Schlaf bei neurodegenerativen Erkrankungen

Zusammenfassung Die neurodegenerativen Erkrankungen bestehen aus einer Gruppe heterogener, progredient verlaufender Erkrankungen unterschiedlicher Ätiologie, die ein oder mehrere Systeme beeinträchtigen. Sie treten überwiegend im höheren Lebensalter auf, in dem sich zusätzlich sowohl die Art wie auch das Ausmaß des Schlafes ändern. Die neurodegenerativen Prozesse verursachen strukturelle Veränderungen der Schlaf-Wach-Generatoren im Hirnstamm, die Schlafstörungen wie Tagesschläfrigkeit, Insomnie, nächtliche bewegungs- und schlafbezogene Atmungsstörungen sowie Störungen des zirkadianen Schlaf-Wach-Rhythmus zur Folge haben können. Bei manchen neurodegenerativen Erkrankungen sind im Vorfeld der Krankheitsmanifestation auftretende Schlafstörungen bereits Krankheitsprädiktoren. Polysomnographisch finden sich Schlaffragmentierung, tonische oder phasische Beinbewegungen, Störungen der Atemmuskulatur, verminderter Tiefschlaf, Abwesenheit von REM-Schlaf oder REM-Schlaf ohne Muskelatonie, vermehrte Arousal- und Weckreaktionen, epileptiforme EEG-Aktivität oder schlafbezogene Atmungsstörungen. Sehr häufig sind REM-Schlaf-Verhaltensstörungen assoziiert mit neurodegenerativen Erkrankungen. In dieser Übersichtsarbeit werden Symptomatik, Pathophysiologie und polysomnographische Befunde von Schlafstörungen häufiger neurodegenerativer Erkrankungen vorgestellt.     

Corneal confocal microscopy reveals small nerve fibre loss correlating with motor function in adult spinal muscular atrophy

Background

5q Spinal muscular atrophy (SMA) is a progressive, inherited, and severely disabling – yet treatable – motor neuron disease. Although treatment options have evolved in recent years, biomarkers for treatment monitoring and prognosis prediction remain elusive. Here, we investigated the utility of corneal confocal microscopy (CCM), a non-invasive imaging technique to quantify small corneal nerve fibres in vivo, as a diagnostic tool in adult SMA.

Methods

In this cross-sectional study, 19 patients with SMA type 3 and 19 healthy controls underwent CCM to measure corneal nerve fibre density (CNFD), corneal nerve fibre length (CNFL), and corneal nerve branch density (CNBD), as well as corneal immune cell infiltration. Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM) scores and a 6-Minute Walk Test (6MWT) were conducted to explore any correlation between CCM findings and motor function.

Results

Corneal nerve fibre parameters were decreased in SMA patients versus healthy controls (CNFD: p = 0.030; CNFL: p = 0.013; CNBD: p = 0.020) in the absence of relevant immune cell infiltration. CNFD and CNFL correlated with HFMSE scores (CNFD: r = 0.492, p = 0.038; CNFL: r = 0.484, p = 0.042) and distance covered in the 6MWT (CNFD: r = 0.502, p = 0.042; CNFL: r = 0.553, p = 0.023).

Conclusions

Corneal confocal microscopy CCM reveals sensory neurodegeneration in SMA, thereby supporting a multisystem view of the disorder. Subclinical small nerve fibre damage correlated with motor function. Thus, CCM may be ideally suited for treatment monitoring and prognosis.     

Degeneration of corpus callosum and recovery of motor function after stroke: A multimodal magnetic resonance imaging study

Animal models of stroke demonstrated that white matter ischemia may cause both axonal damage and myelin degradation distant from the core lesion, thereby impacting on behavior and functional outcome after stroke. We here used parameters derived from diffusion magnetic resonance imaging (MRI) to investigate the effect of focal white matter ischemia on functional reorganization within the motor system. Patients (n = 18) suffering from hand motor deficits in the subacute or chronic stage after subcortical stroke and healthy controls (n = 12) were scanned with both diffusion MRI and functional MRI while performing a motor task with the left or right hand. A laterality index was employed on activated voxels to assess functional reorganization across hemispheres. Regression analyses revealed that diffusion MRI parameters of both the ipsilesional corticospinal tract (CST) and corpus callosum (CC) predicted increased activation of the unaffected hemisphere during movements of the stroke‐affected hand. Changes in diffusion MRI parameters possibly reflecting axonal damage and/or destruction of myelin sheath correlated with a stronger bilateral recruitment of motor areas and poorer motor performance. Probabilistic fiber tracking analyses revealed that the region in the CC correlating with the fMRI laterality index and motor deficits connected to sensorimotor cortex, supplementary motor area, ventral premotor cortex, superior parietal lobule, and temporoparietal junction. The results suggest that degeneration of transcallosal fibers connecting higher order sensorimotor regions constitute a relevant factor influencing cortical reorganization and motor outcome after subcortical stroke. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.     

