The relationship of brain and cervical cord volume to disability in clinical subtypes of multiple sclerosis: a three-dimensional MRI study

OBJECTIVES: Brain and cervical cord volume is a potentially valuable index marker of irreversible pathological processes in multiple sclerosis (MS). Volume in both brain and cervical cord regions in the same patients has only been investigated in a small number of subjects. We aimed at measuring volume in different parts of the central nervous system, and its relationship with clinical measures, in relapsing-remitting (RR) and secondary progressive (SP) MS patients. MATERIAL AND METHODS: Conventional dual echo and three-dimensional (3-D) magnetization prepared rapid acquisition gradient echo imaging was performed on 97 (49 RR and 48 SP) MS patients, and on 31 age- and gender-matched healthy controls. The volumes of the supratentorial brain, lateral ventricles, brainstem, cerebellum and upper cervical cord (UCC) were determined on 3-D magnetic resonance imaging. RESULTS: RR MS patients had significantly smaller supratentorial brain (P=0.002) and larger lateral ventricles (P=0.047) compared with controls, but no differences were found for cerebellum, brainstem and UCC volumes. Significantly smaller supratentorial brain (P<0.0001), cerebellum (P=0.007), brainstem (P=0.0004) and UCC (P<0.0001) volumes, and larger lateral ventricles (P<0.0001) were observed in SP MS patients than in controls. In RR MS, T2-lesion volume correlated with supratentorial (r=-0.46, P=0.0009), lateral ventricular (r=0.65, P<0.0001), cerebellar (r=-0.42, P=0.003) and brainstem (r=-0.35, P=0.01) volumes, but not with UCC volume (r=-0.18, P=0.22). In SP MS, apart from lateral ventricular volume (r=0.52, P=0.0002), none of the estimated structural volumes correlated with T2-lesion volume. The UCC volume correlated with brainstem volume in both RR MS (r=0.35, P=0.016) and SP MS (r=0.38, P=0.007). Multiple regression analysis showed that supratentorial brain volume in RR group, and UCC volume in SP group, were single significant contributors (P=0.01 and 0.04, respectively) to the Expanded Disability Status Scale of all factors entered into the regression model. CONCLUSION: Atrophy is confined to the supratentorial compartment early in the disease course corresponding to the RR stage, but becomes more pronounced in the brain and cervical spinal cord in the SP phase. The estimate of cervical cord volume for SP MS is relevant to functional disability and may be helpful in monitoring MS evolution in the progressive form of disease.     

Relationship of urinary myelin basic protein-like material with cranial magnetic resonance imaging in advanced multiple sclerosis

BACKGROUND: A significant correlation exists between disability and the volume of black holes (BHL VOL), defined as hypointense lesions on T1-weighted cranial magnetic resonance imaging. A consistent correlation has also been reported between urinary myelin basic protein-like material (MBPLM) and the transition toward secondary progression (SP) from relapsing-remitting (RR) multiple sclerosis (MS). OBJECTIVE: To improve the management of MS through a noninvasive and cost-effective test for monitoring disease activity or disease status. DESIGN AND METHODS: From 662 patients with MS (86 with RR MS, 259 with SP MS without continued attacks, and 317 with SP MS with continued attacks), 24-hour urine samples were obtained at enrollment in the phase 3 Linomide (roquinimex) drug study. The urine specimens were analyzed for MBPLM and correlated with clinical features and findings on cranial magnetic resonance imaging. RESULTS: Significant but weak correlations existed between urinary MBPLM and BHL VOL in all patients with MS (r = 0.114, P =.003; n = 662), patients with SP MS without attacks (r = 0.185, P =.003; n = 259), and all patients with SP MS (r = 0.122, P =.003; n = 576). No significant correlations were detected in the RR MS group or any of the disease groups or subgroups whose Expanded Disability Status Scale score was 5.0 or lower. In subgroup analysis, the most significant correlation was detected between urinary MBPLM after adjustment for creatinine and BHL VOL in patients with SP MS with an Expanded Disability Status Scale score of 5.5 or higher but without continued relapses (r = 0.417, P<.001; n = 138). CONCLUSIONS: In patients with advanced SP MS, urinary MBPLM may possibly serve as an indicator of failed remission and axonal damage. Urinary MBPLM correlates with disease status in MS, especially the transition of RR MS to SP MS with advancing disability.     

