Electroencephalographic effects and serum concentrations after intranasal and intravenous administration of diazepam to healthy volunteers.

AIMS: To evaluate the electroencephalographic (EEG) effects, blood concentrations, vehicle irritation and dose-effect relationships for diazepam administered nasally. METHODS: The study had a cross-over design with eight healthy volunteers (one drop out). It consisted of four legs with four different administrations: intranasal (i.n.) placebo, 4 mg diazepam i.n., 7 mg diazepam i.n. and 5 mg intravenous (i.v.) diazepam. Polyethylene glycol 300 (PEG300) was used as a vehicle in the nasal formulations to solubilize a clinically relevant dose of diazepam. Changes in N100, P200 and P300 brain event-related potentials (ERP) elicited by auditory stimulation and electroencephalographic beta-activity were used to assess effects on neurological activity. RESULTS: The mean [95% confidence intervals] differences between before and after drug administration values of P300-N100 amplitude differences were -0.9 [-6.5, 4.7], -6.4 [-10.1, -2,7], -8.6 [-11.4, -5.8] and -9.6 [-12.1, -7.1] for placebo, 4 mg i.n., 7 mg i.n. and 5 mg i.v. diazepam, respectively, indicating statistically significant drug induced effects. The bioavailabilities of 4 and 7 mg i.n. formulations, were found to be similar, 45% [32, 58] and 42% [22, 62], respectively. CONCLUSION: The present study indicates that it is possible to deliver a clinically effective nasal dose of diazepam for the acute treatment of epilepsy, using PEG300 as a solubilizer.

[Incidence of disability in Iceland before and after introduction of a new method of disability evaluation.].

OBJECTIVE: To assess changes in disability evaluation, since the introduction on September 1st 1999 of a new assessment method based on the British functional capacity evaluation, "All work test". Previously, the disability assessment was based on the applicant's medical, social and financial circumstances. MATERIAL AND METHODS: The study includes all those having their disability assessed for the first time at the State Social Security Institute of Iceland in 1997, 1998 and 2000. Information was obtained from the disability register on degree of disability, gender, age and primary diagnoses. RESULTS: After the introduction of the new assessment method, there has been a significant increase in the number of women who have disability more then 75% (p<0.0001). This increase occurs amongst women older than 30 years, having musculoskeletal disorders (mainly soft tissue disorders). There has also been a slight (statistically insignificant) increase in more than 75% disability amongst men (p=0.25). The number of people who have had their disability evaluated as 50-65% has decreased (p<0.0001). No significant change in the total number of new disability pensioners (having their disability assessed as being more than 75% or 50-65%) was observed. CONCLUSIONS: The new method of disability assessment has resulted in a significant rise in the number of women who have had their disability assessed as being more than 75%, but there has not been a rise in the total number of new disability pensioners, as the increased number of women with the higher degree of disability has been balanced by a significant fall in the number of new disability pensioners with the lower degree of disability.

[Educational level, occupation and income of those who became disability pensioners in Iceland in the year 1997.].

INTRODUCTION: All claims for disability benefits in Iceland are managed by the State Social Security Institute of Iceland. The decision to grant a claimant disability benefits was until September 1999 mainly based on medical certificates but social and economic factors were also taken into consideration. As information on social and economic conditions in medical certificates is limited it was decided to investigate these factors particularly. In this paper a comparison of educational level, employment, and income is made between new recipients of disability benefits and a random sample of the Icelandic nation. MATERIAL AND METHODS: All new recipients of disability benefits (full disability pension, partial disability pension and rehabilitation pension) in 1997 were contacted by phone and asked to answer a questionnaire. Their answers were compared with those obtained in a national survey carried out by the Institute of Social Sciences at the University of Iceland in 1996 and 1997 with a sample representing accurately the Icelandic population in terms of gender, age and place of residence. Information about average income of disability pensioners was obtained and compared to that of people in employment. RESULTS: Educational level of those receiving disability benefits was considerably lower than expected in comparison with the population and unskilled workers were overrepresented. Contrary to what might be expected a larger proportion of the recently disabled have been employed at some time than is the case for the national sample, even though 63.6% of the new disability pensioners were women. Considerable number of those receiving disability benefits were still in employment, particularly those with partial disability pension. Mean monthly income of Icelanders participating in the labour market was almost twice that received by those on disability benefits. CONCLUSIONS: Since lower educational level and more restricted employment opportunities characterize disability pensioners as compared to the nation, it seems likely that more varied occupational rehabilitation and educational opportunities could improve the situation of those who have had to leave the labour market because of ill health, lack of education and poor working conditions.

