Decreased plasma tryptophan associated with deep white matter lesions in elderly subjects

The aim was to identify potentially treatable riskfactors for cerebral white matter lesions often found on MRI in elderly persons. findings were assessed on 1.0 T MRI of 178 subjects living inthe community and aged 60 years or older. Participants underwent standardised evaluations including standard questionnaires, a physicaland neurological examination, cognitive function tests, electrocardiogram, a complete blood chemistry panel, and plasma aminoacid measurements. Brain MRI infarcts, deep white matter lesions(DWMLs), and periventricular hyperintensities were found in 26%, 43%,and 29% of the 178 participants, respectively. Subjects with DWMLswere significantly older and had a higher frequency of hypertension,higher systolic blood pressure, and more brain infarcts, but lowerplasma concentrations of tryptophan. In the multivariate model, greaterage and lower plasma tryptophan concentrations were independentlyassociated with DWMLs. Tryptophan concentrations were inversely relatedto DWML grading, whereas hypertension and brain infarction were morecommon in subjects with higher extents of DWMLs. The present studysuggests that greater age and lower plasma tryptophanconcentrations were important in producingDWMLs in elderly subjects.

     

偏头痛右向左分流患者与脑白质病变的关系研究

目的探讨偏头痛右向左分流患者与脑白质病变之间的关系。方法自2014年7月至2017年2月就诊于北京天坛医院门诊,诊断符合国际头痛诊断分类的偏头痛患者。收集基线信息及临床特征等相关资料。所有入组患者均进行经颅多普勒发泡试验及头颅磁共振检查。右向左分流定义为:经颅多普勒发泡试验提示双侧大脑中动脉监测到至少一个及以上栓子信号。脑白质病变的评定为:深部或皮质下白质T2加权像及FLAIR成像高信号。脑白质病变使用Fazekas量表评分。结果最终纳入254个患者(57.1%为女性)。143例受试者存在右向左分流(56.3%)。149例患者存在脑白质病(58.7%)。与脑白质病变阴性组(n=105)相比,右向左分流在脑白质病变阳性组(n=149)明显增高(69.1%vs38.1%,P0.05)。结论偏头痛患者脑白质病变可能与右向左分流相关。     

偏头痛右向左分流患者与脑白质病变的关系研究

目的 探讨偏头痛右向左分流患者与脑白质病变之间的关系。方法 自2014年7月至2017年2月就诊于北京天坛医院门诊,诊断符合国际头痛诊断分类的偏头痛患者。收集基线信息及临床特征等相关资料。所有入组患者均进行经颅多普勒发泡试验及头颅磁共振检查。右向左分流定义为：经颅多普勒发泡试验提示双侧大脑中动脉监测到至少一个及以上栓子信号。脑白质病变的评定为：深部或皮质下白质T2加权像及FLAIR成像高信号。脑白质病变使用Fazekas量表评分。结果 最终纳入254个患者（57.1%为女性）。143例受试者存在右向左分流（56.3%）。149例患者存在脑白质病（58.7%）。与脑白质病变阴性组（n=105）相比,右向左分流在脑白质病变阳性组（n=149）明显增高（69.1% vs 38.1%,P<0.05）。结论 偏头痛患者脑白质病变可能与右向左分流相关。     

Age-related white matter lesions are associated with reduction of the apparent diffusion coefficient in the cerebellum

Cerebellar apparent diffusion coefficient (ADC) was found to be increased after acute cerebral hemispheric stroke. There are no data on cerebellar ADC changes in patients with chronic, age-related white matter lesions (ARWML). We aimed to determine longitudinal ADC variations on cerebral hemispheric and cerebellar white matter regions of patients with ARWML in order to study relations between ADC changes in both regions. ADC was measured serially (1-year interval) on lesioned periventricular frontal white matter, frontal and parietoccipital normal appearing white matter and middle cerebellar peduncles, on 19 aged patients with ARWML, which also underwent gait assessment. We compared regional ADC at 0 and 1 year and calculated variation percentages for each region. Correlation analysis was made between ADC variation in cerebellar regions and in contralateral hemispheric regions and between cerebellar ADC at 1 year and walking speed. After 1 year, ADC was higher on lesioned periventricular frontal white matter and lower on cerebellar regions. ADC variations on these regions were negatively correlated. Cerebellar ADC measured after 1 year was positively correlated with walking speed. This suggests a link between vascular disease progression inside frontal lesions and ADC reduction in contralateral cerebellar peduncles. Chronic ischemia in frontal white matter could have interrupted frontal-cerebellar circuits, producing hypometabolism in cerebellar regions (and worse performance on motor tasks), decreased perfusion and hence ADC reduction.     

