Structural and serum surrogate markers of cerebrovascular disease in obstructive sleep apnea (OSA): association of mild OSA with early atherosclerosis.

There is increasing evidence of a causal interaction between obstructive sleep apnea (OSA) and cerebrovascular disease. The aim of the study was to elucidate the relationship between the polysomnographically (PSG) measured severity of OSA and carotid atherosclerosis determined by ultrasonography and serum surrogate markers. 147 patients (102 males, 45 females) referred to our sleep laboratory for evaluation of snoring and sleep-disordered breathing were investigated. Carotid atherosclerosis was evaluated by serum analysis of high-sensitivity C-reactive protein (hs-CRP) and fibrinogen and four sonographic indices: intima-media thickness (IMT) of the common carotid artery (CCA), IMT from bulb to internal carotid artery (Bulb-ICA), combined IMT measurements from all segments and a plaque score (PlaS). Pearson correlation analysis, intergroup comparison (ANOVA), covariance analysis and a multiple regression were performed to assess the association between surrogate markers and respiratory variables. 44 patients had no OSA (apnea-hypopnea index AHI < 5/h), 27 mild (AHI 5-15), 25 moderate (AHI 15-30) and 51 severe OSA (AHI > 30). After adjusting for potential confounders, significant differences between the controls and all three OSA groups were observed in the CCA-IMT (p = 0.032) and in the PlaS between the controls and the severe group (p = 0.034). Multiple regression revealed the AHI as an independent predictor of CCA-IMT (p = 0.001) and combined IMT (p = 0.001), whereas the percentage of total sleep time with an oxygen saturation below 90 % was associated with Bulb-ICA IMT (p = 0.018) and hs-CRP (p = 0.015). OSA is associated with higher surrogate levels of cerebrovascular disease. Even mild OSA seems to predispose to early atherosclerosis.

Loss of normal circadian profile of urine excretion in idiopathic restless legs syndrome.

BACKGROUND: This study was performed to elucidate preliminary observations of excessive nighttime urine excretion in idiopathic restless legs syndrome (iRLS). METHODS: Seventeen patients, with normal serum creatinine, blood urea nitrogen, and urate, and 11 healthy controls were examined. We measured excretory renal function parameters (urine volume, osmolarity, sodium, chloride, potassium, calcium, phosphate, microalbumin, aldosterone, creatinine) between 7:00 am and 10:00 pm and between 10:00 pm and 7:00 am. RESULTS: During the nighttime, volume (P=0.006), sodium (P=0.009), and chloride excretion (P=0.001) were significantly higher, and osmolarity (P=0.025) was significantly lower in patients as compared to controls. In comparing daytime to nighttime, controls showed the physiological reduced nocturnal excretion of volume (P=0.009) and chloride (P=0.023), and an increased osmolarity (P=0.026), but patients showed similar excretion rates of these parameters (all differences ns). CONCLUSIONS: These data indicate a loss of normal circadian profile of urine excretion in iRLS. The elevated nighttime excretion, with values similar to those in the daytime, hint at a possibly elevated fluid, sodium, and chloride intake during daytime.

The sensitivity of transcranial cortical magnetic stimulation in detecting pyramidal tract lesions in clinically definite multiple sclerosis.

We determined central motor conduction time (CMCT) (motor cortex to root C-8 and motor cortex to root S-1) as well as the amplitude of the compound muscle action potentials in the hypothenar and the abductor hallucis muscles on both sides in 44 patients with definite MS. We compared the values with standards obtained from 86 healthy controls and correlated them with the degree of clinical deficit of the limbs examined. Thirty-nine patients (88.6%) showed a prolonged CMCT. By comparison, only 74.4% of patients had abnormal visual evoked potentials.

Treatment of idiopathic restless legs syndrome (RLS) with gabapentin.

Nine patients with idiopathic restless legs syndrome (RLS) were treated with 300 mg of gabapentin as an initial dose and an up-titration until relief of symptoms for 4 weeks. Subjective symptoms improved significantly. Polysomnographic data showed a reduction of periodic leg movements during sleep (PLMS) (p = 0.003) and PLMS index (p = 0.001). The authors conclude that gabapentin provides a well-tolerated and effective treatment of idiopathic RLS.

