五院區視訊會議2011-03-23

基隆院區R3 許凱翔 / MA 蔡明翰 / MA 江玲美

Background

• A 18-year-old girl presented to ED

with 3-day history of headache,

followed by consciousness disturbance

Background

• Weight 43kg , Height 155cm

• Previously healthy, except ASD/VSD post OP

• Work in a salon

• A dog as pet

• Pigeons in the neighborhood

History

ED-2

• Fever 39.7℃ , with neck pain / sorethroat / weakness

• Visit other hospital, treated as common cold

-1

History

-2 -1 ED

• Neck pain

• Dizziness

• sorethroat/ myalgia

• Neck rigidity

• Kernig sign positive

• No Brudzinski sign

History

-2

• severe headache / neck pain, with vomiting in the morning

• Disoriented

• Fever !

-1 ED

History

-2 -1Aseptic meningitis ?

➡Give Ceftriaxone➡ Admission

ED

open pressure:140 mmH20close pressure:110 mmH20

History

-2 -1 Admission

Influenza :negative

CXR D1

BT 37.4℃ ,P 136/min ,R 24/min ,BP 89/43mmHg

Hospital course :PICU

SHOCK E3V3-4M6

➡ Fluid challenge  ➡ Dopamine (Max: 10mcg/kg/min)

Septic shock➡ Vancomycin / Ceftriaxone➡ Tamiflu

rapidly deterioration at ward→ PICU

Hospital course :PICU

1 2 3

DC Dopamine

Consciousness regain

1st EEG : normal

fever subsided

MSSA Sepsis

Hospital course :PICU

1 2 3 4

Seizure 5min : rigid, spastic, trismus and eye deviation (left): lose of consciousness E1V2M2

➡ response to Valium 10mg➡ loading Dilantin

➡ Brain CT➡ add Acyclovir

fever

Hospital course :Brain CT

Hospital course :PICU

1 2 3 4VancomycinCeftriaxone

TamifluAcyclovir

Hospital course : study

★ HSV-1 IgG       Positive      19.7 /1. 0  ★ HSV-2 IgG       Negative      0.5 /1.0   ★ HSV IgM       Positive       1.4 /1.0    

✓ CSF culture : no growth✓ CSF Cryptococcus : negative✓ CSF Mycobacterium : negative

serum

Hospital course :PICU

1 2 3 4 5 6 7 8 9 10 11

fever subsided

VancomycinCeftriaxone

TamifluAcyclovir

Oxacillin

B/CΘ2D Echo: negative

Day5 Day8

MRI Day9

T2w T2 flair DWI

MRI Day9

T1w +C

MRI Day9T1w +C

MRI Day9

★ Pontine lesion with irregular marginal contrast enhancement, with multiple smaller satellite lesions in the left frontal, right frontal corona radiata, and right parietal regions, favoring abscesses (probably complicated from meningitis or systemic origin)

1st vs 2nd CSF

1 3 5 7 9 11 12seizure

HSV-DNA csf : Negative

HSV-1 IgG csf : Negative HSV-2 IgG csf : Negative HSV-IgM csf   : Negative

Virus culture csf: Negative

post Acyclovir 8 days

HSV serology

★ HSV-1 IgG   19.7 /1. 0  ★ HSV-2 IgG   Negative   ★ HSV IgM    1.4 /1.0

25.5 /1.0 Negative 1.2 /1.0

18-day

throat viral isolation :negative

Neurologic

1 2 3 5 6 7 8 10 119

1st EEG : normal2nd EEG : Diffuse slow activity

12

13 14 15 16 17 18 19

3rd EEG : Focal epileptiform activity on left temporal area

Brain CT

1st LP 2nd LP

1st MRI

20 21 22 25

2nd MRI

4

E1V2M2

21-day Acyclovir(day4-25)

E3V2M4

E4V2M4

2nd MRI Day25

T2 flair T2 TSE flair

2nd MRI Day25

T1w +C

2nd MRI Day25

2nd

1st

T1w +C

2nd MRI Day25

Hospital course

1 4 10 119 12 16 25 26 33

Vancomycin

CeftriaxoneTamiflu

Acyclovir x21

Oxacillin

1st MRI 2nd MRICT

3rd EEG : Focal epileptiform activity on left temporal area

Dilantin Oxcarbazepine

RehabilitationWard AAD

Dopamine E4V2M6

21

Ward

Diagnosis✤ Encephalitis with brain stem involvement,

suspected HSV-1 related✤ Pontine abscess with multiple microabscess✤ Septic shock, MSSA related

✤ seizure with Electroencephalogram showed cortical dysfunction and focal epileptiform activity on left temporal area

✤ electrolyte imbalance

✤ hypoalbuminemia

✤ thrombocytopenia

✤ upper gastrointestinal bleeding

✤ mild mitral regurgitation

Sequelae

๏ E4V2M6, weak muscle power

๏ bilateral hemiplegia

๏ groan , “PaPa”

๏ Insomnia

3 month later : EEG normal5 month later : DC Oxcarbazepine

HSV encephalitisDiscussion

SA abscess

Meningoencephalitis

HSV-1 encephalitis

✤ most common cause of fatal

sporadic encephalitis in the USA

✤ accounting for10%-20% of the

20,000 annual viral encephalitis

✤ 1/3 of all cases occurring in

children and adolescents

(1) fever is one of the most frequent features , and its absence should cast doubt on the diagnosis

(2) headache is present in up to 90%

(3) acute onset, usually less than a week

(4) in pre-PCR era, grey matter dysfunction was a dominant feature:

personality changes, confusion, and disorientation were present in

75% and seizures in 50%; focal neurological signs (hemiparesis) in

about a 1/3 of all patients

Mechanism of HSV entry into the brain?

