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Parasitic invasion of the human nervous system

Heyneman D

Med J Malaya, 1966 Sep;21(1):84-9.
PMID: 4224884
Matched MeSH terms: Central Nervous System Diseases/etiology*
Fulltext Hypomelanosis of Ito

Choo KE

Med J Malaysia, 1983 Jun;38(2):167-9.
PMID: 6621451

Two cases of Hypomelanosis of Ito are described; presenting with depigmented whorl-like, zig-zag, bizzare cutaneous manifestations associated with central nervous system disorders.

Matched MeSH terms: Central Nervous System Diseases*
Brain-eating Amoebae Infection: Challenges and Opportunities in Chemotherapy

Mungroo MR, Anwar A, Khan NA, Siddiqui R

Mini Rev Med Chem, 2019;19(12):980-987.
PMID: 30868950 DOI: 10.2174/1389557519666190313161854

Pathogenic free-living amoeba are known to cause a devastating infection of the central nervous system and are often referred to as "brain-eating amoebae". The mortality rate of more than 90% and free-living nature of these amoebae is a cause for concern. It is distressing that the mortality rate has remained the same over the past few decades, highlighting the lack of interest by the pharmaceutical industry. With the threat of global warming and increased outdoor activities of public, there is a need for renewed interest in identifying potential anti-amoebic compounds for successful prognosis. Here, we discuss the available chemotherapeutic options and opportunities for potential strategies in the treatment and diagnosis of these life-threatening infections.

Matched MeSH terms: Central Nervous System Diseases/diagnosis; Central Nervous System Diseases/drug therapy*; Central Nervous System Diseases/parasitology*
Fulltext A rare case of disseminated sarcoidosis presenting with neurosarcoidosis: a case report

Noorhafini Abdul Sukur, Narisa Sulaiman Sahari, Abdul Aziz Marwan, Rosmadi Ismail

Malaysian Journal of Medicine and Health Sciences, 2020;16(108):81-83.
MyJurnal

Sarcoidosis is characterized by formation of inflammatory granulomas affecting all over the body, with pulmonary predilection (1). Neurosarcoidosis is a rare but potentially dangerous manifestation of sarcoidosis. We report a case of disseminated sarcoidosis presenting with a neurological diagnostic dilemma. Worsening mediastinal lymphade- nopathy, together formation of lung and liver nodules making a sarcoidosis diagnosis favourable. Histology from these lesions showed non-caseating granulomatous inflammation. She was treated as a rare case of disseminated sarcoidosis. To date, there is no specific or clear guideline on the management of disseminated sarcoidosis.

Matched MeSH terms: Central Nervous System Diseases
Does long term supplementation of vitamin E cause detrimental effects on the central nervous system? Morphological and histological study in experimental male Wistar rats

Mohamad Fairuz Y, Azian A, Nursiati MT, Srijit D, Hamzaini AH, Wan Zurinah WN, et al.

Clin Ter, 2013;164(2):119-24.
PMID: 23698204 DOI: 10.7417/CT.2013.1529

Aging is attributed to neuronal loss associated with increased oxidative stress. Vitamin E, and in particular, tocotrienol are potent antioxidants, which have been shown to be neuroprotective. The main aim of the present study was to observe the effect of long term intake of vitamin E in the form of tocotrienol rich fraction (TRF) and refined, bleached, deodorized palm olein (RBDPO) on the brain of experimental rats.

Matched MeSH terms: Central Nervous System Diseases/chemically induced*; Central Nervous System Diseases/pathology*
Second regional plasmapheresis conference and workshop for Southeast Asia (SEA) on the immunomodulatory role of plasma exchange in central and peripheral nervous system disorders, Kuala Lumpur, Malaysia, 9th December 2017

Viswanathan S, Hung SKY, Goyal V, Apiwattanakul M, Thirugnanam UN, Abdullah S, et al.

