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Biomedical subjects

L D Blumhardt

Publications and source records attributed to L D Blumhardt.

At least 37 records · Page 2Linked to original sources
PubMed2000

Short-term ventricular volume changes on serial MRI in multiple sclerosis.

Axonal loss is likely to be an important component of atrophy and the pathological substrate for the fixed disability of MS. To estimate the rate of central white matter reduction we investigated ventricular volume change and disease activity on monthly MRI in 19 patients over 6 months. At baseline, ventricular volumes were largest in primary progressive MS and smallest in relapsing-remitting MS. Over the study period ventricular volumes increased overall by 0.2% (F= 2.75, P = 0.02), but the percentage changes in relapsing-remitting MS were much larger (median increase 14.9%). Lesion volumes were also highest at baseline in relapsing-remitting MS, but serial changes in ventricular volumes were not correlated with serial changes in lesions. This study shows that ventricular enlargement in MS may occur over short epochs, particularly in relapsing-remitting cases. However, the loss of central white matter volume observed in any brief period may be related to inflammatory activity that occurred in a preceding or earlier epoch, a delayed post-inflammatory degenerative process, or most likely, a combination of both.

Adult↗
PubMed2000

Disability outcome measures in therapeutic trials of relapsing-remitting multiple sclerosis: effects of heterogeneity of disease course in placebo cohorts.

OBJECTIVES: Recent phase III clinical trials of immunomodulatory therapies in relapsing-remitting multiple sclerosis have shown significant benefits of active treatment on relapse related end points, but effects on disability outcomes have been inconsistent. These apparent discrepancies could be due to differences in the clinical end points employed, the behaviour of placebo cohorts, or both. METHODS: Disability data from the placebo cohorts of two large phase III studies, the United States glatiramer acetate trial (Copolymer 1 Multiple Sclerosis Study Group) and the multinational interferon beta-1a trial (PRISMS Study Group) were combined and masked (n = 313). Two groups of disability outcome measures were assessed. Firstly, measures of disability change (2 year EDSS difference and area under the EDSS/time curve, AUC) were calculated. Secondly, conventional disease progression end points ("confirmed progression" and "worsening to EDSS 6.0") were evaluated by using Kaplan-Meier analysis and compared with a categorical classification based on EDSS trends. RESULTS: The average increase in disability for the entire cohort as assessed by mean 2 year EDSS change (<0.5 EDSS point) or mean AUC (+0.57 EDSS-years) was small. For the "confirmed progression" end points, increasing the stringency of the definition lowered their incidence (from 32% with 1.0 point at 3 months, to 9% with 2.0 points at 6 months), but did not improve the positive predictive accuracy for "sustained progression" maintained to the end of the study. The error rate for this outcome was about 50%. Worsening to EDSS 6.0 was a more reliable end point, but had even lower sensitivity (incidence <10%). EDSS trend analysis showed markedly heterogeneous disease courses, which were then categorised into "stable" (26%), "relapsing-remitting" (59%), and "progressive" (15%) courses. Patients with the last course had deteriorated considerably by the end of 2 years (mean worsening of 2.0 EDSS points). CONCLUSION: In relapsing-remitting multiple sclerosis treatment trials, the conventional measure of mean EDSS change has low sensitivity, whereas the widely applied confirmed progression end points have high error rates regardless of their definition stringency. Alternative methods with better data utilisation include AUC summary measures and categorical disease trend analysis. The heterogeneity of disability outcomes in short trials, combined with unreliable clinical end points, diminishes the credibility of therapeutic claims aimed at reducing irreversible neurological deficits. The behaviour of patients treated with placebo should be carefully analysed before conclusions are drawn on the efficacy of putative treatments.

Adult↗
PubMed2000

A quality network model for the daily care of multiple sclerosis.

The urgent need to optimise treatment strategies for patients with Multiple Sclerosis (MS) was recognised by the participants at the 1998 European Charcot Foundation (ECF) symposium in Nice. The 'Nice Declaration' led to the formation of a Task Force Essentials Group charged with developing measures of the quality of MS care in Europe. Algorithms for nine critical domains (disability, spasticity, ataxia, pain, cognition, mood, fatigue, bladder function and sexual activity) and 'educated guesses' have been developed to measure interventions and outcomes which reflect the quality of clinical decision-making processes. A generic model called a 'quality network', consisting of a group of clinics connected to a central server, has been successfully applied to the care of diabetes across Europe. This model will now be developed and applied to MS management, to provide clinicians with longitudinal epidemiological data and, to evolve treatment algorithms and further quality measures. The ECF will next validate the system in a 1-year pilot study using a net of 10 clinics. Finally, an extended European network working in a learning environment will continuously assess, update and improve the quality of care of MS patients. Multiple Sclerosis (2000) 6 231 - 236

Algorithms↗
PubMed2000

Long term azathioprine fails to prevent onset of multiple sclerosis: report of two cases.

