Prevalence and associated risk factors of periodic limb movement in sleep in two German population-based studies.

STUDY OBJECTIVES: Periodic limb movements in sleep (PLMS) are frequent motor phenomena; however, population-based data are scarce. We assessed the prevalence of PLMS and factors associated with PLMS within two German population-based cohorts, the SHIP-TREND and BiDirect. METHODS: Single-night polysomnography was performed on 1107 subjects recruited from the general population (mean age: 52.9 years, 54.1% men) in the SHIP-TREND and on 247 participants (mean age: 57.6 years, 50.6% men) in the BiDirect. PLMS were evaluated using the standard criteria of the American Academy of Sleep Medicine. Sociodemographic data, behavioral variables, medical history, current medication, and other sleep disorders were assessed. RESULTS: The prevalence of PLMS index (PLMSI) >15/hour was 32.4% (SHIP-TREND) and 36.4% (BiDirect). In multivariable models, age (odds ratio [OR] = 1.05 per +1 year), male gender (OR = 2.20), restless legs syndrome (OR = 2.32), physical inactivity (OR = 1.52), current smoking (OR = 1.49), diabetes (OR = 2.13), antidepressant use (OR = 2.27), lower serum magnesium (OR per -0.1 mmol/L = 1.27) showed a positive, and the intake of beta-blockers an inverse association with PLMSI >15/hour in SHIP-TREND. In BiDirect, age (OR = 1.13 per +1 year), body mass index (OR = 1.11 per +1 kg/m2), and restless legs syndrome (OR = 8.77) were significantly associated with PLMSI >15/hour. CONCLUSIONS: A high PLMSI is frequent in the German population. Age, male gender, restless legs syndrome, physical inactivity, current smoking, obesity, diabetes, antidepressant use, and lower magnesium were independently associated with PLMSI >15/hour in at least one of the cohorts.

Discontinuous versus Continuous Weaning in Stroke Patients.

BACKGROUND: An increasing number of stroke patients have to be supported by mechanical ventilation in intensive care units (ICU), with a relevant proportion of them requiring gradual withdrawal from a respirator. To date, weaning studies have focused merely on mixed patient groups, COPD patients or patients after cardiac surgery. Therefore, the best weaning strategy for stroke patients remains to be determined. METHODS: Here, we designed a prospective randomized controlled study comparing adaptive support ventilation (ASV), a continuous weaning strategy, with biphasic positive airway pressure (BIPAP) in combination with spontaneous breathing trials, a discontinuous technique, in the treatment of stroke patients. The primary endpoint was the duration of the weaning process. RESULTS: Only the 40 (out of 54) patients failing in an initial spontaneous breathing trial (T-piece test) were included into the study; the failure proportion is considerably larger compared to previous studies. Eligible patients were pseudo-randomly assigned to one of the two weaning groups. Both groups did not differ regarding age, gender, and severity of stroke. The results showed that the median weaning duration was 10.7 days (±SD 7.0) in the discontinuous weaning group, and 8 days (±SD 4.5) in the continuous weaning group (p < 0.05). CONCLUSIONS: To the best of our knowledge, this is the first clinical study to show that continuous weaning is significantly more effective compared to discontinuous weaning in mechanically ventilated stroke patients. We suppose that the reason for the superiority of continuous weaning using ASV as well as the bad performance of our patients in the 2 h T-piece test is caused by the patients' compliance. Compared to patients on surgical and medical ICUs, neurological patients more often suffer from reduced vigilance, lack of adverse-effects reflexes, dysphagia, and cerebral dysfunction. Therefore, stroke patients may profit from a more gradual withdrawal of weaning.

Standardized endoscopic swallowing evaluation for tracheostomy decannulation in critically ill neurologic patients.

