This study is based on the T1 sequence of MR, using Freesurfer software to automatically outline the cortex and nucleus volume of the brain area of interest, by comparing the volume changes between WD and healthy controls, and analyzing the correlation between the volume changes and clinical data , To observe the volume changes of specific areas in the brain of WD patients, and analyze the correlation between the volume changes of different parts and clinical manifestations.
In WD patients, a large amount of copper accumulates in the central nervous system, which can cause nerve cell damage and necrosis in the brain. Through anatomy of 2 WD death cases,Mikol was found that There are different degrees of necrosis and atrophy between gray and white matter and basal ganglia in the brain of WD, and the degree of necrosis on both sides is asymmetric; Many imaging methods have proved that the caudate nucleus and putamen are the most significant areas of copper-induced cell damage in WD patients .In our study, it was also observed that the volume of WD in the bilateral caudate nucleus, putamen, globus pallidus, thalamus, corpus callosum, brainstem, hippocampus, amygdala, and nucleus accumbens was significantly smaller than that of HC. According to the calculation formula of atrophy rate, the areas with the most obvious volume reduction are putamen, caudate nucleus, globus pallidus, and nucleus accumbens, which are consistent with the previous results. In previous studies on WD, everyone paid little attention to the nucleus accumbens area. In this study, we found that the nucleus accumbens is the most significant area of volume reduction after the globus pallidus, and the nucleus accumbens is located at the head of the caudate nucleus. 95% of its neurons are gamma-aminobutyric acid (GABA) projection neurons. Previous studies have found that the nucleus accumbens is associated with the effects of happiness, reward, motivation, reinforcement learning, fear, addiction, impulse, and placebo. When liver function is impaired, the liver's ability to clear GABA decreases, and excessive GABA can cause damage to the nucleus accumbens, which is consistent with the pathogenic mechanism of WD. After neurological WD suffers from liver function damage, the ability to process GABA is reduced, causing excessive GABA in the brain, resulting in damage to the nucleus accumbens. In the onset of many patients with WD, it is often accompanied by various mental symptoms and emotional problems. The relationship between these and the nucleus accumbens is worthy of our in-depth study.
By analyzing the correlation between different parts of the brain and the Hamilton depression scale and MMSE, it was found that the anterior part of the corpus callosum and bilateral thalamus were negatively correlated with the Hamilton depression scale, and the putamen, caudate, and nucleus accumbens volumes were negatively correlated with the MMSE score. In the past, with regard to the changes in the thalamus and putamen of WD patients, more attention has been paid to the effects of muscle tone, movement, executive function, articulation and Parkinson’s symptoms. In our study, We get that the depression score of WD patients is related to the volume of the thalamus. The smaller the volume of the thalamus, the more severe the depression of WD, This is consistent with the results of the coenen study . He has confirmed that the thalamus plays a vital role in arousal function, and is important in emotion and reward processing and the development of depression, and that the thalamus is associated with the amygdala, prefrontal cortex, parietal cortex, and medial temporal lobe. Connected, so it’s no surprise that the thalamus is involved in various emotional and cognitive functions as well as reward-based functions . Dichter et al. also reported thalamus abnormalities in patients with depression. And When shen studied the cognition of patients with Parkinson's disease, she found that the putamen is related to cognitive function. Previous studies have suggested that WD patients rarely affect the corpus callosum, Zhou et al. have used DTI to prove that WD patients have deep fiber bundle damage , The corpus callosum is a fiber bundle plate made up of fibers that connect the left and right cerebral hemispheres. We suspect that patients with WD may have a decrease in the corpus callosum fiber bundles, which will cause a decrease in volume. By subdividing the corpus callosum into five regions, and After a correlation analysis of clinical symptoms, we found that the Hamilton depression scale score was negatively correlated with the anterior volume of the corpus callosum, combined with DTI imaging on the study of corpus callosum fiber bundles, The anterior part of the corpus callosum is mainly assigned to the prefrontal lobe, anterior motor and auxiliary motor cortex areas, and the frontal lobe is related to emotion and cognition. These all support our results. It also reminds us that WD patients should pay more attention to the changes of the corpus callosum.