Azathioprine is an immunosuppressive drug widely used in the treatment of chronic inflammatory diseases, including Multiple Sclerosis (MS). We report two patients who developed the first manifestations of clinically definite multiple sclerosis while on long term (3.5 and 10 years, respectively) treatment with azathioprine for Crohn's disease. Both patients developed the first MS symptoms during a quiescent phase of their inflammatory bowel disease. These cases show that long term azathioprine, while possibly maintaining inflammatory bowel disease under control, could not prevent the onset of MS. Multiple Sclerosis (2000) 6 362 - 363

Adult↗
PubMed1999

Detecting activations in event-related fMRI using analysis of variance.

The most common design of a functional MRI (fMRI) experiment is a block design. The use of rapid imaging, however, and carefully designed paradigms makes the separation of cognitive events possible. Such experiments make use of event-related paradigms, in which a task involving several cognitive processes is repeated. In analyzing data from such experiments, existing methods often prove inadequate, because the prediction of the exact shape or timing of the time course is difficult. Here we present an analysis of variance (ANOVA) method for analyzing fMRI data that does not require any assumptions about the shape of the activation time course. Consequently, this method can simultaneously detect brain areas showing a variety of stimulus-locked time courses in the same experiment. The utility of this technique is demonstrated by the analysis of data from two event-related paradigms in which regions of activation are detected that correspond to a variety of distinct neural processes, yielding significantly different temporal signal changes. Magn Reson Med 42:1117-1122, 1999.

Analysis of Variance↗
PubMed1999

Effects of age on working memory: an event-related potential study.

The effects of age on behavioural performance and event-related potentials recorded during a working memory task using digits presented either acoustically or visually, were studied in 37 healthy subjects with an age range from 19 to 71 years. With increasing age, psychological tests showed a progressive decline in visuo-spatial performance and both auditory and visual reaction times (RT) increased. There were multiple and varying effects of age on both early and late ERP components. For both auditory and visual responses, increasing age was associated with an increased amplitude of early positive waves (auditory P100 and visual P145) and, in the oldest subjects, significant delays of the major late positive waves. Other changes were modality-specific with a progressive shift of amplitude maxima in the early negative waves of the visual ERPs (from an N190 peak maximal at Pz in the young, to an N270 peak maximal at Cz in the older subjects) and an altered amplitude distribution of late potentials (after the P250 wave) in the auditory responses. The age at which ERP changes occurred varied-significant latency prolongations and increases in the amplitude of the major frontal positive waves occurred only in the oldest subjects, whereas a redistribution of late auditory ERPs also occurred in the intermediate age group. There was no interaction between age and increasing memory load, suggesting that there is no specific effect of age on memory scanning in this age range for these levels of task difficulty. Thus, although performance in working memory was apparently unaffected by age, as judged by behavioural parameters (apart from slowing of the reaction times), ERPs revealed significant changes in both early and late electrical brain processes associated with working memory as age increases. These changes which were not symptomatically manifest and only revealed by sensitive tests, may represent subtle dysfunction of working memory (or associated processes) which does not prevent the successful completion of our task, compensatory mechanisms (which are essential to successfully complete the task), or a combination of both age-induced dysfunction and compensatory mechanisms.

Acoustic Stimulation↗
PubMed1999

Infratentorial atrophy on magnetic resonance imaging and disability in multiple sclerosis.

