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W Rashid

Publications and source records attributed to W Rashid.

13 recordsLinked to original sources
PubMed2006

Cord atrophy separates early primary progressive and relapsing remitting multiple sclerosis.

BACKGROUND AND OBJECTIVE: The onset of multiple sclerosis is relapsing remitting or primary progressive. An improved understanding of the causes of early progressive disability in primary progressive multiple sclerosis (PPMS) could provide mechanistic targets for therapeutic intervention. METHODS: Five magnetic resonance imaging (MRI) parameters that could potentially cause progressive disability were investigated in 43 patients with early PPMS and in 37 patients with early relapsing remitting multiple sclerosis (RRMS): atrophy in brain, both grey matter and white matter; intrinsic abnormality in brain, both grey matter and white matter (measured by the magnetisation transfer ratio (MTR)); and atrophy of the upper cervical spinal cord. Both groups were also compared with controls. RESULTS: Patients with PPMS were older and more likely to be men. Both patient groups had atrophy of brain grey matter and white matter, and intrinsic abnormality in MTR of normal-appearing grey matter and white matter. Cord atrophy was present only in the PPMS (mean cord area: PPMS, 67.8 mm2; RRMS, 72.7 mm2; controls, 73.4 mm2; p = 0.007). This was confirmed by multivariate analysis of all five MRI parameters, age and sex. CONCLUSION: Grey matter and white matter of the brain are abnormal in both early RRMS and PPMS, but cord atrophy is present only in PPMS. This is concordant with myelopathy being the usual clinical presentation of PPMS. Measurement of cord atrophy seems to be clinically relevant in PPMS treatment trials.

Adult↗
PubMed2006

Increasing cord atrophy in early relapsing-remitting multiple sclerosis: a 3 year study.

OBJECTIVES: Previous studies have shown that upper cervical cord atrophy (UCCA) occurs in multiple sclerosis (MS), particularly in those disabled and with primary or secondary progressive disease. It is less clear how early it can be detected in relapsing-remitting (RR) MS, and whether early cord atrophy relates to the concurrent or future clinical course. METHODS: Twenty seven RR MS patients (median disease duration 1.7 years, in all cases <3 years from onset) were recruited along with 20 controls. They were followed for up to 3 years with a yearly assessment of UCCA and clinical function measured by the Expanded Disability Status Scale (EDSS) and MS Functional Composite Score (MSFC). Clinical and MRI correlations were investigated. Statistical models adjusted for covariates including total intracranial volume. RESULTS: Longitudinal analysis showed a significant decrease in UCCA in patients both within the patient cohort (p < 0.001) and in comparison with controls (p = 0.001). There was a significant increase in EDSS (p = 0.008) but no significant change in MSFC. The rate of UCCA loss did not correlate with clinical change or with change in brain volume. CONCLUSIONS: In summary, serial UCCA measurement detects the development of spinal cord atrophy in clinically early RR MS.

Adult↗
PubMed2005

Metabolite changes in early relapsing-remitting multiple sclerosis. A two year follow-up study.

Previous in vivo proton magnetic resonance spectroscopic imaging ((1)H-MRSI) studies have found reduced levels of N-acetyl-aspartate (NAA) in multiple sclerosis (MS) lesions, the surrounding normal-appearing white matter (NAWM) and cortical grey matter (CGM), suggesting neuronal and axonal dysfunction and loss. Other metabolites, such as myoinositol (Ins), creatine (Cr), choline (Cho), and glutamate plus glutamine (Glx), can also be quantified by (1)H-MRSI, and studies have indicated that concentrations of these metabolites may also be altered in MS. Relatively little is known about the time course of such metabolite changes. This preliminary study aimed to characterise changes in total NAA (tNAA, the sum of NAA and N-acetyl-aspartyl-glutamate), Cr, Cho, Ins and Glx concentrations in NAWM and in CGM, and their relationship with clinical outcome, in subjects with clinically early relapsing-remitting MS (RRMS). Twenty RRMS subjects and 10 healthy control subjects underwent (1)H-MRSI examinations yearly for two years. Using the LCModel, tNAA, Cr, Cho, Ins and Glx concentrations were estimated both in NAWM and CGM. At baseline, the concentration of tNAA was significantly reduced in the NAWM of the MS patients compared to the control group (-7%, p = 0.003), as well as in the CGM (-8.7%, p = 0.009). NAWM tNAA concentrations tended to recover from baseline, but otherwise tissue metabolite profiles did not significantly change in the MS subjects, or relatively between MS and healthy control subjects. While neuronal and axonal damage is apparent from the early clinical stages of MS, this study suggests that initially it may be partly reversible. Compared with other MR imaging measures, serial (1)H-MRSI may be relatively less sensitive to progressive pathological tissue changes in early RRMS.

