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Biomedical subjects

H Hetherington

Publications and source records attributed to H Hetherington.

15 recordsLinked to original sources
PubMed2002

Modulation of cerebral GABA by topiramate, lamotrigine, and gabapentin in healthy adults.

BACKGROUND: Anticonvulsant drugs have multiple mechanisms of action. Recent in vivo MRS studies suggest that cerebral gamma-aminobutyric acid (GABA) increases occur with the administration of certain anticonvulsants in humans. OBJECTIVE: To investigate the effect of topiramate, gabapentin, and lamotrigine on cerebral GABA concentrations in healthy volunteers and correlate the GABA concentrations with serum drug levels. METHODS: Seventeen healthy adults were randomly assigned to receive topiramate, gabapentin, and lamotrigine and underwent GABA measurements using a 4.1-T magnet from a 13.5-mL volume over the occipital region. GABA concentrations and serum levels were measured at 3 and 6 hours following administration of an acute single dose of one of the drugs. Thereafter, drugs were titrated over 4 weeks to target doses, with GABA measurements performed at 2 and 4 weeks. RESULTS: Cerebral GABA concentrations rose 70% in the acute phase compared with baseline for topiramate. GABA rose 48% at 6 hours with gabapentin but not with lamotrigine. With long-term dosing and once target doses were achieved at 4 weeks, significant elevations in GABA were observed compared with baseline for all three drugs (topiramate 46%, gabapentin 25%, lamotrigine 25%). CONCLUSION: This study demonstrates that single doses of topiramate and gabapentin increase cerebral GABA concentrations acutely (hours) in healthy individuals, but all drugs at clinically utilized doses increase cerebral GABA at 4 weeks. These results suggest that the mechanisms of action of anticonvulsant drugs are more complex and are likely to be multiple in nature.

Acetates↗
PubMed2001

Dorsal subthalamotomy for Parkinson's disease.

We report our experience of unilateral subthalamotomy in patients with Parkinson's disease (PD). Eleven patients were included in a pilot, open-labeled study to assess the effect of unilateral lesion of the subthalamic nucleus (STN) with a minimum of 12 months of follow-up. The guidelines of CAPIT (Core Assessment Program for Intracerebral Transplantation) were followed for recruitment into the study and follow-up assessment. Levodopa equivalents daily intake (mean 967 mg) were unchanged during the first 12 months in all but one patient who stopped medication. The sensorimotor region of the STN was defined by semimicrorecording and stimulation and a thermolytic lesion was placed accordingly. There was a significant reduction in both UPDRS parts II and III in the "off" state at 1-, 6-, and 12-month follow-up. This effect was maintained in four patients up to 24 months. The dyskinesia score did not change postoperatively. Lesion-induced dyskinesias were not a management problem except in one patient who developed a large infarction several days postsurgery. This initial study indicates that a lesion of the STN is not generally associated with hemiballismus in PD. Subthalamotomy may induce considerable motor benefit and could become another surgical option under specific circumstances.

Aged↗
PubMed1999

Predictive value of 1H MRSI for outcome in temporal lobectomy.

OBJECTIVE: To investigate the predictive value of 1H MRSI for outcome in patients with mesial temporal lobe epilepsy (MTLE). BACKGROUND: 1H MRSI has been shown to be highly sensitive in the lateralization of temporal lob epilepsy. METHODS: The authors analyzed the relationship between the 1H MRSI findings and surgical outcome in 40 consecutive patients who underwent temporal lobe surgery for MTLE. Outcome at a mean of 24 months (range 18 to 40 months) was classified as seizure free or not seizure free. RESULTS: At follow-up, 78% of patients were seizure free. Correlations showed no predictive value for the creatine/N-acetylated compound (Cr/NA) ratio of the operated temporal lobe and outcome. However, a relationship was found between surgical failure and the Cr/NA ratio of the nonoperated temporal lobe and with a Cr/NA ratio in the nonoperated lobe above 1.21 in patients with bilateral abnormalities (p < 0.01). CONCLUSIONS: Preoperative elevations in the Cr/NA ratio in the nonoperated temporal lobe or the presence of higher metabolic ratios contralateral to the proposed surgery are associated with surgical failure. The predictive value of 1H MRSI absolute metabolite concentrations for outcome in MTLE requires further investigation.