Psychiatric morbidity in epilepsy: a case controlled study of adults receiving disability benefits.

OBJECTIVE: To compare the prevalence of non-organic psychiatric disorders among disabled patients of normal intelligence with epilepsy with the prevalence of similar psychiatric disorders among age and sex matched disabled patients with other somatic diseases. METHODS: A case-control study was carried out in Iceland among people receiving disability benefits using information available at the State Social Security Institute. There were 344 patients with epilepsy in Iceland 16 to 66 years of age (inclusive) receiving disability benefits in 1995. By excluding mentally retarded patients, autistic patients, and patients with organic psychoses, 241 index cases with epilepsy qualified for the study. For each case two age and sex matched controls were selected from all patients receiving disability benefits who had cardiovascular diseases, respiratory diseases, or arthropathies. The same exclusion criteria were applied to the controls as the index cases. In both patient groups psychiatric diagnoses were classified into one of the four following categories: (1) psychotic illness; (2) neurotic illness or personality disorders; (3) alcohol or drug dependence or misuse; and (4) other mental disorders. RESULTS: Psychiatric diagnosis was present among 35% (85/241) of the cases compared with 30% (143/482) of the controls (p=0.15). There was a difference in the distribution of the two groups into different psychiatric categories (p=0.02). This was mainly due to an excess of men in the index group with psychosis, particularly schizophrenia or paranoid states. CONCLUSION: The results suggest that there is not a difference in the prevalence of non-organic psychiatric disorders among disabled patients of normal intelligence with epilepsy compared with patients with other disabling somatic diseases. However, the data indicate that when psychopathology is present disabled patients with epilepsy are more likely to have psychotic illness than the other disabled patients.

Parallel principal component neural networks for classification of event-related potential waveforms.

Artificial neural networks (ANNs) are discussed in terms of classification of brain auditory event-related potentials (ERPs). A new ANN architecture for the classification of ERPs is proposed. The new architecture is called the parallel principal component neural network (PPCNN). The use of the PPCNN for classification of ERP data obtained from both normal control subjects and chronic schizophrenic patients is discussed. Experimental results are given.

[Wada test. An investigation of language and memory functions in epileptic patients evaluated for temporal lobectomy.].

INTRODUCTION: Intracarotid sodium amytal injection was introduced as a clinical investigation of epileptic patients by Juhn Wada around 1950. The Wada test causes a brief inhibition of cerebral functions of the anaesthetized hemisphere, thus allowing tests to be performed on the contralateral hemisphere. The test is widely used to lateralize language functions and to assess the risk of postoperative amnesia in epileptic patients evaluated for temporal lobectomy Subjects and methods: Five epileptic patients were investigated. Three patients had hippocampal sclerosis and two had a benign tumour in the amygdala region. The sodium amytal was first injected to the hemisphere with seizure onset. After the development of paralysis of the contralateral side of the body, language and memory functions of the non-anaestetized hemisphere were assessed. The test was then repeated for the other hemisphere. RESULTS: The left hemisphere was dominant for language in three patients. In one patient the right hemisphere was dominant for language and in another patient language was bilaterally represented. In the three patients with hippocampal sclerosis, verbal and nonverbal memory was worse on the side of the lesion. This difference was not as marked for the two patients with lesion in the amygdala region. Total memory score was worse on the side of the lesion in all five patients. DISCUSSION: In both right and left handed individuals language is usually located in the left hemisphere. When epileptic seizures, with onset in the left hemisphere, start early in life, the language function can be transferred to the right hemisphere. This is a likely explanation for the right hemisphere language dominance in one patient. In all patients total memory score was lower for the hemisphere with seizure onset. This is in agreement with the suggestion of a lateralizing value of the Wada test.

Auditory event-related potentials, auditory digit span, and clinical symptoms in chronic schizophrenic men on neuroleptic medication.

The aim of this study was to test predictions based on Grossberg's theories of overarousal in neural networks as related to schizophrenic symptomatology. We predicted that symptoms of blunted affect and volition would be associated with reduced P300 amplitude, while impaired attention and short-term memory and symptoms of disorganization would be associated with increased N200 and P300 latency. Event-related potentials, elicited by auditory stimuli, were recorded in 20 chronic schizophrenic men on neuroleptic medication and an age- and sex-matched control group of 20 normal volunteers. The amplitude and latency values of the N200 and P300 waves at the vertex (Cz) were compared with clinical ratings (the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms) and with neuropsychological test scores by means of Spearman rank correlation coefficient. The patients showed a reduced P300 amplitude and an increased N200 latency. No correlation was found between the P300 amplitude and the symptom scores. The N200 latency was negatively correlated with auditory digit span and positively correlated with high global scores for attentional impairment, alogia, and positive formal thought disorder. Our initial predictions are partly confirmed by the apparent association between increased N200 latency and symptoms of disorganization.

