Displaying all 13 publications

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  1. French IT, Muthusamy KA
    PMID: 27242523 DOI: 10.3389/fnagi.2016.00114
    Sleep is an indispensable normal physiology of the human body fundamental for healthy functioning. It has been observed that Parkinson's disease (PD) not only exhibits motor symptoms, but also non-motor symptoms such as metabolic irregularities, altered olfaction, cardiovascular dysfunction, gastrointestinal complications and especially sleep disorders which is the focus of this review. A good understanding and knowledge of the different brain structures involved and how they function in the development of sleep disorders should be well comprehended in order to treat and alleviate these symptoms and enhance quality of life for PD patients. Therefore it is vital that the normal functioning of the body in relation to sleep is well understood before proceeding on to the pathophysiology of PD correlating to its symptoms. Suitable treatment can then be administered toward enhancing the quality of life of these patients, perhaps even discovering the cause for this disease.
  2. Goo ZQ, Muthusamy KA
    J Clin Neurosci, 2022 Feb 15;98:162-167.
    PMID: 35182846 DOI: 10.1016/j.jocn.2022.02.011
    INTRODUCTION: Tracheostomy is performed in patients with prolonged mechanical ventilation, who suffered catastrophic neurologic insult or upper airway obstruction. Thus far, there is no consensus on the optimal timing in performing a tracheostomy. This study aims to test whether early tracheostomy in mechanically ventilated patients in a neurosurgical setting would be associated with a shorter time of mechanical ventilation as compared to standard tracheostomy.

    METHODS: This single-center prospective randomized controlled trial was conducted at University Malaya Medical Centre from July 2019 to July 2021. The likelihood of prolonged ventilation was determined objectively using the TRACH score and the patient's clinical presentation. The outcomes measured were days of mechanical ventilation post-tracheostomy, days of neuro-intensive care unit stay, and days of hospital stay. Tracheostomy-related complications were collected. The data collected were analyzed using Statistical Package for the Social Sciences version 25 for Windows (SPSS Inc., Chicago, IL, USA).

    RESULTS: In all, 39 patients were randomly assigned. Of these, 20 were allocated to the early tracheostomy group (ET) and 19 were allocated to the standard tracheostomy group (ST). The demographic characteristics were similar between the groups. The primary outcome, mean (SD) days of mechanical ventilation post-tracheostomy, was statistically different in the 2 groups- early 11.9 (9.3) days, standard 18.9 (32.5) days; p = 0.014. There were comparable tracheostomy-related complications in both groups.

    CONCLUSION: Early tracheostomy is associated with a shorter duration of mechanical ventilation in a neurosurgical intensive care unit setting.

