Multiple system atrophy
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Multisystémová atrofie (MSA) je relativně vzácné neurodegenerativní onemocnění středního a vyššího věku s fatální prognózou. U MSA se kombinují různé motorické i nonmotorické příznaky. Kauzální léčba neexistuje a účinky symptomatické léčby jsou neuspokojivé. Článek stručně pojednává o patofyziologii a genetice MSA. Detailně se zaměřuje na klinický obraz, praktické aspekty diagnostiky a aktuální terapeutické možnosti MSA v ČR.
Multiple system atrophy (MSA) is relatively rare neurodegenerative disease with fatal prognosis affecting middle-aged and elderly individuals. There is combination of several motor and nonmotor symptoms in MSA. Causal treatment does not exist and symptomatic treatment effect is unsatisfactory. The article briefly discus ses genetics and pathophysiology of MSA with special focus on the clinical picture, practical aspects of diagnostics and cur rent therapeutic options of MSA in the Czech Republic.
- Klíčová slova
- abnormní chování v REM spánku, autonomní dysfunkce, inspirační stridor,
- MeSH
- lidé MeSH
- multisystémová atrofie * diagnóza terapie MeSH
- ortostatická hypotenze MeSH
- parkinsonské poruchy MeSH
- synukleiny MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
V článku prinášame kazuistiky dvoch pacientov s atypickou prezentáciou dvoch rozdielnych neurodegeneratívnych ochorení. U oboch pacientov sa postupne po 60. roku životu vyvinuli znaky kortikobazálneho syndrómu, zahŕňajúce levodopa-rezistentný výrazne asymetrický akineticko-rigidný parkinsonizmus s dystóniou, myoklonom a fokálnym kortikálnym deficitom. Navyše mali títo pacienti cerebelárny syndróm s MR nálezom cerebelárnej a pontínnej atrofie, s postupným rozvojom vegetatívnej dysfunkcie. Na základe klinického obrazu a zobrazovacích vyšetrení suponujeme vzácnu koincidenciu kortikobazálneho syndrómu a cerebelárnej formy multisystémovej atrofie.
The article presents case reports of two patients with an atypical presentation of two distinct neurodegenerative diseases. After 60 years of age, both the patients gradually developed signs of corticobasal syndrome, which included levodopa-resistant, markedly asymmetrical akinetic-rigid parkinsonism with dystonia, myoclonia, and focal cortical deficit. In addition, these patients had cerebellar syndrome with an MRI finding of cerebellar and pontine atrophy, with progressive development of vegetative dysfunction. Based on the clinical presentation and imaging studies, a rare coincidence of corticobasal syndrome and the cerebellar form of multiple system atrophy has been assumed.
- MeSH
- diferenciální diagnóza MeSH
- lidé MeSH
- multisystémová atrofie * diagnóza terapie MeSH
- nemoci mozečku MeSH
- neurodegenerativní nemoci MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
BACKGROUND: Multiple System Atrophy is a rare neurodegenerative disease with alpha-synuclein aggregation in glial cytoplasmic inclusions and either predominant olivopontocerebellar atrophy or striatonigral degeneration, leading to dysautonomia, parkinsonism, and cerebellar ataxia. One prior genome-wide association study in mainly clinically diagnosed patients with Multiple System Atrophy failed to identify genetic variants predisposing for the disease. OBJECTIVE: Since the clinical diagnosis of Multiple System Atrophy yields a high rate of misdiagnosis when compared to the neuropathological gold standard, we studied only autopsy-confirmed cases. METHODS: We studied common genetic variations in Multiple System Atrophy cases (N = 731) and controls (N = 2898). RESULTS: The most strongly disease-associated markers were rs16859966 on chromosome 3, rs7013955 on chromosome 8, and rs116607983 on chromosome 4 with P-values below 5 × 10-6 , all of which were supported by at least one additional genotyped and several imputed single nucleotide polymorphisms. The genes closest to the chromosome 3 locus are ZIC1 and ZIC4 encoding the zinc finger proteins of cerebellum 1 and 4 (ZIC1 and ZIC4). INTERPRETATION: Since mutations of ZIC1 and ZIC4 and paraneoplastic autoantibodies directed against ZIC4 are associated with severe cerebellar dysfunction, we conducted immunohistochemical analyses in brain tissue of the frontal cortex and the cerebellum from 24 Multiple System Atrophy patients. Strong immunohistochemical expression of ZIC4 was detected in a subset of neurons of the dentate nucleus in all healthy controls and in patients with striatonigral degeneration, whereas ZIC4-immunoreactive neurons were significantly reduced inpatients with olivopontocerebellar atrophy. These findings point to a potential ZIC4-mediated vulnerability of neurons in Multiple System Atrophy. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