OBJECTIVES: Decisions regarding tracheostomy tube removal after mechanical ventilation often depend on the physician's individual experience because evidence-based practice guidelines are still scarce, especially for critically ill neurologic patients. In these patients, the prevalence of aspiration is high and regarded as an important contributor to decannulation failure. The presence of severe neurological deficits may, however, give clinicians the subjective impression that a tracheostomy tube is still necessary although decannulation may actually be safe. It is therefore crucial to test swallowing function reliably prior to decannulation in this patient population. DESIGN: Prospective observational study. SETTING: University hospital, neurological ICU. PATIENTS: One hundred tracheostomized patients with acute neurologic disease completely weaned from mechanical ventilation. INTERVENTIONS: An endoscopic protocol evaluating readiness for decannulation and a conventional clinical swallowing examination were carried out by separate, experienced practitioners blinded to each other's decisions. Patient management always followed the decision made with endoscopy. MEASUREMENTS AND MAIN RESULTS: Practitioners' decannulation decisions (yes/no) reached with both assessments were compared. Decannulated patients were monitored throughout their stay for complications related to tube removal. Endoscopy was performed successfully in all subjects without any complications. Following the protocol, the tracheostomy tube was successfully removed in 54 patients, whereas according to the clinical swallowing examination, only 29 patients would have been decannulated at that point. Only one patient needed recannulation due to respiratory problems, resulting in a failure rate of 1.9%. CONCLUSIONS: In neurologic patients, speech-language pathologists' impressions about the patient's state when clinically assessing indirect variables of swallowing function often lead to the unnecessary prolongation of cannulation time. Endoscopic evaluation has the advantage of objectively visualizing the patient's ability to manage secretions directly and allows for faster but, nonetheless, safe decannulation. The endoscopic protocol proposed here is a safe, efficient, and objective bedside tool to guide decannulation decisions.

Sensorimotor cortical activation in patients with sleep bruxism.

Sleep bruxism is assumed to be triggered by a dysfunctional subcortical and cortical network. This study investigates sensorimotor cortical activation in patients with sleep bruxism during clenching and chewing. Nine polysomnographically diagnosed patients and nine healthy control subjects underwent magnetoencephalography (MEG). During clenching and chewing, patients with bruxism revealed significantly larger event-related desynchronization in the somatomotor area (Brodmann area 4) than healthy subjects. Group differences in the muscle activity were ruled out by electromyography (EMG) assessments during MEG. This result might be regarded as a consequence of increased sensorimotor cortical representation of the tongue and chewing musculature due to an enhanced parafunctional muscle activity in bruxers potentially triggered by occlusal factors. Alternatively, a secondary activation of cortical structures during sleep bruxism in the context of an activated network of subcortical and cortical structures might lead to increased cortical representation of the chewing musculature via use dependent plasticity.

Cortical processing of swallowing in ALS patients with progressive dysphagia--a magnetoencephalographic study.

Amyotrophic lateral sclerosis (ALS) is a rare disease causing degeneration of the upper and lower motor neuron. Involvement of the bulbar motor neurons often results in fast progressive dysphagia. While cortical compensation of dysphagia has been previously shown in stroke patients, this topic has not been addressed in patients suffering from ALS. In the present study, we investigated cortical activation during deglutition in two groups of ALS patients with either moderate or severe dysphagia. Whole-head MEG was employed on fourteen patients with sporadic ALS using a self-paced swallowing paradigm. Data were analyzed by means of time-frequency analysis and synthetic aperture magnetometry (SAM). Group analysis of individual SAM data was performed using a permutation test. We found a reduction of cortical swallowing related activation in ALS patients compared to healthy controls. Additionally a disease-related shift of hemispheric lateralization was observed. While healthy subjects showed bilateral cortical activation, the right sensorimotor cortex was predominantly involved in ALS patients. Both effects were even stronger in the group of patients with severe dysphagia. Our results suggest that bilateral degeneration of the upper motor neuron in the primary motor areas also impairs further adjusted motor areas, which leads to a strong reduction of 'swallowing related' cortical activation. While both hemispheres are affected by the degeneration a relatively stronger activation is seen in the right hemisphere. This right hemispheric lateralization of volitional swallowing observed in this study may be the only sign of cortical plasticity in dysphagic ALS patients. It may demonstrate compensational mechanisms in the right hemisphere which is known to predominantly coordinate the pharyngeal phase of deglutition. These results add new aspects to our understanding of the pathophysiology of dysphagia in ALS patients and beyond. The compensational mechanisms observed could be relevant for future research in swallowing therapies.

Cortical swallowing processing in early subacute stroke.

