Brain MRI white matter hyperintensities and one-carbon cycle metabolism in non-geriatric outpatients with major depressive disorder (Part II)

The objective of this study was to investigate the relative impact of brain white matter hyperintensities (WMHs), cardiovascular risk factors and elements of the one-carbon cycle metabolism (including serum folate, vitamin B12 and homocysteine levels) on the outcome of antidepressant treatment in non-elderly subjects with major depressive disorder (MDD). Fifty MDD subjects were administered brain magnetic resonance imaging (MRI) scans at 1.5 T to detect T2 WMHs. The severity of brain WMHs was classified with the Fazekas scale (range = 0–3). We assessed cardiovascular risk factors in all MDD subjects (age, gender, smoking, diabetes, family history, hypertension, cholesterol). MDD patients also had serum folate, vitamin B12 and homocysteine levels measured. All MDD subjects received treatment with fluoxetine 20 mg/day for 8 weeks. In a logistic regression, the severity of subcortical WMHs and the presence of hypofolatemia were independent predictors of lack of clinical response to antidepressant treatment. Separately, hypofolatemia also predicted lack of remission to antidepressant treatment. These associations were independent of the presence of smoking, diabetes, family history, hypercholesterolemia, hyperhomocysteinemia and low B12 levels. Although preliminary, the results of the present work suggest that subcortical brain WMHs and hypofolatemia may have an independent negative impact on the likelihood of responding to antidepressant treatment in non-geriatric subjects with MDD.     

急性期脑梗死FLAIR序列血管高信号形成机制探讨

目的与血管造影对照探讨急性脑梗死磁共振快速液体衰减反转恢复(FLAIR)序列血管高信号(FLAIRvascular hyperintensities,FVH)的形成机制。资料与方法回顾性分析9例急性大脑中动脉闭塞6 h内患者的磁共振FLAIR序列及血管造影图像。评价急性脑梗死患者FVH的发生率、位置及形态学特征,并以血管造影分析其血流动力学特征。结果 9例患者FVH出现率为100%。FVH最常见于外侧裂(100%),颞叶或邻近颞叶为89%,顶叶为22%。FVH于颈内动脉血管造影上显示来自大脑前动脉软脑膜支不同程度侧支循环,微导管通过大脑中动脉闭塞段造影显示对比剂滞留,并无充盈缺损。结论急性脑梗死患者FVH形成的原因可能为近端血管闭塞,软脑膜侧支逆向缓慢血流代偿,而并非血管内血栓形成。     

Regional White Matter Signal Abnormalities and Cognitive Correlates Among Geriatric Patients with Treated Cardiovascular Disease

The purpose of this study was to investigate the relations between regional white matter signal abnormalities (WMSA) and cognitive functioning among individuals being treated for cardiovascular risk factors and/or clinical events. Forty-one participants with cardiovascular disease underwent a comprehensive neuropsychological assessment and MRI. Total WMSAs were quantified using a semi-automated thresholding technique. Unique to this study, total WMSA volume was divided into three separate anatomically related regions: WMSA in the periventricular (PERIWMSA) region, WMSA adjacent to subcortical nuclei (SUBWMSA), and WMSA in the deep white matter (DEEPWMSA). A ratio of these measures to total cerebral brain volume was compared to cognitive measures assessing attention, executive functioning, psychomotor speed, immediate and delayed memory, language, and visuospatial functioning. PERIWMSA, SUBWMSA, and total WMSA were significantly associated with performance on measures of attention/processing speed. No other significant relationships between WMSA and cognition were noted. Secondary analyses suggested that PERIWMSA volume was increased in individuals with clinical evidence of atherosclerosis. These results emphasize the utility of studying the associations between regional WMSA and cognitive/functional performance in patients undergoing cardiovascular treatment.     

