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   Recording of dis...
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Year : 2004  |  Volume : 6  |  Issue : 22  |  Page : 15-26
Arousals and aircraft noise - environmental disorders of sleep and health in terms of sleep medicine

Institut für Rehaforschung an der Klinik Norderney der Universität Witten/Herdecke, (Institute of Rehabilitation Research at Norderney, Clinic of the University of Witten/Herdecke), Norderney, Germany

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  Abstract 

World wide rules for sleep staging originate to 1967. Since then many investigations aimed to give numbers for the degree of sleep disturbances due to air traffic noise. But the variables used, such as the amount of relative sleep stages, total sleep time, or sleep efficiency, could not explain impairment in health and performance sufficiently. The beginning of the eighties has given new insight into the restorative functions of sleep, according to sleep fragmentation by micro-arousals. These are originating in autonomous dysfunctions during sleep, leading to non-restorative sleep. Environmentally related sleep disturbances are described, EEG and vegetative (micro)-arousals, and the actual knowledge in sleep medicine is given in terms of the international classification of sleep disorders (ICSD). The effects on health, and disturbed performance capacity during the day are shown by self ratings of 160 patients. Elevated metabolic rate caused by micro-arousal and/or insomnia, may play an additional role in health impairment.

Keywords: Classification of sleep disorders (ICSD), environmental sleep disorders, micro-arousal, vegetative arousal, EEG arousal, restorative sleep

How to cite this article:
Raschke F. Arousals and aircraft noise - environmental disorders of sleep and health in terms of sleep medicine. Noise Health 2004;6:15-26

How to cite this URL:
Raschke F. Arousals and aircraft noise - environmental disorders of sleep and health in terms of sleep medicine. Noise Health [serial online] 2004 [cited 2019 Jun 18];6:15-26. Available from: http://www.noiseandhealth.org/text.asp?2004/6/22/15/31677

  Problem outline Top


A broad array of sleep research projects in terms of clinical and internal medicine since the beginning of the eighties has produced a depth of new insight into the relaxation functions of sleep. Sleep medicine has since established itself in Germany, or is at least in the process of doing so, as an interdisciplinary field with its own curriculum of fundamental, advanced and specialized medical training, with the result that the knowledge gained cannot yet be expected everywhere. It has, however, been known since the eighties that insomnias due to maintaining sleep, even when exhibiting no visible reactions in EEG or behaviour, may fragment the sleep process to such an extent that the performance capacity or wellbeing on next day is impaired. Nonetheless, many scientists still assume even today that only arousals which lead to complete awakening induce a disturbance of sleep. This causal chain frequently forms the basis of reasoning on the origins of sleep disturbances, caused for example by aircraft noise at night.

Sleep is only then considered as disturbed by noise if its progress has been macroscopically interrupted. The present article describes the basic outline of the newer insight into sleep disturbances, EEG and vegetative arousals, and sketches the current state of knowledge with regard to their effects on health, as well as on disturbed wellbeing and performance capacity during the day.


  Classification of sleep disorders Top


A comprehensive and independent international classification of sleep disturbances, ICSD, (cf. Schramm and Riemann, 1991) has developed today from the psychiatric/psychological classification systems (DSM-III, DSM-IV, cf. Wittchen et al., 1991) using the former ICD-9 - ICD-10. The sleep medicine diagnostic system has 88 clinical features of disturbed sleep. Four main categories are distinguished:

1. Dyssomnias (disturbances with regard to duration, quality and timing of sleep)

2. Parasomnias (disturbances on awakening, of sleep phases and during the sleep process)

3. Sleep disturbances occurring during physical and psychic illnesses (entirely related to psychic, psychiatric or physical illnesses)

4. Suggested sleep disturbances (not yet assigned sufficient data and information to be considered as independent illnesses)

The first main group among these 4 categories represents dyssomnias. [Figure - 1] shows their three dimensions: 1. intrinsic dyssomnias 2. extrinsic dyssomnias 3. circadian rhythm disturbances. This group covers by far the greatest part of all sleep disturbances since both intrinsic and extrinsic sleep disturbances are included. Intrinsic dyssomnias are still divided into the subgroups insomnia (sleep onset and maintaining sleep) and hypersomnia (daytime sleepiness). Environmental causes (noise, climate) belong to the extrinsic dyssomnias. Socioeconomic disturbances of the circadian rhythm (changes in time-zone, shift work) form a category of their own. The illustration shows all clinical features of the 1st main group behind the vertical line of dots-markers. In addition to this, the left or right positioning for intrinsic dyssomnias shows whether the disturbance picture is marked by insomnia (I) or hypersomnia (H). The sequence of abbreviations I and H also indicates which of the two symptoms is dominant in combined forms (cf. DGSM, Fischer et al. 2001).


