Oral appliance therapy versus nasal continuous positive airway pressure in obstructive sleep apnoea syndrome: a randomised, placebo-controlled trial on self-reported symptoms of common sleep disorders and sleep-related problems.

Obstructive sleep apnoea syndrome (OSAS) is associated with several sleep disorders and sleep-related problems. Therefore, the aim of this study was to compare the effects of a mandibular advancement device (MAD) with those of nasal continuous positive airway pressure (nCPAP) on self-reported symptoms of common sleep disorders and sleep-related problems in mild and moderate OSAS patients. In this randomised placebo-controlled trial, sixty-four OSAS patients (52·0 ± 9·6 years) were randomly assigned to an MAD, nCPAP or an intra-oral placebo appliance in a parallel design. All participants filled out the validated Dutch Sleep Disorders Questionnaire (SDQ) twice: one before treatment and one after six months of treatment. With 88 questions, thirteen scales were constructed, representing common sleep disorders and sleep-related problems. Linear mixed model analyses were performed to study differences between the groups for the different SDQ scales over time. The MAD group showed significant improvements over time in symptoms corresponding with 'insomnia', 'excessive daytime sleepiness', 'psychiatric sleep disorder', 'periodic limb movements', 'sleep apnoea', 'sleep paralysis', 'daytime dysfunction', 'hypnagogic hallucinations/dreaming', 'restless sleep', 'negative conditioning' and 'automatic behaviour' (range of P values: 0·000-0·014). These improvements in symptoms were, however, not significantly different from the improvements in symptoms observed in the nCPAP and placebo groups (range of P values: 0·090-0·897). It can be concluded that there is no significant difference between MAD and nCPAP in their positive effects on self-reported symptoms of common sleep disorders and sleep-related problems in mild and moderate OSAS patients. These beneficial effects may be a result of placebo effects.

Do sleep hygiene measures and progressive muscle relaxation influence sleep bruxism? Report of a randomised controlled trial.

The aim of this study was to assess the effects of sleep hygiene measures combined with relaxation techniques in the management of sleep bruxism (SB) in a double-blind, parallel, controlled, randomised clinical trial design. Sixteen participants (mean ± s.d. age = 39·9 ± 10·8 years) were randomly assigned to a control group (n = 8) or to the experimental treatment group (n = 8). Participants belonging to the latter group were instructed to perform sleep hygiene measures and progressive muscle relaxation techniques for a 4-week period. Two polysomnographic recordings, including bilateral masseter electromyographic activity, were made: one prior to the treatment and the other after the treatment period. The number of bruxism episodes per hour, the number of burst per hour and the bruxism time index (i.e. the percentage of total sleep time spent bruxing) were established as outcome variables. No significant differences could be observed between the outcome measures obtained before and after the 4-week period, neither for the sleep bruxism variables nor for the sleep variables. Within the limitations of this study, it was concluded that there is no effect of sleep hygiene measures together with progressive relaxation techniques on sleep bruxism or sleep over a 4-week observation period.

Stroke mimicking conversion disorder: two young women who put our feet back on the ground.

We describe two young female patients with symptoms and signs initially of conversion disorder. It became apparent, however, that both patients had a posterior circulation stroke. These cases remind us of just how broad the clinical presentation of neurological diseases is and illustrate how careful we must be in our own attributions, actions and diagnoses particularly when assessing patients with bizarre behaviour and with apparent inconsistencies on neurological examination.

The effect of raising the bite without mandibular protrusion on obstructive sleep apnoea.

It has recently been suggested that wearing a maxillary occlusal splint (i.e. a hard acrylic resin dental appliance that covers the occlusal surfaces of the maxillary dentition and that is being indicated for the treatment of, e.g. temporomandibular pain) may be associated with a risk of aggravating obstructive sleep apnoea (OSA). The present study tested the hypothesis that raising the bite without mandibular protrusion in OSA patients is associated with an increase in the apnoea-hypopnoea index (AHI). Eighteen OSA patients (13 men; 49·5 ± 8·1 years old) received a mandibular advancement device in 0% protrusion of the mandible (0%MAD). The MAD caused a bite rise of 6 mm as measured interincisally. Polysomnographic recordings were obtained at baseline and with the 0%MAD in situ. No statistically significant difference in AHI was noted between the baseline night and the 0%MAD night. However, nine patients had an aggravation in AHI during the night they used the 0%MAD. Taking into account the previously established smallest detectable difference of 12·8 in AHI, the AHI increased in only two of the patients. The outcomes of this study suggest that an increased jaw gape without mandibular protrusion might be associated with a risk of aggravation of OSA for some, but not for all OSA patients. Dental practitioners should be aware of this possible association when treating patients with oral devices that raise the bite.