Brain MRI white matter hyperintensities and one-carbon cycle metabolism in non-geriatric outpatients with major depressive disorder (Part I)

The objective of the present work was to study the interrelationship between white matter hyperintensities (WMHs), cardiovascular risk factors and elements of the one-carbon cycle including serum folate, vitamin B12, and homocysteine levels in a relatively young sample of outpatients with major depressive disorder (MDD), and to compare the severity of white matter hyperintensities in MDD patients and healthy volunteers. Fifty MDD outpatients (34% women, age 40.6 ± 10.3 years), free of psychotropic medications for at least 2 weeks before enrollment, underwent magnetic resonance imaging (MRI) scans of the brain to detect T2 WMHs and also had (1) serum folate, vitamin B12, homocysteine and cholesterol levels measured, and (2) cardiovascular risk factors assessed during the same study visit. Thirty-five healthy comparison subjects (40% women, age 39.2 ± 9.8 years) also underwent brain MRI scans. Hypofolatemia, hypertension and age independently predicted a greater severity of total brain WMHs. Separately, the same factors also predicted a greater severity of subcortical WMHs. Hypofolatemic and hypertensive patients had more severe WMHs than normal controls. In light of the adverse impact of WMHs on a number of health-related outcomes later in life, hypofolatemia and hypertension may represent modifiable risk factors to prevent the occurrence of such adverse outcomes.     

Increased White Matter Signal Hyperintensities in Long-Term Abstinent Alcoholics Compared with Nonalcoholic Controls

Background: The harmful effects of alcohol dependence on brain structure and function have been well documented, with many resolving with sufficient abstinence. White matter signal hyperintensities (WMSH) are thought to most likely be consequences secondary to the vascular (i.e., hypertension and atherosclerosis) effects of AD. We hypothesized that such effects would persist into long‐term abstinence, and evaluated them in middle‐aged long‐term abstinent alcoholics (LTAA) compared with age and gender comparable nonalcoholic controls (NAC). Methods: Ninety‐seven participants (51 LTAA and 46 NAC) underwent cognitive, psychiatric, and structural brain magnetic resonance image evaluations. WMSH were identified and labeled as deep or periventricular by an automated algorithm developed in‐house. WMSH volumes were compared between groups, and the associations of WMSH measures with demographic, alcohol use, psychiatric, and cognitive measures were examined within group. Results: Long‐term abstinent alcoholics had more WMSH than NAC. There was a significant group by age interaction, with WMSH increasing with age in LTAA, but not in NAC. Within LTAA, WMSH load was independently positively associated with alcohol burden and with age. No associations were evident between WMSH volumes and abstinence duration, family drinking history, years of education, or psychiatric or cognitive variables. Conclusion: The magnitude of alcohol abuse was related to increased WMSH volume. The presence of an age effect in the LTAA but not the controls indicates a synergistic effect wherein alcohol advances the onset of aging‐related WMSH formation. The increased WMSH load did not appear to have any significant clinical correlates, indicating that the white matter lesions in our sample may not have been severe enough to manifest as cognitive deficits. A limitation of the study is that we did not have data on the presence or severity of lifetime or current indices of vascular risk factors such as hypertension, smoking, or diabetes.     

Anatomic location and laterality of MRI signal hyperintensities in late-life depression

OBJECTIVES: Evidence is mounting linking cerebrovascular disease with the development of major depression in the elderly. Lesions in both white and gray matter have been associated with geriatric depression. In addition, the literature on poststroke depression suggests that left-sided lesions are associated with depression. We sought to examine the severity and location of white- and gray-matter lesions in a group of elderly depressives and nondepressed control subjects. METHOD: 115 depressed patients (69 with late onset, 46 with early onset) and 37 controls, all over age 45, received magnetic resonance imaging (MRI). Semiquantitative severity ratings and quantitative measurements of number and size of MRI hyperintensities were obtained, and groups were compared using Cochran-Mantel-Haenszel (CMH) analyses and repeated-measures analyses of covariance adjusting for age. RESULTS: Late-onset depressed patients had more severe hyperintensity ratings in deep white matter than early-onset patients and controls. Late- and early-onset patients had more severe subcortical gray-matter hyperintensities (particularly in the putamen) compared with controls. Left-sided white-matter lesions were significantly associated with older age of depression onset, whereas right-anterior white matter and left-subcortical lesions (particularly in the putamen) were associated with melancholia in the depressed group. CONCLUSION: These findings extend previous reports of an association between cerebrovascular disease and depression, as well as recent studies showing lateralized lesion involvement in geriatric depression. Such vascular pathology may disrupt neural pathways involved in affective processing and the maintenance of a normal mood and psychomotor state.     

