Periventricular Deep White Matter Research Articles

Association between white matter hyperintensity and anxiety/depression.

Although previous studies have explored the associations of white matter hyperintensity with psychiatric disorders, the sample size is small and the conclusions are inconsistent. The present study aimed to further systematically explore the association in a larger sample. All data were extracted from the UK Biobank. First, general linear regression models and logistic regression models were used to assess the association between white matter hyperintensity volume and anxiety/depression. White matter hyperintensity has been classified into periventricular white matter hyperintensity and deep white matter hyperintensity. Anxiety was determined by General Anxiety Disorder-7 score (n = 17,221) and self-reported anxiety (n = 15,333), depression was determined by Patient Health Questionnaire-9 score (n = 17,175), and self-reported depression (n = 14,519). Moreover, we employed Cox proportional hazard models to explore the association between white matter hyperintensity volume and anxiety/depression. The covariates included in fully adjusted model are age, gender, body mass index, Townsend deprivation index, healthy physical activity, cigarette consumption, alcohol consumption, educational attainment, diabetes, hypertension, and coronary heart disease. The results of the fully adjusted model showed that white matter hyperintensity volume was significantly associated with General Anxiety Disorder-7 score (periventricular white matter hyperintensity: β = 0.152, deep white matter hyperintensity: β = 0.094) and Patient Health Questionnaire-9 score (periventricular white matter hyperintensity: β = 0.168). Logistic regression analysis results indicated that periventricular white matter hyperintensity volume (odds ratio = 1.153) was significantly associated with self-reported anxiety. After applying the Cox proportional hazard models, we found that larger white matter hyperintensity volume was associated with increased risk of depression (periventricular white matter hyperintensity: hazard ratio = 1.589, deep white matter hyperintensity: hazard ratio = 1.200), but not anxiety. In summary, our findings support a positive association between white matter hyperintensity volume and depression.

Association between National Institutes of Health Stroke Scale and Functional Independence Measure scores in patients with ischemic stroke from convalescent rehabilitation outcomes.

We investigated the associations among neurological severity, activities of daily living (ADLs), and clinical factors in patients with ischemic stroke in convalescent rehabilitation outcome. The study sample included 723 patients with ischemic stroke (484 men and 239 women; mean age, 73.2 ± 8.5 years) for inpatient convalescent rehabilitation. National Institutes of Health Stroke Scale (NIHSS) was used to measure the neurological severity, and Functional Independence Measure (FIM) was used to assess ADLs at discharge. Leukoaraiosis was graded based on periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH) on magnetic resonance imaging. The correlations between NIHSS scores and total FIM scores were significant but relatively mild (r = -0.684, P < 0.001). Multiple regression analysis revealed that age and PVH grade significantly decreased their total FIM scores and affected the discrepancies between NIHSS scores at discharge (P < 0.001), but DWMH scores did not affect these results. Factors such as positive history of heart disease (P = 0.008) and bilateral infarction (P = 0.038) additionally decreased their total FIM scores and affected the discrepancies between NIHSS scores. These findings suggest that age, PVH, history of heart disease positive, and bilateral infarction in patients with ischemic stroke affected their performance of ADLs and the discrepancies between their neurological severities in convalescent rehabilitation outcomes, probably because the pathophysiological background of leukoaraiosis and these factors strongly decrease their ADL performance in post-phase ischemic stroke.

White matter hyperintensities: a possible link between sarcopenia and cognitive impairment in patients with mild to moderate Alzheimer's disease.

Alzheimer's disease (AD) has been reported to be associated with sarcopenia. White matter hyperintensities (WMH) are common in AD patients. However, the effect of WMH on sarcopenia in AD remains unclear. We hence aimed to investigate the possible association between regional WMH volumes and sarcopenic parameters in AD. 57 mild to moderate AD patients and 22 normal controls (NC) were enrolled. Sarcopenic parameters were assessed, including appendicular skeletal mass index (ASMI), grip strength, 5-times sit-to-stand (5-STS) time, and gait speed. The volumes of periventricular hyperintensities (PVH) and deep white matter hyperintensities (DWMH) were quantified using 3D-slicer software. AD subjects exhibited a lower ASMI, a slower gait speed, an increased 5-STS time, and larger volumes of PVH and DWMH than those in the NC group. In AD subjects, total WMH and PVH volumes were related to cognitive impairment, particularly executive function decline. Moreover, total WMH volume and PVH volume were negatively correlated with gait speed across various clinical stages of AD. Multiple linear regression analysis showed that PVH volume was independently associated with 5-STS time and gait speed, whereas DWMH volume was only independently associated with gait speed. WMH volume was associated with cognitive decline and various sarcopenic parameters. It thereby suggested that WMH may serve as the connection between sarcopenia and cognitive dysfunction in AD. Further studies are needed to confirm these findings and to determine whether sarcopenia interventions reduce WMH volume and improve cognitive function in AD.

