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Biomedical subjects

E J Thompson

Publications and source records attributed to E J Thompson.

At least 55 records · Page 3Linked to original sources
PubMed2001

Poststreptococcal acute disseminated encephalomyelitis with basal ganglia involvement and auto-reactive antibasal ganglia antibodies.

Antibasal ganglia antibodies (ABGA) are associated with Sydenham's chorea and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. We present 10 patients with acute disseminated encephalomyelitis (ADEM) associated with Group A beta hemolytic streptococcal infection. The clinical phenotype was novel, with 50% having a dystonic extrapyramidal movement disorder, and 70% a behavioral syndrome. None of the patients had rheumatic fever or Sydenham's chorea. Enzyme-linked immunosorbent assay, Western immunoblotting, and immunohistochemistry were used to detect ABGA. Neurological (n = 40) and streptococcal (n = 40) controls were used for comparison. Enzyme-linked immunosorbent assay results showed significantly elevated ABGA in the patients with poststreptococcal ADEM. Western immunoblotting demonstrated ABGA reactivity to three dominant protein bands of 60, 67, or 80 kDa; a finding not reproduced in controls. Fluorescent immunohistochemistry demonstrated specific binding to large striatal neurones, which was not seen in controls. Streptococcal serology was also significantly elevated in the poststreptococcal ADEM group compared with neurological controls. Magnetic resonance imaging studies showed hyperintense basal ganglia in 80% of patients with poststreptococcal ADEM, compared to 18% of patients with nonstreptococcal ADEM. These findings support a new subgroup of postinfectious autoimmune inflammatory disorders associated with Group A beta hemolytic streptococcus, abnormal basal ganglia imaging, and elevated ABGA.

Acute Disease↗
PubMed2001

Serum inflammatory markers and clinical/MRI markers of disease progression in multiple sclerosis.

The aim of this study was to assess whether mean serum levels of inflammatory markers when measured serially correlate with disease progression or putative MRI markers of axonal loss in a cohort of well-characterised multiple sclerosis (MS) patients. Serial serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), nitric oxide metabolites nitrate and nitrite (NOx), C-reactive protein (CRP), neopterin and tumour necrosis factor alpha (TNF-alpha) were measured in 29 MS patients, 13 with a relapsing remitting (RR) and 16 with a secondary progressive (SP) course, who were participating in a phase II clinical trial of anti-CD4 therapy. Short-term whole blood stimulated TNF-alpha production was also measured. Patients were studied 12 times over an 18-month period. MRI variables included the number and volume of Gd-enhancing lesions and the change in T2-hyperintense, T1-hypointense lesions and cerebral volume between the baseline and exit studies. Disease progression required a sustained change in the EDSS. There was no correlation between mean levels of inflammatory markers over the study period and disease progression or changes in any of the MRI measures. However, mean sICAM-1 levels from the first 6 months of the study were higher in patients who progressed during the study than in those that did not (443 (SD439) vs. 235 (SD162) ng/mL, p=0.05). Mean levels of NOx were significantly higher in patients with RR MS than in patients with SP disease (59.1 micromol/L (SD 12.8) vs. 48.7 micromol/L (SD 11.9), p=0.02). Patients with either a single relapse or no relapse had significantly higher NOx levels than to patients with multiple relapses during the 18 month follow-up (59.0 micromol/L (SD 12.3) vs. 47.9 micromol/L (SD 12.0), p=0.02). The mean levels of the other inflammatory markers did not correlate with disease course or relapse-rate. Serum levels of many inflammatory markers do not correlate with short-term disease progression. Some of the data suggest that the effects of inflammation on disease progression are delayed. In addition raised levels of serum nitric oxide metabolites are associated with a lower number of clinical relapses and a non-progressive disease course. These findings, although preliminary, pose interesting questions on the role of nitric oxide in the pathogenesis of MS. Inducible NO production in the early stages of the disease may be beneficial.

Adult↗
PubMed2001

Right medial thalamic lesion causes isolated retrograde amnesia.

