comparative study on electromyography (emg) biofeedback...
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“Comparative study on Electromyography (EMG)
biofeedback and Galvanic Skin Resistance (GSR)
biofeedback in Tension Type Headache”.
Thesis Submitted to
The KLE Academy of Higher Education and Research,
Belgaum
(KLE DEEMED UNIVERSITY)
[Declared as Deemed-to-be-University u/s 3 of the UGC Act, 1956 vide Govt. of India
Notification No.F.9-19/2000-U.3 (A)]
(Accredited ’A’ Grade by NAAC)
For the award of the Degree of
Doctor of Philosophy in the Faculty of
Medicine (Physiotherapy)
by
Mrs. Veena Bembalgi M.P.T. (Registration No: KLEU/PhD/08-09/DOUNO8032)
Under the Guidance of
Prof. Dr. Karkal Ravishankar Naik DM (Neurology), Professor and Head, Department of Neurology,
K.L.E. University’s Jawaharlal Nehru Medical College,
Belgaum – 590010. Karnataka, India
September - 2013
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KLE ACADEMY OF HIGHER EDUCATION AND
RESEARCH,
(KLE DEEMED UNIVERSITY) [Declared as Deemed-to-be-University u/s 3 of the UGC Act, 1956 vide Govt. of India
Notification No.F.9-19/2000-U.3 (A)]
(Accredited ’A’ Grade by NAAC)
BELGAUM
DECLARATION
I hereby declare that this thesis entitled “Comparative study on
Electromyography (EMG) biofeedback and Galvanic Skin Resistance
(GSR) biofeedback in Tension Type Headache” is a bonafide and
genuine research work carried out by me under the guidance of
Dr. Karkal Ravishankar Naik DM (Neurology), Professor and Head,
Department of Neurology, KLE University’s Jawaharlal Nehru
Medical College, Belgaum-590010 Karnataka, India. The thesis or
any part thereof has not formed the basis for the award of any
degree/fellowship or similar title to any candidate of any
University.
Date: Mrs. Veena Bembalgi M.P.T
Place: Belgaum KLES College of Physiotherapy,
Hubli
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KLE ACADEMY OF HIGHER EDUCATION AND
RESEARCH,
(KLE DEEMED UNIVERSITY) [Declared as Deemed-to-be-University u/s 3 of the UGC Act, 1956 vide Govt. of India
Notification No.F.9-19/2000-U.3 (A)]
(Accredited ’A’ Grade by NAAC)
BELGAUM
This is to certify that the thesis entitled “Comparative study on
Electromyography (EMG) biofeedback and Galvanic Skin Resistance
(GSR) biofeedback in Tension Type Headache” is a bonafide record
of original research carried out by Mrs. Veena Bembalgi for the
award of DOCTOR OF PHILOSOPHY (PHD) IN FACULTY OF
Medicine (Physiotherapy) under my supervision and guidance.
Date Dr. Karkal Ravishankar Naik DM (Neurology), Place: Belgaum Professor and Head, Department of Neurology,
KLE University’s
Jawaharlal Nehru Medical College,
Belgaum.
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KLE ACADEMY OF HIGHER EDUCATION AND
RESEARCH,
(KLE DEEMED UNIVERSITY) [Declared as Deemed-to-be-University u/s 3 of the UGC Act, 1956 vide Govt. of India
Notification No.F.9-19/2000-U.3 (A)]
(Accredited ’A’ Grade by NAAC)
BELGAUM
This is to certify that the thesis entitled “Comparative study on
Electromyography (EMG) biofeedback and Galvanic Skin Resistance
(GSR) biofeedback in Tension Type Headache” is a bonafide and
genuine research carried out by Mrs. Veena Bembalgi M.P.T under
the guidance of Dr. Karkal Ravishankar Naik DM(Neurology), Professor
and Head, Department of Neurology, KLE University’s
Jawaharlal Nehru Medical College, Belgaum, Karnataka, India.
Date: Dr. A. S. Godhi M.S, FICS Place: Belgaum Dean Faculty of Medicine,
K.L.E. University,
J. N. Medical College,
Belgaum -590010. Karnataka
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KLE ACADEMY OF HIGHER EDUCATION AND
RESEARCH,
(KLE DEEMED UNIVERSITY) [Declared as Deemed-to-be-University u/s 3 of the UGC Act, 1956 vide Govt. of India
Notification No.F.9-19/2000-U.3 (A)]
(Accredited ’A’ Grade by NAAC)
BELGAUM
ENDORSEMENT BY THE PRINCIPAL
This is to certify that the thesis entitled “Comparative study on
Electromyography (EMG) biofeedback and Galvanic Skin Resistance
(GSR) biofeedback in Tension Type Headache” is a bonafide
research work done by Mrs. Veena Bembalgi under the guidance of
Dr. Karkal Ravishankar Naik DM(Neurology), Professor and Head,
Department of Neurology, KLE University’s Jawaharlal Nehru
Medical College, Belgaum, Karnataka, India.
Date: PRINCIPAL,
Place: Belgaum Dr. Sanjiv Kumar
KLEU Institute of
Physiotherapy, Belgaum
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KLE ACADEMY OF HIGHER EDUCATION AND
RESEARCH,
(KLE DEEMED UNIVERSITY) [Declared as Deemed-to-be-University u/s 3 of the UGC Act, 1956 vide Govt. of India
Notification No.F.9-19/2000-U.3 (A)]
(Accredited ’A’ Grade by NAAC)
BELGAUM
Copyright Declaration
We hereby declare that the KLE Academy of Higher Education and
Research, Belgaum, Karnataka, Belgaum, Karnataka shall have the
rights to preserve, use and disseminate this thesis in print or
electronic format for academic / research purpose.
Mrs Veena Bembalgi M.P.T
Dr. Karkal Ravishankar Naik DM(Neurology) Professor and Head,
Department of Neurology,
KLE University’s Jawaharlal Nehru Medical College,
Belgaum, Karnataka, India.
Date:
Place: Belgaum
© KLE ACADEMY OF HIGHER EDUCATION AND RESEARCH,
BELGAUM
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KLE ACADEMY OF HIGHER EDUCATION AND RESEARCH,
BELGAUM
UNDERTAKING
I, Mrs. Veena. A. Bembalgi hereby declare that the information
and the data mentioned in my thesis entitled “Comparative
study on Electromyography (EMG) biofeedback and
Galvanic Skin Resistance (GSR) biofeedback in Tension
Type Headache” belongs to me and is original.
I am aware of the definition of plagiarism as detailed below:
An act or instance of using or closely imitating the language
and thoughts of another author without authorization and the
representation of that author’s work as one’s own, as by not
crediting the original author.
A piece of writing or other work reflecting such unauthorized
use or imitation.
The deliberate or reckless representation of another’s words,
thoughts or ideas as one’s own without attribution in connection
with submission of academic work, whether graded or otherwise.
I hereby declare that the thesis prepared by me is original-one and
does not involve plagiarism anywhere. In case at a later stage it is
found that I have indulged in plagiarism, then I am solely
responsible for the same and the institution is at liberty to take
any disciplinary action against me including cancellation of
dissertation or any other penalties imposed by the university.
Date:
Place: Mrs. Veena Bembalgi M.P.T
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Acknowledgement
I owe my accomplishment of the course to my late mother-in-
law, Mrs. Gurudevi Bembalgi, who was my first motivator to join the
PhD programme. It was solely her motivation and support that
inspired me to join this course. I owe my entire work to her.
I extend sincere gratitude to my guide Dr. Karkal Ravishankar
Naik for his meticulous guidance and encouragement through-out the
study. He was the main driving force for the completion of this study.
He is a perfectionist and very systematic in his work. Being his pupil
has helped me inculcate those qualities too.
I thank all my participants for their participation without which
it would be impossible to perform the study.
With great privilege, I take the opportunity to express my
sincere thanks to Honorable Chancellor KLE University & Chairman
of K.L.E Society, Dr. Prabhakar. B. Kore for providing us the
opportunity to accomplish the course.
I am grateful to Honorable Vice-Chancellor KLE University
Dr. (Prof) C. K. Kokate, Belgaum, for his timely motivation and
inspiration throughout the course.
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I am extremely happy to extend my heartfelt thanks to Dr. P. F.
