Clinical validation of controlled exposure to birch pollen in the Environmental Exposure Unit (EEU).

BACKGROUND: The Environmental Exposure Unit (EEU) in Kingston, Ontario, Canada is a controlled allergen challenge facility (CACF) that has been previously clinically validated for the use of ragweed and grass pollen in clinical studies. In this study we aim to validate the use of birch pollen to challenge allergic participants. METHODS: A total of 59 volunteers were screened and 38 birch allergic participants and ten non-allergics completed the study, outside of tree pollen season. Participants had to have a minimum of 2-year history of allergic rhinoconjunctivitis during the typical tree pollen season and have a positive skin prick test to birch allergen ≥5 mm from the control. Qualified participants were exposed to birch (Betula pendula) pollen for 4 h in the EEU and recorded their symptoms of sneezing, rhinorrhea, nasal congestion, nasal itch which comprised the total nasal symptom score (TNSS), as well as itchy/watery eyes, red/burning eyes and itching of ears/palate/throat which along with the TNSS comprised the total rhinoconjunctival symptom score (TRSS) along with Peak Nasal Inspiratory Flow (PNIF) at baseline and at 30 min intervals for the duration of exposure, then hourly for up to 12 h from the start of exposure. RESULTS: Allergic participants reported a gradual rise in TNSS and TRSS, reaching a mean and standard error of the mean of 7.08 ± 0.45 and 11.58 ± 0.93 respectively by 180 min from the start of exposure. Symptoms gradually declined to near baseline values following departing from the unit, reaching 1.9 and 2.7 by 450 min. Allergic participants reported significantly higher TNSS than non-allergics starting from 30 min (p < 0.01, two-way ANOVA with Bonferroni corrections), maintaining maximum significance from 60 to 300 min (p < 0.0001) and losing significance by 420 min. TRSS and PNIF followed similar trends as those seen with TNSS. Participants were phenotyped using previously published definitions using the TNSS into Early Phase Responders (EPR, 57.8 %), protracted EPR (pEPR, 39.5 %), and Dual Phase Responders (DPR, 2.7 %). CONCLUSIONS: The EEU can competently challenge birch allergic participants and achieve statistically significant changes in symptoms and nasal airflow, while such changes are not reported in non-allergic controls. Trial registration NCT02351830 clinicaltrials.gov.

Transesophageal echocardiography in patients with ischemic stroke accurately detects significant coronary artery stenosis and often changes management.

OBJECTIVES: TEE is performed in many patients with ischemic stroke, and it is possible to examine the proximal coronaries by TEE in these patients. Our purpose was to (1) determine the accuracy of transesophageal echocardiography (TEE) in the diagnosis of proximal coronary stenosis in patients with ischemic stroke and (2) show that TEE detection of proximal coronary stenosis changed management in a substantial number of patients. METHODS: Thirty-two patients with ischemic stroke undergoing TEE, in whom the proximal coronaries were examined and who had angiographic results available, were studied. RESULTS: Proximal coronaries were visualized as follows: left main (LM) in 31 (97%), left anterior descending (LAD) in 32 (100%), left circumflex (LCx) in 30 (94%) and right coronary artery (RCA) in 21 (66%). The sensitivity and specificity of TEE in diagnosing significant coronary stenosis in visualized vessels were as follows: LM 100% and 100%, LAD 100% and 95%, LCx 100% and 96%, and RCA 100% and 100%, respectively. When visualized and nonvisualized segments were considered, TEE detected significant stenosis as follows: 4 of 5 in the LM (80%), 13 of 13 in the LAD (100%), 2 of 3 in the LCx (66%), and 2 of 8 in the RCA (25%). Of the 32 patients, TEE results changed management in 17 patients (53%). Angiographic findings resulted in 10 of the 17 patients (59%) undergoing revascularization. CONCLUSIONS: TEE was very accurate in diagnosing significant coexisting coronary artery disease in patients with ischemic stroke. TEE diagnosis of these lesions prompted coronary angiography and subsequent revascularization in a substantial number of patients.