The qualitative difference of visions and visual hallucinations: a comparison of a general-population and clinical sample.

Our objective was to analyze the frequency and quality of visions in a general-population sample compared with those experienced among schizophrenics. A sample group from the general population (n = 862) was compared with a group of schizophrenic patients (n = 19). Significant and qualitative differences were found in visions experienced by schizophrenic patients compared with subjects in the population sample. Women were more likely to experience visions of relatives than were men. The general population most commonly experienced visions of people, whereas schizophrenics were more likely to experience other phenomena. A qualitative difference thus exists in the type of visions experienced by schizophrenics compared with visions experienced by subjects from the general public.

Electrical activity of the cerebral cortex during induced hypotension in man. A comparison of sodium nitroprusside and trimetaphan.

During the routine use of controlled hypotension the electroencephalogram (EEG) and mean arterial pressure (MAP) were monitored in 20 normotensive patients (younger than 70 years-of-age) receiving either trimetaphan (TMP) or sodium nitroprusside (SNP). The reduction in MAP was quicker and greater with SNP. Significant differences in EEG voltage between the two agents were seen in the range 55-40 mm Hg, electrical activity being better maintained with SNP. However, all patients showed some decline in EEG voltage with hypotension and half of these showed significant correlations with MAP. These pressure-dependent cerebral effects were not predictable in terms of age, preoperative arterial pressure or hypotensive agent. Our work supports previous experimental evidence that, during more profound hypotension, cerebral electrical activity is better maintained with SNP than with TMP. A simple measure of total EEG power, or filtered EEG voltage envelope (CFM) was shown to be a more useful monitor of cerebral electrical activity during controlled hypotension than measurements of power distribution in different frequency bands.

Television epilepsy--the role of pattern.

Patients with photosensitive epilepsy were asked to view normally functioning 625-line televisions while the EEG was monitored. In the first of two studies paroxysmal EEG activity was reliably induced by television at a viewing distance related to a patient's sensitivity to intermittent photic stimulation (IPS); patients who were sensitive to diffuse IPS at 50 Hz were sensitive to the television at greater viewing distances than those who were not. No such relationship was obtained with patterned IPS. On the other hand, patterned IPS was generally more epileptogenic than diffuse IPS with the same luminance. In the second study, where the angular subtense of the television screen and the subtense of its lines were manipulated independently, the convulsive response was found to be a function of both factors, the relative contribution of each depending on the viewing distance at which the patient was sensitive. For patients sensitive at normal viewing distances, where 50 Hz diffuse flicker appeared to be responsible for the induction of paroxysmal activity, the probability with which paroxysmal activity was induced was closely related to the subtense of the screen. For patients sensitive only at closer viewing distances the probability was influenced not by the subtense of the screen but by the subtense of its lines, suggesting that the paroxysmal activity was induced by the 25 Hz pattern alternation produced by the scan. A television with a small screen was considerably less epileptogenic than one with a large screen for all patients, presumably due to the reduced contribution of both diffuse flicker and pattern alternation.

Television epilepsy and pattern sensitivity.

Properly functioning domestic television sets may induce seizures in epileptic patients (TV epilepsy). We investigated the effects of different types of visual stimuli on paroxysmal electroencephalographic (EEG) activity in 32 patients known to be sensitive to intermittent photic stimulation (stroboscopic light). We monitored sensitivity to patterns of horizontal and vertical lines, both stationary and vibrated (pattern sensitivity), and to normal broadcasts on a domestic, black and white (405- or 625-line) TV receiver (TV sensitivity). Twenty-three of the 32 patients were sensitive to pattern. Twenty-two were sensitive to vibrated patterns, and 11 to static patterns (P less than 0-01), All patients sensitive to pattern were also sensitive to TV; The association between sensitivity to pattern and to TV was significant. Clinical history of TV epilepsy (16 out of 32 patients) and laboratory evidence of pattern or TV sensitivity were not significantly associated. The high incidence of pattern sensitivity among flicker-sensitive patients and its association with TV sensitivity suggests that linear patterns produced by the raster of a black and white set as it scans, or "line-jitter" produced by the raster in areas of low TV-signal strength may contribute to the epileptogenic effect of TV.