OBJECTIVE: This study assessed the relationship between speech and language impairment and outcome in a multicenter cohort of isolated/idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD). METHODS: Patients with iRBD from 7 centers speaking Czech, English, German, French, and Italian languages underwent a detailed speech assessment at baseline. Story-tale narratives were transcribed and linguistically annotated using fully automated methods based on automatic speech recognition and natural language processing algorithms, leading to the 3 distinctive linguistic and 2 acoustic patterns of language deterioration and associated composite indexes of their overall severity. Patients were then prospectively followed and received assessments for parkinsonism or dementia during follow-up. The Cox proportional hazard was performed to evaluate the predictive value of language patterns for phenoconversion over a follow-up period of 5 years. RESULTS: Of 180 patients free of parkinsonism or dementia, 156 provided follow-up information. After a mean follow-up of 2.7 years, 42 (26.9%) patients developed neurodegenerative disease. Patients with higher severity of linguistic abnormalities (hazard ratio [HR = 2.35]) and acoustic abnormalities (HR = 1.92) were more likely to develop a defined neurodegenerative disease, with converters having lower content richness (HR = 1.74), slower articulation rate (HR = 1.58), and prolonged pauses (HR = 1.46). Dementia-first (n = 16) and parkinsonism-first with mild cognitive impairment (n = 9) converters had higher severity of linguistic abnormalities than parkinsonism-first with normal cognition converters (n = 17). INTERPRETATION: Automated language analysis might provide a predictor of phenoconversion from iRBD into synucleinopathy subtypes with cognitive impairment, and thus can be used to stratify patients for neuroprotective trials. ANN NEUROL 2024;95:530-543.
BACKGROUND: Speech dysfunction represents one of the initial motor manifestations to develop in Parkinson's disease (PD) and is measurable through smartphone. OBJECTIVE: The aim was to develop a fully automated and noise-resistant smartphone-based system that can unobtrusively screen for prodromal parkinsonian speech disorder in subjects with isolated rapid eye movement sleep behavior disorder (iRBD) in a real-world scenario. METHODS: This cross-sectional study assessed regular, everyday voice call data from individuals with iRBD compared to early PD patients and healthy controls via a developed smartphone application. The participants also performed an active, regular reading of a short passage on their smartphone. Smartphone data were continuously collected for up to 3 months after the standard in-person assessments at the clinic. RESULTS: A total of 3525 calls that led to 5990 minutes of preprocessed speech were extracted from 72 participants, comprising 21 iRBD patients, 26 PD patients, and 25 controls. With a high area under the curve of 0.85 between iRBD patients and controls, the combination of passive and active smartphone data provided a comparable or even more sensitive evaluation than laboratory examination using a high-quality microphone. The most sensitive features to induce prodromal neurodegeneration in iRBD included imprecise vowel articulation during phone calls (P = 0.03) and monopitch in reading (P = 0.05). Eighteen minutes of speech corresponding to approximately nine calls was sufficient to obtain the best sensitivity for the screening. CONCLUSION: We consider the developed tool widely applicable to deep longitudinal digital phenotyping data with future applications in neuroprotective trials, deep brain stimulation optimization, neuropsychiatry, speech therapy, population screening, and beyond. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
- MeSH
- biologické markery MeSH
- chytrý telefon * MeSH
- hlas fyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- Parkinsonova nemoc * patofyziologie komplikace MeSH
- parkinsonské poruchy patofyziologie MeSH
- porucha chování v REM spánku * patofyziologie diagnóza MeSH
- poruchy řeči etiologie MeSH
- prodromální symptomy MeSH
