A patient with seizures and a visual field defect.
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Biomedical subjects
Publications and source records attributed to C Kilpatrick.
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PURPOSE: To evaluate the safety, tolerability, efficacy, and impact on quality of life of gabapentin (Neurontin; GBP) as adjunctive therapy in patients with refractory partial seizures. METHODS: AUS-STEPS was an open-label, multicenter, prospective study in patients experiencing partial seizures who were inadequately controlled with one to three concurrent antiepileptic drugs (AEDs). GBP treatment was titrated to a maximum of 4,800 mg/day, over a treatment period of 24 weeks, to achieve an efficacious and tolerable dosage. Efficacy was assessed by seizure-frequency data. Quality of life was evaluated by using the QOLIE-10 questionnaire, and safety was assessed by adverse-event reports and clinical laboratory findings. RESULTS: A total of 176 patients received treatment with GBP, with 174 evaluable for intention-to-treat (ITT) efficacy analysis. A reduction of >50% in overall seizure frequency was observed in 93 patients (53%). There was a small (4.6%) overall improvement in QOLIE-10 score. The most frequent adverse events were dizziness (31%), fatigue (29%), somnolence (27%), headache (21%), and ataxia (20%), with no major increase seen in adverse events necessitating discontinuation as the dose of GBP was titrated upward. CONCLUSIONS: This study indicates that patients with partial epilepsy may be effectively treated with GBP at dosages of < or =4,800 mg/day, without altering the safety profile of the drug.
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PURPOSE: Despite accurate localization of the seizure focus, not all patients are seizure free after temporal lobectomy. This study determined risk factors for seizure recurrence in patients with proven hippocampal sclerosis. METHODS: The outcome from surgery was assessed in 56 consecutive patients with proven hippocampal sclerosis. The age at surgery, duration of epilepsy, history and age of febrile seizures, age of onset of epilepsy, sex ratio, laterality of seizure focus, and seizure frequency were compared between patients seizure free and those not seizure free, and those seizure and aura free and those with seizure recurrence including auras. RESULTS: During a mean follow-up of 38 months, 48 (86%) of 56 are seizure free. The mean age at surgery (37 vs. 36 years), duration of epilepsy (26 vs. 22 years), age (1.6 vs. 1.1 years), and occurrence (58 vs. 75%) of febrile seizures, age of onset of epilepsy (11 vs. 14 years), sex ratio (50 vs. 75% female), laterality of seizure focus (42 vs. 50% left), greater than weekly seizures (40 vs. 38%), and a history of (69 vs. 75%) and frequency of (2.10 vs. 2.38 per year) secondarily generalized seizures did not differ significantly between the two groups. Similarly there was no significant difference between patients seizure and aura free and those with seizure recurrence including auras. CONCLUSIONS: Clinical factors such as seizure frequency and duration of epilepsy are not risk factors for postoperative seizure recurrence.
PURPOSE: This study investigated the impact of a treatment information package on patients being monitored for possible surgical treatment for temporal lobe epilepsy. METHODS: One hundred patients were randomly assigned to either a high- or low-information preparation condition. Levels of anxiety were tested soon after admission by using the Hospital Anxiety and Depression Scale (HADS), The State-Trait Anxiety Inventory (STAI), and a newly devised questionnaire to assess specific concerns and anxieties of epilepsy patients presenting for monitoring and surgery, the Concerns About Epilepsy Monitoring Questionnaire (CAEMQ). Dispositional desire for information was assessed by the Miller Behavioural Style Scale (MBSS) to investigate whether coping disposition affected coping styles in the hospital setting. Patients assigned to the high-information condition were exposed to an intervention package, which included viewing a video depicting two separate interviews with patients who had undergone surgery as well as an information package, which described the various tests that the patient would undergo in the course of the monitoring procedure. Patients assigned to the low-information group were given information that the hospital provided to all patients in their care. All subjects were then retested on anxiety levels a few days later. RESULTS: Those in the high-information group showed a significant decrease in anxiety and depression levels compared with those in the low-information group. CONCLUSIONS: Within the main findings, an effect of dispositional style was found. Identification as either a monitor or blunter on the MBSS showed different coping strategies on arrival in hospital as measured by the CAEMQ, indicating that the level of information given to patients with epilepsy on arrival needs to be mediated by awareness of these two dispositional styles so that they obtain maximal benefit from the information to which patients with epilepsy are exposed.