  3. French IT, Muthusamy KA
    PMID: 29755338 DOI: 10.3389/fnagi.2018.00099
    The pedunculopontine nucleus (PPN) is situated in the upper pons in the dorsolateral portion of the ponto-mesencephalic tegmentum. Its main mass is positioned at the trochlear nucleus level, and is part of the mesenphalic locomotor region (MLR) in the upper brainstem. The human PPN is divided into two subnuclei, the pars compacta (PPNc) and pars dissipatus (PPNd), and constitutes both cholinergic and non-cholinergic neurons with afferent and efferent projections to the cerebral cortex, thalamus, basal ganglia (BG), cerebellum, and spinal cord. The BG controls locomotion and posture via GABAergic output of the substantia nigra pars reticulate (SNr). In PD patients, GABAergic BG output levels are abnormally increased, and gait disturbances are produced via abnormal increases in SNr-induced inhibition of the MLR. Since the PPN is vastly connected with the BG and the brainstem, dysfunction within these systems lead to advanced symptomatic progression in Parkinson's disease (PD), including sleep and cognitive issues. To date, the best treatment is to perform deep brain stimulation (DBS) on PD patients as outcomes have shown positive effects in ameliorating the debilitating symptoms of this disease by treating pathological circuitries within the parkinsonian brain. It is therefore important to address the challenges and develop this procedure to improve the quality of life of PD patients.
  4. Muthusamy KA, Waran V, Puthucheary SD
    J Clin Neurosci, 2007 Dec;14(12):1213-5.
    PMID: 17964168
    Burkholderia pseudomallei infection of the central nervous system (CNS) is rare with less than 50 cases reported over the last 30 years. The retrospective melioidosis study at University Malaya Medical Centre has documented three cases of CNS melioidosis out of more than 160 cases of melioidosis since 1978. There were two patients with brain abscess and one with spinal epidural abscess. The predisposing factors were: one patient was an aboriginal farmer and the other two were diabetic. Their age ranged from 17 to 45 years. Prominent neurological features were limb weakness, cranial nerve palsy (6th and 7th) and visual disturbance. CT brain scan and MRI spine showed abscess formation, subdural collection, and spinal epidural collection, osteomyelitis of vertebra and occipital bone and also sagital sinus thrombosis. All these patients underwent surgical drainage leading to bacteriological diagnosis as well as appropriate long-term antibiotic therapy. All had good recovery at 6 months after completion of treatment.
  5. Muthusamy KA, Lian LH, Vairavan N, Chua KH, Waran V
    Genet. Mol. Res., 2012;11(3):2939-45.
    PMID: 22782629
    Studies of genetic mutations that have been used in predicting glioma prognosis have revealed a complex relationship between clinical and genetic factors. Epidermal growth factor (EGF) and the NAT2 gene play a central role in carcinogenesis. An adenine (A) to guanine (G) single nucleotide polymorphism at position 61 in the 5'-untranslated region (5'-UTR) of the EGF gene has been found to be associated with levels of EGF production, and the mutations in the NAT2 gene have been postulated as a risk factor for cancer. We investigated EGF and the NAT2 gene in 13 glioma tissue samples and 12 normal controls. In the EGF 5'-UTR 61G polymorphism, the heterozygote GA was the most common genotype in the glioma patients. In the NAT2 polymorphism at nucleotide position 857G/A, the G allele and the GG genotype were the most prevalent forms in both the glioma and normal samples. We did not find any homozygous AA genotypes in the glioma patients. Based on this preliminary evidence, the EGF 5'-UTR at position 61 and the NAT2 SNP at position 857 polymorphisms are associated with increased risk for glioma.
  6. Waran V, Narayanan V, Karuppiah R, Thambynayagam HC, Muthusamy KA, Rahman ZA, et al.
    Simul Healthc, 2015 Feb;10(1):43-8.
    PMID: 25514588 DOI: 10.1097/SIH.0000000000000060
    Training in intraventricular endoscopy is particularly challenging because the volume of cases is relatively small and the techniques involved are unlike those usually used in conventional neurosurgery. Present training models are inadequate for various reasons. Using 3-dimensional (3D) printing techniques, models with pathology can be created using actual patient's imaging data. This technical article introduces a new training model based on a patient with hydrocephalus secondary to a pineal tumour, enabling the models to be used to simulate third ventriculostomies and pineal biopsies.
  7. Waran V, Tang IP, Karuppiah R, Abd Kadir KA, Chandran H, Muthusamy KA, et al.
    Br J Neurosurg, 2013 Dec;27(6):742-6.
    PMID: 23647078 DOI: 10.3109/02688697.2013.791667
    Abstract The endoscopic transnasal, transsphenoidal surgical technique for pituitary tumour excision has generally been regarded as a less invasive technique, ranging from single nostril to dual nostril techniques. We propose a single nostril technique using a modified nasal speculum as a preferred technique. We initially reviewed 25 patients who underwent pituitary tumour excision, via endoscopic transnasal transsphenoidal surgery, using this new modified speculum-guided single nostril technique. The results show shorter operation time with reduced intra- and post-operative nasal soft tissue injuries and complications.
  8. Mehbodniya A, Moghavvemi M, Narayanan V, Muthusamy KA, Hamdi M, Waran V
    World Neurosurg, 2020 Feb;134:e379-e386.
    PMID: 31639505 DOI: 10.1016/j.wneu.2019.10.080
    OBJECTIVES: The evaluation of sources of error when preparing, printing, and using 3-dimensional (3D) printed head models for training purposes.

    METHODS: Two 3D printed models were designed and fabricated using actual patient imaging data with reference marker points embedded artificially within these models that were then registered to a surgical navigation system using 3 different methods. The first method uses a conventional manual registration, using the actual patient's imaging data. The second method is done by directly scanning the created model using intraoperative computed tomography followed by registering the model to a new imaging dataset manually. The third is similar to the second method of scanning the model but eventually uses an automatic registration technique. The errors for each experiment were then calculated based on the distance of the surgical navigation probe from the respective positions of the embedded marker points.

    RESULTS: Errors were found in the preparation and printing techniques, largely depending on the orientation of the printed segment and postprocessing, but these were relatively small. Larger errors were noted based on a couple of variables: if the models were registered using the original patient imaging data as opposed to using the imaging data from directly scanning the model (1.28 mm vs. 1.082 mm), and the accuracy was best using the automated registration techniques (0.74 mm).

    CONCLUSION: Spatial accuracy errors occur consistently in every 3D fabricated model. These errors are derived from the fabrication process, the image registration process, and the surgical process of registration.

