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V L Stevenson

Publications and source records attributed to V L Stevenson.

33 records · Page 2Linked to original sources
PubMed2000

Diagnostic criteria for primary progressive multiple sclerosis: a position paper.

The unique clinical characteristics of primary progressive multiple sclerosis (PPMS) pose particular diagnostic difficulties, both in excluding other causes of progressive syndromes and in confirming the diagnosis of MS, which is not adequately addressed by current diagnostic criteria. This article presents new diagnostic criteria developed by a group of investigators on the basis of a review of their considerable experience with PPMS. (We conclude that at least 1 year of clinical progression must be documented before a diagnosis of PPMS is made.) Three levels of diagnostic certainty have been defined-definite, probable, and possible--based on clinical findings, abnormal cerebrospinal fluid, abnormalities on magnetic resonance imaging (MRI) of the brain and spinal cord, and evoked potentials. In definite PPMS, evidence of intrathecal synthesis of immunoglobulin G together with one of the following three MRI criteria is required: (1) nine brain lesions, (2) two spinal cord lesions, or (3) four to eight brain lesions and one spinal cord lesion. Preliminary testing of these criteria was carried out on a cohort of 156 patients participating in a European natural history study of PPMS: 64% fulfilled the criteria for definite PPMS, 35% for probable PPMS, and only 1% for possible PPMS. These criteria now require prospective validation in a cohort of newly diagnosed patients and by postmortem examination.

Diagnosis, Differential↗
PubMed1999

Primary and transitional progressive MS: a clinical and MRI cross-sectional study.

BACKGROUND: Ten percent of patients with MS have a progressive course from onset with no history of relapses or remissions. A smaller subgroup follow a similar progressive course but have a single relapse at some point (transitional progressive [TP] MS). To date these patients have been excluded from receiving licensed treatments for MS and from most therapeutic trials. OBJECTIVE: To document the clinical and MRI characteristics of a large cohort of progressive patients, including 158 with primary progressive (PP) MS and 33 with TPMS. Data from a small reference group of 20 patients with secondary progressive (SP) MS are also presented for reference. METHODS: Patients were recruited from six European centers. All underwent a clinical assessment including scoring on the Expanded Disability Status Scale (EDSS) and MRI of the brain and spinal cord. RESULTS: The men-to-women ratio was 81:77 (51% men) in the PP group, 14:19 (42% men) in the TP group, and 5:15 (25% men) in the SP group. The mean age at disease onset was significantly higher in the PP group than it was in the other two groups (PP 40.2 years, TP 34.9 years, SP 28.7 years). On MRI the PP group had lower mean brain T2 and T1 hypointensity lesion loads than the SP group (T2 12.02 versus 27.74 cm3, p = 0.001; T1 4.34 versus 7.04 cm3, p = 0.015). The SP and TP cohorts had significantly more T2-weighted lesions in the spinal cord than the PP patients, and the SP cohort had the greatest degree of atrophy. There was a correlation in the PP and TP patients between EDSS score and brain and spinal cord atrophy (r = 0.3, 0.2, p < or = 0.006) but not with brain lesion load. The PP and TP patients who presented with spinal cord pathology had significantly lower brain T2 and T1 lesion loads than those with non-spinal cord presentations (p = 0.002). CONCLUSIONS: The monitoring of disease progression in PPMS is difficult, although measures of atrophy correlate with the EDSS and appear most promising. This study increases our understanding of this unique patient group, which will be further expanded with the acquisition of serial data.

Adult↗
PubMed1999

Problems in designing and recruiting to therapeutic trials in primary progressive multiple sclerosis.

Patients with primary progressive multiple sclerosis have atypical clinical and magnetic resonance imaging (MRI) characteristics which present unique problems in designing and recruiting to therapeutic trials. The first randomised controlled therapeutic trial specifically for primary progressive multiple sclerosis is now underway. Although only an exploratory phase II study, it has provided further insight into difficulties in diagnosis, classification and choice of clinical and MRI outcome measures. Patients with primary progressive multiple sclerosis have a wide differential diagnosis and do not readily conform to the Poser criteria. They may therefore present diagnostic uncertainty, particularly as their classification often relies on a retrospective history. This was highlighted during the recruitment to this study of interferon-beta1a. Of the 138 patients referred with a definite diagnosis of primary progressive multiple sclerosis only 50 were enrolled in the study. Of the 88 patients not included, 50% either did not have primary progressive multiple sclerosis, or the diagnosis was not secure. Outcome measures pose particular problems. Clinically the focus must be on progression, and the measure should be both responsive and reliable. In relation to MRI, the currently recommended measures for therapeutic trials in relapsing/remitting and secondary progressive multiple sclerosis show little change in primary progressive multiple sclerosis, and therefore more pathologically specific MRI measures are required. Strict clinical guidelines and further developments in clinical and MRI measures are required to facilitate future therapeutic trials in primary progressive multiple sclerosis.