Does the Modified Fatigue Impact Scale offer a more comprehensive assessment of fatigue in MS?

BACKGROUND: As a symptom of multiple sclerosis (MS), fatigue is difficult to manage because of its unknown etiology, the lack of efficacy of the drugs tested to date and the absence of consensus about which would be the ideal measure to assess fatigue. OBJECTIVE: Our aim was to assess the frequency of fatigue in a sample of MS patients and healthy controls (HC) using two fatigue scales, the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS) with physical, cognitive and psychosocial subscales. We also studied the relationship fatigue has with depression, disability and interferon beta. METHODS: Three hundred and fifty-four individuals (231 MS patients and 123 HC) were included in this cross-sectional study. Fatigue was assessed using the FSS and MFIS. Depression was measured by the Beck Depression Inventory (BDI), and disability by the Expanded Disability Status Scale (EDSS). A status of fatigue was considered when the FSS > or =5, of non-fatigue when the FSS < or =4, and scores between 4.1 and 4.9 were considered doubtful fatigue cases. RESULTS: Fifty-five percent of MS patients and 13% of HC were fatigued. The global MFIS score positively correlated with the FSS in MS and HC (r =0.68 for MS and r =0.59 for HC, p <0.0001). Nonetheless, the MFIS physical subscale showed the strongest correlation score with the FSS (r =0.75, p <0.0001). In addition, a prediction analysis showed the physical MFIS subscale to be the only independent predictor of FSS score (p <0.0001), suggesting other aspects of fatigue, as cognition and psychosocial functions, may be explored by the FSS to a lesser extent. Depression also correlated with fatigue (r =0.48 for the FSS and r =0.7 for the MFIS, p <0.0001) and, although EDSS correlated with fatigue as well, the scores decreased after correcting for depression. Interferon beta showed no relationship with fatigue. CONCLUSIONS: Fatigue is a frequent symptom found in MS patients and clearly related with depression. Each fatigue scale correlates with one another, indicating that they are measuring similar constructs. Nevertheless, spheres of fatigue as cognition and psychosocial functions are probably better measured by the MFIS, although this hypothesis will need to be confirmed with appropriate psychometrical testing.     

A prospective study of patterns of fatigue in multiple sclerosis

We sought to identify clinical characteristics and socio-demographic variables associated with longitudinal patterns of fatigue in multiple sclerosis (MS) patients. A questionnaire including the Fatigue Severity Scale (FSS) was mailed to a community sample of 502 MS patients three times 1 year apart. Three patterns of fatigue were defined: persistent fatigue (PF) (mean FSS score ≥5 at all time-points), sporadic fatigue (SF) (mean FSS score ≥5 at one or two time-points) and no fatigue (mean FSS score <5 at all time-points). Among the 267 (53%) patients who responded at all time-points, 101 [38%, 95% confidence intervals (CI) 32–44] had persistent, 98 (37%, 95% CI 31–43) sporadic and 68 (25%, 95% CI 20–31) no fatigue. Persistent and sporadic fatigue were more common in patients with, increased neurological impairment ( P  < 0.001), primary progressive MS ( P  = 0.01), insomnia ( P  < 0.001), heat sensitivity ( P  < 0.001), sudden-onset fatigue ( P  < 0.001) or mood disturbance ( P  < 0.001) compared with patients without fatigue. Multivariable analysis showed that depression (PF P  = 0.02, SF P  < 0.001), heat sensitivity (PF P  = 0.04, SF P  = 0.02) and physical impairment (PF P  = 0.004, SF P  = 0.01) were associated with both sporadic and persistent fatigue. About 75% of the patients had persistent or sporadic fatigue over a 2 years observation period. Multivariable analyses confirmed a significant association between levels of depression, physical impairment and persistent fatigue.     