J Clin Apher, 2018 Oct;33(5):559-568.
PMID: 29626354 DOI: 10.1002/jca.21630

In December 2017, 79 delegates attended the 2nd regional plasmapheresis conference and workshop for Southeast Asia (SEA) on the immunomodulatory role of plasma exchange in central and peripheral nervous system disorders in Kuala Lumpur, Malaysia. This meeting featured 6 plenary lectures, interactive sessions dedicated for experience sharing, case presentations, and a practical session for paramedics. Clinical experts and researchers from 7 SEA countries and India shared experience and challenges in treating autoimmune neurological disorders. While the spectrum of diseases and neurology practice remained largely similar, there was great disparities in accessibility of therapeutic plasma exchange (TPE) within SEA countries and between urban or rural settings. Costs, human resources, and healthcare policies are common challenges in providing sustainable TPE services. Novel techniques and innovative ideas in performing TPE were explored. A working consortium comprising of key opinion leaders was proposed to improve standards of TPE and enhance future research.

Matched MeSH terms: Central Nervous System Diseases/immunology; Central Nervous System Diseases/therapy
Fulltext Identification and validation of clinical predictors for the risk of neurological involvement in children with hand, foot, and mouth disease in Sarawak

Ooi MH, Wong SC, Mohan A, Podin Y, Perera D, Clear D, et al.

BMC Infect Dis, 2009 Jan 19;9:3.
PMID: 19152683 DOI: 10.1186/1471-2334-9-3

BACKGROUND: Human enterovirus 71 (HEV71) can cause Hand, foot, and mouth disease (HFMD) with neurological complications, which may rapidly progress to fulminant cardiorespiratory failure, and death. Early recognition of children at risk is the key to reduce acute mortality and morbidity.
METHODS: We examined data collected through a prospective clinical study of HFMD conducted between 2000 and 2006 that included 3 distinct outbreaks of HEV71 to identify risk factors associated with neurological involvement in children with HFMD.
RESULTS: Total duration of fever >or= 3 days, peak temperature >or= 38.5 degrees C and history of lethargy were identified as independent risk factors for neurological involvement (evident by CSF pleocytosis) in the analysis of 725 children admitted during the first phase of the study. When they were validated in the second phase of the study, two or more (>or= 2) risk factors were present in 162 (65%) of 250 children with CSF pleocytosis compared with 56 (30%) of 186 children with no CSF pleocytosis (OR 4.27, 95% CI2.79-6.56, p < 0.0001). The usefulness of the three risk factors in identifying children with CSF pleocytosis on hospital admission during the second phase of the study was also tested. Peak temperature >or= 38.5 degrees C and history of lethargy had the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 28%(48/174), 89%(125/140), 76%(48/63) and 50%(125/251), respectively in predicting CSF pleocytosis in children that were seen within the first 2 days of febrile illness. For those presented on the 3rd or later day of febrile illness, the sensitivity, specificity, PPV and NPV of >or= 2 risk factors predictive of CSF pleocytosis were 75%(57/76), 59%(27/46), 75%(57/76) and 59%(27/46), respectively.
CONCLUSION: Three readily elicited clinical risk factors were identified to help detect children at risk of neurological involvement. These risk factors may serve as a guide to clinicians to decide the need for hospitalization and further investigation, including cerebrospinal fluid examination, and close monitoring for disease progression in children with HFMD.

Matched MeSH terms: Central Nervous System Diseases/etiology*; Central Nervous System Diseases/virology
Clinically Approved Drugs against CNS Diseases as Potential Therapeutic Agents To Target Brain-Eating Amoebae

Anwar A, Rajendran K, Siddiqui R, Raza Shah M, Khan NA

ACS Chem Neurosci, 2019 01 16;10(1):658-666.
PMID: 30346711 DOI: 10.1021/acschemneuro.8b00484

