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White matter hyperintensities increases with traumatic brain injuryseverity: associations to neuropsychological performance and fatigue
Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
(engelsk)Manuskript (preprint) (Annet vitenskapelig)
Abstract [en]

Objective: To examine the prevalence of white matter hyperintensities (WMHs) in patients with traumatic brain injury (TBI) as compared to healthy controls, and to investigate whether there is an association between WMH lesion burden and performance on neuropsychological tests in patients with TBI.

Methods: A total of 59 patients with TBI and 27 age- and gender- matched healthy controls underwent thorough neuropsychological testing and magnetic resonance imaging. The quantification of WMH lesions was performed using the fully automated Lesion Segmentation Tool.

Results: WMH lesions were more common in patients with TBI than in healthy controls (p = 0.032), and increased with higher TBI severity (p = 0.025). Linear regressions showed that WMH lesions in patients with TBI were not related to performance on any neuropsychological tests (p > 0.05 for all). However, a negative relationship between number of WMH lesions in patients with TBI and self-assessed fatigue was found (r = –0.33, p = 0.026).

Conclusion: WMH lesions are more common in patients with TBI than in healthy controls, and WMH lesions burden increases with TBI severity. However, these lesions do not seem to explain the decreased cognitive functioning or the increased fatigue in patients with TBI.

HSV kategori
Identifikatorer
URN: urn:nbn:se:umu:diva-155406OAI: oai:DiVA.org:umu-155406DiVA, id: diva2:1278803
Tilgjengelig fra: 2019-01-15 Laget: 2019-01-15 Sist oppdatert: 2019-09-16
Inngår i avhandling
1. Fatigue after traumatic brain injury: exploring novel methods for diagnosis and treatment
Åpne denne publikasjonen i ny fane eller vindu >>Fatigue after traumatic brain injury: exploring novel methods for diagnosis and treatment
2019 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Alternativ tittel[sv]
Trötthet efter traumatisk skallskada : utforskande av nya metoder för diagnostik och behandling
Abstract [en]

Background: Traumatic brain injury (TBI) is one of the most common causes of disability and mortality. While some patients recover quickly, especially at the mild side of the injury severity continuum, many will experience symptoms for years to come. In this chronic phase, patients report a wide array of symptoms, where fatigue is one the most common. This fatigue makes huge impact in several areas of these patients’ lives. Despite the prevalence of fatigue after TBI, the underlying mechanisms are unclear. Further, there are no standardized way for assessment and diagnosis, and there are no treatments with satisfying empirical support. The aim of this thesis was to examine the effects of the novel compound OSU6162 on fatigue in patients with TBI, and to explore functional and structural brain imaging correlates of fatigue after TBI.

Methods: Studies I and III were based on a placebo-controlled, double-blinded clinical trial examining the effects of the monoaminergic stabilizer OSU6162 on fatigue in patients in the chronic phase of traumatic brain injury. In study I, self-assessment scales of fatigue and neuropsychological tests were used as outcomes, while functional magnetic resonance imaging (fMRI) blood-oxygen-level dependent (BOLD) signal was the primary outcome in study III. Studies II and IV used cross-sectional designs, comparing patients with TBI with age- and gender matched healthy controls. Study II examined whether fMRI BOLD signal could be used to detect and diagnose fatigue in patients with TBI, and study IV whether white matter hyperintensities (WMH) contribute to lower cognitive functioning and presence of fatigue after TBI.

Results: Study I revealed no effects of OSU6162 during 28 days of treatment at maximum doses of 15 mg twice daily on measures of fatigue or any other outcome. The results from study II indicated that fatigue after TBI is linked to alterations in striato-thalamic-cortical loops, and suggested that fMRI could be a promising technique to use in the diagnosis of fatigue after TBI. In study III the results revealed effects of treatment in the right occipitotemporal and orbitofrontal cortex. In these areas, the BOLD response was normalized in the OSU6162 group as compared to healthy controls, while the placebo group showed a steady low activity in these areas. The regional effects were located outside the network shown to be linked to fatigue in study II, which might explain why there were no effects on fatigue after treatment with OSU6162 in study I. Study IV showed that WMH lesions increased with increased TBI severity, but the presence and extent of lesions did not explain lower neuropsychological functioning or fatigue in subjects with previous TBI.

Conclusions: In summary, although no effects on fatigue after treatment with OSU6162 were seen, the results provide support to the theory that fatigue after TBI is linked to alterations in striato-thalamic-cortical loops, and on how fatigue after TBI could be assessed or diagnosed using fMRI. Structural damage within white matter was however not related to fatigue.

sted, utgiver, år, opplag, sider
Umeå: Umeå University, 2019. s. 59
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 2000
Emneord
Traumatic brain injury, fatigue, OSU6162, randomized clinical trials, functional magnetic resonance imaging, neuropsychology, structural magnetic resonance imaging, white matter hyperintensities
HSV kategori
Forskningsprogram
rehabiliteringsmedicin
Identifikatorer
urn:nbn:se:umu:diva-155409 (URN)978-91-7601-979-5 (ISBN)
Disputas
2019-02-08, Aulan, Vårdvetarhuset, Umeå, 09:00 (svensk)
Opponent
Veileder
Tilgjengelig fra: 2019-01-18 Laget: 2019-01-15 Sist oppdatert: 2019-01-17bibliografisk kontrollert

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