Restless legs syndrome in Wilson's disease: frequency, characteristics, and mimics.

OBJECTIVE: To determine characteristics, clinical significance, frequency, and mimics of restless legs syndrome (RLS) in a cohort of Wilson's disease (WD, n = 42/f = 18), compared to healthy, matched controls. MATERIALS AND METHODS: Structured clinical interviews (patients and caregiving family members), repeated neurological examinations (afternoon and presleep), comprehensive laboratory tests, WD-, RLS-, and sleep-specific rating scales, and video-polysomnography. RESULTS: Thirteen patients with WD (13/42 = 31.0%) clearly fulfilled the five diagnostic criteria of RLS; in eight patients (19.1%), the burden of RLS was clinically significant. The RLS was of moderate severity, equally distributed among sexes, manifested mainly in the evening and before falling asleep, and had developed mostly after clinical manifestation of WD (time elapsed 10.2 ± 14.5 years), still at a young mean age (27.5 ± 11.5 years). The known RLS-associated features were absent (normal iron and kidney parameters) or rare (positive family history, polyneuropathy). Compared to WD patients without RLS, patients with RLS were significantly elder and had suffered longer from WD. WD-specific RLS mimics as well as RLS confounding motor comorbidities (dystonia, tremor, chorea) were frequent and a diagnostic challenge; in difficult cases, the differentiation was reached by clinical observation of the motor behavior in the evening or at nighttime. CONCLUSION: RLS was frequent in this cohort of WD and might be causally related to WD. RLS should be included in the diagnostic work-up of WD. In complex motor disorders, differential diagnosis of RLS might require evening/nighttime examination and video-polysomnography. In WD patients with a clinically significant RLS, treatment with dopaminergic substances may be considered.

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.

Amantadine in Parkinson's disease: lymphocyte subsets and IL-2 secreting T cell precursor frequencies.

The antiviral drug amantadine, that is effective in idiopathic Parkinson's disease (PD), may affect the composition and function of peripheral blood lymphocytes. In an explorative study, we therefore compared lymphocyte subpopulations and IL-2 secreting T cell precursors frequencies (HTLp-frequencies) in 15 PD patients without amantadine and six patients on long-term treatment. Five patients were investigated before and three months after the start of treatment. Group comparisons for long-term amantadine treatment showed no differences in subpopulations of B-, T-, and NK cells, and HTLp-frequencies. However, three months after initiation of treatment we noted in all five patients an increase of CD3+CD4+ and decrease of CD3+CD8+ cells, associated with an increase of the CD3+CD4+/CD3+CD8+ ratio. These changes had no effect on the HTLp-frequencies. Thus, at least for a short period of time, amantadine improves the T cell mediated immune system in PD patients.

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.

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.

High-dose olanzapine in Huntington's disease.

The few reports available on olanzapine in Huntington's disease (HD) are insufficiently documented and/or insufficiently dosed. We describe a 30-year-old woman with genetically confirmed HD who presented with severe chorea. She was not able to eat or dress without help and did not respond to haloperidol; the motor scale of the Unified HD Rating Scale (UHDRS-I) revealed 65 of a possible 124 points. After admission, we treated the patient with a high dose of olanzapine (30 mg daily). The chorea almost ceased in the next 2 days, she was able to eat and walk without assistance (UHDRS-I of 21 points), and fine motor tasks improved, as well as gait and eye movements. This effect lasted for 5 months. We conclude that high-dose olanzapine appears to be useful in grave choreatic attacks.

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.

[Sleep disorders in neurology: hyposomnia]. / Schlafstörungen in der Neurologie: Hyposomnien.

Sleep disturbances are an important health problem; about 20-33% of the population suffer from hyposomnias (lack of sleep). Hyposomnias often accompany neurological disorders (head traumas, chronic cephalea, pain, cerebrovascular and neuromuscular disorders, M. Parkinson, and dementia). Slow wave sleep decreases, arousals increase, and sleep is fragmented; these types of hyposomnias are treated by treatment of the basic neurological disease. Some sleep disturbances (e.g. sleep apneas) are a risk factor for cerebrovascular disorders.

Apomorphine in idiopathic restless legs syndrome: an exploratory study.

