When compared with the HC, both LRRK2 and GBA NMCs had significantly
- Higher scores on the MDS-UPDRS total, Part I, II, III
- Lower MoCA scores
- Higher SCOPA-AUT scores
- These findings were present despite of lack of DAT deficit
- There was no difference in daytime sleepiness and RBD scores in either cohort compared to HC
Dx
| Clinical diagnosis | The International Classification of Sleep Disorders (ICSD-3) [1] (1) Repeated episodes of sleep-related vocalization and/or complex motor behaviors. (2) These behaviors are documented by polysomnography to occur during REM sleep or, based on clinical history of dream enactment, are presumed to occur during REM sleep. (3) Polysomnographic recording demonstrates REM sleep without atonia (RWA). (4) The disturbance is not better explained by another sleep disorder, mental disorder, medication or substance abuse. |
| Definite diagnosis | polysomnography (PSG), : excessive EMG activity during REM sleep on video-PSG assessment |
Screening tools of RBD
RBD screening questionnaire (RBDSQ)
- 10-item, patient self-rating instrument
- The maximum total score of the RBDSQ is 13 points.
- 점수 높으면 이상. mean RBDSQ score in the RBD group was 9.5 ±2.8 points compared with 4.6 ±3.0 points in control group 1 ((Stiasny-Kolster et al. 2007, PMID)
- Items 1 to 4 address the frequency and content of dreams and their relationship to nocturnal movements and behavior. Item 5 asks about self-injuries and injuries of the bed partner. Item 6 consists of four subitems assessing nocturnal motor behavior more specifically, e.g., questions about nocturnal vocalization, sudden limb movements, complex movements, or bedding items that fell down. Items 7 and 8 deal with nocturnal awakenings. Item 9 focuses on disturbed sleep in general and item 10 on the presence of any neurological disorder.
- Original
- In 2007, Stiany-Kolster
- Cut-off point to screen RBD
-
5 (Stiasny-Kolster et al. 2007, PMID), (Iwaki et al. 2019, PMID) (PPMI 2019 Annual meeting, see ppt)
-
below (Stiasny-Kolster et al. 2007, PMID)
TABLE 1. RBD Screening Questionnaire
| Question | Answer | |
|---|---|---|
| English | ||
| 1. | I sometimes have very vivid dreams. | yes/no |
| 2. | My dreams frequently have an aggressive or action-packed content. | yes/no |
| 3. | The dream contents mostly match my nocturnal behaviour. | yes/no |
| 4. | I know that my arms or legs move when I sleep. | yes/no |
| 5. | It thereby happened that I (almost) hurt my bed partner or myself. | yes/no |
| 6. | I have or had the following phenomena during my dreams: | |
| 6.1. | speaking, shouting, swearing, laughing loudly | yes/no |
| 6.2. | sudden limb movements, "fights" | yes/no |
| 6.3. | gestures, complex movements, that are useless during sleep, e.g., to wave, to salute, to frighten mosquitoes, falls off the bed | yes/no |
| 6.4. | things that fell down around the bed, e.g., bedside lamp, book, glasses | yes/no |
| 7. | It happens that my movements awake me. | yes/no |
| 8. | After awakening I mostly remember the content of my dreams well. | yes/no |
| 9. | My sleep is frequently disturbed. | yes/no |
| 10. | I have/had a disease of the nervous system (e.g., stroke, head trauma, parkinsonism, RLS, narcolepsy, depression, epilepsy, inflammatory disease of the brain), which? | yes/no |
RBDSQ-J
- {Miyamoto, 2009 #1435} (AUC) = 0.966. In healthy subjects (table1), sensitivity (88.5%), specificity (96.9%), positive predictive value (PPV; 97.9%), and negative predictive value (NPV; 91.4%),
RBDQ-HQ (REM sleep behavior disorder questionnaire—Hong Kong)
- Original
- {Li, 2010 #1434, Questioannire included}
- 13 items,
- The questionnaire was originally developed in Chinese, and the English version was translated by the authors.
- Moderate sensitivity (82.2%), specificity (86.9%), positive predictive value (PPV; 86.3%), and negative predictive value (NPV; 83.0%),
RBDQ-JP
- {Sasai, 2012 #1433} sensitivity of 97.2%, specificity of 97.5%, PPV of 97.5%, NPV of 97.2%, AUC = 0.99) (authors explain that this better performance vs original may be separating out Obstructive sleep apnea syndrome in this study.
Mechanism
cxxvii) the subcoeruleus nucleus (=,
- = SubC =sub-laterodorsal nucleus,
- A reticular nucleus in the pontine hindbrain
- Is composed of REM-active neurons—cells that are predominantly active during episodes of REM sleep (7–11). The majority of REM-active SubC cells are glutamatergic (12),.
