Materials and Methods: All the variants' information was retrieved from the Ensembl genome database, and then different variation prediction analyses were performed. UTRScan was used to predict UTR variants while MaxEntScan was used to predict splice site variants. Meta-analysis by PredictSNP2 was used to predict sSNPs. Parallel prediction analyses by five different software packages including SIFT, PolyPhen-2, Mutation Assessor, I-Mutant2.0 and SNPs&GO were used to predict the effects of nsSNPs. The level of evolutionary conservation of deleterious nsSNPs was further analyzed using ConSurf server. Mutant protein structures of deleterious nsSNPs were modelled and refined using SPARKS-X and ModRefiner for structural comparison.
Results: A total of 56 deleterious variants were identified in this study, including 12 UTR variants, 18 splice site variants, eight sSNPs and 18 nsSNPs. Among these 56 deleterious variants, seven variants were also identified in the Alzheimer's Disease Sequencing Project (ADSP), Alzheimer's Disease Neuroimaging Initiative (ADNI) and Mount Sinai Brain Bank (MSBB) studies.
Discussion: The 56 deleterious variants were predicted to affect the regulation of gene expression, or have functional impacts on these three endocytosis genes and their gene products. The deleterious variants in these genes are expected to affect their cellular function in endocytosis and may be implicated in the pathogenesis of AD as well. The biological consequences of these deleterious variants and their potential impacts on the disease risks could be further validated experimentally and may be useful for gene-disease association study.
METHOD: A case-control study was conducted in the Universiti Putra Malaysia among eight military personnel, four of whom had chronic intermittent exposure to high altitude training. They were divided into two groups, chronic intermittent exposure group (CE) (n=4) and a control group (n=4). They underwent a task-based functional magnetic resonance imaging (fMRI) that utilised spatial working memory task to objectively evaluate the neural activation in response to the Tower of London paradigm. Each correct answer was given a score of one and the maximum achievable score was 100%.
RESULTS: A consecutive dichotomised group of CE (4/8) and control (4/8) of age-matched military aviation personnel with a mean age of 37.23±5.52 years; showed significant activation in the right middle frontal gyrus (MFG). This in turn was positively correlated with response accuracy. A significant difference in the response accuracy was noted among both the groups at p<0.05.
CONCLUSION: At the minimum results of power analysis of this preliminary fMRI study, our group of aviation personnel who had chronic intermittent exposure to hypobaric hypoxic environment, did not have any significant decrease in cognitive function namely attention, decision-making and problem solving compared to controls during a working memory task.
METHODS: 85 participants (43 fallers, 42 non-fallers) were evaluated with conventional MRI and diffusion tensor imaging (DTI) sequences of the brain. DTI metrics were obtained from selected WMT using tract-based spatial statistics (TBSS) method. This was followed by binary logistic regression to investigate the clinical variables that could act as confounding elements on the outcomes. The TBSS analysis was then repeated, but this time including all significant predictor variables from the regression analysis as TBSS covariates.
RESULTS: The mean diffusivity (MD) and axial diffusivity (AD) and to a lesser extent radial diffusivity (RD) values of the projection fibers and commissural bundles were significantly different in fallers (p < 0.05) compared to non-fallers. However, the final logistic regression model obtained showed that only functional reach, white matter lesion volume, hypertension and orthostatic hypotension demonstrated statistical significant differences between fallers and non-fallers. No significant differences were found in the DTI metrics when taking into account age and the four variables as covariates in the repeated analysis.
CONCLUSION: This DTI study of 85 subjects, do not support DTI metrics as a singular factor that contributes independently to the fall outcomes. Other clinical and imaging factors have to be taken into account.
OBJECTIVE: We aimed to correlate the ability of these modalities to differentiate Probable AD and Possible AD using the clinical diagnosis as a gold standard. We also investigated the correlation of severity of amyloid deposit in the brain with the diagnosis of AD.
