1. Moderator : R4. Presenter : R1. Problem Case Conference 2010.7.2 10

2. Brief History Male, GA 40wks, 3190gm, NFS delivery at local hospital , without PNP 2009 8 ( 1) : Pneumonia , 5 2009 9 : . 2010 2 ( 7) , pneumonia . 2010 3 GER L-tube feeding PPI motilium Esophagography (2010.3.12) : Definite GE reflux aspiration . VFSS (2010.3.18) : liquid delayed swallowing reflex spontaneous posterior falling, incomplete velopharyngeal port closure, liquid pre-swallowing, post swallowing aspiration . 3. 2010/3/22 EGD vocal cord : unusual swelling esophagus ring shaped folding eosinophillic esophagitis . >> biopsy chronic nonspecific inflammation without eosinophil >> correlated with GERD 2010/3/23 24 hr PH monitoring acid exposure upright 20.4%, recumbant 12.0%, Total 14.3% Bolus exposure (acid percent time ) upright 2.2%, recumbant 4.3%, total 3.8% (all reflux percent time ) upright 4.1%, recumbant 5.2%, total 4.9% Brief History 4. 2010/4/2 EGD vocal cord swelling was much improved compared with prev. EGD ring shaped morphology of esophagus disappear Allergy test >> egg white, cow milk, peanut, soybean, pork, egg yolk : all negative total IgE ; 13.4 kIU/L (normal) IgG/A/M : 609/20/156 (normal) 2010/2 Sputum culture : S. pneumonia Respiratory virus : (-) Brief History 5. 2010 4 ( 9) 2010 4 12 bloody sputum ( ) ER 1st admission 1st Admission (2010.4/12~4.16) 6. Development (2010 4 ) : , (6-7 ) P/E Wt : 8.8kg (25-50P) Ht : 73.1cm (50P), V/S : BP 118/86mmHg, HR 146/min, RR 40/min, BT 37.1C Chest : coarse breathing sound with severe ronchi, w/o rale N/E : . Initial lab 1st Admission (2010.4/12~4.16) 7. 2010 2 28 2010 3 3 8. 2010 3 14 2010 3 21 9. 2010 4 13 ( ) 10. Initial Problem list Recurrent regurgitation ( 7 ) Recurrent pneumonia ( 1, 7) Grunting sound ( 2) r/o Hemoptysis Mild developmental delay 11. Initial Ass & Plan r/o Hemoptysis Recurrent regurgitation Recurrent pneumonia (2009/8, 2010/2) Grunting sound Mild developmental delay 1. Primary lung disease r/o bronchiectasis Plan 1. Chest CT . 2. L-tube feeding PPI 3. VFSS f/u 4. Metabolic w/u 2. r/o Laryngopharyngeal reflux , r/o GER 3. r/o Cricopharyngeal incoordination 12. Laryngopharyngeal Reflux vs Gastroesophageal Reflux P.Stavroulaki , International Journal of Pediatric Otorhinolaryngology 2006 Higher among infants (20-40%) than among children or adults (7-20%) 13. Laryngopharyngeal Reflux P.Stavroulaki , International Journal of Pediatric Otorhinolaryngology 2006 Infant >> Regurgitation/ vomiting, dysphagia, anorexia, growth failure, abnormal crying, sleep disorder, irritability or torticollis, upper airway problem (recurrent croup, laryngomalacia, subglottic stenosis), chronic respiratory disease Children >> Laryngotracheal complains chronic cough , dyspnea, Pharyngeal complains : persistent sore throat, globus sensation, referred otalgia, dental erosion Rhinologic complains : nasal obstruction, rhinorrhea, headache Chronic respiratory disease Gastrointestinal symptoms: regurgitation/vomiting, nausea, chest or abdominal pain, heartburn 14. HD#1(4/12) Chest CT >> ( ) No evidence of bronchial artery hypertrophy. No evidence of bronchiectasis. No definite evidence of active lung lesion. Multifocal peripheral atelectasis of both lungs. Mosaic pattern in both lower lung. Limited evaluation of the esophagus due to collapsed state. Metabolic w/u >> MS/MS : negative , Lactic acid : 1.0 , Pyruvate 0.6, ammonia 44 TFT free T4 1.06, T3 113, TSH 1.01 , Amino acid (s) : normal Carnitine (s) : normal , Organic acid (u) : normal 1st Admission (2010.4/12~4.16) 15. HD#4(4/15) ENT exam >> mild laryngomalacia Neurologic exam >> DTR (+) , both symmetric Frog leg position VFSS >> ORAL PHASE 0) sucking : G 1) Tongue movement, bolus formation and mastication . 2) Premature bolus loss . PHARYNGEAL PHASE 1) Laryngeal elevation epiglottic closure . 2) Small fluid aspiration, Yoplait penetration . 3) Yoplait vallecular residue Gr1, pyriform sinus residue Gr1 4) Pharyngeal wall coating . 5) Pharyngeal triggering . ESOPHAGEAL PHASE 1) UES relaxation . 2) Pharyngeal reflux . 