Johannes Mathis

Early prognosis in coma after cardiac arrest: a prospective clinical, electrophysiological, and biochemical study of 60 patients.

BACKGROUND: The univariate study of clinical, electrophysiological, or biochemical variables has been shown to predict the outcome in postanoxic coma in about 50% of patients for each type of variable. Previous studies did not, however, consider the prognostic accuracy of a multivariate approach. METHODS: Sixty patients in coma for more than six hours after cardiac arrest were prospectively examined by means of repeated clinical examinations (including Glasgow coma score (GCS)), EEG, and medianus nerve somatosensory evoked potentials (SEPs). In 16 patients, the early concentrations of serum neuron specific enolase and ionised calcium were also measured. RESULTS: Within the first year after cardiac arrest, 20% of patients made a good neurological recovery; 80% remained in a vegetative state or died. Clinical examination correctly predicted outcome in 58% of patients, SEP in 59%, and EEG in 41%. The combination of clinical examination, SEP, and EEG raised the percentage of correct predictions to 82%, without false pessimistic predictions. Concentrations of serum neuron specific enolase and ionised calcium were of no additional prognostic help. Multivariate regression analysis identified the association of GCS < 8 at 48 hours with abnormal or absent early cortical SEPs as highly predictive of a bad outcome (risk = 97%, 95% confidence interval = 86-99%). CONCLUSION: The combination of GCS at 48 hours, SEP, and if these are non-conclusive, EEG, permits a more reliable prediction of outcome in postanoxic coma than clinical examination alone.

High prevalence of glaucoma in patients with sleep apnea syndrome.

OBJECTIVE To determine the prevalence of glaucoma in sleep apnea syndrome (SAS), an entity characterized by repetitive upper airway obstructions during sleep, inducing hypoxia and sleep disruption with the risk of cardiovascular and neurologic sequelae. DESIGN Cross-sectional study. PARTICIPANTS A total of 114 white patients consecutively referred for polysomnographic evaluation of suspected SAS. INTERVENTION Complete ophthalmologic examination, including computerized perimetry and simultaneous stereoscopic optic disc photographs. MAIN OUTCOME MEASURES Spearman rank correlations between the respiratory disturbance index during night sleep (RDI), a value used to diagnose and grade SAS, and visual acuity, intraocular pressure (IOP), visual field indices, presence or absence of glaucomatous optic disc changes, and diagnosis of glaucoma. Each correlation was controlled for age and body mass index. To compare proportions of patients harboring glaucoma, the binomial test was used. RESULTS Sixty-nine (60.5%) of the 114 patients had an RDI > or =10, which indicates SAS. Three patients had primary open-angle glaucoma, and two had normal-tension glaucoma. All patients with glaucoma had SAS. The observed prevalence of glaucoma in patients with SAS (5 of 69, 7.2%) was significantly higher than expected in a white population (2%) (P = 0.01). The RDI correlated positively with IOP (P = 0.025), visual field loss variance (P = 0.03), glaucomatous optic disc changes (P = 0.001), and diagnosis of glaucoma (P = 0.01). CONCLUSIONS Patients with SAS constitute a high-risk population for glaucoma and should therefore be screened for glaucoma.

