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M P Richardson

Publications and source records attributed to M P Richardson.

At least 19 recordsLinked to original sources
PubMed2006

Cortical excitability predicts seizures in acutely drug-reduced temporal lobe epilepsy patients.

OBJECTIVE: To test the hypothesis that cortical excitability changes prior to seizures, using transcranial magnetic brain stimulation (TMS). METHODS: We studied 18 patients with unilateral temporal lobe epilepsy (TLE) twice using TMS: prior to (day 1) and following (day 3) reduction of antiepileptic drugs in a monitored inpatient setting. Short-latency intracortical inhibition (SICI) and intracortical facilitation (ICF) were measured. Time since most recent seizure prior to day 1, and time until next seizure after day 3, were recorded. RESULTS: On day 1, prior to antiepileptic drug withdrawal, there were no correlations with recent or next seizures. On day 3, patients who had seizures in the subsequent 48 hours had weaker SICI and ICF in the hemisphere ipsilateral to seizure onset, vs patients who did not have seizures in the next 48 hours (p = 0.033). Additionally on day 3, there was a strong correlation between the difference between ICF and SICI in the ipsilateral hemisphere and time to next seizure (p < 0.001). CONCLUSIONS: Change in cortical excitability, measured with transcranial magnetic brain stimulation, may reflect a long-lasting and widespread pre-ictal state.

Acute Disease↗
PubMed2005

Material-specific lateralization of memory encoding in the medial temporal lobe: blocked versus event-related design.

Lesion-deficit studies have provided evidence for a functional dissociation between the left medial temporal lobe (MTL) mediating verbal memory encoding and right MTL mediating non-verbal memory encoding. While a small number of functional MRI studies have demonstrated similar findings, none has looked specifically for material-specific lateralization using subsequent memory effects. In addition, in many fMRI studies, encoding activity has been located in posterior MTL structures, at odds with lesion-deficit and positron emission tomography (PET) evidence. In this study, we used an event-related fMRI memory encoding paradigm to demonstrate a material-specific lateralization of encoding in the medial temporal lobes of ten healthy control subjects. Activation was left-lateralized for word encoding, bilateral for picture encoding, and right-lateralized for face encoding. Secondly, we demonstrated the locations of activations revealed using an event-related analysis to be more anterior than those revealed using a blocked analysis of the same data. This suggests that anterior MTL structures underlie memory encoding as judged by subsequent memory effects, and that more posterior activity detected in other fMRI studies is related to deficiencies of blocked designs in the analysis of memory encoding.

Adult↗
PubMed2004

Subthreshold rTMS over pre-motor cortex has no effect on tics in patients with Gilles de la Tourette syndrome.

OBJECTIVE: A previous study showed no effect of 1Hz repetitive transcranial magnetic stimulation (rTMS) on tics in Gilles de la Tourette Syndrome (GTS). We modified the rTMS protocol in order to investigate some of the possible methodological reasons for the negative outcome in that study. METHODS: In a single blinded placebo-controlled cross-over study in five GTS patients without obsessive compulsive disorder we probed whether longer trains (1800 stimuli) of 1 Hz pre-motor cortex rTMS at 80% of active motor threshold and application to both hemispheres can improve tics in GTS. This was measured with the Yale Global Tic severity rating scale, the MOVES self-rating scale and video analysis. RESULTS: We found no significant effect of either left pre-motor cortex stimulation alone, or left pre-motor followed by right pre-motor cortex stimulation. CONCLUSIONS: These results suggest that the rTMS protocol used in this study is not useful for the treatment of tics in GTS. SIGNIFICANCE: rTMS protocols need to be modified substantially in order to explore their potential for the treatment of tics in GTS.

Adult↗
PubMed2002

Abnormalities of grey and white matter [11C]flumazenil binding in temporal lobe epilepsy with normal MRI.

