Biochemical aspirin resistance in stroke patients: a cross-sectional single centre study

Background: Aspirin use is known to reduce the recurrence of stroke. However, the clinical response to aspirin has been mixed. The rate of stroke recurrence whilst on aspirin treatment is still unacceptably high. A plausible explanation for this may be resistance to the effects of aspirin. The causes of aspirin resistance are manifold and multi-factorial. We conducted a study to investigate the prevalence rate of biochemical aspirin resistance in a cohort of aspirin-naïve stroke patients. We also sought to determine the inherent factors that may predispose towards the development of aspirin resistance. Method: This was a cross-sectional, observational study conducted on patients admitted to our centre with an acute stroke who were aspirin-naïve. The diagnosis of an acute stroke was confirmed by clinical history and brain imagi ng. Fifty consecutive patients were prospectively enrolled. Socio demographic data were collected and baseline blood investigations were performed. Patients were tested for biochemical aspirin resistance using Multiplate platelet analyser (Dynabyte, Munich, Germany) after 5 doses of aspirin, corresponding to a total dose of 900 mg. Results: The median age of patients was 65.5 years and 54 % of patients were female. There were 11 smokers; of these 10 were male. Twenty-six (52 %) patients were Chinese, 21 (41%) were Malay and 3 (6.0 %) were Indian. Aspirin resistance was present in 14 % of our patients.There was an inverse relationship between the presence of aspirin resistance and plasma HDL levels (r = -0.394; p = 0.005). There was no relationship observed between aspirin resistance and total cholesterol, triglycerides, LDL, HbA1c, ALT, ALP, urea and creatinine levels. There were no significant differences in demographic profiles or smoking status between the aspirin resistant and non-aspirin resistant groups. We did not find any link between ethnicity and aspirin resistance. Conclusions: Our results indicate that a lower HDL leve l is associated with biochemical aspi-rin resistance. This may increase platelet aggregation and consequently increase the risk of a recurrent stroke. The clinical implications for aspirin resistance are far reaching. Any evidence that correctable factors may negatively influence the action of aspirin warrants further investigation. The prevalence rate of biochemical aspirin resistance in our study is comparable to the findings in other studies performed in an Asian population. Further research is required to determine how our findings translate into clinical aspirin resistance and stroke recurrence

Impulse control behaviours in a Malaysian Parkinson’s disease population

Background: Impulse control behaviours are repetitive and excessive activities that may be sub-syndromal and not fulfill the criteria for impulse control disorder. These activities have potential to negatively impact on the daily lives of sufferers. We conducted a study to investigate the prevalence of impulse control behaviors and its associated features in Parkinson’s disease in our population. Methods: We conducted a prospective cross-sectional study on consecutive patients attending neurology clinic. Inclusion criteria include idiopathic Parkinson’s disease patients with Hoehn & Yahr stage I-IV. Eighty patients were enrolled and screened for impulse control behaviors using the Questionnaire for Impulsive-Compulsive Disorder for Parkinson’s disease (QUIP). Results: Prevalence of impulse control behaviors among our cohort was 11.3%; the features significantly associated with it were higher level of education (p=0.02), advanced stage of disease (p=0.03) and higher levodopa dosage (p= 0.01). The commonest impulse control behavior in our cohort was compulsive medication use (7.5%), followed by hobbyism (6.3%), hypersexuality (5%), compulsive buying (3.75%), punding (2.5%), walkabout (2.5%), compulsive eating (1.25%) and pathological gambling (1.3%). Conclusions: There is an association between impulse control behavior and higher levodopa dosage in a study on patients with Parkinson’s disease in Malaysia. We also found a low prevalence of pathological gambling as compared to studies performed in the West

Defining the causes of sporadic Parkinson's disease in the global Parkinson's genetics program (GP2)

The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Duloxetine for pain in Parkinsons disease

© 2020 Shahrul Azmin Bin Md. RaniPain in Parkinsons disease is common and poorly managed. The body of literature showing that pain adversely impacts on the quality of life of Parkinsons disease patients is overwhelming. Different strategies have been adopted to address pain in Parkinsons disease but results have been mixed. The pathophysiology of pain in Parkinsons disease is thought to involve dopaminergic and extra-dopaminergic factors. Duloxetine, a serotonin and noradrenaline reuptake inhibitor has been used for pain in multiple sclerosis and painful diabetic peripheral neuropathy. We embarked on a project to explore the role of duloxetine in Parkinsons disease patients with pain in a randomized double blind placebo controlled trial using validated pain questionnaires, pain sensitivity measurements and functional imaging techniques. We showed a statistically significant improvement in the pain scores of the affective component of the Short-Form McGill Questionnaire and a trend towards improvement in pain tolerance following evoked pressure stimulus in the duloxetine group as compared to the placebo group. Additionally, the changes were not associated with changes in the affective states of the participants, as measured by the Geriatric Depression Scale and Positive Affect and Negative Affect Schedule. We did not find any statistically significant difference in the task-based fMRI and the resting state fMRI between the groups. In conclusion, our study showed that duloxetine may be most effective in addressing symptoms arising from the affective dimension of pain in Parkinsons disease patients