Time-variant nature of sleep bruxism outcome variables using ambulatory polysomnography: implications for recognition and therapy evaluation.

The aim of this study was to quantify the time-variant nature of sleep bruxism (SB) and to discuss its consequences. Six clinically diagnosed bruxers and six non-bruxers participated. Four ambulatory polysomnographic (PSG) recordings were obtained for every participant. As SB outcome variables, the number of episodes per hour of sleep (Epi h(-1)), the number of bursts per hour (Bur h(-1)) and the bruxism time index (BTI: the percentage of total sleep time spent bruxing) were established. To quantify the time-variant nature of SB, standard errors of measurement (SEMs) were calculated. For the non-bruxers, the SEMs for Epi h(-1), Bur h(-1) and BTI were 1.0, 5.7 and 0.1. For the bruxers, the respective values were 2.1, 14.9 and 0.4. In the discussion, arguments are given that because of the time-variant nature of the PSG recordings, cut-off bands around cut-off points might be useful for the recognition of SB.

Principles for the management of bruxism.

The management of bruxism has been the subject of a large number of studies. A PubMed search, using relevant MeSH terms, yielded a total of 177 papers that were published over the past 40 years. Of these papers, 135 were used for the present review. Apparently, research into bruxism management is sensitive to fashion. Interest in studying the role of occlusal interventions and oral splints in the treatment of bruxism remained more or less constant over the years: between 1966 and 2007, approximately 40-60% of the papers dealt with this subject. The percentage of papers that dealt with behavioural approaches, on the other hand, declined from >60% in the first 2 decades (1966-1986) to only slightly >10% in the most recent decade (1997-2007). In the latter period, >40% of the papers studied the role of various medicines in the treatment of bruxism, while in the preceding decade (1987-1996), only approximately 5% of the studies dealt with the pharmacological management of bruxism. Unfortunately, a vast majority of the 135 papers have a too low level of evidence. Only 13% of the studies used a randomized clinical trial design, and even these trials do not yet provide clinicians with strong, evidence-based recommendations for the treatment of bruxism. Hence, there is a vast need for well-designed studies. Clinicians should be aware of this striking paucity of evidence regarding management of bruxism.

Effects of pergolide on severe sleep bruxism in a patient experiencing oral implant failure.

In the patient described in this study, oral implants failed as a probable consequence of severe, polysomnographically confirmed sleep bruxism. As this patient had the wish to be re-implanted after this failure, we decided to try diminishing the frequency of bruxism and duration first. To that end, two management strategies were used. Their efficacy was evaluated polysomnographically, yielding a total of six overnight recordings. Of the selected management strategies, the administration of low doses of the dopamine D1/D2 receptor agonist pergolide finally resulted in a substantial and lasting reduction in the bruxism outcome measures under study. This result supports the previous suggestion that central neurochemicals like dopamine may be involved in the modulation of sleep bruxism. The case report also illustrates the importance of an extensive history taking (questionnaires as well as oral) and clinical examination of oral implant patients for the presence of severe bruxism before the implant procedure is started. In case of doubt, polysomnography may be considered to definitively confirm or rule out the presence of severe sleep bruxism.

[Oration held at the occasion of the bestowal of the honorary doctor's degree to M. H. J. P Thomassen by the Senate of the University of Groningen on 21 June 1905]. / Rede, gehouden bij de promotie van M. H. J. P. Thomassen op 21 Juni 1905 te Groningen, door prof. Dr. H. J. Hamburger.