Kotur, former Registrar, KLE’s University Belgaum, for his support
and encouragement.
I express sincere thanks to Dr. M.G.Mokashi, for his guidance
and support during my study and thesis writing phase.
I thank Dr. Prashant Mukkannavar and Prof. Steve. Simon
(U.K), who helped me tremendously with the statistical analysis.
My heartfelt thanks to my father-in-law, Dr. M.S. Bembalgi and
my husband Dr. Anilkumar Bembalgi and all my family members for
their constant support and encouragement throughout the course
period. I, also thank Dr. Anilkumar Bembalgi for helping me with the
analysis of data on drugs.
I express my gratitude to Dr. Suresh. DuganiMCH(Neurosurgery),
Dr. Rajendra. DuganiDM(Neurology) and all other physicians for their
guidance and for referring me my study participants.
Dr. Sanjivkumar, former Principal, KLES College of
Physiotherapy, was a source of constant support and motivation. I
thank him sincerely and am grateful to him.
I thank my colleagues Dr. Rashmi Saibannavar and Dr.
Shradhha Bhandari and my students Madhura Palande, Amruta
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Deshpande, Richa Singh and Radhika Galgali for helping me with the
data recordings and calculation of data scores.
I am grateful to Mr. Siddappa and Mr. Basavraj Antannavar,
Assistants at KLES College of Physiotherapy, Hubli for keeping the
treatment room open and meeting the requirements for the therapy
even on holidays.
Sincere thanks to Prof. Richard Sherman, Director, Behavioral
Medicine Research and Training foundation, U.S.A, for answering my
queries and sharing some valuable information.
I also thank Mr. Girish Aladi, Mr. Kumaresh. Hundekar and
Mr. Halemani for their technical support and help.
I extend sincere gratitude to all who have knowingly or
unknowingly contributed in the completion of my study.
Date: Mrs. Veena Bembalgi
Place: Belgaum
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LIST OF ABBREVIATIONS:
AAPB: Association of Applied Psychophysiology and Biofeedback
AHS: American Headache Society
BF: Biofeedback
CDH: Chronic Daily Headache
CI: Confidence Interval
CTTH: Chronic Tension Type Headache
EMG: Electromyography
EMGa: EMG audio group
EMGav: EMG audiovisual group
EMGv: EMG visual group
GSR: Galvanic Skin Resistance
GSRa: GSR audio group
GSRav: GSR audiovisual group
GSRv: GSR visual group
ICHD: International Classification of Headache Disorders
IHS: International Headache Society
ISNR: International Society for Neurofeedback and Research
NIH: National Institute for Health
QoL: Quality of Life
REMG: Relative EMG
RMANOVA: Repeated Measures Analysis of Variance
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SEMG: Surface EMG
SF-36: 36-item Short form health survey
SPSS: Statistical Package for the Social Sciences
TTH: Tension Type Headache
WHO: World Health Organization
ηp2: Partial eta squared value
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ABSTRACT
Background and purpose: Tension type headache (TTH) is the most widespread
and most common primary headache disorder accounting for nearly 90 % of all
headaches. Efficacy of electromyography (EMG) biofeedback (BF) in patients
with tension type headache has been extensively studied and proven. However,
efficacy of galvanic skin resistance (GSR) biofeedback has not been studied
adequately. So far there are no studies on the efficacy of isolated audio, visual and
combined EMG or GSR BF in TTH. The aim of the present study was to compare
the efficacy of electromyography biofeedback and galvanic skin resistance
biofeedback in patients with tension type headache and to study and compare the
efficacy of auditory, visual and audio-visual biofeedback in patients with TTH.
Methodology: This study was a randomized single blinded controlled prospective
study. Out of 232 recruited subjects, 211 (145 females and 66 males) were
randomly assigned to seven groups receiving electromyography feedback auditory
(EMGa) (n =27), visual (EMGv) (n=28), combined audio-visual (EMGav) (n=27),
galvanic skin resistance biofeedback auditory (GSRa) (n =26), visual (GSRv)
(n=29) and combined audio-visual (GSRav) (n=28) and a control group (n = 27).
Each subject (except the control group) received 15 sessions of respective
biofeedback for 30 minutes each in an isolated room. The control group received
only medication prescribed by their treating doctor. Each patient was blinded to
the type of biofeedback (EMG or GSR) being given. Pain variables (average
frequency, duration and intensity of headache per week), SF-36 quality of life
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scores and analgesic usage were recorded at baseline, 1 month, 3 months, 6
months and 1 year after therapy.
Results: All groups showed a significant decrease in pain variables (p
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TABLE OF CONTENTS
Sl. No. Sections Page No.
1. INTRODUCTION 1-12
2. NEED OF THE STUDY 13-14
3. RESEARCH QUESTION 15
4. AIMS AND OBJECTIVES 16
5. REVIEW OF LITERATURE 17-27
6. METHODOLOGY 28-35
7. RESULTS 36-82
8. DISCUSSION 83-99
9. CONCLUSION 100
10. SUMMARY 101-103
11. BIBLIOGRAPHY 104-121
12. ANNEXURE – I PHOTOGRAPHS 122-124
13.
ANNEXURE – II
ETHICAL CLEARANCE, CONSENT FORM,
PROFORMA
125-134
14.
ANNEXURE – III SF-36 QUESTIONNAIRE
KANNADA
ENGLISH
15. ANNEXURE – IV PUBLICATIONS
16. ANNEXURE – V MASTER CHART
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LIST OF TABLES
Table
No. Particulars Page No.
01 Demographic Data 39
02 Baseline pain variables in the study group 41
03 Baseline SF-36 variables in the study group 43
04 Consumption of analgesics 44
05 Intra and Inter group analysis of pain variables of
all groups 46
06 Intra group comparison of pain variables in EMG
groups 48
07 Intra group comparison of pain variables in GSR
groups 49
08 Intra group comparison of pain variables in the
control group 52
09 Intergroup comparison of pain variables at
1month post intervention 53
10 Intergroup comparison of pain variables at 3
months post intervention 54
11 Intergroup comparison of pain variables at 6
months post intervention 55
12 Intergroup comparison of pain variables at 1 year
post intervention 56
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13
Intra and inter group analysis of SF-36 scores
a) Total scores b) Physical scores c) Mental scores
61
62
63
14 Intra group comparison of SF-36 variables in the
EMG groups 64
15 Intra group comparison of SF-36 variables in the
GSR groups 65
16 Intra group comparison of SF-36 variables in the
control group 66
17 Intergroup comparison of SF-36 scores at 1 month
post intervention 67
18 Intergroup comparison of SF-36 scores at 3
months post intervention 68
19 Intergroup comparison of SF-36 scores at 6
months post intervention 69
20 Intergroup comparison of SF-36 scores at 1 year
post intervention 70
21 Intra group comparison of analgesic consumption
for EMG groups 76
22 Intra group comparison of analgesic consumption
for GSR groups 77
23 Intra group comparison of analgesic consumption
for control group 78
24 Improvement in pain variables in percentage 80
25 Improvement in SF-36 scores in percentage 81
26 Effect size for all outcome measures at one year 82
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TABLE OF FIGURES
Figure No Particulars Page No
01 Flow chart of subjects through the trial 38
02 Means of pain variables at baseline 40
03 Means of SF-36 scores at baseline 42
04 Trend of average frequency of headache
through the time measures 47
05 Trend of average duration of headache
through the time measures 51
06 Trend of average intensity of headache
through the time measures 58
07 Trend of SF-36 total scores through the
time measures 60
08 Trend of SF-36 physical scores through the
time measures 72
09 Trend of SF-36 mental scores through the
time measures 74
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LIST OF PHOTOGRAPHS
Photograph
No Particulars Page No
01 EMG biofeedback machine 122
02 GSR biofeedback machine 122
03 Placement of EMG biofeedback electrodes 123
04 Placement of GSR biofeedback electrodes 123
05 Subject receiving EMG audiovisual
biofeedback 124
06 Subject receiving GSR audiovisual
biofeedback 124
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Introduction
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Introduction
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INTRODUCTION
Stress is a frequent occurrence in all our lives. It is a state of
physiological or psychological strain caused by undesirable stimuli, physical,
mental or emotional; internal or external that could likely disturb the functioning
of an individual.1 When stress is being experienced by a person constantly with no
relief or with increased frequency, it is termed as “distress”. Distress leads to
weakened cognitive and physiological control and, as a result, decreased
performance. It can lead to symptoms like headache, gastrointestinal disturbances,
elevated blood pressure, chest pain, insomnia, peptic ulcers, sexual dysfunction,
skin ailments, etc.
