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Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common dose-limiting side effects of paclitaxel (PTX) treatment. Many age-related changes have been hypothesized to underlie susceptibility to damage or impaired regeneration/repair after nerve injury. The results of these studies, however, are inconclusive and other targets, which might be used as potential biomarkers of nerve impairment, need to be investigated.Twenty-four young (2 months of age) and 24 adult (9 months of age) Wistar male rats were randomized to either paclitaxel (PTX) treatment (10 mg/kg i.v. once/ week for 4 weeks) or vehicle administration. Neurophysiological and behavioral tests were performed to investigate nerve damage at baseline, af er 4 eeks and the 2-week follow-up period. Skin biopsies from sacrifced animals were examined for intraepidermal nerve fiber (IENF) density assessment. Blood and liver samples were collected for targeted metabolomics analysis using UltraPerformance Liquid Chromatography-Mass Spectrometry (UPLC-MS/MS). At the end of treatment, the neurophysiological studies revealed a reduction in sensory nerve action potential amplitude (p < 0.05) in the caudal nerve of young PTX-treated animals, and in both the digital and caudal nerve of adult treated animals (p < 0.05). Behavioral tests revealed a significant decrease in the mechanical threshold in young PTX-treated animals (p < 0.001),while adult treated rats showed no signif cant dif erence in mechanical threshold compared to controls. Concerning IENF assessment, both young and adult PTX-rats had reduced IENF density (p < 0.0001), which persisted at the end of follow-up.T argeted metabolomics analysis showed signif cant dif erences in the plasma metabolite prof les between PTX-treated animals developing peripheral neuropathy and age-matched controls, with triglycerides, diglycerides, acylcarnitines, carnosine, long chain ceramides, phingolipids, and bile acids playing a major role in the respo

Background and Aims: Chemotherapy-induced peripheral neurotoxicity (CIPN) is one of the most common dose-limiting side effects of paclitaxel (PTX) treatment. Many age-related changes have been hypothesized to underlie susceptibility to damage or impaired regeneration/repair after nerve injury. The results of these studies, however, are inconclusive and other potential biomarkers of nerve impairment need to be investigated. Methods: Twenty-four young (2 months) and 24 adult (9 months) Wistar male rats were randomized to either PTX treatment (10 mg/kg i.v. once/week for 4 weeks) or vehicle administration. Neurophysiological and behavioral tests were performed at baseline, after 4 weeks of treatment and 2-week follow-up. Skin biopsies and nerve specimens collected from sacrificed animals were examined for intraepidermal nerve fiber (IENF) density assessment and nerve morphology/morphometry. Blood and liver samples were collected for targeted metabolomics analysis. Results: At the end of treatment, the neurophysiological studies revealed a reduction in sensory nerve action potential amplitude (p <.05) in the caudal nerve of young PTX-animals, and in both the digital and caudal nerve of adult PTX-animals (p <.05). A significant decrease in the mechanical threshold was observed only in young PTX-animals (p <.001), but not in adult PTX-ones. Nevertheless, both young and adult PTX-rats had reduced IENF density (p < .0001), which persisted at the end of follow-up period. Targeted metabolomics analysis showed significant differences in the plasma metabolite profiles between PTX-animals developing peripheral neuropathy and age-matched controls, with triglycerides, diglycerides, acylcarnitines, carnosine, long chain ceramides, sphingolipids, and bile acids playing a major role in the response to PTX administration. Interpretation Our study identifies for the first time multiple related metabolic axes involved in PTX-induced peripheral neurotoxicity, and suggests age

