PROGNOSTIC FACTORS AFFECTING THE

FUNCTIONAL RECOVERY IN SPINAL

TUBERCULOSIS PATIENTS WITH NEUROLOGICAL

DEFICIT

BY

HARKEERAT SINGH SUKHDARSHAN SINGH

A dissertation submitted in fulfillment of the requirement for

the degree of Master of Orthopaedic Surgery

Kulliyyah of Medicine

International Islamic University Malaysia

OCTOBER 2019

ii

ABSTRACT

This study is aimed to determine the factors associated with the functional recovery in

spinal tuberculosis patients with neurology deficits. To assess clinical, biochemical and

radiological parametersin relation to the prognostic factors. This cross-sectional study

from July 2017 to June 2018, patients presenting to 3 hospitals in Sabah, with significant

neurology fulfilling the inclusion criteria were enrolled. Diagnosis of spinal

tuberculosis was determined either by clinical radiological factors and confirmed with

histopathology, microbacteriology and immunoassay. Patients with significant

neurology received standard treatment protocol according to the middle pathway

regime, receiving anti tuberculosis for the first 3 weeks and were subjected to surgery

if there were no improvement. Modified Barthel Index (MBI) was used to asses

functional outcome, scores were taken before and after treatment and with improvement

of 4 points or a total of more than 12 were considered as good outcome. After a year,

146 patients (65.1%) had good functional recovery and 78 patients had no significant

improvement. On univariate analysis, there was no significant correlation with age

(p>0.45), duration of symptoms (p>0.68), CRP (p>0.76), WCC (p>0.99), and presence

of soft tissue collection (p>0.21) with functional outcome. High ESR (p<0.008) and

thoracolumbar lesions are associated with a poor functional recovery (p<0.033). In

conclusion, higher ESR values, numbers of vertebrae involved, and thoracolumbar

lesions are associated with poor functional outcome in spinal tuberculosis patients.

iii

APPROVAL PAGE

I certify that I have supervised and read this study and that in my opinion, it conforms

to acceptable standards of scholarly presentation and is fully adequate, in scope and

quality, as a dissertation for the degree of Master of Orthopaedic Surgery

……………………………….

Zamzuri bin Zakaria

Supervisor

I certify that I have read this study and that in my opinion, it conforms to acceptable

standards of scholarly presentation and is fully adequate, in scope and quality, as a

thesis for the degree of Master of Orthopaedic Surgery.

……………………………….

Goh Kian Liang

Internal Examiner

This dissertation was submitted to the Department of Orthopaedic and is accepted as

a fulfillment of the requirements for the degree of Master of Orthopaedic Surgery

……………………………...

Mohd Shukrimi bin Awang

Head, Department of

Orthopaedics, Traumatology and

Rehabilitation

This dissertation was submitted to the Kulliyyah of Medicine and is accepted as a

fulfillment of the requirements for the degree of Master of Orthopaedic Surgery

………………………………

Azmi bin Md Nor

Dean, Kulliyyah of Medicine

iv

DECLARATION

I hereby declare that this thesis is the result of my own investigation, except where

otherwise stated. I also declare that it has not been previously or concurrently submitted

as a whole for any other degrees at IIUM or other institutions.

Harkeerat Singh Sukhdarshan Singh

Signature……………………. Date ……………………..

v

INTERNATIONAL ISLAMIC UNIVERSITY MALAYSIA

DECLARATION OF COPYRIGHT AND AFFIRMATION OF

FAIR USE OF UNPUBLISHED RESEARCH

PROGNOSTIC FACTORS AFFECTING THE FUNCTIONAL

RECOVERY IN SPINAL TUBERCULOSIS PATIENTS WITH

NEUROLOGICAL DEFICIT

I declare that the copyright holders of this dissertation are jointly owned by the

student and IIUM.

Copyright ©2019 Harkeerat Singh Sukhdarshan Singh and International Islamic University

Malaysia. All rights reserved.

No part of this unpublished research may be reproduced, stored in a retrieval system,

or transmitted, or transmitted, in any form or by any means, electronic, mechanical,

photocopying, recording or otherwise without prior written permission of the

copyright holder except as provided below.

1. Any material contained in or derived from this unpublished research may

be used by others in their writing with due acknowledgement.

2. IIUM or its library will have the right to make and transmit copies (print

or electronic) for institutional and academic purposes.

