Central Nervous System Symptoms Research Articles

Methamphetamine Use: A Narrative Review of Adverse Effects and Related Toxicities

Methamphetamine has been labeled "America's most dangerous drug" and has received significant public health attention. Stimulant addiction and tolerance are heavily documented in the literature; increasingly larger doses maintain euphoria in short time periods to withstand stimulant tolerance. Stimulant deaths are high in the United States and abroad. Between 2013 and 2019, deaths related to methamphetamine use quadrupled from 3,616 to 16,127. Methamphetamine use increased four-fold from 2015 to 2016. Due to this increase in methamphetamine use and its associated medical complications, the mortality rate associated with methamphetamine use has doubled over the past ten years. Cardiopulmonary symptoms include chest pain, palpitations, and shortness of breath. Methamphetamine-related myocardial infarction can also occur. Central nervous system symptoms include agitation, anxiety, delusions, hallucinations, and seizures. Methamphetamine-induced psychosis may unmask underlying psychiatric disorders. It can also cause cerebral vasculitis, which elicits cortical blindness and ischemic strokes. Methamphetamine-induced neurotoxicity in serotonergic systems is more diffuse, involving the striatum, hippocampus, septum, amygdala, and hypothalamus leading to mood changes, psychosis, and memory impairment. This narrative review will aim to highlight the adverse effects as well as the toxicity that can occur with methamphetamine use.

Clinical features and risk factors of surgical site infections in HIV-negative patients with cryptococcal meningitis underwent ventriculoperitoneal shunt operations: a retrospective study

BackgroundTo investigate the clinical features and risk factors of ventriculoperitoneal shunt (VPS) associated surgical site infections (SSIs) in HIV-negative patients with cryptococcal meningitis (CM).MethodsWe retrospectively reviewed the medical records of HIV-negative patients with CM underwent VPS operation admitted to The Third Affiliated Hospital of Sun Yat-sen University in Southwest China over the past 7 years.Results193 patients were included, of whom 25 (12.95%) had SSIs in 6 (median duration, 1–48 days) days after operation. Compared with patients without SSIs, patient with SSIs tended to be shorter preoperative stay. 52% patients in SSIs group and 25% patients in no-SSIs group underwent VPS operations within 3 days after admission (p = 0.017). Although body temperature and infectious indicators slightly elevated postoperative in both groups. The patients with SSIs experienced more fever; more central nervous system symptoms; higher PCT value and lower cerebrospinal fluid (CSF) glucose in contrast to the no-SSIs group. Multivariate regression analysis found a 2.653 fold increase in the risk of infection for every 1 °C increase in postoperative body temperature. Among the 25 patients, 9 patients had positive culture results, three samples reported to be oxacillin resistant coagulase-negative Staphylococci.ConclusionsSSIs was one of the serious surgical complications after VPS operation. High body temperature, the occurrence of dizziness and headache, low postoperative hemoglobin are risk factors. Postoperative patients with high fever, high PCT and low CSF glucose should be paid more attention to.

CLASSICAL MIGRAINE

A classic migraine is a recurrent attack of visual, sensory, or other central nervous system symptoms that are unilateral and last several minutes, followed or not followed by a migraine attack. Migraine commonly occurs in 19% of women and 11% of men worldwide, with 20% of sufferers experiencing classic migraine. The etiopathophysiology of classical migraine is not known with certainty, but vascular, neurological, and genetic dysfunction are suspected to be the cause. Classical migraine pathophysiology is associated with the theory of cortical spreading depression, which can explain the process of aura. There are four phases in classical migraine, namely prodromal, aura, headache, and prodromal phases, each of which has its own symptoms. This is the basis for the diagnosis of migraine, which is established based on the history and physical examination. Migraine therapy includes preventive therapy (lifestyle changes and prophylactic administration) as well as abortive therapy (administration of specific and non-specific drugs).

New Myrtenal-Adamantane Conjugates Alleviate Alzheimer's-Type Dementia in Rat Model.