A Fully Automated Visual Grading System for White Matter Hyperintensities of T2-Fluid Attenuated Inversion Recovery Magnetic Resonance Imaging.

The Fazekas scale is one of the most commonly used visual grading systems for white matter hyperintensity (WMH) for brain disorders like dementia from T2-fluid attenuated inversion recovery magnetic resonance (MR) images (T2-FLAIRs). However, the visual grading of the Fazekas scale suffers from low-intra and inter-rater reliability and high labor-intensive work. Therefore, we developed a fully automated visual grading system using quantifiable measurements. Our approach involves four stages: (1) the deep learning-based segmentation of ventricles and WMH lesions, (2) the categorization into periventricular white matter hyperintensity (PWMH) and deep white matter hyperintensity (DWMH), (3) the WMH diameter measurement, and (4) automated scoring, following the quantifiable method modified for Fazekas grading. We compared the performances of our method and that of the modified Fazekas scale graded by three neuroradiologists for 404 subjects with T2-FLAIR utilized from a clinical site in Korea. The Krippendorff's alpha across our method and raters (A) versus those only between the radiologists (R) were comparable, showing substantial (0.694 vs. 0.732; 0.658 vs. 0.671) and moderate (0.579 vs. 0.586) level of agreements for the modified Fazekas, the DWMH, and the PWMH scales, respectively. Also, the average of areas under the receiver operating characteristic curve between the radiologists (0.80 ± 0.09) and the radiologists against our approach (0.80 ± 0.03) was comparable. Our fully automated visual grading system for WMH demonstrated comparable performance to the radiologists, which we believe has the potential to assist the radiologist in clinical findings with unbiased and consistent scoring.

Exosomal miR-320e as a Novel Potential Biomarker for Cerebral Small Vessel Disease.

Cerebral small vessel disease (CSVD) with an insidious onset can cause overall neurological dysfunction and dementia, bringing a massive burden to society. However, thepathogenesisof CSVD iscomplex and reliable non-invasive biomarkers for diagnosis are still not available at present. Our study aimed to investigate abnormal exosomal miRNA patterns via microarray analysis and identify candidate biomarkers for CSVD. We isolated exosomes from the plasma of all subjects and identified exosomes via currently universally accepted methods. The miRNAs were profiled through microarrays, and then the expression of selected differentially expressed miRNAs was validated through RT-PCR. GO and KEGG analysis predicted possible functions of differentially expressed miRNAs. Receiver operating characteristic (ROC) curve was employed to observe the diagnostic value of selective miRNAs. Finally, the relationship between the expression of miR-320e and the CSVD burden was analyzed. A total of 14 miRNAs displayed differential enrichment levels with |fold change|≥1.5 and p<0.05 through miRNA microarray analysis. The RT-PCR analysis validated that exosomal miR-320e was significantly downregulated in CSVD patients (p<0.0001). ROC curve analysis of exosomal miR-320e showed the area under the curve of 0.752. According to the multivariable analysis, miR-320e was an independent predictor of white matter hyperintensity ([aOR]= 0.452, 95% confidence interval [CI]= 0.258-0.792, p=0.006) and exhibited a negative correlation with the load of periventricular white matter hyperintensities (p=0.0021) and deep white matter hyperintensities (p=0.0018), respectively. In addition, it exhibited a negative correlation with total CSVD burden score(r=-0.276, p=0.001). In our study, plasma exosomal miR-320e has a certain diagnostic value for CSVD, and a significant correlation with imaging burden of CSVD. Overall, exosomal miR-320e has the potential to be a novel biomarker for CSVD, but further research with a large sample size is necessary to assess its clinical utility.

