| Part One. Reliability and Validity of Chinese Version of Unified Wilson Disease Rating Scale (UWDRS) and Relevant Factors AnalysisObjective:To evaluate the reliability and validity of Chinese version of UWDRS in Chinese patients with Wilson’s disease (WD). Relevant factors of UWDRS were analyzed.Methods:We translated and back translated the English version of UWDRS developed by Leinweber B in 2008 on Movement disorders into Chinese. Some modifications were made. From June 2011 to September 2013, we recruited 113 WD patients of neurologic and/or psychiatric type from the WD clinic of Huashan hospital, a general-service hospital in Shanghai. Fifty one were females and 62 were males. The average age was 24.53±7.85. Age of onset, duration from onset to diagnosis, duration from treatment to assessment, treatment, initial dose of penicillamine, and operation were recorded. UWDRS was assessed and we evaluated test-retest reliability with Pearson correlation analysis, internal consistency with Cronbach a and item-total correlation, criterion validity and construct validity with exploratory factor analysis (EFA). UPDRS, BFMS, ICARS and Child-Pugh grading were used as criteria. We calculated the average value of UWDRS, UPDRS, BFMS and ICARS and listed the prevalence of each item. The symptoms could be classified into 6 categories. They were ADL, parkinsonism, dystonia, tremor, chorea and cognition and psychiatric problems. We calculated the correlation between ADL and other 5 symptoms. Multiple linear progressive analysis was also been applied to analyze relevant factors of ADL. We also explored the relevant factors of UWDRS with multiple linear regression analysis.Results:1. Descriptive Analysis The total score of UWDRS was 37.33±24.81, neurological subscore 27.48±21.96, hepatic subscore 2.71±2.24, psychiatric subscore 7.14±5.26. Symptoms of high prevalence included activity of daily living (ADL), dysarthria and dysphagia, tremor, dystonia, hypokinesia, general impairment, arthralgia, bleeding, memory failing, focus deficiency, contact, hostile feeling and anxiety. The average score of UPDRS was 19.09±14.39. Items of low prevalence included thought disturbance, falling, parenthesis, freezing, rigidity, stance, gait disturbance, body stability. The average score of BFMS was 11.89±16.61 and the prevalence of dystonia reached 87.6%. The average score of ICARS was 9.65±11.49. Items of low prevalence included unbalance, finger nose test, heel-knee test and eye movement disturbance.2. reliability and validity Eighteen patients received the second evaluation of UWDRS 2-4 weeks after the first one. The test-retest reliability was 0.802 (p<0.01). The Cronbach a of UWDRS was 0.930, the neurological subscale was 0.943, the hepatic subscale was 0.255, psychiatric subscale was 0.661. The Cronbach a of the entire scale in 23 newly-diagnosed WD patients was 0.904, the neurological subscale was 0.908, the hepatic subscale was -0.01, psychiatric subscale was 0.576. The total score of UWDRS was highly correlated with UPDRS (r=0.941), the second part of UPDRS (r=0.930), the third part of UPDRS (r=0.930), BFMS (r=0.731) and ICARS (r=0.884). The correlation between neurological subscale and these criteria was even stronger. Hepatic subscale and psychiatric subscale did not correlated with these scales. The first part of UPDRS moderately correlated with the psychiatric part (r=0.591) Child-Pugh grade did not correlate with hepatic subscale. The KMO value of UWDRS was 0.616. EFA extracted 4 factors. These factors were: 1)ADL+parkinsonism+dystonia,2)tremor,3)chorea and 4)cognition and psychiatric problems. ADL had strong correlation with parkinsonism and dystonia (r=0.778 and r=0.681),but not with tremor, chorea and cognition and psychiatric problems. Parkinsonism strongly correlated with dystonia. (r=0.704) Multiple linear regression analysis indicated parkinsonism (X1, B=0.516) and dystonia (X2, B=0.481) contributed more than tremor did (X3, B=0.206)3. Relevant factors. Multiple linear regressive analysis found duration of treatment and initial dose of penicillamine was related with UWDRS score. Neurological part was related with age of onset, duration of treatment and initial dose of penicillamine. Gender, age and delay of diagnosis had no impact on UWDRS score.Conclusions:1. Chinese