- průřezové studie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The neurodegenerative synucleinopathies, including Parkinson's disease and dementia with Lewy bodies, are characterized by a typically lengthy prodromal period of progressive subclinical motor and non-motor manifestations. Among these, idiopathic REM sleep behaviour disorder is a powerful early predictor of eventual phenoconversion, and therefore represents a critical opportunity to intervene with neuroprotective therapy. To inform the design of randomized trials, it is essential to study the natural progression of clinical markers during the prodromal stages of disease in order to establish optimal clinical end points. In this study, we combined prospective follow-up data from 28 centres of the International REM Sleep Behavior Disorder Study Group representing 12 countries. Polysomnogram-confirmed REM sleep behaviour disorder subjects were assessed for prodromal Parkinson's disease using the Movement Disorder Society criteria and underwent periodic structured sleep, motor, cognitive, autonomic and olfactory testing. We used linear mixed-effect modelling to estimate annual rates of clinical marker progression stratified by disease subtype, including prodromal Parkinson's disease and prodromal dementia with Lewy bodies. In addition, we calculated sample size requirements to demonstrate slowing of progression under different anticipated treatment effects. Overall, 1160 subjects were followed over an average of 3.3 ± 2.2 years. Among clinical variables assessed continuously, motor variables tended to progress faster and required the lowest sample sizes, ranging from 151 to 560 per group (at 50% drug efficacy and 2-year follow-up). By contrast, cognitive, olfactory and autonomic variables showed modest progression with higher variability, resulting in high sample sizes. The most efficient design was a time-to-event analysis using combined milestones of motor and cognitive decline, estimating 117 per group at 50% drug efficacy and 2-year trial duration. Finally, while phenoconverters showed overall greater progression than non-converters in motor, olfactory, cognitive and certain autonomic markers, the only robust difference in progression between Parkinson's disease and dementia with Lewy bodies phenoconverters was in cognitive testing. This large multicentre study demonstrates the evolution of motor and non-motor manifestations in prodromal synucleinopathy. These findings provide optimized clinical end points and sample size estimates to inform future neuroprotective trials.
- MeSH
- biologické markery MeSH
- demence s Lewyho tělísky * diagnóza MeSH
- lidé MeSH
- Parkinsonova nemoc * komplikace diagnóza MeSH
- porucha chování v REM spánku * diagnóza MeSH
- prodromální symptomy MeSH
- progrese nemoci MeSH
- prospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- MeSH
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- neurodegenerativní nemoci diagnóza klasifikace komplikace MeSH
- obstrukční spánková apnoe diagnóza etiologie komplikace MeSH
- parasomnie spojené s REM spánkem * diagnóza klasifikace patofyziologie terapie MeSH
- parasomnie klasifikace MeSH
- porucha chování v REM spánku diagnóza klasifikace patofyziologie terapie MeSH
- posttraumatická stresová porucha etiologie komplikace MeSH
- senioři MeSH
- sny psychologie MeSH
- syndrom neklidných nohou diagnóza MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- lidé MeSH
- polysomnografie MeSH
- porucha chování v REM spánku * komplikace diagnóza MeSH
- spánek REM MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- komentáře MeSH
Parasomnie sú poruchy spánku, z nich niektoré majú väzbu na určité spánkové štádium. NREM (non‐rapid eye movement) parasomnie - tiež nazývané ako poruchy prebúdzania z NREM spánku - sú somnambulizmus, pavor nocturnus, prebúdzanie so zmätenosťou. Poväčšine majú benigný charakter, najvačším nebezpečenstvom je možnosť vzniku tramatu následkom epizódy parasomnie. Najčastejšie vznikajú v detstve a so vzrastajúcim vekom zanikajú. Ak vzniknú v dospelosti, môže to byť na podklade psychopatológie, asociované sú s úzkostne‐depresívnou symptomatikou alebo abúsom návykových látok či alkoholu. K REM (rapid eye movement) parasomniám patria nočné mory, rekurentná izolovaná spánková paralýza a porucha chovania v REM spánku Občasné nočné mory sa vyskytujú vo väčšine detskej populácie, pri vysokej frekvencii epizód s ťažko dysforickými snami, môžeme hovoriť o poruche s nočnými morami. V dospelosti je táto porucha asociovaná s komorbidnou psychopatológiou, najmä postrtaumatickou stresovou poruchou. Porucha chovania v REM spánku má vysokú koreláciu so synukleinopatiami, môže sa objaviť ako prvý príznak neurodegeneratívneho ochorenia, niekedy až roky pred prvými typickými symptómami daného ochorenia.