Validation of the Augmentation Severity Rating Scale (ASRS): a multicentric, prospective study with levodopa on restless legs syndrome

BACKGROUND: Augmentation is the main complication during long-term dopaminergic treatment of restless legs syndrome (RLS) and reflects an overall increase in RLS severity. Its severity varies considerably from a minor problem to a devastating exacerbation of disease. Despite its clinical relevance, systematic evaluations have rarely been undertaken and there has been no development of methods to assess the severity of augmentation. To fill this gap, the European RLS Study Group (EURLSSG) has developed the Augmentation Severity Rating Scale (ASRS), using three items that assess the degree of change in three specific dimensions of augmentation. The changes in each dimension are summed to give an ASRS total score. METHODS: The ASRS was developed to cover the basic dimensions defining RLS augmentation. The items were developed by an interactive process involving professional and patient input. The ASRS that was evaluated included four major items and two alternative forms of one item. The validation was conducted using 63 (85%) mostly untreated RLS patients from six centers, who were treated for six months with levodopa (L-Dopa) (up to 500 mg/day, as clinically needed). Two consecutive assessments before and at baseline measured test-retest reliability. Consecutive ASRS ratings by two independent raters on a subsample of patients evaluated inter-rater reliability. Comparison with clinical severity ratings of two independent experts provided external validation of the ASRS. Comparison of patients with and without augmentation with regard to the items and the total score of the ASRS added discriminant validity. RESULTS: Sixty patients (63% females, mean age: 53 years, baseline International RLS Severity Rating (IRLS) score 24.7+/-5.2) were treated with a median daily dose of 300 mg L-Dopa (range: 50-500 mg). Thirty-six patients (60%) experienced augmentation. Item analyses indicated that one item could be removed as it did not contribute significantly to the test score and only one form of the duplicated item needed to be used. The final ASRS then included three items. Test-retest reliability for the total score was rho=0.72, and inter-rater reliability was rcc=0.94. Cronbach's alpha was 0.62. Validity as assessed by the correlation between the worst ASRS total score during the trial and the expert rating was rho=0.72. ASRS total score differed between patients without versus with augmentation (mean: 7.4 (standard deviation (SD)=4.0) vs. 2.0 (2.7) (P<0.0001). CONCLUSIONS: The ASRS is a reliable and valid scale to measure the severity of augmentation. Due to the need to systematically quantify augmentation for both long-term efficacy and tolerability, the ASRS may become a useful tool to monitor augmentation in future clinical trials.     

Comparing radiographic scores for prediction of complications and outcome of aneurysmal subarachnoid hemorrhage: Which performs best?

Background and purpose

Aneurysmal subarachnoid hemorrhage (aSAH) is characterized by high morbidity and mortality proceeding from the initial severity and following complications of aSAH. Various scores have been developed to predict these risks. We aimed to analyze the clinical value of different radiographic scores for prognostication of aSAH outcome.

Methods

Initial computed tomography scans (≤48 h after ictus) of 745 aSAH cases treated between January 2003 and June 2016 were reviewed with regard to Subarachnoid Hemorrhage Early Brain Edema Score (SEBES), and Claassen, Barrow Neurological Institute (BNI), Hijdra, original Graeb and Fisher scale scores. The primary endpoints were development of delayed cerebral ischemia (DCI), in-hospital mortality and unfavorable outcome (modified Rankin Scale score >3) at 6 months after subarachnoid hemorrhage. Secondary endpoints included the different complications that can occur during aSAH. Clinically relevant cutoffs were defined using receiver-operating characteristic curves. The radiographic scores with the highest values for area under the curve (AUC) were included in the final multivariate analysis.

Results

The Hijdra sum score had the most accurate predictive value and independent associations with all primary endpoints: DCI (AUC 0.678, adjusted odds ratio [aOR] 2.83; p < 0.0001); in-hospital mortality (AUC 0.704, aOR 2.83; p < 0.0001) and unfavorable outcome (AUC 0.726, aOR 2.91; p < 0.0001). Multivariate analyses confirmed the independent predictive value of the radiographic scales for risk of decompressive craniectomy (SEBES and Fisher score), cerebral vasospasm (SEBES, BNI score and Fisher score) and shunt dependency (Hijdra ventricle score and Fisher score) after aSAH.

Conclusions

Initial radiographic severity of aSAH was independently associated with occurrence of different complications during aSAH and the final outcome. The Hijdra sum score showed the highest diagnostic accuracy and robust predictive value for early detection of risk of DCI, in-hospital mortality and unfavorable outcome after aSAH.