Brain↗
PubMed1999

1H magnetic resonance spectroscopy of normal appearing white matter in primary progressive multiple sclerosis.

Recent magnetic resonance imaging (MRI) and pathological studies have indicated that axonal loss is a major contributor to disease progression in multiple sclerosis. 1H magnetic resonance spectroscopy (MRS), through measurement of N-acetyl aspartate (NAA), a neuronal marker, provides a unique tool to investigate this. Patients with primary progressive multiple sclerosis have few lesions on conventional MRI, suggesting that changes in normal appearing white matter (NAWM), such as axonal loss, may be particularly relevant to disease progression in this group. To test this hypothesis NAWM was studied with MRS, measuring the concentration of N-acetyl derived groups (NA, the sum of NAA and N-acetyl aspartyl glutamate). Single-voxel MRS using a water-suppressed PRESS sequence was carried out in 24 patients with primary progressive multiple sclerosis and in 16 age-matched controls. Ratios of metabolite to creatine concentration (Cr) were calculated in all subjects, and absolute concentrations were measured in 18 patients and all controls. NA/Cr (median 1.40, range 0.86-1.91) was significantly lower in NAWM in patients than in controls (median 1.70, range 1.27-2.14; P = 0.006), as was the absolute concentration of NA (patients, median 6.90 mM, range 4.62-10.38 mM; controls, median 7.77 mM, range 6.60-9.71 mM; P = 0.032). There was no significant difference in the absolute concentration of creatine between the groups. This study supports the hypothesis that axonal loss occurs in NAWM in primary progressive multiple sclerosis and may well be a mechanism for disease progression in this group.

Adult↗
PubMed1999

Reproducibility of magnetic resonance imaging measurements of spinal cord atrophy: the role of quality assurance.

A sensitive magnetic resonance imaging (MRI) method to measure spinal cord cross-sectional area with the potential to monitor disease progression has recently been developed. As changes in cord area due to disease are usually small, assessment of the reliability of the methodology is essential in serial studies of spinal cord atrophy. The aim of this study was to institute and evaluate a protocol of quality assurance to determine long-term reproducibility of serial studies. Serial MRI of the spinal cord was carried out in five healthy volunteer controls over 1 year. Cross-sectional spinal cord areas were measured in a total of 46 scans. The mean coefficient of variation of all subjects over one year was 1.35%. The intra-observer coefficient of variation for same scan analysis was 0.63%. This study has confirmed high reliability of our serial data over one year and the on-going quality assurance protocol enables continuing evaluation of the reproducibility of results in serial studies. Quality assurance is an essential and practical component of all serial MRI studies, without which the clinical implications of change cannot be reliably evaluated.

Atrophy↗
PubMed1999

Cognitive function in primary progressive and transitional progressive multiple sclerosis: a controlled study with MRI correlates.

The relative rarity of primary progressive (PP) and transitional progressive (TP) multiple sclerosis has meant that little documentation of cognitive function in such patients is currently available. The aim of this study was to investigate the cognitive skills of patients with PP and TP multiple sclerosis relative to matched healthy controls, and to examine the relationship of this impairment to MRI parameters. Sixty-three patients (43 PP, 20 TP) were individually matched with healthy controls, who undertook the same cognitive tasks as the patient group. The neuropsychological assessment comprised Rao's brief repeatable battery, a reasoning test, and a measure of depression. Patients also underwent T1- and T2-weighted brain MRI. These patients were taken from a larger cohort (158 PP, 33 TP) in whom it had been demonstrated that the re were no significant differences between the mean scores of the PP and TP groups on any of the cognitive variables. The 63 patients were therefore taken as one group for comparison with the healthy controls. These patients performed significantly worse than the controls in tests of verbal memory, attention, verbal fluency and spatial reasoning. An impairment index was constructed and applied to the patient data. This correlated modestly with T2-lesion load (r = 0.45, P = 0.01), T1-hypointensity load (r = 0.45, P = 0.01) and cerebral volume (r = -0.35, P = 0.01). Thus, PP and TP multiple sclerosis patients demonstrate significant cognitive dysfunction when compared with matched healthy controls. The relationship between this impairment and MRI parameters is moderate, suggesting that cognitive dysfunction in PP and TP multiple sclerosis has a complex and multifactorial aetiology, which is not adequately explained by pathology as demonstrated on conventional MRI.