Low-resolution brain electromagnetic tomography revealed simultaneously active frontal and parietal sleep spindle sources in the human cortex.

Analyses of scalp-recorded sleep spindles have demonstrated topographically distinct slow and fast spindle waves. In the present paper, the electrical activity in the brain corresponding to different types of sleep spindles was estimated by means of low-resolution electromagnetic tomography. In its new implementation, this method is based on realistic head geometry and solution space is restricted to the cortical gray matter and hippocampus. In multichannel all-night electroencephalographic recordings, 10-20 artifact-free 1.25-s epochs with frontally, parietally and approximately equally distributed spindles were marked visually in 10 normal healthy subjects aged 20-35years. As a control condition, artifact-free non-spindle epochs 1-3s before or after the corresponding spindle episodes were marked. Low-resolution electromagnetic tomography demonstrated, independent of the scalp distribution, a distributed spindle source in the prefrontal cortex (Brodmann areas 9 and 10), oscillating with a frequency below 13Hz, and in the precuneus (Brodmann area 7), oscillating with a frequency above 13Hz. In extremely rare cases only the prefrontal or the parietal source was active. Brodmann areas 9 and 10 have principal connections to the dorsomedial thalamic nucleus; Brodmann area 7 is connected to the lateroposterior, laterodorsal and rostral intralaminar centrolateral thalamic nuclei. Thus, the localized cortical brain regions are directly connected with adjacent parts of the dorsal thalamus, where sleep spindles are generated. The results demonstrated simultaneously active cortical spindle sources which differed in frequency by approximately 2Hz and were located in brain regions known to be critically involved in the processing of sensory input, which is in line with the assumed functional role of sleep spindles.

Severe hypoglycaemia unawareness is associated with an early decrease in vigilance during hypoglycaemia.

To elucidate neurophysiological characteristics in hypoglycaemia unawareness, we investigated the relationship between electroencephalography (EEG) parameters of vigilance and awareness of various symptom categories early in response to hypoglycaemia in intensively treated diabetic patients with different degrees of hypoglycaemia unawareness. Hypoglycaemia (venous plasma glucose below 2.2 mmol/1) was induced with an intravenous insulin bolus in seven patients with insulin-dependent diabetes mellitus (IDDM) with a history of hypoglycaemia unawareness and repeated severe hypoglycaemia, as well as in a group of seven IDDM patients with good awareness of hypoglycaemia. Both groups were comparable in age, treatment strategy, glycaemic control and level of late complications. Basic cognitive performance and other symptom categories were estimated serially during a period of 2 h following the insulin bolus. A vigilance-controlled EEG was recorded continuously; its automatic analysis included the evaluation of vigilance indices. In the baseline prehypoglycaemic state, hypoglycaemia unaware patients showed higher initial vigilance (p = .05) than the aware group. Unaware patients reported fewer neurogenic (p = .002, mainly cholinergic, p = .009) hypoglycaemia symptoms during hypoglycaemia, and developed an impairment in cognitive performance over time (p = .002). EEG analysis indicated a more rapid decrease in vigilance after the hypoglycaemic stimulus for unaware patients than for aware patients. The lowering of plasma glucose to 3.06-3.89 mmol/l already induced a significant increase in delta and theta, as well as a decrease in alpha relative power only in the unaware group. Differences between groups with regards to the degree of deceleration were most pronounced early, during only slight hypoglycaemia, and topographically spread over central and parietal brain regions. Further lowering of plasma glucose induced an even more pronounced, abrupt increase in slow waves in unaware patients at higher plasma glucose levels than in hypoglycaemia aware subjects (for delta waves at 2.41 +/- 0.16 vs. 1.96 +/- 0.1 mmol/l, p = .04). This preceded the worsening of cognitive performance during hypoglycaemia in unaware patients by 19 +/- 3 min. Hypoglycaemia unawareness associated with previous unconsciousness is associated with- and may be the result of-an early hypoglycaemia-induced reduction in vigilance and an early EEG deceleration, which seems to be a teleologically effective measure for delaying eventual cerebral energy failure in hypoglycaemia.

