Bilateral Frontal White Matter Research Articles

The aftermath of boxing: Longitudinal changes of cerebral retention patterns of 18F‐florzolotau (18F‐APN‐1607) in the former professional boxers

AbstractBackgroundChronic traumatic encephalopathy (CTE), formerly known as “boxer’s encephalopathy” is a neurodegenerative disease associated with mild‐repetitive TBI. CTE is characterized by the deposition of hyperphosphorylated tau as neurofibrillary tangles around small blood vessels of the cortex, typically at the sulcal depths. Although tau PET studies on American football players reported findings consistent with neuropathological changes identified by postmortem brains, there are no reports of tau PET studies in boxers, and longitudinal changes of tau depositions following boxing remains unknown. The present study was aimed to characterize cerebral retention patterns of 18F‐florzolotau (18F‐APN‐1607) in the former professional boxers.MethodTwenty‐nine former boxers (43.4 ± 10.3 years) and 27 age‐matched healthy control (HC) subjects underwent PET scans with 18F‐florzolotau and 11C‐PiB. Eleven former boxers underwent a second tau PET scan (average interval: 874days). Standard uptake value ratio (SUVR) with the optimized reference tissue was calculated. Regions of interest were defined on brain regions of the gray matter (GM), white matter (WM) and the gray‐white matter boundary (GWB). Association of regional SUVR values with neurocognitive symptoms and various indexes related boxing was investigated.ResultOne boxer was [11C]PiB positive. Former boxers showed higher 18F‐florzolotau retentions than HC subjects in the bilateral frontal GM, right parietal GM, bilateral frontal WM, right parietal WM (P < 0.001). There was a significant correlation between SUVR values in the whole GM and the total number of bouts (p = 0.07,r = 0.40). Subtyping using z‐score heatmap with predetermined criteria revealed heterogeneity in 18F‐florzolotau retention patterns in boxers. Of the 29 boxers, (1) 10 showed increased retention of 18F‐florzolotau in GM (GM dominant), (2) 4 showed increased accumulation mainly in WM (WM dominant), (3) 5 showed increased accumulation in GWB (GWB dominant), and (4) 10 showed no significant increased accumulation in the brain (No tau). These types vary in longitudinal changes of 18F‐florzolotau retention patterns, as well as in clinical features.ConclusionThe present study not only supports pathological heterogeneity of late‐sequalae of professional boxing, but also suggests utility of 18F‐florzolotau PET in detection of late‐life neurodegenerative diseases following mild‐repetitive TBI.

A Rare and Novel Pathogenic Variant of the PINK1 Gene Associated with Early-onset of Parkinson’s Disease - A Case Study

We reported a case of rare and novel PINK 1 gene variant associated with Early-onset Parkinson’s Disease (EOPD) in 40-year-old male patient. Patient was presented with clinical indications of dystonia (left>right), hemidystonia and dystonic tremors. Patient has family history (elder sister) of parkinsonism diagnosed with PD at the age of 38 years, and the condition slowly deteriorated and died. Patient was subjected to MRI investigations of brain two years before on clinical condition of right upper limb involuntary movement since from past one year. MRI findings revealed few small non- specific foci of T2 hyperintensity seen scattered in the bilateral frontal white matter (R>L)’ incidental findings of doubtful significance. Patient was referred for whole exome sequencing. The exome data analysis identified a “homozygous autosomal recessive variant” of PINK1 gene with variant nomenclature “c.823_825delATC; p.Ile275del (Chr1:20644531 ACAT>A)” could be associated with EOPD with characterized rare clinical phenotypic manifestations in the form of hemidystonia.

THU234 An Adolescent Patient With Asymptomatic Hypocalcemia And Extensive Cerebral Calcification Due To Pseudohypoparathyroidism Type 1B: A Care Report

