BMC Neurology

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HeMoVal study assessment table. Overview of the different study periods (enrollment, baseline assessment, monitoring, 3-months follow-up, measurements) with the corresponding time schedule and assessments
Introduction Preclinical studies provided a strong rationale for a pathophysiological link between cell-free hemoglobin in the cerebrospinal fluid (CSF-Hb) and secondary brain injury after subarachnoid hemorrhage (SAH-SBI). In a single-center prospective observational clinical study, external ventricular drain (EVD) based CSF-Hb proved to be a promising biomarker to monitor for SAH-SBI. The primary objective of the HeMoVal study is to prospectively validate the association between EVD based CSF-Hb and SAH-SBI during the first 14 days post-SAH. Secondary objectives include the assessment of the discrimination ability of EVD based CSF-Hb for SAH-SBI and the definition of a clinically relevant range of EVD based CSF-Hb toxicity. In addition, lumbar drain (LD) based CSF-Hb will be assessed for its association with and discrimination ability for SAH-SBI. Methods HeMoVal is a prospective international multicenter observational cohort study. Adult patients admitted with aneurysmal subarachnoid hemorrhage (aSAH) are eligible. While all patients with aSAH are included, we target a sample size of 250 patients with EVD within the first 14 day after aSAH. Epidemiologic and disease-specific baseline measures are assessed at the time of study inclusion. In patients with EVD or LD, each day during the first 14 days post-SAH, 2 ml of CSF will be sampled in the morning, followed by assessment of the patients for SAH-SBI, co-interventions, and complications in the afternoon. After 3 months, a clinical follow-up will be performed. For statistical analysis, the cohort will be stratified into an EVD, LD and full cohort. The primary analysis will quantify the strength of association between EVD based CSF-Hb and SAH-SBI in the EVD cohort based on a generalized additive model. Secondary analyses include the strength of association between LD based CSF-Hb and SAH-SBI in the LD cohort based on a generalized additive model, as well as the discrimination ability of CSF-Hb for SAH-SBI based on receiver operating characteristic (ROC) analyses. Discussion We hypothesize that this study will validate the value of CSF-Hb as a biomarker to monitor for SAH-SBI. In addition, the results of this study will provide the potential base to define an intervention threshold for future studies targeting CSF-Hb toxicity after aSAH. Study registration Identifier NCT04998370 . Date of registration: August 10, 2021.
The imaging findings of trigeminal neuritis initial and after treatment. Fluid-Attenuated Inversion Recovery (FLAIR) imaging and gadolinium enhancement T1-weighted imaging shows a high signal intensity lesion in the left trigeminal nerve (arrow) suggestive of trigeminal neuritis (Fig. 1A and 1B). On sagittal FLAIR imaging, there was no evidence of other central nervous system demyelinating disease (Fig. 1C). The follow-up MRI, conducted 3 months later, shows an improved state of the previously observed trigeminal neuritis (arrowhead, Fig. 1D)
The imaging findings of multifocal cerebral arterial stenosis initial and after treatment. Initially conducted brain magnetic resonance angiography (MRA) shows multifocal arterial stenosis in the cavernous portion of the left internal carotid artery and M1 portion of the left middle cerebral artery (dotted arrow, Fig. 2A). The follow-up MRA, conducted 3 months later, shows an improved state of previously seen multifocal cerebral arterial stenosis (circle, Fig. 2B)
Background Trigeminal neuropathy is characterized by numbness in the region innervated by the trigeminal nerves, with or without neuropathic weakness in the muscles of mastication. Trigeminal neuritis is a form of trigeminal neuropathy in which the lesion is caused by an inflammation. Herein, we report a patient with trigeminal neuritis due to central nervous system (CNS) involvement of herpes labialis (HL) infection, which was successfully treated with anti-viral and anti-inflammatory agents. Case presentation A young healthy female presented with numbness in the left hemiface for two weeks. She had a preceding typical HL infection on left facial lip one week before the sensory symptom onset. Brain magnetic resonance imaging revealed high signal intensities and asymmetrical thickening with enhancement along the cisternal segment of the left trigeminal nerve. Additionally, brain MR angiography showed multifocal stenoses in the M1 segment of the middle cerebral artery and the cavernous portion of the internal carotid artery. Cerebrospinal fluid (CSF) examination showed mild pleocytosis with normal protein level, glucose ratio, but CSF polymerase chain reaction assay for specific anti-viral antibodies including herpes simplex virus was negative, and CSF culture also did not identify a specific pathogen. The results of serologic testing including tumor markers and autoimmune markers were all unremarkable. A tentative diagnosis of trigeminal neuritis as a complication of HL involving the CNS was made considering the clinical, neuroradiological, and laboratory findings of the patient. Therefore, the patient was treated with intravenous methylprednisolone and acyclovir for 10 days. After the treatments, her sensory disturbance was markedly improved. Brain MRI at the 3-month follow-up also demonstrated improvement of previously identified high signal intensity lesions and multifocal intracerebral artery stenoses. Conclusion HL is usually a self-limiting, benign disease without complications, but rarely presents as trigeminal neuritis due to CNS involvement. Therefore, meticulous evaluation may be necessary if trigeminal neuritis or CNS involving symptoms occur after HL.
Study design
Background Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP), a rare disorder affecting young adults, causes gradual weakness of the limbs, areflexia and impaired sensory function. New CIDP phenotypes without pathogenic antibodies but with modified cell profiles have been described. Treatments include corticotherapy, intravenous immunoglobulins, and plasmapheresis but the latter’s action mechanisms remain unclear. Plasmapheresis supposedly removes toxic agents like antibodies from plasma but it is uncertain whether it has an immune-modulating effect. Also, the refining mechanisms of the two main plasmapheresis techniques—single plasma exchange and double filtration plasmapheresis (DFPP) – are different and unclear. This study aims to compare the evolution of peripheral lymphocyte profiles in patients with CIDP according to their treatment (single centrifugation plasmapheresis or DFPP) to better grasp the action mechanisms of both techniques. Method In this proof-of-concept, monocentric, prospective, Single-Case Experimental Design study, 5 patients are evaluated by alternating their treatment type (single plasma exchange or DFPP) for 6 courses of treatment after randomization to their first treatment type. Each course of treatment lasts 2–4 weeks. For single plasma exchange, 60 ml/kg plasma will be removed from the patient and replaced with albumin solutes, with a centrifugation method to avoid the immunological reaction caused by the membrane used with the filtration method. For DFPP, 60 ml/kg plasma will be removed from the patient with a plasma separator membrane, then processed via a fractionator membrane to remove molecules of a greater size than albumin before returning it to the patient. This technique requires no substitution solutes, only 20 g of albumin to replace what would normally be lost during a session. The primary outcome is the difference between the two plasmapheresis techniques in the variation of the TH1/TH17 ratio over the period D0H0-D0H3 and D0H0-D7. Secondary outcomes include the variation in lymphocyte subpopulations at each session and between therapeutic plasmapheresis techniques, the clinical evolution, tolerance and cost of treatments. Discussion Understanding the action mechanisms of single plasma exchange and DFPP will help us to offer the right treatment to each patient with CIPD according to efficacy, tolerance and cost. Trial registration under the no. NCT04742374 and date of registration 10 December 2020.
Genealogical and molecular data of the Moroccan family with a novel CNV in the COLQ gene. A The family pedigree illustrates the affected patient (homozygous for the mutation) and both parents (Heterozygous carriers). The black arrow indicates the proband. B The representative amplification plots of the target gene (COLQ). C The representative amplification plots of the endogenous gene (housekeeping gene). Both Real-time PCR amplification plots show various amounts of the amplified region in the proband, both parents and two normal controls with determination of mean threshold cycle (Ct) values using QuantStudioTM Real-Time PCR Software v1.7.1 (Applied Biosystems, Thermo Fisher Scientific). D Bar graph showed the copy number results calculated from delta-delta Ct
Visualization of the aligned sequencing reads representing deletion of exon 13 in the COLQ gene using Integrative Genomics Viewer (IGV) v2.5.0
Protein-protein interaction network of COLQ with predicted functional partners. A Screenshot of network map of predicted interactions from the STRING database v11.5. B Summary view shows predicted protein interactions with the confidence score. The Network nodes represent proteins and edges represent the type of protein-protein associations. Line color indicates the type of interaction evidence between two proteins. Black represents co-expression, turquoise database evidence, pink experimental evidence, light green text mining evidence, and violet protein homology.
Venn diagram showing possible genes with their different intersections involved in the differential diagnoses between myopathic forms and congenital myasthenic syndromes [2, 17–20]
Schematic representation of COLQ domains and the CNV mutations reported in this gene. A Genomic location of COLQ gene (from UCSC browser GRCh37/hg19: with the full transcript contains 17 coding exons (from the Ensembl database GRCh37 release 107 - Jul 2022). BCOLQ exons with the three published pathogenic CNVs in the literature and the deletion described in this study (showed in red color). C Primary structure of COLQ with its three protein domains. D Consequences of mutations in human COLQ protein [11, 32]. Mutations in the N-terminal proline-rich attachment domain (PRAD) prohibit the association of each COLQ strand with an acetylcholinesterase tetramer. Mutations in the central collagen domain containing two heparan sulfate proteoglycan binding (HSPBP) domains cause loss of assembly of the COLQ strands in a triple helix, and mutations in the C-terminal region lead to the synthesis of single- or triple-strands of COLQ-AChE, which are unable to bind to the basal lamina [3, 9, 12, 33].
Background Congenital myasthenic syndromes (CMSs) are rare genetic diseases due to abnormalities of the neuromuscular junction leading to permanent or transient muscle fatigability and weakness. To date, 32 genes were found to be involved in CMSs with autosomal dominant and/or recessive inheritance patterns. CMS with acetylcholinesterase deficiency, in particular, was determined to be due to biallelic mutations of COLQ gene with early-onset clinical signs. Here, we report clinical features and novel molecular findings of COLQ -related CMS in a Moroccan patient with a review of the literature for this rare form. Case presentation In this study, we report the case of a 28-month-old Moroccan female patient with hypotonia, associated to axial muscle weakness, global motor delay, bilateral ptosis, unilateral partial visual field deficiency with normal ocular motility, and fatigable muscle weakness. Clinical exome sequencing revealed a novel homozygous deletion of exon 13 in COLQ gene, NM_005677.4(COLQ):c.(814+1_815-1)_(954+1_955-1) del p.(Gly272Aspfs*11). This finding was subsequently confirmed by quantitative real-time PCR (qPCR) in the proband and her parents. In silico analysis of protein-protein interaction network by STRING tool revealed that 12 proteins are highly associated to COLQ with an elevated confidence score. Treatment with Salbutamol resulted in clear benefits and recovery. Conclusions This clinical observation illustrates the important place of next-generation sequencing in the precise molecular diagnosis of heterogeneous forms of CMS, the appropriate management and targeted treatment, and genetic counseling of families, with a better characterization of the mutational profile of this rare disease in the Moroccan population.
The 12 participating centres of the trial, the study coordination centre in Munich, and the scientific evaluation centres in Greifswald. ■ Study coordination centre: Department of Neurology, University Hospital, Ludwig-Maximilians-University Munich. ○ Regional Outreach Centres, ROC: Schoen Clinic Bad Aibling Harthausen; Therapy Centre Burgau; Clinic for Neurology of the University of Regensburg at medbo district hospital; Clinic for Neurological Early Rehabilitation/Intensive Care, Rhön-Klinikum, Campus Bad Neustadt. △ Participating Neurological Early Rehabilitation centre, NER: Juliusspital Würzburg, VAMED Klinik Kipfenberg, Schoen Clinic Bad Staffelstein, m&i Fachklinik Enzensberg, m&i Fachklinik Herzogenaurach, m&i Fachklinik Bad Heilbrunn, Neurological Centre at the Bezirksklinikum Mainkofen. ● Independent scientific evaluation centres in Greifswald: Greifswald University Medical Center; University of Greifswald. Source maps offered by Maxim Grebeshkov were obtained from Inmagine Lab Pte. Ltd ("123RF") with a license to use and adapt it
Flow chart: Trial course of control and intervention group in the OptiNIV trial. Abbreviations: NR = Neurorehabilitation; FEES = fiberoptic endoscopic evaluation of swallowing; BGA = blood gas analysis
Background Even with high standards of acute care and neurological early rehabilitation (NER) a substantial number of patients with neurological conditions still need mechanical ventilation and/or airway protection by tracheal cannulas when discharged and hence home-based specialised intensive care nursing (HSICN). It may be possible to improve the home care situation with structured specialized long-term neurorehabilitation support and following up patients with neurorehabilitation teams. Consequently, more people might recover over an extended period to a degree that they were no longer dependent on HSICN. Methods This healthcare project and clinical trial implements a new specialised neurorehabilitation outreach service for people being discharged from NER with the need for HSICN. The multicentre, open, parallel-group RCT compares the effects of one year post-discharge specialized outpatient follow-up to usual care in people receiving HSICN. Participants will randomly be assigned to receive the new form of healthcare (intervention) or the standard healthcare (control) on a 2:1 basis. Primary outcome is the rate of weaning from mechanical ventilation and/or decannulation (primary outcome) after one year, secondary outcomes include both clinical and economic measures. 173 participants are required to corroborate a difference of 30 vs. 10% weaning success rate statistically with 80% power at a 5% significance level allowing for 15% attrition. Discussion The OptiNIV-Study will implement a new specialised neurorehabilitation outreach service and will determine its weaning success rates, other clinical outcomes, and cost-effectiveness compared to usual care for people in need for mechanical ventilation and/or tracheal cannula and hence HSICN after discharge from NER. Trial registration The trial OptiNIV has been registered in the German Clinical Trials Register (DRKS) since 18.01.2022 with the ID DRKS00027326 .
