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Derek Armstrong

Publications and source records attributed to Derek Armstrong.

At least 19 recordsLinked to original sources
PubMed2006

Pediatric arteriovenous malformation: University of Toronto experience using stereotactic radiosurgery.

INTRODUCTION AND BACKGROUND: Arteriovenous malformations (AVMs) are congenital vascular lesions of the brain, which behave differently in pediatric population compared to adults. Treatment of pediatric AVMs includes a combination of microsurgery, embolization and radiation therapies. However, the role of radiosurgery in the treatment of pediatric AVMs is not fully accepted because of concerns regarding the long-term effects of radiation on the pediatric brain. DISCUSSION: In this study, we review our experience at the University of Toronto with treating pediatric AVMs using linear accelerator-based (LINAC) radiosurgery over the past 15 years. We report our results, obliteration rates, and complications on a total of 40 patients. In addition, we provide a review of series published to date combined with our own results to determine whether radiosurgery is a safe and reasonable treatment modality for pediatric AVMs.

Adolescent↗
PubMed2006

Primary central nervous system vasculitis in children.

OBJECTIVE: Primary angiitis of the central nervous system (PACNS) is a severe and ill-defined neurologic disease. The goal of this study was to characterize the presenting features, treatment, and neurologic outcome of PACNS in children (cPACNS) and to define the predictors of disease progression in order to identify high-risk patients with cPACNS. METHODS: The cohort comprised consecutive patients diagnosed as having cPACNS based on clinical and vascular imaging findings, including identification of arterial stenosis on conventional angiography or magnetic resonance (MR) angiography. Disease progression was defined angiographically at >3 months after initial angiography. Clinical data obtained in prospectively collected standardized assessments and results of laboratory tests, including detection of cerebrospinal fluid abnormalities, were noted, and neuroimaging studies were reanalyzed. Predictors of progression were identified and tested in multivariate regression models. RESULTS: Sixty-two consecutive patients with cPACNS (38 male, 24 female, median age 7.2 years) were included. Two distinct subgroups were identified, those with progressive disease and those with nonprogressive disease. Progressive cPACNS was found in 20 of 62 children and was predicted by a clinical presentation of neurocognitive dysfunction, multifocal parenchymal lesions on MR imaging, and evidence of distal stenoses on angiography. CONCLUSION: The spectrum of PACNS in children includes both progressive and nonprogressive forms. Characteristic features at diagnosis can be used to predict later progression, to identify a distinct high-risk cPACNS cohort, and to help guide selection of patients for immunosuppressive therapy.

Adolescent↗
PubMed2006

Hemorrhage predisposing to cerebral infarction in children with moyamoya disease.

Two children with a new diagnosis of hemorrhagic type moyamoya disease experienced cerebral infarction after intraventricular hemorrhage. The patients developed ischemia 15 and 2 days after the initial diagnosis of hemorrhage. No provocative factor such as hypoperfusion was identified, but both patients exhibited signs of increased intracranial pressure on computed tomographic scan before infarction. Increased intracranial pressure in the setting of hemorrhage may be a risk factor for ischemic complications in patients with moyamoya disease. The optimal acute management of these patients requires further study.

Acute Disease↗
PubMed2006

Deoxycholate amphotericin B and amphotericin B lipid complex exert additive antifungal activity in combination with pulmonary alveolar macrophages against Fusarium solani.

Fusarium spp. have emerged as important causes of invasive fungal infections in immunocompromised patients. Rabbit pulmonary alveolar macrophages (PAMs) exhibited fungicidal activity against conidia of Fusarium solani and achieved a time-dependent increase in killing. Neither deoxycholate amphotericin B (DAMB) nor amphotericin B lipid complex (ABLC) exerted a suppressive effect on PAMs by decreasing their conidiocidal activity against F. solani. On the contrary, at a concentration of 0.125 microg ml(-1), ABLC and, to a lesser degree, DAMB additively augmented the fungicidal activity of pulmonary alveolar macrophages against conidia of Fusarium solani.

Amphotericin B↗
PubMed2006

Compartmentalized intrapulmonary pharmacokinetics of amphotericin B and its lipid formulations.