1st Admission (2010.4/12~4.16) 16. Diagnosis & Plan Recurrent regurgitation r/o LPR >> GER : PPI , L-tube feeding Aspiration tendency d/t cricopharyngeal incoordination, LPR Bronchiolitis obliterans Budesonide nebulizer start. Mild developmental delay Hypotonia Metabolic w/u . EMG/NCS . 1st Admission (2010.4/12~4.16) 17. 2nd Admission (2010.5.12) 2010/5/5 L-tube insertion swelling oral feeding . ER L-tube insertion 2010/5/9, 2010/5/12 : dyspnea, lip cyanosis ER 2nd admission V/S BP : 131/98mmHg-HR : 163/min- RR : 64/min BT : 38 'C HC : 42.5cm (25-50p) , BW : 8.4kg ( dyspnea 6/1 reintubation PED transferred. (6/7) Hypothermia , BP leukemoid reaction : r/o septic shock Tazo+AMK start Chemotx. cyanosis desaturation CO2 retention -> lung care 5 . antibiotics nebulizer . UGIS : feeding swallowing . Hospital course HD#31 (6/9) HD#34 (6/12) 23. Hospital course 1 (2009/8) 10 (2010.5) 9 (2010.4) 8 (2010.3) 2 (2009/9) 7 (2010.2) Pneumonia VFSS : aspiration Pneumonia ptosisPneumonia Budesonide nebulizer Grunting sound VFSS : aspiration Laryngeal elevation Chest CT : bronchiolitis obliterans L-tube feeding, PPI Brain MRI : brainstem mass Regurgitation 24. 1. Atypical teratoid/rhabdoid tumor in brain stem Poor swallowing : PEG insertion chemotherapy . 2. Recurrent pneumonia Bronchiolitis obliterans Budesonide nebulizer Infection control lung care Final Assessment & Plan 25. AT/RT Dysphagia, GER Central hypotonia Associated lung problem Recurrent pneumonia Bronchiolitis obliterans ? ? 26. Review Case BO & AT/RT 27. Review Case BO & AT/RT 28. Recurrent pneumonia in children Recurrent pneumonia : 2 episodes of pneumonia in a single year, or 3 episodes over any time period. The chest radiograph should show resolution of radiologic changes between episodes. Results from deficiencies in the local pulmonary or systemic host defences or from underlying disorders that modify the lung defences 1. Congenital malformation of upper of lower respiratory tract and cardiovascular system 2. Recurrent aspiration 3. Defects in the clearance of airway secretions- cystic fibrosis and ciliary abnormalities 4. Disorders of systemic and local immunities. 29. Recurrent pneumonia in children - study 2952 Patients admitted to The Hospital for Sick Children, Toronto, with pneumonia during 10 years Recurrent pneumonia : 238 patients Mean age : 3.7 years (2.5months ~15.6years) Underlying illness >> Aspiration syndrome (47.9%) due to oropharyngeal incoordination Immune disorder(14.3%) Congenital heart disease (9.2%) Bronchial asthma (8.0%) Anomalies of the respiratory system (7.6%) Gastroesophageal reflux (5.4%) Unknown (7.6%) Abdullah F. ect .Arch Pediatr Adolesc Med. 2000;154:190-194 30. Recurrent pneumonia in children Timing of Underlying illness Diagnosis Relative to the Number of Pneumonia Episodes Abdullah F. ect .Arch Pediatr Adolesc Med. 2000;154:190-194 31. Aspiration disorder >> Mean age : 6.3years Cerebral palsy (>50%) Recurrent pneumonia prior to diagnosis of underlying aspiration disorder : 4 case Nemaline rod myopathy (EMG ) Brainstem tumor (recurrent bilateral pneumonia from silent aspiration without neurological sign) Recurrent pneumonia in children Abdullah F. ect .Arch Pediatr Adolesc Med. 2000;154:190-194 32. Aspiration syndrome All conditions in which foreign substances are inhaled into the lungs Aspiration syndrome Oral or gastric contents associated with gastroesophageal reflux (GER) Swallowing dysfunction Cricopharyngeal incoordination : transient pharyngeal muscle dysfunction , involves cricopharyngeal muscle spasm or achalasia of the superior esophageal sphincter. Who have a normal suck reflex but have incoordination during swallowing -> possibly associated with cerebral palsy Neurological disorders Structural abnormalities. 