White matter MRI hyperintensities in a hundred and twenty-nine consecutive migraine patients

The most frequently reported abnormal MRI finding in migraine is the presence of high signal white matter foci (WMF) on long TR images. Recently, WMF have been distinguished in periventricular WMF (PVF), when contiguous to ventricles, and deep WMF (DF), when far from these. DF, but not PVF, appear positively correlated with cerebrovascular risk factors and are called leukoaraiosis. In this study the MRI examination was performed in 129 consecutive migraine patients (83 of them had migraine without aura and 46 migraine with aura). In 19.3% of the migraineurs studied we observed WMF on T2 weighted images strictly localized in the deep white matter (DF). No PVF were observed. These findings were independent of the type of migraine and did not correlate with age, sex, disease duration, or frequency of attacks. The presence in a subgroup of migraineurs of leukoaraiosis (DF), for which a vascular genesis has been hypothesized, suggests that migraine could represent, a cerebrovascular risk factor in these patients.     

Striatal dominant lupus encephalitis–Is it vasculitis or an autoimmune process? Literature review & new case report with vessel wall imaging

Neurological and psychiatric symptoms are highly prevalent in the initial manifestation of systemic lupus erythematosus (SLE) and is classified as neuropsychiatric systemic lupus erythematosus (NPSLE). Despite the high prevalence rate of this condition, it is still very poorly understood and often delayed in its diagnosis due to its variety in clinical manifestations. For our case, an eighteen-year-old male who was recently diagnosed with SLE presented with progressive confusion, visual and auditory hallucinations, in addition to high fevers, diarrhea, abdominal and flank pain. Upon initial presentation, he was treated for sepsis while trying to identify a source of infection. However, with the help of laboratory tests like CSF analysis and autoantibody serum studies as well as neuroradiologic imaging, we were able to rule out infectious causes and diagnose our patient with lupus induced striatal encephalitis. We present the first case of striatal encephalitis with vessel wall imaging to ultimately rule out lupus associated vasculitis. The importance of MRI imaging and identification of specific patterns associated with autoimmune encephalitis allowed rapid diagnosis and initiated immediate treatment in the hopes of reducing long term affects from neuroinflammation in our young patient.     

Caudate nucleus volumes in stroke and vascular dementia

We aimed to assess the volume of the nucleus caudatus as a neuroanatomical substrate of fronto-subcortical circuits, in stroke patients with/without dementia, and the relationship to potential determinants of neural circuit integrity such as white matter hyperintensities (WMH) and stroke volume. Stroke only (Stroke) (n = 19) and stroke with Vascular Dementia (VaD) (n = 16) and healthy control (n = 20) subjects, matched on demographic variables, underwent extensive neuropsychiatric assessments and manual MRI-based volumetric measurements for intracranial area (ICA), stroke volume, and bilateral caudate volume. WMH on MRI were quantified using an automated algorithm. Multivariate analysis of covariance (controlling for age and ICA), revealed that across the three groups, caudate volumes were significantly different. There was a significant difference in bilateral caudate nucleus volume between subjects by diagnosis (Stroke, VaD, control). The control group was largest in overall mean volume of the diagnostic groups, followed by the Stroke group (86% of controls), and finally, the VaD group (72%). There was a partial correlation between total caudate volume and the total volume of deep WMH including periventricular regions and brainstem, controlling for ICA; and for total stroke volume. Stroke patients with VaD have smaller caudate nuclei compared to those without dementia and healthy controls, with the stroke-only patients being intermediate in their caudate volume status. There was preliminary evidence of negative correlation of caudate volume with volume of deep WMH and total stroke volume, suggesting cerebrovascular disease contributes to caudate atrophy,which, in turn may disrupt fronto-subcortical circuits.