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Fulltext Dysfunctional problem-based learning curricula: resolving the problem

Lim WK

BMC Med Educ, 2012;12:89.
PMID: 23009729 DOI: 10.1186/1472-6920-12-89

Problem-based learning (PBL) has become the most significant innovation in medical education of the past 40 years. In contrast to exam-centered, lecture-based conventional curricula, PBL is a comprehensive curricular strategy that fosters student-centred learning and the skills desired in physicians. The rapid spread of PBL has produced many variants. One of the most common is 'hybrid PBL' where conventional teaching methods are implemented alongside PBL. This paper contends that the mixing of these two opposing educational philosophies can undermine PBL and nullify its positive benefits. Schools using hybrid PBL and lacking medical education expertise may end up with a dysfunctional curriculum worse off than the traditional approach.
GPCR drug discovery: novel ligands for CNS receptors

Lim WK

Recent Pat CNS Drug Discov, 2007 Jun;2(2):107-12.
PMID: 18221221

G protein-coupled receptors (GPCRs) are the largest class of cell surface receptors in humans. They convey extracellular signals into the cell interior by activating intracellular processes such as heterotrimeric G protein-dependent signaling pathways. They are widely distributed in the nervous system, and mediate key physiological processes including cognition, mood, appetite, pain and synaptic transmission. With at least 30% of marketed drugs being GPCR modulators, they are a major therapeutic target in the pharmaceutical industry's drug discovery programs. This review will survey recently patented ligands for GPCRs implicated in CNS disorders, in particular the metabotropic glutamate, adenosine and cannabinoid receptors. Metabotropic glutamate receptors regulate signaling by glutamate, the major excitatory brain neurotransmitter, while adenosine is a ubiquitous neuromodulater mediating diverse physiological effects. Recent patents for ligands of these receptors include mGluR5 antagonists and adenosine A(1) receptor agonists. Cannabinoid receptors remain one of the most important GPCR drug discovery target due to the intense interest in CB(1) receptor antagonists for treating obesity and metabolic syndrome. Such small molecule ligands are the outcome of the continuing focus of many pharmaceutical companies to identify novel GPCR agonist, antagonist or allosteric modulators useful for CNS disorders, for which more effective drugs are eagerly awaited.
Fulltext Problem Based Learning in Medical Education: Handling Objections and Sustainable Implementation

Lim WK

Adv Med Educ Pract, 2023;14:1453-1460.
PMID: 38164409 DOI: 10.2147/AMEP.S444566

The introduction of problem-based learning (PBL) in 1969 is considered the greatest innovation in medical education of the past 50 years. Since then, PBL has been implemented in different educational settings across virtually all health professions. However, some PBL schools gradually faced resistance from academic staff who were more familiar with traditional teacher-centred curricula. At times this has resulted in reversion to tradition or compromise whereby PBL is implemented within a lecture-based curriculum. Resistance can also emerge in a traditional school when a PBL curriculum is being considered for implementation. One of the first signs of this erosion is doubts about PBL raised in the form of objections or criticisms. This perspective review describes eight objections raised to assert why PBL is inferior or untenable. The background to each objection is provided together with evidence-informed rebuttals derived from professional practice and the published literature. Best practices are discussed for sustainable management of a PBL-based curriculum. A well-implemented PBL curriculum with appropriate and cost-effective infrastructure, training, teaching-learning activities, and assessment will position schools to harness the full benefit of PBL in training medical and health professionals.
Regression of a sphenochoanal polyp in a child

Lim WK, Sdralis T

Laryngoscope, 2004 May;114(5):903-5.
PMID: 15126753

To present an unusual case of a sphenochoanal polyp that regressed and review the etiology of such polyps in comparison to the commoner antrochoanal polyp.
Fulltext Optimisation of a PC12 cell-based in vitro stroke model for screening neuroprotective agents

