Cross-Cultural Adaptation of the Neck Bournemouth Questionnaire: A Methodological Systematic Review.

OBJECTIVE: Neck pain is a common musculoskeletal disorder, and it affects the quality of life of patients. As an effective and reliable multidimensional measurement tool for neck pain, the Neck Bournemouth Questionnaire (NBQ) has been cross-culturally adapted into multiple languages for clinical practice. The aim of this study was to evaluate the translation procedures and measurement properties of cross-cultural adaptations of the NBQ. METHODS: Searches were conducted in the databases PubMed, Web of Science, Embase and Scopus using the keywords: "the Neck Bournemouth Questionnaire," "NBQ," "cross-cultural," and "adaptation." Methodological quality of cross-cultural adaptation processes and measurement properties were comprehensively assessed by the guidelines for Cross-cultural Adaptation Process of Self-Reporting Measures and the Consensus-based Standards for the Selection of Health Measurement Instruments. RESULTS: There were 12 adaptations of NBQ in 10 different languages, including Dutch, simplified Chinese, and German. Among these studies, 11 adaptations completed all cross-cultural adaptation procedures. However, significant variations existed in the specific implementation plans, particularly regarding translator selection and expert committee composition. Most cross-cultural adaptations reported internal consistency, reliability, and construct validity. Only one study conducted factor analysis and hypothesis testing. Five adaptations examined floor and ceiling effects with one reporting a floor effect. A few studies reported protocol responsiveness and interpretability. CONCLUSIONS: The Dutch, German, and Urdu adaptations demonstrate comparatively higher quality than other adaptations. Further research should comprehensively evaluate the measurement properties of the NBQ in the French, Portuguese-Brazilian, and Turkish adaptations.

A critical appraisal of clinical practice guidelines on surgical treatments for spinal metastasis.

PURPOSE: As an important treatment for spinal metastasis, surgery has strict applicable conditions. Although various organizations have formulated different guidelines on surgical treatment for spinal metastasis (SM), there are certain differences in the content, standardization and quality of the guidelines and it is necessary to make a critical appraisal of them. We aim to systematically review and appraise the current guidelines on surgical treatments of SM and summarize the related recommendations with the quality evaluation of supporting evidence, as to provide a reference for the standardization of surgical treatment plans, and help clinical front-line medical workers can make safe and effective clinical decisions faster. METHODS: We searched Pubmed, Web of Science, and Embase for three major databases and online guideline databases. According to certain inclusion and exclusion criteria, the latest guidelines on the surgical treatment of SM were sorted out. AGREE II was used to evaluated the guideline's quality, and we extracted and compared the recommended treatment content of each guideline with evaluating by the evidence-grading scale. RESULTS: Eight guidelines from 2013 to 2019 were included. Seven guidelines are comprehensive guidelines and one related to the reconstructive surgery of SM. Five guidelines were evaluated as "recommended," and three guidelines were evaluated as "recommended with modifications." Regarding the indications of surgery with SM, four guidelines, seven guidelines, seven guidelines, three guidelines and three guidelines recommended surgical treatment for patients with SM with intractable pain, mechanical instability, metastatic epidural spinal cord compression (MESCC), recurrent spinal metastasis (RSM), and survival predication, respectively. Regarding the surgical strategies, three guidelines recommended minimally invasive therapy but had strict indications. Six guidelines and five guidelines recommend palliative surgery and with receiving radiation therapy, respectively. For the aggressive surgery, only one guideline recommended to apply to patients in good general conditions who has isolated symptomatic SM. Regarding the surgical reconstructions, one guideline didn't recommend iliac bone graft and three guidelines recommended PMMA bone cement. CONCLUSION: Most of the guidelines do not provide clear criteria for surgical application and provide more of a basic framework. The level of evidence for these surgical recommendations ranges from LOE B to D, and almost all guidelines recommend vertebroplasty and kyphoplasty, but for palliative and more aggressive surgery, which recommended to personalize specific surgical strategies with multidisciplinary collaboration.

Treatment and Diagnose of Spinal Phosphaturic Mesenchymal Tumor: A Case Report and a Systematic Literature Review.

