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| 6. |
- Adams, David, et al.
(författare)
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Phase 2 open-label extension study of patisiran, an investigational RNAi therapeutic for the treatment of familial amyloid polyneuropathy
- 2015
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 86:11
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Familial amyloid polyneuropathy (FAP) is a progressive disease. Patisiran is an investigational small interfering RNA (siRNA) targeting TTR. The primary objective of the Phase 2 study is to evaluate the safety of 0.3 mg/kg patisiran administered intravenously once every 3 weeks. Twenty-seven patients were enrolled; the mean duration of treatment was 7 months (range 3–12), with 282 doses administered (median of 11 doses/patient). Chronic dosing with patisiran has been generally well tolerated. Two patients experienced serious adverse events regarded as being unrelated to study drug. Infusion-related reactions were observed in 14.8% of the patients, were mild in severity, and did not result in any discontinuations. Sustained TTR lowering of at least 80% was achieved based on serial TTR measurements for over 9 months, with further nadir of up to 89.6% between doses. Neurologic impairment scores were stable after 6 months of treatment with patisiran. A mean decrease from baseline in mNIS+7 of 0.95 points (N=19) observed in this study compared favorably to the estimated increase of 7–10 points in mNIS+7 at 6 months from prior FAP studies in a patient population with similar baseline NIS values. Dosing continues in all patients, and 12–month results will be presented.
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| 7. |
- Adelow, C, et al.
(författare)
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Epilepsy as a risk factor for cancer
- 2006
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Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 77:6, s. 784-786
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Ahmed, R. M., et al.
(författare)
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Biomarkers in dementia: clinical utility and new directions
- 2014
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Ingår i: Journal of Neurology Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 85:12, s. 1426-1434
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Tidskriftsartikel (refereegranskat)abstract
- Imaging, cerebrospinal fluid (CSF) and blood-based biomarkers have the potential to improve the accuracy by which specific causes of dementia can be diagnosed in vivo, provide insights into the underlying pathophysiology, and may be used as inclusion criteria and outcome measures for clinical trials. While a number of imaging and CSF biomarkers are currently used for each of these purposes, this is an evolving field, with numerous potential biomarkers in varying stages of research and development. We review the currently available biomarkers for the three most common forms of neurodegenerative dementia, and give an overview of research techniques that may in due course make their way into the clinic.
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- Alcolea, D., et al.
(författare)
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Use of plasma biomarkers for AT(N) classification of neurodegenerative dementias
- 2021
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 92:11, s. 1206-1214
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: All categories included in the AT(N) classification can now be measured in plasma. However, their agreement with cerebrospinal fluid (CSF) markers is not fully established. A blood signature to generate the AT(N) classification would facilitate early diagnosis of patients with Alzheimer's disease (AD) through an easy and minimally invasive approach. Methods: We measured Aβ, pTau181 and neurofilament light (NfL) in 150 plasma samples of the Sant Pau Initiative on Neurodegeneration cohort including patients with mild cognitive impairment, AD dementia, frontotemporal dementia, dementia with Lewy bodies and cognitively normal participants. We classified participants in the AT(N) categories according to CSF biomarkers and studied the diagnostic value of plasma biomarkers within each category individually and in combination. Results: The plasma Aβ composite, pTau181 and NfL yielded areas under the curve (AUC) of 0.75, 0.78 and 0.88 to discriminate positive and negative participants in their respective A, T and N categories. The combination of all three markers did not outperform pTau181 alone (AUC=0.81) to discriminate A+T+ from A-T- participants. There was a moderate correlation between plasma Aβ composite and CSF Aβ1-42/Aβ1-40 (Rho=-0.5, p<0.001) and between plasma pTau181 and CSF pTau181 in the entire cohort (Rho=0.51, p<0.001). NfL levels in plasma showed high correlation with those in CSF (Rho=0.78, p<0.001). Conclusions: Plasma biomarkers are useful to detect the AT(N) categories, and their use can differentiate patients with pathophysiological evidence of AD. A blood AT(N) signature may facilitate early diagnosis and follow-up of patients with AD through an easy and minimally invasive approach. © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.
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| 12. |
- Alves, Guido, et al.
(författare)
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Cerebrospinal fluid amyloid-β and phenotypic heterogeneity in de novo Parkinson's disease.
- 2013
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Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 84:5, s. 537-43
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Tidskriftsartikel (refereegranskat)abstract
- In Parkinson's disease (PD), the motor presentation characterised by postural instability/gait difficulties (PIGD) heralds accelerated motor, functional and cognitive decline, as compared with the more benign tremor-dominant (TD) variant. This makes the PIGD complex an attractive target for the discovery of prognostic biomarkers in PD.