Abstract Disclosure: R. Alemzadeh: None. J.D. Ross: None. D. Guillen-Mendoza: None. Background: Pseudohypoparathyroidism (PHP) is a heterogeneous group of disorders due to renal resistance to parathyroid hormone (PTH) resulting in biochemical hypoparathyroidism but with skeletal sensitivity to PTH. Case Presentation: A 15-year-old African American male was incidentally found to have biochemical evidence of severe hypocalcemia during routine evaluation of his bilateral slipped capital-femoral epiphyses. The patient was at age-appropriate stage of puberty with normal height and without any features of hereditary osteodystrophy. However, he had history of mild developmental delay requiring school accommodations. On physical exam, there was some mild dyscoordination with finger and toe-tapping and a Myerson’s sign, negative tetany signs. The biochemical screening revealed markedly low serum calcium (4.9 mg/dL) with elevated phosphorus (7.8 mg/dL) and PTH (1314 pg/mL) levels. His hypocalcemia was accentuated by the presence of severe 25 hydroxy-vitamin D deficiency (7.5 ng/mL) with mild hypomagnesemia (1.4 mg/dL). He had normal renal and thyroid function tests with normal growth factors. There were minimal plasma cyclic AMP responses to a single dose of intravenous teriparatide (Ellsworth-Howard test) consistent with diagnosis of pseudohypoparathyroidism. The skeletal survey showed bowing and under-tubulation of the radius, ulna, tibia, and fibula as well as slipped capital femoral epiphysis bilaterally. His brain CT scan showed symmetrical severe dense calcifications in the basal ganglia, bilateral frontal, parietal and temporal subcortical white matter, pons and right dentate nucleus. Genetic testing did not reveal any GNAS mutations. The patient was initially treated with parenteral calcium followed by high-dose oral calcium supplements and calcitriol. His coexisting hypovitaminosis D and hypomagnesemia were corrected with oral high-dose cholecalciferol and magnesium sulfate, respectively. Conclusions: An incidental finding of severe asymptomatic hypocalcemia and elevated PTH without hereditary osteodystrophy phenotype raised the clinical suspicion of pseudohypoparathyroidism type 1B. This was associated with cerebral calcifications with increasing risk of worsening learning disabilities and minimal neurological findings. Presentation: Thursday, June 15, 2023

Posterior Reversible Encephalopathy Syndrome (PRES), Hypoxic Injury and Stroke: A Sequelae of Bath Salt Inhalation? (P2-5.012)

<h3>Objective:</h3> To describe a case of bath salt inhalation causing PRES, hypoxic injury, and acute stroke. <h3>Background:</h3> Bath salts contain 3,4-methylenedioxypyrovalerone, a substance similar to cocaine and amphetamines, and can lead to vasospasm by inhibiting dopamine and norepinephrine reuptake. PRES and stroke can be caused by hypertension, but its coexistence in a patient with bath salt inhalation has been not described. <h3>Design/Methods:</h3> This is a case report of a 48-year-old female patient with a history of heroin abuse was found unresponsive. On arrival, was noted to have a systolic blood pressure over 200s and was seizing. On exam, she had expressive and receptive aphasia. Initial labs including a urine toxicology screen were unremarkable. CTA was concerning for vasospasm vs vasculitis. MRI Brain revealed multiple infarcts in bilateral hemisphere with extensive involvement of left posterior cerebral artery and T2 hyperintensities in the bilateral cerebellum and pons. Moreover, T2 FLAIR hyperintensities were noted in bilateral frontal and parietal white matter indicative of PRES. There was also injury to bilateral thalami and watershed vascular distributions suggestive of hypoxic insult. Extensive workup including TEE and LP failed to show an embolic source or vasculitis. <h3>Results:</h3> On further history, mother reported that patient routinely inhales bath salts. PRES findings were improved on repeat MRI 5 days later, but ischemia persisted. Her BP was hard to manage as stroke requires permissive hypertension and PRES requires BP control. She remained aphasic. <h3>Conclusions:</h3> Bath salt inhalation is shown to be associated with ischemic colitis and myocardial infarction, but no instances of stroke or PRES have been reported. The pathophysiological mechanisms between PRES and stroke differ, but may be secondary to vasospasm in the setting of bath salt inhalation. <b>Disclosure:</b> Dr. Mufti has nothing to disclose. Dr. Shi has nothing to disclose. Dr. Mufti has nothing to disclose. Dr. Hasan has nothing to disclose.