Restless Legs Syndrome: A Clinical Study of 55 Patients

Background: Restless legs syndrome (RLS) is a common sleep disorder. In 1995, clinical criteria for the diagnosis of RLS were defined. Objective: To describe the clinical spectrum in a series of unselected RLS patients meeting the new diagnostic criteria. Methods: We prospectively assessed by questionnaire and clinical assessment the characteristics of 55 consecutive RLS patients (35 women, 20 men; mean age = 62 ± 16 years). Results: In 27% of the patients, RLS started before the age of 20 years (early-onset RLS). Sensory disturbances were painful in 56% of patients and felt in legs (98%), arms (35%), and ‘internally’ (45%). Motor disturbances included ‘dyskinesias while awake’ (36%). Insomnia (58%) was commoner than hypersomnia (24%). In 67% of the patients, no etiology of RLS was found (idiopathic RLS). Early-onset RLS was more commonly familial (p = 0.01) and associated with ‘growing pains’ (p = 0.005) than late-onset RLS. Patients with RLS and hypersomnia were younger (p = 0.01) and less commonly had painful sensations (p = 0.04) than patients with RLS and insomnia. Patients with idiopathic RLS were younger (p = 0.004), and less commonly had insomnia (p = 0.01) than patients with symptomatic RLS. Conclusions: RLS is a clinically pleomorphic syndrome, reflecting the contribution of multiple genetic and acquired factors in the pathogenesis of RLS.

Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy

Narcolepsy is a rare sleep disorder with the strongest human leukocyte antigen (HLA) association ever reported. Since the associated HLA-DRB1*1501-DQB1*0602 haplotype is common in the general population (15–25%), it has been suggested that it is almost necessary but not sufficient for developing narcolepsy. To further define the genetic basis of narcolepsy risk, we performed a genome-wide association study (GWAS) in 562 European individuals with narcolepsy (cases) and 702 ethnically matched controls, with independent replication in 370 cases and 495 controls, all heterozygous for DRB1*1501-DQB1*0602. We found association with a protective variant near HLA-DQA2 (rs2858884; P < 3 × 10−8). Further analysis revealed that rs2858884 is strongly linked to DRB1*03-DQB1*02 (P < 4 × 10−43) and DRB1*1301-DQB1*0603 (P < 3 × 10−7). Cases almost never carried a trans DRB1*1301-DQB1*0603 haplotype (odds ratio = 0.02; P < 6 × 10−14). This unexpected protective HLA haplotype suggests a virtually causal involvement of the HLA region in narcolepsy susceptibility.

Cabergoline compared to levodopa in the treatment of patients with severe restless legs syndrome: results from a multi-center, randomized, active controlled trial.

We report the first large‐scale double‐blind, randomly assigned study to compare two active dopaminergic therapies for Restless Legs Syndrome (RLS), the dopamine agonist cabergoline (CAB) and levodopa/benserazide (levodopa). Patients with idiopathic RLS were treated with fixed daily doses of 2 or 3 mg CAB or 200 or 300 mg levodopa for 30 weeks. Efficacy was assessed by changes in the IRLS (International RLS Severity Scale) and by time to discontinuation of treatment due to loss of efficacy or augmentation. 361 of 418 screened patients (age 58 ± 12 years, 71% females) were randomly assigned and treated (CAB: n = 178; levodopa: n = 183) in 51 centers of four European countries. Baseline IRLS total score was 25.7 ± 6.8. The baseline‐adjusted mean change from baseline to week 6 in IRLS sum score was d = −16.1 in the CAB group and d = −9.5 in the levodopa group (d = −6.6, P < 0.0001). More patients in the levodopa group (24.0%) than in the CAB group (11.9%, P = 0.0029, log‐rank test) discontinued because of loss of efficacy (14.2% vs. 7.9%, P = 0.0290) or augmentation (9.8% vs. 4.0%, P = 0.0412). Adverse events (AEs) occurred in 83.1% of the CAB group and in 77.6% of the levodopa group. In both groups, most frequent AEs were gastrointestinal symptoms (CAB: 55.6%, levodopa: 30.6%, P < 0.0001). This first large‐scale active controlled study in RLS showed superior efficacy of cabergoline versus levodopa after a 30‐week long‐term therapy. Tolerability was found more favorable with levodopa than with cabergoline.