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The relationship between the degree and distribution of hippocampal atrophy measured by volumetric magnetic resonance imaging and severity of memory deficits in 25 patients with temporal lobe epilepsy secondary to mesial temporal sclerosis was assessed. Hippocampal volumes were expressed as a ratio of smaller to larger, normal ratio greater than 0.95. Neuropsychology tests included: subtests of the WAIS-R, Rey Auditory Verbal Learning Task, Rey Figure and the Austin Maze. Degree of left hippocampal atrophy in patients with left temporal lobe epilepsy was associated with severity of verbal memory deficits as measured by RAVLT total recall (P < 0.05), delayed recall (P < 0.001), story recognition (P < 0.001), list recognition (P < 0.001) and final delayed recall (P < 0.001) and recall of the Rey Figure (P < 0.01). There was no association between degree of right hippocampal atrophy and any of the memory tests. Diffuse left hippocampal atrophy was associated with more severe verbal memory deficits than anterior atrophy. We conclude, the association between degree of left hippocampal atrophy and verbal memory provides further evidence of the predominant involvement of the left hippocampus in verbal memory. The finding of a relationship between degree of left hippocampal atrophy and measures of non-verbal function suggests these tests are dependent on verbal memory, or that mesial temporal sclerosis is a bilateral but asymmetrical condition.
PURPOSE: The pathophysiologic basis for the [18F]fluorodeoxyglucose positron-emission tomography (FDG-PET) temporal lobe hypometabolism in patients with hippocampal sclerosis (HS) is uncertain. We tested the hypothesis that hippocampal atrophy, which is strongly correlated with hippocampal cell loss, is largely responsible for the regional hypometabolism in HS. METHODS: Regions of interest (ROIs) on FDG-PET scanning were determined in the medial, lateral, and posterior temporal lobe, thalamus, and basal ganglia. A right/left asymmetry index for each ROI was calculated. These results were correlated with hippocampal magnetic resonance imaging (MRI) volume ratios. RESULTS: There was no correlation between the magnitudes of the FDG-PET asymmetry index and the MRI volume ratio for the mesial or lateral temporal regions (r = -0.09, r = -0.04). When the right/left asymmetry index was compared with the right/left hippocampal volume ratio, correlations for the mesial temporal ROI (r = 0.79, p < 0.0001) and lateral temporal ROI (r = 0.57, p < 0.0005) were found. These, however, simply indicated that both tests accurately reflect the side of the epileptogenic region. The concordance of the side of relative hypometabolism of the FDG-PET with the side of the hippocampal atrophy was higher for the mesial temporal region (100%) than for the lateral (77.5%). CONCLUSIONS: The lack of correlation between the magnitudes of the ratios argues against hippocampal atrophy and cell loss having a central role in the FDG-PET temporal hypometabolism.
OBJECTIVES: There is controversy regarding the need for invasive monitoring in the preoperative assessment of patients with temporal lobe epilepsy. The use of a series of non-invasive investigations in identifying the seizure focus is reported in 75 consecutive adults referred for epilepsy surgery. METHODS: All had video-EEG monitoring using scalp electrodes, high resolution MRI, and neuropsychology assessment. Other investigations included volumetric MRI, PET, and ictal and interictal SPECT. The seizure focus was localised and surgery offered if MRI disclosed unilateral hippocampal atrophy or a foreign tissue lesion and other investigations were either concordant or not discordant. RESULTS: In 68 patients the seizure focus was localised and three patients were inoperable. Sixty five patients have been offered surgery and 50 have undergone temporal lobe surgery and have a follow up of at least 12 months (mean 24 months). All had pathology: hippocampal sclerosis 34, dysembryoblastic neuroepithelial tumour six, cavernoma four, dysplasia two, low grade glioma two, ganglioglioma two. Thirty nine patients (78%) are seizure free postoperatively, 29/34 with hippocampal sclerosis and 10/16 with a foreign tissue lesion. Of the 11 patients with postoperative recurrent seizures, eight have a >90% reduction in seizure frequency and three have <90% reduction in seizure frequency but a worthwhile improvement. CONCLUSIONS: Non-invasive investigations successfully select most patients for temporal lobe surgery.