(1) reactivation of the viral genome in the trigeminal ganglion, with resultant axonal spread via the trigeminal nerve into the frontal and temporal lobes(2) in-situ reactivation of the latent virus from CNS tissue(3) primary infection of the nervous system.

➡ Pathways for entry of HSV to the brain include both the olfactory and trigeminal nerves

Diagnosis :CSF

3

Diagnosis :CSF

‣ Pleocytosis, 80% > 50 WBC/cmm

‣ RBC seen in 75-80%

‣ Elevated protein levels 80-88% (median, 80mg/dl)

‣ Generally normal sugar

‣ HSV almost never grown

CSF findings helpful, not diagnostic

HSV encephalitis :

Diagnosis : Serology

3

HSV antigen can also be detected in CSF, but sensitivity and specificity is lower than PCR assays

Gold standard

Diagnosis : PCR

PCR of HSV DNA has provided a high degree of sensitivity (98%) and specificity (94%)

Culture ?  Viral culture of CSF is rarely positive in the early stages of infection and is only positive later in 4%-5%

of patients with brain biopsy-proven HSV encephalitis

✤ The EEG is universally (80%) abnormal and frequently shows slowing in the temporal and frontal regions.

✤ Classically, intermittent high voltage periodic slowing can be observed, but this pattern is often lacking.

✤ The EEG lacks specificity

Diagnosis : EEG

Diagnosis : Image

Temporal lobe abnormalities are considered strong evidence for herpes simplex encephalitis

Diagnosis : Image

CT scans of the brain have only 50% sensitivity early in the disease, and the presence of abnormalities is generally associated with severe damage and poor prognosis

CT ?

MRI is more sensitivereveals abnormalities of the temporal lobes in 89% of cases confirmed by CSF HSV PCR

MRI of HSV encephalitis

3

DWIdiffusion-weighted imaging

MRI of HSV encephalitis

PONS ?

MEDLINE search from 1970 to December 2009

✴ Only 24 cases to include in this review✴ The mean age was 41.4 years (range 18–71) ✴ 19 cases specified the HSV strain :HSV-1 in 15 cases (79%) , HSV-2 in 4 cases (21%)✴ Immune-compromising conditions：5

our case

PONS ?

✤ Encephalitis limited to brainstem (midbrain, pons, and/or medulla) ： 7 (29%)✤ Both the brainstem and other areas of the brain were affected ： 17 (71%)

★9 patients (41%) died ; 6 of the patients who died did not receive acyclovir

★The mortality rate for patients who received acyclovir was 22% (2/9) compared to 75% (6/8) in patients not treated with acyclovir (p = 0.06) ★7 of the 13 (54%) surviving patients had chronic neurological impairments

Treatment

10mg/kg/dose Q8h

for 14-21 Days

Before loss of consciousnessWithin 24 hours of the onset of symptomsGlasgow Coma Scale score of 9 to 15

Acyclovir

Reduce mortality rate from 70% to 19%Nearly 2/3 of survivors will have neurologic deficits

Early

Corticosteroid ?

no proven benefit

HSE is occasionally complicated by severe, vasogenic cerebral edema with CT or MRI evidence of midline shift where high dose steroids may have a role

Is it a pontine abscess ?

Different thinking...

Uncommon location

Brain abscess

3

‣ Contiguous spread of infection from the oropharynx, middle ear, and paranasal sinuses : Streptococci (eg,

Streptococcus milleri group and viridian group streptococci)

‣ Brain trauma or neurosurgery : Staphylococcus aureus

‣ Hematogenous spread IE : Staphylococcus aureus or viridians group streptococcus GNB are in association with an intra-abdominal or GU source Osteomyelitis

‣ Opportunistic pathogens

Brain abscess: CSF ?

: the WBC and protein may be minimally elevated or normal, and the glucose level may be low: CSF cultures are rarely positive: Aspiration of the abscess is much more likely to establish a bacteriologic diagnosis.

CSF shows variable results

Differential diagnosis

HSV

★ Solitary brainstem abscesses account for only 0.5% of intracranial abscesses ★ pons being the most common site

What’s the final answer?

HSV encephalitis

MSSA brain

abscess

serum serology

clinical bacteremia

CSF

clinical

Uncommon image

HSV

3

THANKS

Prognosis

❖ Severe behavioral abnormalities and severe cognitive impairment are potentially chronic aspects.

❖ The most common residua are dysnomia and impaired new learning for both verbal and visual material, despite normal performances on a standard mental status examination