Alzheimer’s disease (AD) is a neurodegenerative disease associated with memory impairment and other central nervous system (CNS) symptoms. Two myrtenal–adamantane conjugates (MACs) showed excellent CNS potential against Alzheimer’s models. Adamantane is a common pharmacophore for drug design, and myrtenal (M) demonstrated neuroprotective effects in our previous studies. The aim of this study is to evaluate the MACs’ neuroprotective properties in dementia. Methods: Scopolamine (Scop) was applied intraperitoneally in Wistar rats for 11 days, simultaneously with MACs or M as a referent, respectively. Brain acetylcholine esterase (AChE) activity, noradrenaline and serotonin levels, and oxidative brain status determination followed behavioral tests on memory abilities. Molecular descriptors and docking analyses for AChE activity center affinity were performed. Results: M derivatives have favorable physicochemical parameters to enter the CNS. Both MACs restored memory damaged by Scop, showing significant AChE-inhibitory activity in the cortex, in contrast to M, supported by the modeling analysis. Moderate antioxidant properties were manifested by glutathione elevation and catalase activity modulation. MACs also altered noradrenaline and serotonin content in the hippocampus. Conclusion: For the first time, neuroprotective properties of two MACs in a rat dementia model were observed. They were stronger than the natural M effects, which makes the substances promising candidates for AD treatment.

Simultaneous assay of urine sepiapterin and creatinine in patients with sepiapterin reductase deficiency

ObjectivesSepiapterin reductase deficiency (SRD) causes central nervous system symptoms due to dopamine and serotonin depletion because sepiapterin reductase plays an important role in tetrahydrobiopterin biosynthesis. SRD cannot be detected by newborn screening because of the absent hyperphenylalaninemia. To diagnose SRD biochemically, confirmation of reduced monoamine metabolites and elevated sepiapterin in the cerebrospinal fluid (CSF) has been considered necessary, because a past study showed no elevation of urine sepiapterin. Recently, however, the elevation of urine sepiapterin in SRD was reported. MethodsWe developed a fast method to measure sepiapterin and creatinine simultaneously using high-performance liquid chromatography with fluorescence and ultraviolet detection. Urine sepiapterin and creatinine were measured in three SRD patients, two SRD carriers, four SRD siblings, and 103 non-SRD patients. ResultsIn the three SRD cases, concentrations of urine sepiapterin were 1086, 914, and 575 µmol/mol creatinine (upper limit: 101.7 µmol/mol creatinine), and were markedly higher than those in other groups. CSF sepiapterin concentration was also measured in one SRD case and it was 4.1 nmol/L (upper limit: 0.5 nmol/L). ConclusionsThe simultaneous determination of urine sepiapterin and creatinine appears helpful for the diagnosis of SRD. This assay system can also be used to measure sepiapterin in the CSF.

Psychobiotics: the Influence of Gut Microbiota on the Gut-Brain Axis in Neurological Disorders.

Nervous system disorders are one of the common problems that affect many people around the world every year. Regarding the beneficial effects of the probiotics on the gut and the gut-brain axis, their application along with current medications has been the subject of intense interest. Psychobiotics are a probiotic strain capable to affect the gut-brain axis. The effective role of Psychobiotics in several neurological disorders is documented. Consumption of the Psychobiotics containing nutrients has positive effects on the improvement of microbiota as well as alleviation of some symptoms of central nervous system (CNS) disorders. In the present study, the effects of probiotic strains on some CNS disorders in terms of controlling the disease symptoms were reviewed. Finding suggests that Psychobiotics can efficiently alleviate the symptoms of several CNS disorders such as autism spectrum disorders, Parkinson’s disease, multiple sclerosis, insomnia, depression, diabetic neuropathy, and anorexia nervosa. It can be concluded that functional foods containing psychotropic strains can help to improve mental health.Graphical

SARS-CoV-2 infection and seizures: the perfect storm.

Seizures have been increasingly identified as a neurologic manifestation of coronavirus disease 2019 (COVID-19) infection. They may be symptomatic due to systemic infections, as a result of direct central nervous system (CNS) invasion, or occur in response to inflammatory reactions to the virus. It is possible that proinflammatory molecules released in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to hyperexcitability and epileptogenesis, similar to infections caused by other neurotrophic viruses. Cerebral spinal fluid (CSF) in patients with COVID-19 and seizures is negative for SARS-CoV-2 (PCR) in the majority of patients, but has been found to be positive for proinflammatory molecules like IL-6, IL-8, and anti-neuronal autoantibodies. Electroencephalogram (EEG) in COVID-19 patients are nonspecific. However, in the encephalopathic and critically ill subpopulation, EEG is essential in detecting nonconvulsive seizures and status epilepticus which is associated with increased overall mortality in COVID-19 patients. Thus, as encephalopathy is often the only CNS symptom evidenced in patients with nonconvulsive seizures, more judicious use of continuous EEG in encephalopathic COVID-19 patients should be considered. This would facilitate earlier detection and treatment of seizures in this population, which would ultimately improve outcomes. Further research into the onset and potential for development of seizures and epilepsy in patients with COVID-19 is needed.