3. The IIUM library will have the right to make, store in a retrieval system

and supply copies of this unpublished research if requested by other

universities and research libraries.

By signing this form, I acknowledged that I have read and understand the IIUM

Intellectual Property Right and Commercialization policy.

Affirmed by Harkeerat Singh Sukhdarshan Singh

……..……..…………… …………………..

Signature Date

vi

ACKNOWLEDGEMENTS

First and foremost, I would like to thank my supervisor Associate Professor Dr Zamzuri

Bin Zakaria for accepting me as his mentee. He has been great role model and educators

who have been helping me throughout the completion of this thesis. This thesis would

not be completed without his guidance.

I am grateful to have excellent lecturers and specialists who are dedicated in

teaching and providing guidance throughout the completion of this thesis. I would like

to take this opportunity to thank all specialists and colleagues as well as all the staffs in

the Department of Orthopedic, Traumatology and Rehabilitation, in Queen Elizabeth

Hospital, Sabah and IIUM Medical Center, for their contribution, participation and

helpful assistance. My appreciation is also for all the patients who participated in this

study.

Special thanks to my family members for their support and encouragement.

Most importantly, thanks to my colleagues and supporting staffs of the Department of

Orthopedics and Traumatology, IIUM.

Last but not least, I would like to send my regards and dedications to those who

have given me support and help, either directly or indirectly while I struggle to complete

this thesis.

vii

TABLE OF CONTENTS

Abstract .......................................................................................................................... ii Approval page ............................................................................................................... iii Declaration .................................................................................................................... iv Copyright Page ............................................................................................................... v

Acknowledgements ....................................................................................................... vi List of Tables ................................................................................................................ ix List of Figures ................................................................................................................ x

List of Abbreviations .................................................................................................... xi

CHAPTER ONE: INTRODUCTION ........................................................................ 1

1.1 Background of Study .................................................................................... 1 1.2 Objectives and Hypothesis ........................................................................... 3

1.2.1 General Objective............................................................................... 3

1.2.2 Specific Objective .............................................................................. 3

1.2.3 Hypothesis .......................................................................................... 4

CHAPTER TWO: LITERATURE REVIEW ........................................................... 4 2.1 Anatomy of The Spine ................................................................................. 4

2.1.1 Cervical Spine .................................................................................... 4

2.1.2 Thoracic Spine ................................................................................... 6

2.1.3 Lumbar Spine ..................................................................................... 7

2.1.4 Blood Supply of The Spine ................................................................ 8

2.2 Spinal Tuberculosis .................................................................................... 10

2.2.1 Pathophysiology ............................................................................... 10

2.2.2 Clinical Features............................................................................... 12

2.2.3 Investigations ................................................................................... 13

2.2.3.1 Blood Investigations .............................................................. 13

2.2.3.2 Tissue Sampling ..................................................................... 14

2.2.3.3 Imaging .................................................................................. 14

2.2.4 Management ..................................................................................... 16

2.2.4.1 Conservative Management ..................................................... 16

2.2.4.2 Surgical Management ............................................................ 17

2.2.5 Prognostic Factors ............................................................................ 19

2.2.6 Functional Outcome ......................................................................... 20

CHAPTER THREE: MATERIALS AND METHODS ......................................... 21 3.1 Study Design .............................................................................................. 21

3.2 Statistical Analysis ..................................................................................... 24

CHAPTER FOUR: RESULTS AND FINDINGS ................................................... 25 4.1 Sample Population .................................................................................... 25

4.2 Dermographic Factors ................................................................................ 25

4.3 Duration of Symptoms and Functional Recovery of Spinal Tuberculosis

Patients ...................................................................................................... 28

4.4 Patients Age and Functional Recovery of Spinal Tuberculosis Patients ... 28

viii

4.5 Inflammatory Markers and Functional Recovery of Spinal Tuberculosis

Patients ...................................................................................................... 29

4.6 Radiological Findings And Functional Outcome Of Spinal Tuberculosis

Patients ...................................................................................................... 30

4.6 Multivariate Analysis ................................................................................. 33

CHAPTER FIVE: DISCUSSION AND CONCLUSION ....................................... 34

5.1 Discussion .................................................................................................. 34

5.2 Limitation .................................................................................................. 39

5.3 Conclusion .................................................................................................. 39

REFERENCES ........................................................................................................... 40