  Environmental sleep disorders according to ICSD Top


The ICSD covers environmentally induced sleep disturbances in the form of insomnia and daytime sleepiness with ref. code 780.52-6. Noise induced sleep disorders are also included here. Several of the following criteria need to be met concurrently for their diagnosis: A. complaint of insomnia or excessive daytime sleepiness. B. emergence and/or development of the disturbance is connected with an objectively defined stimulus or factor of the surroundings. C. the physical characteristics of the said surroundings factor provide complete clarification of the disorder, but not of its psychological assessment. D. cessation of the disorder leads to immediate restoration of normal sleep. E. duration of the disorder of more than 3 weeks. F. no indications of organic, psychiatric or G. other sleep disorders. For classification according to 780.52-6 at least criteria A - E need to be fulfilled. The ICSD also contains scaling of the severeness of the disorder, derived from the combination and distinct features of different symptoms. Severity ratings of environmentally induced sleep disorders, however, have not been included so far.


  Recording of disorders induced by auditory sleep disturbances - arousals Top


International standardization and quantification for measurement of the depth of sleep exists since 1967 (Rechtschaffen and Kales, 1967). This is based on a division into epochs with a basic unit of 30 seconds. A phase is only assessed as such if predetermined features are evident for more than 50% of the epoch length. To record a disturbed sleep sequence in accordance with the manual, percentage rates of light, deep and REM-sleep, the total duration of sleep, sleep latency and its continuity play significant roles.

It was already known prior to 1967 that exclusive use of intensity as a unidimension of the audio-stimulus responsible for noise disturbances is not effective in production of an interpretable EEG change for measurement of the depth of sleep via the arousal thresholds. Additional functions also play an important part in audio-stimulation: type of noise, frequency spectrum, information content, duration of interval in repeated episodes, sequential number of sleep cycles passed through, exposure time in relation to the phase length of the circadian system (Maschke et al., 1997; Griefahn, 2000) and age in particular. All functions have a modifying effect on the arousal threshold (e.g. MMuffler, ller, 1998). Koella, the well-known Swiss sleep researcher (1988), pursued a differentiated vigilance level assessment in various functional systems instead of the unidimensional threshold determination via macro-arousal. He suggests investigations of vegetative, motoric, sensoric as well as other lower and higher functions, independently of each other.

The fact that multilayer reactions are involved is clear from [Figure - 2]. With a stimulus in the form of a sound of 1000 Hz and 0.5 sec duration, applied in the range of 43 to 80 dB with a 15 cm distance, the reactions of the EEG, momentary heart rate, continuously recorded non-invasive blood pressure (Finapress), integrated sympathetic activity and tidal volume can be read off. All values recorded show short-time response behaviour to the stimulus. Its duration is approx. 10 seconds without leading to awakening - a typical arousal reaction. In the original work, other cardiovascular variables such as cardiac output and stroke volume were measured. Even without the complete set of data, the illustration shows that an arousal mechanism is to be found in several systems at the same time (cf. Koella, 1988), occurring in a specific combination as a stimulus reaction, unique as a fingerprint for each individual. In this process both internal and external stimuli play a part in the arousal reactions. In addition to audio­stimuli, various other sensory signals can induce arousal. These are summarized in [Figure - 3]. The illustration shows the interoceptive and exteroceptive stimulus qualities and localization in which arousal processes are involved. In addition, several arousal systems are also known from research which are hierarchically interconnected and encompass different cerebral zones, according to the demand modality. The spinal arousal system is on the lowest level, followed by the vegetative arousal system. Arousal reactions leading to conscious awakening are designated as macro-arousals and are recordable in the EEG. However, arousals visible in different sleep stages also occur for the purpose of motor-non-conscious regulation (e.g. thermo-regulation), known as micro-arousals, which can be recorded in the cortical EEG. Affective arousals may also occur in dream sleep; they contain emotive perceptions and processing, are generated in the limbic system, but in principle only play a distinct role for activation reaction on awakening. [Figure - 4] depicts the individual systems. Current research results indicate that the arousal reaction from sleep is essentially mediated via the locus coeruleus and the raphe nuclei, where Orexin, an orexigenic hormone also participating in energy metabolism and food ingestion, plays an important role as hormonal transmitter for the intact asleep-awake regulation.