A Machine Learning Approach to Predict the Probability of Brain Metastasis in Renal Cell Carcinoma Patients

Patients with brain metastasis (BM) have a better prognosis when it is detected early. However, current guidelines recommend brain imaging only when there are central nervous system symptoms or abnormal experimental values. Therefore, metastases are discovered later in asymptomatic patients. As a result, there is a need for an algorithm that predicts the possibility of BM using clinical data and machine learning (ML). Data from 3153 patients with renal cell carcinoma (RCC) were collected from the 11-institution Korean Renal Cancer Study group (KRoCS) database. To predict BM, clinical information of 1282 patients was extracted from the database and used to compare the performance of six ML algorithms. The final model selection was based on the area under the receiver operating characteristic (AUROC) curve. After optimizing the hyperparameters for each model, the adaptive boosting (AdaBoost) model outperformed the others, with an AUROC of 0.716. We developed an algorithm to predict the probability of BM in patients with RCC. Using the developed predictive model, it is possible to avoid detection delays by performing computed tomography scans on potentially asymptomatic patients.

Abstract CT558: Capmatinib vs docetaxel as second- or third-line therapy in patients with locally advanced or metastatic METex14-mutated NSCLC: The GeoMETry-III trial

Abstract Background: MET dysregulation is a poor prognostic factor in advanced non-small cell lung cancer (NSCLC). MET exon 14 skipping (METex14) mutations occur in ~3% of patients with NSCLC. There is limited evidence of the efficacy of standard therapies, such as chemotherapy or immunotherapy, in patients with METex14-mutated advanced NSCLC. Capmatinib, a MET inhibitor (METi), is approved for the treatment of adult patients with metastatic METex14-mutated NSCLC, based on the results of the phase 2 GEOMETRY mono-1 study. Results (data cutoff: September 18, 2020) of this study in patients with METex14-mutated NSCLC treated with capmatinib showed an overall response rate (ORR) of 66.7% in first line (N=60), 51.6% in second line (N=31) and 40.6% in second- or third-line (2/3L; N=69). GeoMETry-III (NCT04427072) is a multicenter, open-label, randomized, controlled, global, phase 3 trial that is further evaluating the efficacy and safety of capmatinib vs docetaxel in the 2/3L setting in patients with METex14-mutated NSCLC. Methods: This study began enrollment in September 2020 and is currently recruiting adult patients with EGFR wild-type, ALK-negative, stage IIIB/IIIC/IV METex14-mutated NSCLC, who have progressed on 1 or 2 prior lines of systemic therapy for advanced/metastatic disease and are candidates for single-agent docetaxel. Other eligibility criteria include ≥1 measurable lesion per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), an Eastern Cooperative Oncology Group performance status of ≤1 and no prior treatment with any METi or hepatocyte growth factor-targeting therapies. Patients with neurologically unstable, symptomatic central nervous system (CNS) metastases or those requiring increasing doses of steroids ≤2 weeks prior to study entry to manage CNS symptoms are excluded. Around 90 patients will be randomized 2:1 to receive either oral capmatinib 400 mg twice daily or intravenous docetaxel 75 mg/m2 every 21 days. Randomization is stratified by number of prior lines (1 or 2) of systemic therapy. Patients meeting protocol-specified eligibility criteria can cross over from the docetaxel to the capmatinib arm after blinded independent review committee (BIRC)-confirmed progressive disease as per RECIST 1.1.The primary endpoint is progression-free survival (PFS) by BIRC per RECIST 1.1. The key secondary endpoint is ORR by BIRC per RECIST 1.1. Other secondary endpoints include investigator-assessed ORR and PFS; duration of response, time to response and disease control rate (DCR) by BIRC and investigator; overall survival; safety; pharmacokinetics; patient-reported outcomes; overall intracranial response rate, intracranial DCR, duration of- and time to- intracranial response by BIRC per the Response Assessment in Neuro-Oncology Brain Metastases criteria in patients with baseline CNS lesions. Citation Format: Pierre Jean Souquet, Sang-We Kim, Johan F. Vansteenkiste, Anna Robeva, Aline Jary, Sabine Glaser, Alejandro Yovine, Juergen Wolf. Capmatinib vs docetaxel as second- or third-line therapy in patients with locally advanced or metastatic METex14-mutated NSCLC: The GeoMETry-III trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT558.