Alterations in functional connectivity are associated with white matter lesions and information processing efficiency in multiple sclerosis

Brain Imaging and Behavior - Functional connectivity (FC) is typically altered in individuals with Multiple Sclerosis (MS). However, in relapsing-remitting multiple sclerosis (RRMS) patients, the...     

Impaired cerebrovascular hemodynamics are associated with cerebral white matter damage

White matter hyperintensities (WMH) in elderly individuals with vascular diseases are presumed to be due to ischemic small vessel diseases; however, their etiology is unknown. We examined the cross-sectional relationship between cerebrovascular hemodynamics and white matter structural integrity in elderly individuals with vascular risk factors. White matter hyperintensity volumes, fractional anisotropy (FA), and mean diffusivity (MD) were obtained from MRI in 48 subjects (75±7years). Pulsatility index (PI) and dynamic cerebral autoregulation (dCA) was assessed using transcranial Doppler ultrasound of the middle cerebral artery. Dynamic cerebral autoregulation was calculated from transfer function analysis (phase and gain) of spontaneous blood pressure and flow velocity oscillations in the low (LF, 0.03 to 0.15 Hz) and high (HF, 0.16 to 0.5 Hz) frequency ranges. Higher PI was associated with greater WMH (P<0.005). Higher phase across all frequency ranges was associated with greater FA and lower MD (P<0.005). Lower gain was associated with higher FA in the LF range (P=0.001). These relationships between phase and FA were significant in the territories limited to the middle cerebral artery as well as across the entire brain. Our results show a strong relationship between impaired cerebrovascular hemodynamics (PI and dCA) and loss of cerebral white matter structural integrity (WMH and DTI metrics) in elderly individuals.     

Cerebral white matter lesions are not associated with apoE genotype but with age and female sex in Alzheimer's disease

Cerebral white matter lesions, such as leukoaraiosis, may be a result of damage from cerebral ischaemia, and may also be associated with the degenerative process in Alzheimer's disease. The apolipoprotein epsilon4 (apoepsilon4) genotype is a genetic risk factor for both Alzheimer's disease and ischaemic brain damage through acceleration of atherosclerosis. The aim was to determine whether apoepsilon4 may be related to the formation of cerebral white matter lesions in Alzheimer's disease. The association of apoE genotype, sex, age, and the presence of several vascular risk factors, with the presence of white matter lesions in 55 patients clinically diagnosed with Alzheimer's disease was investigated. The cerebral white matter lesions were identified by T2 weighted MRI and classified on a 4 grade scale from no lesion to diffuse lesion. The odds ratio (OR) of the factors mentioned above to the presence of white matter lesions was determined and tested by Fisher's exact test. The association of the lesion grades with these factors was analysed by non-parametric tests. The apoE 4 genotype was strongly associated with Alzheimer's disease (p=0.0001), but not associated with the presence or the degree of cerebral white matter lesions in Alzheimer's disease (OR=1.09, p>0.99). Aging (>70 years old) was a significant risk factor for white matter lesions (OR=7.2, p=0.0006) and age was significantly correlated with the lesion (p=0.0075). The OR of female sex to the lesion grades was 2.89 (p=0.084) and the lesion grade of female sex was significantly higher than that of the male sex (p=0.047). Other vascular risk factors were not significantly associated with the presence of white matter lesions. These findings suggest that there is a sex difference in white matter pathology in Alzheimer's disease.     