Neuropsychiatric manifestations in multiple sclerosis: correlation of fatigue and depression with disease progression

Abstract

Fatigue is one of the most common disabling symptoms in multiple sclerosis (MS) with significant impact on daily life. The aim of this study is to explore the association among MS fatigue, clinical disability and depression. Fifty-seven patients were assessed by fatigue severity scale (FSS), expanded disability status scale (EDSS) and Beck depression inventory (BDI). Mean FSS score was 4·1 ± 1·6. Based on FSS scores, patients were divided into three groups: Patients with FSS score >5 (n = 10, 32%) were evaluated to present with fatigue symptoms, patients with borderline fatigue (n = 29, 50%) had an FSS score between 4 and 5 and patients with no fatigue (n = 18, 18%) had an FSS<4. When the patients were compared according to the presence of fatigue symptoms, patients with fatigue had significantly higher EDSS scores (p = 0·03). BDI evaluation revealed that 33 (57%) patients had a score 11. MS patients with fatigue showed significantly higher BDI scores when compared to patients without fatigue (p = 0·0002). A significant relationship among fatigue, disease disability and depression was observed in our study, implying the complex interplay of fatigue and depression with disability.     

Fatigue is not associated with raised inflammatory markers in multiple sclerosis

BACKGROUND: The pathogenesis of fatigue in patients with MS is poorly understood. OBJECTIVE: To test the hypothesis that fatigue in MS is related to inflammatory disease activity as measured by systemic markers of inflammation. METHODS: Fatigue as assessed by the Fatigue Questionnaire Scale (FQS) and Krupp's Fatigue Severity Scale (KFSS) was correlated with several inflammatory markers in 38 patients with MS (16 relapsing-remitting [RR; 7 of whom had benign MS), 9 secondary progressive [SP], 13 primary progressive [PP]). The markers included daily urinary neopterin excretion, a marker of interferon-gamma-activated macrophage activity, and serum C-reactive protein (CRP) and soluble intercellular adhesion molecule-1 (sICAM-1) levels. Urinary neopterin excretion was measured daily for 2 weeks. RESULTS: No correlation was found between urinary neopterin excretion, CRP, or sICAM-1 and the fatigue scores. However, patients with a raised serum CRP level had higher KFSS, but not FQS, scores than patients with normal CRP levels (KFSS, 50 +/- 8 vs 41 +/- 14, p = 0.05; FQS, 13 +/- 4 vs 11 +/- 5, p = NS). When assessed using the FQS, patients with RR and SP MS were more fatigued than patients with PP MS (RR = 12.5 [4 to 23] vs SP = 13 [8 to 18] vs PP = 9 [7 to 14], p = 0.02). The patients with benign MS were as fatigued as patients with nonbenign disease. CONCLUSION: The pathogenesis of fatigue in MS is complex and does not appear to be directly related to systemic markers of inflammatory disease activity. Interestingly, patients with PP MS were less fatigued than patients with RR disease.     

Fatigue in multiple sclerosis: relationship with disease duration, physical disability, disease pattern, age and sex

To evaluate the relationship between disease duration, disability, disease pattern, age and sex with fatigue in MS patients. One hundred and seventy-three clinically definite MS patients and 87 age-matched healthy controls enrolled in this cross sectional study. Demographic data (sex, age), duration of the disease and disease pattern extracted from patient’s files and Kurtzke Expanded Disability Status Scale (EDSS) were recorded for each patient by an expert neurologist. Participants were asked to answer the validated and reliable Persian version of beck depression inventory (BDI) and FSS (fatigue severity score) questionnaires. Mean FSS and BDI scores were significantly different between patients and controls (p < 0.001). Patients with longer disease duration, higher EDSS and progressive type of disease had significantly higher FSS and BDI scores. Although men had higher EDSS, FSS and BDI scores were similar in both sex groups. FSS was significantly correlated with age, disease duration, BDI and EDSS. The analysis of covariance revealed that there is no difference in the covariance-adjusted means for fatigue among two disease groups (relapsing remitting and secondary progressive) except for EDSS. MS patients with longer disease duration, higher EDSS and progressive type of disease suffer from fatigue more than cases with lower EDSS, duration of disease and relapsing type of the disease.     