Adolescent↗
PubMed1999

Cognitive effects of topiramate, gabapentin, and lamotrigine in healthy young adults.

OBJECTIVE: To study the acute and steady-state cognitive effects of three new antiepileptic drugs (AEDs): gabapentin, lamotrigine, and topiramate. BACKGROUND: Several newer antiepileptic medications approved recently by the Food and Drug Administration are gaining attention as efficacious alternatives to established AEDs. Greater tolerability with fewer side effects are reported in some. However, the potential cognitive effects of these newer AEDs have received limited attention. METHODS: Healthy young adults randomized to either of the three drugs were administered tests of attention, psychomotor speed, language, memory, and mood at baseline (predrug), acute single-dose period, and after 2 and 4 weeks on the drug. RESULTS: Compared with baseline, the topiramate group had selective, statistically significant declines on measures of attention and word fluency at acute doses, whereas the other two AED groups had no performance changes. At the 2- and 4-week test periods, only the topiramate subjects continued to display neurocognitive effects from drug administration. CONCLUSIONS: Results demonstrate potential acute and steady-state adverse cognitive effects for topiramate, whereas minimal effects were displayed for either gabapentin or lamotrigine in young healthy adults.

Acetates↗
PubMed1999

Rett syndrome: 1H spectroscopic imaging at 4.1 Tesla.

Rett syndrome, a neurodevelopmental disorder predominantly affecting girls, is characterized by regression of psychomotor development, communication dysfunction, and hand stereotypies. Brain morphologic studies demonstrate increased neuronal packing density and reduced dendritic arborizations, suggesting an arrest or interruption of normal maturation. Numerous neurotransmitter systems have been implicated. Among these, cerebrospinal fluid glutamate levels are elevated and glutamate receptors, particularly in putamen, are reduced. Therefore, 1H spectroscopy at 4.1 Tesla was used to evaluate glutamate, creatine, and N-acetylaspartate in six girls with Rett syndrome and four normal sibling controls. The ratio of creatine to N-acetylaspartate was significantly elevated in white matter, primarily reflecting reduced N-acetylaspartate levels, and normal in gray matter. The glutamate to N-acetylaspartate ratio was elevated in gray matter and normal in white matter. These findings are consistent with previous neuropathologic and neurochemical findings and indicate the feasibility of imaging these metabolites in vivo.

Aspartic Acid↗
PubMed1998

Relative utility of 1H spectroscopic imaging and hippocampal volumetry in the lateralization of mesial temporal lobe epilepsy.

OBJECTIVES: To determine the relative utility of 1H MRSI and hippocampal volumetry for the lateralization of mesial temporal lobe epilepsy (MTLE) in patients with intractable epilepsy. BACKGROUND: MTLE is the most common partial-onset seizure disorder in patients undergoing temporal lobe epilepsy surgery. MR volumetry and spectroscopy are reliable preoperative imaging techniques for the lateralization of MTLE. METHODS: We analyzed the 1H MRSI and hippocampal formation volumes preoperatively in 30 consecutive patients who had undergone temporal lobectomy. RESULTS: Volumetry correctly lateralized the side of surgery in 93% of patients and 1H MRSI did so in 97% of patients. Incorrect lateralization occurred by volumetry in two patients and by 1H MRSI in one patient. Concordance between all MRI modalities was 73%. Pearson's analysis revealed no correlation between the degree of hippocampal volume loss and the creatine-to-N-acetylated-compounds ratio. CONCLUSIONS: Volumetry and 1H MRSI correctly lateralized most patients with MTLE and complement each other in final lateralization. The lack of correlation between the severity of volume loss and the degree of metabolic disturbance suggests that the techniques examine distinct pathophysiologic processes in MTLE.

Adolescent↗
PubMed1998

Topiramate increases cerebral GABA in healthy humans.

Topiramate (TOP) is a novel anticonvulsant drug with multiple mechanisms of action used in the treatment of epilepsy. Measurements of cerebral GABA were obtained in six controls using 1H MRS at baseline and at 3 and 6 hours following the administration of 3 mg/kg of TOP. Brain GABA concentrations rose by 72% at 3 hours and by 64% at 6 hours compared with baseline (p < 0.004). This study demonstrates that TOP significantly increases human cerebral GABA concentrations in healthy individuals.