- Pharmacological activation of SubC cells can induce REM sleep motor atonia (6–13); whereas, SubC lesions can prevent REM sleep atonia and/or reduce REM sleep amounts (7, 8).
- SubC cells are thought to induce REM sleep muscle paralysis by recruiting GABA/glycine neurons in the ventromedial medulla (VMM) and spinal cord (Figures 1 and 2). These cells produce motor atonia during REM sleep by inhibiting skeletal motoneurons (8, 13–16).
cxxviii) the pedunculopontine nucleus.
cxxix) the gigantocellular reticular nucleus,
- a subregion of the medullary reticular formation.[1]
- Cholinergic neurons are involved in RBD
Pathology/Imaging
| N | Post-mortem | |||
|---|---|---|---|---|
| Pathology | (Boeve et al. 2007, PMID 17157062) (Boeve et al. 2007, PMID 17157062) | RBD only | 1 | Lewy body disease, but no significant neuronal loss or gliosis was present in the SN or LC. |
| Pathology | (Iranzo et al. 2013, PMID 23562390) (Iranzo et al. 2013, PMID 23562390) | RBD+PD (2), RBD+DLB (1) | 3 | all three patients moderate to-severe neuronal loss, gliosis, Lewy bodies, and Lewy neurites in the brainstem and limbic system, and to a lesser extent in cortical areas (table 2, figures 3 and 4). Particularly, these changes were noted in the structures that mediate REM sleep atonia:
|
| Pathology | (García-Lorenzo, 2013 #1878) 2nd | In humans, rare cases of lesions in the pontine and midbrain tegmentum resulting in RBD were reported (Boeve et al., 2007; Iranzo and Aparicio, 2009). | ||
| Pathology | (García-Lorenzo, 2013 #1878) 2nd | A patient with Parkinson's disease and RBD had numerous alpha-syn deposits within the locus coreuleus/subcoeruleus melanized cells on brain examination (Arnulf et al., 2000). Among | ||
| Pathology? Imaging? | Sleep. 2019 Jun 11;42(6). pii: zsz062. doi: 10.1093/sleep/zsz062. Brain atrophy in Parkinson's disease with polysomnography-confirmed REM sleep behavior disorder. 내용 확인 필요 | |||
| Imaging | (García-Lorenzo, 2013 #1878) | compared 24 patients with Parkinson's disease and rapid eye movement sleep behaviour disorder, 12 patients without rapid eye movement sleep behaviour disorder and 19 age- and gender-matched healthy volunteers. | NEUROmelanin-MRI | ↓ signal in neuromelanin-MRI in LC The signal correlated with RBD severity (REM sleep without atonia) with r=~0.5 |
idiopathic RBD (=RBD only=RBD without PD, etc)
| N | Post-mortem | |
|---|---|---|
| (Boeve et al. 2007, PMID 17157062) | 1 | Lewy body disease, but no significant neuronal loss or gliosis was present in the SN or LC |
| (Iranzo, et al. 2013) | 4 | all four had decreased striatal DAT uptake, one had SN hyperechogenicity on TCS, and two had impaired olfaction |
animal model
| N | ||
|---|---|---|
| (citation) | aSyn PFF based mouse model | we injected preformed α-syn fibrils into the sublaterodorsal tegmental nucleus and performed regular polysomnographic recordings and parkinsonian behavioural and histopathological studies in these mice. As a result, we recapitulated RBD-like behaviours in the mice and further showed that the α-synopathy and neuron degeneration identified within the sublaterodorsal tegmental nucleus acted as the neuropathological substrates. |
→ RBD
- Penetrance (GBA → RBD)
- No report?
- Odds Ratio (GBA in RBD)
- (Gan-Or et al. 2015, PMID 26401515) idiopathic RBD patients (n = 265) and our in-house controls (n = 189). (OR) of 2.63 (95% CI 1.30–5.29, P = 0.0052) for all variants, and OR of 3.46 (95% CI 1.40–8.56, P = 0.0045) for the pathogenic variants. We further compared the frequency of GBA mutations in the RBD cohort to a pooled control population from all studies that performed full sequencing of the GBA gene in European controls (Table S1). In this pooled control group, 40/2240 (1.8%) individuals were
Uncertain Spans
- The first row label of the Pathology/Imaging table appears blank in the source; whether this is intentional (continuation of an above merged cell from the previous photo) or simply an unfilled cell could not be determined from this image alone.
- “Stiany-Kolster” in the RBDSQ Original sub-bullet is reproduced as printed; in surrounding bullets the same author appears as “Stiasny-Kolster” — the difference is preserved without correction because both spellings are visible in the source.
- The “(citation)” placeholder in the animal-model table reflects an empty citation cell whose exact content (likely a reference key) was clipped under the navigation pane on this photo.