Diffusion Tensor Imaging for Interpreting Fractional Anisotropy and Mean Diffusivity in Normal-appearing White Matter of Patients with HIV-associated Neurocognitive Disorders: A Case-control Study

Introduction: {Human Immunodeficiency Virus (HIV)-associated Neurocognitive Disorder (HAND)} affects the everyday functioning of patients. It is usually difficult to diagnose HAND in the outpatient setting as detailed neuropsychological performance testing, such as the International HIV Dementia Scale (IHDS), is required. Neuroimaging techniques hold great promise in the early diagnosis and management of HAND, but there is a paucity of studies on the evaluation of HAND using Diffusion Tensor Imaging (DTI) in the Indian population. Aim: To investigate DTI and interpret Fractional Anisotropy (FA) and Mean Diffusivity (MD) values in the White Matter (WM) of patients with HAND and compare them with age and sex- matched controls. Materials and Methods: A case-control study was conducted at the Department of Radiodiagnosis, ABVIMS and Dr. RML Hospital, New Delhi, India, from January 2021 to May 2022. Thirty subjects (15 cases and 15 controls) were included. HIV-positive patients underwent the IHDS to assess cognitive impairment. Magnetic Resonance Imaging (MRI) examination was performed at three tesla using conventional sequences, and DTI was applied. Maps of FA and MD values were generated. Mean FA and MD values of normal-appearing white matter tracts between cases and controls were compared using a t-test. Spearman's correlation test was applied to assess the correlation between IHDS scores and DTI parameters. Results: The majority of cases in the study were in the age group of 31-40 years, and the mean age of cases was 41.27±11.16 years. The present study revealed significantly lower FA values compared to controls in bilateral Frontal WM, Parieto-occipital WM, genu of the Corpus Callosum (CC), right hippocampal WM, and right corona radiata. The mean MD of bilateral Frontal WM, Parieto-occipital WM, corona radiata, and Hippocampal WM was significantly increased in cases compared to healthy controls. A significant association was found between the IHDS score and FA values of the genu of the CC (rho= 0.7), right corona radiata (rho= 0.7), right Hippocampal WM (rho= 0.9), and MD of the left Parieto-occipital WM (rho= -0.6), and left hippocampal WM (rho= -0.5). Conclusion: Diffusion tensor MR imaging can detect abnormalities that are missed by routine MR imaging. DTI provides a valuable marker to monitor HIV-associated Central Nervous System (CNS) injury, which can lead to neurocognitive impairment.

AN INHERITABLE STROKE DISORDER PRESENTING WITH UNIPOLAR PSYCHOTIC DEPRESSION: CASE REPORT OF A RARE ENTITY

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant rare hereditary angiopathy that causes stroke in young patients. Most frequent clinical presentations include ischemic strokes, recurrent transient ischaemic attacks and migraine with aura. Psychiatric manifestations are conspicuously rare and especially if present as the only presenting manifestation. Here is a case of a female patient in her fties who was diagnosed with major depressive disorder with psychotic features and was on medication for the same for one and a half years with no improvement in symptoms. She was subsequently admitted due to an increased tendency to self-harm and on day 6 of admission had an episode of seizures, which led us to look for organic causes. After a battery of tests and ruling out various differentials, she underwent an MRI which revealed T2 hyperintense signal in bilateral frontal, temporal, parieto-occipetal, and periventricular white matter. Based on MRI ndings, family history of her father passing away due to a stroke at age 68 and poor response to antidepressants, she was suspected to have CADASIL. She underwent genetic testing which conrmed the same. The clinical course and distinct facts of the case are divulged below.

Neuroimaging Correlates of Post-Traumatic Stress Disorder in Traumatic Brain Injury: A Systematic Review of the Literature

IntroductionNeuroimaging has been a highly utilized technique for studying traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) independently of one another, however, neuroimaging has increasingly been identified as a useful tool in better understanding TBI-related psychiatric conditions, such as PTSD.ObjectivesTo complete a systematic review of the literature examining neuroimaging findings in TBI-related PTSD and to highlight the current literature’s limitations in order to strengthen future research.MethodsA PRISMA compliant literature search was conducted in PubMed (MEDLINE), PsychINFO, EMBASE, and Scopus databases prior to May of 2019. The initial database query yielded 4388 unique articles, which were narrowed down based on specified inclusion criteria (e.g., clear TBI definition, clinician-diagnosed PTSD, statistically analyzed relationship between neuroimaging and PTSD, quantified time interval between TBI and neuroimaging).ResultsA final cohort of 10 articles met inclusion criteria, comprising the findings of 482 participants with TBI. Key neuroanatomical findings among the included articles suggest that PTSD is associated with significant changes in whole-brain networks of resting state connectivity and disruptions in bilateral frontal and temporal white matter tracts, fronto-limbic pathways, the internal capsule, and the uncinate fasciculus (Figure 1). Figure 1a:Neuroimaging Findings in TBI-related PTSD.Figure 1b.Replicated Neuroimaging Findings in TBI-related PTSD in the Right Uncinate Fasciculus.ConclusionsAdditional inquiry with attention to specified imaging timing post-injury, consistent TBI definitions, clinician-diagnosed TBI and PTSD, and control groups is crucial to extrapolating discrepancies between primary and TBI-related PTSD. Prospective studies could further differentiate predisposing factors from sequelae of TBI-related PTSD.DisclosureNo significant relationships.

