Displaying publications 1 - 20 of 52 in total

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  1. Law ZK, Appleton JP, Bath PM, Sprigg N
    Clin Med (Lond), 2017 Apr;17(2):166-172.
    PMID: 28365631 DOI: 10.7861/clinmedicine.17-2-166
    Managing acute intracerebral haemorrhage is a challenging task for physicians. Evidence shows that outcome can be improved with admission to an acute stroke unit and active care, including urgent reversal of anticoagulant effects and, potentially, intensive blood pressure reduction. Nevertheless, many management issues remain controversial, including the use of haemostatic therapy, selection of patients for neurosurgery and neurocritical care, the extent of investigations for underlying causes and the benefit versus risk of restarting antithrombotic therapy after an episode of intracerebral haemorrhage.
    Matched MeSH terms: Brain/physiopathology
  2. Prakash A, Dhaliwal GK, Kumar P, Majeed AB
    Int J Neurosci, 2017 Feb;127(2):99-108.
    PMID: 27044501
    Alzheimer's disease (AD) is the most common form of dementia. Several hypotheses have been put forward to explain the basis of disease onset and progression. A complicated array of molecular events has been implicated in the pathogenesis of AD. It is attributed to a variety of pathological conditions that share similar critical processes, such as oxidative stress, proteinaceous aggregations, mitochondrial dysfunctions and energy failure. There is increasing evidence suggesting that metal homeostasis is dysregulated in the pathology of AD. Biometals play an important role in the normal body functioning but AD may be mediated or triggered by disproportion of metal ions leading to changes in critical biological systems and initiating a cascade of events finally leading to neurodegeneration and cell death. The link is multifactorial, and although the source of the shift in oxidative homeostasis is still unclear, current evidence points to changes in the balance of redox transition metals, especially iron, copper (Cu) and other trace metals. Their levels in the brain are found to be elevated in AD. In other neurodegenerative disorders, Cu, zinc, aluminum and manganese are involved. This paper is a review of recent advances of the role of metals in the pathogenesis and pathophysiology of AD and related neurodegenerative diseases.
    Matched MeSH terms: Brain/physiopathology
  3. Sharifat H, Suppiah S
    Med J Malaysia, 2021 05;76(3):401-413.
    PMID: 34031341
    INTRODUCTION: Internet Addiction Disorder (IAD) is an umbrella term for various types of Internet-based behavioural addiction, whereas Internet Gaming Disorder (IGD) addresses a specific type of IAD that is postulated to be due to a lack of control in impulse inhibition. IGD is an area of concern in the Diagnostic and Statistics Manual of Mental Disorders (DSM-5), which can be objectively assessed by dysfunctional behaviour and the increasing time of being online, particularly during the COVID-19 pandemic. Electroencephalography (EEG) identifies amplitude changes in the evoked response potential (ERP) among IGDs, correlated with underlying comorbidities.

    MATERIALS AND METHODS: A scoping review was performed to elaborate on the research regarding resting-state EEG and task-based EEG, particularly for Go/No-go paradigms pertaining to subjects with IAD or specifically IGD. The role of EEG was identified in its diagnostic capability to identify the salient changes that occurred in the response to reward network and the executive control network, using restingstate and task-based EEG. The implication of using EEG in monitoring the therapy for IAD and IGD was also reviewed.

    RESULTS: EEG generally revealed reduced beta waves and increased theta waves in addicts. IGD with depression demonstrated increased theta and decreased alpha waves. Whereas increased P300, a late cognitive ERP component, was frequently associated with impaired excessive allocation of attentional resources of the IAD towards addiction-specific cues. IGD had increased whole brain delta waves at baseline, which showed significant reduction post therapy.

    CONCLUSION: EEG can identify distinct neurophysiological changes among Internet Addiction Disorder and Internet Gaming Disorder that are akin to substance abuse disorders.