Consort flow chart for patient recruitment
Background Patients with a transient ischemic attack (TIA) or ischemic stroke are at increased risk of developing cognitive impairment in the subacute phase. At present, the effects of exercise on cognitive functioning following a TIA or stroke are not fully known. The purpose of this trial was to investigate the effect of exercise on global cognition. Methods The MoveIT trial is a single-centre, observer-blinded, randomized controlled trial involving a 1-year exercise intervention consisting of a 12-week group exercise program, combined with three counselling visits to the physiotherapists over a 9-month period. The control group received standard care. The primary outcome was global cognitive functioning, assessed at one year, using the Montreal Cognitive Assessment (MoCA). Secondary outcomes included cardiorespiratory fitness, the cardiovascular profile, and attainment of secondary prevention targets, anxiety, depression and fatigue at one and two years. Results The experimental group consisted of 60 patients, while the control group consisted of 59 patients. The mean age was 64.3 years and 41% were female. No between-group differences were found on global cognitive functioning (MD, 0.7 out of 30, 95% CI, − 0.2 to 1.6) or on secondary outcome measures at 12 months. The only significant between-group difference was found for fatigue, in favour of the experimental group at 12 months (MD, 0.6 out of 63, 95% CI, 0.1 to 1.1). Conclusions No benefit of this exercise intervention was found regarding global cognition. Future studies need to focus on optimizing rehabilitation strategies for this vulnerable group of patients. Trial registration . Unique identifier: NL3721 . Date first registration: 06-03-2013.
Workflow of pixel value extraction
The architecture of UCATR to generate the mask
Problem background Early detection of acute ischemic stroke (AIS) may provide patients with benefits against harmful health and financial impacts. The use of non-contrast computed tomography images for early detect of the infarct remains controversial. Materials & methods Here, we used the UCATR algorithm to extract the pixel values of the infarct and the corresponding contralateral healthy area as the control surface in each NCCT slice for the whole brain. Magnetic resonance imaging results were used to verify both areas. We found significant pathological changes in the infarct compared with the corresponding contralateral healthy area in each NCCT slice. Attained results Our approach validated that NCCT can be used to detect the lesion area in the early stage of AIS. Conclusions With obvious advantages such as saving time and the ability to quantify the infarct volume, this approach could help more patients survive the fatal and irreversible pathological process of AIS and improve their quality of life after AIS treatment.
Background The objective of this report is to share the clinicopathological features of chemotherapy-induced toxic leukoencephalopathy, which is a rare and under-recognized disease, clinically characterized by rapidly progressive cognitive loss that often leads to sudden death. Case presentation A 64-year-old woman and a 63-year-old man, who had both suffered from a rapid deterioration of consciousness, were autopsied under the clinical impressions of either the central nervous system graft versus host disease (CNS-GVHD), infectious encephalitis, or autoimmune encephalitis. Both patients had been treated with multiple chemotherapy regimens, including adriamycin, cytarabine arabinoside, daunorubicin, fludarabine, azacitidine, and allogeneic peripheral blood stem cell transplantation to treat hematological malignancies (acute myelogenous leukemia and myelodysplastic syndrome). Neuropathological findings at autopsy revealed rarefaction and vacuolar changes of the white matter with axonal spheroids, reactive gliosis, and foamy macrophage infiltration, predominantly in the visual pathways of the occipital and temporal lobes. Damaged axons exhibited immunoreactivity to beta-amyloid, consistent with axonopathy. However, there was no lymphocyte infiltration that suggested CNS-GVHD or any type of encephalitis. Conclusion The neuropathology found in the presented cases had the characteristic features of toxic leukoencephalopathy (chemobrain). Our cases showed that toxic leukoencephalopathy can also be caused by chemotherapy drugs other than methotrexate.
Patient flow chart
Functional outcome and Health-related Quality of Life. A Glasgow Outcome Scale. The Glasgow Outcome Scale (GOS) scores range from 1 (indicating dead) to 5 (Good recovery). Each cell in this graph corresponds with a GOS; the width of the cell indicates the proportion of patients with equivalent scores, and the numbers within the cell indicate the number of patients per category. B Health-related Quality of Life after Brain Injury score. The Quality of Life after Brain Injury score depicts the difference in health-related quality of life between left- and right sided ASDH patients. The Qolibri score is a score to indicate health-related quality of life after traumatic brain injury and is reported on a 0-100 scale (0 = worst possible health-related quality of life, 100 = best possible health-related quality of life). Each point represents a case in the respective groups. In both groups the median is represented by the numbers accompanying the points. Furthermore in this graph, both the highest and the lowest recorded Qolibri score is represented, with the highest score being 99 and the lowest score being 18
Background Traumatic acute subdural haematoma is a debilitating condition. Laterality intuitively influences management and outcome. However, in contrast to stroke, this research area is rarely studied. The aim is to investigate whether the hemisphere location of the ASDH influences patient outcome. Methods For this multicentre observational retrospective cohort study, patients were considered eligible when they were treated by a neurosurgeon for traumatic brain injury between 2008 and 2012, were > 16 years of age, had sustained brain injury with direct presentation to the emergency room and showed a hyperdense, crescent shaped lesion on the computed tomography scan. Patients were followed for a duration of 3-9 months post-trauma for functional outcome and 2-6 years for health-related quality of life. Main outcomes and measures included mortality, Glasgow Outcome Scale and the Quality of Life after Brain Injury score. The hypothesis was formulated after data collection. Results Of the 187 patients included, 90 had a left-sided ASDH and 97 had a right-sided haematoma. Both groups were comparable at baseline and with respect to the executed treatment. Furthermore, both groups showed no significant difference in mortality and Glasgow Outcome Scale score. Health-related quality of life, assessed 59 months (IQR 43-66) post-injury, was higher for patients with a right-sided haematoma (Quality of Life after Brain Injury score: 80 vs 61, P = 0.07). Conclusions This study suggests patients with a right-sided acute subdural haematoma have a better long-term health-related quality of life compared to patients with a left-sided acute subdural haematoma.
Subjective symptom severity ratings on a self-report inventory. Ambulatory (Amb) patients did not differ in symptom severity ratings from patients who required hospitalization (Hosp) for COVID-19
Rates of objective impairment on neurocognitive testing. Patients who were hospitalized (Hosp) for COVID-19 showed higher rates of impairment in visual memory and psychomotor speed compared with patients who remained ambulatory (Amb). Impairment was defined by age-adjusted standardized scores < 9th percentile (red dashed line = 9%). Asterisk indicates p-value < 0.05
Higher subjective complaints of anxiety, depression, fatigue, and pain are associated with lower objective neurocognitive performance in ambulatory, but not hospitalized, patients
Flow diagram to guide decision-making when patients present with cognitive complaints in the post-acute recovery stage following SARS-CoV-2 infection
Background Cognitive complaints are common in patients recovering from Coronavirus Disease 2019 (COVID-19), yet their etiology is often unclear. We assess factors that contribute to cognitive impairment in ambulatory versus hospitalized patients during the sub-acute stage of recovery. Methods In this cross-sectional study, participants were prospectively recruited from a hospital-wide registry. All patients tested positive for SARS-CoV-2 infection using a real-time reverse transcriptase polymerase-chain-reaction assay. Patients ≤ 18 years-of-age and those with a pre-existing major neurocognitive disorder were excluded. Participants completed an extensive neuropsychological questionnaire and a computerized cognitive screen via remote telemedicine platform. Rates of subjective and objective neuropsychological impairment were compared between the ambulatory and hospitalized groups. Factors associated with impairment were explored separately within each group. Results A total of 102 patients (76 ambulatory, 26 hospitalized) completed the symptom inventory and neurocognitive tests 24 ± 22 days following laboratory confirmation of SARS-CoV-2 infection. Hospitalized and ambulatory patients self-reported high rates of cognitive impairment (27–40%), without differences between the groups. However, hospitalized patients showed higher rates of objective impairment in visual memory (30% vs. 4%; p = 0.001) and psychomotor speed (41% vs. 15%; p = 0.008). Objective cognitive test performance was associated with anxiety, depression, fatigue, and pain in the ambulatory but not the hospitalized group. Conclusions Focal cognitive deficits are more common in hospitalized than ambulatory patients. Cognitive performance is associated with neuropsychiatric symptoms in ambulatory but not hospitalized patients. Objective neurocognitive measures can provide essential information to inform neurologic triage and should be included as endpoints in clinical trials.
A and B Abdominal computed tomography scan revealed a patchy, slightly low-density area in the lower right posterior lobe of the liver (arrows), with an area of about 55 × 45 mm
A-D The enhanced magnetic resonance imaging of the liver showed multiple round-like abnormal signals in the liver. After the enhancement, there was obvious uneven ring enhancement. The larger one (arrow) was located in the right lobe of the liver and was about 59 × 49 mm in size, suggesting multiple abscesses in the liver
A and B Contrast-enhanced magnetic resonance imaging revealed the suspicious filling defect of the right transverse sinus, and the larger one (arrow) was about 6 mm, suggesting the possibility of thrombosis in the right transverse sinus. C and D Magnetic resonance venography imaging showed multiple filling defects in the right transverse sinus and sigmoid sinus (arrow), and the luminal visualization was slender than that on the left (arrow), suggesting multiple thrombosis in the right transverse sinus and sigmoid sinus
A-D Enhanced magnetic resonance imaging of the liver obtained at 1-month follow-up showed that lumpy abnormal signal (arrow) was observed in the right posterior lobe of the liver, about 28 × 31 mm in size, which was reduced compared with that of the previous one
A-D Magnetic resonance imaging obtained at 1-month follow-up showed no significant change in the right transverse and sigmoid sinus (arrow)
Background Liver abscess is a common emergency in the emergency department. However, cerebral venous sinus thrombosis (CVST) is a rare and serious cerebrovascular disease. Cases of CVST in patients with Klebsiella pneumoniae primary liver abscess (KLA) have not been described in the literature. We report a case of CVST in patients with KLA. Case presentation A 54-year-old male patient came to our department with a fever for 2 days and altered mental status for 1 day. Abdominal computed tomography (CT) and liver magnetic resonance imaging (MRI) revealed multiple liver abscesses. The blood culture was identified as Klebsiella pneumoniae sepsis. Head contrast-enhanced MRI and magnetic resonance venography (MRV) imaging showed multiple thrombus formation in the right transverse sinus and sigmoid sinus. The patient's infection and thrombosis were controlled within one week of multidisciplinary comprehensive treatment such as antibiotic and antithrombotic therapy, and a good clinical recovery during the 1-month follow-up. Conclusion CVST after liver abscess is rare, clinicians should be aware of this complication and vigilant for the possibility of bacterial meningitis. The underlying mechanisms need to be further studied.
Background Evaluation of the current physical therapy practice for German stroke rehabilitation with respect to the ‘Rehabilitation of Mobility after Stroke (ReMoS)’ guideline recommendations and the associated implementation factors. Methods A descriptive cross-sectional study employing an online survey was performed among German physical therapists in 2019. The survey consisted of three sections with open and closed questions: 1) self-reported use of ReMoS recommendations, 2) barriers of guideline use and 3) socio-demographic characteristics. The benchmark level for guideline adherent physical therapy was set at > 80%. Results Data from 170 questionnaires were eligible for analysis. Participants’ mean age was 41.6 years, 69.4% were female, while 60.1% had no academic degree. The ReMoS guideline was unknown to 52.9% of the responders. Out of all the 46 ReMoS guideline recommendations, only ‘intensive walking training without a treadmill’ was reported to be performed in a guideline adherent manner. Respondents usually denied any personal limitations, such as limited knowledge, or that the ReMoS guideline did not fit their routine practice. Conclusions Among German physical therapists, the ReMoS guideline is not well-known and many interventions are not performed as recommended, illustrating the discrepancies between the ReMoS guideline recommendations and current physical therapy practice. Interventions aimed at overcoming this gap should consider both knowledge of existing barriers and facilitators of guideline usage. Trial registration The study was retrospectively registered to the German Clinical Trials Register ( DRKS00026681 ).
Comparison of the location and number of EPVS among the PD, VaP, and control groups. BG-EPVS in the VaP group were more numerous than in the PD and control groups (adjusted P < 0.017). The CSO-EPVS in the PD and VaP groups was higher than that in the control group (adjusted P < 0.017)
Comparison of the location and number of EPVS among the PD-CI, VaP-CI, and control groups. BG-EPVS in the VaP-CI group were more numerous than in the PD-CI and control groups (adjusted P < 0.017). CSO-EPVS in the PD-CI and VaP-CI groups were higher than that in the control group (adjusted P < 0.017)
ROC curves of BG-EPVS, Fazekas scores, and GCA scores for VaP-CI occurrence. A BG-EPVS numbers, B Fazekas scores, C GCA scores. The PD-CI group was used as the reference group, and the VaP-CI group was used as the measurement group. The diagnostic cutoff value corresponds to the maximum point of the Youden index. The diagnostic cutoff value corresponds to the maximal specificity
Introduction The widespread use of brain magnetic resonance imaging (MRI) has revealed the correlation between enlarged perivascular spaces (EPVS) and cognitive impairment (CI). However, few studies have examined the correlation between MRI-visible EPVS and CI in patients with Parkinson’s disease (PD) and vascular parkinsonism (VaP). This study explored how the number and main location of EPVS in PD and VaP are correlated with the occurrence of CI in these diseases to provide radiology markers and other evidence for early clinical diagnosis in a Chinese cohort. Methods Clinical data were prospectively collected from 77 patients: 26 patients clinically diagnosed with PD or probable PD, 19 patients clinically diagnosed with VaP, and 32 control subjects with normal cognitive function and no stroke or parkinsonism. The patients with PD and VaP were divided into a CI group and a no CI (NCI) group according to the Montreal Cognitive Assessment Beijing version (MoCA-BJ). The relevant clinical data were statistically analysed. Results The centrum semiovale (CSO)-EPVS, lacunes, Fazekas scores, global cortical atrophy scale (GCA) scores, Koedam posterior atrophy visual scale (KS) scores, and medial temporal atrophy (MTA) scores were higher in the PD-CI and VaP-CI groups than in the control group (adjusted P < 0.017). The number of basal ganglia (BG)-EPVS in the VaP group was higher than that in the PD and control groups (adjusted P < 0.017). BG-EPVS, Fazekas scores, GCA scores, KS scores, and MTA scores were higher in the VaP-CI group than in the PD-CI group (adjusted P < 0.017). Multivariate logistic regression analysis showed that the differences in BG-EPVS and Fazekas scores were not significant between PD-CI and VaP-CI patients (P > 0.05). Conclusion VaP-CI results from multiple factors and is significantly associated with BG-EPVS, lacunes, white matter hyperintensities and brain atrophy. BG-EPVS can be used as an imaging marker to distinguish VaP-CI from PD-CI.