Fruit and vegetable consumption in the prevention of cancer: an update.

Fruit and vegetables are considered to be important means of preventing cancer through diet. However, several recent large prospective cohort studies and clinical trials have found no associations regarding several major cancers, including cancers of the colon, breast and stomach. Although these results are disconcerting, especially for health-conscious individuals, there is also mounting evidence that people who avoid fruit and vegetables completely, or consume very little, are indeed at increased risk of these cancers. These individuals in particular should be identified, with the goal of helping them find ways to include more fruit and vegetables in their diets.

Emergency endovascular treatment of cerebral sinus thrombosis with a rheolytic catheter device.

Severe thrombosis of the superior sagittal, transverse, and straight sinuses developed in a 53-year-old woman. This resulted in extensive multifocal hemorrhagic venous infarction and severe intracranial hypertension refractory to intensive management. Endovascular therapy using a rheolytic catheter device in combination with a small amount of fibrinolytic agent led to rapid normalization of the intracranial pressure, allowing optimization of the cerebral perfusion pressures and was followed by steady, albeit protracted, clinical improvement. The patient not only survived but also left the hospital with minimal neurologic deficit. The rheolytic catheter endovascular treatment is, in the opinion of the authors, the treatment of choice for patients with life-threatening cerebral sinus thrombosis.

Evolution of neuronetworks.

Since the 1970s, the care of critically ill neurologic and neurosurgical patients has emerged as a developing subspecialty. Management of these patients involves an enormous amount of data generation and analysis. Review of the history of neuroepidemiology and neurocritical care demonstrates the inevitability of their present unwiedly burden of information. Compelling advantages of computerization in direct patient care include aid in data acquisition, analysis and remote access. Infrastructure and resources used to collect data on individual patients may be augmented to archive data in clinical databases. Several investigators have initiated information management projects including automation of beside clinical documentation, development of systems for remote access to information and patient registries to study the natural history and outcome of specific neurological conditions. These are steps toward the development of integrated systems to aid in patient monitoring, data management, continuous quality improvement and the generation of hypotheses for further clinical investigation. Improvements in information management technology will allow increased efficiency in an era where information generation continues to increase exponentially.

Elective stenting of symptomatic basilar artery stenosis.

BACKGROUND AND PURPOSE: Percutaneous angioplasty of the intracranial arteries still carries the risk of dissection, with acute closure and embolization. Stenting has been shown to improve the safety and durability of angioplasty in every circulatory bed in which it has been applied. However, stenting of the intracranial arteries has been limited by the availability of stents that can be reliably deployed intracranially. METHODS: Twelve patients underwent elective stenting of the basilar artery after episodes of vertebrobasilar ischemia. In all patients, either medical therapy had failed or the patient had a contraindication for long-term anticoagulation. Information from independent neurological examinations, quantitative angiography, and clinical follow-up was collected. Differences between pretreatment and posttreatment degree of stenoses were subjected to 1-way ANOVA for repeated measures. RESULTS: There were 10 men and 2 women, all white, aged 40 to 82 years (mean age, 62.6 years). Stent placement was successful in all patients, leading to statistically significant changes in the degree of stenosis, from 71. 4% (range, 53% to 90%) to 10.3% (range, 0% to 36%) (P<0.0001). There were no deaths, stent thromboses, perforations, ruptures, or myocardial infarctions. Clinical follow-up was available for 0.5 to 16 months (mean, 5.9 months). One patient had nonspecific symptoms, and another had a transient ischemic attack. All other patients remained asymptomatic. CONCLUSIONS: Elective stenting of the basilar artery is feasible, with minimal risk to the patient. Its impact on long-term stroke prevention and its durability are unknown and will require further study.

Hyperechoic middle cerebral artery: acute occlusion detected by transcranial duplex ultrasonography.