Brain and Spinal Cord MRI Findings in Thai Multiple Sclerosis Patients

Previous studies have demonstrated different MRI characteristics in Asian and Western patients with multiple sclerosis (MS). However, the number of studies performed on Thai patients is still limited. Furthermore, these studies were conducted before the revision of the McDonald criteria in 2017. A retrospective descriptive study was performed on Thai patients diagnosed with MS, according to the McDonald criteria (2017), in a tertiary care hospital in Thailand. Thirty-two patients were included (twenty-seven female and five male patients). The mean age was 37.8 years. Most (28 patients) had relapsing remitting MS. Brain MRIs were available for all 32 patients, all of which showed abnormalities. The most common locations were the periventricular regions (78.1%), juxtacortical regions (75%) and deep white matter (62.5%). Dawson's fingers were identified in 20 patients (62.5%). Tumefactive MS was noted in two patients. Gadolinium-enhancing brain lesions were noted in nine patients (28.1%). Optic nerve lesions were found in seven patients. Six of the seven patients showed short segmental lesions with predominant posterior-half involvement. Spinal MRIs were available for 26 patients, with abnormalities detected in 23. Most (11 patients) had lesions both in the cervical and in the thoracic spinal cord. In total, 22 patients (95.7%) showed lesions at the periphery, most commonly at the lateral column. Fifteen patients showed lesions shorter than three vertebral segments (65.2%). Enhancing spinal lesions were noted in 14 patients. Dissemination in space was fulfilled in 31 patients (96.9%). Some of the MRI findings in our study were similar to those of previous studies in Thailand and Asia, emphasizing the difference between Asian and Western MS.

S-03-1: BRAIN IMAGING FOR THE MANAGEMENT OF HYPERTENSION

Small vessels in the brain is susceptible especially for the effect of hypertension. Therefore, longstanding hypertension may induce cerebral small vessel disease (CSVD) which is designated as hypertensive CSVD. The patients with hypertensive CSVD may exhibit various types of lesions including lacunar infarction, white matter lesion, cerebral hemorrhage and microbleeds in brain magnetic resonance (MR) imaging. White matter lesions (WMLs) are one of the most representative lesions which are closely related to hypertension and aging. They are classified into periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH), and the former is more closely involved in cognitive decline than the latter. In the SPRINT MIND trial which examined the significance of intensive blood pressure control, WML volume increased by 0.28 cm3 for 4years in the intensive treatment group whereas by 0.92 cm3 in the standard treatment group, indicating 70% suppression of WML expansion. We quantitatively assessed WML volume in patients with vascular dementia and Alzheimer disease, and as expected, both PVH DWMH were significantly larger in vascular dementia than in Alzheimer disease. The mechanisms for CMBs are not fully understood but may be secondary to blood-brain barrier damages from long-standing hypertension, or alternatively, amyloid deposition in the tissue. In our previous study, we investigated degree of SVD changes using hypertensive arteriopathy SVD (HA SVD) and cerebral amyloid angiopathy SVD (CAA SVD) scores. With the analysis of SVD scores in 53 subjects with CMBs admixed with lobar and deep distributions, mixed CMBs were mainly caused by HA. These neuroimaging markers are crucial for management of hypertension. Small subcortical stroke (SPS3) trial which enrolled patients with symptomatic lacunar infarctions, were divided into two groups: those with a systolic blood pressure target between 130 and 149 mm Hg and those with less than 130 mm Hg. There was no significant difference in the frequency of all strokes, the rate of intracerebral hemorrhage was significantly lower in the group with intensive blood pressure control. This SPS3 trial revealed that a systolic blood pressure target of less than 130 mm Hg is beneficial in reducing risk in lacunar stroke patients. Thus, we overview brain imaging markers in hypertensive patients and their significance for the management of SVD.