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| 13. |
- Alves, Guido, et al.
(författare)
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CSF amyloid-β and tau proteins, and cognitive performance, in early and untreated Parkinson's Disease: the Norwegian ParkWest study
- 2010
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Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 81:10, s. 1080-1086
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Tidskriftsartikel (refereegranskat)abstract
- Background Alzheimer's disease (AD) pathology is found in a considerable portion of patients with Parkinson's disease (PD), particularly those with early dementia (PDD). Altered cerebrospinal fluid (CSF) levels of amyloid-beta (Abeta) and tau proteins have been found in PDD, with intermediate changes for Abeta42 in non-demented PD. The authors investigated whether AD-related CSF protein levels are altered and relate to neuropsychological performance in early, untreated PD. Methods CSF concentrations of Abeta42, Abeta40 and Abeta38 were measured by electrochemiluminiscene and levels of total tau (T-tau) and phosphorylated tau (P-tau) by ELISA in 109 newly diagnosed, unmedicated, non-demented, community-based PD patients who had undergone comprehensive neuropsychological testing, and were compared with those of 36 age-matched normal controls and 20 subjects with mild AD. Results PD patients displayed significant reductions in Abeta42 (19%; p=0.009), Abeta40 (15.5%; p=0.008) and Abeta38 (23%; p=0.004) but not T-tau (p=0.816) or P-tau (p=0.531) compared with controls. CSF Abeta42 reductions in PD were less marked than in AD (53%; p=0.002). Sequential regression analyses demonstrated significant associations between CSF levels of Abeta42 (beta=0.205; p=0.019), Abeta40 (beta=0.378; p<0.001) and Abeta38 (beta=0.288; p=0.001) and memory impairment, but not executive-attentional or visuospatial dysfunction. Tau protein levels did not correlate with cognitive measures. Conclusion CSF Abeta levels are altered in a subset of patients with early PD and relate to memory impairment. Our study suggests that alterations in Abeta protein metabolism may contribute to the heterogeneity in pattern and course of cognitive decline associated with PD. Longitudinal studies are needed to clarify the clinical significance of CSF Abeta peptides as prognostic biomarkers in PD.
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- Anckarsäter, Henrik, et al.
(författare)
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New evidence for an association between the CSF HVA:5-HIAA ratio and psychopathic traits
- 2003
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 74:7, s. 918-921
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To replicate the relation between the CSF HVA:5-HIAA ratio and psychopathic traits previously reported in a pilot group of 22 perpetrators of violent crimes. METHODS: CSF monoamine metabolite concentrations in another 28 violent and sexual offenders, aged 45 or below, referred to pretrial forensic psychiatric investigation, were compared to features of psychopathy according to the Psychopathy Checklist-Revised (PCL-R). RESULTS: Our previous finding was repeated in the new study group, where the HVA:5-HIAA ratio was strongly associated with psychopathic traits (r = 0.50, p = 0.010), particularly its behavioural aspects (r = 0.523, p = 0.004). In subsamples of individuals from both study groups who had no medication (n = 25) or no current axis I disorder, including a history of mood disorder or substance dependence (n = 21), the HVA:5-HIAA ratio remained strongly associated with all psychopathy factors but most closely with the behavioural features. Retrospective assessments of childhood disruptive symptomatology, such as attention deficit hyperactivity disorder or conduct disorder, analysed in relation to the monoamine metabolites, showed the same association with the HVA:5-HIAA ratio. CONCLUSIONS: Violent and aggressive behavioural traits with childhood onset and adult expression as psychopathic features are associated with changed activity in the brain dopaminergic system, possibly as a result of serotonergic dysregulation.
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| 16. |
- Andersen, Oluf, 1941, et al.
(författare)
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Multicentre, randomised, double blind, placebo controlled, phase III study of weekly, low dose, subcutaneous interferon beta-1a in secondary progressive multiple sclerosis
- 2004
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Ingår i: JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY. - : BMJ. - 0022-3050 .- 1468-330X. ; 75:5, s. 706-710
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Tidskriftsartikel (refereegranskat)
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- Appleton, Jason Philip, et al.