Pervasive retrograde amnesia without anterograde memory impairment has rarely been described as a consequence of circumscribed brain damage. We report this phenomenon in a 33 yr-old, right-handed man (JG) in association with the extension in the right thalamus of a previously small, bilateral thalamic lesion. JG presented with a dense amnesia for autobiographical material more than a few years old, with some sparing of recent memories. Furthermore, he was completely unable to recognise famous people or world events. Many other aspects of semantic knowledge were intact and there was no evidence of general intellectual impairment, executive dysfunction or loss of visual imagery. Magnetic resonance imaging revealed an acute lesion in the right thalamus and two small, symmetrical, bilateral non-acute thalamic lesions. Follow-up neuropsychological assessment indicated a stable pattern of impaired retrograde and spared anterograde memory over 18 months and psychiatric assessments yielded no evidence of confabulation, malingering or other symptoms to suggest psychogenic amnesia. JG's profile indicates that the division of declarative memory into just two categories - episodic and semantic - is inadequate. Rather, his case adds to the growing body evidence to suggest that world knowledge pertaining to people and events is stored or accessed similarly to autobiographical information and differently from other types of more general factual knowledge. We hypothesize that the right mediodorsal thalamic nucleus and immediately surrounding regions comprise the central processing mechanism referred to by McClelland (Revue Neurologique, 150 (1994) 570) and Markowitsch (Brain Research Review, 21 (1995) 117) as responsible for inducing and co-ordinating the recall of these sorts of cortically stored memory engrams.

Adult↗
PubMed2001

Antibody responses to Acinetobacter spp. and Pseudomonas aeruginosa in multiple sclerosis: prospects for diagnosis using the myelin-acinetobacter-neurofilament antibody index.

Antibody responses to Acinetobacter (five strains), Pseudomonas aeruginosa, Escherichia coli, myelin basic protein (MBP), and neurofilaments were measured in sera from 26 multiple sclerosis (MS) patients, 20 patients with cerebrovascular accidents (CVA), 10 patients with viral encephalitis, and 25 healthy blood donors. In MS patients, elevated levels of antibodies against all strains of Acinetobacter tested were present, as well as antibodies against P. aeruginosa, MBP, and neurofilaments, but not antibodies to E. coli, compared to the CVA group and controls. The myelin-Acinetobacter-neurofilament antibody index appears to distinguish MS patients from patients with CVAs or healthy controls. The relevance of such antibodies to the neuropathology of MS requires further evaluation.

Acinetobacter↗
PubMed2001

Use of 14-3-3 and other brain-specific proteins in CSF in the diagnosis of variant Creutzfeldt-Jakob disease.

OBJECTIVES: The detection of the protein 14-3-3 in the CSF has been shown to be a reliable and sensitive marker for sporadic Creutzfeldt-Jakob disease (CJD). Other brain-specific proteins such as neuron specific enolase (NSE), S-100b, and tau protein have also been reported to be increased in the CSF of patients with sporadic CJD. In 1996 a variant of CJD (vCJD) was described which is likely to be causally linked to the bovine spongiform encephalopathy agent. This study reports and compares the findings of CSF brain specific protein analysis in 45 patients with vCJD and in 34 control patients. METHODS: The CSF from 45 patients with vCJD and 34 controls were investigated for the presence of 14-3-3 by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting with chemiluminescent detection. Tau protein, S-100b, and NSE concentrations in CSF were measured using enzyme immunoassays. RESULTS: Protein 14-3-3 was detected in the CSF of 22/45 patients with vCJD and in 3/34 controls. The mean concentrations of NSE, S-100b, and tau protein in CSF were significantly raised in patients with vCJD compared with controls. The positive predictive value of CSF 14-3-3 was 86% and the negative predictive value was 63%. These values are lower than those reported for sporadic CJD. An increased CSF tau had a positive predictive value of 93% and a negative predictive value of 81%. The combination of CSF 14-3-3 and/or increased CSF tau had a positive predictive value of 91% and a negative predictive value of 84%. CONCLUSIONS: CSF protein 14-3-3 is not as useful a marker for vCJD as it is for sporadic CJD. Increased concentration of CSF tau was found to be a sensitive marker of vCJD but as concentrations may be increased in many forms of non-CJD dementia, this may limit its usefulness as a diagnostic test.

14-3-3 Proteins↗
PubMed2000

Local synthesis of IgA in the cerebrospinal fluid of patients with neurological diseases.

To date qualitative studies of IgA in the cerebrospinal fluid in neurological disease, particularly multiple sclerosis, have been few and given mixed results. The aim of this study was to identify local synthesis of IgA by detection of clonal IgA bands, in a large cohort of patients with a variety of neurological disorders, using polyacrylamide gel electrophoresis, transfer of protein to nitrocellulose membranes and specific staining. Of 2,097 sequentially analysed patients with suspected neurological disease 54 (2.6%) had locally synthesised IgA; most notably, IgA was present in 39 of 291 (13%) patients with suspected multiple sclerosis. The latter group also had a significant excess of light-chain production, particularly free kappa, when compared to multiple sclerosis patients without local synthesis of IgA. Locally synthesised IgA was also demonstrated in inflammatory, infectious and autoimmune diseases of the central nervous system. This qualitative technique is simple and suitable for routine analysis of cerebrospinal fluid, and further qualitative studies of IgA may be useful in investigating the pathophysiology of certain neurological disorders.

