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- Constantinescu, Radu, 1966, et al.
(author)
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Cerebrospinal fluid biomarkers in patients with neurological symptoms but without neurological diseases
- 2019
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In: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404.
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Journal article (peer-reviewed)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
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| 2. |
- Constantinescu, Radu, 1966, et al.
(author)
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Cerebrospinal fluid neurofilament light and tau protein as mortality biomarkers in parkinsonism
- 2019
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In: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 140:2, s. 147-156
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Journal article (peer-reviewed)abstract
- - Background: Mortality is increased in parkinsonian disorders, moderately in Parkinson's disease (PD) but markedly in atypical parkinsonian disorders (APD), including multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). Still, there are no reliable quantitative biomarkers for mortality. The cerebrospinal fluid (CSF) neurodegeneration biomarkers such as neurofilament light chain (NF-L), total tau (t-tau), and the tau pathology marker phosphorylated tau (p-tau) are related to mortality in other neurological disorders (eg, amyotrophic lateral sclerosis, Alzheimer's disease), but have not been investigated in this respect in parkinsonian disorders. Aims: To investigate the CSF biomarkers' (NF-L, t-tau, and p-tau) relationship to mortality in parkinsonian disorders. Methods: Demographic, mortality, and CSF data were collected from 68 PD and 83 APD patients. Survival analysis was conducted using Cox regression, with age at lumbar puncture, gender, diagnosis, and levels of CSF biomarkers as predictors. Results: NF-L in CSF was associated with increased mortality in synucleinopathies (PD, MSA; HR 3.698 [2.196-6.228, 95% confidence interval (CI)], P<0.001), in PSP (HR 2.767 [1.126-6.802 95% CI], P=0.027), and in the entire cohort (HR 1.661 [1.082-2.55, 95% CI], P=0.02). t-Tau in CSF was associated with increased mortality in PSP (HR 9.587 [1.143-80.418], P=0.037). p-Tau in CSF was associated with decreased mortality in synucleinopathies (HR 0.196 [0.041-0.929, 95% CI], P=0.040). Atypical parkinsonian disorders and tauopathies were associated with higher mortality (HR 8.798 [4.516-17.14, 95% CI] and HR 3.040 [1.904-4.854], respectively, P<0.001). Conclusion: NF-L and tau protein in CSF might be useful for mortality prognosis in patients with parkinsonian disorders and should be investigated in larger studies. © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
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| 3. |
- Constantinescu, Radu, 1966, et al.
(author)
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Cerebrospinal fluid protein markers in PD patients after DBS-STN surgery—A retrospective analysis of patients that underwent surgery between 1993 and 2001
- 2018
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In: Clinical neurology and neurosurgery. - : Elsevier BV. - 0303-8467. ; 174, s. 174-179
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Journal article (peer-reviewed)abstract
- Objective Cerebrospinal fluid (CSF) markers of neurodegeneration [neurofilament light chain (NFL), total Tau (T-Tau)], tau pathology [phosphorylated tau (p-Tau)], glial cell damage or activation [glial fibrillary acidic protein (GFAP)], and brain amyloidosis [β-amyloid 1-42 (Aβ42)] are useful for diagnosis and prognosis in several neurodegenerative disorders. In this paper we investigate these markers and their relationship to key clinical milestones in patients with advanced Parkinson´s disease (PD) operated at our center with subthalamic nucleus deep brain stimulation (STN-DBS) for at least 15 years ago. Patients and methods Retrospective analysis of available cerebrospinal fluid and clinical data in PD-patients, 15 years or more after they underwent STN-DBS surgery. All PD-patients implanted with STN-DBS at Sahlgrenska University Hospital before January 1, 2001, were regularly assessed until January 10, 2018, or until death, or until lost to follow-up. Results Twenty three PD patients were operated with STN-DBS. Sixteen of these (six females and ten males) underwent at least one lumbar puncture (LP) immediately prior to or after STN-DBS. Their age at the latest available LP was 64 (55–75) years [median (range)], PD duration 20 (11–33) years, and Hoehn & Yahr (H&Y) stage 3 (2–4). Time between DBS operation and the last LP was 4.5 (0.3–10.8) years. Time from the last LP to the last follow up was 6 (0.1–18) years, and for the entire cohort 115 person-years. On January 10, 2018, four PD-patients (25%) were still alive. All preoperative CSF marker levels were normal. Between two days and six months after DBS, NFL and GFAP levels increased sharply but they normalized thereafter in most patients, and were normal up to almost 11 years after neurosurgery. Over time, all patients deteriorated slowly. At the last follow up, H&Y was 5 (3–5) and 12/16 were demented. There was no significant correlation between postoperative (> 6 months) CSF NFL, GFAP, T-Tau, p-Tau, β-amyloid levels and the presence of dementia, psychosis, inability to walk or need for nursing home at the time for LP, nor for presence of dementia at the last follow up or for death as of January 10, 2018. Conclusion CSF protein biomarkers remain normal despite long PD duration, severe disability, and chronic STN-DBS. They cannot be used for PD staging or prognostication but may indicate brain damage caused by other pathological factors.
