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Infectious Conference Anne Cortez Hannah Lea David Hazel Ann David Jan Kristoper De Guzman General Data • • • • PAB 14/F GMA, Cavite Catholic CC: Altered Sensorium 3 weeks PTA • Intermittent low grade fever (38.0C) • Lysed by Paracetamol 500 mg/tab q4 • No accompanying symptoms 7 days PTA • Recurrence of fever • Bitemporal throbbing headache (Grade 8/10) • Sought consult at a local hospital :CBC (normal results) and Urinalysis (UTI) • Cefuroxime 250mg/tab BID (12mkd) for 7 days, Paracetamol 500 mg/tab (12mkdose) q4 • Afforded relief of the symptoms 3 days PTC •Recurrence of the symptoms •Continued medications 1 day PTA • Persistence of fever and headache • Generalized weakness • (+) vomiting- 1 episode, 1 cup, non-bloody, previously ingested food • Rushed to a nearby hospital and was assessed again to have UTI • Meds: Cotrimoxazole 500mg/tab BID for 7 days (24 mkd) • Sent home • Altered sensorium Few hours PTA • Difficult to arouse, speaks incomprehensively • Persistent fever • Rashes over the chest and neck area • Hence admission Review of Systems • General: (-) weight loss/gain, (-) anorexia, (-) chills • Cutaneous: (-) pigmentation, (-) bruises, (-) hair loss, (-) pruritus • HEENT: (-) lacrimation, (-) eye redness, (-) eye discharge, (-) blurring of vision (-) nasal discharge, (-) epistaxis (-) sorethroat, (-) oral ulcers • Cardiac: (-) orthopnea, (-) chest pain, (-) cyanosis • Respiratory: (-) difficulty of breathing (-) cough (-) cold • Abdomen: (-) jaundice (-) diarrhea (-) melena (-) hematochezia • GU: (-) dysuria, (-) frequency • Endocrine: (-) palpitations, (-) polyuria, (-) polyphagia (-) polydipsia • Musculoskeletal: (-) swelling, (-) limitation of motion, (-) stiffness (-) edema • Hematopoietic: (-) pallor, (-) petechiae, (-) ecchymoses, (-) easy bruisability • Neurologic: (-) seizures Past Medical History • • • • • (-) Previous hospitalizations (-) Surgeries (-) PTB (-) Asthma (-) Allergies Immunization History • Completed EPI from the Brgy health center • Unrecalled dates • (-) booster doses, MMR, Hep A, Varicella, Flu, Hib vaccines Menstrual History Menarche: 12 yrs. old Interval: every 28-30 days Duration: 5-7 days Amount: 4 pads/day moderately soaked Severity: (-) dysmenorrhea Family History • • • • • (-) HPN, DM, Cardiovascular disease (-) PTB, Asthma,CA (-) Renal disease (-) Blood Dyscrasias (-) Seizure disorders Family Profile Age Sex Relation Educ Occupation Health Attainment status RC 47 M Father HS Grad Watch repair technician Healthy MC 47 F Mother HS Grad Therapist Helathy 26 M Sibling College Grad Supervisor Healthy 22 F Sibling College Grad Cashier Healthy 21 M Sibling College Grad Unemploye d Healthy 19 M Sibling College student Healthy 15 F Sibling HS Student Healthy 24 hour food Recall CHO CHON Fats Kcal Breakfast ½ cup rice 23 Fried pork 2 16 100 2 82 Snack 2 slices of bread 46 Liver spread 4 6 400 1 31 Lunch 1 cup rice 46 Fried chicken 4 8 200 1 41 Dinner 1 cup rice 1 grilled tilapia ACI: 1160 RENI: 2140 % intake 54.2 46 4 32 200 4 106 Socioeconomic and Environmental History • lives with her family in their own two-storey, well-lit, well-ventilated house made of concrete and wood. • Drinking water comes from a commercial purifying station. • Garbage is segregated and collected twice a week. • The family has a pet dog. • There are no factories nearby and no cigarette smoker at home. HE/EADSS FFIRST • Home: good interpersonal relationship, secretive • Education: 2nd year high school student with good grades, 2nd honor; favorite subject is English; a dancer; dreams of becoming a doctor • Eating: picky eater; meat-lover; prefers meat and fish over vegetables • Abuse: denies physical, sexual, and emotional abuse • Drugs: denies use of illicit drugs • Safety: no hazardous activities, does not drive • Sexuality: denies sexual activity • Family/Friends: belongs to a close-knit family, good family relations, closer to her parents, has many friends in school • Image: good sense of self-image, good self-esteem • Recreation: computer addict, prefers to sit in front of the computer (FACEBOOK), seldom goes out with friends, non-smoker, not an alcohol