Progression Of Symptoms Research Articles

Subjective sleep parameters: A marker to PTSD symptoms evolution? A 4-year longitudinal study

Disturbed sleep is a common feature after exposure to a traumatic event, especially when PTSD develops. However, although there is evidence suggesting a potential role of sleep disturbance in the progression of PTSD symptoms, the interrelationship between sleep and PTSD symptoms has yet to be determined. In order to address this knowledge gap, we have investigated the influence of initial sleep characteristics on the evolution of post-traumatic stress disorder (PTSD) symptoms over 4 years of follow-up among individuals exposed to the Brazilian Kiss nightclub fire. Participants were individuals exposed to the 2013 Kiss nightclub fire in Brazil. Sleep characteristics and PTSD symptoms were measured within the 4 years following the fire by self-report questionnaires, such as The Pittsburgh Sleep Quality Index (PSQI), and PTSD Checklist - Civilian version (PCL-C). Generalized estimating equations (GEE) models were used to examine the longitudinal associations (by estimating the relative effects of initial sleep problems on PTSD symptoms after adjusting for covariates). Comprehensive information concerning socio-demographic factors, health status, and sleep complaints were obtained. A total of 232 individuals were included. In GEE models, no significant interactions were observed between sociodemographic variables and PTSD symptoms in the follow-up period, however, associations were found between PTSD at baseline and the following factors: the female gender, the victim individuals and the existence of prior psychiatric disease. Initial subjective sleep parameters were strongly associated with PTSD symptoms over 4 years, mainly the presence of disturbed dreams (p = 0.012), increased sleep latency (p = 0.029), and reduced sleep duration (p = 0.012). Sleep complaints and PTSD symptoms were common among individuals after the disaster. The current study has found that the presence of sleep complaints, especially increased sleep latency, presence of disturbed dreams and short sleep duration, in the initial presentation after the fire was consistently associated with the perpetration of PTSD symptoms in the next 4 years of follow-up. These findings suggest that interventions addressing these sleep complaints have the potential to reduce the persistence and/or severity of PTSD symptoms.

Control of Mal secco disease in lemon by drip irrigation with fungicide

Mal secco disease of citrus is caused by the mitosporic ascomycete fungus Plenodomus tracheiphilus (formerly Phoma tracheiphila [Petri]). Mal secco is a highly destructive vascular disease of lemon and other citrus which is presently confined to the Mediterranean basin and has a marked economic impact on the citrus industry. The fungal pathogen infects the host tree by penetrating through wounds in the roots or canopy. Infection spreads quickly into the main branches and trunk and tree mortality usually ensues. The most typical symptoms are veinal chlorosis, leaf wilt, red discoloration of the xylem and dieback of twigs and branches. Current accepted control of the disease is mainly by sanitation of infected wood, and copper application during the winter to prevent germinating spores from infecting the plant. No effective chemical control for this disease has been reported. We present a drip-irrigation protocol to protect trees and control the disease in which we apply 250 g/ha of the triazole fungicide flutriafol five times a year. Progression of disease symptoms in the treated trees was inhibited by up to 81% compared to the untreated control, thereby significantly shortening the sanitation process and making it less costly than in untreated trees. Moreover, disease symptoms became less severe as the duration of treatment increased. We have treated orchards for 3 years, and present an effective commercial protocol for the growers which will help them control Mal secco disease.

A qualitative exploration of the pathway to diagnosis and treatment of cutaneous squamous cell carcinoma of the head and neck with perineural spread.