Clinical-neuroimaging-pathological relationship analysis of adult onset Neuronal Intranuclear Inclusion Disease (NIID)

BackgroundNeuronal Intranuclear Inclusion Disease (NIID) is a degenerative disease with heterogeneous clinical manifestations. We aim to analysis the relationship between clinical manifestations, neuroimaging and skin pathology in a Chinese NIID cohort.MethodsPatients were recruited from a Chinese cohort. Detail clinical information were collected. Visual rating scale was used for evaluation of neuroimaging. The relationship between clinical presentations and neuroimaging, as well as skin pathology was statistically analyzed.ResultsThirty-two patients were recruited. The average onset age was 54.3 y/o. 28.1% had positive family history. Dementia, autonomic nervous system dysfunction, episodic attacks were three main presentations. CSF analysis including Aβ42 and tau level was almost normal. The most frequently involved on MRI was periventricular white matter (100%), frontal subcortical and deep white matter (96.6%), corpus callosum (93.1%) and external capsule (72.4%). Corticomedullary junction DWI high intensity was found in 87.1% patients. Frontal and external capsule DWI high intensity connected to form a “kite-like” specific image. Severity of dementia was significantly related to leukoencephalopathy (r = 0.465, p = 0.0254), but not cortical atrophy and ventricular enlargement. Grey matter lesions were significantly associated with encephalopathy like attacks (p = 0.00077) but not stroke like attacks. The density of intranuclear inclusions in skin biopsy was not associated with disease duration, severity of leukoencephalopathy and dementia.ConclusionsSpecific distribution of leukoencephalopathy and DWI high intensity were indicative. Leukoencephalopathy and subcortical mechanism were critical in pathogenesis of NIID. Irrelevant of inclusion density and clinical map suggested the direct pathogenic factor need further investigation.

Spinocerebellar ataxia type 17-digenic TBP/STUB1 disease: neuropathologic features of an autopsied patient

Spinocerebellar ataxia (SCA) type 17-digenic TBP/STUB1 disease (SCA17-DI) has been recently segregated from SCA17, caused by digenic inheritance of two gene mutations – intermediate polyglutamine-encoding CAG/CAA repeat expansions (polyQ) in TBP (TBP41 − 49) and STUB1 heterozygosity – the former being associated with SCA17, and the latter with SCA48 and SCAR16 (autosomal recessive). In SCA17, most patients carry intermediate TBP41 − 49 alleles but show incomplete penetrance, and the missing heritability can be explained by a new entity whereby TBP41 − 49 requires the STUB1 variant to be symptomatic. The STUB1 gene encodes the chaperone-associated E3 ubiquitin ligase (CHIP) involved in ubiquitin-mediated proteasomal control of protein homeostasis. However, reports of the neuropathology are limited and role of STUB1 mutations in SCA17-DI remain unknown. Here we report the clinicopathologic features of identical twin siblings, one of whom was autopsied and was found to carry an intermediate allele (41 and 38 CAG/CAA repeats) in TBP and a heterozygous missense mutation in STUB1 (p.P243L). These patients developed autosomal recessive Huntington’s disease-like symptoms. Brain MRI showed diffuse atrophy of the cerebellum and T2WI revealed hyperintense lesions in the basal ganglia and periventricular deep white matter. The brain histopathology of the patient shared features characteristic of SCA17, such as degeneration of the cerebellar cortex and caudate nucleus, and presence of 1C2-positive neurons. Here we show that mutant CHIP fails to generate the polyubiquitin chain due to disrupted folding of the entire U box domain, thereby affecting the E3 activity of CHIP. When encountering patients with cerebellar ataxia, especially those with Huntington’s disease-like symptoms, genetic testing for STUB1 as well as TBP should be conducted for diagnosis of SCA17-DI, even in cases of sporadic or autosomal recessive inheritance.

Association between sub‐classified white matter hyperintensities (WMH) volume and and cognitive function in patients with Alzheimer`s disease