Hamburger, former colleague of Thomassen at the Veterinary School in Utrecht, and then professor of Physiology in Groningen, reviewed the career and merits of Thomassen. After graduation as veterinary surgeon (Utrecht 1869) Thomassen developped a succesful veterinary practice in Maastricht, in the neighbourhood of which city he was born. He attracted attention by his publications in foreign veterinary journals. In 1881 he was appointed as clinical teacher at his old school. Next to internal medicine, his teachings encompassed diagnostics, general therapy, pharmacology and history of veterinary medicine. His inquiring spirit led him to manifold investigations. His therapy of bovine actinomycosis by potassium-iodine (1885) was that succesful that the American government set up a committee of inquiry, that only could confirm the effectiveness. The field of nervous diseases in domestic animals was hardly developed at his time. His broad and systematic research on the pathology and etiology of laryngeal hemiplegia was masterly executed. It was followed by a great number of investigations on the disorders of the peripheral and central nervous system. He made himself familiar with the necessary technics of microscopical pathological investigation. He devoted his attention also to the emerging field of bacteriology and its clinical implications. He studied endocarditis acuta in the horse, bacterial nephritis in calves, chronic nephritis in horses, but especially tuberculosis. His transmission experiments showed reciprocal infectivity of tuberculosis between animals and man. Therefore, he could rightfully oppose Robert Koch, who proclaimed the non-infectivity of bovine tuberculosis for humans at the International Tuberculosis Congress in London of 1901. The author draws a contrasting picture of Thomassen's results with the poor surroundings at the Veterinary School in his days and the shortage of tools that he had at his disposal. His true genius and original mind could overcome those difficulties. His wide range of talents manifested itself in his cultivation of the art of singing, his language abilities and his historical writings on Dutch national history of the 16th century and on veterinary medicine in classical Antiquity. He was an excellent teacher and very much appreciated as speaker at international congresses.

Short-term effects of a mandibular advancement device on obstructive sleep apnoea: an open-label pilot trial.

Obstructive sleep apnoea (OSA) is a common sleep disorder, which is, among others, associated with snoring. OSA has a considerable impact on a patient's general health and daily life. Nasal continuous positive airway pressure (nCPAP) is frequently used as a "gold standard" treatment for OSA. As an alternative, especially for mild/moderate cases, mandibular advancement devices (MADs) are prescribed increasingly. Their efficacy and effectiveness seem to be acceptable. Although some randomized clinical trials (RCTs) have been published recently, most studies so far are case studies. Therefore, our department is planning a controlled RCT, in which MADs are compared with both nCPAP and a control condition in a parallel design. As a first step, an adjustable MAD was developed with a small, more or less constant vertical dimension at different mandibular positions. To test the device and the experimental procedures, a pilot trial was performed with 10 OSA patients (six mild, four moderate; one women, nine men; mean age = 47.9 +/- 9.7 years). They all underwent a polysomnographic recording before as well as 2-14 weeks after insertion of the MAD (adjusted at 50% of the maximal protrusion). The apnoea-hypopnoea index (AHI) was significantly reduced with the MAD in situ (P = 0.017). When analysed as separate groups, the moderate cases showed a significantly larger decrease in AHI than the mild cases (P = 0.012). It was therefore concluded from this pilot study that this MAD might be an effective tool in the treatment of, especially, moderate OSA.

Craniomandibular pain, oral parafunctions, and psychological stress in a longitudinal case study.

In a single case study, the most frequently suggested contributing factors to craniomandibular pain, viz., oral parafunctions and psychological stress, were studied in more detail. During a 13-week study period, questionnaires were completed, in which, among others, jaw muscle pain, bruxism behaviour, and experienced/anticipated stress were noted. During about 40% of the nights, nocturnal masticatory muscle activity (NMMA) was recorded, using single-channel electromyography (EMG). The number of NMMA events per recorded hour was scored, using a detection threshold of 10% of the maximum voluntary contraction level. This threshold was established in a separate study, in which EMG was compared with polysomnography. Stepwise regression analyses indicated, that morning jaw muscle pain could be explained by evening jaw muscle pain for 64% and by alcohol intake for another 2%. In turn, evening jaw muscle pain was explained by daytime clenching for 56% and by vacuum sucking of the tongue for an additional 6%. Finally, daytime clenching was significantly explained by experienced stress for 30%. Data of the recorded nights showed, that variations in NMMA did not contribute to variations in morning jaw muscle pain. This case study corroborates the paradigm that experienced stress may be related to daytime clenching and, in turn, to evening and morning jaw muscle pain.

Neurophysiological evaluation of late effects of adjuvant high-dose chemotherapy on cognitive function.

