[Sleep disorders in neurological diseases]. / Schlafstörungen bei neurologischen Erkrankungen.

Sleep disorders can be diagnosed in approximately 15 % of the population and have been shown to increase with age. The relationship between sleep disorders and neurological disorders, however, is still insufficiently considered in the clinical practice. Sleep disorders can be an early symptom of the disease, such as the presence of rapid eye movement (REM) sleep behavior disorder (RBD) as an early indicator of neurodegeneration. Sleep disorders have also been shown to be a main symptom of various neurological syndromes, such as in restless legs syndrome (RLS), periodic limb movement disorder (PLMD) and narcolepsy. The international classification of sleep disorders 2nd edition (ICSD 2) describes the main diagnoses, insomnia, circadian rhythm sleep disorders, sleep-related breathing disorders and hypersomnia but all of these can also appear as symptoms in various neurological diseases. Parasomnias are largely considered a differential diagnosis to nocturnal epilepsy. In this review, the main sleep disorders are described with a particular focus on how they relate to neurological diseases; in particular, how they influence disease-related symptoms and how they affect the course of the disease.

[Health-related consequences of obstructive sleep apnea: daytime sleepiness, accident risk and legal aspects]. / Gesundheitliche Auswirkungen der obstruktiven Schlafapnoe: Schläfrigkeit, Unfallgefahr und Begutachtung.

Daytime sleepiness for any reason leads to impairment of daytime performance and an increased accident rate. The consequences are an increase of illness- and accident-related costs for the health system. Obstructive sleep apnea (OSA) is one of the major reasons for increased daytime sleepiness, especially in professional drivers. The accident frequency in OSA can be significantly reduced by adequate continuous positive airway pressure (CPAP) therapy. Up till now there are no uniform legal regulations about the handling of OSAS patients or patients with daytime sleepiness due to other diseases as far as driving ability is concerned.

Driving performance in patients with chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) present with impairments of their cognitive performance. It is still unknown whether cognitive deficits influence driving abilities in patients with COPD. The present study investigates driving performance in patients with COPD and healthy controls. Driving simulation was performed in 17 patients with COPD and 10 healthy controls. Patients with COPD demonstrated significantly worse results in terms of accident frequency in the simulated driving situation. No correlations existed between the severity of disease, assessed from the polysomnographical findings (e.g., lung function, blood gas analysis, sleep disturbance, nocturnal ventilation, and oxygen saturation), and driving performance. We conclude that impairments of driving performance in patients with COPD cannot be predicted on the basis of the severity of the disease. The impairment of driving performance in the simulated driving situation in COPD patients may have crucial consequences for driving licensing in these patients.

[Influence of nocturnal oxygen therapy on quality of life in patients with COPD and isolated sleep-related hypoxemia: a prospective, placebo-controlled cross-over trial]. / Einfluss der nächtlichen Sauerstofftherapie auf die Lebensqualität bei Patienten mit COPD und isolierter schlafbezogener Hypoxämie: Eine prospektive, plazebokontrollierte cross-over Studie.

BACKGROUND: In patients with COPD and isolated night time hypoxemia, oxygen administration has not shown any effects on life expectancy and the development of pulmonal arterial hypertension. The aim of the present pilot study was to investigate the influence of nocturnal oxygen therapy on the quality of life in daytime normoxemic COPD patients with nocturnal oxygen desaturations. PATIENTS AND METHODS: 19 patients with COPD, in a stable phase of the disease without need for oxygen supplementation under rest (PaO2 62.7 +/- 4.9 mmHg) and nocturnal hypoxemia (t90 = 55.5 +/- 33.4 % of registration time, mean SaO2 89.8 +/- 1.9 %, minimal SaO2 81.1 +/- 4.8 %) were randomly assigned to either oxygen or placebo treatment, both generated by identical concentrator devices. Each treatment period lasted 6 weeks, after six weeks a cross-over was performed by a technician. Quality of life was assessed before and at the end of each treatment period by the SF-36, Nottingham Health Profile and Saint George's Respiratory Questionnaire. RESULTS: Significant differences for the comparison of placebo and verum were only seen for the dimension sleep (NHP), all other dimensions showed no differences between placebo and oxygen. However, both placebo and oxygen improved the majority of the quality of life items significantly. CONCLUSIONS: The prescription of supplemental oxygen in COPD patients with isolated nocturnal hypoxemia in the present pilot study is not able to improve the quality of life within 6 weeks after initiation of therapy. It cannot, therefore, be generally recommended, but may be indicated in patients with a documented improvement of sleep quality.

