Long-term stabilization after bone marrow transplantation in juvenile metachromatic leukodystrophy.
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Adolescent↗
Biomedical subjects
D Kidd
Publications and source records attributed to D Kidd.
The transverse magnetisation decay characteristics of longstanding lesions and normal-appearing white matter in multiple sclerosis.
The characteristics of transverse magnetisation decay of 120 longstanding lesions and 40 regions of normal-appearing white matter have been analysed in 40 patients with multiple sclerosis (MS) and 10 normal controls. Fifty lesions showed a biexponential decay in which two water compartments-one probably intracellular, the other extracellular-could be defined. There was a higher frequency of biexponential lesions in patients with a primary progressive course but no significant difference between benign and secondary progressive groups. Seventy lesions showed a monoexponential decay, of which 31 showed a T2 of greater than 200 ms, implying that these lesions were predominantly composed of extracellular rather than intracellular water. The results imply that an expanded extracellular space within chronic MS brain lesions is a common finding at all levels of disability and disease course. In so far as an expanded extracellular space implies axonal loss, the results suggest that the latter occurs commonly in longstanding MS lesions. The lack of correlation with disability suggests a limited role for the technique in therapeutic monitoring.
Adult↗
Cost-effectiveness analysis of spinal cord stimulation in treatment of failed back surgery syndrome.
This article presents an analysis of the medical costs of spinal cord stimulation (SCS) therapy in the treatment of patients with failed back surgery syndrome (FBSS). We compared the medical costs of SCS therapy with an alternative regimen of surgeries and other interventions. Externally powered (external) and fully internalized (internal) SCS systems were considered separately. Clinical management models of each of the therapy alternatives were derived from the clinical literature, retrospective data sets, expert opinion, and published diagnostic and therapy protocols. No value was placed on pain relief or improvements in the quality of life that successful SCS therapy can generate. We found that by reducing the demand for medical care by FBSS patients, SCS therapy can lower medical costs. On average, given current screening and efficacy rates, SCS therapy pays for itself within 5.5 years. For those patients for whom SCS therapy is clinically efficacious, the therapy pays for itself within 2.1 years.
Back Pain↗
Daily urinary neopterin excretion as an immunological marker of disease activity in multiple sclerosis.
The aim of this study was to assess neopterin, a marker of interferon gamma (IFN-gamma) induced macrophage activity, as a possible surrogate marker of inflammation in patients with multiple sclerosis. Urinary neopterin to creatinine ratios (UNCRs) were measured daily in 10 primary progressive (PP). 10 relapsing remitting (RR) and 11 secondary progressive (SP) patients with multiple sclerosis, and 14 normal control (NC) subjects, for periods of up to 12 weeks. After excluding measurements related to infection, the median of the individuals' average UNCRs was significantly higher in patients than in controls (P < 0.001 for all patients and P < 0.01 for each of the three groups of patients); the median UNCRs (and interquartile ranges) were 187 (135-231), 187 (165-277), 218 (164-517) and 134 (97-152) mumol/mol for PP, RR, SP patients and controls, respectively. Similarly, patients had a greater median proportion of days with a UNCR above normal (P < 0.001 for all patients and P < 0.01 for each group); the median percentage (and interquartile ranges) were 16 (6-62), 28 (21-36), 49 (14-86) and 0 (0-6)% for PP, RR, SP patients and controls, respectively. They also had a greater number of peaks in their serial UNCR measurements than controls (P < 0.001 for all patients and P < 0.01 for each group); the means +/- SD peaks/subject/month were: 2.1 +/- 1.8; 3.0 +/- 1.7; 3.3 +/- 2.3 and 0.2 +/- 0.6 for PP, RR, SP patients and controls, respectively. Nine relapses occurred in nine patients during the study, and all were associated with increased neopterin excretion, which tended to be greater than that on days not associated with a relapse. Three of the nine relapses were preceded by an upper respiratory tract infection. In eight out of 13 patients who had infections during the study, increased neopterin excretion was noted for periods of up to 6 weeks post-infection, significantly longer than that which occurred after infections in controls. This confirms infection as a potent inducer of symptomatic and asymptomatic disease activity in mutiple sclerosis, and provides further support of a pivotal role for IFN-gamma in te pathogenesis of mutiple sclerosis. Urinary neopterin excretion is increased in patients with both progressive and relapsing mutiple sclerosis, and therefore has potential as a surrogate marker of the inflammatory component of mutiple sclerosis disease activity.
