Fatigue and physical disability in patients with multiple sclerosis: a structural equation modeling approach

Although fatigue is one of the most common and disabling symptoms in patients with multiple sclerosis (MS), its pathogenesis is still poorly understood and it is difficult to treat. The aim of the current study was to test the assumptions of a cognitive-behavioral model that explains fatigue and physical disability in MS patients, by comparing this approach with a more traditional biomedical approach. Structural equation modeling was applied to a sample of 262 MS patients. Neither the cognitive-behavioral, nor the biomedical model showed an adequate fit of our data. The modification indices supported an integration of both models, which showed a better fit than those of the separate models. This final model, is notable for at least three features: (1) fatigue is associated with depression and physical disability, (2) physical disability is associated with disease severity and fatigue-related fear and avoidance behavior, and (3) catastrophic interpretations about fatigue, fueled by depression, mediated the relationship between fatigue and fatigue-related fear and avoidance behavior. Our results suggest that an integrated approach, including the modification of catastrophic thoughts about fatigue, would be beneficial in the treatment of fatigue in MS patients

Fatigue in neuromuscular disorders: focus on Guillain–Barré syndrome and Pompe disease

Fatigue accounts for an important part of the burden experienced by patients with neuromuscular disorders. Substantial high prevalence rates of fatigue are reported in a wide range of neuromuscular disorders, such as Guillain–Barré syndrome and Pompe disease. Fatigue can be subdivided into experienced fatigue and physiological fatigue. Physiological fatigue in turn can be of central or peripheral origin. Peripheral fatigue is an important contributor to fatigue in neuromuscular disorders, but in reaction to neuromuscular disease fatigue of central origin can be an important protective mechanism to restrict further damage. In most cases, severity of fatigue seems to be related with disease severity, possibly with the exception of fatigue occurring in a monophasic disorder like Guillain–Barré syndrome. Treatment of fatigue in neuromuscular disease starts with symptomatic treatment of the underlying disease. When symptoms of fatigue persist, non-pharmacological interventions, such as exercise and cognitive behavioral therapy, can be initiated

Gray matter imaging in multiple sclerosis: what have we learned?

At the early onset of the 20th century, several studies already reported that the gray matter was implicated in the histopathology of multiple sclerosis (MS). However, as white matter pathology long received predominant attention in this disease, and histological staining techniques for detecting myelin in the gray matter were suboptimal, it was not until the beginning of the 21st century that the true extent and importance of gray matter pathology in MS was finally recognized. Gray matter damage was shown to be frequent and extensive, and more pronounced in the progressive disease phases. Several studies subsequently demonstrated that the histopathology of gray matter lesions differs from that of white matter lesions. Unfortunately, imaging of pathology in gray matter structures proved to be difficult, especially when using conventional magnetic resonance imaging (MRI) techniques. However, with the recent introduction of several more advanced MRI techniques, the detection of cortical and subcortical damage in MS has considerably improved. This has important consequences for studying the clinical correlates of gray matter damage. In this review, we provide an overview of what has been learned about imaging of gray matter damage in MS, and offer a brief perspective with regards to future developments in this field

Managing fatigue : clinical correlates, assessment procedures and therapeutic strategies

The majority of patients with Multiple Sclerosis (MS) experience fatigue and for many susabjects concerned it is the most disabling symptom. Fatigue is most prominent in the afternoon and may be aggravated by heat. It has a tremendous negative impact on quality of life and is often one of the major reasons for early retirement and unemployment. Against further assumptions, fatigue can occur at all stages and is often present at the onset of the disease. Reliable assessment however, is difficult as it is a subjectively perceived lack of physical and/or mental energy interfering with intended activities and has to be differentiated from depression, consequences of sleep disorders, cognitive decline, and side-effects of medication. Moreover, fatigue is not directly related to overall disease evolution, to disability levels or localized lesions, although an association with dysfunction of fronto-thalamo-basal-ganglia circuits seems likely. Several therapeutic approaches including pharmacological as well as non-pharmacological strategies are available but an evidence-based specific gold-standard for the treatment of fatigue is still missing

Assessment of post-stroke fatigue : the fatigue scale for motor and cognitive functions

BACKGROUND/AIMS: Post-stroke fatigue (PSF) is an important but still controversial issue since knowledge on its nature is still humble. The aim of the present study was to characterize PSF beyond the subacute phase. METHODS: Thirty-one stroke patients (gender: 6 female, 25 male; age range: 35-76 years; 28 patients with ischemic stroke, 3 patients with hemorrhagic stroke; mean delay after stroke: 50.65 +/- 31.57 days) were recruited and assessed by measures of fatigue (Fatigue Scale for Motor and Cognitive Functions [FSMC], Fatigue Severity Scale, and Modified Fatigue Impact Scale), depression (Beck Depression Inventory Fast Screen), cognition (Brief Repeatable Battery of Neuropsychological Tests) and upper and lower extremity functions (Nine-Hole Peg Test and 25-foot walk). RESULTS: Depending on the different scales, PSF prevalence ranged from 16.1 to 58.1%. Depression measures correlated significantly (r(29) 0.01) with the results of all fatigue scales. Seventy-one percent of patients showed cognitive deficits in at least one cognitive domain. Cognitive fatigue measured by one subscale of the FSMC correlated most significantly with mental speed, working memory, and verbal short-term memory, while the motor subscale was associated with upper and lower extremity functions, mental speed, visual short-term memory, and working memory. A differentiation between lesion localization and fatigue severity in the motor or cognitive domain was only possible when applying the FSMC. Patients with cortical lesions scored higher on the cognitive subscale, while patients with subcortical lesions showed higher physical subscale scores. CONCLUSION: The present pilot study revealed differences between lesion localization and subdomains of fatigue after stroke by applying a new fatigue scale (FSMC). The results underline the necessity for separate assessment of motor and cognitive fatigue in stroke patients

Lipid binding promotes oligomerization and focal adhesion activity of vinculin

The cerebellum is known to be involved not only in motor but also cognitive and affective processes. Structural changes in the cerebellum in relation to cognitive dysfunction are an emerging topic in the field of neuro-psychiatric disorders. In Multiple Sclerosis (MS) cerebellar motor and cognitive dysfunction occur in parallel, early in the onset of the disease, and the cerebellum is one of the predilection sites of atrophy. This study is aimed at determining the relationship between cerebellar volumes, clinical cerebellar signs, cognitive functioning and fatigue in MS. Cerebellar volumetry was conducted using T1-weighted MPRAGE magnetic resonance imaging of 172 MS patients. All patients underwent a clinical and brief neuropsychological assessment (information processing speed, working memory), including fatigue testing. Patients with and without cerebellar signs differed significantly regarding normalized cerebellar total volume (nTCV), normalized brain volume (nBV) and whole brain T2 lesion volume (LV). Patients with cerebellar dysfunction likewise performed worse in cognitive tests. A regression analysis indicated that age and nTCV explained 26.3% of the variance in SDMT (symbol digit modalities test) performance. However, only age, T2 LV and nBV remained predictors in the full model (r(2) = 0.36). The full model for the prediction of PASAT (Paced Auditory Serial Addition Test) scores (r(2) = 0.23) included age, cerebellar and T2 LV. In the case of fatigue, only age and nBV (r(2) = 0.17) emerged as significant predictors. These data support the view that cerebellar abnormalities contribute to disability, including cognitive impairment in MS. However, this contribution does not seem to be independent of, and may even be dominated by wider spread MS pathology as reflected by nBV and T2 LV