Magnetic resonance spectroscopy shows associations between neurometabolite levels and perivascular space volume in Parkinson's disease: a pilot and feasibility study.

Higher volume fraction of perivascular space (PVS) has recently been reported in Parkinson's disease (PD) and related disorders. Both elevated PVS and altered levels of neurometabolites, assayed by proton magnetic resonance spectroscopy (MRS), are suspected indicators of neuroinflammation, but no published reports have concurrently examined PVS and MRS neurometabolites. In an exploratory pilot study, we acquired multivoxel 3-T MRS using a semi-Localization by Adiabatic SElective Refocusing (sLASER) pulse-sequence (repetition time/echo time = 2810/60 ms, voxels 10 × 10 × 10 mm3) from a 2D slab sampling bilateral frontal white matter (FWM) and anterior middle cingulate cortex (aMCC). PVS maps obtained from high-resolution (0.8 × 0.8 × 0.8 mm3) T1-weighted MRI were co-registered with MRS. In each MRS voxel, PVS volume and neurometabolite levels were measured. Linear regression accounting for age, sex, and BMI found greater PVS volume for higher levels of choline-containing compounds (Cho; P = 0.047) in FWM and lower PVS volume for higher levels of N-acetyl compounds (NAA; P = 0.012) in aMCC. Since (putatively) higher Cho is associated with inflammation while NAA has anti-inflammatory properties, these observations add to evidence that higher PVS load is a sign of inflammation. Additionally, lower Montreal Cognitive Assessment scores were associated with lower NAA in aMCC (P = 0.002), suggesting that local neuronal dysfunction and inflammation contribute to cognitive impairment in PD. These exploratory findings indicate that co-analysis of PVS and MRS is feasible and may help elucidate the cellular and metabolic substrates of glymphatic and inflammatory processes in PD.

Quantitative Susceptibility Mapping of Brain Iron Relating to Cognitive Impairment in Hypertension.

Hypertension (HTN) might impair cognition. Brain iron deposition correlates with cognitive impairment. The relationship between brain iron and cognition in HTN patients is less clear. To measure brain susceptibility in HTN patients using quantitative susceptibility mapping (QSM) and to explore the relationship between brain iron and cognition. Retrospective cross-sectional study. Sixty HTN patients (35 with mild cognitive impairment [MCI] and 25 without MCI) and 24 age, gender, and education matched controls. 3 T; strategically acquired gradient echo (STAGE) imaging protocol for QSM analysis. All subjects underwent Montreal Cognitive Assessment (MoCA) scoring of visuospatial/executive, naming, attention, abstraction, language, delayed memory, and orientation functions. HTN patients were divided into two groups (with and without MCI) depending on the MoCA score. Regions of interest (ROIs) were manually demarcated on the STAGE images by three independent radiologists and susceptibility were determined for bilateral frontal white matter, parietal white matter, occipital white matter, caudate nucleus (CN), putamen (PU), globus pallidus (GP), thalamus (TH), red nucleus (RN), substantia nigra (SN), and dentate nucleus (DN). Analysis of variance with post-hoc least significant difference (LSD) tests and Pearson correlation coefficients (r). A P-value <0.05 was considered to be statistically significant. The susceptibility was significantly different in CN, PU, and DN among the three groups. The susceptibility of right CN and left PU were correlated with MoCA scores (r=-0.429 and r=-0.389, respectively). The susceptibility of left PU was also correlated with delayed memory scores (r=-0.664). The susceptibility of left and right GP were correlated with naming scores (r=-0.494 and r=-0.446, respectively) and the susceptibility of left DN were correlated with visuospatial/executive scores (r=0.479). QSM measured brain iron was significantly higher in CN, PU, and DN in HTN patients. Cognitive impairment was correlated with regional brain iron deposition. 2 TECHNICAL EFFICACY: Stage 3.