Chua P, Lim WK

Sci Rep, 2021 04 14;11(1):8096.
PMID: 33854099 DOI: 10.1038/s41598-021-87431-4

Stroke causes death and disability globally but no neuroprotectant is approved for post-stroke neuronal injury. Neuroprotective compounds can be identified using oxygen glucose deprivation (OGD) of neuronal cells as an in vitro stroke model. Nerve growth factor (NGF)-differentiated PC12 pheochromocytoma cells are frequently used. However, investigators often find their clonal variant undifferentiable and are uncertain of optimal culture conditions. Hence we studied 3 commonly used PC12 variants: PC12 Adh, PC12 from Riken Cell Bank (PC12 Riken) and Neuroscreen-1 (NS-1) cells. We found DMEM the optimal media for PC12 Riken and NS-1 cells. Using a novel serum-free media approach, we identified collagen IV as the preferred adhesive substrate for both cell lines. We found PC12 Adh cells cannot attach without serum and is unable to differentiate using NGF. NS-1 cells differentiated to a maximal 72.7 ± 5.2% %, with substantial basal differentiation. We optimised differentiated NS-1 cells for an in vitro stroke model using 3 h of OGD resulting in ~ 70% viable cells. We screened 5 reported neuroprotectants and provide the first report that serotonin is antiapoptotic in a stroke model and the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) is neuroprotective in PC12 cells. Thus we demonstrate the optimisation and validation for a PC12 cell-based in vitro stroke model.
Fulltext The strategic uses of collagen in adherent cell cultures

Chua P, Lim WK

Cell Biol Int, 2023 Feb;47(2):367-373.
PMID: 36423248 DOI: 10.1002/cbin.11966

The culture of adherent mammalian cells involves adhesion to the tissue culture vessel. This requires attachment factors from serum and/or a suitable substrate on the vessel surface. Some cells require collagen or other substrates to promote neurite outgrowth, differentiation or growth. However, laboratories often lack guidance on the selection and/or optimisation of collagen. We model such selection/optimisation work in the PC12 neuronal cell line. PC12 (NS-1 variant) cells require a substrate for adherence. Comparing cell attachment against a series of substrates, we found collagen IV to be optimal. We show by comparison of morphology against a range of concentrations that 10 µg/ml is sufficient for supporting cell attachment, and also differentiation. PC12 cells from Riken Cell Bank do not require a substrate for routine culturing but only for differentiation. As all substrates supported attachment equally well, we used a novel serum-free approach and identified collagen IV as its preferred substrate. For these cells, Dulbecco's modified eagle's medium but not Roswell Park Memorial Institute (RPMI) media supports normal cell attachment. However, coating with collagen IV enabled the cells to grow equally well in RPMI. Hence the strategic use of collagen is essential in laboratories working with anchorage-dependent cell lines.
Image signal-to-noise ratio estimation using Shape-Preserving Piecewise Cubic Hermite Autoregressive Moving Average model

Sim KS, Wee MY, Lim WK

Microsc Res Tech, 2008 Oct;71(10):710-20.
PMID: 18615490 DOI: 10.1002/jemt.20610

We propose to cascade the Shape-Preserving Piecewise Cubic Hermite model with the Autoregressive Moving Average (ARMA) interpolator; we call this technique the Shape-Preserving Piecewise Cubic Hermite Autoregressive Moving Average (SP2CHARMA) model. In a few test cases involving different images, this model is found to deliver an optimum solution for signal to noise ratio (SNR) estimation problems under different noise environments. The performance of the proposed estimator is compared with two existing methods: the autoregressive-based and autoregressive moving average estimators. Being more robust with noise, the SP2CHARMA estimator has efficiency that is significantly greater than those of the two methods.
An impacted fish bone in the subglottis manifesting as protracted stridor: photodocumentation

Rahmat O, Lim WK, Prepageran N

Ear Nose Throat J, 2007 May;86(5):264.
PMID: 17580799
Fulltext Stenting of vertical vein in an infant with obstructed supracardiac total anomalous pulmonary venous drainage

