Longitudinal T1 relaxation rate (R1) captures changes in short-term Mn exposure in welders

ObjectivesWe demonstrated recently that the T1 relaxation rate (R1) captured short-term Mn exposure in welders with chronic, relatively low exposure levels in a cross-sectional study. In the current study, we used a longitudinal design to examine whether R1 values reflect the short-term dynamics of Mn exposure.MethodsTwenty-nine welders were evaluated at baseline and 12 months. Occupational questionnaires estimated short-term welding exposure using welding hours in the 90 days prior to each study visit (HrsW₉₀). In addition, blood Mn levels, the pallidal index (PI; globus pallidus T1-weighted intensity (T1WI)/frontal white matter T1WI), and R1 values in brain regions of interest (ROIs) were determined as Mn biomarkers at each visit. Associations between changes in estimated welding exposure and changes in purported Mn biomarkers were assessed by Spearman’s correlations with adjustment for age and baseline R1, HrsW₉₀, and blood Mn values.ResultsChanges in welding hours (HrsW₉₀: the short-term welding exposure estimate), was associated significantly with changes in R1 values in the putamen (r = 0.541, p = 0.005), caudate (R = 0.453, p = 0.023), globus pallidus (R = 0.430, p = 0.032), amygdala (R = 0.461, p = 0.020), and hippocampus (R = 0.447, p = 0.025), but not with changes in blood Mn levels or the PI.DiscussionChanges in R1 values correlated with changes in the short-term welding exposure estimate, but not with more traditional measures of Mn exposure (blood Mn levels or PI). These results suggest that R1 may serve as a useful marker to capture the short-term dynamics in Mn brain accumulation related to welding exposure.     

Association of neurobehavioral performance with R2* in the caudate nucleus of asymptomatic welders

ObjectivesWelding fumes contain several metals including manganese (Mn) and iron (Fe) that may affect the nervous system. Previous studies of potential welding-related neurotoxicity have focused primarily on Mn exposure. The current study examined neurobehavioral and brain imaging changes in asymptomatic welders and their associations with both Mn and Fe exposure measurements.MethodsData were obtained from subjects with (n = 46) and without (controls; n = 31) a history of welding exposure. Occupational questionnaires estimated recent (HrsW; welding hours and E₉₀; cumulative exposure, past 90 days) and lifetime (YrsW; total welding years and ELT; cumulative exposure, lifetime) exposure. Brain MRI pallidal index (PI), R1 (1/T1), and R2* (1/T2*) were measured to estimate Mn and Fe concentrations in the basal ganglia [caudate nucleus (CN), putamen, and globus pallidus], amygdala, and hippocampus. Comprehensive neuropsychological tests were conducted to examine behavioral differences between welders and controls. Correlation analyses were conducted between neuropsychological tests and those exposure measurements that showed significant group differences.ResultsCompared to controls, welders had significantly higher R2* in the CN and lower performance on the Phonemic Fluency test. Correlation analyses revealed that welders’ Phonemic Fluency scores were inversely associated with R2* in the CN, but not with the PI or R1 in any brain region of interest studied.DiscussionThe results showed that neurobehavioral performance for the asymptomatic welders in our study was worse than individuals who had not welded, and suggest the differences may be associated with higher Fe accumulation in the CN.     