beverage drinker • Spirituality: claims to regularly attend mass • Threats & Violence: denies self-harm or harm to others, no cruelty to animals, never been arrested, no fights in school, no suicidal ideations Physical examination • Lethargic, arousable, well hydrated, adequately nourished, wheel chair borne, not in cardio-respiratory distress • BP 110/70 PR 95 RR 28 Temp 37.0°C • Wt 42kg Length 155 cm (below 0) BMI 17.48 (below 0) • Warm, moist, no active dermatoses • Normocephalic head, atraumatic, no lumps, bumps, normal hair distribution • Pink palpebral conjunctiva, anicteric sclera, pupils sluggishly reactive to light • No tragal tenderness, slightly hyperemic EAC AS, retained cerumen AD, TM intact • Oral cavity not visulaized • Supple neck, no palpable LN, thyroid not enlarged • Symmetric chest expansion, no retractions, resonant on percussion, clear and equal breath sounds on both lung field`s • Adynamic precordium, apex beat 5th LICS MCL, no murmurs • Abdomen globular, normoactive bowel sounds, soft, non-tender, no hepatosplenomegaly • Genitalia: SMR 1 Breast: SMR 2 • Pulses full and equal, no cyanosis, no deformities, no edema Neurologic Examination • Drowsy, easily arousable to voice and painful stimulation, no verbal output • Pupils 4-5 mm OS • 3-4 mm OD; conjugate gaze • No facial asymmetry • DTRs ++ on all extremities • No Babinski • No meningeal irritation • With nuchal rigidity Salient features • 14/F • Altered sensorium • 3 week history of intermittent, low grade fever, headache, vomiting,generalized weakness • Lethargic, GCS? • Pupils 4-5 mm, sluggishly reactive to light • DTRs ++ on all extremities • (+) Nuchal rigidity, (-) kernig’s (-) brudzinski • (-) Babinski Approach to Diagnosis • Look for a symptom, sign, or laboratory finding pointing to an organ system Headache Altered Sensorium Nuchal Rigidity Vomiting CNS Focal Neurologic Deficit Is there a neurologic problem? What is the problem? Meningeal Irritation Increase ICP Working Diagnosis • t/c Meningitis Differential Diagnosis Infectious Meningeal Non Irritation infectious Non Infectious • Present in the Patient – Altered Sensorium – Fever – Bitemporal throbbing headache – Generalized weakness – Vomiting – Rashes – Sluggish pupils – (+) Nuchal Rigidity • Subarachnoid Hemorrhage – – – – – – – Afebrile Acute Headache Loss of consciousness Vomiting +/- neurologic deficit Lumbar tap: bloody CSF Infectious • Present in the Patient – Altered Sensorium – Fever – Bitemporal throbbing headache – Generalized weakness – Vomiting – Rashes – Sluggish pupils – (+) Nuchal Rigidity • Meningitis – – – – – – – – Headache Fever Nausea Vomiting Altered consciousness Anorexia Irritability Neck Pain Meningitis Bacterial Viral Fungal Lumbar Tap BACTERIAL VIRAL FUNGAL TB Opening Pressure Elevated (100-300) Normal or Slightly Elevated Usually Elevated Usually elevated WBC 100-10,000 or more; usually 300-2,000 PMNs predominate Rarely >1,000 PMNs early but mononuclear cells predominate through most of the course 5-500 10-500 Protein 100-500 50-200 25-500 100-3,000 Glucose Decreased usually <40 (or <50% serum glucose) Normal or decreased to <40 <50 <50 COURSE IN THE WARD Upon Admission • Upon admission, patient was put NPO and given D5NSS run at 18-19gtts/min (100%). • She was given Paracetamol 300mg/SIVP q4h. • CBC with platelet revealed leukocytosis. • Serum sodium was low while serum potassium and creatinine were normal. • Cranial CT scan with contrast was done and result was suggestive of meningitis with hydrocephalus with undue hypodensity involving the right lentiform nucleus and right caudate nucleus may be due to vasculitic changes. • The patient developed rash over the abdomen thus Diphenhydramine 50mg/IV was administered. Upon Admission • Patient was referred to Pedia-Neurology. • On neurological examination, patient was drowsy, easily arousable to voice (occasional) and painful stimulation, no verbal output, pupils 4-5mm OS and 3-4mm OD both sluggishly reactive to light, (+) conjugate gaze, (+) nuchal rigidity, no facial asymmetry, moves head side to side, moves all extremities equally, DTR ++ on all extremities. There was no atrophy, fasciculation, sensory deficits, pathological