Autoimmune Diseases↗
PubMed2000

Cerebrospinal fluid tau concentrations in HIV infected patients with suspected neurological disease.

OBJECTIVES: To measure cerebrospinal fluid (CSF) tau in HIV infected patients with acute neurological episodes and to correlate the findings with the type and severity of neurological disease. METHODS: CSF tau was prospectively measured in 76 consecutive HIV infected patients admitted to a specialist unit at UCL Hospitals, London, for investigation of acute neurological episodes: the results were compared with the clinical diagnoses. RESULTS: 24 patients had HIV associated dementia complex (HADC), 10 had lymphoma (including four with primary CNS lymphoma), 20 had cerebral infections (including five with CMV encephalitis, five with VZV infection, seven with cryptococcal meningitis, two with toxoplasmosis, and one with progressive multifocal leucoencephalopathy); 22 patients had miscellaneous conditions, including nine with self limiting headache/fever. 62 patients (82%) had normal CSF tau concentration and 14 patients (18%) had elevated tau. In those with HADC, there was no correlation between the degree of dementia or atrophy on magnetic resonance imaging and CSF tau. Elevated CSF tau was associated with poor outcome as six of eight patients who died within 4 weeks of lumbar puncture had elevated tau (p = 0.0024, two tailed Fisher's exact test). CONCLUSIONS: CSF tau levels are not elevated in the majority of HIV infected patients presenting with acute neurological episodes. CSF tau levels show no correlation with severity of dementia/atrophy on magnetic resonance imaging. Although elevated CSF tau was observed in some patients with conditions causing cerebral necrosis, the finding did not delineate underlying pathology but was associated with poor outcome.

AIDS Dementia Complex↗
PubMed2000

Immunological time-course of gadolinium-enhancing MRI lesions in patients with multiple sclerosis.

In multiple sclerosis (MS) gadolinium (Gd)-enhanced MRI activity correlates weakly with immunological markers of disease activity. We, therefore, tested the hypothesis that the poor correlation could be partly explained by the temporal profile of Gd enhancement. We measured urinary neopterin:creatinine ratios (neopt.:creat.(urine)) in 5 patients with active MS undergoing weekly Gd-enhanced MRI studies of the brain. The neopt.:creat.(urine) associated with new Gd-enhancing lesions (<8 days) was significantly higher than the ratio not associated with new Gd-enhancing lesions [mean(geometric) neopt.: creat.(urine) = 413 micromol/mol (range = 207-521) vs. 250 micromol/mol (range = 132-492), p = 0.03]. Pro-inflammatory immunological markers, which are probably produced early on in the life cycle of an active MS lesion, should preferably be correlated with newly enhancing lesions (<8 days). Failure to do this may explain the poor and unpredictable correlations between immunological markers and Gd-enhanced MRI activity, which cannot be accurately aged in cross-sectional and serial monthly MRI studies.

Adrenal Cortex Hormones↗
PubMed1999

I.v. immunoglobulin reduces circulating proinflammatory cytokines in Guillain-Barré syndrome.

BACKGROUND: Treatment with human i.v. immunoglobulin (IVIg) modifies the course of Guillain-Barré syndrome (GBS), but its specific mode of action is unknown. Cellular interactions mediated through the release of cytokines play a role in the pathogenesis of GBS and may be regulated by IVIg therapy. OBJECTIVE: To delineate possible immunoregulatory mechanisms of IVIg in patients with GBS. METHODS: Circulating levels of the proinflammatory cytokines, tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta, were assayed in 21 patients with GBS before and serially after IVIg therapy. Comparisons were made with serum concentration of the anti-inflammatory cytokines, soluble TNF-alpha receptor and IL-10. Serial measurements were also performed in 12 untreated patients with relatively mild disease and 7 patients treated by plasma exchange. RESULTS: Circulating levels of TNF-alpha and IL-1beta decreased after treatment with IVIg but remained relatively high in untreated patients and in those treated by plasma exchange. Clinical improvement in patients treated with IVIg was associated with a reduction in unbound TNF-alpha during the acute phase of the illness. Circulating levels of anti-inflammatory cytokines were not affected by IVIg treatment. CONCLUSION: Data presented here suggest a novel mechanism of action of IVIg that involves selective modulation of circulating proinflammatory cytokines.