APPENDIX I: PATIENT INFORMATION SHEET AND INFORMED

CONSENT FORM (ENGLISH) ............................................................................... 44

APPENDIX II: PATIENT INFORMATION SHEET AND INFORMED

CONSENT FORM (MALAY VERSION) ............................................................... 49

APPENDIX III: DATA COLLECTION FORM .................................................... 54

ix

LIST OF TABLES

Table 4.1 Demographic data of patients 27

Table 4.2 Associated factors with Functional recovery in mean and

standard deviation (n=224) 31

Table 4.3 Table 4.3 Associated factors with Functional recovery by

Simple Logistic Regression (n=224) 32

Table 4.4 Difference in Barthel index and Frankel scoring from baseline

& at final follow-up 33

Table 4.5 Associated factors with Functional Outcome by Multiple

Logistic Regression (n=224) 34

x

LIST OF FIGURES

Figure 2.1 Diagrammatic presentation of the typical cervical

vertebra 6

Figure 2.2 Diagrammatic presentation of the typical thoracic

vertebra 7

Figure 2.3 Diagrammatic presentation of the typical lumbar

vertebra 8

Figure 2.4 Diagrammatic presentation of the blood supply to the

spine 10

Figure 2.5 Diagrammatic presentation of the sites of vertebral

tuberculosis 12

Figure 2.6 Spine at risk as described by (Rajasekaran et al, 2001) 18

Figure 4.1 Flow chart of study protocol 25

Figure 4.2 Distribution of patients based on sex 26

Figure 4.3 Number of patients and age grouping 27

xi

LIST OF ABBREVIATIONS

ADL Activities of daily living

CRP C-Reactive Protein

CT Computerized Tomography

DNA Deoxyribonucleic Acid

ESR Erythrocyte Sedimentation Rate

HQE Hospital Queen Elizabeth

MDI Modified Barthel Index

MRI Magnetic Resonance Imaging

PCR Polymerase Chain Reaction

ROM Range of Movement

TB Tuberculosis

WCC White Cell Count

1

CHAPTER ONE

INTRODUCTION

1.1 BACKGROUND OF STUDY

Spinal tuberculosis has been on the rise due to reemergence of immunocompromised

populations. Majority of the countries involved are developing countries especially

patients with postive HIV (with CD4+ of 50 to 200). Extrapulmonary tuberculosis

accounts for 15% of the total tuberculosis patients and spinal tuberculosis represents

5% of the total number of tuberculosis patient. The most common site of involvement

in the spine is the thoracic spine.

The causative organism for tuberculosis is Mycobacterium Tuberculosis, it is an

acid-fast bacilli which thrives in an aerobic environment. It has a very low tendency to

adhere to implants and does not form biofilms, thus allowing implants to be used safely

in spinal tuberculosis.

The pathogenesis of spinal tuberculosis is commonly due to a secondary

infection, the primary lesion is normally seen in the lung, gastrointestinal tract or the

genitourinary tract. The bacilli then travel via hematogenous spread to the vertebrae

(presence of valveless venous plexus) and seed over the narrow hair pin metaphyseal

vessels of the anterior vertebral body. They remain dormant and express an delayed

hypersensitivity immune response which will trigger the inflammatory cascade and for

a granulomatous lesion with bone destruction and central casseation. It then spreads

beneath the anterior longitudinal ligament as it is the pathway with the least resistance

and causes contiguous and non-contiguous multilevel destruction. Spinal tuberculosis

is also notorious in forming huge psoas abscesses. Intervertebral discs being relatively

2

avascular are preserved until late disease. The bony destruction will result in collapse

and kyphosis, anterior vertebral collapse results in sharp kyphosis aka “gibbus”

increasing the risk of cord compression.

Potts disease introduced by Sir Percival Pott in 1979 is defined as paraplegia

secondary to spinal tuberculosis. Its etiology can be further divided into early and late

onset of paralysis. In early paralysis it can be due to the mechanical pressure exerted by

the abscess, caseous granuloma or the sequestra, or spinal artery thrombosis or

tuberculous arachnoiditis. Late onset paralysis is commonly due to increasing

deformity, reactivation of tuberculosis or the fibrosis of the dura.