The physiological responses to stress may differ with regards to acute and
chronic stress. Acute stress generally is short lived and causes no actual damage,
whereas chronic stress can cause a sustained response to stress causing damage
and chronic pain.
Stress reactions (response to stress) cause amplification of physiological
parameters such as muscle tension, blood pressure, increased sweating, etc. This
causes disorders in the body like headaches, irritable bowel syndrome, ulcers,
hyperhidrosis, chest pain, etc. Eventually, it results into a vicious cycle wherein
stress causes pain or stress related disorders and increased pain or other
symptoms, which leads to further amplification of stress.
Stress related disorders are often termed as “psychosomatic” disorders
which involves the mind and body. These are the disorders in which the mind
makes the body vulnerable for disorders. Tension-type headache (TTH) is one of
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Introduction
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the common and chief diseases in psychosomatic medicine because of its
correlation with psychosocial factors.2
Mental stress and tension are the most frequently reported triggers of
tension-type headache.3,4
Genetic or family-related environmental factors are also
associated with TTH.5 Major life events such as surgery, divorce and deaths of
close family members induce major negative effect. Such events in the prior year
have been modestly related to the persistence of headache.6 In addition to physical
variables like muscle tension, electro-dermal activity, temperature, etc and other
demographic variables of pain, psychological risk factors have been empirically
associated with the occurance of headache. These comprise, social support,
hypnotizability, affect, life events, and negative thinking.7 Trait negative
affectivity is raised in chronic headache causing over reporting of somatic
symptoms like headache pain, irrespective of organic disease.8,9
This indicates
that mental health is largely affected in patients with TTH and therefore a good
deal of attention should be paid to the psychological component in terms of
assessing and taking measures to improve the mental health of patients with TTH.
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Introduction- Biofeedback
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BIOFEEDBACK
The term “Biofeedback” was voted against the term Autoregulation in
1969. The organization who coined this word was named the Biofeedback
Research Society (BRS). In 1976, the BRS was renamed Biofeedback Society of
America (BSA). The present name of the society, the Association for Applied
Psychophysiology and Biofeedback came into existence in 1989.
Edmund Jacobson, a physician was one of the earliest contributors in the
field of biofeedback. In 1938 he monitored electromyography (EMG) of patients
practicing progressive muscle relaxation to find out if the muscles actually
relaxed.
Previously, it was believed that autonomic responses could not be
controlled voluntarily. Miller and Leo DiCara in 1962 demonstrated that
curarized rats could learn to control their autonomic functions (breathing patterns,
muscle tone, blood pressure, salivation, GSR, etc).
In 1966, Joe Kamiya, who is popularly known as “the father of
biofeedback” found that some subjects could learn to discriminate the presence of
alpha waves when electroencephalography (EEG) was performed on them. He
also found that they could learn to manipulate their alpha frequency by about 1
Hz, thus establishing that subjects could control their own neuro-biological
rhythm.
Physicians Marinacci and Whatmore practiced biofeedback even before
the term was founded. They used EMG biofeedback to treat stroke patients. But
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Introduction- Biofeedback
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their work on neuromuscular re-education was not continued by others and
remained undeveloped till it was rediscovered.
Significant contributions to this field have been made by researchers in the
clinical aspects like (a) Basmajin, who used surface EMG to study role of
different muscles in movements and used the information for rehabilitation, (b)
A.Kegel, who used pneumatic biofeedback devices to train pelvic floor muscles,
(c) Johan Stovya used biofeedback for treating anxiety and (d) Thomas
Budzynski used SEMG for treatment of headaches.10
The Association for Applied Psychophysiology and Biofeedback (AAPB),
the Biofeedback Certification Institute of America (BCIA), and the International
Society for Neurofeedback and Research (ISNR) convened a task force of
renowned scientists and clinicians in late 2007 who worked together to craft a
standard definition for biofeedback. They defined biofeedback as " a process that
enables an individual to learn how to change physiological activity for the
purposes of improving health and performance.”.11
Precise instruments measure physiological activity such as, heart function,
, muscle activity, breathing, electroencephalogram, skin temperature etc. These
biofeedback instruments rapidly and accurately "feed back" information to the
user. The use of this information, often in combination with changes in thinking,
emotions, and behavior supports needed physiological changes.11
Patients with the
use of this information (biofeedback) learn enhanced control over the
physiological process (operant learning model).12
Over time, these changes can be
preserved without continued use of an instrument.10
Any learning is facilitated by
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Introduction- Biofeedback
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feedback. The same principle is used in biofeedback therapy whose main aim is to
assist the patients in self regulation of psycho-physiological factors, thereby
allowing them to gain voluntary control over physiological parameters.
Learned behavioral control over physiological responses was first
published in 1961. In the 1960s and 1970s, human studies revealed that through
operant feedback methods, voluntary control could be learnt over many
physiologic responses (e.g., heart rate, blood pressure, skin conductance, muscle
tension, skin temperature, evoked potentials and various rhythms of EEG).13
Biofeedback therapies are non-pharmacologic treatments that use scientific
instruments to measure, amplify, and feed back physiological information to the
patient being monitored, thereby promoting control and manipulation of
physiological parameters. It is virtually free of any adverse side effects and
therefore seemingly the preferable choice for treatment of psychosomatic
disorders.14
Biofeedback therapy has evolved over the last 30 years, and today there
are innumerable disorders for which biofeedback therapy has been used.
Biofeedback therapy is now used for a variety of disorders, such as headache
(migraine, tension and mixed), urinary incontinence, essential hypertension etc
with reliable results.
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Introduction- Tension Type Headache
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TENSION TYPE HEADACHE
Headache is a clinical syndrome affecting 91% of all males and 96% of all
females at some time during their life span.15
The World Health Organization
recognized that primary headaches are among the first 20 major causes of
disability.16
In the primary care practice, tension type headache is the most
commonly diagnosed variety of primary headache .17
Tension type headache, formerly called tension headache or muscle
contraction headache is the most frequently occuring headache disorder.18
It is the
commonest among primary headaches. It is the most dominant and costly
headache.19
Tension type headaches are responsible for nearly 90% of all
headaches. As per the International Headache Society (IHS), its lifetime
occurance in the general population ranges in different studies from 30 to 78%.
Inspite of its high prevalence and regardless of the fact that it has the highest
socio-economic impact, it is still the least studied of the primary headache
disorders.20
Population based studies have established that 24–37% of the adult
populations have TTH several times a month; 10% have it weekly; and 2–3%
have chronic TTH, usually lasting for many years. 21, 22
A study of the global
prevalence and burden of headaches showed that the community burden resulting
from disability caused by TTH is greater than that of migraine.19
Tension type headache is more common in women, in a ratio of 1.5:1,23
whereas other studies have shown that the female to male ratio of TTH is 5:4.19, 24
Published estimates of the prevalence of tension type headache vary over a wide
range from 1.3% to 65% in men and 2.7% to 86% in women.18, 25-35
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Introduction- Tension Type Headache
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A World Health Organization (WHO) statement released in 2000 on
headache disorders and public health quotes that the onset of TTH is often in the
teen and prevalence peaks in the fourth decade and subsequently declines23
,
whereas the average age of onset of TTH was found to be 25–30 years in cross-
sectional epidemiological studies21
. The prevalence peaks between the age of 30
to 39 and decreases slightly with age.22
Some of the risk factors for developing TTH have been reported to be poor
self-rated health, unable to relax after work and sleeping few hours per night.22
Two Danish studies have shown that the number of workdays missed was three
times higher for TTH than for migraine in the population, 21, 22
and a US study has
also found that absenteeism because of TTH is considerable.36
In a study by Fuh et al, 2008 where a cohort study was conducted to study
the outcome of elderly patients with chronic tension type headache (CTTH) in a
span of 13 years, the authors found 30% of patients with CTTH evolved to
chronic migraine (CM) or episodic migraine.37
Therefore it is important to curb
the tension type headache before it transforms to migraine which could lead to
difficulty in treating due to its complex nature.
