[Melatonin: physiological and pathophysiological aspects and possible applications].
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Biomedical subjects
Publications and source records attributed to A W de Weerd.
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In three patients, a man aged 46 years and two women aged 74 and 38 years, respectively, restless legs syndrome (RLS) was diagnosed. The second patient had a low serum ferritin concentration. The patients were successfully treated with ropirinol, iron suppletion and gabapentine, and pramipexol, respectively. With a prevalence of 7% in the general population, RLS is a frequent disease. Patients complain about unpleasant feelings in the legs and have an urge to move the legs, causing discomfort during rest. Sleep is disturbed significantly, which interferes with normal functioning of the patients during the day. RLS may be caused by anaemia, uraemia or as a side effect of drugs such as selective serotonin uptake inhibitors (SSRIs), lithium and tricyclic antidepressants. RLS can be treated successfully by dopaminergic agents, especially dopamine agonists.
CONTEXT: Recently, several cases of sudden death in GH-treated and non-GH-treated, mainly young Prader-Willi syndrome (PWS), patients were reported. GH treatment in PWS results in a remarkable growth response and an improvement of body composition and muscle strength. Data concerning effects on respiratory parameters, are however, limited. OBJECTIVE: The objective of the study was to evaluate effects of GH on respiratory parameters in prepubertal PWS children. DESIGN: Polysomnography was performed before GH in 53 children and repeated after 6 months of GH treatment in 35 of them. PATIENTS: Fifty-three prepubertal PWS children (30 boys), with median (interquartile range) age of 5.4 (2.1-7.2) yr and body mass index of +1.0 sd score (-0.1-1.7). INTERVENTION: Intervention included treatment with GH 1 mg/m2.d. RESULTS: Apnea hypopnea index (AHI) was 5.1 per hour (2.8-8.7) (normal 0-1 per hour). Of these, 2.8 per hour (1.5-5.4) were central apneas and the rest mainly hypopneas. Duration of apneas was 15.0 sec (13.0-28.0). AHI did not correlate with age and body mass index, but central apneas decreased with age (r = -0.34, P = 0.01). During 6 months of GH treatment, AHI did not significantly change from 4.8 (2.6-7.9) at baseline to 4.0 (2.7-6.2; P = 0.36). One patient died unexpectedly during a mild upper respiratory tract infection, although he had a nearly normal polysomnography. CONCLUSIONS: PWS children have a high AHI, mainly due to central apneas. Six months of GH treatment does not aggravate the sleep-related breathing disorders in young PWS children. Our study also shows that monitoring during upper respiratory tract infection in PWS children should be considered.
BACKGROUND: Electrocardiographic (ECG) abnormalities frequently occur after subarachnoid haemorrhage (SAH), and have been linked with poor outcome. The pathogenesis behind this relation is unclear. We hypothesized that cardiac dysfunction may contribute to the development of delayed cerebral ischemia (DCI) and investigated if electrocardiographic repolarization abnormalities on admission, representing this cardiac dysfunction, are related to DCI. We also assessed the additional value of ECG characteristics to establish prognosticators for clinical outcome (WFNS, age and Hijdra score). METHOD: In a series of 121 consecutive patients with aneurysmal SAH we related individual repolarization-like ECG changes (ST and T-wave changes, QTc prolongation, a U-wave) to the occurrence of DCI by means of Cox proportional hazard modelling and to poor outcome (death or dependence) with logistic regression analysis. We used ROC curves to assess the additional prognostic value of the most important ECG characteristics to established prognosticators. FINDINGS: Only ST segment depression had a statistically significant relationship with the occurrence of DCI (HR 2.4 [95%CI 1.2-4.9]) in univariate analysis. In a similar analysis ST-elevation (OR 4.9; [95%CI 0.99-24.0]), ST-depression (OR 10.6; [95%CI 2.3-48.8]), T-wave inversion (OR 2.5; [95%CI 1.1-5.5]) and ischemic like ECG abnormalities (OR 8.3; [95%CI 3.0-22.2]) were significantly related to poor outcome. In multivariate models with extension of these ECG characteristics for establishing prognosticators the AUC of the ROC improved from 0.81 to 0.84. CONCLUSIONS: ECG abnormalities did not contribute to the prediction of DCI and have limited value in prognosticating poor outcome. The occurrence of DCI is not the explanation of this relationship between ECG characteristics and outcome.