33. Dysphagia in children Act of swallowing Oral phase chew solid food to semisolid consistency , liquid to the back of the oral cavity Cranial nerve V,(trigeminal) VII(facial), XII(hypoglossal) Coordination activity : jaw, facial, orobucal, lingual muscle Pharyngeal phase Soft palate rise : closes nasal cavity tongue pushes food into the laryngopharynx Laynx moves up and forward , closing glottis Cranial nerve V, VII, X, XI, XII Esophageal phase Food pushed down toward the stomach, by esophageal motility Disturbance in act of swallowing : Dysphagia 34. Most commonly presents as feeding or respiratory difficulty Newborns and infants Sucking difficulty / or Sucking without swallowing Pooling of food in the mouth, slow sucking , nasal reflux, failure to weight gain , coughing during feeding , apnea, noisy breathing during feeding Aspiration : choking, coughing , tachypnea, cyanosis Silent aspiration - Cough reflex is absent in 75% of premature infant and 50% of newborn - Absent in infants who have sufferd a neurologic insult Dysphagia in children 35. Repeated episode of respiratory infection and experience chronic bronchial congestion Examination Finding a cause of dysphagia Oropharyngeal malformation : small jaw, large tongue like Pierre Robin syndrome or Beckwith syndorme , or cleft lip and palate, mandibular ankylosis , choanal atresia -> sucking difficulty Feeding choking stridor : TEF Thorough Neurologic Examination !! (cranial nerve V, VII, IX, X, XI,XII) - Jaw jerk or Jaw clonus : suprabulbar palsy - Muscle tone , strength, evaluation of stretch reflex and sensation - Central hypotonia uncoordinate suck, swallow . - Congenital myopathy, dystrophy dysphagia . Dysphagia in children 36. Video analysis of sucking and swallowing Chromosomal karyotyping (Prader willi syndrome specific DNA test) Brain MRI : significant upper motor neuron finding !! (CNS injury malformation , neuromuscular dystrophy ) EMG/NCS Dysphagia in children 37. Selected neurologic cause of Dysphagia 38. Question Recurrent pneumonia aspiration syndrome CNS Imaging ? 39. Brain tumors in children under 1 years Intracranial neoplasm in neonates and infants Diagnostic & Therapeutic problem 1. Lack of specificity in the symptoms 2. The ability of the immature brain and skull to adapt to increased intracranial pressure -> Diagnostic Delay!! 3. Surgical resection of the tumor is the most effective therapeutic modality due to limited roles of radiation and chemotherapy 4. High operative mortality 40. Department of Neurosurgery, Seoul National University Hospital During 20 years (1977-1996) , 21 children Mean age : 5.8 months Brain tumors in children under 1 years SNUCH study S.K. Chung et al, J Korean Med Sci 1998;13: 65-70 41. IICP sign : 11 patients (large head, vomiting, irritability) Head circumference : 4 patients 90p . 1 tumor size 4-5cm 3-10P. Congenital tumor : 2 case (diagnosed with fetal US) Prognosis : depend on pathological diagnosis, extent of surgical removal , general condition (allows chemotherapy) and patients permission to treat Brain tumors in children under 1 years SNUCH study 42. Brain tumors in children under 1 years study S.K. Chung et al, J Korean Med Sci 1998;13: 65-70 43. Neurologic evaluation of infant Tone Hypotonic Hypotonic and weak Development Motor delay only Motor and cognitive delay Careful history , examination and frequently requiring serial examinations !!!!! 44. Supraspinal conditions : brain, brainstem , cervical spinal junction - Central hypotonia Basal ganglia, red nucleus damage : extremity passive movement Cerebellum damage : axial, appendicular hypotonia Segmental conditons: anterior horn cell , peripheral nerve, neuromuscular junction, muscle - Motor unit hypotonia Afferent & efferent limb reflex . Neurologic evaluation of infant 45. (A) pull to sit, (B) scarf sign, (C) shoulder suspension, and (D) ventral suspension. 46. Central hypotonia vs Peripheral hypotonia Amirsalari S. et al., Pak J Med Sci 2008;24(5):744-47 47. Central hypotonia vs Peripheral hypotonia Amirsalari S. et al., Pak J Med Sci 2008;24(5):744-47 48. Review Case BO & AT/RT 49. AT/RT with recurrent pneumonia case 1st admission due to pneumonia at age 2 months two subsequent admission at age 4 months Chest x-ray during 3 admission showed rt. upper lobe pneumonia . w/u for recurrent pneumonia Immunoglobulin level : normal Culture, pertussis w/u , enterovirus, chlamydia all (-) Hypoallergic diet unsuccessful Barium swallowing study : nasopharyngeal reflux, mild GER