METHODS: A retrospective study of 47 subjects (17 Probable AD and 30 Possible AD) who were referred for PET/CT amyloid scans to our centre was conducted. Hypoperfusion in the temporo-parietal lobes on Tc99m-HMPAO SPECT and loss of grey-white matter contrast in cortical regions on PET/CT Amyloid scans indicating the presence of amyloid β deposit were qualitatively interpreted as positive for AD. SPECT and PET/CT were also read in combination (Combo reading). The severity of amyloid β deposit was semiquantitatively assessed in a visual binary method using a scale of Grade 0-4. The severity of amyloid β deposit was assessed in a visual binary method and a semi-quantitative method using a scale of Grade 0-4.
RESULTS: There was significant correlation of Tc99m-HMPAO SPECT, PET/CT amyloid findings and Combo reading with AD. The sensitivity, specificity, PPV and NPV were 87.5%, 73.7%, 58.3% and 93.3% (SPECT); 62.5%, 77.4%, 58.8% and 80.0% (PET/CT) and 87.5%, 84.2%, 70.0% and 30.0% (Combo reading) respectively. The grade of amyloid deposition was not significantly correlated with AD (Spearman's correlation, p=0.687).
CONCLUSION: There is an incremental benefit in utilizing PET/CT amyloid imaging in cases with atypical presentation and indeterminate findings on conventional imaging of Alzheimer's disease.
OBJECTIVE: The current review was aimed to present a comprehensive overview and critical appraisal of majorly employed neuroimaging techniques for rational diagnosis and effective monitoring of effectiveness of employed therapeutic intervention for NPH. Moreover, a critical overview of recent developments and utilization of pharmacological agents for treatment of hydrocephalus has also been appraised.
RESULTS: Considering the complications associated with the shunt-based surgical operations, consistent monitoring of shunting via neuroimaging techniques hold greater clinical significance. Despite having extensive applicability of MRI and CT scan, these conventional neuroimaging techniques are associated with misdiagnosis or several health risks to patients. Recent advances in MRI (i.e., Sagittal-MRI, coronal-MRI, Time-SLIP (time-spatial-labeling-inversion-pulse), PC-MRI and diffusion-tensor-imaging (DTI)) have shown promising applicability in diagnosis of NPH. Having associated with several adverse effects with surgical interventions, non-invasive approaches (pharmacological agents) have earned greater interest of scientists, medical professional, and healthcare providers. Amongst pharmacological agents, diuretics, isosorbide, osmotic agents, carbonic anhydrase inhibitors, glucocorticoids, NSAIDs, digoxin, and gold-198 have been employed for management of NPH and prevention of secondary sensory/intellectual complications.
CONCLUSION: Employment of rational diagnostic tool and therapeutic modalities avoids misleading diagnosis and sophisticated management of hydrocephalus by efficient reduction of cerebrospinal fluid (CSF) production, reduction of fibrotic and inflammatory cascades secondary to meningitis and hemorrhage, and protection of brain from further deterioration.
OBJECTIVE: The current review was aimed to present a comprehensive overview and critical appraisal of majorly employed neuroimaging techniques for rational diagnosis and effective monitoring of the effectiveness of the employed therapeutic intervention for NPH. Moreover, a critical overview of recent developments and utilization of pharmacological agents for the treatment of hydrocephalus has also been appraised.
RESULTS: Considering the complications associated with the shunt-based surgical operations, consistent monitoring of shunting via neuroimaging techniques hold greater clinical significance. Despite having extensive applicability of MRI and CT scan, these conventional neuroimaging techniques are associated with misdiagnosis or several health risks to patients. Recent advances in MRI (i.e., Sagittal-MRI, coronal-MRI, Time-SLIP (time-spatial-labeling-inversion-pulse), PC-MRI and diffusion-tensor-imaging (DTI)) have shown promising applicability in the diagnosis of NPH. Having associated with several adverse effects with surgical interventions, non-invasive approaches (pharmacological agents) have earned greater interest of scientists, medical professional, and healthcare providers. Amongst pharmacological agents, diuretics, isosorbide, osmotic agents, carbonic anhydrase inhibitors, glucocorticoids, NSAIDs, digoxin, and gold-198 have been employed for the management of NPH and prevention of secondary sensory/intellectual complications.
CONCLUSION: Employment of rational diagnostic tool and therapeutic modalities avoids misleading diagnosis and sophisticated management of hydrocephalus by efficient reduction of Cerebrospinal Fluid (CSF) production, reduction of fibrotic and inflammatory cascades secondary to meningitis and hemorrhage, and protection of brain from further deterioration.
