R2 陳柏嵩 Case discussion

General data Chief complain Acute onset upper limbs convulsion with loss of conscious General data Name：劉XX Sex：男 Age：4 Bed No：4P107 Occupation：學生 Ethnicity：台灣

Present illness Fever 39.7°C, sore throat, dry cough 04/18 morning Fever 39.7°C, sore throat, dry cough Clinic: acute tonsilitis, treated with Augmentin Intermittent fever, interval 3 hours 04/18 ~13:00 Vomit once, food content; no change in spirit Fell on floor of bathroom, no headache, no dizziness, no change in activity 04/18 ~15:00 Mother noted bilateral eye gazing right or left, cannot focus, following both forearm flexion and hand shaking; duration 14 mins Then he was brought to 新樓H. Seizure did not stop even under valium use. The brain CT showed brain swelling, but no evidence of acute hemorrhage. However, this patient was then intubated because of status epilepticus and then further transferred to our PICU. After admission, we found seizure persisted and his conscious was unclear. And 新樓H. had informed us his rapid test for influenza was positive for type A influenza. Under the impression of 1. status epilepticus 2. acute encephalitis , suspect of acute necrotizing encephalitis 3. influenza A infection, he was admitted to our PICU for further evaluation and treatment. He did not receive Influenza vaccine His elder sister had Flu-like symptoms No travel history, No contact history

Present illness Ambulance to 新樓H. 04/18 Ambulance to 新樓H. Treat with Valium *4 time (補充dose) ; poor response to Valium Brain CT: severe swelling Transfer to 成大

Past history Birth History: G2P2 Routine vaccination: as scheduled Additional vaccination: Pneumococcal polysaccharide vaccine: vaccinated Influenza vaccinate: not vaccintaed Grow and development BH: 106 cm = 50-85th percentile BW: 16 kg = 15-50th percentile Hospitalization : febrile convulsion, 2016/04

Family history

Physical examination T: 35.1°C ; P: 127/min R: 23/min ; BP: 110/75mmHg Appearance: ill looking Appetite: poor; Activity: poor Conscious: stupor, E4 Vt M5 HEENT: Sclerae: anicterus; Eardrum: not injected; Tonsil: not injected, no enlargement, no exudate CHEST: Breath pattern: smooth, bilateral symmetric expansion No use of accessory muscle Breathing sound: bilateral clear and symmetric breathing sound, no crackle, wheezing, stridor, rhonchi HEART: regular heart beat, no murmur ABDOMEN: Tactile: soft and flat; no tenderness; no rebounding pain Bowel sound: normoactive EXTREMITIES: No pitting edema SKIN: No rash; no petechiae Cranial nerve: II. Pupil: 3/3 Light reflex: +/+ VII. Facial motor: no facial palsy ANS: Urine- normal Stool- normal

Tentative diagnosis Fever with status epilepticus, suspect CNS infection(meningitis or encephalitis) 2.Head injury

Lab data

Lab data

CXR

CT

Diagnosis Influenza type A related enecphalitis

Treatment Antiviral antibiotics (influenza): Pulse therapy: Peramivir 200 mg QD IVD x5天 Pulse therapy: Methylprednisolone 480 mg IVD QD x5天 Intravenous immunoglobulin Empiric antibiotics: Vancomycin and Ceftriaxone meningitis dose Hypothermia therapy

EEG MRI

Lab data Influenza virus A+B antigen: HSV IgM: 1.229 ; positive Type A antigen: positive Type B antigen: negative HSV IgM: 1.229 ; positive HSV IgG type I: 4.957 ; positive HSV IgG type II: 0.164 ; negative Mycoplasma Pneumonia IgM: positive

EEG Epileptiform discharge over right temporal area (T4) and spread to right hemisphere especially frontal area (F4)

MRI ADC ADC

Severe Influenza complication Discussion

Clinical symptoms

Epidermiology

臨床條件 出現類流感症狀後四週內，發生符合以下臨床狀況至少一項者 肺部併發症(Pulmonary complications)且住院者 出現類流感症狀後四週內，發生符合以下臨床狀況至少一項者  肺部併發症(Pulmonary complications)且住院者  神經系統併發症(Neurological complications)  心肌炎(myocarditis)或心包膜炎(pericarditis)  侵襲性細菌感染(Invasive bacterial infection)  其他(Other)：非符合上述1-4項臨床症狀，但個案需於加護病房治療，或死亡者。 

檢驗條件 流行病學條件 流感病毒培養(influenza virus isolation in cell culture)陽性。 流感病毒反轉錄聚合?連鎖反應(influenza virus RT-PCR)陽性。 流感病毒抗原測試(influenza virus antigen detection)陽性。 流感病毒血清效價，在急性期 (acute) 與恢復期 (convalescent) 有四倍(含) 以上的效價上升。 流行病學條件 曾經與經實驗室證實之確定病例具有密切接觸（closecontact），即照護、同住、或與其呼吸道分泌物、體液之直接接觸。

Treatment

Severe influenza treatment guideline Korean J Intern Med 2014;29:132-147 http://dx.doi.org/10.3904/kjim.2014.29.1.132 Severe influenza treatment guideline

Included method for IVIG, ECMO, Macrolide, Statin, Steroid, High dose therapy, Combination therapy, Plasmaphoresis

Dose for oseltamivir •Standard-dose oseltamivir is recommended for the treatment of severe influenza (BI).

Duration of the antiviral If the clinical course remains severe or progressive, the duration of the antiviral treatment is recommended to be extended longer than the usual treatment duration (e.g., 5 days for oseltamivir) (BIII) No clinical studies have evaluated the effectiveness of a longer duration of antiviral treatment for treating severe influenza patients

About combination therapy Antiviral combination therapy is not generally recommended for the treatment of severe influenza (BII)

Antibiotics-1 An antibiotic along with an antiviral agent is recommended to be administered from the beginning of the treatment to a severe influenza patient with accompanying pneumonia (BII). An antibiotic is recommended to be administered to a patient with severe influenza complicated by acute otitis media or sinusitis (BII).

Antibiotics-2 Antibiotics such as ampicillin/sulbactam, amoxicillin/ clavulanate, third-generation cephalosporins, and respiratory quinolones that show an antibacterial activity to Staphylococcus aureus, Streptococcus pneumonia, Streptococcus pyogenes, and Moraxella catarrhalis are recommended (BII).

ECMO ECMO is recommended to be applied to an influenza patient presenting continued hypoxia which does not respond to a conventional treatment (BIII)

Steroid Systemic corticosteroid administration should not performed for the treatment of a severe influenza patient (BII) The exception is that a corticosteroid could be administered for the treatment of a disease for which the therapeutic effect of a steroid has already been proven, such as asthma, COPD, and adrenal insufficiency (BIII)

IVIG There is not sufficient evidence to recommend implementation of IVIG, statin, or plasmapheresis for treatment of a severe influenza patient Because all the case reports showed good prognosis after the administration of IVIG, according to the clinician’s judgment based on the case reports

Plasmapheresis All the clinical case reports showed that plasmapheresis was effective, but the number of subjects was too small

The End