Cerebrovascular Changes in Multiple Sclerosis Patients
关键词
抽象
描述
Multiple sclerosis (MS) MS is a chronic disease containing the inflammatory, demyelinating, anddegenerative processes of the central nervous system[FrischerJMet al, 2009]. The inflammation, microglial activation, astrocyticgliosis, demyelination, and somewhat axonal loss inwhite matter and grey matter was present in the brainsof the patients with MS [Wegner C et al, 2006]. Moreover, MS patientspresented a reduction in the cerebral blood flow (CBF)affecting both grey and white matter in positronemission tomography (PET) studies [Sun X et al, 1998].
MS is the most common autoimmune disorder of the central nervous system[Berer K et al,2014]. As of 2010, the number of people with MS was 2-2.5 million (approximately 30 per 100,000) globally, with rates varying widely in different regions. [Milo R et al ,2010] MS affects approximately 1000000 people between 17 and 65 years old world wide, the projected prevalence rate of MS for the white US population was 191 per 1000000 and the incidence rate was 7.3 per 1000000 persons [Mayr WTet al, 2003]. Another study of prevalence of Multiple Sclerosis in Egypt in age group >17years in a population number 21774 was about 13.74 per 100000 [El-Tallawy HNet al, 2013].
The contribution of neurodegenerative processes in the disease pathogenesis has been increasingly recognized, especially with respect to possible mechanisms of progression. These may include axonal degeneration, mitochondrial injury, energy failure, hypoxia, oxidative damage, iron accumulation or global cerebral hypoperfusion [Mahad DH et al, 2015, D'haeseleer M et al, 2015]. Interestingly, Cerebral vasomotor reactivity (CVMR) in MS may be impaired as well.
Although the cause of CVMR impairment in MS is not clear, several potential factors mightcontribute to this phenomenon.
For the purpose of clarity,we divide them into (1) vascular factors, (2) glial factors, and (3) neuronal factors:
1. Vascular factor
Blood-brain barrier (BBB) disruption might be anotherfactor contributing to CVMR impairment in neurodegenerative disorders [Alvarez JI, et al, 2013]. CVMR impairment could also be caused by an increase inthe concentration of vasoconstrictive agents. For instance,endothelin-1 (ET-1) - a potent vasoconstrictor, is overexpressed in the cerebral vessels of MS and elevated in both serumand cerebrospinal fluid of patients with MS [Haufschild T, et al,2001, D'haeseleer M, et al,2013].
2. Glial factors
Reactive astrocytes, i.e. hypertrophied astrocytes that overexpress GFAP (glial fibrillary acidic protein) have been described in virtually all CNS disorders including MS [Ben Haim L, et al, 2015]. they could also contribute to CVMR impairment through the production of ET-1 and possibly other vasoconstrictors Another way in which glial cells could contribute to the impairment of CVMR might be associated with their involvement in oxidative stress pathways [Haider L et al, 2011]. Glial pathology may also cause BBB dysfunction [Alvarez JI, et al, 2013].
3. Neuronal factors
It has been shown that cholinergic projections originating from the nucleus basalis induce cerebral vasodilation directly through the release of acetylcholine and indirectly through the stimulation of NO-releasing interneurons [Hamel E. et al, 2006] there is evidence of a cholinergic deficit in MS [Kooi E-J, et al, 2011].
From a clinical point of view, reduced white and gray matter CBF in patients with MS has thus far been associated with cognitive manifestations [-Inglese M, et al, 2008, D'Haeseleer M et al, 2013].
Cognitive impairment occurs in 40 to 65% of patients with MS and can have a considerable impact on occupational and social life [Amato MP, et al, 2001]. also reduced deep gray matter perfusion in MS negatively correlated with fatigue [Vucic S, et al, 2010].
Cerebrovascular reactivity (CVR) is an inherent indicator of the dilatory capacity of cerebral arterioles for a vasomotor stimulus for maintaining a spontaneous and instant increase of CBF) in response to neural activation. The integrity of this mechanism is essential to preserving healthy neurovascular coupling. Transcranial Doppler ultrasound (TCD) is defined as a non-invasive ultrasound procedure to evaluate the changes in cerebral blood flow velocity (CBFV) [Powers J et al,2009]. The high temporal resolution and non-invasive nature of TCD make it a useful tool in the assessment of integrative cerebrovascular function in terms of cerebral reactivity, autoregulation and neurovascular coupling (NVC).
日期
最后验证: | 06/30/2020 |
首次提交: | 10/14/2018 |
提交的预估入学人数: | 10/15/2018 |
首次发布: | 10/16/2018 |
上次提交的更新: | 07/23/2020 |
最近更新发布: | 07/26/2020 |
实际学习开始日期: | 09/30/2020 |
预计主要完成日期: | 11/30/2020 |
预计完成日期: | 12/30/2021 |
状况或疾病
干预/治疗
Radiation: mri
相
手臂组
臂 | 干预/治疗 |
---|---|
1st group 30 patients were diagnosed with MS according to revised MacDonald's criteria 2017 & collected from Neuropsychiatry department in Assuit university hospital | |
2nd group 30 healthy volunteers subjects matched with age, sex & education level were recruited from outpatient clinic neuropsychiatry department and included only if they had no current or previous history of any neurological illness and their neurological examination was free |
资格标准
有资格学习的年龄 | 18 Years 至 18 Years |
有资格学习的性别 | All |
取样方式 | Non-Probability Sample |
接受健康志愿者 | 是 |
标准 | Inclusion Criteria: 1. Patients diagnosed with MS or diagnosis of CIS highly suggestive of MS according to revised McDonald's criteria 2010. 2. MS patients aged (18-60 years) of both sexes. 3. EDSS score (1-7). Exclusion Criteria: 1. History or current evidence of CNS diseases other than MS which may affect brain volume &cognition e.g. (Dementia prior to MS, parkinsonism, other inflammatory CNS diseases). 2. History or current evidence of medical illness as endocrinal or metabolic which may affect cognitive function e.g. (hepatic, renal impairment or hypothyrodism). 3. History or current intake of any drug that may affect cognitive function e.g (Antiepileptic, antipsychotic…). 4. History or current evidence of depression (according to DSM -5- criteria &Hamilton depression scale) or any psychiatric disorder. |
结果
主要结果指标
1. evaluate cerebrovascular changes in patients with MS byTCD, which is an easy applicable and non-invasivebedside technique [1 year]