La neuropatia periferica indotta da chemioterapia (CIPN) rappresenta da tempo uno degli effetti collaterali neurologici più rilevanti delle terapie oncologiche. Tuttavia, nonostante i progressi dei regimi terapeutici oncologici, la comparsa di importanti eventi avversi influisce ancora sull’efficacia della terapia antineoplastica, portando alla riduzione o all’interruzione del trattamento. Il paclitaxel è un efficace agente antitumorale utilizzato nel trattamento di diversi tumori, sebbene il suo uso clinico sia spesso limitato dall’insorgenza della neuropatia periferica indotta da paclitaxel (PIPN). Si è ipotizzato che numerose alterazioni legate all’invecchiamento siano alla base della suscettibilità al danno nervoso in età avanzata. Tuttavia, i risultati di questi studi non sono conclusivi e altri potenziali biomarcatori di danno nervoso meritano di essere considerati. Su queste basi, lo scopo del nostro studio è stato quello di indagare gli effetti legati all'età del trattamento con paclitaxel sul sistema nervoso periferico e i cambiamenti metabolici che potrebbero essere indotti dalla somministrazione di paclitaxel a diverse età. Il nostro progetto comprendeva esperimenti di neurotossicità basati su valutazioni neurofisiologiche, comportamentali e istopatologiche per valutare le alterazioni fenotipiche indotte dalla chemioterapia in relazione all’età in un modello neuropatico di PIPN. Abbiamo inoltre analizzato, attraverso un approccio metabolomico mirato basato sulla cromatografia liquida ad alta prestazione e sulla spettrometria di massa (UPLC-MS), le differenze nei profili dei metaboliti plasmatici ed epatici, al fine di identificare potenziali biomarcatori di sviluppo e progressione della PIPN, in base all'età. Le nostre analisi hanno rivelato che l’età potrebbe essere un potenziale fattore di rischio per una CIPN più severa e dovrebbe essere presa in considerazione in studi futuri per adattare il regime terapeutico e il dosaggio del chemiotera, Chemotherapy-induced peripheral neuropathy (CIPN) has long represented one of the most relevant neurological side effects of oncological therapies. Nevertheless, despite the progress in drug regimens, the occurrence of troublesome adverse events still affects the efficacy of antineoplastic therapy, leading to the reduction or discontinuation of the treatment. Paclitaxel is an anti-tubulin drug which has emerged as an efficacious antitumor agent in the treatment of different cancers. However, its clinical use is often limited by the onset of paclitaxel-induced peripheral neuropathy (PIPN). Numerous alterations related to aging have been hypothesized to underlie age-related susceptibility to nerve damage. Nevertheless, the results of these studies are inconclusive and other targets, which might be used as potential biomarkers of nerve impairment, deserve to be considered. On these bases, the aim of our study was to investigate the age-related effects of paclitaxel treatment on the peripheral nervous system, and the metabolic changes that might be induced by paclitaxel administration at different ages. Our project included neurotoxicity experiments based on neurophysiological, behavioral and histopathological evaluations to assess age-related chemotherapy-induced phenotypic alterations in a neuropathic model of PIPN. We additionally investigated through a targeted Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) based metabolomics approach differences in the plasma and liver metabolite profiles in order to identify potential biomarkers of PIPN development and progression, according to age. Our results suggest that age might be a potential risk factor for more severe CIPN, and should be considered in future studies in order to tailor the chemotherapy regimen and dosage on individual susceptibility of older cancer patients. Our study also identifies for the first time multiple related metabolic axes involved in paclitaxel-induced neurotoxicity, as prom

Background: In the aftermath of COVID-19 outbreak, there is a strong need to find strategies to monitor SARSCoV-2 transmission. While the application of screening techniques plays a major role to this end, there is evidence challenging the real significance of seroconversion. We reported a case of COVID-19 reactivation associated with a neurosurgical operation with early neuropsychiatric involvement presumably promoted by olfactory and gustatory impairment in the first infection. Case Descriptio: A 57-year-old man was referred for a 2-month history of progressive development of imbalance, dizziness, and vomiting. Magnetic resonance imaging showed two bilateral hemispheric cerebellar lesions. In line with our triage protocol, the patient underwent a nasopharyngeal swab for RNA of SARS-CoV-2 detection, which resulted positive. Of note, the patient had reported in the previous month hyposmia and hypogeusia. After a period of 14 days, three new swabs were performed with negative results, leading the way to surgery. In the early post-operative period, the patient manifested acute onset of psychotic symptoms with hyperactive delirium, followed by fever and acute respiratory failure. A chest computed tomography revealed a specific pattern of ground-glass opacities in the lower lobes bilaterally, suggesting a viral pneumonia. Serological tests demonstrated the seroconversion and a new nasopharyngeal swab confirmed SARS-CoV-2 infection. Conclusion: Our report highlights the importance of comprehensive screening assessments in sensitive cases highly susceptible to COVID-19 recurrence.