MRI pallidal signal in children exposed to manganese in drinking water

BackgroundManganese (Mn) can have neurotoxic effects upon overexposure. We previously reported poorer cognitive and motor development in children exposed to Mn through drinking water, suggesting possible neurotoxic effects from Mn in water. Hyperintensity in the globus pallidus (GP) on T1-weighted magnetic resonance imaging (MRI) indicates excessive brain Mn accumulation. Previous studies have reported GP hyperintensity related to Mn exposure in occupationally exposed individuals. However, no study has used MRI in children exposed to Mn in drinking water and who show no sign of overt intoxication.ObjectiveTo examine MRI signal intensity in the GP in children exposed to contrasted levels of Mn in drinking water.MethodsWe enrolled 13 children exposed to low Mn concentration in water and 10 children (ages 9–15 years) with high concentration (median of 1 and 145 μg/L, respectively). We calculated three MRI T1 indexes: (i) standard pallidal index (PI) using frontal white matter as reference; (ii) PI using pericranial muscles as reference; and (iii) T1 relaxation time. Each MRI index was compared between exposure groups, and with respect to the estimated Mn intake from water consumption.ResultsThe standard PI did not differ between Mn-exposure groups. However, children in the group with high water-Mn concentration had significantly lower pericranial muscles PI than those with lower exposure and, accordingly, higher T1 relaxation time. Mn intake from water consumption was not correlated with the standard PI, but was significantly related to the pericranial muscles PI and T1 relaxation time. Motor performance was significantly lower in the high-exposure group.ConclusionWe observed lower signal intensity in the GP of children with higher exposure to Mn from drinking water. This result stands in contrast to previous MRI reports showing GP hyperintensity with greater Mn exposure. Differences in exposure pathways are discussed as a potential explanation for this discrepancy.     

Brain MR imaging changes in patients with hepatic schistosomiasis japonicum without liver dysfunction

BackgroundThe hyperintense signal on T1-weighted magnetic resonance (MR) images in the globus pallidus and substantia nigra of the brain can be found in patients with liver cirrhosis. The abnormality has been considered resulting from the manganese (Mn) deposition caused by liver failure and portal-systemic shunting. However, similar finding may also be found in hepatic schistosomiasis patients, who lack the biochemical evidence of liver dysfunction.ObjectivesTo describe the brain MR imaging findings in patients with hepatic schistosomiasis japonicum (HSJ) without liver dysfunction.MethodsBrain MR and CT images of 18 patients with HSJ without liver dysfunction and 9 healthy volunteers were reviewed by two radiologists in consensus. The signal index (SI) in globus pallidus was obtained on T1-weighted images. Whole blood Mn, serum iron, serum calcium, and other laboratory tests of liver function were investigated.ResultsSymmetric hyperintense signal in the globus pallidus and substantia nigra was observed in 15 of 18 HSJ patients (83.3%) and in none of controls on T1 weighted imaging. No abnormal CT findings were seen in both groups. Blood Mn level in patients was significantly higher than controls (p < 0.05). Significant correlations were demonstrated between blood Mn and SI (p < 0.05). No significantly abnormal results of serum iron, serum calcium and other laboratory tests were shown (p > 0.05).ConclusionThe portal-systemic shunting leading to Mn deposition may be the main cause of the basal ganglia hyperintense signal on T1-weighted MR imaging, which is a frequent finding in patients with HSJ without liver dysfunction.     

Reversible and irreversible cranial MRI findings associated with status epilepticus

ObjectiveThere is limited information on neuroimaging changes in status epilepticus (SE). The objective of this study was to characterize the abnormalities associated with SE in cranial MRI of patients with SE.MethodsA retrospective review of our records from 2001 to 2010 identified 203 patients with SE. Magnetic resonance imaging (MRI) changes considered were not attributable to any neurological disorder.ResultsTen patients who met the inclusion criteria were found to have significant abnormalities. Magnetic resonance imaging findings included increased T2 signal changes in the gray and/or white matter with corresponding diffusion-weighted imaging (DWI) abnormalities (n = 9). Apparent diffusion coefficient (ADC) values were both reduced (n = 3) and increased (n = 3). Other findings included changes affecting one hemisphere, a perilesional and homologous region, hippocampal changes, and findings in the thalamus, basal ganglia, brain stem, and cerebellum.ConclusionsMagnetic resonance imaging changes were diffuse. Notably, MRI changes were found to involve the brain stem, cerebellum, basal ganglia, and thalamus. Magnetic resonance imaging changes in the latter areas have not been previously well described. In addition, MRI changes tended to evolve after 1 week; therefore, serial MRI is recommended in order to follow and highlight the MRI changes related to the neuroanatomic involvement seen in status epilepticus.     