Fatigue and regulation of the hypothalamo-pituitary-adrenal axis in multiple sclerosis

BACKGROUND: Fatigue is a common and disabling symptom in patients with multiple sclerosis (MS). Underlying mechanisms postulated so far have involved localization of brain lesions and abnormalities of the neuroendocrine system and cytokine regulation. OBJECTIVE: To investigate the relationship between fatigue and the hypothalamo-pituitary-adrenal (HPA) axis in patients with MS. DESIGN: A prospective survey. SETTING: Outpatient and inpatient study at the Max Planck Institute of Psychiatry, Munich, Germany. PATIENTS: Thirty-one patients with clinically definite MS, a relapsing-remitting disease course, and without MS-specific treatment. INTERVENTIONS: Assessment of fatigue with 3 questionnaires: the Fatigue Severity Scale (FSS), the Modified Fatigue Impact Scale (MFIS), and the Visual Analog Scale. Assessment of HPA axis regulation with the combined dexamethasone-corticotropin releasing hormone (Dex-CRH) test. RESULTS: The FSS score was significantly correlated with the MFIS score. Patients with fatigue had significantly elevated adrenocorticotropin (ACTH) levels in the combined Dex-CRH test. CONCLUSIONS: In contrast to results for chronic fatigue syndrome, where a hyporeactivity of the HPA axis has been shown, MS patients with fatigue exhibited a higher activity of the HPA axis than those without fatigue, as evidenced by significantly increased ACTH concentrations. Proinflammatory cytokines, known to be elevated in patients with MS, may cause both HPA axis alterations and fatigue.     

Inflammation and atrophy in multiple sclerosis: MRI associations with disease course

Brain atrophy may be a useful surrogate marker of axonal loss and disease progression in multiple sclerosis (MS). Several studies have suggested that inflammatory disease activity is a risk factor for atrophy in the early stages of the disease, but may become less important later in the disease course. We aimed to investigate the relationships between atrophy and active inflammation at different stages of the disease course using brain volume measurements from magnetic resonance imaging (MRI) in patients with both relapsing-remitting (RR) (n=95) and secondary progressive (SP) (n=76) MS. Conventional dual echo and three-dimensional magnetization-prepared rapid-acquisition gradient echo imaging were performed in all patients and in 31 healthy controls. Supratentorial and infratentorial brain, and lateral ventricular volumes were determined using modern design stereology.Patients with SP MS had smaller supratentorial (p=0.003) and infratentorial brain volumes (p=0.0003), and larger lateral ventricles (p=0.02) than patients with RR MS. RR MS patients with T(1)-enhancing lesions had smaller supratentorial (p=0.02) and infratentorial (p=0.002) brain volumes and larger ventricles (p=0.002) than those without enhancing lesions. SP MS patients with enhancing lesions also had significantly larger lateral ventricles (p=0.03). Categorical analysis showed that more RR MS patients with enhancing lesions had smaller supratentorial brain (p=0.005), or larger lateral ventricular (p=0.028) volumes, and more SP MS patients with enhancing lesions had increased lateral ventricle volumes (p=0.013), than patients without enhancements. The number of enhancing lesions was significantly correlated with lateral ventricular volumes in both RR MS (r=0.39, p=0.0001) and SP MS (r=0.46, p<0.0001). Our data shows that the presence of active inflammation on a single MRI in the course of RR and SP MS, is associated with a higher risk and higher level of brain atrophy. These findings emphasise the important long-term relationship between inflammation and atrophy in MS and provide additional support for the strategy of early anti-inflammatory treatment to protect tissue integrity.     

Differential patterns of memory performance in relapsing, remitting and secondary progressive multiple sclerosis