    Matched MeSH terms: Brain/physiopathology*
  4. Motlagh F, Ibrahim F, Menke JM, Rashid R, Seghatoleslam T, Habil H
    J Neurosci Res, 2016 Apr;94(4):297-309.
    PMID: 26748947 DOI: 10.1002/jnr.23703
    Neuroelectrophysiological properties have been used in human heroin addiction studies. These studies vary in their approach, experimental conditions, paradigms, and outcomes. However, it is essential to integrate previous findings and experimental methods for a better demonstration of current issues and challenges in designing such studies. This Review examines methodologies and experimental conditions of neuroelectrophysiological research among heroin addicts during withdrawal, abstinence, and methadone maintenance treatment and presents the findings. The results show decrements in attentional processing and dysfunctions in brain response inhibition as well as brain activity abnormalities induced by chronic heroin abuse. Chronic heroin addiction causes increased β and α2 power activity, latency of P300 and P600, and diminished P300 and P600 amplitude. Findings confirm that electroencephalography (EEG) band power and coherence are associated with craving indices and heroin abuse history. First symptoms of withdrawal can be seen in high-frequency EEG bands, and the severity of these symptoms is associated with brain functional connectivity. EEG spectral changes and event-related potential (ERP) properties have been shown to be associated with abstinence length and tend to normalize within 3-6 months of abstinence. From the conflicting criteria and confounding effects in neuroelectrophysiological studies, the authors suggest a comprehensive longitudinal study with a multimethod approach for monitoring EEG and ERP attributes of heroin addicts from early stages of withdrawal until long-term abstinence to control the confounding effects, such as nicotine abuse and other comorbid and premorbid conditions.
    Matched MeSH terms: Brain/physiopathology*
  5. Najib NHM, Nies YH, Abd Halim SAS, Yahaya MF, Das S, Lim WL, et al.
    CNS Neurol Disord Drug Targets, 2020;19(5):386-399.
    PMID: 32640968 DOI: 10.2174/1871527319666200708124117
    Parkinson's Disease (PD) is one of the most common neurodegenerative disorders that affects the motor system, and includes cardinal motor symptoms such as resting tremor, cogwheel rigidity, bradykinesia and postural instability. Its prevalence is increasing worldwide due to the increase in life span. Although, two centuries since the first description of the disease, no proper cure with regard to treatment strategies and control of symptoms could be reached. One of the major challenges faced by the researchers is to have a suitable research model. Rodents are the most common PD models used, but no single model can replicate the true nature of PD. In this review, we aim to discuss another animal model, the zebrafish (Danio rerio), which is gaining popularity. Zebrafish brain has all the major structures found in the mammalian brain, with neurotransmitter systems, and it also possesses a functional blood-brain barrier similar to humans. From the perspective of PD research, the zebrafish possesses the ventral diencephalon, which is thought to be homologous to the mammalian substantia nigra. We summarize the various zebrafish models available to study PD, namely chemical-induced and genetic models. The zebrafish can complement the use of other animal models for the mechanistic study of PD and help in the screening of new potential therapeutic compounds.
    Matched MeSH terms: Brain/physiopathology*
  6. Sase T, Kitajo K
    PLoS Comput Biol, 2021 04;17(4):e1008929.
    PMID: 33861737 DOI: 10.1371/journal.pcbi.1008929
    Metastability in the brain is thought to be a mechanism involved in the dynamic organization of cognitive and behavioral functions across multiple spatiotemporal scales. However, it is not clear how such organization is realized in underlying neural oscillations in a high-dimensional state space. It was shown that macroscopic oscillations often form phase-phase coupling (PPC) and phase-amplitude coupling (PAC), which result in synchronization and amplitude modulation, respectively, even without external stimuli. These oscillations can also make spontaneous transitions across synchronous states at rest. Using resting-state electroencephalographic signals and the autism-spectrum quotient scores acquired from healthy humans, we show experimental evidence that the PAC combined with PPC allows amplitude modulation to be transient, and that the metastable dynamics with this transient modulation is associated with autistic-like traits. In individuals with a longer attention span, such dynamics tended to show fewer transitions between states by forming delta-alpha PAC. We identified these states as two-dimensional metastable states that could share consistent patterns across individuals. Our findings suggest that the human brain dynamically organizes inter-individual differences in a hierarchy of macroscopic oscillations with multiple timescales by utilizing metastability.