Neuroimages of LPRM. Brain CT in 2016 (A) showed left frontal dural hyperdensity. Axial (B), sagittal (C) and coronal (D) post contrast T1WI showed diffuse dural enhancement involving both convexity and falx cerebri. Brain CT in 2020 (E) showed left frontal dural hyperdense mass. Axial (F) and sagittal (G) post contrast T1WI showed significant enlargement of left frontal lesion and more diffuse dural enhancement than that in 2016. After corticotherapy MRI showed significant resolution of the dural enhancement. (H)
Histopathological changes of the lesion. The mass lesion showed scattered nests of meningothelial cells in a mixed inflammatory background with follicular center formation (A, HE*40). Nests of neoplastic meningothelial whorls were identified in lymphocytes and collagen (B, C, HE*100). Neoplastic cells were positive for EMA (D, *100) and PR (E, *100) in immunohistochemistry staining. Lymphocytes were composed of CD20 positive B cells (F, *100) and CD3 positive T cells (G, *100). Rare plasma cells were positive for IgG4 (H, *100). Fewer S100 positive cells existed (I, *100)
Background Lymphoplasmacyte-rich meningioma (LPRM) is a rare form of meningioma characterized by prominent lymphoplasmacytic infiltrates into the tumor. Report of flat growth of LPRM mimicking pachymeningitis is rare in the literature. Case presentation A 55-year-old female who suffered from episodes of headache and seizures has been diagnosed with pachymeningitis for 4 years because post contrast brain MRI demonstrated enhanced carpet-like dura lesion in the left frontal lobe. The lesion kept unchanged on yearly follow-ups until a recent brain MRI found the lesion grew significantly into a mass. The lesion was resected and pathology suggested LPRM. Conclusion LPRM may present as carpet-like growth pattern on MRI. Long-term follow-up in patients with pachymeningitis is necessary.
Background While several studies investigated the epidemiology and burden of stroke in the North Africa and Middle East region, no study has comprehensively evaluated the age-standardized attributable burden to all stroke subtypes and their risk factors yet. Objective The aim of the present study is to explore the regional distribution of the burden of stroke, including ischemic stroke, subarachnoid hemorrhage, and intracerebral hemorrhage, and the attributable burden to its risk factors in 2019 among the 21 countries of North Africa and Middle East super-region. Methods The data of the Global Burden of Disease Study (GBD) 2019 on stroke incidence, prevalence, death, disability-adjusted life years (DALYs), years of life lost (YLLs), years lived with disability (YLDs) rates, and attributed deaths, DALYs, YLLs, and YLDs to stroke risk factors were used for the present study. Results The age-standardized deaths, DALYs, and YLLs rates were diminished statistically significant by 27.8, 32.0, and 35.1% from 1990 to 2019, respectively. Attributed deaths, DALYs, and YLLs to stroke risk factors, including high systolic blood pressure, high body-mass index, and high fasting plasma glucose shrank statistically significant by 24.9, 25.8, and 28.8%, respectively. Conclusion While the age-standardized stroke burden has reduced during these 30 years, it is still a concerning issue due to its increased burden in all-age numbers. Well-developed primary prevention, timely diagnosis and management of the stroke and its risk factors might be appreciated for further decreasing the burden of stroke and its risk factors and reaching Sustainable Development Goal 3.4 target for reducing premature mortality from non-communicable diseases.
Flow Chart. All patients completed the follow-up with complete data, there were 30 patients in the rt-PA + T group and 30 in the rt-PA group
Efficacy of the outcomes at the time of admission and at 7d. The solid horizontal line indicates the median values; the box indicates the 25th to 75th percentiles, and the vertical bar indicates the 5th to 95th percentiles* P < 0.01, NIHSS: National Institutes of Health Stroke Scale
Distribution of the mRS at 90 days after the stroke. More patients in the rt-PA + T group (25/30, 83.3%) had favorable functional outcomes (mRS of 0–2) than the rt-PA group (18/30, 60.0%), P = 0.045
Background and purpose The recanalization rate after intravenous thrombolysis (IVT) is not enough and there is still the possibility of re-occlusion. We aim to investigate the effectiveness and safety of infusing tirofiban after IVT. Methods We performed a prospective controlled study of 60 patients with acute non-cardiogenic ischemic stroke who were hospitalized in Yantai Yuhuangding Hospital from January 2018 to December 2019. The patients were divided into 2 groups: those who received tirofiban for 24 h after IVT (rt-PA + T group) and those who did not receive postprocedural intravenous tirofiban (rt-PA group). The rt-PA + T group received low-dose rt-PA (0.6 mg/kg). The rt-PA group received standard dose rt-PA (0.9 mg/kg). The main outcome measure were safety, included the symptomatic intracranial hemorrhage (sICH), any ICH, severe systemic bleeding, and mortality. The secondary outcome measure is curative efficacy which were evaluated by the 7d-NIHSS score and functional outcomes at 90 days. During hospitalization, the deterioration of neurological function was recorded. Results All patients completed the follow-up with complete data, there were 30 patients in each of groups. The general characteristics between the two group patients had no statistically significant differences. Compared with the rt-PA + T group and the rt-PA group, in terms of safety, the rates of the sICH, severe systemic bleeding, and mortality in both groups were 0, and there was no statistically significant difference in the rates of any ICH between the two groups (10.0% vs. 3.3%, P = 0.306). In terms of efficacy, the rate of the early neurological deterioration events (END) was no statistical significance (0 vs. 6.6%, P = 0.246). There was no significant difference in the NIHSS score between the two groups before the IVT, and also at 24 h, however, the 7d-NIHSS score was lower in the rt-PA + T group compared with the rt-PA group (2.33 ± 1.85 vs. 4.80 ± 4.02, P = 0.004). At 90 days, 83.3% of patients in the rt-PA + T group had favorable functional outcomes compared with 60.0% of patients in the rt-PA group (P = 0.045). Conclusions Low-dose rt-PA combined with tirofiban in acute non-cardiogenic ischemic stroke did not increase the risk of ICH, and mortality, and it was associated with neurological improvement. Trial Registration The trial has been registered at the ChiCTR and identified as ChiCTR1800014666 (28/01/2018).
MRI sequences on the first admission. These images demonstrated irregular lesions in the left caudate nucleus, putamen and insula with restricted diffusion (A-C). Medulla oblongata was not affected (D). There was no obvious enhancement of the lesion on contrast-enhanced MRI (E, F). (A) DWI, (B) ADC, (C and D) FLAIR, and (E and F) T1 postcontrast
MRI sequences on the second admission. These images demonstrated new lesion which was hyperintensity on FLAIR sequences in the left hippocampus
MRI sequence at 5-month follow up showed the left hippocampus was smaller than the contralateral side
Background Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis, an autoimmune disorder, is characterized by faciobrachial dystonic seizures, epilepsy, memory deficits and altered mental status while hiccup is not commonly found in patients. Case presentation A 62-year-old male was presented with slurred speech, abnormal gait, faciobrachial dystonic seizures and impaired cognition. Besides, the hiccup was one of the initial symptoms. His brain magnetic resonance images (MRI) revealed multiple lesions with left caudate nucleus, putamen, insula and left hippocampus involvement. Because a diagnosis of antibody-related limbic encephalitis was suspected, studies including an autoimmune profile were done by cell-based assays. After anti-LGI1 antibodies were detected in both cerebrospinal fluid and serology, pulse methylprednisolone and intravenous immunoglobulin were started and hence hiccups disappeared along with other symptoms. Conclusions Clinicians should be aware that persistent hiccups might be one of the initial manifestations of LGI1 subtype of voltage-gated potassium channel complex antibody associated autoimmune encephalitis.
Non-classical monocytes (CD14 + CD16 + +) were significantly lower in the peripheral blood of migraine group compared with the matched control group. (A) First, the lymphocytes and monocytes populations are highlighted, and the single cell population was selected only. Then NK cells, T cells were removed. HLA-DR and SSC-A subset was selected, and three populations within the monocytes were identified by CD14 and CD16 markers. (B) Bar graph showed that non-classical monocytes (CD14 + CD16 + +) were significantly lower (11.9 ± 10.5 vs. 33.9 ± 21.4), **p = 0.005 in the peripheral blood of migraine group compared with the matched control group, *p < 0.05, **p < 0.01. Data are represented as means ± SD, significance was determined by nonparametric Wilcoxon signed rank test
CD4 T cell populations from migraineurs were significantly lower than controls. (A) CD4⁺ T cell populations from migraineurs were significantly lower than controls (64.0 ± 5.45 vs. 70.6 ± 8.92), *p = 0.035. (B) CD4⁺/CD8⁺ ratio was lowed in the migraineurs, yet the change was not significant (not shown). *p < 0.05, **p < 0.01. Data are represented as means ± SD, significance was determined by nonparametric Wilcoxon signed rank test
CD4 ⁺ CD25 ⁺ T cell populations from migraineurs were significantly lower than controls. (A) The lymphocytes and monocytes populations are highlighted, and the single cell population was selected only. CD3 + and CD4 ⁺ population were selected, respectively. Finally, CD4 + CD25⁺ population was highlighted. (B) CD4⁺ CD25⁺ T cell populations from migraineurs were significantly lower than controls (5.66 ± 1.35 vs. 8.29 ± 2.31), **P = 0.001. Data are represented as means ± SD, significance was determined by nonparametric Wilcoxon signed rank test
Both CD4 + helper T cells and CD8 + killer T cells demonstrated lowered expression by mean fluorescence intensity (MFI) of integrin CD18, but not significantly. MFI of CD18 was lower in both CD4 ⁺ T cells and CD8 + T cells in migraineurs compared with controls, with p = 0.06 and p = 0.09, respectively. Data are represented as means ± SD, analysis was determined by nonparametric Wilcoxon signed rank test
Cytokine analysis with 24-h LPS stimulation revealed no significant difference in inflammatory cytokine levels (IL-1 beta and TNF-a) between migraineurs and controls. Pre-stimulation and post-stimulation of IL-1β (Fig. 5A) and TNF-α (Fig. 5B) were processed using Stata software, no significant changes were found
Background Migraine is a neurological condition characterized by chronic inflammation. However, not much is known about the potential role of peripheral blood immune cells in the pathophysiology of migraine. Methods We investigated the status of peripheral blood immune cells of 15 adults with frequent episodic or chronic migraine recruited chronologically from a randomized clinical trial (RCT) on Nutrition for Migraine (NCCIH 5R01AT007813-05) and 15 non-migraine, healthy volunteers (control) matched by age, gender, and Body Mass Index (BMI). Continuous variables were presented as means ± standard deviationas well as medians, and comparisons between patients and healthy volunteers were performed with non-parametric Wilcoxon signed rank tests. Statistical analysis was performed using Stata (StataCorp. 2019. Stata Statistical Software). Fluorescence-Activated Cell Sorting (FACS) data were processed using FlowJo software (Ashland, OR: Becton, Dickenson and Company; 2019). Results We observed that migraineurs had a significantly lower percentage of non-classical monocytes (CD14⁺CD16⁺⁺) in blood circulation, compared to the control group. In addition, Migraineurs also showed a significantly lower percentage of blood CD3⁺CD4⁺ helper T cells and CD4⁺CD25⁺ regulatory T cells, compared to controls. Differences in leukocyte surface markers between chronic migraine patients and their matched controls were more prominent than those between episodic migraine patients and their matched controls. Conclusions Our results suggest that migraine is associated with dysregulated peripheral immune homeostasis and that inflammation and autoimmunity may play a role in its pathophysiology.
A Gut microbiota composition in controls and anti-NMDAR encephalitis patients. B Lefse-based comparison of patients and controls
Results of α and β diversity. A Shannon, B Simpson and C Pielou_e indexes were used to calculate the α diversity. D Weighted and E unweighted UniFrac distance were used to calculate the β diversity
Background Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a type of autoimmune encephalitis. The underlying mechanism(s) remain largely unknown. Recent evidence has indicated that the gut microbiome may be involved in neurological immune diseases via the "gut-brain axis". This study aimed to explore the possible relationship between anti-NMDAR encephalitis and the gut microbiome. Methods Fecal specimens were collected from 10 patients with anti-NMDAR encephalitis and 10 healthy volunteers. The microbiome analysis was based on Illumina sequencing of the V3-V4 hypervariable region of the 16S rRNA gene. The alpha, beta, and taxonomic diversity analyses were mainly based on the QIIME2 pipeline. Results There were no statistical differences in epidemiology, medication, and clinical characteristics (except for those related to anti-NMDAR encephalitis) between the two groups. ASV analysis showed that Prevotella was significantly increased, while Bacteroides was reduced in the gut microbiota of the patients, compared with the controls. Alpha diversity results showed a decrease in diversity in the patients compared with the healthy controls, analyzed by the Shannon diversity, Simpson diversity, and Pielou_E uniformity based on the Kruskal–Wallis test ( P = 0.0342, 0.0040, and 0.0002, respectively). Beta diversity analysis showed that the abundance and composition of the gut microbiota was significantly different between the two groups, analyzed by weighted and unweighted UniFrac distance ( P = 0.005 and 0.001, respectively). Conclusions The abundance and evenness of bacterial distribution were significantly lower and jeopardized in patients with anti-NMDAR encephalitis than in healthy controls. Thus, our findings suggest that gut microbiome composition changes might be associated with the anti-NMDAR encephalitis. It could be a causal agent, or a consequence.
