Margherita Fabbri

Slow eye movements distribution during nocturnal sleep

OBJECTIVE To assess the distribution across nocturnal sleep of slow eye movements (SEMs). METHODS We evaluated SEMs distribution in the different sleep stages, and across sleep cycles in nocturnal recordings of 10 healthy women. Sleep was scored according to standard criteria, and the percentage of time occupied by the SEMs was automatically detected. RESULTS SEMs were differently represented during sleep stages with the following order: wakefulness after sleep onset (WASO): 61%, NREM sleep stage 1: 54%, REM sleep: 43%, NREM sleep stage 2: 21%, NREM sleep stage 3: 7%, and NREM sleep stage 4: 3% (p<0.0001). There was no difference between phasic and tonic REM sleep. SEMs progressively decreased across the NREM sleep cycles (38%, 15%, 13% during NREM sleep stage 2 in the first three sleep cycles, p=0.006), whereas no significant difference was found for REM, NREM sleep stage 1, slow-wave sleep and WASO. CONCLUSIONS Our findings confirm that SEMs are a phenomenon typical of the sleep onset period, but are also found in REM sleep. The nocturnal evolution of SEMs during NREM sleep stage 2 parallels the homeostatic process underlying slow-wave sleep. SIGNIFICANCE SEMs are a marker of sleepiness and, potentially, of sleep homeostasis.

Automatic slow eye movement (SEM) detection of sleep onset in patients with obstructive sleep apnea syndrome (OSAS): Comparison between multiple sleep latency test (MSLT) and maintenance of wakefulness test (MWT)

OBJECTIVE To determine whether automatic slow eye movement (SEM) analysis performs comparably to standard sleep onset criteria at the multiple sleep latency test (MSLT) and at the maintenance of wakefulness test (MWT) in patients with obstructive sleep apnea syndrome (OSAS). METHODS We compared sleep latencies obtained upon standard analysis of MSLT and MWT recordings with automatically detected SEM latencies in a population of 20 severe OSAS patients that randomly underwent the two tests 1 week apart. RESULTS Eight of 20 OSAS patients had EDS as answered by the Epworth Sleepiness Scale (ESS). Mean SEM latency performed comparably to standard sleep onset in both the MSLT (6.4+/-5.5 min versus 7.4+/-5.1 min, p=0.25) and the MWT (25.2+/-14.5 min versus 24.4+/-14.0 min, p=0.45) settings. Mean SEM latency significantly correlated with the sleep latency at the MSLT (r=0.52, p<0.05) and at the MWT (r=0.74, p<0.001). Finally, the Epworth Sleepiness Scale score correlated with SEM latency at the MWT (r=-0.62, p<0.01), but not at the MSLT. CONCLUSIONS Automatic SEM detection performed comparably to standard polysomnographic assessment of sleep onset, thus providing a simplified technical requirement for the MSLT and the MWT. Further studies are warranted to evaluate SEM detection of sleep onset in other sleep disorders with excessive daytime sleepiness.

Detection of sleep onset by analysis of slow eye movements: a preliminary study of MSLT recordings.

BACKGROUND Excessive daytime sleepiness (EDS) adversely impacts daily activity and quality of life. Evaluation of EDS should be as easy and effective as possible. Multiple sleep latency test (MSLT) represents the standard in EDS evaluation. It is, however, a long and expensive test. Slow eye movements (SEMs) occurring at the wake-sleep transition could be an easy and reliable marker of sleepiness. We have developed an automatic method for the detection of SEMs. In the present preliminary work we compare standard measurement of EDS with visual and automatic detection of SEMs, both performed on MSLT recordings. METHODS We compared sleep latency, obtained upon standard analysis of MSLT with visually and automatically detected SEM latency, in MSLT tests performed in a population of 20 subjects, (10 Obstructive Sleep Apnea Syndrome (OSAS) patients and 10 patients with normal MSLT). RESULTS There were no significant differences between SEMs latency and standard determined sleep latency both in OSAS and normal MSLT patients. Automatic and visual analysis of SEMs gave comparable results. Both SEMs latency and sleep latency were significantly shorter in OSAS patients than normal MSLT patients. CONCLUSION SEMs can be easily detected automatically and represent an effective marker of sleepiness in those conditions usually characterised by sleep onset with NREM sleep. Their performance equals that of standard measurements of sleep onset in MSLT recordings at least for OSAS and normal MSLT patients. Our study is, however, still preliminary and needs confirmation on a larger number of patients and in other clinical conditions characterised by EDS.

Subthalamic deep brain stimulation effects on odor identification in Parkinson's disease

Olfactory dysfunction is common in Parkinsons disease (PD) and it is one of the earliest non‐motor symptoms. A few studies have suggested that deep brain stimulation of the subthalamic nucleus (STN‐DBS) could improve olfactory function. Our aim was to evaluate the acute effect of bilateral STN‐DBS on a commonly used smell test in PD patients.

Gait disorders in fatal familial insomnia

Fatal familial insomnia (FFI) is a hereditary autosomal‐dominant prion disease linked to a mutation of the prion protein gene and characterized by sleep and autonomic abnormalities at onset followed by motor disturbances. We describe gait abnormalities in 13 FFI cases with different disease durations.

Clinical and polygraphic study of familial paroxysmal kinesigenic dyskinesia with PRRT2 mutation.