Tension type headache is clinically and patho-physiologically
heterogeneous. The complex interrelation of the various pathophysiological
factors of TTH; makes this disorder often difficult to treat. Various therapeutic
measures have been recommended to be used in sequence or in combination.
Therapies for TTH can be subdivided into short term, abortive treatment of each
attack (mainly pharmacological) and long term, prophylactic treatments
(pharmacological and/or non-pharmacological).38
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Introduction- Tension Type Headache
8
Several non-pharmacological treatments have been recommended for
management of TTH, them being physical therapy,39,40,41
craniocervical training,42
oro-mandibular treatment43,44
acupuncture,45,46,47
relaxation therapies,48,49
cognitive-training50,51
biofeedback52,53
etc. However, the scientific evidence for
efficacy of most treatment modalities is sparse.54, 55, 56, 57
Biofeedback is one of the most prominent behavioural headache
treatments. It is an established non-pharmacologic technique commonly used in
the treatment of migraine and tension type headaches.58
Several published studies
have suggested that biofeedback is effective in reducing the frequency and
severity of headaches, thereby limiting the patient’s dependence on medication.
Conforming to this, studies have also proposed that biofeedback may effect a
reduction in medical utilization in headaches.59, 60, 61, 62
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Introduction- Biofeedback in TTH
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BIOFEEDBACK IN TENSION TYPE HEADACHE
Enormous research carried out in the mid-20th century on stress and
illness, formed the basis needed to establish headache as a psycho-physiological
disorder, thereby justifying the application of contemporary behavioral headache
treatments. Over the past thirty years, these behavioral treatments for headache
have gathered a sizeable evidence base.
Budzynski and colleagues were the first to publish demonstration of
biofeedback for tension headache treatment. They developed the EMG
biofeedback model and protocol for tension headache63
and pursued to
demonstrate initial headache improvements in uncontrolled64
and controlled
experiments.65
The American Headache Society recognized biofeedback as a valid form
of headache therapy in 1978.66
The U.S. Headache Consortium, which was a
multi-disciplined assemblage of seven professional practice organizations also
endorsed behavioral therapy including biofeedback for headache as important
evidence based treatment.12
Meta-analytic reviews of the literature consistently have shown behavioral
interventions to yield 35% to 55% improvements in migraine and tension-type
headache and that these outcomes are significantly superior to control conditions.
The positive evidence from these studies has lead many professional practice
organizations to recommend use of behavioral headache treatments alongside
pharmacologic treatments for primary headache.12
A Task Force of the Association for Applied Psychophysiology and
Biofeedback and the Society for Neuronal Regulation was formed in 2001, which
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Introduction- Biofeedback in TTH
10
developed guidelines for the evaluation of the clinical efficacy of psycho-
physiological interventions. The criteria for levels of evidence of efficacy was
laid down and approved by both associations. These criteria were used to assign
efficacy levels for the vast number of conditions for which biofeedback has been
used. Use of biofeedback for headaches in adults was awarded
“level 4-efficacious”, the criteria for which were:
a. In a comparison with a no-treatment control group, alternative treatment group,
or placebo control utilizing randomized assignment, the investigational
treatment is shown to be statistically significantly superior to the control
condition, or the investigational treatment is equivalent to a treatment of
established efficacy in a study with sufficient power to detect moderate
differences, and
b. The studies have been conducted with a population treated for a specific
problem, for whom inclusion criteria are delineated in a reliable, operationally
defined manner, and
c. The study used valid and clearly specified outcome measures related to the
problem being treated, and
d. The data are subjected to appropriate data analysis, and
e. The diagnostic and treatment variables and procedures are clearly defined in a
manner that permits replication of the study by independent researchers, and
f. The superiority or equivalence of the investigational treatment has been shown
in at least two independent research settings. 67
The task force included all studies in which biofeedback was used and
found the therapy efficacious.
-
Introduction- Biofeedback in TTH
11
Later, in 2008 a review article on efficacy of Biofeedback in TTH quoted
that BF in TTH can be supported as an efficacious and specific treatment option,
which according to the Association of Applied Psychophysiology and
Biofeedback (AAPB) and International Society for Neurofeedback and Research
(ISNR), criteria this constitutes the highest level of evidence (Level 5), reserved
for psycho-physiological interventions, that have established Level 4 evidence and
have shown additional superior treatment results in comparisons to credible sham
therapy or alternative bona fide treatments.68
The past three decades have shown, behavioral interventions (chiefly
relaxation, biofeedback, and stress management) to have become standard
components in the varied choice of treatments for management of migraine and
tension type headaches. Meta-analytic literature reviews have consistently
demonstrated clinically significant reductions in recurrent headache through
behavioral interventions . Behavioral interventions have yielded approximately
35-50% reduction in migraine and tension type headache activity. Although
comparisons between standard drug and non-drug treatments for headache have
been initiated only recently, the available evidence suggests that the level of
headache improvement with behavioral interventions may prove beneficial over
those obtained with widely used pharmacologic therapies in representative patient
samples. In recent years, some efforts have been made to increase the availability
and cost effectiveness of behavioral interventions through alternative delivery
formats and mass communications.13,52
Biofeedback treatments for TTH provide patients with feedback of
physiological processes, thereby assisting them to gain voluntary control over
-
Introduction- Biofeedback in TTH
12
bodily functions by manipulation of physiological parameters (e.g., to reduce
dysfunctional muscle tension, increase skin resistance etc) and thereby augment
self efficacy in dealing with pain episodes.53
Of all biofeedback therapies or techniques, EMG biofeedback has been
extensively reviewed and used the most. A recent extensive and thorough meta-
analysis including 53 studies concluded that biofeedback has a medium to large
effect and the effect was found to be long lasting up to 15 months.68
GSR BF has been used in treatment of stress69
and related psychosomatic
disorders like hypertension1, hyperhidrosis,
70 Raynaud’s disease,
70 epilepsy
71 etc
but has been infrequently used in management of TTH.12, 48, 68
-
Need of the Study
2
-
Need for the study
13
NEED FOR THE STUDY
Pharmacotherapy remains the mainstay of treatment for all types of
headaches and vast amounts of prescription and over-the-counter medications are
used. Side effects frequently occur with these medications which at times can be
life-threatening. The medications themselves often contribute to the reduced
productivity among headache sufferers.14
A number of treatment strategies used in the treatment of TTH, either in
isolation or combined with one another. These consist of pharmacological
treatment, physical therapy, acupuncture, relaxation therapy or alternative
medicine. Biofeedback though has proven its efficacy in the treatment of TTH, is
not widely used in India by health professionals. Biofeedback therapy is still a
novel and an infrequently used therapy for treating practitioners as well as the
common people in India. Therefore, a study of this nature was required to create
an awareness of this field of therapy among the health practitioners as well as the
community. Of all biofeedback techniques, EMG biofeedback has been
extensively studied in the management of TTH. However, despite the fact that
GSR biofeedback is used in many other disorders with psychosomatic components
in the pathogenesis like hypertension, epilepsy, hyperhidrosis, etc it has been
infrequently evaluated and used in the management of TTH.
Therefore, there was a need to find the efficacy of GSR biofeedback in
TTH and also compare its efficacy with EMG biofeedback in patients with TTH.
A novel attempt has also been made in studying and comparing the
efficacy of auditory, visual and combined biofeedback in both EMG and GSR
-
Need for the study
14
biofeedback in TTH subjects. The implications of this could be used in designing
and manufacturing of EMG and GSR biofeedback units for therapeutic benefits.
-
Research Question
3
-
Research Question
15
RESEARCH QUESTION
Which type of biofeedback (electromyographic or galvanic skin resistance) and in
which form, is effective in the treatment of tension type headache?
HYPOTHESIS
The working hypotheses of this study were:
1. Electromyography (EMG) biofeedback is more effective than Galvanic
Skin Resistance (GSR) biofeedback in the treatment of tension type
headache (TTH).
2. There is no difference in effectiveness of auditory, visual or combined
EMG biofeedback in the treatment of TTH.
3. There is no difference in effectiveness of auditory, visual or combined
GSR biofeedback in the treatment of TTH.
-
Aims & Objectives
4
-
Aims and Objectives
16
AIMS AND OBJECTIVES
Aims
To study and compare the efficacy of EMG biofeedback with GSR
biofeedback in patients with Tension Type Headache.