BACKGROUND: Dysphagia is a major complication in hemispheric as well as brainstem stroke patients causing aspiration pneumonia and increased mortality. Little is known about the recovery from dysphagia after stroke. The aim of the present study was to determine the different patterns of cortical swallowing processing in patients with hemispheric and brainstem stroke with and without dysphagia in the early subacute phase. METHODS: We measured brain activity by mean of whole-head MEG in 37 patients with different stroke localisation 8.2+/-4.8 days after stroke to study changes in cortical activation during self-paced swallowing. An age matched group of healthy subjects served as controls. Data were analyzed by means of synthetic aperture magnetometry and group analyses were performed using a permutation test. RESULTS: Our results demonstrate strong bilateral reduction of cortical swallowing activation in dysphagic patients with hemispheric stroke. In hemispheric stroke without dysphagia, bilateral activation was found. In the small group of patients with brainstem stroke we observed a reduction of cortical activation and a right hemispheric lateralization. CONCLUSION: Bulbar central pattern generators coordinate the pharyngeal swallowing phase. The observed right hemispheric lateralization in brainstem stroke can therefore be interpreted as acute cortical compensation of subcortically caused dysphagia. The reduction of activation in brainstem stroke patients and dysphagic patients with cortical stroke could be explained in terms of diaschisis.

Age-related changes in cortical swallowing processing.

The cortical organization of swallowing has been mainly studied in young and healthy subjects. Aging effects on human deglutition have been found in several behavioral studies and are known to affect both the oral and pharyngeal phases of swallowing. The aim of this study was to evaluate a potential cortical compensation of age-related swallowing impairment. Whole-head MEG was employed in 9 healthy elderly subjects (mean age 71.6 years) and compared to 9 healthy young participants (mean age 23.8 years). Data were analyzed by means of time-frequency plots and synthetic aperture magnetometry (SAM). Group analysis of individual SAM data was performed using a permutation test. The main finding of this study was an increase of somatosensory cortical activation during swallowing execution in elderly subjects compared to the young control group. This effect was present in both hemispheres. These results point to adaptive cerebral changes in response to aging effects on the complex process of swallowing. Our finding underlines the relevance of age matched control groups in neuroimaging studies related to deglutition or other complex sensorimotor processes.

Measurement of pharyngeal sensory cortical processing: technique and physiologic implications.

BACKGROUND: Dysphagia is a major complication of different diseases affecting both the central and peripheral nervous system. Pharyngeal sensory impairment is one of the main features of neurogenic dysphagia. Therefore an objective technique to examine the cortical processing of pharyngeal sensory input would be a helpful diagnostic tool in this context. We developed a simple paradigm to perform pneumatic stimulation to both sides of the pharyngeal wall. Whole-head MEG was employed to study changes in cortical activation during this pharyngeal stimulation in nine healthy subjects. Data were analyzed by means of synthetic aperture magnetometry (SAM) and the group analysis of individual SAM data was performed using a permutation test. RESULTS: Our results revealed bilateral activation of the caudolateral primary somatosensory cortex following sensory pharyngeal stimulation with a slight lateralization to the side of stimulation. CONCLUSION: The method introduced here is simple and easy to perform and might be applicable in the clinical setting. The results are in keeping with previous findings showing bihemispheric involvement in the complex task of sensory pharyngeal processing. They might also explain changes in deglutition after hemispheric strokes. The ipsilaterally lateralized processing is surprising and needs further investigation.

Tactile thermal oral stimulation increases the cortical representation of swallowing.

BACKGROUND: Dysphagia is a leading complication in stroke patients causing aspiration pneumonia, malnutrition and increased mortality. Current strategies of swallowing therapy involve on the one hand modification of eating behaviour or swallowing technique and on the other hand facilitation of swallowing with the use of pharyngeal sensory stimulation. Thermal tactile oral stimulation (TTOS) is an established method to treat patients with neurogenic dysphagia especially if caused by sensory deficits. Little is known about the possible mechanisms by which this interventional therapy may work. We employed whole-head MEG to study changes in cortical activation during self-paced volitional swallowing in fifteen healthy subjects with and without TTOS. Data were analyzed by means of synthetic aperture magnetometry (SAM) and the group analysis of individual SAM data was performed using a permutation test. RESULTS: Compared to the normal swallowing task a significantly increased bilateral cortical activation was seen after oropharyngeal stimulation. Analysis of the chronological changes during swallowing suggests facilitation of both the oral and the pharyngeal phase of deglutition. CONCLUSION: In the present study functional cortical changes elicited by oral sensory stimulation could be demonstrated. We suggest that these results reflect short-term cortical plasticity of sensory swallowing areas. These findings facilitate our understanding of the role of cortical reorganization in dysphagia treatment and recovery.

Auditory temporal processing in healthy aging: a magnetoencephalographic study.