Adult↗
PubMed2005

Increasing normal-appearing grey and white matter magnetisation transfer ratio abnormality in early relapsing-remitting multiple sclerosis.

Abnormalities within normal-appearing grey and white matter (NAGM and NAWM) occur early in the clinical course of multiple sclerosis (MS) and can be detected in-vivo using the magnetisation transfer ratio (MTR). To better characterize the rates of change in both tissues and to ascertain when such changes begin, we serially studied a cohort of minimally disabled, early relapsing-remitting MS patients, using NAGM and NAWM MTR histograms. Twenty-three patients with clinically definite early relapsing-remitting MS (mean disease duration at baseline 1.9 years), and 19 healthy controls were studied. A magnetisation transfer imaging sequence was acquired yearly for two years. Twenty-one patients and 10 controls completed followup. NAWM and NAGM MTR histograms were derived and mean MTR calculated. A hierarchical regression analysis, adjusting for brain parenchymal fraction,was used to assess MTR change over time. MS NAWM and NAGM MTR were significantly reduced in comparison with controls at baseline and, in patients, both measures decreased further during follow-up: (-0.10 pu/year, p=0.001 and -0.18 pu/year, p<0.001 respectively). The rate of MTR decrease was significantly greater in NAGM than NAWM (p=0.004). Under the assumption that such changes are linear, backward extrapolation of the observed rates of change suggested that NAWM abnormality began before symptom onset. We conclude that increasing MTR abnormalities in NAWM and NAGM are observed early in the course of relapsing-remitting MS. It is now important to investigate whether these measures are predictive of future disability, and consequently, whether MTR could be used as a surrogate marker in therapeutic trials.

Adult↗
PubMed2005

Gray and white matter volume changes in early RRMS: a 2-year longitudinal study.

BACKGROUND: Brain atrophy, in excess of that seen with normal aging, has been observed early in the clinical course of relapsing-remitting multiple sclerosis (RRMS). Previous work has suggested that at this stage of the disease, gray matter (GM) atrophy progresses more rapidly than the white matter (WM) atrophy. OBJECTIVES: To characterize the evolution of GM and WM volumes over 2 years, and their associations with lesion loads in a cohort of patients with clinically early RRMS. METHODS: Twenty-one patients with RRMS (mean age 37.5 years, mean disease duration from symptom onset 2.1 years) and 10 healthy control subjects (mean age 37.1 years) were studied. Tissue volumes, as fractions of total intracranial volumes, were estimated at baseline and 1- and 2-year follow-up. Brain parenchymal fractions (BPF), GM fractions (GMF), and WM fractions (WMF) were estimated. In subjects with MS, brain lesion loads were determined on conventional T2-weighted along with pre- and post-gadolinium (Gd) enhanced T1-weighted images at each timepoint. RESULTS: A decrease in GMF was observed in subjects with MS vs normal controls over the 2 years of the study (mean -2.1% vs -1.0%, p = 0.044), while no change was seen in WMF over the same period (mean -0.09% vs +0.09%, p = 0.812). However, when the MS cohort was divided in half, dependent upon change in Gd-enhancing lesion load over 2 years (n = 20), a decrease in WMF was seen in the group (n = 10) with the largest decline in Gd volume, whereas WMF increased in the other half (n = 10) concurrent with a net increase in volume of Gd-enhancing lesions (difference between groups: p = 0.034). CONCLUSIONS: Increasing gray matter but not white matter (WM) atrophy was observed early in the clinical course of relapsing-remitting multiple sclerosis. Fluctuations in inflammatory WM lesions appear to be related to volume changes in WM over this time period.

