Paraneoplastic opsoclonus myoclonus syndrome associated with inflammatory myofibroblastic tumor in a pediatric patient.

Opsoclonus myoclonus syndrome (OMS) is a rare neurological syndrome caused by a paraneoplastic autoimmune process that affects children with neuroblastic tumors. Treatment includes corticosteroids, intravenous gamma globulin (IVIG), rituximab, and other immunosuppressive therapies. Here, we describe a patient diagnosed with OMS associated with a localized inflammatory myofibroblastic tumor. The patient has no evidence of tumor recurrence following surgical resection with 8-month follow-up. The neurologic symptoms resolved with corticosteroids and IVIG. This case demonstrates that in children, neoplasms other than neuroblastoma may be associated with this paraneoplastic syndrome, and highlights the importance of evaluating patients with OMS for underlying malignancies.

Bitot-like spots in children with normal vitamin A levels.

BACKGROUND/AIMS: A Bitot spot is a conjunctival lesion, classically associated with severe vitamin A deficiency. In this paediatric series, we describe conjunctival lesions indistinguishable from Bitot spots, seen in the presence of normal vitamin A levels. METHODS: This descriptive case series was performed by retrospective review of case notes, including all patients with Bitot-like spots found to have normal serum vitamin A levels, seen at the Hospital for Sick Children, Toronto, between 2006 and 2016. Data collected included age at presentation, ophthalmic and systemic diagnoses, and the presence of recognised genetic mutations. Histopathology was reviewed in one case. RESULTS: Ten patients with Bitot-like spots with laboratory-confirmed normal serum vitamin A levels were identified. The conjunctival lesions were indistinguishable clinically and histopathologically from classic Bitot spots and were noted to occur in a range of anterior segment pathologies, including aniridia, WAGR syndrome, Axenfeld-Rieger syndrome, and blepharokeratoconjunctivitis. CONCLUSIONS: Bitot-like spots are found in children with a number of anterior segment pathologies in the absence of vitamin A deficiency.

The addition of autologous stem cell transplantation to neoadjuvant chemotherapy, radiation, and HIPEC for patients with unresectable desmoplastic small round cell tumor: a single center case series.

Desmoplastic small round cell tumor (DSRCT) is a rare, highly aggressive malignancy primarily affecting children and young adults. Although modest improvements have been gained by intensification of chemotherapy and radiation, survival of patients with DSRCT remains poor, particularly in those with unresectable or disseminated disease. We report 3 pediatric patients who were treated with a combination of therapy including chemotherapy, surgical debulking, hyperthermic intraperitoneal chemotherapy, whole abdominal irradiation, and autologous hematopoietic stem cell transplantation following busulfan and melphalan conditioning. We find that this approach is well tolerated and may offer improved survival in patients with DSRCT.

Outcomes in acute ischemic stroke patients without angiographically documented arterial occlusion.

BACKGROUND AND PURPOSE: Patients with acute ischemic stroke who undergo emergent cerebral angiography for consideration of intra-arterial treatment and do not have an angiographically demonstrable occlusion pose a management dilemma. The authors reviewed their experience to determine the clinical out comes of patients with ischemic stroke evaluated within 6 hours of symptom onset in whom negative angiograms were obtained. METHODS: A prospective registry was maintained for all patients (N = 56) who were considered for intra-arterial thrombolysis. Patients without angiographic arterial occlusion were not treated with thrombolytics, and data pertaining to clinical characteristics and neuroimaging findings was collected. Follow-up data were acquired through clinic visits or telephone interviews at 5.5 +/- 5.0 months (mean +/- SD), range 1 to 15 months, after onset of stroke. RESULTS: Of the 56 patients, no arterial occlusion was observed in 17 (30%) patients (mean age 65.8 +/- 13.0 years; 7 were men). The mean (+/- SD) baseline National Institute of Health stroke scale score was 10.2 +/- 7.1. Symptoms were referable to the anterior or posterior circulation in 76% and 18% of the patients, respectively; they could not be localized to either circulation in 6%. Follow-up neuroimaging studies demonstrated cerebral infarction in 12 of 14 patients. Eleven of the 17 had a favorable long-term recovery as assessed by the modified Rankin Scale (score 0 or 1). Five other patients had modified Rankin Scale scores of 3 (n = 1), 4 (n = 2), or 5 (n = 2). One patient died during the follow-up period. With regard to location of ischemic deficits, the highest rate of death or dependency was observed in patients with pontine infarction (three of four patients). CONCLUSION: Although the outcome following ischemic stroke in patients without angiographically documented occlusion appears to be better than that reported for patients with angiographically documented occlusion, death or disability is observed in at least one third of the patients. There fore, acute ischemic stroke in the absence of angiographic occlusion is not entirely a "benign" entity and can be particularly devastating when the brainstem is involved.

