Nens van Alfen

Neuromuscular involvement in various types of Ehlers-Danlos syndrome.

Ehlers–Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of heritable connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Muscle involvement is plausible based on recently discovered interactions between muscle cells and extracellular matrix molecules; however, muscle symptoms are only sporadically reported. We designed a cross‐sectional study to find out whether neuromuscular features are part of EDS.

The neuralgic amyotrophy consultation

Neuralgic amyotrophy is a distinct clinical syndrome with acute severe pain and patchy paresis in the shoulder and arm region. The clinical phenotype was recently found to be more comprehensive and the long-term prognosis less optimistic than usually assumed for many patients. The disorder can be idiopathic or hereditary in an autosomal dominant fashion, with only few phenotypical variations between the two. This article provides a practical overview of current knowledge on the clinical presentation, diagnosis, pathogenesis and the treatment of pain and complications.

Intermediate CAG repeat lengths (53,54) for MJD/SCA3 are associated with an abnormal phenotype

We report on a Dutch family in which 4 members in 2 generations have intermediate repeat lengths (53 and 54) for Machado‐Joseph Disease/ Spinocerebellar Ataxia (MJD/SCA3). All but the youngest have a restless legs syndrome with fasciculations and a sensorimotor axonal polyneuropathy. Central neurological abnormalities are only present in 2. This family shows that intermediate repeat lengths can be pathogenic and may predispose for restless legs and peripheral nerve disorder.

Skeletal muscle ultrasound

Abstract Muscle ultrasound is a convenient technique to visualize normal and pathological muscle tissue as it is non-invasive and real-time. Neuromuscular disorders give rise to structural muscle changes that can be visualized with ultrasound: atrophy can be objectified by measuring muscle thickness, while infiltration of fat and fibrous tissue increases muscle echo intensity, i.e. the muscles become whiter on the ultrasound image. Muscle echo intensity needs to be quantified to correct for age-related increase in echo intensity and differences between individual muscles. This can be done by gray scale analysis, a method that can be easily applied in daily clinical practice. Using this technique, it is possible to detect neuromuscular disorders with predictive values of 90%. Only in young children and metabolic myopathies the sensitivity is lower. Ultrasound is a dynamic technique and therefore capable of visualizing normal and pathological muscle movements. Fasciculations can easily be differentiated from other muscle movements. Ultrasound appeared to be even more sensitive in detecting fasciculations compared to Electromyography (EMG) and clinical observations, because it can visualize a large muscle area and deeper located muscles. With improving resolution and frame rate it has recently become clear that also smaller scale spontaneous muscle activity such as fibrillations can be detected by ultrasound. This opens the way to a broader use of muscle ultrasound in the diagnosis of peripheral nerve and muscle disorders.

Quantitative muscle ultrasound is a promising longitudinal follow-up tool in Duchenne muscular dystrophy.

Responsive outcome measures are needed to follow the disease status of Duchenne muscular dystrophy (DMD) patients, as new therapeutic approaches become available for affected boys. Quantitative muscle ultrasound (QMUS) is potentially an attractive follow up tool for DMD because it reflects the severity of the dystrophic process without the need for invasive procedures, by quantifying echo intensity (i.e., mean grey level of muscle images) and muscle thickness. We performed a longitudinal follow-up of lower and upper extremity QMUS in 18 DMD patients and compared this with physical functioning in 11 of these patients. QMUS could be performed in every patient, and no patient was subjected to more than a total of 20min of ultrasound scanning time for this study. As expected we found a significant increase of echo intensity with age, reflecting increasing dystrophic muscle changes. This increase was related to ambulatory status, functional grading, muscle strength and motor ability. Our study establishes QMUS as a practical and child-friendly tool for the longitudinal follow up of DMD patients.

Predictors of poor neurologic outcome in patients after cardiac arrest treated with hypothermia: a retrospective study

INTRODUCTION Outcome studies in patients with anoxic-ischemic encephalopathy focus on the early and reliable prediction of an outcome no better than a vegetative state or severe disability. We determined the effect of mild therapeutic hypothermia on the validity of the currently used clinical practice parameters. METHODS We conducted a retrospective cohort study of adult comatose patients after cardiac arrest treated with hypothermia. All data were collected from medical charts and laboratory files and analyzed from the day of admission to the intensive care unit until day 7, discharge from the intensive care unit or death using the Utstein definitions for the registration of the data. RESULTS We analyzed the data of 103 patients. The combination of an M1 or M2 on the Glasgow Coma Scale or absent pupillary reactions or absent corneal reflexes on day 3 was present in 80.6% of patients with an unfavourable and 11.1% of patients with a favourable outcome. The combination of M1 or M2 and absent pupillary reactions to light and absent corneal reflexes on day 3 was present in 14.9% of patients with an unfavourable and none of the patients with a favourable outcome. None of the patients with a favourable outcome had a bilaterally absent somatosensory evoked potential of the median nerve. The value of electroencephalogram patterns in predicting outcome was low, except for reactivity to noxious stimuli. CONCLUSIONS No single clinical or electrophysiological parameter has sufficient accuracy to determine prognosis and decision making in patients after cardiac arrest, treated with hypothermia.

Assisted bicycle training delays functional deterioration in boys with Duchenne muscular dystrophy: the randomized controlled trial "no use is disuse".

