Neurofilament light chain in demyelinating conditions of the central nervous system: a promising biomarker

Neurofilaments are the major structural proteins of the neuronal cytoskeleton and are classified according to molecular weight into heavy, intermediate, and light chains. They are released into the interstitial fluid and cerebrospinal fluid (CSF) as a consequence of axonal damage. In particular, the light chain (NfL) represents the most abundant and soluble subunit and has been demonstrated to be increased in the CSF of patients with inflammatory, degenerative, vascular, or traumatic injuries in correlation with clinical and radiological activity. Similar results have been obtained measuring serum NfL with high-sensitivity single-molecule array, which enables reliable and repeatable measurement of the low NfL concentrations in serum. In particular, CSF and serum NfL values are strongly correlated in patients with multiple sclerosis (MS) and have been demonstrated to be increased in patients with MS and clinically isolated syndromes (CIS) in accordance with clinical and radiological activity. NfL levels increase in patients with a recent relapse and seem to predict cognitive impairment, long-term outcome, and conversion of CIS to MS. The few available data on patients with other demyelinating diseases suggest that NfL levels are also increased in neuromyelitis optica spectrum disorders and related conditions in correlation with attack severity, suggesting that axonal damage may occur in these disorders. We herein report and discuss published data on the role of NfL as a possible predictor of disease activity, clinical outcome and treatment response in patients with demyelinating conditions of the central nervous system

Three-dimensional mandibular motion after closed and open reduction of unilateral mandibular condylar process fractures

Objective: To detect the changes in 3D mandibular motion after two types of condylar fracture therapies. Materials and methods: Using a 3D motion analyzer, free mandibular border movements were recorded in 21 patients successfully treated for unilateral fractures of the mandibular condylar process (nine patients: open reduction, rigid internal fixation, and functional treatment; 12 patients: closed reduction and functional treatment; follow-up: 6-66 months), and in 25 control subjects. Results: No differences were found among the groups at maximum mouth opening (MO), protrusion and in lateral excursions. During opening, the patients had a larger maximal deviation to the fractured side than the controls (controls 2.3 mm, open treatment 3.9 mm, closed treatment 4.2 mm; Kruskal-Wallis test, p = 0.014; closed treatment vs. controls, p = 0.004), with a larger coronal plane angle (controls 2.4\ub0, open treatment 3.6\ub0, closed treatment 4.4\ub0; p = 0.016; closed treatment vs. controls, p = 0.013). In the closed treatment patients, a longer follow-up was related to increased maximum MO (p = 0.04), sagittal plane angle (p = 0.03), and reduced lateral mandibular deviation during MO (p = 0.03). Conclusion: Mandibular condylar fractures can recover good function; some kinematic variables of mandibular motion were more similar to the norm in the open treatment patients than in closed treatment patients. \ua9 2010 European Association for Cranio-Maxillo-Facial Surgery

Surgical Navigation in Mandibular Reconstruction: Accuracy Evaluation of an Innovative Protocol

Aim: the purpose of this work is to present an innovative protocol for virtual planning and surgical navigation in post-oncological mandibular reconstruction through fibula free flap. In order to analyze its applicability, an evaluation of accuracy for the surgical protocol has been performed. Methods: 21 patients surgically treated for mandibular neoplasm have been included in the analysis. The Brainlab Vector Vision 3.0® software for surgical navigation has been used for preoperative surgical planning and intra-operative navigation. A post-operative accuracy evaluation has been performed matching the position of mandibular landmarks between pre-operative and post-operative CT scans. Results: the maximal discrepancy observed was included between −3.4 mm and +3.2 mm, assuming negative values for under correction and positive values for overcorrection. An average grade of accuracy included between 0.06 ± 0.58 mm and 0.43 ± 0.68 mm has been observed for every mandibular landmark examined, except for mandibular angles that showed a mean discrepancy value included between 1.36 ± 1.73 mm and 1.46 ± 1.02 mm when compared to preoperative measurements. Conclusion: a satisfying level of accuracy has been observed in the protocol presented, which appears to be more versatile if compared to closed custom-made systems. The technique described may represent a valid option for selected patients, but it cannot be considered for routine activity because of the complexity of the method, the mobility of the jaw, the necessity of surgical navigator and the long surgical learning curve that is required

Ameloblastic carcinoma in a young patient

Owing to the rarity of publications describing ameloblastic carcinoma, little is known about this entity in pediatric patients. To our knowledge, malignant transformation from an odontogenic cyst into an ameloblastic carcinoma in a pediatric patient has not been documented to date. We present the case of a 14-year-old boy in whom a large osteolytic lesion associated with an impacted right maxillary third molar germ was fortuitously detected by orthopanoramic radiography. With a preoperative clinical-radiographic diagnosis of odontogenic cyst, the patient underwent surgical enucleation of the lesion. Histologic evaluation rendered a diagnosis of follicular cyst with a focal area of ameloblastic carcinoma. The literature addressing ameloblastic carcinoma is reviewed

Long-term follow-up of syndromic craniosynostosis after Le Fort III halo distraction: A cephalometric and CT evaluation