reflexes, nor meningeal irritations. • Later that day, IVF rate was increased to 20-21gtts/min (100%) and later shifted to PNSS 1L run at 23-24gtts/min. Upon Admission • • • • • • • • • Correction of hyponatremia was started. RBS and Hgt were also done 30mins prior to LP. Mannitol was started 0.5g/kg and then revised to 20% given 105mL/SIVP q6h. Initial anti-TB regimen was Isoniazid 200mg/5mL 9mL qd (10mkd), Rifampicin 200mg/5mL 9mL qd (10mkd), Pyrazinamide 250mg/5mL 15mL qd (21mkd), Ethambutol 400mg/tab 2tabs qd (22mkd), and Streptomycin 1g/vial + 2cc sterile water 1.7cc/IM qd (20 mkd). Lumbar puncture with CSF analysis was done with an opening pressure of 47cm H2O and closing pressure of 42cm H2O. Specimen for routine CSF analysis was sent as follows: Test tube#1 Sugar, protein and cell count differential count , Test tube#2 Gram stain, CSF C & S, with ARD AFB & India Ink for the fungal, Test tube#3 TB Bactec, Test tube#4 save specimen. CSF was xanthochromic and slightly turbid. CSF protein was high and differential count revealed 100% lymphocytes. Total CSF protein was high. PPD and Chest x-ray (portable) were done. IVF rate was decreased to 20gtts/min and Mannitol was maintained. She was started on Dexamethasone 4mg/SIVP (0.14 mkd) q6h and Ranitidine 30mg/SIVP (2.9 mkd) q6h. 2nd Hospital Day • NGT was inserted. • Anti-Koch’s medications were revised: – Isoniazid 200mg/5mL 7.5mL qd – Rifampicin 200mg/5mL 12.5mL qd – Pyrazinamide 250mg/5mL 15mL qd, all given via NGT 30mins prebreakfast. • Patient was on 2-point restraint. • IVF rate of 20gtts/min was maintained. • Chest x-ray (portable) revealed suspicious haziness is seen on left apex. Official Reading: Suspicious haziness is seen on left apex 3rd Hospital Day • PNSS 1L run at 20gtts/min. • PPD reading was 0.5cm right volar surface, no induration. • Patient was referred to neurosurgery. • She was still drowsy, awakens to mild stimulus and occasionally follows commands, pupils were still dilated 4-5mm OS and 3-4mm OD both sluggishly reactive to light, (+) nuchal rigidity. • She was given Paracetamol 500mg/tab 1tab/NGT q4h for temp > 38.5oC. 4th Hospital Day • PNSS 1L run at 20gtts/min (100%). • Repeat cranial CT scan with contrast was requested. • She was given Hydrocortisone (Solucortef) 100mg/vial 1vial 1 hour prior to the CT scan and Diphenhydramine 50mg/IV right before the procedure. • Ethambutol 400mg/tab 2tabs once a day was started. • Repeat sodium and potassium were both low. 5th Hospital Day • • • • • • • • • • blood chemistry showed low serum osmolality, normal urine osmolality, normal urine sodium & potassium, low serum sodium & normal potassium, high FBS, normal BUN and low creatinine was requested. She was referred to Nephrology. She was still infused with PNSS 1L run at 15gtts/min (75%). Patient was euvolemic (no edema). A> most probable cause of hyponatremia is syndrome of inappropriate antidiuretic hormone (SIADH). Medications given were Furosemide 40mg/SIVP single dose with BP precaution, NaCl 1gm/tab 1 tab q8h. Patient was GCS 12 (E4V3M5) with adequate urine output. Neurosurgery offered CSF diversion procedure for ventriculo-peritoneal shunt insertion after 2 weeks of anti-Koch’s medications. She was prescribed with Acetozolamide 250mg/tab 1tab q8h. Later that day, IVF was discontinued. Patient was given 6 scoops of milk formula (ENSURE) + 190mL water to make 230mL via NGT every 3 hours. 6th Hospital Day • Patient had low-grade fever. She was started on Trimetroprim-Sulfamethoxazole (Cotrimoxazole) 800mg/160mg tablet 1tab BID. 7th Hospital Day • patient went into respiratory distress. She became tachypneic (RR=44) and irritable, had rapid, shallow breathing, suprasternal & subcostal retractions, coarse crackles, wheezing on inspiration and expiration, and fair air entry. O2sat was 88%. • Salbutamol challenge was done. • She was given O2 per nasal cannula at 1-2 lpm and salbutamol nebulization 1neb q6h. • After 2 hours, patient’s condition improved with respiratory rate of 34 and 02 sat of 95-96%. • Patient was comfortable but still showed rapid shallow breathing, good air entry, minimal supraclavicular and subcostal retractions, decreased crackles and wheezing. • ABG, chest x-ray (portable), and CBC with platelet were requested. Repeat serum Na K. Feeding was decreased to every 4 hours. Official reading: Hazed infiltrates superimposed over the left cardiac shadow, which may represent pneumonic process 8th Hospital Day • Patient had low-grade fever • Salbutamol nebulization was decreased to 1neb every 8 hours. • Relatives were instructed to turn the patient side to side every 2 hours. 