Chronic ataxias with onset after the age of 50 differ significantly from ataxias with childhood or early adulthood onset. This article focuses on late-onset hereditary ataxias, particularly on new subtypes such as CANVAS (Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome) and SCA27B (Spinocerebellar Ataxia type 27B). It describes their clinical manifestations and diagnostic methods, including genetic testing and differential diagnosis against other sporadic ataxias, such as Multiple system atrophy type C. We present the main principles of diagnosing hereditary ataxias and the diagnostic approach used at the Center of Hereditary Ataxias at the Motol University Hospital, which includes a combination of laboratory, imaging, and genetic tests that allow for the exclusion of acquired causes and a pragmatic diagnosis of hereditary diseases.
- Klíčová slova
- CANVAS, FXTAS,
- MeSH
- ataxie * diagnóza genetika klasifikace MeSH
- diferenciální diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- multisystémová atrofie diagnóza genetika MeSH
- senioři MeSH
- spinocerebelární ataxie * diagnóza genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
While diagnostic criteria have been established and validated for most neurodegenerative diseases, the considerable overlap between individual nosological entities remains a significant diagnostic challenge. Increasing evidence suggests that neurodegeneration is often initiated by inflammation within the central nervous system. The identification of inflammation could serve as a first signal of the pathophysiological process. As such, validated biological markers ("biomarkers") of neuroinflammation are critically important. This study aimed to assess the presence and levels of inflammatory biomarkers in three neurodegenerative diseases: Lewy body diseases (LBD), multiple system atrophy (MSA), and 4-repeat tauopathies (4RT). A total of 83 LBD, 24 MSA, and 31 4RT patients were included, with 83 control subjects for comparison. Six immune-related proteins were analysed in cerebrospinal fluid (CSF) and blood serum (serum): C3 complement, C4 complement, haptoglobin, transferrin, orosomucoid, and β2 microglobulin (β2M). ANCOVA statistical analysis revealed significantly lower levels of several inflammatory biomarkers in LBD (CSF: transferrin, C3 complement, orosomucoid; Serum: orosomucoid, β2M) and MSA (CSF: transferrin, C3 complement, C4 complement, orosomucoid) compared to controls. Significant differences were also observed between the synucleinopathy patient groups (LBD and MSA) and 4RT in serum levels of C3 complement. Additionally, the CSF/serum quotients for transferrin (LBD and MSA) and C3 complement (LBD) were significantly lower in disease relative to controls. These findings suggest that inflammatory processes may play a role in the pathophysiology of neurodegenerative proteinopathies, warranting further research to confirm these associations. The identification of potential fluid biomarkers would then represent a promising step forward in the field.
- MeSH
- biologické markery krev mozkomíšní mok MeSH
- demence s Lewyho tělísky * krev mozkomíšní mok MeSH
- lidé středního věku MeSH
- lidé MeSH
- multisystémová atrofie * krev mozkomíšní mok MeSH
- neurozánětlivé nemoci * krev mozkomíšní mok MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- tauopatie * krev mozkomíšní mok MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie 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
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
PURPOSE: This study aimed to evaluate the reliability of different approaches for estimating the articulation rates in connected speech of Parkinsonian patients with different stages of neurodegeneration compared to healthy controls. METHOD: Monologues and reading passages were obtained from 25 patients with idiopathic rapid eye movement sleep behavior disorder (iRBD), 25 de novo patients with Parkinson's disease (PD), 20 patients with multiple system atrophy (MSA), and 20 healthy controls. The recordings were subsequently evaluated using eight syllable localization algorithms, and their performances were compared to a manual transcript used as a reference. RESULTS: The Google & Pyphen method, based on automatic speech recognition followed by hyphenation, outperformed the other approaches (automated vs. hand transcription: r > .87 for monologues and r > .91 for reading passages, p < .001) in precise feature estimates and resilience to dysarthric speech. The Praat script algorithm achieved sufficient robustness (automated vs. hand transcription: r > .65 for monologues and r > .78 for reading passages, p < .001). Compared to the control group, we detected a slow rate in patients with MSA and a tendency toward a slower rate in patients with iRBD, whereas the articulation rate was unchanged in patients with early untreated PD. CONCLUSIONS: The state-of-the-art speech recognition tool provided the most precise articulation rate estimates. If speech recognizer is not accessible, the freely available Praat script based on simple intensity thresholding might still provide robust properties even in severe dysarthria. Automated articulation rate assessment may serve as a natural, inexpensive biomarker for monitoring disease severity and a differential diagnosis of Parkinsonism.
