Abnormalities of the Descending Inhibitory Nociceptive Pathway in Functional Motor Disorders.

BACKGROUND: Pain is a common disabling non-motor symptom affecting patients with functional motor disorders (FMD). OBJECTIVE: We aimed to explore ascending and descending nociceptive pathways with laser evoked potentials (LEPs) in FMD. METHODS: We studied a "bottom-up and top-down" noxious paradigm applying a conditioned pain modulation (CPM) protocol and recorded N2/P2 amplitude in 21 FMD and 20 controls following stimulation of both right arm and leg at baseline (BS) (bottom-up), during heterotopic noxious conditioning stimulation (HNCS) with ice test (top-down) and post-HNCS. RESULTS: We found a normal ascending pathway, but reduced CPM response (lower reduction of the N2/P2 amplitude) in FMD patients, by stimulating both upper and lower limbs. The N2/P2 amplitude ratio*100 (between the HNCS and BS) was significantly higher in patients with FMD than HC. CONCLUSIONS: Our results suggest that pain in FMD possibly reflects a descending pain inhibitory control impairment, therefore, providing a novel venue to explore the pathophysiology of pain in FMD. © 2024 International Parkinson and Movement Disorder Society.

Defect of the Endogenous Inhibitory Pain System in Idiopathic Restless Legs Syndrome: A Laser Evoked Potentials Study.

BACKGROUND: Restless legs syndrome (RLS) is a complex sensorimotor disorder. Symptoms worsen toward evening and at rest and are temporarily relieved by movement. Symptoms are perceived as painful in up to 45% of cases, and nociception system may be involved. OBJECTIVES: To assess the descending diffuse noxious inhibitory control in RLS patients. METHODS: Twenty-one RLS patients and twenty age and sex-matched healthy controls (HC) underwent a conditioned pain modulation protocol. Cutaneous heat stimuli were delivered via laser evoked potentials (LEPs) on the dorsum of the right hand (UL) and foot (LL). N2 and P2 latencies, N2/P2 amplitude and pain ratings (NRS) were recorded before (baseline), during, and after a heterotopic noxious conditioning stimulation (HNCS) application. The baseline/HNCS ratio was calculated for both UL and LL. RESULTS: N2 and P2 latencies did not vary between groups at each condition and limbs. Both groups showed a physiological N2/P2 amplitude and NRS reduction during the HNCS condition in UL and LL in comparison to baseline and post conditions (all, P < 0.003). Between-groups comparisons revealed a significant lower amplitude reduction in RLS at the N2/P2 amplitude during the HNCS condition only for LL (RLS, 13.6 µV; HC, 10.1 µV; P = 0.004). Such result was confirmed by the significant difference at the ratio (RLS, 69%, HC, 52.5%; P = 0.038). CONCLUSIONS: The lower physiological reduction during the HNCS condition at LL in RLS patients suggests a defect in the endogenous inhibitory pain system. Further studies should clarify the causal link of this finding, also investigating the circadian modulation of this paradigm. © 2023 International Parkinson and Movement Disorder Society.

Reduced Interoception Abilities in Patients with Restless Legs Syndrome.

Background: Restless legs syndrome (RLS) is a complex sensorimotor disorder occurring with a typical circadian fashion. Association with additional features, like alexithymia and nocturnal compulsive behaviors further complicates the framework. Objectives: To assess interoception in RLS. Methods: A total of 25 RLS patients and 28 controls underwent the heartbeat tracking task (interoceptive accuracy [IAC]). RLS symptoms' frequency, disturbance and duration, nocturnal behaviors, interoceptive awareness (IAW), alexithymia, depressive and anxiety symptoms were also collected. Results: RLS patients showed significant lower IAC (P = 0.0003) and IAW (P = 0.012), and reported more nocturnal eating behaviors (P < 0.001). IAC positively correlated with IAW (R = 0.32), and negatively correlated with age (R = -0.58). Nocturnal eating behavior negatively correlated with IAC (R = -0.44) and IAW (R = -0.50). Conclusions: RLS patients presented reduced interoceptive abilities correlating with higher nocturnal eating behaviors. Future studies are needed to explore the role of interoception in RLS pathophysiology, also in relation to other sensorimotor aspects.

REM sleep behavior disorder: Mimics and variants.

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia with dream-enactment behaviors occurring during REM sleep and associated with the lack of the physiological REM sleep muscle atonia. It can be isolated and secondary to other neurological or medical conditions. Isolated RBD heralds in most cases a neurodegenerative condition due to an underlying synucleinopathy and consequently its recognition is crucial for prognostic implications. REM sleep without atonia on polysomnography is a mandatory diagnostic criterion. Different conditions may mimic RBD, the most frequent being obstructive sleep apnea during sleep, non-REM parasomnia, and sleep-related hypermotor epilepsy. These diseases might also be comorbid with RBD, challenging the evaluation of disease severity, the treatment choices and the response to treatment evaluation. Video-PSG is the gold standard for a correct diagnosis and will distinguish between different or comorbid sleep disorders. Careful history taking together with actigraphy may give important clues for the differential diagnosis. The extreme boundaries of RBD might also be seen in more severe and complex conditions like status dissociatus or in the sleep disorders' scenario of anti IgLON5 disease, but in the latter both clinical and neurophysiological features will differ. A step-by-step approach is suggested to guide the differential diagnosis.