Cortical Lesions in the Primary Sensorimotor Hand Area and Their Impact on Dexterity in Multiple Sclerosis: a 7T MRI Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Number of cortical lesions in the primary sensorimotor cortex (SM1)
研究概览
简要总结
Multiple sclerosis (MS) is an autoimmune disease, leading to inflammation and degeneration of neurons in the entire central nervous system (CNS). Not only does MS attack CNS white matter, the wiring of the brain, but it also affects so called grey matter, involved in communication between brain cells. Some studies have shown that grey matter damage and lesions to the outermost layer of the brain, the cortex, might serve as a better diagnostic and prognostic tool for MS patients. The issue is that cortical lesions only to a limited extent can be visualized by conventional magnetic resonance imaging (MRI) at 3 tesla. The new generation of ultra-high field MR scanners with a field strength of 7 tesla, has a higher sensitivity towards detecting these cortical lesions. We therefore wish to use the improved sensitivity of ultra-high field MRI to improve detection of cortical lesions, and to elucidate the detrimental effects of single lesions to the cortex, thereby improving both diagnosis and prognosis of the disease.
By implementing newly developed ultra-high-resolution MR-sequences the amount and extent of cortical lesions to the area of the brain responsible of the sensory and motor function of the hand (sensorimotor hand area - SM1-HAND) will be investigated in patients with relapsing remitting and secondary progressive MS. We will also assess how these lesions affect manual dexterity and sensory function and how cortical lesions affect communication within brain areas. It is hypothesized that the amount and size of cortical lesions is highly involved in brain communication and manual function, a major problem in MS, and that this project will shed new light on how the disease damages this important brain area.
详细描述
BACKGROUND. In recent years, several lines of research have shown that multiple sclerosis (MS) affects cortical grey matter and that the degree of cortical grey matter involvement is associated with cognitive and physical disability, but the specific impact of a cortical lesion on regional function remains to be clarified.
High-field Magnetic Resonance Imaging (MRI) at 3T has been used to detect cortical lesions in MS, but histological examinations have shown that only 'the tip of the iceberg' is detected. Ultra-high field 7T MRI has a higher diagnostic sensitivity than 3T MRI. Although not every cortical lesion is detected even at 7T, a recent post-mortem verification study concluded that ultra-high field MRI "more than doubles detection of cortical MS lesions, compared to 3T MRI". Implementing 7T MRI in detection of cortical lesions and elucidating the behavioural and neurophysiological impact of cortical lesions is therefore a good candidate in aiding to resolve the clinico-radiological paradox reported in MS.
AIMS and HYPOTHESES. This study is designed to clarify the occurence of cortical lesions within the primary sensory-motor hand area (SM1-HAND) and their impact on manual motor and sensory function, as well as regional cortical connectivity. The SM1-HAND is well suited to address this question, because functional integration in SM1-HAND can be studied in detail with transcranial magnetic stimulation (TMS) and high-resolution fMRI.
Exploiting the increased sensitivity of 7T MRI to detect cortical lesions, the number, size and regional distribution of cortical lesions in SM1-HAND will be assessed and lesion load in SM1-HAND will be related to MRI-based, electrophysiological, and behavioral correlates of hand function.
Specifically the following parameters will be assessed:
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Expanded Disability Status Scale of < 7.5
- •Diagnosed with either relapsing-remitting or secondary progressive multiple sclerosis
- •No clinical relapse within last three months
- •Have the ability to comply with all requirements of the study protocol, as determined by the investigator
- •Healthy controls
- •Able bodied
- •Have the ability to comply with all requirements of the study protocol, as determined by the investigator
排除标准
- •Pregnancy
- •Pacemaker or other implanted electronic devices
- •Claustrophobia
- •Psychiatric disorder
- •Administration of acute cortisol
- •Changes in pharmacological treatment within the last 3 months
- •Close relatives suffering from epilepsy (only relevant for TMS)
- •Migraine (only relevant for TMS)
- •Any contraindication to TMS or MRI
- •Persons who do not wish to be informed about abnormal findings as part of the investigations
- •Healthy controls
- •Pregnancy
- •Under medication at the time of the experiment (with the exception of contraceptive drugs)
- •History of neurologic disease
- •Pacemaker or other implanted electronic devices
- •Close relatives suffering from epilepsy (only relevant for TMS)
- •Migraine (only relevant for TMS)
- •History of cerebral hemorrhage or brain damage
- •Claustrophobia
- •Psychiatric disorder
- •Any contraindication to TMS or MRI
结局指标
主要结局
Number of cortical lesions in the primary sensorimotor cortex (SM1)
时间窗: Data collected on day 1 and 2
Quantified as cortical lesion number on a unihemispheric level in patients with relapsing remitting and secondary progressive multiple sclerosis (RRMS \& SPMS) The extent of damage to the SM1 is unknown, but based on clinical symptoms of motor function we expect that up to 40% of patients show focal cortical lesions in this area. Additionally we wish to explore the relationship between cortical lesions in SM1 and other MRI metrics (e.g. white matter lesion load of the cortico-spinal tract, cortical myelination, cortical thickness, metabolite levels of SM1-HAND and diffusion metrics of the cortico-spinal tract)
Unimanual motor function
时间窗: Data acquired on day 1
A composite score computed as the mean of Z-scores from the health population (expected range +-4, lower being better motor performance) for unimanual performance in: 9-hole peg test (time in seconds, lower being better), Jebsen Taylor Hand Function Test (time in seconds, lower being better), Finger Tapping (mean times/10seconds from all 5 digits, higher being better). We hypothesize that unimanual motor function correlates negatively with the total cortical lesion load within the contralateral SM1-HAND area, independent of age, gender handedness, white matter lesion volume and axonal integrity of the cortico-spinal tract, central motor conduction time (CMCT) and cortical thickness of the primary sensorimotor cortex.
次要结局
- Motor fatigue(Assessed on day 1)
- Unimanual sensory acuity(Data acquired on day 1)
- Expanded Disability status scale (EDSS) score(Data collected on day 1)
- Functional brain activation pattern as revealed by task related blood oxygenation level dependent (BOLD) signal changes.(Data acquired on day 2)
- Regional NAA concentration of the SM1(Data acquired on day 2)
- Intra-cortical inhibition and facilitation (Exploratory outcome measure)(Data acquisition on day 3)
- Volume of cortical lesions in the primary sensorimotor cortex (SM1)(Data collected on day 1 and 2)
- Cortical lesion subtype (Exploratory outcome measure)(Data acquisition on day 1 and 2)