The Diagnosis of

SUBARACHNOIDHEMORRHAGE

Rob Hall

PGY2 Emergency Medicine

January 10th, 2002

SubarachnoidHEMORRHAGE

OBJECTIVESWhat does the Literature Say?

• What is the sensitivity of CT?

• When should the LP be done?

• What is a positive LP?

• Should we be using spectophotometry?

• Does a -ve CT and -ve LP rule out SAH?

• Is lumbar puncture without CT safe?

The Diagnosis of SUBARACHNOID HEMORRHAGE

•WHY?• Misdiagnosis

• Mortality

• Angiography

• Literature

SENSIVITITY OF CT

L ite ra tu re R eview o f3 rd G en era tion C T scan n ers

S id m an 1 9 9 6 S am es 1 9 9 6

van d er W ee 1 9 9 5 M org en s te rn 1 9 9 8

K asse l 1 9 9 0

Reading Literature on CT and SAH

• Generation

• Technique

• Radiologist

• Time

• Prospective

• Spectrum Bias

SPECTRUM BIAS

• POSITIVE CT NEUROSURG

WARD

• POSITIVE CT EMERG PT (R/O SAH)

TIMING OF CT:Kassel 1990

Cooperative Aneurysm Study

0102030405060708090

100

day 0 day 1 day 2 day 3 day 4 day 5

Sensitivity of CT

Sensitivity of CT

• Sidman 1996– Retrospective

– Sensitivity 100% < 12hrs

• Sames 1996– Retrospective

– Sensitivity 93% < 24hrs

• SPECTRUM BIAS

• IGNORE RESULTS

van der Wee 1995Journal of Neurology, Neurosurgery, and Psychiatry

• Prospective, N=175

• All <12hrs with SUDDEN ONSET H/A

• 3rd generation CT done < 12hrs

• Neuroradiologist + 2 general radiologists

• Diagnosis of SAH in -ve CT – LP > 12 hrs– Xanthochromia by spectophotometry

Van der Wee 1995

• CT +ve in 117/175 ---->LP +ve in 2/58

• Sensitivity < 12 hrs 98% (94.0 - 99.8)

• Comments– probably the best study available– good diagnosis of SAH in CT -ve group– rate of SAH 68% (?spectrum bias)– note CI as low as 94%– note who read the films

Morgenstern 1998Annals of Emergency Medicine

• Prospective, N = 107

• Spectrum: “worst headache ever”

• Only 107 enrolled of eligible 170

• 3rd generation CT

• 2 Neuroradiologists

• Diagnosis of SAH in -ve CT questionable

Morgenstern 1998:Annals of Emergency Medicine

• Diagnosis of SAH in CT -ve patients:

• rbcs > 1000 in 1st tube and no decrease of 25% w.r.t. 3rd tube PLUS one of ……– visual xanthochromia– spec xanthocrhomia– positive d-dimer

Morgenstern 1998:Annals of Emergency Medicine

• Negative Predictive Value Overall

– 97.5% (CI 91.2 - 99.7%)

• Sensitivity < 24hrs

– 93% (no confidence interval)

Morgenstern 1998:Annals of Emergency Medicine

• Only 107/170 enrolled• 10% refused LP• 25% of LPs < 12hrs• Questionable

definition of +ve LP – 20 patients with +ve

spec defined as NO SAH, but no problems at 2yr follow up

• What if they missed even ONE patient < 24hrs

– 14/15 = 93.3%

– 13/15 = 86.7%

SUMMARY ON CT AND SAH

• TRUE sensitivity UNKNOWN

• EARLIER is BETTER• PGY2 versus NEURORAD• BEST estimate of sensitivity

– 0-24hrs 95%

– 24-48hrs 85%

– 48-72% 75%

• TO RULE OUT SAH, A LUMBAR PUNCTURE IS REQUIRED AFTER A NEGATIVE CT HEAD

LUMBAR PUNCTUREPathophysiology

• RBCs passively lysed and oxidized to OXYHEMOGLOBIN – detectible as early as 2 hrs (Barrows 1955)

• Oxyhemoblobin is actively converted to BILIRUBIN by hemoxidase enzyme found in choriod plexus and leptomeninges – bilirubin present by 6hrs (Barrows 1955)– max hemoxidase activity by 12hrs (Roost 1972)

What is Xanthochromia?

• The change in coloration of CSF

• Due to oxyhemoblobin, bilirubin, or methemoglobin

• BUT ----------> detected by VISION or SPECTOPHOTOMETRY?