(författare)
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The TOS2 study: An international multi-centre audit assessing the standard of neurological examination
- 2015
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 86:11
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Konferensbidrag (refereegranskat)abstract
- Having previously demonstrated that in-patients referred to neurology at two UK hospitals were not fully examined prior to referral, we designed an audit with 80% power to detect a 10% increase in tendon hammer or ophthalmoscope use following an educational intervention. In-patients referred to neurology over a 4 month period in the UK, Jordan, Sweden and the United Arab Emirates were asked whether they recalled examination with a Tendon hammer, Ophthalmoscope and Stethoscope since admission. Results were disseminated to local medical teams and data were collected for a further 4 months. Pre and post-intervention data were available for 11 centres with 407 and 391 patients in each arm. 264 patients (64.86%) recalled examination with a tendon hammer preintervention, which significantly improved to 298 (76.21%) (p
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| 19. |
- Asztely, Fredrik, 1961, et al.
(författare)
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Long term follow-up of the first 70 operated adults in the Goteborg Epilepsy Surgery Series with respect to seizures, psychosocial outcome and use of antiepileptic drugs
- 2007
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Ingår i: J Neurol Neurosurg Psychiatry. - 1468-330X. ; 78:6, s. 605-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To compare long term (10 years) seizure outcome, psychosocial outcome and use of antiepileptic drugs (AED) with the 2 year follow-up in adults after resective epilepsy surgery. METHODS: All adults (n = 70) who underwent resective epilepsy surgery from 1987 to 1995 in the Goteborg Epilepsy Surgery Series were included. Fifty-four had undergone temporal lobe resections and 16 extratemporal resections (12 frontal). A cross-sectional follow-up in the form of a semistructured interview was performed in late 2003. RESULTS: Mean follow-up was 12.4 years (range 8.6-16.2). Of the 70 patients (51% males), five (7%) were dead (three as a result of non-epilepsy related causes). Of the 65 patients interviewed, 38 (58%) were seizure-free at the long term follow-up: 65% of the patients with temporal lobe resections and 36% of the patients with extratemporal resections. Of the 35 patients who were seizure-free at the 2 year follow-up, 3 (9%) had seizures at the long term follow-up. Of the 30 patients who had seizures at the 2 year follow-up, 6 (20%) were seizure-free at the long term follow-up. Of all 65 patients, 45 (69%) had the same seizure status as the 2 year follow-up. Sixteen (25%) had an improved seizure status and 4 (6%) had a worsened status. Of the seizure-free patients, 11 (29%) had ceased taking AED, 28 (74%) were working and 25 (66%) had a driving license. CONCLUSIONS: Adult patients who are seizure-free 2 years after resective epilepsy surgery are most likely to still be seizure-free 10 years later. Most are working and have obtained a driving license.
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- Ayton, Scott, et al.
(författare)
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CSF ferritin in the clinicopathological progression of Alzheimer's disease and associations with APOE and inflammation biomarkers
- 2023
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 94:3, s. 211-219
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Tidskriftsartikel (refereegranskat)abstract
- Background: A putative role for iron in driving Alzheimer's disease (AD) progression is complicated by previously reported associations with neuroinflammation, apolipoprotein E and AD proteinopathy. To establish how iron interacts with clinicopathological features of AD and at what disease stage iron influences cognitive outcomes, we investigated the association of cerebrospinal fluid (CSF) biomarkers of iron (ferritin), inflammation (acute phase response proteins) and apolipoproteins with pathological biomarkers (CSF Aβ42/t-tau, p-tau181), clinical staging and longitudinal cognitive deterioration in subjects from the BioFINDER cohort, with replication of key results in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Methods: Ferritin, acute phase response proteins (n=9) and apolipoproteins (n=6) were measured in CSF samples from BioFINDER (n=1239; 4 years cognitive follow-up) participants stratified by cognitive status (cognitively unimpaired, mild cognitive impairment, AD) and for the presence of amyloid and tangle pathology using CSF Aβ42/t-tau (A+) and p-tau181 (T+). The ferritin and apolipoprotein E associations were replicated in the ADNI (n=264) cohort. Results: In both cohorts, ferritin and apoE were elevated in A-T+ and A+T+ subjects (16%-40%), but not clinical diagnosis. Other apolipoproteins and acute phase response proteins increased with clinical diagnosis, not pathology. CSF ferritin was positively associated with p-tau181, which was mediated by apolipoprotein E. An optimised threshold of ferritin predicted cognitive deterioration in mild cognitive impairment subjects in the BioFINDER cohort, especially those people classified as A-T- and A+T-. Conclusions: CSF markers of iron and neuroinflammation have distinct associations with disease stages, while iron may be more intimately associated with apolipoprotein E and tau pathology.
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| 22. |
- Baldvinsdóttir, Bryndís, et al.