Can plasma exchange therapy be an option for the treatment of SARS-CoV-2 Related Splenial Lesion Syndrome: Two cases from the pediatric intensive care unit

BackgroundReversible splenial lesion syndrome (RESLES) is characterized by a temporary lesion in the splenium of the corpus callosum. RESLES is one of the most common causes of Mild encephalitis/encephalopathy reversible splenial lesion (MERS) and a rare clinical syndrome for the pediatric population. In a limited number of pediatric case reports, association with SARS-COV-2 in was reported. We aimed to increase the awareness of neurological involvement and treatment options of RESLES in children diagnosed with MIS-C. Case presentationWe report two cases with a diagnosis of multisystem inflammatory syndrome-children who developed RESLES during the disease course. Fever, blurred vision, ataxia and encephalopathy were the main central nervous system symptoms. In our first case, we observed a rapid recovery in clinical symptoms and complete resolution of the splenial lesion in with intravenous immunoglobulin (IVIG) and methylprednisolone treatment. However, our second case did not respond to IVIG and methylprednisolone treatment. We performed therapeutic plasma exchange therapy and observed a successful recovery both in brain magnetic resonance imaging and echocardiographic findings. ConclusionAlthough IVIG and methylprednisolone are the first choice treatment methods in MIS-C cases progressing with RESLES, therapeutic plasma exchange may be an option for the treatment of unresponsive cases.

A Case Series of Indian Red Scorpion Bite and Rare Clinical Presentation of Central Nervous System

Indian red scorpion (Hottentotta tamulus) is a very dangerous venomous animal found in Indian Territory; its venom contains various toxins which causes direct effect on the central nervous system (CNS). We report a case series of 12 patients who were bitten and had atypical clinical presentation affecting CNS. We evaluated 12 patients of Indian red scorpion sting by taking history, routine blood investigations, CT scan of brain, and CNS examination at a tertiary care hospital in Gujarat. We observed that if patient takes longer time after sting to visit hospital, there are more chances of development of CNS signs and symptoms and indicates poor prognosis. Indian red scorpion venom is a potent sympathetic stimulant and cardio-toxic agent. It can also cause haemorrhagic and thrombotic stroke, cerebellar stroke and cerebellitis. Prazosin is the treatment of sting as there is no availability of anti-venom for sting. Prognosis is directly related to duration between scorpion sting and initiation of treatment. Keywords: 5’nucleotidase, roving eye movements, acute cerebellitis.

Protective Immune Responses Induced by an mRNA-LNP Vaccine Encoding prM-E Proteins against Japanese Encephalitis Virus Infection.

Japanese encephalitis virus (JEV) is an important zoonotic pathogen, which causes central nervous system symptoms in humans and reproductive disorders in swine. It has led to severe impacts on human health and the swine industry; however, there is no medicine available for treating yet. Therefore, vaccination is the best preventive measure for this disease. In the study, a modified mRNA vaccine expressing the prM and E proteins of the JEV P3 strain was manufactured, and a mouse model was used to assess its efficacy. The mRNA encoding prM and E proteins showed a high level of protein expression in vitro and were encapsulated into a lipid nanoparticle (LNP). Effective neutralizing antibodies and CD8+ T-lymphocytes-mediated immune responses were observed in vaccinated mice. Furthermore, the modified mRNA can protect mice from a lethal challenge with JEV and reduce neuroinflammation caused by JEV. This study provides a new option for the JE vaccine and lays a foundation for the subsequent development of a more efficient and safer JEV mRNA vaccine.

