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Paraneoplastic autoimmune movement disorders

Lim TT

Parkinsonism Relat Disord, 2017 Nov;44:106-109.
PMID: 29097081 DOI: 10.1016/j.parkreldis.2017.08.017

PURPOSE OF REVIEW: To provide an overview of paraneoplastic autoimmune disorders presenting with various movement disorders.
RECENT FINDINGS: The spectrum of paraneoplastic autoimmune disorders has been expanding with the discovery of new antibodies against cell surface and intracellular antigens. Many of these paraneoplastic autoimmune disorders manifest as a form of movement disorder. With the discovery of new neuronal antibodies, an increasing number of idiopathic or neurodegenerative movement disorders are now being reclassified as immune-mediated movement disorders. These include anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis which may present with orolingual facial dyskinesia and stereotyped movements, CRMP-5 IgG presenting with chorea, anti-Yo paraneoplastic cerebellar degeneration presenting with ataxia, anti-VGKC complex (Caspr2 antibodies) neuromyotonia, opsoclonus-myoclonus-ataxia syndrome, and muscle rigidity and episodic spasms (amphiphysin, glutamic acid decarboxylase, glycine receptor, GABA(A)-receptor associated protein antibodies) in stiff-person syndrome.
SUMMARY: Movement disorders may be a presentation for paraneoplastic autoimmune disorders. Recognition of these disorders and their common phenomenology is important because it may lead to the discovery of an occult malignancy.
Fulltext Adult-Onset Satoyoshi Syndrome and Axial Spondyloarthritis

Chee YC, Lim TT, Ong BH

J Clin Neurol, 2021 Oct;17(4):593-595.
PMID: 34595874 DOI: 10.3988/jcn.2021.17.4.593
Editorial: Inclusion, equity, diversity and social justice in movement disorders research

Miyasaki JM, Lim TT, Bhidayasiri R

Parkinsonism Relat Disord, 2021 04;85:114-116.
PMID: 33840573 DOI: 10.1016/j.parkreldis.2021.03.022
Exploring bedside clinical features of parkinsonism: A focus on differential diagnosis

Bhidayasiri R, Rattanachaisit W, Phokaewvarangkul O, Lim TT, Fernandez HH

Parkinsonism Relat Disord, 2019 Feb;59:74-81.
PMID: 30502095 DOI: 10.1016/j.parkreldis.2018.11.005

The proper diagnosis of parkinsonian disorders usually involves three steps: identifying core features of parkinsonism; excluding other causes; and collating supportive evidence based on clinical signs or investigations. While the recognition of cardinal parkinsonian features is usually straightforward, the appreciation of clinical features suggestive of specific parkinsonian disorders can be challenging, and often requires greater experience and skills. In this review, we outline the clinical features that are relevant to the differential diagnosis of common neurodegenerative parkinsonian disorders, including Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration. We aim to make this process relatable to clinicians-in-practice, therefore, have categorised the list of clinical features into groups according to the typical sequence on how clinicians would elicit them during the examination, starting with observation of facial expression and clinical signs of the face, spotting eye movement abnormalities, examination of tremors and jerky limb movements, and finally, examination of posture and gait dysfunction. This review is not intended to be comprehensive. Rather, we have focused on the most common clinical signs that are potentially key to making the correct diagnosis and those that do not require special skills or training for interpretation. Evidence is also provided, where available, such as diagnostic criteria, consensus statements, clinicopathological studies or large multi-centre registries. Pitfalls are also discussed when relevant to the diagnosis. While no clinical signs are pathognomonic for certain parkinsonian disorders, certain clinical clues may assist in narrowing a differential diagnosis and tailoring focused investigations for the individual patient.
A South East Asian perspective of neuropsychiatric startle syndromes of latah

Lim TT, Tan K, Eow GB, Bhidayasiri R

Parkinsonism Relat Disord, 2022 Jan 26.
PMID: 35120841 DOI: 10.1016/j.parkreldis.2022.01.013