Outline of care and tests provided to PwMS involved in this study
Trial flow using the Consort flow diagram
Difference in change of HADS-D over 3 and 6 months. *P-value was calculated by Wilcoxon signed-rank test
Difference in change of HADS-A over 3 and 6 months. *P-value was calculated by Wilcoxon signed-rank test
Changes in patient-reported outcome measures between NP-led care and Usual care at each time point – baseline, 3 months, and 6 months
Background Care for People with Multiple Sclerosis (PwMS) is increasingly complex, requiring innovations in care. Canada has high rates of MS; it is challenging for general neurologists to optimally care for PwMS with busy office practices. The aim of this study was to evaluate the effects of add-on Nurse Practitioner (NP)-led care for PwMS on depression and anxiety (Hospital Anxiety and Depression Scale, HADS), compared to usual care (community neurologist, family physician). Methods PwMS followed by community neurologists were randomized to add-on NP-led or Usual care for 6 months. Primary outcome was the change in HADS at 3 months. Secondary outcomes were HADS (6 months), EQ5D, MSIF, CAREQOL-MS, at 3 and 6 months, and Consultant Satisfaction Survey (6 months). Results We recruited 248 participants; 228 completed the trial (NP-led care arm n = 120, Usual care arm n = 108). There were no significant baseline differences between groups. Study subjects were highly educated (71.05%), working full-time (41.23%), living independently (68.86%), with mean age of 47.32 (11.09), mean EDSS 2.53 (SD 2.06), mean duration since MS diagnosis 12.18 years (SD 8.82) and 85% had relapsing remitting MS. Mean change in HADS depression (3 months) was: -0.41 (SD 2.81) NP-led care group vs 1.11 (2.98) Usual care group p = 0.001, sustained at 6 months; for anxiety, − 0.32 (2.73) NP-led care group vs 0.42 (2.82) Usual care group, p = 0.059. Other secondary outcomes were not significantly different. There was no difference in satisfaction of care in the NP-led care arm (63.83 (5.63)) vs Usual care (62.82 (5.45)), p = 0.194). Conclusion Add-on NP-led care improved depression compared to usual neurologist care and 3 and 6 months in PwMS, and there was no difference in satisfaction with care. Further research is needed to explore how NPs could enrich care provided for PwMS in healthcare settings. Trial registration Retrospectively registered on ( Identifier: NCT04388592 , 14/05/2020).
Background While numerous neuroimaging studies have demonstrated that glaucoma is associated with smaller volumes of the visual cortices in the brain, only a few studies have linked glaucoma with brain structures beyond the visual cortices. Therefore, the objective of this study was to compare brain imaging markers and neuropsychological performance between individuals with and without glaucoma. Methods We identified 64 individuals with glaucoma and randomly selected 128 age-, sex-, and education level-matched individuals without glaucoma from a community-based cohort. The study participants underwent 3 T brain magnetic resonance imaging and neuropsychological assessment battery. Regional cortical thickness and subcortical volume were estimated from the brain images of the participants. We used a linear mixed model after adjusting for potential confounding variables. Results Cortical thickness in the occipital lobe was significantly smaller in individuals with glaucoma than in the matched individuals (β = − 0.04 mm, P = 0.014). This did not remain significant after adjusting for cardiovascular risk factors (β = − 0.02 mm, P = 0.67). Individuals with glaucoma had smaller volumes of the thalamus (β = − 212.8 mm ³ , P = 0.028), caudate (β = − 170.0 mm ³ , P = 0.029), putamen (β = − 151.4 mm ³ , P = 0.051), pallidum (β = − 103.6 mm ³ , P = 0.007), hippocampus (β = − 141.4 mm ³ , P = 0.026), and amygdala (β = − 87.9 mm ³ , P = 0.018) compared with those without glaucoma. Among neuropsychological battery tests, only the Stroop color reading test score was significantly lower in individuals with glaucoma compared with those without glaucoma (β = − 0.44, P = 0.038). Conclusions We found that glaucoma was associated with smaller volumes of the thalamus, caudate, putamen, pallidum, amygdala, and hippocampus.
Left and right NPi (left y-axis) and their difference (right y-axis) for two patients with stroke measured several times during the day. The presence of an NPi differential is indicated by the horizontal dashed line at the cutoff value of 0.7 and arrows. Note how neither the left nor right NPi ever fell below the critical value of 3 (horizontal solid line). Modified Rankin Score at discharge (DC mRS) for these patients were 5 (poor outcome, upper panel) and 6 (death, lower panel)
Patients divided in two cohorts for stroke & TBI and difference between pairs of NPi’s: < high diff > are patients that had at least one occurrence of an NPi differential. i.e. (abs[ NPi(left) – NPi(right)] ≥ 0.7); < low diff > are patients whose difference was always lower than 0.7. NPi differentials are associated with poorer DC mRS outcomes as represented. Asterisks indicates P < .001, error bars are 95% Cis
Patients of the two cohorts divided by their NPis and NPi differentials. < NPi = 0 > are patients that had at least one occurrence of a non-responsive pupil. < low NPi high diff > are patients that had at least one abnormal NPi (NPi < 3) and at least one NPi differential (abs[NPi(left) – NPi(right)] ≥ 0.7); finally, < normal > , are patients with all normal NPi’s and no NPi differentials. The group with < NPi = 0 > was associated with the most severe mRS. The two groups with one or both abnormalities were all significantly better than < NPi = 0 > (asterisks indicates P < .001) but all equally poorer than the group with normal NPi’s and no NPi differentials. Error bars are 95% Cis
Percent of patients and their distribution of NPi for four reference DC mRS values and the two cohorts Stroke and TBi show increasing NPi differentials for increased DC mRS
For each patient in the < low NPi high diff > group, time of the first occurrence of an NPi differential is included in a histogram relative to the first time of occurrence of an abnormal NPi (set at zero). The peak of the distribution at time zero reveals a marked synchronicity between the two types of abnormalities and, its skewness towards the negative axis, a leading effect of the NPi differential
Background: Automated infrared pupillometry (AIP) and the Neurological Pupil index (NPi) provide an objective means of assessing and trending the pupillary light reflex (PLR) across a broad spectrum of neurological diseases. NPi quantifies the PLR and ranges from 0 to 5; in healthy individuals, the NPi of both eyes is expected to be ≥ 3.0 and symmetric. AIP values demonstrate emerging value as a prognostic tool with predictive properties that could allow practitioners to anticipate neurological deterioration and recovery. The presence of an NPi differential (a difference ≥ 0.7 between the left and right eye) is a potential sign of neurological abnormality. Methods: We explored NPi differential by considering the modified Rankin Score at discharge (DC mRS) among patients admitted to neuroscience intensive care units (NSICU) of 4 U.S. and 1 Japanese hospitals and for two cohorts of brain injuries: stroke (including subarachnoid hemorrhage, intracerebral hemorrhage, acute ischemic stroke, and aneurysm, 1,200 total patients) and 185 traumatic brain injury (TBI) patients for a total of more than 54,000 pupillary measurements. Results: Stroke patients with at least 1 occurrence of an NPi differential during their NSICU stay have higher DC mRS scores (3.9) compared to those without an NPi differential (2.7; P < .001). Patients with TBI and at least 1 occurrence of an NPi differential during their NSICU stay have higher discharge modified Rankin Scale scores (4.1) compared to those without an NPi differential (2.9; P < .001). When patients experience both abnormalities, abnormal (NPi < 3.0) and an NPi differential, the latter has an anticipatory relationship with respect to the former (P < .001 for z-score skewness analysis). Finally, our analysis confirmed ≥ 0.7 as the optimal cutoff value for the NPi differential (AUC = 0.71, P < .001). Conclusion: The NPi differential is an important factor that clinicians should consider when managing critically ill neurological injured patients admitted to the neurocritical care units. Trial registration: NCT02804438 , Date of Registration: June 17, 2016.
Flow diagram of patient inclusion and exclusion
The decline rate of CSF cryptococci within 2 weeks follow-up
Background: Our previous study explored Amphotericin B (AMB) plus 5-flucytosine (5-FC) combined with fluconazole (FLU) therapy in the induction period, which seemed to be better than the previous AMB + 5-FC antifungal therapy in non-HIV and non-transplant-associated CM. However, based on our clinical finding, the outcomes of some CM patients who received AMB plus 5-FC combined with FLU antifungal therapy were still poor. Therefore, we need to explore new antifungal methods in non-HIV and non-transplant-associated CM during the induction period. Methods: Clinical data from 148 patients admitted to the Third Affiliated Hospital of Sun Yat Sen University from January 2011 to December 2020 were collected. These patients were stratified based on antifungal treatment methods in the induction period (group I with AMB + 5-FC + VOR, group II with AMB + 5-FC + FLU, group III with AMB + 5-FC). Results: The first hospitalization time of Group I (median: 25 days, IQR: 20-34.5) was significantly shorter than that of Group II (median: 43 days, IQR: 29-62) (p < 0.001) and Group III (median: 50.5 days, IQR: 43-77.5) (p < 0.001). After 2 weeks of follow-up, Group I (26/49) had more patients reaching CSF clearance (p = 0.004) than Group II (18/71) and Group III (7/28). In multivariable analysis, Group II (OR: 3.35, 95%CI 1.43-7.82, p = 0.005) and Group III (OR: 3.8, 95%CI 1.23-11.81, p = 0.021) were associated with higher risk about CSF clearance failure at 2 weeks follow-up than Group I. After 10 weeks of follow-up, the incidence of hypokalemia in Group I was significantly lower than that in Group II (p = 0.003) and Group III (p = 0.004), and the incidence of gastrointestinal discomfort in Group I was significantly lower than that in Group II (p = 0.004). Conclusion: AMB plus 5-FC combined with VOR may rapidly improve clinical manifestation, decrease CSF OP and clear the cryptococci in CSF during the early phase, substantially shorten the hospitalization time, and reduce the incidences of hypokalemia and gastrointestinal discomfort.
General overview of the study. Health questionnaire survey,physical examination and multiomics assays will be performed to collect data on the volunteers’ general health. Horizontal cohort (cohort difference analysis) and longitudinal cohort (dynamic analysis of health assessment, molecular dynamic expression analysis) data analysis will be performed to develop a precise health promotion model for the CRD population
Background Circadian rhythm disorders (CRDs) are closely associated with the occurrence and development of various diseases, such as inflammatory and cardiovascular diseases, as well as tumors. The impact of a CRD on bodily health is a complex and comprehensive process, and its molecular mechanisms and signaling pathways are still unclear. We therefore aimed to investigate the molecular mechanism variation and adverse outcomes associated with CRDs in a prospective cohort of CRD cases and controls at term using multiomics data. The study has been tasked with developing a precise health promotion model for the prevention and management of CRDs. Methods This will be a 5-year prospective cohort study centered on the health management of individuals with CRDs. One hundred volunteers were recruited and had undergone baseline specimen collection, health examination, and health assessment. All of them will be followed up every year using the same protocol, and their biological specimens will be subjected to multiomics analysis after standardized processing. Discussion Longitudinal health examination, health assessment, and multiomics data will be analyzed to study the impact of CRDs on the volunteers’ health status. The results of this study will promote the development of targeted health management programs based on precision medicine. Trial registration The clinical study registration has been completed (Trial Registration No. ChiCTR2100047242).
Figures of negative control cell lines. Negtive control in serum (A and B) and CSF (C and D) by transfected cell-based assay. A and C show plasmid transfection, while B and D show antigen-antibody reaction. (magnification: 200×)
Positive GFAP-IgG in serum (B) and CSF (D) by transfected cell-based assay. A and C show plasmid transfection, while B and D show antigen-antibody reaction. (magnification: 200×)
Negtive AQP4-IgG in serum (B) and CSF (D) by transfected cell-based assay. Negtive MOG-IgG in serum (F) and CSF (H) by transfected cell-based assay. A/C/E/G show plasmid transfection, while B/D/F/H show antigen-antibody reaction. (magnification: 200×)
Background Area postrema syndrome (APS) as the isolated manifestation in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy has been rarely reported. Case presentation A 61-year-old male patient presented with intractable hiccup. He was first admitted to the department of Gastroenterology because he had no symptoms other than hiccup. Then he was diagnosed with possible digestive system disease and started on treatment. 2 weeks later, his symptom didn’t improve at all. After consultation, the patient was referred to our department. Cerebrospinal fluid (CSF) analysis revealed lymphocytes pleocytosis, elevated protein level. Cell-based assays demonstrated GFAP antibodies in blood and CSF. His symptom improved with steroid pulse therapy (methylprednisolone, 1 g for 5 days), followed by a gradual tapering of oral prednisolone. Three months after the initial presentation, he showed no relapses. Conclusions We report atypical manifestation of autoimmune GFAP astrocytopathy which presented as APS, suggesting that autoimmune GFAP astrocytopathy should be added to the list of possible cause of APS.