Perineural spread (PNS) is associated with a poor prognosis in cutaneous squamous cell carcinoma of the head and neck (cSCCHN). Hence, investigating facilitators and barriers of early diagnosis and treatment of PNS in cSCCHN may improve outcomes. Patients were recruited from an institutional database. Semi-structured interviews were conducted according to the Model of Pathways to Treatment. Thematic analysis was based on the four main intervals in the framework using a data-driven analytical method. Seventeen participants were interviewed. Facilitators included patients' past experiences, symptom progression, trust in healthcare professionals (HCPs), and capacity to leverage relationships. Barriers included difficult diagnoses, limited access to cancer services, lack of care coordination, and lack of awareness of PNS among primary health care providers. These findings emphasise the complexity early diagnosis and treatment of PNS. Interventions like clinical practice guidelines, education for HCPs, and telehealth could facilitate timely detection and management.

Telemedicine at a University Ophthalmology Practice During the Beginning of the COVID-19 Pandemic.

The aim of the research was to evaluate the use of teleophthalmology at a university practice during the COVID-19 pandemic, specifically examining precision, effectiveness, and patient satisfaction. Telemedicine visits were offered to new and established patients requesting appointments with the Stony Brook University Department of Ophthalmology between March 30 and June 2, 2020. Records from these visits were reviewed for chief complaint, past medical and ocular history, diagnoses, treatment/management, and providers' sub-specialty. Precision was determined by comparing agreement between diagnoses of the telemedicine visit with those of the subsequent in-person visit. The decision to follow up in person was made by the physician and patient. Diagnostic precision as well as progression, improvement, or stability of patients' symptoms were determined by the physician's assessment at follow-up visits. Post-telemedicine visit satisfaction surveys were sent to all patients. Telemedicine visits were offered to 783 patients, 520 (66.4%) of whom accepted. Of these 520 patients, 409 (78.7%) were established and 105 (20.2%) had in-person, follow-up visits. Overall, the diagnostic precision of the follow-up visits was 89.5%. Precision differed significantly across ophthalmologic subspecialties. Of the patients who had in-person follow-up visits, 56.8% remained stable, 32.4% improved, and 10.8% worsened. Established patients presented with more extensive ocular histories/procedures and experienced a higher percentage of worsening symptoms/disease stage compared to new patients. Oculoplastics/orbit was the most prevalent diagnostic subspecialty that worsened. Surveys were sent to all patients completing telemedicine visits, 15.0% of whom responded. Overall satisfaction was 91.9%, although only 23.0% of respondents preferred telemedicine to an in-office visit. Telehealth provides high levels of precision and patient satisfaction for a wide range of ophthalmologic visits, although most patients still prefer in-office examinations. Employing teleophthalmology for follow-up and emergency care may provide patients with an effective alternative during pandemic situations and beyond.

Update on systemic sclerosis

The updates to the European recommendations and the German guidelines for the treatment of systemic sclerosis are expected shortly, which are very good evidence-based guidelines for all those treating the disease; however, there are still disease manifestations with insufficient studies and current study results that were published after the review of the literature for the guidelines and might be of interest to the reader. The aim of this work is to provide an overview of the publications in the last year that are interesting from the authors' point of view. The aim is to provide practically relevant information on the current state of knowledge that can supplement the guidelines. The pathogenesis of systemic sclerosis (SSc) is becoming better understood in its interplay between environmental factors and the development of autoantibodies. There have also been overviews of the manifestation and prognosis of cardiac involvement in the last year. The American Thoracic Society issued the first guidelines for the treatment of interstitial lung disease in SSc. There are an increasing number of studies that suggest that disease-modulating combination therapies, such as rituximab and mycophenolate mofetil (MMF) are beneficial. Work addressing the involvement of joints suggests that inflammatory changes are common. Current options for the treatment of gastrointestinal involvement are presented. The diagnosis and treatment of systemic sclerosis is making progress and many symptoms and complications are treatable. Nevertheless, much remains to be done to improve the quality of life of the patients.

Motor progression trajectories and risk of mild cognitive impairment in Parkinson's disease: A latent class trajectory model from PPMI cohort.

