Latency To N3 Interruption In Arousal Disorders.

STUDY OBJECTIVES: To help expert witnesses in criminal cases using the "sleepwalking defense", we studied the time of first and last interruptions from stage N3 in patients with arousal disorders, including sexsomnia, as well as their determinants. METHODS: The epochs of lights off, sleep onset, first N3 interruption (with and without behaviors), and last N3 interruption were determined by videopolysomnography on two consecutive nights in 163 adults with disorders of arousal, including 46 with and 117 without sexsomnia. RESULTS: The first N3 interruption (independently of concomitant behavior) occurred as early as 8 minutes after sleep onset and within 100 minutes of falling asleep in 95% of cases. The first motor arousal from N3 occurred as early as 25 min after lights off time, a timing more variable between participants (between 30 and 60 minutes after lights off time in 25% of participants and within 60 minutes of falling asleep in 50%). These latencies did not differ between the groups with and without sexsomnia. No correlation was found between these latencies and the young age, sex or clinical severity. The latency of motor arousals was shorter when they were associated with a fast-wave EEG profile and were not preceded by another type of N3 arousal. CONCLUSION: The first motor arousal may occur early in the night in patients with arousal disorders, with or without sexsomnia, suggesting that abnormal behaviors occurring as early as 25 min after lights off time in clinical and criminal cases can be a parasomnia manifestation.

Idiopathic hypersomnia and Kleine-Levin syndrome.

Idiopathic hypersomnia (IH) and Kleine-Levin syndrome (KLS) are rare disorders of central hypersomnolence of unknown cause, affecting young people. However, increased sleep time and excessive daytime sleepiness (EDS) occur daily for years in IH, whereas they occur as relapsing/remitting episodes associated with cognitive and behavioural disturbances in KLS. Idiopathic hypersomnia is characterized by EDS, prolonged, unrefreshing sleep at night and during naps, and frequent morning sleep inertia, but rare sleep attacks, no cataplexy and sleep onset in REM periods as in narcolepsy. The diagnosis requires: (i) ruling out common causes of hypersomnolence, including mostly sleep apnea, insufficient sleep syndrome, psychiatric hypersomnia and narcolepsy; and (ii) obtaining objective EDS measures (mean latency at the multiple sleep latency test≤8min) or increased sleep time (sleep time>11h during a 18-24h bed rest). Treatment is similar to narcolepsy (except for preventive naps), including adapted work schedules, and off label use (after agreement from reference/competence centres) of modafinil, sodium oxybate, pitolisant, methylphenidate and solriamfetol. The diagnosis of KLS requires: (i) a reliable history of distinct episodes of one to several weeks; (ii) episodes contain severe hypersomnia (sleep>15h/d) associated with cognitive impairment (mental confusion and slowness, amnesia), derealisation, major apathy or disinhibited behaviour (hypersexuality, megaphagia, rudeness); and (iii) return to baseline sleep, cognition, behaviour and mood after episodes. EEG may contain slow rhythms during episodes, and rules out epilepsy. Functional brain imaging indicates hypoactivity of posterior associative cortex and hippocampus during symptomatic and asymptomatic periods. KLS attenuates with time when starting during teenage, including less frequent and less severe episodes. Adequate sleep habits, avoidance of alcohol and infections, as well as lithium and sometimes valproate (off label, after agreement from reference centres) help reducing the frequency and severity of episodes, and IV methylprednisolone helps reducing long (>30d) episode duration.

REM behavior disorder: When Parkinson's disease meets Morpheus.

