Antiepileptic drug-related cognitive complaints in seizure-free children with epilepsy before and after drug discontinuation.

The cognitive complaints reported by children and their parents, as subjectively associated with antiepileptic drug (AED) treatment, were evaluated in seizure-free children before and after drug discontinuation. The aim of the design was to isolate the cognitive side effects of AEDs from other factors, such as the effect of seizures. Our inventory explored the following areas: "alertness," "concentration," "activation/ tiredness," "memory," "drowsiness," "depression," "aggressiveness," and "hyperactivity," using a 5-point Likert scaling procedure. One hundred two eligible patients were selected, each matched with a healthy control and assessed when still on antiepileptic medication. All children were seizure free for at least 1 year. The medication was then discontinued gradually over a 3-month period. Four months after the children were completely medication free, a second assessment was carried out, but only in the 83 children who remained seizure free and in their matched controls. The results of the reports made by the children themselves did not show differences with the matched controls, and only showed improvement after drug discontinuation for complaints about "tiredness." Parents of the children with epilepsy reported significant improvement in all areas related to "alertness and activation" after discontinuation of the drugs. The finding that only a limited number of children have cognitive complaints, both when still on AEDs and after discontinuation, may be in line with the reports that the major factor contributing to quality of life is whether patients are seizure free or still have seizures. All patients in this study were seizure free for a period >1 year, which may have caused the favorable pattern of response in our patient group.

Role of I-123-iomazenil SPECT imaging in drug resistant epilepsy with complex partial seizures.

Fifteen patients with therapy resistant partial complex seizures with no structural lesions were examined interictally with 123-I-IOMAZENIL SPECT for measurement of benzodiazepine receptor distribution and with 99m-Tc-HMPAO SPECT for measurement of cerebral blood flow distribution. Regional abnormalities were correlated with the seizure onset patterns in EEG later recorded with implanted subdural strips. SPECT scans were made immediately after and at 1 and 2 h after intravenous injection of 123-I-Iomazenil. During that time there was a continuous change from an immediate flow-related distribution toward a more specific receptor distribution. The decay of radioactivity of I-123 in the brain was linear over time. Two patients on benzodiazepine treatment showed much faster elimination and showed no focal abnormalities. Eight patients with clear-cut unifocal seizure onset showed concordant focal benzodiazepine defects. These patients showed a progressive focus/homotopic non-focus enhancement over time much larger than the HMPAO scans in the same patients. Also the estimated focal area of abnormality was more restricted in the Iomazenil scans than in HMPAO scans. Five patients had more complex seizure onset patterns. In these patients a mismatch between the locations of abnormalities in Iomazenil and HMPAO scans were often found but benzodiazepine receptor abnormalities were more circumscribed also in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

SPECT imaging of gliomas with Thallium-201 and Technetium-99m-HMPAO.

Sequential Thallium-201 and Technetium-99m-HMPAO SPECT images were obtained from 7 patients with high-grade gliomas and 5 patients with low-grade gliomas. The histo-pathological tumor-type was verified from either biopsy specimens or resected tissue from surgery. There was an intense uptake of Thallium-201 in all high-grade gliomas. Compared to the contralateral hemisphere the mean uptake was 4.6 times higher. Low-grade gliomas showed only a marginally increased Thallium-201 uptake (1.4 times). No overlap existed between the two groups. There was no correlation between Technetium-99m-HMPAO uptake and tumor type. Thallium-201 appears to be a promising radiopharmaceutical for differentiating high- and low-grade gliomas, whereas Technetium-99m-HMPAO is not.

Withdrawal of antiepileptic medication in children. Correlation of cognitive function and plasma concentration--the multicentre 'Holmfrid' study.

Eighty-three patients with epilepsy and 83 matched controls completed 12 computerized cognitive tests while on antiepileptic drugs and six months later when they had been medication-free for three to four months. All patients had been seizure-free for more than one year and were on monotherapy with carbamazepine (CBZ, n = 56), valproate (VPA, n = 17), or phenytoin (PHT, n = 10). The tests and plasma concentration collection were done at noon. The mean peak plasma concentrations in the CBZ patients were as follows: 31% below 30 mumol/l, 48% between 30 and 42 mumol/l and 21% above 42 mumol/l. No difference in performance could be detected between the groups. One significant correlation between plasma concentration and test results was found. The mean VPA concentration was 625 mumol/l (S.D. 189). A tendency towards a weak negative correlation between test results and plasma concentration was present. The PHT patients' therapeutic range had a mean concentration of 32.0 mumol/l (S.D. 18.5). One significant correlation between a memory test and plasma concentration could be detected. Overall, the patients in the different antiepileptic groups performed less good than the control group and in a few cases the differences were statistically significant when compared either before or after withdrawal. A comparison of the changes after withdrawal showed improvement in the majority of tests, but these changes were also present in the matched control group.