Rare studies have investigated the association between heterogeneity of motor progression and risk of early cognitive impairment in Parkinson's disease (PD). In this study, we aim to identify distinct trajectories of motor progression longitudinally and investigate their impact on predicting mild cognitive impairment (MCI). A 5-year cohort including 415 PD patients at baseline was collected from the Parkinson's Progression Markers Initiative. The severity of motor symptoms was evaluated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale part III. The latent class trajectory model and nonlinear mixed-effects model were used to analyze and delineate the longitudinal changes in motor symptoms. Propensity score matching (PSM) was used to minimize the impact of potential confounders. Cox proportional hazard models were applied to calculate hazard ratios for MCI, and a Kaplan-Meier curve was generated using the occurrence of MCI during the follow-up as the time-to-event. Two latent trajectories were identified: a mild and remitting motor symptoms class (Class 1, 33.01%) and a severe and progressive motor symptom class (Class 2, 66.99%). Patients in Class 2 initially exhibited severe motor symptoms that worsened progressively despite receiving anti-PD medications. In comparison, patients in Class 1 exhibited milder symptoms that improved following drug therapy and a slower progression. During a 5-year follow-up, patients in Class 2 showed a higher risk of developing MCI compared to those in Class 1 before PSM (Log-Rank 28.58, p < 0.001) and after PSM (Log-Rank 8.20, p = 0.004). PD patients with severe and progressive motor symptoms are more likely to develop MCI than those with mild and stable motor symptoms.

Purple Carrot Extract Exhibits a Neuroprotective Profile in th e Nigrostriatal Pathway in the Reserpine-induced Model of Parkinson 's Disease.

Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the nigrostriatal pathway. Even with scientific and technological advances, the therapeutic approaches used for the treatment of PD have shown to be largely ineffective in controlling the progression of symptoms in the long term. There is a growing demand for the development of novel therapeutic strategies for PD treatment. Different herbs and supplements have been considered as adjuvant to treat the symptoms of Parkinsonism. The carrot is one of the most consumed vegetable species worldwide, and its root is known for its content of anthocyanins, which possess antioxidant and antiinflammatory properties. This study evaluated the neuroprotective effect of purple carrot extract (CAR) in rats on the reserpine (RES)-induced progressive parkinsonism model. Male rats (6-month-old) received orally the CAR (400 mg/kg) or vehicle and subcutaneously RES (0.01 mg/kg) or vehicle for 28 days (Preventive Phase). From the 29th day, rats received CAR or vehicle daily and RES (0.1 mg/kg) or vehicle every other day (for 23 days, Protective phase). Behavioral tests were conducted throughout the treatment. Upon completion, the animals' brain were processed for tyrosine hydroxylase (TH) immunohistochemical assessment. Our results showed that the chronic treatment of CAR protected against motor disabilities, reducing the time of catalepsy behavior and decreasing the frequency of oral movements, possibly by preserving TH levels in the Ventral Tegmental Area (VTA) and SNpc. CAR extract is effective to attenuate motor symptoms in rats associated with increased TH+ levels in the Ventral Tegmental Area (VTA) and SNpc, indicating the potential nutraceutical benefits of CAR extract in a progressive parkinsonism model induced by RES.

Predictors of patient satisfaction in the surgical treatment of cervical spondylotic myelopathy.