AbstractBackgroundWMH in MRI are common among the elderly. WMH are associated with increased cognitive impairment and risk of Alzheimer`s disease (AD). Although WMH contribute to AD pathology, their clinical implications are not fully understood. This study aimed to assess whether WMH predict AD and investigate the association between WMH (including subclassified WMH volume) and cognitive function in AD.MethodThis study enrolled 171 patients with AD. All participants underwent clinical evaluations including brain MRI study and neuropsychological tests using the CERAD‐K neuropsychological assessment battery. In addition, Charlson comorbidity index, the Korean version of the Geriatric Depression Scale short from were administered. WMH volume was calculated using automated quantification method with SPM and MATLAB image processing software. WMH were classified according to the distance from the ventricular surface. WMH located in juxtaventricular areas, within 3 mm from the ventricular surface, were classified as juxtaventricular with matter hyperintensities (JVWMH). WMH located within 3–13 mm or farther than 13 mm from the ventricular surface were classified as periventricular white matter hyperintensities (PVWMH) or deep white matter hyperintensities (DWMH), respectively. WMH volume data were right‐skewed. Consequently, WMH volume data were logarithmic transformed.ResultThe AD group had a higher mean WMH volume(20.7 ± 18.2 ml). Multivariate linear regression analysis showed that total WMH volume in AD was associated with poor performance in categorical verbal fluency test (p = 0.008) and word list memory test (p = 0.023). JVWMH volume in AD was associated with poor performance on categorical verbal fluency test (p = 0.013) and digit span test forward (p = 0.037). PVWMH volume in AD was associated with poor performance on categorical verbal fluency test (p = 0.011) and word list memory test (p = 0.021), whereas DWMH volume showed no association with cognitive dysfunction in AD.ConclusionTotal WMH, JVWMH and PVWMH were associated specifically with executive function, immediate memory, and working memory, independently of hippocampal atrophy in AD. WMH were associated with AD risk and cognitive dysfunction differentially according to the distance from the ventricular surface.

Mediating roles of leukoaraiosis and infarcts in the effects of unilateral carotid artery stenosis on cognition.

Background and objectivesLeukoaraiosis and infarcts are common in patients with carotid artery stenosis (CAS), and CAS severity, leukoaraiosis and infarcts all have been implicated in cognitive impairments. CAS severity was not only hypothesized to directly impede specific cognitive domains, but also transmit its effects indirectly to cognitive function through ipsilateral infarcts as well as periventricular leukoaraiosis (PVL) and deep white matter leukoaraiosis (DWML). We aimed to delineate the contributions of leukoaraiosis, infarcts and CAS to different specific cognitive domains.Materials and methodsOne hundred and sixty one participants with unilateral CAS (>50%) on the left (n = 85) or right (n = 76) side and 65 volunteers without significant CAS (<50%) were recruited. The PVL, DWML, and infarct severity were visually rated on MRI. A comprehensive cognitive battery was administered and standardized based on age norms. Correlation and mediation analyses were adopted to examine the direct and indirect influence of CAS, leukoaraiosis, and infarct on specific cognitive domains with adjustment for education, hypertension, diabetes mellitus, and hyperlipidemia.ResultsCarotid artery stenosis severity was associated with ipsilateral leukoaraiosis and infarct. Left CAS had direct effects on most cognitive domains, except for visual memory and constructional ability, and transmitted its indirect effects on all cognitive domains through ipsilateral PVL, and on constructional ability and psychomotor through infarcts. Right CAS only had negative direct effects on visual memory, psychomotor, design fluency and color processing speed, and transmitted its indirect effects on visual memory, word and color processing speed through ipsilateral infarcts. The trends of direct and indirect cognitive effects remained similar after covariate adjustment.ConclusionLeft and right CAS would predominantly lead to verbal and non-verbal cognitive impairment respectively, and such effects could be mediated through CAS-related leukoaraiosis and infarct. Given that cognition is subject to heterogeneous pathologies, the exact relationships between markers of large and small vessel diseases and their composite prognostic effects on cognition requires further investigation.

Association between white matter lesions and Parkinson’s disease: an impact on Postural/Gait difficulty phenotype and cognitive performance

ABSTRACT Background White matter hyperintensities (WMHs) may be observed on Magnetic Resonance Imaging (MRI) in patients with Parkinson disease with or without vascular risk factors. Whether WMHs may influence motor and non-motor aspects of Parkinson disease is a subject of debate. The aim of this study is to evaluate the impact of WMH severity on various aspects of Parkinson disease in combination to the estimation of the impact of cerebrovascular risk factors. Materials and Methods We included a cohort of patients with Parkinson’s disease who underwent MRI examination. The Fazekas visual rating scale was used to assess the severity and location of WMHs, and patient clinical characteristics were correlated with MRI data. Results All vascular risk factors were associated with higher Fazekas score in both periventricular and deep white matter. Periventricular white matter hyperintensities (PWMHs) and deep white matter hyperintensities (DWMHs) were associated with lower scores in the ACE-R cognitive assessment scale (p < 0.001). Furthermore, PWMHs and DWMHs severity was associated with higher UPDRS motor score (p < 0.001), while the Postural Instability Gait Difficulty (PIGD) phenotype was correlated with higher burden of WMHs. Conclusions Comorbid WMHs may contribute to multi-dimension dysfunction in patients with Parkinson disease and consequently the management of vascular risk factors may be crucial to maintain motor and non-motor functions in PD.