This study aims to determine whether there are important clinico-electrical differences between patients with temporal lobe epilepsy (TLE) secondary to mesial temporal sclerosis (MTS) and those with TLE secondary to a discrete temporal neocortical lesion (NL). The case histories, interictal EEG, seizure semiology, ictal EEG and postoperative outcome of 46 pathologically proven patients (31 MTS and 15 NL) were compared. A history of febrile convulsions (FC) was more common in MTS patients (58% versus 26%, P < 0.05), as was a history of a significant cerebral event at < 4 years of age (22% versus 0%, P < 0.05). There were no statistically significant differences in the incidence or nature of auras. No statistically significant differences between the groups were found in the interictal-EEG. With ictal semiology dystonic posturing occurred more frequently in MTS patients (mean 52% versus 26%, P < 0.05). Facial grimacing/ twitching occurred earlier in the seizures of NL patients (median 19 s versus 35 s, P < 0.05). There was an increased frequency of fast rhythmic sharp waves (> 4 Hz) in the ictal-EEG of MTS patients (mean 81% versus 60%, P = 0.05). The patients with NL developed bilateral ictal EEG changes more often (mean 55% versus 26%, P < 0.05) and more rapidly (mean 23 s versus 74 s, P < 0.005). The onset of ictal EEG seizure activity was bilateral more often in patients with NL (20% versus 4%, P < 0.005). There were no significant differences between the two groups for any of the video-EEG features, in terms of whether or not the feature occurred at least once in an individual patients. There was a tendency for MTS patients to have a higher seizure-free postsurgical outcome (87% versus 60%, P = 0.057). However, all the NL patients who were not free of seizures had had an incomplete lesion resection. We conclude that there are a number of clinico-electrical differences between patients with mesial TLE (MTLE) and patients with neocortical TLE (NCTLE), but that none of these are sufficient to allow a distinction to be made in an individual patient.
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Neuroimaging in epilepsy now includes magnetic resonance imaging, positron emission tomography (PET), single-photon emission tomography (SPECT), magnetoencephalography, and magnetic resonance spectroscopy. Recent advances in neuroimaging include improved rates of detection of lesions on structural imaging using quantitative methods, identification of metabolic patterns on functional imaging with PET, and recognition of the value of ictal SPECT in seizure localization.
A 69-year-old woman with classic glucagonoma syndrome had associated progressive neurologic disease manifest as dementia, ataxia, optic atrophy, and lower limb weakness. Visual evoked responses (VERs) were absent bilaterally. After an attempt at resection was unsuccessful, therapy was started with somatostatin analogue (Sandostatin, SMS 201-995). Over the ensuing 3 months, there was a decrease in the plasma glucagon level, resolution of the rash, weight gain, reversal of the dementia, and an improvement in coordination and limb weakness. Subsequent VERs revealed bilateral delayed responses.
The Poser criteria for diagnosing multiple sclerosis (MS) includes clinical, paraclinical and laboratory information. We studied the influence of cerebrospinal fluid (CSF) biochemistry results on the categorisation of patients with suspected MS. A retrospective study was made of 138 patients who had CSF samples sent over a 1 year period to the laboratory for examination for oligoclonal bands. Using the Poser criteria, 23 patients were diagnosed as having definite MS and one patient as probable MS. Cerebrospinal fluid biochemistry upgraded the categorisation from probable to definite MS in 16 of these 24 patients (66%). In this study, we found oligoclonal bands to be more sensitive in the diagnosis of MS (96%) than either the concentration of IgG in the CSF (43.5%) or the IgG expressed as a percentage of the total protein in the CSF (71%). We conclude that CSF biochemistry is a valuable investigation in the evaluation of patients with suspected MS.
Clobazam, a 1,5-benzodiazepine, is a potent anticonvulsant but the development of tolerance limits its use. It has been suggested that low dose clobazam may prevent or delay the onset of tolerance. This study aimed to assess, by an open trial, the anticonvulsant activity of low dose clobazam in 11 adult patients with frequent intractable seizures. Serum clobazam and N-desmethylclobazam levels were assayed and correlated with clinical effect, adverse effects, drug dose and the development of tolerance. Clobazam was given in addition to conventional antiepileptic therapy, beginning with a dose of 20 mg at night. A 50% or greater reduction in the frequency of seizures was noted, at least transiently, in all patients. In 8 of the 11 patients there was a subsequent deterioration in control of epilepsy and in all patients this relapse occurred within 3 months of commencing treatment. There was a relationship between plasma concentrations of N-desmethylclobazam (but not of clobazam) and therapeutic and toxic effects. Tolerance was not associated with a fall in plasma levels. It is concluded that clobazam is of limited value as a long term anticonvulsant and that the high incidence of tolerance is not reduced by the use of low doses.
Isolated, spontaneously beating atrial pairs from rabbits and guinea-pigs were used to determine and to compare the activity of ranitidine and tiotidine as antagonists of histamine stimulated chronotropic activity. Ranitidine produced a classical competitive, reversible antagonism of histamine effects with a pA2 in rabbit atria of 8.2. In contrast, tiotidine produced both a dextral shift of the log dose-response curve, as well as a previously unreported suppression in the maximal response produced by histamine. In accordance with receptor theory, this type of activity represents a dualistic antagonism of histamine chronotropic responses.
Rhinocerebral mucormycosis is a rare fungal infection which is frequently fatal. Survival depends on early diagnosis and immediate aggressive treatment. Previously described radiological changes have been non-specific. The CT features of two cases are described. Non-enhancement of the superior ophthalmic vein and ophthalmic artery appears to be a CT sign specific to this disease.
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