Clinical and angiographic results of dilatation procedures for symptomatic intracranial atherosclerotic disease.

BACKGROUND AND PURPOSE: The authors determined the technical success and the clinical and angiographic results of angioplasty and/or stent placement for intracranial atherosclerotic disease (ICAD) at a tertiary-care referral hospital. METHODS: Angiographic and clinical outcomes occurring within the 1-month follow-up interval were recorded. Patients were followed up for a mean period of 20.5 +/- 9.2 months, and a neurovascular imaging study was performed in 18 of the 21 patients alive after a mean period of 19.7 +/- 9.2 months. Stroke-free survival and ipsilateral stroke-prevention rates were estimated using Kaplan Meier analyses. RESULTS: Twenty-four patients (mean age = 61.0 +/- 13.5 years; 15 were men) underwent 30 procedures for treatment of ICAD. The procedures included angioplasty (n = 18) and attempted primary stent placement (n = 14). In 2 procedures, angioplasty was performed in the same session after unsuccessful stent placement. There was immediate stenosis reduction (mean +/- SD) from 84% +/- 17% to 27% +/- 21%. The overall 1-month composite rate of major stroke, death, and major bleeding complications was 7% for the 30 procedures. Overall stroke-free survival at 36 months was estimated as 79% (95% confidence interval, 57%-91%), and the ipsilateral stroke-prevention rate was estimated to be 87% (95% confidence interval, 65%-95%). Among the 15 patients who underwent repeat angiography, restenosis requiring second intervention was observed in 1 patient. No restenosis could be identified in 3 patients who underwent computed tomographic or magnetic resonance angiography. CONCLUSION: This single-center study demonstrates the feasibility and effectiveness (for secondary stroke prevention) of angioplasty and/or stent placement for treatment of ICAD.

Clinical potential of intra-arterial thrombolytic therapy in patients with acute ischaemic stroke.

Acute ischaemic stroke is a leading cause of mortality and morbidity around the world. An arterial occlusive lesion is found in the majority of patients with acute ischaemic stroke, and recanalisation has been shown to result in a better clinical outcome. The only widely approved recanalisation strategy is the use of intravenous alteplase (recombinant tissue-type plasminogen activator; tPA) within 3 hours of stroke onset. However, this therapy has limitations, and alternative or supplemental recanalisation strategies need to be considered in a large number of patients with acute ischaemic stroke. One such promising strategy is intra-arterial thrombolysis. This article reviews the pharmacology of the various drugs used for intra-arterial thrombolysis in the setting of acute ischaemic stroke and the results of the clinical trials that have studied their benefit. Three generations of thrombolytic agents have been available for clinical use so far. The first-generation agents such as streptokinase and urokinase were the first to be studied in acute stroke, and a number of positive case reports and series of their intra-arterial use have been reported from around the world. Second-generation products include alteplase and pro-urokinase. The clinical benefits of intra-arterial pro-urokinase were recently proven in a randomised, placebo-controlled study. Third-generation agents, such as reteplase, lanoteplase and tenecteplase, offer superior recanalisation rates with limited systemic adverse effects and might prove to be the agents of choice for intra-arterial acute stroke thrombolysis in the future. The exact administration regimens as well as the identification of patient sub-populations most likely to benefit from intra-arterial thrombolysis are subjects of current investigations, and hopefully firmer guidelines will be established in the next few years, once the results of the clinical trials are available.

Reocclusion of recanalized arteries during intra-arterial thrombolysis for acute ischemic stroke.