Latah is a culture-specific syndrome characterized by exaggerated startle response, echolalia, palilalia, echopraxia, coprolalia, forced obedience and involuntary vocalization in response to startle. Latah is stimulus-induced and is associated with behavior and psychiatric features. The aim of this review is to provide a comprehensive description on latah from a regional perspective based on previous literature and clinical experiences and highlight the clinical characteristics of latah from a movement disorders perspective. The pathophysiology of latah is complex and poorly understood although psychological stressors have been implicated. In view of the distressing psychosocial impact of latah, this neuropsychiatric startle syndrome warrants further studies to understand the pathophysiology and identify the appropriate treatments.
Fulltext A Paradoxical Phenomenon: Hemichorea-Hemiballismus Resolution After Stroke in Moyamoya Disease

Por CY, Lim TT, Chee YC, Raymond AA

J Clin Neurol, 2023 Jul;19(4):410-412.
PMID: 37417437 DOI: 10.3988/jcn.2023.0009
Suprasellar lymphoma masquerading as tuberculosis of the central nervous system

Dang YL, Hor JY, Chia YK, Lim TT, Eow GB

Acta Neurol Belg, 2014 Sep;114(3):239-41.
PMID: 23757110 DOI: 10.1007/s13760-013-0217-3
A novel real-time monitoring and control system for waste-to-energy gasification process employing differential temperature profiling of a downdraft gasifier

Chan WP, Veksha A, Lei J, Oh WD, Dou X, Giannis A, et al.

J Environ Manage, 2019 Mar 15;234:65-74.
PMID: 30616190 DOI: 10.1016/j.jenvman.2018.12.107

A novel, cost-effective and real-time process monitoring and control system was developed to maintain stable operation of waste-to-energy gasification process. It comprised a feedback loop control that utilized the differential temperatures of the oxidation and reduction zones in the gasifier to determine the regional heat-flow (endothermic or exothermic), to assess the availability of oxidizing agent (for instance, air or O2) at the char bed and to calculate the fuel feeding rate. Based on the correlations developed, the air-to-fuel ratio or the equivalence air ratio (ER) for air gasification could be instantaneously adjusted to maintain stable operation of the gasifier. This study demonstrated a simplification of complex reaction dynamics in the gasification process to differential temperature profiling of the gasifier. The monitoring and control system was tested for more than 70 h of continuous operation in a downdraft fixed-bed gasifier with refuse-derived fuel (RDF) prepared from municipal solid wastes (MSW). With the system, fuel feeding rate could be adjusted accurately to stabilize the operating temperature and ER in the gasifier and generate syngas with consistent properties. Significant reductions in the fluctuations of temperature profiles at oxidation and reduction zones (from higher than 100 °C to lower than 50 °C), differential temperatures (from ±200 to ±50 °C) in gasifier and the flow rate (from 16 ± 6.5 to 12 ± 1.8 L/min), composition of main gas components, LHV (from 6.2 ± 3.1 to 5.7 ± 1.6 MJ/Nm3) and tar content (from 8.0 ± 9.7 to 7.5 ± 4.2 g/Nm3) of syngas were demonstrated. The developed gasifier monitoring and control system is adaptable to various types (updraft, downdraft, and fluidized-bed) and scales (lab, pilot, large scale) of gasifiers with different types of fuel.
Elucidation of stoichiometric efficiency, radical generation and transformation pathway during catalytic oxidation of sulfamethoxazole via peroxymonosulfate activation

Bao Y, Oh WD, Lim TT, Wang R, Webster RD, Hu X

Water Res, 2019 03 15;151:64-74.
PMID: 30594091 DOI: 10.1016/j.watres.2018.12.007

In this work, nano-bimetallic Co/Fe oxides with different stoichiometric Co/Fe ratios were prepared using a novel one-step solution combustion method. The nano-bimetallic Co/Fe oxides were used for sulfamethoxazole (SMX) degradation via peroxymonosulfate (PMS) activation. The stoichiometric efficiencies of the as-prepared nano-bimetallic catalysts were calculated and compared for the first time. The radical generation was identified by electron paramagnetic resonance (EPR) as well as chemical quenching experiments, in which different scavengers were used and compared. The catalytic PMS activation mechanism in the presence of catalyst was examined by Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The results showed that besides SO4•- and •OH, •OOH was also detected in the PMS/CoFeO2.5 system. Meanwhile, in addition to the previously proposed radical oxidation pathway, the results showed that SMX degradation also involved a non-radical oxidation, which could be verified by the degradation experiment without catalyst as well as the detection of 1O2. In the PMS activation process, cobalt functioned as the active site on CoFeO2.5 while Fe oxide functioned as the adsorption site. The electron transfer mechanism was proposed based on the XPS and metal leaching results. Additionally, via the detection of transformation products, different SMX transformation pathways involving nitration, hydroxylation and hydrolysis in the PMS/CoFeO2.5 system were proposed.
High-sulfur capacity and regenerable Zn-based sorbents derived from layered double hydroxide for hot coal gas desulfurization