  EEG Arousals Top


As shown in [Figure - 4], all micro- and macro­arousals appear in the cortical EEG. Arousal reactions not leading to macroscopic awakening were not included in the definition by Rechtschaffen and Kales (1968). For this reason, use of this subdivision does not permit the quantification of typical EEG phenomena of only a few seconds duration relating to sleep, such as the count of β-spindles, K complexes or vertex potentials. Waking reactions only cover macro-arousals on complete awakening. All sub­vigilant arousals in turn are ignored by definition. Motor behaviour reactions for adjusting the extremities, the whole body's position, the thermal comfort, or the bed gear, as a rule remain unrecognized for this reason. From this point of view it's not surprising that the further development of sleep medicine needs new scales in terms of disturbed sleep. With reference to the growing insight from the field of internal medicine in the early eighties, mentioned at the beginning, these must be developed as indicators for the symptoms of non-restorative sleep which cannot be explained using the 30 second epochs. It has been clear since the results of the intrinsic dyssomnia investigation that excessive daytime sleepiness could not be assessed in accordance with Recht­schaffen and Kales since in spite of pronounced daily symptoms only minimal changes in the amount of the depth of sleep occurred. The American Sleep Disorders Association (ASDA) devised a scoring system, taking sequences of 3-15 seconds into account for such transient arousals which are not transferred to macroscopic behavioural awakening. An arousal is present when abrupt EEG frequency changes, including theta-waves, delta-waves, alpha-waves or frequencies of over 16 Hz but no spindles occur. 11 further criteria must be met. More particularly in such cases, EEG arousals assessed on the basis of EEG, EOG and EMG were viewed as micro-arousals. For the first time, the new indicator was able to display sub-vigilant sleep fragmentation, caused by intrinsic sensory (cf. [Figure - 3]) and autonomic alarm reactions such as respiratory arousals, restless or periodic leg movements. In the meantime it has been proven that these autonomic arousals are decisive in causing daytime sleepiness, although they only occur as transients and the person asleep is unaware of them.

Standardized international propagation became possible in the light of these 11 criteria which can be transformed into a decision tree by means of computer programs analyzing the time sequence. It was put into practice within 2 - 3 years in various polysomnographic assessment systems (cf. Ruhle et al. 2001). An arousal index providing the arousal density (events / hour of sleep) was taken as a measure of the degree of severeness.


  Vegetative Arousals Top


The EEG or micro-arousals as defined by ASDA are cortically detectable. However, by no means all vegetative arousals appear in the cortex. A considerable disadvantage of the method was that there was no differentiation of the individual forms of arousal in [Figure - 4], which is why in the assessment EEG arousals were considered as being with or without synchronous occurrence of vegetative arousals, and to date no definition has been established and no agreement exists as to which arousals should be taken as standardized for the findings. Counted among the vegetative arousals are respiratory incidents such as obstructive apnea, oxygen deficiency, increased effort in thorax/diaphragm activity or in esophagus pressure, cardiovascular incidents such as acceleration of the heart rate, or blood pressure and sympathetic activation. Neurological incidents such as periodic leg movements were either counted as synchronous with EEG arousals or viewed as separate. This confusing multiplicity of measures has not improved to date. The following vegetative micro-arousals are being taken into account at present:

- Respiratory arousal

a. Oxygen deficiencies of at least 3%

b. Increases in minute ventilation, tidal air, respiratory effort / esophagus pressure and respiratory flow rate

- Heart rate arousal

a. Transient increases in the momentary heart rate (time limited tachycardic events of more than 10 pulses)

b. Heart rate variability as a global statistics measure of sympathetic heart rate increase

Spectral analysis of the power density (derived from epochs of momentary heart rate)

- Blood pressure arousal

a. Rises in systolic blood pressure by more than 10 mm Hg during a continuous non-invasive measurement of the arterial blood pressure

b. Rises in continuous blood measurements of arterial systolic blood pressure

- Pulse transit time

a. Shortening of the duration by 10 msec is assessed as arousal

- Movement arousal

a. Micro-arousal accompanied by periodic leg movement

b. Movement arousal with submental EMG or extremities motor activity of short duration (<15 sec)