To study and compare the efficacy of auditory feedback, visual feedback
and both visual and auditory feedback together.
Objectives
To examine the efficacy of EMG biofeedback in tension type headache
patients.
To examine the efficacy of GSR biofeedback in tension type headache
patients.
To compare the efficacy of EMG biofeedback and GSR biofeedback in
tension type headache patients.
To compare the effectiveness of isolated visual, isolated auditory or
combined visual and auditory biofeedback together of EMG biofeedback
in tension type headache patients.
To compare the effectiveness of isolated visual, isolated auditory or
combined visual and auditory biofeedback together of GSR biofeedback in
tension type headache patients.
-
Review of
Literature
5 5
-
Review of literature
17
REVIEW OF LITERATURE
Pharmacotherapy has remained the main mode of treatment of people
affected with TTH. Though pharmacotherapy is modestly effective in the reducing
the frequency and intensity of TTH 72
, it has some evident drawbacks. First, the
widely used antidepressant medications are associated with multiple potential
adverse effects. Second, chronic TTH (CTTH) constitutes a risk factor for
analgesic medication overuse and the development of medically induced headache
in addition to the adverse effects due to long term consumption.73, 74
Behavioural treatments (Biofeedback)
Behavioural treatments have been recommended as an adjunct to
pharmacotherapy. Of these behavioural treatments, biofeedback has formed an
evidence based treatment option for TTH. These treatments involve the patient’s
active role in preventing and management of headache episodes and thereby
improving the coping with the physiological and psycho-physiological
consequences of pain.53
Previous quantitative reviews and meta-analyses have assessed the
outcome of various behavioural treatments for TTH, such as cognitive therapy,
biofeedback, relaxation and hypnotherapy75,76,77,78,79
and have shown average
improvement rates that exceeded those of no treatment conditions.76
The
maximum treatment gains were achieved for electromyography feedback (EMG-
FB) alone or in combination with relaxation, which is the predominantly applied
biofeedback modality for TTH. Average improvement scores ranged from 46% 78
to 61%75
.
-
Review of literature
18
One meta-analysis investigated psychological headache treatments and
provided standardized measures of treatment success, which resulted in a medium
to large average effect size for EMG-FB in adults.79
Investigations of specific
versus nonspecific effects of biofeedback in comparison with other behavioural
headache treatments were not meta-analytically integrated in that study. Also, the
long-term effects of the efficacy on different outcome variables, and treatment
mediators of biofeedback were not systematically analyzed. These limitations
were targeted in another meta-analysis whose objective was to present an up to
date and comprehensive evaluation of the efficacy of biofeedback for TTH. Its
first aim was to establish the short and long term efficacy of biofeedback as well
as the treatment specificity in comparison to various control groups. Another aim
was to determine, differential treatment effects in the form of pain measures and
of psychological, behavioural, and physiological outcome categories. In
continuation, analyses of potentially moderating effects of treatment and patient
characteristics were incorporated. Lastly, specific meta-analytical techniques were
applied to control for possible confounding effects of selective publication,
dropout, and study validity. Meta-analytic integration of 53 studies resulted in a
significant medium to large effect size (d=0.73; 95% confidence interval=0.61,
0.84) that was stable over an average follow up phase of fifteen months.
Biofeedback proved to be more effective than headache monitoring, relaxation
therapies and placebo. The strongest improvements resulted for frequency of
headache episodes. In addition significant effects were observed for self-efficacy,
muscle tension, depression, symptoms of anxiety and analgesic medication. The
meta-analysis also found that biofeedback for TTH can be supported as an
-
Review of literature
19
efficacious and specific treatment option. According to the AAPB and ISNR
criteria this constitutes the highest level of evidence (Level 5), reserved for psycho
physiological interventions.68
Andrasik80
reviewed meta-analyses and evidence-based reviews of
behavioural treatments for headaches in adults. After considering all meta-
analyses to date he concluded that the effects of behavioural treatments were
superior to various control and placebo conditions and similar to current
medications for both migraine and tension type headache. Combining behavioural
and pharmacological treatments may increase effectiveness even further.
Several reports of unsuccessful biofeedback training have appeared in the
research literature since the inception of biofeedback training three decades ago.
Many of the unsuccessful studies conducted in the early development of the field
reflect failure to thoroughly train the patients. For example, some unsuccessful
studies provided only minimal training with the biofeedback instrumentation
(often one to four sessions of brief duration), offered little coaching, involved no
home practice, and failed to conform to clinical criteria.12
Biofeedback is a time tested therapy for psychosomatic disorders. Various
forms of biofeedback targeting the psycho-physiological parameters either directly
or indirectly have been used in the treatment of TTH, namely EMG biofeedback,
temperature biofeedback, GSR biofeedback, blood volume pulse biofeedback and
electroencephalogram (EEG) biofeedback. Of these EMG BF is the most
frequently used one and GSR BF has been used seldom.68
-
Review of literature
20
EMG Biofeedback
A recent review article including 11 studies concluded that owing to low
power of studies, the evidence to support or refute EMG biofeedback’s role in
TTH compared to placebo or any other treatments is conflicting.56
Since the
conclusion was drawn from a small set of studies, its results cannot be
generalised. Another critical review by Krishnan and Silver81
on the meta-analysis
by Nestrouric et al53
found insufficient evidence to determine whether EMG
biofeedback is effective in treating CTTH. It is difficult to comment on their
outcome, since the conclusion was drawn from critical analysis of one meta-
analysis only.
An assessment conducted by National Institutes of Health (NIH) panel on
efficacy of behavioural and relaxation therapies in chronic pain, established that
EMG biofeedback was more effective than psychological placebo but equivalent
to relaxation therapy for TTH.82
When analysis was done to no treatment or to
pseudo-placebo therapy, EMG BF alone or combined with relaxation therapy
were found to be more superior in a meta-analytic review of 78 articles with 2866
patients receiving cognitive feedback, relaxation therapy, EMG BF or EMGBF in
combination with relaxation therapy.76
Another meta-analysis found a 48% decrease in headache activity in which
EMG biofeedback/relaxation therapy was used with limited therapist contact.83
Reducing therapist contact time with no loss in efficacy is an important
consideration in terms of cost to the patient and in improving the confidence of the
patient to cope with headache.
-
Review of literature
21
Maintenance of the therapeutic effects of EMG BF is an important
consideration, which should not be overlooked. Nine TTH patients receiving
EMG BF/relaxation therapy were followed up to 5 years after treatment. A
headache index computed from the headache diary found that 78% of the patients
remained improved.84
GSR Biofeedback
A thorough literature search yielded two studies using GSR biofeedback
in tension type headache85,86
. The study by Collet et al85
was a comparative study
between GSR feedback (n = 16) and Schultz relaxation (n = 15) in patients with
tension headaches. They found no significant improvement in the group treated by
relaxation at the end of the treatment whereas the group treated by GSR feedback
showed significant improvements with respect to frequency and intensity of
headaches and to anxiety as measured by subjects' self-evaluation (p
-
Review of literature
22
investigators found that there was a significant increase in electrodermal activity
(p
-
Review of literature
23
pharmacological treatments. Their main intention is to improve the design of trials
and the reporting of results of studies on behavioural interventions for headache.
Measuring sites for EMG and GSR biofeedback
The American Headache Society (AHS) recommends measurement of GSR
from middle or distal phalanx of any two fingers or the palm.88
Similarly, the
psycho-physiological guidelines for techniques in measurement of electro-dermal
activity, also recommends that electro-dermal resistance be measured form either
middle or distal phalanges of two fingers, or thenar or hypothenar eminence of
palmar surface.89
Many researchers have preferred middle phalanx to distal as it is
thought to have less scarring and movement as compared to distal phalanx90,91,92,93
.
In a review of articles from 1985 to 1990 in the Psychophysiology journal,
the reviewers found that among 53 studies that used skin conductance as their
dependant variable 18 (34%) measured skin resistance from distal phalanx, 10
(19%) from the middle phalanx, 14 (26%) from the palm and three (6%) from
other sites; the remaining eight studies (15%) did not mention the site of
recording.94
Therefore it was seen that maximum studies used either distal or
middle phalanx for recording skin resistance. The variation of electrodermal
responses recorded from the distal and middle phalanx was studied by the same
group, which showed that distal phalanges were more electrodermaly active than
middle phalanx and that distal phalanx provide a more sensitive measure of electro
dermal activity than the middle phalanx.