Normal-tension glaucoma is associated with sleep apnea syndrome

Introduction: In normal-tension glaucoma, optic nerve damage occurs without elevated intraocular pressures, hence vascular and pathogenic mechanisms other than intraocular pressure effects have been postulated. However, the exact cause(s) remain unknown. We have looked for an association between normal-tension glaucoma and sleep apnea syndrome, a disease characterized by repetitive upper airway obstructions during sleep, inducing hypoxia and sleep disruption with the risk of late cardiovascular and neurological sequelae. Methods: We performed overnight polysomnography in 16 consecutive Caucasian patients with normal-tension glaucoma. The respiratory disturbance index (RDI) during night sleep was used to diagnose and grade obstructive sleep apnea. Patients with an RDI of 10 or more were diagnosed as having obstructive sleep apnea. Results: We observed the following prevalences of obstructive sleep apnea in normal-tension glaucoma patients: 0% (0 of 2) for the group of patients younger than 45 years, 50% (3 of 6) for the age group 45–64 years, and 63% (5 of 8) for the group older than 64 years. Prevalences in the middle and older age group were significantly higher than in a historic control group (p < 0.025 for both, binomial test). Conclusion: Normal-tension glaucoma patients constitute a high-risk population for sleep apnea syndrome. Therefore, they should be screened for sleep apnea syndrome, and, if necessary, be treated to avoid late cardiovascular and neurological sequelae.

Primary open-angle glaucoma is associated with sleep apnea syndrome.

Introduction: The etiology of primary open-angle glaucoma remains unclear. Various risk factors, including vascular abnormalities, have been associated with this disease. Sleep-associated diseases, like sleep apnea syndrome, might also represent a risk factor. Sleep apnea syndrome is characterized by repetitive upper airway obstructions during sleep, inducing hypoxia and sleep disruption with the risk of cardiovascular and neurological sequelae. In this study, we determined the prevalence of sleep apnea syndrome in primary open-angle glaucoma patients. Methods: Overnight transcutaneous finger oximetry was performed in 30 consecutive patients having primary open-angle glaucoma. We assessed the oximetry disturbance index during night sleep, a parameter used to diagnose sleep apnea syndrome and to grade its severity. Results: Sleep apnea syndrome was more prevalent among primary open-angle glaucoma patients compared to normal historic controls of the same age and sex distribution (χ2 = 9.35, d.f. = 3, p < 0.025). The oximetry disturbance index grade was significantly larger in the primary open-angle glaucoma group compared to normal controls (U = 3,352, p = 0.01). According to the oximetry disturbance index, 20% (6/30) of primary open-angle glaucoma patients had sleep apnea syndrome. Conclusion: Primary open-angle glaucoma is associated with sleep apnea syndrome. Early recognition and treatment of sleep apnea syndrome are important to avoid cardiovascular and neurological complications.

Evolution of Neurological, Neuropsychological and Sleep-Wake Disturbances After Paramedian Thalamic Stroke

Background and Purpose— The clinical features and natural course of paramedian thalamic stroke is poorly known. The aim of this study was to characterize the evolution of neurological, neuropsychological, and sleep–wake deficits after paramedian thalamic stroke. Methods— Forty-six consecutive patients, aged 48.4±16.6 years, were studied. Fourteen had bilateral, 16 left-sided, and 16 right-sided lesions. Assessment included neurological examinations, estimation of sleep needs, formal neuropsychological tests (n=27), and polysomnographies (n=31). Functional outcome was followed up over 1 year in 31 patients with the modified Rankin Scale and Barthel index. Results— Oculomotor palsy (76% of patients), mild gait ataxia (67%), deficits of attention (63%), fluency and error control (59%), learning and memory (67%), and behavior (67%) were common in the acute stroke phase. Outcome was excellent with right-sided infarcts but mostly incomplete with bilateral and left-sided lesions. This was mainly related to persistent frontal lobe-related and cognitive deficits found in 100% bilateral and 90% left-sided, but only 33% right-sided strokes. Initially, hypersomnia was present in all patients associated with increased stage 1 sleep, reduced stage 2 sleep, and reduced sleep spindles. Sleep needs improved in patients with bilateral and almost disappeared with unilateral lesions after 1 year. Sleep architecture remained abnormal with the exception of sleep spindles that increased. Conclusions— Whereas neurological deficits and hypersomnia recover to large extent in patients with paramedian thalamic stroke, the frontal lobe-related and cognitive deficits, which are mainly linked with bilateral and left-sided lesions, often persist. As such, stroke outcome is better in right-sided than bilateral or left-sided infarcts.