Lim WK, Leong MC, Samion H

Ann Pediatr Cardiol, 2016 5 24;9(2):183-5.
PMID: 27212859 DOI: 10.4103/0974-2069.173549

A 1.7 kg infant with obstructed supracardiac total anomalous pulmonary venous drainage (TAPVD) presented with severe pulmonary hypertension secondary to vertical vein obstruction. The child, in addition, had a large omphalocele that was being managed conservatively. The combination of low weight, unoperated omphalocele, and severe pulmonary hypertension made corrective cardiac surgery very high-risk. Therefore, transcatheter stenting of the stenotic vertical vein, as a bridge to corrective surgery was carried out. The procedure was carried out through the right internal jugular vein (RIJ). The stenotic segment of the vertical vein was stented using a coronary stent. After procedure, the child was discharged well to the referred hospital for weight gain and spontaneous epithelialization of the omphalocele. Stenting of the vertical vein through the internal jugular vein can be considered in very small neonates as a bridge to repair obstructed supracardiac total anomalous venous drainage.
Fulltext Melioidosis of the head and neck

Lim WK, Gurdeep GS, Norain K

Med J Malaysia, 2001 Dec;56(4):471-7.
PMID: 12014768

Melioidosis is a potentially deadly infection that can affect any organ system. Reports of melioidosis of the ENT/head and neck region are relatively uncommon. Four cases are presented: (i) parotid abscess evolving into necrotising fasciitis, (ii) acute sinusitis and parapharyngeal cellulitis resulting in upper airway obstruction, (iii) acute suppurative lymphadenitis (iv) and chronic suppurative otitis media causing meningoencephalitis. Three of the four cases are believed to be unique, as a literature review of melioidosis in ENT/head and neck is also presented. Some practical issues of management are also discussed. Not suspecting melioidosis does not change contemporary empirical broadspectrum antibiotic therapy. The value of suspicion or on confirmation of diagnosis lies in anticipating and planning for rapid change.
Regulation of G protein signaling by the 70kDa heat shock protein

Lim WK, Kanelakis KC, Neubig RR

Cell Signal, 2013 Feb;25(2):389-96.
PMID: 23153586 DOI: 10.1016/j.cellsig.2012.11.002

G protein-coupled receptors (GPCRs) transduce extracellular signals to the interior of the cell by activating membrane-bound guanine nucleotide-binding regulatory proteins (G proteins). An increasing number of proteins have been reported to bind to and regulate GPCRs. We report a novel regulation of the alpha(2A) adrenergic receptor (α(2A)-R) by the ubiquitous stress-inducible 70kDa heat shock protein, hsp70. Hsp70, but not hsp90, attenuated G protein-dependent high affinity agonist binding to the α(2A)-R in Sf9 membranes. Antagonist binding was unchanged, suggesting that hsp70 uncouples G proteins from the receptor. As hsp70 did not bind G proteins but complexed with the α(2A)-R in intact cells, a direct interaction with the receptor seems likely. In the presence of hsp70, α(2A)-R-catalyzed [(35)S]GTPγS binding was reduced by approximately 70%. In contrast, approximately 50-fold higher concentrations of hsp70 were required to reduce agonist binding to the stress-inducible 5-hydroxytryptamine(1A) receptor (5-HT(1A)-R). In heat-stressed CHO cells, the α(2A)-R was significantly uncoupled from G proteins, coincident with an increased localization of hsp70 at the membrane. The contrasting effect of hsp70 on the α(2A)-R compared to the 5-HT(1A)-R suggests that during stress, upregulation of hsp70 may attenuate signaling from specific GPCRs as part of the stress response to foster survival.
Fulltext Emergency stenting of vertical vein in a neonate with obstructed supracardiac total anomalous pulmonary venous drainage