All these forms can also occur in combination. Some authors still distinguish in terms of intensity, complexity (number of variables involved) or duration (1, 3, 5 or 10 sec; e.g. Stradling et al. 1999). The markers presented here were implemented for the purposes of automatic recognition in various polysomnographs as part of program development. Unfortunately no standards of the minimum variables to be used exist at present. Nonetheless, a substantially more sensitive categorization of excessive daytime sleepiness, cognitive loss of performance capacity, disturbances in wellbeing, lack of attentiveness and quality of life has become available than was possible so far using the Rechtschaffen and Kales parameters and the gold standard-test of sleep medicine, the multiple sleep latency test (MSLT).

Sympathetic activation has always played an important role in all activation reactions, but as a continuous method using the tibial needle for electrode measurement in the calf, was always coupled with considerable dropouts and unreasonable exposure to pain in the test person. Automated determination of the pulse transit time (PTT) via synchronous recording of the ECG and photo-plethysmographic recording of oxygen desaturation at the finger tip was introduced in the middle of the nineties as an additional simplification for recording sympathetic activation. The time sequence of arterial pulsation was calculated from the two measured quantities (cf. Riihle et al., 2001) which together with their modulators, stroke volume and cardiac output, provided an indirect measure of sympathetic activation. As well as this, Peripheral arterial tonometry (PAT) which revived finger pulse amplitude as a classical sensitive indicator of vegetative noise reactions (Jansen et al., 1980) in arousal research (e.g. O'Donnell et al. 2001), has played a certain role in determining autonomic arousal reactions in recent times. This procedure enables measurement of the arterial wall tone, leading to acceleration of the pulse wave velocity on the one hand, or the reduction of the photo­plethysmographic finger pulse amplitude on the other. Finger pulse amplitude is known to be a significant, non-invasive and stress-sensitive dimension. The reactions shown are sympathetic or alpha-adrenergic respectively. The disadvantage of both these procedures, however, is that the measuring technique of pulse transit time is uncertain and on the other hand, the finger pulse amplitudes may show ambiguous reactions which in turn mask all stress-induced reactions even during sleep, due to thermoregulation prevailing in the capillary bed. This implies that any further use depends on whether standardization of the thermoregulatory confounder variables is achieved. In the meantime, however, experiments have clearly shown that the sole use of EEG arousals with the ASDA definition provides no sufficient explanation of daytime sleepiness (Pitson and Stradling, 1998; Ayas et al. 2001) unless they are accompanied by vegetative arousals.

As conclusion, the micro-arousals of the ASDA are non-applicable as indicators of sleep disturbances and noise disturbance in noise effects research since they are valued at between 10 and 20 / hour in healthy persons anyway, and can be considered as normal in this range. They record position changes for the purpose of thermal comfort in a normal night's sleep as well, and occur without accompanying vegetative arousals.


  Arousals and restorative functions of sleep Top


If, on the other hand, only such micro-arousals in conjunction with vegetative arousals in the form of transient heart rate, rises in systolic and diastolic blood pressures, increases in sympathetic activity, ventilation increases in respiratory amplitude, rate of flow or exertion are taken into account, a much stronger connection between the number of arousals and decreased performance capacity during the day can be established. This was achieved for example in the study by Pitson and Stradling (1998). With this approach, it is primarily these vegetative arousal reactions which come into question as markers for reduced wellbeing and vigilance during the day. PTT and PAT values are also suggested as markers for daytime drowsiness. Naturally, catecholamine secretions or release disturbances contribute or are expected to contribute extensively to such activation reactions involving various hormones, relevant for restoration (acetylcholine, growth hormones, serotonin, orexin, leptin and others). They are, however, incomparably more difficult to assess. Only unrealistically dense laboratory samples would be able to record their transient character. As a rule they don't appear as cumulative substrate either, which could be identified in the morning by a single measurement (e.g. cortisol in accumulated urine).