and aspiration Diala et al. Golisano Childrens Hospital. Pediatric annals 35:9 ,2006 50. AT/RT with recurrent pneumonia case During 3rd admission , left side upper and lower extremity weakness and hypotonia , left head tilt, rt. tougue deviation , left eye ptosis detected in P/E brain MRI : trilobed cystic mass arising within the left foramen of Luschka Excisional biopsy : atypical rhabdoid- teratoid tumor Diala et al. Golisano Childrens Hospital. Pediatric annals 35:9 ,2006 51. Brain tumor with aspiration pneumonia- case C/C : 5year old girl, choking and breathless/ short generalized convulsion Past history : Noisy, irregular breathing at night beginning at age 18 months diagnosed as mild asthma On admission , she was postictal and cyanotic, with costal retractions and crackles heard at both lung bases Dx : hypoxic convulsion associated with aspiration pneumonia Oades et al. Hillingdon hospital, AJDC vol 146(2), 1992 52. Brain tumor with aspiration pneumonia- case barium esophagogram Next 6 weeks, dizziness, unsteady on feet started . Developed apnea, pneumonia N/E : truncal ataxia/ fasciculating tongue/ poor gag reflex Brain MRI was performed. -> Gr 2 astrocytoma was confirmed by biopsy Oades et al. Hillingdon hospital, AJDC vol 146(2), 1992 53. Brain tumor with chronic intermittent stridor case C/C : Persistent noisy breathing (2months ago) 30 months old previously hearlthy girl P/I : Upper respiratory infection with rhinorrhea, cough, noisy breathing , wheezing 2 months earlier. All symptoms had resolved except abnormal breathing P/E : unremarkable Examination: Neck lateral x-ray : subglottic narrowing Bronchoscopy : collapsing, inflamed, edematous arytenoid/ paradoxical movement of vocal cord on inspiration Dx : Layngomalacia with paradoxical movement of vocal cord. Tx : PPI (for suspected GER) A Brain Tumor Presenting as Chronic Intermittent Stridor- Erin et al. Oregon health and Sciences university 2008, 54. Brain tumor with chronic intermittent stridor case 6 weeks later : dyspnea on exertion oxygen supplementation , corticosteroid & epinephrine tx. MRI scan (evaluate for possible Arnold Chiari malformation) Posterior displacement of the medulla by a 0.8x 1.6x 2.7cm mass Final Dx : anaplastic astrocytoma with features of a plomorphic xanthoastrocytoma A Brain Tumor Presenting as Chronic Intermittent Stridor- Erin et al. Oregon health and Sciences university 2008, 55. Brain tumor presenting as GER Case 1. A boy, at age of 8 months started to vomit Chest , skull x-ray , Barium meal follow thorough examination, jejunal biopsy, metabolic screening, abdomen CT -> Vomiting continud to 11months -> wt 5.7kg ( Nissens fundoplication After operation, stridor and sign of pseudobulbar palsy Brain scan : dilatation of ventricle, tumor mass surrounding fourth ventricle -> biopsy poorly differentiated glioma Brain stem glioma presenting as gastro-oesophageal reflux, Mahony et al. Archives of Disease in Childhood, 1987, 62 56. Review Case BO & AT/RT 57. Bronchiolitis Obliterans in children Bronchiolitis obliterans : histologically defined by the presence of granulation tissue plugs within the lamina of small airways and/or complete destruction of small airways leaving a scar Chronic obstructive lung disease insult to the low respiratory tract , result in narrowing and/or complete obliteration of the small airways. HRCT of children with respiratory disease has enhanced the ability of clinicians to diagnose BO noninvasively Etiology : drug, exposures to toxic fumes, allergy reaction, collagen vascular disease, organ transplantation, or infection In children ; following severe infection is m/c (usually adenovirus) In adults : occupational inhalation injury, hypersensitivity pneumonia, autoimmune disorder 58. Bronchiolitis Obliterans in children Etiology of bronchiolitis obliterans 59. 