Adult↗
PubMed2005

Emergence of thalamic magnetization transfer ratio abnormality in early relapsing-remitting multiple sclerosis.

While there is now evidence for thalamic abnormality in established secondary progressive and relapsing-remitting multiple sclerosis (MS), it remains unclear when such abnormality begins. This study investigated the emergence of thalamic abnormality in relapsing-remitting MS by assessing the thalamic magnetization transfer ratio (MTR) in a cohort with clinically early disease. Twenty-three patients with early relapsing-remitting MS (mean age 37; mean disease duration 1.9 years; Expanded Disability Status Scale (EDSS) range 0-3) and 19 healthy controls (mean age 34) were imaged yearly with a magnetization transfer imaging sequence. Twenty-two MS patients and 14 controls completed two-year follow-up. Regions of interest were placed in both thalami and mean thalamic MTR calculated. At baseline, significant differences between patient and control thalamic MTR were not observed. However, at years one and two, the thalamic MTR in patients was significantly lower than control MTR. Although baseline lesion volume did not correlate with baseline thalamic MTR, at year one, an association between baseline lesion volume and year one thalamic MTR emerged. There was also a significant inverse correlation between EDSS and thalamic MTR (r = -0.47, P = 0.02). The study suggests that thalamic involvement occurs within the first five years of MS onset, when most patients are still minimally disabled.

Adult↗
PubMed2004

Evidence for grey matter MTR abnormality in minimally disabled patients with early relapsing-remitting multiple sclerosis.

OBJECTIVES: To establish whether magnetisation transfer ratio (MTR) histograms are sensitive to change in normal appearing grey matter (NAGM) in early relapsing-remitting multiple sclerosis (RRMS) in the absence of significant disability; and to assess whether grey or white matter MTR measures are associated with clinical measures of impairment in early RRMS METHODS: 38 patients were studied (mean disease duration 1.9 years (range 0.5 to 3.7); median expanded disability status scale (EDSS) 1.5 (0 to 3)), along with 35 healthy controls. MTR was determined from proton density weighted images with and without MT presaturation. SPM99 was used to generate normal appearing white matter (NAWM) and NAGM segments of the MTR map, and partial voxels were minimised with a 10 pu threshold and voxel erosions. Mean MTR was calculated from the tissue segments. Atrophy measures were determined using a 3D fast spoiled gradient recall sequence from 37 patients and 17 controls. RESULTS: Mean NAGM and NAWM MTR were both reduced in early RRMS (NAGM MTR: 31.9 pu in patients v 32.2 pu in controls; p<0.001; NAWM MTR: 37.9 v 38.3 pu, p = 0.001). Brain parenchymal fraction (BPF) correlated with NAGM MTR, but when BPF was included as a covariate NAGM MTR was still lower in the patients (p = 0.009). EDSS correlated with NAGM MTR (r = 0.446 p = 0.005). CONCLUSIONS: In early RRMS, grey matter MTR abnormality is apparent. The correlation with mild clinical impairment (in this essentially non-disabled cohort) suggests that NAGM MTR could be a clinically relevant surrogate marker in therapeutic trials.

Adult↗
PubMed2004

Abnormalities of cerebral perfusion in multiple sclerosis.