In search of sensitive markers it is necessary by definition to focus on the autonomic control mechanisms deviating the organism for a short period out of homeostosis, i.e. its self-chosen optimum. [Figure - 5] shows the typical polysomnographic data over a period of 5 minutes from a patient with serious obstructive sleep apnea syndrome and the respiratory arousals associated with it. The black areas in the cardiotachogram represent heart rate arousals synchronous with the respiratory arousals and clearly indicate tachycardias with instantaneous rate increases from 10 to 30 pulses per minute and a duration of 20 - 35 seconds in each case. One may also assume further additional activation of the cardiovascular system not shown in this illustration (blood pressure, cardiac output, sympathetic activation, vasoconstriction). These could also be observed in [Figure - 2] as a result of the acoustic stimuli. It is known that these extensive cardiovascular and endocrine activations can disturb the restorative function of sleep to a considerable degree since they increase the average overall metabolism and thus the pulse rate. In fact such a correlation can easily be shown for patients with respiratory disorders and sleep apnea syndrome, as represented in [Figure - 6]. We presented a questionnaire covering sleep disturbances and performance limitations to 160 patients the day before investigation in the sleep laboratory of our clinic, wherein the factor "vigilance and performance" distinguishes between pronounced and non-existent symptomatics on a scale of 0 - 100. The figure shows that 9.5% of the diminished vigilance and performance capacity are explicable solely on the average heart rate during sleep. Sleep disturbances in the form of intrinsic dyssomnia [Figure - 1], of which they are not aware in the morning as a rule, frequently occur in these patients, which is why such a high correlation is also to be found with sleep disturbances not consciously experienced (sleep onset, maintaining sleep and awakening disturbances). If one specifically views the heart rate arousals shown in [Figure - 5], a much closer mutuality between transient heart rate increases and respiratory arousals in the overall time of sleep becomes apparent [Figure - 7]. The variance explained here is already 38.2%, giving clear evidence of the close coupling between respiratory and cardiovascular incidents. It must be emphasized again that the individual patient neither perceives nor can otherwise detect these abnormal sequences in the sleep profile, except when asked how he feels today, in which case the answer is usually "I'm so tired, if only I knew why."


  Effects of sleep onset and disorders of maintaining sleep on health and performance Top


As the previous observations revealed, the physical reactions to a stimulus are multidimensional. It is no surprise therefore that the psychic, psychosocial and communicative functions are also disturbed in a complex way when the causes of these disorders involve the processes of sleep onset and maintaining sleep.

Similarly to the physiological sequences, one or more markers are needed which are sensitive and specific to a disturbance. These are placed in readiness in social and rehabilitation medicine using the assessment procedure. In addition, quality of life research has developed extensive generic instruments in the last few years (Bullinger et al. 1995), i.e. instruments independent of the basic disorder, capable of determining the state of health and also applicable in the field of sleep medicine (Raschke and Fischer, 2002). An instrument of wide international application is questionnaire SF-36, which consists of 36 items with 8 sub­scales being evaluated in the German translation by Bullinger et al. (1995). The assessment of their own health rated 261 by patients suffering from insomnia was examined by Zammit et al. (1999) and compared to a control group of 101 test persons [Figure - 8].

The Figure shows the 8 dimensions of the score, scaled from 1 - 100. 100 points corresponds to the maximal value "best functional value possible". Several aspects are clear from the illustration: 1. not all sub-scales are rated to the same extent, even in healthy people. 2. All scores are much lower for patients with disorders relating to sleep onset and maintaining sleep. 3. The impairment is different in the individual categories. 4. The category "Vitality" is most affected.

If it is desired to transfer the effects of these symptoms to functions of physical health, [Figure - 9] impressively reveals where the health disturbances exhibit organic correlation, namely in metabolic processes where the overall metabolism is increased. This investigation by Bonnet and Arand (1995), in which the energy expenditure of 10 insomniacs is contrasted by means of indirect calorimetry with that of 10 control persons of comparable age, sex and bodyweight, was conducted under conditions of bed-rest for 35 hrs following laboratory sleep. The values of those with sleep disturbances are approx. 10% higher over the whole period, the sequence curves result from the endogenously anchored and chronobiologically determined basic metabolic rate. The results clearly show that disturbed sleep is associated with basic functional changes, which may have long-term after-effects or be of chronic recurrence. In consequence impact to the metabolic, endocrine and cardiovascular systems through changes in the metabolic conditions cannot be excluded.


