Ethical Considerations for Identifying Individuals in the Prodromal/Early Phase of Parkinson's Disease: A Narrative Review.

The ability to identify individuals in the prodromal phase of Parkinson's disease has improved in recent years, raising the question of whether and how those affected should be informed about the risk of future disease. Several studies investigated prognostic counselling for individuals with isolated REM sleep behavior disorder and have shown that most patients want to receive information about prognosis, but autonomy and individual preferences must be respected. However, there are still many unanswered questions about risk disclosure or early diagnosis of PD, including the impact on personal circumstances, cultural preferences and specific challenges associated with different profiles of prodromal symptoms, genetic testing or biomarker assessments.

Plasma biomarkers of Alzheimer's disease in the continuum of dementia with Lewy bodies.

Introduction: Patients with dementia with Lewy bodies (DLB) may have Alzheimers disease (AD) pathology that can be detected by plasma biomarkers. Our objective was to evaluate plasma biomarkers of AD and their association with positron emission tomography (PET) biomarkers of amyloid and tau deposition in the continuum of DLB, starting from prodromal stages of the disease.

Methods: The cohort included patients with isolated rapid eye movement (REM) sleep behavior disorder (iRBD), mild cognitive impairment with Lewy bodies (MCI-LB), or DLB, with a concurrent blood draw and PET scans.

Wake and non-rapid eye movement sleep dysfunction is associated with colonic neuropathology in Parkinson's disease.

Study Objectives: The body-first Parkinson's disease (PD) hypothesis suggests initial gut Lewy body pathology initially propagates to the pons before reaching the substantia nigra, and subsequently progresses to the diencephalic and cortical levels, a disease course presumed to likely occur in PD with rapid eye movement sleep behavior disorder (RBD). We aimed to explore the potential association between colonic phosphorylated alpha-synuclein histopathology (PASH) and diencephalic or cortical dysfunction evidenced by non-rapid eye movement (NREM) sleep and wakefulness polysomnographic markers.

Methods: In a study involving 43 patients with PD who underwent clinical examination, rectosigmoidoscopy, and polysomnography, we detected PASH on colonic biopsies using whole-mount immunostaining.

Contemporary diagnostic visual and automated polysomnographic REM sleep without atonia thresholds in isolated REM sleep behavior disorder.

Study Objectives: Accurate diagnosis of isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is crucial due to its injury potential and neurological prognosis. We aimed to analyze visual and automated REM sleep without atonia (RSWA) diagnostic thresholds applicable in varying clinical presentations in a contemporary cohort of patients with iRBD using submentalis (SM) and individual bilateral flexor digitorum superficialis (FDS) and anterior tibialis electromyography limb recordings during polysomnography.

Methods: We analyzed RSWA in 20 patients with iRBD and 20 age-, REM-, apnea-hypopnea index-matched controls between 2017 and 2022 for phasic burst durations, density of phasic, tonic, and "any" muscle activity (number of 3-second mini-epochs containing phasic or tonic muscle activity divided by the total number of REM sleep 3-second mini-epochs), and automated Ferri REM atonia index (RAI).

The Accuracy and Reliability of Sleep Staging and Sleep Biomarkers in Patients with Isolated Rapid Eye Movement Sleep Behavior Disorder.

Purpose: This study aimed to establish the diagnostic accuracy of a previously validated sleep staging system in patients with probable isolated REM sleep behavior disorder (iRBD), and to compare physicians' diagnoses of iRBD based on REM sleep without atonia (RSWA) to non-REM hypertonia (NRH), a sleep measure independently associated with Parkinsonian spectrum disorders.

Patients And Methods: Twenty-six patients with a history of dream enactment behavior underwent a diagnostic PSG with simultaneous Sleep Profiler (SP) acquisition at two sites. PSG and SP records were sleep staged, and two sleep neurologists independently diagnosed iRBD based on the presence or absence of polysomnographic identified RSWA.

Treatment with the novel TAAR1 agonist ulotaront is associated with reductions in quantitative polysomnographic REM sleep without atonia in healthy human subjects: Results of a post-hoc analysis.

Background: Isolated REM sleep behavior disorder (RBD) is a potentially injurious parasomnia lacking an established treatment. Ulotaront is a trace amine-associated receptor 1 (TAAR1) agonist with 5-HT receptor agonist activity that has demonstrated efficacy in patients with schizophrenia. In a single dose challenge study in humans, ulotaront 50 mg demonstrated significant REM suppressant effects.

Clinical considerations for the diagnosis of idiopathic hypersomnia.

Idiopathic hypersomnia is a sleep disorder of neurologic origin characterized by excessive daytime sleepiness, with sleep inertia, long, unrefreshing naps, and prolonged nighttime sleep being key symptoms in many patients. Idiopathic hypersomnia is described in the International Classification of Sleep Disorders, 3rd Edition as a central disorder of hypersomnolence with distinct clinical features and diagnostic criteria; however, confirming the diagnosis of idiopathic hypersomnia is often challenging. Diagnosis of idiopathic hypersomnia is based on objective sleep testing and the presence of associated clinical features but may be difficult for clinicians to recognize and correctly diagnose because of its low prevalence, clinical heterogeneity, and symptoms, which are similar to those of other sleep disorders.