Examples of focal and diffuse spinal cord lesions (left PD sequence and right T2W sequence) on diagnostic MRI of the cervical and upper thoracal spinal cord in two patients with MS. A: focal lesion without diffuse lesions in a 24-year-old patient (EDSS 2.0) B: diffusely abnormal signal without clearly demarcated focal lesions in a 40-year-old patient (EDSS 3.5)
Representative images of brainstem and cerebellar lesions in patients with early MS. Typical lesions in cerebellar peduncles and discrete subpial ‘linings’ along the periphery of the brainstem (marked with arrows). A: 40-year-old patient, DD 4 months, EDSS 3.5; B: 44-year-old patient, DD 1 month, EDSS 2.0; C: 31-year-old patient, DD 25 months, EDSS 1.5; D1-D4: 51-year-old patient, DD 4 months, EDSS 4.0; E: 45-year-old patient, DD 3 months, EDSS 1.0; F: 23-year-old patient, DD 1 month, EDSS 2.0; G: 40-year-old patient, DD 4 months, EDSS 2.0. DD = disease duration, EDSS = Expanded Disability Status Scale
Association between spinal cord involvement and the presence of brainstem and cerebellar lesions
Comparison of (A) normalized MUCCA and (B) normalized thalamus volume among healthy controls, patients with and without diffuse spinal cord lesions. ** = p < 0.01. Legend: DL = diffuse lesions; MUCCA = mean upper cervical cord cross-sectional area
Background: Early infratentorial and focal spinal cord lesions on magnetic resonance imaging (MRI) are associated with a higher risk of long-term disability in patients with multiple sclerosis (MS). The role of diffuse spinal cord lesions remains less understood. The purpose of this study was to evaluate focal and especially diffuse spinal cord lesions in patients with early relapsing-remitting MS and their association with intracranial lesion topography, global and regional brain volume, and spinal cord volume. Methods: We investigated 58 MS patients with short disease duration (< 5 years) from a large academic MS center and 58 healthy controls matched for age and sex. Brain, spinal cord, and intracranial lesion volumes were compared among patients with- and without diffuse spinal cord lesions and controls. Binary logistic regression models were used to analyse the association between the volume and topology of intracranial lesions and the presence of focal and diffuse spinal cord lesions. Results: We found spinal cord involvement in 75% of the patients (43/58), including diffuse changes in 41.4% (24/58). Patients with diffuse spinal cord changes exhibited higher volumes of brainstem lesion volume (p = 0.008). The presence of at least one brainstem lesion was associated with a higher probability of the presence of diffuse spinal cord lesions (odds ratio 47.1; 95% confidence interval 6.9-321.6 p < 0.001) as opposed to focal spinal cord lesions (odds ratio 0.22; p = 0.320). Patients with diffuse spinal cord lesions had a lower thalamus volume compared to patients without diffuse spinal cord lesions (p = 0.007) or healthy controls (p = 0.002). Conclusions: Diffuse spinal cord lesions are associated with the presence of brainstem lesions and with a lower volume of the thalamus. This association was not found in patients with focal spinal cord lesions. If confirmed, thalamic atrophy in patients with diffuse lesions could increase our knowledge on the worse prognosis in patients with infratentorial and SC lesions.
a Diffusion-weighted magnetic resonance images at the time of admission revealing a small high-intensity area in the midlateral portion of the right middle medulla. b Three-dimensional computed-tomography angiography (3D-CTA) performed 10 days after admission showing stenosis in the right vertebral artery. c Fluid-attenuated inversion recovery (FLAIR) MRI conducted 14 days after admission showing a faint high-intensity area almost exactly coinciding with the high-intensity area observed in diffusion-weighted images at admission.
Medial nerve somatosensory evoked potential tests indicating that the N20 distal latency and the P15-N20 amplitude were 18.7 msec/2.086 μV at C3’-A1 and 18.7 msec/2.586 μV at C4’-A2, respectively.
Background A small lateral medullary lesion could produce isolated impairment of temperature sensation without concomitant impaired pain sensation. However, only one such case has ever been reported, and there are no reports on subjective symptoms and detailed somatosensory testing. Case presentation Herein, we report the case of a 53-year-old female patient presenting with impaired temperature sensation on the left half of her body, from the neck down, following a small infarction of the right midlateral medulla. The chronological changes in the patient's introspection regarding impairment of thermoception and the results of detailed somatosensory tests, including thermal sense, are shown in this report. Conclusions Thorough somatosensory tests, personal descriptions of symptoms, and electrophysiological quantification of similar cases are needed to improve our understanding of the neurological separation of the sensations of pain and temperature at the medullary level.
DecodeME study design involving the potential participant (green shapes), the DecodeME team (white), the NIHR Biosample Centre (blue) and the genotyping provider (brown), ThermoFisher/Affymetrix. Participants are told that they are not obliged to consent to participate in the study. At any point potential participants can contact DecodeME with questions. If progress is not made on consent or the questionnaire or returning the saliva collection kit then DecodeME contacts the participant. If DNA from the sample fails quality control then a second kit is sent to the participant
Screenshots from a video released for ME Awareness Week in May 2021: Other videos and webinars are available from the DecodeME YouTube channel
Numbers of registration sign-ups over time. Prior to DecodeME study launch, 28,966 people pre-registered to participate (19 January 2022)
Most respondents know little about genetics. Answers to a Twitter Poll launched by on 18 June 2021. Its question was “How much do you know about genetics?” The poll received 133 votes
Over 75% of respondents have experienced ME/CFS symptoms for over 6 years. Answers to a Twitter Poll launched by on 23 September 2021. Its question was “If you have ME/CFS, how long have you had #MEcfs symptoms? Or how long as the person you care for…?” The poll received 1,166 votes
Background Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a common, long-term condition characterised by post-exertional malaise, often with fatigue that is not significantly relieved by rest. ME/CFS has no confirmed diagnostic test or effective treatment and we lack knowledge of its causes. Identification of genes and cellular processes whose disruption adds to ME/CFS risk is a necessary first step towards development of effective therapy. Methods Here we describe DecodeME, an ongoing study co-produced by people with lived experience of ME/CFS and scientists. Together we designed the study and obtained funding and are now recruiting up to 25,000 people in the UK with a clinical diagnosis of ME/CFS. Those eligible for the study are at least 16 years old, pass international study criteria, and lack any alternative diagnoses that can result in chronic fatigue. These will include 5,000 people whose ME/CFS diagnosis was a consequence of SARS-CoV-2 infection. Questionnaires are completed online or on paper. Participants’ saliva DNA samples are acquired by post, which improves participation by more severely-affected individuals. Digital marketing and social media approaches resulted in 29,000 people with ME/CFS in the UK pre-registering their interest in participating. We will perform a genome-wide association study, comparing participants’ genotypes with those from UK Biobank as controls. This should generate hypotheses regarding the genes, mechanisms and cell types contributing to ME/CFS disease aetiology. Discussion The DecodeME study has been reviewed and given a favourable opinion by the North West – Liverpool Central Research Ethics Committee (21/NW/0169). Relevant documents will be available online ( ). Genetic data will be disseminated as associated variants and genomic intervals, and as summary statistics. Results will be reported on the DecodeME website and via open access publications.
Pedigree diagram and brain computed tomography (CT). A Pedigree of the family with primary familial brain calcification (PFBC). The proband is indicated by an arrow. The black shaded symbols indicate the symptomatic patients with PFBC. The grey shaded symbols indicate the asymptomatic patients with PFBC. B Patient II: 4, brain CT showed calcification in the cerebellum, basal ganglia, subcortical and deep white matter. C Patient I: 1, brain CT showed calcification in the basal ganglia, white matter adjacent to the lateral ventricle and subcortical white matter. D Patient III: 1, brain CT showed calcification in the basal ganglia and subcortical white matter. E-F Patient II: 1 and patient III: 5, brain CT showed symmetrical calcification only in the bilateral basal ganglia. G Patient III: 3, brain CT showed mild unsymmetrical scattered punctate calcifications only in the basal ganglia (arrows)
DNA sequencing results. A The heterozygous SLC20A2 gene mutation, c.1723G > T, in this family. Black frames indicate the c.1723 nucleotide. B Wild-type SLC20A2 gene sequence
Background Primary familial brain calcification (PFBC) is a rare inherited neurological disorder characterized by bilateral basal ganglia calcification with a series of motor and nonmotor symptoms. Mutations in the SLC20A2 gene, encoding the PiT2 protein, are the major cause of the disease. Here, we report a Chinese PFBC family carrying a SLC20A2 gene mutation, and the proband presented with purely acute psychiatric symptoms, which has been rarely reported in this disease. Case presentation A 38-year-old woman was hospitalized due to disorganized speech; disordered thought contents; disorganized behaviour; emotional instability and lability; and grandiose words, actions and facial expressions. Brain computerized tomography (CT) revealed calcification in the basal ganglia; cerebellar dentate nuclei; and subcortical, periventricular, and deep white matter regions in she and her family members. Through mutation analysis, a heterozygous truncating mutation, c.1723G > T, p.(Glu575*), was identified in the SLC20A2 gene in this family. Thus, this patient was diagnosed with genetically confirmed PFBC, and she responded well to a low dose of antipsychotic drugs. The penetrance of the disease in this family was only 33%, which was significantly lower than that in most families carrying SLC20A2 gene mutations. Conclusions Patients with SLC20A2- related PFBC might present with psychiatric symptoms alone, and the penetrance of the disease may be quite low, which adds to the clinical heterogeneity of the disease.
TAS Test Reaction Time Tests: a) simple choice test and b) five choice test
Benson Figure Test (a) Viewing phase to register the shape over a 1-minute duration and (b) delayed recall phase to identify whether a sub-section was part of the original figure
Spatial Span test; the participant is shown a sequence of yellow circles and then asked to repeat the sequence by clicking on the circles. The length of sequence increases each time a sequence is correctly recalled, up to a maximum of 9 circles
Background The worldwide prevalence of dementia is rapidly rising. Alzheimer’s disease (AD), accounts for 70% of cases and has a 10–20-year preclinical period, when brain pathology covertly progresses before cognitive symptoms appear. The 2020 Lancet Commission estimates that 40% of dementia cases could be prevented by modifying lifestyle/medical risk factors. To optimise dementia prevention effectiveness, there is urgent need to identify individuals with preclinical AD for targeted risk reduction. Current preclinical AD tests are too invasive, specialist or costly for population-level assessments. We have developed a new online test, TAS Test, that assesses a range of motor-cognitive functions and has capacity to be delivered at significant scale. TAS Test combines two innovations: using hand movement analysis to detect preclinical AD, and computer-human interface technologies to enable robust ‘self-testing’ data collection. The aims are to validate TAS Test to [1] identify preclinical AD, and [2] predict risk of cognitive decline and AD dementia. Methods Aim 1 will be addressed through a cross-sectional study of 500 cognitively healthy older adults, who will complete TAS Test items comprising measures of motor control, processing speed, attention, visuospatial ability, memory and language. TAS Test measures will be compared to a blood-based AD biomarker, phosphorylated tau 181 (p-tau181). Aim 2 will be addressed through a 5-year prospective cohort study of 10,000 older adults. Participants will complete TAS Test annually and subtests of the Cambridge Neuropsychological Test Battery (CANTAB) biennially. 300 participants will undergo in-person clinical assessments. We will use machine learning of motor-cognitive performance on TAS Test to develop an algorithm that classifies preclinical AD risk (p-tau181-defined) and determine the precision to prospectively estimate 5-year risks of cognitive decline and AD. Discussion This study will establish the precision of TAS Test to identify preclinical AD and estimate risk of cognitive decline and AD. If accurate, TAS Test will provide a low-cost, accessible enrichment strategy to pre-screen individuals for their likelihood of AD pathology prior to more expensive tests such as blood or imaging biomarkers. This would have wide applications in public health initiatives and clinical trials. Trial registration Identifier: NCT05194787 , 18 January 2022. Retrospectively registered.
Patient flow diagram
Background Stent-assisted coiling (SAC) has been reported as a feasible and effective treatment of wide-neck cerebral aneurysms. However, the evidence of SAC of ruptured cerebral aneurysm is lacking. There are no prospective multicenter studies regarding SAC of acutely ruptured aneurysms within 72 hours after subarachnoid hemorrhage. The purpose of the study is to evaluate the safety and efficiency of SAC of acutely ruptured cerebral aneurysms. Methods This study is a prospective, multicenter, and observation registry of consecutive patients with acutely ruptured cerebral aneurysms treated with SAC. Acutely ruptured aneurysms were confirmed within 72 h after the onset of the syndrome. This study will enroll at least 300 patients in 7 high-volume tertiary hospitals (more than 150 cerebral aneurysms treated per year). The primary outcomes are treatment-related thromboembolic complications within 30 days of the treatment. The secondary outcomes are any hemorrhagic complications and aneurysm recurrence at 6 months of angiographic follow-up. The clinical outcomes are measured with the Modified Rankin Scale (mRS) at discharge and at the 6 months of follow-up. The favorable outcomes are defined as an mRS of grades 0 and 2. Discussion We will perform a prospective, multicenter, and observational registry study of consecutive patients with wide-neck acutely ruptured cerebral aneurysms to improve the safety strategy of SAC of acutely ruptured cerebral aneurysms. Trial registration Chinese Clinic Trial Registry: ChiCTR2000036972 ; Registration date: Aug 26, 2020
Flowchart of study participants
Distribution of TG/HDL-c ratio. It presented a skewed distribution while being in the range from 0.31 to 8.83
Incidence of unfavorable outcomes according to the quartiles of TG/HDL-c ratio
The nonlinear relationship between TG/HDL-c ratio and the risk of unfavorable outcomes. The nonlinear relationship between TG/HDL-c ratio and the risk of unfavorable outcomes. A nonlinear relationship was detected after adjusting for age, gender, HGB, BMI, HCT, AST, BUN, ALB, FBG, FIB, DM, Previous stroke or TIA, hypertension, CHD, stroke etiology, smoking, and NIHSS score
Objective Evidence regarding the relationship between serum triglyceride-to-high density lipoprotein cholesterol (TG/HDL-c) ratio and outcomes in acute ischemic stroke (AIS) patients is still mixed. Therefore, the present study was undertaken to explore the link between the TG/HDL-c ratio and unfavorable outcomes in patients with AIS. Methods This was a second analysis based on a cohort study. The study population was 1764 patients with AIS collected from January 2010 to December 2016 at a hospital in South Korea. We used a binary logistic regression model to assess the linear association between the TG/HDL-c ratio and unfavorable outcomes for AIS patients. A generalized additive model (GAM) and smooth curve fitting (penalized spline method) was conducted to explore the nonlinear relationship between TG/HDL-c ratio and unfavorable outcomes for AIS patients. Additionally, we compute the inflection point using a recursive algorithm and then build a two-piece binary logistic regression model on both sides of the inflection point. A log-likelihood ratio test was used to determine the most appropriate model describing the association of TG/HDL-c ratio and unfavorable outcomes in patients with AIS. Results The incidence rate of unfavorable outcomes was 28.2%, and the median TG/HDL-c ratio was 2.130. After adjusting covariates, the results of the binary logistic regression model suggested that the relationship between the TG/HDL-c ratio and the risk of unfavorable outcomes for AIS patients was not statistically significant. However, there was a nonlinear relationship between them, and the inflection point of the TG/HDL-c ratio was 3.515. On the left side of the inflection point, each 1-unit increase in the TG/HDL-c ratio was associated with a 22.6% lower risk of unfavorable outcomes (OR = 0.774, 95%CI:0.656 to 0.914, p = 0.002). On the right side of the inflection point, the effect size (OR) was 1.195 (95%CI:1.004 to1.423, p = 0.003). Conclusion There is a nonlinear relationship and threshold effect between the TG/HDL-c ratio and 3-month unfavorable outcomes in AIS patients. When the TG/HDL-c ratio is lower than 3.515, the TG/HDL-c ratio is significantly negatively related to the risk of unfavorable outcomes. When the TG/HDL-c ratio is greater than 3.515, the TG/HDL-c ratio was positively associated with the risk of unfavorable outcomes in AIS patients. This provides a reference for optimizing lipidemia intervention and promoting clinical communication in patients with AIS.