patients with WD scored higher than German patients. Dystonia and dysarthria were more prominent in our group. Chinese patients with WD suffered from more severe dystonia which had more impact on ADL than tremor and chorea did.2. Test-retest reliability of Chinese version of UWDRS was good. The internal consistency of UWDRS was acceptable except the hepatic part.3. UWDRS had good criterion validity except the hepatic subscale. The construct validity of UWDRS in Chinese patients with WD differed from that in German patients.4. The relevant factors of UWDRS score included age of onset, duration of treatment and initial dose of penicillamine.5. Some modifications were needed to UWDRS before applying in Chinese patients with WD. The suggestions included:1) lower the weight of tremor and chorea and elevate weight of dystonia,2) redesign the hepatic subscale and included more laboratory variables,3) more weight should be added on dysarthria, but the characteristic should be studied before modification,4) abridge the psychiatric subscale.Part Two. Evaluating dysarthria in Patients with WD with Frenchay Dysarthria AssessmentObjective:To analyze the features of dysarthria in Chinese patients with WD with Frenchay Dysarthria Assessment (FDA). To provide data support to scale development.Methods:The participants were the same as the first part. We categorized the cases into the following five groups according to UWDRS and clinicians’subjective feeling: 1)nearly normal group,2)pseudoparkinsonism group,3)pseudosclerotic group, 4)dystonic group and 5) mixed group. We calculated the FDA total score, score of 8 aspects and FDA and UWDRS score in 5 subgroups. We compared the score among these five subgroups. We further explored the relation between FDA score and UWDRS score in these subgroups and FDA score with symptoms of pseudoparkinsonism, dystonia and pseudoslerosis. Multiple linear regressive analysis was used to explore the relevant factors of FDA. The possible factors included gender, age, age of onset, delay of diagnosis, duration of treatment and initial dose of penicillamine.Results:1. Descriptive results and data comparison The average score of FDA in 113 was 18.00±19.28,7.24±8.17 in nearly normal group,16.20±12.99 in pseudoparkinsonism group,7.73±6.24 in pseudosclerotic group,28.16±18.51 in dystonia group and 38.81±25.42 in mixed group. FDA score did not show significant difference between nearly normal group and pseudoparkinsonism group or pseudosclerotic group. FDA score in dystonic group was different from that in pseudoparkinsonism group and pseudosclerotic group. UWDRS score in nearly normal group did not differ from that in pseudoparkinsonism group, but did from that in pseudosclerotic group. Dystonic patients did not show sign of difference in UWDRS score from pseudosclerotic cases.2. Correlation between FDA and UWDRS To the entire cohort, dystonic group and mixed group, FDA score had moderate-strong correlation with UWDRS score. In the dystonic group, reflexes, voice, tongue and intelligence correlated moderately or strongly with UWDRS score. In the mixed group, dystonia and pseudoparkinsonism had moderate-strong correlation with FDA score, but this relation did not exist between pseudoclerosis and FDA.3. Relevant factor of FDA score Age, gender, delay of diagnosis, and initial dose of penicillamine did not correlated with FDA according to multiple linear regressive analysis. Age of onset and duration of treatment were relevant factors.Conclusions:1. Dysarthria was severe in dystonic and mixed group, moderate in pseudoparkinsonism and mild in nearly normal and pseudosclerotic group.2. Pharynx, larynx and tongue involvement occurred early in the disease course. Disturbed reflexes were prominent in pseudosclerotic group and tongue movement disturbance was prominent in pseudoparkinsonism group.3. In dystonic group, the severity of reflexes, voice, tongue and intelligence were parallel to the total health condition.4. In mixed group, dystonia was the main cause for dysarthria.5. Duration of treatment and onset of age influenced the severity of dysarthria.Part Three. The reliability and validity of Chinese Wilson’s Disease Rating ScaleObjective:To develop a specific scale for WD and evaluate the reliability and validity of this scale.Methods:We