Biomedical subjects

D R Altmann

Publications and source records attributed to D R Altmann.

At least 19 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

Probabilistic diffusion tractography: a potential tool to assess the rate of disease progression in amyotrophic lateral sclerosis.

The goal of probabilistic tractography is to obtain a connectivity index along a white matter pathway that reflects fibre organization and is sensitive to pathological abnormalities contributing to disability. Here, we present the development of voxel-based connectivity measures along the tractography-derived corticospinal tract (CST). We investigated whether these connectivity measures are different in patients with amyotrophic lateral sclerosis (ALS) and correlate with the rate of disease progression. We also investigated whether fractional anisotropy (FA), which reflects directional coherence of fibre tracts, is reduced in the CST of ALS patients and relates to disease progression rate. Thirteen patients with probable or definite ALS and 19 healthy subjects were studied. The probabilistic tractography algorithm segmented the bilateral CST, along which FA and connectivity values were obtained. To take into account the asymmetric distribution of connectivity values, two summary statistic measures that focused on voxels with higher connectivity values were selected and then used in the analysis, together with the mean connectivity and the mean FA. To complete the analysis, the same summary measures for FA were included. Differences in all these indices between patients with moderate or rapid disease progression rate and controls were investigated using linear regression, adjusted for age and white matter fraction. The association between FA or connectivity in the CST and the disease progression rate was assessed using linear regression. Patients with a rapid disease progression rate had significantly lower summary connectivity measures than controls in the left CST, but there was only a borderline statistical difference in mean connectivity. Patients with rapid progression had a significantly lower mean FA, and any other FA measure, in both CSTs than controls. When only patients were considered, strong associations between the rate of disease progression and all the connectivity measures in the left CST were found (P-values between P < 0.001 and P = 0.002, partial correlation coefficients between -0.90 and -0.82). However, there was no evidence of an association between disease progression rate and any of the FA measures in the bilateral CST. Our findings suggest that FA and connectivity provide complementary information, since FA is sensitive to the detection of all the group differences, whereas the summary connectivity measures correlate with disease progression rate. The development of such connectivity measures raises their potential as markers of disease progression in ALS, and provides guidance for their use in other neurological diseases.

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

Long-term clinical outcome of primary progressive MS: predictive value of clinical and MRI data.

The authors sought to identify clinical and MRI predictors of outcome in primary progressive multiple sclerosis (PPMS). Clinical and MRI assessments were performed at baseline and 2 and 5 years (clinical only). At baseline, disease duration, expanded disability status scale (EDSS) and brain volume predicted outcome. Adding short-term change variables, baseline EDSS, changes in T2* lesion load and cord area, and number of new lesions were predictive. Clinical and MRI variables predict long-term outcome in PPMS.

Atrophy↗

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

Chronic inflammatory demyelinating polyradiculoneuropathy: MRI study of brain and spinal cord.

CNS demyelinating lesions have been reported in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). There are no studies of cord atrophy in CIDP. Ten patients with CIDP underwent brain and spinal cord MRI to investigate CNS demyelination and cord atrophy. No CNS demyelination was found, but the mean cervical cord area was significantly smaller in CIDP patients vs control subjects. Spinal cord atrophy may be related to degeneration secondary to axonal loss.

Adult↗

PubMed2005

Correlation of apparent myelin measures obtained in multiple sclerosis patients and controls from magnetization transfer and multicompartmental T2 analysis.

Two relatively new techniques purport to give measures of the myelin content of brain tissue. These measures are the myelin water fraction from multicompartmental T(2) analysis, and the semisolid proton fraction from analysis of magnetization transfer (MT). The myelin water fraction is the fraction of signal with a T(2) of less than 50 ms measured from a 32-echo sequence. It is believed to originate from water trapped between the myelin bilayers. The semisolid proton fraction is thought to include protons within phospholipid bilayers and macromolecular protons, and may also be a measure of myelin content. Multicompartmental T(2) and MT imaging were carried out on controls and patients with multiple sclerosis (MS), and estimates of the semisolid proton and myelin water fractions were obtained from white matter (WM), gray matter (GM), and MS lesions. These were then correlated for each tissue and subject group. Positive correlations were seen for MS lesions (r approximately 0.2) and in WM in patients (r = 0.6). A negative correlation (r approximately -0.3) was seen for GM. These results indicate that the two techniques measure, to some extent, the same thing (most likely myelin content), but that other factors, such as inflammation, mean they may provide complementary information.