9th Hospital Day • Patient had 3 episodes of loose stools, nonmucoid, non-bloody. • ORS 75 was given through NGT to replace losses volume per volume. 10th Hospital Day • NaCl tablets were discontinued. P • atient had persistent febrile episode and abdominal pain. • She still had loose watery stools. • Urinalysis and CBC with platelet were requested. 11th Hospital Day • Patient had 2 episodes of watery stools. PLRS was given to replace losses volume per volume. • Mannitol was decreased to every 8 hours. Dexamethasone was consumed and then shifted to Prednisone 10mg/5mL, 15mL BID. • Ranitidine was discontinued once Dexamethasone was consumed. 12th Hospital Day • Patient followed commands, pupils anisocoric, (+) ptosis L>R, (+) lateral rectus palsy OD, medial rectus palsy OS, grade 5/10 headache, and febrile episodes. • No nuchal rigidity noted. • Repeat Na and K was requested. • Cotrimoxazole was discontinued. Discussion Meningitis • Diffuse infection which primarily involves the meninges • Most common cause of fever associated with signs and symptoms of CNS disease in children Etiology Causative Agents Neonates 2 M to 12 years Groups B and D Streptococci E. Coli Listeria monocytogenes N. Meningitidis S. Pneumoniae H. Influenzae Type b Pathogenesis Bacterial colonization of the nasopharynx Attachment to the epithelial cells , breach the mucosa and enter the circulation Bacterial capsules interfere with opsonic phagocytosis CSF through the choroid plexus of the lateral ventricles meninges Extracerebral CSF then Subsrachnoid space Bacterial Proliferation Chemotactic Factors Inflammatory mediators Clinical Manifestations • • • • • • • • Fever Anorexia Poor feeding Headache Myalgias, arthralgias Petechiae Purpura Vomiting • • • • • • Nuchal rigidity Back pain (+) Kernig’s sign (+) Brundzinski sign Increase ICP 10-20% focal neurologic signs • Seizures • Alteration of mental status Diagnosis • Lumbar Tap - CSF analysis Management Specific • β-lactam drugs, vancomycin (60 mg/kg/24 hr, given every 6 hr) and 3rd-generation cephalosporins (200 mg/kg/24 hr, given every 6 hr) or ceftriaxone (100 mg/kg/24 hr administered once per day or 50 mg/kg/dose, given every 12 hr) is recommended as part of initial empirical therapy • Duration of 10-14 days Supportive • • • • Ventriculo-peritoneal shunt Furosemide Mannitol Dexamethasone Preventive • Rifampin 10 mg/kg/dose every 12 hr (maximum dose of 600 mg) for 2 days – close contact • Pneumococcal vaccine JOURNAL Central Nervous System Tuberculosis in Children: A Review of 214 Cases Ahmet Yarami *, Fuat Gurkan*, Murat Elevli ,Murat Söker*, Kenan Haspolat*, Gökhan Kirba *,§, and M. Ali Ta * From the * Division of Pediatric Diseases, Medical School, Dicle University, Diyarbakir, Turkey; Division of Pediatric Diseases, Medical School, Kocaeli University, Kocaeli, Turkey; and§ Department of Pulmonology, Medical Clinic, University of Freiburg, Freiburg, Germany. PEDIATRICS Vol. 102 No. 5 November 1998, p. e49 Objective: To study the clinical, laboratory, and treatment features observed in pediatric patients with tuberculous meningitis in Turkey. Study Design: retrospective case review study Methods: Review of medical records for demographic data, medical history, clinical manifestations, auxiliary test results, complications, and treatment of 214 children with central nervous system tuberculosis (TB) admitted to Dicle University's hospital between August 1988 and February 1996. TABLE 1 Case Definition of CNS TB by Either Microbiologic or Clinical Criteria Microbiologic case definition; one of the following: Isolation of M tuberculosis from CSF Abnormal neurologic signs and symptoms, CSF, or cranial CT consistent with CNS TB, and isolation of Mtb from any site. Clinical