Safety of nurse-directed triage intranasal fentanyl protocol for acute pain management in a European pediatric emergency department: A retrospective observational analysis.

Background: Nurse-directed pain protocols for intranasal fentanyl administration are not widely implemented in European (EU) pediatric emergency departments (PED). Barriers include perceived safety concerns for intranasal (IN) fentanyl. The aim of this study is to describe our experience with a nurse-directed triage IN fentanyl protocol with a focus on safety in a tertiary EU PED. Methods: We conducted a retrospective analysis of patient records of children aged 0-16 years who received nurse-directed IN fentanyl between January 2019 and December 2021 at the PED of the University Children's Hospital of Bern, Switzerland. Extracted data points included demographics, presenting complaint, pain score, IN fentanyl dosage, concomitant pain medication use, and adverse events. Results: A total of 314 patients were identified with ages ranging from 9 months to 15 years. The main indication for nurse-directed fentanyl administration was musculoskeletal pain due to trauma (n = 284, 90%). Mild adverse events (vertigo) were reported in two patients (0.6%), without a correlation to concomitant pain medication or protocol violation. The only reported severe adverse event of syncope and hypoxia in a 14-year-old adolescent occurred in a setting where the institutional nurse-directed protocol was violated. Conclusion: In accordance with previous studies outside of Europe, our data support the case that when appropriately used, nurse-directed IN fentanyl is a safe potent opioid analgesic for pediatric acute pain management. We strongly encourage the introduction of nurse-directed triage fentanyl protocols Europe-wide in order to provide effective and adequate acute pain management in children.

Field stitching in thermal probe lithography by means of surface roughness correlation.

A novel stitching method is presented which does not require special purpose alignment markers and which is particularly adapted to probe lithographic methods, enabling the writing of large patterns exceeding the size limitations imposed by high precision scan stages. The technique exploits the natural roughness of polymeric resist surfaces as a fingerprint marker for the sample position. Theoretical and experimental evidence is provided that sub-nanometer metrological accuracy can be achieved by inspecting the surface roughness in areas with 1 µm linear dimensions. The method has been put to the test in a thermal probe lithography experiment by writing a composite pattern consisting of five 10 µm × 10 µm fields which are seamlessly joined together. The observed stitching error of 10 nm between fields is dominated by inaccuracies of the scanning hardware used in the experiment and is not fundamentally limited by the method per se.

Myocardial infarction after chronic ergotamine abuse.

As a result of chronic ergotamine abuse, reversible arterial narrowing has been documented angiographically in peripheral, but not in coronary arteries. We report on a patient with no cardiovascular risk factors, but because of chronic ergotamine abuse suffered on acute myocardial infarction, complicated by ventricular fibrillation. Coronary angiography performed 3 days after resuscitation revealed a distal occlusion of the left anterior descending artery. Three months later, spontaneous recanalization had occurred, and no residual narrowing was seen angiographically. Thus, surveillance of patients with migraine headache to avoid chronic ergotamine abuse is recommended to prevent cardiovascular complications.

Speech arrest as first symptom of a tumour in the supplementary motor area.

There are only few reports in the literature on isolated episodes of speech arrest as first symptom of a tumour in the supplementary motor area. These episodes of speech arrest are due to seizure activity and must be distinguished from speech arrest due to transient ischaemic attacks. The diagnosis may be difficult because the tumour may erroneously be suspected in the lower portion of the sensorimotor strip and may, hence, be missed on CT if apical sections of the regions are not performed. Clinical and experimental aspects of this problem are discussed on the basis of a case report and a review of the literature.

Longterm prognosis of analgesic withdrawal in patients with drug-induced headaches.