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| 4. |
- Constantinescu, Radu, 1966, et al.
(author)
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Key clinical milestones 15 years and onwards after DBS-STN surgery-A retrospective analysis of patients that underwent surgery between 1993 and 2001
- 2017
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In: Clinical Neurology and Neurosurgery. - : Elsevier BV. - 0303-8467. ; 154, s. 43-48
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Journal article (peer-reviewed)abstract
- Objective: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for motor fluctuations in Parkinson's disease (PD), but does not halt disease progression. The long-term deterioration of key functions such as cognition, speech, ability to swallow, gait, urinary bladder control, orientation and reality perception is decisive for patients' independency in daily life. In this paper we investigated patients with advanced PD operated at our center with STN-DBS for at least 15 years ago, in respect to key clinical milestones reflecting their overall function in daily living. Patients and methods: Retrospective analysis of clinical data concerning key clinical milestones including death in PD-patients, 15 years or more after they underwent STN-DBS surgery. All PD-patients implanted with STN-DBS at Sahlgrenska Hospital before January 1, 2001, were regularly assessed until death, dropout, or January 11, 2016. Results: Sixteen men and seven women with a median (range) disease duration of 18 (10-28) years were operated with STN-DBS. The median (range) follow-up time post-surgery was 12 (2-18) years and 692 person-years of disease duration were observed. In January 2016, nine PD-patients (39%) were still alive (eight with active STN-DBS). Initially, motor symptoms improved in all patients. Sustained benefit (implying active stimulation at the last follow up) was maintained in 19 of them (83%) but STN-DBS was inactivated in four (17%) due to inefficacy. Over time, all patients deteriorated slowly, and a majority developed severe non-motor and axial symptoms such as dementia, inability to talk, swallow and walk, urinary incontinence, psychosis, and need for nursing home care. At the last follow up, 16/23 (70%) patients were treated with antidepressants. Conclusion: A majority of PD-patients experience sustained motor benefit with continuous STN-DBS. However, over time, non-motor and axial symptoms slowly and severely restrict PD-patients' function in their daily living. (C) 2017 Elsevier B.V. All rights reserved.
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| 6. |
- Larsson, Barbro, 1952-, et al.
