Joke S. Kalkman

Experienced fatigue in facioscapulohumeral dystrophy, myotonic dystrophy, and HMSN-I

Objective: To assess the prevalence of severe fatigue and its relation to functional impairment in daily life in patients with relatively common types of neuromuscular disorders. Methods: 598 patients with a neuromuscular disease were studied (139 with facioscapulohumeral dystrophy, 322 with adult onset myotonic dystrophy, and 137 with hereditary motor and sensory neuropathy type I). Fatigue severity was assessed with Checklist Individual Strength (CIS-fatigue). Functional impairments in daily life were measured with the short form 36 item health questionnaire (SF-36). Results: The three different neuromuscular patient groups were of similar age and sex. Severe experienced fatigue was reported by 61–74% of the patients. Severely fatigued patients had more problems with physical functioning, social functioning, mental health, bodily pain, and general health perception. There were some differences between the three disorders in the effects of fatigue. Conclusions: Severe fatigue is reported by the majority of patients with relatively common types of neuromuscular disorders. Because experienced fatigue severity is associated with the severity of various functional impairments in daily life, it is a clinically and socially relevant problem in this group of patients.

Increase in prefrontal cortical volume following cognitive behavioural therapy in patients with chronic fatigue syndrome

Chronic fatigue syndrome (CFS) is a disabling disorder, characterized by persistent or relapsing fatigue. Recent studies have detected a decrease in cortical grey matter volume in patients with CFS, but it is unclear whether this cerebral atrophy constitutes a cause or a consequence of the disease. Cognitive behavioural therapy (CBT) is an effective behavioural intervention for CFS, which combines a rehabilitative approach of a graded increase in physical activity with a psychological approach that addresses thoughts and beliefs about CFS which may impair recovery. Here, we test the hypothesis that cerebral atrophy may be a reversible state that can ameliorate with successful CBT. We have quantified cerebral structural changes in 22 CFS patients that underwent CBT and 22 healthy control participants. At baseline, CFS patients had significantly lower grey matter volume than healthy control participants. CBT intervention led to a significant improvement in health status, physical activity and cognitive performance. Crucially, CFS patients showed a significant increase in grey matter volume, localized in the lateral prefrontal cortex. This change in cerebral volume was related to improvements in cognitive speed in the CFS patients. Our findings indicate that the cerebral atrophy associated with CFS is partially reversed after effective CBT. This result provides an example of macroscopic cortical plasticity in the adult human brain, demonstrating a surprisingly dynamic relation between behavioural state and cerebral anatomy. Furthermore, our results reveal a possible neurobiological substrate of psychotherapeutic treatment.

Gray matter volume reduction in the chronic fatigue syndrome

The chronic fatigue syndrome (CFS) is a disabling disorder of unknown etiology. The symptomatology of CFS (central fatigue, impaired concentration, attention and memory) suggests that this disorder could be related to alterations at the level of the central nervous system. In this study, we have used an automated and unbiased morphometric technique to test whether CFS patients display structural cerebral abnormalities. We mapped structural cerebral morphology and volume in two cohorts of CFS patients (in total 28 patients) and healthy controls (in total 28 controls) from high-resolution structural magnetic resonance images, using voxel-based morphometry. Additionally, we recorded physical activity levels to explore the relation between severity of CFS symptoms and cerebral abnormalities. We observed significant reductions in global gray matter volume in both cohorts of CFS patients, as compared to matched control participants. Moreover, the decline in gray matter volume was linked to the reduction in physical activity, a core aspect of CFS. These findings suggest that the central nervous system plays a key role in the pathophysiology of CFS and point to a new objective and quantitative tool for clinical diagnosis of this disabling disorder.