Loss of tissue volume in the central nervous system may provide an index of fixed neurological dysfunction in multiple sclerosis. Recent magnetic resonance studies have shown a modest relationship between clinical disability rating scores and transverse sectional area of the cervical spinal cord. To explore further the relationship between atrophy and disability in multiple sclerosis, we estimated the volumes of infratentorial structures from MRIs in a cross-sectional study of 41 patients, 21 with relapsing-remitting multiple sclerosis and 20 with secondary progressive multiple sclerosis. We used the Cavalieri method of modern design stereology with point counting to estimate the volume of brainstem, cerebellum and upper cervical spinal cord from three-dimensional MRIs acquired with an MPRAGE (Magnetization-prepared Rapid Acquisition Gradient Echo) sequence. The volume of the upper (C1-C3) cervical spinal cord was significantly correlated with a composite spinal cord score derived from the appropriate Functional Scale scores of the Expanded Disability Status Scale (r = -0.50, P < 0.01). The cerebellar (r = 0.49, P < 0.01) and brainstem (r = 0.34, P < 0.05) volumes correlated with the Scripp's Neurological Disability Rating Scale scores. The upper cervical cord volumes (r = -0.39, P < 0.01), but not the brainstem or cerebellar volumes, were significantly associated with disease duration. MRI-estimated structural volumes may provide a simple index of axonal and/or myelin loss, the presumed pathological substrates of irreversible impairment and disability in multiple sclerosis.

Activities of Daily Living↗
PubMed1999

Three dimensional MRI estimates of brain and spinal cord atrophy in multiple sclerosis.

OBJECTIVE: The association between brain atrophy and permanent functional deficits in multiple sclerosis and the temporal relation between atrophy and the clinical disease course have seldom been investigated. This study aims to determine the amount of infratentorial and supratentorial atrophy in patients by comparison with healthy controls, to establish the relation between atrophy and disability, and to derive the rates of volume loss in individual patients from their estimated disease durations. METHODS: Three dimensional acquired MRI was performed on 20 relapsing-remitting and 20 secondary progressive multiple sclerosis patients and 10 control subjects. Volume data on infratentorial and supratentorial structures were obtained using the Cavalieri method of modern design stereology in combination with point counting. Corpus callosal sectional area and "T2 lesion load" were also determined. RESULTS: Significantly reduced infratentorial and cerebral white matter volumes and corpus callosal sectional areas occurred in all patients compared with controls (p=0.0001-0.004). Mean estimates of volume loss in the cohort were -21%, -19%, -46%, and -12% for the brain stem, cerebellum, upper cervical cord and white matter, respectively, and -21% for the corpus callosal sectional area. Analysis of the amount of atrophy (volume differences between patients and controls) showed that upper cervical cord and cerebral white matter atrophy correlated with the expanded disability status scale (r=-0.37 and -0.37, p=0.018-0.023) and the Scripps neurologic rating scale scores (r=+0.49 and +0.43, p=0.002-0.007). There was no relation between estimated volume loss in the supratentorial and infratentorial compartments. The "T2 lesion load" was associated with ventricular enlargement and corpus callosal atrophy (r=+0.50 and -0.55, p=0.0003-0.0012). Infratentorial atrophy rates correlated with baseline exacerbation rates (r=-0.50 to -0.48, p=0.0016-0.0021) and were higher in relapsing-remitting than secondary progressive patients (p=0.009-0.02). CONCLUSIONS: Significant cerebral and spinal cord volume reductions occurred in both patient subgroups compared with controls. Functional correlates were found with estimated volume loss in the upper cervical cord and cerebral white matter. Particularly for infratentorial structures, estimated rates of atrophy were higher in relapsing-remitting than secondary progressive patients, suggesting that atrophy, perhaps mainly due to tract degeneration, begins early in multiple sclerosis and may relate predominantly to acute inflammatory events, with or without other gradual non-inflammatory processes later in the disease course.

Adult↗
PubMed1999

Randomised, double blind, placebo controlled study of interferon beta-1a in relapsing-remitting multiple sclerosis analysed by area under disability/time curves.