Sudden quadriparesis after non-overdose local anesthesia

BackgroundA well-known anesthetic, lidocaine is the most widely used local anesthetic. Local anesthetic systemic toxicity (LAST) is a life-threatening event with common and prominent presentations of central nervous system (CNS) toxicity and cardiovascular toxicity. The most frequent and prominent early warning signs and symptoms of LAST are central nervous system symptoms. While rare, cases quadriparesis after the administration of lidocaine has been reported.Case presentationIn this paper, we report a very rare case of quadriparesis after local anesthesia administration for vocal cord cyst-removal surgery, which dramatically improved after treatment. LAST can occur during various routes of lidocaine administration, such as local spray. A possible mechanism of our case could be the local diffusion of lidocaine to the spinal cord, which caused the symptoms to mimic anterior cord syndrome.ConclusionsOur case presented a favorable outcome following the administration of intravenous lipid emulsion (ILE) for non-over dose local anesthetic drug induced spinal cord inhibition symptoms. These findings highlight the need for further research on the use of ILE to reverse LAST and other adverse effects of local anesthetics.

Autologous stem cell transplantation in a patient with scleromyxedema.

A 46-year-old male was diagnosed with scleromyxedema on a skin biopsy in 2014. Scleromyxedema is a rare disorder characterized by papular lichenoid eruption with sclerosing skin infiltration due to the deposition of glycosaminoglycan in the papular and reticular dermis, which leads to thickened skin in almost in entire body. Monoclonal paraproteinemia is a common finding. However, it is associated with disorders of other organs/systems, including gastrointestinal system, cardiopulmonary system, central nervous system, and thus it can be life-threatening. Because of its similarities with other serious low tumor burden plasma cell diseases (amyloidosis or Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes [POEMS] syndrome), autologous hematopoietic cell transplantation (autoHCT) has been performed with some success in this rare disease with no standard therapy. The mechanism of action of autoHCT is unknown. The patient underwent autoHCT due to failed response to plasma cell-directed therapies (e.g., lenalidomide, bortezomib) and intravenous immunoglobulin (IVIG). His disease progressed in the skin, also affecting the gastrointestinal system (e.g., not able to open his mouth, esophageal dysfunction) causing malnutrition and thus severe weight loss as well as central nervous system symptoms (e.g., seizure). The picture depicts the patient's face affected by scleromyxedema before and after autoHCT performed in 2019 following high dose melphalan. One can easily see that in addition to skin changes there is improved mouth mobility (he could not open his mouth). Although the patient benefitted from autoHCT in the skin, his clinical course has been complicated by renal and pulmonary complications later in his course requiring high dose steroids and plasmapheresis. The patient recently died of Coronovirus disease 2019 caused by SARS-CoV-2 virus (COVID-19). Scleroderma is a rare, serious systemic disease with unknown etiopathology (e.g., it includes characteristics of plasma cell dyscrasia, autoimmune diseases, or chronic inflammatory diseases). Although autoHCT might be effective in some patients, its treatment remains disappointing. None. The authors declare they have no conflicts of interest.

Management of pulmonary arteriovenous malformations involves additional factors aside from the diameter of feeding arteries: a 3-year case-case retrospective analysis

BackgroundPulmonary arteriovenous malformations (PAVMs) are rare but cause various manifestations. Although the diameter of feeding arteries has been linked to treatment decisions, relationships among the characteristics of PAVMs, clinical symptoms, and treatment effect remain unclear. The present study was performed to investigate how collective characteristics of PAVMs relate to clinical symptoms and to provide proper treatment recommendations for patients with PAVMs.MethodsWe retrospectively analysed 838,447 patients’ radiographic data and medical records from January 2018 to December 2020. Patients were included if a PAVM was radiographically detected for the first time in our hospital. Ordered multivariable logistic regression and hierarchical multiple regression were performed to analyse the relationships between characteristics of PAVMs and various clinical symptoms. We investigated the management of PAVMs in four tertiary university hospitals.ResultsDetection rate of PAVMs was 0.025% (207/838,447), and 37.6% of patients (78/207) also had hereditary haemorrhagic telangiectasia. Eight patients were diagnosed with bilateral diffuse PAVMs. Two hundred thirty-six lesions were detected in 199 patients, and the mean diameter of the feeding artery was 4.13 ± 1.92 mm. Most PAVMs were the simple type and located in the peripheral pulmonary area. In total, 34.3% of patients (71/207) were symptom-free; remaining patients showed various manifestations, and respiratory symptoms were most common (dyspnoea on exertion, 47.8%). The diameter of the feeding artery and the type and the number of PAVMs were correlated with hypoxaemia (P < 0.001, P < 0.001, and P = 0.037, respectively). The collective characteristics of PAVMs were not related to the severity of central nervous system symptoms (largest diameter of feeding artery, P = 0.8; largest diameter of sac, P = 0.42; number of PAVMs, P = 0.35; type of PAVMs, P = 0.99). Various symptoms were greatly relieved after treatment. The hospital investigation showed that management of PAVMs was not generally appreciated in clinical practice.ConclusionsOur study revealed a low detection rate of PAVMs and a low degree of association with hereditary haemorrhagic telangiectasia in the general population. Considering the connection between collective characteristics of PAVMs and various clinical symptoms, clinicians should consider the type and number of PAVMs, the largest diameter of the feeding artery, and clinical symptoms when managing patients with PAVMs.

