Differential Diagnosis Cerebrovascular Disease
5.5.3 Etiology of Stroke in Pediatric
Cancer Patients The underlying etiology of stroke in pediatric cancer patients is complex and poorly studied. In about 30 of children presenting with an acute ischemic stroke, no cause could be elucidated despite extensive investigations Roach 2000 . No long-term, prospective study is available to better defi ne the risk and underlying mechanisms of stroke in pediatric cancer patients. Current studies lack rigorous imaging correlates of stroke symptoms and are often based on self- reports from patients or their caregivers. Stroke can occur during neurosurgery in pedi- atric intracranial tumors with close proximity of tumor and intracranial vessels. Further, several chemotherapeutic agents have been associated with increased risk of stroke such as mentioned with asparaginase and notably with the monoclo- nal antibody bevacizumab, which is directed against vascular endothelial growth factor receptor VEGFR. In adult patients bevacizumab has been associated with a small but signifi cant increase in arterial thrombotic events as well as risk for intracerebral hemorrhage Taugourdeau-Raymond et al. 2012 . The incidence of bevacizumab-associ- ated cerebral hemorrhage in children is unknown. Previous studies have shown that children treated for CNS tumors, leukemia, Hodgkin lym- phoma, and other cancers carry a signifi cantly increased stroke risk Fig. 5.4 , with cranial radi- ation therapy CRT a particularly strong risk fac- tor Bowers et al. 2005 , 2006 ; Haddy et al. 2011 . How CRT increases stroke risk in cancer survi- vors is not well understood. Few risk factors for stroke and arteriopathy in children treated with CRT have been described and include optic path- way tumors associated with NF-1, younger age and higher radiation dose to the circle of Willis Grill et al. 1999 . Current literature has focused on arteriopathies that develop within a relative short time following CRT Bitzer and Topka 1995 ; Laitt et al. 1995 ; Omura et al. 1997 ; Grill et al. 1999 ; Fouladi et al. 2000 . Moyamoya, a specifi c type of cerebral arteriopathy character- ized by progressive stenosis of the terminal inter- nal carotid arteries, has been shown more prevalent in children who undergo CRT for ALL and brain tumors as compared to children who do not receive CRT Kikuchi et al. 2007 ; Ullrich et al. 2007 . Others have shown that children treated with CRT are at increased risk for lacunar Fig. 5.4 Ischemic stroke. This 19-year-old young woman, whose MRI is shown in this fi gure, presented with acute dysarthria and right-handed sensory changes. The diffusion-weighted images shown here demonstrate bilateral strokes with restricted diffusion, which appear bright in this sequence. The patient had a history of Hodgkin lymphoma diagnosed 4 years prior which had relapsed and subsequently treated with an autologous and then allogeneic hematopoietic stem cell transplant. Although the patient did have irradiation as part of her therapy, no arteriopathy could be detected on magnetic resonance angiography to explain the origin of her stroke 5 Neurologic strokes, thought secondary to small vessel vascu- lopathy Fouladi et al. 2000 . There is an additional body of literature that raises concern for long-term effects of radiation therapy by accelerating atherosclerosis, the most common etiology of stroke in adults Dorresteijn et al. 2005 . In pediatric and adult cancer patients, neck irradiation increased cervical carotid artery wall thickness, a marker for atherosclerosis O’Leary et al. 1999 ; Hollander et al. 2002 ; Dorresteijn et al. 2005 ; Meeske et al. 2009 . In a retrospective cohort study of 367 adult patients with head and neck tumors, neck irradiation increased risk of carotid artery-related strokes by almost tenfold compared to normal adults, and that risk was enhanced by hypertension Dorresteijn et al. 2002 . In animal models, irradiation of hypercholesterolemic mice and rabbits leads to accelerated atherosclerotic plaque formation Vos et al. 1983 . Hence, it is plausible that CRT leads to accelerated intracranial atherosclerosis and thereby increases long-term stroke risk as child- hood cancer survivors become young adults.5.5.4 Management of Acute Stroke
In the child with acute neurologic defi cits, the initial evaluation should include a detailed neu- rologic examination to localize the site of stroke as well as careful review of the prior history and current medications. Brain imaging studies should be performed at the time of presentation if the onset of symptoms is acute. The type of imaging used will depend on availability and on the age of the child. MRI is preferred over CT given the radiation exposure associated with CT as well as the differences in time delay and reso- lution. CT will reliably identify hemorrhage as the cause of stroke but may fail to show ischemic stroke if the images are obtained within the fi rst hours of presentation, if the stroke is small, and especially if located within the posterior fossa, due to bone artifact. MRI will detect hemorrhage and small strokes even in the early hours after onset of symptoms. MR angiography can iden- tify stenosis of large intracranial vessels as well as arterial dissection. Transcranial Doppler TCD is another method to noninvasively assess and follow narrowing of intracranial vessels. Additional imaging with conventional angiogra- phy might be indicated depending on severity. Children with stroke should be treated by a spe- cialized team including a pediatric stroke spe- cialist, a pediatric neurosurgeon, an interventional radiologist and a rehabilitation team to ensure the best possible outcome.5.5.4.1 Ischemic Stroke After an ischemic stroke is diagnosed, the patient