OBJECTIVES: The commonly employed outcome measures on disability and relapse rates in treatment trials of relapsing-remitting multiple sclerosis have well demonstrated sensitivity to treatment effects, but their clinical interpretation is problematic. An alternative method of analysis, which is more clinically meaningful and statistically appropriate to a condition with a fluctuating disease course, uses the summary measure statistic "area under the disability/time curve (AUC)", to estimate each patient's total in trial morbidity experience. METHODS: The AUC technique was applied in an intention to treat analysis of serial disability data derived from the expanded disability status scale (EDSS), the Scripps neurologic rating scale (SNRS), and the ambulation index (AI), collected during a double blind, randomised, placebo controlled, phase III trial of subcutaneous interferon beta-1a (INFbeta-1a) in relapsing-remitting multiple sclerosis (PRISMS Study). The results were compared with the often quoted "conventional" end point of mean change in rating scores from baseline to trial completion. Analyses were also carried out on subgroups with entry EDSS stratified above and below 3.5. RESULTS: EDSS data analysed by AUC normalised to baseline scores disclosed that both doses of IFNbeta-1a (22 or 44 microg) were superior to placebo (p= 0.008 and 0.013, respectively). In addition, the high dose (44 microg) was more beneficial than placebo using SNRS (p= 0.038) and AI data (p= 0.039). AUC analysis of SNRS scores also showed that for patients with baseline EDSS>3.5, the 44 microg (but not the 22 microg) dose was more advantageous than placebo (p=0.028). CONCLUSIONS: Summary measure analysis using the AUC of serial disability/time plots, confirms and extends the results of conventional end point analysis of disability from the PRISMS Study data. AUC evaluations show that high dose INFbeta-1a (44 microg three times weekly) was beneficial on all of the clinical rating scale scores used in this study. This method provides a statistically powerful and clinically meaningful assessment of treatment effects on in trial disability in patients with multiple sclerosis with fluctuating and highly heterogeneous disease courses.

Analysis of Variance↗
PubMed1999

Assessing relapses in treatment trials of relapsing and remitting multiple sclerosis: can we do better?

Published Phase III immunomodulatory treatment trials in relapsing and remitting multiple sclerosis have demonstrated a modest decline in attack rates, but only a minor effect on disability. As genuine disability progression is difficult to ascertain in relatively short studies with the conventional rating scales available, the acquisition and analysis of relapse data are critical. However, there are as yet unresolved questions related to the latter. We will first discuss the problems associated with relapse definitions by trial investigators, the paucity of the data collected (especially on the magnitude and duration of exacerbations) and statistical issues in their analysis. We will then suggest practical points for obtaining more accurate information on relapses and evaluating them meaningfully. While there is still general consensus among neurologists that primary endpoints for therapeutic trials should be clinical, improvements for future protocols are essential.

Clinical Trials as Topic↗
PubMed1998

Which event-related potentials reflect memory processing in a digit-probe identification task?

Auditory and visual event-related potentials (ERPs) generated by digit-probe identification and matching in a modified Sternberg paradigm have been recorded in 37 healthy subjects with the aim of identifying the potentials which best reflect the memory processes associated with this task. We analysed the effects of memory load (one, three or five digits to memorise), probe type (probe digit present or absent from the preceding memory set) and recording site, on the ERPs. With conventional methods of determining component amplitudes and latencies, the main effects of increasing memory load on the major positive wave varied according to stimulus modality-there was an amplitude decrease for the auditory ERPs and a latency increase for the visual ERPs. However, subjective component identification methods may be prone to errors when comparing responses recorded under different stimulus conditions. Waveform changes with increasing memory load may be misinterpreted as latency (or amplitude) effects if non-analogous potentials are compared. Further, component analysis may provide only partial information, because of its relative insensitivity to sustained amplitude shifts. For these reasons, an objective computer method was used to determine the mean amplitudes for multiple '50 ms' epochs. This showed, for both auditory and visual stimuli, that the main effect of increasing memory load was a 'negative amplitude shift'. It was seen between 315 and 525 ms for auditory stimuli and between 210 and 472 ms for visual stimuli and could be distinguished from other ERP features that were sensitive to stimulus modality. These changes are either specific to the memory processes involved in carrying out this task or reflect other parallel processing which covaries with memory processing.

Adult↗
PubMed1998

"Summary measure" statistic for assessing the outcome of treatment trials in relapsing-remitting multiple sclerosis.

OBJECTIVES: To review the outcome measures commonly used in phase III treatment trials of relapsing-remitting multiple sclerosis and to introduce a method of data analysis which is clinically appropriate for the often reversible disability in this type of multiple sclerosis. METHODS: The conventional end point measures for disability change are inadequate and potentially misleading. Those using the disability difference between study entry and completion do not take into account serial data or disease fluctuations. Rigid definitions of "disease progression" based on two measurements of change in disability several months apart, do not assess worsening after the defined "end point", nor the significant proportion of erroneous "treatment failures" which result from subsequent recovery from relapses that outlast the end point. Assessing attacks merely by counting their frequency ignores the variation in magnitude and duration. These problems can be largely circumvented by integrating the area under a disability-time curve (AUC), a technique which utilises all serial measurements at scheduled visits and during relapses to summarise the total neurological dysfunction experienced by an individual patient on any particular clinical scale during a study period. CONCLUSIONS: The "summary measure" statistic AUC incorporates both transient and progressive disability into an overall estimate of the dysfunction that was experienced by a patient during a period of time. It is statistically more powerful and clinically more meaningful than conventional methods of assessing disability changes, particularly for trials which are too short to expect to disclose major treatment effects on irreversible disability in patients with a fluctuating disease.

