MyMedR

Fulltext Parkinson's Disease is Predominantly a Genetic Disease

Lim SY, Klein C

J Parkinsons Dis, 2024;14(3):467-482.

The discovery of a pathogenic variant in the alpha-synuclein (SNCA) gene in the Contursi kindred in 1997 indisputably confirmed a genetic cause in a subset of Parkinson's disease (PD) patients. Currently, pathogenic variants in one of the seven established PD genes or the strongest known risk factor gene, GBA1, are identified in ∼15% of PD patients unselected for age at onset and family history. In this Debate article, we highlight multiple avenues of research that suggest an important - and in some cases even predominant - role for genetics in PD aetiology, including familial clustering, high rates of monogenic PD in selected populations, and complete penetrance with certain forms. At first sight, the steep increase in PD prevalence exceeding that of other neurodegenerative diseases may argue against a predominant genetic etiology. Notably, the principal genetic contribution in PD is conferred by pathogenic variants in LRRK2 and GBA1 and, in both cases, characterized by an overall late age of onset and age-related penetrance. In addition, polygenic risk plays a considerable role in PD. However, it is likely that, in the majority of PD patients, a complex interplay of aging, genetic, environmental, and epigenetic factors leads to disease development.

The Genetic Epidemiology of Parkinson's Disease view - Authors' reply

Lim SY, all the authors

Lancet Neurol, 2025 Apr;24(4):285-286.

PMID: 40120606 DOI: 10.1016/S1474-4422(25)00073-0

Historical perspective: The pros and cons of conventional outcome measures in Parkinson's disease

Lim SY, Tan AH

Parkinsonism Relat Disord, 2018 Jan;46 Suppl 1:S47-S52.

PMID: 28793970 DOI: 10.1016/j.parkreldis.2017.07.029

BACKGROUND: Conventional outcome measures (COMs) in Parkinson's disease (PD) refer to rating scales, questionnaires, patient diaries and clinically-based tests that do not require specialized equipment.

METHODS: It is timely at this juncture - as clinicians and researchers begin to grapple with the "invasion" of digital technologies - to review the strengths and weaknesses of these outcome measures.

RESULTS: This paper discusses advances (including an enhanced understanding of PD itself, and the development of clinimetrics as a field) that have led to improvements in the COMs used in PD; their strengths and limitations; and factors to consider when selecting and using a measuring instrument.

CONCLUSIONS: It is envisaged that in the future, a combination of COMs and technology-based objective measures will be utilized, with different methods having their own strengths and weaknesses. Judgement is required on the part of the clinician and researcher in terms of which instrument(s) are appropriate to use, depending on the particular clinical or research setting or question.

Levodopa and Parkinson Disease-Myths Revisited

Lim SY, Poewe W, Tan AH

JAMA Neurol, 2017 10 01;74(10):1270.

PMID: 28973082 DOI: 10.1001/jamaneurol.2017.2560

Osmotic Demyelination Syndrome With Evolving Movement Disorders

Tan AH, Lim SY, Ng RX

JAMA Neurol, 2018 07 01;75(7):888-889.

PMID: 29799978 DOI: 10.1001/jamaneurol.2018.0983

Teaching Video NeuroImages: Purposeless groaning in progressive supranuclear palsy

Low SC, Tan AH, Lim SY

Neurology, 2017 01 03;88(1):e9.

PMID: 28025406 DOI: 10.1212/WNL.0000000000003465

Fulltext Improvement of "Bouncy Gait" in Lance-Adams Syndrome with Perampanel

Lim SY, Jasti DB, Tan AH

Cureus, 2020 Jan 25;12(1):e6773.

PMID: 32117660 DOI: 10.7759/cureus.6773

Lance-Adams syndrome (LAS) is chronic post-hypoxic myoclonus that is often associated with sudden lapses in muscle tone (negative myoclonus) in the legs, causing a disabling "bouncy gait." Given its relative rarity, there are no controlled treatment studies of LAS. The majority of cases require polypharmacy management, with an incomplete response. "Bouncy gait," in particular, is notoriously medication-refractory. Here, we report a patient with long-standing LAS who improved markedly when low-dose perampanel was added to his existing treatment regime consisting of clonazepam, levetiracetam, sodium valproate, and acetazolamide.

Fulltext Bilateral thalamic internal medullary lamina involvement in a case of dengue encephalitis

Sherrini Bazir Ahmad, Chin, Sum Cheong, Lim, Shen-Yang, Kartini Rahmat, FaizatulIzza Rozalli, Sekaran, Shamala Devi, et al.