Design of the self-reported outcomes scoring in the multiple N-of-1 trials of every individual patient
Background Parkinson’s disease (PD) is a neurodegenerative disease, for which no disease-modifying therapies exist. Preclinical and clinical evidence suggest that hypoxia-based therapy might have short- and long-term benefits in PD. We present the contours of the first study to assess the safety, feasibility and physiological and symptomatic impact of hypoxia-based therapy in individuals with PD. Methods/Design In 20 individuals with PD, we will investigate the safety, tolerability and short-term symptomatic efficacy of continuous and intermittent hypoxia using individual, double-blind, randomized placebo-controlled N-of-1 trials. This design allows for dose finding and for including more individualized outcomes, as each individual serves as its own control. A wide range of exploratory outcomes is deployed, including the Movement Disorders Society Unified Parkinson’s Disease Rating scale (MDS-UPDRS) part III, Timed Up & Go Test, Mini Balance Evaluation Systems (MiniBES) test and wrist accelerometry. Also, self-reported impression of overall symptoms, motor and non-motor symptoms and urge to take dopaminergic medication will be assessed on a 10-point Likert scale. As part of a hypothesis-generating part of the study, we also deploy several exploratory outcomes to probe possible underlying mechanisms of action, including cortisol, erythropoietin and platelet-derived growth factor β. Efficacy will be assessed primarily by a Bayesian analysis. Discussion This evaluation of hypoxia therapy could provide insight in novel pathways that may be pursued for PD treatment. This trial also serves as a proof of concept for deploying an N-of-1 design and for including individualized outcomes in PD research, as a basis for personalized treatment approaches. Trial registration Identifier: NCT05214287 (registered January 28, 2022).
Diagram of the amyotrophic lateral sclerosis patients with edaravone treatment
Serial changes in total amyotrophic lateral sclerosis Functional Rating Scale (ALSFRS)-R score during edaravone treatment in 16 patients. Based on the time point from ALS diagnosis, the first mark indicates ALSFRS-R score at the baseline of edaravone treatment; the second mark indicates the score at 24 weeks; the third mark indicates the score at 48 weeks; and the fourth mark indicates the score at 72 weeks. The circle indicates an evaluation that was conducted for 72 weeks, the diamond indicates 48 weeks, the triangle indicates 24 weeks, and the X mark indicates the patient died
The mean amyotrophic lateral sclerosis Functional Rating Scale ALSFRS-R scores at each time point during edaravone treatment. The baseline score is the mean (standard deviation) ALSFRS-R for 16 patients, the score at week 24 is the score for 15 patients, the score at week 48 is the score for 11 patients, and the score at week 72 is the score for 11 patients
Changes in amyotrophic lateral sclerosis Functional Rating Scale-R scores at each interval
Background Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease characterized by the gradual loss of upper and lower motor neurons that leads to progressive muscle atrophy and weakness. Edaravone, a free-radical scavenger, was approved as an ALS treatment in 2015 in South Korea. Methods This study investigated the long-term effects and safety of edaravone by reviewing the medical records of 16 Korean patients with ALS who received extended edaravone between 2015 and 2021 in a single tertiary ALS center. Results Among sixteen patients, eleven patients underwent extended edaravone therapy for more than 18 cycles (72 weeks). The mean monthly changes in the revised ALS Functional Rating Scale (ALSFRS-R) were − 0.96 ± 0.83 (0–24 weeks), − 0.70 ± 0.76 (24–48 weeks), − 1.18 ± 1.67 (48–72 weeks), and − 0.81 ± 0.60 (0–72 weeks). The mean decline in forced vital capacity (FVC) was 17.4 ± 24.1. The changes were significant in both ALSFRS-R ( p < 0.001) and FVC ( p = 0.048); however, the mean change in compound muscle action potential of phrenic nerves was not. Patients experienced only minor adverse events, which were well tolerated. Conclusions This study verifies previous reported outcomes of edaravone in 16 Korean ALS patients, indicating a modest effect with a favorable safety profile.
Background: Lumbar puncture (LP) is a common and relatively safe neurological procedure. It can be complicated by post-dural puncture headache (PDPH) after both diagnostic and therapeutic procedures. The aim of this study is to identify the incidence, risk factors and clinical characterization of PDPH in the inpatient setting of the main tertiary neurology hospital in Kuwait. Methods: We conducted a prospective observational cohort study that included patients who were admitted to neurology department at Ibn Sina hospital, Kuwait, from January 1, 2019 to December 31, 2020, on whom, LP was performed for diagnostic and/or therapeutic reasons. Multivariate logistic regression analysis was performed to evaluate the association between PDPH and different clinical parameters. Results: A total of 285 patients were included; 225 females (78.9%), mean age of 32.9 ± 11.7 years. PDPH was reported by 84 patients (29.5%), with mean headache onset of 1.7 ± 0.8 days, and mean duration of 2.4 ± 2.1 days. The commonest headache type was dull aching in 49 patients (58.3%). Headache severity was mild to moderate in 64 patients (76.2%), with mean NRS of 4.1 ± 0.9. Most PDPH (99.3%) resolved with conservative medical management, with only 2 patients (0.7%) requiring epidural blood patch. In multivariate logistic regression model, there was a statistically significant correlation between development of PDPH and young age (p = 0.001), female gender (p = 0 .001), low BMI (p < 0 .001), pre-LP headache (p = 0.001), history of previous PDPH (p = 0.001), and number of LP attempts (p < 0.001). PDPH was statistically significantly higher in patients with optic neuritis (p = 0.009), and cerebral venous thrombosis (p = 0.007), and lower in patients with peripheral neuropathy (p = 0.011) and spinal muscular atrophy (p = 0.042). Conclusions: Findings from clinical practice in the main tertiary neurology hospital in Kuwait were in line with literature findings. Younger age, female gender, lower BMI, pre-procedural headache, previous history of PDPH, and number of LP attempts were found to be independent risk factors for developing PDPH. To our knowledge, this study represents the first comprehensive description of PDPH in a population from the Arabian Gulf Region.
A A right frontal parasagittal meningioma, middle front vein injury during operation. B A small amount of hematoma in the operative area one day after operation. C Massive hemorrhage around the operative area and disturbance of consciousness two day after operation. D Cleared hematoma and removed the bone flap, GOS was 5 score one month after operation. E-G A left parietal falx meningioma, post front vein injury during operation. H Bleeding around the operative area one day after operation, right side muscle strength level 2. I Cleared hematoma GOS was 5 score one month after operation
A CT showed intratumoral calcification. B Peritumoral edema was obvious. C-D The tumor invaded the skull. E MRV showed peritumoral vein accompanying (yellow and red arrows). F During the operation, the tumor was completely removed, peritumoral vein remained intact (yellow and red arrows), and the tumor invaded the pia mater and brain tissue (blue arrows). G Pathology showed atypical meningioma; H A small amount of hematoma in the operative area one day after operation, sober with right side muscle strength level 5. I Drowsiness with right side muscle strength level 3 three day after operation. J Lethargy with right side muscle strength level 1 five day after operation. K Drowsiness with right side muscle strength level 3 ten day after operation. L Sober with right side muscle strength level 4 fifteen day after operation. M Right side muscle strength level 4 one month after operation. N-O Right side muscle strength level 5 three month after operation
Patient and tumor characteristics
Risk factors related to the venous infarction after meningioma resection
Background Cerebral venous infarction (CVI) is a serious complication after meningioma resection. The risk factors of postoperative cerebral venous infarction after surgical resection of meningioma can be determined through large samples and this study can add evidence to the literature. Methods The clinical and imaging data of 1127 patients with intracranial meningiomas who underwent resection in our hospital were retrospectively collected and analyzed. CVI was evaluated by postoperative imaging and clinical manifestations. Univariate and multivariate analyses were performed to identify risk factors associated with CVI. Results Overall, 4.7% (53/1127) of patients experienced CVI after meningioma resection. Multivariate analysis revealed superficial meningioma, moderate to severe peritumoral edema, peritumoral critical vein and WHO grade II-III as independent predictors of a postoperative CVI. After timely intervention, the symptoms were clearly alleviated in one month, and the prognosis was good, but injury to key veins could cause irreversible neurological disorders. Conclusions Intraoperative protection of veins is the primary way to prevent CVI. The present study identified several significant and independent risk factors for postoperative venous infarction, thereby enabling the identification of high-risk patients who require special attention during clinical and surgical management.
Background Leber Hereditary Optic Neuropathy (LHON) is a rare, maternally-inherited mitochondrial disease that primarily affects retinal ganglion cells (RGCs) and their axons in the optic nerve, leading to irreversible, bilateral severe vision loss. Lenadogene nolparvovec gene therapy was developed as a treatment for patients with vision loss from LHON caused by the most prevalent m.11778G > A mitochondrial DNA point mutation in the MT-ND4 gene. Lenadogene nolparvovec is a replication-defective recombinant adeno-associated virus vector 2 serotype 2 (AAV2/2), encoding the human wild-type MT-ND4 protein. Lenadogene nolparvovec was administered by intravitreal injection (IVT) in LHON patients harboring the m.11778G > A ND4 mutation in a clinical development program including one phase 1/2 study (REVEAL), three phase 3 pivotal studies (REVERSE, RESCUE, REFLECT), and one long-term follow-up study (RESTORE, the follow-up of REVERSE and RESCUE patients). Case presentation A 67-year-old woman with MT-ND4 LHON, included in the REVERSE clinical study, received a unilateral IVT of lenadogene nolparvovec in the right eye and a sham injection in the left eye in May 2016, 11.4 months and 8.8 months after vision loss in her right and left eyes, respectively. The patient had a normal brain magnetic resonance imaging with contrast at the time of diagnosis of LHON. Two years after treatment administration, BCVA had improved in both eyes. The product was well tolerated with mild and resolutive anterior chamber inflammation in the treated eye. In May 2019, the patient was diagnosed with a right temporal lobe glioblastoma, IDH-wildtype, World Health Organization grade 4, based on histological analysis of a tumor excision. The brain tumor was assessed for the presence of vector DNA by using a sensitive validated qPCR assay targeting the ND4 sequence of the vector. Conclusion ND4 DNA was not detected (below 15.625 copies/μg of genomic DNA) in DNA extracted from the brain tumor, while a housekeeping gene DNA was detected at high levels. Taken together, this data shows the absence of detection of lenadogene nolparvovec in a brain tumor (glioblastoma) of a treated patient in the REVERSE clinical trial 3 years after gene therapy administration, supporting the long-term favorable safety of lenadogene nolparvovec.
Acute right T-ICA occlusion at ophthalmic tract (with arrow in a and b). Neuronmax 088 guide catheter is advanced as distal as possible in the proximal cavernous tract of right ICA (white arrow in c and d), and tip of JET 7 thromboaspiration device is advanced to contact and incorporate the long clot, reaching the middle cerebral artery (black arrow in c and d). After one attempt with ADAPT technique, eTICI 3 was obtained. Please note Neuronmax-induced mechanical vasospasm and reduction of ICA caliber after recanalization (white arrow in e)
Demographic and clinical baseline data
Background To describe technical features and initial results of a novel large-bore reperfusion catheter as first thromboaspiration approach for endovascular stroke treatment in terminal internal carotid artery (T-ICA) occlusions. Methods All patients treated with A Direct Aspiration first-Pass Technique (ADAPT) using JET 7 “Standard Tip” Penumbra Reperfusion catheter for acute T-ICA occlusion were retrospectively included in the study. Baseline data, puncture to recanalization time, number of attempts, switch to second device/technique rate and successful recanalization rate were assessed. Successful recanalization was defined by a thrombolysis in cerebral infarction (TICI) score ≥ 2b and favorable functional outcome was defined according to modified Rankin scale (score, 0–2). Catheter specifics and thromboaspiration reperfusion technique with JET 7 were reported. Results A total of 21 patients who underwent ADAPT with JET 7 Reperfusion catheter were enrolled for the final analysis. ADAPT was performed as first approach in all cases (100%). First attempt successful recanalization (eTICI ≥2b) was obtained in 90,5% of cases. Mean puncture to recanalization time was 16 minutes. Final successful recanalization was reached in 96.5%. Functional independence at 90 was achieved in 57,1% cases. Symptomatic intracranial hemorrhage occurred in one patient within 24 h. Conclusion The large-bore JET 7 reperfusion catheter could be considered as first-line in patients with acute T-ICA occlusion, allowing rapid recanalization and low rate of rescue therapy with stent retriver. Further series and/or trial evaluation are required to confirm our results.
Observed outcome rates: CAN score and PREVENT score
Comparison of the CAN Score versus PREVENT Score
PREVENT risk models for each outcome
Comparison of unadjusted outcomes by risk deciles for the validation sample
Background Risk-stratification tools that have been developed to identify transient ischemic attack (TIA) patients at risk of recurrent vascular events typically include factors which are not readily available in electronic health record systems. Our objective was to evaluate two TIA risk stratification approaches using electronic health record data. Methods Patients with TIA who were cared for in Department of Veterans Affairs hospitals (October 2015—September 2018) were included. The six outcomes were mortality, recurrent ischemic stroke, and the combined endpoint of stroke or death at 90-days and 1-year post-index TIA event. The cohort was split into development and validation samples. We examined the risk stratification of two scores constructed using electronic health record data. The Clinical Assessment Needs (CAN) score is a validated measure of risk of hospitalization or death. The PREVENT score was developed specifically for TIA risk stratification. Results A total of N = 5250 TIA patients were included in the derivation sample and N = 4248 in the validation sample. The PREVENT score had higher c-statistics than the CAN score across all outcomes in both samples. Within the validation sample the c-statistics for the PREVENT score were: 0.847 for 90-day mortality, 0.814 for 1-year mortality, 0.665 for 90-day stroke, and 0.653 for 1-year stroke, 0.699 for 90-day stroke or death, and 0.744 for 1-year stroke or death. The PREVENT score classified patients into categories with extreme nadir and zenith outcome rates. The observed 1-year mortality rate among validation patients was 7.1%; the PREVENT score lowest decile of patients had 0% mortality and the highest decile group had 30.4% mortality. Conclusions The PREVENT score had strong c-statistics for the mortality outcomes and classified patients into distinct risk categories. Learning healthcare systems could implement TIA risk stratification tools within electronic health records to support ongoing quality improvement. Registration Identifier: NCT02769338 .
