Abstract:
:Background: Essential tremor (ET) is a common, progressive neurological syndrome with bilateral upper-limb dysfunction of at least 3-year duration, with or without tremor in other body locations. This disorder has a negative impact on daily function and quality of life. A single oral therapy has been approved by FDA for ET. Off-label pharmacotherapies have inadequate efficacy and poor tolerability with high rates of patient dissatisfaction and discontinuation. Safe and efficacious pharmacotherapies are urgently needed to decrease tremor and improve daily living. T-CALM (Tremor-CAv3 modulation) protocol is designed to assess safety and efficacy of CX-8998, a selective modulator of the T-type calcium channel, for ET therapy. Methods/Design: T-CALM is a phase 2, proof of concept, randomized, double-blind, placebo-controlled trial. Titrated doses of CX-8998 to 10 mg BID or placebo will be administered for 28 days to moderate to severe ET patients who are inadequately treated with existing therapies. The primary endpoint will be change from baseline to day 28 of The Essential Tremor Rating Assessment Performance Subscale (TETRAS-PS). Secondary efficacy endpoints for clinician and patient perception of daily function will include TETRAS Activity of Daily Living (ADL), Quality of Life in Essential Tremor Questionnaire (QUEST), Clinical Global Impression-Improvement (CGI-I), Patient Global Impression of Change (PGIC), and Goal Attainment Scale (GAS). Kinesia One, Kinesia 360, and iMotor will biometrically evaluate motor function and tremor amplitude. Safety will be assessed by adverse events, physical and neurological exams and laboratory tests. Sample size of 43 patients per group is estimated to have 90% power to detect a 5.5-point difference between CX-8998 and placebo for TETRAS-PS. Efficacy analyses will be performed with covariance (ANCOVA) and 2-sided test at 0.05 significance level. Discussion: T-CALM has a unique design with physician rating scales, patient-focused questionnaires and scales and objective motor measurements to assess clinically meaningful and congruent efficacy. Patient perception of ET debilitation and therapy with CX-8998 will be key findings. Overall goal of T-CALM is generation of safety and efficacy data to support a go, no-go decision to further develop CX-8998 for ET. Design of T-CALM may guide future clinical studies of ET pharmacotherapies. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03101241.
journal_name
Front Neuroljournal_title
Frontiers in neurologyauthors
Papapetropoulos S,Lee MS,Boyer S,Newbold EJdoi
10.3389/fneur.2019.00597subject
Has Abstractpub_date
2019-06-11 00:00:00pages
597issn
1664-2295journal_volume
10pub_type
杂志文章abstract::Disrupted sleep is more common in older adults (OLD) than younger adults (YOUNG), often co-morbid with other conditions. How these sleep disturbances affect cognitive performance is an area of active study. We examined whether brain activation during verbal encoding correlates with sleep quantity and quality the night...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2012.00049
更新日期:2012-04-03 00:00:00
abstract::Studies of traumatic brain injury from all causes have found evidence of chronic hypopituitarism, defined by deficient production of one or more pituitary hormones at least 1 year after injury, in 25-50% of cases. Most studies found the occurrence of posttraumatic hypopituitarism (PTHP) to be unrelated to injury sever...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2012.00011
更新日期:2012-02-07 00:00:00
abstract::Ischemic stroke is one of the leading causes for death and disability worldwide. In patients with large space-occupying infarction, the subsequent edema complicated by transtentorial herniation poses a lethal threat. Especially in patients with malignant middle cerebral artery infarction, brain swelling secondary to t...
journal_title:Frontiers in neurology
pub_type: 杂志文章,评审
doi:10.3389/fneur.2018.01119
更新日期:2019-01-09 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative condition, most widely characterized by the selective vulnerability of motor neurons and the poor life expectancy of afflicted patients. Limited disease-modifying therapies currently exist, which only further attests to the substantial heterogeneity...
journal_title:Frontiers in neurology
pub_type: 杂志文章,评审
doi:10.3389/fneur.2020.00377
更新日期:2020-05-27 00:00:00
abstract::Objective: To explore the clinical features and correlates of excessive daytime sleepiness (EDS) in a Chinese population of Parkinson's disease (PD) patients. Methods: Patients with clinically established or clinically probable PD were recruited. Clinical and demographic data were collected, and participants were eval...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2019.00121
更新日期:2019-02-19 00:00:00
abstract::Background: This study's aim was to investigate a large cohort of dystonia patients for pathogenic and rare variants in the ATM gene, making use of a new, cost-efficient enrichment technology for NGS-based screening. Methods: Single molecule Molecular Inversion Probes (smMIPs) were used for targeted enrichment and seq...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2019.01332
更新日期:2019-12-18 00:00:00
abstract::Light impinging on the retina fulfils a dual function: it serves for vision and it is required for proper entrainment of the endogenous circadian timing system to the 24-h day, thus influencing behaviors that promote health and optimal quality of life but are independent of image formation. The circadian pacemaker loc...
