from n=30 videos, revealing the occurrence of collective grooming. We then demonstrate how this phenomenon is sustained and enhanced by YouTube search algorithms. Following, we detail a model framework to contextualise our findings. Finally, we propose specific amendments to the 2018 Online Harms White Paper that might tackle this phenomenon. Our results reveal a new form of child abuse, as of yet undescribed, wherein the core features of online grooming are translated to social media, the fundamental principles of which act as a powerful incentive. Because the victim’s manipulation is enacted collectively, we believe that responsibility ultimately rests with society as a whole. The principal aim here is to raise awareness of this issue, in an attempt to kick-start discussion of its causes, implications and potential solutions.

Pathological mechanisms underlying Down syndrome (DS)/Trisomy 21, including dysregulation of essential signalling processes remain poorly understood. Combining bioinformatics with RNA and protein analysis, we identified downregulation of the Wnt/β-catenin pathway in the hippocampus of adult DS individuals with Alzheimer’s disease and the ‘Tc1’ DS mouse model. Providing a potential underlying molecular pathway, we demonstrate that the chromosome 21 kinase DYRK1A regulates Wnt signalling via a novel bimodal mechanism. Under basal conditions, DYRK1A is a negative regulator of Wnt/β-catenin. Following pathway activation, however, DYRK1A exerts the opposite effect, increasing signalling activity. In summary, we identified downregulation of hippocampal Wnt/β-catenin signalling in DS, possibly mediated by a dose dependent effect of the chromosome 21-encoded kinase DYRK1A. Overall, we propose that dosage imbalance of the Hsa21 gene DYRK1A affects downstream Wnt target genes. Therefore, modulation of Wnt signalling may open unexplored avenues for DS and Alzheimer’s disease treatment.

LRRK2 mutations and risk variants increase susceptibility to inherited and idiopathic Parkinson’s disease, while recent studies have identified potential protective variants. This, and the fact that LRRK2 mutation carriers develop symptoms and brain pathology almost indistinguishable from idiopathic Parkinson’s disease, has led to enormous interest in this protein. LRRK2 has been implicated in a range of cellular events, but key among them is canonical Wnt signalling, which results in increased levels of transcriptionally active β-catenin. This pathway is critical for the development and survival of the midbrain dopaminergic neurones typically lost in Parkinson’s disease. Here we use Lrrk2 knockout mice and fibroblasts to investigate the effect of loss of Lrrk2 on canonical Wnt signalling in vitro and in vivo. Micro-computed tomography was used to study predicted tibial strength, while pulldown assays were employed to measure brain β-catenin levels. A combination of luciferase assays, immunofluorescence and co-immunoprecipitation were performed to measure canonical Wnt activity and investigate the relationship between LRRK2 and β-catenin. TOPflash assays are also used to study the effects of LRRK2 kinase inhibition and pathogenic and protective LRRK2 mutations on Wnt signalling. Data were tested by Analysis of Variance. Loss of Lrrk2 causes a dose-dependent increase in the levels of transcriptionally active β-catenin in the brain, and alters tibial bone architecture, decreasing the predicted risk of fracture. Lrrk2 knockout cells display increased TOPflash and Axin2 promoter activities, both basally and following Wnt activation. Consistently, over-expressed LRRK2 was found to bind β-catenin and repress TOPflash activation. Some pathogenic LRRK2 mutations and risk variants further suppressed TOPflash, whereas the protective R1398H variant increased Wnt signalling activity. LRRK2 kinase inhibitors affected canonical Wnt signalling differently due to off-targeting; however, specific LRRK2 inhibition reduced canonical Wnt signalling similarly to pathogenic mutations. Loss of LRRK2 causes increased canonical Wnt activity in vitro and in vivo. In agreement, over-expressed LRRK2 binds and represses β-catenin, suggesting LRRK2 may act as part of the β-catenin destruction complex. Since some pathogenic LRRK2 mutations enhance this effect while the protective R1398H variant relieves it, our data strengthen the notion that decreased canonical Wnt activity is central to Parkinson’s disease pathogenesis.