We studied long-term prognosis and prognostic variables for therapeutic outcome of analgesic withdrawal in 54 patients with drug-induced headaches. The duration of headache history was 21.9 +/- 12.8 years. Each patient took an average of 38.8 +/- 22.8 tablets or suppositories a week and an average of 2.5 distinct drugs. Most patients used drugs containing several components. Caffeine was contained in at least one drug in all cases, ergotamine in 80.0% and pyrazolone in 77.1%. All patients were admitted to the hospital for two weeks. The analgesics were discontinued abruptly and the withdrawal symptoms were alleviated by neuroleptics and neurotropics. During the second week of hospital stay we started a basic therapy with calcium antagonists or beta blockers in patients suffering from migraine initially and with tricyclic antidepressants, physical therapy or biofeedback in patients suffering from tension type headaches initially. At the end of the study (mean follow-up period = 16.8 +/- 13.6 months) 38 patients (70.1%) were evaluated. 76.3% of these patients had significantly reduced their analgesic intake, 60.5% had experienced a significant relief of headache both in intensity and frequency, and 23.7% were therapeutic failures. Analysis of the time course of relapse revealed the first six months after hospital discharge as the critical period determining long-term success. The variables tested for prognostic relevance (age, sex, duration of headache history, number of tablets or suppositories taken a week, organic mental syndrome, and type of initial headaches) were not statistically significant.

Quantification of regional cerebral blood flow with IMP-SPECT. Reproducibility and clinical relevance of flow values.

Single-photon emission computed tomography with N-isopropyl[123I]-p-iodoamphetamine (IMP-SPECT) was performed in 14 normal volunteers (seven men and seven women aged 25.1 +/- 5.3 years) and 29 patients with cerebrovascular disease (18 men and 11 women aged 54.1 +/- 13.7 years). The fluid microsphere model was used to estimate cerebral blood flow (CBF). Normal subjects were scanned twice, 1 week apart, to determine the reproducibility of the CBF estimates. Hemispheric blood flow (hCBF) was calculated as the mean of regional cerebral blood flow (rCBF) values in 16 gray matter regions per hemisphere. In normal subjects mean hCBF was 68 ml/100 g/min. The highest rCBF was found in the occipital cortex, followed by the frontal, temporal, and parietal cortexes. CBF values were reproducible (p less than 0.001 except the right thalamic region, where p less than 0.01). Intraindividual variation ranged between 0.3% and 15%. Women exhibited significantly higher (16%, p less than 0.02) CBF than men. Patients were subdivided into groups with reversible (n = 19) and persistent (n = 10) symptoms. Significant hCBF differences between the affected and the contralateral hemispheres were recorded only in the group with reversible symptoms (p less than 0.005), whereas the group with persistent symptoms showed a significant bilateral decrease of hCBF compared with normal subjects and patients with reversible symptoms. Focal CBF was significantly lower in patients with completed stroke than in patients with transient symptoms (p less than 0.001). Our results indicate that IMP-SPECT can be used for the routine estimation of CBF in normal and pathologic states.

[Persistent changes in tissue-type plasminogen activator and plasminogen activator inhibitor fibrinolytic parameters in patients following juvenile ischemic cerebral infarct]. / Untersuchung zur Frage von persistierenden Veränderungen der Fibrinolyseparameter t-PA und PAI bei Patienten nach juvenilem ischämischem cerebralem Insult.

In diseases associated with thrombotic or thromboembolic complications, a reduction in the fibrinolytic potential may contribute to the risk to develop thrombosis. To investigate whether juvenile cerebral infarction is associated with a permanent defect of the fibrinolytic system we measured the main components of the fibrinolytic system, tissue plasminogen activator (t-PA) and its fast acting inhibitor (PAI) in plasma samples of 21 patients (aged 21-44 years) 3-24 months after the acute event. The data obtained were compared to those from thirteen healthy young volunteers (22-46 years). A direct effect of known risk factors on the fibrinolytic system could be excluded because patients avoided their risk factors immediately after the ischemic cerebral attack. Hypertension and the combination of oral contraceptives and smoking had been the most striking original risk factors. Levels of t-PA antigen and t-PA activity before and after venous occlusion, or PAI activity were not different between patients and controls suggesting that at least a permanent decrease in the activity of the fibrinolytic system does not exist in these patients. However, our findings do not exclude that a temporary defect in fibrinolysis might have contributed to the acute onset of the thrombotic cerebral event possibly induced by the risk factors originally present.

[Does alcohol consumption promote the manifestation of strokes? Considerations on pathophysiology]. / Begünstigt Alkoholkonsum die Manifestation von Schlaganfällen? Uberlegungen zur Pathophysiologie.