BACKGROUND: Dopaminergic and opioidergic drugs have been found to be effective in patients with restless legs syndrome (RLS). OBJECTIVES: To test the effect of apomorphine--a combined opioidergic and dopaminergic agonist--and subsequent selective antagonism by naloxone and metoclopramide on subjective and objective symptoms in patients with idiopathic RLS. METHODS: Nine patients with RLS were pretreated with oral domperidone for three days. A modified suggested immobilisation test (SIT) was carried out between 8 pm and 1 am under the following conditions of intravenous drug administration: baseline-apomorphine-apomorphine plus naloxone-apomorphine plus metoclopramide. Outcome variables were a visual analogue scale (VAS) of subjective RLS symptoms and EMG documented periodic leg movements while awake (PLMW). RESULTS: Compared with baseline, apomorphine resulted in a rapid and significant improvement in subjective RLS symptoms as measured by VAS (54.5% improvement; p = 0.011), and an almost immediate cessation of PLMW, measured by PLMW index (98.0% improvement; p = 0.012). Neither additional naloxone nor metoclopramide blocked this effect significantly. While given apomorphine with metoclopramide, there was a trend to reappearance of PLMW. CONCLUSIONS: Apomorphine may be an effective treatment for idiopathic RLS. Its effectiveness may reflect both to its dopaminergic and its opioidergic activity, and is not diminished significantly by blocking only one of these pathways. The trend to a worsening of the PLMW index with metoclopramide hints at a primarily dopaminergic effect of apomorphine in idiopathic RLS.

Effects of socio-demographic variables on health-related quality of life determined by the quality of life index--German version.

STUDY OBJECTIVE: The purpose of this study was to determine subjective health-related quality of life (HRQoL) in a sample of the Austrian population over 14 years of age in order to evaluate the effect of socio-demographic variables on HRQoL. DESIGN/SETTING: HRQoL was determined by means of the quality of life index-German version (QLI-Ge). The influence of socio-demographic variables on HRQoL was assessed by statistical analysis using the Kruskal-Wallis test and an analysis of variance. PARTICIPANTS: A random-quota procedure was used to get balanced representation from regions and demographic groups of the Austrian population. The sample consisted of 1049 participants, 493 men and 556 women. MAIN RESULTS: Age was found to influence the QLI-Ge total score (index score) and most individual items, with increasing age resulting in a decrease in HRQoL. Differences between the sexes were observed in three dimensions: males scored higher in 'physical well-being', 'psychological well-being' and 'occupational functioning'. Marital status impacted most items with married persons showing better values than divorced persons or singles. Profession had only a minor effect on HRQoL, the level of education showed no influence at all. CONCLUSIONS: The socio-demographic variables age, sex and objective living conditions had a major influence on subjectively rated HRQoL, whereas profession and education were found to play a minor role in this context. It is recommended that in the interpretation of studies assessing HRQoL the above-mentioned objective factors be considered. This will be of particular importance when determining the effect of a pharmacotherapy on HRQoL in patients.

Outcome after shunt implantation in severe head injury with post-traumatic hydrocephalus.

OBJECT: Post-traumatic hydrocephalus (PTH) is considered a frequent complication after severe head injury (HI). There is little known about outcome following shunt implantation. METHODS: A hospital-based retrospective cross-over study investigated the outcome of 48 patients after severe HI, who had undergone ventricular shunt implantation due to PTH (40 males, mean age at injury 36 years, mean duration from HI to shunt implantation 27 weeks). Telephone interviews with the patients or with caring family members by means of a detailed questionnaire were performed after a mean observation period of 3.3 years after shunt implantation. Outcome was categorized using the Glasgow Outcome Scale (GOS): I: 12 patients, II: 7, III: 16, IV: 9, V: 4 at follow-up. CONCLUSIONS: 52.1% had a clear-cut benefit from shunt implantation, whereas 47.9% had not. Post-traumatic seizures were observed in 31 of 48 patients. Other complications after shunt implantation occurred in 20) patients. Revision of shunt implantation was performed in 15 patients (nine due to technical failure, three haemorrhage, one delayed primary wound closure, and two unknown). Two patients clearly deteriorated after operation (one severe frontal bleeding, one sepsis). The best predictive parameter for outcome after shunt implantation was the pre-operative status, patients in a better clinical condition (pre-operative GOS score 3-severe disabled vs 4-persistent vegetative state) had a better outcome. Patient's age at injury did not seem to influence the outcome. Clinical and computertomographic findings were of rather moderate predictive value as regards short- and long-term outcome after shunt implantation. Cisternography does not seem to be of additional help in the establishment of definite diagnosis of PTH.

Changes of serum lipid patterns during long-term anticonvulsive treatment.