BACKGROUND: Spinal phosphaturic mesenchymal tumor (PMT) is a rare disorder but can be cured once the diagnosis is clear and a complete removal by surgery is performed. To the best of our knowledge, only 22 cases in the spine have been described, and we report a case with the largest number of spinal segments (T12-L5) affected among spine PMT cases. METHODS: A comprehensive literature search was performed until May 23, 2023, following the Preferred Reporting Items for Systematic Reviews guidelines. Studies were chosen through relevant PubMed, Web of Science, and EMBASE searches to prioritize obtaining the largest studies. The Medical Subject Headings and Boolean operators employed for this search were ("PMT" or "TIO" or "Tumor-induced osteomalacia" or "phosphaturic mesenchymal tumor") and ("spine" or "spinal"). Two researchers (L.S.Z. and D.B.C) independently reviewed and evaluated the included articles. Any differing opinions were discussed until a consensus was reached. A total of 18 studies were included. A case report is also presented. RESULTS: We report a case of spinal PMT. The full text of the relevant articles was construed. A total of 18 studies were reviewed and consolidated. These articles are roughly divided into the following 5 subcategories: 1) clinical features and baseline distribution, 2) laboratory and imaging findings, 3) pathological manifestations, and 4) surgical methods and treatment options. CONCLUSIONS: Spinal PMT is very rare with a high rate of misdiagnosis and debilitating complications, so it is of significance to increase awareness of the disease among spine surgeons consulted by patients with spinal PMT. 68Ga-DOTATOC-PET/CT shows very high sensitivity to the spinal PMT but there is no way to exactly determine the location of the tumor. PMT has unique immunohistochemical characteristics and malignant PMT is rare. Once diagnosed, complete surgical excision is the recommended treatment. Burosumab is one of the available options, especially in cases that are recurrent and difficult to surgically resect.

Long-term postoperative outcomes of spinal cellular schwannoma: study of 93 consecutive cases.

BACKGROUND CONTEXT: Cellular schwannoma (CS) is a rare tumor that accounts for 2.8%-5.2% of all benign schwannomas. There is a dearth of up-to-date information on spinal CS in the literature. PURPOSE: The aims of this study were to identify the proportion of CS cases amongst spinal benign schwannoma, describe the clinical features of spinal CS, and identify prognostic factors for local recurrence by analyzing data from 93 consecutive CS cases. STUDY DESIGN: Retrospective review. PATIENT SAMPLE: We analyzed 93 PSGCT screened from 1,706 patients with spine CS who were treated at our institute between 2008 and 2021. OUTCOME MEASURES: Demographic, radiographic, operative and postoperative data were recorded and analyzed. METHODS: We compared the clinical features of spinal CS from the cervical, thoracic, lumbar and sacral segments. Prognostic factors for local recurrence-free survival (RFS) were identified by the Kaplan-Meier method. Factors with p≤.05 in univariate analysis were subjected to multivariate analysis by Cox regression analysis. RESULTS: The proportion of spinal CS in all benign schwannomas was 6.7%. The mean and median follow-up times for the 93 patients in this study were 92.2 and 91.0 months respectively (range 36-182 months). Local recurrence was detected in 11 cases, giving an overall recurrence rate of 11.7%, with one patient death. Statistical analysis revealed that tumor size ≥5 cm, intralesional resection, and Ki-67 ≥5% were independent negative prognostic factors for RFS in spinal CS. CONCLUSIONS: Whenever possible, en bloc resection is recommended for spinal CS. Long-term follow-up should be carried out for patients with tumor size ≥5 cm and postoperative pathological Ki-67 ≥5%.

Real-world experience with Deutetrabenazine management in patients with Huntington's disease using video-based telemedicine.