Background and purpose: Although Labrune syndrome is a well-known disorder characterized by a typical neuroradiological triad, namely leukoencephalopathy, intracranial calcifications and cysts, there are no reports of systemic involvement in this disorder. This paper attempts to describe a peculiar clinical manifestation related to a novel mutation in the SNORD118 gene. Methods: Clinical examination, brain and total-body imaging, and neurophysiological and ophthalmological investigations were performed. Amplification of the SNORD118 gene and Sanger sequencing were integrated to investigate potential causative mutations. Results: A 69-year-old woman, with a long history of episodes of vertigo and gait imbalance, was referred to our hospital for progressive cognitive and motor deterioration. Computed tomography and magnetic resonance imaging disclosed diffuse bilateral leukoencephalopathy in periventricular and deep white matter, widespread calcifications and numerous cysts in the brain, liver, pancreas and kidneys. The genetic analysis revealed two biallelic variants in the SNORD118 gene, one of which is novel (n.60G>C). Conclusions: This is the first report of adult-onset Labrune syndrome with an unusual systemic involvement presenting a novel mutation in the SNORD118 gene.

Background: Volitional control of involuntary movements has so far been considered a hallmark of tic disorders. However, modulation of involuntary movements can also be observed in other hyperkinesias. Cases: Here, we present 6 patients with chorea able to suppress their involuntary movements, on demand. In 3 of them, surface electromyography was used to quantify degree of suppression and confirmed a reduction of muscle activity up to 68%, during volitional control. Conclusion: This observation represents a first step toward a description of a new clinical feature in choreic syndromes and an opportunity to redefine the role of volitional inhibition in hyperkinetic movement disorders.

Introduction: Intradiploic pseudomeningoceles, also called intradiploic cerebrospinal fluid (CSF) fistulas, are abnormal CSF collection between the two bony tables of the calvaria resulting from post-surgical CSF leakage. To date, only six cases of intradiploic pseudomeningocele have been reported, all occurring in the occipital area. In this paper, we report the seventh case of late-onset occipital intradiploic pseudomeningocele (OIP) occurring in a young female patient who underwent surgery for the removal of a cerebellar pilocytic astrocytoma. At this regard, we also review the literature on the few recognized cases of OIP. Case presentation: The case of an 18-year-old female patient known to our institute for an operation 12 years earlier to remove a pilocytic astrocytoma is illustrated. At admission the patient complained only of occasional orthostatic headache. Brain imaging demonstrated a pseudomeningocele extended intradiploically from the occipital squama to the condylar and clivus regions, thinning both occipital bone tables and dilating the CSF-filled diploe. Watertight duroplasty and cranioplasty were effectively performed. Conclusion: Pediatric patients undergoing posterior cranial fossa craniotomy/craniectomy may postoperatively develop OIP. In this setting, treatment of any dural CSF fistula should be considered because of the risk of progressive extension and bone erosion.

Background and purpose: Intradural disc herniation (IDH) can manifest with radicular or medullary syndrome. In about 15% of cases, IDH may be responsible, through a dural laceration, for a CSF leak, determining spontaneous intracranial hypotension (SIH) and CNS superficial siderosis (CNSss). This paper attempts to present an overview on IDH as the cause for both CSF leak, and subsequent SIH, and CNSss, and to describe a peculiar clinical and neuroradiological scenario related to this condition. Methods: A search on the PUBMED database was performed. Although the investigation did not rigorously follow the criteria for a systematic review (we consider only articles about thoracic IDH), nonetheless, the best quality evidence was pursued. Furthermore, an illustrative case was presented. Results: A 69-year-old woman was referred to our hospital for slowly progressive gait disturbances and hearing impairment. Brain imaging revealed diffuse bilateral supratentorial and infratentorial superficial siderosis, mostly of the cerebellum, the eighth cranial nerves, and the brainstem. Spinal imaging disclosed a posterior disc herniation determining a dural tear at D6-D7. Lumbar puncture revealed low opening pressure and hemorrhagic CSF with siderophages. A posterior transdural herniectomy and dural sealing determined a stabilization of hearing and a significant improvement in both gait and balance. Conclusions: The diagnostic workup of CNSss with suspected CNS leak demands whole neuraxis imaging, especially in cases presenting SIH or myelopathic symptoms. This may avoid delays in detection of IDH and spinal dural leaks. The different forms of treatment available depend on the type and severity of the clinical picture.

