scholarly journals Longitudinal diffusion imaging across the C9orf72 clinical spectrum

2017 ◽  
Vol 89 (1) ◽  
pp. 53-60 ◽  
Author(s):  
Mary Kay Floeter ◽  
Laura E Danielian ◽  
Laura E Braun ◽  
Tianxia Wu

IntroductionDiscrepancies between diffusion tensor imaging (DTI) findings and functional rating scales in amyotrophic lateral sclerosis (ALS) may be due to symptom heterogeneity, particularly coexisting cognitive-behavioural dysfunction affecting non-motor regions of the brain. Carriers of expansion mutations in the C9orf72 gene, whose motor and cognitive-behavioural symptoms span a range from ALS to frontotemporal dementia, present an opportunity to evaluate the relationship between symptom heterogeneity and DTI changes.MethodsTwenty-eight C9orf72 mutation carriers with varied cognitive and motor symptoms underwent clinical evaluation and DTI imaging. Twenty returned for two or more follow-up evaluations. Each evaluation included motor, executive and behavioural scales and disease staging using the King’s college staging system.ResultsWidespread reduction of white matter integrity occurred in C9orf72 mutation carriers compared with 28 controls. The ALS Functional Rating Scale (ALSFRS-R) and King’s stage correlated with DTI measures of the corticospinal tract and mid-callosum. Cognitive and behavioural scores correlated with diffusion measures of frontal white matter. King’s stage, but not ALSFRS-R, correlated with anterior callosum DTI measures. Over a 6-month follow-up, DTI changes spread from anterior to posterior, and from deep to superficial subcortical white matter. In C9orf72 carriers with ALS or ALS-FTD, changes in corticospinal tractography measures correlated with changes in ALSFRS-R.ConclusionDiscrepancies between DTI findings and clinical measures of disease severity in ALS may partly be accounted for by cognitive-behavioural deficits affecting extramotor white matter tracts. Both ALSFRS-R and King’s stage correlated with corticospinal DTI measures. Group-level DTI changes could be detected over 6 months.

2018 ◽  
Vol 128 (6) ◽  
pp. 1865-1872 ◽  
Author(s):  
Joshua D. Burks ◽  
Andrew K. Conner ◽  
Phillip A. Bonney ◽  
Chad A. Glenn ◽  
Cordell M. Baker ◽  
...  

OBJECTIVEThe orbitofrontal cortex (OFC) is understood to have a role in outcome evaluation and risk assessment and is commonly involved with infiltrative tumors. A detailed understanding of the exact location and nature of associated white matter tracts could significantly improve postoperative morbidity related to declining capacity. Through diffusion tensor imaging–based fiber tracking validated by gross anatomical dissection as ground truth, the authors have characterized these connections based on relationships to other well-known structures.METHODSDiffusion imaging from the Human Connectome Project for 10 healthy adult controls was used for tractography analysis. The OFC was evaluated as a whole based on connectivity with other regions. All OFC tracts were mapped in both hemispheres, and a lateralization index was calculated with resultant tract volumes. Ten postmortem dissections were then performed using a modified Klingler technique to demonstrate the location of major tracts.RESULTSThe authors identified 3 major connections of the OFC: a bundle to the thalamus and anterior cingulate gyrus, passing inferior to the caudate and medial to the vertical fibers of the thalamic projections; a bundle to the brainstem, traveling lateral to the caudate and medial to the internal capsule; and radiations to the parietal and occipital lobes traveling with the inferior fronto-occipital fasciculus.CONCLUSIONSThe OFC is an important center for processing visual, spatial, and emotional information. Subtle differences in executive functioning following surgery for frontal lobe tumors may be better understood in the context of the fiber-bundle anatomy highlighted by this study.


2011 ◽  
Vol 33 (10) ◽  
pp. 2390-2406 ◽  
Author(s):  
Andreas Engvig ◽  
Anders M. Fjell ◽  
Lars T. Westlye ◽  
Torgeir Moberget ◽  
Øyvind Sundseth ◽  
...  

