Rositsa Poryazova

Excessive daytime sleepiness in Parkinson's disease: characteristics and determinants.

Background/Aims: Excessive daytime sleepiness (EDS) is frequent in patients with Parkinson’s disease (PD). Occasionally, EDS in PD exhibits narcolepsy-like features. We aimed to assess characteristics and determinants of EDS in consecutive patients with PD. Methods: Thirty consecutive patients with PD underwent a detailed clinical examination. EDS was assessed using the Epworth Sleepiness Scale (ESS) and Multiple Sleep Latency Test (MSLT). Sleep was assessed using video-polysomnography. Cerebrospinal fluid (CSF) hypocretin-1 levels were obtained in 3 patients. Results: ESS was >10 in 17 patients (57%). Mean sleep latency (MSL) on MSLT was <5 min in 11 patients (37%). There was a significant negative correlation between ESS and MSL. None of the 11 patients with MSL <5 min showed a sleep onset REM (SOREM) episode. Patients with EDS had higher dopamine agonists/levodopa equivalent doses, higher apnea/hypopnea index and exhibited wearing-off symptoms more often. Hypocretin-1 was normal in 3 patients tested. Conclusion: EDS, which can sometimes be severe, is common in PD patients even in the absence of SOREM and detectable CSF-hypocretin deficiency. In PD, EDS is a multifaceted phenomenon, the determinants of which include severity of PD, wearing-off symptoms, dosage of antiparkinsonian drugs and sleep-disordered breathing.

Abnormal activity in reward brain circuits in human narcolepsy with cataplexy.

Hypothalamic hypocretins (or orexins) regulate energy metabolism and arousal maintenance. Recent animal research suggests that hypocretins may also influence reward‐related behaviors. In humans, the loss of hypocretin‐containing neurons results in a major sleep‐wake disorder called narcolepsy‐cataplexy, which is associated with emotional disturbances. Here, we aim to test whether narcoleptic patients show an abnormal pattern of brain activity during reward processing.

Progressive dopamine and hypocretin deficiencies in Parkinson's disease: is there an impact on sleep and wakefulness?

Sleep–wake disturbances are frequent in patients with Parkinson’s disease, but prospective controlled electrophysiological studies of sleep in those patients are surprisingly sparse, and the pathophysiology of sleep–wake disturbances in Parkinson’s disease remains largely elusive. In particular, the impact of impaired dopaminergic and hypocretin (orexin) signalling on sleep and wakefulness in Parkinson’s disease is still unknown. We performed a prospective, controlled electrophysiological study in patients with early and advanced Parkinson’s disease, e.g. in subjects with presumably different levels of dopamine and hypocretin cell loss. We compared sleep laboratory tests and cerebrospinal fluid levels with hypocretin‐deficient patients with narcolepsy with cataplexy, and with matched controls. Nocturnal sleep efficiency was most decreased in advanced Parkinson patients, and still lower in early Parkinson patients than in narcolepsy subjects. Excessive daytime sleepiness was most severe in narcolepsy patients. In Parkinson patients, objective sleepiness correlated with decrease of cerebrospinal fluid hypocretin levels, and repeated hypocretin measurements in two Parkinson patients revealed a decrease of levels over years. This suggests that dopamine and hypocretin deficiency differentially affect sleep and wakefulness in Parkinson’s disease. Poorer sleep quality is linked to dopamine deficiency and other disease‐related factors. Despite hypocretin cell loss in Parkinson’s disease being only partial, disturbed hypocretin signalling is likely to contribute to excessive daytime sleepiness in Parkinson patients.

Reduced Amygdala Activity during Aversive Conditioning in Human Narcolepsy

Narcolepsy with cataplexy is a sleep‐wake disorder caused by a loss of hypothalamic hypocretins. Here we assessed the time course of amygdala activation during aversive conditioning in unmedicated patients with narcolepsy. Unlike healthy matched control subjects, narcolepsy patients had no enhancement of amygdala response to conditioned stimuli and no increase in functional coupling between the amygdala and medial prefrontal cortex. These findings suggest that human narcolepsy is accompanied by abnormal emotional learning, and that, in line with animal data, the hypocretin system and the amygdala are involved in this process. ANN NEUROL 2010;67:394–398