Central nervous system (CNS) infections caused by free-living amoebae such as Acanthamoeba species and Naegleria fowleri are rare but fatal. A major challenge in the treatment against the infections caused by these amoebae is the discovery of novel compounds that can effectively cross the blood-brain barrier to penetrate the CNS. It is logical to test clinically approved drugs against CNS diseases for their potential antiamoebic effects since they are known for effective blood-brain barrier penetration and affect eukaryotic cell targets. The antiamoebic effects of clinically available drugs for seizures targeting gamma-amino butyric acid (GABA) receptor and ion channels were tested against Acanthamoeba castellanii belonging to the T4 genotype and N. fowleri. Three such drugs, namely, diazepam (Valium), phenobarbitone (Luminal), phenytoin (Dilantin), and their silver nanoparticles (AgNPs) were evaluated against both trophozoites and cysts stage. Drugs alone and drug conjugated silver nanoparticles were tested for amoebicidal, cysticidal, and host-cell cytotoxicity assays. Nanoparticles were synthesized by sodium borohydride reduction of silver nitrate with drugs as capping agents. Drug conjugated nanoconjugates were characterized by ultraviolet-visible (UV-vis) and Fourier transform infrared (FT-IR) spectroscopies and atomic force microscopy (AFM). In vitro moebicidal assay showed potent amoebicidal effects for diazepam, phenobarbitone, and phenytoin-conjugated AgNPs as compared to drugs alone against A. castellanii and N. fowleri. Furthermore, both drugs and drug conjugated AgNPs showed compelling cysticidal effects. Drugs conjugations with silver nanoparticles enhanced their antiacanthamoebic activity. Interestingly, amoeba-mediated host-cell cytotoxicity was also significantly reduced by drugs alone as well as their nanoconjugates. Since, these drugs are being used to target CNS diseases, their evaluation against brain-eating amoebae seems feasible due to advantages such as permeability of the blood-brain barrier, established pharmacokinetics and dynamics, and United States Food and Drug Administration (FDA) approval. Given the limited availability of effective drugs against brain-eating amoebae, the clinically available drugs tested here present potential for further in vivo studies.

Matched MeSH terms: Central Nervous System Diseases/drug therapy*; Central Nervous System Diseases/parasitology
Human enterovirus 71 disease in Sarawak, Malaysia: a prospective clinical, virological, and molecular epidemiological study

Ooi MH, Wong SC, Podin Y, Akin W, del Sel S, Mohan A, et al.

Clin Infect Dis, 2007 Mar 01;44(5):646-56.
PMID: 17278054

BACKGROUND: Human enterovirus (HEV)-71 causes large outbreaks of hand-foot-and-mouth disease with central nervous system (CNS) complications, but the role of HEV-71 genogroups or dual infection with other viruses in causing severe disease is unclear.
METHODS: We prospectively studied children with suspected HEV-71 (i.e., hand-foot-and-mouth disease, CNS disease, or both) over 3.5 years, using detailed virological investigation and genogroup analysis of all isolates.
RESULTS: Seven hundred seventy-three children were recruited, 277 of whom were infected with HEV-71, including 28 who were coinfected with other viruses. Risk factors for CNS disease in HEV-71 included young age, fever, vomiting, mouth ulcers, breathlessness, cold limbs, and poor urine output. Genogroup analysis for the HEV-71-infected patients revealed that 168 were infected with genogroup B4, 68 with C1, and 41 with a newly emerged genogroup, B5. Children with HEV-71 genogroup B4 were less likely to have CNS complications than those with other genogroups (26 [15%] of 168 vs. 30 [28%] of 109; odds ratio [OR], 0.48; 95% confidence interval [CI], 0.26-0.91; P=.0223) and less likely to be part of a family cluster (12 [7%] of 168 vs. 29 [27%] of 109; OR, 0.21; 95% CI, 0.10-0.46; P

Matched MeSH terms: Central Nervous System Diseases/complications; Central Nervous System Diseases/epidemiology; Central Nervous System Diseases/virology
Neonatal herpes simplex virus type-1 central nervous system disease with acute retinal necrosis

Fong CY, Aye AM, Peyman M, Nor NK, Visvaraja S, Tajunisah I, et al.