Arterial hypertension is the most important risk factor in all types of stroke. The significance of alcohol in the pathogenesis of stroke is less well defined. Chronic alcoholism leads to an elevation of blood pressure. Thus, the association between alcohol and stroke might be the blood pressure effect of alcohol. However, some studies have shown a significant influence of alcohol on the incidence of stroke--especially of intracerebral haemorrhage and subarachnoid haemorrhage--even after adjustment for blood pressure. Many possible pathomechanisms are discussed. Alcohol inhibits aggregation of thrombocytes, and chronic alcohol abuse may induce thrombocytopenia, which could lead to a haemorrhagic stroke. Alcohol withdrawal leads to rebound thrombocytosis. Acute alcohol ingestion induces a decrease in fibrinolytic activity and an increase in factor VIII activity, which enhances the thrombotic potential. Additionally, alcohol increases plasma osmolarity, erythrocyte aggregability, haematocrit and blood viscosity, and decreases deformability of erythrocytes. The effects of alcohol on cerebral blood flow are still under debate; there is a deterioration in autoregulation of cerebral blood flow anyway. In animal studies alcohol induced dose-dependent vasospasm of the cerebral blood vessels, which could be a possible pathomechanism in ischaemic, as well as in haemorrhagic stroke. Chronic alcoholism is the most common cause of secondary non-ischaemic cardiomyopathy, which can lead to cerebral embolism via rhythm disorders or intracardiac thrombus formation.(ABSTRACT TRUNCATED AT 250 WORDS)

[On the problem of post-traumatic headache]. / Zur Frage posttraumatischer Kopfschmerzen.

Posttraumatic headache is a general term for pain localized in the head or neck, occurring after head trauma and of varied aetiology and pathogenesis. In many cases one only finds a time-dependent relation to trauma, but no causal one. There is no uniform, typical "posttraumatic headache". The headaches are commonly caused by injury to scalp, cervical spine and intracranial structures. A reciprocal influence exists between these functionally disturbed structures and a relation to psychogenic factors, which are essential co-factors. Usually it is difficult to decide whether posttraumatic headaches are exclusively caused by organic or psychogenic factors. Probably both factors are involved to an individually different degree.

[Creutzfeldt-Jakob disease. Clinical aspects and diagnosis based on 2 cases]. / Die Creutzfeldt-Jakobsche Erkrankung. Klinik und Diagnose an Hand von 2 Fällen.

The case histories are presented of two patients with Creutzfeldt-Jakob disease. The clinical diagnosis was confirmed on autopsy. A 51-year-old man and a 63-year-old woman developed--after a period of non-specific prodromal symptoms--a rapidly progressive dementia accompanied by cerebellar, pyramidal and extrapyramidal signs. The clinical features, the course of the disease and the results of investigations are discussed, as well as the differential diagnosis.

[Prevention of migraine using flunarizine (results of a pilot study using Amalium)]. / Zur Migräneprophylaxe mit Flunarizin (Ergebnisse einer Pilotstudie mit Amalium).

A short episode of focal cortical hypoxia seems to be the turning-point in the genesis of the migraine attack. This pathophysiological situation induces vascular changes according to the hypothesis of Wolff. Under such conditions some Ca-antagonists develop antihypoxic and antivasoconstrictive properties. The efficiency of Flunarizine as potent prophylactic drug in migraine therapy is well documented in many double-blind randomized studies versus placebo or other antimigrainous drugs. Based on the positive results of these studies, we liked to investigate the efficiency and tolerability of Flunarizine also in a sample on n = 44 adults Austrian patients recruited from the Headache-Ambulance of the Neurological Department, University of Vienna. After a 3 months treatment with Flunarizine, 10 mg daily, there was a drug free follow-up period of 4 to 12 months. After this time in 29 patients (66.6%) there was a decrease of attack frequency of more than 50%. 12 (27.3%) of them were completed free of attacks. Beside this, the intake of attack ameliorating drugs (ergotamine, analgetics) was markedly reduced. Treatment was well tolerated. Weight gain was observed in 20.3% of patients likely correlating with the therapeutic efficiency. Due to its efficiency, safety and its long-lasting therapeutic effect, Flunarizine appears to be a very suitable agent in the prophylaxis of migraine.

Unilateral stenosis of the vertebral artery--secondary finding with no prognostic relevance?