Wu M, Chang B, Lim TT, Oh WD, Lei J, Mi J

J Hazard Mater, 2018 Oct 15;360:391-401.
PMID: 30130697 DOI: 10.1016/j.jhazmat.2018.08.015

The Zn-Al mixed metal oxide (ZnAl-MMO) with a plate-like structure was derived from Zn-Al layered double hydroxide. The ZnAl-MMO with a Zn/Al molar ratio of 3:1 exhibits superior absorption ability for H2S in a simulated coal gas at 600 ℃ due to the special structure of the ZnAl-MMO. Besides ZnS, elemental sulfur is also produced during the desulfurization process. The deactivation model could well simulate the absorption behavior of H2S. The sulfidation reaction over the sorbent shows large initial reaction rate constants (1110-5390 m3 min-1 kg-1) and low activation energy (29.5 kJ mol-1). The regeneration rate of the used sorbent can reach 99.8% under the optimum conditions. The regenerated sorbents still show high sulfur capacity (ca. 30%), implying its great application potential for industrial-scale desulfurization of the hot coal gas.
Multi-heteroatom-doped carbocatalyst as peroxymonosulfate and peroxydisulfate activator for water purification: A critical review

Choong ZY, Lin KA, Lisak G, Lim TT, Oh WD

J Hazard Mater, 2022 03 15;426:128077.
PMID: 34953256 DOI: 10.1016/j.jhazmat.2021.128077

Catalytic activation of peroxymonosulfate (PMS) and peroxydisulfate (PDS) (or collectively known as persulfate, PS) using carbocatalyst is increasingly gaining attention as a promising technology for sustainable recalcitrant pollutant removal in water. Single heteroatom doping using either N, S, B or P is widely used to enhance the performance of the carbocatalyst for PS activation. However, the performance enhancement from single heteroatom doping is limited by the type of heteroatom used. To further enhance the performance of the carbocatalyst beyond the limit of single heteroatom doping, multi-heteroatom doping can be conducted. This review aims to provide a state-of-the-art overview on the development of multi-heteroatom-doped carbocatalyst for PS activation. The potential synergistic and antagonistic interactions of various heteroatoms including N and B, N and S, N and P, and N and halogen for PS activation are evaluated. Thereafter, the preparation strategies to develop multi-heteroatom-doped carbocatalyst including one-step and multi-step preparation approaches along with the characterization techniques are discussed. Evidence and summary of the performance of multi-heteroatom-doped carbocatalyst for various recalcitrant pollutants removal via PS activation are also provided. Finally, the prospects of employing multi-heteroatom-doped carbocatalyst including the need to study the correlation between different heteroatom combination, surface moiety type, and amount of dopant with the PS activation mechanism, identifying the best heteroatom combination, improving the durability of the carbocatalyst, evaluating the feasibility for full-scale application, developing low-cost multi-heteroatom-doped carbocatalyst, and assessing the environmental impact are also briefly discussed.
Treatment of startle and related disorders

Lim TT, Por CY, Beh YY, Schee JP, Tan AH

Clin Park Relat Disord, 2023;9:100218.
PMID: 37808566 DOI: 10.1016/j.prdoa.2023.100218
Anti-hypertensive prescription practices in private hospitals in Malaysia: a prospective, non-interventional, observational study

Ng WK, Philip AZ, Lim TT, Wong M, Goh EL, Tengku Ismail TS, et al.