BACKGROUND: Memory dysfunction is common in multiple sclerosis (MS). A retrieval failure has been reported as the primary cause for the memory deficits, although some studies also described a faulty acquisition. AIMS: The aim of the study was to examine memory function in relapsing remitting (RR) and secondary progressive (SP) MS patients, analyze the patterns of performance and to investigate whether disease course influences this performance. DESIGN AND SETTINGS: Case-control prospective study conducted in a clinical setting. MATERIALS AND METHODS: Fifty-five RR, 23 SP MS patients and 80 normal subjects were evaluated with a comprehensive neuropsychological battery. Memory was assessed with tasks from the Signoret memory battery. Attention and executive function were also assessed. STATISTICAL ANALYSIS: Univariate analysis of variance, Mann-Whitney U-test, multivariate logistic regression and Chi-square test were used as appropriate. RESULTS: MS patients performed significantly worse than controls on almost all measures of memory (P < 0,001). MS subgroups differed in tasks of delayed recall (logical memory- P =0,019; wordlist delayed recall, P < 0,001), semantic cued recall (P < 0,001), recognition trials (P =0,006) rate of forgetting (P < 0,001) and confabulation and intrusion errors (P =0,004). CONCLUSIONS: Memory is consistently impaired in MS patients and disease course differentially affects the pattern of performance. SP patients show greater difficulties and a more pervasive pattern of dysfunction than RR patients. Delayed recall was the most affected memory measure and performance on this task discriminates between RR and SP MS patients. Relapsing remitting patients performed within the mildly impaired range while SP patients showed a moderate to severe impairment.     

Fatigue in multiple sclerosis: a comparison of different rating scales and correlation to clinical parameters

OBJECTIVES: Fatigue is one of the most common, yet poorly defined, disabling symptoms in patients with multiple sclerosis (MS). To delineate more clearly the frequency and type of fatigue, we first compared four widely used fatigue scales in consecutive MS patients. Secondly, to further clarify the nature of fatigue, we investigated its relation to physical disability, course of the disease, immunotherapy, and depression. PATIENTS AND METHODS: Between February and September 2000, 151 consecutive MS patients entering our outpatient clinic (94 relapsing-remitting, 50 secondary progressive, and 7 primary progressive patients; mean age 29.0 +/- 7.3 years, mean disease duration 9.9 +/- 6.7 years, median EDSS 3.5) filled in a standardized questionnaire induding four fatigue scales--Fatigue Severity Scale (FSS), MS-specific FSS (MFSS), Modified Fatigue Impact Scale (MFIS), and Visual Analogue Scale (VAS). Patients were included in the 'MS-related fatigue group' (MS-F) when they stated in the questionnaire that fatigue: 1) is one of their three most disabling symptoms; 2) occurs daily or on most of the days; and 3) limits their activities at home or at work Patients fulfilling none of these criteria were classified as 'MS-related nonfatigue group' (MS-NF). Depression was measured by Beck's Depression Inventory (BDI). RESULTS: Although all scales showed significant differences between MS-F and MS-NF, correlation between these scales was, at best moderate (correlation coeffcients ranging from 0.06 to 0.56). The most discriminative scales were FSS and MFIS, showing no overlap of the 10th and 90th percentiles for the MS-F and MS-NF groups, with cut-off values of 4.6 and 38, respectively. Depression (BDI > or = 18) was present in 24 of 148 patients who filled in the BDI (16%). FSS was significantly correlated with physical disability (r=0.33, p<0.0001) and BDI (r=0.41, p<0.0001), but not with age, disease duration, clinical activity, and treatment with interferon-beta. In multivariate analysis, however, only BDI independently predicted fatigue. CONCLUSIONS: The association of fatigue and depression suggests that there might be either common underlying mechanisms or interdependence by a cause-and-effect relationship that requires further investigation. The weak correlation within various fatigue scales is best explained by the fact that fatigue is a multidimensional symptom and, therefore, the available tests measure and weight different aspects of fatigue. Our findings underline the necessity for a more exact definition of fatigue and the development of more valid tools if these are to be used to evaluate treatments.     

Urinary myelin basic protein-like material in patients with multiple sclerosis during interferon beta-1b treatment.