T2 hyperintense signal in patients with temporal lobe epilepsy with MRI signs of hippocampal sclerosis and in patients with temporal lobe epilepsy with normal MRI

BackgroundIncreased MRI T2 signal is commonly present not only in the hippocampus but also in other temporal structures of patients with temporal lobe epilepsy (TLE), and it is associated with histological abnormalities related to the epileptogenic lesion.ObjectiveThis study aimed to verify the distribution of T2 increased signal in temporal lobe structures and its correlations with clinical characteristics of TLE patients with (TLE-HS) or without (TLE-NL) MRI signs of hippocampal sclerosis.MethodsWe selected 203 consecutive patients: 124 with TLE-HS and 79 with TLE-NL. Healthy controls (N = 59) were used as a comparison group/comparative group. T2 multiecho images obtained via a 3-T MRI were evaluated with in-house software. T2 signal decays were computed from five original echoes in regions of interest in the hippocampus, amygdala, and white matter of the anterior temporal lobe. Values higher than 2 standard deviations from the mean of controls were considered as abnormal.ResultsT2 signal increase was observed in the hippocampus in 78% of patients with TLE-HS and in 17% of patients with TLE-NL; in the amygdala in 13% of patients with TLE-HS and in 14% of patients with TLE-NL; and in the temporal lobe white matter in 22% of patients with TLE-HS and in 8% of patients with TLE-NL. Group analysis demonstrated a significant difference in the distribution of the T2 relaxation times of the hippocampus (ANOVA, p < 0.0001), amygdala (p = 0.003), and temporal lobe white matter (p < 0.0001) ipsilateral to the epileptogenic zone for patients with TLE-HS compared with controls but only for the amygdala (p = 0.029) and temporal lobe white matter (ANOVA, p = 0.025) for patients with TLE-NL compared with controls. The average signal from the hippocampus ipsilateral to the epileptogenic zone was significantly higher in patients with no family history of epilepsy (two-sample T-test, p = 0.005).ConclusionIncreased T2 signal occurs in different temporal structures of patients with TLE-HS and in patients with TLE-NL. The hippocampal hyperintense signal is more pronounced in patients without family history of epilepsy and is influenced by earlier seizure onset. These changes in T2 signal may be associated with structural abnormalities related to the epileptogenic zone or to the nature of the initial precipitating injury in patients with TLE.     

Multi-voxel magnetic resonance spectroscopy at 3 T in patients with idiopathic generalised epilepsy

PurposeThe objective of our study was to gain further insight into the extent of local metabolic alterations in patients with idiopathic generalised epilepsy (IGE), respectively, the subgroup with generalised tonic–clonic seizures (GTCS). The extent of regional metabolic involvement perhaps indicates the key structures in generation of seizures and involvement of specific network of dysfunction.MethodsUsing the multi-voxel technique at a 3 T MRI Scanner metabolite levels of 25 age-matched healthy controls and 18 patients with GTCS were obtained from the basal ganglia, insular cortex, cingulum, hippocampus and along both hemispheres in the fronto-parietal white and grey matter.ResultsGroup analysis of GTCS patients versus healthy controls revealed significant (p < 0.05) decrease of tNAA in the cortex of the central region and cingulum, but also in the thalami. Glx was elevated broadly in both hemispheres, in particular in central region, cingulum, insular cortex and left putamen, yet also in the right thalamus. Cho and mI demonstrated a significant coincidental decrease pronounced in the grey and white matter of the central region. Significant metabolic correlation (p ≤ 0.05) based on tNAA, respectively, Glx occurred between the thalamus and the central region, cingulum, putamen and medial frontal cortex. In patients with >2 tonic–clonic seizures in the last 12 months a trend towards higher Glx and lower tNAA levels was observed.DiscussionOur results demonstrate the altered metabolic interconnection of cerebral anatomic regions in patients with GTCS, in particular the major role of basal ganglia-central region relay in seizure generation.     