What can cause a false +ve LP for Xanthochromia?

• Jaundice

• Rifampin

• Previous traumatic LP

• Traumatic tap -----> CSF sits in lab > few hours

TIMING OF LUMBAR PUNCTURE

• Barrows 1955: oxyHb in 2hrs, bili in 6hrs

• Roost 1972: hemoxidase max at 12hrs

• Where does the 12hr delay come from?– Vermeulen 1989– Walton 1956

TIMING OF LP:Vermeulen 1989

Journal of Neurology, Neurosurgery, and Psychiatry

• Retrospective review of 111 patients with SAH diagnosed by blood on CT

• ALL lumbar punctures done > 12hrs

• Xanthochromia detected by spectophotometry

• DOES NOT LOOK AT CT -ve PATIENTS

• DOES NOT LOOK AT LP < 12hrs

TIMING OF LP:Vermeulen 1989

Journal of Neurology, Neurosurgery, and Psychiatry

• TIMING SENSITIVITY– 12hrs - 2weeks 100%

– 2 - 3 weeks 91%

– 3 - 4 weeks 71%

TIMING OF LP:Walton 1956

Subarachnoid Hemorrhage. E & S Livingstone LTD.

• Retrospective look at 256 cases of SAH

• How was SAH diagnosed?

• Xanthochromia detected visually.

• Some results missing

TIMING OF XANTHOCHROMIA:Walton 1956

0102030405060708090

100

0-2hr 2-4hr 4-6hr 6-12hr 12-24hr

>24hr

XanthochromiaBlood

What is a positive LP?

• RED BLOOD CELL COUNT?– LEAK versus MAJOR HEMORRHAGE

– NO literature (Tourtelloote 1964 - none < 1000/mm3)

– How can you tell from traumatic tap?

SAH versus Traumatic LP

• Opinion, crenated rbcs, erythrophages, d-dimer unreliable

• Repeat LP only helpful if clear

• FOUR tube method UNRELIABLE and does not detect SAH + traumatic tap– Vandermeulen 1996– Buruma 1981

SAH versus Traumatic LP

• XANTHOCHROMIA is the only way to reliably distinguish between SAH and traumatic LP

So how should we detect Xanthochromia?

• Visual detection?– ? Poor

sensitivity

• Spectophoto-metry?– ? Poor

specificity

LITERATURE REVIEW:Visual versus spectophotometric

detection of Xanthochromia

X an th och rom ia

S od ers trom 1 9 7 7 M acD on a ld 1 9 8 8

V isu a l d e tec tionIN S E N S ITIV E

M org en s te rn 1 9 9 8 F oo t 2 0 0 1

S p ec top h o tom etryN O N S P E C IF IC

L ite ra tu re R eview

Visual detection of Xanthochromiais INSENSITIVE:

Soderstrom 1977:

• N=32

• 12 ICH, 12 SDH, 8 SAH

• Dx by CT + OR, angiogram, or autopsy

• Vision detected 16 of 32 cases of xanthochromia on spectophotometry– Sensitivity 50%– ?when spec done

Visual detection of Xanthochromiais INSENSITIVE:

MacDonald 1988

• Retrospective review of 61 patients with angiographically proven aneurysms who had LP done

• 28/61 had xanthochromia by vision for sensitivity of 46%

• 13 LPs were done < 24hrs (any < 12hrs?)– exlcude LP < 24hrs….28/48 ------> 67%

Spectophotometry is NONSPECIFIC: Morgenstern 1998

• 18 patients with +ve spectophotometry who didn’t meet their criteria for +ve LP

• Followed for 2 years with no problems

Spectophotometry is NONSPECIFIC: Foot 2001

• Retrospective study looking at the use/results of CT and LP in ED r/o SAH

• +ve Xanthochromia = > 0.02 absorbance units at 415nm

• 21 CT-ve, Xanthochromia +ve– 19 angiograms normal– 2 aneurysms

Xanthochromia

• Cruikshank 2001– “A prospective study of LP on CT -ve patients

undergoing r/o SAH to compare visual and spectophotometric detection of xanthochromia has never been done”.

UNPUBLISHED DATA:J. Croft, G. Sutherland, A. Gibb

• ALL CSF samples from calgary ED over a 14 months period

• R/O SAH in 110• Recorded

– rbcs count– visual xanthochromia– spectophotometry absorption peak– spectophotometry optical density criteria

LOCAL DATAN Blood

(<10)Visual Spec Peak Spec O.D.