Pediatr Infect Dis J, 2014 Apr;33(4):424-6.
PMID: 24378951 DOI: 10.1097/INF.0000000000000137

We report a case of neonatal herpes simplex virus (HSV)-1 central nervous system disease with bilateral acute retinal necrosis (ARN). An infant was presented at 17 days of age with focal seizures. Cerebrospinal fluid polymerase chain reaction was positive for HSV-1 and brain magnetic resonance imaging showed cerebritis. While receiving intravenous acyclovir therapy, the infant developed ARN with vitreous fluid polymerase chain reaction positive for HSV-1 necessitating intravitreal foscarnet therapy. This is the first reported neonatal ARN secondary to HSV-1 and the first ARN case presenting without external ocular or cutaneous signs. Our report highlights that infants with neonatal HSV central nervous system disease should undergo a thorough ophthalmological evaluation to facilitate prompt diagnosis and immediate treatment of this rapidly progressive sight-threatening disease.

Matched MeSH terms: Central Nervous System Diseases/drug therapy; Central Nervous System Diseases/pathology*; Central Nervous System Diseases/virology
Fulltext Central nervous system Erdheim Chester disease presenting with raised intracranial pressure and cerebellar signs mimicking neurosarcoidosis with secondary cerebral venous thrombosis

Viswanathan S, Kadir NA, Lip AC, Rafia MH

Neurol India, 2014 Jul-Aug;62(4):446-8.
PMID: 25237960 DOI: 10.4103/0028-3886.141250
Matched MeSH terms: Central Nervous System Diseases/diagnosis*
Fulltext Lithium neurotoxicity

Suraya Y, Yoong KY

Med J Malaysia, 2001 Sep;56(3):378-81.
PMID: 11732087

Inspite of the advent of newer antimanic drugs, lithium carbonate remains widely used in the treatment and prevention of manic-depressive illness. However care has to be exercised due to its low therapeutic index. The central nervous system and renal system are predominantly affected in acute lithium intoxication and is potentially lethal. The more common side effect involves the central nervous system. It occurs early and is preventable. We describe three cases of lithium toxicity admitted to Johor Bahru Hospital, with emphasis on its neurological preponderance.

Matched MeSH terms: Central Nervous System Diseases/chemically induced
Entero-and myxoviral infections of the central nervous system

Tan DS

Med J Malaya, 1968 Dec;23(2):140-5.
PMID: 4308419
Matched MeSH terms: Central Nervous System Diseases/etiology*
Adenosine Receptors in Modulation of Central Nervous System Disorders

Choudhury H, Chellappan DK, Sengupta P, Pandey M, Gorain B

Curr Pharm Des, 2019;25(26):2808-2827.
PMID: 31309883 DOI: 10.2174/1381612825666190712181955

The ubiquitous signaling nucleoside molecule, adenosine is found in different cells of the human body to provide its numerous pharmacological role. The associated actions of endogenous adenosine are largely dependent on conformational change of the widely expressed heterodimeric G-protein-coupled A1, A2A, A2B, and A3 adenosine receptors (ARs). These receptors are well conserved on the surface of specific cells, where potent neuromodulatory properties of this bioactive molecule reflected by its easy passage through the rigid blood-brainbarrier, to simultaneously act on the central nervous system (CNS). The minimal concentration of adenosine in body fluids (30-300 nM) is adequate to exert its neuromodulatory action in the CNS, whereas the modulatory effect of adenosine on ARs is the consequence of several neurodegenerative diseases. Modulatory action concerning the activation of such receptors in the CNS could be facilitated towards neuroprotective action against such CNS disorders. Our aim herein is to discuss briefly pathophysiological roles of adenosine on ARs in the modulation of different CNS disorders, which could be focused towards the identification of potential drug targets in recovering accompanying CNS disorders. Researches with active components with AR modulatory action have been extended and already reached to the bedside of the patients through clinical research in the improvement of CNS disorders. Therefore, this review consist of recent findings in literatures concerning the impact of ARs on diverse CNS disease pathways with the possible relevance to neurodegeneration.