Background. Physical training might delay the functional deterioration caused by disuse in boys with Duchenne muscular dystrophy (DMD). The “No Use Is Disuse” study is the first explorative, randomized controlled trial in boys with DMD to examine whether assisted bicycle training is feasible, safe, and beneficial. Methods. Ambulatory and recently wheelchair-dependent boys with DMD were allocated to the intervention or control group. The intervention group received assisted bicycle training of the legs and arms during 24 weeks. The control group received the same training after a waiting period of 24 weeks. The primary study outcomes were the Motor Function Measure (MFM) and the Assisted 6-Minute Cycling Test (A6MCT). Group differences were examined by an analysis of covariance. Results. Thirty boys (mean age 10.5 ± 2.6 years, 18 ambulant and 12 wheelchair-dependent) were allocated to the intervention (n = 17) or the control (n = 13) group. All boys in the intervention group (except one) completed the training. After 24 weeks, the total MFM score remained stable in the intervention group, whereas it had significantly decreased in the control group (Δ = 4.9, 95% confidence interval = 2.2-7.6). No significant group differences were found for the A6MCT. No serious adverse events were observed. Conclusions. Our results suggest that assisted bicycle training of the legs and arms is feasible and safe for both ambulant and wheelchair-dependent children and may decline the deterioration due to disuse. Progressive deterioration, however, may compromise the design of trials for DMD.

Endotoxemia-induced inflammation and the effect on the human brain

IntroductionEffects of systemic inflammation on cerebral function are not clear, as both inflammation-induced encephalopathy as well as stress-hormone mediated alertness have been described.MethodsExperimental endotoxemia (2 ng/kg Escherichia coli lipopolysaccharide [LPS]) was induced in 15 subjects, whereas 10 served as controls. Cytokines (TNF-α, IL-6, IL1-RA and IL-10), cortisol, brain specific proteins (BSP), electroencephalography (EEG) and cognitive function tests (CFTs) were determined.ResultsFollowing LPS infusion, circulating pro- and anti-inflammatory cytokines, and cortisol increased (P < 0.0001). BSP changes stayed within the normal range, in which neuron specific enolase (NSE) and S100-β changed significantly. Except in one subject with a mild encephalopathic episode, without cognitive dysfunction, endotoxemia induced no clinically relevant EEG changes. Quantitative EEG analysis showed a higher state of alertness detected by changes in the central region, and peak frequency in the occipital region. Improved CFTs during endotoxemia was found to be due to a practice effect as CFTs improved to the same extent in the reference group. Cortisol significantly correlated with a higher state of alertness detected on the EEG. Increased IL-10 and the decreased NSE both correlated with improvement of working memory and with psychomotor speed capacity. No other significant correlations between cytokines, cortisol, EEG, CFT and BSP were found.ConclusionsShort-term systemic inflammation does not provoke or explain the occurrence of septic encephalopathy, but primarily results in an inflammation-mediated increase in cortisol and alertness.Trial registrationNCT00513110.

Muscles alive: Ultrasound detects fibrillations

OBJECTIVE Muscle ultrasound is capable of visualizing muscle movements. Recent improvements in ultrasound technology have raised the question whether it is also possible to detect small-scale spontaneous muscle activity such as denervation. In this study we investigated the ability of dynamic muscle ultrasound to detect fibrillations. METHODS Eight patients with fibrillations were measured simultaneously by ultrasound and EMG to verify which movements on ultrasound examination corresponded to fibrillation potentials on EMG. The temperature dependency of ultrasound detected fibrillations and the observer agreement was assessed in five healthy subjects with focal denervation induced by botulinum toxin. RESULTS Fibrillations appeared on ultrasound examination as small, irregularly oscillating movements within the muscle while the overall shape of the muscle remains undisturbed. Visibility of fibrillations with ultrasound decreased with lower temperatures, with a 32% decrease at 30 degrees C compared to 39 degrees C. The interobserver agreement was substantial with a kappa of 0.65 for experienced observers. CONCLUSION Fibrillations could be visualized with ultrasound. Consistent results could be obtained from trained observers. Care has to be taken to ensure an optimal muscle temperature to avoid false negative results, especially in distal muscles. SIGNIFICANCE Visualization of fibrillations by muscle ultrasound opens the way for a new diagnostic application of this technique.

Long-term pain, fatigue, and impairment in neuralgic amyotrophy.

OBJECTIVES Recently, it has become clear that neuralgic amyotrophy (NA; idiopathic and hereditary brachial plexus neuropathy) has a less optimistic prognosis than usually assumed. To optimize treatment and management of these patients, one needs to know the residual symptoms and impairments they suffer. Therefore, the objective of this study was to describe the prevalence of pain, psychologic symptoms, fatigue, functional status, and quality of life in patients with NA. SETTING Neurology outpatient department of an academic teaching hospital. PARTICIPANTS NA patients (N=89) were studied, and clinical details were recorded. Self-report data were on average collected 2 years after the onset of the last NA episode. MAIN OUTCOME MEASURES Pain was assessed with the McGill Pain Questionnaire, fatigue with the Checklist Individual Strength, and psychologic distress with the Symptom Checklist 90. Functional status and handicap were assessed with the modified Rankin Scale and Medical Outcomes Study 36-Item Short-Form Health Survey. RESULTS Pain was usually localized in the right shoulder and upper arm, matching the clinical predilection site for paresis in NA. About a quarter to a third of the patients reported significant long-term pain and fatigue, and half to two thirds still experienced impairments in daily life. Over one third of the individual patients suffered from severe fatigue. The group did not fulfill the criteria of chronic fatigue or major psychologic distress. There was no correlation of pain or fatigue with the level of residual paresis on a Medical Research Council scale, but patients with a comorbid condition fared worse than patients without. CONCLUSIONS A significant number of NA patients suffer from persistent pain and fatigue, leading to impairment. Symptoms were not correlated with psychologic distress. This makes it likely that they are caused by residual shoulder or arm dysfunction but not as part of a chronic pain or fatigue syndrome in these patients.