journal_title:Frontiers in neurology
pub_type: 杂志文章,评审
doi:10.3389/fneur.2017.00541
更新日期:2017-10-20 00:00:00
abstract::X-linked adrenoleukodystrophy (X-ALD) is a rare neurological disorder with a highly complex clinical presentation. Adrenal function, spinal cord, peripheral nerves, and cerebral white matter are commonly affected in adult-onset male patients. Here, we report a family with unusual presentation of X-ALD. The 19-year-old...
journal_title:Frontiers in neurology
pub_type:
doi:10.3389/fneur.2018.00271
更新日期:2018-04-23 00:00:00
abstract::Localization of the epileptogenic zone (EZ) is crucial in the surgical treatment of focal epilepsy. Recently, EEG studies have revealed that the EZ exhibits abnormal connectivity, which has led investigators to now consider connectivity as a biomarker to localize the EZ. Further, abnormal connectivity of the EZ may pr...
journal_title:Frontiers in neurology
pub_type: 杂志文章,评审
doi:10.3389/fneur.2020.569699
更新日期:2020-11-25 00:00:00
abstract::Hemorrhagic cerebrovascular disease in the pediatric population can have devastating and long-term effects. Progress in the fields of genetics, neuroimaging, pharmacology, and surgical techniques has led to improved diagnosis and management of pediatric cerebrovascular diseases. In this review we discuss the current e...
journal_title:Frontiers in neurology
pub_type: 杂志文章,评审
doi:10.3389/fneur.2020.01055
更新日期:2020-09-17 00:00:00
abstract::Previous consensus statements on sports concussion have highlighted the importance of Attention Deficit Hyperactivity Disorder (ADHD) and loss of consciousness (LOC) as risk factors related to concussion management. The present study investigated how self-reported history of either ADHD diagnosis or history of previou...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2019.00396
更新日期:2019-04-24 00:00:00
abstract::Background and Aim: Reliable, valid and sensitive measures of dual-task-associated impairments in patients with Parkinson's disease (PD) may reveal progressive deficits unnoticed under single-task walking. The aim of this study was to quantitatively identify markers of progressive gait deficits in idiopathic PD while ...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2019.00372
更新日期:2019-05-14 00:00:00
abstract::Maternal smoking is a risk factor for both sudden infant death syndrome (SIDS) and sudden intrauterine unexplained death syndrome (SIUDS). Both SIDS and SIUDS are more frequently observed in infants of smoking mothers. The global prevalence of smoking during pregnancy is 1.7% and up to 8.1% of women in Europe smoke du...
journal_title:Frontiers in neurology
pub_type: 杂志文章,评审
doi:10.3389/fneur.2020.586068
更新日期:2020-10-23 00:00:00
abstract::The cingulate island sign (CIS) on fludeoxyglucose (FDG)-positron emission tomography (PET) is a supporting biomarker of dementia with Lewy bodies (DLB). Its diagnostic accuracy has only been investigated in FDG-PET, however. The present prospective study compared the CIS on I-iodoamphetamine-single photon emission co...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2020.568438
更新日期:2020-11-19 00:00:00
abstract::Single time point positron emission tomography (PET) studies of patients with amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD), have demonstrated hypometabolism or hypermetabolism in certain brain regions. To determine whether longitudinal (at baseline and 20.4 months later) PET and magnetic resonan...
journal_title:Frontiers in neurology
pub_type:
doi:10.3389/fneur.2019.00234
更新日期:2019-03-19 00:00:00
abstract::The relaxation rates and contractile properties of inspiratory muscles are altered with inspiratory muscle weakness and fatigue. This fact plays an important role in neuromuscular disorders patients and had never been extensively studied in amyotrophic lateral sclerosis (ALS). In this cross-sectional study, these para...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2018.00306
更新日期:2018-05-02 00:00:00
abstract::Despite the advent of and exciting advances in novel endovascular therapies, t-PA remains the only proven treatment for acute ischemic stroke to date. Although a variety of reasons likely underlie why past trials of endovascular strategies have been unsuccessful, we address in this perspective piece one critical unkno...
journal_title:Frontiers in neurology
pub_type: 杂志文章,评审
doi:10.3389/fneur.2013.00164
更新日期:2013-10-21 00:00:00
abstract::Guillain-Barré syndrome (GBS) is mainly associated with preceding exposure to an infectious agent, although the precise pathogenic mechanisms and causes remain unknown. Increasing evidence indicates an association between trauma-related factors and GBS. Here, we performed a systematic review, summarized the current sc...