Background To compare the effectiveness of dimethyl fumarate (DMF) with subcutaneous interferon beta-1a (IFNβ-1a) in controlling disease activity in patients with relapsing–remitting Multiple Sclerosis (MS). Methods Clinical and imaging data from patients treated with either IFNβ-1a or DMF for at least one year were reviewed. The proportion of patients with at least one clinical relapse within 3–15 months after treatment onset, the proportion of patients with new T2 or gadolinium-enhancing lesions, and the proportion of subjects who achieved no evidence of disease activity (NEDA) status were assessed. Results Three hundred sixteen (98 on IFNβ-1a, 218 on DMF) subjects were included. Baseline demographics were comparable between groups except for age, disease duration, and the number of previous treatments being higher and relapse rate in the prior year being lower in the DMF-treated group. The proportion of patients having a clinical relapse (24.5% vs. 9.6%; OR = 3.04; P < 0.001) or a new MRI lesion (28.6% vs. 8.7%; OR = 4.19, P < 0.001) at 15 months were higher on IFNβ-1a. 79.9% of the patients achieved NEDA status at 15 months on DMF (vs. 51.1% for IFNβ-1a; OR = 0.26, P < 0.001). Further adjustment for demographics, disease characteristics, treatment and relapse history, and subgroup analyses confirmed these findings. Conclusion DMF was associated with less clinical and radiological disease activity compared to IFNβ-1a.
A brief description of the progress of the patient. Note that CSF IL-6 (light blue bar graph) level is temporally correlated with the daily seizure frequency (line graph). SARS-CoV-2 PCR cycle threshold values for each gene (E, RdRP, N) are marked as square, triangle, and cross. Serum CRP level is shown in rhombus with connecting lines and was maintained below 1 mg/dl throughout the treatment period. CLB, clobazam; CRP, C-reactive protein; CSF, cerebrospinal fluid; IL-6, interleukin-6; IV, intravenous; IVIG, intravenous immunoglobulin G; LCM, lacosamide; LEV, levetiracetam; LMWH, low molecular weight heparin; OXC, oxcarbazepine; PCR, polymerase chain reaction; PER, perampanel; PGB, pregabalin
A-C are magnetic resonance imaging findings along the treatment period. A shows fluid-attenuated inversion recovery images at presentation, 7th day, and 15th day, from left to right. Note that high signal intensities involving bilateral insula intensify over time. B shows diffusion-weighted imaging at presentation, 7th day, and 15th day, from left to right. The red circle indicates the evolution of ischemic stroke lesion in the right frontal lobe, which developed on the 7th day and normalized on the 15th day. A and B show different aging stages of each lesion, supporting that the newly developed focal diffusion restriction in B is more likely due to an ischemic nature. C shows arterial spin labeling signals at presentation and two months after seizure resolution, from top to bottom. Note that the focal increase in bilateral insula, suggestive of ictal perfusion increase, is resolved. D shows the electroencephalogram findings of the patient. High amplitude polymorphic delta activities from the right frontotemporal area evolving to generalized 1-2 Hz spike-wave discharges were noted. The blue arrow indicates seizure onset from the right frontal and anterior temporal region. E is a chest computed tomography (CT) finding at presentation, which shows patchy ground-glass opacities in the right upper lung field, suggestive of COVID-19 pneumonia. F is a follow-up chest CT on day 10. Previously seen COVID-19 pneumonia is completely cleared
Background Neurological manifestations of COVID-19 are thought to be associated with the disease severity of COVID-19 and poor clinical outcomes. Dysregulated immune responses are considered to be mediating such complications. Our case illustrates multiple critical neurological complications simultaneously developed in a patient with non-severe COVID-19 and successful recovery with a multifaceted therapeutic approach. The cerebrospinal fluid (CSF) interleukin-6 (IL-6) level was temporally correlated with the clinical severity of the status epilepticus in our patient, suggesting a causal relationship. Case presentation A previously healthy 20-year-old female patient presented with a first-onset seizure. Concomitant non-severe COVID-19 pneumonia was diagnosed. CSF study showed lymphocytic pleocytosis with elevated IL-6 levels in CSF. During hospitalization under the diagnosis of autoimmune encephalitis, status epilepticus developed, and the seizure frequency was temporally correlated with the CSF IL-6 level. Furthermore, a new embolic stroke developed without a significant cardioembolic source. Contrary to the exacerbated COVID-19-associated neurological complications, COVID-19 pneumonia was cleared entirely. After treatment with antiseizure medications, antithrombotics, antiviral agents, and immunotherapy, the patient was discharged with near-complete recovery. Conclusion Active serological, and radiological evaluation can be helpful even in non-severe COVID-19, and multidimensional treatment strategies, including immunotherapy, can successfully reverse the neurological complication.
Substantia nigra pars compacta dopaminergic neuron density in relation to height, weight, age and brain weight. There were no sex differences in patient SNc neuron density over the whole sample (p = 0.25). A Height in patients with LBDs (open circles) and healthy controls (solid circles) in relation to neuron density (n = 55, r = 0.402, p = 0.002). B Age in relation to neuron density in patients with LBDs (open circles) and healthy controls (solid circles) (nonsignificant). C Linear (r = 0.563, p < 0.0001) and quadratic (r = 0.592, p = 0.001) relationships between height and neuron density in patients with LBDs (n = 36). Two individual patients are pointed out and correspond to nigral sections in Panels G and H. D Nonsignificant correlation between age and neuron density in patients. E Nonsignificant correlation between brain weight and neuron density in patients. F Nonsignificant correlation between weight and neuron density in patients. G A representative section of TH staining in the SNc of a PD patient with short stature (height 155 cm, female, age at death = 76 years, HY stage 5, symptom duration 18 years). Note the faint staining intensity indicating fewer neuromelanin containing dopaminergic neurons compared to the nigral section in Panel H. H A representative section of TH staining in the SNc of a PD patient with tall stature (height 180 cm, male, age at death = 74 years, HY stage 5, symptom duration 14 years). Note the stronger staining intensity compared to Panel G
Background The dopaminergic system modulates growth hormone secretion and previous results have suggested a link between short stature and an increased risk of Parkinson’s disease (PD). Methods In 36 Lewy body spectrum disease (LBD) cases (PD = 22) and 19 controls, nigral TH-positive neuron densities were measured postmortem from midbrain sections and corrected with the Abercrombie method. Body measurements were collected from autopsies or patient records. Our aim was to investigate the possible relationship between height and the density of neurons in the substantia nigra pars compacta (SNc). Results SNc neuron density (n/mm ² ) had an inverse association with height, (R ² = 0.317, p < 0.0001) in patients. The association was not explained by weight, age, sex, brain weight, medication, or disease motor severity. The association was also separately observed in patients with PD ( n = 22), but not in subjects who died without diagnosed neurological diseases. Conclusions Individual adult height may be connected to nigral neuron numbers in patients with LBDs, including PD.
Small ruptured aneurysms with a high modified Fisher grade due to widespread, thick haemorrhage in the expanded subarachnoid space caused by obvious brain atrophy
Treatment, complications and prognosis of elderly patients with intracranial aneurysms
Background Although the characteristics of intracranial aneurysms (IAs) in different age groups have been well documented, they remain relatively unclear in elderly patients due to a lack of large sample studies. Methods Data from IA patients aged more than 70 years who were treated in our centre from January 2016 to January 2020 were retrospectively collected. Results A total of 290 elderly patients (75.9% female) with a mean age of 74.0 ± 4.7 years were analysed. Rupture occurred in 60.7% of patients, 38.6% of whom presented with meningeal irritation, and seizures were noted in 2.3%. A total of 48.9% of the patients with ruptured IAs had initial symptoms presenting with slow development, and the mean delay from ictus was prolonged to 264.2 ± 914.0 hours. In addition, 61.9% of the patients with ruptured IAs had lesions with a maximum diameter of less than 5 mm. A total of 30.3% of the patients had multiple aneurysms, 35.5% had aneurysms with irregular shapes and 54.8% had cerebrovascular atherosclerotic stenosis (CAS). Pulmonary infection ( n = 138, 47.6%), hydrocephalus ( n = 72, 24.8%), and thrombosis ( n = 35, 12.1%) were common complications during hospitalization. By the end of the 1-year follow-up, 22.1% of the patients had unfavourable clinical outcomes, and the mortality rate was 23.4%. Conclusions Several characteristics regarding IAs in elderly patients were reported, including an obvious female predominance; mild, slow initial symptom development causing prolonged admission delay; a low incidence of meningeal irritation and seizures due to decreased electrophysiological activity of the neurons; increased percentages of CAS, multiple aneurysms, and aneurysms with daughter sacs causing a high risk of rupture even for small lesions; a high risk of complications during hospitalization; and relatively poor clinical outcomes.
Study Design and Procedures. Patients received LEV during a perioperative period of nine days. Levetiracetam plasma levels were measured two days after onset of LEV administration and three days postoperative. Hematotoxicity was measured through blood samples one week after surgery. Neuropsychological assessment (NeuroCogFX), including HRQoL questionnaire (QOLIE-31) and self-reported side effects, was conducted at four timepoints: one day before administration of levetiracetam (Baseline/no LEV), on the second day after onset of levetiracetam administration (Pre-Op/with LEV), four to six days after surgery (Post-Op/with LEV) and three weeks after surgery (Follow-Up/no LEV). The total study duration was 25 days
Flow chart of patient inclusion and dropouts. Inclusion criteria comprised seizure-naive, adult patients (> 18 years) with a suspected primary supratentorial brain tumor and a planned surgery. Exclusion criteria included contraindication against LEV and pre-existing anticonvulsive medication
(A) Estimated marginal means and corresponding standard error bars in standard value points across the four timepoints for the cognitive domain scores and Total score. Neuropsychological assessment of cognitive functioning was measured at four timepoints (Fig. 1). Total Score consists of the following domains: attention, working memory, memory and language. Which subtests constitute domains, see methods section. (B) Estimated marginal mean differences and corresponding 95%, Bonferroni adjusted confidence intervals of standard value points for cognitive domain scores and Total score between Pre-Op and Baseline testing. Cognitive functioning at Baseline (no levetiracetam) was measured one day before administration of levetiracetam and at Pre-Op (with levetiracetam) on the third day after onset of levetiracetam administration. Vertical dotted line represents the clinically meaningful deterioration margin. Bonferroni adjustment was made for six pairwise comparisons. Total Score consists of the domain attention, working memory, memory, and language. Which subtests constitute domains, see methods section
Introduction In seizure-naive brain tumor patients, the efficacy of perioperative prophylactic antiepileptic drug treatment remains controversial. In case of administration, the common preferred drug is levetiracetam (LEV) because of its favorable pharmacological profile. Research to date has not sufficiently determined how LEV affects cognition in the short term, as is the case in the perioperative period. The objective of this prospective study was to examine the neurocognitive functioning of seizure-naive brain tumor patients after receiving LEV perioperatively. Methods Fortythree patients with supratentorial brain tumor scheduled for surgery received LEV three days before until six days after surgery as seizure prophylaxis. Cognitive functioning (NeuroCogFX), LEV plasma-levels, hematotoxicity, side-effects, as well as health-related quality of life (HRQoL, Qolie31), were recorded preoperatively before (Baseline) and after onset of LEV (Pre-Op), 4–6 days postoperatively (Post-Op) and 21 days postoperatively (Follow-Up). Results No significant changes in cognitive functioning and HRQoL were seen after onset of preoperative LEV. There was a significant improvement of NeuroCogFX total-score at Follow-Up ( p = 0.004) compared to Baseline. The overall-score Qolie31 showed simultaneous improvement patterns as cognitive functioning ( p < 0.001). The most frequent side effect related to study drug was somnolence (in 28.6% of patients). Conclusions A significant improvement of cognitive functioning, as well as an improvement in HRQoL, were detected postoperatively. This is presumably due to the debulking effect of the surgery. Nevertheless, LEV has no detrimental effect on cognitive functioning in the perioperative phase in seizure-naive brain tumor patients. Trial registration This study was registered prospectively (Date: 25/11/2015; EudraCT: 2015–003,916-19).