Central nervous system infection with Seoul Orthohantavirus in a child after hematopoietic stem cell transplantation: a case report

BackgroundPatients with allogeneic hematopoietic stem cell transplantation (allo-HSCT) are prone to complicate viral infection. Central nervous system (CNS) involvement caused by the viruses is rare but with poor prognosis. Hantavirus, which usually cause hemorrhagic fever with renal syndrome (HFRS), and none case has been reported about these infection in allo-HSCT patients.Case presentationIn August 2021, a 13-year-old male child developed intermittent fever and refractory hypotension after allo-HSCT. Magnetic resonance imaging of the head revealed abnormal signal foci in the left midbrain cerebral peduncle and bilateral thalamus. His family reported traces of mouse activity in the patient’s home kitchen. HFRS was suspected, but with no significant kidney damage. The specific immunoglobulin (Ig) G and M of hantavirus were negative. The metagenomic next-generation sequencing (mNGS) detected Seoul Orthohantavirus (SEOV) sequences directly in cerebrospinal fluid and blood.ConclusionsAllo-HSCT patients are a high-risk group for infection. Usually the causative agent of infection is difficult to determine, and sometimes the site of infection is concealed. This report highlights the importance of suspecting hantavirus infection in allo-HSCT patients with CNS symptoms despite the absence of renal syndromes. The mNGS is a powerful tool for detecting pathogens. CNS infection with Seoul orthohantavirus in transplant patients is rare but possible as demonstrated in this case. To the best of our knowledge, this is the first reported case employing mNGS to diagnose SEOV caused CNS infection in an allo-HSCT patient.

A severe case of human rhinovirus A45 with central nervous system involvement and viral sepsis

BackgroundRhinovirus is a common viral aetiology of upper respiratory infection and is mostly associated with common cold or flu-like illness. Although rhinovirus has been recognized as a pathogen for lower respiratory infections in severe cases credited to advances in molecular detection, central nervous system involvement and multiorgan dysfunction are extremely rare.Case presentationA previously healthy 10-year-old girl developed fever, sore throat and conjunctive injection after contact with an upper respiratory infection patient, followed by seizures, haematuria, and severe diarrhoea. She experienced viral sepsis and multiorgan dysfunction after admission. Cerebral computed tomography showed significant diffuse encephaledema. Cerebrospinal fluid analysis showed significantly elevated protein levels. After her consciousness disturbance improved, she still took a long time to recover from haematuria and diarrhoea. We identified a rarely reported rhinovirus A45 in her oropharyngeal and anal swabs by metagenomic next-generation sequencing, and bacterial culture of blood specimens yielded negative results.ConclusionsThis case presents a patient with severe rhinovirus infection, which was very likely responsible for her central nervous system symptoms and viral sepsis.

Validation of the BC-Brain Patient-Reported Outcome Questionnaire for Patients with Central Nervous System Tumours Treated with Radiotherapy.