Adult↗
Late functional deterioration following paralytic poliomyelitis.
Many patients with previous poliomyelitis develop 'post-polio syndrome' (PPS) in which late functional deterioration follows a period of relative stability. The frequency with which PPS can be attributed to clearly defined causes remains uncertain. We reviewed 283 newly-referred patients with previous poliomyelitis seen consecutively over a 4-year period; 239 patients developed symptoms of functional deterioration at a mean of 35 (5-65) years after the paralytic illness. Functional deterioration was associated with orthopaedic disorders in 170 cases, neurological disorders in 35, respiratory disorders in 19 and other disorders in 15. Progressive post-polio muscular atrophy was not observed. Functional deterioration following paralytic polio-myelitis is common, and associated with orthopaedic, neurological, respiratory and general medical factors which are potentially treatable.
Adult↗
Prospective study of neurorehabilitation in multiple sclerosis.
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Adult↗
Lymphocyte-endothelial cell interactions in multiple sclerosis: disease specificity and relationship to circulating tumour necrosis factor-alpha and soluble adhesion molecules.
This study addressed two questions; first, whether the supranormal adherence of blood lymphocytes from patients with multiple sclerosis (MS) to endothelial cell monolayers treated with tumour necrosis factor-alpha (TNF alpha) was a feature common to other inflammatory disorders; and second, whether the adherence properties of blood lymphocytes from MS patients were related to changes in disease activity and to levels of circulating TNF alpha and soluble adhesion molecules. In the first part of the investigation, lymphocytes from 14 patients with MS were more adherent to TNF alpha-treated endothelial cells (P < 0.01) than those from healthy controls, whereas the adherence properties of lymphocytes from 12 patients with rheumatoid arthritis, eight patients with psoriasis and ten patients with neurological diseases other than MS were normal. In the second phase of the work, measurement of the adhesive properties of lymphocytes isolated at monthly intervals from a further six MS patients over a 5-8 month period, found that changes in binding to TNF alpha-treated endothelial cells, directly paralleled changes in circulating levels of TNF alpha (r = 0.77; P < 0.001) and soluble vascular cell adhesion molecule-I (sVCAM-1) r = 0.67; P = 0.001). An increase in disease activity, measured by T2-weighted and gadolinium-enhanced magnetic resonance imaging of the central nervous system (CNS), occurred in two patients and was associated with heightened lymphocyte adhesiveness and a rise in serum TNF alpha levels. Further analysis of the 34 serum samples from the six MS patients revealed a direct relationship between the concentration of sL-selectin and soluble intercellular adhesion molecule-I (sICAM-I) (r = 0.65; P < 0.001) and between sL-selectin and sTNF alpha (r = 0.42; P < 0.02). These findings support the view that disease activity in MS is associated with an increased adhesive interaction of blood lymphocytes with vascular endothelium at inflammatory sites within the CNS.
Adult↗
Longitudinal study of soluble adhesion molecules in multiple sclerosis: correlation with gadolinium enhanced magnetic resonance imaging.