should be monitored and treated in a pediatric intensive care unit. Treatment is mainly support- ive. Similar to hemorrhagic stroke, the fi rst steps are to stabilize the child and assess the airway, breathing and circulation. Permissive hyperten- sion is indicated to assure collateral fl ow to the area of ischemia and minimize injury. Fever is detrimental and children should be treated with antipyretics to achieve normothermia. Glucose levels should be carefully monitored and normal- ized as needed. Intravenous recombinant tissue plasminogen activator tPA is used in the acute setting in patients ≥18 years of age within the fi rst 4.5 h after onset of symptoms if no contrain- dications to tPA are present. There is limited understanding of the safety and effi cacy of tPA in pediatric patients, and therefore it is not yet the standard of care in this patient population. The Thrombolysis in Pediatric Stroke Study TIPS is a multicenter trial with the goal to assess the safety and effi cacy of tPA in children with isch- emic stroke; results from this study are pending Amlie-Lefond et al. 2009 . To assess the under- lying etiology of ischemic stroke, children often have vascular imaging performed, particularly MR angiography. The necessity of assessment of an underlying prothrombotic state in pediatric stroke is unclear, and testing has not been shown useful in improving clinical outcomes Raffi ni 2008 . For all pediatric stroke cases, the reported prevalence of prothrombotic conditions ranges from 20–50 Mackay and Monagle 2008 . Assessment of the most common thrombophilias including antithrombin defi ciency, protein C or protein S defi ciency, hyperhomocysteinemia, prothrombin 20210 gene mutation, elevatedParts
» Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Introduction Supportive Care in Pediatric Oncology irantextbook.ir 93df
» History and Physical Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Defi ning the Risk for Serious
» Initial Laboratory Evaluation Diagnostic Evaluation
» Chest Radiography CXR A supine CXR may identify pleural effusions,
» Computed Tomography CT Radiographic Imaging
» Magnetic Resonance Imaging MRI
» Positron Emission Tomography PET
» Aspergillus Galactomannan GMN Biomarkers for Invasive
» 1,3-β- Biomarkers for Invasive
» Polymerase Chain Reaction PCR
» Viral Studies Diagnostic Evaluation
» Invasive Procedures: Diagnostic Evaluation
» Adult FN Guidelines Empiric Management
» Monotherapy Versus Combination Therapy
» Which Monotherapy to Choose A Cochrane review of antipseudomonal beta-
» Alterations in Initial Empiric FN Antibiotic Management
» Outpatient Management of FN Although there remains a lack of one uniform
» Choice of Empiric Antifungal Therapy
» Duration of Antimicrobial Empiric Management
» Endovascular Sources Empiric Management
» Adjunctive Treatment Empiric Management
» Emergence of Resistant Empiric Management
» Red Blood Cell Administration
» Granulocyte Transfusion Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Hemolytic Transfusion Risks of Blood Product
» Infection and Sepsis Risks of Blood Product
» Allergic Reactions Risks of Blood Product
» Febrile Nonhemolytic Risks of Blood Product
» Transfusion-Related Acute Risks of Blood Product
» Transfusion-Associated Risks of Blood Product
» Iron Overload Risks of Blood Product
» Laboratory Risk Factors Supportive Care in Pediatric Oncology irantextbook.ir 93df
» General Management Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Alkalinization Urinary alkalinization has been a long-standing
» Allopurinol Allopurinol inhibits xanthine oxidase, an enzyme
» Rasburicase Rasburicase, recombinant urate oxidase, converts
» Renal Interventions Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Pathophysiology Superior Vena Cava
» History and Physical Exam SVCSSMS should be suspected in a patient
» Imaging Studies The diagnosis of SVCSSMS is often made on
» Other Studies Tissue is required to make a defi nitive diagnosis
» Treatment Superior Vena Cava
» History and Physical Exam Small pericardial effusions are frequently asymp-
» Imaging and Other Studies The presence of a pericardial effusion can be
» History and Physical Exam Many patients with small pleural effusions are
» Imaging Studies When a pleural effusion is suspected, a chest
» History and Physical Exam Patients with pheochromocytoma typically have