OBJECTIVE: To get more insight in the pathophysiological basis of periodic limb movement disorder (PLMD) with or without restless legs syndrome (RLS), we investigated whether these patients have spontaneous changes in H-reflexes or show altered reflex patterns after (external) inhibition or excitation of the relevant spinal segment. METHODS: The ratio of the peak-to-peak values of the maximal soleus H-reflex and the maximal direct muscle potential (H/M ratio), H-reflex recruitment curves, vibratory inhibition and recovery curves of the soleus H-reflex in double stimulus experiments were measured in 9 PLMD patients and 11 controls. RESULTS: In comparison to controls the vibratory inhibition, predominantly reflecting pre-synaptic inhibitory action, was depressed in PLMD patients. The soleus H-reflex recovery curves showed increased late facilitation and depressed late inhibition, both reflecting diminished inhibition due to post-synaptic central activity. CONCLUSIONS: Our data indicate diminished inhibition at spinal level in PLMD patients. This is probably due to altered function of the descending spinal tracts, peripheral influence or changes at the inter-neural circuitry at spinal level itself, or combinations of these 3 possibilities. SIGNIFICANCE: The results of this study give further insight in the pathophysiology of PLMD and RLS by stressing the importance of diminished central inhibition.
Three teenagers, two girls aged 14 years and one boy aged 10 years, had had difficulty with getting to sleep in the evening and waking up in the morning from a very early age. These difficulties led to underperformance at school and/or tension in the household. The anamneses and a sleep study led to the following conclusions: 'delayed sleep phase syndrome', 'sleep state misperception' and 'aberrant interaction between the child and its parents'. Treatment with phototherapy and regulation of the bedtimes, information and regulation of the bedtimes, and pedagogic advice, respectively, was successful within a few months. Teenagers often complain about problems with sleeping, in particular about late onset of sleep and difficulties with awakening. These problems are self-limiting in most cases, but can have a disastrous influence on social life and education.
OBJECTIVE: Local steroid injections are used for treatment for the carpal tunnel syndrome (CTS). Study of changes in neurophysiological parameters after such treatment for idiopathic CTS might be a supportive argument for the effectiveness of steroid treatment. METHODS: Twenty-one patients with CTS were included and evaluated before and at 1, 3 and 6 months after treatment. At the inclusion date patients received a single 1 ml local steroid injection. Various electrophysiological tests were used. For clinical evaluation, we used the Boston Carpal Tunnel Questionnaire (BCTQ) and the General Outcome Score. RESULTS: The mean nerve conduction parameters had significantly improved at 1 month, except the SNAP4 and CMAP. This improvement was still present at 3 months. At 6 months follow-up, the improvement in the SDL4, SNAP4, M-U, DML and CMAP remained significant. In 6 patients (29%), the nerve conduction parameters normalized and remained so until the end of the study. The BCTQ and the General Outcome Score significantly improved as well. However, there was no correlation between the electrophysiological data, the BCTQ and the General Outcome Score. CONCLUSIONS: The improvements of nerve conduction parameters independently support the ideas on effectiveness of steroid injection therapy in CTS.