Analysis of Variance↗
PubMed1998

Clinical relapses and disease activity on magnetic resonance imaging associated with viral upper respiratory tract infections in multiple sclerosis.

BACKGROUND: Although the risk of clinical attacks of multiple sclerosis seems to be significantly increased with viral upper respiratory tract infections (URTI), serological evidence for the reported association remains controversial. In addition, although MRI is six to 10 times more sensitive than clinical exacerbations in indexing disease activity, any possible association between URTI and MRI activity has yet to be investigated. OBJECTIVES: To examine the relation between URTI and disease activity, in multiple sclerosis patients participating in a placebo controlled trial of interferon beta-1a, as indexed both by clinical exacerbation rate and by the number and volume of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) enhancing lesions on MRI. "At risk" periods were defined around symptomatic URTI, with or without serological confirmation. RESULTS: The relative risk of clinical relapse for serologically unconfirmed symptomatic URTI was 2.1 (p=0.004). Raised antiviral antibody titres conferred a relative risk of multiple sclerosis exacerbations that was 3.4 times higher than the "not at risk" periods (annual attack rates of 5.7 v 1.6, respectively, p=0.006). There was no definite relation between the number or the volume of active lesions on MRI and either symptomatic or serologically defined at risk periods. CONCLUSIONS: These results confirm the previously reported association between viral infections and multiple sclerosis exacerbations and indicate that the relative risk may be even higher when viral infection is serologically confirmed. However, the results, perhaps because of the confounding effects of interferon beta-1a, do not provide convincing evidence of increased blood-brain barrier breakdown or inflammation during periods of virally induced immune stimulation.

Adult↗
PubMed1997

A prospective survey of the causes of non-traumatic spastic paraparesis and tetraparesis in 585 patients.

OBJECTIVE: To ascertain the relative frequencies of the causes of non-traumatic paraparesis and tetraparesis in adults. DESIGN: Survey of patients enrolled prospectively over a 3 year period between 1986 and 1989 and review of their case notes 1 year after enrollment ceased (mean duration of follow up 30 months). SETTING: Regional neurosciences centre in the UK serving over three million people in Merseyside and North Wales. PATIENTS: Experienced clinicians from the centre saw most patients in the region with non-traumatic spastic paraparesis or tetraparesis. Primary investigation of patients was by myelography, for which patients were admitted to the centre. 585 consecutive patients with spastic paraparesis or tetraparesis were identified by daily screening of all 2104 patients undergoing myelography or radiculography during the 3 year period, ie selection by the intention to investigate them for myelopathy. EXCLUSIONS: age under 15 years, previous myelography for myelopathy. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Numbers and proportions of patients with each condition or category of disease. RESULTS: Commonest diagnoses were cervical spondylotic myelopathy (23.6%), extrinsic neoplastic or developmental tumour (16.4%), multiple sclerosis (9.1% rising to 17.8% after MRI of a selected group), and motor neurone disease (4.1%). Diagnosis was uncertain in 27.4%, falling to 18.6% after MRI. CONCLUSIONS: This survey shows the pattern of diseases producing non-traumatic myelopathy in the Mersey Region and in North Wales. Changing patterns of referral, investigation in peripheral hospitals and by non neurologically trained practitioners, and increasing use of outpatient MRI for primary investigation may make comparable surveys impossible in the future.

Adolescent↗
PubMed1997

Working memory impairment in early multiple sclerosis. Evidence from an event-related potential study of patients with clinically isolated myelopathy.