2005 ◽  
Vol 186 (4) ◽  
pp. 324-330 ◽  
Author(s):  
Lucia R. Valmaggia ◽  
Mark van der Gaag ◽  
Nicholas Tarrier ◽  
Marieke Pijnenborg ◽  
Cees J. Slooff

BackgroundThere is increasing evidence that cognitive–behavioural therapy can be an effective intervention for patients experiencing drug-refractory positive symptoms of schizophrenia.AimsTo investigate the effects of cognitive–behavioural therapy on in-patients with treatment-refractory psychotic symptoms.MethodManualised therapy was compared with supportive counselling in a randomised controlled study. Both interventions were delivered by experienced psychologists over 16 sessions of treatment. Therapy fidelity was assessed by two independent raters. Participants underwent masked assessment at baseline, after treatment and at 6 months' follow-up. Main outcome measures were the Positive and Negative Syndrome Scale and the Psychotic Symptoms Rating Scale. The analysis was by intention to treat.ResultsParticipants receiving cognitive–behavioural therapy had improved with regard to auditory hallucinations and illness insight at the post-treatment assessment, but these findings were not maintained at follow-up.ConclusionsCognitive–behavioural therapy showed modest short-term benefits over supportive counselling for treatment-refractory positive symptoms of schizophrenia.


1995 ◽  
Vol 167 (5) ◽  
pp. 653-658 ◽  
Author(s):  
K. C. M. Wilson ◽  
M. Scott ◽  
M. Abou-Saleh ◽  
R. Burns ◽  
J. R. M. Copeland

BackgroundWe examine the effects of cognitive-behavioural therapy (CBT) as an adjuvant to acute physical treatment and lithium maintenance therapy in reducing depression severity over a follow-up year in elderly depressed patients.MethodThe study consists of three phases. During the acute treatment and continuation phase, 17 of 31 patients received CBT as an adjuvant to treatment as usual. During the maintenance phase of 1 year, subjects were entered into a double-blind, placebo-controlled study of low-dose lithium therapy.ResultsReceiving adjuvant CBT significantly reduced patients' scores on the Hamilton Rating Scale for Depression during the follow-up year (repeated measures analyses of variance; P = 0.007). No significant differences were found between lithium and placebo maintenance therapy.ConclusionsCBT can be adapted as an adjuvant therapy in the treatment of severely depressed elderly patients and reduces depression severity during follow-up. The prophylactic failure of long-term lithium therapy may be explained through poor compliance.


1991 ◽  
Vol 8 (2) ◽  
pp. 70-78 ◽  
Author(s):  
Peter W. Dunne ◽  
Matthew R. Sanders ◽  
John A. Rowell ◽  
William R. McWhirter

Three adults with haemophilia participated in a study designed to determine the effectiveness of cognitive-behavioural techniques in the alleviation of chronic arthritic pain. The intervention comprised cognitive-coping skills, primarily relaxation training and guided imagery techniques, as well as identifying and altering antecedents and consequences that may have influenced their pain experience. The dependent measures included visual analogue rating scales, the Arthritis Impact Measurements Scale, the Beck Depression Inventory and pedometer readings. All three men showed significant reductions in pain, which were largely maintained at six-month follow-up. This study supports earlier findings with this population, and highlights the importance of monitoring the implementation of independent measures.


2020 ◽  
Vol 11 ◽  
Author(s):  
Ovidiu C. Andronesi ◽  
Katharine Nicholson ◽  
Kourosh Jafari-Khouzani ◽  
Wolfgang Bogner ◽  
Jing Wang ◽  
...  