Tuberculosis may affect the vertebrae in many locations, however three

common patterns have been described being, peridiscal, central and anterior. Peridiscal

being the most common form occurs adjacent to the vertebral endplate and spreads

around a single intervertebral disc as the subligamentous spread occurs. Central occurs

in the middle of the vertebral body which leads to vertebral collapse and kyphotic

deformity. Anterior lesions begin as tuberculosis spreads beneath the anterior

longitudinal ligament which may be seen a scalloping of the anterior vertebral bodies.

Common investigations performed are the Mantoux/ Tuberculin skin test, ESR, CRP,

chest Xrays, whole spine Xrays, CT and MRI scans. Mantoux test is an unreliable test

as patients from endemic areas with subclinical exposures or previous BCG

vaccinations may elicit a false positive result. Two thirds of patients with spinal

tuberculosis may present with chest xray findings. Literature has shown ESR to be

mildly elevated with 25% of patients presenting within normal levels. The gold standard

investigation for spinal tuberculosis is tissue biopsy which may be performed

percutaneously, CT guided or via the open technique.

3

Biopsy samples are sent for histopathological analysis which reveal a

granulomatous lesion with surrounding multinucleated giant cells and central necrosis.

Ziehl Neelson staining for acid fast bacilli may also be performed but may only be

positive in 50% of patients. Another investigation is to perform a Tuberculosis PCR

(polymerase chain reaction) which amplifies DNA of the Mycobacterium for

identification, this test is quick and highly sensitive with a PPV of 95-98% in smear

positive patients. Mycobacterium tuberculosis is cultured in Lowenstine-Jensen

medium typically yielding positive growth in 6-10-week period.

Treatment of spinal tuberculosis comprise of three main goals, to eradicated

disease, to prevent and correct deformity and to prevent neurological insult. Anti-

tuberculous therapy remains the mainstay of treatment in tuberculosis supplemented

with surgery and/or orthosis. Recovery is not easily predictable and very variable, some

recover completely but some are left with debilitating weakness. We aim to investigate

and look into potentially identify clinical, biochemical and radiological factors that

might affect functional outcome recovery in spinal tuberculosis patients.

1.2 OBJECTIVES AND HYPOTHESIS

1.2.1 General Objectives

To evaluate the relationship of clinical parameters and functional recovery in patients

treated as spinal tuberculosis patients with neurology.

1.2.2 Specific Objectives

Specific objectives of this study are:

1. To compare the duration of symptoms with the functional recovery in patients

treated as spine tuberculosis with neurology.

4

2. To identify correlations of patients age and functional recovery in patients

treated as spine tuberculosis with neurology.

3. To analyze the correlation of inflammatory markers (white cell count, ESR &

CRP) with the functional recovery in patients treated as spine tuberculosis with

neurology.

4. To study the relationship of radiological findings (Xray & MRI determining

levels of involved vetebrae, soft tissue or spinal extension of the tuberculous

abscess) with the functional recovery in patients treated as spine tuberculosis

with neurology.

1.2.3 Hypothesis

There is a positive correlation between the clinical presentation of spinal tuberculosis

patients and improvement in functional recovery in patients treated as spine tuberculosis

with neurology.

5

CHAPTER TWO

LITERATURE REVIEW

2.1 ANATOMY OF THE SPINE

2.1.1 Cervical spine

The cervical spine consists of seven vertebrae, among which there are typical vertebrae

(C3 - C6) and the atypical vertebrae (C1, C2, and C7). The typical cervical vertebrae

have a broad kidney shaped body that is similar or smaller than the size of its vertebral

foramen and is concave in its anterior surface. There are also the presences of uncus

process a posterolateral lip projection of the lateral edge. Typical cervical spine pedicles

are attached to the body and has a foramen from its expansion with the cervical

transverse process which have tubercles over their far lateral lips. The transverse

process foramen is perforated by the vertebral artery with its accompanying sympathetic

nerve fibers. The vertebral foramen is triangular in cross section bounded by the lamina,

the lamina from its articular processes at its junction with the pedicle. The facets of the

upper cervical spine face upwards and backwards, and the lower ones face downwards

and forwards. Lastly the spinous process in the cervical spine is bifid. The intervetebral

discs are also thick compared to the size of the cervical body.