Fatal encephalitis in a patient with chronic graft-versus-host disease.

A 32-year-old male patient with chronic myelocytic leukemia in accelerated phase received a bone marrow allograft from his 42-year-old HLA/MLC-identical sister. He recovered from acute graft-versus-host disease (GVHD) grade III-IV of skin, liver and gut, but chronic GVHD of progressive onset developed. On day 556 post-graft severe thrombocytopenia was resistant to prednisolone, cyclophosphamide and high dose immunoglobulin. Splenectomy was followed by a normalization of platelet counts. The subsequent clinical course was characterized by progressive muscular atrophy and weight loss. Dysphagia, dysarthria, cachexia and ultimately recurrent pneumonic episodes ensued. The cachectic patient developed a highly abnormal breathing pattern with hypoventilation and intermittent apnea requiring mechanical ventilation. Auditory evoked potentials revealed a considerable dysfunction of the brainstem. The patient died on day 1120 post-graft from pneumonia, aggravated by thoracic muscular insufficiency. Postmortem examination revealed diffuse predominantly lymphoid perivascular infiltration in meninges and CNS tissue; proliferation of activated microglial cells expressing the HLA-DR antigen was prominent in the brainstem. These histologic changes are similar to those observed in the CNS in experimental GVHD. We suggest that this case represents the first documentation of CNS involvement in chronic GVHD.

Sleeping habits in the Austrian population.

OBJECTIVES: To gain reliable data on sleeping habits and sleep disturbances of the Austrian population. BACKGROUND: Exact data on sleeping habits are of interest in relation to assessment of sleep disturbance-related illnesses and general social processes. METHODS: A prospective, cross-sectional study was performed with recruitment of a representative sample of 1049 Austrians (aged 15-82 years), according to the Federal Statistics population characteristics. Interviews were conducted in the households of the participants by specially trained interviewers of an institute for empirical research. RESULTS: Men consider their quality of sleep to be significantly better than women (P=0.00234), and younger persons consider their quality of sleep to be significantly better than older persons (P=0.00001). In comparison, women and people over the age of 50 report worse subjective sleep quality, worse sleep efficiency, more difficulty in falling asleep and sleep maintenance, more apneic events, more pathologic limb movements, more daytime dysfunction, and more intake of sleeping medication. Other sociodemographic factors influence sleep reports to a lesser extent. CONCLUSIONS: Subjectively disturbed sleep (prevalence in the total population 24.9%), excessive hypnotic drug intake (prevalence 13.0%), and daytime dysfunction (prevalence 17.4%) are a widespread problem, especially in women and older people. With increasing life expectancy in Western societies, the prevalence of sleep disturbances will increase.

BAEP abnormalities in tardive dyskinesia.

To evaluate brainstem dysfunction, brainstem auditory-evoked potentials (BAEPs) were recorded in 13 patients with tardive dyskinesia. Only patients under 60 years of age were included because of the spontaneous dyskinetic syndromes that frequently occur in elderly persons. Clinical assessment was performed with the Abnormal Involuntary Movement Scale (AIMS). BAEP measurements were taken in order to detect lesions in the brainstem. In 14 of 26 pathways (13 patients), abnormalities in the BAEPs were found which corresponded well to lesions found in former neuropathological reports of patients with tardive dyskinesia. The functional disturbance causing abnormal BAEPs may be an expression of structural brain changes in tardive dyskinesia patients.

Single photon emission computerized tomography during and between seizures.