Predicting outcome in childhood diffuse midline gliomas using magnetic resonance imaging based texture analysis

BackgroundDiffuse midline gliomas (DMG) are aggressive brain tumours, previously known as diffuse intrinsic pontine gliomas (DIPG), with 10% overall survival (OS) at 18 months. Predicting OS will help refine treatment strategy in this patient group. MRI based texture analysis (MRTA) is novel image analysis technique that provides objective information about spatial arrangement of MRI signal intensity (heterogeneity) and has potential to be imaging biomarker.ObjectivesTo investigate MRTA in predicting OS in childhood DMG.MethodsRetrospective study of patients diagnosed with DMG, based on radiological features, treated at our institution 2007–2017. MRIs were acquired at diagnosis and 6 weeks after radiotherapy (54 Gy in 30 fractions). MRTA was performed using commercial available TexRAD research software on T2 W sequence and Apparent Diffusion Coefficient (ADC) maps encapsulating tumour in the largest single axial plane. MRTA comprised filtration-histogram technique using statistical and histogram metrics for quantification of texture. Kaplan-Meier survival analysis determined association of MRI texture parameters with OS.ResultsIn all, 32 children 2–14 years (median 7 years) were included. MRTA was undertaken on T2W (n = 32) and ADC (n = 22). T2W-MRTA parameters were better at prognosticating than ADC-MRTA. Children with homogenous tumour texture, at medium scale on diagnostic T2W MRI, had worse prognosis (Mean of Positive Pixels (MPP): P = 0.005, mean: P = 0.009, SD: P = 0.011, kurtosis: P = 0.037, entropy: P = 0.042). Best predictor MPP was able to stratify patients into poor and good prognostic groups with median survival of 7.5 months versus 17.5 months, respectively.ConclusionsDMG with more homogeneous texture on diagnostic MRI is associated with worse prognosis. Texture parameter MPP is the most predictive marker of OS in childhood DMG.     

Larger putamen size in antipsychotic-naïve individuals with schizotypal personality disorder

ObjectiveTo (a) compare the size of the dorsal and ventral striatum (caudate and putamen) in a large sample of antipsychotic-naïve individuals with schizotypal personality disorder (SPD) and healthy control participants; (b) examine symptom correlates of striatal size in SPD.MethodsThe left and right caudate and putamen were hand-traced on structural MRI at five dorsal to ventral slice levels in 76 SPD and 148 healthy control participants. A Group × Region (caudate, putamen) × Slice (1–5: ventral, 2, 3, 4, dorsal) × Hemisphere (left, right) mixed-model MANOVA was conducted on size relative to whole brain.ResultsPrimary results showed that compared with the controls, the SPD group showed (a) larger bilateral putamen size overall and this enlargement was more pronounced at the most ventral and dorsal levels; in contrast, there were no between-group differences in caudate volume; (b) larger bilateral size of the striatum ventrally, averaged across the caudate and putamen. Among the SPD group, larger striatal size ventrally, particularly in the left hemisphere was associated with less severe paranoid symptoms.ConclusionsStriatal size is abnormal in SPD and resembles that of patients with schizophrenia who respond well to antipsychotic treatment. The results suggest that striatal size may be an important endophenotype to consider when developing new pharmacological treatments and when studying factors mitigating psychosis.     

Reduced expression of PARK2 in manganese-exposed smelting workers

Manganese (Mn) is widely used in modern industries. Occupational exposure to Mn is known to cause clinical syndromes similar, but not identical to, Parkinson’s disease. This human cohort study was designed to investigate if workers exposed to Mn altered the PARK2 gene expression, leading to Mn-induced neurotoxicity. Workers (n = 26) occupationally exposed to Mn were recruited from a Mn-iron (Fe) alloy smelter, and control workers (n = 20) without Mn-exposure were from an Fe smelter from Zunyi City in China. Subjects were matched with socioeconomic status and background for environmental factors. Metal concentrations were determined by atomic absorption spectrophotometry (AAS). Total RNA from the blood samples was isolated and analyzed by RT-PCR to quantify PARK2. The data showed that Mn concentrations in plasma, red blood cell (RBC) and saliva, and the cumulative Mn-exposure were about 2.2, 2.0, 1.7 and 3.0 fold higher, respectively, in Mn-exposed workers than those in control subjects (p < 0.01). The expression of PARK2 in Mn-exposed workers was significantly decreased by 42% as compared to controls (p < 0.01). Linear regression analysis further established that the expression of PARK2 mRNA was inversely correlated with Mn levels in plasma, RBC and saliva, as well as the cumulative Mn exposure (p < 0.01). Taken together, it seems likely that Mn exposure among smelters may lead to a reduced expression of PARK2, which may partly explain the Mn-induced Parkinsonian disorder.     

