Systematic review and meta-analysis of the effect of pertussis vaccine in pregnancy on the risk of chorioamnionitis, non-pertussis infectious diseases and other adverse pregnancy outcomes.

BACKGROUND: Several countries have introduced maternal immunisation with pertussis vaccine to provide protection against pertussis in early infancy. There is increasing interest in non-specific effects of vaccines including that non-live vaccines may enhance susceptibility to non-targeted infections in females. Some studies have shown increased risk of chorioamnionitis among women receiving pertussis vaccine during pregnancy. We aimed to conduct a systematic review and meta-analysis of the effect of maternal pertussis immunisation on the risk of chorioamnionitis, as well as the secondary outcomes of non-pertussis infections in women, non-pertussis infections in infants, spontaneous abortion or stillbirth, maternal death and infant death. METHODS: We searched PubMed and Embase for articles published until January 14, 2021. We screened articles for eligibility and extracted data using Covidence. Quality was assessed using Cochrane RoB tool and Newcastle-Ottawa Scale. Data were imported into RevMan for pooling and conduction of a meta-analysis stratified by study type. Outcomes are presented as risk ratios. RESULTS: We identified 13 observational studies and six randomized controlled trials eligible for inclusion. We pooled data on chorioamnionitis from six observational studies and found maternal pertussis vaccine (mostly compared with other maternal immunizations with non-live vaccines) to be associated with an increased risk among the pertussis vaccinated women, RR = 1.27 [CI 95%: 1.14-1.42]. We found no difference in the analysis of our secondary outcomes of non-pertussis infections, spontaneous abortion or stillbirth and death. CONCLUSION: We found an increased risk of chorioamnionitis among women who received pertussis vaccine in pregnancy. The large number of women receiving pertussis vaccine during pregnancy, as well as the growing evidence of non-live vaccines causing increased susceptibility to infections, indicates a need for further randomised trials to assess potential adverse effects of maternal immunisation with pertussis-containing vaccines.

The effect of i.v. L-NG methylarginine hydrochloride (L-NMMA: 546C88) on basal and acetazolamide (Diamox) induced changes of blood velocity in cerebral arteries and regional cerebral blood flow in man.

The aim of this study was to estimate the effect of Nitric Oxide synthase (NOS)-inhibition (L-NMMA) on the diameter of the middle cerebral artery (MCA) and on regional cerebral blood flow (rCBF). Furthermore, to assess the effect of L-NMMA on acetazolamide induced increases in MCA blood velocity (Vmean) and rCBF. In an open crossover design 12 healthy subjects attended the laboratory twice. The first day 6 mg/kg L-LNMMA i.v. over 15 min preceded 1 g acetazolamide i.v. over 5 min. Eight days later only acetazolamide was given. V(mean) in MCA was determined with transcranial Doppler (TCD) and rCBF with Xe-133 inhalation SPECT at baseline, after L-NMMA and 25 and 55 min after acetazolamide infusion. After L-NMMA the decrease in rCBF(MCA) was 6.8% (+/- 7.4) (P < 0.019, n = 12), whereas V(mean) was not affected (P = 0.83, n = 8). The change in MCA diameter was estimated to - 1.3% (P = 0.44, n = 8). L-NMMA did not affect acetazolamide increases in Vmean (P = 0.67, n = 8) nor rCBF (P = 0.29, n = 12). The percentage increase of V(mean) was 1.5 times that of rCBF (n = 8). Our data suggest that the basal tone of human cerebral arterioles but not of conduit arteries is NO-dependent. The action of acetazolamide in man is not NO-dependent.

Trends in symptoms of obstructive lung disease in Norway.

SETTING: Evidence is accumulating that there has been an increase in the adult population burden of obstructive lung disease. Has this increased the burden of symptoms? It is possible that diagnostic efficiency has improved, so that milder asthma cases are being diagnosed. OBJECTIVE: To investigate changes in symptom burden by asthma diagnosis, age and sex. DESIGN: We performed two postal cross-sectional studies among adults aged 15-70 years in Oslo, Norway, in 1972 and again in 1998/1999 (total = 39998). Changes in 11 self-reported respiratory symptoms were investigated. RESULTS: The prevalence of having at least one symptom increased from 50% to 60% (P < 0.001), and the distribution of symptoms showed an overall increase. Nine symptoms increased in prevalence. The increase was largest among the young and females, and was present in both those with and those without asthma. For any given number of reported symptoms, asthma prevalence was higher in 1998 than in 1972, suggesting increased case finding. CONCLUSION: There has been an increase in the population burden of respiratory symptoms matching the observed increase in young adult asthma, together with a probable increase in the clinical willingness to give an asthma diagnosis.