OBJECTIVE: To assess the efficacy, safety, and tolerability of ropinirole in the treatment of patients with restless legs syndrome. METHODS: A 12 week, prospective, double blind, randomised comparison involving 284 patients from 10 European countries. All participants had a score of > or =15 on the international restless legs scale (IRLS). Patients were randomised (1:1) to receive either ropinirole 0.25-4.0 mg once daily or placebo. The primary efficacy end point was mean change from baseline to week 12 in total IRLS score. Global improvements (clinical global impression (CGI) scale) and improvements in sleep, health related quality of life (QoL; using generic and disease specific measures), work, and other activities were also assessed. RESULTS: 112/146 patients (76.7%) taking ropinirole and 109/138 (79.0%) taking placebo completed the study. Improvement in IRLS at week 12 with ropinirole (mean (SD) dose, 1.90 (1.13) mg/day) was greater than with placebo (mean (SE): -11.04 (0.719) v -8.03 (0.738) points; adjusted difference = -3.01 (95% confidence interval (CI), -5.03 to -0.99); p = 0.0036). More patients in the ropinirole group (53.4%) showed improvement on the CGI scale at week 12 than in the placebo group (40.9%; adjusted odds ratio = 1.7 (1.02 to 2.69); p = 0.0416). Significant differences on both IRLS and CGI scales favouring ropinirole were apparent by week 1. Ropinirole was also associated with significantly greater improvements in sleep and QoL end points. The most common adverse events were nausea and headache. CONCLUSIONS: Ropinirole improves restless legs syndrome compared with placebo, with benefits apparent by week 1. It is generally well tolerated.
The movements of leg muscles in reference to periodic limb movement disorder (PLMD) have only been described in global terms. The sequences of contracting muscles that cause the PLMs are said to be stereotypical. There is, however, doubt about this fixed sequencing in PLMD. Our goal was to define the sequence of muscle movements in PLMs and then analyse their patterns. We recorded with surface EMG all movements of the muscles said to be involved in PLMs (extensor digitorum brevis, EDB; tibialis anterior, TA; biceps femoris, BF; tensor fasciae latae; TFL) as well as the quadriceps (Q) and soleus (S) muscles in 12 patients with restless legs syndrome combined with PLMD. Accompanying polysomnography provided the sleep parameters. In total, 469 movements were analysed. In only 12% was there the appearance of the classic movement (EDB-TA-BF-TFL) or its direct variants. The most frequent sequences were characterised by contraction of only the TA, TA-EDB only, or TA-EDB followed by all other combinations (32%). The pattern EDB only, EDB-TA, or EDB-TA followed by contraction of one or more other muscles, was seen in 18%. All other combinations appeared in much smaller numbers or only once. Eight patients had specific patterns. Three consistently started with the same muscle. One patient always contracted all six muscles. Six patients never contracted more than three muscles. The number of muscles contracted correlated positively with the appearance of arousal from sleep. The interval between onset of contractions within the PLMs varied randomly in a range of 0-1 s. Within PLMs many variations of muscle movements were documented. Patterns were recognisable, individually determined, and related to arousal from sleep.
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BACKGROUND AND PURPOSE: We initiated this prospective study to investigate the usefulness of contrast enhancement in combination with color Doppler-assisted duplex imaging (CDDI) for the distinction of subtotal internal carotid artery (ICA) stenosis and ICA occlusion. METHODS: During 1 year all patients with a previously unknown subtotal ICA stenosis (>90%) or ICA occlusion on routine CDDI were included in the study. These patients underwent a CDDI with and without intravenous contrast, Levovist 300 mg/ml. RESULTS: The study group consisted of 32 patients, 15 with subtotal stenosis and high velocity at the ICA stenosis, two with subtotal stenosis and minimal residual color flow and relative low velocity at the ICA stenosis and 15 with ICA occlusion. In all patients the diagnosis by CDDI without and with contrast were the same. Image quality was improved with contrast in 13 of the 17 patients at the subtotal ICA stenosis. There was no significant difference in mean velocities at the subtotal ICA stenoses without and with contrast. CONCLUSION: The usefulness of contrast enhancement with CDDI for differentiating subtotal ICA stenosis and ICA occlusion is limited. Possibly it is useful in patients with moderate image quality of the CCA and ICA and in patients with a subtotal stenosis with minimal residual color flow and relative low velocity at the ICA stenosis.