Putaminal volume and diffusion in early familial Creutzfeldt–Jakob Disease

BackgroundThe putamen is centrally implicated in the pathophysiology of Creutzfeldt–Jakob Disease (CJD). To our knowledge, its volume has never been measured in this disease. We investigated whether gross putaminal atrophy can be detected by MRI in early stages, when the diffusion is already reduced.MethodsTwelve familial CJD patients with the E200K mutation and 22 healthy controls underwent structural and diffusion MRI scans. The putamen was identified in anatomical scans by two methods: manual tracing by a blinded investigator, and automatic parcellation by a computerized segmentation procedure (FSL FIRST). For each method, volume and mean Apparent Diffusion Coefficient (ADC) were calculated.ResultsADC was significantly lower in CJD patients (697 ± 64 µm²/s vs. 750 ± 31 µm²/s, p < 0.005), as expected, but the volume was not reduced. The computerized FIRST delineation yielded comparable ADC values to the manual method, but computerized volumes were smaller than manual tracing values.ConclusionsWe conclude that significant diffusion reduction in the putamen can be detected by delineating the structure manually or with a computerized algorithm. Our findings confirm and extend previous voxel-based and observational studies. Putaminal volume was not reduced in our early-stage patients, thus confirming that diffusion abnormalities precede detectible atrophy in this structure.     

Associations between former exposure to manganese and olfaction in an elderly population: Results from the Heinz Nixdorf Recall Study

Occupational exposure to manganese (Mn) has been associated with impairments in olfaction and motor functions, but it has yet to be determined if such effects persist upon cessation of exposure. The objective of this study was to evaluate the influence of former occupational Mn exposure on olfaction within the framework of a prospective cohort study among an elderly German population. Information on job tasks with recognized Mn exposure and data on odor identification assessed with Sniffin’ sticks was collected during the second follow-up of the Heinz Nixdorf Recall Study. The study population consisted of 1385 men aged 55–86 years, 354 of whom ever worked in jobs with potential Mn exposure (median 58.3 μg/m³ years, interquartile range 19.0–185 μg/m³ years). Multiple exposure measures, including job tasks, cumulative Mn exposure, and Mn determined in blood samples (MnB) archived at baseline, were used to estimate effects of Mn on olfaction. Having ever worked as welder was associated with better olfaction compared to other blue-collar workers without Mn exposure. Blue-collar workers identified less odors in comparison to white-collar workers. Concentrations of previous Mn exposure >185 μg/m³ years or MnB ≥15 μg/L were not associated with impaired olfaction. In addition to a strong age effect, participants with lower occupational qualification identified less odors. We found no relevant association of former Mn exposure at relatively low levels with impaired olfaction. Possible neurotoxic Mn effects may not be persistent after cessation.     

Diagnostic challenges of primary diffuse leptomeningeal melanomatosis in early adolescence: A case report

IntroductionPrimary diffuse leptomeningeal melanomatosis is an extremely rare variant of primary melanoma of the central nervous system. It is characterized by a variety of nonspecific clinical, radiological, and histopathological features requiring differential diagnosis from a variety of diseases. Here, we aimed to use our own clinical case as an example of the difficulties in the diagnosis of this disease.Case presentationA 14-year-old boy presented with focal to bilateral tonic-clonic seizures. Brain MRI showed diffuse cortical surface and subcortical lesions, isointense on T1-weighted images and hypointense on T2-weighted images, respectively, with diffuse leptomeningeal gadolinium enhancement. Cytology of the cerebrospinal fluid revealed atypical mononuclear cells, but characteristic melanoma cells were not found. Although we suspected meningeal carcinomatosis, we did not perform a brain biopsy under the tentative diagnosis of Sturge–Weber syndrome. A definitive diagnosis of primary diffuse leptomeningeal melanomatosis was made with a brain biopsy after he developed non-convulsive status epilepticus. Despite treatment, he died of hydrocephalus 1 year and 8 months after onset.ConclusionPrimary diffuse leptomeningeal melanomatosis poses a clinical diagnostic and therapeutic challenge. Leptomeningeal enhancement extending into the cerebral sulci and signal changes in T1/T2 weighted images of cortical and subcortical lesions on MRI are key to an early decision regarding whether to perform a biopsy, even in the pediatric population.     