Adult↗
PubMed1999

Magnetic resonance imaging in the monitoring of disease progression in multiple sclerosis.

Disease progression and irreversible disability in multiple sclerosis results from incomplete recovery from relapses, but most importantly from insidious disease progression. Although magnetic resonance imaging parameters, such as new lesion rate and gadolinium enhancement, reflect inflammation and disease activity they have no bearing on disease progression. Until now the T2 lesion load or disease burden has been relied upon for this, despite its poor relationship with disability measures. This paper looks at the mechanisms responsible for disease progression and discusses the MR techniques now available to reflect these pathological processes.

Atrophy↗
PubMed1999

Magnetisation transfer of normal appearing white matter in primary progressive multiple sclerosis.

Patients with primary progressive multiple sclerosis may develop severe disability despite a paucity of lesions on conventional magnetic resonance imaging, raising the possibility that intrinsic changes in normal appearing white matter (NAWM) contribute to disability. This study has measured magnetisation transfer ratio (MTR), an index of tissue damage, of NAWM in 52 patients with primary progressive multiple sclerosis and 26 healthy controls. Absolute values of MTR were obtained from the genu of the corpus callosum and pons, and mean values were calculated from bilateral regions in the centrum semiovale, frontal white matter, parieto-occipital white matter and posterior limb of the internal capsule. The median MTR was lower in all regions in patients compared to controls. Median values (per cent units) were significantly lower in corpus callosum (39.73 vs 40.63; P=0.01), frontal white matter (39.11 vs 39.59; P=0.01) and centrum semiovale (37.21 vs37.82; P<0.05). This study has demonstrated small but widespread decreases in MTR in NAWM in primary progressive multiple sclerosis supporting the hypothesis that there are intrinsic changes in NAWM which may contribute to disability in this patient group.

Adult↗
PubMed1998

Improved imaging of the spinal cord in multiple sclerosis using three-dimensional fast spin echo.

We report assessment of a new three-dimensional fast spin echo (3D FSE) sequence in ten patients with clinically definite multiple sclerosis, comparing it with standard 2D FSE, and in ten normal controls. We saw 29 focal lesions on the 2D images and 53 on the 3D FSE images (P = 0.05); none were seen in controls. Lesion length was significantly smaller on the 3D FSE than on to the 2D FSE images (3D: 1.36; 2D 2.0; P = 0.03). This may relate in part to separation into several lesions on the 3D images of confluent abnormal signal seen on 2D and in part to detection of small lesions missed by the thicker 2D FSE slices (3 mm compared to 1.5 mm). The 3D FSE sequence looks promising in improving spinal cord imaging.

Adult↗
PubMed1998

Spinal cord atrophy and disability in MS: a longitudinal study.

OBJECTIVE: To assess whether it is possible to measure changes in cord cross-sectional area during a 1-year period in patients with MS reliably. BACKGROUND: Involvement of the spinal cord in MS is extremely common and an important element in the development of disability. Although little relation has been shown between the cord lesion load and disability, a strong correlation between spinal cord atrophy and the expanded disability status scale (EDSS) has been demonstrated in cross-sectional studies. METHOD: A highly reproducible semiautomated technique that measures the cross-sectional area of the cord at the C2 level was applied to 13 healthy control subjects and 28 patients serially. RESULTS: This study confirms that patients have significantly smaller cords than control subjects at baseline (control subjects: mean 80.95 mm2, patients: mean 71.25 mm2, p = 0.01) and demonstrates that patients have a significant loss in cord cross-sectional area during 12 months, which was not seen in control subjects (p < 0.001). This reduction in cord size was most marked in the primary progressive patients who had a mean cord cross-sectional area loss of 3.52 mm2 (5.2%) and least in the secondary progressive (-0.26 mm2, 0.7%) and benign patients (-0.41 mm2, 0.8%). The baseline cord cross-sectional area correlated strongly with the EDSS (r = -0.52, p = 0.005) and with disease duration (r = -0.75, p < 0.001); however, there was no significant difference in cord area (p = 0.69) or change in cord area (p = 0.51) between those patients with a definite increase in EDSS and those without. CONCLUSION: This study demonstrates, for the first time, that it is possible to measure changes in cord cross-sectional area over time. The serial measurement of spinal cord atrophy may thus make an important contribution to the evaluation of therapeutic efficacy, especially in primary progressive disease.

Adult↗
PubMed1998

The management of multiple sclerosis: current and future therapies.