6

Figure 2.1 Diagrammatic presentation of the typical cervical vertebra

2.1.2 Thoracic Spine

Thoracic vertebra presents with two costal facets for articulation with the ribs. The body

of the thoracic vertebra is heart shaped with the spinal canal circular in shape. The

pedicles project from the upper half of the body and its upper border in line with the

upper surface of the body. The lamina is flat and slope downwards and backwards, the

facets are facing laterally and backwards, with circular articular surfaces to allow some

amount of rotation. The spinous processes of thoracic vertebrae slope downwards up to

T7 and begin to progressively level out by T12. Thoracic transverse processes project

backwards and laterally and articulate with the adjacent ribs.

7

Figure 2.2 Diagrammatic presentation of the typical thoracic vertebra

2.1.3 Lumbar Spine

Lumbar spine bodies are kidney shaped and increase in width as they progress distally.

The spinal canal is triangular in cross section. Pedicles are attached to the upper half of

the body simmilar to the thoracic spine. The articular processes face downwards and

laterally the transverse process of L4 is the longest among the lumbar spine with a

quadrangular spinous process. The presence of mamillary bodies as posterior

projections of the superior articular process. Lumbar spine has massive intervetebral

discs among the other regions.

8

Figure 2.3 Diagrammatic presentation of the typical lumbar vertebra

2.1.4 Blood Supply of The Spine

Spinal blood supply was first studied by Albert Wojciech Adamkiewicz a Polish

pathologist, in 1881. Blood supply to the spinal cord is mainly via one anterior median

spinal artery and two posterior spinal arteries. The anterior spinal artery is formed by

the two vertebral arteries at the foramen magnum supplies 85% of blood supply to the

cord throughout its length in the anterior median fissure. The two posterior vertebral

arteries originate from the two posterior inferior cerebellar arteries at the level of

foramen magnum and lie on the posterolateral sulcus where it divides into two collateral

arteries which travel with the nerve roots.

In the cervical spine majority of the radicular arteries arise from the vertebral

artery. In this region basilar artery also provides contribution via anastomoses with the

anterior spinal artery

In the thoracic spine, the radicular arteries branch off intercostal arteries at the

level of costotransverse joint. Here there is the radicular artery of Adamkiewicz, which

9

is the largest segmental artery and is the major blood supply to the lower cord. In 80%

of the population it arises from the left side of the body and usually accompanies ventral

root of the thoracic nerves 9-10 but may originate anywhere from T5 to L5 verterbrae.

(ACM Amato, 2015) Reported that the watershed region of the spinal cord is said to be

at the thoracic region as it has a limited number of segmental arteries. Branches of

anterior spinal artery supply the ventral 2/3 of the cord and the posterior artery branches

supply the dorsal 1/3 of the cord. The watershed region is said to be at the junction of

these two zones as its vascularity is the poorest. Based on the cross-sectional anatomy

of the spinal cord it can be understood that injuries to the anterior spinal artery results

in mainly motor deficits and posterior spinal artery injuries usually result in sensory

deficits. Another region of the thoracic spine that is said to have a critical vascular zone

is the zone between the 4th to 9th thoracic vertebrae, as it has the least profuse blood

supply and clinically is the narrowest region of the spinal canal.

In the lumbar spine blood supply to each vertebral body is via the lumbar

segmental arteries. The segmental arteries arise from the aorta for the levels L1-L4 and

from the iliolumbar artery from the L5 level. These arteries than traverse towards the

intervetebral foramina where it has three divisions, an anterior branch to the anterior

abdominal wall, a posterior branch to the paraspinal muscles & facet joints and a

foraminal branch to the spinal canal and its contents. In the lumbar spine the venous

supply parallels the arterial supply.

Batson’s venous plexus is a system of valveless veins within the spinal canal

and around the vertebral body and is in continuity with pelvic plexus. It provides an

alternative route of venous drainage to IVC in instances of an increase in abdominal

10

pressure where the venous return would be preferred via the spinal canal. This makes

this system a potent pathway for metastasis and infection to invade the lumbar spine.