BACKGROUND AND PURPOSE: Early reocclusion of recanalized arteries has been observed after thrombolysis for acute coronary occlusion and has been attributed to platelet activation after exposure to thrombolytic agents. We conducted a retrospective study to determine the rate of reocclusion during intra-arterial thrombolysis for acute ischemic stroke and the effect of reocclusion on functional outcome. METHODS: Patients treated for acute ischemic stroke at our center between September 2000 and May 2002 received a maximum total dose of 4 U of reteplase intra-arterially in 1-U increments via superselective catheterization. Pharmacologic thrombolysis was supplemented by mechanical thrombolysis with balloon angioplasty or snare manipulation at the occlusion site. Angiography was performed after each unit of reteplase or mechanical maneuver, and the images were interpreted by a blinded reviewer. Reocclusion was defined as partial or complete initial recanalization with occlusion recurring at the same site as documented by angiography during the endovascular treatment. Reocclusions were treated by further pharmacologic and/or mechanical thrombolysis according to the discretion of the treating physician. Clinical evaluations were performed before and 24 hr, 7 to 10 days, and 1 to 3 months after treatment. RESULTS: Forty-six consecutive patients underwent intra-arterial thrombolysis. Reocclusion was observed in eight (17%). Among these patients, initial sites of occlusion were in the following arteries: intracranial internal carotid artery (n = 2), M1 segment of the middle cerebral artery (n = 3), M1 and M2 segments of the middle cerebral artery (n = 2), and basilar artery (n = 1). The mean initial National Institutes of Health Scale score for these eight patients was 23.3 +/- 6.2; mean time from symptom onset to treatment was 4.4 +/- 1.2 hr. The reocclusions were treated by using additional doses of reteplase alone (n = 1), reteplase with snare maneuver and/or angioplasty (n = 5), reteplase with angioplasty or snare and then stent placement (n = 1), and angioplasty with stent placement (n = 1). The reocclusions resolved in six of eight patients after further treatment. Six patients died and two survived but were severely disabled at 1 month (modified Rankin Scale scores of 4 and 5, respectively). Independent functional outcome scores (modified Rankin Scale scores of 0-2) were significantly lower among patients with angiographically shown reocclusion than in those without (0 of 8 versus 17 of 38, P =.02). CONCLUSION: Reocclusion occurs relatively frequently during intra-arterial thrombolysis for ischemic stroke and seems to be associated with poor clinical outcomes.

Safety of high-dose intravenous eptifibatide as an adjunct to internal carotid artery angioplasty and stent placement: a prospective registry.

OBJECTIVE: Eptifibatide, a competitive platelet glycoprotein IIb-IIIa receptor inhibitor with high selectivity for platelet glycoprotein IIb-IIIa receptors and a short half-life, has been shown to reduce the risk of ischemic events associated with coronary interventions, particularly when used in high doses. However, its role in conjunction with neurointerventional procedures needs to be determined. We report the results of an open-label prospective registry to evaluate the safety (in terms of avoiding hemorrhagic complications) and effectiveness (in terms of preventing ischemic complications such as stroke) of administering high-dose eptifibatide during internal carotid artery angioplasty and stent placement (CAS) for extracranial carotid artery stenosis. METHODS: After femoral artery access was established and intravenous heparin (30 U/kg bolus) was administered, each patient was administered intravenous eptifibatide (two 180-microg/kg single-dose boluses before CAS, then a 2.0-microg/kg/min infusion for 20-24 hours thereafter). The primary end point was the 30-day composite occurrence of death, cerebral infarction, and unplanned or urgent endovascular or surgical intervention. The primary safety end point was bleeding, for which complications were classified according to the Thrombolysis in Myocardial Infarction scheme as major (hemoglobin decrease of more than 5 g/dl), minor (hemoglobin decrease of 3-5 g/dl), or insignificant. Platelet aggregation was measured in 13 consecutive patients with a rapid platelet-function analyzer. RESULTS: Twenty-six patients (mean age, 68.1 +/- 9.4 yr; 16 men) underwent treatment. The infusion and the CAS procedure were discontinued in one patient who developed angioneurotic edema after being administered intravenous heparin and the first bolus dose of eptifibatide. Among the 25 patients who underwent the procedure, no intracerebral hemorrhages and one minor ischemic stroke occurred during the 1-month follow-up period. The minor stroke was observed on postprocedure Day 7 in a patient for whom antiplatelet therapy was discontinued before a coronary artery bypass graft operation was performed. Another patient was discharged after an uncomplicated hospitalization but died as a result of urinary sepsis 12 days after CAS. One episode of major bleeding from the femoral insertion site required surgical repair and blood transfusions. Minor bleeding occurred in one patient. Platelet aggregation measurements obtained in 13 patients revealed a high degree (mean, 96%; range, 86-100%) of platelet inhibition after the administration of the second bolus dose of intravenous eptifibatide. CONCLUSION: High-dose eptifibatide administered as an adjunct to CAS seems to be safe. Further studies are required to analyze its effectiveness and role in neurointerventional procedures.