Parasomnias are sleep disorders, some of which are connected to specific sleep phases. Among NREM (non-rapid eye movement) parasomnias belong somnambulism or sleep walking, pavor nocturnus or sleep terrors, confusional arousal. Most of the time they are bening, the biggest danger is occurrence of injuries as a consequence of episode of parasomnia. The onset is most common in childhood and they disappear with age. The onset is in adulthood can be due to psychopathology, based on research there is association with anxiety and depressive disorders or with alcoholism or substance abuse. Among REM (rapid eye movement) parasomnias belong nightmare disorder, recurrent isolated sleep paralysis and REM sleep behavior disorder (RBD). Occasional nightmares occur in most of children, if the frequency of the episodes is too high and the dreams are quite distressing, we can talk about nightmare disorder. In adulthood it ́s associated with comorbid psychopathology, most commonly post-traumatic stress disorder. REM sleep behavior disorder has high correlation with synucleinopathies. It can be one of the first symptoms of neurodegenerative disease, sometimes years before disease-specific symptoms appear.
- MeSH
- lidé MeSH
- parasomnie * klasifikace patofyziologie MeSH
- porucha chování v REM spánku diagnóza patofyziologie MeSH
- poruchy příjmu potravy diagnóza terapie MeSH
- poruchy probouzení ze spánku diagnóza patofyziologie terapie MeSH
- somnambulismus patofyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND: PSAP encodes saposin C, the co-activator of glucocerebrosidase, encoded by GBA. GBA mutations are associated with idiopathic/isolated REM sleep behavior disorder (iRBD), a prodromal stage of synucleinopathy. OBJECTIVE: To examine the role of PSAP mutations in iRBD. METHODS: We fully sequenced PSAP and performed Optimized Sequence Kernel Association Test in 1,113 iRBD patients and 2,324 controls. We identified loss-of-function (LoF) mutations, which are very rare in PSAP, in three iRBD patients and none in controls (uncorrected p = 0.018). RESULTS: Two variants were stop mutations, p.Gln260Ter and p.Glu166Ter, and one was an in-frame deletion, p.332_333del. All three mutations have a deleterious effect on saposin C, based on in silico analysis. In addition, the two carriers of p.Glu166Ter and p.332_333del mutations also carried a GBA variant, p.Arg349Ter and p.Glu326Lys, respectively. The co-occurrence of these extremely rare PSAP LoF mutations in two (0.2%) GBA variant carriers in the iRBD cohort, is unlikely to occur by chance (estimated co-occurrence in the general population based on gnomAD data is 0.00035%). Although none of the three iRBD patients with PSAP LoF mutations have phenoconverted to an overt synucleinopathy at their last follow-up, all manifested initial signs suggestive of motor dysfunction, two were diagnosed with mild cognitive impairment and all showed prodromal clinical markers other than RBD. Their probability of prodromal PD, according to the Movement Disorder Society research criteria, was 98% or more. CONCLUSION: These results suggest a possible role of PSAP variants in iRBD and potential genetic interaction with GBA, which requires additional studies.
BACKGROUND: Patients with synucleinopathies frequently display language abnormalities. However, whether patients with isolated rapid eye movement sleep behavior disorder (iRBD) have prodromal language impairment remains unknown. OBJECTIVE: We examined whether the linguistic abnormalities in iRBD can serve as potential biomarkers for conversion to synucleinopathy, including the possible effect of mild cognitive impairment (MCI), speaking task, and automation of analysis procedure. METHODS: We enrolled 139 Czech native participants, including 40 iRBD without MCI and 14 iRBD with MCI, compared with 40 PD without MCI, 15 PD with MCI, and 30 healthy control subjects. Spontaneous discourse and story-tale narrative were transcribed and linguistically annotated. A quantitative analysis was performed computing three linguistic features. Human annotations were compared with fully automated annotations. RESULTS: Compared with control subjects, patients with iRBD showed poorer content density, reflecting the reduction of content words and modifiers. Both PD and iRBD subgroups with MCI manifested less occurrence of unique words and a higher number of n-grams repetitions, indicating poorer lexical richness. The spontaneous discourse task demonstrated language impairment in iRBD without MCI with an area under the curve of 0.72, while the story-tale narrative task better reflected the presence of MCI, discriminating both PD and iRBD subgroups with MCI from control subjects with an area under the curve of up to 0.81. A strong correlation between manually and automatically computed results was achieved. CONCLUSIONS: Linguistic features might provide a reliable automated method for detecting cognitive decline caused by prodromal neurodegeneration in subjects with iRBD, providing critical outcomes for future therapeutic trials. © 2022 International Parkinson and Movement Disorder Society.