Adult↗

PubMed2005

Increase in daytime symptoms is a sensitive and specific criterion for predicting corticosteroid-treated exacerbations in a clinical asthma trial.

BACKGROUND: To determine which diary card variables are the most predictive for administration of additional courses of corticosteroids using the TRUST (The Regular Use of Salbutamol Trial) data set. METHODS: Logistic regression models were used to identify the extent to which a change in diary card variable affected the odds ratio (OR) for administering a course of oral or increased inhaled corticosteroids. The complete TRUST diary card data were used with over 200,000 days of diary card observations from 983 mild to moderate asthmatic subjects. RESULTS: An increase in daytime symptoms of 1-5 U over baseline was associated with an increase in the OR for starting all types of corticosteroids from two- to 60-fold. CONCLUSIONS: These results indicate that an increase in daytime symptoms of two or more over baseline strongly predicts the administration of additional corticosteroids. The results have significant implications for both clinical practice and design of clinical trials in asthma.

Acute Disease↗

PubMed2005

Improvements in an oral aspirin challenge protocol for the diagnosis of aspirin hypersensitivity.

Oral aspirin challenge (OAC) is used to confirm aspirin hypersensitivity (AHs) but there is no consensus on a standardized protocol. As a prior clinical history of adverse reactions to aspirin is poorly predictive of a positive result from formal aspirin challenge, many patients have an OAC performed. We retrospectively identified and prospectively validated how a 1-day OAC protocol could be modified, and patient selection improved, to deliver a safe and more efficient service. In a retrospective audit of 45 OACs using a 2 h dose interval, all reactions occurred within 90 min of the threshold dose. Forty OACs were then performed using a 90-min dose interval. This reduced the mean duration of a positive and negative OAC from 6 to 5 h and from 8 to 6 h, respectively. Histories of multiple manifestations of AHs were found in 91.6% (11) of those with asthma, 87.5% (7) with angiooedema, 70.6% (12) with rhinosinusitis, 63.6% (7) with chronic non-vasculitic urticaria and all with anaphylaxis, who developed a positive OAC. None of those with anaphylaxis, 8.3% (1) with asthma and 12.5% (1) with angiooedema, with a positive OAC, had a history of a single manifestation of AHs. The efficiency of an OAC service can safely be improved by reduction of the dose interval from 2 to 1 (1/2) h, and more targeted patient selection, as the likelihood of a positive OAC increases among patients with a history of asthma, angiooedoema or anaphylaxis with multiple manifestations of AHs.

Administration, Oral↗

PubMed2005

The corpus callosum in first episode schizophrenia: a diffusion tensor imaging study.

BACKGROUND: Neuropathological and imaging studies suggest that corpus callosum abnormalities (CC) are present in schizophrenia, but it remains to be determined whether these abnormalities are present at illness onset. Diffusion tensor imaging (DTI), which is more sensitive than conventional magnetic resonance imaging (MRI) in detecting subtle structural changes in the organisation and integrity of white matter tracts, is an ideal tool to investigate this question. OBJECTIVE: To determine whether CC abnormalities are present at illness onset in schizophrenia. METHODS: Twenty patients (14 men, six women) with first episode schizophrenia and 29 controls (11 men, 18 women) were studied. Both high resolution volumetric T1-weighted images and DTI were acquired. Regions of interest (ROI) were placed in the splenium and genu of the CC and fractional anisotropy (FA) and diffusivity (D) measured. RESULTS: No differences in FA or D were detected in these regions between patients and controls. In women, irrespective of group membership, FA was significantly lower and there was a trend for D to be higher than in men, indicating less barriers to diffusion in females. CONCLUSION: The negative findings of this study suggest that in the early stages of schizophrenia there is no disruption to the integrity of the CC and raise the possibility that the neuropathological abnormalities may appear later and be progressive, at least in some patients.

Adolescent↗

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↗

PubMed2005

Acute axonal damage predicts clinical outcome in patients with multiple sclerosis.

