Can we overcome the ‘clinico-radiological paradox’ in multiple sclerosis?

The association between common neuroradiological markers of multiple sclerosis (MS) and clinical disability is weak, a phenomenon known as the clinico-radiological paradox. Here, we investigated to which degree it is possible to predict individual disease profiles from conventional magnetic resonance imaging (MRI) using multivariate analysis algorithms. Specifically, we conducted cross-validated canonical correlation analyses to investigate the predictive information contained in conventional MRI data of 40 MS patients for the following clinical parameters: disease duration, motor disability (9-Hole Peg Test, Timed 25-Foot Walk Test), cognitive dysfunction (Paced Auditory Serial Addition Test), and the expanded disability status scale (EDSS). It turned out that the information in the spatial patterning of MRI data predicted the clinical scores with correlations of up to 0.80 (p?相似文献   

The spasticity paradox: movement disorder or disorder of resting limbs?

BACKGROUND: Spasticity is defined/assessed in resting limbs, where increased stretch reflex activity and mechanical joint resistance are evident. Treatment with antispastic agents assumes that these features contribute to the movement disorder, although it is unclear whether they persist during voluntary contraction. OBJECTIVES: To compare reflex amplitude and joint resistance in spastic and normal limbs over an equivalent range of background contraction. METHODS: Thirteen normal and eight hemiparetic subjects with mild/moderate spasticity and without significant contracture were studied. Reflex and passive joint resistance were compared at rest and during six small increments of biceps voluntary contraction, up to 15% of normal maximum. A novel approach was used to match contraction levels between groups. RESULTS: Reflex amplitude and joint mechanical resistance were linearly related to contraction in both groups. The slopes of these relations were not above normal in the spastic subjects on linear regression. Thus, reflex amplitude and joint resistance were not different between groups over a comparable range of contraction levels. Spastic subjects exhibited a smaller range of reflex modulation than normals because of decreased maximal contraction levels (weakness) and significant increases of resting contraction levels. CONCLUSIONS: Spasticity was most evident at rest because subjects could not reduce background contraction to normal. When background contractions were matched to normal levels, no evidence of exaggerated reflex activity or mechanical resistance was found. Instead, reduced capacity to modulate reflex activity dynamically over the normal range may contribute to the movement disorder. This finding does not support the routine use of antispastic agents to treat the movement disorder.     

Testing a somatization hypothesis to explain the Black–White depression paradox

Social Psychiatry and Psychiatric Epidemiology - Epidemiologic studies document a lower prevalence of major depression in Blacks than Whites in the United States. This is paradoxical from the...     

Cholesterol paradox: Is high total or low HDL cholesterol level a risk for Alzheimer's disease?

Cholesterol is an essential component of membranes for maintaining their structure and functions. The discovery that possession of apolipoprotein E (apoE), allele epsilon4 is a strong risk factor for Alzheimer's disease (AD) leads us to focus on the role of cholesterol in the pathogenesis of AD. Accumulating epidemiological and biological evidence suggests the link between the serum cholesterol level and the development of AD, and the potential therapeutic effectiveness of statins for AD and mild cognitive impairment (MCI), whereas other lines of evidence show controversial results. Cholesterol is known to interact with amyloid beta-protein (Abeta) in a reciprocal manner: cellular cholesterol levels modulate Abeta generation, whereas Abeta alters cholesterol dynamics in neurons, leading to tauopathy. In this review, the relationship between the cholesterol levels in serum or cerebrospinal fluid (CSF) and the induction of AD is discussed. The mechanism(s), if this is the case, of how cholesterol in the central nervous system (CNS) is involved in the induction of pathologies of AD including Abeta generation and tauopathy, and how statins prevent it are also discussed.     

Racial differences in depression in the United States: how do subgroup analyses inform a paradox?

Purpose

Non-Hispanic Blacks in the US have lower rates of major depression than non-Hispanic Whites, in national household samples. This has been termed a “paradox,” as Blacks suffer greater exposure to social stressors, a risk factor for depression. Subgroup analyses can inform hypotheses to explain this paradox. For example, it has been suggested that selection bias in household samples undercounts depression in Blacks; if selection is driving the paradox, Black–White differences should be most pronounced among young men with low education.

Methods

We examined Black–White differences in lifetime major depression in subgroups defined simultaneously by sex, age, and education using data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) and the Collaborative Psychiatric Epidemiology Surveys (CPES).

Results

In NESARC and CPES, Blacks had lower odds than Whites of lifetime major depression in 21 and 23 subgroups, respectively, of 24. All statistically significant differences were in subgroups favoring Blacks, and lower odds in Blacks were more pronounced among those with more education.