- MeSH
- dysartrie diagnóza etiologie MeSH
- lidé MeSH
- multisystémová atrofie * MeSH
- Parkinsonova nemoc * komplikace diagnóza MeSH
- řeč MeSH
- reprodukovatelnost výsledků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Magnetická rezonancia (MR) je štandardnou súčasťou diferenciálne diagnostického procesu u pacientov s extrapyramídovými ochoreniami, pričom po vylúčení poliekového, toxického alebo funkčného pôvodu ťažkostí zvykne byť prvým štandardným krokom v ďalšom diagnostickom procese. V tomto článku budú bližšie prediskutované nálezy, ktoré s pomerne veľkou pravdepodobnosťou poukazujú na špecifické ochorenia pri danej klinickej fenomenológii, rozdelené na parkinsonské syndrómy, ochorenia asociované s akumuláciou kovov v mozgu (železo, mangán, meď) a ostatné ochorenia s typickými MR nálezmi vrátane Huntingtonovej choroby, syndrómu tremoru/ataxie asociovaného s fragilným X chromozómom (FXTAS) a hemichorey pri hyperglykémii.
Magnetic resonance imaging (MRI) is a standard part of the differential diagnostic process in movement disorders and is typically performed as the first diagnostic step after excluding drug-induced, toxic or functional origin of the disorder. This review discusses MRI findings which are rather typical for different movement disorders in combination with a specific clinical phenomenology divided into three subcategories: atypical parkinsonism, disorders associated with brain metal accumulation (iron, manganese and copper) and other movement disorders.
- MeSH
- Creutzfeldtova-Jakobova nemoc diagnostické zobrazování diagnóza MeSH
- hepatolentikulární degenerace diagnostické zobrazování diagnóza MeSH
- Huntingtonova nemoc diagnostické zobrazování diagnóza MeSH
- magnetická rezonanční tomografie metody MeSH
- multisystémová atrofie diagnostické zobrazování diagnóza MeSH
- nemoci bazálních ganglií * diagnostické zobrazování diagnóza MeSH
- neuroaxonální dystrofie diagnostické zobrazování diagnóza MeSH
- parkinsonské poruchy * diagnostické zobrazování diagnóza MeSH
- poruchy metabolismu železa diagnostické zobrazování diagnóza MeSH
- progresivní supranukleární obrna diagnostické zobrazování diagnóza MeSH
- syndrom fragilního X diagnostické zobrazování diagnóza MeSH
BACKGROUND: Various cerebrospinal fluid (CSF) biomarkers are studied in Parkinson's disease (PD) and atypical parkinsonian syndromes (APS). Several studies found reduced 5-hydroxyindoleacetic acid (5-HIAA), the main serotonin metabolite, in PD. There is little evidence regarding its levels in APS. METHODS: We measured 5-HIAA in the CSF of 90 PD patients, 16 MSA patients, 26 progressive supranuclear palsy (PSP) patients, 11 corticobasal syndrome (CBS) patients, and 31 controls. We also compared the values in depressed and nondepressed patients. RESULTS: There was a statistically significant difference in CSF 5-HIAA in PD and MSA compared to the control group (median in PD 15.8 μg/L, in MSA 13.6 μg/L vs. 24.3 μg/L in controls; p = 0.0008 in PD, p = 0.006 in MSA). There was no statistically significant difference in CSF 5-HIAA in PSP and CBS compared to the control group (median in PSP 22.7 μg/L, in CBS 18.7 μg/L vs. 24.3 μg/L in controls; p = 1 in both PSP and CBS). CSF 5-HIAA levels were lower in PD patients with depression compared to PD patients without depression (median 8.34 vs. 18.48, p < 0.0001). CONCLUSIONS: CSF 5-HIAA is decreased in PD and MSA. The CSF 5-HIAA levels in PSP and CBS did not differ from those of the control group. There was a tendency toward lower CSF 5-HIAA in MSA than in PD; however, the results did not reach statistical significance. These results may be explained by more severe damage of the serotonergic system in synucleinopathies (PD and MSA) than in tauopathies (PSP and CBS).