Lim WK, Wong MN, Tan SK

Med J Malaysia, 2014 Jun;69(3):138-9.
PMID: 25326356 MyJurnal

A late preterm newborn baby presented with respiratory distress and increasing cyanosis within 2 hours of birth. Bedside transthroracic echocardiography showed a critically obstructed vertical vein in a supracardiac total anomalous pulmonary venous drainage (TAPVd). Emergency stenting of the vertical vein was successfully performed at 24 hours of life.
Fulltext Performance of new signal-to-noise ratio estimation for SEM images based on single image noise cross-correlation

Sim KS, Nia ME, Tso CP, Lim WK

J Microsc, 2012 Nov;248(2):120-8.
PMID: 22900970 DOI: 10.1111/j.1365-2818.2012.03657.x

A new technique for estimation of signal-to-noise ratio in scanning electron microscope images is reported. The method is based on the image noise cross-correlation estimation model recently developed. We derive the basic performance limits on a single image signal-to-noise ratio estimation using the Cramer-Rao inequality. The results are compared with those from existing estimation methods including the nearest neighbourhood (the simple method), the first order linear interpolator, and the autoregressive based estimator. The comparisons were made using several tests involving different images within the performance bounds. From the results obtained, the efficiency and accuracy of image noise cross-correlation estimation technique is considerably better than the other three methods.
Real-time image quality assessment with mixed Lagrange time delay estimation autoregressive (MLTDEAR) model

Sim KS, Tso CP, Tan YY, Lim WK

J Microsc, 2007 Jun;226(Pt 3):230-43.
PMID: 17535262

A proposal to assess the quality of scanning electron microscope images using mixed Lagrange time delay estimation technique is presented. With optimal scanning electron microscope scan rate information, online images can be quantified and improved. The online quality assessment technique is embedded onto a scanning electron microscope frame grabber card for real-time image processing. Different images are captured using scanning electron microscope and a database is built to optimally choose filter parameters. An optimum choice of filter parameters is obtained. With the optimum choice of scan rate, noise can be removed from real-time scanning electron microscope images without causing any sample contamination or increasing scanning time.
Incidental magnetic resonance image sinus abnormalities in asymptomatic Australian children

Lim WK, Ram B, Fasulakis S, Kane KJ

J Laryngol Otol, 2003 Dec;117(12):969-72.
PMID: 14738607

Plain X-rays, computed tomography (CT) and magnetic resonance imaging (MRI) scans performed for non-ENT reasons often reveal incidental sinus mucosal changes. These changes need to be correlated clinically before diagnosing rhinosinusitis. This study examined the prevalence of such changes in MRI scans in children up to age 16. Scans were scored using an adapted Lund-Mackay classification and were positive when one or more sinuses showed abnormalities. Randomly selected scans in the retrospective arm revealed a prevalence of 20 of 62 (32.3 per cent). In the prospective arm 45 of 60 children were defined as truly asymptomatic, of which 14 scans (31 per cent) were positive. Other studies in adults and children using CT and MRI report a prevalence range of roughly 30 to 45 per cent. This variability may be attributed to differences of study design, definitions of population age, definitions of asymptomatic and definition of abnormal sinus. Other plausible factors to explain regional differences are climate and frequency of upper respiratory tract infections.
Chloral hydrate as a sedating agent for neurodiagnostic procedures in children

Fong CY, Lim WK, Li L, Lai NM

Cochrane Database Syst Rev, 2021 08 16;8:CD011786.
PMID: 34397100 DOI: 10.1002/14651858.CD011786.pub3