Subacute Sclerosing Panencephalitis: Restricted Diffusion and Clinical Evolution.

Subacute sclerosing panencephalitis (SSPE) is a rare entity characterized by a protracted course and progressive neurological deterioration. We present patterns of diffusion restriction in eight cases of SSPE, a seldom described imaging attribute. A retrospective analysis was performed on the clinical and neuroimaging data obtained from records of patients with proven SSPE. Patients whose magnetic resonance imaging (MRI) showed evidence of diffusion restriction were included in the analysis. MRI was performed on 3 T and 1.5-T clinical MR systems. Imaging characteristics were reviewed and tabulated by two neuroradiologists. Eight SSPE patients (seven men, one woman; age range: 5-15 years; mean age: 11 years) diagnosed and managed at our institute were included in the analysis. Restricted diffusion was evident in the basal ganglia (n = 3), corpus callosum (n = 2), white matter (n = 2) and in bilateral middle cerebellar peduncles (MCP) (n = 2). One patient had diffusion restriction in the genu of the corpus callosum and bilateral frontal cortical white matter. None of the diffusion-restricted lesions showed contrast enhancement or susceptibility. Six cases fulfilled the diagnostic criteria for fulminant SSPE (fSSPE). The extent of neuroparenchymal involvement was greater in this subset of patients. Restricted diffusion in SSPE, hitherto infrequently described, can indeed occur in both grey and white matter structures and in both supratentorial and infratentorial compartments. Parenchymal diffusion restriction in SSPE possibly reflects an early time point in the clinical evolution. A greater extent of parenchymal diffusion restriction may portend a rapid downhill course, possibly qualifying for fSSPE.

Diagnostic performance of arterial spin-labeled perfusion imaging and diffusion-weighted imaging in full-term neonatal hypoxic-ischemic encephalopathy.

We evaluated the performance of arterial spin-labeled perfusion imaging and diffusion-weighted imaging in diagnosing full-term neonatal hypoxic-ischemic encephalopathy. Arterial spin-labeled, diffusion-weighted imaging and conventional magnetic resonance imaging (T1-weighted imaging, T2-weighted imaging and T2 fluid-attenuated inversion recovery) were performed in 23 full-term neonates with hypoxic-ischemic encephalopathy group 10 normal neonates (Control group). The cerebral blood flow and the apparent diffusion coefficient were measured in the bilateral basal ganglia, thalamus and frontal white matter. The effect of neonatal age on the CBF and apparent diffusion coefficient values were further investigated after dividing the 23 ischemic encephalopathy cases into three subgroups (1-3 days, 4-7 days, and 8-15 days). The cerebral blood flow values in the thalamus and lenticular nucleus were significantly higher. The apparent diffusion coefficient values in the thalamus, frontal white matter and lenticular nucleus head were significantly lower in the hypoxic-ischemic encephalopathy group than those in the Control group (p < 0.05). There were no significant differences between the ischemic encephalopathy and Control groups in the cerebral blood flow values in the caudate nucleus head and frontal lobe white matter (p > 0.05). The cerebral blood flow and apparent diffusion coefficient values in the thalamus and lenticular nucleus were negatively correlated. Comparison among different age subgroups of hypoxic-ischemic encephalopathyneonates showed that the cerebral blood flow value was higher. In comparison, the apparent diffusion coefficient value was lower in the 1-3 days old neonates than those in the older neonates (p < 0.05). Arterial spin-labeled and diffusion-weighted imaging could reflect the ischemic encephalopathy pathological processes more comprehensively. The cerebral blood flow measurement and apparent diffusion coefficient values in the thalamus and the lenticular nucleus may represent a novel way to diagnose ischemic encephalopathy early.

Distinct patterns of progressive gray and white matter degeneration in amyotrophic lateral sclerosis.