Background: In a precedent paper, we validated part IV of the Unified Parkinson’s Disease Rating Scale (UPDRS) for detecting motor fluctuations in Parkinson’s Disease (PD) patients using a 12-h Waking-Day Motor Assessment (WDMA) as gold standard, showing a high sensitivity (> 80%) and a lower specificity (< 45%). The aim of this study was to validate the Movement Disorder Society-UPDRS (MDS-UPDRS) part IV, especially items 4.3 and 4.5, using the same methodology. Methods: PD patients attending the Movement Disorders Clinic at the University Hospital in Catania were consecutively enrolled in the study. A diurnal WDMA was performed to detect motor fluctuations. At each time interval, the motor impairment was evaluated using the motor section of the MDS-UPDRS. Presence or absence of motor fluctuations and the type of motor fluctuation were assessed by four blinded expert raters in movement disorders, by evaluating the graphical representations of the WDMA. We evaluated sensitivity and specificity together with 95% Confidence Interval (CI) of items 4.3 and 4.5, using WDMA as gold standard. Results: We estimated for item 4.3 of the MDS-UPDRS a sensitivity of 74.3% (95% CI 56.7–87.5) and a specificity of 70.6% (95% CI 44–89.7), while for item 4.5, a sensitivity of 67.9% (95% CI 47.6–84.1) and a specificity of 66.7% (95% CI 44.7–84.4). Conclusions: The present showed a higher specificity level for MDS-UPDRS with respect to the UPDRS, while a slightly lower sensitivity mainly for predictable OFF.

Background: Self-injurious behaviour has historically been associated with borderline personality disorder. Nevertheless, over recent years, it has been reported in numerous neurological syndromes, especially hyperkinesias. Case report: Two cases of SCA17 manifested self-injurious behaviour, namely repetitive scratching of the skin resulting in severe excoriations. In one of them, the abnormal behaviour was associated with the inability to resist the impulse to commit the act along with relief following the damage. Discussion: This is the first report describing self-injurious behaviour in SCA17, but the mechanisms underlying it are still not clear. Further studies are needed to clarify the pathophysiology of such manifestation in hyperkinetic syndromes.

Background: Huntington’s disease (HD) is a neurodegenerative disorder characterized by involuntary movements, cognitive decline, and behavioral changes. The complex constellation of clinical symptoms still makes the therapeutic management challenging. In the new era of functional neurosurgery, deep brain stimulation (DBS) may represent a promising therapeutic approach in selected HD patients. Methods: Articles describing the effect of DBS in patients affected by HD were selected from Medline and PubMed by the association of text words with MeSH terms as follows: “Deep brain stimulation,” “DBS,” and “HD,” “Huntington’s disease,” and “Huntington.” Details on repeat expansion, age at operation, target of operation, duration of follow-up, stimulation parameters, adverse events, and outcome measures were collected. Results: Twenty eligible studies, assessing 42 patients with HD, were identified. The effect of globus pallidus internus (GPi) DBS on Unified Huntington’s Disease Rating Scale (UHDRS) total score revealed in 10 studies an improvement of total score from 5.4 to 34.5%, and in 4 studies, an increase of motor score from 3.8 to 97.8%. Bilateral GPi-DBS was reported to be effective in reducing Chorea subscore in all studies, with a mean percentage reduction from 21.4 to 73.6%. Conclusions: HD patients with predominant choreic symptoms may be the best candidates for surgery, but the role of other clinical features and of disease progression should be elucidated. For this reason, there is a need for more reliable criteria that may guide the selection of HD patients suitable for DBS. Accordingly, further studies including functional outcomes as primary endpoints are needed.

The increased survival of cancer patients has raised growing public health concern on associated long-term consequences of antineoplastic treatment. Chemotherapy-induced peripheral neuropathy (CIPN) is a primarily sensory polyneuropathy, which may be accompanied by pain, autonomic disturbances, and motor deficit. About 70% of treated cancer patients might develop CIPN during or after the completion of chemotherapy, and in most of them such complication persists after six months from the treatment. The definition of the potential risk of development and resolution of CIPN according to a clinical and biochemical profile would be certainly fundamental to tailor chemotherapy regimen and dosage on individual susceptibility. In recent years, patient-reported and clinician-related tools along with quality of life instruments have been featured as primary outcomes in clinical setting and randomized trials. New studies on metabolomics markers are further pursuing accurate and easily accessible indicators of peripheral nerve damage. The aim of this review is to outline the strengths and pitfalls of current knowledge on CIPN, and to provide a framework for future potential developments of standardized protocols involving clinical and biochemical markers for CIPN assessment and monitoring.

Chemotherapy-induced peripheral neuropathy (CIPN) has long been recognized as a clinically significant issue in patients treated with antineoplastic drugs. This common long-term toxic side-effect which negatively impacts the outcome of the disease can lead to disability and have detrimental effects on patients' quality of life. Since axonal injury is a prominent feature of CIPN, responsible for several sensory symptoms, including pain, sensory loss and hypersensitivity to mechanical and/or cold stimuli in the hands and feet, neurophysiological assessments remain the gold standard for clinical diagnosis of CIPN. Given the large impact of CIPN on cancer patients, there is increasing emphasis on biomarkers of adverse outcomes in safety assessment and translational research, to prevent permanent neuroaxonal damage. Since the results on reliable blood molecular markers for axonal degeneration are still controversial, here we provide a brief overview of blood molecular biomarkers used for assessing and/or predicting CIPN in preclinical and clinical settings.