BACKGROUND: Huntington's disease (HD) is a rare progressive neurological disorder, and telemedicine has the potential to improve the quality of care for patients with HD. Deutetrabenazine (DTBZ) can reduce chorea symptoms in HD; however, there is limited experience with this medication in Asian countries. METHODS: Retrospective and prospective studies were employed to explore the feasibility and reliability of a video-based telemedicine system for HD patient care. Reliability was demonstrated through consistency between selected-item scores (SIS) and total motor scores (TMS) and the agreement of scores obtained from hospital and home videos. Finally, a single-centre real-world DTBZ management study was conducted based on the telemedicine system to explore the efficacy of DTBZ in patients with HD. RESULTS: There were 77 patients included in the retrospective study, and a strong correlation was found between SIS and TMS (r = 0.911, P < 0.0001), indicating good representativeness. There were 32 patients enrolled in the prospective study. The reliability was further confirmed, indicated by correlations between SIS and TMS (r = 0.964, P < 0.0001) and consistency of SIS derived from the in-person and virtual visits (r = 0.969, P < 0.0001). There were 17 patients included in the DTBZ study with a mean 1.41 (95% confidence interval, 0.37-2.46) improvement in chorea score and reported treatment success. CONCLUSIONS: A video-based telemedicine system is a feasible and reliable option for HD patient care. It may also be used for drug management as a supplementary tool for clinical visits.

Measurement properties of health-related quality of life measures for people living with metastatic disease of the spine: a systematic review.

PURPOSE: Patients with spinal metastases (SM) suffer from a significant quality of life (QoL) deterioration. The measurement of QoL has garnered significant attention. In this study, the authors aimed to investigate the frequency of QoL measurement, systematically appraise the measurement properties of identified instruments, and facilitate the effective selection of an appropriate QoL instrument for patients with SM. METHODS: This systematic review adhered to the newly revised Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement guidelines. The methodological quality of the studies was assessed using the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) checklist. Measurement property results were assessed using the adapted criteria. Each measurement property was allocated a separate rating (excellent, good, fair, or poor). 'Best evidence synthesis' was performed using COSMIN outcomes and the quality of findings. RESULT: Two hundred and nine publications were included, and 18 instruments were identified. ECOG, EuroQol-5D, SF-36, SOSGOQ, and EORTC-QLQ-C30 were the top five instruments used for patients with SM in published literature. The measurement properties evaluated included internal consistency (four instruments), reliability (three instruments), validity (five instruments), validity (nine measures), floor and ceiling effects (four instruments), responsiveness (four instruments), and interpretability (three measures). Based on the limited evidence, the Brief Pain Inventory (BPI) had the best methodological quality. CONCLUSIONS: Owing to the limitations of BPI in assessment domains, we cannot fully support the use of BPI. For the lack of high-quality research, it is challenging to nominate a single appropriate measure. Additional studies are needed to explore the evidence before a confirmatory decision is made.

Assessing Cross-Cultural Adaptation of the Spine Oncology Study Group Outcomes Questionnaire 2.0: A Methodological Systematic Review Regard to Consensus-Based Standards for the Selection of Health Measurement Instruments Guideline.

STUDY DESIGN: systematic review of cross-cultural adaptation. OBJECTIVES: SOSGOQ 2.0 was widely used to assess the HRQQOL of patients with spinal metastasis. Due to the lack of methodological quality assessment, it is a challenge to use the questionnaire in routine practice. This study aims to comprehensively evaluate the translation procedures and measurement attributes of SOSGOQ 2.0 according to COSMIN guidelines. METHODS: The literature was reviewed adhering to the PRISMA guidelines. Each translation process and different cultural adaptation methods were classified according to the guidelines for Cross cultural Adaptation Process of Self Reporting Measures, and the methodological quality of the identified research was evaluated according to the consensus based on the selection criteria of health measurement tools. RESULTS: 6 publications finally met the inclusion criteria. As for the evaluation of translation procedures and cross-cultural adaptability, two adaptations did not report the detailed information in translation and cross-cultural adaptation (synthesis, back translation, review by expert committee, pre-test), factor analysis and sample size calculation were only mentioned in two studies, and only one adaptation met the minimum sample size standard. Regard to the methodological quality assessment of measurement attributes, all adaptations completed internal consistency, structural effectiveness and reliability. However, none of the adaptations reported measurement errors and only one reported response sensitivity. CONCLUSIONS: We found that the methodological quality of the current adaptation was uneven, and the report of measurement attribute results was not comprehensive. We recommend higher quality German, Italian and Chinese adaptation.

Metal deposits associated with brain atrophy in the deep gray matter nucleus in Wilson's disease.