BACKGROUND: Measuring perfusion provides a potential indication of metabolic activity in brain tissue. Studies in multiple sclerosis (MS) have identified areas of decreased perfusion in grey matter (GM) and white matter (WM), but the pattern in clinical subgroups is unclear. OBJECTIVES: This study investigated perfusion changes in differing MS clinical subgroups on or off beta-interferon therapy using a non-invasive MRI technique (continuous arterial spin labelling) to investigate whether different clinical MS subtypes displayed perfusion changes and whether this could give a further insight into the pathological mechanisms involved. METHODS: Sixty patients (21 relapsing remitting, 14 secondary progressive, 12 primary progressive, 13 benign) and 34 healthy controls were compared. Statistical parametric mapping (SPM '99) was used to investigate regional variations in perfusion in both GM and WM. Global WM perfusion was derived by segmenting WM from images using T(1) relaxation times. RESULTS: Regions of lower perfusion in predominantly GM were observed in the primary and secondary progressive cohorts, particularly in the thalamus. Increased WM perfusion was seen in relapsing remitting and secondary progressive cohorts. CONCLUSIONS: Low GM perfusion could reflect decreased metabolism secondary to neuronal and axonal loss or dysfunction with a predilection for progressive forms of MS. Increased WM perfusion may indicate increased metabolic activity possibly due to increased cellularity and inflammation. Improved methodology and longitudinal studies may enable further investigation of regional and temporal changes, and their relationship with physical and cognitive impairment.

Adolescent↗
PubMed2004

Progressive grey matter atrophy in clinically early relapsing-remitting multiple sclerosis.

Brain atrophy appears to occur in patients with multiple sclerosis (MS) in excess of that associated with normal ageing, and may be observed early in the clinical course of the disease. The dynamics and tissue specificity of this process remain unclear This preliminary study explored the evolution of brain grey matter (GM) and white matter (WM) volume loss (as fractions of total intracranial volumes) in 13 subjects with relapsing-remitting MS (mean disease duration 1.9 years at first scan), compared with nine normal control (NC) subjects. Subjects were scanned every six months for 18 months. In MS compared with NC subjects, significant differences in WM fractional volumes were observed at baseline (mean - 5.8%, P = 0.008) but no apparent progressive WM tissue loss was detected. In contrast, while no significant differences in GM fractional volumes were observed at baseline, there was significantly greater time-related volume loss in MS compared with NC subjects over the follow-up period (circa - 0.0086 per year in MS subjects, - 0.0021 per year in the NC subjects, difference P = 0.010). These results suggest that while both GM and WM atrophy are seen early in the clinical course of MS, they may not occur concurrently and may evolve at different rates.

Adult↗
PubMed2004

Diffusion tensor imaging of early relapsing-remitting multiple sclerosis with histogram analysis using automated segmentation and brain volume correction.

Diffusion tensor magnetic resonance imaging (DTI) reveals measurable abnormalities in normal-appearing brain tissue (NABT) in established multiple sclerosis (MS). However, it is unclear how early this occurs. Recent studies have employed whole brain histogram analysis to improve sensitivity, but concern exists regarding reliability of tissue/cerebrospinal fluid segmentation and possible intersubject brain volume differences, which can introduce partial volume error: To address this, 28 early relapsing-remitting MS subjects [median disease duration 1.6 years; median Expanded Disability Status Scale (EDSS) score 1.5] and 20 controls were compared with whole brain histogram analysis using an automated segmentation algorithm to improve reproducibility. Brain parenchymal volumes (BPV) were estimated for each subject in the analysis. The mean, peak height and peak location were calculated for DTI parameters [fractional anisotropy (FA), mean diffusivity and volume ratio]. An increased FA peak height in MS subject NABT was observed (P = 0.02) accounting for age, gender and BPV. Removing BPV revealed additional abnormalities in NABT. The main conclusions are i) FA peak height is increased in NABT in early MS, ii) partial volume edge effects may contribute to apparent NABT histogram abnormalities, and iii) correction for brain volume differences should reduce potential partial volume edge effects.

Adult↗