[Sleep apnoea in women?--The forgotten gender]. / Schlafapnoe bei Frauen?--Das vergessene Geschlecht.

The prevalence of clinically relevant, obstructive sleep apnoea syndrome (OSAS) in the general population is 2% in women and 4% in men. With increasing age and onset of postmenopausal status, the prevalence of OSAS in women becomes comparable to that of males. However, compared to prevalence data, women are under-represented in clinical sleep laboratories. The present overview deals with the potential reasons for clinical under-recognition of OSAS in women. The fact that OSAS frequency is underestimated in women probably derives from the atypical clinical symptoms, dominated by difficulties of initiating and maintaining sleep and by a depressive mood. There are several protecting mechanisms in women that prevent or postpone OSAS development to higher age groups or until the onset of menopause. These factors include craniofacial morphology and function, gender-specific body-fat distribution and hormonal influences on ventilation and dilating muscles in the oropharynx. Physicians should be aware of the presence of sleep-disordered breathing in women and of their special features.

[Expert opinions regarding daytime sleepiness in neurological diseases and obstructive sleep apnea syndrome]. / Begutachtung der Tagesschläfrigkeit bei neurologischen Erkrankungen und dem obstruktiven Schlafapnoesyndrom (OSAS).

Patients with increased daytime sleepiness are impaired in all areas of their social environment. Expert opinions are recommended for pension proceedings, regarding driving licenses as well as for restrictions at the workplace. All possibilities should be considered in the differential diagnosis of sleep disorders, which have to be treated before an expert opinion is submitted. Statutory regulations on evaluation of sleepiness are contained in the guidelines for assessing a patient's fitness to drive. The importance of daytime sleepiness in other occupations should be assessed according to the respective workplace. The patient should be informed of the appraisal with regard to career choice and workplace design. The expert thus has the responsible task of carrying out interdisciplinary differential diagnosis of pathological sleepiness and monitoring treatment success with appropriate test methods. In the present paper the legal guidelines in Germany and available test methods are presented.

[Cognitive deficits in patients with chronic obstructive pulmonary disease (COPD)]. / Kognitive Defizite bei Patienten mit chronisch-obstruktiver Atemwegserkrankung (COPD).

INTRODUCTION: Patients with COPD present with impairments of their cognitive performance. The present study compares intelligence and memory performance as well as different aspects of attention in COPD patients and healthy controls. Additionally, potential factors influencing daytime performance are analyzed. PATIENTS AND METHODS: Neuropsychological testing was performed in 32 patients with COPD and 10 normal controls. The following aspects were evaluated: memory, intelligence, simple, selective and divided attention, sustained attention under stress and under monotonous conditions. RESULTS: There were no differences between COPD patients and normals with regard to divided attention, vigilance and memory. Patients with COPD demonstrated significantly worse results in terms of intelligence (p < 0.01) as well as simple (p < 0.01), selective (p < 0.05) and sustained attention (p < 0.01). No correlation existed between the severity of the disease (lung function, blood gas analysis, nocturnal oxygen saturation) and neuropsychological findings. Merely a relationship between memory function and slow-wave sleep or REM sleep was demonstrated. CONCLUSION: Impairments of cognitive performance in patients with COPD cannot be predicted on the basis of the severity of the disease. Therefore neuropsychological testing is recommended, especially when impairment of daytime function has to be quantified.

[Long-term compliance of cpap-therapy--update, predictors and interventions]. / Langzeit-Compliance der CPAP-Therapie--aktueller Stand, Prädiktoren und Interventionsmöglichkeiten.

CPAP (continuous positive airway pressure) is the therapy of choice for obstructive sleep apnea syndrome (OSAS). About 70 % of patients on CPAP use their device for at least 70 % of nights with an application-time of at least 4 hours per night. Severity of breathing disorder respectively disturbance of sleep architecture, degree of daytime sleepiness and patients' satisfaction with diagnostic and therapeutic procedures are good predictors of long-term CPAP-compliance. CPAP-compliance can be increased by intensive patient education. Alternative devices like for example Bilevel or auto-CPAP respectively cannot augment CPAP compliance.