Auditory and visual event-related potentials were recorded during a short-term memory task in 24 patients who had recently presented with symptomatically and clinically isolated spinal cord syndromes suspected to be due to multiple sclerosis, and in 24 matched control subjects. Event-related potentials (ERPs) were recorded during two sequential components of the working memory task, first the temporary active memorizing of sets of digits and secondly, their subsequent manipulation, namely digit-probe recognition and matching. The patients' reaction times were slower and showed larger increments than those of the control subjects as the number of items to be memorized was increased. The patients' ERPs during both memorizing and probe matching/recognition phases differed significantly from control subjects for both auditory and visual presentations. The more marked changes were seen in a subgroup of eight patients who had the lowest levels of performance on a battery of general tests of memory and who also made significantly more errors in the working memory task as the memory load increased. In this subgroup, the abnormalities of the ERPs during recognition and matching tests occurred in the component of the response that has been shown to be sensitive to memory loading in healthy control subjects. This study provides objective evidence of subclinical working memory dysfunction in patients at an early stage of demyelinating disease, i.e. when they first present with clinically isolated spinal cord lesions and before they have developed symptoms of cognitive or memory dysfunction. The defect at this early stage is either restricted to processes involved in the formation of a memory trace or, more probably, involves both trace formation and the mechanisms that underly recognition ('retrieval') and matching of memory traces in working memory.

Adult↗
PubMed1996

Retinal venous sheathing and the blood-retinal barrier in multiple sclerosis.

OBJECTIVE: To assess the temporal relations among retinal appearance, disruption of the blood-retinal barrier, clinical subgroup, disease course, and disruption of the blood-brain barrier in multiple sclerosis. DESIGN: A 6-month prospective study involving monthly clinical ocular examinations, color fundus photography, fundus fluorescein angiograms, and magnetic resonance brain scans with gadolinium-diethylenetriamine-pentaacetic acid (Gd-DPTA) enhancement. SETTING: University-based ophthalmology and neurology departments. PATIENTS: Twenty-three patients with relapsing-remitting, primary-progressive, or secondary-progressive multiple sclerosis. RESULTS: Retinal venous sheathing was seen in six patients. The appearances observed included focal venous sheathing, diffuse venous sheathing, sheathing centered on sites of arteriovenous crossover, and focal perivenous hemorrhage. Arteriolar sheathing was also observed in one patient. Venous leakage on fundus fluorescein angiogram was detected in three patients, all of whom also had sheathing. The following three patterns of disruption of the blood-retinal barrier were seen on fundus fluorescein angiogram: focal leakage, extensive leakage, and very late wall staining. In one patient, the leakage was transitory. No correlations were observed between ophthalmologic features and multiple sclerosis clinical subgroup, disease course, or the number of new (Gd-DTPA-enhancing) lesions on magnetic resonance imaging. CONCLUSIONS: Disruption of the blood-retinal barrier, like the more frequent disruption of the blood-brain barrier seen on magnetic resonance imaging, is often unrelated to clinical neurologic relapses and occurs with apparently similar frequency in different patients independent of clinical disease course.

Adult↗
PubMed1996

Working memory in temporal lobe epilepsy: an event-related potential study.

Event-related potentials (ERPs) were recorded to a digit-probe identification and matching task (modified 'Sternberg paradigm') in 29 patients with temporal lobe epilepsy (TLE) and 26 healthy subjects. Our main aim was to identify the neurophysiological correlates of abnormal short term memory function in patients with TLE. Neuropsychological tests allowed the definition and comparison of two patient groups according to the presence or absence of memory dysfunction. These two groups did not differ significantly in mean age, education years, IQ, seizure duration, seizure frequency, anti-epileptic drug (AED) regimes, or on findings on neuroimaging. ERPs recorded under different levels of memory load were analysed both by conventional component identification and by an objective computer method of determining mean amplitudes of multiple 50 ms epochs (MMA analysis). We found that some significant abnormalities were common to both groups of patients; these included slow reaction times, a reduced amplitude of the N170 wave (and the corresponding 157-210 ms epoch in the MMA analysis) and a broad late negative shift between 577 and 735 ms. Other findings, including a significantly reduced performance accuracy as the level of memory load increased, were restricted to patients with abnormal memory function. The ERP changes that were specific to these patients occurred within a latency band of 200-420 ms and included a relatively preserved, but delayed P250 component and a delayed and attenuated N290 wave. When compared with either healthy subjects or with patients with normal memory, the responses in patients with abnormal memory showed an abnormal 'positive shift' between 262 and 315 ms after probe presentation and a further positive shift between 315 and 420 ms as memory load increased. These abnormalities of 'memory scanning' ERPs in patients with TLE which paralleled neuropsychological and behavioural evidence of memory dysfunction, and which occurred in the section of the response that is sensitive to memory loading in healthy subjects, provide further objective evidence that abnormalities of short term memory processes contribute to the memory deficits of TLE.

Adult↗