Cerebral blood flow in patients with severe hypertension, and acute and chronic effects of felodipine.

OBJECTIVES: To evaluate whether a spontaneous increase in cerebral blood flow (CBF) could be observed in subjects with severe hypertension and to study the effect of a calcium antagonist, felodipine, on blood pressure and CBF after acute and chronic administration. DESIGN: Patients with severe hypertension were recruited at the emergency ward. Patients with previous treatment with calcium antagonists, women of child-bearing potential, severe uraemia, nephrotic syndrome, heart failure, manifest cerebrovascular lesions and pathological liver function tests were excluded. METHODS: CBF was measured by single-photon emission computed tomography after intravenous administration of xenon-133 before (CBF1) and after intravenous infusion of felodipine, 0.01 mg/min during 40-60 min (CBF2) in 12 patients aged 25-67 years with no antihypertensive treatment except for beta-blockers in four patients and beta-blockers plus a diuretic in one patient. CBF was repeated after 3 weeks of oral therapy with felodipine, 5-10 mg twice a day with the addition of beta-blockers in 10/12 patients (CBF3). RESULTS: During the felodipine infusion blood pressure decreased. There were no neurological symptoms or signs before or during the felodipine administration. CBF1 was within normal limits with no significant differences between previously treated and untreated patients. There was a non-significant tendency to increase in global CBF after felodipine administration, associated with a significant reduction in the physiological side differences in blood flow. CONCLUSIONS: In spite of the initially very high blood pressure, no general or focal hyperaemia was observed, and thus no evidence for a 'breakthrough' of the cerebral autoregulation. Felodipine gives a smooth blood pressure reduction with a maintained CBF.

Beta camera low activity tumor imaging.

A new technique, the beta camera, to complement film autoradiography, with fast quantitative imaging of beta particle-emitting radionuclides has been developed. It consists of a thin plastic scintillator and a light-sensitive microchannel plate detector. The thin tissue sample is mounted on the scintillator. Our first system had a high background and a moderate spatial resolution of 900 microns. We now report an improved system with a photomultiplier tube mounted on the scintillator of the microchannel plate detector. Only events registered by both detectors are accepted. A fast coincidence unit processes the signals, and if a time overlap exists, an event is generated in the beta camera. In the coincidence mode, images with low activity distribution of 201Tl (count rate 1 s-1) in 50 microns-thick slices of a human glioma tumor could be recorded with a spatial resolution of 500 microns.

Withdrawal of antiepileptic medication in children--effects on cognitive function: The Multicenter Holmfrid Study.

We present 100 children diagnosed with epilepsy who were seizure-free for more than 1 year and still on monotherapy of antiepileptic drugs (AEDs). We matched each child with a healthy classmate and performed neuropsychological testing and EEG before and after complete withdrawal of the AEDs. The withdrawal phase lasted 3 months, but the dose decrease was individualized for each patient. Three to 4 months after complete withdrawal of the drug all patients were reassessed. Patients with seizure relapse are excluded from the study. Seventeen patients are regarded as dropout, 11 because of seizure relapse and six because of protocol violation. The remaining 83 patients were treated with carbamazepine (n = 56), valproic acid (n = 17), or phenytoin (n = 10). Serum concentrations of the AEDs were measured using peak plasma levels that were taken immediately before or after psychological testing. We used neuropsychological tests to assess psychomotor function and "central" cognitive processing such as information processing or memory function. We found significant improvement attributable to drug withdrawal on only one of the cognitive tests, namely, psychomotor speed, suggesting that the impact of AED treatment on higher-order cognitive function is rather limited. In addition, we found group differences between the epilepsy group and the control group at baseline that persisted after drug withdrawal. Subsequent analysis showed some factors that may have contributed to these group differences. First, patients with a former diagnosis of absence seizures show lower scores both at baseline and after drug withdrawal. We may assume that the seizure propensity has not disappeared completely in these patients. Some evidence is found that phenytoin may have a different cognitive profile than carbamazepine, with more impairment on tests that measure motor and mental speed. Again, this impairment persists after drug withdrawal.