Plastic Changes Following Imitation-Based Speech and Language Therapy for Aphasia: A High-Density Sleep EEG Study

Background. Objective measurement of plastic brain changes induced by a novel rehabilitative approach is a key requirement for validating its biological rationale linking the potential therapeutic gains to the changes in brain physiology. Objective. Based on an emerging notion linking cortical plastic changes to EEG sleep slow-wave activity (SWA) regulation, we aimed to assess the acute plastic changes induced by an imitation-based speech therapy in individuals with aphasia by comparing sleep SWA changes before and after therapy. Methods. A total of 13 left-hemispheric stroke patients underwent language assessment with the Western Aphasia Battery (WAB) before and after 2 consecutive high-density (hd) EEG sleep recordings interleaved by a daytime session of imitation-based speech therapy (Intensive Mouth Imitation and Talking for Aphasia Therapeutic Effects [IMITATE]). This protocol is thought to stimulate bilateral connections between the inferior parietal lobule and the ventral premotor areas. Results. A single exposure to IMITATE resulted in increases in local EEG SWA during subsequent sleep over the same regions predicted by the therapeutic rationale, particularly over the right hemisphere (unaffected by the lesion). Furthermore, changes in SWA over the left-precentral areas predicted changes in WAB repetition scores in our group, supporting the role of perilesional areas in predicting positive functional responses. Conclusions. Our results suggest that SWA changes occurring in brain areas activated during imitation-based aphasia therapy may reflect the acute plastic changes induced by this intervention. Further testing will be needed to evaluate SWA as a non-invasive assessment of changes induced by the therapy and as a predictor of positive long-term clinical outcome.

Unusually prolonged rebound cataplexy after withdrawal of fluoxetine

We report an unusually prolonged cataplectic attack in a patient with narcolepsy who stopped fluoxetine to perform sleep investigations. A 57-year-old woman with a 24-year history of clinically definite narcolepsy with cataplexy was referred for reassessment of treatment because of increasing insomnia. The patient reported excessive daytime sleepiness (Epworth Sleepiness Scale score 20/24) and maintenance insomnia with creeping and itching sensations in the legs accompanied by an urge to move. She had daily episodes of cataplexy with sagging of the face, jaw, and eyelids, slurred speech, and rarely head drooping. The episodes were triggered by positive or negative emotions and lasted a few seconds up to 1 minute. She had also monthly episodes of sleep paralysis and auditory hypnagogic hallucinations. The Ullanlinna Narcolepsy Scale score was 30 of 44 (a score of >14 suggests narcolepsy), and the Swiss Narcolepsy Scale score was −66 (a score of <0 suggests narcolepsy). …

Topographic sleep EEG changes in the acute and chronic stage of hemispheric stroke.

After stroke, the injured brain undergoes extensive reorganization and reconnection. Sleep may play a role in synaptic plasticity underlying stroke recovery. To test this hypothesis, we investigated topographic sleep electroencephalographic characteristics, as a measure of brain reorganization, in the acute and chronic stages after hemispheric stroke. We studied eight patients with unilateral stroke in the supply territory of the middle cerebral artery and eight matched controls. All subjects underwent a detailed clinical examination including assessment of stroke severity, sleep habits and disturbances, anxiety and depression, and high‐density electroencephalogram examination with 128 electrodes during sleep. The recordings were performed within 10 days after stroke in all patients, and in six patients also 3 months later. During sleep, we found higher slow‐wave and theta activity over the affected hemisphere in the infarct area in the acute and chronic stage of stroke. Slow‐wave, theta activity and spindle frequency range power over the affected hemisphere were lower in comparison to the non‐affected side in a peri‐infarct area in the patients’ group, which persisted over time. Conversely, in wakefulness, only an increase of delta, theta activity and a slowing of alpha activity over the infarct area were found. Sleep slow‐wave activity correlated with stroke severity and outcome. Stroke might have differential effects on the generation of delta activity in wakefulness and sleep slow waves (1–8 Hz). Sleep electroencephalogram changes over both the affected and non‐affected hemispheres reflect the acute dysfunction caused by stroke and the plastic changes underlying its recovery. Moreover, these changes correlate with stroke severity and outcome.