The authors describe the appearance of acute thromboembolic occlusion of the middle cerebral artery (MCA) using transcranial duplex ultrasonography. Acute occlusion of the MCA commonly leads to severe cerebral infarction. In patients with acute MCA occlusion, secondary edema and elevated intracranial pressure are major causes of increased morbidity and mortality. Thus, the prompt detection of occlusion influences early therapy, including thrombolysis and increased control of intracranial pressure. The hyperdense appearance of the acutely occluded MCA as seen using computed tomography (CT) has been extensively reported in the literature. However, its appearance using transcranial duplex ultrasonography has not been reported. The authors report four patients who had clinical features of ischemia throughout the MCA territory. All patients were studied with CT and transcranial duplex ultrasonography within 6 hours of the onset of symptoms. Head CT of all four patients showed a hyperdense MCA sign with infarction of the MCA territory. Transcranial duplex studies using either pulsed Doppler or color Doppler sonography displayed a hyperechoic MCA with no evidence of flow. Subsequent duplex ultrasonography and magnetic resonance angiography showed all four patients had ipsilateral occlusion of the internal carotid artery. Transcranial duplex ultrasonography assists in the early diagnosis of acute MCA occlusion. The affected vessel is displayed as a hyperechoic structure associated with no flow using Doppler examination.

Neuroendovascular rescue. Nonthrombolytic approach to acute brain ischemia.

The field of neuroendovascular therapy is rapidly growing. New technology and operators' expertise is developing at a pace that will make this discipline progressively more available and successful. For the intensive care of patients who have acute brain ischemia, new techniques of recanalizing occluded arteries are progressively being introduced. Thus, the concept of neuroendovascular rescue has gone beyond the use of thrombolytic drugs, expanding our capability to restore flow to ischemic brain tissue after prolonged therapeutic windows. It is important for the interventionalist and the intensivist to work closely together to guarantee the most favorable outcome possible.

Endovascular therapy of traumatic injuries of the extracranial cerebral arteries.

The field of neuroendovascular therapy is rapidly growing. New technology and operators' expertise are developing at a pace that will make this discipline progressively more available and successful. For patients who have traumatic injuries of the extracranial arteries, endovascular therapy offers a new dimension to the treatment of these injuries and the prevention of stroke. Because many of these patients are likely to be critically ill, it is important to keep in mind the principles of their management before, during, and after the procedure, thus assuring the best chance for a successful outcome. Furthermore, some of the issues related to their neurointensive care will serve as guides for the need for endovascular therapy, as well as its timing.

Endovascular therapy of traumatic carotid-cavernous fistulas.

Traumatic carotid-cavernous fistulas (CCF) are capable of causing a large variety of signs and symptoms, including visual loss, glaucoma, chemosis, exophthalmos, and orbital cranial nerve palsies. The high pressure in the veins that normally drain the globe can cause them to engorge and produce local compression of adjacent structures. At present, endovascular closure of the fistula is the treatment of choice, particularly in patients with progressive neurologic deterioration. Endovascular repair of CCF most commonly involves the use of detachable balloons, although coils are also used. Effective closure of the fistula leads to rapid resolution of the symptoms.

Extracranial vertebral artery stent placement: in-hospital and follow-up results.

OBJECT: The authors summarize their experience with stent deployment in the treatment of vertebrobasilar artery (VBA) insufficiency. This is an underdiagnosed condition, and the incidence of significant vertebral artery (VA) stenosis has been underappreciated. Medical therapy has been the mainstay of treatment because of the high rate of morbidity associated with surgical correction of VA stenosis. Recently, some authors have reported acceptable results with the use of percutaneous transluminal angioplasty, but this technique has significant weaknesses such as elastic recoil and problems in achieving safe treatment of dissections. METHODS: The authors investigated the feasibility, safety, and outcome of VA stent placement in 50 patients in whom 55 vessels were treated using stents. Technical success was achieved in 54 (98%) of 55 vessels, with no procedure-related complications. However, one patient (2%) died of nonneurological causes, and one (2%) suffered a stroke that occurred within the 30-day postprocedural period and was related to a complicated coronary intervention. Clinical follow-up review performed at a mean of 25 +/- 10 months revealed two patients (4%) with recurrence of VBA symptoms. Six-month angiographic follow up was completed in 90% of eligible patients, with a 10% incidence of restenosis as defined by greater than 50% luminal narrowing. CONCLUSIONS: Vertebral artery stent placement is feasible in patients who have significant VA stenosis, with predictably good angiographically demonstrated and clinical results. The 6-month angiographically confirmed restenosis rate appears to be low, as does the clinical recurrence rate. This technique solves the problems of elastic recoil and the treatment of angioplasty-induced dissections. Further prospective comparison with medical preventive strategies is warranted.