  9. Waran V, Devaraj P, Hari Chandran T, Muthusamy KA, Rathinam AK, Balakrishnan YK, et al.
    J Clin Neurosci, 2012 Apr;19(4):574-7.
    PMID: 22305869 DOI: 10.1016/j.jocn.2011.07.031
    In neurosurgery and ear, nose and throat surgery the application of computerised navigation systems for guiding operations has been expanding rapidly. However, suitable models to train surgeons in using navigation systems are not yet available. We have developed a technique using an industrial, rapid prototyping process from which accurate spatial models of the cranium, its contents and pathology can be reproduced for teaching. We were able to register, validate and navigate using these models with common available navigation systems such as the Medtronic StealthStation S7®.
  10. Lim SY, Lim JL, Ahmad-Annuar A, Lohmann K, Tan AH, Lim KB, et al.
    Neurodegener Dis, 2020;20(1):39-45.
    PMID: 32580205 DOI: 10.1159/000508131
    Pathogenic and risk variants in the LRRK2 gene are among the main genetic contributors to Parkinson's disease (PD) worldwide, and LRRK2-targeted therapies for patients with PARK-LRRK2are now entering clinical trials. However, in contrast to the LRRK2 G2019S mutation commonly found in Caucasians, North-African Arabs, and Ashkenazi Jews, relatively little is known about other causative LRRK2 mutations, and data on genotype-phenotype correlations are largely lacking. This report is from an ongoing multicentre study in which next-generation sequencing-based PD gene panel testing has so far been conducted on 499 PD patients of various ethnicities from Malaysia. We describe 2 sisters of Chinese ancestry with PD who carry the R1441C mutation in LRRK2 (which in Asians has been reported in only 2 Chinese patients previously), and highlight interesting clinical observations made over a decade of close follow-up. We further explored the feasibility of using a brief, expert-administered rating scale (the Clinical Impression of Severity Index; CISI-PD) to capture data on global disease severity in a large (n = 820) unselected cohort of PD patients, including severely disabled individuals typically excluded from research studies. All patients in this study were managed and evaluated by the same PD neurologist, and these data were used to make broad comparisons between the monogenic PD cases versus the overall "real world" PD cohort. This report contributes to the scarce literature on R1441C PARK-LRRK2, offering insights into natural history and epidemiological aspects, and provides support for the application of a simple and reliable clinical tool that can improve the inclusion of under-represented patient groups in PD research.
  11. Closas AMFD, Lohmann K, Tan AH, Ibrahim NM, Lim JL, Tay YW, et al.
    J Mov Disord, 2023 Jan;16(1):91-94.
    PMID: 36537064 DOI: 10.14802/jmd.22109
    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.
  12. Lim JL, Lohmann K, Tan AH, Tay YW, Ibrahim KA, Abdul Aziz Z, et al.
    J Neural Transm (Vienna), 2022 Jan;129(1):37-48.
    PMID: 34779914 DOI: 10.1007/s00702-021-02421-0
    GBA variants are associated with increased risk and earlier onset of Parkinson's disease (PD), and more rapid disease progression especially with "severe" variants typified by p.L483P. GBA mutation screening studies from South-East Asia, with > 650 million inhabitants of diverse ancestries, are very limited. We investigated the spectrum of GBA variants, and associated clinico-demographic features, in a multi-ethnic PD cohort in Malaysia. Patients (n = 496) were recruited from seven centres, primarily of Chinese (45%), Malay (37%), and Indian (13%) ethnicities. All GBA coding exons were screened using a next-generation sequencing-based PD gene panel and verified with Sanger sequencing. We identified 14 heterozygous GBA alleles consisting of altogether 17 missense variants (8 classified as pathogenic or likely pathogenic for PD) in 25 (5.0%) patients, with a substantially higher yield among early (
  13. Tay YW, Tan AH, Lim JL, Lohmann K, Ibrahim KA, Abdul Aziz Z, et al.
    Parkinsonism Relat Disord, 2023 Jun;111:105399.
    PMID: 37209484 DOI: 10.1016/j.parkreldis.2023.105399
    BACKGROUND: About 5-10% of Parkinson's disease (PD) cases are early onset (EOPD), with several genes implicated, including GBA1, PRKN, PINK1, and SNCA. The spectrum and frequency of mutations vary across populations and globally diverse studies are crucial to comprehensively understand the genetic architecture of PD. The ancestral diversity of Southeast Asians offers opportunities to uncover a rich PD genetics landscape, and identify common regional mutations and new pathogenic variants.

    OBJECTIVES: This study aimed to investigate the genetic architecture of EOPD in a multi-ethnic Malaysian cohort.

    METHODS: 161 index patients with PD onset ≤50 years were recruited from multiple centers across Malaysia. A two-step approach to genetic testing was used, combining a next-generation sequencing-based PD gene panel and multiplex ligation-dependent probe amplification (MLPA).

    RESULTS: Thirty-five patients (21.7%) carried pathogenic or likely pathogenic variants involving (in decreasing order of frequency): GBA1, PRKN, PINK1, DJ-1, LRRK2, and ATP13A2. Pathogenic/likely pathogenic variants in GBA1 were identified in thirteen patients (8.1%), and were also commonly found in PRKN and PINK1 (11/161 = 6.8% and 6/161 = 3.7%, respectively). The overall detection rate was even higher in those with familial history (48.5%) or age of diagnosis ≤40 years (34.8%). PRKN exon 7 deletion and the PINK1 p.Leu347Pro variant appear to be common among Malay patients. Many novel variants were found across the PD-related genes.

    CONCLUSIONS: This study provides novel insights into the genetic architecture of EOPD in Southeast Asians, expands the genetic spectrum in PD-related genes, and highlights the importance of diversifying PD genetic research to include under-represented populations.

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