Experienced and physiological fatigue in neuromuscular disorders

OBJECTIVE Fatigue has been described as a typical symptom of neurological diseases. It might be caused both by changes at the peripheral and at the central level. This study measured the level of experienced fatigue and physiological correlates of fatigue in three genetically defined neuromuscular disorders. METHODS Sixty-five facioscapulohumeral dystrophy (FSHD), 79 classical myotonic dystrophy (DM), 73 hereditary motor and sensory neuropathy type I (HMSN) patients and 24 age-matched healthy controls made a 2-min sustained maximal voluntary contraction of the biceps brachii muscle. Experienced fatigue at the current moment was assessed with the abbreviated fatigue questionnaire just before the physiological measurement. Peripheral fatigue was quantified by comparing the amplitudes of an initial and a final stimulated force response during rest. Muscle fibre conduction velocity was determined from a 5-channel surface EMG recording in order to show peripheral changes during the contraction. Central aspects of fatigue were measured using superimposed electrical endplate stimulation. RESULTS Patients showed an increased level of experienced fatigue. Total physiological and peripheral fatigue were smaller in patients compared to controls, and central fatigue was normal. The most interesting result of this study was the presence of a large central activation failure (CAF) in all groups of neuromuscular patients; they showed CAF values of 36-41% already directly at the start of sustained contraction, whereas the control group showed only 12%. CAF slightly correlated with the level of experienced fatigue just before the test. CONCLUSIONS The cause of the large CAF in patients is unclear. Reduced concentration, motivation or effort can lead to lower central activation. In neuromuscular patients especially fear of physical activity or fear to damage the muscle or nerve tissue may contribute. Besides, also physiological feedback mechanisms or changes at the motocortical level may be a cause of reduced central activation. SIGNIFICANCE For the clinician it is important to know that experienced fatigue is part of the clinical spectrum of neuromuscular patients. Besides, the weakness in these patients is aggravated by reduced central activation. Potentially, both problems could be subject of an intervention.

Effects of training and albuterol on pain and fatigue in facioscapulohumeral muscular dystrophy

AbstractBackgroundWe recently reported a randomised controlled trial on the efficacy of strength training and the β 2-adrenergic agonist albuterol in patients with facioscapulohumeral muscular dystrophy (FSHD). Strength training and albuterol appeared safe interventions with limited positive effect on muscle strength and volume. We concurrently explored the prevalence and the characteristics of pain and fatigue in the participating FSHD patients, because these are probably underreported but clinically relevant symptoms in this disorder. Next, we studied the effects of albuterol and strength training on pain, experienced fatigue, healthrelated functional status and psychological distress.MethodsSixty-five patients were randomised to strength training of elbow flexors and ankle dorsiflexors or nontraining. After 26 weeks, albuterol (sustained-release, 8 mg bid) was added in a randomised, doubleblind, placebo-controlled design. Outcomes comprised self-reported pain, experienced fatigue, functional status and psychological distress obtained with validated questionnaires at 52 weeks.ResultsEighty percent of patients reported chronic persistent or periodic, multifocal pains. Thirtyfour percent of the participants were severely fatigued. Strength training and albuterol failed to have a significant effect on all outcomes.ConclusionsPain and fatigue are important features in FSHD. Strength training and albuterol do not have a positive or negative effect on pain, experienced fatigue, functional status and psychological distress.

Psychiatric disorders appear equally in patients with myotonic dystrophy, facioscapulohumeral dystrophy, and hereditary motor and sensory neuropathy type I

Objectives –  To study the presence of psychiatric comorbidity assessed by the use of a structured clinical interview and self‐reported questionnaires in a large sample of patients with adult‐onset myotonic dystrophy (DM), facioscapulohumeral muscular dystrophy (FSHD), and hereditary motor and sensory neuropathy type I (HMSN‐I), and to assess whether psychiatric comorbidity is related to fatigue severity and/or muscle strength.

Different types of fatigue in patients with facioscapulohumeral dystrophy, myotonic dystrophy and HMSN-I. Experienced fatigue and physiological fatigue

Although fatigue is a common symptom in neuromuscular disorders, little is known about different types of fatigue. Sixty-five FSHD, 79 adult-onset MD and 73 HMSN type I patients were studied. Experienced fatigue was assessed with the CIS-fatigue subscale. Physiological fatigue was measured during a 2-min sustained maximal voluntary contraction of the biceps brachii muscle using the twitch interpolation technique to assess central activation failure (CAF) and peripheral fatigue. Experienced fatigue, CAF and peripheral fatigue appeared to be predominantly separate types of fatigue.