[Clinical value of SPECT scanning in children with neurological disorders]. / Den kliniske vaerdi af SPECT-scanning hos børn med neurologiske sygdomme.

We retrospectively evaluated the clinical value of Tc-99-HMPAO brain single photon emission tomography (SPECT) in 21 children with neurological disorders of varied aetiology. All 21 patients were examined with electroencephalograms (EEGs), 17 with computed tomography (CT) and ten with magnetic resonance imaging (MR). New relevant information was obtained from SPECT in all 21 cases and in four of these cases the investigation directly led to a change in diagnosis and better assessment of the prognosis. It is concluded that SPECT is an important investigational method in children with neurological symptoms of partly or completely unknown aetiology.

Interictal SPECT of rCBF is of clinical utility in the preoperative evaluation of patients with partial epilepsy.

Fifty-eight patients with drug-resistant partial epilepsy were studied preoperatively by interictal rCBF measurements using 99mTc-HMPAO and a dedicated brain SPECT camera (Tomomatic 64). Follow-up of seizure outcome, using the "Engel score", was at least 3 years. The data were analyzed in a blinded set-up, first visually and subsequently quantitatively by an automatic regional analysis. By visual analysis 95% of the patients were considered abnormal in one part of the brain, of whom 27% were abnormal on CT, 45% on MRI and 98% on scalp EEG. Using a quantitative regional analysis subdividing each hemisphere into 17 larger regions, 85% of the patients had an abnormal rCBF compared to an age-matched control population of healthy volunteers (using the Wilcoxon 2-sample test with Bonferroni's correction). The average number of abnormal regions of interest was 4.7. The percentage of patients with abnormal SPECT-CBF or the total number of abnormal regions of interest (ROIs) per patient showed no correlation to duration of epilepsy or seizure load (number of seizures per year x epilepsy duration) or seizure type. Neither were the rCBF changes prognostic for the outcome as measured by the Engel score. In 20 patients ictal SPECT of rCBF was additionally performed. In 2 cases it added further information to the patient evaluation.

[Preoperative EEG in medically intractable epilepsy]. / Praeoperativt eeg ved medicinsk intraktabel epilepsi.

The aim of the preoperative neurophysiological investigations is to identify the primary epileptogenic focus and its relation to functional cortical areas. The investigations include interictal and ictal extracranial (scalp) electroencephalography (EEG) and invasive methods (depth, subdural, foramen ovale electrodes and peroperative electrocorticography). If an epileptic focus is located in the anterior part of the temporal lobe by the use of scalp EEG, this is normally regarded as sufficient for an anterior lobectomy. However, because of poor spatial resolution by scalp EEG, it is difficult to separate mesial from lateral foci, identify the exact extent of posterior temporal or extra-temporal foci, identify the primary focus in patients with bilateral abnormalities and identify cases with minor scalp EEG-changes. As invasive EEG shows higher spatial resolution and gives an opportunity to evaluate functional areas, invasive EEG has significant advantages in these patients. Use of invasive EEG bears a slightly increased risk and discomfort to the patient, but is necessary in the presurgical evaluation of some patients suffering from medically intractable epilepsy.

Utility of interictal SPECT of rCBF for focal diagnosis of the epileptogenic zone(s).

With Single Photon Emission Computed Tomography (SPECT) of regional cerebral bloodflow (rCBF) ictally and interictally, regional changes of rCBF can be detected in many cases with medically intractable complex partial seizures. Interictal SPECT shows abnormal rCBF in the epileptogenic temporal lobe in 40% to 85% of the patients. A critical survey of the methodological problems considering isotopes, scanners, data analysis and patient population is presented here as well as a few semi-quantitative studies including our own. It is concluded, that SPECT of rCBF is a useful, non-invasive method of localizing the epileptogenic zone in patients with severe partial focal epilepsy. Ictal SPECT of rCBF has a higher predictive value and is more sensitive than interictal studies for localization of the seizure focus. Interictal SPECT using a high-resolution system obtains an almost as high frequency of localization of the focus. With low resolution scanners, a minor frequency is observed. Both interictal and ictal SPECT recordings should be obtained for localization of the epileptogenic focus in presurgical cases as interictal hypoperfusion and ictal hyperperfusion demonstrated in the same focal area are highly characteristic of a seizure focus.

Brain extraction and distribution of 99mTc-bicisate in humans and in rats.