OBJECTIVES: To determine levels of urinary myelin basic protein-like material (MBPLM) in patients with multiple sclerosis (MS) openly treated with interferon beta-1b and to correlate these with clinical changes. BACKGROUND: Levels of urinary MBPLM correlate with the presence of the progressive phase of MS and with the disease burden detected on T2-weighted, cranial magnetic resonance imaging. Measurement of urinary MBPLM level may be a feasible test for monitoring or predicting response to therapeutic measures. DESIGN AND METHODS: In a prospective study at one site, 166 patients with MS (131 with relapsing-remitting [RR] and 35 with secondary progressive [SP] disease) were treated for a minimum of 1 year and up to 3 years with interferon beta-1b and underwent assessment for neurologic disability (Expanded Disability Status Scale and Scripps Neurological Rating Scale) and change in disease subtype. Urine samples were obtained at 1219 of 1378 clinic visits, and urinary MBPLM level was determined and related to creatinine level to adjust for renal function. RESULTS: Statistical analysis using the general linear models procedure confirmed previous findings that the level of urinary MBPLM related to urinary creatinine level (MBPLM/creatinine) was higher (P<.001) in patients with SP than RR MS. Of the 131 patients with RR MS, SP disease developed in 13 during the observation period. Compared with those in the RR group, the RR to SP group had a higher level (P<.001) of urinary MBPLM and did not differ from the SP group. CONCLUSIONS: The level of urinary MBPLM is higher in SP MS than RR MS but not in RR MS that converts to SP MS. Level of urinary MBPLM may permit the examination of treatment tested to prevent RR disease from becoming progressive.     

Intrathecal IgG synthesis: marker of progression in multiple sclerosis patients

OBJECTIVES: We study the power of IgG synthesis value as a marker of disease activity in multiple sclerosis (MS). MATERIAL AND METHODS: Link index was calculated in 202 MS patients. Time between first, second and third attack and progression index (PI) were compared in patient with normal (NLI) high (HL) or very high Link index (VHLI). RESULTS: Secondary progressive (SP) patients had a higher LI than relapsing-remitting (RR) and primary progressive (PP) courses (1.10 +/- 0.5 for SP vs 0.86 +/- 0.5 for RR and 0.81 +/- 0.5 for PP, P=0.01 and 0.03, respectively). Having a HLI in MS RR and SP patients has no time effect in the development of the second and third attack. PI was higher in patients with VHIL (0.67 +/- 0.7) vs patients with NLI (0.42 +/- 0.4, P=0.008) and with HLI (0.39 +/- 0.3, P=0.001). CONCLUSIONS: This study confirmed that LI is a good marker of subsequent progression of MS.     

Fatigue in early Parkinson’s disease. Minor inconvenience or major distress?

Background and purpose: Although fatigue is recognized as a common and debilitating symptom in patients with Parkinson’s disease (PD), little is known on how and when this symptom emerges during disease progression. The aim of the study was to explore the presence and severity of fatigue in patients with PD at the time of diagnosis, before dopaminergic treatment has been instituted. Methods: The present study is part of the Norwegian ParkWest project, a large cohort study of patients with incident PD in Norway. PD was diagnosed according to the Gelb criteria. The study population comprised 199 patients with untreated, newly diagnosed PD and 172 control subjects, matched for gender and age. Fatigue was measured by the Fatigue Severity Scale (FSS). Results: Fifty‐five percent of the patients with PD had clinical significant fatigue (FSS > 4), compared with about 20% of the controls (RR = 2.9). The mean score in patients on the FSS was 4.4 (SD 1.7) and in controls 3.1 (SD 1.3). In addition, there were highly significant differences between patients and controls in each of the nine FSS items. In a regression analysis, only the Montgomery and Åsberg Depression Rating Scale and Unified Parkinson’s Disease Rating Scale‐Activities of Daily Living scores were significantly associated with fatigue. There was no correlation between fatigue and cognitive impairment and hypersomnia. Conclusion: Fatigue is a common symptom in PD, also in patients with early, untreated disease, and it has a negative impact on these patients’ activity of daily living. Also in early PD, fatigue is an important consideration in the management of patients with the disease.     