MTX-induced white matter changes are associated with polymorphisms of methionine metabolism

Methotrexate (MTX) is a folate antagonist inhibiting nucleic acid and methionine synthesis. Methionine is necessary for CNS myelination. In 42 patients with primary CNS lymphoma (PCNSL) treated with a systemic and intraventricular high-dose MTX-based polychemotherapy, the presence of a risk haplotype defined by polymorphisms influencing methionine metabolism referred a relative risk for CNS white matter changes of 4.7 (p = 0.001). The authors conclude that methionine metabolism influences MTX neurotoxicity.     

Subclinical white matter lesions and medial temporal lobe atrophy are associated with EEG slowing in a memory clinic cohort

Objective

The aim of the study was to describe the relationship between electroencephalographic (EEG) findings obtained by standardized visual analysis, subclinical white matter lesions (WML) and brain atrophy in a large memory clinic population.

Visual attentional disturbance with unilateral lesions in the basal ganglia and deep white matter.

To elucidate the role of the basal ganglia and deep white matter in the visual attention mechanism, a new visual attention task was carried out by 15 patients, 9 with left-side and 6 with right-side basal ganglia and/or deep white matter damage without visual field defects, and by 12 normal subjects. Their reaction times were recorded in response to a random visual stimulation by pushing a button with the hand ipsilateral to the side of the lesion. All the patients with damage to the right side of the brain had a longer reaction time in the left space than in the right or middle space. With conventional test, only one of them showed left unilateral spatial neglect. Seven of the 9 patients with a left lesion had a significantly longer reaction time in the right space than in the left. None had unilateral spatial neglect. Both the right and left brain-damaged groups showed longer reaction times in both spaces, compared to the normal groups. There was no significant difference in reaction time among the control subjects. These findings suggest that the basal ganglia and deep white matter in each hemisphere play some role in directing visual attentional factors into both spaces. Visual attentional disturbance was highly evident even with left-side brain damage, and this kind of disturbance is not usually revealed with the current tasks used for testing unilateral spatial neglect.     

Genetic variants in the ErbB4 gene are associated with white matter integrity

Variations in the signalling NRG1-ErbB4 pathway have been associated with genetic susceptibility for both bipolar disorder and schizophrenia, although the underlying neural mechanisms are still uncertain. Reduced integrity of the anterior limb of the internal capsule (ALIC) has been found in association with risk-associated genetic variation in the 5′ region of the NRG1 gene. We hypothesised that variation in the gene encoding the NRG1 receptor, ErbB4, would also be associated with reduced ALIC integrity and with cognitive impairments characteristic of individuals with bipolar disorder and schizophrenia. Using diffusion tensor imaging (DTI), we examined the white matter integrity associations of the ErbB4 polymorphism rs4673628, which resides within intron 12 of the gene encoding ErbB4, in 36 healthy individuals. We also sought to clarify the cognitive effects of any findings. We found that genetic variation at the rs4673628 locus in the ErbB4 gene was significantly associated with ALIC white matter integrity which was also significantly and positively associated with mnemonic function. These findings provide further evidence to support a key role of NRG1-ErbB4 signalling in the pathophysiology of major mental disorders.     

Cerebellar white matter pathways are associated with reading skills in children and adolescents

Reading is a critical life skill in the modern world. The neural basis of reading incorporates a distributed network of cortical areas and their white matter connections. The cerebellum has also been implicated in reading and reading disabilities. However, little is known about the contribution of cerebellar white matter pathways to major component skills of reading. We used diffusion magnetic resonance imaging (dMRI) with tractography to identify the cerebellar peduncles in a group of 9‐ to 17‐year‐old children and adolescents born full term (FT, n = 19) or preterm (PT, n = 26). In this cohort, no significant differences were found between fractional anisotropy (FA) measures of the peduncles in the PT and FT groups. FA of the cerebellar peduncles correlated significantly with measures of decoding and reading comprehension in the combined sample of FT and PT subjects. Correlations were negative in the superior and inferior cerebellar peduncles and positive in the middle cerebellar peduncle. Additional analyses revealed that FT and PT groups demonstrated similar patterns of reading associations within the left superior cerebellar peduncle, middle cerebellar peduncle, and left inferior cerebellar peduncle. Partial correlation analyses showed that distinct sub‐skills of reading were associated with FA in segments of different cerebellar peduncles. Overall, the present findings are the first to document associations of microstructure of the cerebellar peduncles and the component skills of reading. Hum Brain Mapp 36:1536–1553, 2015. © 2014 Wiley Periodicals, Inc.     