journal_title:Frontiers in neurology
pub_type:
doi:10.3389/fneur.2020.588290
更新日期:2020-11-06 00:00:00
abstract::This study reports the case of an acoustic shock injury (ASI), which did not result in a significant hearing loss, but was followed by manifold chronic symptoms both within (tinnitus, otalgia, tingling in the ear, tension in the ear, and red tympanum) and outside the ears (blocked nose, pain in the neck/temporal regio...
journal_title:Frontiers in neurology
pub_type:
doi:10.3389/fneur.2017.00420
更新日期:2017-08-16 00:00:00
abstract::Background and objective: The trajectories of long-term and domain-specific cognitive alterations over a decade after stroke are largely unknown. This study aims to investigate the dynamic alterations of domain-specific cognitive performance among young stroke survivors over 10 years after their first stroke. Methods:...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2019.00097
更新日期:2019-02-12 00:00:00
abstract::Importance: Coronavirus disease 2019 (COVID-19) is a newly emerging infectious disease that has caused a global pandemic. The presenting symptoms are mainly respiratory symptom, yet studies have reported nervous system involvement in the disease. A systematic review and meta-analysis of these studies are required to u...
journal_title:Frontiers in neurology
pub_type:
doi:10.3389/fneur.2020.00565
更新日期:2020-05-29 00:00:00
abstract:UNLABELLED:Management of West syndrome is unsatisfactory. In our clinic we observed that a significant proportion of patients respond to usual dose of valproate. OBJECTIVE:To prospectively assess the efficacy of valproate in controlling infantile spasms in West syndrome. METHODS:Consecutive patients presenting with W...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2012.00166
更新日期:2012-11-23 00:00:00
abstract::A decrease in glutamate in the medial prefrontal cortex (mPFC) has been extensively found in animal models of chronic pain. Given that the mPFC is implicated in emotional appraisal, cognition and extinction of fear, could a potential decrease in glutamate be associated with increased pessimistic thinking, fear and wor...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2019.01110
更新日期:2019-12-03 00:00:00
abstract::We describe three patients diagnosed with bilateral vestibular dysfunction associated with the jet propellant type-eight (JP-8) fuel exposure. Chronic exposure to aromatic and aliphatic hydrocarbons, which are the main constituents of JP-8 military aircraft jet fuel, occurred over 3-5 years' duration while working on ...
journal_title:Frontiers in neurology
pub_type:
doi:10.3389/fneur.2018.00351
更新日期:2018-05-16 00:00:00
abstract::Perinatal hypoxic-ischemic encephalopathy (HIE) can lead to neurodevelopmental disorders, including cerebral palsy. Standard care for neonatal HIE includes therapeutic hypothermia, which provides partial neuroprotection; magnetic resonance imaging (MRI) is often used to assess injury and predict outcome after HIE. Imm...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2018.00304
更新日期:2018-05-08 00:00:00
abstract::Background: Pediatric migraine is among the most common primary or comorbid neurologic disorders in children. Psychological stressors are widely acknowledged as potential triggers involved in recurring episodes of pediatric migraine. As the COVID-19 emergency may have affected the levels of stress perceived by childre...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2020.579047
更新日期:2020-10-08 00:00:00
abstract:AIMS:To construct and validate a short scale for the assessment of the severity of visual height intolerance (vHI) and acrophobia. METHODS:The questionnaire was developed from two earlier representative epidemiological studies (n = 5,529). Items were applied in a telephone survey of a representative population-based s...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2017.00211
更新日期:2017-06-01 00:00:00
abstract::Patients with epilepsy and treated with antiepileptic drugs (AEDs) may develop metabolic bone disease; however, the exact pathogenesis of bone loss with AEDs is still unclear. Included were 75 adults with epilepsy (mean age: 31.90 ± 5.62 years; duration of treatment with AEDs: 10.57 ± 3.55 years) and 40 matched health...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2014.00142
更新日期:2014-08-04 00:00:00
abstract::Introduction: Eslicarbazepine acetate (ESL) is an antiepileptic drug approved as monotherapy or add-on for the treatment of epilepsy with seizures of focal onset. ESL owns a good profile in terms of efficacy and tolerability, but its effects on EEG activity and connectivity are unknown. The purpose of this study was t...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2018.01054
更新日期:2018-12-11 00:00:00
abstract::The persistent primitive hypoglossal artery (PPHA) is the second most common persistent carotid-vertebrobasilar anastomosis, with an incidence of 0.027-0.26%. PPHAs change the hemodynamics of the carotid and vertebrobasilar system and may be associated with intracranial vascular anomalies, but basilar bifurcation aneu...
journal_title:Frontiers in neurology
pub_type:
doi:10.3389/fneur.2017.00168
更新日期:2017-04-26 00:00:00