Management of the patient with multiple sclerosis (MS) encompasses a number of distinct, if overlapping, areas. They include anticipation and prevention of problems, symptom control, drug therapies aimed at reducing disease activity and finally, rehabilitation and service delivery. The recent advent of new immunosuppressant treatments for MS is extremely exciting. Beta-interferons (1a and 1b) are now licensed worldwide and glatiramer acetate (Copaxane) is in use in the United States. Many more drugs, including intravenous immunoglobulin, mitoxantrone, methotrexate and cladribine, are undergoing trials and some are showing promising results. Future therapies with monoclonal antibodies and adhesion molecules are also undergoing extensive research. Realistically, however, these new treatments aimed at reducing disease activity will have little impact on existing problems or the degree of disability. Consequently, much of the management of a patient with MS relates to control of the vast array of symptoms. These range from the obvious problems of weakness and spasticity, ataxia and sphincter disturbance, to less common but still important problems such as visual, cognitive, swallowing and respiratory difficulties. Some of the most common, and to the patient most disabling, symptoms are fatigue, thermal sensitivity and pain, areas often neglected by the physician in the face of more obvious physical needs. Much can be done for the patient in all areas. A combination of education, physiotherapy and drug therapy is usually required but occasionally there is a place for more invasive treatments such as intrathecal baclofen administration for severe spasticity or thalamic surgery for cerebellar tremor. A multidisciplinary team approach is essential in the overall management of the patient with MS, particularly when assessing their needs as a basis for both inpatient rehabilitation programs and in the provision of a comprehensive community-based service.

Journal Article↗
PubMed1997

Imaging of the spinal cord and brain in multiple sclerosis: a comparative study between fast FLAIR and fast spin echo.

Recent reports have suggested that fluid attenuated inversion recovery (FLAIR) is a technique superior to conventional (CSE) or fast spin echo (FSE) T2-weighted sequences in detecting intrinsic lesions both in the brain and spinal cord. We report our experience of an inversion recovery prepared FSE, which we refer to as fast FLAIR, in a comparative study of ten patients with clinically definite multiple sclerosis (MS) who underwent cervical cord and brain imaging with both FSE and fast FLAIR. The results showed that in the cerebral hemispheres fast FLAIR detected more lesions than FSE (P < 0.001). However, FSE detected more lesions than fast FLAIR in the posterior fossa (P = 0.02) and in the cord fast FLAIR was much inferior detecting only 2 of 33 lesions seen on FSE. Estimating the T2 relaxation times of lesions in each of three areas (periventricular, posterior fossa, cervical cord) showed that the T2 value of posterior fossa and cervical cord lesions was significantly lower than that of periventricular lesions, suggesting that the lesion composition is different and consequently their imaging appearances are different. In conclusion, although fast FLAIR improves the detection of MS lesions in the cerebral hemispheres, its substantially lower sensitivity in the posterior fossa and spinal cord is a potentially important limitation to its use as a tool for the diagnosis of MS and for monitoring therapies. Further studies are needed to elucidate the mechanisms underlying the loss of sensitivity.

Brain↗
PubMed1996

Rehabilitation of incomplete spinal cord pathology: factors affecting prognosis and outcome.

To determine the factors affecting the outcome of patients with incomplete spinal cord lesions, a retrospective study was performed of all such patients (n = 49) admitted to the neurorehabilitation unit of the National Hospital for Neurology and Neurosurgery, London, over a 2-year period. Disability on admission and discharge as measured by the Functional Independence Measure (FIM), change in disability, presence or absence of neurological recovery, patient age, level of the lesion and length of inpatient stay were the main outcome measures. Data were complete on 39 patients. There were 20 patients with cervical myelopathy, 15 with intrinsic cord abnormalities including syrinxes, 7 with spinal cord infarcts and 7 with other conditions such as tropical spastic paraparesis and hereditary paraparesis. Age ranged from 17 to 88 years (mean 53). Mean duration of stay was 40 days and the duration was related to the diagnosis. Nineteen of the patients made some neurological improvement, while all but one improved on the FIM. This functional gain did not correlate with the patients' age, initial disability or level of the lesion, but was related to the length of stay in the unit, and neurological improvement. We conclude that the needs of patients with progressive incomplete spinal cord lesions due to neurological disease differ from those of patients with acute traumatic spinal cord lesions and are best managed in a neurological rehabilitation unit. Efficacy appears to be related to neurological recovery and the duration of rehabilitation. This study underlines the value of combined neurological and rehabilitation expertise in the management of this patient group and the need to incorporate both disciplines in planning service provision.

Adolescent↗