OBJECTIVES: To evaluate late neurotoxicity of adjuvant high-dose (HD) chemotherapy versus standard-dose (SD) chemotherapy by event-related potentials (ERP) and quantitative electroencephalography (qEEG). PATIENTS AND METHODS: From a randomized study in high-risk breast cancer patients on the efficacy of high-dose versus standard-dose adjuvant chemotherapy, late effects on cognitive functioning were analyzed by neuropsychological tests. Cognitive impairment was found in 32% of the HD group, 17% of the SD group and in 9% of a control group of stage I breast cancer patients not treated with chemotherapy. In 17 consecutive patients in the HD group and 16 consecutive patients in the SD group neurophysiological tests were performed, consisting of P300 and qEEG. Results of patients treated with chemotherapy were compared with results of 14 control patients not treated with chemotherapy. All patients were tested two years after treatment. RESULTS: Asymmetry of the alpha rhythm of > or =0.5 Hz was found in 7 HD patients, 2 SD patients and in none of the control patients (p = 0.01). No differences were found between the groups with regard to frequency of alpha rhythm, alpha blocking and latency of P300. No correlation was found between neurophysiological parameters and neuropsychological performance, except for an overall relation between the P300 latencies and the total number of deviant test scores. CONCLUSION: Although the neurophysiological differences are subtle and the relation with the cognitive functioning in individual patients as measured by the neuropsychological examination is equivocal, the results suggest that there is neurophysiological support for cognitive dysfunction as a late complication of high-dose systemic chemotherapy in breast cancer.

Outcome of cervical spine surgery in patients with rheumatoid arthritis.

OBJECTIVES: Cervical spine instability in patients with rheumatoid arthritis (RA) may lead to cervical myelopathy or occipital neuralgia, or both. Morbidity and mortality in patients with RA treated with cervical spine surgery during two years of follow up were evaluated. METHODS: Between 1992 and 1996 55 patients with RA underwent cervical spine surgery because of occipital neuralgia or cervical myelopathy, or both. Patients were classified according to the Ranawat criteria for pain and neurological assessment before operation and three months and two years postoperatively. For occipital neuralgia a successful operation was defined as complete relief of pain and for cervical myelopathy as neurological improvement. RESULTS: Occipital neuralgia was present in 17 patients, cervical myelopathy in 14 patients, and 24 had both. Surgical treatment in the patients with symptoms of occipital neuralgia who were still alive two years after surgery was successful in 18/29 (62%). In the surviving patients with cervical myelopathy neurological improvement of at least one Ranawat class was seen in 16/24 (67%). Postoperative mortality within six weeks was 3/51 (6%). Within two years after the operation 14 /51 (27%) of the patients had died; in most patients the cause of death was not related to surgery. The highest mortality (50%) was found in the group of six patients with quadriparesis and very poor functional capacity (Ranawat IIIB). CONCLUSION: Cervical spine surgery in patients with RA performed because of occipital neuralgia or cervical myelopathy, or both, is successful in most patients who are alive two years after surgery. However, the mortality rate during these two years is relatively high, which seems to be largely related to the severity of the underlying disease and not to the surgery itself.

[Antibiotic pre-hospital treatment and the course of meningococcal disease]. / Antibiotisk behandling før indlaeggelse og forløbet af meningokoksygdom.

The aim of the study was to assess the effect of pre-hospital antibiotic treatment given by general practitioners to patients with meningococcal disease. It was carried out as a 16-year population-based historical follow-up study based on referral letters and hospital records in the County of North Jutland, Denmark, and included 320 patients with meningococcal disease, of whom 302 were examined by a general practitioner before admission to hospital. The main outcome measure was death. We found that 44 patients (14.6%) were given antibiotic treatment by the referring general practitioner. Nine of these (20.5%) died, compared with 16 (6.2%) patients who did not receive pre-hospital antibiotic treatment. The presence of skin bleeding, petechiae and impaired consciousness were strongly associated with case fatality. Even after adjustment for these variables the odds ratio for death in patients treated with antibiotics was high (3.2; 95% CI 0.9-10.6). In the 15 patients with skin bleeding (ecchymoses, suggillations) the case fatality rate was 100% in patients treated with antibiotics, and 50% in patients who did not receive antibiotics before hospitalization. It is concluded that pre-hospital treatment is mainly given to the most severe cases with expected high case fatality, and this confounding by indication was probably not fully adjusted for with the available data. The results contradict previous findings and provide reason to doubt the benefit of pre-hospital antibiotic treatment in patients with meningococcal disease.