- MeSH
- diferenciální diagnóza MeSH
- kyselina hydroxyindoloctová MeSH
- lidé MeSH
- multisystémová atrofie * diagnóza MeSH
- Parkinsonova nemoc * diagnóza MeSH
- parkinsonské poruchy * metabolismus MeSH
- progresivní supranukleární obrna * MeSH
- tauopatie * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Neurodegenerativní onemocnění tvoří širokou a heterogenní skupinu nemocí. Jejich společnou vlastností je ukládání určitého patologického proteinu v mozkové tkáni. U synukleinopatií je tímto proteinem α-synuklein, jehož abnormálně složená depozita v centrálním i periferním nervovém systému definují na základě své lokalizace a struktury jednotlivá onemocnění. V současné době jsou mezi synukleinopatie řazeny Parkinsonova nemoc, Parkinsonova nemoc s demencí, demence s Lewyho tělísky, multisystémová atrofie, čisté autonomní selhání a idiopatická porucha chování v REM spánku. Průkaz samotného α-synukleinu u těchto nemocí má efekt v odlišení od jiných neurodegenerativních onemocnění, nicméně jeho specificita v diferenciální diagnostice jednotlivých synukleinopatií je poměrně nízká. Proto je třeba hledat další diagnostické biomarkery, které by přispěly k časné a přesné diagnóze jednotlivých onemocnění. Zároveň nejde jen o to pátrat po nových markerech, ale hledat i dostupnější biologické vzorky nebo tělesné tekutiny, v nichž lze tyto biomarkery účinně detekovat. V této práci jsou v úvodu velmi stručně shrnuta jednotlivá onemocnění a následně je uveden stručný přehled převážně diagnostických laboratorních biomarkerů. Uvádíme nejprve biomarkery mozkomíšního moku, které odrážejí přímé neuropatologické změny, dále několik biomarkerů nacházejících se v periferních tkáních.
Neurodegenerative diseases represent a large and heterogeneous group of disorders. Their common feature is the deposition of a certain pathological protein in brain tissue. The location and distribution of abnormally constituted α-synuclein deposits in central and peripheral nervous system define each respective disorder. The location and distribution of a-synuclein deposits define each respective disorder. Synucleinopathies currently include Parkinson‘s disease, Parkinson‘s disease with dementia, Lewy body dementia, multiple system atrophy, pure autonomic failure, and idiopathic REM sleep disorder. The detection of α-synuclein alone in these diseases has the effect in differentiating them from other neurodegenerative diseases; however, its specificity in the differential diagnosis of individual synucleinopathies is relatively low. Therefore, it is necessary to look for other diagnostic biomarkers that would contribute to the early and accurate diagnosis of individual diseases. At the same time, it is not just a matter of looking for new markers, but also of looking for more available biological samples or body fluids in which these biomarkers can be effectively detected. In the introduction of this review there is a brief description of each disorder and subsequently there is a brief overview of mostly diagnostic laboratory biomarkers. We first present the cerebrospinal fluid biomarkers that reflect the direct neuropathological changes, and then several biomarkers found in peripheral tissues.
- MeSH
- alfa-synuklein analýza MeSH
- biologické markery MeSH
- demence s Lewyho tělísky diagnóza patologie terapie MeSH
- lidé MeSH
- multisystémová atrofie diagnóza patologie MeSH
- Parkinsonova nemoc diagnóza patologie MeSH
- synukleinopatie * diagnóza patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
- Klíčová slova
- ortostatický test,
- MeSH
- levodopa aplikace a dávkování MeSH
- lidé MeSH
- multisystémová atrofie * diagnostické zobrazování farmakoterapie klasifikace terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy 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.