Influence of age upon complications of carotid artery stenting. UAB Neurovascular Angioplasty Team.

PURPOSE: To examine the impact of age upon the development of neurological and major systemic complications during or after carotid artery stenting. METHODS: We reviewed the complications that occurred in patients undergoing elective carotid stent implantation between September 1994 and August 1996. The study population was then divided into 3 groups according to age: > or = 80 (group A), 75 to 79 (group B), and < or = 74 (group C) years. The rates of death, major and minor stroke, and myocardial infarction were compared among the groups, as well as with the rates reported by the major carotid endarterectomy (CEA) trials. RESULTS: During the study period, 182 patients (216 vessels) were treated with carotid stenting. There were 19 (10.4%) complications: 1 (0.5%) death, 2 (1.1%) major strokes, 15 (8.2%) minor strokes, and 1 (0.5%) myocardial infarction. Neurological complications were clearly related to increased age with rates of 25.0% in group A versus 8.6% in group C (p = 0.042). The overall per patient rate of death or major stroke was 1.6% (1.4% per vessel). CONCLUSIONS: Increasing age has a negative impact on the rate of complications in carotid stent patients. However, the majority of those complications are minor. The relative roles of medical therapy, stenting, and CEA in patients > 80 years of age must await the results of randomized trials.

Neurological monitoring during carotid artery stenting: the Duck Squeezing Test.

PURPOSE: To examine the usefulness of a novel method for neurological monitoring during carotid artery stenting (CAS). METHODS: The records of patients who underwent elective CAS between June 1996 and October 1998 were reviewed to identify those who had neurological changes during the procedure. We examined whether the neurological change had been detected by a change in the ability of the patient to respond to predetermined commands involving a small rubber duck placed in the contralateral hand. RESULTS: hundred seventy patients (320 vessels) underwent monitoring using the Duck Squeezing Test; 10 suffered neurological events during the procedure. Four of these were transient and temporally related to balloon inflation. Another 6 were tentatively ascribed to distal embolism. All instances were accompanied by a change in the patient's ability to perform the Duck Squeezing Test, which allowed the identification of the abnormal clinical situation. In addition, there were 4 false-positive tests secondary to the patient accidentally dropping the rubber duck. CONCLUSIONS: The Duck Squeezing Test is a sensitive and specific method for monitoring patients during elective CAS. Its practical applicability is based on sound neurophysiological concepts, which underscore the clinical importance of the test.

Anticonvulsant effect of anterior thalamic high frequency electrical stimulation in the rat.

Evidence suggests that a specific subcortical pathway synaptically linking the anterior thalamic nuclear complex (AN) to the hypothalamus and midbrain is important in the expression of pentylenetetrazol (PTZ) seizures. Perturbation of neuronal activity along this path via focal disruption or chemical inhibition significantly raises seizure threshold. Recent data has demonstrated that focal electrical stimulation within the hypothalamic component of this pathway inhibited seizure expression in a current and frequency dependent fashion. Similar experiments were conducted in the AN to investigate the hypothesis that stimulation of this thalamic nuclear region can prevent the propagation of PTZ seizures between cortical and subcortical regions. Our results indicate that high frequency (100 Hz) stimulation of AN did not alter the expression of low dose PTZ induced cortical bursting but did raise the clonic seizure threshold compared to naive animals or those stimulated at sites near, but not in AN (P < 0.01). Low frequency stimulation (8 Hz) was in contrast, proconvulsant and could induce behavioral arrest responses accompanied by rhythmic high voltage EEG even without PTZ challenge. This data further highlights the role of AN in mediating the expression of seizures and provides experimental support for the concept that this thalamic region may be a promising target for focal stimulation to treat intractable seizures in humans.