Trend in incidence and case fatality of meningococcal disease over 16 years in Northern Denmark.

The incidence and case fatality rates of meningococcal disease were assessed in the county of Northern Jutland, Denmark, during the 16-year period from 1980 to 1995. A total of 320 patients were identified from the Meningococcal Research Database, which comprises information from the following sources: (i) the Department of Public Health, to whom notification of meningococcal disease is obligatory; (ii) the Regional Hospital Discharge Registry; and (iii) the register of the regional department of clinical microbiology. In order to assess prognostic indicators assessable at admission, information was collected for each patient from hospital records regarding contacts, symptoms and signs on arrival, laboratory data, and course of disease. The mean incidence was 4.3 cases per 100000 persons per year (range, 2.7-7.7). The incidence increased slightly during the period studied. Overall, the case fatality rate was 9.7%, with a significant rise occurring during the period (P=0.016) and a peak occurring in 1992. Advanced age (> or = 50 years), seizures, impaired consciousness, and skin bleeding on arrival at hospital were predictors of death.

Outcome of pre-hospital antibiotic treatment of meningococcal disease.

OBJECTIVE: To assess the effect of pre-hospital antibiotic treatment given by general practitioners to patients with meningococcal disease. DESIGN: A 16-year population-based historical follow-up study based on referral letters and hospital records in the County of North Jutland, Denmark. SUBJECTS: 320 patients with meningococcal disease, of whom 302 were examined by a general practitioner before admission to hospital. MAIN OUTCOME MEASURES: Death. RESULTS: 44 patients (14.6%) were given antibiotic treatment by the referring general practitioner. Nine of these (20.5%) died, compared with 16 (6.2%) patients who did not receive pre-hospital antibiotic treatment. The presence of skin bleeding, petechiae, and impaired consciousness were strongly associated with case fatality. Even after adjustment for these variables the odds ratio (OR) for death in patients treated with antibiotics was high (OR = 3.2; 95% CI, 0.9-10.6). In the 15 patients with skin bleeding (ecchymoses, suggillations) the case fatality rate was 100% in patients treated with antibiotics, and 50% in patients who did not receive antibiotics before hospitalization. If skin bleeding was replaced in the models by the presence of disseminated intravascular coagulation on admission, the OR for death in patients with pre-hospital antibiotic treatment was 35.9 (95% CI, 2.9-441.8) in the presence of disseminated intravascular coagulation and 1.9 (95% CI, 0.2-19.5) in its absence. CONCLUSIONS: Pre-hospital treatment is mainly given to the most severe cases with expected high case fatality, and this confounding by indication was probably not fully adjusted for with the available data. The results contradict previous findings but provide reason to doubt the benefit of pre-hospital antibiotic treatment in patients with meningococcal disease.

Sleep apnoea caused by rheumatoid arthritis.

Sleep apnoea syndrome (SAS) is a rarely documented, but possibly lethal, complication of the instability of the cervical spine in rheumatoid arthritis. Five patients with SAS of a central or peripheral origin are presented, and the problems of recognizing and diagnosing the syndrome are discussed. We hope that clinicians will become more aware of the existence and the different aetiologies of SAS, thus improving early recognition and appropriate treatment. Adequate treatment has proven to increase survival in peripheral SAS and seems to be successful in doing so in central SAS.

Accessing the embryo interior without microinjection.

For decades it has been assumed that in order to insert macromolecules into the embryo blastocoel for numerous experimental purposes, microinjection was required. Microinjection, however, can be only performed on a few embryos at a time, thus precluding many studies that could involve large populations of embryos. Laser scanning confocal microscopy, with its optical sectioning advantage, showed that fluorochrome-labeled macromolecular lectins and bovine albumin enter the blastocoel of living, swimming sea urchin embryos following a period of incubation without microinjection. A procedure is also described that shows macromolecular entry is substantially accelerated in low calcium seawater. The information gained from this study should greatly facilitate experiments on entire populations of millions of embryos at a time that require access of macromolecules to the embryo interior.