REM Sleep Behavior Disorder is not Linked to Postural Instability and Gait Dysfunction in Parkinson

To evaluate a potential association of REM‐sleep behavior disorder (RBD) with gait and postural impairment in Parkinsons disease (PD). Gait difficulties and postural impairment are frequent in PD and are a major cause of disability. Animal studies indicate a key role of the pedunculopontine nucleus (PPN) in gait, postural control, and REM sleep, and also in the pathophysiology of RBD. In humans, such an association has not been investigated. Twenty‐six patients with mild‐to‐moderate PD (13 with polysomnography confirmed and 13 with excluded RBD), and 20 age‐matched healthy controls were prospectively investigated. Gait assessment on a treadmill, and static and dynamic posturography were performed. PD patients with RBD do not differ from those without RBD in gait and postural control. Greater severity of PD or prevalence of gait and postural disturbances in the presence of RBD were not found. RBD was not associated with any particular motor phenotype. We found no association of RBD with gait disturbances and postural impairment. Human gait and postural control and RBD appear to depend upon different neuronal circuits.

Excessive Daytime Sleepiness in Idiopathic Restless Legs Syndrome: Characteristics and Evolution under Dopaminergic Treatment

Background/Aims: Whereas insomnia is frequent in restless legs syndrome (RLS), little is known about daytime sleepiness. We studied a series of 27 consecutive patients with idiopathic RLS in order to identify the characteristics and evolution of excessive daytime sleepiness (EDS) under dopaminergic treatment. Methods: Patients were assessed by clinical examination, questionnaires and video-polysomnography (PSG). Sleepy patients, as defined by Epworth Sleepiness Scale (ESS) >10, were also assessed by the multiple sleep latency test (MSLT). We excluded RLS patients with other sleep-wake disorders, in particular chronic sleep deprivation. Results: Mean age was 56 years, the mean International RLS Study Group Rating Scale score was 24 at baseline. Ten (37%) of the 27 patients reported EDS. RLS patients with sleepiness had a higher amount of total sleep time (p = 0.029) on PSG and a mean sleep latency of 6.4 min on MSLT. No other differences regarding clinical or polysomnographic parameters were found. RLS severity improved in all patients under dopaminergic treatment (p = 0.001); this was also the case for the ESS score in sleepy patients (p = 0.007). Conclusion: In our series of RLS patients, EDS was common, characterized by longer sleep (PSG) and reduced sleep latencies on MSLT. Under dopaminergic treatment, both RLS severity and ESS improved.

Sleep-Disordered Breathing and Periodic Limb Movements in Narcolepsy with Cataplexy: A Systematic Analysis of 35 Consecutive Patients

Background: Disturbed sleep is a core feature of narcolepsy with cataplexy (NC). Few studies have independently assessed sleep-disordered breathing (SDB) and periodic limb movements (PLMs) in non-homogeneous series of patients with and without cataplexy. We systematically assessed both SDB and PLMs in well-defined NC patients. Methods: We analyzed the clinical and polysomnographic features of 35 consecutive NC patients (mean age 40 ± 16 years, 51% males, 23/23 hypocretin-deficient) to assess the prevalence of SDB (apnea-hypopnea index >5) and PLMs (periodic leg movements in sleep (PLMI) >15) together with their impact on nocturnal sleep and daytime sleepiness using the multiple sleep latency test. Results: 11 (31%) and 14 (40%) patients had SDB and PLMs, respectively. SDB was associated with older age (49 ± 16 vs. 35 ± 13 years, p = 0.02), higher BMI (30 ± 5 vs. 27 ± 6, p = 0.05), and a trend towards higher PLMI (25 ± 20 vs. 12 ± 23, p = 0.052), whereas PLMs with older age (50 ± 16 vs. 33 ± 11 years, p = 0.002) and reduced and fragmented sleep (e.g. sleep efficiency of 82 ± 12% vs. 91 ± 6%, p = 0.015; sleep time of 353 ± 66 vs. 395 ± 28, p = 0.010). SDB and PLMs were also mutually associated (p = 0.007), but not correlated to daytime sleepiness. Conclusions: SDB and PLMs are highly prevalent and associated in NC. Nevertheless, SDB and PLMs are rarely severe, suggesting an overall limited effect on clinical manifestations.