Adult↗
PubMed1997

Proton spectroscopic imaging at 4.1 tesla in patients with malformations of cortical development and epilepsy.

We used proton magnetic resonance spectroscopic imaging (MRSI) at 4.1 tesla in patients with malformations of cortical development (MCDs) and epilepsy. We compared the spectroscopic results with normative data using 2 SDs (95% confidence) above normal values for detection of significant abnormalities for creatine-N-acetylated compounds (Cr/NA) ratio and choline-N-acetylated compounds (Cho/NA). The results were correlated with clinical, EEG, and histologic findings. Patients with focal cortical dysplasia showed significant metabolic abnormalities in correspondence with the structural lesions, whereas patients with heterotopia and polymicrogyria demonstrated no subcortical MRSI abnormalities. Significant correlations were found between the metabolic abnormalities and the frequency of seizures but not with the degree of interictal EEG discharges. Quantitative neuronal and glial cell counts revealed no statistically significant correlation between cell loss and the abnormal metabolic ratios in those who underwent surgery. These preliminary findings suggest that MRSI-based metabolic abnormalities in patients with MCDs are variable and are likely to be associated with complex cellular mechanisms involving the regulation of NA, total Cr content, and Cho.

Acetylation↗
PubMed1995

Proton nuclear magnetic resonance spectroscopic imaging of human temporal lobe epilepsy at 4.1 T.

We performed proton magnetic resonance spectroscopic imaging (MRSI) at high magnetic field (4.1 T) to study N-acetylaspartate, creatine, and choline levels in the brains of normal control subjects and patients with intractable temporal lobe epilepsy. We compared the results of MRSI to those of other presurgical techniques to determine the sensitivity of this method in the lateralization of the epileptic focus. The normal hippocampal creatine-N-acetylaspartate ratio was 0.71 +/- 0.14 with no differences between left and right. Using the mean control hippocampal creatine-N-acetylaspartate ratio plus 2 standard deviations to identify statistically significant changes, we found lateralizing metabolic abnormalities corresponding to the operated temporal lobe in all patients. Four patients (40%) had contralateral abnormalities, and 2 of them had bilateral independent seizure onset confirmed by intracranial electroencephalographic studies. Statistically significant increases in the choline-N-acetylaspartate ratio in comparison to healthy volunteers were observed in 8 of the 10 patients. With the creatine-N-acetylaspartate ratio, MRSI demonstrated a 100% sensitivity compared to magnetic resonance imaging, which identified pathology in 70% of the patients. These findings suggest that proton MRSI yields a distinctive metabolic profile in patients with temporal lobe epilepsy and is sensitive in detecting bilateral metabolic abnormalities in some patients. These preliminary findings suggest that MRSI is more sensitive than magnetic resonance imaging in the lateralization of epileptic foci in temporal lobe epilepsy.

Adult↗
PubMed1995

The disability status of injured patients measured by the functional independence measure (FIM) and their use of rehabilitation services.

The type and severity of disability following major trauma was evaluated using the Functional Independence Measurement (FIM) in 93 patients brought to the Royal London Hospital (RLH) by helicopter. The range of values for FIM is from 18 (dependent) to 126 (fully independent) in the six sections of self-care, sphincter control, mobility, locomotion, communication and social cognition. The sections are divided into 18 separate items and graded 1-7. Forty-eight patients were discharged directly to home with a median FIM score of 124; 11 were transferred to another acute hospital with a median FIM of 63 and seven went to rehabilitation unit with a median FIM of 58. At six months, 79 per cent of the patients reported no disability and 89 per cent of the original 93 patients were at home with a median FIM of 126. The mean amount of rehabilitation provided at the RLH for all patients was 11 h 20 min with a mean in-patient length of stay of 14 days. The actual and optimal amount of therapy for rehabilitation worked out at less than 1 h per day in the acute hospital. FIM is a useful, practical and simple methodology for recording disability in the acute hospital. It provides a measure for assessing the original disability, its progress and residual limitations. Nurses, doctors and therapists can use it for establishing care plans and goals as well as deciding the transfer of the patient to the most appropriate place for future care.