[Driving simulator performance in patients with obstructive sleep apnea syndrome: what consequences for driving capability?]. / Fahrsimulatoruntersuchung bei Patienten mit obstruktivem Schlafapnoe-Syndrom: Konsequenzen für die Beurteilung der Fahrtüchtigkeit?

BACKGROUND AND OBJECTIVE: Patients with obstructive sleep apnea (OSA) have an increased accident risk. The German Society of Sleep Research and Sleep Medicine (DGSM) recommends for patients with OSA and daytime sleepiness that their driving ability should be re-established 6 weeks after the initiation of CPAP (continuous positive airway pressure), with documentation of therapeutic effects on daytime symptoms and performance. The present study was conducted to investigate whether an improvement of driving ability can be documented in neuropsychological tests and a simulated driving situation 14 days after the initiation of CPAP. PATIENTS AND METHODS: Driving simulation and neuropsychological tests of vigilance were conducted in 36 patients (36 males, aged 54 9 years) with OSAS before and 2 (n=23), 14 (n=18) and 42 days (n=17) after initiation of CPAP. RESULTS: Vigilance tests showed only slight changes under CPAP. Frequency of accidents during driving simulation was reduced after 14 days of CPAP, but a statistically remarkable decrease was achieved only on day 42. In contrast, concentration faults were reduced after 2 and 14 days of CPAP. CONCLUSIONS: In OSA-patients improvement of daytime performance in a simulated driving situation can be documented 14 days after initiation of CPAP. There is need for investigating larger cohorts of patients so that current recommendations for driving licensing can be modified and permission to drive can be given earlier.

Driving simulator and neuropsychological [corrected] testing in OSAS before and under CPAP therapy.

Patients with obstructive sleep apnoea syndrome (OSAS) have an increased car accident rate. Investigations on accident frequency are based on case history, insurance reports and driving simulator studies. The present study combines neuropsychological testing of different attention aspects engaged in driving a car and driving simulation to evaluate a suitable instrument for assessing therapeutic effects of continuous positive airway pressure (CPAP). Driving simulator investigation and neuropsychological testing of alertness, vigilance and divided attention were performed in 31 patients with polysomnographically confirmed OSAS (apnoea-hypopnoea index 24.8+/-21.5.h(-1)) before, and 2 and 42 days after initiation of CPAP. Divided attention and alertness improved significantly during CPAP, whereas vigilance remained unchanged. However, accident frequency (OSAS before therapy: 2.7+/-2.0; 2 days after CPAP: 1.5+/-1.4; 42 days after CPAP: 0.9+/-1.3) and frequency of concentration faults (OSAS before therapy: 12.4+/-5.1; 2 days after CPAP: 6.5+/-3.9; 42 days after CPAP: 4.9+/-3.3) decreased in the simulated driving situation after 2 and 42 days of therapy. There was no relation between accident frequency, concentration faults and daytime sleepiness, as measured by the Epworth Sleepiness Scale, and polysomnographic or neuropsychological findings, respectively. In conclusion, the present results suggest that driving simulation is a possible benchmark parameter of driving performance in obstructive sleep apnoea syndrome patients.

Diagnosis of multiple sclerosis: comparison of the Poser criteria and the new McDonald criteria.

OBJECTIVES: A confident and accurate diagnosis of multiple sclerosis (MS) is important, but a specific diagnostic test for the disease does not exist. The traditional diagnostic criteria of Poser et al. were published in 1983, and recently, McDonald et al. recommended new criteria for the diagnosis of MS. PATIENTS AND METHODS: In this study these two diagnostic schemes were compared by prospectively applying both of them to 76 patients with clinical features suggesting a new diagnosis of MS. RESULTS: Using the Poser criteria, 29 patients (38%) were classified as clinically definite and 35 patients (46%) as laboratory definite MS. According to the new McDonald criteria, MS was diagnosed in 39 (52%) patients, 37 patients (48%) had 'possible MS'. All patients with a clinically definite MS with the Poser criteria were also given the diagnosis of MS as recommended by McDonald et al. Of those 35 patients with laboratory definite MS according to Poser et al., four patients could be classified as having MS with the McDonald criteria, 89% of them had 'possible MS'. Conversely, 75% of the 39 patients, who fulfilled the new McDonald criteria for MS were assigned to the category of clinically definite MS according to the Poser criteria, and 83% of the patients with a 'possible MS' using the McDonald criteria, had a laboratory definite MS with the Poser criteria. CONCLUSION: MS according to the McDonald criteria was diagnosed more often than 'clinically definite MS' according to Poser et al., but combining the categories of clinically and laboratory definite MS, the diagnosis of MS could clearly be established more frequently using the Poser criteria.