Matched MeSH terms: Central Nervous System Diseases/physiopathology*
Fulltext Evaluation of difference in the neurotoxicity produced by dermal application of chlorpyrifos on the neonatal and adult mice

Mitra NK, Lee MS, Nadarajah VD

Trop Biomed, 2010 Apr;27(1):19-29.
PMID: 20562809

Dermal exposure to organophosphate pesticide is important because of its popular use. This study planned to compare the changes in serum acetylcholinesterase, paraoxonase and neuronal density of hippocampus and iso-cortex between two age groups of Swiss albino mice (18-day-old and 150-day-old) after dermal application of (1/2) LD50 of chlorpyrifos for 14 days. Statistically significant reduction was observed in serum acetylcholinesterase (Mann-Whitney test, p<0.05) and neuronal density (Independent samples t-test, p<0.05) in exposed groups compared to the control. The reduction in serum AChE and neuronal density was more pronounced in exposed adult mice than in exposed neonatal mice. The paraoxonase level was insignificant in control neonatal mice, whereas it was 890-fold more in exposed neonatal mice. Upregulated paraoxonase levels may be extrapolated to produce relatively lower reduction of cholinesterase and neuronal density in neonatal mice.

Matched MeSH terms: Central Nervous System Diseases/chemically induced*
Coma and consciousness

Black W, Arumugasamy N

Med J Malaya, 1971 Jun;25(4):241-9.
PMID: 4261293
Matched MeSH terms: Central Nervous System Diseases/complications
Fulltext Emodin Derivatives as Multi-Target-Directed Ligands Inhibiting Monoamine Oxidase and Antagonizing Vasopressin V1A Receptors

Paudel P, Shrestha S, Park SE, Seong SH, Fauzi FM, Jung HA, et al.

ACS Omega, 2020 Oct 20;5(41):26720-26731.
PMID: 33110998 DOI: 10.1021/acsomega.0c03649

The brain neurotransmitter level is associated with the pathology of various neurodegenerative diseases, and age-dependent increase in the blood level of vasopressin, human brain monoamine oxidase (hMAO) level, oxidative stress, and imbalance in aminergic signaling are common disease-modifying factors leading to various neurodegenerative disorders. Based on the reports of emodin in hMAO inhibition and antagonist effect on the vasopressin V1A receptor, in this study we synthesized six emodin derivatives and evaluated their effects on MAO activity and G protein-coupled receptors. Among them, 4-hydroxyemodin and 5-hydroxyemodin were potent inhibitors of hMAO, and 2-hydroxyemodin and 5-hydroxyemodin were good V1AR antagonists. In silico molecular docking simulation revealed that the hydroxyl group at C2, C4, and C5 of the respective compounds interacted with prime residues, which corroborates the in vitro effect. Likewise, these three derivatives were predicted to have good drug-like properties. Overall, our study demonstrates that the hydroxyl derivatives of emodin are multi-target-directed ligands that may act as leads for the design and development of a therapy for central nervous system disorders.

Matched MeSH terms: Central Nervous System Diseases
Fulltext TRPM2 Channel in Microglia as a New Player in Neuroinflammation Associated With a Spectrum of Central Nervous System Pathologies

Malko P, Syed Mortadza SA, McWilliam J, Jiang LH

Front Pharmacol, 2019;10:239.
PMID: 30914955 DOI: 10.3389/fphar.2019.00239

Microglial cells in the central nervous system (CNS) are crucial in maintaining a healthy environment for neurons to function properly. However, aberrant microglial cell activation can lead to excessive generation of neurotoxic proinflammatory mediators and neuroinflammation, which represents a contributing factor in a wide spectrum of CNS pathologies, including ischemic stroke, traumatic brain damage, Alzheimer's disease, Parkinson's disease, multiple sclerosis, psychiatric disorders, autism spectrum disorders, and chronic neuropathic pain. Oxidative stress is a salient and common feature of these conditions and has been strongly implicated in microglial cell activation and neuroinflammation. The transient receptor potential melastatin-related 2 (TRPM2) channel, an oxidative stress-sensitive calcium-permeable cationic channel, is highly expressed in microglial cells. In this review, we examine the recent studies that provide evidence to support an important role for the TRPM2 channel, particularly TRPM2-mediated Ca2+ signaling, in mediating microglial cell activation, generation of proinflammatory mediators and neuroinflammation, which are of relevance to CNS pathologies. These findings lead to a growing interest in the TRPM2 channel, a new player in neuroinflammation, as a novel therapeutic target for CNS diseases.