Patients with cervical spondylotic myelopathy (CSM) experience progressive neurological impairment. Surgical intervention is often pursued to halt neurological symptom progression and allow for recovery of function. In this paper, the authors explore predictors of patient satisfaction following surgical intervention for CSM. This is a retrospective review of prospectively collected data from the multicenter Quality Outcomes Database. Patients who underwent surgical intervention for CSM with a minimum follow-up of 2 years were included. Patient-reported satisfaction was defined as a North American Spine Society (NASS) satisfaction score of 1 or 2. Patient demographics, surgical parameters, and outcomes were assessed as related to patient satisfaction. Patient quality of life scores were measured at baseline and 24-month time points. Univariate regression analyses were performed using the chi-square test or Student t-test to assess patient satisfaction measures. Multivariate logistic regression analysis was conducted to assess for factors predictive of postoperative satisfaction at 24 months. A total of 1140 patients at 14 institutions with CSM who underwent surgical intervention were included, and 944 completed a patient satisfaction survey at 24 months postoperatively. The baseline modified Japanese Orthopaedic Association (mJOA) score was 12.0 ± 2.8. A total of 793 (84.0%) patients reported satisfaction (NASS score 1 or 2) after 2 years. Male and female patients reported similar satisfaction rates (female sex: 47.0% not satisfied vs 48.5% satisfied, p = 0.73). Black race was associated with less satisfaction (26.5% not satisfied vs 13.2% satisfied, p < 0.01). Baseline psychiatric comorbidities, obesity, and length of stay did not correlate with 24-month satisfaction. Crossing the cervicothoracic junction did not affect satisfactory scores (p = 0.19), and minimally invasive approaches were not associated with increased patient satisfaction (p = 0.14). Lower baseline numeric rating scale neck pain scores (5.03 vs 5.61, p = 0.04) and higher baseline mJOA scores (12.28 vs 11.66, p = 0.01) were associated with higher satisfaction rates. Surgical treatment of CSM results in a high rate of patient satisfaction (84.0%) at the 2-year follow-up. Patients with milder myelopathy report higher satisfaction rates, suggesting that intervention earlier in the disease process may result in greater long-term satisfaction.

A RARE CASE OF JUVENILE MYASTHENIA GRAVIS

Juvenile Myasthenia Gravis is arare auto immune disorder affecting children and adolescents, characterized by ptosis, muscle weakness and fatigability, untreated patients may progress to paralysis of the respiratory muscles and the risk of aspiration, particularly at times when they have an upper respiratory tract infection. Early recognition of this disease helps avoid unnecessary testing, prevent undue parental anxiety and stop the progression of symptoms. An 18 months old girl admitted with progressive dropping of eyelids, swallowing difficulty, loss of head control and generalized fatigability. She had positive acetyl cholinesterase test. Investigation releavedelectro decrementalresponsonse in electromyography. Patient treated with oral pyridostigmine bromide and steroid resulted in improvement in muscle strength and functional ability with regularly followed in OPD.JMG requires prompt recognition and management to prevent complications. This case highlights the importance of considering JMG in children with persistent weakness and fatigue.

Exploring circular RNAs as biomarkers for Parkinson's disease and their expression changes after aerobic exercise rehabilitation.

Circular RNAs (circRNAs) are circularized single-stranded ribonucleic acids that interacts with DNA, RNA, and proteins to play critical roles in cell biology. CircRNAs regulate microRNA content, gene expression, and may code for specific peptides. Indeed, circRNAs are differentially expressed in neurodegenerative disorders like Parkinson's disease (PD), playing a potential role in the mechanisms of brain pathology. The RNA molecules with aberrant expression in the brain can cross the blood-brain barrier and reach the bloodstream, which enable their use as non-invasive PD disease biomarker. Promising targets with valuable discriminatory ability in combined circRNA signatures include MAPK9_circ_0001566, SLAIN1_circ_0000497, SLAIN2_circ_0126525, PSEN1_circ_0003848, circ_0004381, and circ_0017204. On the other hand, regular exercises are effective therapy for mitigating PD symptoms, promoting neuroprotective effects with epigenetic modulation. Aerobic exercises slow symptom progression in PD by improving motor control, ameliorating higher functions, and enhancing brain activity and neuropathology. These improvements are accompanied by changes circRNA expression, including hsa_circ_0001535 (circFAM13B) and hsa_circ_0000437 (circCORO1C). The sensitivity of current methods for detecting circulating circRNAs is considered a limitation. While amplification kits already exist for low-abundant microRNAs, similar kits are needed for circRNAs. Alternatively, the use of digital PCR can help overcome this constraint. The current review examines the potential use of circRNAs as non-invasive biomarkers of PD and to assess the effects of rehabilitation. Although circRNAs hold promise as targets for PD diagnosis and therapeutics, further validation is needed before their clinical implementation.