By analyzing the correlation between the different parts of the brain area and the modified Young scale, it was found that the left caudate nucleus volume was negatively correlated with the modified young total score, the ataxia score was negatively correlated with the left globus pallidus volume, and the gait score was negatively correlated with the left side. The volume of the caudate nucleus is negatively correlated. The above results indicate that with the severe atrophy of the caudate nucleus, the higher the modified YOUNG scale score, the more severe the patient's neurological symptoms. The more severe the atrophy of the left globus pallidus, the more it may affect the patient's mutual aid movement. The smaller the left caudate nucleus, the more difficult it is for the patient to walk independently. The selective deposition of copper in different parts of the brain in WD patients can cause a variety of clinical symptoms.
Ceruloplasmin (Cp) is a protein in human serum. It contains 95% serum copper , copper metabolism disorder will aggravate the production of ceruloplasmin-free, thus losing the ability to oxidize Fe 2+ to Fe 3+, Fe 2+ will produce harmful oxygen free radicals, causing cell damage, ceruloplasmin genes can be expressed in the liver, brain, lung, spleen and testis, mainly involved in iron metabolism. In this experiment, we found that the serum ceruloplasmin value is negatively correlated with the left globus pallidus, bilateral amygdala, bilateral nucleus accumbens, and the anterior volume of the corpus callosum. This result may be meaningless, because WD patients There is not much difference between the ceruloplasmin.
In this study, there is no correlation between the course of the disease and the volume of the region of interest, which is a common clinical phenomenon. The disease of WD is relatively rare, with various onset modes and hidden onset. It is easy to be misdiagnosed in clinical work. The severity of the patient's condition and the rate of progress vary, and the severity is related to genetic types and environmental factors, so it is not simply Affected by the course of the disease.
Combined with the modified YOUNG scale, the patients were subdivided into type 4 (dyskinesia, Parkinson's symptom, oroma-mandibular dystonia, mental disorder). We found that the main difference between type 1 and type 2 lies in the right In the lateral globus pallidus, the volume of the globus pallidus in patients with dyskinesia-type WD is significantly smaller than that of patients with Parkinson's symptomatic WD. At 1561.35 on the right globus pallidus, the two types of WD can be best distinguished. Types 1 and 3 patients have significant differences in the brainstem, bilateral hippocampus, and left amygdala. The dyskinesia type is significantly smaller than the oro-mandibular dystonia type in the above-mentioned difference area, and it has 4143.50 in the right hippocampus. Best discrimination. Type 2 and type 3 patients have significant differences in bilateral thalamus, bilateral hippocampus, brainstem, and left amygdala. The Parkinson’s symptom type is significantly smaller than the oral-mandibular dystonia type in the above-mentioned difference area, and it is in the left thalamus. 6513.10 has the best discrimination. Compared with the oral-mandibular dystonia, the mental disorder has a smaller volume in the right hippocampus, and has the best discrimination at 3,99.90 in the right hippocampus. Based on the above results, we can see the globus pallidus, brainstem, and hippocampus. Volume changes can cause dyskinesias and Parkinson-like symptoms in patients, and changes in hippocampal volume are related to patients' mental symptoms.
In this study, starting from the nucleus in the basal ganglia of WD patients, the local study of the nucleus volume change and the clinical correlation, we have the following conclusions: (1) The thickness of the cerebral cortex and nucleus volume of WD patients are generally reduced compared with normal controls; (2) The degree of regional volume reduction may be related to clinical manifestations; however, the overall changes in cortex and white matter may be ignored in this experiment. Zhou and others found that by subdividing the volume difference of each subregion of the basal nucleus, the decrease in volume between different subregions of the basal nucleus corresponds to different cortical projection areas. Combining these findings, we have reason to believe that there is atrophy in both the cortex and the basal nucleus area of WD, and the common changes of the two may lead to different clinical manifestations of WD patients.