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%.

Guanidine and neuromuscular transmission. II. Effect on transmitter release in response to repetitive nerve stimulation.

The effect of guanidine on the neuromuscular transmission in human intercostal and mouse diaphragm muscle in vitro during repetitive nerve stimulation was studied. The drug greatly increased the release of acetylcholine (ACh) quanta by nerve impulses at low frequencies of nerve stimulation and at the beginning of tetani at high frequencies of stimulation. The effect was shown to be produced by an increase in fractional release from an unchanged store of ACh quanta available fro immediate release. This seems to explain why guanidine has a poor therapeutic effect in myasthenia gravis but a good effect in the myasthenic syndrome.

Guanidine and neuromuscular transmission. I. Effect on transmitter release occurring spontaneously and in response to single nerve stimuli.

The effect of guanidine on neuromuscular transmission was studied in human intercostal muscle and mouse diaphragm preparations in vitro. Guanidine greatly increased the number of acetylcholine (ACh) quanta released by a single motor nerve action potential. This effect of guanidine was greater at junctions with a low quantum content. The spontaneous release of ACh quanta was not substantially changed by guanidine. No change was found in the postsynaptic sensitivity to ACh released from the motor nerve or iontophoretically applied to the muscle fiber. Effects of the drug had slow onset and were very long-lasting and resistant to wash.

Acetylcholine receptor protein. Neuromuscular transmission in immunized rabbits.

Rabbits injected with purified acetylcholine (ACh) receptor protein produce antibodies against the receptor and develop generalized muscle weakness. The compound muscle action potentials show a decremental fall in amplitude with repetitive nerve stimulation. Both the weakness and the decrement is counteracted by reversible cholinesterase inhibitors. Intracellular recordings from muscle endplates show that the amplitude of the miniature end-plate potentials is considerably reduced. A reduced binding of neurotoxin to muscles from immunized rabbits was observed. Nerve impulses release a normal number of ACh packages (quanta) from the motor nerve terminals. The muscle weakness in immunized rabbits thus has the same features as the muscle weakness in myasthenia gravis and may be a good animal model of myasthenia gravis.

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.

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.

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.

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.

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.

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.

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.

Sleep apnea syndrome--an alternative treatment to tracheostomy.

Two patients with obstructive sleep apnea syndrome had polygraphic recordings demonstrated upper airway obstruction and sleep with extremely short sleep latency, severely disturbed nightsleep resulting in sleep deprivation, and excessive daytime sleepiness. Radiological investigation showed the upper airway obstruction to be caused by the tongue falling back occluding the pharynx. Nasopharyngeal intubation relieved the symptoms. The patients were trained to perform this treatment themselves every night, demonstrating that this treatment is an attractive alternative to the conventional tracheotomy.

Cardiovascular and neurological function in elderly patients sustaining a fracture of the neck of the femur.

Cardiac and neurological functions were evaluated at the time of operation in 81 randomly selected elderly patients who had sustained a fracture of the neck of the femur. Although only one-fifth of the patients had clinical signs of senile dementia or cerebrovascular disease on admission to hospital, more than half had seriously abnormal EEGs including 12 of the 15 patients who died within six months. ECGs before operation showed that patients with signs of arrhythmia or previous myocardial infarction had a much lower survival rate than those with normal or other pathological ECG signs. Nerve conduction velocity findings proved inconclusive when correlated with survival or return home. Routine EEG and ECG examinations are of value in detecting underlying dysfunctions which may not be observable clinically on admission but are important prognostic indicators for survival or return home, and may be implicated as causative factors of fracture in the elderly.

Hemifacial spasm. Nerve block with phenol under electromyographic control.

Seven cases of hemifacial spasm are described. Six were operated upon with intra-osseal exposure of the facial nerve. In all 6 cases transient peripheral facial paresis developed. When the paresis disappeared the patients had a recurrence of the spasms. As an alternative to surgical procedures a method for selective nerve block under E. M. G. control with 3% phenol is described and 5 cases have been treated with this method. Ambulatory treatment with deposition of 3% phenol in the main branch of the facial nerve appears to have an equally good effect to the surgical methods hitherto used. Examination with E. M. G. suggested that the hemifacial spasm is of central origin.