Adult↗
PubMed1999

Heightened intrathecal release of proinflammatory cytokines in Creutzfeldt-Jakob disease.

The authors report high intrathecal release of tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-1beta in five patients with sporadic or new-variant Creutzfeldt-Jakob disease (CJD) without activation of the humoral or lymphocytic immune responses. Increased release of TNF-alpha and IL-1beta was also detected in some patients with progressive dementias. CJD is associated with a local cerebral host response that involves the release of proinflammatory cytokines.

Creutzfeldt-Jakob Syndrome↗
PubMed1999

Increased tau in the cerebrospinal fluid of patients with frontotemporal dementia and Alzheimer's disease.

Cerebrospinal fluid (CSF) concentrations of tau protein were measured using an enzyme-linked immunosorbent assay which measures both normal and hyperphosphorylated tau. Levels of CSF tau were measured in 17 patients with Alzheimer's disease and 23 patients with frontotemporal dementia, and were compared to age-matched healthy controls. The CSF tau concentration in control subjects was 198+/-49 pg/ml and no relationship was found between age and CSF tau concentrations in these subjects. CSF tau concentrations were significantly raised in patients with both Alzheimer's disease and frontotemporal dementia when compared to healthy controls (802+/-381 pg/ml, P<0.001; 612+/-382 pg/ml, P<0.05, respectively). In neither disease did CSF tau correlate with disease severity as assessed by the Mini Mental State Examination score (MMSE). This study shows that CSF tau is significantly raised in patients with frontotemporal dementia.

Alzheimer Disease↗
PubMed1999

Central nervous system sarcoidosis--diagnosis and management.

A series of 68 patients with neurosarcoidosis is reported, with particular emphasis on clinical aspects, diagnosis and treatment. A classification system based on clinical diagnostic probability is proposed, consisting of probable and definite disease, the latter being dependent on finding sarcoid granulomas on nervous system histology, which was obtained in 12 patients (18%). The role of investigations, including magnetic resonance imaging (MRI), chest radiography, Kveim skin test, Gallium 67 isotope scanning and cerebrospinal fluid (CSF) studies, is considered. Sixty-two percent of patients presented with nervous system disease, most commonly affecting the optic nerve and chiasm. Other common presentations included cranial nerve palsies, spinal cord and brainstem manifestations. Investigations yielding most diagnostic information included the Kveim test (41/48, 85% positive), raised CSF protein and/or cells (50/62, 81%) and gallium 67 scan (14/31, 45%). Eleven out of 29 patients (38%) patients showed meningeal enhancement on MRI scanning and 43% of scans demonstrated multiple white-matter lesions. Mean follow-up for the group was 4.6 years. Forty-seven patients were seen for > 18 months, and over half of these patients progressed despite corticosteroid and other immunosuppressive therapies. The benefit of a large patient database prospectively studied, with extended follow-up is discussed in order to learn more about prognosis and advance therapy in neurosarcoidosis.

Adrenal Cortex Hormones↗
PubMed1999

CNS tumours: oligoclonal immunoglobulin D in cerebrospinal fluid and serum.

Oligoclonal immunoglobulin D bands were detected by isoelectric focusing in 7 out of 25 unconcentrated cerebrospinal fluid (CSF) samples obtained from patients with tumours of the central nervous system (CNS). The tumours were confirmed by clinical and histological findings. Two patients with CNS malignancy had intrathecal synthesis of oligoclonal bands both IgD and IgG. Four patients with a variety of CNS tumours had a systemic IgD immune response but no oligoclonal IgG bands. One patient with the most malignant tumour histology had a systemic IgD response as well as local synthesis of IgG. The study reveals several new aspects regarding CNS tumours: they are immunologically active and are capable of invoking oligoclonal immunoglobulin production both within the CNS and systemically. Multiple immunoglobulin activation can be found in malignant CNS tumours, and systemic IgD production may occur independently from IgG synthesis and may represent an immune response to a neoantigen produced in the CNS compartment.

Antigens, Neoplasm↗
PubMed1999

Imaging and laboratory investigation in herpes simplex encephalitis.

A 14 day old baby presented with signs of an acute encephalitis. Clinically, herpes simplex encephalitis (HSE) was suspected. Early MRI and EEG were normal and there was rapid clinical improvement. A negative polymerase chain reaction (PCR) result on the initial CSF sample seemed to make HSE most unlikely. This diagnosis was subsequently proved after demonstration of specific antibody production using immunoelectrophoresis of the CSF. The child had extensive damage to brain tissue. The need for sequential analysis of CSF in making or refuting this diagnosis is illustrated.

Antibodies, Viral↗