BACKGROUND: This is an updated version of a Cochrane Review published in 2017. Paediatric neurodiagnostic investigations, including brain neuroimaging and electroencephalography (EEG), play an important role in the assessment of neurodevelopmental disorders. The use of an appropriate sedative agent is important to ensure the successful completion of the neurodiagnostic procedures, particularly in children, who are usually unable to remain still throughout the procedure.
OBJECTIVES: To assess the effectiveness and adverse effects of chloral hydrate as a sedative agent for non-invasive neurodiagnostic procedures in children.
SEARCH METHODS: We searched the following databases on 14 May 2020, with no language restrictions: the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 12 May 2020). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy.
SELECTION CRITERIA: Randomised controlled trials that assessed chloral hydrate agent against other sedative agent(s), non-drug agent(s), or placebo.
DATA COLLECTION AND ANALYSIS: Two review authors independently evaluated studies identified by the search for their eligibility, extracted data, and assessed risk of bias. Results were expressed in terms of risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data, with 95% confidence intervals (CIs).
MAIN RESULTS: We included 16 studies with a total of 2922 children. The methodological quality of the included studies was mixed. Blinding of the participants and personnel was not achieved in most of the included studies, and three of the 16 studies were at high risk of bias for selective reporting. Evaluation of the efficacy of the sedative agents was also underpowered, with all the comparisons performed in small studies. Fewer children who received oral chloral hydrate had sedation failure compared with oral promethazine (RR 0.11, 95% CI 0.01 to 0.82; 1 study; moderate-certainty evidence). More children who received oral chloral hydrate had sedation failure after one dose compared to intravenous pentobarbital (RR 4.33, 95% CI 1.35 to 13.89; 1 study; low-certainty evidence), but there was no clear difference after two doses (RR 3.00, 95% CI 0.33 to 27.46; 1 study; very low-certainty evidence). Children with oral chloral hydrate had more sedation failure compared with rectal sodium thiopental (RR 1.33, 95% CI 0.60 to 2.96; 1 study; moderate-certainty evidence) and music therapy (RR 17.00, 95% CI 2.37 to 122.14; 1 study; very low-certainty evidence). Sedation failure rates were similar between groups for comparisons with oral dexmedetomidine, oral hydroxyzine hydrochloride, oral midazolam and oral clonidine. Children who received oral chloral hydrate had a shorter time to adequate sedation compared with those who received oral dexmedetomidine (MD -3.86, 95% CI -5.12 to -2.6; 1 study), oral hydroxyzine hydrochloride (MD -7.5, 95% CI -7.85 to -7.15; 1 study), oral promethazine (MD -12.11, 95% CI -18.48 to -5.74; 1 study) (moderate-certainty evidence for three aforementioned outcomes), rectal midazolam (MD -95.70, 95% CI -114.51 to -76.89; 1 study), and oral clonidine (MD -37.48, 95% CI -55.97 to -18.99; 1 study) (low-certainty evidence for two aforementioned outcomes). However, children with oral chloral hydrate took longer to achieve adequate sedation when compared with intravenous pentobarbital (MD 19, 95% CI 16.61 to 21.39; 1 study; low-certainty evidence), intranasal midazolam (MD 12.83, 95% CI 7.22 to 18.44; 1 study; moderate-certainty evidence), and intranasal dexmedetomidine (MD 2.80, 95% CI 0.77 to 4.83; 1 study, moderate-certainty evidence). Children who received oral chloral hydrate appeared significantly less likely to complete neurodiagnostic procedure with child awakening when compared with rectal sodium thiopental (RR 0.95, 95% CI 0.83 to 1.09; 1 study; moderate-certainty evidence). Chloral hydrate was associated with a higher risk of the following adverse events: desaturation versus rectal sodium thiopental (RR 5.00, 95% 0.24 to 102.30; 1 study), unsteadiness versus intranasal dexmedetomidine (MD 10.21, 95% CI 0.58 to 178.52; 1 study), vomiting versus intranasal dexmedetomidine (MD 10.59, 95% CI 0.61 to 185.45; 1 study) (low-certainty evidence for aforementioned three outcomes), and crying during administration of sedation versus intranasal dexmedetomidine (MD 1.39, 95% CI 1.08 to 1.80; 1 study, moderate-certainty evidence). Chloral hydrate was associated with a lower risk of the following: diarrhoea compared with rectal sodium thiopental (RR 0.04, 95% CI 0.00 to 0.72; 1 study), lower mean diastolic blood pressure compared with sodium thiopental (MD 7.40, 95% CI 5.11 to 9.69; 1 study), drowsiness compared with oral clonidine (RR 0.44, 95% CI 0.30 to 0.64; 1 study), vertigo compared with oral clonidine (RR 0.15, 95% CI 0.01 to 2.79; 1 study) (moderate-certainty evidence for aforementioned four outcomes), and bradycardia compared with intranasal dexmedetomidine (MD 0.17, 95% CI 0.05 to 0.59; 1 study; high-certainty evidence). No other adverse events were significantly associated with chloral hydrate, although there was an increased risk of combined adverse events overall (RR 7.66, 95% CI 1.78 to 32.91; 1 study; low-certainty evidence).
AUTHORS' CONCLUSIONS: The certainty of evidence for the comparisons of oral chloral hydrate against several other methods of sedation was variable. Oral chloral hydrate appears to have a lower sedation failure rate when compared with oral promethazine. Sedation failure was similar between groups for other comparisons such as oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam. Oral chloral hydrate had a higher sedation failure rate when compared with intravenous pentobarbital, rectal sodium thiopental, and music therapy. Chloral hydrate appeared to be associated with higher rates of adverse events than intranasal dexmedetomidine. However, the evidence for the outcomes for oral chloral hydrate versus intravenous pentobarbital, rectal sodium thiopental, intranasal dexmedetomidine, and music therapy was mostly of low certainty, therefore the findings should be interpreted with caution. Further research should determine the effects of oral chloral hydrate on major clinical outcomes such as successful completion of procedures, requirements for an additional sedative agent, and degree of sedation measured using validated scales, which were rarely assessed in the studies included in this review. The safety profile of chloral hydrate should be studied further, especially for major adverse effects such as oxygen desaturation.
Fulltext Reducing scanning electron microscope charging by using exponential contrast stretching technique on post-processing images