On the contrary, Edelberg suggested that there are greater skin responses
from areas of greater tactile sensitivity.95
Ruch found that two-point discrimination
is higher (distance between the two points to be discriminated/recognised as two
-
Review of literature
24
points) in fingertips meaning that, finger tips are more sensitive than middle
phalanges.96
Therefore these areas show greater skin responses. In addition to this
there are greater numbers of sweat glands present on distal phalanx therefore
giving a greater skin conduction response.97
Therefore in this study the distal
phalanx of index and ring fingers are being used to assess the GSR activity, as
used by investigators in a recent study in which GSR BF was used in stressed
individuals.1
The most commonly used and popular placement of surface EMG
(SEMG) electrodes for TTH is on the frontalis muscle.98
In our study, the EMGBF
electrodes were placed 2.5cm above the centre of each eyebrow after appropriate
skin preparation as was followed in a study by Cohen et al.99
Outcome variables
As per the recommendation of the American Headache Society
behavioural clinical trials workgroup, 88
measure of frequency of headache should
be reported as the primary dependent variable. The recommendation for headache
frequency reporting is consistent with the IHS guidelines for controlled trials of
drug treatments100,101
and will facilitate meta-analyses and other comparisons
across studies of various interventions.102,103
The IHS clinical trials guidelines for
migraine prefer headache frequency to headache index because there is no
consistent definition of headache index, and changes in this measure can be more
difficult to interpret clinically.99
The guidelines have also mentioned a high desire for trials to include a
sufficiently wide spectrum of secondary outcome measures to capture possible
differential outcomes of drug and behavioural therapy. This is because, even if
-
Review of literature
25
drug and behavioural therapies are found to exert a similar impact on the primary
outcome variable, the impact of these two treatment modalities may differ on
other measures of functioning (e.g., psychological symptoms, quality of life,
efforts to manage headaches, etc).102,104,105,106
Identification of potential
differences in the impact of the two therapy modalities requires the inclusion of
outcome measures that assess a range of outcomes likely to be impacted by either
therapy modality.107,108
Moreover, studies have shown that genetic or family related environmental
factors are associated with about 50% of all cases.109
Major life events such as
surgery, divorce and deaths of close family members induce negative effect. Such
events in the prior year have been modestly related to the persistence of
headache.6 In addition to physical variables like muscle tension, electro-dermal
activity, temperature, etc and other demographic variables of pain, psychological
risk factors have been empirically associated with the incidence of headache.
These include life events, social support, hypnotisability, affect and negative
thinking.7 Trait negative affectivity is elevated in chronic headache and has been
related to over reporting of somatic symptoms like headache pain, independent of
organic disease.8, 9
. Inspite of TTH being the most prevalent type of headache,
little has been published about effect or burden of TTH on the health related
quality of life (HRQoL). Most of the research on HRQoL has been focussed on
migraine.110
Only a few studies pertaining to HRQoL have been done on chronic
TTH patients in general population111
or in specialised headache clinics112
.
Pain variables like frequency, intensity and duration of pain, can only
provide information about pain but not the impact that it has on the patient’s life.
-
Review of literature
26
Above review suggests that TTH has an impact on physical and mental health of
the patients, thereby affecting the quality of life in social life, at work place etc
causing impairment in overall functioning.
Therefore, in lieu of this secondary outcome variables chosen in our study
SF-36 QoL (Quality of life) total, physical and mental scores could cover a
broader aspect of the physical, mental and social aspects of the patient which
would represent the global health of the patient and impact of the headache on the
patients’ health.
In a population based study in Spain, the investigators found SF-36 to be a
reliable and valid tool for measuring the health related quality of life of patients
with chronic daily headache (CDH) and that it could be used as an effective tool
in studying the effectiveness of therapeutic agents for CDH.112
Another, similar
study done in the Italian population, found SF-36 tool was sensitive to clinical
changes in patients with primary chronic daily headaches.113
A first of its kind
survey, done on 901 patients with CDH, demonstrated that the SF-36 scores
varied among headache diagnoses. The SF-36 scores were greatly influenced by
psychological distress, as well as the percentages of the types of patients. Their
findings also suggested that improvement in the pain profile as well as
psychological well-being could predict a generalized improvement in the SF-36
scales in headache patients.114
Considering these studies, SF-36 QoL tool seems to
be a fairly reliable tool to assess effectiveness of intervention in TTH patients as
well.
The American Headache Society guidelines also urged the investigators to
employ a daily self-report headache diary as their principal dependent measure for
-
Review of literature
27
assessing treatment outcome whenever possible. Accordingly, a headache diary
was given to all our subjects in which they reported the frequency, duration and
intensity of every headache episode. They were asked to report the consumption
of medications as well, which we reported as one of our secondary outcome
measure.
Concurrent v/s terminal biofeedback:
Biofeedback may be concurrent or terminal. Concurrent BF is information
that is present all the time a person is receiving BF therapy. Terminal BF is
knowledge of results coming after an action, and is more likely to assist in
learning than is concurrent feedback.115
Giving concurrent feedback only
intermittently to supplement terminal knowledge of results appears to be of
probable value in permanent learning.116
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Methodology
6
-
Methodology
28
METHODOLOGY
Study design: This study was a randomized, single blinded, prospective
controlled trial.
Source of data: Data was obtained from the subjects recruited from various
neurology clinics and subjects referred by neurologists to the outpatient
department of KLES College of Physiotherapy, Hubli for biofeedback therapy.
Study duration: Subjects were recruited from January 2009 up to August 2011
and followed up till August 2012.
Informed consent: Subjects were recruited in the trial only after obtaining
informed consent from them. (Informed Consent Form approved by the ethical
committee attached)
Ethical clearance: Ethical clearance was granted by the ethical committee formed
by KLE University, Belgaum. (Ref: KLEU/08-09/D-10502)
Sampling design: Simple random sampling was used with lottery method for
allocation of subjects to seven groups.
Subjects with TTH were enrolled in the study. Subjects who did not
consent and who did not meet the eligibility criteria were excluded from the study.
The rest of the subjects were randomized using the lottery method for allocation.
Allocation procedure: Chits numbered one to seven were placed in a bowl and
the subjects were asked to pick the chits. Subjects with the following chit numbers
were allocated to the corresponding groups:
1 : EMG auditory biofeedback (EMGa) group
2 : EMG visual biofeedback (EMGv) group
3 : EMG auditory +visual (EMGav) group
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Methodology
29
4 : GSR auditory (GSRa) group
5 : GSR visual (GSRv) group
6 : GSR auditory +visual (GSRav) group
7 : Control group
Sample size: Sample size was calculated using the following formula:
N=2(Zα+Zβ)2×pq/(p1-p2)
2
Probability of Type I error was set at 0.05
Power of the study was set at 80% (0.8)
p1= 1.0 and p2=0.75 were the mean differences of pre and post (baseline to one
year) average frequency of headache per month in the EMG biofeedback training
group and pain management group respectively from a study by Mullay et al
2009117
.
p=0.875 was calculated as (p1+p2)/2 and q=0.125 was calculated as 1-p.
The sample size thus calculated was 26.6 per group. To accommodate for drop
outs the sample size was chosen as 30 per group.
STUDY POPULATION
Inclusion criteria: Subjects included in the study were:
• Subjects with headache fulfilling the criteria for TTH laid down by
International Headache Society.20
• Both males and females between 18 to 65 years.
Exclusion criteria: Subjects excluded from the study were:
• Subjects who underwent complementary alternative medicine
interventions in the past 6 months.
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Methodology
30
• Subjects with other headache types as described in International
Classification of Headache Disorders (ICHD) - II classification.
• Subjects with the presence of more than one type of headache in
addition to tension type headache.
• Subjects whose headache began after the age of 50 years.
• Subjects with serious somatic or psychiatric disease.
• Subjects with history of drug abuse or use of analgesics and triptans
>10 days per month.