The objectives of this study were (1) to determine how cerebrospinal fluid (CSF) neurofilament heavy chain (NfH(SM134) and NfH(SM135)) levels relate to clinical outcome in optic neuritis (ON) and multiple sclerosis (MS) relapse patients treated with high dose oral methylprednisolone; and (2) to correlate neurofilament and myelin basic protein (MBP) concentrations, particularly as the latter was previously associated with clinical disability. Fifty subjects participated in two double-blind, randomized, placebo-controlled clinical trials. Eight/18 patients in the ON trial and 15/32 subjects in the MS attack trial were treated with oral methylprednisolone. In the MS attack trial group, CSF NfH(SM134) and NfH(SM135) measured at week 3 and deltaCSF NfH(SMI34) levels from baseline to week 3 were predictive of clinical outcome at week 8 and 52. In the ON group, no such association was seen. When both groups were combined, baseline CSF NfH(SHM134) and NfH(SM135) correlated positively with baseline enhancing lesion volume (ELV) (r(s) =0.50, P <0.01 and rS =0.53, P <0.01, respectively). Levels of NfH(SM135) at baseline and week 3 also strongly correlated with the MBP concentration. This study supports the view that acute inflammation in ON and MS results in axonal pathology and that the latter has a role in determining functional impairment.

Acute Disease↗

PubMed2004

Serial magnetization transfer imaging in acute optic neuritis.

In serial studies of multiple sclerosis lesions, reductions in magnetization transfer ratio (MTR) are thought to be due to demyelination and axonal loss, with later rises due to remyelination. This study followed serial changes in MTR in acute optic neuritis in combination with clinical and electrophysiological measurements to determine if the MTR changes over time mirror the picture in multiple sclerosis lesions, further validating MTR as a marker of tissue integrity. Twenty-nine patients were recruited who had acute optic neuritis for a median of 13 days (range 7-24 days) since the onset of visual symptoms. A clinical examination and measurement of visual evoked potentials (VEP) was performed on each patient. Their optic nerves were imaged with a fat-saturated fast spin echo (FSE) sequence and a magnetization transfer sequence. Twenty-one had multiple subsequent examinations over the course of 1 year. In addition, 27 control subjects had their optic nerves imaged up to three times over 1 year. A blinded observer segmented the optic nerves from the MTR maps. Lesions were defined on the acute FSE images and, from the coordinates, the ratio of mean lesion MTR : healthy nerve MTR (lesion ratio) was calculated for each dataset. The time-averaged mean MTR in control optic nerves was 47.7 per cent units (pu). In diseased optic nerves, baseline mean MTR was 47.3 pu, with a mean lesion ratio of 0.98. The diseased optic nerve MTR and lesion ratio declined over time with a nadir at about 240 days at a mean MTR value of 44.2 pu and mean lesion ratio of 0.91. Subsequently, diseased optic nerve MTR appeared to rise; after 1 year the diseased optic nerve mean MTR was 45.1 pu (mean lesion ratio 0.93), although the difference was not significant compared with the nadir value. For each 0.01 increase in time-averaged lesion ratio logMAR visual acuity recovery improved by 0.03 (95% CI, 0.002, 0.08, P = 0.02). Time-averaged VEP central field latency was shorter by 6.1 ms (95% CI 1.5, 10.7, P = 0.012) per 1 pu rise in time-averaged diseased optic nerve MTR. The early fall in diseased optic nerve MTR is consistent with demyelination and Wallerian degeneration of transected axons. The late nadir compared with studies of multiple sclerosis lesions may have been due to slow clearance of myelin debris. Remyelination may have influenced subsequent MTR changes. The observations support using MTR to monitor symptomatic demyelinating lesions.

Acute Disease↗

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↗

PubMed2003

The longitudinal relation between brain lesion load and atrophy in multiple sclerosis: a 14 year follow up study.

BACKGROUND: Studies have suggested that T2 lesion activity is prominent in early relapsing-remitting multiple sclerosis, whereas brain atrophy, while seen early, appears more evident in later progressive disease. The temporal relation between these processes remains unclear. OBJECTIVE: To explore the association between changing brain lesion loads and subsequent tissue atrophy in multiple sclerosis. METHODS: 28 subjects with clinically probable or definite multiple sclerosis (mean age 46.0 years; 17 female and 11 male) were followed for 14 years after first onset of symptoms. T2 lesion loads were estimated soon after symptom onset and at around five, 10, and 14 years later. Disease related atrophy was estimated at the 14 year follow up by comparing brain tissue volumes (proportional to total intracranial volumes) determined in the multiple sclerosis group with data from 29 normal control subjects (mean age 36.7 years; 16 female, 13 male) using multiple linear regression analyses to allow for differences in age and sex distributions. RESULTS: Change in lesion load in the first five years was more closely correlated to disease related brain atrophy at 14 years than later changes in lesion load, although the correlation was only moderate (Spearman correlation = -0.528, p = 0.004). CONCLUSIONS: From this, it appears that early rather than later focal lesion accumulation relates to subsequent brain atrophy, but factors unconnected directly with lesion formation probably also play a significant role in determining such atrophy.

Adult↗