Cognitive fatigue in multiple sclerosis: findings from a two-wave screening project

BACKGROUND: Multiple sclerosis (MS) patients commonly suffer from fatigue and define it as one of their most disabling symptom profoundly disrupting their lives. However, the relationship of fatigue to cognitive functions and its impact on quality of life have not been widely studied. AIM: To define (1) "cognitive fatigue", (2) survey its frequency and (3) characterize severity and impact on quality of life in MS patients in the first 10 years of the disease. METHODS: A two-wave design was utilized to enrich the studied population in subjects whose fatigue is significant. In the first wave, fatigue was measured by the self-reported fatigue severity scale (FSS) in randomly selected MS patients from our computerized database. Patients responding to the 9th item of the FSS i.e., "Fatigue interferes with my work, family, or social life" by a grade of 3 or higher (of 7) were further assessed (wave two) by the fatigue impact scale (FIS) and the RAYS quality of life questionnaire. RESULTS: Of the 259 patients that completed the first-wave screening, 158 patients (61%, 118 females, mean age 41.1+/-9.2 years, mean disease duration 6.2+/-5.5 years) satisfied the additional criterion and were defined to suffer from significant fatigue. The great majority of these patients-91.7%-had a relapsing-remitting disease course, mean FIS score was 77+/-25.9 and their mean EDSS was 2.9+/-2.6. Fatigue was reported to occur most of the day in 30.9% of patients, persist in 69% for more than 1 year, and in 59.8%, it was reported not to be associated with effort. No correlations were found between age, gender, disease duration or neurological disability and FIS cognitive subscale score. Significant correlations were found between the FIS cognitive subscale score and the three domains (physical, psychological and social-familial) of the RAYS quality of life questionnaire (p<0.001). CONCLUSIONS: Cognitive fatigue was found in more than half of MS patients in the first decade from onset that were particularly selected for significant fatigue in their lives. This aspect of fatigue correlated with all quality of life domains and especially with psychological everyday tasks.     

Fatigue: an important feature of late-onset Pompe disease

Abstract Objective To investigate the prevalence and severity of fatigue in adult patients with Pompe disease. Methods The Fatigue Severity Scale (FSS) was assessed in an international population of 225 adults with Pompe disease, a metabolic disorder presenting as a slowly progressive proximal myopathy. The FSS scores were compared to those of healthy controls and the relationship between the level of fatigue and other patient characteristics was investigated. Results The mean age of the participants was 47 (SD 13) years and the mean disease duration 11 (SD 8) years. 43% used a wheelchair and 46% had respiratory support, 29% needed both. 67% of the participants had a FSS score ≥5, indicating severe fatigue. The mean FSS score was 5.2 (SD 1.5), which was significantly higher than that of healthy controls (p < 0.001). Fatigue was not related to age, sex or disease duration. Patients who used a wheelchair or respiratory support were on average more fatigued than those who did not (p = 0.01). However, of the patients who did not use these aids, 59% also had a FSS score ≥5. FSS scores were highest among patients who reported a high frequency of sleep disorders, but patients who never experienced sleep difficulties were also fatigued (mean FSS score = 4.8). Conclusion Fatigue is highly prevalent among both mildly and severely affected adult patients with Pompe disease. The FSS appears a useful tool in assessing fatigue in Pompe disease.     

Evaluating functional decline in patients with Multiple Sclerosis

Multiple Sclerosis (MS) is a disease with a wide-ranging impact on functional status. The aim of the study was to examine the added value of simultaneously evaluating fatigue, personal ADL and handwriting performance as indicators for functional decline among patients with MS. Participants were 50 outpatients with MS and 26 matched healthy controls. Data collection instruments included a disability status scale, the Fatigue Severity Scale (FSS), and the Physical Self-Maintenance Scale (PSMS). Handwriting performance was evaluated by objective computerized measures of the handwriting process (ComPET). Significant differences were found between patients with MS and control subjects in their fatigue level, their PSMS score and In-air time per stroke while writing. The FSS together with specific PSMS items and handwriting measures achieved correct classification of 87.7% of the participants. These results are the first step towards demonstrating the added value of evaluating body function outcomes (fatigue) together with activity performance (handwriting and ADL) to document functional decline among patients with MS. These results may contribute to the development of practical intervention strategies targeted at improving performance abilities among patients with MS.     