Regional atrophy and metal deposition are typical manifestations in Wilson's disease, but their relationship has not been systematically investigated. We aim to investigate the association of regional brain atrophy and metal deposition in the deep gray matter nucleus at MRI in Wilson's disease. We acquired the structural and susceptibility mapping and performed a cross-sectional comparison of volume and susceptibility in deep gray matter nucleus. The most extensive and severe atrophy was detected in brain regions in neuro-Wilson's disease, as well as the most widespread and heaviest metal deposits. Metal deposits were significantly negatively correlated with volume in the bilateral thalamus, caudate, and putamen. None of correlation was found between the clinical score with volume or susceptibility in the focused regions. In the 1-year follow-up analysis, the volume of right thalamus, globus pallidus, and brainstem and the susceptibility of the left caudate have decreased significantly as the symptom improvement. In Wilson's disease, phenotypes have varied scope and extend of volumetric atrophy and metal deposits. This study is expected to take the lead in revealing that in neuro-Wilson's disease, greater regional atrophy associated with heavier metal deposits in Wilson's disease. Moreover, after 1-year treatment, the imaging data have changed as the patient's condition improvement.

Multiple Langerhans cell histiocytosis with spinal involvement.

Aims: The aim of this study was to report the long-term prognosis of patients with multiple Langerhans cell histiocytosis (LCH) involving the spine, and to analyze the risk factors for progression-free survival (PFS). Methods: We included 28 patients with multiple LCH involving the spine treated between January 2009 and August 2021. Kaplan-Meier methods were applied to estimate overall survival (OS) and PFS. Univariate Cox regression analysis was used to identify variables associated with PFS. Results: Patients with multiple LCH involving the spine accounted for 15.4% (28/182 cases) of all cases of spinal LCH: their lesions primarily involved the thoracic and lumbar spines. The most common symptom was pain, followed by neurological dysfunction. All patients presented with osteolytic bone destruction, and 23 cases were accompanied by a paravertebral soft-tissue mass. The incidence of vertebra plana was low, whereas the oversleeve-like sign was a more common finding. The alkaline phosphatase was significantly higher in patients with single-system multifocal bone LCH than in patients with multisystem LCH. At final follow-up, one patient had been lost to follow-up, two patients had died, three patients had local recurrence, six patients had distant involvement, and 17 patients were alive with disease. The median PFS and OS were 50.5 months (interquartile range (IQR) 23.5 to 63.1) and 60.5 months (IQR 38.0 to 73.3), respectively. Stage (hazard ratio (HR) 4.324; p < 0.001) and chemotherapy (HR 0.203; p < 0.001) were prognostic factors for PFS. Conclusion: Pain is primarily due to segmental instability of the spine from its destruction by LCH. Chemotherapy can significantly improve PFS, and radiotherapy has achieved good results in local control. The LCH lesions in some patients will continue to progress. It may initially appear as an isolated or single-system LCH, but will gradually involve multiple sites or systems. Therefore, long-term follow-up and timely intervention are important for patients with spinal LCH.

The regulating effect of boron doping and its concentration on the photocatalytic overall water splitting of a polarized g-C3N5 material.

Photocatalytic overall water splitting with two-dimensional materials is a promising strategy to solve the problems of environmental pollution and energy shortage. However, conventional photocatalysts are often limited to a narrow visible photo-absorption range, low catalytic activity, and poor charge separation. Herein, given the intrinsic polarization facilitating the improvement of photogenerated carrier separation, we adopt a polarized g-C3N5 material combining the doping strategy to alleviate the abovementioned problems. Boron (B), as a Lewis acid, has a great chance to improve the capture and catalytic activity of water. By doping B into g-C3N5, the overpotential for the complicated four-electron process of the oxygen reduction reaction is only 0.50 V. Simultaneously, the B doping-induced impurity state effectively reduces the band gap and broadens the photo-absorption range. Moreover, with the increase of B doping concentration, the photo-absorption range and catalytic activity can be gradually improved. Whereas when the concentration exceeds 33.3%, the reduction potential of the conduction band edge will not meet the demand for hydrogen evolution. Therefore, excessive doping is not recommended in experiments. Our work affords not only a promising photocatalyst but also a practical design scheme by combining polarizing materials and the doping strategy for overall water splitting.

Multisystem Involvement Induced by Human Parvovirus B19 Infection in a Non-immunosuppressed Adult: A Case Report.

