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- Abdulle, Sahra, 1970, et al.
(författare)
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CSF neurofilament protein (NFL) - a marker of active HIV-related neurodegeneration.
- 2007
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Ingår i: Journal of neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 254:8, s. 1026-32
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND METHODS : The light subunit of the neurofilament protein (NFL), a major structural component of myelinated axons, is a sensitive indicator of axonal injury in the central nervous system (CNS) in a variety of neurodegenerative disorders. Cerebrospinal fluid (CSF) NFL concentrations were measured by ELISA (normal < 250 ng/l) in archived samples from 210 HIV-infected patients not taking antiretroviral treatment: 55 with AIDS dementia complex (ADC), 44 with various CNS opportunistic infections/tumours (CNS OIs), 95 without neurological symptoms or signs, and 16 with primary HIV infection (PHI). The effect of highly active antiretroviral treatment (HAART) was studied by repeated CSF sampling in four of the ADC patients initiating treatment. RESULTS : CSF NFL concentrations were significantly higher in patients with ADC (median 2590 ng/l, IQR 780-7360) and CNS OIs (2315 ng/l, 985-7390 ng/l) than in neuroasymptomatic patients (<250 ng/l, <250-300) or PHI (<250 ng/l, <250-280), p < 0.001. Among patients with ADC, those with more severe disease (stage 2-4) had higher levels than those with milder disease (stage 0.5-1), p < 0.01. CSF NFL declined during HAART to the limit of detection in parallel with virological response and neurological improvement in ADC.CSF NFL concentrations were higher in neuroasymptomatic patients with lower CD4-cell strata than higher, p < 0.001. This increase was less marked than in the ADC patients and noted in 26/58 neuroasymptomatic patients with CD4 counts <200/mul compared to 1/37 with CD4-cells >/=200/mul. CONCLUSIONS : The findings of this study support the value of CSF NFL as a useful marker of ongoing CNS damage in HIV infection. Markedly elevated CSF NFL concentrations in patients without CNS OIs are associated with ADC, follow the grade of severity, and decrease after initiation of effective antiretroviral treatment. Nearly all previously suggested CSF markers of ADC relate to immune activation or HIV viral load that do not directly indicate brain injury. By contrast NFL is a sensitive marker of such injury, and should prove useful in evaluating the presence and activity of ongoing CNS injury in HIV infection.
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- Fazel, Seena, et al.
(författare)
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Neurological disorders and violence : a systematic review and meta-analysis with a focus on epilepsy and traumatic brain injury
- 2009
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 256:10, s. 1591-1602
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Forskningsöversikt (refereegranskat)abstract
- The objectives of this study were to systematically review and meta-analyze the research literature on the association of common neurological disorders and violence. Keywords relating to neurological disorders and violence were searched between 1966 and August 2008. Case-control and cohort studies were selected. Odds ratios of violence risk in particular disorders compared with controls were combined using fixed-effects meta-analysis with the data presented in forest plots. Sensitivity analyses were conducted to identify possible differences in risk estimates across surveys. Information on risk factors for violence was extracted if replicated in more than one study. Nine studies were identified that compared the risk of violence in epilepsy or traumatic brain injury compared with unaffected controls. For the epilepsy studies, the overall pooled odds ratio for violent outcomes was 0.67 [95% confidence interval (CI) 0.46-0.96]. For traumatic brain injury, the odds ratio was 1.66 (95% CI 1.12-2.31). An additional 11 case-control studies investigated factors associated with violence in epilepsy and traumatic brain injury. It was not possible to meta-analyze these data. Comorbid psychopathology was associated with violence. Data on other neurological conditions was limited and unreplicated. In conclusion, although the evidence was limited and methodological quality varied, epilepsy and traumatic brain injury appeared to differ in their risk of violence compared with control populations. Longitudinal studies are required to replicate this review's provisional findings that epilepsy is inversely associated with violence and that brain injury modestly increases the risk, and further research is needed to provide information on a broader range of risk factors.
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- Hagell, Peter, et al.
(författare)
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Testing the SF-36 in Parkinson's disease. Implications for reporting rating scale data
- 2008
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Ingår i: Journal of Neurology. - 0340-5354 .- 1432-1459. ; 255:2, s. 246-254
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Tidskriftsartikel (refereegranskat)abstract
- Rating scales are increasingly the primary outcome measures in clinical trials. However, clinically meaningful interpretation of such outcomes requires that the scales used satisfy basic requirements (scaling assumptions) within the data. These are rarely tested. The SF-36 is the most widely used patient-reported rating scale. Its scaling assumptions have been challenged in neurological disorders but remain untested in Parkinson's disease (PD). We therefore tested these by analyzing SF-36 data from 202 PD patients (54% men; mean age 70) to determine if it was legitimate to report scores for the eight SF-36 scales and its two summary measures of physical and mental health, and if those scores were reliable and valid. Results supported generation of the eight SF-36 scale scores and their reliabilities were generally good (> or = 0.74 in all but one instance). However, we found limitations that question the meaningfulness of four scales and other limitations that restrict the ability of four scales to detect change in clinical trials (floor/ceiling effects, 19.6-46.2 %). The two SF-36 summary measures were not found to be valid indicators of physical and mental health. This study demonstrates important limitations of the SF-36 and provides the first evidence-based guidelines for its use in PD. The limitations of the SF-36 demonstrated here may explain some unexpected findings in previous studies. However, the main implication is a general one for the clinical research community regarding requirements for reporting rating scale endpoints. Specifically, investigators should routinely provide scale evaluations based on data from within major clinical trials.
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| 7. |
- Hagell, Peter, et al.
(författare)
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Testing the SF-36 in Parkinson's disease : Implications for reporting rating scale data.
- 2008
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 1432-1459 .- 0340-5354. ; 255:2, s. 246-254
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Tidskriftsartikel (refereegranskat)abstract
- Rating scales are increasingly the primary outcome measures in clinical trials. However, clinically meaningful interpretation of such outcomes requires that the scales used satisfy basic requirements (scaling assumptions) within the data. These are rarely tested. The SF-36 is the most widely used patient-reported rating scale. Its scaling assumptions have been challenged in neurological disorders but remain untested in Parkinson's disease (PD).We therefore tested these by analyzing SF-36 data from 202 PD patients (54% men; mean age 70) to determine if it was legitimate to report scores for the eight SF-36 scales and its two summary measures of physical and mental health, and if those scores were reliable and valid. Results supported generation of the eight SF-36 scale scores and their reliabilities were generally good (>/= 0.74 in all but one instance). However, we found limitations that question the meaningfulness of four scales and other limitations that restrict the ability of four scales to detect change in clinical trials (floor/ceiling effects, 19.6-46.2 %). The two SF-36 summary measures were not found to be valid indicators of physical and mental health. This study demonstrates important limitations of the SF-36 and provides the first evidence- based guidelines for its use in PD. The limitations of the SF-36 demonstrated here may explain some unexpected findings in previous studies. However, the main implication is a general one for the clinical research community regarding requirements for reporting rating scale endpoints. Specifically, investigators should routinely provide scale evaluations based on data from within major clinical trials.
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- Hillert, J, et al.
(författare)
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Editorial
- 2008
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Ingår i: Journal of neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 255255 Suppl 1, s. 1-2
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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