Small molecule targeting NaV1.7 via inhibition of CRMP2-Ubc9 interaction reduces pain-related outcomes in a rodent osteoarthritic model.

Osteoarthritis (OA) is a highly prevalent and disabling joint disease, characterized by pathological progressive joint deformation and clinical symptoms of pain. Disease-modifying treatments remain unavailable, and pain-mitigation is often suboptimal, but recent studies suggest beneficial effects by inhibition of the voltage-gated sodium channel NaV1.7. We previously identified compound 194 as an indirect inhibitor of NaV1.7 by preventing SUMOylation of the NaV1.7-trafficking protein, collapsin response mediator protein 2. Compound 194 reduces the functional activity of NaV1.7 channels and produces effective analgesia in a variety of acute and neuropathic pain models. However, its effectiveness has not yet been evaluated in models of OA. Here, we explore the effects of 194 on pain-related outcomes in the OA-like monoiodoacetate model using behavioral assessment, biochemistry, novel in vivo fiber photometry, and patch clamp electrophysiology. We found that the monoiodoacetate model induced (1) increased pain-like behaviors and calcium responses of glutamatergic neurons in the parabrachial nucleus after evoked cold and mechanical stimuli, (2) conditioned place aversion to mechanical stimulation, (3) functional weight bearing asymmetry, (4) increased sodium currents in dorsal root ganglia neurons, and (5) increased calcitonin gene-related peptide-release in the spinal cord. Crucially, administration of 194 improved all these pain-related outcomes. Collectively, these findings support indirect inhibition of NaV1.7 as an effective treatment of OA-related pain through the inhibition of collapsin response mediator protein 2-SUMOylation via compound 194.

Exploring the complex nexus of Alzheimers disease in down syndrome

In recent years, the life expectancy of individuals with Down Syndrome (DS) has increased significantly thanks to the advancements in healthcare and treatments, giving rise to an older population of people with DS. However, this demographic shift has brought about new concerns: as individuals with DS age, they face a higher incidence of early-onset Alzheimers Disease (EOAD) (i.e. the development of AD before the age of 65). Research has revealed an accelerated progression of symptoms, from onset of dementia to death, in DS patients. Thus, it is essential to identify the factors (both genetic and environmental) that underlie the development of different stages of AD-DS. Concomitantly, there is a pressing need to initiate intervention trials that could slow down or prevent the rapid advancement of AD-DS. This paper underscores the growing importance of addressing AD-DS in an ageing DS population. By elucidating genetic and environmental factors, clinical features, diagnostic challenges, roles of genes in the development of AD-DS, and potential future research directions, the article aims to contribute to a deeper understanding of dementia of the Alzheimer Type (DAT) and facilitate the development of effective treatments that could improve the lives of DS individuals affected by DAT.

Wolfram Syndrome 1: A Neuropsychiatric Perspective on a Rare Disease.

