Yu-Xin Wang

Genetics of Parkinson’s disease and related disorders

Parkinson’s disease (PD) is a complex and heterogeneous neurological condition characterised mainly by bradykinesia, resting tremor, rigidity and postural instability, symptoms that together comprise the parkinsonian syndrome. Non-motor symptoms preceding and following clinical onset are also helpful diagnostic markers revealing a widespread and progressive pathology. Many other neurological conditions also include parkinsonism as primary or secondary symptom, confounding their diagnosis and treatment. Although overall disease course and end-stage pathological examination single out these conditions, the significant overlaps suggest that they are part of a continuous disease spectrum. Recent genetic discoveries support this idea because mutations in a few genes (α-synuclein, LRRK2, tau) can cause partially overlapping pathologies. Additionally, mutations in causative genes and environmental toxins identify protein homeostasis and the mitochondria as key mediators of degeneration of dopaminergic circuits in the basal ganglia. The evolving mechanistic insight into the pathophysiology of PD and related conditions will contribute to the development of targeted and effective symptomatic treatments into disease-modifying therapies that will reduce the burden of these dreadful conditions.

The efficacy of homemade tolcapone in the treatment of patients with Parkinson's disease

The aim of the study was to investigate the efficacy of homemade tolcapone in treatment of patients with Parkinsons disease (PD). Eighty patients with PD were subjected to randomized, double-blind, placebo-controlled and parallel-group study. PD patients were randomly divided into the tolcapone treatment group (41 cases) and placebo group (39 cases). Each patient received 1 pill of tolcapone or placebo, 3 times per day for 26 weeks. Efficacy was evaluated using the internationally used unified Parkinsons disease rating scale (UPDRS) scoring system for PD symptoms. After the treatment for 26 weeks, the cognitive function, tremor, muscle stiffness, voluntary movement and autonomic nerve symptoms were compared between the two groups using UPDRS scores. Compared with the placebo group, cognitive function, muscle stiffness and voluntary movement reduction were significantly improved in patients of the tolcapone group (P<0.05). However, no significant differences in UPDRS scores of autonomic nerve symptoms and tremor were found between two groups after treatment (P>0.05). Tolcapone, a catechol-O-methyl transferase (COMT) inhibitor, can improve the motor function of patients with PD, especially exercise and muscle stiffness. Tolcapone can also improve the cognitive function of patients.

Intravenous Thrombolytic Therapy for Acute Ischemic Stroke with Subclavian Arterial Steal Syndrome: A Case Report

This case study is of a patient who was a 71-year-old man, admitted to the emergency room due to ‘‘slurred speech and right limb weakness for 3.5 h’’. His symptoms started at 20:00 h, and the patient came to the hospital at 23:30 h on August 13, 2012. The patient had history of hypertension for 2 years, but no history of smoking/drinking or familial genetics. He experienced sudden slurred speech and right limb weakness at 20:00 h. The symptoms worsened quickly, and he was soon unable to express himself or understand words of others. Accompanying symptoms included poor mobility of the right limbs, and he was unable to lift or hold objects with the right upper limb, or could stand and walk with the right lower limb. There was no headache, dizziness, nausea, vomiting, unconsciousness, limb convulsion, or incontinence of urine and feces. As the patient’s symptoms persisted without relief, he visited the emergency room of our hospital immediately. Examination showed his blood pressure was 140/90 mmHg, heart rate 94 beats/min, irregular heart sound intensity with arrhythmia, and no pathological murmurs over all valve auscultation areas. The patient was alert with complete mixed aphasia. Both eye pupils were 3:3 mm, light reaction was positive, with eyes gazing to the left but no sign of nystagmus. Forehead wrinkles of the patient were symmetric. The patient could close the eyelids completely, but the right nasolabial fold was shallow. The tongue was in the midline, gag reflexes were positive, uvula centered in the midline, and the soft palate could lift naturally. The neck was soft, the myodynamia of left limb was achieved grade 5, and the myodynamia of right limb was achieved grade 1. The patient was uncooperative for other neurological examinations. National Institutes of Health Stroke Scale (NIHSS) of USA score was 15 points. Head CT scan suggested a widespread demyelination of bilateral cerebral hemispheres, as shown in Fig. 1. The relevant blood tests (including blood, coagulation, electrolytes, glucose, liver, and kidney function) did not show obvious abnormalities but ECG showed atrial fibrillation. Based on the guidelines of intravenous thrombolysis for acute ischemic cerebrovascular diseases, and the clinical and laboratory evaluations, the patient required intravenous rt-PA thrombolysis after admission. Therefore, rtPA thrombolytic therapy was administered 4 h after onset. The rt-PA dose was calculated at 0.9 mg/kg, 55 mg in total, which was first delivered with a 5.5 mg intravenous bolus for 1 min, and by intravenous infusion for the rest of 1 h. One hour after thrombolysis, the symptoms of speech disorders and the right limb weakness were slightly improved. Physical examinations showed that the patient was alert with complete motor aphasia and incomplete sensory aphasia. Pupils of both eyes were 3:3 mm, light reaction was positive; both eyes were gazing incompletely to the right, without nystagmus. Forehead wrinkles were symmetric. The patient could close the eyelids completely, but the right nasolabial fold was shallow. The tongue was in the midline, gag reflexes were positive, uvula centered in the midline, and the soft palate could lift naturally. The neck was soft, the myodynamia of left leg was achieved grade 5, the myodynamia of right upper limb was achieved grade 1, and the myodynamia of right lower limb was achieved grade 2. All limb muscle tensions were normal, tendon reflexes were positive, and right-side Babinski sign X.-G. Tong Y. Wang Y. Chen C. Zhang C.-H. Li Z. Dong X.-W. Zhang F.-F. Zhang H. Yin J.-H. Wang P.-L. Zhang (&) Department of Neurology, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, No. 122, Qixiangtai Road, Tianjin 300060, China e-mail: peilanzhng@sina.com