Background: Human parvovirus B19 (B19V) infection is usually symptomless and occurs in the childhood. While in immunocompromised adults, B19V infection also presents various clinical symptoms due to the host's immune status. The classic symptoms include erythema, anemia, arthropathy, and edema, but neurological involvement is rare. Case Presentation: In this report, we present a case of B19V infection caused multiple organ dysfunction in a non-immunosuppressed adult. Metagenomic next-generation sequencing (mNGS) was used and successfully detected the pathogen in multiple types of samples, including blood, cerebrospinal fluid (CSF), and bronchoalveolar lavage fluid (BALF). The diagnosis was subsequently confirmed by polymerase chain reaction (PCR). He was treated with intravenous gamma globulin, resulting in a significant resolution of symptoms after 1 month. Conclusion: Multisystem involvement induced by B19V infection was found in this case report. mNGS performed great advantages in rapidly and accurately diagnosing B19V infection in multiple types of samples, which helps the timely adjustment of treatment and improves the prognosis.

Clinical and Genetic Analysis in Neurological Wilson's Disease Patients With Neurological Worsening Following Chelator Therapy.

Objectives: None of the previous studies have focused on the genetic effect on neurological worsening in neurological Wilson's disease (WD) patients following chelator therapy. We aimed to evaluate the clinical and genetic role in the occurrence of neurological worsening. Methods: We retrospectively reviewed the medical records of neurological WD patients who received initial chelator therapy and genetic test. Clinical, laboratory, and genetic data were collected. The genotype was classified into two types: 1) severe mutation genotype: patients who carried at least one of the following three types of mutations: frameshift mutation, splicing mutation, or nonsense mutation; 2) non-severe mutation genotype: patients who only carried missense mutations. Then, the clinical features and genotype of the patients with and without neurological worsening were investigated. Results: Forty-seven neurological WD patients were identified with a median age at onset of 16.17 years (range 7.75-47 years) and 35 (74.5%) males. The mean interval from onset to diagnosis was 0.6 years (range: 0.5 months-6.25 years). Neurological deterioration was observed in 29 patients (61.7%) and the other 18 patients (38.3%) were stable or improved during anti-copper treatment. The neurological worsening was completely irreversible in 6 cases (20.7%) and partially irreversible in 16 cases (55.2%). The common deteriorated symptoms were as follows: rigidity in 20 cases (69%), speech difficulties in 20 cases (69%)), walking difficulties in 13 cases (44.8%), dysphagia in 9 cases (31%), and salivation in 9 cases (31%). The patients with neurological worsening had significantly younger age (p = 0.028), shorter delayed diagnosis time (p = 0.011), higher rate of dystonia (p = 0.003), and severe mutation genotype (p = 0.036), compared to those without neurological worsening. Conclusion: We found that younger age of onset, the presence of dystonia, and genotype with severe mutations may be predictive of neurological worsening in the neurological WD patients that received chelator therapy. For those patients, chelator therapy should be given with caution and needs closer observation during follow-up.

Plasma neurofilament light chain as a biomarker in Wilson's disease.

INTRODUCTION: Neurofilament light chain (NfL) was recently proposed as a promising blood biomarker for nervous system diseases, including Wilson's disease (WD). In this study, we investigated plasma NfL concentrations in patients with different types of WD and their correlations with clinical manifestations and brain atrophy. METHODS: Seventy-five WD cases (54 neurological type, 21 hepatic type) and 27 age-matched healthy controls were included in this study. We compared plasma NfL concentrations between the different types and correlated them with Unified Wilson's Disease Rating Scale (UWDRS) scores. Patients were allocated to stable and unstable groups according to changes in UWDRS scores and clinical assessment. We compared the differences in plasma NfL concentrations between groups. Voxel-based morphometry (VBM) and FreeSurfer software were used to analyze MRI images. We investigated the correlation between plasma NfL concentrations and volume of gray matter, white matter, and several areas of interest in the brain MRI of 24 patients. RESULTS: Plasma NfL concentrations were significantly higher in neurological type WD than in hepatic type WD (8.16 vs. 3.19 pg/mL, p < 0.001). Plasma NfL concentrations were positively correlated with UWDRS scores (r = 0.291, p = 0.035) in patients with neurological type WD. Plasma NfL was significantly higher in unstable patients than in stable patients (10.74 vs. 7.23 pg/mL, p = 0.004). Significant negative associations were found between plasma NfL level and the volumes of total gray matter, bilateral caudate nucleus, putamen, and nucleus accumbens. CONCLUSION: Plasma NfL is valuable as a biomarker for neurological damage in patients with WD.