Sleep and wakefulness in preadolescent children with deficits in attention, motor control and perception.

In 10 children with deficits in attention, motor control and perception (DAMP), the relation between daytime vigilance and night-time sleep quality was examined with polygraphic sleep recordings, multiple sleep latency tests and measurements of reaction times. Two girls and eight boys, 6-12 years of age were studied. Eighteen normal children served as controls. Normal sleep regulation and sleep quality was found, but the children with DAMP tolerated the recording procedure less well than the controls. Most patients did not suffer from increased daytime sleepiness, but at MSLT 3, patients had short sleep latencies as in daytime hypersomnolence. Reaction times were significantly longer among the patients than among the controls. It is proposed that the findings may be related to functional changes in the forebrain.

Daytime sleep tendency before and after discontinuation of antiepileptic drugs in preadolescent children with epilepsy.

In 9 preadolescent children treated for epilepsy who had been free from seizures long enough for treatment to be discontinued, daytime vigilance was studied before and after discontinuation of antiepileptic drugs (AEDs). Comparisons were made with healthy controls. Multiple sleep latency test (MSLT), EEG, and a questionnaire were used. As part of the analysis of the MSLT, a new measure, the daily average sleep tendency (DAST), was constructed to overcome the problems with data censoring of the classic MSLT analysis. The patients had significantly (p less than 0.001) higher daytime sleep tendency, even after drug discontinuation, than controls, a result that could neither be attributed to AED treatment nor to recent epileptic seizures or complicated epilepsy.

Sleep and wakefulness after treatment for craniopharyngioma in childhood; influence on the quality and maturation of sleep.

Craniopharyngiomas are situated in immediate vicinity of sleep regulating structures in the basal forebrain area, and the tumor and its treatment might influence the regulation of sleep and wakefulness. In 10 patients treated for craniopharyngioma nighttime sleep quality and daytime vigilance were examined with polygraphic sleep records and multiple sleep latency tests (MSLT). Two girls and 8 boys, 7.1-22.9 years of age, were studied after a follow-up time of 1.5-16.1 years postoperatively. The results were compared to those of 18 normal children. The regulation of the ultradian sleep rhythm was normal but the ability to maintain nighttime sleep was severely disturbed. The patients had an increased number of awakenings and spent long time awake during two recorded nights. Two patients had excessive daytime somnolence during this examination, one after severe sleep disturbance, the other without any known cause. The pattern of sleep and vigilance did not change in puberty in the expected fashion. The disturbances may well have an impact on the psychosocial situation of the patients.

Neurophysiologic studies of patients with Crohn's disease on long-term treatment with metronidazole.

Fifty-three patients with Crohn's disease were chosen for this study. They were divided into three groups: the first group (19 patients) was treated with metronidazole and had been receiving the drug for at least 1 year; the second group (13 patients) had previously had the same type of long-term treatment but had been off the drug for at least 3 months before entering the study; the third group (21 patients) had never received treatment with metronidazole. The maximum daily dose of metronidazole used was 800 mg. All patients were examined with a broad set of neurophysiologic investigations devised to reveal signs of peripheral neuropathy. No significant difference was found between the three groups. The conclusion was that a daily dose of metronidazole not exceeding 800 mg is well tolerated by patients with Crohn's disease with regard to objective signs of neurotoxicity. A few patients from all three groups showed a raised perception threshold for changes of temperature in the feet (as compared with the department's normal standard). The results of the test were almost identical in the three groups and thus not connected with the metronidazole treatment. During the study, patients were asked about subjective neurologic symptoms such as tingling and numbness. A few patients from all three groups reported such paresthesias from time to time, but they were of a transient nature, not perpetual, and, in patients taking metronidazole, not aggravated despite continuing treatment with unchanged dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of single doses of propiomazine, a phenothiazine hypnotic, on sleep and oxygenation in patients with stable chronic obstructive pulmonary disease.