Investigation of the causes of clinical symptom aggravation in process of intravenous thrombolysis with alteplase

Objective To explore the causes of aggravation of microcirculation disorders in the process of intravenous thrombolysis with alteplase and the clinical outcomes. Methods The clinical data of the aggravated signs and symptoms of 13 cases treated by alteplase were reported, and the onset characteristics and clinical outcomes were analysed to summarize emergency experiences. Results There were 13 patients with stenosis of intracranial large arteries occurred perforating branch infarctions caused by the blocking of carried arteries (8 cases in internal carotid system, 5 cases in vertebral-basilar system). In the process of thrombolytic therapy, main aggravated presentations including cortical ischemic symptom, quadriplegia, exacerbated disturbance of consciousness were seen. Imaging examinations showed multiple new petechial ischemic foci in cortex and watershed region or increasing of infarct foci in cerebellum and brain stem. The prognosis was favorable after expectant treatment. NIHSS score was 8.69 ± 3.42 at 24 h after treatment, and mRS score was 0.94 ± 0.37 at 3 month-follow-up. Neurologic deficit and quality of life were evidently improved. Conclusion In the course of intravenous thrombolytic therapy with alteplase. Aggravated clinical signs and symptoms may be related to various factors. Emboli disintegration inducing microcirculation disorder is inferred to be the main cause. For patients presenting aggravated signs and symptoms in thrombolysis process, favorable outcomes may occur as long as intensive care and timely treatment are performed.

The clinical research of intravenous thrombolysis with alteplase in the treatment for acute ischemic stroke

Objective The incidence of stroke in China has been growing year by year and has become the first cause of death exceeding cancer and heart disease. However, non-standard thrombolytic drug dose and therapeutic time window have seriously affected the treating effect of acute ischemic stroke. This study aims to explore the effect of intravenous alteplase with standard dose and reperfusion injury of ischemic brain tissue and prognosis of patients receiving thrombolytic therapy within therapeutic time window. Methods Clinical data of 86 patients with acute ischemic stroke receiving thrombolytic therapy with alteplase were retrospectively analyzed. Efficacy at 24 h and 3 months after thrombolysis was evaluated according to the multi-modal MRI, and the U.S. National Institutes of Health Stroke Scale (NHISS) and modified Rankin Scale (mRS) were used to identify the extent of neurological function improvement and prognosis of patients. Results Among 86 patients, 56 cases were anterior circulation ischemia, and 30 cases were posterior circulation ischemia. At 24 h after thrombolysis, 62 cases with favorable neurological function outcome accounted for 72.09%, and 24 cases with poor outcome accounted for 27.91%. The NHISS scores before and after thrombolysis were statistically different ( P = 0.023). Based on multi⁃modal MRI of 42 cases at 24 h after thrombolysis, there were 18 cases with complete vascular recanalization (42.86%), 6 cases with partial recanalization (14.28%) and 18 cases with occlusion (42.86%). The difference before and after thrombolytic thearpy was statistically significant ( P = 0.073). In the follow-up of 3 months, 78 patients with favorable function outcome accounted for 90.70%, and 8 cases with poor outcome accounted for 9.30%, which were significantly different from that before thrombolysis ( P = 0.008). Conclusion Cerebral vascular recanalization and reperfusion of brain tissue are reliable indicators of clinical efficacy for intravenous thrombolysis with alteplase.