Nonmotor Symptoms in a Malaysian Parkinson’s Disease Population

Background. The nonmotor symptoms are important determinants of health and quality of life in Parkinson’s disease but are not well recognized and addressed in clinical practice. This study was conducted to determine the prevalence of nonmotor symptoms and their impact on quality of life in patients with Parkinson’s disease. Methods. This was a cross-sectional study among patients with idiopathic Parkinson’s disease. Exclusion criteria were a Mini Mental State Examination score of <21/30. Prevalence of nonmotor symptoms was determined using the NMSQuest. The severity of nonmotor symptoms and the quality of life were assessed using validated disease-specific questionnaires (PDQ-39 and NMSS). Results. A total of 113 patients consisting of 60 males and 53 females were recruited. The median duration of illness was 5.0 (2.0–8.0) years. The prevalence rate of nonmotor symptoms in our cohort was 97.3%. The most common reported nonmotor symptom in our cohort was gastrointestinal (76.1%). We found that the severity of the nonmotor symptoms was associated with poorer quality of life scores (rs: 0.727, P<0.001). Conclusions. Nonmotor symptoms were highly prevalent in our patients with Parkinson’s disease and adversely affected the quality of life of our patients. In contrast to western studies, the most common nonmotor symptom is gastrointestinal. The possibility of an Asian diet playing a role in this observation requires further study

Eradication of <i>Helicobacter pylori</i> Infection Improves Levodopa Action, Clinical Symptoms and Quality of Life in Patients with Parkinson's Disease

<div><p>Background</p><p>Previous studies have demonstrated a higher prevalence of <i>Helicobacter pylori (H. pylori)</i> infection in patients with Parkinson's disease (PD) compared to controls. <i>H. pylori</i> infection affects levodopa absorption and its eradication significantly improves clinical response to levodopa. Here, we studied the prevalence of <i>H. pylori</i> infection and its eradication effects among our PD patients.</p><p>Methods</p><p>A prospective study involving idiopathic PD patients on levodopa therapy. ¹³C-urea breath test (UBT) was used to detect <i>H. pylori</i>. UBT-positive patients were given standard eradication therapy and followed up at 6 and 12 weeks in an open label single arm design. Repeat UBT was performed at 12 weeks. The UPDRS, PD NMQ, PD NMSS and PDQ-39 were administered at baseline and post-eradication (6 and 12 weeks). Levodopa ‘onset’ time and ON-duration were recorded.</p><p>Results</p><p>Of 82 patients recruited, 27 (32.9%) had positive UBT. <i>H. pylori</i>-positive patients had significantly poorer total UPDRS (p = 0.005) and PDQ39 (p<0.0001) scores compared to <i>H. pylori</i>-negative patients. At 12 weeks post-eradication, the mean levodopa onset time shortened by 14 minutes (p = 0.011). The mean ON duration time increased by 56 minutes at week 6 (p = 0.041) and 38 minutes at week 12 (p = 0.035). The total UPDRS scores (p<0.0001), scores for parts II (p = 0.001), III (p<0.0001) and IV (p = 0.009) were significantly better. The total PDQ-39 scores (p = 0.001) and subdomains mobility (p = 0.002), ADL (p = 0.001), emotional well being (p = 0.026) and stigma (p = 0.034) significantly improved. The PD NMSQ did not show significant improvement.</p><p>Conclusions</p><p><i>H. pylori</i> eradication improved levodopa onset time, ON duration, motor severity and quality of life parameters. Screening and eradication of <i>H. pylori</i> is inexpensive and should be recommended in PD patients, particularly those with erratic response to levodopa.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT02112812" target="_blank">NCT02112812</a></p></div

Clinical Effects at baseline and following <i>H. pylori</i> eradication therapy (n = 21).

<p>All analyses were performed using ANOVA.</p><p>Clinical Effects at baseline and following <i>H. pylori</i> eradication therapy (n = 21).</p