Evaluation of Blood Glial Fibrillary Acidic Protein as a Potential Marker in Huntington's Disease.

Objective: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. Neurofilament light protein (NfL) is correlated with clinical severity of HD but relative data are the lack in the Chinese population. Reactive astrocytes are related to HD pathology, which predicts their potential to be a biomarker in HD progression. Our aim was to discuss the role of blood glial fibrillary acidic protein (GFAP) to evaluate clinical severity in patients with HD. Methods: Fifty-seven HD mutation carriers (15 premanifest HD, preHD, and 42 manifest HD) and 26 healthy controls were recruited. Demographic data and clinical severity assessed with the internationally Unified Huntington's Disease Rating Scale (UHDRS) were retrospectively analyzed. Plasma NfL and GFAP were quantified with an ultra-sensitive single-molecule (Simoa, Norcross, GA, USA) technology. We explored their consistency and their correlation with clinical severity. Results: Compared with healthy controls, plasma NfL (p < 0.0001) and GFAP (p < 0.001) were increased in Chinese HD mutation carriers, and they were linearly correlated with each other (r = 0.612, p < 0.001). They were also significantly correlated with disease burden, Total Motor Score (TMS) and Total Functional Capacity (TFC). The scores of Stroop word reading, symbol digit modalities tests, and short version of the Problem Behaviors Assessments (PBAs) for HD were correlated with plasma NfL but not GFAP. Compared with healthy controls, plasma NfL has been increased since stage 1 but plasma GFAP began to increase statistically in stage 2. Conclusions: Plasma GFAP was correlated with plasma NfL, disease burden, TMS, and TFC in HD mutation carriers. Plasma GFAP may have potential to be a sensitive biomarker for evaluating HD progression.

Therapeutic reversal of Huntington's disease by in vivo self-assembled siRNAs.

Huntington's disease is an autosomal-dominant neurodegenerative disease caused by CAG expansion in exon 1 of the huntingtin (HTT) gene. Since mutant huntingtin (mHTT) protein is the root cause of Huntington's disease, oligonucleotide-based therapeutic approaches using small interfering RNAs (siRNAs) and antisense oligonucleotides designed to specifically silence mHTT may be novel therapeutic strategies for Huntington's disease. Unfortunately, the lack of an effective in vivo delivery system remains a major obstacle to realizing the full potential of oligonucleotide therapeutics, especially regarding the delivery of oligonucleotides to the cortex and striatum, the most severely affected brain regions in Huntington's disease. In this study, we present a synthetic biology strategy that integrates the naturally existing exosome-circulating system with artificial genetic circuits for self-assembly and delivery of mHTT-silencing siRNA to the cortex and striatum. We designed a cytomegalovirus promoter-directed genetic circuit encoding both a neuron-targeting rabies virus glycoprotein tag and an mHTT siRNA. After being taken up by mouse livers after intravenous injection, this circuit was able to reprogramme hepatocytes to transcribe and self-assemble mHTT siRNA into rabies virus glycoprotein-tagged exosomes. The mHTT siRNA was further delivered through the exosome-circulating system and guided by a rabies virus glycoprotein tag to the cortex and striatum. Consequently, in three mouse models of Huntington's disease treated with this circuit, the levels of mHTT protein and toxic aggregates were successfully reduced in the cortex and striatum, therefore ameliorating behavioural deficits and striatal and cortical neuropathologies. Overall, our findings establish a convenient, effective and safe strategy for self-assembly of siRNAs in vivo that may provide a significant therapeutic benefit for Huntington's disease.

Zinc monotherapy for young patients with oligosymptomatic Wilson disease: A single center, retrospective study.