BACKGROUND: Impaired speech perception is one of the major sequelae of aging. In addition to peripheral hearing loss, central deficits of auditory processing are supposed to contribute to the deterioration of speech perception in older individuals. To test the hypothesis that auditory temporal processing is compromised in aging, auditory evoked magnetic fields were recorded during stimulation with sequences of 4 rapidly recurring speech sounds in 28 healthy individuals aged 20 - 78 years. RESULTS: The decrement of the N1m amplitude during rapid auditory stimulation was not significantly different between older and younger adults. The amplitudes of the middle-latency P1m wave and of the long-latency N1m, however, were significantly larger in older than in younger participants. CONCLUSION: The results of the present study do not provide evidence for the hypothesis that auditory temporal processing, as measured by the decrement (short-term habituation) of the major auditory evoked component, the N1m wave, is impaired in aging. The differences between these magnetoencephalographic findings and previously published behavioral data might be explained by differences in the experimental setting between the present study and previous behavioral studies, in terms of speech rate, attention, and masking noise. Significantly larger amplitudes of the P1m and N1m waves suggest that the cortical processing of individual sounds differs between younger and older individuals. This result adds to the growing evidence that brain functions, such as sensory processing, motor control and cognitive processing, can change during healthy aging, presumably due to experience-dependent neuroplastic mechanisms.

Time-dependent hemispheric shift of the cortical control of volitional swallowing.

An important part of the cortical processing of swallowing takes place in the sensorimotor cortex, predominantly in the left hemisphere. However, until now, only deglutition related brain activation with low time resolution exceeding a time interval of 1 s has been reported. In this study, we have examined the chronological sequence of cortical swallowing processing in humans by means of high temporal resolution magnetoencephalography (MEG). The cortical MEG activity was recorded during self-paced volitional swallowing in 10 healthy subjects. Data were analyzed using synthetic aperture magnetometry and the group analysis was performed using a permutation test. Swallowing-related muscle activity was recorded by electromyography. Within the time interval of 1 s of the most pronounced muscular swallowing execution, the MEG analysis revealed neural activation in the primary sensorimotor cortex. During the first 600 ms, only left hemispheric activation was found, bihemispheric activation during the next 200 ms and a right hemispheric activation during the last 200 ms. Thus, our results demonstrate a time-dependent shift of neural activation from left to right sensorimotor cortex during deglutition with left hemispheric dominance in the early stage of volitional swallowing and right hemispheric dominance during its later part.

Local sphere-based co-registration for SAM group analysis in subjects without individual MRI.

Synthetic aperture magnetometry (SAM) is a powerful MEG source localization method to analyze evoked as well as induced brain activity. To gain structural information of the underlying sources, especially in group studies, individual magnetic resonance images (MRI) are required for co-registration. During the last few years, the relevance of MEG measurements on understanding the pathophysiology of different diseases has noticeable increased. Unfortunately, especially in patients and small children, structural MRI scans cannot always be performed. Therefore, we developed a new method for group analysis of SAM results without requiring structural MRI data that derives its geometrical information from the individual volume conductor model constructed for the SAM analysis. The normalization procedure is fast, easy to implement and integrates seamlessly into an existing landmark based MEG-MRI co-registration procedure. This new method was evaluated on different simulated points as well as on a pneumatic index finger stimulation paradigm analyzed with SAM. Compared with an established MRI-based normalization procedure (SPM2) the new method shows only minor errors in single subject results as well as in group analysis. The mean difference between the two methods was about 4 mm for the simulated as well as for finger stimulation data. The variation between individual subjects was generally higher than the error induced by the missing MRIs. The method presented here is therefore sufficient for most MEG group studies. It allows accomplishing MEG studies with subject groups where MRI measurements cannot be performed.

Cortical compensation associated with dysphagia caused by selective degeneration of bulbar motor neurons.