We investigated the compartmentalized intrapulmonary pharmacokinetics of amphotericin B and its lipid formulations in healthy rabbits. Cohorts of three to seven noninfected, catheterized rabbits received 1 mg of amphotericin B deoxycholate (DAMB) per kg of body weight or 5 mg of either amphotericin B colloidal dispersion (ABCD), amphotericin B lipid complex (ABLC), or liposomal amphotericin B (LAMB) per kg once daily for a total of 8 days. Following sparse serial plasma sampling, rabbits were sacrificed 24 h after the last dose, and epithelial lining fluid (ELF), pulmonary alveolar macrophages (PAM), and lung tissue were obtained. Pharmacokinetic parameters in plasma were derived by model-independent techniques, and concentrations in ELF and PAM were calculated based on the urea dilution method and macrophage cell volume, respectively. Mean amphotericin B concentrations +/- standard deviations (SD) in lung tissue and PAM were highest in ABLC-treated animals, exceeding concurrent plasma levels by 70- and 375-fold, respectively (in lung tissue, 16.24 +/- 1.62 versus 2.71 +/- 1.22, 6.29 +/- 1.17, and 6.32 +/- 0.57 microg/g for DAMB-, ABCD-, and LAMB-treated animals, respectively [P = 0.0029]; in PAM, 89.1 +/- 37.0 versus 8.92 +/- 2.89, 5.43 +/- 1.75, and 7.52 +/- 2.50 mug/ml for DAMB-, ABCD-, and LAMB-treated animals, respectively [P = 0.0246]). By comparison, drug concentrations in ELF were much lower than those achieved in lung tissue and PAM. Among the different cohorts, the highest ELF concentrations were found in LAMB-treated animals (2.28 +/- 1.43 versus 0.44 +/- 0.13, 0.68 +/- 0.27, and 0.90 +/- 0.28 microg/ml in DAMB-, ABCD-, and ABLC-treated animals, respectively [P = 0.0070]). In conclusion, amphotericin B and its lipid formulations displayed strikingly different patterns of disposition in lungs 24 h after dosing. Whereas the disposition of ABCD was overall not fundamentally different from that of DAMB, ABLC showed prominent accumulation in lung tissue and PAM, while LAMB achieved the highest concentrations in ELF.

Amphotericin B↗
PubMed2006

Craniocervical arterial dissection in children: clinical and radiographic presentation and outcome.

Craniocervical arterial dissection is a recognized cause of arterial ischemic stroke in children. Whether children with craniocervical arterial dissection have dissection characteristics different from those of adults is unclear. A retrospective review of children, 1 month to 18 years of age, with dissection from two Canadian pediatric ischemic stroke registry centers was conducted. From 213 patients with arterial ischemic stroke, 16 (7.5%) were identified with dissection, 37.5% had warning symptoms, and 50% had a history of head or neck trauma. The clinical presentation included headache (44%), altered consciousness (25%), seizures (12.5%), and focal deficits (87.5%). Dissection involved extracranial vessels in 75% and anterior circulation in 56%. Follow-up included complete recovery in 43%, mild to moderate deficits in 44%, and severe deficits in 13%. Fourteen (87.5%) children received antithrombotic treatment. Follow-up angiography showed resolution of abnormalities in 60% of vessels. Total occlusion had the worst outcome for recanalization. In conclusion, the etiology of arterial dissection in the majority of children appears to be either trauma or idiopathic. Long-term angiography shows variable outcomes, depending on the initial findings. The relationship of angiographic outcomes with recurrent strokes requires further study in pediatric dissection. (J Child Neurol 2006;21:8-16).

Adolescent↗
PubMed2005

Limitations and technical considerations of endovascular treatment in neonates with high-flow arteriovenous shunts presenting with congestive heart failure: report of two cases.

CASE REPORT: We report two neonatal patients with high-flow intracranial or cervical arteriovenous (AV) shunts who presented with congestive heart failure and were successfully managed with endovascular treatment. One with vein of Galen malformation with body weight of only 2.0 kg is, to our knowledge, the smallest neonate successfully treated with endovascular treatment. The other neonate is, to our knowledge, the first vertebro-vertebral fistula patient presenting with heart failure and treated successfully with endovascular treatment. CONCLUSION: Even in neonates, endovascular treatment is the procedure of choice for high-flow AV shunts presenting with progressive congestive heart failure resistant to medical management. We discuss limitations and technical considerations of endovascular treatments in small neonates with high-flow AV shunts and congestive heart failure.