The outcome of 142 patients suffering from ischemic cerebral circulation disorders was followed up over a period of 33 months on average. The spontaneous course of 25 patients with unilateral, hemodynamically ineffective stenoses of the vertebral artery was compared with that of 107 patients without vertebral artery stenoses. Within the first 12 months, novel clinically manifest cerebrovascular events were observed in 16.0% of patients without vertebral artery stenosis (deaths 5.0%), but in only 4.3% of the patients with vertebral artery stenosis (no deaths). Within 30 months, only 2 of the 13 patients with vertebral artery stenosis had suffered a new cerebrovascular attack. At the end of the observation period, 39.3% of the patients without vertebral artery stenosis and 48.0% of the patients with vertebral artery stenosis were significantly disabled in their social life or had died. An additional unilateral hemodynamically irrelevant vertebral artery stenosis did not influence the rate of reinfarction or the remission of neurological deficits, independently of age, the degree of the circulatory disorder, the vascular territory involved, the presence of an organic psychosyndrome, or of additional stenoses in the carotid arteries. Consequently, a vertebral artery stenosis narrowing the vessel diameter to less than 1/3 is without prognostic relevance.

[Rare pathomorphologic findings in complicated migraine]. / Seltene pathomorphologische Befunde bei komplizierter Migräne.

137 patients suffering from classical or complicated migraine were investigated in the Neurology Department of the University of Vienna between 1971 and 1984. 13 of these patients were found to have pathological alterations and their case histories are presented. Clinically, 11 patients suffered from migraine accompagnée (in 2 cases accompanied by epileptic seizures), 1 patient had ophthalmoplegic migraine and 1 had a subarachnoid haemorrhage imitating migraine. The underlying pathological findings were: 1 tumour, 4 arteriovenous malformations, 4 aneurysms, 1 arterio-venous shunt, 1 pathological vascular network, 1 Moya-Moya syndrome and 1 intracerebral haemorrhage without detectable source of bleeding. 8 of the patients underwent successful surgery and most of them showed subsequent clinical improvement. The family history was positive in only 2 patients. The time interval between the occurrence of the first symptoms and the establishment of the final diagnosis was up to 25 years. The neurologist should undertake extensive investigation of the patient, including cerebral angiography, if the following criteria apply: hemicrania consistently on the same side; change in type of headache after a number of years; uniform complicating neurological symptoms; additional occurrence of epileptic seizures; manifestation of neurological symptoms after the prodromal phase; persistent neurological signs without remission; negative family history; persisting diffuse or locally accentuated EEG changes; pathological CAT results.

[Status of oral contraceptives as a risk factor in cerebrovascular diseases]. / Zum Stellenwert der oralen Kontrazeptiva als Risikofaktor zerebraler Gefässerkrankungen.

A critical review of the relevant literature revealed that the incidence of subarachnoid haemorrhage is increased in women taking oral contraceptives and the mortality rate is higher. The data concerning correlation between the use of oral contraceptives and other cerebrovascular disorders are less conclusive. Taking oral contraceptives seems to result in a higher risk of stroke, but there is no definite correlation to the incidence of strokes with a fatal outcome. However, in the case of the coexistence of more than one risk factor, including cigarette smoking, the risk of cerebrovascular disease is considerably increased for women using oral contraceptives. Age also seems to be a significant factor. Women older than 44 should avoid oral contraceptives in general; women between 35 and 44 should use oral contraceptives only if additional risk factors are absent, i.e. if they are non-smokers. Indeed, in the presence of this or other risk factors younger women should also avoid taking oral contraceptives.

[Prognostic significance of initial loss of consciousness in cerebrovascular disorders]. / Zur prognostischen Bedeutung eines initialen Bewusstseinsverlustes bei zerebralen Durchblutungsstörungen.

An initial loss of consciousness is of grave prognostic significance in patients with acute ischaemic cerebrovascular disorders, both as regards the early course as well as the long-term prognosis. The aim of this study was to assess the prognostic importance of an initial loss of consciousness in patients who had survived the acute stage. Thus, 133 out of 139 patients suffering from ischaemic cerebrovascular disorders who survived the first 3 weeks after a stroke were clinically re-examined after a mean follow-up period of more than two years. The other 6 patients had died as a result of a second stroke in the post-acute period. Patients with an initial loss of consciousness suffered cerebrovascular disturbances or fatal strokes in the follow-up period slightly more frequently than patients without an initial loss of consciousness. However, there were no convincing differences between the two groups. Indeed, on follow up, patients with an initial loss of consciousness were slightly less socially disabled than patients without an initial loss of consciousness. The results suggest that an initial loss of consciousness is no longer a factor of prognostic importance in patients who have survived the initial stage.

