Neural indicators of fatigue in chronic diseases : A systematic review of MRI studies

The authors would like to thank the Sir Jules Thorn Charitable Trust for their financial support.Peer reviewedPublisher PD

Multiple indices of diffusion identifies white matter damage in mild cognitive impairment and Alzheimer's disease

The study of multiple indices of diffusion, including axial (DA), radial (DR) and mean diffusion (MD), as well as fractional anisotropy (FA), enables WM damage in Alzheimer's disease (AD) to be assessed in detail. Here, tract-based spatial statistics (TBSS) were performed on scans of 40 healthy elders, 19 non-amnestic MCI (MCIna) subjects, 14 amnestic MCI (MCIa) subjects and 9 AD patients. Significantly higher DA was found in MCIna subjects compared to healthy elders in the right posterior cingulum/precuneus. Significantly higher DA was also found in MCIa subjects compared to healthy elders in the left prefrontal cortex, particularly in the forceps minor and uncinate fasciculus. In the MCIa versus MCIna comparison, significantly higher DA was found in large areas of the left prefrontal cortex. For AD patients, the overlap of FA and DR changes and the overlap of FA and MD changes were seen in temporal, parietal and frontal lobes, as well as the corpus callosum and fornix. Analysis of differences between the AD versus MCIna, and AD versus MCIa contrasts, highlighted regions that are increasingly compromised in more severe disease stages. Microstructural damage independent of gross tissue loss was widespread in later disease stages. Our findings suggest a scheme where WM damage begins in the core memory network of the temporal lobe, cingulum and prefrontal regions, and spreads beyond these regions in later stages. DA and MD indices were most sensitive at detecting early changes in MCIa

Occasional essay: upper motor neuron syndrome in amyotrophic lateral sclerosis

The diagnosis of amyotrophic lateral sclerosis (ALS) requires recognition of both lower (LMN) and upper motor neuron (UMN) dysfunction.1 However, classical UMN signs are frequently difficult to identify in ALS.2 LMN involvement is sensitively detected by electromyography (EMG)3 but, as yet, there are no generally accepted markers for monitoring UMN abnormalities,4 the neurobiology of ALS itself, and disease spread through the brain and spinal cord,.5 Full clinical assessment is therefore necessary to exclude other diagnoses and to monitor disease progression. In part, this difficulty regarding detection of UMN involvement in ALS derives from the definition of ‘the UMN syndrome’. Abnormalities of motor control in ALS require reformulation within an expanded concept of the UMN, together with the neuropathological, neuro-imaging and neurophysiological abnormalities in ALS. We review these issues here

Neuroimaging of structural pathology and connectomics in traumatic brain injury: Toward personalized outcome prediction.

Recent contributions to the body of knowledge on traumatic brain injury (TBI) favor the view that multimodal neuroimaging using structural and functional magnetic resonance imaging (MRI and fMRI, respectively) as well as diffusion tensor imaging (DTI) has excellent potential to identify novel biomarkers and predictors of TBI outcome. This is particularly the case when such methods are appropriately combined with volumetric/morphometric analysis of brain structures and with the exploration of TBI-related changes in brain network properties at the level of the connectome. In this context, our present review summarizes recent developments on the roles of these two techniques in the search for novel structural neuroimaging biomarkers that have TBI outcome prognostication value. The themes being explored cover notable trends in this area of research, including (1) the role of advanced MRI processing methods in the analysis of structural pathology, (2) the use of brain connectomics and network analysis to identify outcome biomarkers, and (3) the application of multivariate statistics to predict outcome using neuroimaging metrics. The goal of the review is to draw the community's attention to these recent advances on TBI outcome prediction methods and to encourage the development of new methodologies whereby structural neuroimaging can be used to identify biomarkers of TBI outcome

mr imaging of gray matter involvement in multiple sclerosis implications for understanding disease pathophysiology and monitoring treatment efficacy