In 20% of potential surgical candidates with refractory epilepsy, current optimal MRI does not identify the cause. GABA is the principal inhibitory neurotransmitter in the brain, and GABA(A) receptors are expressed by most neurones. [(11)C]Flumazenil (FMZ) PET images the majority of GABA(A) receptor subtypes. We investigated abnormalities of FMZ binding in grey and white matter in 18 patients with refractory temporal lobe epilepsy (TLE) and normal quantitative MRI. Parametric images of FMZ volume of distribution (FMZ-V(d)) were calculated. Twenty-one healthy controls were scanned for comparison. Statistical parametric mapping (SPM99) was used to localize significant changes in FMZ-V(d) in individual patients and between groups, specifically including the entire white matter in all subjects through explicit masking. Sixteen of 18 patients showed single or multiple abnormalities of FMZ-V(d). Six had hippocampal decreases of FMZ-V(d). Eleven patients showed increased FMZ-V(d) in the temporal lobe white matter (TLWM). Outside the mesial temporal structures, seven showed multiple areas of increase or decrease and only one a single area of decrease. In seven of the 16 patients with abnormalities, findings were concordant with EEG and clinical data, enabling further presurgical evaluation. Group findings were: (i) decreased FMZ-V(d) in the ipsilateral (Z = 3.01) and contralateral (Z = 2.56) hippocampus; (ii) increased FMZ-V(d) in the ipsilateral (Z = 3.71) and contralateral TLWM (two clusters, Z = 3.11 and 2.79); and (iii) increased FMZ-V(d) in the ipsilateral frontal lobe white matter between the superior and medial frontal gyrus (Z = 3.80) with similar changes contralaterally (Z = 4.87). No changes were found in the thalamus and basal ganglia. Region-of-interest analyses indicated an average increase in FMZ binding of 16% in the TLWM ipsilateral to the epileptic focus. PET findings were corroborated by invasive EEG or pathology in five cases. FMZ-PET, analysed by SPM with explicit masking, was sensitive in patients with normal MRI, and hippocampal abnormalities were detected in a third of these patients. Furthermore, increases in FMZ binding in TLWM, indicating microdysgenesis, were detected in the majority of these patients and may represent the structural basis of their epilepsy.

Adolescent↗
PubMed2002

Measurement of amygdala T2 relaxation time in temporal lobe epilepsy.

OBJECTIVES: To implement and validate the use of coronal dual echo T2 maps for the measurement of T2 relaxation time of the amygdala (AT2) as a rapid and reproducible method for identifying amygdala abnormality. METHODS: 20 healthy subjects and 25 patients with known hippocampal sclerosis (HS) were studied using a dual echo CSE sequence on a 1.5T MRI GE scanner. The T2 relaxation time of the amygdala was calculated and measured using a previously validated method. RESULTS: The mean control AT2 was 88.1 ms (SD 2 ms). The coefficient of reliability was good at 6.3% test-retest and 7.4% inter-rater. The upper limit of normal AT2 was 92 ms. AT2 was abnormal ipsilaterally in six, and bilaterally in three, of 20 patients with unilateral HS. Two of five patients with bilateral HS had unilateral abnormal AT2. CONCLUSION: Reliable T2 measurements can be obtained in the amygdala, and may be useful in the detection of amygdala abnormality.

Amygdala↗
PubMed2002

Congenital syphilis following negative antenatal screening.

We report a case of severe early congenital syphilis in the infant of a mother who acquired syphilis in mid pregnancy. The mother had received full antenatal care including serological screening for syphilis. Congenital syphilis is re-emerging in a number of industrialised countries and this report demonstrates that some of the most serious cases cannot be prevented by routine antenatal screening.

Contact Tracing↗
PubMed2001

Molecular cloning and genomic structure of a gene encoding interferon regulatory factor in the pufferfish (Fugu rubripes).

Interferon regulatory factors (IRFs) are a large family of transcription factors involved in regulating the transcriptional response of vertebrates to interferons and viral infection. In this report we describe the cloning and genomic organization of an IRF gene from the pufferfish (Fugu rubripes). The fugu IRF gene spans 2.7 kb from the transcription start site to the polyadenylation signal. It consists of 10 exons and 9 introns and encodes a protein of 296 amino acids. The overall amino acid sequence of fugu IRF displays 55% identity to flounder IRF and approximately 44% identity to avian and mammalian IRF-1 and IRF-2. On the basis of the genomic structure and the absence of a transcriptional repression domain, we conclude that the fugu IRF is a member of the IRF-1 family. The fugu IRF gene is expressed in a wide range of tissues. While a single transcript of 1.4 kb was detected in most tissues, several larger transcripts generated using alternative polyadenylation signals were found in the gills.

Journal Article↗
PubMed2001

Benzodiazepine-GABA(A) receptor binding is very low in dysembryoplastic neuroepithelial tumor: a PET study.