Arteriovenous Shunt, Surgical↗
PubMed2005

The role of endovascular treatment for pediatric aneurysms.

OBJECTIVES: To review all cases of pediatric aneurysms, we treated and evaluated their characteristics. The objective of the study is to compare between surgical and endovascular approaches regarding treatment and outcome. METHODS: All cases of pediatric intracranial aneurysms diagnosed and managed by our team in the last 12 years were prospectively collected in our vascular malformation data base and reviewed. CONCLUSION: Pediatric aneurysms differ in their features when compared to adult aneurysms. Over the last years, there has been a gradual shift from traditional surgical approaches towards endovascular treatment of pediatric aneurysms. In our experience, patients treated by endovascular means had a better outcome than when treated by surgery. Whenever possible, endovascular treatment for pediatric aneurysms is the recommended approach. This offers both constructive and deconstructive techniques. Improved understanding with respect to the etiology of pediatric aneurysms will be the next step that will likely lead us to even better treatment decisions.

Adolescent↗
PubMed2005

Post-varicella arteriopathy of childhood: natural history of vascular stenosis.

OBJECTIVE: To determine the course of vascular changes in childhood post-varicella arteriopathy (PVA) and its relationship to recurrent arterial ischemic stroke or TIA (AIS/TIA). METHODS: Subjects were children with AIS/TIA occurring <1 year after varicella, ischemic localization consistent with unilateral disease affecting the supraclinoid internal carotid artery or proximal anterior or middle cerebral arteries, and no identified AIS/TIA etiology other than PVA. Charts, brain MRI, and sequential cerebral vessel imaging (selective cerebral angiography or MR angiography [SCA/MRA]) were retrospectively reviewed. RESULTS: Twenty-three children had varicella at age 1.0 to 10.4 years and had single or multiple AIS/TIAs 4 to 47 weeks later. Initial SCA/MRA was performed within 1 month of presentation, and each child had one to five repeat SCA/MRAs during a 4- to 87-month period. There was vascular stenosis in 19 children, maximal on initial studies in 15 of these. Subsequent stenosis regression occurred in 17 children. In 11 of these, one or two additional SCA/MRAs showed further regression as long as 48 months after presentation; there was no restenosis. Eight of 23 children had recurrent AIS/TIA with antithrombotic therapy within 33 weeks of presentation, including 1 of 17 children with documented stenosis regression. CONCLUSION: Vascular stenosis of childhood post-varicella arteriopathy takes a monophasic course, generally with subsequent stenosis regression and only occasional stenosis progression after arterial ischemic stroke/TIA. Arterial ischemic stroke/TIA rarely recurs with antithrombotic prophylaxis after stenosis regression occurs.

Anticoagulants↗
PubMed2005

Angiography-negative primary central nervous system vasculitis in children: a newly recognized inflammatory central nervous system disease.

Inflammatory central nervous system (CNS) diseases in childhood comprise a wide spectrum of heterogeneous conditions. We studied 4 children with primary CNS vasculitis in whom results of magnetic resonance imaging studies were abnormal but results of conventional angiography were normal. We determined that angiography-negative, biopsy-confirmed primary small-vessel CNS vasculitis is a previously unrecognized distinct disease entity in children. The diagnosis must be considered in a child with a progressive, acquired diffuse or focal neurologic deficit, even if the results of conventional angiography are normal. A lesional brain biopsy is required to confirm the diagnosis. Use of immunosuppressive therapy plus aspirin leads to an excellent neurologic outcome.

Adolescent↗
PubMed2005

Use of fluorescent probes to determine MICs of amphotericin B and caspofungin against Candida spp. and Aspergillus spp.