Fatigue and its association with sleep disorders,depressive symptoms and anxiety in patients with multiple sclerosis

Background and purposeThe aetiopathogenesis of fatigue in multiple sclerosis (MS) is not clear. It could be associated with structural changes of the central nervous system, but also with mood and sleep disorders. The purpose of the study was to evaluate frequency of fatigue and its association with sleep and mood disorders in MS patients.Material and methodsThe examined group consisted of 122 MS patients (mean age 37.7 ± 10.8 years). The following questionnaires were used: Fatigue Severity Scale (FSS), Epworth Sleepiness Scale (ESS), Athens Insomnia Scale (AIS), Montgomery-Asberg Depression Rating Scale (MADRS), and Hospital Anxiety and Depression Scale (HADS).ResultsFatigue was present in 75 MS patients (61.5%). Excessive daytime sleepiness was observed in 25 (20.5%), insomnia in 73 patients (59.8%). According to MADRS, depressive symptoms were present in 33 (27%), according to HADS in 15 people (12.3%). Anxiety was present in 32 patients (26.2%). We observed an association between fatigue (FSS) and sleep disorders (ESS, AIS) and also between fatigue and either depression (MADRS, HADS-D) or anxiety (HADS-A). The FSS score was not associated with age, sex, disease course and duration, Expanded Disability Status Stage (EDSS), treatment or level of education in MS patients. In inactive professionally people we noted significantly higher FSS scores (44.8 ± 13.8) in comparison with active individuals (37.2 ± 14.9; p = 0.0053).ConclusionsFatigue is a very common symptom in MS, sometimes associated with sleep disorders, depressive symptoms or anxiety. The treatable causes of fatigue in MS such as sleep and mood disturbances should be identified and treated.     

Fatigue,sleepiness, and physical activity in patients with multiple sclerosis

Fatigue is a frequent and disabling symptom in patients with multiple sclerosis (MS). The objective of the study was to compare fatigue and sleepiness in MS, and their relationship to physical activity. Eighty patients with MS rated the extent of experienced fatigue (Fatigue Severity Scale, FSS) and sleepiness (Epworth Sleepiness Scale, ESS). The relationship between the scales was analysed for the scales as a whole and for single items. The clinical status of the patients was measured with the Extended Disability Status Scale (EDSS). In addition, physical activity was recorded continuously for 1 week by wrist actigraphy. The mean scores of fatigue and sleepiness were significantly correlated (FSS vs. ESS r = 0.42). Single item analysis suggests that fatigue and sleepiness converge for situations that demand self-paced activation, while they differ for situations in which external cues contribute to the level of activation. While fatigue correlated significantly with age (r = 0.40), disease severity (EDSS, r = 0.38), and disease duration (r = 0.25), this was not the case for sleepiness. Single patient analysis showed a larger scatter of sleepiness scores in fatigued patients (FSS > 4) than in non-fatigued patients. Probably, there is a subgroup of MS patients with sleep disturbances that rate high on ESS and FSS. The amount of physical activity, which was measured actigraphically, decreased with disease severity (EDSS) while it did not correlate with fatigue or sleepiness.     

Fatigue and processing speed are related in multiple sclerosis

Background: Fatigue is common in multiple sclerosis (MS) and could be related to impaired processing speed caused by MS specific brain alterations. The objective of this study was to examine the relationship between processing speed and fatigue in patients with relapsing remitting MS. Methods: Patients with EDSS score ≤3.5 were grouped as fatigued [Fatigue Severity Scale (FSS) score ≥5.0] or non‐fatigued (FSS score ≤4.0). Patients with FSS scores ≥5 were categorized as primary or secondary fatigued according to various indices. A cognitive test battery obtained from Wechsler’s Adult Intelligence Scale‐III/Wechsler’s Memory Scale‐III was applied. Results: Processing speed (Digit Symbol Coding) was lower amongst all MS patients being 9.4(2.9) in primary fatigued, 8.3(2.8) in secondary fatigued and 10.3(2.7) in non‐fatigued versus 12.3(3.0) in healthy controls. In the combined group of primary and secondary fatigued MS patients, processing speed was slower than that in non‐fatigued MS patients and inversely related to fatigue (r = ?0.35; P < 0.05). No such relationship could be established in non‐fatigued MS patients or in healthy controls. Conclusion: The degree of fatigue in MS is related to processing speed impairment and longitudinal studies should clarify their mutual dependency.