| 1. |
- Nilsson, Johanna, 1993, et al.
(författare)
-
Cerebrospinal fluid biomarkers of synaptic dysfunction are altered in Parkinson's disease and related disorders
- 2023
-
Ingår i: Movement Disorders. - : John Wiley & Sons. - 0885-3185 .- 1531-8257. ; 38:2, s. 267-277
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Synaptic dysfunction and degeneration are central contributors to the pathogenesis and progression of parkinsonian disorders. Therefore, identification and validation of biomarkers reflecting pathological synaptic alterations are greatly needed and could be used in prognostic assessment and to monitor treatment effects.Objective: To explore candidate biomarkers of synaptic dysfunction in Parkinson's disease (PD) and related disorders.Methods: Mass spectrometry was used to quantify 15 synaptic proteins in two clinical cerebrospinal fluid (CSF) cohorts, including PD (n1 = 51, n2 = 101), corticobasal degeneration (CBD) (n1 = 11, n2 = 3), progressive supranuclear palsy (PSP) (n1 = 22, n2 = 21), multiple system atrophy (MSA) (n1 = 31, n2 = 26), and healthy control (HC) (n1 = 48, n2 = 30) participants, as well as Alzheimer's disease (AD) (n2 = 23) patients in the second cohort.Results: Across both cohorts, lower levels of the neuronal pentraxins (NPTX; 1, 2, and receptor) were found in PD, MSA, and PSP, compared with HC. In MSA and PSP, lower neurogranin, AP2B1, and complexin-2 levels compared with HC were observed. In AD, levels of 14-3-3 zeta/delta, beta- and gamma-synuclein were higher compared with the parkinsonian disorders. Lower pentraxin levels in PD correlated with Mini-Mental State Exam scores and specific cognitive deficits (NPTX2; rho = 0.25–0.32, P < 0.05) and reduced dopaminergic pre-synaptic integrity as measured by DaTSCAN (NPTX2; rho = 0.29, P = 0.023). Additionally, lower levels were associated with the progression of postural imbalance and gait difficulty symptoms (All NPTX; β-estimate = −0.025 to −0.038, P < 0.05) and cognitive decline (NPTX2; β-estimate = 0.32, P = 0.021).Conclusions: These novel findings show different alterations of synaptic proteins in parkinsonian disorders compared with AD and HC. The neuronal pentraxins may serve as prognostic CSF biomarkers for both cognitive and motor symptom progression in PD.
|
|
| 2. |
- Constantinescu, Clara, 1995, et al.
(författare)
-
Persons with suspicious onset of multiple sclerosis but with undetermined diagnosis had persistent lower cognition and reduced quality of life
- 2021
-
Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier BV. - 2211-0348. ; 52
-
Tidskriftsartikel (refereegranskat)abstract
- Backgound: Differential diagnosis of multiple sclerosis (MS) includes a variety of disorders and misdiagnosis is common. Objective: To follow-up persons with suspected onset of MS but in whom the diagnostic investigation was negative. Methods: In a prospective study including 271 persons with clinical features of suspected MS onset, 136 persons were diagnosed with MS or clinically isolated syndrome (PwMS), 46 had other disorders, and 89 persons had a negative diagnostic work-up, i.e. persons with undetermined diagnosis (PwUD). They underwent diagnostic reassessment, and those who remained without a diagnosis were investigated for signs of pathology including cognitive tests and assessments of quality of life (QoL). Results were compared with those of PwMS and 24 age and sex matched healthy controls (HC). Results: After reassement 55 (20%) persons still had undetermined diagnosis (PwUD). They had similar age and gender distribution as PwMS. In 76% of PwUD, the suspected clinical onset included sensory symptoms. PwUD and PwMS scored similarly in cognitive tests and QoL but significantly lower than HC. At 3 years follow-up, PwMS and PwUD improved in most test parameters, but PwUD scored lower than PwMS in cognition. Conclusion: PwUD constituted the dominating differential diagnosis in persons with suspected clinical onset of MS. QoL and cognition were comparable with those of PwMS but significantly lower than in HC.
|
|
| 3. |
- Constantinescu, Radu, 1966, et al.
(författare)
-
Cerebrospinal fluid biomarkers in patients with neurological symptoms but without neurological diseases
- 2019
-
Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404.
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Elevated levels of the cerebrospinal fluid (CSF) neuronal injury markers (neurofilament light chain [NF-L] and total tau protein [t-tau]) and of the astroglial marker glial fibrillary acidic protein (GFAP) are found in etiologically different neurological disorders affecting the peripheral and the central nervous system. Aims: To explore the role of CSF biomarkers in the clinical management of patients admitted for alarming neurological symptoms, but in whom neurological disorders could be excluded. Methods: Study participants were patients seeking medical attention for neurological symptoms primarily considered to be caused by a neurological diagnosis and investigated according to clinical routine. Demographic, clinical, and CSF data were extracted retrospectively from medical records. Patients with a final neurological diagnosis were excluded. Results: Out of 990 patients, 900 with a neurological diagnosis were excluded leaving 90 patients without a final neurological diagnosis. Sixty-eight (75.6%) were females. Median (range) age at lumbar puncture was 34.7 (16.9-65.1) years. Age-adjusted CSF-NF-L, CSF-t-tau, and CSF-GFAP concentrations were normal in 89 (98.9%), 86 (95.6%), and 87 (96.7%) patients, respectively. Conclusion: In patients with significant neurological symptoms but in whom a neurological diagnosis could not be made, the CSF markers NF-L, t-tau, and GFAP did not indicate signs of neuronal or astroglial cell damage close to symptom onset. Consequently, increased levels of CSF markers are not expected in this patient group and, if present, should raise suspicion of underlying neurological disorders and motivate further investigations. © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
|
|
| 4. |
- Fernandes Gomes, Bárbara, et al.