Introduction: Metabolomics is an emerging approach providing new insights into the metabolic changes and underlying mechanisms involved in the pathogenesis of neurological disorders. Areas covered: Here, the authors present an overview of the current knowledge of metabolic profiling (metabolomics) to provide critical insight on the role of biochemical markers and metabolic alterations in neurological diseases. Expert opinion: Elucidation of characteristic metabolic alterations in neurological disorders is crucial for a better understanding of their pathogenesis, and for identifying potential biomarkers and drug targets. Nevertheless, discrepancies in diagnostic criteria, sample handling protocols, and analytical methods still affect the generalizability of current study results.

Objectives To provide a quantitative estimation of motor fluctuations in PD through a 12-h Waking-day Motor Assessment (WDMA) and to develop new WDMA-based tools, the Motor Fluctuation Indices. Methods Two independent samples of PD patients (exploratory population N = 51, testing population N = 109) were examined. Patients underwent a WDMA using the Unified Parkinson's Disease Rating Scale (UPDRS) and were classified as either having or not having motor fluctuations. To quantify motor fluctuations, the Worsening Index (WI), the Mean Fluctuation Index (MFI) and the Coefficient of Variation (CV) were computed. The optimal cut-off for each index distinguishing patients with or without fluctuations was calculated on the exploratory population. Cut-offs’ accuracy was then verified in the testing population. Results Optimal cut-off scores to differentiate stable patients from fluctuating ones were 8.3 for WI, 5 for MFI and 12.9 for CV. Sensitivity and a specificity were 91.2% (95%CI: 85.9 to 96.5) and 87.8% (95%CI: 81.7 to 93.9) for WI; 75% (95%CI: 66.9 to 83.1) and 90.2% (95%CI: 84.7 to 95.8) for MFI; 69.1% (95%CI: 60.4 to 77.8) and 95.1% (95%CI: 91.1 to 99.2) for CV. Patients with a larger magnitude of fluctuation had higher values for all three indices, whereas patients with multiple daily fluctuations presented only higher WI values. Conclusions WDMA-derived Motor Fluctuation Indices may represent reliable tools for evaluating and quantifying the severity of motor fluctuations in PD patients. Even if WDMA is a time-consuming procedure, the detection of Motor Fluctuation Indices could be helpful in assessing therapeutic efficacy on motor fluctuations.

It is well established the relationship between the enjoyment within the physical activities and the personal motivation to follow up a healthy lifestyle. Therefore, the aim of this study was to assess the level of enjoinment during and after the practice of physical and sport activities in school sector. The sample was recruited from a primary school in the south of Italy and the participants had the following characteristics: male: 75; female: 75; mean age: 9.45. The participants were divided into two groups: control group (children did not practice any physical activities) and experimental group (children performed structured physical and sport activities). Two scales have been used for assessing the level of enjoy in such groups: the Italian version of the Physical Activity Enjoyment Scale (PACES-IT) and the Enjoy Scale. The scales provided valid and interesting data for comparing the differences between the two groups. The obtained notes will be useful for supporting the work of the physical education teachers

Introduction The UPDRS-IV represents the most common screening tool to assess motor fluctuations in patients with PD despite the lack of a clinimetric validation. Objectives We evaluated sensitivity and specificity of UPDRS-IV using a 12-h waking-day motor assessment as the gold standard. Methods We consecutively enrolled PD patients who underwent a 12-h waking-day motor assessment in the study. Patients were clinically evaluated every 2 h for 12 h using the UPDRS-III. Motor scores were reported as a line graph and six blinded raters classified patients as having or not having motor fluctuations. The UPDRS-IV was used in order to assess the presence of predictable and unpredictable motor fluctuations according to items 36–38. Results Sixty two PD patients were enrolled in the study. According to the raters’ evaluations, 39 (62.9%) were classified as having motor fluctuations, while according to the UPDRS-IV 47 (75.8%) presented a motor fluctuation giving a sensitivity of 87.2% (95%CI 72.6–95.7) and a specificity of 43.5% (95%CI 23.2–65.5). Conclusion Our study results confirm the high level of sensitivity with a lower level of specificity of UPDRS-IV to screen motor fluctuations in PD patients.