Introduction
Little is known regarding the educational needs and perspectives of people living with Parkinson’s disease (PD), particularly in Asia.
Objective
To assess knowledge and perceptions ...regarding PD in a large multiethnic urban Asian cohort of patients and caregivers.
Methods
We conducted a survey at a university hospital neurology clinic, using a novel Knowledge and Perception of Parkinson’s Disease Questionnaire (KPPDQ).
Results
The KPPDQ had satisfactory psychometric properties among patients and caregivers. Five hundred subjects were recruited with a 97% response rate (211 patients, 273 caregivers). Non-motor symptoms such as urinary problems, visual hallucinations and pain were relatively poorly recognized. Many (≈ 50–80%) respondents incorrectly believed that all PD patients experience tremor, that PD is usually familial, and that there is a cure for PD. About one-half perceived PD to be caused by something the patient had done in the past, and that PD medications were likely to cause internal organ damage. Issues of stigma/shame were relevant to one-third of patients, and 70% of patients perceived themselves to be a burden to others. Two-thirds of participants felt that PD imposed a heavy financial toll. Participants were about equally divided as to whether they would consider treatment with deep brain stimulation, tube feeding or invasive ventilation. Over three-quarters of patients expressed a preference to die at home.
Conclusions
Important knowledge gaps, misperceptions and perspectives on PD were identified, highlighting the need for further efforts to raise awareness and provide accurate information regarding PD, and to address patient’s and caregivers’ needs and preferences.
An improved understanding of the genetic determinants of Parkinson's disease (PD) in underrepresented populations, and better characterization of genotype-phenotype correlations in monogenic PD, are ...needed. Scarce literature exists regarding the genetic aetiology of PD in Malays, who comprise 200 million individuals in South-East Asia. Phenotypic data regarding PARK-PINK1 are also limited.
A multi-ethnic cohort of PD patients from Malaysia (n = 499, including 185 Malays) were tested using a next-generation sequencing-based PD gene panel. The prevalence and clinico-radiological features of patients with the PINK1 p. Leu347Pro mutation are described. This mutation has previously only been reported in people of Filipino or Chamorro (native Guamanian) ancestry.
Homozygous p. Leu347Pro mutations were found in five unrelated Malay patients, yielding a prevalence of 6.9% among Malays with PD onset ≤50 years (2.7% of the Malay group overall). This variant was not detected in the homozygous state in 300 Malay controls, but two were heterozygous carriers (0.67%) indicating a relatively high population frequency in keeping with the high frequency of PARK-PINK1 among Malay patients. Interesting clinical features were observed, e.g., differences in the age at PD onset and clinical progression, despite having the same point mutations. Previously unreported brain MRI abnormalities involving the corticospinal tract and hypothalamus, and “loss of the swallow tail” sign, were documented.
This report contributes to the very limited literature on PD genetics in the Malay population, and more broadly to the epidemiological, phenotypic and neuroimaging characterization of PARK-PINK1. It also further supports the pathogenicity of the p. Leu347Pro variant.
•PARK-PINK1 is a relatively common form of monogenic PD in the Asia-Pacific.•PINK1 p. Leu347Pro was previously thought to be restricted to Filipinos.•We found PINK1 p. Leu347Pro to be a common cause of early-onset PD in Malays.•Patients with the same mutation may have quite varied clinical phenotype.•Some patients have MRI abnormalities in the corticospinal tract and hypothalamus.
Background
Genome-wide association studies (GWAS) have shown that variants in the 3-methylcrotonyl-CoA carboxylase (
MCCC1
)/lysosome-associated membrane protein 3 (
LAMP3
) loci (rs10513789, ...rs12637471, rs12493050) reduce the risk of Parkinson’s disease (PD) in Caucasians, Chinese and Ashkenazi-Jews while the rs11248060 variant in the diacylglycerol kinase theta (
DGKQ)
gene increases the risk of PD in Caucasian and Han Chinese cohorts. However, their roles in Malays are unknown. Therefore, this study aims to investigate the association of these variants with the risk of PD in individuals of Malay ancestry.
Methods
A total of 1114 subjects comprising of 536 PD patients and 578 healthy controls of Malay ancestry were recruited and genotyped using Taqman® allelic discrimination assays.
Results
The G allele of rs10513789 (OR = 0.83,
p
= 0.001) and A allele of rs12637471 (OR = 0.79,
p
= 0.007) in the
MCCC1/LAMP3
locus were associated with a protective effect against developing PD in the Malay population. A recessive model of penetrance showed a protective effect of the GG genotype for rs10513789 and the AA genotype for rs12637471. No association with PD was found with the other
MCCC1/LAMP3
rs12493050 variant or with the
DGKQ
(rs11248060) variant. No significant associations were found between the four variants with the age at PD diagnosis.
Conclusion
MCCC1/LAMP3
variants rs10513789 and rs12637471 protect against PD in the Malay population.
Lysosomal dysfunction plays an important role in neurodegenerative diseases, including Parkinson's disease (PD) and possibly Parkinson-plus syndromes such as progressive supranuclear palsy (PSP). ...This role is exemplified by the involvement of variants in the GBA1 gene, which results in a deficiency of the lysosomal enzyme glucocerebrosidase and is the most frequently identified genetic factor underlying PD worldwide. Pathogenic variants in the SMPD1 gene are a recessive cause of Niemann-Pick disease types A and B. Here, we provide the first report on an association between a loss-of-function variant in the SMPD1 gene present in a heterozygous state (p.Pro332Arg/p.P332R, which is known to result in reduced lysosomal acid sphingomyelinase activity), with PSP-Richardson syndrome in three unrelated patients of Chinese ancestry.