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by the absence of normal muscle atonia during REM sleep, resulting in excessive motor activity while dreaming. RBD can be classified as isolated which is the strongest clinical marker of prodromal synucleinopathy, or secondary, associated with other neurological diseases, mainly Parkinson's disease (PD) and dementia with Lewy bodies. The diagnosis of RBD must be systematically documented by a video polysomnography in the case of isolated RBD. PD associated with RBD may represent a distinct phenotype compared to PD without RBD, indicating a more severe and widespread synucleinopathy. Clinically, it is associated with poorer motor and cognitive performance, more severe non-motor symptoms, and faster disease progression. Imaging studies have revealed broader brain damage and significant alterations in cerebral metabolism and neurotransmission in PD patients with RBD. The management of RBD involves safety precautions and pharmacotherapy. Safety measures aim to minimize the risk of injury during RBD episodes and include creating a safe sleeping environment and separating the patient from their bed partner if necessary. Pharmacotherapy options include clonazepam and melatonin. Clonazepam must be cautiously prescribed in older patients due to potential side effects.

Kleine-Levin syndrome: A neuropsychiatric disorder.

Kleine-Levin syndrome (KLS) is a rare, relapsing-remitting disease that affects mostly adolescents. It is characterized by episodes lasting from 1 to several weeks, and comprises neurological (hypersomnia, confusion, slowness, amnesia) and neuropsychiatric symptoms (derealization and apathy). Some psychiatric symptoms (megaphagia, hypersexuality, anxiety, depressed mood, hallucinations, delusions) arise during episodes, albeit less frequently, while patients are normal between episodes. However, sudden severe (>18h/day of sleep) and recurrent hypersomnia helps to differentiate KLS from other psychiatric mimics. Derealization, the striking feeling of unreality or of being in a dream-like environment, is strongly associated with hypoperfusion of the associative temporoparietal junction cortex, whereas apathy is almost complete loss of autoactivation: teenagers stop using their cell phones and their only spontaneous initiative is to sleep. The cause of KLS is not known, but evidence suggests it could be a recurrent inflammatory encephalitis. Up to 5% of cases are familial, although no abnormal gene has yet been found. Hypersomnia episodes tend to become less frequent and to disappear with advancing age. However, 28% of patients have long-lasting episodes (>30 days), and around 15% have no signs of recovery after >20 years of living with the disorder. Patients' cognitive and psychiatric status should be regularly checked during asymptomatic periods, as 20-40% develop long-term mild cognitive impairment or mood disorders. Lithium therapy is beneficial for reducing episode frequency, and intravenous steroids can reduce the duration of long episodes.

"De-novo" consultation: Evaluation of an outpatient's clinic dedicated to early diagnosis of parkinsonian syndromes.

INTRODUCTION: In the absence of specific clinical signs, imaging or biomarkers, the differential diagnosis of degenerative parkinsonian syndromes may be difficult at early stages of the disease. To reduce the risk of misdiagnosis or delayed diagnosis and referral to multiple medical centers at disease onset, easier access to expert centers should be available. To improve the initial care of parkinsonian patients, the Parkinson's disease Expert Center (PEC) at Pitié-Salpêtrière Academic Hospital has set up a specific outpatients clinic with short waiting times dedicated to the diagnosis of early Parkinson's disease and related disorders. METHODS: The PEC setup first identifies requests for diagnostic confirmation of parkinsonian syndromes, then specific outpatients clinic visits are scheduled weekly, with examinations carried out by neurologists at the PEC on a rotating schedule. Data from the first year of the new procedure were analyzed retrospectively through self-administered questionnaires sent to patients seen during this period. The main outcomes were to confirm the ability to keep to short delays for patients' examinations and to assess patients' satisfaction with the setup. RESULTS: Both study outcomes were achieved. The creation of an outpatients clinic dedicated to the early diagnosis of parkinsonian syndromes allowed shorter delays before the first examination of 5 weeks instead of several months. Keeping to the weekly schedule and limited time taken for each visit was also achieved. Following this initial outpatients visit, diagnosis of a parkinsonian syndrome was clinically confirmed or further specified in 80% of cases. A survey of patients' satisfaction showed a rate of over 91% in terms of the timing and course of clinical examinations at our PEC. DISCUSSION/CONCLUSION: This study of our quality-improvement program for Parkinson's disease management has shown that specific consultations with shorter waiting times aiming to allow early specialized assessment of parkinsonian syndromes is beneficial for patients and reduces the risk of delayed diagnoses.