- MeSH
- alfa-synuklein metabolismus MeSH
- autoprotilátky MeSH
- celogenomová asociační studie MeSH
- lidé MeSH
- multisystémová atrofie * genetika patologie MeSH
- olivopontocerebelární atrofie * MeSH
- pitva MeSH
- proteiny nervové tkáně genetika MeSH
- striatonigrální degenerace * MeSH
- transkripční faktory genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
BACKGROUND AND OBJECTIVES: Patients with synucleinopathies such as multiple system atrophy (MSA) and Parkinson's disease (PD) frequently display speech and language abnormalities. We explore the diagnostic potential of automated linguistic analysis of natural spontaneous speech to differentiate MSA and PD. METHODS: Spontaneous speech of 39 participants with MSA compared to 39 drug-naive PD and 39 healthy controls matched for age and sex was transcribed and linguistically annotated using automatic speech recognition and natural language processing. A quantitative analysis was performed using 6 lexical and syntactic and 2 acoustic features. Results were compared with human-controlled analysis to assess the robustness of the approach. Diagnostic accuracy was evaluated using sensitivity analysis. RESULTS: Despite similar disease duration, linguistic abnormalities were generally more severe in MSA than in PD, leading to high diagnostic accuracy with an area under the curve of 0.81. Compared to controls, MSA showed decreased grammatical component usage, more repetitive phrases, shorter sentences, reduced sentence development, slower articulation rate, and increased duration of pauses, whereas PD had only shorter sentences, reduced sentence development, and longer pauses. Only slower articulation rate was distinctive for MSA while unchanged for PD relative to controls. The highest correlation was found between bulbar/pseudobulbar clinical score and sentence length (r = -0.49, p = 0.002). Despite the relatively high severity of dysarthria in MSA, a strong agreement between manually and automatically computed results was achieved. DISCUSSION: Automated linguistic analysis may offer an objective, cost-effective, and widely applicable biomarker to differentiate synucleinopathies with similar clinical manifestations.
- MeSH
- diferenciální diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- multisystémová atrofie * diagnóza patofyziologie komplikace MeSH
- Parkinsonova nemoc * diagnóza komplikace patofyziologie MeSH
- řeč fyziologie MeSH
- senioři MeSH
- zpracování přirozeného jazyka MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
AIM: The cutaneous silent period (CSP) is a spinal inhibitory reflex primarily mediated by A-delta fibers. Prolonged CSPs have been reported in patients with restless legs syndrome (RLS) and idiopathic Parkinson's disease (IPD). Dopaminergic medication normalizes the CSP, concurring with the effect of levodopa on CSPs. To date, CSPs have not been extensively studied in patients with multiple system atrophy (MSA). The purpose of this study was to confirm abnormal CSP findings in a group of MSA patients and to affirm the lack of influence of levodopa on CSPs during long-term treatment. METHODS: We investigated 15 patients (4 males, 11 females, age 58-71 years) who fulfilled the diagnostic criteria for possible MSA. Thirteen patients had predominant parkinsonian symptoms (MSA-P), 2 had predominant cerebellar signs (MSA-C). We recorded CSPs in thenar muscles following noxious digit II stimulation. Sixteen healthy volunteers (6 males, 10 females, range 24-56 years) served as control subjects for CSP recordings. RESULTS: Group average CSP onset was mildly delayed (P<0.01), whereas CSP end latency (P<0.001) were markedly delayed and CSP duration prolonged (P<0.001) in MSA patients compared to healthy controls. MSA patients on levodopa treatment did not differ in their CSPs from those without levodopa. The dose of levodopa did not correlate to any CSP parameter. CONCLUSION: The observed CSP prolongation corroborates previous findings in a limited number of MSA patients. The ineffectiveness of long-term levodopa on CSP abnormalities is consistent with its poor clinical effect in MSA.