OBJECTIVE: To assess whether serial serum levels of soluble forms of intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) are useful as surrogate markers of disease activity in multiple sclerosis (MS). BACKGROUND: Increased levels of sICAM-1 and sVCAM-1 have been described in cross-sectional, but not longitudinal, studies of patients with MS. Although they appear to correlate with clinical and MRI markers of disease activity, their role as potential surrogate markers remains undefined. METHODS: Serial serum levels of sICAM-1 and sVCAM-1 were measured in patients with MS undergoing monthly gadolinium-enhanced MRI studies of the brain (462 gadolinium-enhanced MRI in 57 patients) and in 12 normal control subjects. Ten patients had primary progressive (PP), 22 relapsing remitting (RR), and 25 secondary progressive (SP) disease. RESULTS: Levels of sICAM-1 and sVCAM-1 were increased intermittently in patients with all subtypes of MS. Median levels of sICAM-1 were elevated in patients with MS compared with normal controls (normal controls median [interquartile range] = 176[119-209] compared with PP = 502[194-1768], RR = 419[158-481], and SP = 352[196-469] ng/mL; p = 0.04). After excluding patients with PP MS, patients with high sICAM-1 levels had a greater number of gadolinium-enhancing lesions per study (1.9[0.9-4.3]) than patients with normal levels (0.4[0-2.7], p = 0.03), and patients with MRI studies with no gadolinium-enhancing lesions had lower associated sICAM-1 levels (200 ng/mL[85-561]) than patients with only persistent (349 ng/mL[82-615]) or new enhancing lesions (497 ng/mL[108-667], p = 0.03). Patients with RR or SP disease that progressed clinically during the study had a greater number of gadolinium-enhancing lesions per MRI study (3.5[0.4-5.5]) than did patients in whom disease did not progress (1.2 [0.3-2.7], p = 0.03). The patients with progressive disease tended to have higher sICAM-1 levels (469 ng/mL [196-1019]) than patients in whom disease did not progress (353 ng/mL [171-469], p = 0.07). Although MS patients tended to have higher sVCAM-1 levels than did normal controls, this finding was not significant. No correlation could be found between levels of sVCAM-1 and gadolinium enhancement on MRI. CONCLUSIONS: Patients with MS have elevated levels of sICAM-1, which correlate with gadolinium enhancement on MRI and possibly short-term disease progression. Soluble ICAM-1, and not sVCAM-1, may therefore be suitable as a long-term surrogate marker of disease activity in MS.
Adult↗
LK6, a short lived protein kinase in Drosophila that can associate with microtubules and centrosomes.
A number of polyclonal mouse sera were raised against Drosophila proteins that bound to microtubules in vitro (Kellogg et al. (1989) J. Cell Biol. 109, 2977-2991). Some of these sera recognised centrosomes in vivo, and we have been using these to screen expression libraries to isolate cDNAs encoding these putative centrosomal microtubule-associated proteins. Here we report the cloning of one such cDNA that encodes a novel serine/threonine protein kinase called LK6. The protein appears to exist in two forms: an abundant 185 kDa form and a rarer approximately 220 kDa form that interacts with microtubules. At least some of the LK6 protein is located in centrosomes at all stages of the cell cycle in fly embryos. Interestingly, the protein contains a PEST-like sequence and is rapidly turned over in vivo. Constitutive overexpression of LK6 is deleterious to flies and causes defects in microtubule organisation in both eggs and early embryos, whereas constitutive overexpression of a mutant form containing a point mutation that severely impairs the kinase activity is without effect. These findings suggest that LK6 may play a role in regulating microtubule function.
Amino Acid Sequence↗
Spinal MRI in patients with suspected multiple sclerosis and negative brain MRI.
Although MRI detects the white matter lesions of multiple sclerosis within the brain with high sensitivity, a minority of patients have normal brain MRI. We describe 20 patients, selected from over 170 who had undergone brain imaging with minimal (n = 12) or no (n = 8) abnormalities (median number of lesions = I, range, 0-3) but in whom spinal MRI was abnormal. Twelve had clinically definite or laboratory supported definite multiple sclerosis according to the Poser criteria; one had clinically probable disease and seven, not fulfilling the Poser criteria, were classified as possible multiple sclerosis. All had presented with symptoms and signs referable to the spinal cord or optic nerves. Eleven had a primary progressive course, eight relapsing-remitting and only one secondary progressive. Moderate or severe disability was the rule in the primary progressive cases; all the relapsing-remitting patients had minimal disability. All had at least one lesion visible in the spinal cord (median 2; range 1-6). In patients in whom the diagnosis of multiple sclerosis is not supported by abnormalities on brain MRI, imaging of the spinal cord can be of considerable value.