In three patients, patterns of brain activity were measured by 99mTc-hexamethyl-propyleneamineoxime (99mTc-HM-PAO) brain SPECT (single photon emission computerized tomography) in ictal and interictal states. Increased relative blood flow indicated the focus of partial seizures, its spreading to adjacent cortical regions and to distant brain structures via neuronal pathways. Ictal patterns of regional cerebral blood flow (rCBF) were in agreement with clinical symptomatology. Successive SPECT studies were performed after 3-7 days in the absence of electroencephalographic and clinical signs of seizures but still revealed increased relative blood flow in the focus of the seizures. SPECT studies, performed 2-6 weeks after the last clinically observable seizures, demonstrated the transition from increased to decreased relative blood flow in the focus of the seizures. In one patient, the EEG was complementary to and corresponded with the rCBF patterns in the ictal state. However, the dynamics of interictal changes could only be assessed by brain SPECT.

EEG-tomographic studies with LORETA on vigilance differences between narcolepsy patients and controls and subsequent double-blind, placebo-controlled studies with modafinil.

The aim of the present study was to identify brain regions associated with vigilance in untreated and modafinil-treated narcoleptic patients by means of low-resolution brain electromagnetic tomography (LORETA). 16 drug-free narcoleptics and 16 normal controls were included in the baseline investigation. Subsequently patients participated in a double-blind, placebo-controlled crossover study receiving a three-week fixed titration of modafinil (200, 300, 400 mg) and placebo. Measurements comprised LORETA, the Multiple Sleep Latency Test (MSLT) and the Epworth Sleepiness Scale (ESS) obtained before and after three weeks' therapy. Statistical overall analysis by means of the omnibus significance test demonstrated significant inter-group differences in the resting (R-EEG), but not in the vigilance-controlled recordings (V-EEG). Subsequent univariate analysis revealed a decrease in alpha-2 and beta 1-3 power in prefrontal, temporal and parietal cortices, with the right hemisphere slightly more involved in this vigilance decrement. Modafinil 400 mg/d as compared with placebo induced changes opposite to the aforementioned baseline differences (key-lock principle) with a preponderance in the left hemisphere. This increase in vigilance resulted in an improvement in the MSLT and the ESS. LORETA provided evidence of a functional deterioration of the fronto-temporo-parietal network of the right-hemispheric vigilance system in narcolepsy and a therapeutic effect of modafinil on the left hemisphere, which is less affected by the disease.

Human somatosensory cortical finger representation as studied by combined neuromagnetic and neuroelectric measurements.

We studied somatotopy of human hand somatosensory cortex using evoked responses recorded on magnetoencephalogram (MEG) and scalp-electroencephalogram (EEG) in conjunction with dipole modeling. We found a somatotopic arrangement of cortical digit representations with a sensory sequence from lateral inferior to medial superior in the anatomical order thumb, index finger, middle finger, ring finger, and little finger. MEG alone was able to reproduce this sensory sequence more accurately than scalp-EEG alone. However, the combined information provided by both techniques improved localization accuracy even further. As MEG and scalp-EEG are complementary and confirmatory techniques, this combined approach was useful to get more complete information on the functional organization of human hand somatosensory cortex.

Monitoring of median nerve somatosensory evoked potentials in carotid surgery.

The purpose of this study was to compare median somatosensory evoked potentials (SEP) in patients undergoing carotid endarterectomy (CEA) with routine shunting and nonshunting (excluding the option of selective shunting) and to evaluate the significance of a decrease in the amplitude of the cortically generated waveforms of the SEP and/or an increase in the central conduction time (CCT) on the one hand, and that of a loss of the cortical SEP, on the other. Somatosensory evoked potentials were recorded in 32 patients before, during, and after CEA with routine shunting or nonshunting. The N13 and N20 latency, the CCT, and the N20/P25 amplitude were evaluated. In addition, a meta-analysis of 15 previous studies was performed comprising a total of 3,136 patients. The intraoperative cortical SEP showed no differences between shunted and nonshunted patients, apart from the preclamping value of the N20/P25 amplitude which was lower in the nonshunted subjects. The number of patients with decreased and/or delayed cortical SEP (findings frequently used as criterion for selective shunting) was similar in the two study groups. A loss of the cortical SEP occurred in one patient operated on without an indwelling shunt. None of these patients had a new neurologic deficit after surgery. In the meta-analysis, the positive predictive value of decreased and/or delayed cortical SEP was extremely poor, that of absent cortical SEP was poor to moderate and the prevalence of new neurologic deficits was similar in patients undergoing CEA with routine shunting-nonshunting and those with selective shunting-nonshunting. Our study suggests that decreased and/or delayed cortical SEP are unreliable predictors of the neurological outcome of CEA patients and consequently an unsuitable criterion for selective shunting. The meta-analysis confirms this finding and shows that the neurologic outcome is not improved by using an indwelling shunt selectively based on SEP monitoring.