Blood-brain barrier (BBB) passage of the flow tracer ethylenediylbis-L-cystein diethylester (bicisate, ECD) was measured repeatedly in five patients by means of the intravenous (i.v.) double-indicator technique using 24Na+ as an intravascular cotracer. After i.v. injection, the arterial concentration curve of 99mTc-bicisate was delayed and dispersed compared with that of the intravascular cotracer, presumably due to lung retention of the flow tracer. The corrected cerebral venous output curves were fitted using a three-compartment model with four parameters. At resting cerebral blood flow (CBF) values, the unidirectional brain extraction was 0.57 +/- 0.05, the permeability-surface area product for passage from blood to brain (PS1) was 0.48 +/- 0.07 ml/g/min, and the distribution volume for bicisate was 0.74 +/- 0.20 (mean +/- SD). In a single patient, BBB transport after i.v. injection of bicisate was compared with that of a similar flow tracer, d,l-hexamethylpropyleneamine oxime (HM-PAO), and similar values were found for the two tracers. In 19 rats, the brain extraction of bicisate was measured by means of the intracarotid double-indicator technique. The brain extraction was measured at resting, decreased, and increased CBF values. Low CBF values were obtained by hyperventilation and high values by hypercapnia. The degree of backflux of tracer from brain to blood was evaluated by means of the three-compartment model and was found to be negligible in these experiments. The brain extraction was 0.70 +/- 0.1 and PS1 was 0.94 +/- 0.27 ml/g/min. During hypercapnia, CBF increased from 0.77 to 1.09 ml/g/min, leading to a significant decrease in brain extraction, from 0.70 to 0.56.(ABSTRACT TRUNCATED AT 250 WORDS)

Retention of 99mTc-bicisate in the human brain after intracarotid injection.

99mTc-bicisate (ECD) was injected as a bolus into the internal carotid artery, and cerebral uptake and retention were recorded with fast-rotating single photon emission computed tomography (SPECT) equipment in four patients suffering from temporal lobe epilepsy. Quantitative regional cerebral blood flow (rCBF) was measured tomographically with the 133Xe inhalation technique. We applied a three-compartment kinetic model and algorithms modified from a previous analysis of 99mTc d,l-hexamethylpropyleneamine oxide (HM-PAO) kinetics. The bicisate brain uptake and retention curve was very similar to that of HM-PAO, and it can be described by a triexponential function including an initial steep component representing the vascular transmitted spike, a second less steep component representing back-diffusion from brain tissue to blood, and a third, very slow component, representing the very slow loss due to incomplete retention of the deesterified hydrophilic metabolites. Computerized curve-fitting on data from three patients gave average kinetic values for the first-passage (unilateral) extraction of E = 0.60 (range, 0.59-0.61); the overall retained fraction of the tracer supplied was R = 0.44 (0.43-0.45), and the conversion/clearance ratio was alpha = k3/k2 = 2.59 (2.38-2.77). This alpha is higher than that for HM-PAO, and therefore bicisate uptake as a function of blood flow is more linear than in HM-PAO. Less correction for backdiffusion is therefore needed. From 1 to 24 h there was an average loss of hydrophilic tracer of 3.5%/h, but the late distribution images were essentially unchanged over time, pointing to practically the same rate of loss in all regions.

99mTc-bicisate (neurolite) SPECT brain imaging and cognitive impairment in dementia of the Alzheimer type: a blinded read of image sets from a multicenter SPECT trial.

A blinded read of images obtained with 99mTc-bicisate and single photon emission computed tomography (SPECT) was conducted to determine if a relationship exists between the severity of abnormalities on SPECT brain images and the severity of cognitive impairment in patients with dementia of the Alzheimer type (DAT) and to examine the interreader agreement for visual reading of images in a multicenter SPECT study. Images for a total of 86 subjects were available for the blinded read. The images for 28 subjects were rated as noninterpretable due to technical inadequacies. Images for 58 subjects (45 DAT patients and 13 normal volunteers) from 10 SPECT centers were selected for further analyses. The severity of abnormality was rated as mild, moderate, or severe by three readers. In DAT patients, a significant negative correlation (p < 0.05) of Mini-Mental State Examination (MMSE) score with global severity of abnormality was noted for two of the three readers. A significant correlation (p < 0.05) between MMSE score and severity of abnormality was observed for all three readers for the posterior temporoparietal region. The blinded readers rated a median of 92.3% of normal volunteers' images as normal and a median of 82.2% of DAT patients' images as abnormal. For the regional severity of abnormality, the median percentage interrater agreement across all regions ranged from 95 to 100% in normal volunteers and from 81 to 98% in DAT patients. These results suggest that SPECT brain imaging with 99mTc-bicisate provides functional information about the severity of cognitive impairment in DAT patients.(ABSTRACT TRUNCATED AT 250 WORDS)

High resolution SPECT with [99mTc]-d,l-HMPAO in normal pressure hydrocephalus before and after shunt operation.