A significant proportion of adult-onset neurological disorders remain diagnostic odysseys despite extensive evaluation. Hypomyelination with Brainstem and Spinal Cord Involvement and Leg Spasticity ...(HBSL) is an autosomal recessive disorder caused by mutations in the cytoplasmic aspartyl-tRNA synthetase (DARS) gene involved in mRNA translation. Clinical features of patients with DARS mutations include developmental delay, leg spasticity, cerebellar dysfunction, cognitive impairment and epilepsy. Most reported cases have been infantile-onset with severe neurological disability and neuroimaging abnormalities. To our knowledge, late- or adult-onset cases have never been reported in the literature. Here, we report for the first time, with video documentation and six-year clinical follow-up, an ethnic Malay patient with onset of spasticity and ataxia in late-adulthood, carrying a pathogenic DARS mutation discovered via whole-genome sequencing. His clinical and radiological findings were consistent with HBSL, but this diagnosis was not considered as, up until now, HBSL has only been reported with childhood/adolescent-onset. This case highlights that HBSL/DARS mutations should now be considered in the differential diagnosis of adult-onset spastic paraplegia and/or leukoencephalopathy.
KMT2B-linked dystonia (DYT-KMT2B) is a childhood-onset dystonia syndrome typically beginning in the lower limbs and progressing caudocranially to affect the upper limbs with eventual prominent ...craniocervical involvement. Despite its recent recognition, it now appears to be one of the more common monogenic causes of dystonia syndromes. Here, we present an atypical case of DYT-KMT2B with oromandibular dystonia as the presenting feature, which remained restricted to this region three decades after symptom onset. This appears to be the first reported case of DYT-KMT2B from Southeast Asia and provides further supporting evidence for the pathogenic impact of the KMT2B c.6210_6213delTGAG variant.
Introduction. Although PD most commonly affects older individuals, it is not rare for people to be diagnosed in their 40 or 50s, in whom genetic factors presumably contribute a greater role in ...aetiology. To date, literature regarding epidemiology and genetics of PD in Malays remains very scarce.
Methods. We analysed data from the PD registry of a tertiary hospital in East Peninsular Malaysia, collected over 2011–2019. Diagnosis of PD was assigned by neurologists using clinical diagnostic criteria. Patients with revised diagnoses during follow-up were removed from the registry. EOPD was defined using two age cut-offs: age of diagnosis 40 years and 50 years. Positive family history was defined as having at least one member in the immediate or extended family diagnosed with PD or having motor features that could be consistent with PD.
Results. Two hundred and thirty-one Malay patients were included in this study. The frequency of EOPD was 4.32% (10/231) using the 40-years cut-off and 16.9% (39/231) using 50-years. Of 136 patients in whom family history information was available, 25 (18.4%) had a positive family history. Interestingly, none of those with PD diagnosis 40 years had a positive family history, while (4/31) 12.9% of those diagnosed at 50 years had a positive family history.
Conclusion. This pilot study revealed a relatively high frequency of EOPD in Malays. Further studies to elucidate the role of genetics as well as environmental factors among Malay PD patients may potentially unravel new insights into disease causation.
OBJECTIVE:To determine whether probiotics are effective for constipation, a common and often difficult-to-treat problem, in Parkinson’s disease (PD).
METHODS:In this double-blind, randomized ...placebo-controlled single-centre trial, 280 PD patients were screened and 72 eligible patients were block-randomized (1:1) to receive either multi-strain probiotics capsules (n=34), or identical-appearing placebo (n=38), for four weeks. The primary endpoint was the change in the average number of spontaneous bowel movements (SBM) per week during the last two weeks of intervention, compared with the two-week pre-intervention phase, recorded by daily stool diary. Secondary outcome measures included changes in stool consistency, constipation severity score, and quality of life related to constipation. Satisfaction with intervention received was assessed. Change in levels of fecal calprotectin, a marker of intestinal inflammation, was an exploratory outcome.
RESULTS:SBM increased by 1.0±1.2/week after treatment with probiotics, and decreased by 0.3±1.0/week in the placebo group (mean difference 1.3, 95%CI0.8-1.8, P<0.001). Significant improvements were also seen for secondary outcomes after correction for multiple comparisons, including stool consistency (P=0.009) and quality of life related to constipation (P=0.001). In the treatment group, 65.6% reported satisfaction with the intervention, vs. only 21.6% in the placebo group (P<0.001). One patient (2.9%) in the treatment group withdrew due to a non-serious adverse event. Fecal calprotectin did not change significantly during the study.
CONCLUSIONS:Multi-strain probiotics treatment was effective for constipation in PD. Further studies are needed to investigate the long-term efficacy and safety of probiotics in PD, as well as their mechanisms of action.
CLASSIFICATION OF EVIDENCE:This study provides Class I evidence that for people with PD, multi-strain probiotics significantly increased the average number of spontaneous bowel movements per week.
CLINICALTRIALS.GOV IDENTIFIER:NCT03377322
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