Therapeutic Advances in Neurological Disorders

Alzheimer's disease (AD) is an untreatable cause of dementia, and new therapeutic approaches are urgently needed. AD pathology is defined by extracellular amyloid plaques and intracellular neurofibrillary tangles. Research of the past decades has suggested that neuroinflammation plays a critical role in the pathophysiology of AD. This has led to the idea that anti-inflammatory treatments might be beneficial. Early studies investigated non-steroidal anti-inflammatory drugs (NSAIDS) such as indomethacin, celecoxib, ibuprofen, and naproxen, which had no benefit...

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and fatigability. The fluctuating nature of the disease course impedes the clinical management. OBJECTIVE: The purpose of the study was to establish and validate a machine learning (ML)-based model for predicting the short-term clinical outcome in MG patients with different antibody types. METHODS: We studied 890 MG patients who had regular follow-ups at 11 tertiary centers in China from 1 January 2015 to 31 July 2021 (653 patients for derivation and 237 for validation)...

BACKGROUND: Spinal muscular atrophy (SMA) results from a loss-of-function mutation in the SMN1 gene. SMA patients suffer progressive motor disability, although no intellectual impairments have been described. Three drugs have been recently approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). These drugs result in longer life expectancy for SMA type 1 (SMA1) patients. OBJECTIVE: The objective of the study was to assess longitudinally the psychomotor development of patients with SMA1 treated after the symptom onset and of patients treated presymptomatically...

BACKGROUND: Due to the absence of robust biomarkers, and the low sensitivity and specificity of routine imaging techniques, the differential diagnosis between Parkinson's disease (PD) and multiple system atrophy (MSA) is challenging. High-field magnetic resonance imaging (MRI) opened up new possibilities regarding the analysis of pathological alterations associated with neurodegenerative processes. Recently, we have shown that quantitative susceptibility mapping (QSM) enables visualization and quantification of two major histopathologic hallmarks observed in MSA: reduced myelin density and iron accumulation in the basal ganglia of a transgenic murine model of MSA...

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BACKGROUND: Pipeline embolization device (PED) is becoming increasingly common in therapeutic practice. In idealized model studies, treatment effectiveness may vary with different stent sizes in the same vasculature. The true effect of stent size selection in the clinical setting remains unknown, however. OBJECTIVE: To determine the true effect of stent size selection in the clinical setting. DESIGN: It is a retrospective review. METHODS: A retrospective review was conducted on consecutive patients with aneurysms treated with a PED at our institution...

BACKGROUND: Resourceful endpoints of axonal loss are needed to predict the course of multiple sclerosis (MS). Corneal confocal microscopy (CCM) can detect axonal loss in patients with clinically isolated syndrome and established MS, which relates to neurological disability. OBJECTIVE: To assess corneal axonal loss over time in relation to retinal atrophy, and neurological and radiological abnormalities in MS. METHODS: Patients with relapsing-remitting (RRMS) ( n  = 68) or secondary progressive MS (SPMS) ( n  = 15) underwent CCM and optical coherence tomography...

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a rare relapsing autoimmune disease of the central nervous system, affecting mainly optic nerves and spinal cord. NMOSD pathophysiology is associated with anti-aquaporin-4 (AQP4) immunoglobulin G (IgG) autoantibodies. Rapid extracorporeal elimination of autoantibodies with apheresis techniques, such as immunoadsorption (IA), was proven to be an effective treatment of NMOSD attacks. Data on the long-term use of IA to prevent attacks or progression of NMOSD are lacking...

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare and challenging demyelinating disorder. It is necessary to increase our understanding of potential connections between imaging, electromyography, and clinical characteristics. OBJECTIVE: The aim of this study was to evaluate the relationships between multisequence magnetic resonance neurography (MRN) findings, electrophysiological parameters, and clinical characteristics in CIDP patients...

BACKGROUND: Clinical and radiological signs of recurring disease activity (RDA) have been described in patients with multiple sclerosis (pwMS) after discontinuation of fingolimod (FGL). OBJECTIVE: To describe frequency, severity and potential risk factors for RDA after FGL discontinuation in a large real-world cohort of pwMS. METHODS: Post-FGL RDA was defined as evidence of clinical and/or radiological activity within 6 months after FGL discontinuation...

BACKGROUND: Whether low-dose alteplase is similar to standard-dose bridging alteplase prior to endovascular mechanical thrombectomy in patients with acute ischemic stroke (AIS) remains uncertain. AIMS: The aim of this study was to compare the efficacy and safety outcomes of low- versus standard-dose bridging alteplase therapy (BT) in patients with acute ischemic stroke (AIS) who are eligible for intravenous thrombolysis (IVT) within 4.5 h after onset. METHODS: We conducted an indirect comparison of low- versus standard-dose bridging alteplase before mechanical thrombectomy in AIS of current available clinical randomized controlled trials (RCTs) that compared direct mechanical thrombectomy treatment (dMT) to BT...

