Restless legs syndrome: From clinic to personalized medicine.

Restless legs syndrome (RLS) is a common neurological sensorimotor disorder that impairs sleep, mood and quality of life. RLS is defined by an urge to move the legs at rest that increases in the evening and at night, and is frequently associated with metabolic and cardiovascular diseases. Symptoms frequency, age at RLS onset, severity, familial history and consequences of RLS vary widely between patients. A genetic susceptibility, iron deficiency, dopamine deregulation, and possible hypo-adenosinergic state may play a role in the pathophysiology of RLS. Polysomnographic recordings found often periodic leg movements during sleep and wakefulness in patients with RLS. RLS can be classified as primary or comorbid with major diseases: iron deficiency, renal, neurological, rheumatological and lung diseases. First-line treatments are low-dose dopamine agonists, and alpha-2-delta ligands depending on the clinical context, and second/third line opiates for pharmacoresistant forms of RLS. Augmentation syndrome is a serious complication of dopamine agonists and should be prevented by using the recommended low dose. Despite an increase in knowledge, RLS is still underdiagnosed, poorly recognized, resulting in substantial individual health burden and socioeconomic coast, and education is urgently needed to increase awareness of this disabling disorder.

Narcolepsies, update in 2023.

Narcolepsy type 1 (NT1) and type 2 (NT2), also known as narcolepsy with and without cataplexy, are sleep disorders that benefited from major scientific advances over the last two decades. NT1 is caused by the loss of hypothalamic neurons producing orexin/hypocretin, a neurotransmitter regulating sleep and wake, which can be measured in the cerebrospinal fluid (CSF). A low CSF level of hypocretin-1/orexin-A is a highly specific and sensitive biomarker, sufficient to diagnose NT1. Orexin-deficiency is responsible for the main NT1 symptoms: sleepiness, cataplexy, disrupted nocturnal sleep, sleep-related hallucinations, and sleep paralysis. In the absence of a lumbar puncture, the diagnosis is based on neurophysiological tests (nocturnal and diurnal) and the presence of the pathognomonic symptom cataplexy. In the revised version of the International Classification of sleep Disorders, 3rd edition (ICSD-3-TR), a sleep onset rapid eye movement sleep (REM) period (SOREMP) (i.e. rapid occurrence of REM sleep) during the previous polysomnography may replace the diurnal multiple sleep latency test, when clear-cut cataplexy is present. A nocturnal SOREMP is very specific but not sensitive enough, and the diagnosis of cataplexy is usually based on clinical interview. It is thus of crucial importance to define typical versus atypical cataplectic attacks, and a list of clinical features and related degrees of certainty is proposed in this paper (expert opinion). The time frame of at least three months of evolution of sleepiness to diagnose NT1 was removed in the ICSD-3-TR, when clear-cut cataplexy or orexin-deficiency are established. However, it was kept for NT2 diagnosis, a less well-characterized disorder with unknown clinical course and absence of biolo biomarkers; sleep deprivation, shift working and substances intake being major differential diagnoses. Treatment of narcolepsy is nowadays only symptomatic, but the upcoming arrival of non-peptide orexin receptor-2 agonists should be a revolution in the management of these rare sleep diseases.

French consensus: Pharmacoresistant restless legs syndrome.

Dopaminergic agonists, α2δ ligands and opioids are, as single-drug therapy, the first line treatment for restless legs syndrome (RLS/Willis-Ekbom disease). However, despite treatment efficacy, exacerbations of RLS may occur with overall worsening in symptoms severity, development of pain and symptoms spreading to other parts of the body, without meeting augmentation syndrome criteria. This development of "drug-resistant" RLS can cause pain, severe insomnia and psychiatric disorders that affect considerably patients' quality of life. The lack of French recommendations for this form of RLS leave physicians with few options to help patients with physical and emotional distress. Our group of neurological experts and sleep specialists proposes a diagnostic and therapeutic strategy to provide better care and appropriate treatment through searching for the organic, psychiatric and/or iatrogenic causes of drug resistance. Once a drug-resistant RLS diagnosis has been confirmed, we recommend an obligatory work-up including: a video-polysomnogram, a biological evaluation including iron status, standard numeration and C-reactive protein level. Treatment will be comorbidity-dependent: dopaminergic agonist would be recommended in case of depression or associated periodic leg movements, α2δ ligand in case of insomnia, complaint of pain, or general anxiety, in association with low-dose opioids if necessary. Strong opioids should be preferred for multiresistant RLS.