Non-Wilsonian hepatolenticular degeneration: Clinical and MRI observations in four families from south India

Non-Wilsonian hepatolenticular degeneration (NWHD) is a heterogeneous neurological disorder occurring secondary to chronic acquired liver disease. Genetically determined familial NWHD is rare, poorly understood, and often mistaken for Wilson’s disease (WD). We analysed clinical and MRI profiles of NWHD patients who did not have obvious cause for acquired liver disease, such as alcohol intake or hepatitis. Six patients from four families (four males, two females, mean age: 17.0 ± standard deviation 7.9 years), presenting with chronic extrapyramidal disorder resembling WD and imaging (abdominal ultrasound/MRI) evidence of cirrhosis were studied. They lacked Kayser–Fleischer rings or biochemical and/or genetic evidence of WD. Clinical features included dystonia (n = 6), parkinsonism (n = 3), tremor (n = 1), cerebellar ataxia (n = 3), orofacial dyskinesia (n = 1), behavioural abnormalities (n = 3), and cognitive decline (n = 1). Brain MRI revealed T1-weighted hyperintensity in the pallidum (n = 6), crus cerebri (n = 4), putamen (n = 1), caudate (n = 1), thalamus (n = 1), and red nucleus (n = 1) with T2-weighted shortening in some of these regions. Additional findings included giant cisterna magna (n = 1), face of giant panda sign (n = 1) and thin corpus callosum (n = 1). Areas of “blooming” on susceptibility weighted images were noted in two patients in the caudate (n = 2) and putamen (n = 1). The finding of T1 shortening is distinct from that of WD where the majority of lesions are T1-hypointense and T2-hyperintense. Extrapallidal T1-hyperintensity is also an exceptional observation in NWHD. The MRI appearance of intense T1 shortening coupled with the lack of increased susceptibility changes suggests that the most likely mineral deposited is manganese. The association of this neurological disorder and cirrhosis of the liver in the absence of an acquired liver disease is a distinct disease entity. This syndrome may represent a disorder of manganese metabolism resulting in its toxic deposition.     

Retinal nerve fiber thickness and MRI white matter abnormalities in healthy relatives of multiple sclerosis patients

ObjectivesTo compare retinal nerve fiber (RNFL) thickness and conventional and non-conventional MRI characteristics of healthy controls (HCs) from the general population (non-fHC) to healthy relatives of multiple sclerosis (MS) patients (fHC).MethodsSixty-eight (68) HCs underwent optical coherence tomography (OCT) and 3T MRI examination. Subjects were classified based on whether or not there was a family history of MS. The study enrolled 40 non-fHC who had no relatives with MS and 28 fHC with at least one relative affected with MS. The associations between OCT parameters and conventional and non-conventional MRI measures were investigated.ResultsThere were no significant OCT or conventional and non-conventional MRI measureable differences between the non-fHC and fHC groups. Periventricular localization and total volume of white matter (WM) signal abnormalities (SA) were more common in the fHC group but the differences did not reach a level of significance. A significant association between decreased RNFL thickness with increased volume (p = 0.001), number (p = 0.003) and frequency of ≥9 T2 (p = 0.003) WM SAs on MRI was found in the fHC group. No association between OCT and MRI parameters was detected in the non-fHC group.ConclusionThere is an association between decreased RNFL thickness on OCT and increased WM injury in healthy relatives of MS patients. Further studies should explore the pathophysiology of these findings.     