V průběhu spánku se může objevit celá řada záchvatových motorických projevů s různou etiologií. Při jejich hodnocení je klíčové zejména odlišení epileptických záchvatů od jiných poruch spánku. Epileptické záchvaty ve spánku jsou relativně časté a v přibližně 12 % jsou téměř výhradně vázány na spánek. Nejčastějším typem epileptických záchvatů ve spánku jsou fokální hyperkinetické záchvaty v rámci tzv. na spánek vázané hypermotorické epilepsie (sleep-related hypermotor epilepsy - SHE), dříve známé pod názvem noční frontální epilepsie, přičemž po stránce etiologie a lokalizace epileptického ložiska se jedná o heterogenní skupinu. Odlišení SHE může být obtížné zejména od NREM parasomnií vzhledem k některým společným patofyziologickým mechanismům a časté koincidenci obou poruch. Další typy záchvatových projevů ve spánku představuje porucha chování v REM spánku, poruchy pohybu souvisejících se spánkem, jakými jsou rytmické pohyby vázané na spánek, hypnagogické záškuby, periodické pohyby dolními končetinami a různé formy myoklonu. V neposlední řadě se během noci můžeme setkat s panickými atakami a psychogenními neepileptickými záchvaty.
There is a wide range of different paroxysmal motor events with various aetiology during sleep. The most important issue in their evaluation is to distinguish epileptic seizures from other sleep disorders. Sleep-related epileptic seizures are relatively frequent and they may occur predominantly or exclusively during sleep in approximately 12 %. The most frequent seizure type during sleep is a focal hyperkinetic seizure in the frame of the sleep-related hypermotor epilepsy (SHE), previously known as nocturnal frontal lobe epilepsy, which is a heterogeneous group in terms of aetiology and localization of epileptic focus. The differentiation of SHE from NREM parasomnia may sometimes be difficult, because of relatively frequent cooccurrence of both disorders and because of some shared pathophysiological mechanisms. Other possibilities of paroxysmal motor events during sleep represent REM sleep behaviour disorder, sleep-related movement disorders including sleep-related rhythmic movement disorder, sleep startle, periodic leg movement and various forms of myoclonus. Last but not least the psychogenic non-epileptic seizures or panic attacks may occur during the night.
- Klíčová slova
- záchvatové stavy ve spánku,
- MeSH
- epilepsie diagnóza terapie MeSH
- lidé MeSH
- parasomnie spojené s REM spánkem diagnóza terapie MeSH
- porucha chování v REM spánku * diagnóza terapie MeSH
- poruchy spánku a bdění * diagnóza terapie MeSH
- spánek pomalých vln MeSH
- záchvaty * diagnóza terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
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. However, the boundary between prodromal and definite RBD is still unclear. As a common effort of the Neurophysiology Working Group of the International RBD Study Group, this manuscript addresses the need for comprehensive and unambiguous v-PSG recommendations to diagnose RBD and identify prodromal RBD. These include: (1) standardized v-PSG technical settings; (2) specific considerations for REM sleep scoring; (3) harmonized methods for scoring REM sleep without atonia; (4) consistent methods to analyze video and audio recorded during v-PSGs and to classify movements and vocalizations; (5) clear v-PSG guidelines to diagnose RBD and identify prodromal RBD. Each section follows a common template: The current recommendations and methods are presented, their limitations are outlined, and new recommendations are described. Finally, future directions are presented. These v-PSG recommendations are intended for both practicing clinicians and researchers. Classification and quantification of motor events, RBD episodes, and vocalizations are however intended for research purposes only. These v-PSG guidelines will allow collection of homogeneous data, providing objective v-PSG measures and making future harmonized multicentric studies and clinical trials possible.
- MeSH
- lidé MeSH
- pohyb MeSH
- polysomnografie MeSH
- porucha chování v REM spánku * diagnóza MeSH
- prodromální symptomy MeSH
- spánek REM fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