    Matched MeSH terms: Brain/physiopathology*
  7. Ay B, Yildirim O, Talo M, Baloglu UB, Aydin G, Puthankattil SD, et al.
    J Med Syst, 2019 May 28;43(7):205.
    PMID: 31139932 DOI: 10.1007/s10916-019-1345-y
    Depression affects large number of people across the world today and it is considered as the global problem. It is a mood disorder which can be detected using electroencephalogram (EEG) signals. The manual detection of depression by analyzing the EEG signals requires lot of experience, tedious and time consuming. Hence, a fully automated depression diagnosis system developed using EEG signals will help the clinicians. Therefore, we propose a deep hybrid model developed using convolutional neural network (CNN) and long-short term memory (LSTM) architectures to detect depression using EEG signals. In the deep model, temporal properties of the signals are learned with CNN layers and the sequence learning process is provided through the LSTM layers. In this work, we have used EEG signals obtained from left and right hemispheres of the brain. Our work has provided 99.12% and 97.66% classification accuracies for the right and left hemisphere EEG signals respectively. Hence, we can conclude that the developed CNN-LSTM model is accurate and fast in detecting the depression using EEG signals. It can be employed in psychiatry wards of the hospitals to detect the depression using EEG signals accurately and thus aid the psychiatrists.
    Matched MeSH terms: Brain/physiopathology*
  8. Sahu R, Dash SR, Cacha LA, Poznanski RR, Parida S
    J Integr Neurosci, 2020 Mar 30;19(1):1-9.
    PMID: 32259881 DOI: 10.31083/j.jin.2020.01.24
    Electroencephalography is the recording of brain electrical activities that can be used to diagnose brain seizure disorders. By identifying brain activity patterns and their correspondence between symptoms and diseases, it is possible to give an accurate diagnosis and appropriate drug therapy to patients. This work aims to categorize electroencephalography signals on different channels' recordings for classifying and predicting epileptic seizures. The collection of the electroencephalography recordings contained in the dataset attributes 179 information and 11,500 instances. Instances are of five categories, where one is the symptoms of epilepsy seizure. We have used traditional, ensemble methods and deep machine learning techniques highlighting their performance for the epilepsy seizure detection task. One dimensional convolutional neural network, ensemble machine learning techniques like bagging, boosting (AdaBoost, gradient boosting, and XG boosting), and stacking is implemented. Traditional machine learning techniques such as decision tree, random forest, extra tree, ridge classifier, logistic regression, K-Nearest Neighbor, Naive Bayes (gaussian), and Kernel Support Vector Machine (polynomial, gaussian) are used for classifying and predicting epilepsy seizure. Before using ensemble and traditional techniques, we have preprocessed the data set using the Karl Pearson coefficient of correlation to eliminate irrelevant attributes. Further accuracy of classification and prediction of the classifiers are manipulated using k-fold cross-validation methods and represent the Receiver Operating Characteristic Area Under the Curve for each classifier. After sorting and comparing algorithms, we have found the convolutional neural network and extra tree bagging classifiers to have better performance than all other ensemble and traditional classifiers.
    Matched MeSH terms: Brain/physiopathology*
  9. Lee PF, Kan DPX, Croarkin P, Phang CK, Doruk D
    J Clin Neurosci, 2018 Jan;47:315-322.
    PMID: 29066239 DOI: 10.1016/j.jocn.2017.09.030
    BACKGROUND: There is an unmet need for practical and reliable biomarkers for mood disorders in young adults. Identifying the brain activity associated with the early signs of depressive disorders could have important diagnostic and therapeutic implications. In this study we sought to investigate the EEG characteristics in young adults with newly identified depressive symptoms.