- MeSH
- abnormální reflex fyziologie MeSH
- kosterní svaly fyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- multisystémová atrofie patofyziologie MeSH
- nemoci míchy patofyziologie MeSH
- parkinsonské poruchy patofyziologie MeSH
- reakční čas fyziologie MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Although motor speech disorders represent an early and prominent clinical feature of multiple system atrophy (MSA), the potential usefulness of speech assessment as a diagnostic tool has not yet been explored. This cross-sectional study aimed to provide a comprehensive, objective description of motor speech function in the parkinsonian (MSA-P) and cerebellar (MSA-C) variants of MSA. Speech samples were acquired from 80 participants including 18 MSA-P, 22 MSA-C, 20 Parkinson's disease (PD), and 20 healthy controls. The accurate differential diagnosis of dysarthria subtypes was based on quantitative acoustic analysis of 14 speech dimensions. A mixed type of dysarthria involving hypokinetic, ataxic and spastic components was found in the majority of MSA patients independent of phenotype. MSA-P showed significantly greater speech impairment than PD, and predominantly exhibited harsh voice, imprecise consonants, articulatory decay, monopitch, excess pitch fluctuation and pitch breaks. MSA-C was dominated by prolonged phonemes, audible inspirations and voice stoppages. Inappropriate silences, irregular motion rates and overall slowness of speech were present in both MSA phenotypes. Speech features allowed discrimination between MSA-P and PD as well as between both MSA phenotypes with an area under curve up to 0.86. Hypokinetic, ataxic and spastic dysarthria components in MSA were correlated to the clinical evaluation of rigidity, cerebellar and bulbar/pseudobulbar manifestations, respectively. Distinctive speech alterations reflect underlying pathophysiology in MSA. Objective speech assessment may provide an inexpensive and widely applicable screening instrument for differentiation of MSA and PD from controls and among subtypes of MSA.
- MeSH
- akustika řeči MeSH
- dysartrie diagnóza etiologie patofyziologie MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- multisystémová atrofie komplikace patofyziologie MeSH
- nemoci mozečku komplikace patofyziologie MeSH
- parkinsonské poruchy komplikace patofyziologie 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
Distinct speech characteristics that may aid in differentiation between Parkinson's disease (PD), progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) remain tremendously under-explored. Here, the patterns and degree of consonant articulation deficits across voiced and voiceless stop plosives in 16 PD, 16 PSP, 16 MSA and 16 healthy control speakers were evaluated using acoustic and perceptual methods. Imprecise consonant articulation was observed across all Parkinsonian groups. Voice onset time of voiceless plosives was more prolonged in both PSP and MSA compared to PD, presumably due to greater severity of dysarthria and slower articulation rate. Voice onset time of voiced plosives was significantly shorter only in MSA, likely as a consequence of damage to cerebellar structures. In agreement with the reduction of pre-voicing, MSA manifested increased number of voiced plosives misclassified as voiceless at perceptual evaluation. Timing of articulatory movements may provide important clues about the pathophysiology of underlying disease.
- MeSH
- dysartrie patofyziologie MeSH
- hlas MeSH
- lidé středního věku MeSH
- lidé MeSH
- lingvistika * MeSH
- mozeček patofyziologie MeSH
- multisystémová atrofie patofyziologie MeSH
- Parkinsonova nemoc patofyziologie MeSH
- progresivní supranukleární obrna patofyziologie MeSH
- řeč * MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Clear speech refers to intentionally modifying conversational speech to maximise intelligibility. This study aimed to compare the speech behaviour of patients with progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and Parkinson's disease (PD) under conversational and clear speech conditions to gain greater pathophysiological insight. A total of 68 participants including 17 PD, 17 MSA, 17 PSP and 17 healthy controls (HC) performed two readings of the same standardized passage. During the first reading, participants were instructed to read the text in an ordinary way, while during the second reading to read the text as clearly as possible. Acoustic analyses were based upon measurements of mean loudness, loudness variability, pitch variability, vowel articulation, articulation rate and speech severity. During clear speech production, PD patients were able to achieve improvements mainly in loudness (p < 0.05) and pitch variability (p < 0.001), leading to a reduction in overall speech severity (p < 0.001), whereas PSP and MSA patients were able to modulate only articulation rate (p < 0.05). Contrary to HC and PD groups, which slowed or maintained articulation rate, PSP and MSA groups employed a markedly faster articulation rate under the clear speech condition indicating an opposing approach to speech adaptation. Patients with atypical Parkinsonism showed a different strategy to intentionally improve their speech performance following a simple request to produce speech more clearly compared to PD, suggesting important therapeutic implications for speech rehabilitation management.