Volume,metabolites and neuroinflammation of the hippocampus in bipolar disorder – A combined magnetic resonance imaging and positron emission tomography study

BackgroundThe hippocampus is one of the brain regions that is involved in several pathophysiological theories about bipolar disorder (BD), such as the neuroinflammation theory and the corticolimbic metabolic dysregulation theory. We compared hippocampal volume and hippocampal metabolites in bipolar I disorder (BD-I) patients versus healthy controls (HCs) with magnetic resonance imaging (MRI) and spectroscopy (MRS). We post hoc investigated whether hippocampal volume and hippocampal metabolites were associated with microglial activation and explored if potential illness modifying factors affected these hippocampal measurements and whether these were associated with experienced mood and functioning.Materials and methodsTwenty-two BD-I patients and twenty-four HCs were included in the analyses. All subjects underwent psychiatric interviews as well as an MRI scan, including a T1 scan and PRESS magnetic resonance spectroscopy (MRS). Volumetric analysis was performed with Freesurfer. MRS quantification was performed with LC Model. A subgroup of 14 patients and 11 HCs also underwent a successful [¹¹C]-(R)-PK11195 neuroinflammation positron emission tomography scan.ResultsIn contrast to our hypothesis, hippocampal volumes were not decreased in patients compared to HC after correcting for individual whole-brain volume variations. We demonstrated decreased N-acetylaspartate (NAA) + N-acetyl-aspartyl-glutamate (NAAG) and creatine (Cr) + phosphocreatine (PCr) concentrations in the left hippocampus. In the explorative analyses in the left hippocampus we identified positive associations between microglial activation and the NAA + NAAG concentration, between alcohol use and NAA + NAAG concentration, between microglial activation and the depression score and a negative relation between Cr + PCr concentration and experienced occupational disability. Duration of illness associated positively with volume bilaterally.ConclusionCompared to HCs, the decreased NAA + NAAG concentration in the left hippocampus of BD-I patients suggests a decreased neuronal integrity in this region. In addition we found a positive relation between microglial activation and neuronal integrity in vivo, corresponding to a differentiated microglial function where some microglia induce apoptosis while others stimulate neurogenesis.     

The effect of war stress on multiple sclerosis exacerbations and radiological disease activity

ObjectiveThe relationship between stressful life events and multiple sclerosis (MS) exacerbations or radiological disease activity is at best controversial. The aim of this study is to examine the relationship between exposure to war-related events incurred during the July 2006 Israeli–Lebanese war and clinical relapses and MRI disease activity among Lebanese MS patients.MethodsWe studied a group of 216 patients with clinically definite relapsing remitting MS (RRMS), on whom clinical data was available for the war period and for the preceding and following year(s). The number of relapses was determined during the war period and during similar periods over a 3-year span. All patients with brain MRI during the war period had their scans reviewed for evidence of disease activity as defined by the presence of gadolinium enhancing (Gd+) lesions. A group of patients with brain MRI performed outside the war period was used for comparison.ResultsThe total number of relapses during the war period (n = 23) was significantly higher than during non-war periods (mean = 8.4, SD = 0.86) (p = 0.006). Of the 18 patients with brain MRI during the war, 5/7 with relapses and 1/11 without relapses had Gd+ lesions (p = 0.013). More patients had Gd+ lesions during the war period (33%) compared to controls (13%) (p = 0.075).InterpretationOur study shows that exposure to war-related events is likely to lead to an increase in both clinical relapses and MRI disease activity in patients with MS.     

Clinical equivalence assessment of T2 synthesized pediatric brain magnetic resonance imaging

Background and purposeAutomated synthetic magnetic resonance imaging (MRI) provides qualitative, weighted image contrasts as well as quantitative information from one scan and is well-suited for various applications such as analysis of white matter disorders. However, the synthesized contrasts have been poorly evaluated in pediatric applications. The purpose of this study was to compare the image quality of synthetic T2 to conventional turbo spin-echo (TSE) T2 in pediatric brain MRI.Materials and methodsThis was a mono-center prospective study. Synthetic and conventional MRI acquisitions at 1.5 Tesla were performed for each patient during the same session using a prototype accelerated T2 mapping sequence package (TA_synthetic = 3:07 min, TA_conventional = 2:33 min). Image sets were blindly and randomly analyzed by pediatric neuroradiologists. Global image quality, morphologic legibility of standard structures and artifacts were assessed using a 4-point Likert scale. Inter-observer kappa agreements were calculated. The capability of the synthesized contrasts and conventional TSE T2 to discern normal and pathologic cases was evaluated.ResultsSixty patients were included. The overall diagnostic quality of the synthesized contrasts was non-inferior to conventional imaging scale (P = 0.06). There was no significant difference in the legibility of normal and pathological anatomic structures of synthetized and conventional TSE T2 (all P > 0.05) as well as for artifacts except for phase encoding (P = 0.008). Inter-observer agreement was good to almost perfect (kappa between 0.66 and 1).ConclusionsT2 synthesized contrasts, which also provides quantitative T2 information that could be useful, could be suggested as an equivalent technique in pediatric neuro-imaging, compared to conventional TSE T2.     