[Sleepiness and fatigue in multiple sclerosis - comparison of different measuring instruments]. / Differenzierung von Müdigkeit und Fatigue bei Multipler Sklerose - Vergleich unterschiedlicher Messinstrumente.

INTRODUCTION: Patients suffering from multiple sclerosis often complain of fatigue and sleepiness. Patients often cannot distinguish between these symptoms. Daytime sleepiness, attention and concentration deficits affect life quality severely. Usually symptoms of MS are characterized by the Expanded Disability Status Scale (EDSS). In new studies the MSFC proves to be a more sensitive method especially estimating the cognitive deficits. METHODS: 31 RRMS patients (18 women, 13 men, mean age 35.6 +/- 8.3 years) and 19 healthy controls (9 men, 1 woman, age: 55.1 +/- 7.8 years) were assessed by: 1) morning and evening protocols of the German Sleep Society, 2) Epworth Sleepiness Scale (ESS), 3) Extended Disability Status Scale (EDSS), 4) MS Functional Composite (MSFC) based on arm function, ambulation and cognition (paced auditory serial addition test, PASAT), 5) Fatigue Severity Scale (FSS). RESULTS: The EDSS-Score ranged from 1.0 to 6.5 (2.8 +/- 1.4). Mean Z-Score of MSFC was -0.19 +/- 0.63. Most deficits could be shown in the PASAT. Total sleep time correlated with recovery capacity of sleep (r = 0.42, P < 0.05). The ESS-Score was 6.1 +/- 2.9 (1 - 14). FSS-Score was raised with intraindividual variability (4,33 +/- 1.62, 1.4 - 7). The EDSS failed to correlate with the ESS- or FSS-Score. FSS correlated significantly with arm function (r = 0.465) und ambulation (r = 0.436) in the MSFC (P < 0.05). DISCUSSION: MS-Patients are often not able to distinguish between fatigue and sleepiness. By using different scales judging sleepiness and fatigue significant differences could be evaluated. Fatigue is mainly linked to motoric deficits scored by the MSFC. Therefore medication with stimulants seems not to be useful in fatigue therapy.

[Accidents caused by sleepiness--prediction by neurophysiologic/psychologic testing and simulated driving studies]. / Unfälle durch Müdigkeit--Prädiktionsmöglichkeit durch neurophysio-/psychologische Testung und Fahrsimulatoruntersuchungen.

Daytime sleepiness is a leading symptom of various diseases, and is an important cause of accidents at the workplace and on the road. For the evaluation of accident frequency, the medical history, neurophysiological and neuropsychological tests, and driving simulator performance are applied. The present paper describes these different methods, and assesses their value in predicting accidents. In the last resort, no single test suffices to evaluate the accident risk of patients suffering from daytime sleepiness--rather, a combination of the methods described is needed, in particular when an expert opinion on a patient's ability to drive is required. To date, no controlled studies have been done to compare the predictive value of the methods considered herein. Our results suggest that the nearness of driving simulation to reality makes it a suitable additional test method, in particular for the monitoring of results under treatment.

[Estimation of accident risk in obstructive sleep apnea syndrome (OSAS) by driving simulation]. / Abschätzung des Unfallrisikos bei obstruktivem Schlafapnoe-Syndrom (OSAS) durch Fahrsimulation.