Matched MeSH terms: Central Nervous System Diseases
The effects of ethnicity on disease patterns in 472 Orientals with systemic lupus erythematosus

Thumboo J, Fong KY, Chng HH, Koh ET, Chia HP, Leong KH, et al.

J Rheumatol, 1998 Jul;25(7):1299-304.
PMID: 9676760

OBJECTIVE: To determine the effects of ethnicity on disease manifestations in Oriental patients with systemic lupus erythematosus (SLE) and to describe the risk of developing renal or central nervous system (CNS) involvement with time.
METHODS: A retrospective study of 472 patients with SLE seen at the only Rheumatology Unit in Singapore. The effect of ethnicity on selected disease manifestations at diagnosis was assessed after adjusting for demographic variables using multiple logistic regression. The probability of developing selected disease manifestations with time was determined using the Kaplan-Meier product limit method.
RESULTS: At diagnosis, Malays had a higher risk of renal or CNS involvement than Chinese (OR 2.26, 95% CI 1.21 to 4.21, and OR 3.07, 95% CI 1.01 to 9.34, respectively), and Indians a lower risk of malar rash and a higher risk of oral ulcers than Chinese (OR 0.30, 95% CI 0.13 to 0.68, and OR 2.90, 95% CI 1.45 to 7.34, respectively). The prevalence of renal or CNS involvement in the entire cohort increased with time, reaching 75.6% (95% CI 66.1% to 85.0%) and 16.7% (95% CI 11.7% to 21.6%), respectively, after 18 years of disease.
CONCLUSION: Ethnicity influenced disease manifestations at diagnosis in this cohort of Oriental patients with SLE. Renal or CNS involvement developed in previously unaffected patients up to 18 years after diagnosis, highlighting the need for continued vigilance in patients with lupus.

Matched MeSH terms: Central Nervous System Diseases/complications
Fulltext Pharmacological perturbation of CXCL1 signaling alleviates neuropathogenesis in a model of HEVA71 infection

Gunaseelan S, Ariffin MZ, Khanna S, Ooi MH, Perera D, Chu JJH, et al.

Nat Commun, 2022 Feb 16;13(1):890.
PMID: 35173169 DOI: 10.1038/s41467-022-28533-z

Hand, foot and mouth disease (HFMD) caused by Human Enterovirus A71 (HEVA71) infection is typically a benign infection. However, in minority of cases, children can develop severe neuropathology that culminate in fatality. Approximately 36.9% of HEVA71-related hospitalizations develop neurological complications, of which 10.5% are fatal. Yet, the mechanism by which HEVA71 induces these neurological deficits remain unclear. Here, we show that HEVA71-infected astrocytes release CXCL1 which supports viral replication in neurons by activating the CXCR2 receptor-associated ERK1/2 signaling pathway. Elevated CXCL1 levels correlates with disease severity in a HEVA71-infected mice model. In humans infected with HEVA71, high CXCL1 levels are only present in patients presenting neurological complications. CXCL1 release is specifically triggered by VP4 synthesis in HEVA71-infected astrocytes, which then acts via its receptor CXCR2 to enhance viral replication in neurons. Perturbing CXCL1 signaling or VP4 myristylation strongly attenuates viral replication. Treatment with AZD5069, a CXCL1-specific competitor, improves survival and lessens disease severity in infected animals. Collectively, these results highlight the CXCL1-CXCR2 signaling pathway as a potential target against HFMD neuropathogenesis.

Matched MeSH terms: Central Nervous System Diseases/pathology; Central Nervous System Diseases/virology*

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