(författare)
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Adverse events associated with microsurgial treatment for ruptured intracerebral aneurysms: a prospective nationwide study on subarachnoid haemorrhage in Sweden
- 2023
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Ingår i: Journal of Neurology Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 94:7, s. 575-580
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAdverse events (AEs) or complications may arise secondary to the treatment of aneurysmal subarachnoid haemorrhage (SAH). The aim of this study was to identify AEs associated with microsurgical occlusion of ruptured aneurysms, as well as to analyse their risk factors and impact on functional outcome. MethodsPatients with aneurysmal SAH admitted to the neurosurgical centres in Sweden were prospectively registered during a 3.5-year period (2014-2018). AEs were categorised as intraoperative or postoperative. A range of variables from patient history and SAH characteristics were explored as potential risk factors for an AE. Functional outcome was assessed approximately 1 year after the bleeding using the extended Glasgow Outcome Scale. ResultsIn total, 1037 patients were treated for ruptured aneurysms, of which, 322 patients were treated with microsurgery. There were 105 surgical AEs in 97 patients (30%); 94 were intraoperative AEs in 79 patients (25%). Aneurysm rerupture occurred in 43 patients (13%), temporary occlusion of the parent artery >5 min in 26 patients (8%) and adjacent vessel injury in 25 patients (8%). High Fisher grade and brain oedema on CT were related to increased risk of AEs. At follow-up, 38% of patients had unfavourable outcome. Patients suffering AEs were more likely to have unfavourable outcome (OR 2.3, 95% CI 1.10 to 4.69). ConclusionIntraoperative AEs occurred in 25% of patients treated with microsurgery for ruptured intracerebral aneurysm in this nationwide survey. Although most operated patients had favourable outcome, AEs were associated with increased risk of unfavourable outcome.
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| 23. |
- Barnes, D, et al.
(författare)
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SAFETY AND TOLERABILITY OF TERIFLUNOMIDE IN CLINICAL STUDIES
- 2015
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Ingår i: JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY. - : BMJ. - 0022-3050 .- 1468-330X. ; 86:11
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Teriflunomide, approved for the treatment of relapsing-remitting multiple sclerosis, has a well-characterized safety profile based on individual clinical studies. We report pooled safety and tolerability data from four, double-blind, placebo-controlled trials of teriflunomide. Post-approval updates on hair thinning and pregnancy outcomes, sometimes concerns for patients initiating teriflunomide, are reported.MethodsData were pooled from phase 2 (NCT01487096) and phase 3 TEMSO (NCT00134563), TOWER (NCT00751881), and TOPIC (NCT00622700) studies. Patients were randomized to receive teriflunomide 14 mg, 7 mg, or placebo. Safety analyses were performed for all patients exposed to teriflunomide.ResultsThe pooled dataset included 3044 patients. Commonly reported adverse events (AEs) were in accordance with individual clinical studies, most being transient and mild-to-moderate in intensity. Incidence of hepatic AEs was higher in teriflunomide groups; however, serious hepatic AEs were similar across groups (∼2–3%). Hair thinning was higher in teriflunomide than placebo groups, but typically resolved on treatment without intervention and led to discontinuation in <2% of patients. No structural or functional abnormalities were reported in 42 newborns from teriflunomide-exposed parents.ConclusionsThese data from >6800 patient-years of teriflunomide exposure were consistent with individual studies and no new, unexpected safety signals were observed. (Study supported by Genzyme, a Sanofi company).
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| 24. |
- Bartek, J, et al.
(författare)
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Key concepts in glioblastoma therapy
- 2012
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Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 83:7, s. 753-760
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Tidskriftsartikel (refereegranskat)
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| 25. |
- Bellner, Johan, et al.
(författare)
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Diagnostic criteria and the use of ICD-10 codes to define and classify minor head injury.
- 2003
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 74:3, s. 351-352
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Epidemiological research on the incidence of traumatic head injuries relies on the correct definition and classification of the injury. OBJECTIVE: To address the use of diagnostic criteria and ICD-10 codes to define minor head injury in Swedish hospitals managing patients with head injury. METHODS: A questionnaire was mailed to all 76 Swedish hospitals managing head injuries. The hospitals were asked what diagnostic criteria they use to define minor head injury, and which ICD-10 codes they use to classify such injuries. RESULTS: 72 hospitals (95%) responded to the survey. The most common criterion was loss of consciousness (76%), followed by post-traumatic amnesia (38%). Almost half the hospitals used other signs and symptoms to define minor head injury. The ICD-10 code S.06 (intracranial injury) was used by 51 of the hospitals (91%). CONCLUSIONS: It is essential that there should be common definitions, classifications, and registration of minor head injuries. The wide variation in definition and classification found in this study emphasises the importance of improved implementation of the present guidelines.
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