(författare)
-
α-Synuclein seed amplification assay as a diagnostic tool for parkinsonian disorders.
- 2023
-
Ingår i: Parkinsonism & related disorders. - 1873-5126. ; 117
-
Tidskriftsartikel (refereegranskat)abstract
- Synucleinopathies such as Parkinson's disease (PD) and multiple system atrophy (MSA) can be challenging to diagnose due to the symptom overlap with, for example, atypical parkinsonisms like progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Seed amplification assays (SAA), developed for the detection of α-synuclein (αSyn) aggregates in CSF, have been successful when used as a biomarker evaluation for synucleinopathies. In this study, we investigated the potential of this assay to not only detect αSyn seeds in CSF, but also discriminate between movement disorders.The αSyn-SAA was tested in a Scandinavian cohort composed of 129 CSF samples from patients with PD (n = 55), MSA (n = 27), CBD (n = 7), and PSP (n = 16), as well as healthy controls (HC, n = 24).The αSyn seed amplification assay (αSyn-SAA) was able to correctly identify all PD samples as positive (sensitivity of 100%) while also discriminating the PD group from HC (70.8% specificity, p < 0.0001) and tauopathies [CBD (71% specificity) and PSP (75% specificity), p < 0.0001)]. The αSyn-SAA was also able to identify almost all MSA samples as positive for αSyn aggregation (sensitivity of 92.6%). In general, this assay is able to discriminate between the synucleinopathies and tauopathies analyzed herein (p < 0.0001) despite the overlapping symptoms in these diseases.These findings suggest the αSyn-SAA is a useful diagnostic tool for differentiating between different parkinsonian disorders, although further optimization may be needed.
|
|
| 5. |
- Stevens-Jones, Oskar, et al.
(författare)
-
Presence of neural surface and onconeural autoantibodies in cerebrospinal fluid and serum in neurological diseases presents a potential risk for misdiagnosis
- 2023
-
Ingår i: European Journal of Neurology. - 1351-5101. ; 30:9, s. 2602-2610
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Autoantibodies have been found to contribute to pathology and are used in the diagnosis of some neurological diseases. We examined the prevalence of autoantibodies in patients with various neurological diseases and whether patients who had autoantibodies differed in age, sex, or disability from those who did not.Methods: We examined the prevalence of neural surface and onconeural autoantibodies in cerebrospinal fluid (CSF) and serum from patients with multiple sclerosis (n = 64), Parkinson disease plus atypical parkinsonism (n = 150), amyotrophic lateral sclerosis (n = 43), or autoimmune encephalitis (positive control; n = 7) and a healthy control group (n = 37). A total of 12 onconeural autoantibodies and six neural surface autoantibodies were tested in all participants.Results: Autoantibodies were present in all cohorts. The prevalence of autoantibodies was high (>80%) in the autoimmune encephalitis cohort but low (<20%) in all other cohorts. When comparing patients within cohorts who were positive for autoantibodies to patients who were not, there was no difference in age, sex, and disability. This was apart from the multiple sclerosis and Parkinson disease plus atypical parkinsonism cohorts, where those with positivity for autoantibodies in the CSF were significantly older.Conclusions: The presence of the autoantibodies examined does not appear to have a substantial clinical impact within the diseases examined in this study. The presence of autoantibodies in all cohorts presents a risk for misdiagnosis when the method is used incorrectly on patients with atypical clinical presentation.
|
|
| 6. |
- Weiner, Sophia, et al.