Neurology Asia, 2016;21(4):374-379.

MyJurnal

There are 50-100 million dengue infections each year, but dengue encephalitis is relatively
uncommon. The aetiology of neuronal injury is proposed to be due to direct viral neurotropism or
host immune response-mediated inflammation causing neuronal damage. We report a case of severe
dengue encephalitis, presenting during the acute viraemic phase of the disease. This was associated
with inflammation and haemorrhage of the internal medullary lamina of both thalami which, to our
knowledge, has not yet been reported in other infections of the central nervous system.

Deep brain stimulation in Dopa-Responsive Parkinsonism - Look out for red flags: Expert commentary

Lim SY, Tan AH, Tay YW

Parkinsonism Relat Disord, 2023 Jan 10.

PMID: 36641339 DOI: 10.1016/j.parkreldis.2022.105276

The microbiome-gut-brain axis in Parkinson disease - from basic research to the clinic

Tan AH, Lim SY, Lang AE

Nat Rev Neurol, 2022 Aug;18(8):476-495.

PMID: 35750883 DOI: 10.1038/s41582-022-00681-2

Evidence for a close bidirectional link between the brain and the gut has led to a paradigm shift in neurology, especially in the case of Parkinson disease (PD), in which gastrointestinal dysfunction is a prominent feature. Over the past decade, numerous high-quality preclinical and clinical publications have shed light on the highly complex relationship between the gut and the brain in PD, providing potential for the development of new biomarkers and therapeutics. With the advent of high-throughput sequencing, the role of the gut microbiome has been specifically highlighted. Here, we provide a critical review of the literature on the microbiome-gut-brain axis in PD and present perspectives that will be useful for clinical practice. We begin with an overview of the gut-brain axis in PD, including the potential roles and interrelationships of the vagus nerve, α-synuclein in the enteric nervous system, altered intestinal permeability and inflammation, and gut microbes and their metabolic activities. The sections that follow synthesize the proposed roles of gut-related factors in the development and progression of, in responses to PD treatment, and as therapeutic targets. Finally, we summarize current knowledge gaps and challenges and delineate future directions for the field.

Fulltext Purposeless Groaning in Parkinson's Disease

Lim SY, Tan AH, Lim JL, Ahmad-Annuar A

J Mov Disord, 2018 May;11(2):87-88.

PMID: 29860787 DOI: 10.14802/jmd.18004

Purposeless groaning has been reported in advanced progressive supranuclear palsy. We present a case of purposeless groaning occurring as a primary complaint in a patient with advanced Parkinson's disease. Purposeless groaning is thought to be a manifestation of disinhibition and perseveration due to frontal-subcortical dysfunction. Proper recognition of this phenomenon will help clinicians to avoid unnecessary investigations and treatment (e.g., prescription of opioid medications).

Methylmalonic Aciduria: A Treatable Disorder of Which Adult Neurologists Need to Be Aware

Tan AH, Mah JSY, Thong MK, Lim SY

Mov Disord Clin Pract, 2015 09 16;3(1):104-105.

PMID: 30713905 DOI: 10.1002/mdc3.12237

Brief Clinical Rating Scales Should Not Be Overlooked

Lim SY, Lim KB, Hor JW, Tan AH

Mov Disord, 2020 10;35(10):1884-1885.

PMID: 33068479 DOI: 10.1002/mds.28274

Fulltext Probiotics for Parkinson's disease: Current evidence and future directions

Tan AH, Hor JW, Chong CW, Lim SY

JGH Open, 2021 Apr;5(4):414-419.

PMID: 33860090 DOI: 10.1002/jgh3.12450

The gut-brain axis is a hot topic in Parkinson's disease (PD). It has been postulated that gut pathogens and dysbiosis can contribute to peripheral inflammatory states or trigger downstream metabolic effects that exacerbate the neurodegenerative process in PD. Several preclinical and clinical studies have demonstrated disrupted intestinal permeability, intestinal inflammation, altered gut microbiome, and reduced fecal short-chain fatty acids in PD. In this regard, microbial-directed therapies such as probiotics are emerging as potential therapeutic options. Probiotic supplementation is postulated to confer a variety of health benefits due to the diverse functions of these live microorganisms, including inhibition of pathogen colonization, modulation/"normalization" of the microbiome and/or its function, immunomodulatory effects (e.g. reducing inflammation), and improved host epithelial barrier function. Interestingly, several PD animal model studies have demonstrated the potential neuroprotective effects of probiotics in reducing dopaminergic neuronal degeneration. Notably, two randomized placebo-controlled trials have provided class I evidence for probiotics as a treatment for constipation in PD. However, the effects of probiotics on other PD aspects, such as motor disability and cognitive function, and its long-term efficacy (including effects on PD drug absorption in the gut) have not been investigated adequately. Further targeted animal and human studies are also warranted to understand the mechanisms of actions of probiotics in PD and to tailor probiotic therapy based on individual host profiles to improve patient outcomes in this disabling disorder.