Figure 2.4 Diagrammatic presentation of the blood supply to the spine

2.2 SPINAL TUBERCULOSIS

2.2.1 Pathophysiology

The causative organism of tuberculosis is the mycobacterium tuberculosis complex

which is a bacillus with a thick mycolate-rick outer covering which functions as an

excellent barrier. It is an aerobic organism and fortunately does not form biofilm, thus

allowing the usage of spinal implants to provide stability. The mycobacterium makes

its way to the vertebrae via haematogenous spread from a primary foci commonly seen

in the lungs, the gastrointestinal and genitourinary systems. The oxygen hungry bacilli

usally disseminates into the vertebra through the anterior spinal artery, the segmental

arteries that branch from the abdominal aorta and pelvic organs may assist in

dissemination. The fact that the Adankiewicsz Artery is in the thoracic region explains

why the commonest site of spinal tuberculosis to be in the thoracic region. The bacilli

usually diseminates after a prolonged latent phase slowly progressing to from a foci of

11

chronic inflammation with epitheloid cells, followed by Langerhan giant cells,

lyphocytes. This causes progressive bony destruction resulting in central caseous

necrosis, these foci of chronic inflammation are the pathognomonic finding in

histopathological analysis of suspected cases. There are two gross types of tuberculous

infections, the caseous exudative type which is commonly seen in children with massive

destruction, exudation and gross abscess formation. The other is a granular type more

commonly seen in adults, it is a slow and latent type of infection which is less

destructive and has minimal abscess formation. The types of tuberculous lesions in the

spine can present in five variants, the commonest, paradiscal type via arterial spread,

where the bacilli lodge in the subcondral marrow on either side of the disc. The

avascular disc is usually spared in early spinal tuberculosis and is only affected in late

disease. The central type due to venous spread causes vertebral body destruction, the

posterior or appendicular type which involves the posterior elements only is nortorius

for destabalizing the spine. The fourth of anterior type is due to subligamentous spread

of tuberculosis under the anterior longitudinal ligament, this group usually present with

anterior scalloping of the vertebral bodies. The final type is the least understood type

and affects the articular joints of the spine only.

12

Figure 2.5 Diagrammatic presentation of the sites of vertebral tuberculosis

2.2.2 Clinical Features

Clinical features of spinal tuberculosis are very variable, it is a chronic spine disease

commonly with an acute onset of symptoms. Pain, neurological deficits, cold abscess,

kyphotic deformities are characteristic findings. 100% of patients in (Azzam and

Tammawy, 1988) study reported back pain as their presenting symptom. Pott’s disease

or Potts paraplegia is paraplegia secondary to spinal tuberculosis. Neurology in spinal

tuberculosis may be present in up to 40-50% of cases and can be due to acute causes

such as soft compression from the abscess, caseous granuloma or the sequestra,

infective thrombosis of the vasculature leading to ischaemia or arachdonitis which is

meningeal inflammation and fibrosis. Late causes of neurology are, dura fibrosis,

progression of deformity and reactivation. Kyphosis in spinal tuberculosis is commonly

acute and presents as a gibbus deformity, (Rajasekar at al, 1998) divided spinal

tuberculosis deformities as knuckle deformity (single vertebra deformity), gibbus

13

deformmity (collapse of two or three vertebra) or global rounded kyphosis (involvement

of multiple adjacent vertebra). Constitutional symptoms fever, profuse night sweats and

malaise may be reported by patients, but are more commonly seen in patients with

pulmonary tuberculosis

2.2.3 Investigations

2.2.3.1 Blood Investigations

Investigations can be divided into routine blood investigations, tissue sampling, and

imaging investigations. Routine blood works include erythrocyte sedimentation rate

(ESR), C-reactive protien (CRP), and white cell counts. All blood parameters lack

specificity to spinal tuberculosis as they have many false positive triggers. Among them

the ESR has been seen to be elevated in more than 60% of patients across different

studies, with mean values of 61mm/hr, keep in mind that ESR levels can be raised by

non-infectious causes, tumors and even trauma. In Guo et al’s study, it was noted that

69% of spinal tuberculosis patients had elevated CRP, it was also noted that this

elevation was more specific for acute infective lesions compared to disseminated ones.

ESR and CRP levels may even be normal in approximately 20% of patients. WCC has

not been shown to provide a role in diagnosing spinal tuberculosis. Tuberculin skin test

also displays high false positive cases due to previous exposure or in patients with

Bacilus Calmette-Guerin (BCG) vaccination. The QuantiFERON-TB that measures

interferon-gamma levels from suspected patients has been reported to have sensitivity

of 84% and spcificity of 95% by Kumar et al. However, its cost and availability are

some of the reasons it is not routinely done.