BACKGROUND AND AIMS: Few studies have focused on the treatment failure of zinc monotherapy for oligosymptomatic Wilson disease (WD) patients. Therefore, we aimed to evaluate the long-term efficacy of zinc monotherapy in oligosymptomatic patients and to analyze the possible factors that may influence the outcome of this treatment. METHODS: We retrospectively reviewed the medical records of oligosymptomatic WD patients who received zinc monotherapy from the time of diagnosis. Then, the characteristics of patients who were treated with zinc monotherapy successfully and those who experienced treatment failure were investigated. RESULTS: Forty oligosymptomatic WD patients were identified that have received zinc monotherapy as initial treatment, with a median age of 3.83 years at the time of diagnosis. 36 (90%) patients had abnormal alanine transaminase/aspartate transaminase levels at baseline. None of the patients became symptomatic during zinc monotherapy. 28 (70%, Group 1) patients were treated with zinc monotherapy successfully for a median period of 2.4 years. In Group 1, serum aminotransferase levels significantly decreased 6 and 12 months after zinc therapy compared to the baseline levels (P <  0.05). 12 (30%, Group 2) patients experienced treatment failure with zinc monotherapy due to uncontrolled serum liver enzyme levels, and d-penicillamine was combined. The baseline 24-hour urine copper levels before treatment were significantly higher in Group 2 compared to that in Group 1 (182.5 vs 90.92 µg /day, P = 0.018). Comparing the age at onset; ceruloplasmin, serum copper, ALT, and AST levels; and proportions of abdominal ultrasonography abnormality at baseline between Group 1 and 2 revealed no statistically significant differences. CONCLUSIONS: We found that high initial 24 -h urinary copper levels may lead to treatment failure of zinc monotherapy in oligosymptomatic WD patients. It might be reasonable to follow up liver function tests more closely during zinc monotherapy and to begin combination treatment with chelators early in patients with high level of 24 -h urinary copper.

Study on different pathogenic factors in different disease stages of patients with Wilson disease.

OBJECTIVE: To investigate in different stages of patients with Wilson disease (WD), there are different pathogenic factors such as metal deposition, oxidative stress, and inflammatory response in the brain. METHODS: A total of 32 untreated WD patients and 10 normal controls were enrolled in the study. The neurological symptoms were evaluated using the modified Young scale. Liver function, metal metabolism, susceptibility-weighted imaging (SWI), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS) examination were done. The clinical disease stages were divided into metal deposition period, fiber damage period, and neuronal necrosis period according to the imaging results. The content of 24-h urine copper, serum copper, and serum iron; and the levels of catalase (CAT), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), nitric oxide (NO), nitric oxide synthase (NOS), superoxide dismutase (SOD), interleukin (IL-1), and tumor necrosis factor alpha (TNF-α) were detected. RESULTS: The contents of urinary copper in WD patients at neuronal necrosis stage were lower than those in patients at the metal deposition stage (P = 0.011) and fiber injury stage (P = 0.023). The contents of NOS (P = 0.039) and NO (P = 0.047) in WD patients at the stage of fiber injury were higher than those of the normal control, while GSH-PX (P = 0.025) and CAT (P = 0.041) were lower in the neuronal necrosis stage. In the stage of neuronal necrosis, the levels of IL-1 (P = 0.030) and TNF-α were higher than those of the normal control (P = 0.042). The neurological symptom scores in patients with fiber injury (P = 0.013) and neuron injury were higher than those with metal deposition (P = 0.026). CONCLUSION: There are different pathogenic factors in different stages of WD. At the neuronal necrosis stage, copper deposition was decreased in WD patients. In the stage of fiber injury and neuronal necrosis, there is oxidative stress injury in WD patients. In the neuronal necrosis phase, WD patients have an inflammatory response.

Late-onset MADD in Yemen caused by a novel ETFDH mutation misdiagnosed as ADEM.

We report a case of late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) with recurrent abdominal pain, vomiting, and impaired consciousness as the initial symptoms in Yemen; the case showed distinctive characteristics from those of Asian or Caucasian patients. Initially, he was misdiagnosed with pancreatitis, acute disseminated encephalomyelitis(ADEM), and fatty liver. Final diagnosis was further confirmed by electromyography, muscle biopsy, uric organic acid analysis, and a novel missense mutation in exon 7 (c.807A>C) of ETFDH was identified by next-generation sequencing. To our knowledge, we report this mutation in an adult MADD patient as well as late-onset MADD in a Middle East country for the first time. MADD is characterised by varied genotypes and broad spectrum of clinical manifestations among different populations and ages, which requires more attention and awareness in the clinic.