Fulltext A Hot Cross Bun sign from diffusion tensor imaging and tractography perspective

Loh KB, Rahmat K, Lim SY, Ramli N

Neurol India, 2011 Mar-Apr;59(2):266-9.

PMID: 21483130 DOI: 10.4103/0028-3886.79143

A "Hot Cross Bun" sign on T2-weighted MRI was described as a result of selective loss of myelinated transverse pontocerebellar fibers and neurons in the pontine raphe with preservation of the pontine tegmentum and corticospinal tracts (CST). However, neuropathologic studies showed contradicting results with no sparing of the CST. This is a pictorial and quantitative demonstration of the sign on diffusion tensor imaging and tractography, which provides the imaging evidence that is consistent with neuropathologic findings.

Involuntary movements in an elderly woman with recently diagnosed diabetes

Lim SY, Ramli N, Tai SM, Nair SR

J Clin Neurosci, 2011 Apr;18(4):539, 590.

PMID: 21476221

Idiopathic paroxysmal kinesigenic dyskinesia in Malaysia, a multi-racial Southeast Asian country

Tai ML, Lim SY, Tan CT

J Clin Neurosci, 2010 Aug;17(8):1089-90.

PMID: 20542699 DOI: 10.1016/j.jocn.2009.11.034

Paroxysmal kinesigenic dyskinesia is a rare disorder, and there are few reports of Asian patients with this condition. We reviewed the clinical features of all patients with idiopathic paroxysmal kinesigenic dyskinesia (PKD) seen at a major neurological centre in Malaysia. The charts of 11 patients with idiopathic PKD seen between 1995 and 2008 were reviewed retrospectively. The male:female ratio was 9:2. Ten patients were of Chinese ethnicity, and one was Malay. Three patients (from two families) had a family history of PKD. The involuntary movement was dystonia in 73% of patients. In one patient, attacks were precipitated by vestibular stimulation. One patient had generalized epilepsy. Another patient who did not have epilepsy demonstrated epileptiform discharges. Only slightly over one-quarter of patients had a positive family history. Males, and people of Chinese ancestry, seem to be affected more frequently by PKD in certain Asian populations.

Advice to People with Parkinson's in My Clinic: Probiotics and Prebiotics

Hor JW, Toh TS, Lim SY, Tan AH

J Parkinsons Dis, 2024 Aug 23.

PMID: 39213091 DOI: 10.3233/JPD-240172

There is increasing evidence that microbial-based therapies can be useful in people with Parkinson's disease (PD). In this viewpoint, we provide a state-of-the-art review of the clinical and pre-clinical evidence for probiotics and prebiotics in PD. Currently, short-term clinical studies, including double-blind placebo-controlled randomized clinical trials, have demonstrated safety, and efficacy primarily in improving constipation-related symptoms. Pre-clinical studies consistently reported improvements in a range of biological markers and outcomes, including evidence for attenuation of gut dysfunction and neuroprotection. Bacteria from the genus Lactobacillus and Bifidobacterium have been the most frequently studied both in clinical and pre-clinical probiotics studies, while research into prebiotics is still limited and primarily involved resistant starch and fructooligosaccharides. We provide practical suggestions for clinicians on how to advise patients in the clinic regarding these popular treatments, and important caveats to be aware of. Finally, areas for further advancements are highlighted. It is envisaged that in the future, microbial-based therapies may benefit from personalization based on an enhanced understanding of a whole range of host factors and host-microbiome interactions.

Authors' reply to "Perfection is the enemy of good - A Letter to the editor on "Orthostatic hypotension in Parkinson's disease: Sit-to-stand vs. supine-to-stand protocol and clinical correlates"

Lim SY, Lim KB, Hor JW, Tan AH

Parkinsonism Relat Disord, 2025 Feb;131:107221.

PMID: 39690080 DOI: 10.1016/j.parkreldis.2024.107221

Is there a link between progressive supranuclear palsy and bullous pemphigoid?

Han WH, Yong SS, Kwan Z, Lim SY

J Mov Disord, 2025 Apr 08.

PMID: 40194789 DOI: 10.14802/jmd.25019

Displaying publications 1 - 20 of 113 in total