Serum lipids were determined in 97 patients (56 men, 41 women; ages 42 +/- 15 years) undergoing long-term anticonvulsive treatment (longer than 6 months). The total group showed increased total cholesterol, decreased high-density lipoprotein HDL cholesterol, an increased ratio of total to HDL cholesterol, and decreased apolipoprotein A1 and B values compared to population means. Considering males and females separately, all differences were significant (P < 0.01) in men, whereas in women only the differences in HDL cholesterol, ratio of total to HDL cholesterol, and apolipoproteins A1 and B reached the level of statistical significance. Considering the different anticonvulsant groups, cholesterol was significantly increased only in phenytoin-treated males; HDL cholesterol was significantly lowered and the ratio of total to HDL cholesterol significantly increased in all groups. Apolipoprotein A1 levels were significantly decreased in phenytoin-treated females and valproate-treated patients of both sexes. Apolipoprotein B levels were significantly decreased in all groups except carbamazepine-treated males. Especially in men treated with anticonvulsants these lipid levels may be considered a risk factor for atherosclerosis.

EEG topography during insulin-induced hypoglycemia in patients with insulin-dependent diabetes mellitus.

A group of young patients with insulin-dependent diabetes mellitus (n = 14; 8 men, 6 women; 33.1 +/- 8.9 years) were examined by topographic EEG mapping under normoglycemic and hypoglycemic conditions (glucose levels after intravenous insulin injection down to 32.6 +/- 7.6 mg/dl). From the clinical aspect, 7 of them had a good and 7 had a poor awareness of hypoglycemia. During hypoglycemia, a decrease in alpha activity (p < 0.05), an increase in delta (p < 0.05), and especially in theta activity (p < 0.05) were found. The most sensitive parameter was the alpha/theta ratio. In the range of slight hypoglycemia (50-60 mg/dl) the increase in delta and theta activity showed a topographic maximum in lateral frontal regions. During deep hypoglycemia there was a topographic maximum of slow frequencies in posterior parts of the brain (centrotemporal to parieto-occipital regions). The differences between the group with good and with poor awareness of hypoglycemia were most pronounced during slight hypoglycemia in C3, C4, and Pz (p < 0.05). At lower glucose levels group distinction was no longer possible. These EEG changes correspond to a temporary organic brain syndrome.

Sequential MRI in a case of Creutzfeldt-Jakob disease.

A 48-year-old man suddenly developed clinically and electroencephalographically nonspecific dementia. On MRI sequences, only diffusion-weighted images (DWI) of the cortex were unequivocally pathological. Obvious atrophy and basal ganglia signal changes appeared only 9 months after the onset. Brain biopsy confirmed Creutzfeldt-Jakob disease (CJD). In rapidly progressive dementia, we recommend DWI for early diagnosis of CJD.

Are there predictive factors for long-term outcome after withdrawal in drug-induced chronic daily headache?

OBJECTIVES: To investigate prognostic factors for long-term outcome of patients after inpatient withdrawal because of drug-induced chronic daily headache. PROCEDURES: Fifty-five patients (36 females) were re-examined by means of a standardized interview after inpatient withdrawal. The mean observation period was 9.28 +/- 2.85 years (mean +/- SD; median 8.58; range 5.00-13.50). RESULTS: Five years after withdrawal, one-third of the patients (34.6%) had an overall favourable outcome, one-third (32.7%) had no recurrent drug overuse and reported a clear-cut improvement of headache, and one-third (32.7%) developed recurrent drug overuse. Most relapses occurred within 2 years, and a small percentage within 5 years. No predictors for long-term outcome after inpatient withdrawal were found. CONCLUSIONS: All patients with drug-induced chronic daily headache should be considered as good candidates for inpatient withdrawal, and no patient should be excluded from that therapy.

Sleep and quality of life in the Austrian population.

PURPOSE: To compare the self-reported estimation of sleep quality evaluated by the Pittsburgh Sleep Quality Index (PSQI) and life quality assessed by the Quality of Life Index (QLI). BACKGROUND: The PSQI comprised 19 questions and assessed a wide variety of factors relating to sleep quality. The QLI consisted of 10 items for self assessment of different dimensions of life quality. SUBJECTS: A representative Austrian sample (n = 1049) aged above 15 years. PROCEDURE: Interviews in the homes of the participants. RESULTS: 32.1% could be classified as poor sleepers (37% females, 26.5% males). Sleep quality decreased with increasing age, especially in women. Overall quality of life was highest in younger (15-29 years) and lowest in elderly subjects (over 50 years). Life quality decreased with increasing age. Between subjective sleep quality and quality of life a moderate, significant correlation was found (r2= 0.6721). CONCLUSIONS: Complaints about a bad quality of sleep could be used as a screening method in the exploration of patients' quality of life (QoL).