To analyze several proteins simultaneously, two-dimensional. This study was approved by the local ethics committee, and each participant provided written informed consent. Subjects were recruited between January 2007 and January 2016 at the outpatient movement disorder clinic of multiple medical centers. All consecutive patients and healthy subjects underwent brain magnetic resonance imaging (MRI) to evaluate the extent of cerebral ischemic lesion (CIL) and to exclude the presence of other brain lesions. In addition, an experienced radiologist and a neurologist, who were both blinded to the clinical status of all subjects, assessed the brain MRIs until consensus on the presence of CIL was achieved. Evaluation procedures consisted of a detailed medical history, physical and neurological examination, and neuropsychological assessment using the Mini-Mental State Examination (MMSE), the extended version of the Clinical Dementia Scale (CDR) with the sum of the box score of the CDR (SOB) and Global Deterioration Scale (GDS). All PD patients were diagnosed according to the United Kingdom Parkinson's Disease Society Brain Bank Clinical Diagnosis Criteria for Parkinson's Disease. Motor severity of PD patients was evaluated according to the Hoehn and Yahr stage (HY stage). Severity of CIL in all subjects was evaluated by white matter changes induced by ischemic lesions, which were classified according to Fazekas grade[8]. In addition, patients in the PD group were classified into two subgroups to evaluate the severity of ischemic white matter lesions according to motor severity of PD patients. The subgroups were defined as follows: group 1, patients with HY stage 1 or 2; group 2, patients with HY stage 3, 4, or 5. The healthy control (HC) group was matched based on age, gender, and education level to patients in the PD group. The HCs did not have any history or symptoms of PD, memory impairment, or other cognitive dysfunctions, and they did not have a history of other neurological diseases such as head trauma, epilepsy, or stroke or brain surgery or medical diseases. The presence of hypertension, diabetes mellitus, hypercholesterolemia, and cigarette smoking were also assessed by evaluating medical histories and laboratory findings since these risk factors can affect the occurrence of ischemic white matter lesions. Therefore, we excluded all subjects with the above-mentioned risk factors from this study. Hypertension was defined as systolic blood pressure ≥ 140 mm Hg, diastolic blood pressure ≤ 90 mm Hg, and/or the current use of antihypertensive medications. Diabetes mellitus (DM) was defined as a history of fasting glucose level ≥ 110 mg/dl or the current use of hypoglycemic agents. Hypercholesterolemia was defined as total cholesterol concentration ≥ 220 mg/dl or the current use of lipid-lowering agents. Cigarette smoking was defined as present if the patient reported smoking cigarettes at least once during the past five years. All statistical analyses were performed using the SPSS software version 18.0 package. The independent T-test was used for the comparison of continuous variables, and Pearson's Chi-square analyses were used for the comparison of categorical variables. Values are expressed as means and standard deviations. Statistical significance was assumed at a false detection rate less than 5%.

This study was approved by the local ethics committee, and each participant provided written informed consent. Subjects were recruited between January 2007 and January 2016 at the outpatient movement disorder clinic of multiple medical centers. All consecutive patients and healthy subjects underwent brain magnetic resonance imaging (MRI) to evaluate the extent of cerebral ischemic lesion (CIL) and to exclude the presence of other brain lesions. In addition, an experienced radiologist and a neurologist, who were both blinded to the clinical status of all subjects, assessed the brain MRIs until consensus on the presence of CIL was achieved. Evaluation procedures consisted of a detailed medical history, physical and neurological examination, and neuropsychological assessment using the Mini-Mental State Examination (MMSE), the extended version of the Clinical Dementia Scale (CDR) with the sum of the box score of the CDR (SOB) and Global Deterioration Scale (GDS). All PD patients were diagnosed according to the United Kingdom Parkinson's Disease Society Brain Bank Clinical Diagnosis Criteria for Parkinson's Disease. Motor severity of PD patients was evaluated according to the Hoehn and Yahr stage (HY stage). Severity of CIL in all subjects was evaluated by white matter changes induced by ischemic lesions, which were classified according to Fazekas grade[8]. In addition, patients in the PD group were classified into two subgroups to evaluate the severity of ischemic white matter lesions according to motor severity of PD patients. The subgroups were defined as follows: group 1, patients with HY stage 1 or 2; group 2, patients with HY stage 3, 4, or 5. The healthy control (HC) group was matched based on age, gender, and education level to patients in the PD group. The HCs did not have any history or symptoms of PD, memory impairment, or other cognitive dysfunctions, and they did not have a history of other neurological diseases such as head trauma, epilepsy, or stroke or brain surgery or medical diseases. The presence of hypertension, diabetes mellitus, hypercholesterolemia, and cigarette smoking were also assessed by evaluating medical histories and laboratory findings since these risk factors can affect the occurrence of ischemic white matter lesions. Therefore, we excluded all subjects with the above-mentioned risk factors from this study. Hypertension was defined as systolic blood pressure ≥ 140 mm Hg, diastolic blood pressure ≤ 90 mm Hg, and/or the current use of antihypertensive medications. Diabetes mellitus (DM) was defined as a history of fasting glucose level ≥ 110 mg/dl or the current use of hypoglycemic agents. Hypercholesterolemia was defined as total cholesterol concentration ≥ 220 mg/dl or the current use of lipid-lowering agents. Cigarette smoking was defined as present if the patient reported smoking cigarettes at least once during the past five years. All statistical analyses were performed using the SPSS software version 18.0 package. The independent T-test was used for the comparison of continuous variables, and Pearson's Chi-square analyses were used for the comparison of categorical variables. Values are expressed as means and standard deviations. Statistical significance was assumed at a false detection rate less than 5%..

Postoperative pain management was standardized as follows: For postoperative pain relief tramadol was administered in increments of 50 mg on patient demand with a lock-out time of 4 h and a maximum dose of 300mg/day. One ward nurse, who was blinded to group allocation, documented the postoperative pain intensity using VAS at the first rescue analgesics request, and at 1, 2, 4, 6, 8, 12, and 24 hours after surgery at rest. The time to the first request and the number of times tramadol was used in the first 24 hours after surgery were recorded. If the patients experienced severe nausea and vomiting, 10 mg metoclopramide iv was administered. Sufentanil consumption during surgery and 24 h 4-point rating scale satisfaction score (0 very unsatisfied, 1 unsatisfied, 2 satisfied, 3 very satisfied) on analgesic therapy were both recorded blindly by one of the authors. Side effects related to the regional anesthetic technique, such as cervical epidural analgesia and diaphragmatic palsy, were recorded. Particularly, patients were clinically evaluated by an experienced anesthesiologist for respiratory distress related to bilateral diaphragmatic palsy at recovery and in the PACU. Should this occur, dynamic chest radiograph examination would be performed to ascertain the diagnosis. Other side effects associated with flurbiprofen, such as vomiting and antiemetic requirements, were recorded..

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