» Laboratory Studies The diagnosis of pheochromocytoma is best made
» Imaging Studies Clinical Presentation
» Pulmonary Leukostasis Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Presentation Spinal Cord Compression
» Differential Diagnosis Spinal Cord Compression
» Imaging MRI of the spine can help narrow the differential
» Surgery Surgery in spinal cord compression can be uti-
» Radiation Therapy The advantages of external beam radiation ther-
» Outcomes Spinal Cord Compression
» Presentation Altered Mental Status
» Initial Management Altered Mental Status
» Metabolic The metabolic causes of AMS or seizure in pedi-
» Chemotherapy-Associated Neurotoxicity Differential Diagnosis
» Posterior Reversible Encephalopathy Syndrome
» Outcomes Altered Mental Status
» Initial Management Increased Intracranial
» Soft Tissue A large meta-analysis of published data suggests
» Cerebrospinal Fluid Hydrocephalus is an excess of CSF within the
» Hemorrhage and Thrombosis Differential Diagnosis
» Idiopathic Intracranial Hypertension Differential Diagnosis
» Presentation of Stroke Cerebrovascular Disease
» Differential Diagnosis Cerebrovascular Disease
» Etiology of Stroke in Pediatric
» Ischemic Stroke After an ischemic stroke is diagnosed, the patient
» Hemorrhagic Stroke Hematomas can expand over several hours from
» Acute Lymphoblastic Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Acute Myelogenous Leukemia Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Acute Promyelocytic Leukemia Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Chronic Myelogenous Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Management of Tumor Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Leukapheresis Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Hyperhydration Other Treatment Modalities
» Hydroxyurea Other Treatment Modalities
» Cranial Irradiation Other Treatment Modalities
» Pseudohyperkalemia Hyperleukocytosis has been noted to cause pseudo-
» Pseudohypoxemia Due to the rapid consumption of oxygen by leu-
» Pseudohypoglycemia Consumption of glucose by excess leukocytes
» Pseudothrombocytosis Leukemic blast lysis can lead to cell fragmenta-
» Transfusion Practice with Other Supportive Care
» Anesthetic Procedures Other Supportive Care
» Neutropenic Enterocolitis Gastrointestinal Infection
» Perirectal Abscess Gastrointestinal Infection
» Gastrointestinal Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Pancreatitis Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Bowel Obstruction Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Abdominal Compartment Supportive Care in Pediatric Oncology irantextbook.ir 93df
» ALL Risk Factors Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Other Malignancies Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Central Venous Catheters Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Diagnosis Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Nociceptive Pain Types of Pain
» Neuropathic Pain Types of Pain
» World Health Organization Pharmacologic Treatment
» Intermittent Opioid Use Pharmacologic Treatment
» Long-Acting Opioids Pharmacologic Treatment
» Breakthrough Dosing Pharmacologic Treatment
» Opioid Rotation Pharmacologic Treatment
» Patient-Controlled Analgesia Pharmacologic Treatment
» Constipation Side Effects of Opioids
» Nausea and Vomiting Nausea and vomiting are rare opioid side effects
» Pruritus Pruritus is a common side effect of opioid use
» Sedation Side Effects of Opioids
» Confusion and Agitation Renal and hepatic function should be checked
» Respiratory Depression When dosed appropriately, opioids rarely result
» Myoclonus Patients receiving very high doses of opioids for
» Urinary Retention Urinary retention can be caused by any opioid but
» Calcium Channel Blockers Neuropathic Pain
» Serotonin and Norepinephrine Neuropathic Pain
» Tricyclic Antidepressants Neuropathic Pain
» Interventional Techniques Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Vincristine-Related Peripheral Oncology-Specifi c Pain
» Osteonecrosis Oncology-Specifi c Pain
» Post-lumbar Puncture Oncology-Specifi c Pain
» Mucositis Pain Oncology-Specifi c Pain
» Pathophysiology of Emesis Chemotherapy-Induced
» Principles of Emesis Control in the Cancer Patient
» Emetogenicity of Chemotherapy Chemotherapy-Induced
» Dopamine Receptor Antagonists Classes of Antiemetics
» Corticosteroids Classes of Antiemetics
» Cannabinoids The plant Cannabis contains more than 60 differ-
» Other Antiemetic Agents Antihistamines
» Alternative Therapies Ginger Classes of Antiemetics
» Management of CINV Management of CINV Table
» Special Considerations Anticipatory Nausea and Vomiting
» Radiation-Induced Nausea Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Initiation The initiation stage occurs immediately following
» Primary Damage Response Pathophysiology of Oral Mucositis
» Signal Amplifi cation Pathophysiology of Oral Mucositis
» Ulceration Ulceration is the phase with the most clinical sig-
» Healing Pathophysiology of Oral Mucositis
» Clinical Course of Oral Mucositis