Activities of Daily Living↗
PubMed1995

Measurement of disability after multiple injuries: the functional independence measure. Clinical review.

Collection of data about injured patients must include a description of the injuries using the International Classification of Disease (ICD9) and their severity using the Anatomical Injury Scale (AIS) from which the Injury Severity Score (ISS) is calculated. This method was developed for assessing the risk of mortality and is a good way of defining the extent of injury or impairment. Morbidity after injury is equally important. The terms "disability", (relating to the individual person's behaviour and performance of activities) and "handicap" (relating more to the disadvantage for a given patient in society) are accepted as the two main sub headings of long term morbidity. There are limitations to total overall health measurements and a functional disability approach is necessary for patients with multiple injuries. Of the different assessment tools the Functional Independence Measure, originally developed in Buffalo, USA, has been chosen as the most reliable and valid as it has the additional advantage of a large database containing the records of 200,000 patients throughout the world. This has been introduced at the Royal London Hospital to measure the disability outcome of patients brought there by the Helicopter Emergency Medical Service.

Disability Evaluation↗
PubMed1994

Rehabilitation after injury and the need for coordination.

The outcome of treatment after injury can be measured using the general terms of mortality and morbidity. Mortality is an all-or-none phenomenon, but morbidity is a graded response to injury and its medical treatment, varying from complete return to normality at one end of the scale to total dependence on other people requiring residence in an institution at the other end. The words disability (the individual's response) and handicap (society's reaction) specify the morbidity. Rehabilitation affects these two outcomes of disability and handicap and is a complex process involving the patient, carers and a team of specialists. The rehabilitation team is comprised of professionals each with specialist skills who aim to rehabilitate the individual as far as possible back to his former health and independence. All aspects of an individual's life are treated, including the physical, functional, psychological and social. The team operates in a number of ways according to the setting and treatment approaches used. The rehabilitation process should remain consistent throughout and focus on the patient's strengths and deficits. The key to effective rehabilitation is good organization with a comprehensive team approach working towards common goals and aims. Whether the patient is located in an acute hospital, rehabilitation unit, nursing home or in his own house, rehabilitation must be continuous. It is a mistake to believe that the rehabilitation process can only exist in a special centre; it must start in the acute hospital and be maintained even when at home, although its intensity may vary at different stages.(ABSTRACT TRUNCATED AT 250 WORDS)

Costs and Cost Analysis↗
PubMed1989

Clinical magnetic resonance spectroscopy of brain, heart, liver, kidney, and cancer. A quantitative approach.

Clinical studies using 31P and 1H MRS with a whole body 2.0 T MRI/MRS system are described. In most cases, techniques to quantitate absolute molar concentrations of metabolites in various organs were used. In the brain, AIDS, chronic stroke, and white matter lesions were associated with alterations of brain 31P metabolites. Epilepsy was associated with increased pH in the seizure focus. In the heart, dilated cardiomyopathy was associated with increased PDE/ATP while PCr/ATP was unchanged. In the liver, alcoholic hepatitis and cirrhosis were associated with diminished hepatic ATP while alcoholic hepatitis had increased pH and cirrhosis had decreased pH. This allowed differentiation of normal liver, alcoholic hepatitis, and alcoholic cirrhosis without biopsy. In the prostate, malignancy was associated with increased PME/ATP and decreased PCr/ATP. The PME/PCr was greatly increased in malignant prostate with no overlap in normals. Other cancers outside the brain had increased PME and effective treatment was often associated with diminished PME. 1H MRS of the brain was performed using ISIS and outer volume suppression pulses for volume localization. Excellent high resolution 1H water-suppressed spectra were obtained at echo times as short as 30 ms, showing well resolved peaks for lactate, N-acetylaspartate, glutamate, choline, creatinine, and inositol. 1H MRS demonstrated that the uptake of ethanol by the brain was slower than the rise of ethanol in blood. 31P spectroscopic imaging of the brain with resolution of 2.25 x 2.25 x 2.5 cm produced metabolic images and high resolution spectra from desired regions of interest.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