Wolfram syndrome 1 (WS1) is an uncommon autosomal recessive neurological disorder that is characterized by diabetes insipidus, early-onset non-autoimmune diabetes mellitus, optic atrophy, and deafness (DIDMOAD). Other clinical manifestations are neuropsychiatric symptoms, urinary tract alterations, and endocrinological disorders. The rapid clinical course of WS1 results in death by the age of 30. Severe brain atrophy leads to central respiratory failure, which is the main cause of death in WS1 patients. Mutations in the WFS1 gene, located on chromosome 4p16, account for approximately 90% of WS1 cases. The gene produces wolframin, a transmembrane glycoprotein widely distributed and highly expressed in retinal, neural, and muscular tissues. Wolframin plays a crucial role in the regulation of apoptosis, insulin signaling, and ER calcium homeostasis, as well as the ER stress response. WS1 has been designated as a neurodegenerative and neurodevelopmental disorder due to the numerous abnormalities in the ER stress-mediated system. WS1 is a devastating neurodegenerative disease that affects patients and their families. Early diagnosis and recognition of the initial clinical signs may slow the disease's progression and improve symptomatology. Moreover, genetic counseling should be provided to the patient's relatives to extend multidisciplinary care to their first-degree family members. Regrettably, there are currently no specific drugs for the therapy of this fatal disease. A better understanding of the etiology of WS1 will make possible the development of new therapeutic approaches that may enhance the life expectancy of patients. This review will examine the pathogenetic mechanisms, development, and progression of neuropsychiatric symptoms commonly associated with WS1. A thorough understanding of WS1's neurophysiopathology is critical for achieving the goal of improving patients' quality of life and life expectancy.

Describing an old trick in posterior thoracal and lumbar ımplant removal surgery: follow-up results for at least 10 years

Study designRetrospective case series.ObjectivesWe aimed to describe with a novel surgical approach for the removal of posterior thoracolumbar implant in patients with symptomatic failure of the implant and present our preliminary results with this method.MethodsThis retrospective, single-center study was performed in the neurosurgery department of a university hospital. Data were gathered from the medical files of 314 patients (243 women, 77.39%; 71 men, 22.61%) with symptomatic thoracolumbar implant failure that underwent implant removal operation using our novel technique between 2010 and 2020. Symptoms, radiological findings, intraoperative findings as well as clinical outcomes were evaluated.ResultsIn our series, the average age was 46.5 years (range: 21–84) with a mean follow-up duration of 7 years (range: 3 months to 10 years). Preoperatively, the most common symptoms were leg pain and numbness of the lower extremity. Postoperatively, no major complications were noted. Clinical progression of symptoms was avoided by surgery in all patients, while we came across removal difficulties due to screw–screwdriver mismatch in 15 of 314 surgeries (4.78%). Our novel approach allowed successful screw removal including these challenging cases.ConclusionsWe suggest that our novel approach is a practical and effective for the removal of posterior thoracolumbar implant in cases with symptomatic failure attributed to screw–screwdriver mismatch. Further trials are warranted to assess the efficacy of this technique to overcome surgical problems associated with screw removal.

HEREDITARY CONGENITAL NEPHROTIC SYNDROME IN CHILDREN: FEATURES OF THE COURSE, MODERN PROSPECTS FOR LIFE AND HEALTH

Every pediatrician-nephrologist repeatedly have to deal with cases of the birth of childrenwith early onset of nephrotic syndrome, which is characterized by a severe course, persistent progression ofsymptoms, resistance to standard immunosuppressive therapy, questionable and, often, unfavorable prognosesfor life and health, which requires constant improvement of existing professional knowledge, diagnostic andtherapeutic skills. The article presents a review of the scientific literature of domestic and foreign authors,which allows changing the perception of the disease, improving outcomes, giving chances to the patient andhis family in conditions of modern and timely diagnosis and the correct choice of patient management strategy.

Disease Progression of Data-Driven Subtypes of Parkinson's Disease: 5-Year Longitudinal Study from the Early Parkinson's Disease Longitudinal Singapore (PALS) Cohort.