Progressive cerebral degeneration in amyotrophic lateral sclerosis (ALS) remains poorly understood. Here, three‐dimensional (3D) texture analysis was used to study longitudinal gray and white matter cerebral degeneration in ALS from routine T1‐weighted magnetic resonance imaging (MRI). Participants were included from the Canadian ALS Neuroimaging Consortium (CALSNIC) who underwent up to three clinical assessments and MRI at four‐month intervals, up to 8 months after baseline (T 0). Three‐dimensional maps of the texture feature autocorrelation were computed from T1‐weighted images. One hundred and nineteen controls and 137 ALS patients were included, with 81 controls and 84 ALS patients returning for at least one follow‐up. At baseline, texture changes in ALS patients were detected in the motor cortex, corticospinal tract, insular cortex, and bilateral frontal and temporal white matter compared to controls. Longitudinal comparison of texture maps between T 0 and T max (last follow‐up visit) within ALS patients showed progressive texture alterations in the temporal white matter, insula, and internal capsule. Additionally, when compared to controls, ALS patients had greater texture changes in the frontal and temporal structures at T max than at T 0. In subgroup analysis, slow progressing ALS patients had greater progressive texture change in the internal capsule than the fast progressing patients. Contrastingly, fast progressing patients had greater progressive texture changes in the precentral gyrus. These findings suggest that the characteristic longitudinal gray matter pathology in ALS is the progressive involvement of frontotemporal regions rather than a worsening pathology within the motor cortex, and that phenotypic variability is associated with distinct progressive spatial pathology.

Effects of Age on White Matter Microstructure in Children With Neurofibromatosis Type 1.

Children with neurofibromatosis type 1 (NF1) often report cognitive challenges, though the etiology of such remains an area of active investigation. With the advent of treatments that may affect white matter microstructure, understanding the effects of age on white matter aberrancies in NF1 becomes crucial in determining the timing of such therapeutic interventions. A cross-sectional study was performed with diffusion tensor imaging from 18 NF1 children and 26 age-matched controls. Fractional anisotropy was determined by region of interest analyses for both groups over the corpus callosum, cingulate, and bilateral frontal and temporal white matter regions. Two-way analyses of variance were done with both ages combined and age-stratified into early childhood, middle childhood, and adolescence. Significant differences in fractional anisotropy between NF1 and controls were seen in the corpus callosum and frontal white matter regions when ages were combined. When stratified by age, we found that this difference was largely driven by the early childhood (1-5.9 years) and middle childhood (6-11.9 years) age groups, whereas no significant differences were appreciable in the adolescence age group (12-18 years). This study demonstrates age-related effects on white matter microstructure disorganization in NF1, suggesting that the appropriate timing of therapeutic intervention may be in early childhood.

Medico-Legal Opinion Based on Autopsy Findings of a Victim of an Explosion Involving Mass Fatality.

Investigation into explosions is one of the major areas in forensic medicine and pathology. Medico legal issues associated with these deaths are diverse and forensic experts are often expected to make clarifications. Assistance of a methodical scientific investigation of such a death in evaluation of unanswered medico legal issues, of an autopsy of one of the victims of Easter Sunday explosions is discussed. The deceased was a 15-year-old girl who was participating in the Easter mass at St. Sebastian's Church - Kattuwapaitya, Negombo, Sri Lanka when a suicide bomber blew himself up. The mother of the deceased noticed the deceased being rushed to the hospital. However, she was pronounced dead on admission. Pre-autopsy radiology revealed spherical shrapnel in the temporal region. At autopsy, the fatal injury was found on the head and a detailed study revealed skull fractures associated with penetration by 3 shrapnels. There was a keyhole lesion among the penetrations. Internal examination revealed an extensive dural tear underlying the compound fracture. The brain was grossly edematous with lacerations on the frontal and parietal lobes associated with localized subarachnoid hemorrhage. There were multiple underlying contusions on bilateral frontal white matter. Small subarachnoid haemorrhage was noted on the basal aspect of the brain. Careful evaluation of the autopsy findings assisted in formulating the opinion scientifically on event reconstruction including the proximity of the victim to the epicenter of explosion and nature of explosive device, period of survival, mechanism of causation of skull fractures and the mechanism of death in addition to the cause of death. A forensic pathologist following a meticulous autopsy examination, along with a team of ballistic experts and specially trained police personnel play a pivotal task in analyzing a scene of explosion and an autopsy of a victim, in concluding the case and in bringing justice to all the victims and survivors of the catastrophe.

Characteristics of diffusion tensor imaging of central nervous system in children with tourette's disease.