Background: Oxidative stress and protein aggregation are key mechanisms in amyotrophic lateral sclerosis (ALS) disease. Reduced glutathione (GSH) is the most important intracellular antioxidant that protects neurons from reactive oxygen species. We hypothesized that levels of GSH measured by MR spectroscopic imaging (MRSI) in the motor cortex and corticospinal tract are linked to clinical trajectory of ALS patients.Objectives: Investigate the value of GSH imaging to probe clinical decline of ALS patients in combination with other neurochemical and structural parameters.Methods: Twenty-four ALS patients were imaged at 3 T with an advanced MR protocol. Mapping GSH levels in the brain is challenging, and for this purpose, we used an optimized spectral-edited 3D MRSI sequence with real-time motion and field correction to image glutathione and other brain metabolites. In addition, our imaging protocol included (i) an adiabatic T1ρ sequence to image macromolecular fraction of brain parenchyma, (ii) diffusion tensor imaging (DTI) for white matter tractography, and (iii) high-resolution anatomical imaging.Results: We found GSH in motor cortex (r = −0.431, p = 0.04) and corticospinal tract (r = −0.497, p = 0.016) inversely correlated with time between diagnosis and imaging. N-Acetyl-aspartate (NAA) in motor cortex inversely correlated (r = −0.416, p = 0.049), while mean water diffusivity (r = 0.437, p = 0.033) and T1ρ (r = 0.482, p = 0.019) positively correlated with disease progression measured by imputed change in revised ALS Functional Rating Scale. There is more decrease in the motor cortex than in the white matter for GSH compared to NAA, glutamate, and glutamine.Conclusions: Our study suggests that a panel of biochemical and structural imaging biomarkers defines a brain endophenotype, which can be used to time biological events and clinical progression in ALS patients. Such a quantitative brain endophenotype may stratify ALS patients into more homogeneous groups for therapeutic interventions compared to clinical criteria.


2004 ◽  
Vol 10 (2) ◽  
pp. 188-196 ◽  
Author(s):  
Emmanuelle Cassol ◽  
Jean-Philippe Ranjeva ◽  
Danielle Ibarrola ◽  
Claude Mékies ◽  
Claude Manelfe ◽  
...  

Our objectives were to determine the reproducibility of diffusion tensor imaging (DTI) in volunteers and to evaluate the ability of the method to monitor longitudinal changes occurring in the normal-appearing white matter (NAWM) of patients with multiple sclerosis (MS). DTI was performed three-mo nthly for one year in seven MS patients: three relapsing-remitting (RRMS), three secondary progressive (SPMS) and one relapsing SP. They were selected with a limited cerebral lesion load. Seven age- and sex-matched controls also underwent monthly examinations for three months. Diffusivity and anisotropy were quantified over the segmented whole supratentorial white matter, with the indices of trace (Tr) and fractional anisotropy (FA). Results obtained in volunteers show the reproducibility of the method. Patients had higher trace and lower anisotropy than matched controls (P B-0.0001). O ver the follow-up, both Tr and FA indicated a recovery after the acute phase in RRMS and a progressive shift towards abnormal values in SPMS. A lthough this result is not statistically significant, it suggests that DTI is sensitive to microscopic changes occurring in tissue of normal appearance in conventional images and could be useful for monitoring the course of the disease, even though it was unable to clearly distinguish between the various physiopathological processes involved.


2016 ◽  
Vol 46 (12) ◽  
pp. 2549-2560 ◽  
Author(s):  
M. Hu ◽  
X. Zong ◽  
J. Zheng ◽  
J. J. Mann ◽  
Z. Li ◽  
...  

BackgroundIt remains unclear whether the topological deficits of the white matter network documented in cross-sectional studies of chronic schizophrenia patients are due to chronic illness or to other factors such as antipsychotic treatment effects. To answer this question, we evaluated the white matter network in medication-naive first-episode schizophrenia patients (FESP) before and after a course of treatment.MethodWe performed a longitudinal diffusion tensor imaging study in 42 drug-naive FESP at baseline and then after 8 weeks of risperidone monotherapy, and compared them with 38 healthy volunteers. Graph theory was utilized to calculate the topological characteristics of brain anatomical network. Patients’ clinical state was evaluated using the Positive and Negative Syndrome Scale (PANSS) before and after treatment.ResultsPretreatment, patients had relatively intact overall topological organizations, and deficient nodal topological properties primarily in prefrontal gyrus and limbic system components such as the bilateral anterior and posterior cingulate. Treatment with risperidone normalized topological parameters in the limbic system, and the enhancement positively correlated with the reduction in PANSS-positive symptoms. Prefrontal topological impairments persisted following treatment and negative symptoms did not improve.ConclusionsDuring the early phase of antipsychotic medication treatment there are region-specific alterations in white matter topological measures. Limbic white matter topological dysfunction improves with positive symptom reduction. Prefrontal deficits and negative symptoms are unresponsive to medication intervention, and prefrontal deficits are potential trait biomarkers and targets for negative symptom treatment development.


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