Sim KS, Tan YY, Lai MA, Tso CP, Lim WK

J Microsc, 2010 Apr 1;238(1):44-56.
PMID: 20384837 DOI: 10.1111/j.1365-2818.2009.03328.x

An exponential contrast stretching (ECS) technique is developed to reduce the charging effects on scanning electron microscope images. Compared to some of the conventional histogram equalization methods, such as bi-histogram equalization and recursive mean-separate histogram equalization, the proposed ECS method yields better image compensation. Diode sample chips with insulating and conductive surfaces are used as test samples to evaluate the efficiency of the developed algorithm. The algorithm is implemented in software with a frame grabber card, forming the front-end video capture element.
Fulltext Cell-mediated immunity in nasopharyngeal carcinoma and allergic rhinitis: a controlled study

Wong HT, Shahrizal TA, Prepageran N, Lim WK, Raman R

Ear Nose Throat J, 2007 May;86(5):292-4.
PMID: 17580811

We conducted a prospective study of 60 patients in a tertiary care referral center to ascertain the status of cell-mediated immunity as determined by delayed hypersensitivity reactions in patients with nasopharyngeal carcinoma (NPC) or allergic rhinitis. Delayed hypersensitivity as detected by Mantoux testing is generally accepted as a reflection of the level of cell-mediated immunoactivity-the less hypersensitivity reaction that occurs, the lower the level of immunoactivity is, and vice versa. Our study population was made up of three groups: 20 newly diagnosed patients with NPC (pretreatment), 20 age- and sex-matched patients with allergic rhinitis, and 20 matched controls without either disease. A negative Mantoux test (0- to 5-mm induration) was seen in 13 patients with NPC (65.0%), in 17 patients with allergic rhinitis (85.0%), and in 16 controls (80.0%); none of these differences was statistically significant. However, it is interesting that while the NPC group had the lowest percentage of negative Mantoux results overall, it had the highest percentage of patients who had no reaction at all (i.e., 0-mm induration); a complete absence of any reaction was seen in 7 of the 13 Mantoux-negative NPC patients (53.8%), compared with 2 of the 17 Mantoux-negative allergic rhinitis patients (11.8%) and 3 of the 16 Mantoux-negative controls (18.8%). An absence of a reaction generally indicates a very limited degree of cell-mediated immunoactivity. Therefore, we conclude that patients with NPC appear to have significantly less cell-mediated immunity than do patients with allergic rhinitis and normal controls; no statistically significant difference was noted between the latter two groups.
Study site: ENT clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
Extensive intracranial haemorrhage as a complication of acute lymphoblastic leukaemia with hyperleukocytosis