Serious respiratory depression may occur in patients with chronic obstructive pulmonary disease (COPD), receiving hypnotics during acute exacerbations. However, in a previous study on oxygenation during sleep in patients with stable hypoxemic non-hypercapnic COPD, we were unable to demonstrate a significant negative effect from single doses of nitrazepam and flunitrazepam. We have now investigated the effects of propiomazine, a phenothiazine hypnotic, in a double-blind randomized cross-over study of oxygen saturation and apneas during sleep and other sleep variables in 12 non-obese hypoxemic but clinically stable theophylline-treated COPD patients (PaO2 8.1 kPa, PaCO2 5.6 kPa, FEV1 31% of predicted value). None of the respiratory variables were adversely affected by a single oral dose of 25 mg propiomazine, whereas total sleeping time and the sleep efficiency index increased.

Delayed decrease in hemispheric cerebral blood flow during Wada test demonstrated by 99mTc-HMPAO single photon emission computer tomography.

We describe how brain regions with a flow (and metabolism) decrease can be visualized after an injection of short-acting barbiturate in one of the internal carotid arteries during a Wada test. An intravenous administration of 99mTc-HMPAO (Ceretec) was used to mark the relative flow distribution. The 99mTc-HMPAO distribution in the brain was recorded three-dimensionally about 1 h later, by means of a single photon emission computer tomograph. We show that the timing of the intravenous 99mTc-HMPAO administration during the Wada test is important for the visualization of the low-flow regions. The administration of the tracer substance should be delayed at least 30 s after the first signs of the barbiturate effect. The rCBF decrease in the barbiturate-injected cerebral hemisphere was associated with a simultaneous decrease in the contralateral, pharmacologically not directly affected, cerebellar hemisphere (crossed cerebellar diaschisis).

Sleep and wakefulness in normal preadolescent children.

Eighteen healthy children, 9 boys and 9 girls, between 8 and 12 years of age were examined with polygraphic sleep records, multiple sleep latency tests (MSLTs), and measurements of reaction times. Sleep was recorded at home on Oxford Medilog 9 channel cassette tape recorders (Oxford Medical Systems, Abingdon, U.K.) and sleep staging was performed from the screen of the display unit. Two consecutive nights were recorded. MSLT was done in the laboratory. The subjects were given 30 min to fall asleep on four occasions during the day after the last recorded night of sleep. Reaction times were measured repeatedly between each MSLT trial. More slow wave sleep was found in this study compared to others. Also, the first night effect was slight. It is proposed that this is due to the fact that the recordings were performed at home. The initial sleep cycle was incomplete in almost all subjects. A sleep stage with traits of both rapid eye movement (REM) and non-REM could be seen in this cycle, probably representing an abortive REM period. MSLT confirmed the low daytime sleepiness in healthy preadolescent children. A sleep latency of 10 min or less on two or more sleep trials, or a daily mean sleep latency of less than 20 min, is rarely seen in this age group. The reaction times were within normal limits for the age of the subjects. Nighttime sleep values, daytime sleep latencies, and reaction times were not correlated in these normal-sleeping children.

Automatic versus visual EEG sleep staging in preadolescent children.

Ambulant sleep polygrams were obtained from 14 normal subjects (9 boys and 5 girls) and from 3 boys with attention deficit disorder. The children were aged 8-12 years. Two consecutive nights were recorded with an eight-channel electroencephalographic (EEG) tape cassette recorder. The results were analyzed automatically by the Oxford Medilog 9000 Sleep Stager and by visual scoring from the Medilog Display Unit. Twenty-seven nights were analyzed; 7 nights were excluded because of electrode problems or other technical failures. The main sleep stage shifts and the length of sleep cycles as measured from the hypnogram of the automatic printout agreed well with corresponding values from our visual scoring. In the automatic scoring, rapid eye movement (REM) sleep time was shorter and slow wave sleep was longer than in the visual rating. This can be explained partly by specific properties of the EEG in this age group. The Oxford Medilog 9000 sleep stager can be used to survey sleep quality, but the results must be carefully checked visually. In cases of EEG pathology or sleep abnormalities in childhood it is doubtful if any time or labor is saved by using automatic scoring.

The effects of nitrazepam and flunitrazepam on oxygen desaturation during sleep in patients with stable hypoxemic nonhypercapnic COPD.