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Periodic limb movement disorder (PLMD) and restless legs syndrome (RLS) are well-known entities from a clinical and polysomnographic point of view. PLMD and RLS are seen mostly as primary or hereditary diseases, but may occur in conjunction to other diseases such as uremia, polyneuropathy, Parkinson's disease, and deficiencies of iron and magnesium. This review will discuss the prevalence, etiology and pathophysiology of secondary PLMD and RLS.
OBJECTIVE: Description of driving behaviour of patients with excessive daytime sleepiness (EDS) and the influence on their driving of diagnosis, therapy, legal guidelines and advices. DESIGN: Inventory based on questionnaires. SETTING: Centre for Sleep and Wake Disorders, The Hague, the Netherlands. METHODS: All patients with EDS who were in a stable condition for at least 6 months after therapy were sent a questionnaire (n = 138). The questions concerned actual driving behaviour, EDS and the effects of diagnosis, therapy and advice given by the Centre. RESULTS: The response was 67% (n = 92). Eighteen patients had never driven a car. Eighteen of the other 74 patients quit driving or drove less. Fifty-six patients did not change their behaviour or drove even more. There was little effect on driving behaviour of diagnosis, therapy and advice to stop driving. CONCLUSION: Patients with EDS often participate as drivers in modern traffic. Legal guidelines and advice given by physicians have only little influence on this behaviour. As general measures seem to be ineffective, approaches tailored to the individual patient may lead to more acceptable results.
BACKGROUND: Studies on determinants of quality of life (QOL) after a stroke focus on one aspect (most important: neurological deficit, mood disorders or cognitive failure) and as such provide no insight in the relative contribution of each factor on QOL. The groups of patients studied often contain victims of different types of stroke. This inhomogenity in patients leads to further confusion about QOL after stroke. OBJECTIVE: To evaluate in one study factors important for QOL in the period 3-12 months after a first one-sided ischemic stroke in the region of the middle cerebral artery. DESIGN: Measures for QOL (Sickness Impact Profile, SIP), cognitive status (Wechsler Adult Intelligence Scale revised), mood and neurological deficit were scored 3. 6 and 12 months after the stroke. SETTING: Successive patients admitted to a general hospital and rehabilitation clinic in The Hague, The Netherlands. PATIENTS: A complete examination was performed three times in 35 patients. The results were compared to those of 20 controls matched for age, last occupation and educational level. RESULTS: There was no significant neurological improvement between 3 and 12 months after the stroke. Cognition was impaired when compared to the estimated premorbid level and to the controls. There was incomplete recovery over the study interval. The patients as a group were depressed and remained so over the period of the study. The resulting quality of life scores were abnormal at 3 months and improved only slightly. Stepwise regression analysis revealed that depression and degree of paresis were the most important variables for the SIPtotal outcome. CONCLUSIONS: In a homogenous group of stroke patients the QOL improved somewhat in the period 3 to 12 months after the stroke but was still highly abnormal after 1 year. The decrease in QOL was correlated with depression and - to some degree - with neurological deficit, but not to cognitive disturbances.
Coactivation of the ulnar nerve at the wrist can be a source of error in tests for carpal tunnel syndrome (CTS). We compared the effects of coactivation in two tests for CTS: the abductor pollicis brevis-distal motor latency (APB-DML) and lumbrical-interosseus-distal motor latency difference (2LI-DML). We studied 33 hands of 25 consecutive patients referred for suspected CTS. In severe CTS, when selective supramaximal stimulation of the median nerve was impossible, all APB-compound muscle action potentials (CMAP) showed abnormalities, indicating volume conduction of ulnar muscle activation. 2LI-DML in these hands led to falsely normal test results, as two identical CMAP were obtained after median and ulnar stimulation. In less severe CTS, warning signs indicating coactivation were observed in APB-DML virtually as often as in 2LI-DML. Undetected coactivation was more likely to be associated with false normal test results in 2LI-DML than in APB-DML.