PURPOSE: To determine the nature of abnormalities of gamma-aminobutyric acid (GABA)A-central benzodiazepine (BZD) receptor binding in patients with dysembryoplastic neuroepithelial tumor (DNET) in comparison with normal controls. METHODS: Five patients with DNET and 24 normal controls underwent (11C)flumazenil positron emission tomography (PET) to measure (11C)flumazenil volume of distribution (FMZVD) at the voxel level. Patients were compared with normal controls by using statistical parametric mapping (SPM) and also a partial-volume effect (PVE) corrected volume-of-interest (VOI) analysis covering the entire brain. First, using SPM, the highest Z-score for the entire image representing FMZVD decreases in comparison with the normals was found. Second, regions of abnormal FMZVD were located using SPM, p < 0.001 uncorrected, corrected p < 0.05. Finally, PVE-corrected measures of FMZVD were calculated for each patient VOI and compared wih those of normals, using significance levels of >2.5 standard deviations (SD) for the DNET and >3 SD for all other regions. RESULTS: In all cases, the highest Z-score across the whole image representing decreased FMZVD was within the DNET. In three cases SPM revealed a single region of significantly reduced FMZVD, within the DNET in all three. VOI analysis showed PVE-corrected FMZVD was significantly low in the DNET in four cases. VOI analysis also showed seven other regions of abnormal FMZVD; three were adjacent to a DNET, and two were in mesial temporal areas not affected by DNET. CONCLUSIONS: FMZVD is low in DNET, probably contributing to epileptogenicity.

Adult↗
PubMed2001

CPD - education and self-assessment: functional imaging in epilepsy.

Functional imaging plays a growing role in the clinical assessment and research investigation of patients with epilepsy. This article reviews the literature on functional MRI (fMRI) investigation of EEG activity, fMRI evaluation of cognitive and motor functions, magnetic resonance spectroscopy (MRS), single photon emission computed tomography (SPECT) and positron emission tomography (PET) in epilepsy. The place of these techniques in clinical evaluation and their contribution to a better neurobiological understanding of epilepsy are discussed.

Brain↗
PubMed2001

Central benzodiazepine receptors in malformations of cortical development: A quantitative study.

We calculated [(11)C]flumazenil volume of distribution ([(11)C]FMZ-V(d)) after correction for partial volume effect in 10 patients with malformations of cortical development (MCDs) and partial seizures, to quantify the GABA(A)-central benzodiazepine receptor complex. Abnormal grey matter and adjacent or overlying cortex were outlined individually and added to an individualized anatomical template for correction for partial volume effect. Nine of 10 patients showed single or multiple increases or decreases in [(11)C]FMZ-V(d) in or around MCDs. Two of three patients with band heterotopia showed multiple increases in the overlying cortex. In three of four patients with subependymal nodular heterotopia, nodules had lower [(11)C]FMZ-V(d) than the overlying cortex, which was normal. Decreases in [(11)C]FMZ-V(d) were found in two of three clefts and one of six adjacent regions in one schizencephalic patient; another had normal [(11)C]FMZ-V(d) in the thickened cortex itself but increases in all adjacent regions. Binding was reduced within focal cortical dysplasia but increased in adjacent cortex. [(11)C]FMZ-V(d) was normal within one patient's polymicrogyric cortex but increased in one of six adjacent volumes of interest. The localization of abnormalities correlated with EEG and clinical data in cortical MCDs. Flumazenil binding was decreased in some MCDs with increased grey matter volume and increased in some adjacent or overlying areas of normal-appearing cortex, suggesting functional abnormalities beyond MRI- detectable structural changes.

Adolescent↗
PubMed2000

Long-term changes of GABAergic function in the sensorimotor cortex of amputees. A combined magnetic stimulation and 11C-flumazenil PET study.

Primary sensory and motor areas of the cerebral cortex contain organised maps of the body. These maps appear to reorganise after damage to the peripheral parts of the sensory or motor systems, so that the cortical representation of undamaged structures expands at the expense of the damaged parts. Several studies in animals have suggested that decreased activity of the inhibitory GABAergic neurones is responsible for driving these changes. However, whether similar mechanisms sustain the effects in the longer term in humans is unknown. The present study addressed this question by examining reorganisation of sensorimotor areas of cortex in six unilateral upper limb amputees several years after the initial injury. We measured two independent indices of GABAergic function. Volumes of distribution of GABA(A) receptors were determined from 11C-flumazenil binding measured with positron emission tomography (PET). The strength of inhibition in the motor cortex was measured with paired-pulse transcranial magnetic stimulation. In the six amputees taken as a whole and compared with 24 normal subjects, there was a highly significant increase in 11C-flumazenil binding in the upper limb region of primary sensorimotor cortex bilaterally and in medial frontal cortex of the hemisphere contralateral to the amputation. Surprisingly, however, there was no change in the time course or strength of intra-cortical inhibition in the motor cortex of the amputees compared with matched control subjects. The increased 11C-flumazenil binding may reflect up-regulation of GABA(A) receptors to compensate for a decrease in the GABA content or activity of inhibitory neurones. Up-regulation of GABA(A) receptors may also indicate that long-term changes require stabilisation of cortical organisation.

Adult↗
PubMed2000

Extramotor involvement in ALS: PET studies with the GABA(A) ligand [(11)C]flumazenil.