Aggressive mechanical clot disruption and low-dose intra-arterial third-generation thrombolytic agent for ischemic stroke: a prospective study.

OBJECTIVE: We prospectively evaluated the safety and effectiveness of aggressive mechanical disruption of clot in conjunction with intra-arterial administration of a low-dose third-generation thrombolytic agent (reteplase) to treat ischemic stroke in patients who were considered poor candidates for intravenous alteplase therapy or who failed to improve after intravenous thrombolysis. Mechanical clot disruption was used if low-dose pharmacological thrombolysis was ineffective. This strategy was adopted to increase the recanalization rate without increasing the risk of intracerebral hemorrhage. METHODS: Patients were considered poor candidates for intravenous therapy because of severity of neurological deficits, interval from symptom onset to presentation of at least 3 hours, or recent major surgery. We administered a maximum total dose of 4 U of reteplase intra-arterially in 1-U increments via superselective catheterization. After the initial doses were administered, we performed mechanical angioplasty (for proximal occlusion) or snare manipulation (for distal occlusion) at the occlusion site if recanalization had not occurred. The remaining doses of thrombolytics were subsequently administered if required for further recanalization. Angiographic responses were graded using modified Thrombolysis in Myocardial Infarction (TIMI) criteria. Clinical evaluations were performed before and 24 hours, 7 to 10 days, and 1 to 3 months after treatment. RESULTS: Nineteen consecutive patients were treated (mean age, 64.3 +/- 16.2 yr; 10 were men). Initial National Institutes of Health Stroke Scale scores ranged from 11 to 42. Time from onset to treatment ranged from 1 to 9 hours. Occlusion sites were in the following arteries: cervical internal carotid (n = 7), intracranial internal carotid (n = 1), middle cerebral (n = 9), and basilar (n = 2). Of the 19 patients, thrombolysis alone was used in 5 patients, angioplasty was performed in 11 patients, and snare maneuvers were used in 5 patients. Complete restoration of blood flow (modified TIMI Grade 4) was observed in 12 patients, near-complete restoration of flow (modified TIMI Grade 3) in 4 patients, minimal response (modified TIMI Grade 1) in 1 patient, and no response in 2 patients (modified TIMI Grade 0). Neurological improvement at 24 hours (decline of at least 4 points in National Institutes of Health Stroke Scale score) was observed in seven patients. Five other patients experienced further improvement in National Institutes of Health Stroke Scale score at 7 to 10 days. No vessel rupture, dissection, or symptomatic intracranial hemorrhages were observed. At the time of follow-up evaluation, 7 of 19 patients were functionally independent. CONCLUSION: A high rate of recanalization and clinical improvement can be observed in patients with ischemic stroke using low-dose thrombolytic agents with adjunctive mechanical disruption of clot. Moreover, this strategy may reduce the risk of intracerebral hemorrhage observed with thrombolytics.

Emergency stent placement for symptomatic acute carotid artery occlusion after endarterectomy. Case report.

The authors report a case of emergency carotid artery (CA) stent placement for a symptomatic acute CA occlusion following carotid endarterectomy (CEA). This 43-year-old man underwent a right-sided CEA for an asymptomatic 80% CA stenosis detected using duplex ultrasound testing. The patient experienced hypotension and possibly a myocardial infarction intraoperatively and a left hemiplegia immediately postoperatively. He was referred to the authors' institution for consideration of emergency coronary intervention and evaluation of stroke. A computerized tomography scan of the head demonstrated subtle early ischemic changes in the right posterior parietal region. Cerebral angiography revealed occlusion of the right common CA (CCA) at the CA bifurcation. Two coronary stents (Magic Wall; Boston Scientific Scimed, Maple Grove, MN) were placed in tandem in the right CCA and internal CA (ICA), overlapping at the proximal cervical ICA. Complete recanalization of the CA was achieved, and the patient made a clinically significant recovery. Diagnostic angiography can provide important information about CA and intracranial circulation that will aid in the evaluation of postoperative stroke after CEA. Stent placement should be considered as an alternative method of treatment for acute CA occlusion or dissection following CEA.

