Магнитно-резонансно спектроскопски и невропсихологически характеристики на процеса на невродегенерация при пациенти с пристъпно-ремитентна множествена склероза // Magnetic resonance spectroscopic and neuropsychological characteristics of the neurodegeneration process in patients with relapsing-remitting multiple sclerosis
Зареждане...
Дата
2024
Автори
Петрова, Василена Георгиева // Petrova, Vasilena Georgieva
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Издател
Медицински университет - София // Medical University - Sofia
Резюме
ХИПОТЕЗА:
Нашата хипотеза е, че при пациенти с ПРМС със срок на заболяване до 10 години и степен на инвалидност EDSS до 3.5 е налице връзка между някои морфометрични промени – атрофия на хипокампа, метаболитните промени в области с нормално изглеждащо бяло мозъчно вещество (зони без плаки на демиелинизация) и невропсихологичното функциониране като прояви на функционална и анатомична дисконекция.
ЦЕЛ:
Да се оценят невродегенеративните промени при пациенти с пристъпно-ремитентна форма на множествена склероза с давност до 10 години от началото на болестта посредством 3-D Т1 МРТ хипокамп-волуметрия и се потърсят значими корелации с промените в обема на хипокампа, когнитивните функции и някои мозъчни метаболити, оценявани с МРТ спектроскопия.
Осъществяването на поставената цел налага изпълнението на следните ЗАДАЧИ:
1. Да се изследват промените в ляв хипокамп чрез 3-D T1 MRT хипокампална волуметрия при здрави контроли и болни с МС.
2. Да се измерят метаболитните маркери холин, N-ацетиласпартат и креатин в зони на NAWM (мозъчни области в бялото мозъчно вещество без лезии на демиелинизация) чрез Протонна Магнитнорезонансна Спектроскопия (ПрМРС).
3. Да се изследват промените в когнитивния статус при болни с ПРМС и давност на болестта до 10 години с помощта на батерия от психологични тестове, емоционалният статус и синдрома на умора при тези болни.
4. Да се потърсят полово-детерминирани разлики за изследваните параметри, както и корелации с давността на заболяването, и тежестта на инвалидност, оценена с EDSS скала при болни с МС.
5. Да се потърси корелация между обема на хипокампа, невропсихологичните тестове и метаболитните маркери, оценявани с ПрМРС, и да се сравнят получените резултати с тези от контролна група здрави индивиди в същата възрастова група.
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SUMMARY:
Multiple sclerosis is a chronic progressive autoimmune disease of the central nervous system with genetic predisposition. Environmental factors trigger immune response cascade with subsequent morphological changes in the white and gray matter. Magnetic resonance methods like proton magnetic resonance spectroscopy reveal specific tissue pathology within the plaques of demyelination. MRS gives the opportunity to assess metabolite brain tissue pattern within the normal appearing white matter. The method provides insight into metabolite behavior in the zones free of inflammation. Patients with multiple sclerosis develop neuropsychological deterioration years before detection of focal neurological deficit. Cognitive functioning is a substantial factor for quality of life. Progressive cognitive decline is specific for cognitive functioning in MS. So are the affective disorders. They might be the first signs of neurodegeneration.
The aim of this study was to evaluate neurodegenerative changes in relapsing-remitting multiple sclerosis patients with up to 10 years of disease duration through 3-D T1 MRT hippocamp volumetry. The second aim was to search for significant correlation between hippocampal volume, cognitive functioning, and brain metabolites, measured by magnetic resonance spectroscopy within the normal appearing white matter.
Materials and methods: 50 RRMS patients signed an informed consent and underwent neurological examination, blood testing and neuropsychological assessment with a battery of neuropsychological tests evaluating general cognitive functioning, working memory, visual-spatial memory, attention, information processing speed, depression, and fatigue. The results were compared to the findings in 28 healthy controls with matching demographic criteria. Both groups underwent conventional MRT imaging with subsequent 3-D T1 MRT hippocamp volumetry. MRS was applied for measuring brain metabolites Choline, Creatine and N-acetylaspartate in lesion free brain regions (NAWM).