We used the benzodiazepine GABA(A) marker [(11)C] flumazenil to study cerebral dysfunction in amyotrophic lateral sclerosis (ALS) with PET. Seventeen non-demented patients with clinically definite or probable ALS were scanned and statistical parametric maps were derived to localize changes in regional flumazenil volumes of distribution (FMZVD), which correlate closely with receptor density (B(max)), and the results were compared with those of 17 controls. The ALS group showed statistically significant decreases in relative FMZVD in the prefrontal cortex (areas 9 and 10 bilaterally), parietal cortex (area 7 bilaterally), visual association cortex (area 18 bilaterally) and left motor/premotor cortex (including area 4) (P < 0.001). Relative reductions in FMZVD were also seen in the left ventrolateral and dorsolateral prefrontal cortex (areas 45, 46 and 47), Broca's area and the right temporal (area 21) and right visual association cortex (area 19). These observations suggest that cerebral dysfunction in ALS involves motor/premotor and extramotor areas, particularly the prefrontal regions.

Adult↗
PubMed2000

Increased availability of central benzodiazepine receptors in patients with chronic hepatic encephalopathy and alcohol related cirrhosis.

BACKGROUND/AIMS: To measure cerebral benzodiazepine receptor binding using (11)C-flumazenil positron emission tomography in patients with stable chronic hepatic encephalopathy, who were also characterised by proton magnetic resonance spectroscopy. METHODS: Six abstinent patients of mean age 61 years with alcohol related cirrhosis and grade I-II hepatic encephalopathy and 11 matched healthy volunteers were studied. Each patient's encephalopathy was defined according to clinical, psychometric, electroencephalographic, and magnetic resonance spectroscopy criteria. Using positron emission tomography, the brain volume of distribution of (11)C-flumazenil was obtained; this reflects benzodiazepine receptor availability. Proton magnetic resonance spectra were acquired at 1.5 T using a multivoxel technique; peak area ratios were calculated for choline, glutamine/glutamate, N-acetylaspartate, and creatine resonances. RESULTS: The mean volume of distribution of (11)C-flumazenil was significantly higher in the cortex, cerebellum, and the basal ganglia in the patients compared with controls (p<0.001). In the patient group, the mean glutamine/glutamate to creatine ratio was significantly increased and the mean choline to creatine ratio was significantly decreased in all brain areas, compared with healthy volunteers. However, the N-acetylaspartate to creatine ratio was unchanged compared with controls. CONCLUSIONS: The spectroscopy results reflect the cerebral metabolic derangement associated with hepatic encephalopathy. Stable grade I-II chronic hepatic encephalopathy in alcohol related cirrhosis may be associated with increased cerebral benzodiazepine receptor availability. However, a direct effect of previous chronic exposure to alcohol cannot be excluded.

Adult↗
PubMed1998

A simple flow cytometry assay using dihydrorhodamine for the measurement of the neutrophil respiratory burst in whole blood: comparison with the quantitative nitrobluetetrazolium test.

The neutrophil respiratory burst is essential for the host's ability to kill ingested microorganisms. Several flow cytometric assays have recently been developed to measure this process. These assays are largely unvalidated. In this study a whole blood flow cytometry assay using dihydrorhodamine 123 (DHR) as a substrate was compared with the quantitative nitrobluetetrazolium (NBT) test, an accepted measure of the earliest events in the respiratory burst. Because whole blood is used, the new assay is quicker and simpler than existing flow cytometry assays. Specimens as small as 0.1 ml can be used which makes the assay ideal for use in neonates and young children. There was a high degree of correlation between the DHR assay and the quantitative NBT test (r(s) = 0.76, P < 0.01). It is concluded that the whole blood DHR assay is an accurate and sensitive measure of the respiratory burst.

Adult↗
PubMed1998

Focal cortical release of endogenous opioids during reading-induced seizures.

BACKGROUND: Studies in animals implicate endogenous release of opioid peptides as a mechanism for terminating partial and generalised seizures. To localise dynamic changes in opioid neurotransmission associated with partial seizures and higher cognitive function, we investigated the release of endogenous opioids in patients with reading-induced seizures compared with healthy controls. METHODS: Five patients who had reading epilepsy and six controls had 11C-diprenorphine (DPN) positron-emission-tomography (PET) scans while reading a string of symbols (baseline) or a scientific paper (activation). Statistical parametric mapping was used to find areas with differences in opioid-receptor binding. FINDINGS: On activation scans mean 11C-DPN binding to opioid receptors was significantly lower (p<0.05 corrected for multiple non-independent comparisons) in the left parieto-temporo-occipital cortex (Brodmann area 37) in reading-epilepsy patients compared with controls. INTERPRETATION: These findings suggest that opioid-like substances are involved in the termination of reading-induced seizures.

Adult↗