MIDAS headache days* across 2 years: A mean headache days ± standard error, and B mean change ± standard error in headache days. MIDAS, Migraine Disability Assessment. *Number of headache days occurring over 3-month (12-week) periods over the course of the trial
MIDAS pain severity* over 2 years: A mean pain severity score ± standard error, and B mean change in pain severity score ± standard error. MIDAS, Migraine Disability Assessment. *Pain severity graded on 0‒10 scale
Change from baseline in MIDAS item scores measuring absenteeism* and presenteeism† over 2 years. MIDAS, Migraine Disability Assessment. *Absenteeism comprises the average of Items 1, 3, and 5. Item 1: missed work/school; Item 3: no household work; Item 5: missed family/social/leisure activities. The average at baseline was 9.7 †Presenteeism comprises the average of Items 2 and 4. Item 2: work/school productivity ≤ half; Item 4: household productivity ≤ half. The average at baseline was 14.2
MIDAS total score ± standard error at baseline, Week 12, Week 84, and Week 104: A total safety population and subgroup with very severe MIDAS disability*, and B patients with < 50%, 50‒74%, or ≥ 75% HRR at Week 12. HRR, headache responder rate assessed by MIDAS; MIDAS, Migraine Disability Assessment. *Level of disability based on MIDAS total score: little or no disability (0–5), mild disability (6–10), moderate disability (11–20), severe disability (21–40), very severe disability (41–270)
Background Eptinezumab is an anti-calcitonin gene-related peptide humanized monoclonal antibody approved for the preventive treatment of migraine in adults. The PREVAIL study demonstrated a favorable safety profile with sustained reductions in overall migraine-related burden in patients with chronic migraine (CM). This post hoc analysis aimed to examine item-level changes in the Migraine Disability Assessment (MIDAS) questionnaire over 2 years in participants with CM on eptinezumab treatment. Methods PREVAIL was an open-label, phase 3 trial that included 96 weeks of treatment where 128 adults received intravenous eptinezumab administered over 30 min every 12 weeks (wks) for up to 8 doses of 300 mg. MIDAS was administered at baseline, Wk12, and every 12wks thereafter. Two supplementary MIDAS items not included in the total score calculation assessed number of headache days in the past 3 months (MIDAS headache) and average headache pain severity (from 0 [none] to 10 [worst]). MIDAS total scores were summed from 5 items, each quantifying the number of days in the past 3 months with migraine-related disability. Items 1, 3, and 5 assessed absenteeism, namely how many days the patient missed work/school (Q1), household work (Q3), or family/social/leisure activities (Q5). Items 2 and 4 were measures of presenteeism, namely how many days the patient had reduced productivity in work/school (Q2) or household work (Q4). Results Mean MIDAS headache days decreased from 47.4 (baseline) to 17.1 (Wk12) and 16.3 (Wk104). The average headache pain severity score (0‒10) decreased from a mean of 7.3 (baseline) to 5.5 (Wk12) to 4.5 (Wk104). Mean MIDAS scores measuring absenteeism (Q1, 3, 5) changed from 9.7 days at baseline to 3.2 days (Wk12) and to 3.9 days (Wk104). Mean MIDAS scores measuring presenteeism (Q2, 4) at Wk12 decreased from 14.2 days at baseline to 5.2 days (Wk12, 104). Patients categorized with very severe MIDAS disability had a mean total MIDAS score of 84.8, with an average reduction of 56.7 days (Wk12), which was maintained at 32 days at Wk104. Conclusions Long-term treatment with eptinezumab in patients with CM suggested sustained reductions in MIDAS-quantified disability, consistent with the sustained reductions in headache frequency and pain severity. Trial registration identifier: NCT02985398 .
Flowchart of the screening and enrollment of the study participants. AIS, acute ischemic stroke; ALP, alkaline phosphatase; mRS, modified Rankin Scale; eGFR, estimated glomerular filtration rate; Q, quintiles
The fitted curve showing the relationship between serum ALP level and poor 3-month prognosis in AIS patients with preserved renal function. The solid and dashed lines indicate adjusted odds ratios and the 95% confidence interval bands, respectively. Histogram represents the kernel density distribution of ALP. ALP, alkaline phosphatase
Background In recent years, alkaline phosphatase (ALP) has been considered as one of the independent risk factors of acute ischemic stroke (AIS) and leads to worse clinical outcomes in patients with renal failure. In this study, we aim to investigate whether serum ALP level is associated with poor early-term prognosis in relationship of AIS patients with preserved renal function. Methods A prospectively collected database of AIS patients hospitalized in the Xi’an district of China from January to December, 2015 was analyzed. The demographics, serum ALP levels and stroke outcomes of all patients at 3 months were reviewed. Patients were routinely followed-up for 3 months. Serum ALP level was analyzed as a continuous variable and quintiles (Q1-Q5). Multivariate logistic regression model and a two-piecewise linear regression model were used to investigate the relationship and to determine the threshold effect regarding serum ALP levels and poor 3-month prognosis of AIS patients with preserved renal function. Results Overall, 1922 AIS patients were enrolled with 62.3% of them being men. The risk of having a poor 3-month prognosis was significantly increased in Q1, Q2, Q3 and Q5, when compared to that in Q4 being as the reference. The highest risk was noted in Q5 (odds ratio 2.21, 95% confidence interval: 1.32–3.73, P = 0.003) after being adjusted for confounders. Further analysis revealed a J-shaped curvilinear relationship between ALP levels and a poor 3-month prognosis of strokes (optimal threshold ALP level = 90 U/L). The relationship between both parameters was not significantly affected by age, sex, drinking, hypertension and leukocyte count (stratified by 10 × 10⁹/L) (P for interaction > 0.05). Conclusions Serum ALP was noted as an independent risk factor for a poor 3-month prognosis of AIS patients with preserved renal function. ALP levels higher than 90 U/L could cause an increased risk of a poor 3-month prognosis.
(A-F): A The initial plain CT scan on December 12 showed a cerebral contusion and laceration in bilateral frontal lobes and an intracerebral haematoma in left frontal lobe; B Plain CT scan on December 23 showed high-density thrombosis in the left transverse sinus; C Plain CT scan on December 23 revealed thrombosis in the sinus confluence and straight sinus, cerebral parenchymal infarction in the left parieto-occipital lobe, swelling of the left hemisphere, and compression of the left ventricle; D CT venography of December 23 showed absence of flow-related enhancement in the superior sagittal sinus, confluence of sinuses, and bilateral transverse sinuses, suggesting venous sinus thrombosis with open peripheral collateral vessels. E Plain CT scan on December 29 showed progression of the low-density lesion of the left parietotemporal occipital lobes and obvious brain swelling. F MRI on January 24 showed a patchy infarct lesion in the left parietal lobe and improvement of the surrounding brain swelling. The white solid arrows show the lesions
FT3 and FT4 gradually decreased with the implementation of the antihyperthyroidism treatment during the course of CVST. FT3/FT4 units: pmol/L (FT3 NR: 3.1 ~ 6.8, FT4 NR: 12 ~ 22); TSH units: mIU/L (NR: 0.27 ~ 4.2)
The fluctuation of plasma D-dimer and anti-Xa activity. Plasma D-dimer reached the highest point on December 23, which was the most serious moment of the disease. With the implementation of anticoagulation on December 23, the anti-Xa activity fluctuated with an increasing trend, while D-dimer gradually decreased, and the anticoagulant effect was ultimately achieved. D-dimer units: mg/L (NR: 0 ~ 0.55); anti-Xa activity units: U/ml (effective range: 0.4 ~ 1.0)
A-C Reexamination of MRI half a year after discharge: A Recanalization of the superior sagittal sinus, straight sinus, sinus confluence, and a small thrombus was still visible near the sinus confluence; B Good enhancement was seen in the sinus confluence and bilateral transverse sinuses, and some residual thrombus could be seen in the initial segments of the bilateral transverse sinuses; C MRI showed a focal lesion of encephalomalacia with gliosis in the left parieto-occipital lobes. The white solid arrows show the lesions
Introduction Cerebral venous sinus thrombosis (CVST) is an uncommon cerebrovascular disease with diverse predisposing factors. We report a case of CVST caused by a thyroid storm induced by traumatic brain injury. Case presentation A 29-year-old male patient with a history of Graves’ disease with hyperthyroidism presented to our hospital with head trauma of cerebral contusion and laceration in both frontal lobes confirmed by admission CT scan. He received mannitol to lower intracranial pressure, haemostatic therapy, and antiepileptic treatment. Eight days later, he presented with signs of thyroid storms, such as tachycardia, hyperthermia, sweating and irritation, and his thyroid function tests revealed high levels of TPO-Ab, TR-Ab, TG-Ab, FT3 and FT4. Then, he entered a deep coma. His brain CT showed a thrombosis of multiple venous sinuses, along with the opening of peripheral collateral vessels, congestive infarction with haemorrhage and brain swelling. He regained consciousness after treatment with antithyroid drugs, anticoagulants, respiratory support and a regimen of sedation/analgesia. After a half-year follow-up, most of the patient’s blocked cerebral venous sinuses had been recanalized, but there were still some sequelae, such as an impaired fine motor performance of the right hand and verbal expression defects. Conclusions CVST can be induced by thyroid storms, and trauma-related thyroid storms can develop on the basis of hyperthyroidism. The purpose of this case report is to raise clinicians’ awareness and improve their ability to diagnose CVST early in patients with traumatic brain injury complicating thyroid storms to improve the neurological prognosis among similar patients.
Schedule of study enrolment, interventions, and assessments. PROMPT: PROMPTs for Restructuring Oral Muscular Phonetic Targets. SC: standard care. VMPAC: Verbal Motor Production Assessment. ICS-ITA: Intelligibility in Context Scale. VSS: Viking Speech Scale. DDK: Diadochokinetic rate
Background Children with cerebral palsy (CP) often have communication impairments, including speech altered intelligibility. Multiple levels of disrupted speech have been reported in CP, which negatively impact on participation and quality of life, with increase of care needs. Augmentative Alternative Communication (AAC) is an option, with debated benefits and limitations, in particular for its functional use. This is supported by a substantial lack of defined evidences in favor of direct speech articulation intervention in CP. Motor learning-based interventions are effective in CP and are the basis of speech motor interventions such as PROMPT (Prompts for Restructuring Oral Muscular Phonetic Targets). The PROMPT speech motor treatment provides tactile-kinesthetic inputs to facilitate articulatory movements by dynamic modelling, resulting in more efficient motor patterns that can be integrated into speech and communication. In CP, exploratory evidences support the feasibility and preliminarily advantages on intelligibility of motor speech treatments, such as PROMPT, with increased speech motor control, also documented by kinematic analyses. Methods A randomized waitlist-control trial will be conducted in children aged between 3- and 10-years having CP and dysarthria (estimated sample size = 60 children). Children will be allocated in the immediate intervention or in the waitlist control group. The intervention consists of an intensive 3 weeks period of twice-a-day administration of PROMPT. Standard care will be administered in the control (waitlist) group. After repeated baseline assessments (T0), the PROMPT treated group will undergo the experimental 3-week intervention period, with T1 assessment at the end. A further T2 assessment will be provided at medium term (3 months after the end of the intervention) for evaluating the stability of intervention. Primary and secondary speech clinical and kinematics outcome measures will be collected at T0, T1 and T2. Discussion This paper describes the study protocol consisting of a RCT with two main objectives: (1) to evaluate the or short-term benefits of an intensive speech motor intervention on speech and intelligibility in children with CP and the stability of the intervention at medium term; (2) to describe the kinematic correlates of speech motor control modifications. Trial registration Trial registration date 06/12/2019; Identifier: NCT04189159.
Neuroimaging features of the patient. A-E Brain MRI performed before the administration of corticosteroids. A-C T2-FLAIR images demonstrate multiple hyperintense lesions at different levels, which mainly located in the basal ganglia, internal capsule, external capsule, periventricular, corona radiata, frontal and temporal lobes. D Conventional T2-weighted image shows multiple lesions with poorly defined boundaries in the bilateral basal ganglia. E Gadolinium-enhanced T1-weighted image shows multiple ring-shaped zones of peripheral contrast enhancement in the right basal ganglia and nodular contrast enhancement in the bilateral basal ganglia (white arrows). F-J Brain MRI performed on the day 54 after treatment with corticosteroids. F-H T2-FLAIR images show almost complete disappearance of previous lesions (I) Conventional T2-weighted image shows that lesions in the bilateral basal ganglia were significantly reduced. J Gadolinium-enhanced T1-weighted image shows most of the contrast-enhancing lesions disappeared. Note: MRI = magnetic resonance imaging; FLAIR = fluid-attenuated inversion recovery
Background Cryptococcal meningoencephalitis (CM) is a severe infection of central nervous system with high mortality and morbidity. Infection-related inflammatory syndrome is a rare complication of CM. Herein, we report a case of CM complicated by infection-related inflammatory syndrome. Case presentation A 42-year-old man with chronic hepatitis B presented with a 3-day history of aphasia and left hemiparesis at an outside medical facility. The brain magnetic resonance imaging (MRI) showed symmetric and confluent hyperintense signal abnormalities mainly located in the basal ganglia, internal capsule, external capsule, periventricular, corona radiata, frontal and temporal lobes. Cerebrospinal fluid (CSF) examinations revealed elevated leukocyte and protein. India ink staining was positive for Cryptococcus. CSF culture and metagenomic next-generation sequencing (mNGS) confirmed Cryptococcus neoformans. Initial response was observed with intravenous fluconazole (400 mg per day). However, 11 days later, he developed impaired consciousness and incontinence of urine and feces. A repeat brain MRI showed the lesions were progressive and enlarged. The patient was referred to our department at this point of time. Repeat CSF analysis (India ink staining, culture and mNGS) re-confirmed Cryptococcus. However, clinical worsening after initial improvement, laboratory examinations and brain MRI findings suggested a diagnosis of infection-related inflammatory syndrome. Therefore, a combination of corticosteroids and antifungal therapy was initiated. At follow-up, a complete neurological recovery without any relapse was documented. The repeat brain MRI showed complete resolution of the previous lesions. Conclusions This case demonstrated that cryptococcal inflammatory syndromes must be suspected in cases of CM if an otherwise unexplained clinical deterioration is observed after initial recovery. The same can happen even before the primary infection is controlled. Thus, timely identification and prompt treatment is vital to reduce the mortality and disability of CM. The administration of corticosteroids in combination with antifungal therapy is an effective strategy in such cases. Graphical abstract Clinical course and treatment process of the patient. Hemiparalysis and aphasia improved after the initiation of antifungal treatment. However, the patient developed impaired consciousness companied by deterioration of brain MRI findings. He was treated with adjunctive glucocorticoid taper therapy consisting of dexamethasone (20 mg/day, intravenously) for 1 week followed by oral prednisone 1 mg/kg/day, tapered based on clinical and radiological response, along with amphotericin B (0.6 mg/kg/day, intravenously), voriconazole (400 mg/day in 2 divided doses, intravenously), and 5-flucytosine (100 mg/kg/day in 4 divided doses, orally). Two weeks later, his symptoms improved significantly. After discharge, he began oral voriconazole for consolidation and maintenance therapy for 8 weeks and 9 months respectively. He recovered without any neurological sequelae at 6-month follow-up. Note: MRI = magnetic resonance imaging.
Top-cited authors
Steven Laureys
  • University of Liège
Caroline Schnakers
  • University of Liège
Audrey Vanhaudenhuyse
  • University Hospital of Liège, GIGA Consciousness, University of Liège, Belgium
Melanie Boly
  • University of Wisconsin–Madison
Steve Majerus
  • University of Liège