1. Combination of history, physical exam . Infectious disease evaluation, imaging study, PFT , lung biopsy (occasionally) Viral culture (especially adenovirus ) , Mycoplasma culture/PCR Imaging : 40% of the patients had patchy consolidation and focal atelectasis on initial imaging ( in contrast to the usually unremarkable radiographs of patients with classical viral bronchiolitis) HRCT : mosaic perfusion, vascular attenuation, central bronchiectasis (29 of 30 children with bronchiolitis obliteranse Kim et al . Chest 2001) Bronchiolitis Obliterans in children Diagnosis of bronchiolitis obliterans 60. HRCT bronchiolitis obliterans 61. Lung biopsy : gold standard for diagnosis But because heterogenous distribution of airway involvement, open lung biopsies nondiagnostic in up to 1/3 of patients. Treatment Azithromycin Systemic corticosteroids Frequently used. Corticosteroid would not be expected to favorably impact the largely fibrotic component of the disease. Should be given early while disease process is in the developing phase before airway fibrosis is complete Pulse tx : IV methyl PD 30mg /kg over 1h daily for 3 days, repeated monthly, for 3-6 months fewer side effect compared with oral corticosteroids. IV immunoglobulin (1-2g/kg) : monthly Bronchiolitis Obliterans in children 62. Atypical teratoid/rhabdoid tumor Highly malignant, CNS tumor occurs less than 2 years of age 1ST Described in 1987 by Rorke et al. PNET or choroid plexus carcinoma prior to its recognition. 15% of children less than 36 months with malignant brain tumors have AT/RT (Pediatric Oncology Group and Pediatric Brain Tumor Consortium study ) Histologically resembles Rhabdoid tumor of the kidney accurate diagnosis is difficult. Frequently located in the posterior fossa, but also be located in supratentorial or multifocal compartment. 63. AT/RT clinical and radiographic feature Signs and symptom : reflect location of the tumor Young patients with posterior fossa tumors : hydrocephalus , early morning headache, vomiting, lethargy, regression of motor skills Because of highly malignant tumor, typically have a fairly short history of progressive symptoms measured in days to weeks (unusual for symptoms to present for more than a few months) No way to distinguish AT/RT from other malignant brain tumor based on clinical history Imaging : nonspecific Posterior fossa : invade cerebellar pontine angle, may have area of necrosis Supratentorial : large, invasive, necrotic components 64. Atypical teratoid/rhabdoid tumor- Pathology AT/RT contains sheets of rhabdoid cells against a background of primitive neuroectodermal cells, mesenchymal cells, or epithelial cells . Some tumors are composed almost entirely of rhabdoid cell (round nucleus with prominent nucleolus and abundant cytoplasm ) 65. Atypical teratoid/rhabdoid tumor- Pathology Immunohistochemistry : Rhabdoid cells : vimentin (+) , smoth muscle actin (+) , epithelial membrane antigen (+) Primitive neuroectodermal cells: NFP (+) GFAP(+) Molecular cytogenetic screening : Abnormal tumor suppressor gene , INI-1 (especially rhabdoid tumor, immunohistochemical staining . ) -> INI-1 mutation (stain ) + PNET w/o clear rhabdoid component : AT/RT !! 66. Surgery Chmotherapy : post surgical adjuvant therapy Combination of cyclophosphamide, cisplatin, etoposide, vincristine, carboplatin, ifosfamide Of the 33 patients with AT/RT 69% progressed by 12 -24 weeks on therapy, 83% progressed by 12 months. Median survival was 193 days) Radiation therapy Atypical teratoid/rhabdoid tumor- Treatment 67. ATRT- associated lung problm ? 1. Metastasis High incidence of leptomeningeal dissemination (59% of them at relapse) , but systemic metastasis to other extraneural sites is extremely rare in children- 0.98% (ali et al. Journal of Neuro-Oncology ,2006) - One report of a patient with atypical teratoid rhabdoid tumor disseminating via a ventriculoperitoneal shunt (Korones et al. Med Pediatr Oncol,1999) - 6 year old AT/RT patient without VP shunt showed lung metastasis after 15 months after diagnosis (Elif et al. Journal of Neuro-Oncology ,2001). - Since craniotomy may cause tumoral implantation into the incised cutaneous tissue and migration of cells into the veins - In central nervous system tumors, metastases may occur soon after initiation of therapy or may be detected several years after diagnosis (mean time : 18 months (3-60months))