Clinical significance of autoimmune thyroid disease in myasthenia gravis.

We investigated thyroid function and autoimmunity in 74 (61% females) consecutive patients with MG. 30 of these patients were tested twice: the time between the investigations ranging from 1 to 4 years. MG was diagnosed on the basis of typical clinical symptoms, a positive tensilone-test, and/or detectable acetylcholine antibodies and/or repetetive stimulation tests. Eye involvement was present in 86%, concurrent thymomas in 56%. The following parameters were measured in the serum of these patients by commercially available kits: free and total T4, TSH, TSH-Receptor-Antibodies ("TRAB"), antibodies against thyroglobulin (Tg-Ab), against thyroid microsomes (M-Ab) and against acetyl-choline-receptors . An age matched group of 50 patients (54% females) with no known thyroid disease from a cardiological ward and from the neurological outpatient department served as control. There was only 1 MG patient with overt thyroid dysfunction (iodine induced thyrotoxicosis in a patient with autonomous adenoma and no circulating thyroid autoantibodies detected at the second investigation). There were, moreover, 1 euthyroid MG-patient on L-thyroxine therapy with a history of Hashimoto's disease and positive thyroid autoantibodies and 1 other MG-patient with mildly elevated TSH without elevated thyroid antibodies, who has had subtotal thyroidectomy without substitution therapy years before for unknown reasons. Tg-Ab were positive (>360 IU/ml) in 5%, M-Ab were positive (>154 IU/ml) in 15% of the MG patients. The control group had 4% Tg-Ab and 6% M-Ab. TRAB levels were normal in all patients and controls. The relative increase in M-Ab frequency was not statistically significant (x-square test). We conclude from our results, that autoimmune thyroid disease may be associated with MG but that the occurrence of thyroid dysfunction induced by autoimmunity is a very rare phenomenon in MG.

Automatic sleep-spindle detection procedure: aspects of reliability and validity.

The paper describes a reliable and valid method for the automatic detection of sleep spindles in whole night polygraphy. The recording of a multi-channel EEG during sleep polysomnography was performed in 10 healthy volunteers aged 20-35 years. This objective method should improve the time-consuming and subjective visual evaluation by increasing the accuracy and allowing the calculation of quantitative variables (i.e., frequency and amplitude), thereby facilitating scientific work with quantitative data. An important part of the method is the treatment of artifacts (i.e., muscle and spindle-like alpha activity). Compared to hardware solutions, our software method has the advantage of higher flexibility in regard to artifact identification and usual spindle definitions.

Normal striatal D2 receptor binding in idiopathic restless legs syndrome with periodic leg movements in sleep.

Dopaminergic treatment is very effective in restless legs syndrome (RLS) and periodic leg movements in sleep (PLMS). However, neuroreceptor imaging studies that addressed altered striatal dopaminergic function have given controversial results. In this present study, 14 patients with idiopathic RLS (iRLS) and PLMS with a good response to dopaminergic and non-dopaminergic treatment and ten healthy sex- and age-matched controls were investigated off-medication by using 123I-IBZM and SPECT. RLS symptoms and sleep disturbances were evaluated using three nights of polysomnography, the Pittsburgh Sleep Quality Index, and the International RLS Study Group (IRLSSG) rating scale. The patients presented with sleep disturbances, a high PLMS index (56.2 +/- 33.1 per h), and severe RLS symptoms during SPECT (IRLSSG rating scale 23.1 +/- 8.0), and showed no significant differences in striatal to frontal IBZM binding to D2 receptors compared to controls (ratio striatum/frontal cortex, right side 1.60 +/- 0.10 vs 1.63 +/- 0.08, P = 0.35, NS; left side 1.61 +/- 0.11 vs 1.63 +/- 0.08, P = 0.51, NS). These findings show normal function of striatal D2 receptors in successfully treated patients with iRLS and PLMS. Dopaminergic and non-dopaminergic pretreatment does not appear to change striatal D2 receptor binding as compared to healthy controls. Structures other than striatal D2 receptors are discussed as possible causes of the treatment effects in RLS.