Lim WK, Fong CY, Li L, Foo JC, Yap TY

J Clin Neurosci, 2019 Jun;64:11-14.
PMID: 30948308 DOI: 10.1016/j.jocn.2019.03.056

We report a rare case of distinctive extensive punctate intracranial haemorrhage associated with acute lymphoblastic leukaemia with hyperleukocytosis. A 7-year-old girl presented with hyperleukocytosis (white cell count 788.7 × 109/L; 94% peripheral blasts) and laboratory tumour lysis syndrome. The diagnosis of T-cell acute lymphoblastic leukaemia was established and confirmed by immunophenotyping of peripheral blood and chemotherapy was commenced promptly. On day 3 of treatment, she developed progressive encephalopathy, left sided hemiparesis with left 6th and upper motor neuron 7th cranial nerve palsy. Brain MRI scan showed extensive punctate haemorrhages with perilesional oedema over the frontal, parietal, occipital, temporal, brainstem and cerebellar regions. The lesions were predominantly over the juxtacortical grey matter. She made a full neurological recovery after 3 months. Our report widens the neuroradiological features of intracranial haemorrhage associated with hyperleukocytosis and highlights the importance of prompt chemotherapy in these patients.
Fulltext Therapeutic roles of natural remedies in combating hereditary ataxia: A systematic review

Phang MWL, Lew SY, Chung I, Lim WK, Lim LW, Wong KH

Chin Med, 2021 Jan 28;16(1):15.
PMID: 33509239 DOI: 10.1186/s13020-020-00414-x

BACKGROUND: Hereditary ataxia (HA) represents a group of genetically heterogeneous neurodegenerative diseases caused by dysfunction of the cerebellum or disruption of the connection between the cerebellum and other areas of the central nervous system. Phenotypic manifestation of HA includes unsteadiness of stance and gait, dysarthria, nystagmus, dysmetria and complaints of clumsiness. There are no specific treatments for HA. Management strategies provide supportive treatment to reduce symptoms.
OBJECTIVES: This systematic review aimed to identify, evaluate and summarise the published literature on the therapeutic roles of natural remedies in the treatment of HA to provide evidence for clinical practice.
METHODS: A systematic literature search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Web of Science, PubMed and Science Direct Scopus were thoroughly searched for relevant published articles from June 2007 to July 2020.
RESULTS: Ten pre-clinical and two clinical studies were eligible for inclusion in this systematic review. We identified the therapeutic roles of medicinal plants Brassica napus, Gardenia jasminoides, Gastrodia elata, Ginkgo biloba, Glycyrrhiza inflata, Paeonia lactiflora, Pueraria lobata and Rehmannia glutinosa; herbal formulations Shaoyao Gancao Tang and Zhengan Xifeng Tang; and medicinal mushroom Hericium erinaceus in the treatment of HA. In this review, we evaluated the mode of actions contributing to their therapeutic effects, including activation of the ubiquitin-proteasome system, activation of antioxidant pathways, maintenance of intracellular calcium homeostasis and regulation of chaperones. We also briefly highlighted the integral cellular signalling pathways responsible for orchestrating the mode of actions.
CONCLUSION: We reviewed the therapeutic roles of natural remedies in improving or halting the progression of HA, which warrant further study for applications into clinical practice.

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