  Which arousals are relevant? Top


Discussions about the function of sleep and the mechanisms of its restorative functions have obsessed mankind for many hundreds of years (cf. e.g. Lauer, 1998). Numerous theories are discussed since then. A central role among the many approaches, however, is the hypothesis that restorative sleep is represented by tissue restoration processes (Adam u. Oswald, 1977), minimization of metabolic rate (Shapiro, 1982) and optimization of the overall energy metabolism (Pack, 2001). For example all recent indications on the mechanism of genetic fixation of narcolepsy points into this direction. Growing evidence is also arising from the numerous results of current studies on neurotransmitters such as noradrenaline, serotonin, histamine, acetylcholine and orexin. All findings in neuroendocrinology also point in this direction. If this is the case, however, further investigations should aim at those studies revealing that sleep disorder are equivalent to an increased metabolic rate. Seen in this light, it is no surprise that pure EEG arousals are hardly adverse to restorative sleep since they are too weak as a neurological epiphenomena to effect metabolic changes. Things look different, however, for microscopic awakening reactions which interrupt the process of sleep. These are undoubtedly associated with metabolic transitions. On the other hand, those which are exogenously induced, lead to increases in metabolism [Figure - 2]. This is certified by the transient heart rate increases shown in this illustration since it is generally known that these are directly related to the oxygen uptake and thus to the overall metabolism.

An analogy exists between reactions to acoustic arousals and intrinsic dyssomnia. An important question to be clarified is to determine what part, amount and interval of intermittent noise causes sleep disturbances and impact on health, because up to now no individually threshold values are known. An estimate of the reactions from [Figure - 5] (respiratory arousal) and [Figure - 2] (acoustic arousal) indicates that the heart rate reactions, expressed as a sum of elevated heart rate over the period of a respiratory arousal, are approx. 3 times higher than for acoustic arousals. If the short click-impulse in [Figure - 2] is replaced by the real time noise level of a low-flight jet plane landing, however, the duration of the disturbance is approx. half a minute, with the result that the respiratory arousal effect is now only a factor 2 higher than the acoustic arousal. Intrinsic and environmentally related arousal reactions are reaching questionable proximity under these conditions.

Both macroscopic as well as microscopic arousals have to be taken into account in determining the environmentally induced sleep disorders. Assessment of sleep fragmentation has at least comparable significance as the traditional indicators such as measurement of sleep depths and profile. This may involve overlap, addition or possibly even potentiation of the effects induced by different mechanisms. No investigations are available in this so far. However, it can no longer be assumed on the basis of the results presented here, that health impairment is necessarily directly linked to its perception. As far as this is concerned, the results of the studies represent an extension of our knowledge to date on health impairment by traffic noise (cf. Ising and Maschke, 1996). On the other hand, further development and especially enhancement of the specificity of the methods is required. New approaches to the improved use of markers for disturbances of health, quality of life, and performance have already been addressed (Ayas et al., 2001; Raschke and Fischer 2001a).

An answer to the question how many macro- and autonomous micro-arousals are tolerated so that health and performance capacity achieved are not impaired over long time, is not possible with any certainty at the moment. A vegetative arousal index of more than 30 / h is certainly considered as serious, more than 20 / h as intermediate, and more than 10 as light forms of sleep disorder. Values for the impact of macro­arousals in number, distribution and intensity on health are not available. It isn't even clear how many EEG arousals occurring during normal night sleep, define the age-related norm.


  Open Questions Top


Whereas measurement of the depth of sleep got international standardization and quantification via the Manual of Rechtschaffen and Kales since 1967, the diagnostic procedures for the detection of sleep disturbances according to the ICSD have remained without standardization so far. In consequence neither the instruments of psychodiagnosis nor the instruments of arousal effects are standardized. The missing link between sleep quality and performance on the next day is also a multidimensional function. Development of assessment instruments is in progress. Advances by means of clarifying investigations are to be expected in the near future, taking into account the worldwide intensity of research on this subject. But it will be much more difficult answering the question as to which amount and quality of noise induced sleep disturbances contribute to short (the day after), and long term (chronically persistent) effects. Prospective, and clinically based, psychologically oriented studies on this subject won't be possible for ethical reasons. Instead, developing concomitant epidemiological research over long episodes for many years may be useful in reality. These however, could be shortened by realization of preventive strategies at the right time.[28]

 
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Correspondence Address:
F Raschke
Institut für Rehaforschung an der Klinik Norderney der Universität Witten/Herdecke, (Institute of Rehabilitation Research at Norderney, Clinic of the University of Witten/Herdecke), Norderney
Germany
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Source of Support: None, Conflict of Interest: None


PMID: 15070525

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