CriteriaSAHdx

71 - - - 20+,51- 0

11 + - - 5+,6- 0

4 + + Hb/Bili 4+ 4

14 +/- 3+11-

Hb 12+,2- 0

9 +/- 1+8-

Bili 9+ 1

Optical Density Criteria

• SAH No SAH• OD+ve 5 45 • OD-ve 0 60

• Sensitivity– 5/5 = 100%

• Specificity– 60/105 = 57%

• NPV– 60/60 = 100%

• PPV– 5/50 = 10%

Visual Detection

• SAH NO SAH• Visual 5 4

xantho• No visual 0 101

xantho

• Sensitivity– 5/5 = 100%

• Specificity– 101/105 = 96%

• NPV– 101/101= 100%

• PPV– 5/9 = 56%

LOCAL DATA

• CONCLUSIONS– Visual Xanthochromia

did NOT miss any SAH

– Spectophotometry was not specific for SAH

• COMMENTS– NO gold standard for

SAH diagnosis

– NO long term f/u to prove that SAH wasn’t missed

– Small numbers

– One missed SAH ---> 5/5 to 5/6 ---> 83%

Summary on Lumbar Puncture

• LP isn’t perfect either

• LP should be done > 10 - 12 hrs (spectrum)

• Xanthochromia is only way to reliably distinguish SAH from traumatic tap

• Literature is unclear whether visual or spectophotometric detection of xanthochromia is superior

Does a negative CT and LP rule out SAH?

• Evidence this does NOT occur….– van Ginn1988: 71 patients

followed to 3 years, no problems

– Markus 1991: 16 patients followed to 20 months, no problems

– Harling 1994: 14 pts followed 18-30 mo, no problems

• Evidence that this DOES occur…..– Nine case reports

in literature

– Some had LP < 12hrs

– Some used visual, some used spec

PERSPECTIVE ON POSSIBLE MISSED DIAGNOSIS RATE

2 0 0 ,0 0 0 E D V is its in C a lg ary p er year

L P 5 0 % sen s it ive5 m issed S A H

5 /2 0 0 0 = 0 .2 5 %

L P 9 0 % sen s it ive1 m issed S A H

1 /2 0 0 0 = 0 .0 5 %

C T 9 5 % sen s it iveC T m isses 1 0

R /O S A H in 1 /1 0 H ead ach es2 0 0

H ead ach e 1 % o f E D vis its2 ,0 0 0

Does a -ve CT and LP rule out SAH?

• If LP done > 12hrs --------->

YES• Risk of angiogram > chance of

SAH with -ve CT and LP

DIAGNOSTIC ALGORITHM

R /O S u b arach n o id H em orrh ag e

D iag n os is = S A H

V isu a l X an th och rom ia

V ery s tron gc lin ica l su sp ic ion

con su lt N S xcon s id er an g io

R u led ou t S A HD /C h om e

N o N S x con su lt

N o V isu a l X an th och rom ia

C T h eadL P > 1 0 - 1 2 h rs

LP without CT

• Why wouldn’t you want to do this?– Risk of herniation– CT provides much additional information – How do you know this is a SAH?– How do you know there aren’t complications of

the SAH that increase the risk of herniation

LP without CT

• Herniation– Mass effect from hematoma or hydrocephalus

with a SAH, or a different dx (ICH, tumor, etc)

• Normal LOC and NO focal signs – Hillman 1986: 2.2% acute deterioration after

LP; 10% had hematomas associated with SAH– Duffy 1982: 12% with proven SAH (spectrum

bias) deteriorated while needle in back

LP without CT

• Additional information on CT– dx of non-aneurysmal causes: AVM, tumor,

ICH, hypertensive hem, perimesencephalic– look for acute complications: hydrocepahlus,

ICH, intraventricular blood requiring a drain– amount of bleeding is prognostic– bleeding on CT can help localize aneurysm and

identify multiple aneurysms

LP without CT

• How do you know that the acute H/A isn’t due to an intraparenchymal hemorrhage?– Van Gijn 1980: retrospective review of all

patients with initial dx as SAH – 15% had intraparenchymal hemorrhage– 8% were in posterior fossa

LP without CT

• Summary– There is NO literature supporting LP without

CT (Schull 1999: model only)– There is SOME literature documenting the risks – Risks and lack of additional information are not

justified in a tertiary care center– May be reasonable in periphery if no access to

CT although transfer in for CT is preferable