    METHODS: Based on the initial screening, a total of 100 participants (n = 50 euthymic, n = 50 depressive) underwent 32-channel EEG acquisition. Simple logistic regression and C-statistic were used to explore if EEG power could be used to discriminate between the groups. The strongest EEG predictors of mood using multivariate logistic regression models.

    RESULTS: Simple logistic regression analysis with subsequent C-statistics revealed that only high-alpha and beta power originating from the left central cortex (C3) have a reliable discriminative value (ROC curve >0.7 (70%)) for differentiating the depressive group from the euthymic group. Multivariate regression analysis showed that the single most significant predictor of group (depressive vs. euthymic) is the high-alpha power over C3 (p = 0.03).

    CONCLUSION: The present findings suggest that EEG is a useful tool in the identification of neurophysiological correlates of depressive symptoms in young adults with no previous psychiatric history.

    SIGNIFICANCE: Our results could guide future studies investigating the early neurophysiological changes and surrogate outcomes in depression.

    Matched MeSH terms: Brain/physiopathology*
  10. Khaing M, Lim KS, Tan CT
    Epileptic Disord, 2014 Sep;16(3):370-4.
    PMID: 25166001 DOI: 10.1684/epd.2014.0672
    We report a patient with juvenile myoclonic epilepsy who subsequently developed temporal lobe epilepsy, which gradually became clinically dominant. Video telemetry revealed both myoclonic seizures and temporal lobe seizures. The temporal lobe seizures were accompanied by a focal recruiting rhythm with rapid generalisation on EEG, in which the ictal EEG pattern during the secondary generalised phase was morphologically similar to the ictal pattern during myoclonic seizures. The secondary generalised seizures of the focal epilepsy responded to sodium valproate, similar to the myoclonic epilepsy. In this rare case of coexistent Juvenile Myoclonic Epilepsy and Temporal lobe epilepsy, the possibility of focal epilepsy recruiting a generalised epileptic network was proposed and discussed.
    Matched MeSH terms: Brain/physiopathology*
  11. Yuvaraj R, Murugappan M, Ibrahim NM, Sundaraj K, Omar MI, Mohamad K, et al.
    J Neural Transm (Vienna), 2015 Feb;122(2):237-52.
    PMID: 24894699 DOI: 10.1007/s00702-014-1249-4
    Parkinson's disease (PD) is not only characterized by its prominent motor symptoms but also associated with disturbances in cognitive and emotional functioning. The objective of the present study was to investigate the influence of emotion processing on inter-hemispheric electroencephalography (EEG) coherence in PD. Multimodal emotional stimuli (happiness, sadness, fear, anger, surprise, and disgust) were presented to 20 PD patients and 30 age-, education level-, and gender-matched healthy controls (HC) while EEG was recorded. Inter-hemispheric coherence was computed from seven homologous EEG electrode pairs (AF3-AF4, F7-F8, F3-F4, FC5-FC6, T7-T8, P7-P8, and O1-O2) for delta, theta, alpha, beta, and gamma frequency bands. In addition, subjective ratings were obtained for a representative of emotional stimuli. Interhemispherically, PD patients showed significantly lower coherence in theta, alpha, beta, and gamma frequency bands than HC during emotion processing. No significant changes were found in the delta frequency band coherence. We also found that PD patients were more impaired in recognizing negative emotions (sadness, fear, anger, and disgust) than relatively positive emotions (happiness and surprise). Behaviorally, PD patients did not show impairment in emotion recognition as measured by subjective ratings. These findings suggest that PD patients may have an impairment of inter-hemispheric functional connectivity (i.e., a decline in cortical connectivity) during emotion processing. This study may increase the awareness of EEG emotional response studies in clinical practice to uncover potential neurophysiologic abnormalities.
    Matched MeSH terms: Brain/physiopathology*
  12. Yuvaraj R, Murugappan M, Mohamed Ibrahim N, Iqbal M, Sundaraj K, Mohamad K, et al.
    Behav Brain Funct, 2014;10:12.
    PMID: 24716619 DOI: 10.1186/1744-9081-10-12
    While Parkinson's disease (PD) has traditionally been described as a movement disorder, there is growing evidence of disruption in emotion information processing associated with the disease. The aim of this study was to investigate whether there are specific electroencephalographic (EEG) characteristics that discriminate PD patients and normal controls during emotion information processing.
    Matched MeSH terms: Brain/physiopathology*
  13. Yuvaraj R, Murugappan M, Omar MI, Ibrahim NM, Sundaraj K, Mohamad K, et al.
    Int J Neurosci, 2014 Jul;124(7):491-502.
    PMID: 24168328 DOI: 10.3109/00207454.2013.860527
    Although an emotional deficit is a common finding in Parkinson's disease (PD), its neurobiological mechanism on emotion recognition is still unknown. This study examined the emotion processing deficits in PD patients using electroencephalogram (EEG) signals in response to multimodal stimuli.
    Matched MeSH terms: Brain/physiopathology*
  14. Asaduzzaman K, Reaz MB, Mohd-Yasin F, Sim KS, Hussain MS
    Adv Exp Med Biol, 2010;680:593-9.
    PMID: 20865544 DOI: 10.1007/978-1-4419-5913-3_65