Microglial nodules in early multiple sclerosis white matter are associated with degenerating axons

Microglial nodules in the normal-appearing white matter have been suggested as the earliest stage(s) of multiple sclerosis (MS) lesion formation. Such nodules are characterized by an absence of leukocyte infiltration, astrogliosis or demyelination, and may develop into active demyelinating MS lesions. Although the etiology of MS is still not known, inflammation and autoimmunity are considered to be the central components of this disease. Previous studies provide evidence that Wallerian degeneration, occurring as a consequence of structural damage in MS lesions, might be responsible for observed pathological abnormalities in connected normal-appearing white matter. As innate immune cells, microglia/macrophages are the first to react to even minor pathological changes in the CNS. Biopsy tissue from 27 MS patients and autopsy and biopsy tissue from 22 normal and pathological controls were analyzed to determine the incidence of microglial nodules. We assessed MS periplaque white matter tissue from early disease stages to determine whether microglial nodules are associated with altered axons. With immunohistochemical methods, the spatial relation of the two phenomena was visualized using HLA-DR antibody for MHC II expression by activated microglia/macrophages and by applying antibodies against damaged axons, i.e., SMI32 (non-phosphorylated neurofilaments) and amyloid precursor protein as well as neuropeptide Y receptor Y1, which marks axons undergoing Wallerian degeneration. Our data demonstrate that the occurrence of microglial nodules is not specific to MS and is associated with degenerating as well as damaged axons in early MS. In addition, we show that early MS microglial nodules exhibit both pro- and antiinflammatory phenotypes.     

Acute paraplegia with vanishing white matter lesions

Young adults presenting with an acute myelopathy often represent a diagnostic challenge. We present the case of a 20-year-old man who demonstrated many of the diagnostic issues involved in the evaluation of this syndrome.     

Postinfectious encephalitis with multifocal white matter lesions

Two cases of multifocal white matter lesions occurring after viral illness are reported. Evoked potentials study and cranial magnetic resonance imaging (T2-weighted image) showed early abnormalities while CT scan was initially normal. Patients improved dramatically with steroid therapy. It would seem that because of a considerable responsiveness to steroids this affection should be differentiated from other types of encephalitis. Relations with multiple sclerosis are discussed.     

Are white matter lesions directly associated with cognitive impairment in patients with lacunar infarcts?

Forty-four patients (mean age 66, SD 8 years) with either clinical evidence of a focal lacunar syndrome (n=36) or with disorders of memory or gait (n=8) in the presence of a lacunar infarct on CT were studied for cognitive functioning and for the presence of white matter lesions on MRI. MR images were assessed by a neurologist and a neuro-radiologist blinded to the clinical data. Thirty-six patients had one or more lacunar infarets on CT or MRI (in the thalamus in 5, in the caudate nucleus in 3 and in the internal capsule or corona radiata in the remaining patients). Twelve patients had multiple infarcts. Severe lesions of the white matter were found in 13 patients, mild to moderate lesions in 20 patients. Scores on Digit Span, Digit Symbol and delayed recall of the 15-Words test were significantly lower in the group with severe lesions, whilst there was a trend in the same direction for the Cognitive part of the Cambridge Examination of Mental Disorders in the Elderly, the Trailmaking B, Stroop colour interference test and the delayed visual reproduction of the Wechsler Memory Scale. These findings suggest that diffuse lesions of the white matter are an independent factor in the pathogenesis of intellectual dysfunction, also in patients with lacunar infarcts, but a truly independent analysis is difficult because the most severe involvement of the white matter tended to be associated with the largest number of lacunar infarcts.