Serious respiratory depression has been described in COPD patients receiving hypnotics during acute exacerbations. There are few studies quantifying the effects of hypnotics on oxygenation during sleep in patients with stable hypoxemic COPD. In this study, the effects of single therapeutic doses of nitrazepam and flunitrazepam on SaO2, apneas during sleep and other sleep variables were measured in 14 COPD patients. All patients used theophylline. Sleep-induced decrease in mean SaO2 was 1.3 percent after placebo, 1.4 percent after nitrazepam and 1.9 percent after flunitrazepam (no significant differences). Sleep apneas were not more common or longer after nitrazepam or flunitrazepam, but sleep quality seemed to improve. It is concluded that oxygenation during sleep in these nonobese patients with stable hypoxemic nonhypercapnic COPD, all on maintenance theophylline therapy, was affected very little by single therapeutic doses of nitrazepam or flunitrazepam.

SPECT measurements with 99mTc-HM-PAO in focal epilepsy.

The ability of SPECT measurements with [99mTc]-HM-PAO (Ceretec) to find the location of the epileptic focus was studied in patients under consideration for neurosurgical treatment for therapy-resistant focal epilepsy. The location of low [99mTc]-HM-PAO uptake regions found at interictal measurements, and of high [99mTc]-HM-PAO uptake regions found at ictal measurements, was compared to the findings of extensive ictal and interictal EEG examinations, and to the results of CT and MRT. While EEG revealed focal epileptic activity in all of the 14 patients, SPECT showed regional abnormalities in 13 (93%). CT and MRT showed abnormal findings in 30%.

Risk of seizures after myelography: comparison of iohexol and metrizamide.

A parallel, double-blind, randomized study comparing iohexol and metrizamide--both 180 mg l/ml--in lumbar myelography was carried out in 60 consecutive patients. Eight to 15 ml of contrast medium were administered with the upper level at the middle thoracic column. A detailed neurologic examination was performed before and 24 hr after myelography. EEG recordings--evaluated visually and with fast Fourier transformation analysis--and somatosensory evoked responses were registered before, 6 hr after, and 24 hr after myelography. All patients were observed for adverse reactions for 24-48 hr. Iohexol did not produce any epileptiform activity but epileptiform activity was detected in five patients receiving metrizamide. Iohexol produced significantly less frequent and less severe EEG changes than did metrizamide both at visual evaluation (p less than .0025) and at fast Fourier transformation analysis (p less than .04). No significant changes occurred in the early components of the somatosensory evoked potentials after either contrast medium. Iohexol caused significantly (p less than .002) less frequent and less severe adverse reactions than did metrizamide. The neurologic examination revealed no changes of clinical importance with either contrast agent.

Nocturnal hypoxaemia in severe scoliosis.

The relationship between spirometry and daytime blood gases on the one hand and hypoxaemia during sleep on the other was studied in 13 patients with severe thoracic scoliosis. Eight patients had hypoxaemia (mean Sao2 less than 90%) during sleep. They were characterized by a lower vital capacity (30 versus 50% of predicted, P less than 0.01) and by a greater fall in vital capacity from sitting to supine (26 versus 7% of sitting VC, P less than 0.05). All patients with hypoxaemia during sleep were hypercapnic during the daytime. The fall in Sao2 with sleep was related to the increase in transcutaneous PCO2, indicating hypoventilation as the main mechanism behind hypoxaemia during sleep in scoliosis patients.

Oxygen desaturation during sleep and exercise in patients with interstitial lung disease.

The relations between mean and maximum fall in arterial oxygen saturation (SaO2) during sleep, hypoxaemia during moderate and maximum exercise, and lung mechanics were studied in 16 patients with interstitial lung disease. Mean and minimum SaO2 during sleep were significantly related to each other and to daytime oxygenation but not to lung mechanics. Although the maximum fall in SaO2 during sleep was similar to the fall during maximum exercise (a level seldom achieved during normal daily activities), profound hypoxaemic episodes during sleep were rare and brief and therefore contributed little to the mean SaO2. The fall in mean SaO2 during sleep was not significant and was considerably less than during moderate exercise (average 0.5 v an estimated 4.5%, p less than 0.05). It is therefore concluded that in patients with interstitial lung disease oxygen desaturation during sleep is mild and less severe than hypoxaemia during exercise.