The BC-brain questionnaire was developed by BC Cancer to detect health problems in patients with central nervous system (CNS) tumours in routine clinical care, treated with radiotherapy (RT), as part of the Prospective Outcomes and Support Initiative (POSI). This study aimed to present and validate the BC-brain questionnaire in patients with brain metastases (BrM) treated with RT. The BC-brain questionnaire was constructed with three subscales: mobility, thinking and CNS symptoms. Patients with BrM from five BC Cancer centres completed this questionnaire at first visit and subsequent follow-up appointments. A total of 365 patients finished the first and 105 finished the follow-up questionnaire. Summary scores of each subscale were calculated. Mobility, thinking and subtotal score showed good reliability with Cronbach’s α > 0.7. Multitrait scaling analysis showed good convergent and divergent validity. The correlations between subscales ranged from 0.262 to 0.456 for baseline and from 0.378 to 0.597 for follow-up. Patients on dexamethasone had worse performance. Patients with a KPS of </=70 had worse performance than patients with a KPS of >70. In general, this BC-brain questionnaire has good reliability and validity, and is proper to use as an option for a patient-reported outcome (PRO) instrument to measure the quality of life in BrM patients treated with RT.

Reversal of neuroinflammation in novel GS model mice by single i.c.v. administration of CHO-derived rhCTSA precursor protein

Galactosialidosis (GS) is a lysosomal cathepsin A (CTSA) deficiency. It associates with a simultaneous decrease of neuraminidase 1 (NEU1) activity and sialylglycan storage. Central nervous system (CNS) symptoms reduce the quality of life of juvenile/adult-type GS patients, but there is no effective therapy. Here, we established a novel GS model mouse carrying homozygotic Ctsa IVS6+1g→a mutation causing partial exon 6 skipping with concomitant deficiency of Ctsa/Neu1. The GS mice developed juvenile/adult GS-like symptoms, such as gargoyle-like face, edema, proctoprosia due to sialylglycan accumulation, and neurovisceral inflammation, including activated microglia/macrophage appearance and increase of inflammatory chemokines. We produced human CTSA precursor proteins (proCTSA), a homodimer carrying terminal mannose 6-phosphate (M6P)-type N-glycans. The CHO-derived proCTSA was taken up by GS patient-derived fibroblasts via M6P receptors and delivered to lysosomes. Catalytically active mature CTSA showed a shorter half-life due to intralysosomal proteolytic degradation. Following single i.c.v. administration, proCTSA was widely distributed, restored the Neu1 activity, and reduced the sialylglycans accumulated in brain regions. Moreover, proCTSA suppressed neuroinflammation associated with reduction of activated microglia/macrophage and up-regulated Mip1α. The results show therapeutic effects of intracerebrospinal enzyme replacement utilizing CHO-derived proCTSA and suggest suppression of CNS symptoms.

Evaluation of suspected adverse drug reactions of oral anti-diabetic drugs in a tertiary care hospital of Bihar, India: An observational study

Diabetic patients generally require life-long treatment and continuous follow up. In spite of their benefit of achieving glycemic control, there are many safety concerns with antidiabetic drugs such as gastrointestinal side effects, metabolic complications, central nervous system (CNS) symptoms, musculo-skeletal problems, genito-urinary disorders like UTI, development of peripheral oedema, weight gain etc. To highlight pattern of Adverse Drug Reactions with use of oral anti-diabetic drugs.All suspected Adverse Drug Reaction Reporting Form having any anti-diabetic drug as suspected cause of ADR were collected. The reported ADRs on the notification forms, after being confirmed by the physician-in-charge, were assessed for causality using WHO-UMC Causality Categories14, preventability using Modified-Schumock and Thornton scale15 and severity using Modified Hartwig and Siegel scale.: The data from the forms was presented in tabular form and data will be interpreted by using Microsoft Excel 365 software. Adverse drug reaction related to gastrointestinal system were most reported ADRs (41.31%). Among GI adverse events, nausea was mostly reported ADR and it was mostly associated with DPP-4 inhibitors. Hypoglycemia was most frequently observed in patients taking sulfonylureas. Causality assessment according to WHO-UMC criteria showed 61.68% ADRs had probable causality while 37.43% had possible causality and only 0.90% had certain causality. Most of the ADRs in our study were non-preventable (57.78%) &amp; were of mild to moderate grade. Hypoglycemia continues to be major concern in patients taking anti-diabetic medications and sulfonylureas were commonest drugs responsible for it. As anti-diabetic medication is generally taken for lifetime, the risk of development of adverse effects related to concurrent related co-morbidities of patients shouldn’t be ignored while prescribing. The physician should report these adverse effects to ADR monitoring centre, so that proper signal could be generated for the welfare of the society.