BackgroundParoxysmal kinesigenic dyskinesia is a neurological condition characterised by brief attacks of involuntary movements triggered by sudden voluntary movements.MethodsWe describe the clinical, polygraphic, and genetic features of an Italian family with paroxysmal kinesigenic dyskinesia.ResultsParoxysmal kinesigenic dyskinesia manifested as brief choreoathetosic-dystonic attacks precipitated by sudden movements, varying in severity and frequency, amongst the four affected family members. The disorder follows an autosomal dominant transmission and affects female members. Mutation of SLC2A1, MR1, CACNA1A, and ATP1A2 genes was excluded by direct sequencing. Mutation analysis of the PRRT2 gene revealed a single nucleotide duplication, c.649dupC, resulting in the frameshift mutation p.Arg217Profs*8 in all affected members.ConclusionParoxysmal kinesigenic dyskinesia is the most common type of paroxysmal movement disorder and is often misdiagnosed clinically as epilepsy. We describe a family with paroxysmal kinesigenic dyskinesia associated with PRRT2 gene mutation, mild intrafamilial clinical heterogeneity, and benign course.

Autosomal dominant partial epilepsy with auditory features: A new locus on chromosome 19q13.11–q13.31

To clinically and genetically characterize a large Brazilian family with autosomal dominant partial epilepsy with auditory features (ADPEAF) not related to leucine‐rich, glioma‐inactivated 1 (LGI1) gene.

Late Onset Bipolar Disorder due to a Lacunar State

Objective. To describe a patient with a new onset bipolar disorder (BD) type II, secondary to a lacunar state. Background. Poststroke BD is rare and mainly associated with lesion in the prefrontal-striatal-thalamic circuit. Materials and Methods. A 51-year-old woman came to our attention for a mood disorder of recent onset. At 49, she had suffered acute left-sided limb weakness that improved spontaneously four days later. Arterial hypertension was subsequently diagnosed. After 6 months, she began to suffer from alternating brief periods of expansive and elevated mood with longer periods of depressed mood, with a suicide attempt. We performed extensive laboratory and instrumental investigations, as well as, psychiatric consultation, and a cognitive assessment, which was repeated 9 months later. Results. Brain magnetic resonance disclosed leukoaraiosis and a lacunar state of the basal ganglia. Transcranial Doppler showed a patent foramen ovale. A psychiatric consultation led to the diagnosis of BP type II. Neuropsychological evaluation detected deficits in attention/executive functions, verbal fluency, and memory. Nine months later, after specific psychiatric therapy, the psychiatric symptoms were remarkably improved. Conclusion. Our case sheds light on the role of the basal ganglia in mood disorders and the importance of ruling out brain injury in late onset BP.

Speech and Voice Response to a Levodopa Challenge in Late-Stage Parkinson's Disease

Background Parkinson’s disease (PD) patients are affected by hypokinetic dysarthria, characterized by hypophonia and dysprosody, which worsens with disease progression. Levodopa’s (l-dopa) effect on quality of speech is inconclusive; no data are currently available for late-stage PD (LSPD). Objective To assess the modifications of speech and voice in LSPD following an acute l-dopa challenge. Method LSPD patients [Schwab and England score <50/Hoehn and Yahr stage >3 (MED ON)] performed several vocal tasks before and after an acute l-dopa challenge. The following was assessed: respiratory support for speech, voice quality, stability and variability, speech rate, and motor performance (MDS-UPDRS-III). All voice samples were recorded and analyzed by a speech and language therapist blinded to patients’ therapeutic condition using Praat 5.1 software. Results 24/27 (14 men) LSPD patients succeeded in performing voice tasks. Median age and disease duration of patients were 79 [IQR: 71.5–81.7] and 14.5 [IQR: 11–15.7] years, respectively. In MED OFF, respiratory breath support and pitch break time of LSPD patients were worse than the normative values of non-parkinsonian. A correlation was found between disease duration and voice quality (R = 0.51; p = 0.013) and speech rate (R = −0.55; p = 0.008). l-Dopa significantly improved MDS-UPDRS-III score (20%), with no effect on speech as assessed by clinical rating scales and automated analysis. Conclusion Speech is severely affected in LSPD. Although l-dopa had some effect on motor performance, including axial signs, speech and voice did not improve. The applicability and efficacy of non-pharmacological treatment for speech impairment should be considered for speech disorder management in PD.

Clinical pharmacology review of opicapone for the treatment of Parkinson's disease

Two catechol-O-methyl transferase inhibitors are currently used as add-on therapy to levodopa for the amelioration of end-of-dose motor fluctuations in Parkinsons disease patients: entacapone, which has moderate efficacy and requires multiple dosing, and tolcapone, which has a poor safety profile. Opicapone (OPC) is a novel, long-acting, peripherally selective, once daily, third-generation catechol-O-methyl transferase inhibitor. Two Phase III clinical trials demonstrated OPC efficacy in reducing OFF-time by an average of about 60 min daily compared with placebo, without increasing ON-time with troublesome dyskinesias, with a good drug safety profile. In June 2016, the European Commission granted a marketing authorization valid throughout the European Union for OPC, indicated as adjunctive of levodopa decarboxylase inhibitors in adult patients with Parkinsons disease and end-of-dose motor fluctuations.