A prospective multicenter study to evaluate the feasibility and safety of aggressive antihypertensive treatment in patients with acute intracerebral hemorrhage.

The authors performed a multicenter prospective observational study to evaluate the feasibility and safety of intravenous antihypertensive protocol for acute hypertension in patients with intracerebral hemorrhage (ICH). Twenty-seven patients with ICH and acute hypertension (mean age 61.37 +/- 14.27; 10 were men) were treated to maintain the systolic blood pressure (BP) below 160 mm Hg and diastolic BP below 90 mm Hg within 24 hours of symptom onset. Neurological deterioration (defined as a decrease in initial Glasgow Coma Scale score > or = 2) was observed in 2 (7.4%) of 27 patients during treatment. Among patients who underwent follow-up computed tomography, hematoma expansion (more than 33% increase in hematoma size at 24 hours) was observed in 2 (9.1%) of 22 patients. Patients treated within 6 hours of symptom onset were more likely to be functionally independent (modified Rankin scale < or = 2) at 1 month compared with patients who were treated between 6 and 24 hours (8 of 18 versus 0 of 9,P = .03). Aggressive pharmacological treatment of acute hypertension in patients with ICH can be initiated early with a low rate of neurological deterioration and hematoma expansion.

Computed tomographic angiography for diagnosis of brain death.

The authors report two patients with suspected brain death who required confirmatory tests other than clinical examination because of prolonged barbiturate administration for intracranial hypertension. Absence of intracranial blood flow was documented on CT angiography and confirmed by CT perfusion images. Cerebral angiography confirmed the findings consistent with brain death. CT angiography with CT perfusion may represent a rapid noninvasive method for diagnosis of brain death.

Effect of endovascular treatment on headaches in patients with unruptured intracranial aneurysms.

BACKGROUND: Patients with unruptured intracranial aneurysms often present with headaches. OBJECTIVE: To determine the effect of endovascular treatment on the character and frequency of headaches in patients with unruptured intracranial aneurysms. METHODS: We reviewed the medical records of all patients who underwent endovascular treatment for unruptured intracranial aneurysms within a 9.5-year period. These patients were mailed a standard questionnaire in which they were asked about the frequency and character of any headache experienced before or after (or both) endovascular treatment. They were also asked to grade improvement or worsening of headaches after the procedure as mild (activities of daily living were not affected), moderate (activities of daily living were affected), or significant (the change resulted in an ability to perform new activities of daily living or an inability to perform previous activities of daily living). RESULTS: Forty-seven patients with unruptured aneurysms who underwent Guglielmi detachable coil embolization responded to the questionnaire. Of these, 32 patients (mean age, 52.7 years [SD, 13.4]; 22 were women) had experienced headaches before the procedure. Nineteen patients (59%) reported improvement in severity of headaches after embolization. Improvement was graded as significant by 7 patients, moderate by 8, and mild by 4. Two patients (6%) reported worsening severity of headaches graded as moderate. Five of 15 patients without headaches before embolization reported onset of mild (n = 4) or severe (n = 1) headaches after treatment. CONCLUSION: Guglielmi detachable coil embolization of unruptured intracranial aneurysms was associated with reduction in severity of headaches in the majority of patients who had experienced preprocedural headaches.

Buffalo metropolitan area and Erie County stroke study: rationale, design, and methods.

OBJECTIVES: The primary objective of this study was to define the incidence, disability, and death associated with stroke in the Buffalo metropolitan area and Erie County. This area has the highest stroke rate in New York State and therefore represents an ideal site to develop a successful model for prevention and management of stroke. DESIGN: A cross-sectional design to study all new and recurrent strokes that occurred in the calendar year 2000 in the geographical location of Buffalo metropolitan area and Erie County. PATIENTS AND DATA COLLECTED: A retrospective review of an estimated 5,000 patients with new stroke will be performed at regional hospitals and the coroner's office to determine the stroke subtypes, cerebrovascular risk factors, diagnostic investigations, treatment provided, and outcome. The total population residing in Buffalo in the year 2000 is available through the recent census. The study will also evaluate the quality of care provided for stroke patients including effectiveness of primary and secondary stroke prevention measures within this geographical region. CONCLUSIONS: We believe that this information will assist in allocation of resources and implementation of steps to improve stroke prevention and treatment.