Med J Malaysia, 2023 May;78(3):350-356.
PMID: 37271845

INTRODUCTION: In managing hypertension, monotherapy and sometimes a combination of more than one agent are used to achieve blood pressure (BP) control. The objective of this prospective, observational, multi-centre study was to assess the level of BP control in patients receiving one or more anti-hypertensive drugs in private medical centres in Malaysia according to the treatment regimens (monotherapy, free drug combinations and single pill combinations).
MATERIALS AND METHODS: Data were collected through medical records and interview sessions with patients on current pharmacotherapy for hypertension management at baseline and 2-3 months later. Results are expressed as mean ± SD for continuous data and as frequencies and percentages for categorical data.
RESULTS: Among 182 recruited patients, 89 (49%) achieved BP control by the end of the study. Majority (62/89) patients were on single-pill (monotherapy or SPC) antihypertensives. Majority (63/89) required more than two antihypertensives to achieve BP control.
CONCLUSION: Both SPC and free drug combination antihypertensives reduced BPs, but physicians preferred SPC to improve BP control and increase treatment compliance.
Fulltext Tardive dyskinesia in Asia- current clinical practice and the role of neurologists in the care pathway

Bhidayasiri R, Phokaewvarangkul O, Shang HF, Lim TT, Cho JW, Pal PK, et al.

Front Neurol, 2024;15:1356761.
PMID: 38419696 DOI: 10.3389/fneur.2024.1356761

Tardive dyskinesia (TD) is a movement disorder that can arise as a side effect of treatment with dopamine receptor-blocking agents (DRBAs), including antipsychotic drugs (APDs) used to manage psychotic illnesses. Second-generation APDs (SGAs) are often preferred to first-generation drugs due to their lower propensity to cause TD, however many SGAs-treated patients still develop the condition. Although TD is a global health concern, evidence regarding the occurrence of TD and how it is managed in Asian countries is currently limited. This article reports the results of a systematic review of the published literature on TD focusing on its prevalence, types of patients, knowledge of the condition, causative factors, and usual treatment pathways in clinical practice in Asian countries. Epidemiological data suggest that the prevalence of TD is increasing globally due to an overall rise in APD use, contributing factors being polypharmacy with multiple APDs, the use of higher than necessary doses, and off-label use for non-psychotic indications. Although exact prevalence figures for TD in Asian countries are difficult to define, there is a similar pattern of rising APD use which will result in increasing numbers of TD patients in this region. These issues need to be addressed and strategies developed to minimize TD risk and manage this disabling condition which impacts patients' quality of life and daily functioning. To date, both research into TD has been predominantly psychiatry focused and the perspectives from neurologists regarding the clinical management of this challenging condition are scarce. However, neurologists have an essential role in managing the movement disorders manifestations that characterize TD. Optimum management of TD, therefore, should ideally involve collaboration between psychiatrists and neurologists in joint care pathways, wherever practical. Collaborative pathways are proposed in this article, and the challenges that will need to be addressed in Asian countries to improve the care of people with TD are highlighted, with a focus on the neurologist's viewpoint and the implications for the management of TD globally.
Fulltext Neurological perspectives should be integrated into the management of tardive dyskinesia - expert opinion and proposed educational initiatives in Asia

Bhidayasiri R, Phokaewvarangkul O, Lim TT, Pal PK, Watanabe H, Cho JW, et al.

J Mov Disord, 2024 Apr 11.
PMID: 38600683 DOI: 10.14802/jmd.24068
A previously misdiagnosed cohort of aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder with disease duration of >10 years in multi-ethnic Penang, Malaysia: Clinical features and disease course

Hor JY, Lim TT, Chow HB, Tan K, Cheah CF, Ching YM, et al.

Mult Scler Relat Disord, 2016 Jan;5:89-90.
PMID: 26856950 DOI: 10.1016/j.msard.2015.11.008
Eleven episodes of recurrent optic neuritis of the same eye for 22 years eventually diagnosed as neuromyelitis optica spectrum disorder

Yew YC, Hor JY, Lim TT, Kanesalingam R, Ching YM, Arip M, et al.

Mult Scler Relat Disord, 2016 Nov;10:22-25.
PMID: 27919493 DOI: 10.1016/j.msard.2016.08.009