    Electroencephalogram (EEG) serves as an extremely valuable tool for clinicians and researchers to study the activity of the brain in a non-invasive manner. It has long been used for the diagnosis of various central nervous system disorders like seizures, epilepsy, and brain damage and for categorizing sleep stages in patients. The artifacts caused by various factors such as Electrooculogram (EOG), eye blink, and Electromyogram (EMG) in EEG signal increases the difficulty in analyzing them. Discrete wavelet transform has been applied in this research for removing noise from the EEG signal. The effectiveness of the noise removal is quantitatively measured using Root Mean Square (RMS) Difference. This paper reports on the effectiveness of wavelet transform applied to the EEG signal as a means of removing noise to retrieve important information related to both healthy and epileptic patients. Wavelet-based noise removal on the EEG signal of both healthy and epileptic subjects was performed using four discrete wavelet functions. With the appropriate choice of the wavelet function (WF), it is possible to remove noise effectively to analyze EEG significantly. Result of this study shows that WF Daubechies 8 (db8) provides the best noise removal from the raw EEG signal of healthy patients, while WF orthogonal Meyer does the same for epileptic patients. This algorithm is intended for FPGA implementation of portable biomedical equipments to detect different brain state in different circumstances.
    Matched MeSH terms: Brain/physiopathology
  15. Lim KS, Cheong KL, Tan CT
    Lupus, 2010 May;19(6):748-52.
    PMID: 20133346 DOI: 10.1177/0961203309351539
    A 13-year-old girl with a known diagnosis of systemic lupus erythematosus presented with seizures and psychosis. An electroencephalogram (EEG) revealed continuous, non-evolving periodic lateralized epileptiform discharges (PLEDs) in the left temporal region, which did not resolve with benzodiazepine. A magnetic resonance imaging (MRI) brain scan demonstrated a focal hyperintensity in the left medial temporal and left occipital lobes, left thalamus and bilateral cerebellar white matter, with evidence of vasculitis in the magnetic resonance angiography. Intravenous immunoglobulin was given because of failed steroid therapy, which resulted in a full resolution of clinical, EEG and MRI abnormalities. Lupus cerebritis should be considered as a possible aetiology in PLEDs, and immunoglobulin can be effective in neuropsychiatric lupus.
    Matched MeSH terms: Brain/physiopathology
  16. Salim MA, van der Veen FM, van Dongen JD, Franken IH
    Biol Psychol, 2015 Sep;110:50-8.
    PMID: 26188154 DOI: 10.1016/j.biopsycho.2015.07.001
    Psychopathy has been associated with behavioral adaptation deficits, which might be associated with problems in feedback and reward processing. In the present study, we examined the relation between psychopathic traits and reward processing in a passive gambling task. A total of 39 male participants who scored high (HP) and 39 male participants who scored low (LP) on the Triarchic Psychopathy Measure (TriPM), total score were tested. Feedback-related Event-Related Potentials (ERPs; i.e., P2, FRN, and P3) on predicted and unpredicted rewards and reward omissions were compared between both groups. It was found that in HP individuals, the P2 was enhanced for predicted rewards and reward omissions, but not for unpredicted stimuli. Moreover, HP individuals as compared to the LP individuals demonstrated a generally reduced P3 amplitude. The FRN amplitude, however, did not differ between the two groups. In addition, HP individuals showed enhanced reward sensitivity on the self-report level. Taken together, these findings suggest that HP individuals show enhanced sensitivity to early and reduced sensitivity to later markers of processing reinforcement learning signals, which points in the direction of compromised behavioral adaptation.
    Matched MeSH terms: Brain/physiopathology*
  17. Lim LW, Prickaerts J, Huguet G, Kadar E, Hartung H, Sharp T, et al.
    Transl Psychiatry, 2015;5:e535.
    PMID: 25826110 DOI: 10.1038/tp.2015.24
    Deep brain stimulation (DBS) is a promising therapy for patients with refractory depression. However, key questions remain with regard to which brain target(s) should be used for stimulation, and which mechanisms underlie the therapeutic effects. Here, we investigated the effect of DBS, with low- and high-frequency stimulation (LFS, HFS), in different brain regions (ventromedial prefrontal cortex, vmPFC; cingulate cortex, Cg; nucleus accumbens (NAc) core or shell; lateral habenula, LHb; and ventral tegmental area) on a variety of depressive-like behaviors using rat models. In the naive animal study, we found that HFS of the Cg, vmPFC, NAc core and LHb reduced anxiety levels and increased motivation for food. In the chronic unpredictable stress model, there was a robust depressive-like behavioral phenotype. Moreover, vmPFC HFS, in a comparison of all stimulated targets, produced the most profound antidepressant effects with enhanced hedonia, reduced anxiety and decreased forced-swim immobility. In the following set of electrophysiological and histochemical experiments designed to unravel some of the underlying mechanisms, we found that vmPFC HFS evoked a specific modulation of the serotonergic neurons in the dorsal raphe nucleus (DRN), which have long been linked to mood. Finally, using a neuronal mapping approach by means of c-Fos expression, we found that vmPFC HFS modulated a brain circuit linked to the DRN and known to be involved in affect. In conclusion, HFS of the vmPFC produced the most potent antidepressant effects in naive rats and rats subjected to stress by mechanisms also including the DRN.
    Matched MeSH terms: Brain/physiopathology*
  18. Boo NY, Chandran V, Zulfiqar MA, Zamratol SM, Nyein MK, Haliza MS, et al.
    J Paediatr Child Health, 2000 Aug;36(4):363-9.
    PMID: 10940172
    OBJECTIVES: To identify the types of early cranial ultrasound changes that were significant predictors of adverse outcome during the first year of life in asphyxiated term infants.