Cranial CT and high resolution measurements of regional cerebral blood flow (rCBF) with brain dedicated single photon emission computer tomography (SPECT) and [99mTc]-d,l-hexamethylpropyleneamine oxime ([99mTc]-d,l-HMPAO) were performed before and after shunt operation in 14 consecutive patients with dementia and normal pressure hydrocephalus (NPH). When compared with a control group of 14 age matched healthy volunteers, the group of NPH patients was characterised by an enlarged subcortical low-flow region, significantly reduced rCBF and enhanced side-to-side asymmetry of rCBF in the central white matter, and enhanced side-to-side asymmetry in the inferior and mid-temporal cortex. Global CBF was normal. Shunt operation reduced the mean area of the ventricles on CT and of the subcortical low-flow region on SPECT. Global CBF was unchanged. All 14 patients had an abnormal pre-shunt rCBF pattern with enlargement of the subcortical low flow region, focal cortical blood flow deficits, or both. Shunt operation improved the clinical status in 11 patients, and the area of the subcortical low flow region correctly classified 3/3 unimproved and 10/11 improved patients. Shunt operation normalised or reduced the area of the subcortical low flow region in nine of 10 patients. It is concluded that SPECT with [99mTc]-d,l-HMPAO is a useful supplement in the diagnosis of NPH versus normal ageing, and that SPECT may help to identify patients not likely to benefit clinically from surgery.

Ischaemia-induced (symptomatic) migraine attacks may be more frequent than migraine-induced ischaemic insults.

Fifteen consecutive patients with a diagnostic problem of ischaemia-induced migraine with aura (symptomatic migraine) or migraine-associated ischaemia (migrainous infarction) were studied in order to elucidate the mechanisms. Three had a 1 month flurry of daily attacks of migraine auras with or without headache. A severe internal carotid stenosis/occlusion and reduced regional cerebral blood flow (rCBF) was demonstrated. Borderline ischaemia may thus prime the brain for developing migrainous aura with or without migraine (symptomatic migraine). Four patients had a combination of permanent deficits after the very first migraine attack, severe atherosclerosis, risk factors for stroke, high age and no family history of migraine. In these cases the evidence indicates that thromboembolic ischaemia had triggered an attack of migraine with aura (likely symptomatic migraine). Three young females presented long-lasting typical and severe idiopathic migraine with aura. Attack-associated rCBF reduction was likely to have caused permanent, mild, visual or somatosensory deficits (migrainous infarction). In five patients the relationship between migraine and stroke remained unresolved. It seems that ischaemia-induced migraine attacks may be more frequent than migraine-induced ischaemic insults. Therefore, migraine is not as strong a risk factor for stroke as indicated by the mere coincidence of the two disorders.

Regional cerebral blood-flow measured by HMPAO and SPECT in a 5-year-old boy with Landau-Kleffner syndrome.

We present a 5-year-old boy with Landau-Kleffner syndrome, whose clinical manifestations were very similar to cases previously reported in the literature. CT and MRI scan failed to document any morphological abnormalities of his brain. However, high resolution rCBF imaging by HMPAO and SPECT demonstrated relatively low-flow areas in the left middle frontal gyrus and the right mesiotemporal/hippocampal region corresponding to the localization of EEG changes.

Reduced regional cerebral blood flow in Huntington's disease studied by SPECT.

Regional cerebral blood flow (rCBF) was studied in 18 patients with Huntington's disease (HD) and 19 age- and sex-matched controls with high resolution single photon emission computerised tomography (SPECT), using Tc-99m-HMPAO. Significant reductions in tracer uptake were found in the caudate and lentiform nuclei (20 and 8%) and in the cerebral cortex, especially in the frontal and parietal areas (11-13%). No significant reductions were found in the thalamus, mesial temporal cortex, and occipital cortex. Fourteen patients had neuropsychological testing. Relationship between rCBF and cognitive function was tested by regression analysis. A linear relationship was found between test scores of Wisconsin Card Sorting Test, Picture Arrangement Test and blood flow in the caudate nucleus. Other tests of cognitive function (Block Design Test, Face and Word Recognition Test, Street Fragmented Pictures Test, and Similarities Test) correlated better with flow in the cortical regions believed to be involved in solving those particular tests. These findings indicate, that blood flow is reduced in both cortical and subcortical structures in symptomatic HD, and that both reductions in cortical and subcortical blood flow may be related to cognitive function in HD.