Intervention: After allocation of subjects to the seven groups, all subjects were
informed about the treatment procedure in detail. Biofeedback training was given
in an isolated room in KLES College of Physiotherapy research laboratory, which
had minimal lighting and external noise, to facilitate relaxation. All subjects
underwent respective (EMG/GSR) BF training for 30 minutes per session for 15
sessions. Subjects underwent 15 biofeedback sessions with one session per day. If
the subject missed a session, the biofeedback session was provided when the
subject reported for therapy again, avoiding interval more than two days between
the sessions to avoid unlearning and deconditioning. The EMG BF was provided
using EMG-IR Retrainer (Chattanooga group Inc, U.S.A.) and GSR BF was
provided by GSR biofeedback Biotrainer GPF-2000 (Biotech, India).
EMG BF machine provided auditory and visual feedback. Auditory
feedback was in the form of clicks which increased in frequency and became a
continuous sound with increase in frontalis muscle tension and to no sound with
relaxation of frontalis muscle. Visual feedback on the display monitor was in the
form of glowing bars along with a numerical display which displayed the relative
-
Methodology
31
EMG activity of frontalis muscle in figures. The number of glowing bars was
directly proportional to tension in the frontalis muscle.
GSR BF machine similarly provided visual and auditory feedback. Visual
display was in the form of glowing bars and numerical display of real time skin
resistance in kilo-Ohms. The increase in number of red glowing bars depicted
increase in tension (fall in skin resistance) and decrease in the number of red bars
and increase in number of green bars indicated decrease in stress or tension
(increase in skin resistance). Auditory feedback was similar to EMG i.e. in the
form of clicks which became a continuous noise with increase in stress and to no
sound with relaxation. The training was given at 2% sensitivity with actual GSR.
No changes in sensitivity were made throughout the training sessions.
Skin preparation was done prior to attachment of electrodes by cleaning
the skin using spirit soaked cotton pad. After skin preparation surface EMG
electrodes (Ag-AgCl, triode electrodes) were applied 2.5cm above the centre of
each eyebrow118
and the GSR electrodes were applied on the middle phalanx of
the index and ring finger.89
Both EMG and GSR BF electrodes were placed on all
the subjects including the control group irrespective to which group they belonged
or what training they were to get. The subjects were unaware to whether they were
receiving EMG BF or GSR BF. The investigator was aware of the group the
subject belonged to and instructed the subject accordingly.
Both EMG and GSR BF auditory groups received only respective auditory
feedback. The subjects were instructed to reduce the tone and frequency of the
sound which would help them achieve relaxation. During the session the monitor
-
Methodology
32
on which the visual display was present was moved away from the field of vision
of the subject.
Similarly, both EMG and GSR BF visual groups were instructed to reduce
the number of glowing bars. In case of GSR, to decrease the number of red bars
and increase number of green bars to indicate relaxation. During the treatment
session the volume of the auditory tone was muted.
Both EMG and GSR audiovisual groups were instructed to reduce the tone
and frequency of sound as well as decrease the number of bars simultaneously.
Subjects in the control group were not asked to manipulate either the
visual or auditory display. They were only informed that their stress levels were
being recorded through the machines.
The subjects were instructed to practice relaxation at home, both during
the course of therapy and at the end of 15 sessions, in a way similar to the
relaxation during the biofeedback therapy sessions. However, compliance of the
subjects in the home program was not monitored. All subjects were allowed to
take the medications prescribed by their treating physicians especially if they were
preventive/prophylactic medications. They were requested to avoid taking any
analgesic / abortive / palliative medication unless the headache was unbearable.
Outcome parameters:
Primary variables:
As per the recommendations of the American Headache Society
Behavioral Clinical Trials Workgroup, 2005, 88
the primary variables selected for
our study were:
Average frequency of headache per week.
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Methodology
33
Average duration of headache per week.
Average intensity of headache per week.
The recommendation for headache frequency reporting is consistent with
the IHS guidelines for controlled trials of drug treatments100, 101
and will facilitate
meta-analyses and other comparisons across studies of various interventions.102, 103
Secondary variables: The secondary variables considered in our study were
SF-36 Quality of Life – total, physical and mental scores.
Analgesic consumption.
These secondary variables are also termed as “secondary non headache
measures” by the American Headache Society Behavioral Clinical Trials
Workgroup, 2005.88
Assessment of outcome variables:
The demographic data in regards to age, gender and chronicity of headache
was collected from all the subjects in the trial.
Pain Diary119: As per the guidelines of the American Headache
Society Behavioral Clinical Trials Workgroup, 200588
, a pain diary was given to
all the subjects in which they were asked to note down the headache episodes,
duration and intensity of headache they experienced in a week. At the end of the
week, the averages of the headaches in that week were calculated. The variables
were recorded as:
1. Average frequency of headache per week: number of headache
episodes per week.
2. Average duration of headache per week: total hours of all episodes
of headache that week divided by the number of episodes in that week.
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Methodology
34
3. Average intensity of headache per week: average of the ten-point
visual analogue score (VAS) per headache that week.
The subjects were also requested to note down the use of analgesics during
any of the pain episodes.
To assess the secondary variables, a licensed SF-36 questionnaire was
procured from Quality Metric Incorporated, USA in the regional language
(Kannada) and in English. It is a multi-purpose, short-form health survey with 36
questions and yields a psychometrically based physical and mental health
summary measures and a total score. The SF-36 was judged the most widely
evaluated generic patient assessed health outcome.120
Its reliability has been
estimated using both internal consistency and test-retest methods. Most of the
published reliability statistics have exceeded 0.80. Validity studies generally
support the intended objective of high and low SF-36 scores as documented in the
original user’s manuals.112,111,121
Analgesic consumption was recorded from the pain dairy of the subjects as
well as from the prescriptions of medications given to the subjects by their
treating physician.
Data collection:
All data was collected at the following time measures:
Baseline: scores of primary and secondary variables the week prior to
the start of the treatment.
Scores at one, three, six months and one year were the scores of the
last week of the corresponding month.
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Methodology
35
Statistical Analysis
SPSS version 16 was used for analysis of data. Repeated measures analysis
of variance (RMANOVA) was performed since the data was collected over
various time measures. Data spherecity was checked using Mauchly test and when
significant differences were found, data was corrected using Greenhouse Geisser
correction. Post hoc analysis was performed with modified Bonferroni correction
to find the point of significance for intragroup comparison and intergroup
comparison. Consumption of analgesics over one year was analysed using
Kruskall Wallis test and when significant differences were found Wilcoxson’s
signed rank test was done to find the point of significance. Partial eta squared
value (ηp2) was calculated for all primary and secondary variables to find the
effect size at one year inter group analysis. Percentage improvement was
calculated by subtracting the monthly scores from the baseline and dividing it by
baseline scores. This end product was then converted to percentage by multiplying
it by 100. Significance for the results was set at p< 0.05.
-
Results
7
-
Results
36
RESULTS
A total of 232 subjects were enrolled in the study. Twenty-one subjects
were excluded because they did not meet the eligibility criteria or did not consent
to be a part of the study or quoted as the place and timing of treatment being
inconvenient to them. 211 subjects were randomized using lottery method for
allocation as described in the methodology. Nineteen subjects failed to complete
the treatment (thirteen subjects did not report for their treatment schedules, four
subjects switched over to other complementary therapies, two reported
inconvenient place for treatment). There were five dropouts in the first follow-up
(one month), of which two developed another health problem not related to
headache and three switched to alternative medicine. Additional ten were lost to
follow-up in the second follow-up at three months, of which four did not report
for follow-up, two subjects had a change of residence and four subjects switched
to alternative medicine. We lost ten subjects in the third follow-upat six months,
of these three subjects could not be contacted due to change in phone number, five
switched to alternative medicine, one subject developed a health problem and one
failed to report for follow up. Further sixteen subjects were lost to follow-up in the
fourth follow-up at one year, of whom seven subjects could not be contacted due
to change in phone numbers and residence; three subjects reported other health
problems and six subjects switched to alternative medicine. Overall in the study
period, eighteen subjects switched to alternative therapy (Homeopathy, Ayurveda,
Accupuncture, etc) at various follow up periods. At one month (3 subjects;
EMGv=2, EMGav=1), at three months (4 subjects; EMGav=2, GSRa=1,
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control=1), at 6 months (5 subjects; EMGa=1, EMGv=1, GSRav=1, GSRv=2) and
at one year (6 subjects; EMGa=1, EMGav=1, GSRav=2 and Control=2).