According to recent neuroimaging studies, swallowing is processed within multiple regions of the human brain. In contrast to this, little is known about the cortical contribution and compensatory mechanisms produced by impaired swallowing. In the present study, we therefore investigated the cortical topography of volitional swallowing in patients with X-linked bulbospinal neuronopathy (Kennedy disease, KD). Eight dysphagic patients with genetically proven KD and an age-matched healthy control group were studied by means of whole-head magnetoencephalography using a previously established swallowing paradigm. Analysis of data was carried out with synthetic aperture magnetometry (SAM). The group analysis of individual SAM results was performed using a permutation test. KD patients showed significantly larger swallow-related activation of the bilateral primary sensorimotor cortex than healthy controls. In contrast to the control group, in KD patients the maximum activity was located in the right sensorimotor cortex. Furthermore, while in nondysphagic subjects a previously described time-dependent shift from the left to the right hemisphere was found during the one second of most pronounced swallow-related muscle activity, KD patients showed a strong right hemispheric activation in each time segment analyzed. Since the right hemisphere has an established role in the coordination of the pharyngeal phase of swallowing, the stronger right hemispheric activation observed in KD patients indicates cortical compensation of pharyngeal phase dysphagia.

Cortical recovery of swallowing function in wound botulism.

BACKGROUND: Botulism is a rare disease caused by intoxication leading to muscle weakness and rapidly progressive dysphagia. With adequate therapy signs of recovery can be observed within several days. In the last few years, brain imaging studies carried out in healthy subjects showed activation of the sensorimotor cortex and the insula during volitional swallowing. However, little is known about cortical changes and compensation mechanisms accompanying swallowing pathology. METHODS: In this study, we applied whole-head magnetoencephalography (MEG) in order to study changes in cortical activation in a 27-year-old patient suffering from wound botulism during recovery from dysphagia. An age-matched group of healthy subjects served as control group. A self-paced swallowing paradigm was performed and data were analyzed using synthetic aperture magnetometry (SAM). RESULTS: The first MEG measurement, carried out when the patient still demonstrated severe dysphagia, revealed strongly decreased activation of the somatosensory cortex but a strong activation of the right insula and marked recruitment of the left posterior parietal cortex (PPC). In the second measurement performed five days later after clinical recovery from dysphagia we found a decreased activation in these two areas and a bilateral cortical activation of the primary and secondary sensorimotor cortex comparable to the results seen in a healthy control group. CONCLUSION: These findings indicate parallel development to normalization of swallowing related cortical activation and clinical recovery from dysphagia and highlight the importance of the insula and the PPC for the central coordination of swallowing. The results suggest that MEG examination of swallowing can reflect short-term changes in patients suffering from neurogenic dysphagia.

Functional oropharyngeal sensory disruption interferes with the cortical control of swallowing.

BACKGROUND: Sensory input is crucial to the initiation and modulation of swallowing. From a clinical point of view, oropharyngeal sensory deficits have been shown to be an important cause of dysphagia and aspiration in stroke patients. In the present study we therefore investigated effects of functional oropharyngeal disruption on the cortical control of swallowing. We employed whole-head MEG to study cortical activity during self-paced volitional swallowing with and without topical oropharyngeal anesthesia in ten healthy subjects. A simple swallowing screening-test confirmed that anesthesia caused swallowing difficulties with decreased swallowing speed and reduced volume per swallow in all subjects investigated. Data were analyzed by means of synthetic aperture magnetometry (SAM) and the group analysis of the individual SAM data was performed using a permutation test. RESULTS: The analysis of normal swallowing revealed bilateral activation of the mid-lateral primary sensorimotor cortex. Oropharyngeal anesthesia led to a pronounced decrease of both sensory and motor activation. CONCLUSION: Our results suggest that a short-term decrease in oropharyngeal sensory input impedes the cortical control of swallowing. Apart from diminished sensory activity, a reduced activation of the primary motor cortex was found. These findings facilitate our understanding of the pathophysiology of dysphagia.

Responsiveness to repeated speech stimuli persists in left but not right auditory cortex.

Activation of the auditory cortex habituates with repeated stimulation. While behaviorally adaptive in most circumstances, decreasing auditory responsiveness could interfere with speech perception. We therefore tested whether auditory habituation differs for speech and non-speech stimuli and for left and right auditory cortex. We examined seven right-handed subjects in whom we had determined left-hemispheric language dominance by event-related blood flow assessment. We recorded magnetoencephalographic-evoked responses to trains of four sine tones or vowels and measured the decrement from the first to the last stimulus of the response component about 100 ms after stimulus onset (N1). For the sine tones there was a decrement in both hemispheres. Conversely, for vowels there was significant attenuation of the auditory decrement in the left compared with the right hemisphere (p=0.017). This left-hemisphere persistence in auditory responsiveness to vowels demonstrates that the human brain processes speech stimuli differently than non-speech stimuli and that the left-hemisphere plays a dominant role in this speech-specific auditory processing.