Adult↗
MRI dynamics of brain and spinal cord in progressive multiple sclerosis.
OBJECTIVE: To assess the usefulness of serial cord MRI in patients with progressive multiple sclerosis. METHODS: Monthly MRI of the brain and spinal cord with and without gadolinium enhancement was carried out in 19 patients with progressive multiple sclerosis (10 primary progressive, nine secondary progressive) over the course of one year. RESULTS: During this period there were 132 active lesions in the brain and only six in the cord. One hundred and twelve (85%) active brain lesions occurred in the secondary progressive group; three new cord lesions occurred in each group. In the secondary progressive group MRI activity was high in patients who had superimposed relapses, whereas in those who progressed without relapse and in the primary progressive group it was low. Cross sectional areas of the cord decreased at the C5 level in both groups, implying progressive atrophy of fibre tracts. There was no relation between either brain or cord MRI activity and change in disability over the study period. CONCLUSIONS: Although the detection of new lesions by frequent cord imaging using current technology has little role in the monitoring of disease activity in progressive multiple sclerosis, the serial measurement of cord cross sectional area may be important. There is also evidence to suggest that the mechanism underlying irreversible disability in patients with progressive multiple sclerosis may be different in patients who continue to relapse than in those who do not.
Atrophy↗
Soluble E-selectin in multiple sclerosis: raised concentrations in patients with primary progressive disease.
OBJECTIVE: To determine whether concentrations of soluble E-selectin (sE-selectin), an immunological marker of endothelial activation, were correlated with gadolinium-DPTA enhancement on MRI in patients with multiple sclerosis. METHODS: Serial sE-selectin concentrations were measured in 28 patients with multiple sclerosis undergoing monthly gadolinium (Gd) enhanced MRI of the brain and spinal cord, and in 10 control subjects. C reactive protein (CRP), von Willebrand factor (vWF), and tumour necrosis factor-alpha (TNF alpha) were also determined. RESULTS: Primary progressive patients had significantly increased sE-selectin concentrations compared with the relapsing remitting and secondary progressive patients who had normal sE-selectin concentrations (22.2 (SD1 6.1) ng/ml v 9.8 (SD2.1) ng/ml and 7.7 (SD2.7) ng/ml, respectively, P = 0.03). This difference was attributable to five of the 10 primary progressive patients who had persistently raised sE-selectin concentrations, with relatively inactive MRI studies. No correlation could be found between sE-selectin concentrations and Gd enhancement on MRI, but a close correlation existed between mean concentrations of sE-selectin and TNF alpha (r = 0.71, P < 0.001). Despite raised sE-selectin and TNF alpha concentrations, primary progressive patients had normal CRP concentrations (1.03 (SD1.14) mg/l), which were significantly lower than the relapsing remitting (3.16 (SD2.54) mg/l) and secondary progressive patients (2.28 (SD2.1) mg/l, P = 0.03). Raised CRP concentrations did correlate with infectious episodes, clinical relapse, and Gd enhancement, and were significantly raised when no MRI activity was found. Concentrations of vWF were normal in all patient groups. CONCLUSIONS: The results further high-light the differences between patients with primary progressive and those with relapsing remitting/secondary progressive multiple sclerosis.
Adult↗
A study of oligoclonal band negative multiple sclerosis.
