The Brain Diffusion Tensor Imaging And Pathogenesis Of Cognitive Impairment In Multiple Sclerosis

Multiple sclerosis(MS) is a central nervous system inflammatory demyelinating disease, have various clinical manifestations, and is the common disease leading to neurological disability among young adult. Neuropsychological studies have shown that the cognitive impairment is common in MS patients. Overseas studies have reported that incidence of different clinical manifestations of cognitive dysfunction.is 40%-65%, 10% of patients have very serious clinic symptoms. Cognitive dysfunction is an important reason for MS patients leaving an job and seriously affects the life quality of patients , the treatment and prognosis of primary disease. In clinic work, we find that some MS patients have had cognitive impairment while no lesion being found in MRI imaging.MS is an autoimmune disease of central nervous system. The demyelination of nerve fibers is the main pathological basis and result to the white matter damage. Resolution of conventional MRI of the lesions is limited, less able to distinct the different pathological changes of MS, and are not well used to study cognitive function based on the pathological anatomy. DTI is the rapid development of MR technology on the base of the DWI. DTI is mainly used for observation of structural characteristics of white matter fiber. Recent studies suggest that MS patients have diffuse brain damage exiting the normal white matter,widespread gray matter and cortex. These parts of the brain tissue can be reltatively intact myelin, have normal appearance, but axonal injury has occurred. We call these occult lesions. It also can cause varying degrees of motor, sensory and cognitive dysfunction.. Currently , it is accepted that multiple sclerosis is a T lymphocyte mediated autoimmune disease. Multiple sclerosis is the result of abnormal function of self-induced immune tolerance due to regulatory T cell dysfunction. Regulatory T lymphocytes have a seris of phenotypic, and mainly regulate the immune function of peripheral functions and immune tolerance. Most of the regulatory T lymphocytes are CD4 subtype, and there are also part of CD8 subtype. CD4+CD25+T cells and CD8+CD28-T cells have been identified as function of the immune suppression and immune tolerance, and have been studied in a variety of disease model. In this study, we determined and compared the T-lymphocyte subsets of MS patients and normal controls, in order to further clarify the pathogenesis of cognitive dysfunction and find a new direction to clinical treatment.【Methods】The case group have 40 patients, male 10 and 30 female. They are hospitalized in our hospital neurology from 2008 to 2011 and aged 37土2.92 years. The control group have 40 disease-free immune system healthy, aged 35士1.08 years, age and sex match the case group. The 40 patients in the case group were clinically diagnosed MS patients. They all meet the diagnostic criteria of McDonald 2001 and all the patients had never used the immunosuppressive agents and corticosteroids. At 6 o'clock in the next morning of hospital, we collected peripheral venous blood of MS patients and control group. We detected the lymphocyte subsets ratio in the peripheral blood of the case group and the control group.In the first three days after admission, we assess the cognitive function of patients and assess them with EDSS score.We checked the MS patients of the case group within three days of hospitallization and the control group in MRI, DTI imaging.【Results】1. In the global cognitive function and other cognitive function, the test results showed that the VIQ, PIQ and FIQ test scores of the case group were lower than that of healthy control group, the difference was significant (P <0.05); It is no statistically significant difference that MMSE total score and the orientation, computing power, sense, spatial structure between the two group; the language and memory tests between the two groups was significant (P <0.05).2. Executive function test results: The CLOX result of MS patients was worse than that of the control group, the differences between the two groups was statistically significant ( P<0.05). In the Stroop test, the differences of the number of errors and the reaction between the two groups were statiscally significant( P <0.05).3. In the hippocampus and internal capsule, the brain ADC values of DTI in MS patients was larger than that of the healthy control group, the brain FA values of MS patients lower than that of the healthy control group. These differences were statistically significant ( P<0.05). In the corpus callosum and frontal lobe, the differences of ADC values and FA values in DTI imaging were no statiscally significant.4. The EDSS score of MS patients had a weak correlation with the brain lesion level, number of lesion, ADC value, the FA value. The CLOX, FIQ and Stroop2 test scores, had the most correlation with the ADC valus and the FA value. FIQ statistically associated with the number of lesions, and there were no other significant correlation.5. In peripheral blood, CD4~+CD25~+,CD8~+CD28~-T cells in the proportion of all of the T lymphocytes of MS group was significantly higher than that of the healthy control group, the difference was significant (P <0.05).6. The EDSS scores had a strong correlation with the proportion of CD4~+CD25~+,CD8~+CD28~-T cells in MS group. The test results of the global cognitive function of MS group had correlation with the proportion of CD4~+CD25~+,CD8~+CD28~-T cells.【Conclusions】1. There is a wide range of demyelinating lesions in multiple sclerosis, and there is also small lesions in NAWM and NAGM.2. The ADC values and FA values in DTI imaging of MS patients may reflect the extent of demyelinating injury and degree of executive dysfunction.3. T lymphocyte subsets changes in the number and function take part in the patho~- genesis of multiple sclerosis and the global cognitive dysfunction of MS.