We investigated the utility of mechanism-based fluorescent probes for determination of MICs (FMICs) of amphotericin B and caspofungin against Candida spp. and Aspergillus spp. Amphotericin B was selected as a membrane-active antifungal agent, and caspofungin was selected as a cell wall-active agent. FMICs were also compared to the MIC determined by CLSI (formerly NCCLS) methods. Five isolates per species of Candida albicans, Candida glabrata, Candida parapsilosis, Aspergillus fumigatus, and Aspergillus terreus were studied with either amphotericin B or caspofungin. The fluorescent probes, carboxyfluorescein diacetate (CFDA) for cytoplasmic esterase activity and dihexyloxacarbocyanine iodide (DiOC6) for cell membrane potential, were each added to their respective plates. MICs and FMICs were determined in at least three separate experiments (in duplicate). Fluorescence was measured using a 96-well plate fluorometer. For amphotericin B and caspofungin, the FMIC end point was the lowest concentration of drug at which the percent growth inhibition from treated organisms versus control organisms displayed 80% inhibition for amphotericin B and 50% inhibition for caspofungin as measured by a fluorescent signal. The MIC for amphotericin B was defined as the lowest concentration of antifungal displaying no visible growth for both Aspergillus and Candida spp. The MIC for caspofungin was the lowest concentration of drug that displayed a minimum effective concentration for Aspergillus spp. For Candida spp., the MIC for caspofungin was defined as the concentration at which the antifungal agent significantly inhibits the organism. The FMICs of both antifungals, as measured by the DiOC6 membrane probe, showed good agreement (83% to 100%), within one well dilution, with the MICs against amphotericin B and caspofungin for all species. Also, the FMICs measured by the CFDA cytoplasmic esterase probe reflecting damage due to cell wall or cell membrane showed strong agreement (79 to 100%) with the MICs of both amphotericin B and caspofungin for all species. There was no significant difference in comparisons of MIC and FMIC values (P > or = 0.05). The use of fluorescent probes provides a mechanism-based method of determination of MICs of amphotericin B and caspofungin against Candida spp. and Aspergillus spp. that correlates well with standard methods.

Amphotericin B↗
PubMed2005

Hypomelanosis of Ito and Moyamoya disease.

Moyamoya disease is a cerebrovascular disease characterized by stenosis and occlusion of the arteries of the circle of Willis, with abnormal telangiectatic collateral circulation at the base of the brain. An association between moyamoya disease and neurofibromatosis 1, a neurocutanoeus disorder, is well established in the literature. However, its association with other neurocutaneous syndromes is infrequently reported. Hypomelanosis of Ito, another neurocutaneous syndrome, is characterized by macular hypopigmented skin whorls and variable neurologic involvement. Only one case study of an association between hypomelanosis of Ito and moyamoya disease has been reported in the English literature. We report a 17-year-old girl with both hypomelanosis of Ito and angiographic moyamoya disease. She presented with intractable seizures, progressive left hemiparesis, and skin manifestations of hypomelanosis of Ito. Although one might consider a coincidental association, this second case points to an association between the two disorders. Detailed neuroimaging, in particular angiography, should be considered in children with hypomelanosis of Ito and abnormal neurologic findings.

Adolescent↗
PubMed2004

Separation of craniopagus twins in the era of modern neuroimaging, interventional neuroradiology, and frameless stereotaxy.

INTRODUCTION: Craniopagus twinning is a rare embryological event occurring in 1 in 2.5 million births. CASE REPORT: We present our recent experience with the separation of total vertical craniopagus twins in the modern era of neuroimaging and interventional neuroradiology. Three-dimensional CT images revealed the twins' heads were axially rotated 30 degrees. MRI showed deficient dura between the brains of the twins, and some sharing of parietal brain tissue. Cerebral angiography showed a dominant arterial circulation of one twin with unilateral middle cerebral artery (MCA) branches feeding the other twin. The twins shared a common superior sagittal sinus in its middle segment where a circular sinus was formed. Prior to surgery, endovascular separation of the twins' arterial and venous circulations was achieved in part using tantalum coils for the MCA feeders in one twin, and balloon occlusion of the anterior superior sagittal sinus of the other. Using the ISG wand intraoperatively, surgery proceeded stepwise and included the circumferential removal of bone and opening of the dura, separation of the twins' brains along leptomeningeal planes, and identification of the major draining veins from the superficial cerebral cortex. DISCUSSION: The separation of craniopagus twins demands a multidisciplinary team approach. Utilizing preoperative neuroendovascular techniques to occlude shared vascular anastomotic channels, complex total vertical craniopagus twins can now be successfully separated in a one-stage procedure.