The detailed trajectory of data-driven subtypes in Parkinson's disease (PD) within Asian cohorts remains undisclosed. To evaluate the motor, non-motor symptom (NMS) progression among the data-driven PD clusters. In this 5-year longitudinal study, NMS scale (NMSS), Hospital Anxiety Depression Scale (HADS), and Epworth sleepiness scale (ESS) were carried out annually to monitor NMS progression. H& Y staging scale, MDS-UPDRS part III motor score, and postural instability gait difficulty (PIGD) score were assessed annually to evaluate disease severity and motor progression. Five cognitive standardized scores were used to assess detailed cognitive progression. Linear mixed model was performed to assess the annual progression rates of the longitudinal outcomes. Two hundred and six early PD patients, consisting of 43 patients in cluster A, 98 patients in cluster B and 65 subjects in cluster C. Cluster A (severe subtype) had significantly faster progression slope in NMSS Domain 3 (mood/apathy) score (p = 0.01), NMSS Domain 4 (perceptual problems) score (p = 0.02), NMSS Domain 7 (urinary) score (p = 0.03), and ESS Total Score (p = 0.04) than the other two clusters. Cluster A also progressed significantly in PIGD score (p = 0.04). For cognitive outcomes, cluster A deteriorated significantly in visuospatial domain (p = 0.002), while cluster C (mild subtype) deteriorated significantly in executive domain (p = 0.04). The severe cluster had significantly faster progression, particularly in mood and perceptual NMS domains, visuospatial cognitive performances, and postural instability gait scores. Our findings will be helpful for clinicians to stratify and pre-emptively manage PD patients by developing intervention strategies to counter the progression of these domains.

An efficient and successful outcome after haematopoietic stem cell transplantation in a patient with an LPS-responsive beige-like anchor gene mutation.

Lipopolysaccharide (LPS)-responsive beige ankyrin (LRBA) gene mutations were first reported as the cause of immunodeficiency syndromes and autoimmunity in 2012. The majority of LRBA patients have multiple organ system involvement and a complex clinical phenotype. Herein we present a comprehensive account on the disease progression and transplantation procedure in a patient with LRBA deficiency who exhibited progressive autoimmune disease symptoms along with recurrent pulmonary infections since the age of 6 years old. Despite receiving abatacept therapy and immunoglobulin replacement treatments to manage the symptoms, but the symptoms still progressed. Therefore, nine years after disease onset, patients were treated with allogeneic haematopoietic stem cell transplantation (allo-HSCT). The patient experienced acute and chronic graft-versus-host disease (GVHD) and recurrent infections after transplantation. During one and a half years of follow-up, we found that allogeneic haematopoietic stem cell transplantation can relieve the symptoms of autoimmune disease in patients with LRBA deficiency, and marked clinical improvement and recovery of immune function were observed following stem cell transplantation.

Longitudinal Quality-of-Life Outcomes of Skull Base Chondrosarcoma Patients following Surgical Resection

Abstract Objective Owing to the rarity of skull base chondrosarcomas (CS), much of its natural history and long-term impact on patient quality of life (QoL) are not well studied. This novel study demonstrates QoL among CS patients following radical treatment constituting surgery and postoperative radiotherapy over 2 decades. Study Design Retrospective review and prospective data collection to obtain patient demographic, tumor characteristics, clinical symptoms, and patient-reported QoL outcomes using the 36-Item Short Form Health Survey (SF-36). Setting/Participants Patients diagnosed with CS who underwent radical intent surgical resection by the senior author and adjuvant early postoperative proton beam therapy. Results Twenty-eight skull base CS patients were identified, with 19 patients completing full treatment course. Mean long-term follow-up was 148.9 months. Diplopia symptom resolution was high. No significant deterioration in SF-36 Physical Health Component (PHC) and Mental Health Component (MHC) scores was observed at postoperative and long-term follow-up. General health was stable initially but deteriorated in long term (Δ −18.88, minimal clinically important difference [MCID]: 9.86, p = 0.04). Compared with age-matched Canadian control patients, CS patients reported similar PHC scores at baseline and follow-up. CS patients reported lower MHC scores (45.8 vs. 50.9, p = 0.13) preoperatively, which persisted at follow-up decreasing by 1.9 (43.9 vs. 53.7, p = 0.03); this difference, however, did not reach MCID threshold of Δ 5.9. Conclusion We present the longest follow-up data on CS demonstrating stable long-term QoL with aggressive surgery. Tumor control was high and preoperative tumor size did not affect long-term QoL. Preoperative QoL was lower among CS compared with Canadian normative data. Postoperatively, only the decline in physical functioning QoL scores exceeded MCID. At long-term follow-up, the decline in physical functioning, social functioning, and general health exceeded MCID. Overall, QoL among CS patients remained lower at long-term follow-up despite absence of tumor progression and resolution of symptoms.