Sleep-wake habits and disorders in a series of 100 adult epilepsy patients—A prospective study

The aim of the study was to assess sleep-wake habits and disorders and excessive daytime sleepiness (EDS) in an unselected outpatient epilepsy population. Sleep-wake habits and presence of sleep disorders were assessed by means of a clinical interview and a standard questionnaire in 100 consecutive patients with epilepsy and 90 controls. The questionnaire includes three validated instruments: the Epworth Sleepiness Scale (ESS) for EDS, SA-SDQ for sleep apnea (SA), and the Ullanlinna Narcolepsy Scale (UNS) for narcolepsy. Sleep complaints were reported by 30% of epilepsy patients compared to 10% of controls (p=0.001). The average total sleep time was similar in both groups. Insufficient sleep times were suspected in 24% of patients and 33% of controls. Sleep maintenance insomnia was more frequent in epilepsy patients (52% vs. 38%, p=0.06), whereas nightmares (6% vs. 16%, p=0.04) and bruxism (10% vs. 19%, p=0.07) were more frequent in controls. Sleep onset insomnia (34% vs. 28%), EDS (ESS >or=10, 19% vs. 14%), SA (9% vs. 3%), restless legs symptoms (RL-symptoms, 18% vs. 12%) and most parasomnias were similarly frequent in both groups. In a stepwise logistic regression model loud snoring and RL-symptoms were found to be the only independent predictors of EDS in epilepsy patients. In conclusion, sleep-wake habits and the frequency of most sleep disorders are similar in non-selected epilepsy patients as compared to controls. In epilepsy patients, EDS was predicted by a history of loud snoring and RL-symptoms but not by SA or epilepsy-related variables (including type of epilepsy, frequency of seizures, and number of antiepileptic drugs).

Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy: a European Narcolepsy Network study

The aim of this study was to describe the clinical and PSG characteristics of narcolepsy with cataplexy and their genetic predisposition by using the retrospective patient database of the European Narcolepsy Network (EU‐NN). We have analysed retrospective data of 1099 patients with narcolepsy diagnosed according to International Classification of Sleep Disorders‐2. Demographic and clinical characteristics, polysomnography and multiple sleep latency test data, hypocretin‐1 levels, and genome‐wide genotypes were available. We found a significantly lower age at sleepiness onset (men versus women: 23.74 ± 12.43 versus 21.49 ± 11.83, P = 0.003) and longer diagnostic delay in women (men versus women: 13.82 ± 13.79 versus 15.62 ± 14.94, P = 0.044). The mean diagnostic delay was 14.63 ± 14.31 years, and longer delay was associated with higher body mass index. The best predictors of short diagnostic delay were young age at diagnosis, cataplexy as the first symptom and higher frequency of cataplexy attacks. The mean multiple sleep latency negatively correlated with Epworth Sleepiness Scale (ESS) and with the number of sleep‐onset rapid eye movement periods (SOREMPs), but none of the polysomnographic variables was associated with subjective or objective measures of sleepiness. Variant rs2859998 in UBXN2B gene showed a strong association (P = 1.28E‐07) with the age at onset of excessive daytime sleepiness, and rs12425451 near the transcription factor TEAD4 (P = 1.97E‐07) with the age at onset of cataplexy. Altogether, our results indicate that the diagnostic delay remains extremely long, age and gender substantially affect symptoms, and that a genetic predisposition affects the age at onset of symptoms.