Monitoring set-up for selection of parameters for detection of hypoglycaemia in diabetic patients.

Recurrent severe hypoglycaemia is often an unsolved problem in diabetic patients under intensified insulin treatment. As no reliable long-term stable blood glucose sensor has yet been developed, registration of other body function changes could help to detect severe hypoglycaemia. A measuring system is described, capable on the one hand of recording EEG, heart rate, peripheral pulse, skin temperature, respiratory movements, skin impedance and arterial blood pressure, and capable of registering plasma glucose, counter-regulatory hormones, symptoms and cognitive performance under experimental conditions during hypoglycaemia, on the other. In a clinical study involving both insulin-induced hypoglycaemia in healthy subjects and insulin-dependent diabetic patients, the practical value and the character of changes of the recorded parameters are investigated. Currently insensitivity to hypoglycaemia, impracticability, complexity or susceptibility to artefacts make use of most parameters unsuitable for hypoglycaemia prevention. It is believed, however, that future efforts could result in indirect registration of hypoglycaemia, including a qualified combination of different parameters, individual adaptation in accordance with particular responses of individual patients, together with new measuring and sensor techniques.

[Syncopal consciousness disorders and drop attacks from the neurologic viewpoint]. / Synkopale Bewusstseinsstörungen und Sturzanfälle aus neurologischer Sicht.

The most important neurological disorders leading to syncope and/or drop attack are presented. With respect to epilepsy it is important to consider generalized absence seizures (petit mal), generalized tonic-clonic seizures (grand mal) and some types of complex partial seizures. Additionally, some sleep and arousal disorders must be mentioned, such as narcolepsy, disorders of excessive somnolence associated with sleep-induced respiratory impairment, as well as the Kleine-Levin-Critchley syndrome. Vagotonic, asympathicotonic, sympathicotonic and central autonomic disorders are comprised in the group of autonomic attacks. Among other brain diseases manifesting syncope and/or drop attack, cerebrovascular disorders are of major importance in view of their high incidence. Psychogenic seizures also have to be taken into account in the differential diagnosis.

[Myasthenia gravis and sleep]. / Myasthenia gravis und Schlaf.

In myasthenia gravis respiratory function is often disturbed in the night, especially during REM sleep, despite of normal daytime respiratory function. Nevertheless, nocturnal respiratory problems are rarely diagnosed. Sleepiness, concentration and memory problems can be symptoms of a sleep related breathing disorder. Reports of reduction of REM sleep, memory dysfunction, and detection of acetylcholine receptor (AchR)-antibodies in the cerebrospinal fluid have lead to the hypothesis of a central nervous system involvement in myasthenia gravis. Possible mechanisms are centrally acting AchR-antibodies, unspecifically acting cytokines and hypoxia, possibly the most important influence upon REM sleep reduction and impaired cognitive function. In a patient presenting possible CNS-involvement (cephalea, fatigue, concentration and memory problems), a polysomnographic investigation should therefore be performed to detect a sleep related breathing disorder.

[Sleep-related headaches]. / Schlafgebundene Kopfschmerzen.

Headaches and sleep disorders are frequent and can be associated with each other. Some headache syndromes are related to certain sleep phases or circadian rhythms. These so-called sleep-related headache syndromes include specific types of migraine, cluster headache, chronic paroxysmal hemicrania, and the hypnic headache syndrome. Except for the latter, they were included in the International Classification of Sleep Disorders and are described in this article.