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Background: Use of nitrous oxide (N2O) gas for recreational purposes by young people is increasingly recognized as a public health hazard in the UK., Methods: We looked at the hospital records of patients admitted over the last 4 years to a single neurological centre in Essex to determine the demographics, presentation, and management of patients presenting with symptoms of N2O toxicity from its recreational use., Results: Of the 17 patients (mean age = 22.9 ± 3 years) admitted between September 2018 and October 2022, 70% were admitted between January and October 2022. All patients reported limb paraesthesiae and 16/17 reported (95%) imbalance; 11/17 (65%) showed objective limb weakness. Serum B12 concentration was low in 9/17 (53%). Plasma methylmalonic acid (n = 7) and homocysteine (n = 8) levels were elevated in all patients tested. Spinal cord Magnetic Resonance Imaging (MRI) imaging was abnormal in 10/17 (59%) patients. Nerve conduction studies were abnormal in 10/13 (77%) patients, with evidence of a symmetric, length-dependent, large fibre neuropathy., Conclusions: There has been a recent surge of cases with neurological complications of recreational N2O abuse in the UK, with a relatively greater rate in 2022. Greater awareness of this condition amongst clinicians and health regulators is urgently required to prevent harm from N2O misuse in young people., (© The Author(s) 2023. Published by Oxford University Press on behalf of Fellowship of Postgraduate Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Resistance of advanced hormone-dependent endometrial carcinoma to endocrine therapy remains a worldwide clinical issue. We recently reported that the combination of Vistusertib (V, mTOR inhibitor) and Anastrozole (A, aromatase inhibitor) improves the progression-free rate compared to Anastrozole alone. However, a better patient selection based on biomarkers would improve patient outcome. We evaluate for the first time the usage of ribosome biogenesis (RiBi) factors as a source of innovative markers. Using 47 FFPE tumours (A n = 18; V + A n = 29), 32 blood samples (A n = 13; V + A n = 19) and 30 samples of total RNAs (A n = 12; V + A n = 18) from the VICTORIA clinical trial, we observed an association between RiBi-associated markers and drug activity or prediction of treatment response. NOP10 and NHP2 mRNA levels were significantly higher in non-responders compared to responders in the Vistusertib + Anastrozole arm (P = 0.0194 and P = 0.0002 respectively; i.e. 8 weeks progression-free survival as endpoint). This study provides RiBi-based markers relevant for a better selection of patients with advanced endometrial carcinoma by predicting the response of endocrine therapy combined with mTOR inhibitor., (© 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

SCAs are autosomal dominant neurodegenerative disorders caused by a gain-of-function protein with toxic activities, containing an expanded polyQ tract in the coding region. There are no treatments available to delay the onset, stop or slow down the progression of these pathologies. In this work we focus our attention on SCA1 which is one of the most common genotypes circulating in Italy. Here, we develop a CRISPR/Cas9-based approach to reduce both forms of the ATXN1 protein, normal and mutated with expanded polyQ. We started with the screening of 10 different sgRNAs able to target Exon 8 of the ATXN1 gene. The two most promising sgRNAs were validated in fibroblasts isolated from SCA1 patients, following the identification of the best transfection method for this type of cell. Our silencing approach significantly downregulated the expression of ataxin1, due to large deletions and the introduction of small changes in the ATXN1 gene, evidenced by NGS analysis, without major effects on cell viability. Furthermore, very few significant guide RNA-dependent off-target effects were observed. These preliminary results not only allowed us to identify the best transfection method for SCA1 fibroblasts, but strongly support CRISPR/Cas9 as a promising approach for the treatment of expanded polyQ diseases. Further investigations will be needed to verify the efficacy of our silencing system in SCA1 neurons and animal models., (© 2022. The Author(s).)

Background: A current critical need remains in the identification of prognostic and predictive markers in early breast cancer. It appears that a distinctive trait of cancer cells is their addiction to hyperactivation of ribosome biogenesis. Thus, ribosome biogenesis might be an innovative source of biomarkers that remains to be evaluated., Methods: Here, fibrillarin (FBL) was used as a surrogate marker of ribosome biogenesis due to its essential role in the early steps of ribosome biogenesis and its association with poor prognosis in breast cancer when overexpressed. Using 3,275 non-metastatic primary breast tumors, we analysed FBL mRNA expression levels and protein nucleolar organisation. Usage of TCGA dataset allowed transcriptomic comparison between the different FBL expression levels-related breast tumours., Results: We unexpectedly discovered that in addition to breast tumours expressing high level of FBL, about 10% of the breast tumors express low level of FBL. A correlation between low FBL mRNA level and lack of FBL detection at protein level using immunohistochemistry was observed. Interestingly, multivariate analyses revealed that these low FBL tumors displayed poor outcome compared to current clinical gold standards. Transcriptomic data revealed that FBL expression is proportionally associated with distinct amount of ribosomes, low FBL level being associated with low amount of ribosomes. Moreover, the molecular programs supported by low and high FBL expressing tumors were distinct., Conclusion: Altogether, we identified FBL as a powerful ribosome biogenesis-related independent marker of breast cancer outcome. Surprisingly we unveil a dual association of the ribosome biogenesis FBL factor with prognosis. These data suggest that hyper- but also hypo-activation of ribosome biogenesis are molecular traits of distinct tumors., (© 2022. The Author(s).)