The Spectrum of MRI Findings in Dengue Encephalitis.

BackgroundIn this study, we aimed to describe eight cases of dengue encephalitis along with their magnetic resonance imaging (MRI) findings. Dengue encephalitis is caused by an arbovirus that has four strains DENV1-DENV4. The dengue virus is usually non-neurotropic but DENV2 & DENV3 are neurotropic. Dengue encephalitis is characterized by headaches, seizures, and altered consciousness.MethodologyAt our facility, we performed 3T MRI on eight suspected cases of dengue encephalitis using the criteria established by Varatharaj et al. We were able to diagnose dengue encephalitis based on the proposed criteria which included symptoms, serology, cerebrospinal fluid (CSF) analysis results, MRI findings, and routine blood laboratory workup in dengue encephalitis. Because numerous brain regions are potentially impacted in severe cases of dengue encephalitis, an MRI of the brain can reveal the severity of the condition. In deteriorating situations, it may detect whether or not further regions are being impacted. Hence, MRI should be done in all suspected cases of dengue encephalitis.ResultsThe changes observed on MRI of the eight cases were in the supra-tentorium (deep periventricular white matter, subcortical white matter, and deep gray matter of the brain, which includes basal ganglia and thalami), infra-tentorium (cerebellar white matter and brainstem, which includes pons), and occasionally in cortical gray matter. The MRI showed mild-to-moderate hyperintensities on T2-weighted images and fluid-attenuated inversion recovery sequence (FLAIR); diffusion restriction is seen on diffusion-weighted images. The neurological clinical features included non-localizing signs and symptoms such as altered mental status, headache with vomiting, and fever.ConclusionsThe commonly affected areas of the brain in dengue encephalitis are the basal ganglia, thalamus, brainstem, cerebellum, cortical white matter, periventricular white matter, and cortical gray matter, which are all hyperintense on T2-weighted images and FLAIR. The lesions are iso or hypointense on T1-weighted images and micro-hemorrhages appear as blooming on susceptibility-weighted MRI. MRI is a crucial initial investigation in suspected cases of dengue encephalitis and known cases of dengue fever experiencing worsening neurological conditions.

The Prevalence, Demographics, Clinical Features, Neuroimaging, and Inter-ethnic Differences of MOGAD in Malaysia with Global Perspectives

IntroductionCNS IIDDs11Central Nervous System Idiopathic Inflammatory Demyelinating Diseases tested positive for anti-MOG22Myelin Oligodendrocyte Glycoprotein are known to have a distinct clinical profile with a better overall prognosis. ObjectivesWe 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. MethodsThis 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. ResultsAnti-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. ConclusionMalaysian 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.

Associations of depressive symptoms with white matter abnormalities and regional cerebral blood flow in patients with amnestic mild cognitive impairment.

Depressive symptoms are one of the most common neuropsychiatric symptoms in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD), although the pathophysiologies of the depressive symptoms that occur in these diseases have not been elucidated to date. In this study, we therefore investigated the associations between depressive symptoms and cognitive performance, white matter abnormalities, and regional cerebral blood flow (rCBF) in amnestic MCI patients. Thirty-eight patients with amnestic MCI were analyzed. The volumes of periventricular hyperintensities (PVH) and deep white matter hyperintensities (DWMH) were measured on T2-fluid-attenuated inversion recovery magnetic resonance imaging using the imaging software 3D-slicer. Associations between the Geriatric Depression Scale (GDS) score and other neuropsychological test scores on the one hand and the PVH and DWMH volumes on the other were analyzed. Voxel-wise correlations of rCBF with GDS score, after controlling for the effects of age, were investigated using SPM8 software. Significant correlations were identified between GDS score, Trail Making Test B and apathy scale scores on the one hand and PVH volume on the other. A significant negative association between GDS score and rCBF was identified in the right dominant bilateral dorsolateral prefrontal cortex (DLPFC). Depressive symptoms are significantly associated with PVH volume in MCI patients. The rCBF of the DLPFC was significantly associated with depressive symptoms, suggesting that this area might be closely involved in the pathogenesis of the depressive symptoms observed in MCI patients. Geriatr Gerontol Int 2022; 22: 846-850.