Abstract. Patients with obstructive sleep apnea syndrome (OSAS) have an accident rate between two and seven times higher than normals. Investigations on accident frequency are based on case history, insurancy reports, and driving simulator investigations. The present controlled study was planned to test whether an increased accident risk could be demonstrated in patients with OSAS before and on CPAP (continuous positive airway pressure)-therapy using the driving simulator C.A.R. Driving simulator performance was investigated in 31 patients with polysomnographically confirmed OSAS (apnea-hypopnea-index 24.8 +/- 21.5/h) before, 2 and 42 days after initiation of CPAP and was compared to 10 healthy controls in whom OSAS was excluded by polysomnography. Driving simulator performance was significantly worse in OSAS as compared to normals especially in terms of accident frequency (OSAS: 2.7 +/- 2.0, controls: 1.3 +/- 1.5, p < 0.05) and concentration faults (OSAS: 12.4 +/- 5.1, controls: 7.1 +/- 3.2, p < 0.01). On CPAP accident frequency (OSAS before therapy: 12.4 +/- 5.1, 2 days CPAP: 1.5 +/- 1.4, p < 0.01; 42 days CPAP: 0.9 +/- 1.3, p < 0.001) and frequency of concentration faults (OSAS before therapy: 12.4 +/- 5.1, 2 days CPAP: 6.5 +/- 3.9, p < 0.001; 42 days CPAP: 4.9 +/- 3.3, p < 0.001) could be lowered significantly both in the short and medium term of therapy. The driving simulator C.A.R. is an adequate tool for the evaluation of an increased accident risk in OSAS-patients and demonstrates the efficiency of CPAP-therapy.

Respiratory monitoring in neuromuscular disease - capnography as an additional tool?

Daytime complaints like fatigue, sleepiness and cognitive dysfunction in neuromuscular disease can be due to nocturnal hypercapnia and hypoxemia. Daytime respiratory diagnostics does not reflect sleep disordered breathing. Nocturnal pulse oxymetry and capnography were performed in 11 patients (15-75 years old) with different slowly progressive neuromuscular diseases. Only four patients complained of dyspnea. Pulmonary function was abnormal in three patients. Blood gas samples showed a hypoxemia in three patients. Pulse oxymetry results were pathological in six patients. Nine patients presented abnormal capnographies. According to these results either nocturnal oxygen application was initiated or ventilatory parameters were modified. Daytime symptoms and muscular strength improved markedly. Capnography and pulse oxymetry should be performed during the course of neuromuscular disease to detect respiratory insufficiency. Capnography seems to be a more sensitive indicator for respiratory impairment especially when artificial ventilation has been initiated.

Hemifacial spasm or somatoform disorder--postexcitatory inhibition after transcranial magnetic cortical stimulation as a diagnostic tool.

Hemifacial spasm (HFS) presents a frequent movement disorder. It is thought to have an organic origin. It therefore has to be distinguished from other facial involuntary movements, especially psychogenic tics, because the therapeutic approach differs. The present study opted to evaluate the diagnostic value of the postexcitatory inhibition (pI) after transcranial magnetic stimulation (TMS). After stimulating the contralateral hemisphere with the conventional flat coil and recording from the mentalis muscle, in 10 healthy controls and 10 patients postexcitatory inhibition was determined. PI showed no side to side difference in healthy controls (96.9 + 12.7 ms right, 87.9 +/- 10.8 ms left side, interhemispheric difference 6.4 +/- 3.8 ms). In 8 patients with hemifacial spasm, the duration of pI on the non-affected side did not differ from the healthy controls (87.9+/-43.5 ms). During spasm, pI on the affected side shortened increasingly until no inhibition could be induced. Afterwards the spasm pI was prolonged significantly (up to 140 ms longer than opposite side) before returning to normal values. Two patients presented no side differences of pI during the "spasm". An emotional conflict situation could be evaluated, supporting the diagnosis of somatoform disorder. As postexcitatory inhibition is mainly due to cerebral mechanisms, the electrophysiological results of the study pointed to a cortical influence on the hemifacial spasm. TMS seems to be an electrophysiological tool which allows a differentiation between organic and psychogenic spasm and enables a different therapeutic approach.

Cytomegalovirus infection in systemic necrotizing vasculitis: causative agent or opportunistic infection?

