Problem Rounds August 31, 2006

15 year-old Hispanic male with dizziness and neck pain for 3 days

CC: Dizziness and neck pain x 3 days

HPI: 15 year-old Hispanic male was in his usual state of health until 15 days prior to admission, when patient had severe right ear pain and was brought to the ER at Hollywood Presbyterian. Per hospital records, he was diagnosed with R otitis media, and given amoxicillin, phenergan and motrin. CBC and UA were sent and showed WBC 15.7 PMN88%, L6%, M6%; Hct 39; Plt 396; UA with pH 5, SG 1.017, ketones 40 mg/dL, otherwise negative.

4 days later (11 days PTA), the patient complained of headache and continued R ear pain. Mom brought him back to the same hospital in the early evening. He complained of pain at his forehead, and at the back of his neck that worsened with movement. Per mom, a head CT and lumbar puncture were performed at this time and were normal.

HPI Continued: Per hospital record, vital signs were: T 97.6, P50, R24, BP 122/67, SaO2 99% on RA, pain 8/10. Patient was noted to be in moderate distress, with a resolving ear infection. CT head was done, showing bilateral mastoiditis. LP was performed; opening pressure was 24, with clear CSF showing 1 RBC, 2 WBC (100% monocytes), glucose 59, protein 16.8. Blood culture and CSF culture showed no growth.

He received Toradol 30 mg, Rocephin 2 g, and Versed 4 g, and was discharged home 5 hours after his arrival in the ER with a diagnosis of R otitis media, mastoiditis, and headache (per discharge papers). No written record could be found regarding discharge medications or follow-up care. However, it was noted that treatment and aftercare were explained to the family.

HPI Continued: 1 day later (10 days PTA), patient still had headache. Mom then brought him to an herbal medicine doctor who said that the patient did not have an ear infection and did not need to take any medication. He gave some natural herbal medicine and vitamins. Mom agreed with the suggestion and stopped the antibiotics.

The patient continued to have mild headache, but no ear pain.

3 days PTA, the patient started to have dizziness and neck pain. He would not move his neck secondary to the pain. Mom said he was dizzy with getting up and walking, so he mostly sat in a chair. He reported no ear pain, headache, URI, or change in PO intake.

On the day of admission, his older sister noted that the patient looked ill, had a tactile fever and was sweating with chills. He was brought to the Peds ER.

Take a moment to consider your differential diagnosis

PMH: History of kidney stones diagnosed in Mexico 1 year ago. No h/o any recurrent OM. No h/o frequent HA.

PSH: none

ALL: NKDA

Meds: vitamins and herbal meds; post-amoxicillin for 10 days and one dose of Rocephin

Imm: Per card, needs Hepatitis A #2, hepatitis B #3; last PPD was 01/2006 and was negative

PMD: none

FH: Dad is 44 years old, Mom is 43 years old. Patient has 3 older siblings and 2 younger sisters. No family h/o HTN, DM, CA. Older brother also had renal stones about 1 year ago.

Birth Hx: Born in Mexico, full-term, NSVD. No complications.

Social Hx: Patient moved to Los Angeles from Durango, Mexico 8 months ago. He lives in a 1 bedroom apartment with his parents, older sister and her husband, and 2 younger sisters. He denies any recent travel, sick contacts, or visitors in the home. There are no pets, guns, tobacco, alcohol, or domestic violence in the home. Patient feels safe at home.

He is in the 9th grade, but does not speak English yet. He is not employed. He likes to watch TV, play video games and football. Other HEADDS exam was negative.

Peds ER:VS @ presentation: T 102.8, BP 140/68, P 80, RR 20,

SaO2 100% on RA, pain 0/10

On exam noted to be: •toxic-appearing WDWN, poorly interactive, uncomfortable-appearing, holds his neck stiff, sweaty and pale•Red bulging R tympanic membrane with R mastoid tenderness, no fluctuance•PERRL; R eye ptosis, and unable to look up and laterally on R•Neck stiff, unable to forward flex/turn head•Negative Kernig and Brudzinski•No rash/petechiae•Grade 1-2/6 systolic murmur over precordium•Increased tone with clonus; normal DTRs; slow speech

LabsPeds ER:Patient was started on NS@80 cc/hr; Tylenol 650 mg PO;

Cefotaxime 2g IV; decadron 10 mg IV; Vancomycin 1g IV

Neurosurgery and ENT were called for consultation.

Labs were drawn and CT head was done.

136 96 7 101 CRP 23.7 Ca 9.3 Mg 2.4 Phos 4.4 UA 3.3 4.4 27 0.6 AP 144 tprot 7.6 Alb 3.9 CK 71 LDH 302

AST 255 ALT 412 Tbili 0.5 Dbili 0.2 12.714.5 406 N80 L8 M13 37.8 PT 16.6; PTT 38.3

UA: pH 7.0, SG 1.022, trace prot o/w neg VBG: 7.4/50/28/30

Take a moment to consider your differential diagnosis

CT

CT

CT Head: R post parietal osteo, mastoiditis, otitis media, sm fluid in L mastoid air cells possible thrombosis of R sigmoid sinus. Also, e/o dural enhancement of the tentorium which may suggest underlying meningitis.