OBJECTIVES: We aim to determine the prevalence, demographic and clinical characteristics of MOG antibody disease (MOGAD) specifically identifying any ethnic variations unique to our local population, with global perspectives.
METHODS: This is a cross-sectional study conducted at the Neurology Department, Kuala Lumpur Hospital from January 2018 to January 2021. Out of 750 CNS IIDDs, seventy-eight consecutive anti-AQP4 antibody negative NMOSD/high risk undifferentiated relapsing or monophasic CNSIIDD subjects were tested for anti-MOG.
RESULTS: Anti-MOG was positive in thirty six out of seventy-eight (%)(46.1%) seronegative patients. The prevalence of MOGAD in our Malaysian population is 0.12 per 100,000 persons with less marked female preponderance of 2:1 and younger age at onset of 23.8 ± 14.4 years. Despite a predominantly ethnic Malay population, a high proportion of our MOGAD patients were Indian (Proportion of Malay:Chinese:Indian:others; 16:9:10:1, prevalence 0.5 per 100,000 population for Indians) with favourable disease course in the most with minor exceptions. Monophasic and relapsing disease course was seen in 11.2% and 88.8% of patients respectively. However, fulminant aggressive disease can occur especially amongst the Chinese and paediatric cohorts. Optic neuritis, NMOSD and ADEM were the commonest presentations at onset and first relapse. EDSS at diagnosis, first relapse, and last follow-up were 4.5±2.5, 3±2.0, and 1.75(range 1-3). Neuroimaging showed large, fluffy, PRES- like supratentorial cortical, periventricular deep white matter ,diencephalon lesions,enhancing anterior optic nerve with or without chiasmal sparring lesions and cervical/cervicothoracic involvement. Area post rema lesions were rare. Threshold steroid levels exist relapsing on withdrawal some fulminantly requiring Immunosuppressants(rituximab) and intravenous immunoglobulins to maintain remission.
CONCLUSION: Malaysian MOGAD profile was similar to its international descriptions of the disease with ethnic selectivity for Indians. Prolonged steroid maintenance is essential to prevent relapses. Fulminant aggressive cases of MOGAD especially amongst Paediatric patients and the Chinese cohort have been reported.
AIM: To compare the quality of CT brain images produced by a fixed CT scanner and a portable CT scanner (CereTom).
METHODS: This work was a single-centre retrospective study of CT brain images from 112 neurosurgical patients. Hounsfield units (HUs) of the images from CereTom were measured for air, water and bone. Three assessors independently evaluated the images from the fixed CT scanner and CereTom. Streak artefacts, visualisation of lesions and grey-white matter differentiation were evaluated at three different levels (centrum semiovale, basal ganglia and middle cerebellar peduncles). Each evaluation was scored 1 (poor), 2 (average) or 3 (good) and summed up to form an ordinal reading of 3 to 9.
RESULTS: HUs for air, water and bone from CereTom were within the recommended value by the American College of Radiology (ACR). Streak artefact evaluation scores for the fixed CT scanner was 8.54 versus 7.46 (Z = -5.67) for CereTom at the centrum semiovale, 8.38 (SD = 1.12) versus 7.32 (SD = 1.63) at the basal ganglia and 8.21 (SD = 1.30) versus 6.97 (SD = 2.77) at the middle cerebellar peduncles. Grey-white matter differentiation showed scores of 8.27 (SD = 1.04) versus 7.21 (SD = 1.41) at the centrum semiovale, 8.26 (SD = 1.07) versus 7.00 (SD = 1.47) at the basal ganglia and 8.38 (SD = 1.11) versus 6.74 (SD = 1.55) at the middle cerebellar peduncles. Visualisation of lesions showed scores of 8.86 versus 8.21 (Z = -4.24) at the centrum semiovale, 8.93 versus 8.18 (Z = -5.32) at the basal ganglia and 8.79 versus 8.06 (Z = -4.93) at the middle cerebellar peduncles. All results were significant with P-value < 0.01.
CONCLUSIONS: Results of the study showed a significant difference in image quality produced by the fixed CT scanner and CereTom, with the latter being more inferior than the former. However, HUs of the images produced by CereTom do fulfil the recommendation of the ACR.