recruited 25 cases of WD from the WD clinic of Huashan hospital from January 2014 to March 2014. We investigated these patients with CWDRS, UWDRS and SF36. Reliability and validity of CWDRS were calculated. The data were compared with that of UWDRS.Results:1. The inter-rater reliability of CWDRS was 0.998 with Kappa value of each item greater than 0.6. The Cronbach a representing internal consistency of CWDRS was 0.958, while that of UWDRS was 0.972. Item-total correlation of twelve items in CWDRS was lower than 0.4, while the number of UWDRS was 38.2. Eight factors were extracted from CWDRS with EFA. These factors account for 83.02% of the variance. Six factors have unambiguous definitions. These factors could be described as dystonia and hypokinesia, hyperkinesias, dysarthria, abnormal hand posture, tremor and liver function. CWDRS score negatively correlated with SF36(r=-0.659, p<0.01). The correlation coefficient between UWDRS and SF36 was-0.674. CWDRS had strong correlation with UWDRS (r=0.953). Neurological symptoms strong correlated with the first part of UWDRS(r=0.953); psychiatric symptoms moderately with the third part of UWDRS(r=0.658). Liver function did not correlate with the second part of UWDRS.3. Dysarthia symptoms in CWDRS had negative correlation with physical function, social function, body pain and mental health.Conclusions:4. CWDRS had only half items as UWDRS did, but still maintain high reliability and validity, suggesting the possibility of CWDRS surrogating UWDRS.5. Construct validity revealed six factors which were in line with our previous assumption.6. The hepatic symptoms in CWDRS did not show its clinical significance. More hepatic cases should be included.Part Four. A pilot cephalometric study in patients with WDObjective:To study the facial bone deformity in Chinese patients with WD with cephalometic methods and provide reasonable causal assumption.Methods:From June 2012 to February 2014, we recruited 54 WD patients (10 adolescences and 44 adults) of neurological type from the WD clinic of Huashan hospital, a general-service hospital in Shanghai. A control group of 70 normal individuals was also settled. All the cases took lateral cephalometric radiograph. The films were stored in the computer and analyzed with Viewbox3.1.1.14. The measuring methods included Steiner and Downs methods. We calculated the average of the variables in male WD, female WD, male control and female control groups and tested the value with t test and Fisher’s exact test. The WD group could be divided into <20 and ≥20 subgroups according to the onset age. Average was calculated and t-test was used.Results:1. Comparison of variables SNA of male WD group was greater than the control group (84.23±3.55 vs 81.52± 3.53, p=0.006),so as ANB (5.30±1.83 vs 3.20±2.55, p=0.001) and lower facial proportion (60.87±12.92 vs 56.58±2.51, p=0.048). SNA of female WD group was greater than the control group (83.20±3.75 vs 81.06±3.37, p=0.039), so as ANB (5.50±4.20 vs 2.89±2.19, p=0.007)2. Chi square test Chi square test indicated higher prevalence of maxillary protrusion and greater mandibular plane angle.3. Comparison between groups with different onset age In male WD group, onset age above or below 20 years old made not difference in all variables. Female patients whose onset age was below 20 had greater SN-MP angle (p=0.004), lower facial proportion (p=0.03), Y axis (p=0.004) and facial angle (p=0.009)4. Data analysis in pure SNA elevation and pure SNB decrease patients Eight female cases in WD group had pure decreased SNB and 6 of them had ANB above the upper limitation. Eleven cases in control group had pure decreased SNB but only 2 cases had abnormal ANB (p<0.05). Great mandibular plane angle could accompany with pure SNA elevation and pure SNB decrease.Conclusions:1. WD patients were prone to have type Ⅱ malocclusion. The main cause was protruded maxillary.2. Female patients had more serious mandibular retrusion. It was an important cause in female patients.3. WD paints had the inclination of vertical facial growth.4. Patients with onset age before 20 years old were subject to having facial bone deformity.5. We assumed mouth breath and decreased muscle strength were the major causes of facial bone deformity. |
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