Effect of White Matter Hyperintensities on Daily Function via Depressive Symptoms: A Longitudinal Study in Patients With Dementia Including Alzheimer's Disease and Subcortical Ischemic Vascular Dementia.

Objective This study aimed to investigate the mediation effect of depressive symptoms on the relationship between white matter hyperintensities and the basic activities of daily living (BADL) using an integrated approach to overcome the limitations of previous studies and examine the relationship among the three variables simultaneously. Methods We performed structural equation modeling using cross-sectional data from 497 Alzheimer’s disease (AD), AD with small vessel disease, and subcortical ischemic vascular dementia patients enrolled in the Clinical Research for Dementia of South Korea registry who were diagnosed with mild-to-moderate dementia. Periventricular white matter hyperintensities (PWMHs) and deep white matter hyperintensities (DWMHs) were visualized separately at baseline using magnetic resonance imaging. Depressive symptoms were assessed using the Korean Form of the Geriatric Depression Scale at the follow-up assessment conducted after 1 year. BADL were assessed using the Barthel Index at the follow-up assessment conducted after 2 years. Results The direct and indirect effects of DWMHs on the BADL as mediated via depression were significant. However, neither the direct effect of PWMHs on the BADL nor the indirect effect of PWMHs on the BADL via depression were significant. Conclusion This study presented a mediation model that included a longitudinal developmental pathway from DWMHs to deterioration in the BADL mediated via depressive symptoms. Moreover, the mediation model of depressive symptoms could not be applied to the longitudinal developmental pathway from DWMHs to the deterioration in BADL.

Different mechanisms in periventricular and deep white matter hyperintensities in old subjects.

ObjectiveAlthough multiple pieces of evidence have suggested that there are different mechanisms in periventricular white matter hyperintensities (PWMHs) and deep white matter hyperintensities (DWMHs), the exact mechanism remains uncertain.MethodsWe reviewed clinical and imaging data of old participants from a local She Ethnic group. We assessed the cerebral blood flow of white matter (WM-CBF) on arterial spin-labeling, deep medullary veins (DMVs) visual score on susceptibility-weighted imaging, and index for diffusion tensor image analysis along the perivascular space (ALPS index), indicating glymphatic function on diffusion tensor imaging. Furthermore, we investigated their relationships with volumes of PWMHs and DWMHs.ResultsA total of 152 subjects were included, with an average age of 63 ± 8 years old. We found that higher age and history of hypertension were independently related to higher volumes of both PWMHs and DWMHs (all p < 0.05). Lower ALPS index was independently associated with higher PWMHs volumes (β = 0.305, p < 0.001), and this relationship was accounted for by the indirect pathway via DMVs score (β = 0.176, p = 0.017). Both lower ALPS index and WM-CBF were independent risk factors for higher DWMHs volumes (β = −0.146, p = 0.041; β = −0.147, p = 0.036).ConclusionsOur study indicated that there were different mechanisms in PWMHs and DWMHs. PWMHs were mainly attributed to the damage of veins due to the dysfunction of the glymphatic pathway, while DWMHs could be affected by both ischemia-hypoperfusion and dysfunction of the glymphatic pathway.Advances in knowledgeThe relationship between glymphatic dysfunction and PWMHs might be accounted for by the indirect pathway via venous abnormalities, a glymphatic dysfunction, and lower CBF in white matter were independent risk factors for DWMHs.