SUMMARY: Recent pathologic and MR imaging studies have challenged the classic view of MS as a chronic inflammatory-demyelinating condition affecting solely the WM of the central nervous system. Indeed, an involvement of the GM has been shown to occur from the early stages of the disease, to progress with time, and to be only moderately correlated with the extent of WM injury. In this review, we summarize how advances in MR imaging technology and methods of analysis are contributing to ameliorating the detection of focal lesions and to quantifying the extent of "occult" pathology and atrophy, as well as to defining the topographic distribution of such changes in the GM of patients with MS. These advances, combined with the imaging of brain reorganization occurring after tissue injury, should ultimately result in an improved understanding and monitoring of MS clinical manifestations and evolution, either natural or modified by treatment. Cereb : cerebellum Cho : choline CIS : clinically isolated syndromes DIR : double inversion recovery DTI : diffusion tensor imaging EDSS : Expanded Disability Status Scale FA : fractional anisotropy FLAIR : fluid-attenuated inversion recovery fMRI : functional MR imaging GM : gray matter L : left MD : mean diffusivity MS : multiple sclerosis MT : magnetization transfer MTR : magnetization transfer ratio NAA : N -acetylaspartate NAWM : normal-appearing white matter PM : premotor cortex PPMS : primary-progressive MS R : right RRMS : relapsing-remitting MS RT : relaxation time SII : secondary sensorimotor cortex SMA : supplementary motor area SMC : sensorimotor cortex SPM : statistical parametric mapping SPMS : secondary-progressive MS Thal : thalamus WM : white matte