Quantification of subfield pathology in hippocampal sclerosis: A systematic review and meta-analysis

BackgroundThe utility of MRI-based hippocampal subfield volumetry as a diagnostic test for hippocampal sclerosis (HS) is based on the hypothesis that specific hippocampal subfields are differentially affected in HS. While qualitative studies suggest selective involvement of certain hippocampal subfields in this condition, whether quantifiable differences exist remains unclear. Neuronal density measurement is the most widely used technique for measuring subfield pathological change in HS. Therefore, a systematic review and meta-analysis of studies reporting neuronal densities in temporal lobe epilepsy was performed in order to quantify subfield pathology in hippocampal sclerosis.MethodsStudies were identified by searching the Medline and Embase databases using the search terms: cell count, hippocampus, and epilepsy. Of the 192 studies identified by the literature search, seven met all inclusion and exclusion criteria. Random effects meta-analyses were performed, comparing: (i) neuronal densities in control (n = 121) versus HS (n = 371) groups for subfields CA1-4; and (ii) amount of neuronal loss in HS between subfields CA1-4.ResultsStatistically significant neuronal loss was observed comparing HS to control groups in all subfields CA1-4 (p < 0.001 for all comparisons). Significantly greater neuronal loss was demonstrated in HS comparing CA1 versus CA2 (p < 0.001), CA3 (p = 0.005), and CA4 (p = 0.003). Greater pyramidal cell loss was also demonstrated in CA3 relative to the CA2 subfield (p = 0.003). No significant differences were identified comparing CA2 and CA4 (p = 0.39); or comparing CA3 and CA4 (p = 0.64).ConclusionsHS is characterized by pathology in all hippocampal subfields. Quantifiable differences exist in the involvement of specific hippocampal subfields in HS. Neuronal loss is greatest in CA1, intermediate in CA3 and CA4, and least in CA2. Further studies are required to determine if this pattern can be detected using in vivo MRI.     

Conséquences familiales du diagnostic de FXTAS : le conseil génétique aux apparentés à risque

IntroductionFragile X associated Tremor/Ataxia Syndrome (FXTAS) is related to premutation expansions of the FMR1 gene, including 55 to 200 CGG repeats, whereas full expansions, over 200 repeats, cause Fragile X mental retardation. FXTAS is observed in about one-third of men with premutation, generally in their 1950s and over, and less commonly in women. It is characterized by action tremor, ataxia, cognitive, parkinsonism, behavioral difficulties, autonomic dysfunction and peripheral neuropathy. Brain magnetic resonance imaging (MRI) often shows symmetric increases in T2-weighted signal intensity in the middle cerebellar peduncles. The diagnosis of FXTAS in a patient raises important family issues.Case reportA 47-year-old male patient complained of an abnormal hearing sensation and dizziness for several months. Neurological examination was normal. Brain MRI showed the common signal intensity in middle cerebellar peduncles and bilateral punctual increases in T2-weighted signal intensity in the cerebral white matter. Genetic analysis showed 87 CGG repeats, in favor of a possible FXTAS. At the time of diagnosis, fragile X syndrome was subsequently suspected and confirmed in his 10-month-old grandson.DiscussionDue to X-linked inheritance and to the specific related mutational mechanism, the diagnosis of FXTAS in a patient raises major issues for relatives over several generations, including males and females, who should be considered as obligate or potential premutation carriers. Premutated females are not only at risk of transmitting a full mutation to their children but also of developing Fragile X related premature ovarian failure (FXPOI) that may influence their choices in family planning.ConclusionThe diagnosis of FXATS in a patient should induce delivery of extensive information and genetic counseling for potential carrier relatives.