OBJECTIVES: To determine whether oligoclonal band (OCB) negative multiple sclerosis is a reliable diagnosis and, if so, whether it has a distinctive prognosis. METHODS: Retrospective and matched prospective comparison of the clinical and laboratory features of patients with clinical definite multiple sclerosis with and without intrathecal synthesis of oligoclonal IgG. RESULTS: Thirty four patients were identified with apparent OCB negative clinically definite multiple sclerosis. The results of oligoclonal banding proved to have been equivocal in 14 of 34; the clinical diagnosis of multiple sclerosis was questionable in 8 of 34. The remaining 12 patients with "true" OCB negative multiple sclerosis were significantly less disabled than matched OCB positive controls. Re-examination of CSF-serum pairs from six OCB negative patients showed that three remained OCB negative while three showed evidence of intrathecal synthesis of OCBs. CONCLUSIONS: OCB negative clinically definite multiple sclerosis is rare and should be diagnosed with caution; in unequivocal cases it seems to have a relatively benign prognosis.
Adult↗
Poliomyelitis.
1996 is polio awareness year. This paper reviews the clinical syndrome of acute paralytic poliomyelitis and its sequelae. We discuss epidemiological studies of the syndrome of late functional deterioration many years after the acute infection and the current hypotheses of the pathophysiology of such disorders. Recent evidence has suggested that potentially treatable factors may be implicated in the majority of such patients and it is therefore important to exclude such disorders before attributing late functional deterioration to progressive post-polio muscular atrophy.
Acute Disease↗
Acute paralytic illness.
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Acute Disease↗
Serial gadolinium-enhanced MRI of the brain and spinal cord in early relapsing-remitting multiple sclerosis.
Although serial MRI studies of the brain in relapsing-remitting MS have demonstrated frequent asymptomatic disease activity, less is known about the spinal cord. We carried out monthly gadolinium-enhanced brain and spinal cord MRI scans over 1 year in 10 patients with relapsing-remitting MS. Six of the patients had a total of 11 clinical relapses, eight of which involved the spinal cord. A total of 167 active (enhancing or new nonenhancing) lesions in the brain and 19 in the spinal cord were present. Only one active brain lesion was symptomatic compares with six spinal cord lesions. Overall, one-third of new spinal cord lesions were symptomatic, and three-quarters of clinical spinal cord relapses were associated with a new MRI lesion in a location appropriate to the symptoms. Activity in both the spinal cord and brain was more common around the time of relapse. There was a strong association between the spinal cord and brain MRI activity. We did not detect progressive spinal cord atrophy from measurements of a spinal cord cross-sectional area. We conclude that, in relapsing-remitting MS, imaging of the brain alone will detect 90% of active lesions; spinal cord MRI using current technology will therefore provide only modest gains in treatment trials in which lesion activity is the primary outcome measure. The lack of ++progressive spinal cord atrophy in these patients, suggesting that significant axonal loss has not occurred, is in keeping with their good recovery after relapse. That brain and spinal cord lesions occur concurrently implies a systemic trigger for disease activity.
Adult↗
The assessment of acute stroke in general medical wards.
In order to assess the completeness of clinical clerking, a retrospective study was made of the medical notes of 194 patients admitted with acute stroke over a 1-year period. The noting of clinical features associated with disease severity and prognosis, such as level of consciousness, proprioception, neglect, mental test score and continence was assessed. These features were rarely noted. Factors likely to influence placement following recovery were also poorly reported. In order to allow an accurate guide to stroke severity and prognosis these factors must be noted. An alternative form of clinical clerking is suggested in order to improve patient management.
Cerebrovascular Disorders↗
Pharyngeal sensation and gag reflex in healthy subjects.
The gag reflex is often used in the assessment of swallowing, yet its absence does not predict aspiration in acute stroke. Disordered pharyngeal sensation has been found to be a sensitive predictor. The occurrence of gag reflex and pharyngeal sensation in healthy people is unknown. We studied these tests in 140 healthy subjects (half elderly and half young). Gag reflex was absent in 37% of subjects whereas pharyngeal sensation was absent in only 1. The results largely explain the low predictive value of gag reflex in the assessment of aspiration in acute stroke. Testing pharyngeal sensation would be more likely to be useful in these circumstances.
Adult↗