To investigate the characteristics of diffusion tensor imaging (DTI) of the central nervous system in children with Tourette syndrome (TS).Fifteen children with TS (TS group) and 15 normal children (control group) were studied, and all of them underwent DTI. The apparent diffusion coefficient (ADC) and fractional anisotropy (FA) parameters were calculated using the DTIStudio software. The region of interest was delineated manually. The ADC and FA values of the bilateral caudate nucleus, bilateral globus pallidus, bilateral putamen, bilateral thalamus, and bilateral frontal lobe white matter were measured using the region of interest editor software. The differences of FA values and ADC values between the same brain areas were compared. The associations between ADC, FA values and Yale Global Tic Severity Scale (YGTSS) scores were evaluated by Pearson correlation analyses.The FA values of left globus pallidus and left thalamus were significantly lower in the TS group than in the control group (P < .05), while the ADC values of the right caudate nucleus and bilateral thalamus were significantly higher in the TS group than in the control group (P < .05). The decrease in FA in the left thalamus significantly correlated with the YGTSS score (r = 0.692; P < .05). No correlation was found between FA and ADC values in other brain regions and the YGTSS score (P > .05).After the DTI analyses, abnormalities were found in the left globus pallidus, right caudate nucleus, and bilateral thalamus in children with TS. Especially the changes in the left thalamus structure was crucial in the pathophysiological clock of TS.

Novel gene mutation of molybdenum cofactor deficiency

Molybdenum cofactor deficiency is a rare metabolic condition characterized by brain dysfunction (encephalopathy) that worsens over time. Molybdenum cofactor deficiency is caused by mutations in the ΜΟSC1, ΜΟSC2, or GPHN gene. There are three forms of the disorder, named types A, B, and C. The forms have the same signs and symptoms but are distinguished by their genetic cause: ΜΟSC1 gene mutations cause type A, ΜΟSC2 gene mutations cause type B, and GPHN gene mutations cause type C. Herein we are reporting a 2 months old child who presented to our hospitals with seizure disorders, post cardiac arrest. After clinical evaluation, and thorough investigations, uric acid was undetectable. MRI brain showed periventricular leukomalacia- HIE picture, with bilateral frontal lobe white matter loss with extensive cystic formation and thinning of corpus callosum. Molecular genetic testing showed pathogenic deletion c.604_624del p.( Gly202_glu208del) in exon 4 of MOCS1 gene in homozygous state. to best of our knowledge this variant was not yet reported in any literature yet.

Peripheral Innate Immune Activation Correlates With Disease Severity in GRN Haploinsufficiency.

Objective: To investigate associations between peripheral innate immune activation and frontotemporal lobar degeneration (FTLD) in progranulin gene (GRN) haploinsufficiency.Methods: In this cross-sectional study, ELISA was used to measure six markers of innate immunity (sCD163, CCL18, LBP, sCD14, IL-18, and CRP) in plasma from 30 GRN mutation carriers (17 asymptomatic, 13 symptomatic) and 29 controls. Voxel based morphometry was used to model associations between marker levels and brain atrophy in mutation carriers relative to controls. Linear regression was used to model relationships between plasma marker levels with mean frontal white matter integrity [fractional anisotropy (FA)] and the FTLD modified Clinical Dementia Rating Scale sum of boxes score (FTLD-CDR SB).Results: Plasma sCD163 was higher in symptomatic GRN carriers [mean 321 ng/ml (SD 125)] compared to controls [mean 248 ng/ml (SD 58); p < 0.05]. Plasma CCL18 was higher in symptomatic GRN carriers [mean 56.9 pg/ml (SD 19)] compared to controls [mean 40.5 pg/ml (SD 14); p < 0.05]. Elevation of plasma LBP was associated with white matter atrophy in the right frontal pole and left inferior frontal gyrus (p FWE corrected <0.05) in all mutation carriers relative to controls. Plasma LBP levels inversely correlated with bilateral frontal white matter FA (R2 = 0.59, p = 0.009) in mutation carriers. Elevation in plasma was positively correlated with CDR-FTLD SB (b = 2.27 CDR units/μg LBP/ml plasma, R2 = 0.76, p = 0.003) in symptomatic carriers.Conclusion: FTLD-GRN is associated with elevations in peripheral biomarkers of macrophage-mediated innate immunity, including sCD163 and CCL18. Clinical disease severity and white matter integrity are correlated with blood LBP, suggesting a role for peripheral immune activation in FTLD-GRN.

Characterizing Fatigue-Related White Matter Changes in MS: A Proton Magnetic Resonance Spectroscopy Study.