Frontal lobe ataxia.

BACKGROUND: Gait abnormalities often result from disorders intrinsic to the cerebellum. Gait difficulties resulting from frontal lobe disease are less common but well recognized. The pathophysiologic mechanism of this type of ataxia is not well understood. One promising explanation implicates involvement of the frontopontocerebellar tract (Arnold's bundle). This tract originates in the frontal lobe in Brodmann's area 10 and carries information on intended movement to the contralateral cerebellum via the pontocerebellar peduncle. Interruption of this tract deprives the cerebellum of this information, thus impairing coordination and locomotion. METHODS: A patient is described with a large bilateral, medialorbital, frontal lobe lesion, progressive gait impairment, and dysarthria. The lesion is defined by magnetic resonance imaging (MRI) and positron emission tomography (PET) using 18-fluorodeoxyglucose. The cystic component of the lesion was drained surgically. RESULTS: The PET scan using 18-fluorodeoxyglucose showed a normal metabolic rate in the brain stem, a 10%-15% decrease in metabolism in the thalmus and a symmetric decrease of only 15% in the cerebellum bilaterally. The MRI of the cerebellum did not show any significant atrophy. The patient's speech improved, but there was minimal change in her gait ataxia after surgical drainage and partial removal of the cystic frontal lobe lesion. CONCLUSIONS: The patient's syndrome supports the view that frontal lobe ataxia is an established although rare clinical entity, and this report adds original information defining the syndrome with MRI and PET studies. The 15% metabolic decrease in the cerebellum with PET is highly supportive of the syndrome of frontal lobe ataxia and not pathology intrinsic to the cerebellum. The syndrome of frontal lobe ataxia in this patient is due to interruption of the frontopontocerebellar pathway originating in Brodmann's area 10.

Effect of LiCl pretreatment on cholinomimetic-induced seizures and seizure-induced brain edema in rats.

Male Sprague-Dawley rats received LiCl (5 mEq/kg; sc) or saline 24 h prior to injection of cholinomimetics. Physostigmine (PHY, 0.54-0.80 mg/kg), diisopropylfluorophosphate (DFP, 1.3-2.5 mg/kg), pilocarpine (PIL, 23-30 mg/kg), or saline was injected subcutaneously at time 0. Rats were observed for seizure activity for 2 h, survivors were killed 24 h later and edema was measured in samples from parietal and piriform cortices, dorsal thalmus, and hippocampus. None of the rats pretreated with saline had seizures when given doses of cholinomimetics alone. However, rats pretreated with LiCl had the following incidence of seizures: PHY 68%, DFP 71% and PIL 100%. Rats given cholinomimetic agents alone did not have brain edema. In contrast, all LiCl-pretreated rats that seized had pronounced brain edema which was greatest in the piriform cortex. Thus, these studies demonstrate that LiCl pretreatment potentiates cholinomimetic-induced seizures. Further, cholinomimetic-induced seizures produce brain changes resulting in edema.

Convulsions and cerebral inositol-1-phosphate levels in rats treated with diisopropyl fluorophosphate.

In order to examine the relationship of organophosphate-induced cholinergic stimulation to phosphoinositide (PI) hydrolysis in the brain, diisopropyl fluorophosphate (DFP; 1.3 or 1.5 mg/kg subcutaneously) was given to rats pretreated with saline or LiCl (5 meq/kg subcutaneously). Behaviour was monitored 60 min. after the administration of DFP, and inositol-1-phosphate (IP1), an intermediate in PI metabolism, was measured in the brain DFP alone caused tremors, whereas with LiCl pretreatment, DFP caused tremors and tonic-clonic convulsions. DFP alone did not increase IP1 above control levels. LiCl alone elevated IP1 2-5 fold but did not alter rat behavior. With LiCl pretreatment, DFP caused IP1 to increase 2-4 fold above LiCl control values in convulsing rats. LiCl increased the potential of DFP to induce convulsions and greatly amplified IP1 elevations induced by DFP.