Background: Midface distraction osteogenesis (DO) in craniofacial synostosis (CFS) patients has been described by several authors. However, very few cephalometric and computed tomography (CT) long-term follow-up studies are available.Method: A total of 40 consecutive patients affected by CFS subjected to Le Fort III and rigid external distraction (RED) were examined. All patients had pre-DO cephalometric records, immediately post-DO and 6e12 months post-DO. Twenty-seven patients had mid-term records (3 years post-DO) and 20 patients had long-term records (5e10 years post-DO). Fourteen patients had CT data within 1-year of DO, while 10 patients had long-term CT data (range 5e9 years). Results: Excellent post-surgical stability was recorded. Short- and long-term CT data demon- strated excellent ossification at the osteotomy sites post-DO. In the growing patients, surface resorption in the zygomatic-temporal and in the subspinal area (p < 0.05) was observed in the long-term follow-up, as well as a mild increment of the corrected exorbitism (p < 0.05), as only appositional and no sutural growth occurs post Le Fort III, whereby orbital volume does not increase after surgery.Conclusion: Significant advancement of the midface can be achieved and maintained through Le Fort III and RED. In the long term, in growing patients, in general a class III malocclusion does not re-occur, but physiological remodelling processes at the maxillary-zygomatic level, not coupled with sutural growth, tend to mildly re-express the original midfacial phenotype and the exorbitism

HPV-related papillary squamous cell carcinoma of the tonsil during treatment with fingolimod

Fingolimod is a commonly used treatment for highly active relapsing-remitting multiple sclerosis (MS). We describe the case of a 50-year old man on fingolimod since 2011 who presented, in April 2017, with a voluminous swelling of the left tonsil. A left tonsillectomy was performed, and histological exam disclosed a papillary squamous cell carcinoma of the palatine tonsil, with an in situ hybridization positive for human papillomavirus (HPV)-16 DNA. Neither lymph nodes involvement nor other metastases were detected. Fingolimod was stopped as a precautionary measure in May 2017, and the patient currently continues his follow up at our Department. Immunocompromised patients are at risk for developing HPV-related malignancies probably in light of the suppression of T-cell immunity, therefore an increased risk for HPV activation in MS patients treated with disease modifying therapies (DMTs) characterized by a more pronounced immunosuppressant activity cannot be excluded. Given the absence of studies on larger cohorts of MS patients exposed to DMTs, additional monitoring for HPV infection during fingolimod treatment is not currently recommended. However, vigilance for this possible association is warranted

Doxifluridine and leucovorin: an oral treatment combination in advanced colorectal cancer

Purpose: This study was designed to test the activity and feasibility of an all-oral regimen of levo-leucovorin and doxifluridine (dFUR) in the treatment of advanced colorectal cancer and to establish whether the pharmacokinetics of dFUR and fluorouracil (FU) are affected by demographic and/or biologic parameters. Materials and Methods: One hundred eight patients with histologically proven colorectal cancer received orally administered levo-leucovorin 25 mg followed 2 hours later by dFUR 1,200 mg/m2 on days 1 to 5, with the cycle being repeated every 10 days. Results: Among 62 previously untreated patients, two complete responses (CRs) and 18 partial responses (PRs) were observed (overall response rate, 32%; 95% confidence interval, 21% to 45%). The median response duration was 4 months (range, 2 to 13) and the median survival time, 14 months. Among 46 pretreated patients, there were three CRs and three PRs (response rate, 13%; 95% confidence interval, 5% to 26%). In this group of patients, the median response duration was 4 months (range, 1 to 12) and the median survival time, 12 months. No toxic deaths were observed. The only World Health Organization (WHO) grade 3 to 4 side effect was diarrhea (32 patients). Conclusion: This regimen is active in previously untreated colorectal cancer patients and combines good compliance with safety. Limited but definite efficacy was also detected in the patients previously treated with FU, which suggests incomplete cross- resistance between the two drugs. The pharmacokinetic results suggest that the conversion rate of dFUR to FU increases between days 1 and 5, but that FU levels remain low in comparison to those measured after classical FU therapy. Under the experimental conditions used in this study, the interpatient variability of pharmacokinetic parameters remains largely unexplained by the tested variables.info:eu-repo/semantics/publishe

SARS-CoV-2 encephalitis is a cytokine release syndrome: evidences from cerebrospinal fluid analyses

Background: Recent findings indicated that SARS-CoV-2 related neurological manifestations involve cytokine release syndrome along with endothelial activation, blood brain barrier dysfunction, and immune-mediated mechanisms. Very few studies have fully investigated the CSF correlates of SARS-CoV-2 encephalitis. Methods: Patients with PCR-confirmed SARS-CoV-2 infection and encephalitis (COV-Enc), encephalitis without SARS-CoV-2 infection (ENC) and healthy controls (HC) underwent an extended panel of CSF neuronal (NfL, T-tau), glial (GFAP, TREM2, YKL-40) and inflammatory biomarkers (IL-1\u3b2, IL-6, Il-8, TNF- \u3b1, CXCL-13 and \u3b22-microglobulin). Results: Thirteen COV-Enc, 21 ENC and 18 HC entered the study. In COV-Enc cases, CSF was negative for SARS-CoV-2 real-time PCR but exhibited increased IL-8 levels independently from presence of pleocytosis/hyperproteinorracchia. COV-Enc patients showed increased IL-6, TNF- \u3b1, and \u3b22-microglobulin and glial markers (GFAP, sTREM-2, YKL-40) levels similar to ENC but normal CXCL13 levels. Neuronal markers NfL and T-Tau were abnormal only in severe cases. Conclusions: SARS-CoV-2-related encephalitis were associated with prominent glial activation and neuroinflammatory markers, whereas neuronal markers were increased in severe cases only. The pattern of CSF alterations suggested a cytokine-release syndrome as the main inflammatory mechanism of SARS-CoV-2 related encephalitis