    METHODOLOGY: This was a prospective cohort study. Shortly after birth, cranial ultrasonography was carried out via the anterior fontanelles of 70 normal control infants and 104 asphyxiated infants with a history of fetal distress and Apgar scores of less than 6 at 1 and 5 min of life, or requiring endotracheal intubation and manual intermittent positive pressure ventilation for at least 5 min after birth. Neurodevelopmental assessment was carried out on the survivors at 1 year of age.

    RESULTS: Abnormal cranial ultrasound changes were detected in a significantly higher proportion (79.8%, or n = 83) of asphyxiated infants than controls (39.5%, or n = 30) (P < 0.0001). However, logistic regression analysis showed that only three factors were significantly associated with adverse outcome at 1 year of life among the asphyxiated infants. These were: (i) decreasing birthweight (for every additional gram of increase in birthweight, adjusted odds ratio (OR) = 0.999, 95% confidence interval (CI) 0.998, 1.000; P = 0.047); (ii) a history of receiving ventilatory support during the neonatal period (adjusted OR = 8.3; 95%CI 2.4, 28.9; P = 0.0009); and (iii) hypoxic-ischaemic encephalopathy stage 2 or 3 (adjusted OR = 5.8; 95%CI 1.8, 18.6; P = 0.003). None of the early cranial ultrasound changes was a significant predictor.

    CONCLUSIONS: Early cranial ultrasound findings, although common in asphyxiated infants, were not significant predictors of adverse outcome during the first year of life in asphyxiated term infants.

    Matched MeSH terms: Brain/physiopathology*
  19. Sakharkar MK, Kashmir Singh SK, Rajamanickam K, Mohamed Essa M, Yang J, Chidambaram SB
    PLoS One, 2019;14(9):e0220995.
    PMID: 31487305 DOI: 10.1371/journal.pone.0220995
    Parkinson's disease (PD) is an irreversible and incurable multigenic neurodegenerative disorder. It involves progressive loss of mid brain dopaminergic neurons in the substantia nigra pars compacta (SN). We compared brain gene expression profiles with those from the peripheral blood cells of a separate sample of PD patients to identify disease-associated genes. Here, we demonstrate the use of gene expression profiling of brain and blood for detecting valid targets and identifying early PD biomarkers. Implementing this systematic approach, we discovered putative PD risk genes in brain, delineated biological processes and molecular functions that may be particularly disrupted in PD and also identified several putative PD biomarkers in blood. 20 of the differentially expressed genes in SN were also found to be differentially expressed in the blood. Further application of this methodology to other brain regions and neurological disorders should facilitate the discovery of highly reliable and reproducible candidate risk genes and biomarkers for PD. The identification of valid peripheral biomarkers for PD may ultimately facilitate early identification, intervention, and prevention efforts as well.
    Matched MeSH terms: Brain/physiopathology
  20. Mizuguchi T, Nakashima M, Moey LH, Ch'ng GS, Khoo TB, Mitsuhashi S, et al.
    J Hum Genet, 2019 Apr;64(4):347-350.
    PMID: 30626896 DOI: 10.1038/s10038-018-0556-2
    We report the second case of early infantile epileptic encephalopathy (EIEE) arising from a homozygous truncating variant of NECAP1. The boy developed infantile-onset tonic-clonic and tonic seizures, then spasms in clusters. His electroencephalogram (EEG) showed a burst suppression pattern, leading to the diagnosis of Ohtahara syndrome. Whole-exome sequencing revealed the canonical splice-site variant (c.301 + 1 G > A) in NECAP1. In rodents, Necap1 protein is enriched in neuronal clathrin-coated vesicles and modulates synaptic vesicle recycling. cDNA analysis confirmed abnormal splicing that produced early truncating mRNA. There has been only one previous report of a mutation in NECAP1 in a family with EIEE; this was a nonsense mutation (p.R48*) that was cited as EIEE21. Decreased mRNA levels and the loss of the WXXF motif in both the families suggests that loss of NECAP1 function is a common pathomechanism for EIEE21. This study provided additional support that synaptic vesicle recycling plays a key role in epileptogenesis.
    Matched MeSH terms: Brain/physiopathology
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