Patient values and preferences regarding prognostic counseling in isolated REM sleep behavior disorder.

Study Objectives: Isolated REM sleep behavior disorder (iRBD) carries a high lifetime risk for phenoconversion to a defined neurodegenerative disease (NDD) including Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. We aimed to examine iRBD patient values and preferences regarding prognostic counseling.

Methods: One hundred thirteen iRBD patient participants enrolled in the Mayo Clinic iRBD Patient Registry were sent an email survey concerning their values and preferences concerning NDD prognostic counseling and their experiences following diagnosis with iRBD.

Cognition and driving ability in isolated and symptomatic REM sleep behavior disorder.

Study Objectives: To analyze cognitive deficits leading to unsafe driving in patients with REM Sleep Behavior Disorder (RBD), strongly associated with cognitive impairment and synucleinopathy-related neurodegeneration.

Methods: Twenty isolated RBD (iRBD), 10 symptomatic RBD (sRBD), and 20 age- and education-matched controls participated in a prospective case-control driving simulation study. Group mean differences were compared with correlations between cognitive and driving safety measures.

Abnormal rapid eye movement sleep atonia control in chronic post-traumatic stress disorder.

Study Objectives: Post-traumatic stress disorder (PTSD) and rapid eye movement (REM) sleep behavior disorder (RBD) share some common features including prominent nightmares and sleep disturbances. We aimed to comparatively analyze REM sleep without atonia (RSWA) between patients with chronic PTSD with and without dream enactment behavior (DEB), isolated RBD (iRBD), and controls.

Methods: In this retrospective study, we comparatively analyzed 18 PTSD with DEB (PTSD+DEB), 18 PTSD without DEB, 15 iRBD, and 51 controls matched for age and sex.

Confirmation of Cause of Death Via Comprehensive Autopsy and Whole Exome Molecular Sequencing in People With Epilepsy and Sudden Unexpected Death.

Background Sudden cardiac arrest is the leading mode of death in the United States. Epilepsy affects 1% of Americans; yet epidemiological data show a prevalence of 4% in cases of sudden cardiac arrest. Sudden unexpected death in epilepsy (SUDEP) may share features with sudden cardiac arrest.

QT prolongation in patients with index evaluation for seizure or epilepsy is predictive of all-cause mortality.

Background: Refractory epilepsy confers a considerable lifetime risk of sudden unexplained death in epilepsy (SUDEP). Mechanisms may overlap with sudden cardiac death (SCD), particularly regarding QTc prolongation. Guidelines in the United States do not mandate the use of electrocardiography (ECG) in diagnostic evaluation of seizures or epilepsy.

Video-polysomnography procedures for diagnosis of rapid eye movement sleep behavior disorder (RBD) and the identification of its prodromal stages: guidelines from the International RBD Study Group.

Video-polysomnography (v-PSG) is essential for diagnosing rapid eye movement (REM) sleep behavior disorder (RBD). Although there are current American Academy of Sleep Medicine standards to diagnose RBD, several aspects need to be addressed to achieve harmonization across sleep centers. Prodromal RBD is a stage in which symptoms and signs of evolving RBD are present, but do not yet meet established diagnostic criteria for RBD.

Differential Impact on Isolated REM Sleep without Atonia by Varying Antidepressant Therapies.

Background: REM sleep without atonia (RSWA) is characterized by increased phasic or tonic muscle activity in electromyography channels during polysomnography and usually causes REM sleep behaviour disorder, but RSWA also exists within healthy populations without dream-enactment behaviour, especially in psychiatric populations receiving antidepressant therapies. Evidence for differential impact of antidepressants on RSWA, and whether RSWA persists or resolves following changes in antidepressant therapy, remains limited.

Case: We present a 56-year-old woman with depression undergoing 3 polysomnograms while receiving 3 different distinct antidepressants.

Restless Legs Syndrome: Contemporary Diagnosis and Treatment.

Restless legs syndrome (RLS) is characterized by an uncomfortable urge to move the legs while at rest, relief upon movement or getting up to walk, and worsened symptom severity at night. RLS may be primary (idiopathic) or secondary to pregnancy or a variety of systemic disorders, especially iron deficiency, and chronic renal insufficiency. Genetic predisposition with a family history is common.

Speech Biomarkers in Rapid Eye Movement Sleep Behavior Disorder and Parkinson Disease.

Objective: This multilanguage study used simple speech recording and high-end pattern analysis to provide sensitive and reliable noninvasive biomarkers of prodromal versus manifest α-synucleinopathy in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) and early-stage Parkinson disease (PD).

Methods: We performed a multicenter study across the Czech, English, German, French, and Italian languages at 7 centers in Europe and North America. A total of 448 participants (337 males), including 150 with iRBD (mean duration of iRBD across language groups 0.