(författare)
-
SCRN1: A cerebrospinal fluid biomarker correlating with tau in Alzheimer's disease
- 2023
-
Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:10, s. 4609-4618
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Secernin-1 (SCRN1) is a neuronal protein that co-localizes with neurofibrillary tangles in Alzheimer's disease (AD), but not with tau inclusions in corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), or Pick's disease. METHODS: We measured SCRN1 concentration in cerebrospinal fluid (CSF) using a novel mass spectrometric parallel reaction monitoring method in three clinical cohorts comprising patients with neurochemically characterized AD (n = 25) and controls (n = 28), clinically diagnosed Parkinson's disease (PD; n = 38), multiple system atrophy (MSA; n = 31), PSP (n = 20), CBD (n = 8), healthy controls (n = 37), and neuropathology-confirmed AD (n = 47). RESULTS: CSF SCRN1 was significantly increased in AD (P < 0.01, fold change = 1.4) compared to controls (receiver operating characteristic area under the curve = 0.78) but not in CBD, PSP, PD, or MSA. CSF SCRN1 positively correlated with CSF total tau (R = 0.78, P = 1.1 × 10−13), phosphorylated tau181 (R = 0.64, P = 3.2 × 10−8), and Braak stage and negatively correlated with Mini-Mental State Examination score. DISCUSSION: CSF SCRN1 is a candidate biomarker of AD, reflecting tau pathology. HIGHLIGHTS: We developed a parallel reaction monitoring assay to measure secernin-1 (SCRN1) in cerebrospinal fluid (CSF). CSF SCRN1 was increased in Alzheimer's disease compared to healthy controls. CSF SCRN1 remained unchanged in Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, or corticobasal degeneration compared to controls. CSF SCRN1 correlated strongly with CSF phosphorylated tau and total tau. CSF SCRN1 increased across Braak stages and negatively correlated with Mini-Mental State Examination score.
|
|
| 7. |
- Senek, Marina, et al.
(författare)
-
Levodopa/carbidopa microtablets in Parkinson's disease : a study of pharmacokinetics and blinded motor assessment
- 2017
-
Ingår i: European Journal of Clinical Pharmacology. - Heidelberg, Germany : Springer. - 0031-6970 .- 1432-1041 .- 0014-2999. ; 73:5, s. 563-571
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Motor function assessments with rating scales in relation to the pharmacokinetics of levodopa may increase the understanding of how to individualize and fine-tune treatments.Objectives: This study aimed to investigate the pharmacokinetic profiles of levodopa-carbidopa and the motor function following a single-dose microtablet administration in Parkinson’s disease.Methods: This was a single-center, open-label, single-dose study in 19 patients experiencing motor fluctuations. Patients received 150% of their individual levodopa equivalent morning dose in levodopa-carbidopa microtablets. Blood samples were collected at pre-specified time points. Patients were video recorded and motor function was assessed with six UPDRS part III motor items, dyskinesia score, and the treatment response scale (TRS), rated by three blinded movement disorder specialists.Results: AUC0–4/dose and Cmax/dose for levodopa was found to be higher in Parkinson’s disease patients compared with healthy subjects from a previous study, (p = 0.0008 and p = 0.026, respectively). The mean time to maximum improvement in sum of six UPDRS items score was 78 min (±59) (n = 16), and the mean time to TRS score maximum effect was 54 min (±51) (n = 15). Mean time to onset of dyskinesia was 41 min (±38) (n = 13).Conclusions: In the PD population, following levodopa/carbidopa microtablet administration in fasting state, the Cmax and AUC0–4/dose were found to be higher compared with results from a previous study in young, healthy subjects. A large between subject variability in response and duration of effect was observed, highlighting the importance of a continuous and individual assessment of motor function in order to optimize treatment effect.
|
|
| 8. |
- Aghanavesi, Somayeh, 1981-, et al.
(författare)
-
A multiple motion sensors index for motor state quantification in Parkinson's disease
- 2020
-
Ingår i: Computer Methods and Programs in Biomedicine. - : Elsevier BV. - 0169-2607 .- 1872-7565. ; 189
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: To construct a Treatment Response Index from Multiple Sensors (TRIMS) for quantification of motor state in patients with Parkinson's disease (PD) during a single levodopa dose. Another aim was to compare TRIMS to sensor indexes derived from individual motor tasks. Method: Nineteen PD patients performed three motor tests including leg agility, pronation-supination movement of hands, and walking in a clinic while wearing inertial measurement unit sensors on their wrists and ankles. They performed the tests repeatedly before and after taking 150% of their individual oral levodopa-carbidopa equivalent morning dose.Three neurologists blinded to treatment status, viewed patients’ videos and rated their motor symptoms, dyskinesia, overall motor state based on selected items of Unified PD Rating Scale (UPDRS) part III, Dyskinesia scale, and Treatment Response Scale (TRS). To build TRIMS, out of initially 178 extracted features from upper- and lower-limbs data, 39 features were selected by stepwise regression method and were used as input to support vector machines to be mapped to mean reference TRS scores using 10-fold cross-validation method. Test-retest reliability, responsiveness to medication, and correlation to TRS as well as other UPDRS items were evaluated for TRIMS. Results: The correlation of TRIMS with TRS was 0.93. TRIMS had good test-retest reliability (ICC = 0.83). Responsiveness of the TRIMS to medication was good compared to TRS indicating its power in capturing the treatment effects. TRIMS was highly correlated to dyskinesia (R = 0.85), bradykinesia (R = 0.84) and gait (R = 0.79) UPDRS items. Correlation of sensor index from the upper-limb to TRS was 0.89. Conclusion: Using the fusion of upper- and lower-limbs sensor data to construct TRIMS provided accurate PD motor states estimation and responsive to treatment. In addition, quantification of upper-limb sensor data during walking test provided strong results. © 2019
|
|
| 9. |
|
|
| 10. |
|
|