[Further therapeutic possibilities with valproic acid (Convulex)]. / Weitere Therapiemöglichkeiten mit Valproinsäure (Convulex).

Valproic acid is used in first case as an antiepileptic; own clinical observance and references from the literature show other indication-fields outside of the group of cerebral fits; so Convulex was employed successfully also in the therapy of perioral dyskinesia of variable etiology and in the medical treatment of therapy-resistant pains within the bounds of Polyneuropathy-Polyneuritis Syndrome. Our own experience is presented by the description of the 10 case histories.

[The cerebral angiogram in patients with complicated migraine]. / Das zerebrale Angiogramm bei Patienten mit Migraine accompagnée.

38 patients (mean age: 29 years) were investigated by means of complete 4-vessel angiography: all of them were suffering from complicated migraine without detectable vascular malformation. Stenoses of the great craniocervical vessels were found in 11 patients (28.9%), but there was not a single case of vascular occlusion. A correlation between the localization of the stenosis, the localization of the headache and the presumed region of the transient cerebral function disturbance was found only in a few patients. Concerning the morphological changes of the small intracranial arterial branches, there was hardly any difference between clinically affected and non-affected territories of the middle cerebral artery. The angiograms of the 38 cases of complicated migraine were compared with the angiograms of 40 patients suffering from strokes in the young and those of 49 patients with transient ischaemic attacks. There were remarkably fewer stenoses or occlusions in the great craniocervical arteries of patients suffering from complicated migraine (28.9%) than in the vessels of cases of stroke in the young (52.5%). However, the incidence was comparable with the results in patients with transient ischaemic attacks (34.7%). The degree of morphological changes in the small intracranial arterial branches is likely to depend primarily on the patient's age and less on the diagnosis. The results suggest that in almost 30% of patients with complicated migraine-even at juvenile age-stenoses of the great craniocervical vessels might be found.(ABSTRACT TRUNCATED AT 250 WORDS)

Apraxia of the left limbs in a case of callosal disconnection: the contribution of medial frontal lobe damage.

A 40 year old right-handed woman suffered hemorrhage from an anterior cerebral artery aneurysm. CT scan showed destruction of the anterior two thirds of the corpus callosum, both cingulate gyri, and the white matter underlying the medial frontal lobes. The left limbs displayed apraxia on verbal command, in imitation, and in actual object use. There were antagonistic actions of both hands, and the patient accused her left hand of disobeying her. We interpret the leftsided apraxia as resulting from a lack of interhemispheric transfer combined with a deficit in ipsilateral motor control stemming from damage to the left supplementary motor area. Right frontal lobe damage may have impaired the motor learning capacity of the right hemisphere and thus its ability to compensate for the lack of left hemisphere motor control.

[Cerebral angiography in complicated migraine--reactions, incidents]. / Zerebrale Angiographie bei komplizierter Migraine--Reaktionen, Zwischenfälle.

Seventy-one patients (ages: 15-58 years) suffering from complicated migraine were investigated by means of cerebral angiography which was not performed during an attack. Angiography was carried out to exclude stenoses or occlusions of the cranio-cervical vessels and above all vascular malformations (arterial aneurysms, arteriovenous angiomas). In 18 cases (25.4%) organic lesions were found, including three vessel malformations (4.2%). Thirty-one patients (43.7%) suffered from headache reactions or other complications during or within 24 h following angiography. In 15 cases (21.1%) attacks of complicated migraine were observed, three patients (4.2%) suffered from headache and bilateral flickering visual disturbances, another 11 patients (15.5%) developed headache and vegetative symptoms requiring therapeutic management. One patient (1.4%) got an epileptic seizure, another patient (1.4%) developed a generalized urticaria exanthema. There were more headache reactions in women than in men. However, the highest percentage of reactions was observed in patients in whom migraine headache had occurred clearly set off from the transient cerebral functional disturbances. Neurological complications (transient functional disturbances) occurred in 16 of 71 patients (22.5%). The neurological complication rate was significantly (P less than 0.001) higher than that in an unselected group of patients (3.0%).(ABSTRACT TRUNCATED AT 250 WORDS)