CT Temporal: R mastoiditis with erosion of inner table of bone and underlying transverse sinus thrombosis; fluid in R middle ear but ossicles intact

CT Neck: No abscess seen

ENT placed right PET and sent ear drainage for culture

Take a moment to consider your differential diagnosis

Physical Exam in PICU:

Wt: 82 kg (90-95%) Ht: 180 cm (75-90%) BMI: 25 (90%)VS: T99, BP 124/62, P61, RR 16, Pain 0/10Gen: Awake, calm, NADHEENT: NCAT, PERRL

Left eye with left lateral gaze defect with nystagmus No proptosis, no diplopia

Visual acuity 20/200 with card b/l B/l optic disc edema Left TM normal, R TM bulging/red; nl pinnas b/l. TTP and sl. red at R mastoid but no fluctuance Nares nl; Clear OP with no lesions, MMM

Neck: No lymphadenopathy, limitation of neck movement secondary to pain at R mastoidCVS: Systolic murmur 1-2/6 @ LLSB; good pulses, cap refillLungs: CTAB, good air movement

Physical Exam in PICU:

Abd: Soft, obese, NTND, no HSM, no massesGU: Tanner 4, uncircumcised male with b/l descended testesExt: No c/c/eSkin: No rashNeuro: CN showed L lateral gaze paresis

Good toneNormal strength at all extremitiesNormal sensationPatellar reflexes +1 b/lNo clonusNegative Kernig and Brudzinski signsUnable to assess gait due to patient dizzinessPt with slow responses to questions, but normal orientation

Take a moment to consider your differential diagnosis

PICU Assessment/Plan:

1. Pt with R acute OM/mastoiditis/osteomyelitis by head CT• s/p myringotomy and PET placement on night of admission

by ENT; Cultures sent• Pt started on Vancomycin, Cefotaxime, Flagyl IV• Floxin otic drops to R ear BID

2. Pt with R sigmoid sinus thrombosis by CT head on DOA• MRI/MRV was ordered for hospital day #1• IV Abx started at meningitic dose as could not r/o meningitis• Continue to c/o dizziness intracranial process (increased

ICP from thrombosis) vs ear process as explanation• IVF at 2/3XM

3. Pt with transaminitis • Hepatitis panels sent• RUQ ultrasound was ordered

MRI

MRI

MRV

Hospital Course:

• MRI/MRV showed acute R sigmoid sinus thrombosis and transverse sinus thrombosis; R otomastoiditis with adjacent thickening and enhancement; no e/o extra-axial (epidural) fluid collection/abscess • Pt was started on Lovenox on HD #1 for thrombosis. Patient continued to have neurological findings of increased ICP with dizziness, L lateral gaze palsy, worsening visual acuity with decreased color perception, and unchanged optic disc edema. Started on Decadron on HD #3. Lovenox was then discontinued on HD#5 as plan was for therapeutic LP at this time to decrease ICP, but parents would not consent. Patient was then started on Diamox per Optho recs.

Hospital Course:

• Pt remained on IV Abx Vancomycin, Cefotaxime, and Flagyl. ID was consulted and recommended treatment for 6 weeks. PPD was placed and was negative. Fluid Cultures from R ear grew out 1+ coag negative Staph and 2+ microaerophilic Strep; Negative AFB smear

• Abdominal US was normal. Hepatitis A, B, and C titers were negative; EBV and CMV IgM levels were negative. AST and ALT levels decreased to 42 and 205, respectively, by HD#10

• Thrombophilia work-up was initiated including: ANA, antiphospolipid Ab, Factor V Leiden, Antithrombin III, Prot C, Prot S, and prothrombin III mutation. He was found to be a heterozygote for G20210A Prothrombin mutation; Lovenox was restarted while on the ward.

Hospital Course:

•On HD#10, pt with microscopic hematuria and flank pain. Abdominal US done, showing b/l stones. Renal service signed on. CT A/P done on HD#11 showing R hydronephrosis with 10 mm stone in inferior collecting system and 3.3 mm stone in proximal ureter; L kidney with moderate renal pelvis dilation, 8.5 mm stone in lower collecting system

Otogenic Intracranial Complications: •Otitis media (acute > chronic) can cause a variety of intracranial complications, although their incidence has been dramatically reduced with the use of antibiotics.

•They include: meningitis, extradural abscess, brain abscess, subdural abscess (empyema), sigmoid sinus thrombosis, thrombophlebitis, and otitis hydrocephalus.

•Incidence of complications is low in the antibiotic era (0.36%).