It is difficult to predict whether a particular attack of neuromyelitis optica spectrum disorder (NMOSD) will affect the optic nerve [optic neuritis (ON): unilateral or bilateral], spinal cord (myelitis), brain or brainstem, or a combination of the above. We report an interesting case of recurrent ON of the same eye for a total of 11 episodes in a Chinese woman. Over a period of 22 years, the attacks only involved the left eye, and never the right eye and also no myelitis. For a prolonged duration, she was diagnosed as recurrent idiopathic ON. Only until she was tested positive for aquaporin 4 antibody that her diagnosis was revised to NMOSD. Optical coherence tomography revealed thinning of the retinal nerve fibre layer (RNFL) for the affected left eye, while the RNFL thickness was within normal range for the unaffected right eye. The disability accrual in NMOSD is generally considered to be attack-related - without a clinical attack of ON, there shall be no visual impairment, and no significant subclinical thinning of RNFL. Our case is in agreement with this notion. This is in contrast to multiple sclerosis where subclinical RNFL thinning does occur. This case highlights the importance of revisiting and questioning a diagnosis of recurrent idiopathic ON particularly when new diagnostic tools are available.
From parasomnia to agrypnia excitata - An illustrative case on diagnostic approach

Fong SL, Dy Closas AMF, Lim TT, Lean PL, Loh EC, Lim SY, et al.

Parkinsonism Relat Disord, 2023 Apr;109:105332.
PMID: 36948111 DOI: 10.1016/j.parkreldis.2023.105332

The diagnostic approach to sleep-related movements disorders is seldom discussed. We report a case of fatal familial insomnia who initially presented with persistent limb movements in sleep, which later progressed to a state of agrypnia excitata. Here, the evaluation of abnormal movements in sleep is discussed using a step-by-step diagnostic approach. Although no cure is available for fatal familial insomnia, prompt recognition of this condition is important to facilitate proper management, including the involvement of interdisciplinary neuropalliative care.
Thymoma-associated myasthenia gravis and LGI1-encephalitis, with nephrotic syndrome post-thymectomy

Hor JY, Lim TT, Cheng MC, Chia YK, Wong CK, Lim SM, et al.

J Neuroimmunol, 2018 04 15;317:100-102.
PMID: 29395322 DOI: 10.1016/j.jneuroim.2018.01.011

Thymoma is associated with a wide spectrum of autoimmune paraneoplastic syndromes, though it is uncommon for multiple paraneoplastic syndromes to be present in a single individual. We report a rare case of an elderly gentleman who was found to have thymoma-associated myasthenia gravis and LGI1-encephalitis with myokymia, who presented with nephrotic syndrome (minimal change glomerulopathy) after thymectomy. The latter two paraneoplastic syndromes had manifested when prednisolone was tapered down to low dose. This case serves to remind neurologists that apart from paraneoplastic neurological manifestations, thymoma may also be associated with renal disease. Nephropathy in myasthenia patients with thymoma should be properly evaluated, as it is treatable with immunotherapy, and it may even occur post-thymectomy.
Prevalence of neuromyelitis optica spectrum disorder in the multi-ethnic Penang Island, Malaysia, and a review of worldwide prevalence

Hor JY, Lim TT, Chia YK, Ching YM, Cheah CF, Tan K, et al.

Mult Scler Relat Disord, 2018 Jan;19:20-24.
PMID: 29100047 DOI: 10.1016/j.msard.2017.10.015

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) occurs worldwide in all ethnicities. Recently, population-based studies have shown that NMOSD is more common among non-White populations. There is scarce data about NMOSD prevalence in South East Asian populations.
METHODS: (1) A population-based study was undertaken to estimate NMOSD prevalence in the multi-ethnic Penang Island, Malaysia, comprising Chinese, Malays, and Indians. Medical records of NMOSD patients followed up at the Penang General Hospital (the neurology referral centre in Penang Island) were reviewed. The 2015 diagnostic criteria of the International Panel for NMO Diagnosis were used for case ascertainment. (2) A review of population-based prevalence studies of NMOSD worldwide was carried out. PubMed and conference proceedings were searched for such studies.
RESULTS: Of the 28 NMOSD patients, 14 were residents of Penang Island on prevalence day [13 (93%) Chinese and one (7%) Malay]. All 14 patients were females and aquaporin 4 seropositive. The prevalence of NMOSD in Penang Island was 1.99/100,000 population; according to ethnicities, the prevalence in Chinese was significantly higher than in Malays (3.31/100,000 vs 0.43/100,000, respectively, p = 0.0195).
CONCLUSION: Based on our and other population-based studies, among Asians, East Asian origin populations (Chinese and Japanese) appear to have higher NMOSD prevalence than other Asian ethnic groups. Worldwide, Blacks seem to have the highest NMOSD prevalence. More studies in different geographical regions and ethnic groups will be useful to further inform about potential factors in NMOSD pathogenesis.

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