Association of sudden sensorineural hearing loss and its prognosis with the brain white matter hyperintensity

Objective:To explore the relationship between white matter hyperintensity（WMH） and sudden sensorineural hearing loss（SSHL） and evaluate the influence of WMH on the prognosis of SSHL. Methods:Fifty hospitalized unilateral SSHL patients and 50 age and gender matched routine physical examination individuals without SSHL history from June 2019 to June 2020 were included for a case-control study. All included subjects underwent 3.0 Tesla cranial magnetic resonance examination, and the Fazekas scale was applied to evaluate periventricular white matter hyperintense（PVWMH） and deep white matter hyperintense（DWMH）. Fazekas score and distribution proportions of Fazekas score was compared between SSHL and control. Ordered logistic regression was used to study the relationship between prognosis of SSHL and WMH. Results:The Fazekas score of WMH in SSHL group was significantly higher than that of control group（PVWMH: P=0.004, DWMH: P=0.010）; There was a significant difference in the distribution proportions of Fazekas scores between SSHL and control（PVWMH: P=0.036, DWMH: P=0.047）; The results of ordered logistic regression showed that patients without WMH（Fazekas=0） is an independent predictor of good prognosis in SSHL（P=0.025, OR=12.779）. Conclusion:The prevalence of WMH in SSHL patients was higher than that of control. SSHL patients without WMH has a better prognosis than those with WMH.

A Rare Case Report on Opsoclonus Myoclonus Syndrome Associated with a Developmental Regression

Published on:June 2022 Journal of Young Pharmacists, 2022; 14(2):256-257 Case Report | doi:10.5530/jyp.2022.14.49 Authors: Neha Suratiya*, Khevna Shah, Preya Soni, Sarvajeet Khare Department of Pharmacy Practice, Sumandeep Vidyapeeth (Deemed University), Vadodara, Gujarat, INDIA. Abstract: Developmental regression can be described as the progressive loss of previously acquired skills which is relatively rare. Opsoclonus myoclonus syndrome is an uncommon autoimmune disorder in which a patient’s body attacks its own nervous system. It usually affects young children. Complicated developmental regression may lead to diagnosis of Opsoclonus Myoclonus Syndrome (OMS). A 3 years and 1 month old, the female child presented the history of convulsion, tonic contraction of upper and lower limb, up rolling of eye ball, frothing from mouth and post ictal drowsiness at the age of 1.5 years. On examination her general condition was unstable and systemic examination was not normal (Temp- 102.2 F). Her hematological and hepatic tests were done. Magnetic Resonance Imaging (MRI) report of her brain conclude that few T2 and FLAIR hyper intense foci are noted in bilateral periventricular deep white matter possibility of myelin pallor likely. We show that Opsoclonus myoclonus syndrome can be associated with developmental regression. Neurologist must be aware of such presentation. Our findings highlighted the need for increased recognition of developmental regression leading OMS as an urgent and treatable condition.Key words: Opsoclonus myoclonus syndrome (OMS), Developmental regression, Paraneoplastic, Myelin pallor, Ataxia, Cerebellar nuclei degeneration.

Quantitative Analysis of White Matter Hyperintensity: Comparison of Magnetic Resonance Imaging Image Analysis Software

ObjectiveWhite matter hyperintensity (WMH), defined as abnormal signals on magnetic resonance imaging (MRI), is an important clinical indicator of aging and dementia. Although MRI image analysis software can automatically detect WMH, the quantitative accuracy of periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH) is unknown. Materials and MethodsThis study was a sub-analysis of MRI data from an ongoing hospital-based prospective cohort study (the Gimlet study). Between March 2016 and March 2017, we enrolled patients who visited our memory clinic and agreed to undergo medical assessments of cognitive function and fecal examination to study the gut microbiome. Participants with a history of stroke were excluded. WMH was independently quantitatively analyzed using two MRI imaging analysis software modalities: SNIPER and FUSION. Intraclass correlation coefficients and the mean difference in volume were calculated and compared between modalities. ResultsThe data of 87 patients (49 women, mean age 74.8 ± 7.9 years) were analyzed. Both total WMH and DWMH volumes obtained using FUSION were greater (p < 0.001), and PVH volume was smaller (p < 0.001) than those obtained using SNIPER. Intraclass correlation coefficients for the lesion measurements of WMH, PVH, and DWMH between the different software were 0.726 (p < 0.001), 0.673 (p < 0.001), and 0.048 (p = 0.231), respectively. ConclusionsThere were significant differences in the quantitative data of WMH between the two MRI imaging analysis software modalities. Thus, care should be taken for quantitative assessments of WMH.