Tumors in primary sensory area are challenging to remove without causing a neurological deficit, especially in musicians who present complex neuronal networks. Indeed, in this kind of patients, somatosensory evoked potentials (SSEPs) are not plenty. We describe our experience for sensory and proprioception preservation in a professional clarinet player undergoing surgery for a right parietal glioblastoma. The patient underwent surgery for a right parietal glioblastoma. Intraoperative monitoring and awake surgery while playing instrument, were performed. During resection, intraoperative stimulation caused a transient impairment of left hand movements, without SSEPs alteration. The resection was stopped anytime there was a movement impairment. We obtained a gross total tumor resection. Patient did not present neurological deficits. Standard neurophysiological monitoring is fundamental but cannot be sufficient. More complex strategies of monitoring, such as awake surgery and playing an instrument could be of help for preserving complex sensory-motor functions., (© 2020. Belgian Neurological Society.)

This cross-sectional multicentre study aimed at investigating frequency and features of painful diabetic polyneuropathy. We consecutively enrolled 816 patients attending hospital diabetic outpatient clinics. We first definitely diagnosed diabetic polyneuropathy and pure small-fibre polyneuropathy using clinical examination, nerve conduction study, and skin biopsy or quantitative sensory testing. Adhering to widely agreed criteria, we then identified neuropathic pain and diagnosed painful polyneuropathy using a combined approach of clinical examination and diagnostic tests. Of the 816 patients, 36% had a diabetic polyneuropathy associated with male sex, age, and diabetes severity; 2.5% of patients had a pure small-fibre polyneuropathy, unrelated to demographic variables and diabetes severity. Of the 816 patients, 115 (13%) suffered from a painful polyneuropathy, with female sex as the only risk factor for suffering from painful polyneuropathy. In this large study, providing a definite diagnosis of diabetic polyneuropathy and pure small-fibre polyneuropathy, we show the frequency of painful polyneuropathy and demonstrate that this difficult-to-treat complication is more common in women than in men.

Intraoperative monitoring during cerebellopontine angle surgery is widely accepted. While techniques which monitor cranial motor nerves are commonly used, monitoring the sensory afferents has been challenging. Considering the reflex arc, blink reflex (BR) might be useful in monitoring the sensory part of the trigeminal nerve, the brainstem connections and the facial nerve. We describe the case of a patient who developed hemifacial hypoesthesia after microvascular decompression surgery for trigeminal neuralgia. Intraoperative BR showed a severe loss of R1 amplitude. BR might be a useful intraoperative technique to monitor the sensory part of the trigeminal nerve.

We report a case of midbrain malformation characterized by right deviation of the medulla oblongata associated with elongation and ectasia of the basilar and left vertebral arteries in a patient with a long history of migraine-like headache with autonomic symptoms., (© 2013 American Headache Society.)

Study Objectives: To verify the existence of a symptomatic form of restless legs syndrome (RLS) secondary to multiple sclerosis (MS) and to identify possible associated risk factors., Design: Prospective, multicenter, case-control epidemiologic survey., Settings: Twenty sleep centers certified by the Italian Association of Sleep Medicine., Patients: Eight hundred and sixty-one patients affected by MS and 649 control subjects., Interventions: N/A., Measures and Results: Data regarding demographic and clinical factors, presence and severity of RLS, the results of hematologic tests, and visual analysis of cerebrospinal magnetic resonance imaging studies were collected. The prevalence of RLS was 19% in MS and 4.2% in control subjects, with a risk to be affected by RLS of 5.4 (95%confidence interval: 3.56-8.26) times greater for patients with MS than for control subjects. In patients with MS, the following risk factors for RLS were significant: older age; longer MS duration; the primary progressive MS form; higher global, pyramidal, and sensory disability; and the presence of leg jerks before sleep onset. Patients with MS and RLS more often had sleep complaints and a higher intake of hypnotic medications than patients with MS without RLS. RLS associated with MS was more severe than that of control subjects., Conclusions: RLS is significantly associated with MS, especially in patients with severe pyramidal and sensory disability. These results strengthen the idea that the inflammatory damage correlated with MS may induce a secondary form of RLS. As it does in idiopathic cases, RLS has a significant impact on sleep quality in patients with MS; therefore, it should be always searched for, particularly in the presence of insomnia unresponsive to treatment with common hypnotic drugs.