The relation between daytime sleepiness, fatigue, and reduced motivation in patients with adult onset myotonic dystrophy

Daytime sleepiness, apathy, and lack of motivation are established clinical manifestations of myotonic dystrophy.1,2 A recent study showed that modafinil reduced daytime sleepiness and average sleep latency in a group of nine patients with myotonic dystrophy.3 This finding suggests that daytime sleepiness in patients with myotonic dystrophy and without obstructive sleep apnoea might be central in origin. A magnetic resonance imaging study indeed found evidence for a possible association between cerebral abnormalities in myotonic dystrophy and excessive daytime sleepiness.4 Although several studies have measured levels of fatigue with validated questionnaires in different neurological patient populations,5,6 fatigue questionnaires have not yet been related to the symptoms of daytime sleepiness in myotonic dystrophy. With the results of the modafinil study mentioned above in mind, our goal was to test the relations between excessive daytime sleepiness, experienced fatigue, and reduced motivation. ### Patients The study was conducted at the outpatient clinic of the Neuromuscular Centre Nijmegen, based at the Institute of Neurology of the University Medical Centre Nijmegen in the Netherlands. Consecutive ambulant patients with a genetically confirmed diagnosis of (adult onset) myotonic dystrophy and an expanded CTG repeat on chromosome 19q13.3 (DM1) were invited to take part. Fatigue was not a criterion …

EMPLOYMENT STATUS OF PATIENTS WITH NEUROMUSCULAR DISEASES IN RELATION TO PERSONAL FACTORS, FATIGUE AND HEALTH STATUS: A SECONDARY ANALYSIS

OBJECTIVE To determine the number of employed people in a group of patients with neuromuscular diseases and in 3 separate subgroups (facioscapulo-humeral dystrophy, hereditary motor and sensory neuropathy, and myotonic dystrophy) to investigate any differences in employment status between the patient groups, and to identify factors related to employment status. DESIGN Cross-sectional study. PATIENTS A total of 591 patients with neuromuscular diseases participated in the study, 138 with facioscapulo-humeral dystrophy, 135 with hereditary motor and sensory neuropathy, and 318 with myotonic dystrophy. METHODS Self-report questionnaires, the Checklist Individual Strength (CIS) and the Short Form-36 (SF-36). RESULTS Of the patients with neuromuscular diseases in the study, 56.7% were employed. Younger age, being male, and higher education contributed significantly to employment status of the neuromuscular diseases group and the hereditary motor and sensory neuropathy and myotonic dystrophy subgroups. Significant between-group differences for employed vs not employed subjects were present in the total neuromuscular diseases group on all subscales of the CIS and SF-36. Factors related to employment status differed for the 3 neuromuscular diseases subgroups. CONCLUSION More than half of the patients with neuromuscular diseases were employed. Patients with facioscapulo-humeral dystrophy and patients with hereditary motor and sensory neuropathy were more often employed than patients with myotonic dystrophy. Between-group analyses for differences in baseline factors revealed 11 significant factors related to employment. Multivariate logistic analyses revealed 6 factors contributing to employment for the group of patients with neuromuscular diseases.

Severe fatigue in narcolepsy with cataplexy.

Excessive daytime sleepiness (EDS) is the core symptom of narcolepsy. However, there have been indications that fatigue – which should be separated from EDS – is also a frequent complaint. We determined the prevalence of severe fatigue in a group of narcolepsy patients and its relation with excessive daytime sleepiness, psychological distress, functional impairment and quality of life. We included 80 patients fulfilling the International Classification of Sleep Disorders (ICSD)‐2 diagnostic criteria of narcolepsy with cataplexy. Fatigue was measured using the Checklist Individual Strength (CIS). In addition psychological distress, including symptoms of depression, functional impairment and quality of life, were assessed. Comparisons were made between patients with (CIS‐fatigue score ≥ 35) and without severe experienced fatigue. Fifty patients (62.5%) reported severe fatigue. There were no sex or age differences between patients with and without severe fatigue. Both fatigued and non‐fatigued patients had the same amount of daytime sleepiness (Epworth Sleepiness Score 14.3 ± 4.2 versus 13.1 ± 4.4, P = 0.22), confirming the separation between sleepiness and fatigue. Interestingly, fatigued patients more often used stimulant medication (64% versus 40%, P = 0.02). Severe fatigue was associated with a significantly increased functional impairment, increased depressive symptoms and a lowered general quality of life. In conclusion, a majority of patients with narcolepsy suffer from severe fatigue, which can be distinguished from daytime sleepiness, and results in severe functional impairment.