Child, Preschool↗
PubMed2004

Predictors of mortality and neurological morbidity in children undergoing extracorporeal life support for cardiac disease.

OBJECTIVES: The objective of this study was to determine the incidence and risk factors for death and adverse neurological outcomes in children receiving extracorporeal life support (ECLS) for cardiac indications. METHODS: A retrospective single centre consecutive cohort study was conducted in children who received ECLS for cardiac indications between January 1990 and June 2000. Health records and neuroimaging films were assessed, and long-term outcomes were obtained by standardized telephone follow-up or by assessments performed in outpatient clinic. Clinical, neuroimaging and surgical predictors of outcome were tested. RESULTS: Of 90 children studied, short-term clinical neurological events (during hospitalization) occurred in 20 children (22%) during or following ECLS. Long-term neurological sequelae were present in 11 of 31 children discharged alive, after a mean follow-up interval of 4.5 years (range 4 months to 9 years). Death occurred in 59 children (66%) during hospitalisation, and in 3 following discharge. Of the 28 long-term survivors, only 15 children (17%) survived without neurological sequelae. Abnormal neuroimaging was associated with short-term neurological events (P = 0.03, OR 10.5), and the use of CPR prior to ECLS (P = 0.02, OR 2.9) was the only significant predictor of death. There were no significant predictors of long-term neurological sequelae. CONCLUSIONS: More than two-thirds of the children receiving ECLS died, and 39% (11/28) of long-term survivors had neurological deficits. Although mortality is close to 100% without this type of support, there is still a significantly high morbidity and mortality with this type of support.

Adolescent↗
PubMed2004

Effect of intracranial bleeds on the health and quality of life of boys with hemophilia.

OBJECTIVES: To compare the health, physical function, and quality of life (QoL) of boys with hemophilia with and without a history of intracranial hemorrhage (ICH). STUDY DESIGN: Of 172 patients with hemophilia A or B, 18 (10%) had at least one episode of ICH. For outcome assessments, 16 of 18 (89%) boys with ICH and 32 controls, matched (1:2) for age and severity of hemophilia, were available. The outcome measures were neurologic function, physical function, and QoL. RESULTS: The median age of the boys at the first ICH was 5.9 months (range, 1 day to 2.7 years). Boys with ICH had a higher incidence of inhibitors and lower mean household income. Neurologic examination was abnormal in seven of 16 (44%) boys with ICH and nine of 32 (28%) controls (P=.3). The mean physical function in boys with ICH was lower (82%+/-25%) compared with controls (93.5%+/-12%, P=.045). The QoL was decreased in boys with ICH compared with controls (6.8+/-3.2 vs 8.5+/-1.4, P=.02), whereas health-related QoL was not significantly different between groups. CONCLUSION: The poorer long-term outcomes of boys with hemophilia appropriately treated for ICH, especially in the domain of QoL, suggest that new strategies to prevent ICH and to manage ICH effectively in this population are needed.

Adolescent↗
PubMed2004

Tattoos and MRI.

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Adolescent↗
PubMed2003

Experimental pulmonary aspergillosis due to Aspergillus terreus: pathogenesis and treatment of an emerging fungal pathogen resistant to amphotericin B.

Aspergillus terreus is an uncommon but emerging fungal pathogen, which causes lethal infections that are often refractory to amphotericin B (AmB). In comparison to Aspergillus fumigatus, A. terreus was resistant to the in vitro fungicidal effects of safely achievable concentrations of AmB. These in vitro findings correlated directly with resistance of A. terreus to AmB in experimental invasive pulmonary aspergillosis. Residual fungal pulmonary burden and galactomannan antigenemia demonstrated persistent infection, despite therapy with deoxycholate AmB or liposomal AmB. By comparison, posaconazole and itraconazole resolved GM antigenemia, reduced residual fungal burden, and improved survival. There were no differences in phagocytic host response to A. terreus versus A. fumigatus; however, the rate of conidial germination of A. terreus was slower. The strain of A. terreus with the highest minimum inhibitory and minimum lethal concentration of AmB also had the lowest membrane ergosterol content. The hyphae of A. terreus in vivo displayed distinctive aleurioconidia, which may be a practical microscopic feature for rapid preliminary diagnosis.

Amphotericin B↗