Otogenic Intracranial Complications:

In a retrospective chart review by Migirov et al, 28 patients developed a complication out of 7792 patients admitted for OM over 18 year study period

•Meningitis 46%, brain abscess 21%, epidural abscess 18% were most common•Underlying cholesteatoma assoc with thrombosis and abscess•Meningitis had equal frequency in adults and children•Brain abscess 3x more common in adults•Epidural abscess 2x more common in children•High morbidity rate (71%) related to hearing impairment for patients who recovered from otogenic complications

Otitic Hydrocephalus:

• In the case presentation, the patient was unsuccessfully treated for acute OM, which progressed to mastoiditis and osteomyelitis, with the further complication of R sigmoid and transverse sinus thrombosis.

•He also had signs/symptoms of increased ICP, including papilledema, headache, gaze palsy, and decreasing visual acuity and color perception.

•These signs of increased ICP can be explained by otitic hydrocephalus a non-obstructive hydrocephalus that does not demonstrate ventricular dilation that occurs as a result of decreased venous return secondary to cerebral venous thrombosis.

Cerebral Venous Sinus Thrombosis:

• In general, the incidence of cerebral venous sinus thrombosis is very low in children (0.67 per 100,000 children/yr)

•In children, CBST is most commonly associated with regional infections (OM or mastoiditis) and chronic systemic illness (leukemia or its treatment, sickle cell)

•According to De Schryver et al, who studied the long-term neuropsychological sequelae in 12 survivors of CBST, all children had average or high intelligence scores.

•One had impairment of skilled movement•2 had mild cognitive deficits (difficulty with written language; decreased attention)•The group concluded that children had a fair prognosis, although mild cognitive deficits can occur

Role of Anticoagulation for Sinus Thrombosis?

• It is generally accepted that sigmoid sinus thrombosis occurring as a complication of OM is managed with antibiotics and possible surgical drainage

•Literature regarding the recommendations for anticoagulation in relation to SST is from neurology and hematology patients, who often have underlying trauma, neoplasm, autoimmune DO, hypercoaguable state, or surgical intervention that influences this indication

•Anti-coagulation is considered when there is concern for embolization, venous infarction, or persistent septic thrombophlebitis.

•Potential risks of anticoagulation include bleeding, drug interactions, thrombocytopenia, osteoporosis, and hemorrhagic skin necrosis.

Role of Anticoagulation for Sinus Thrombosis?

In a retrospective review of 9 patients with otogenic SST, Bradley et al found that all patients were treated with broad spectrum antibiotics, 5 were anticoagulated with LMWH, and 1 with heparin-coumadin.

•HA, otalgia, otorrhea, and imbalance were more common in non-anticoagulated group at 6 mo.•They concluded that thrombus confined to sigmoid sinus did not necessarily require anticoagulation.•Criteria to consider use of anticoagulation: e/o thrombus progression, thrombus extension to adjacent sites at presentation, neurological changes, persistent fevers, embolic events.

Prothrombin Mutation:

•Pt is positive for one copy of the G20210A (prothrombin/factorII) mutation

•Per lab report, heterozygotes for this mutation are at elevated risk for venous thrombosis. This mutation is the 2nd most common inherited risk factor for thrombosis. Individuals who have one copy of the mutation are 3-6 fold increased risk for thrombosis. Other family members may also be carriers, and should consider genetic counseling and DNA testing to determine their status.

•Studies have shown a higher prevalence of prothrombin G20210A mutation in patients with cerebral vein thrombosis than healthy controls (OR 5.7-10.2)

References:

• Bradley DT, Hashisaki GT, Mason JC. Otogenic sigmoid sinus thrombosis: what is the role of anticoagulation? Laryngoscope. 2002 Oct;112(10):1726-9.

•De Schryver EL, Blom I, Braun KP, Kappelle LJ, Rinkel GJ, Peters AC, Jennekens-Schinkel A.

Long-term prognosis of cerebral venous sinus thrombosis in childhood. Dev Med Child Neurol. 2004 Aug;46(8):514-9.

•Migirov L, Duvdevani S, Kronenberg J. Otogenic intracranial complications: a review of 28 cases. Acta Otolaryngol. 2005 Aug;125(8):819-22.

References:

•Reuner KH, Ruf A, Grau A, Rickmann H, Stolz E, Juttler E, Druschky KF, Patscheke H.

Prothrombin gene G20210-->A transition is a risk factor for cerebral venous thrombosis.Stroke. 1998 Sep;29(9):1765-9.

•Sztriha LK, Voros E, Vecsei L. Endovascular thrombolytic treatment of extensive dural sinus thrombosis in a heterozygous carrier of prothrombin gene G20210A mutation. Eur J Neurol. 2004 Mar;11(3):214-5.

•Villa G, Lattere M, Rossi A, Di Pietro P. Acute onset of abducens nerve palsy in a child with prior history of otitis media: a misleading sign of Gradenigo syndrome.Brain Dev. 2005 Mar;27(2):155-9.