Conclusions

These results suggest that hypotheses to explain the paradox must posit global mechanisms that pertain to all subgroups defined by sex, age, and education. Results do not lend support for the selection bias hypothesis.     

Clinically benign multiple sclerosis despite large T2 lesion load: can we explain this paradox?

Magnetic resonance imaging (MRI) techniques such as magnetization transfer imaging and magnetic resonance spectroscopy (MRS) may reveal otherwise undetectable tissue damage in multiple sclerosis (MS) and can serve to explain more severe disability than expected from conventional MRI. That an inverse situation may exist where non-conventional quantitative MRI and MRS metrics would indicate less abnormality than expected from T2 lesion load to explain preserved clinical functioning was hypothesized. Quantitative MRI and MRS were obtained in 13 consecutive patients with clinically benign MS (BMS; mean age 44 +/- 9 years) despite large T 2 lesion load and in 15 patients with secondary progressive MS (SPMS; mean age 47 +/- 6 years) matched for disease duration. The magnetization transfer ratio (MTR), magnetization transfer rate (kfor), brain parenchymal fraction (BPF) and brain metabolite concentrations from proton MRS were determined. BMS patients were significantly less disabled than their SPMS counterparts (mean expanded disability status score: 2.1 +/- 1.1 versus 6.2 +/- 1.1; P < 0.001) and had an even somewhat higher mean T2 lesion load (41.2 +/- 27.1 versus 27.9 +/- 24.8 cm3; P = 0.19). Normal appearing brain tissue histogram metrics for MTR and kfor, mean MTR and kfor of MS lesions and mean BPF were similar in BMS and SPMS patients. Levels of N-acetyl-aspartate, choline and myoinositol were comparable between groups. This study thus failed to explain the preservation of function in our BMS patients with large T2 lesion load by a higher morphologic or metabolic integrity of the brain parenchyma. Functional compensation must come from other mechanisms such as brain plasticity.     

Do racial patterns in psychological distress shed light on the Black–White depression paradox? A systematic review

Purpose

Major epidemiologic studies in the US reveal a consistent “paradox” by which psychiatric outcomes such as major depressive disorder (MDD) are less prevalent among Blacks relative to Whites, despite greater exposure to social and economic stressors and worse physical health outcomes. A second paradox, which has received less attention and has never been systematically documented, is the discrepancy between these patterns and Black–White comparisons in psychological distress, which reveal consistently higher levels among Blacks. By systematically documenting the latter paradox, this paper seeks to inform efforts to explain the first paradox.

Methods

We conduct a systematic review of the literature estimating the prevalence of MDD and levels of psychological distress in Blacks and Whites in the US.

Results

The literature review yielded 34 articles reporting 54 relevant outcomes overall. Blacks have a lower prevalence of MDD in 8 of the 9 comparisons observed. In contrast, Blacks have higher levels of psychological distress (in terms of “high distress” and mean scores) than Whites in 42 of the 45 comparisons observed. Tests of statistical significance, where available, confirm this discrepant pattern.

Conclusions

A systematic review of the epidemiologic evidence supports the existence of a “double paradox” by which Blacks’ lower prevalence of MDD relative to Whites’ is inconsistent with both the expectations of social stress theory and with the empirical evidence regarding psychological distress. Efforts to resolve the Black–White depression paradox should account for the discordant distress results, which seem to favor artifactual explanations.

     

The “self-awareness–anosognosia” paradox explained: How can one process be associated with activation of,and damage to,opposite sides of the brain?

Healthy volunteers engaged in self-referential tasks such as reflecting on their personality traits exhibit mostly left lateralized brain activation, yet patients with lack of awareness of their deficit suffer from predominantly right hemisphere damage. How can the same basic process of self-awareness be associated with opposite sides of the brain? Anosognosia and self-awareness substantially differ on important dimensions and thus should not be equated. It is proposed that (1) anosognosia does not actually result from uniquely right hemisphere damage; (2) self-awareness and anosognosia do not constitute unitary concepts and encompass multiple other related processes, most likely associated with activity in distinct anatomical networks; and (3) impaired awareness of deficit is mostly caused by problems with self-monitoring, pre-/post-brain damage comparisons of performance, and episodic memory, and is more passive, unintentional, and about the body. Self-awareness produced by inviting participants to intentionally and actively think about more mental aspects of the self relies on judgements, inferential reasoning, imagination, and semantic memory. Consequently, the “self-awareness–anosognosia” paradox is only apparent. Furthermore, the claim that healthy self-awareness is located in the right hemisphere because anosognosia results from damage to this side of the brain must be fallacious.