Magnetic Resonance Imaging Follow-up and JCV Serology in Multiple Sclerosis

Magneettikuvausta (MK) käytetään nykyään yleisesti multippeliskleroosin (MS) diagnostiikassa ja taudin seurannassa. Konventionaalinen MK (T1 ja T2 painotteiset sekvenssit) ei kuitenkaan ole spesifinen MS-taudin patologian suhteen. Lisäksi radiologiset löydökset korreloivat vain kohtalaisesti kliinisen kokonaistoimintakyvyn kanssa. Tehokkaat MS-taudin lääkehoidot, kuten natalitsumabi (NTZ), lisäävät progressiivisen multifokaalisen leukoenkefalopatian (PML) riskiä. PML on vakava demyelinoiva keskushermoston sairaus, jonka aiheuttaa neurotrooppisen JC- viruksen reaktivaatio. PML:n riskin vuoksi MS-potilailta tutkitaan JC-virusvasta- aineet ennen NTZ:n lääkehoidon aloitusta. Väitöskirjatutkimuksen päätavoitteena oli tutkia uusien MK:een perustuvien kuvantamismenetelmien, volumetrian ja diffuusiotensorikuvauksen (DTI) avulla aivoparenkyymissä tapahtuvia muutoksia MS-potilailla ja kliinisesti eriytyneessä oireyhtymässä (KEO) neljän vuoden seurantatutkimuksessa. Tavoitteena oli selvittää voidaanko volumetrialla tai DTI-muutosten arvioinnilla ennustaa progressiota KEO:sta MS-tautiin. MS-potilailla selvitettiin myös korreloivatko havaitut muutokset toimintakyvyn huononemiseen expanded disability status scale-asteikon avulla mitattuna. Kolmannessa osatyössä tutkittiin JC-virusvasta-aineiden seroprevalenssia suomalaisessa MS-potilasaineistossa sekä selvitettiin JC-virusvasta- aineiden stabiliteettia neljän vuoden seurannassa. Myös MS-taudin immunomoduloivan hoidon ja muiden kliinisten tekijöiden vaikutusta JC-viruksen esiintymiseen selvitettiin. Tuloksien mukaan suurempi MS-plakkien tilavuus lähtötilanteessa on yhteydessä progressioon KEO:sta MS-tautiin. Sen sijaan MS-potilailla aivoatrofia tai plakkien volyymi eivät selkeästi korreloineet kokonaistoimintakyvyn huononemiseen neljän vuoden seurannassa. DTI:n avulla havaitut aivoparenkyymin muutokset olivat merkittävämmät KEO- ja MS- potilailla kuin terveillä verrokeilla. Lisäksi havaittiin, että DTI-arvojen huononeminen seurannassa oli yleisempää sellaisessa KEO- ryhmässä, joka eteni MS-tautiin. Lähtötilanteen DTI-muutokset eivät kuitenkaan ennustaneet konversiota. MS-potilailla corpus callosumin DTI-arvojen ja kokonaistoimintakyvyn huononemisen välillä oli heikko yhteys. Kuvantamistulokset viittaavat siihen, että DTI:lla on potentiaalia taudin aktivisuuden monitoroinnissa sekä KEO:ssa että MS-taudissa. Volumetriassa havaitut muutokset olivat yhteydessä taudin progressiossa vain KEO:ssa. Tulosten varmentaminen edellyttää kuitenkin suurempaa potilasaineistoa ja pidempää seuranta-aikaa. JC-virusvasta-aineiden merkitystä selvittävässä tutkimuksessa havaittiin korkea JC-virusvasta-aineiden seroprevalenssi sekä KEO- että MS-potilailla (57%). Seurannassa oli huomattavaa vasta-aineiden vaihtelua. Korkeampi ikä ja miessukupuoli olivat yhteydessä JC-virusvasta-ainepositiivisuuteen. Yhteenvetona todetaan, että JC-viruksen seroprevalenssi suomalaisilla MS potilailla on korkea kuten muissakin maissa. JC-virusvasta-ainestatuksen vaihtelu on syytä huomioida kliinisessä toiminnassa.Currently, magnetic resonance imaging (MRI) plays an important role in the diagnostic process and monitoring of the disease course in multiple sclerosis (MS). However, routinely used conventional MRI (T1- and T2-weighted sequences) is not specific to underlying MS pathology, and correlations between radiological findings and clinical measures are only modest. Potent therapies for MS, such as natalizumab (NTZ), have been associated with progressive multifocal leukoencephalopathy (PML). PML is a severe demyelinating disease caused by the reactivation of neurotropic JC virus (JCV). Due to the risk of PML, the serological assessment of antibodies against JCV is performed before starting NTZ. The main goal of this four-year follow-up study was to determine changes in the brain using nonconventional MRI techniques, such as volumetric measurements and diffusion tensor imaging (DTI), in clinically isolated syndrome (CIS) and MS. Whether volumetric and DTI-derived metrics could play prognostic roles in the prediction of the conversion of CIS to MS and whether these nonconventional measures correlate with disability progression expressed by an increase in the expanded disability status scale score in MS were also evaluated. In the third part of this thesis, the seroprevalence of the anti-JCV antibodies and temporal changes in JCV serostatus in a Finnish cohort of patients with CIS and MS were evaluated. The effect of demographic factors and MS therapies on JCV status was also determined. In the first and second part of this study, the higher baseline volumes of focal brain lesions related to MS pathology were associated with the conversion of CIS to MS. In contrast, whole brain atrophy and volumes of focal lesions were not clearly correlated with disability progression over four years in MS. With regard to DTI, diffusivity changes in the brain were stronger in CIS and MS when compared to healthy controls. Moreover, the worsening of DTI metrics was primarily observed in the CIS group that converted to MS. However, a clear correlation between baseline DTI metrics and the conversion to MS was not found. In MS, a tendency for a correlation between the DTI metric in the corpus callosum (CC) and disability progression was observed. The results suggest a potential role for DTI in monitoring disease activity in CIS and MS. Volumetric measurements seem to be helpful in evaluating disease progression in CIS but not in MS. However, further studies with larger populations and longer follow-up times are required to confirm these results. The third part of the thesis showed a high seroprevalence of anti-JCV antibodies (57%) in a cohort of CIS and MS patients. Moreover, marked temporal fluctuations in JCV serostatus were observed over four years. Demographics, such as higher age and male gender, were associated with anti-JCV antibody seropositivity. These observations are consistent with the reports from multinational studies and confirm high JCV seroprevalence in Finnish MS patients. Moreover, temporal changes in JCV serostatus should be considered in clinical practice