We report on a 69-year-old woman who presented with myalgia, hearing impairment, fever, night sweats, weight loss, muscular weakness, paresthesia, hypesthesia, and hypalgesia. Sural nerve biopsy showed demyelinative and axonal polyneuropathy due to necrotizing vasculitis with fibrinoid necrosis. A positive test for antineutrophil cytoplasmic antibodies (ANCA) with a perinuclear immunofluorescence pattern directed against myeloperoxidase was more suggestive of microscopic polyangiitis (MPA) than of polyarteritis nodosa (PAN), the possible differential diagnoses. In addition, positive tests for cytomegalovirus (CMV) antibodies (immunoglobulin (Ig)M and IgG) and the detection of CMV-DNA in sputum specimens by polymerase chain reaction (PCR) were indicative of active CMV infection. Treatment with ganciclovir and anti-CMV immunoglobulin in addition to prednisolone medication for 6 months resulted in rapid improvement of the clinical symptoms without relapse. CMV infection has been described to be related to ANCA-associated vasculitis in non-immunocompromized patients and may be either a causative agent or an opportunistic infection. Identification of a viral etiology in patients with atypical ANCA-associated vasculitides may lead to different, less aggressive treatment approaches, including antiviral therapy.

Neuropsychological investigations and event-related potentials in obstructive sleep apnea syndrome before and during CPAP-therapy.

Patients with obstructive sleep apnea syndrome (OSAS) suffer from daytime sleepiness and a decline of cognitive functions. The study evaluated whether special cognitive disabilities predominate in OSAS. Besides the number connection test (ZVT), judging information processing and working velocity, computer-assisted (Wiener Testsystem and Zimmermann Testbatterie) neuropsychological testing was performed in 31 OSAS patients (50.1 +/- 9.4 years) before starting nasal continuous positive airway pressure (nCPAP) therapy. Identical test battery was performed in 10 male healthy volunteers (48 +/- 9.9 years). In addition visual evoked event-related potentials (ERPs) were recorded, the P3-component was evaluated. Impairment of alertness (P < 0.001), selective attention (P < 0.001) and continuous attention (P < 0.001) could be revealed, vigilance was not altered. Cognitive deficits were correlated with the degree of nocturnal hypoxemia. They were not linked to the apnea/hypopnea-index (AHI), arousal index or vigilance parameters. During 6 months of nCPAP-therapy (15 patients) alertness and continuous attention improved significantly (P < 0.01), intra-individual different pathological results persisted however. P3 latencies also remained prolonged. Chronic intermittent nocturnal hypoxemia in OSAS-patients obviously leads to cognitive deficits. ERP partially generated in subcortical cerebral structures represent a neurophysiological tool indicating brain dysfunction which cannot be evaluated by neuropsychological tests. Objective neuropsychological testing is needed in revealing therapeutic effects in OSAS-patients. Remaining deficits during sufficient nCPAP-therapy may reflect irreversible hypoxic cerebral damage.

[Event related potentials and neuropsychological studies in sleep apnea patients]. / Ereigniskorrelierte Potentiale und neuropsychologische Untersuchungen bei Schlafapnoepatienten.

Patients with obstructive sleep apnoea syndrome (OSAS) commonly complain about daytime sleepiness and a decline of cognitive functions. Several diagnostic tools have been established to judge objectively vigilance and cognitive impairment. Forty OSAS patients aged between 34 and 74 years were examined via several neuropsychological tests (e.g. vigilance test of the Wiener Testsystem, number connection test ("Zahlenverbindungstest-ZVT") to assess working velocity and information processing, d2-test to rate concentration on exertion) before starting continuous positive airway pressure (CPAP) therapy. In addition, visual evoked event-related potentials (ERPs) were recorded; the P3-component was evaluated. All patients subjectively stated daytime sleepiness and cognitive dysfunctions to variable degrees. Each patient showed at least one pathological result in the neuropsychological tests; vigilance impairment could be revealed only in 7 patients. P3-latencies were increased in OSAS patients when compared to age-matched controls (408.1 +/- 44.4 ms versus 373.4 +/- 32.5 ms; p < 0.03). P3-latencies and concentration on exertion showed a significant correlation with respect to the relative part of the total sleep time in which the patient's oxygen saturation was below 90% (p < 0.05). Thus it could be demonstrated that cognitive deficits in OSAS patients are a result of chronic intermittent oxyhaemoglobin desaturation rather than of a decline in daytime vigilance. ERPs represent an objective neurophysiological tool in neuropsychological examination. As they are also generated in subcortical cerebral structures they may indicate cognitive dysfunctions which cannot be evaluated by neuropsychological tests. If lead of ERPs is possible in special sleep centres they should be additionally used in the assessment of cognitive functions in OSAS patients.