Results and discussion: Data analysis revealed statistically significant reduction in hippocampal volume in RRMS patients in comparison with healthy controls. Gender determined significant difference was found. The female group of RRMS patients had statistically significant smaller hippocampal volume. Male RRMS patients demonstrated identical changes though without statistically significant difference. The findings stated an accompanying process of neurodegeneration.
The assessment of brain metabolite levels revealed elevated levels of Choline, Creatine and N-acetylaspartate in the RRMS group. N-acetylaspartate is a marker for neuronal integrity. The elevation is associated with axonal viability. Choline is a marker for membrane turnover. Thus, the results might be presumed to be an increase in membrane synthesis. The elevated Creatine levels supported this conclusion. The analysis of metabolite ratios in both groups showed a decrease in NAA/Cr ratio and increase in Cr/NAA ratio in MS group. Statistically significant difference was found for both variables in comparison to the control group. The finding might be interpreted as a marker for an increase both in energy utilization in MS patients and in energy demands. We found an increase in Cho/NAA, decrease in NAA/Cho and Cho/Cr ratios, though with no statistical difference between both groups. Metabolite changes and ratio changes demonstrated the presence of morphological damage in the normal appearing white matter. These changes might be assumed as an early indicator for energy and structural deterioration, which in return provoked neuron- neuron communication interference. Dementia is not a clearly defined condition in MS. Different clinical findings can present a state of dementia. Cortical lesions can cause aphasia, apraxia, agnosia thus presenting a state of dementia. Nevertheless, the term dementia is not used for marking the neurocognitive changes in MS because of the subtle manifestation and slower progression of symptoms. The clinical findings are defined as cognitive deterioration usually. The symptoms might present cortical type of dementia when they are associated with gray matter lesions. Subcortical type of dementia is observed more frequently, because of the disconnection syndrome caused by plaques of demyelination. Information processing speed is a domain of primary deficit, independent from the disease progression in MS. The assessment of neuropsychological changes in both groups revealed deterioration in cognitive functioning, information processing speed, attention, working memory, visual-spatial memory and affect. The subjects from the RRMS group had worse presentation in all the categories. The subjects had lower scores for both Paced Auditory Serial Addition Test (PASAT) and Symbol Digit Modalities Test (SDMT). Statistically significant difference was found for SDMT when compared to control group. SDMT is applied for evaluation of cognitive functioning in the context of visual-spatial information processing and working memory. Statistically significant worsening in SDMT presentation for male RRMS subjects was found. Hippocampal volume changes did not corelate to cognitive functioning deterioration assessed by PASAT and SDMT. Depression scores were higher in the RRMS group. Goldberg Depression Inventory detected changes in 40% of the subjects, while Beck’s Depression Inventory found changes in 28% of the subjects tested. Less than 10% of the MS patients demonstrated moderate to severe level of depression. According to both tests female subjects had higher scores in comparison to male. Most of them stated for having symptoms indicative of mild depression. Though gender did not determine depression severity. Fatigue scores were exponential for no presence of fatigue in both RRMS group and healthy control group. Significant to strong correlation was found between depression and fatigue in the RRMS group. Both variables were assessed by self-evaluating questionnaires (Goldberg DI and Fatigue Severity Scale). The data analysis of neuropsychological tests Goldberg DI, BDI, FSS and PASAT revealed no gender impact on cognitive functioning. Neither did the disease duration. EDSS had a negative impact on cognitive functioning. Weak inversely proportional relationship was found between disability, evaluated by EDSS and the hippocampal volume changes.
Описание
Ключови думи
неврология; нервна система; мултиплена склероза - диагностика; невродегенеративни болести; ядрено-магнитен резонанс; пристъпно-ремитентна мултиплена склероза; невропсихология // nervous system diseases; multiple sclerosis - diagnosis; neurodegenerative diseases; magnetic resonance imaging; relapsing-remitting multiple sclerosis; neurophysiology