case definition; abnormal neurologic signs and/or symptoms and more than two of the following: Discovery of adult source case with contagious TB who had significant contact with child Presence of Mantoux (5 TU) skin test reaction >10 mm of induration, or >5 mm of induration if child had close contact with infected adult* CSF abnormalities without evidence of other infectious cause Abnormalities on cranial CT consistent with CNS TB * >15 mm of induration was considered positive for children with BCG (BCG is in the routine immunization program of Turkey). Severity of the disease • Stage I: involves patients with nonspecific symptoms such as fever, anorexia, intermittent headache, or vomiting, and with no definiteneurologic manifestations. • Stage II: includes patients with drowsiness and disorientation and with signs of meningeal irritation and/or evidence of increased intracranial pressure. • Stage III: patients were usually unconscious with paralysis and signs indicating severe intracranial hypertension. RESULTS Demographic and Clinical Characteristics • 112 out of 214 patients (52%) were boys (male-tofemale ratio was 1.1:1.0) • Age ranged from 3 months to 15 years, with a mean age of 4.1 years. • Seventy-seven percent of the children were younger than 5 years, and ~44% of the patients were between 12 and 24 months of age. • More than half (52%) of the patients came from rural areas (villages), 73 (34%) from townships, and the remainder (14%) from cities (urban areas). • 141 (66%) of the patients had a family history of TB, and 64 (30%) had a Mantoux skin test result of >10 mm of induration. • Only 22 (13%) of 164 children had a positive acid-fast bacilli smear in cerebrospinal fluid, and Mycobacterium tuberculosis was isolated in 49 patients (30%). • A small percentage of patients were admitted in the first stage of disease (10%). The other 90% had a neurologic manifestation (120 in the second stage and 72 in the third stage), with a longer duration of preadmission symptoms. TABLE 3 Symptoms and Signs at Presentation N = 214 % Fever 91 Vomiting 87 Changes in personality 63 Seizures 62 Nuchal rigidity 59 Headaches 58 Loss of appetite 45 Weight loss 38 Irritability 30 Cough 29 Cranial nerve paresis 26 Diarrhea/constipation 10 Laboratory data • 80% of CSF results were compatible with TBM (ie, predominance of lymphocytes with elevated protein and reduced glucose concentrations) Radiographical features Hydrocephalus was seen on cranial CT in 80%, parenchymal disease in 26%, and basilar meningitis in 15%. Radiographic studies demonstrated abnormal chest findings in 187 patients (87%) (hilar adenopathy, 33%; infiltrates, 33%; miliary pattern, 20%; and pleural effusions, 1%, and 172 (80%) cases with hydrocephalus,26% with parenchymal disease, 15% with basilar meningitis, and 2% with tuberculomas. . Clinical Course • All the patients were hospitalized for diagnosis and initial treatment, and the median hospital stay was 38 days (range, 11-95 days). • Our patients were treated with a 12-month regimen, initially with Isoniazid, rifampin, and pyrazinamide or streptomycin, and changed to only two drugs (Isoniazid and rifampin) after 2 months of therapy. • Steroids were used as adjunctive therapy in all patients for 3 to 4 weeks and then gradually tapered as tolerated over a period of 7 to 10 days. • Of 172 cases with hydrocephalus, 140 (81%) underwent surgical management. • Forty-nine patients (23%) died; 32 (65%) of these deaths occurred during the first 3 days after admission to hospital. Sixty-three percent of deaths were of children age 5 years or younger, 31% were of children 6 to 10 years of age, and only 6% (3) were of children older than age 10 years. Outcome of treatment TABLE 6 Outcome of Treatment Stage I II III Total No. % No. % No. % No. % Complete recovery 13 59 67 56 6 8 86 40 Seizures 1 5 8 7 6 8 15 7 Developm ental sequela 8 36 31 26 27 38 66 31 Deaths 0 0 14 12 35 49 49 23 Conclusion One or more of these findings: a family history of TB, positive tuberculin skin test results, abnormal cranial computed tomography, and/or cerebrospinal fluid analysis compatible with TBM were found in all but 3 children in the study.