(author)
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Test–retest reliability of EMG and peak torque during repetitive maximum concentric knee extensions
- 2003
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In: Journal of Electromyography & Kinesiology. - 1050-6411 .- 1873-5711. ; 13:3, s. 281-287
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Journal article (peer-reviewed)abstract
- The aim of this study was to investigate the reliability of peak torque and surface electromyography (EMG) variable’s root mean square (RMS) and mean frequency (MNF) during an endurance test consisting of repetitive maximum concentric knee extensions. Muscle fatigue has been quantified in several ways, and in isokinetic testing it is based on a set of repetitive contractions. To assess test–retest reliability, two sets of 100 dynamic maximum concentric knee extensions were performed using an isokinetic dynamometer. The two series were separated by 7–8 days. The subjects relaxed during the passive flexion phase. Twenty (10 men and 10 women) clinically healthy subjects volunteered.Peak torque and EMG from rectus femoris, vastus medialis, vastus lateralis and biceps femoris were recorded. RMS and MNF were calculated from the EMG signal. The reliability was calculated with intraclass correlation coefficient ICC (1.1) and standard error of measurements (SEM). The reliability of peak torque was good (ICC=0.93) and SEM showed low values. ICC was good for absolute RMS of rectus femoris (ICC≥0.80), vastus medialis (ICC≥0.88) and vastus lateralis (ICC≥0.82) and MNF of rectus femoris (ICC≥0.82) and vastus medialis (ICC≥0.83). Peak torque, and MNF and RMS of rectus femoris and vastus medialis are reliable variables obtained from an isokinetic endurance test of the knee extensors.
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| 7. |
- Zackrisson, Theresa, 1971, et al.
(author)
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Patients with hyperhidrosis have changed grip force, coefficient of friction and safety margin
- 2008
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In: Acta Neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 117:4, s. 279-284
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Journal article (peer-reviewed)abstract
- Objective – To evaluate whether subjects with palmar hyperhidrosis have functional problems with the handgrip caused by the wet slippery surface of palm and fingertips. We used two different dosages of botulinum toxin to explore its impact on sweating and on muscle strength in the hand.Method – Using an object equipped with force sensors we measured the muscle strength and calculated the coefficients of friction and safety margin (SM) in the precision grip before and 2, 4, 6, 8 10–12 weeks and 6 months after treatment of 13 patients with two different doses of botulinum toxin. Sweat evaporation was measured simultaneously.Results – A significant decrease in evaporation and a parallel reduction of grip force in the dominant hand of the patients were observed. The SM used by the patients was significantly lower after the treatment, and increased gradually when sweating reappeared.Conclusion – These measurements showed, for the first time, that hyperhidrosis of the palms may cause an objective perturbation of the hand function which may be partially corrected by botulinum toxin treatment.
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| 8. |
- Örlefors, Håkan, et al.
(author)
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Whole-body 11C-5-hydroxytryptophan positron emission tomography as a universal imaging technique for neuroendocrine tumors : Comparison with somatostatin receptor scintigraphy and computed tomography
- 2005
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 90:6, s. 3392-3400
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Journal article (peer-reviewed)abstract
- Neuroendocrine tumors (NETs) can be small and situated almost anywhere throughout the body. Our objective was to investigate whether whole-body (WB) positron emission tomography (PET) with 11C-5-hydroxytryptophan (5-HTP) can be used as a universal imaging technique for NETs and to compare this technique with established imaging methods. Forty-two consecutive patients with evidence of NET and a detected lesion on any conventional imaging (six bronchial, two foregut, 16 midgut, and two thymic carcinoids; one ectopic Cushing’s syndrome; four gastrinomas; one insulinoma; six nonfunctioning endocrine pancreatic tumors; one gastric carcinoid, one paraganglioma; and two endocrine-differentiated pancreatic carcinomas) were studied. The WB-11C-5-HTP-PET examinations were compared with WB-computed tomography (CT) and somatostatin receptor scintigraphy (SRS). Tumor lesions were imaged with PET in 95% of the patients. In 58% of the patients, PET could detect more lesions than SRS and CT and equal numbers in 34%, whereas in three cases, SRS or CT showed more lesions. In 84% (16 of 19 patients), PET could visualize the primary tumor compared with 47 and 42% for SRS and CT, respectively. The surgically removed PET-positive primary tumor sizes were 6–30 mm. To conclude, this study indicates that WB-11C-5-HTP-PET can be used as a universal imaging method for detection of NETs. This study also shows that WB-11C-HTP-PET is sensitive in imaging small NET lesions, such as primary tumors, and can in a majority of cases image significantly more tumor lesions than SRS and CT.
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