A preclinical mice model of multiple sclerosis based on the toxin-induced double-site demyelination of callosal and cerebellar fibers

BackgroundMultiple sclerosis (MS) is an irreversible progressive CNS pathology characterized by the loss of myelin (i.e. demyelination). The lack of myelin is followed by a progressive neurodegeneration triggering symptoms as diverse as fatigue, motor, locomotor and sensory impairments and/or bladder, cardiac and respiratory dysfunction. Even though there are more than fourteen approved treatments for reducing MS progression, there are still no cure for the disease. Thus, MS research is a very active field and therefore we count with different experimental animal models for studying mechanisms of demyelination and myelin repair, however, we still lack a preclinical MS model assembling demyelination mechanisms with relevant clinical-like signs.ResultsHere, by inducing the simultaneous demyelination of both callosal and cerebellar white matter fibers by the double-site injection of lysolecithin (LPC), we were able to reproduce CNS demyelination, astrocyte recruitment and increases levels of proinflammatory cytokines levels along with motor, locomotor and urinary impairment, as well as cardiac and respiratory dysfunction, in the same animal model. Single site LPC-injections either in corpus callosum or cerebellum only, fails in to reproduce such a complete range of MS-like signs.ConclusionWe here report that the double-site LPC injections treatment evoke a complex MS-like mice model. We hope that this experimental approach will help to deepen our knowledge about the mechanisms of demyelinated diseases such as MS.

Primary diffuse large B-cell lymphoma of the central nervous system identified with CSF biomarkers

BackgroundDiagnosis of primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) is challenging and often delayed. MRI imaging, CSF cytology and flow cytometry have a low sensitivity and even brain biopsies can be misleading. We report three cases of PCNSL with various clinical presentation and radiological findings where the diagnosis was suggested by novel CSF biomarkers and subsequently confirmed by brain biopsy or autopsy.Case presentations.The first case is a 79-year-old man with severe neurocognitive dysfunction and static ataxia evolving over 5 months. Brain MRI revealed a nodular ventriculitis. An open brain biopsy was inconclusive. The second case is a 60-year-old woman with progressive sensory symptoms in all four limbs, evolving over 1 year. Brain and spinal MRI revealed asymmetric T2 hyperintensities of the corpus callosum, corona radiata and corticospinal tracts. The third case is a 72-year-old man recently diagnosed with primary vitreoretinal lymphoma of the right eye. A follow-up brain MRI performed 4 months after symptom onset revealed a T2 hyperintense fronto-sagittal lesion, with gadolinium uptake and perilesional edema. In all three cases, CSF flow cytometry and cytology were negative. Mutation analysis on the CSF (either by digital PCR or by next generation sequencing) identified the MYD88 L265P hotspot mutation in all three cases. A B-cell clonality study, performed in case 1 and 2, identified a monoclonal rearrangement of the immunoglobulin light chain lambda (IGL) and kappa (IGK) gene. CSF CXCL-13 and IL-10 levels were high in all three cases, and IL-10/IL-6 ratio was high in two. Diagnosis of PCNSL was later confirmed by autopsy in case 1, and by brain biopsy in case 2 and 3.ConclusionsTaken together, 5 CSF biomarkers (IL-10, IL-10/IL-6 ratio, CXCL13, MYD88 mutation and monoclonal IG gene rearrangements) were strongly indicative of a PCNSL. Using innovative CSF biomarkers can be sensitive and complementary to traditional CSF analysis and brain biopsy in the diagnosis of PCNSL, potentially allowing for earlier diagnosis and treatment.