» Assessment Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Palifermin Prevention and Treatment
» Low-Level Laser Therapy Prevention and Treatment
» Glutamine Prevention and Treatment
» Cryotherapy Prevention and Treatment
» Oral Care Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Oral Infections Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Nutrition Assessment Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Dietary Counseling Nutrition Intervention
» Appetite Stimulants Nutrition Intervention
» Enteral Tube Feeding Nutrition Intervention
» Parenteral Nutrition Nutrition Intervention
» Nutrition and Survivorship Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Management of Neutropenia Hematologic Toxicity
» Management of Thrombocytopenia Hematologic Toxicity
» Management of Anemia Hematologic Toxicity
» Somnolence Syndrome Central Nervous System
» Lhermitte’s Sign Central Nervous System
» Skin Complications Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Oral Mucositis Head and Neck
» Ear Complications Head and Neck
» Laryngeal Complications Head and Neck
» Dysphagia and Esophagitis Gastrointestinal
» Nausea, Vomiting and Anorexia
» Pneumonitis Major Organ Infl ammation
» Pericarditis Major Organ Infl ammation
» Hepatitis Major Organ Infl ammation
» Nephropathy Major Organ Infl ammation
» Cystitis Major Organ Infl ammation
» Risk Stratifi cation Prevention of Bacterial
» Adult Data Antimicrobial Approaches
» Pediatric Data Data regarding the utility of bacterial prophylaxis
» Risks of Prophylaxis Prevention of Bacterial
» Guidelines and Current Usage of Antibacterial Prophylaxis
» Protocols for Line Placement and Care
» Antibiotic and Ethanol Locks
» Chlorhexidine Cleansing Chlorhexidine gluconate CHG is a bactericidal
» Future Directions Prevention of Bacterial
» Risk Stratifi cation Prevention of Fungal
» Approaches to Antifungal Prophylaxis
» Guideline Recommendations for Antifungal Prophylaxis
» Limitations of Current Options for Antifungal Prophylaxis
» Risks of Prophylaxis Prevention of Fungal
» Biomarkers Prevention of Fungal
» Future Directions Prevention of Fungal
» Risk Stratifi cation Prevention of Pneumocystis
» Approaches to PCP Prophylaxis
» Summary of the Recommendations
» Future Directions Prevention of Pneumocystis
» Postexposure Chemoprophylaxis Prevention of Viral Infections
» Suppressive Therapy Prevention of Viral Infections
» Future Directions Prevention of Viral Infections
» Hand Hygiene Infection Control Practices
» Mandatory Vaccination Infection Control Practices
» Hospital Isolation Practices Infection Control Practices
» Visitor Screening Policies Infection Control Practices
» Work Restriction Infection Control Practices
» Cytomegalovirus CMV Status of Transfused Blood
» Treatment of Myelosuppression with
» Prevention of Febrile Neutropenia, Delay
» Treatment of Febrile Neutropenia
» Treatment of Myelosuppression Clinical Usage of Myeloid Growth Factors
» Comparison of Granulocyte Colony-Stimulating Factor
» Optimal Dosing Adult guidelines recommend dosing of 5 mcgkg
» Route of Administration Optimal Administration of Colony-Stimulating Factors
» Optimal Timing Optimal Administration of Colony-Stimulating Factors
» Erythropoietin Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Interleukin-11 Platelet Growth Factors
» Thrombopoietin Receptor Agonists Platelet Growth Factors
» Immune Status Prior Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Immune Status During Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Immune Recovery After Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Immunization Practice Prior Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Diphtheria, Tetanus, and Acellular Pertussis
» Pneumococcal Conjugate Vaccine Recommendations
» Hemophilus Infl uenzae Type b
» Inactivated Infl uenza Vaccine Although in a Cochrane review Goossen et al.
» 2009 H1N1 Pandemic Vaccine Seven studies have reported on effi cacy of the
» Live Attenuated Infl uenza Vaccine
» Meningococcal Conjugate Vaccine Recommendations
» Varicella Zoster Virus Recommendations
» Recommendations Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Treatment of Hypogammaglobulinemia Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Vaccination of Household Contacts
» Peripherally Inserted Central Catheter
» External Tunneled Central Venous Catheter
» Implanted Port Types of Central Venous
» Catheter Insertion Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Exit Site Infection Infection
» Prevention of Infection Infection
» Drug Precipitate or Lipid Residue Occlusion Thrombotic Occlusion
» Evaluation of Catheter- Related Thrombosis
» Treatment of Catheter- Related Thrombosis
» Special Considerations During Anticoagulation Therapy
» Contraindications of Anticoagulant Therapy
» Skin Antisepsis Catheter Maintenance
» Central Venous Catheter Dressings
» Hub Care Catheter Maintenance
» Central Venous Catheter Flushing and Locking
» Chlorhexidine Bathing Chlorhexidine has been shown to be effective in
» Antiseptic Needleless Connectors and Antiseptic
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