BACKGROUND: Natalizumab is a highly effective monoclonal antibody for the treatment of multiple sclerosis (MS), which can diffuse in different anatomical compartments, including cerebrospinal fluid (CSF) and milk. OBJECTIVES: Starting from incidental detection of natalizumab in the CSF of MS patients, the objective of this study was to develope a flow-cytometry-based assay and apply it to quantify natalizumab in body fluids, including milk collected from nursing patients over 180 days and in patients with neutralizing antibodies against natalizumab...

BACKGROUND: Plasma extracellular vesicle (EV) contents are promising biomarkers of Parkinson's disease (PD). The pathognomonic proteins of PD, including α-synuclein, tau, and β-amyloid, are altered in people with PD (PwP) and are associated with clinical presentation in previous cross-sectional studies. However, the dynamic changes in these plasma EV proteins in PwP and their correlation with clinical progression remain unclear. OBJECTIVE: We investigated the dynamic changes in plasma EV α-synuclein, tau, and β-amyloid and their correlation with/prediction of clinical progression in PwP...

BACKGROUND AND AIMS: Intravenous thrombolysis (IVT) is standard of care for disabling acute ischemic stroke (AIS) within a time window of ⩽ 4.5 h. Some AIS patients cannot be treated with IVT due to limiting contraindications, including heparin usage in an anticoagulating dose within the past 24 h or an elevated activated prothrombin time (aPTT) > 15 s. Protamine is a potent antidote to unfractionated heparin. OBJECTIVES: The objective of this study was to investigate the safety and efficacy of IVT in AIS patients after antagonization of unfractionated heparin with protamine...

BACKGROUND: There are limited data on the impact of myasthenia gravis (MG) on real-world healthcare resource use (HCRU) and patient burden in the United States. OBJECTIVES: This study aims to assess HCRU in patients with MG using data from a US health claims database. DESIGN: A retrospective, database study of adult patients newly diagnosed with MG, using the IBM® MarketScan® Commercial Claims and Encounters and Medicare supplemental health insurance claims database...

BACKGROUND: Adeno-associated virus (AAV) vectors are a promising platform for in vivo transfer of transgenes designed to treat diseases. Pre-existing humoral immunity to these vectors can potentially impact the safety and efficacy of gene therapies. Consequently, individuals with pre-existing antibodies to the specific AAV serotypes used may be excluded from clinical trials and treatments. Recombinant AAV serotype rh74 (rAAVrh74), a vector originally isolated from rhesus monkeys and potentially less immunogenic than other serotypes isolated from humans (e...

BACKGROUND: There is still no precise knowledge of the causes of progression in patients with acute ischemic stroke (AIS), and we are unable to predict patients at risk. OBJECTIVE: To explore the frequency, predictive factors, and the prognosis of early neurological deterioration (END) in patients with AIS. METHODS: In this prospective multicenter observational study, we assessed patients with AIS admitted to 18 hospitals in Henan, China. We defined END as an increase of ⩾2 points in total National Institutes of Health Stroke Scale (NIHSS) score or ⩾1 point in the motor items of the NIHSS within 7 days after admission...

Although the understanding of secondary progressive multiple sclerosis (SPMS) is evolving, early detection of relapse-independent progression remains difficult. This is further complicated by superimposed relapses and compensatory mechanisms that allow for silent progression. The term relapsing multiple sclerosis (RMS) subsumes relapsing-remitting multiple sclerosis (RRMS) and SPMS with relapses. The latter is termed 'active' SPMS, for which disease-modifying therapies (DMTs) approved for either RMS or active SPMS can be used...

BACKGROUND: Intraplaque neovascularisation (IPN) is a component of vulnerable atherosclerotic plaque, which is a biomarker of cardiovascular events. However, the identification of patients with high probability of ischaemic events after carotid artery stenting (CAS) is mainly based on vascular risk factors. Prospective studies on the development of plaques are lacking. OBJECTIVES: The purpose of this study was to investigate whether IPN detected by contrast-enhanced ultrasound is related to the occurrence of ischaemic events after CAS...

Despite advances in the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and other common autoimmune neuropathies (AN), still-many patients with these diseases do not respond satisfactorily to the available treatments. Repurposing of disease-modifying therapies (DMTs) from other autoimmune conditions, particularly multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), is a promising strategy that may accelerate the establishment of novel treatment choices for AN...