[Psychosocial consequences and surgical treatment of epilepsy. A review]. / Psykosociale konsekvenser af epilepsi og epilepsikirurgi. En oversigt.

Epilepsy is one the commonest neurological diseases. In 25% of the cases, particularly in patients with temporal foci, the seizures prove to be resistant to medicinal treatment. Several investigations have stressed that these patients have pronounced psychosocial problems which may be more important to the patient than the actual seizures. Taking into consideration the WHO definition of health as complete physical, mental and social well-being, patients with epilepsy have problems in all of these dimensions. The major problems are social isolation and employment. Surgical treatment of epilepsy has a pronounced effect on the seizures in 90% of the operations in the best series but it is still uncertain whether reduction in the number of seizures also implies better quality of life. The present data suggest improvement in the psychosocial conditions of the patients who functioned best preoperatively and who became seizure-free after operation. The importance of further longitudinal studies emphasizing the psychosocial aspects is stressed.

[Surgical treatment of epilepsy resistant to drug therapy. A review]. / Kirurgisk behandling af medikamentelt intraktabel epilepsi. En oversigt.

The prevalence of epilepsy is 7-9 cases per 1,000 population, corresponding to 440,000 individuals in Denmark. Approximately 1/4 of these individuals have seizures refractory to anticonvulsant medications and most of them have an epileptic focus in the temporal lobe. Epilepsy refractory to anticonvulsant medication is an incapacitating disease with high costs for the person and the society. The main problems are polypharmacy with side effects, suspicion of neurodegenerative consequences and a higher mortality. The modern era of epilepsy surgery began more than 100 years ago and since then, the developments in neurophysiology and neuroimaging have made it possible to demonstrate the epileptic focus with relatively high precision. As a consequence of this, the volume of the resected tissue has diminished and the operative complications become less frequent. The somatic and neuropsychological effects of a cortical resection are discrete and compensated by a general improvement in performance. Surgical treatment of epilepsy should no longer be considered as a last resort, but as a realistic treatment in cases of medication failure.

[3-year experiences with surgical treatment of epilepsy at the Hvidovre hospital]. / Tre års erfaringer med epilepsikirurgi på Hvidovre Hospital.

The results of a retrospective survey of 48 patients submitted to neurosurgery for medically intractable epilepsy are presented. Twenty-eight patients were treated with selective amygdalohippocampectomy, one with temporal lobe resection, 12 with anterior callosotomy and seven with a total callosotomy. Of the amygdalohippocampectomized patients and the one with temporal lobe resection (n = 29), 52% were seizure free, 17% experienced rare seizures, 7% had a worthwhile improvement while 24% observed no worthwhile improvement (follow-up time 6 to 36 months). Of the callosotomized patients, 11% were free from generalized seizures, 69% had a significant seizure reduction and 18% experienced no worthwhile improvement. The observed neurological complications were: one patient had hemianopia, one had superior quadrant anopia, four developed unilateral anosmia and one complete anosmia. The callosotomized patients, with two exceptions, were all mentally and physically handicapped. In the callosotomy group, two patients died, one from a intracerebral hematoma three months after the operation and another patient seven months postoperatively from unknown causes.

99mTc-d,l-HMPAO and SPECT of the brain in normal aging.

Single photon emission computed tomography (SPECT) with 99mTc-d,l-hexamethylpropyleneamine oxime (99mTc-d,l-HMPAO) was used to determine global and regional CBF in 53 healthy subjects aged 21-83 years. For the whole group, global CBF normalized to the cerebellum was 86.4% +/- 8.4 (SD). The contribution of age, sex, and atrophy to variations in global CBF was studied using stepwise multiple regression analysis. There was a significant negative correlation of global CBF with subjective ratings of cortical atrophy, but not with ratings of ventricular size, Evans ratio, sex, or age. In a subgroup of 33 subjects, in whom volumetric measurements of atrophy were performed, cortical atrophy was the only significant determinant for global CBF, accounting for 27% of its variance. Mean global CBF as measured with the 133Xe inhalation technique and SPECT was 54 +/- 9 ml/100 g/min and did not correlate significantly with age. There was a preferential decline of CBF in the frontal cortex with advancing age. The side-to-side asymmetry of several regions of interest increased with age. A method was described for estimation of subcortical CBF, which decreased with advancing cortical atrophy. The relative area of the subcortical low-flow region increased with age. These results are useful in distinguishing the effects of age and simple atrophy from disease effects, when the 99mTc-d,l-HMPAO method is used.