Few cross-sectional studies have investigated the correlation between neurochemical changes and multiple sclerosis (MS) fatigue, but little is known on the fatigue-related white matter differences between time points. We aim to investigate the longitudinal neurometabolite profile of white matter in MS fatigue. Forty-eight relapsing remitting multiple sclerosis (RRMS) patients with an expanded disability status scale (EDSS) ≤ 4 underwent high field 1H-multivoxel magnetic resonance spectroscopy (MRS) at baseline and year 1. Fatigue severity was evaluated by the fatigue severity scale (FSS). Patients were divided into low (LF, FSS ≤ 3), moderate (MF, FSS = 3.1–5), and high fatigue (HF, FSS ≥ 5.1) groups. In a two-way analysis of variance (ANOVA), we observed a decline in the ratio of the sum of N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) to the sum of creatine (Cr) and phosphocreatine (PCr) in the right anterior quadrant (RAQ) and left anterior quadrant (LAQ) of the MRS grid in the HF group at baseline and year 1. This decline was significant when compared with the LF group (p = 0.018 and 0.020). In a one-way ANOVA, the fatigue group effect was significant and the ratio difference in the right posterior quadrant (RPQ) and left posterior quadrant (LPQ) of the HF group was also significant (p = 0.012 and 0.04). Neurochemical changes in the bilateral frontal white matter and possibly parietooccipital areas were noted in the HF group at two different time points. Our findings may shed some light on the pathology of MS fatigue.

The Impact of Alcohol Use on Frontal White Matter in HIV.

Alcohol use disorder (AUD) is prevalent among individuals diagnosed with human immunodeficiency virus (HIV), and both HIV and alcohol use have been shown to negatively affect the integrity of white matter pathways in the brain. Behavioral, functional, and anatomical impairments have been linked independently to HIV and alcohol use, and these impairments have bases in specific frontally mediated pathways within the brain. Magnetic resonance imaging data were acquired for 37 HIV+ participants without dementia or hepatitis C. Imaging data were processed through the FreeSurfer and TraCULA pipelines to obtain 4 bilateral frontal white matter tracts for each participant. Diffusion metrics of white matter integrity along the highest probability pathway for each tract were analyzed with respect to demographics, disease-specific variables, and reported substance use. Significantly increased axial diffusivity (decreased axonal integrity) and a trending increase in mean diffusivity were observed along the anterior thalamic radiation (ATR) in participants with a history of AUD. A diagnosis of AUD explained over 36% of the variance in diffusivity along the ATR overall when accounting for clinical variables including nadir CD4 and age-adjusted HIV infection length. This study provides evidence of HIV-related associations between alcohol use and indicators of axonal integrity loss along the ATR, a frontal pathway involved in the inhibition of addictive or unwanted behaviors. Reduced axonal integrity of this pathway was greatest in HIV+ participants with an AUD, even when considering the effect of age-adjusted disease length and severity (nadir CD4). This finding implicates a potential biological mechanism linking reduced integrity of frontal white matter to the high prevalence of AUD in an HIV+ population without dementia or hepatitis C.

White matter correlates of temporal discounting in older adults.

Temporal discounting, the tendency to select a smaller reward offered sooner over a larger reward offered at a later time, has been associated with a number of real-world decision-making outcomes important for health and wellbeing. Neurobiological mechanisms supporting temporal discounting have been explored among younger participants, and these have considered white matter integrity. However, the white matter correlates of temporal discounting in older adults are unclear. We hypothesized that greater temporal discounting would be associated with poorer white matter integrity measures, more specifically lower fractional anisotropy and higher trace, in older adults. Participants were 302 older persons without dementia (mean age = 81.38, mean years of education = 15.75, 75.5% female, mean MMSE = 28.29) from the Rush Memory and Aging Project, a community-based longitudinal study of aging. Temporal discounting was assessed using standard elicitation questions. White matter integrity was assessed with diffusion tensor imaging (DTI). Regression models were adjusted for the effects of age, sex, education, and white matter lesions. Secondary models further adjusted for global cognition. Results revealed significant associations between temporal discounting and white matter integrity measures (FA and trace) in bilateral frontal, frontostriatal, and temporal-parietal lobe white matter tracts, and results remained significant after further accounting for global cognition. These results suggest that temporal discounting is inversely associated with white matter integrity in old age and that this association is independent of global cognition.