Eventually, 151 subjects were analysed (Figure 1). In total, sixty subjects
dropped out from the initially recruited and randomised 211 subjects with 28.4%
drop out rate, which was more than the acceptable norms of 20% for randomised
controlled trials. However, anticipating a large dropout in the longitudinal study,
this limitation of dropouts was accommodated by increasing the sample size by 21
subjects more than the total calculated sample size.
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Figure 1: Flow chart of subjects through the trial
232 subjects assessed for eligibility Excluded n= 21, Not
meeting inclusion Criteria (n=9)
Declined to participate (n=7), Inconvenient
timings and place (n= 5)
Allocated to EMGa (n=30) Failed to receive treatment (n=3)
Allocated to EMGv (n=30) Failed to receive treatment (n=2)
Allocated to EMGav (n=30) Failed to receive treatment (n=3)
Group EMG,n= 90, Electromyography Biofeedback + Progressive relaxation
Group GSR, n= 90, Galvanic skin resistance Biofeedback + Progressive relaxation
Group C, Control group, n= 31 Progressive relaxation only
Allocated to GSRa (n=30) Failed to receive treatment (n=4)
Allocated to GSRv (n=30) Failed to receive treatment (n=1)
Allocated to GSRav (n=30) Failed to receive treatment (n=2)
211 subjects randomised
Allocated to Control (n=31) Failed to receive treatment (n=4)
(n=27) (n=26),Lost to follow up (n=2) (failed to report for follow-up)
(n=26), Lost to follow up (n=1) (failed to report for follow-up)
(n=26)
(n=28), Lost to follow up (n=1) (failed to report for follow-up)
(n=28)
(n=26), Lost to follow up (n=1) (failed to report for follow-up)
(n=25)Lost to follow up (n=2) (failed to report for follow-up)
(n=25)Lost to follow up (n=1) (failed to report for follow-up)
(n=25)Lost to follow up (n=1) (failed to report for follow-up)
(n=24)Lost to follow up (n=2) (failed to report for follow-up)
(n=26)Lost to follow up (n=2) (failed to report for follow-up)
(n=27)Lost to follow up (n=1) (failed to report for follow-up)
(n=25)Lost to follow up (n=1) failed to report for follow-up)
(n=25)
n=24) Lost to follow up (n=1)
(n=23) Lost to follow up (n=2)
(n=23) Lost to follow up (n=1)
(n=23) Lost to follow up (n=3)
(n=25) Lost to follow up (n=2)
(n=24) Lost to follow up (n=1)
(n=23) Lost to follow up (n=2)
(n=21) Lost to follow up (n=3)
(n=22) Lost to follow up (n=1)
(n=21) Lost to follow up (n=2)
(n=20) Lost to follow up (n=3)
(n=22) Lost to follow up (n=3)
(n=22) Lost to follow up (n=2)
Analysed n=23 Analysed n=21 Analysed n=22 Analysed n=21 Analysed n=20 Analysed n=22 Analysed n=22
Eval
uate
d at
6
mon
ths
Eval
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d at
1
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th
Eval
uate
d at
1
yea
r Ev
alua
ted
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Allo
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Demographic data:
Demographic data in terms of age, gender, chronicity of headache and education level was collected from the subjects in the trial.
There was no significant difference between any of the groups in regards to age and chronicity of headache (p>0.05). Number of females
in all groups was more in comparison to males (Table 1). Education level too showed an insignificant difference between groups
(p=0.49).
Table 1: Demographic Data [Mean (95%CI)]
Variables EMGa
n=27
EMGv
n=28
EMGav
n=27
GSRa
n=26
GSRv
n=29
GSRav
n=28
Control
n=27 P
Age (years) 36.7
(32.2-39.3)
39.2
(36.2-44.1)
37.4
(33.5-41.3)
35.2
(30.1-36.2)
38.1
(32.4-40.3)
35.6
(32.5-38.7)
37.3
(33.5-41) 0.43
Chronicity of
headache
(years)
11.9
(8.2-13.9)
13.9
(12.7-15.0)
12.5
(9.6-14.45)
14.2
(11.7-16.6)
11.7
(9.2-14.13)
10.9
(7.4-14.3)
11.2
(8.6-15.3) 0.55
Gender
no. females(%) 22(81.4) 22(78.5) 19(70.3) 21(80.7) 20(72.4) 21(75) 20(74) --
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40
Baseline variables:
I] Pain variables:
Average frequency of headache per week was lower inGSRv (4.6+2.3)
than all the other groups. At baseline itself there were significant
differences between EMGv (p=0.04) and EMGav (p=0.05) when
compared to GSRv. Significant difference was found in average duration
of headache per week between EMGa and control (p=0.01) at baseline.
There were significant differences noticed in average intensity of headache
per week between EMGv v/s GSRav (p=0.01) and EMGv v/s control
(p=0.007) at baseline.(Figure 2, Table 2)
Figure 2: Means of pain variables at baseline.
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41
Table 2: Baseline pain variables in the study group
Comparison of
variables at baseline p value (Mean difference)
Pain variables
Average
frequency
of headache
Average
duration
of headache
Average
intensity
of headache
EMGa vs EMGv 1.0(-.93) 1.0(2.6) 1.0(-.60)
EMGav 1.0(-.63) 1.0(.56) 1.0(-0.6)
GSRa 1.0(1.2) 1.0(2.3) 1.0(.76)
GSRv 0.12(2.5) 1.0(1.3) 1.0(.06)
GSRav 1.0(1.0) 0.38(3.6) 1.0(1.2)
Control 1.0(.13) 0.01(4.1) 0.40(.93)
EMGv vs EMGav 1.0(.30) 1.0(-2.0) 1.0(.53)
GSRa 0.19(2.1) 1.0(-.33) 0.08(1.3)
GSRv 0.04(2.0) 1.0(-1.3) 1.0(.66)
GSRav 0.30(1.2) 1.0(-1.0) 0.01(1.8)
Control 1.0(1.0) 1.0(1.5) 0.007(1.5)
EMGav vs GSRa 0.76(1.8) 1.0(1.7) 0.86(.83)
GSRv 0.05(1.9) 1.0(.76) 1.0(.13)
GSRav 0.12(1.7) 1.0(3.1) 0.36(1.2)
Control 1.0(.76) 0.56(3.5) 0.44(1.0)
GSRa vs GSRv 1.0(.70) 1.0(-.96) 1.0(-.70)
GSRav 1.0(-.13) 1.0(1.3) 1.0(.43)
Control 1.0(-1.0) 1.0(1.8) 1.0(.16)
GSRv vs GSRav 1.0(-.83) 1.0(2.3) 0.75(1.1)
Control 0.07(-1.7) 1.0(2.8) 1.0(.86)
GSRav vs Control 1.0(-.93) 1.0(.46) 1.0(-.26)
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42
II] SF-36 scores
Significant differences were found in total SF-36 scores at baseline when
pair wise comparisons were made between GSRa v/s EMGv (p=0.05),
EMGav (p=0.03), GSRv (p=0.007) and GSRv v/s control (p=0.02).No
significant differences were found in the physical and mental scores of SF-
36 between any comparisons; therefore in this regard all groups were
homogenous. (Figure 3, Table 3)
Figure 3: Means of SF-36 scores at baseline
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Table 3: Baseline SF-36 variables in the study group
Comparison of
variables
at Baseline
p value (Mean difference)
SF-36 Total score Physical score Mental score
EMGa vs EMGv 1.0(-2.1) 1.0(-5.2) 1.0(-5.1)
EMGav 1.0(-2.4) 1.0(-1.6) 1.0(-2.6)
GSRa 1.0(5.9) 1.0(3.2) 1.0(2.2)
GSRv 1.0(-3.4) 1.0(1.7) 1.0(-3.9)
GSRav 1.0(-.26) 1.0(.96) 1.0(-1.8)
Control 1.0(5.5) 1.0(4.4) 1.0(2.9)
EMGv vs EMGav 1.0(-.3) 1.0(3.6) 1.0(2.4)
GSRa 0.05(8.0) 0.27(8.4) 0.22(7.3)
GSRv 1.0(-1.3) 0.55(6.9) 1.0(1.1)
GSRav 1.0(1.8) 0.50(6.1) 1.0(3.2)
Control 0.46(7.6) 0.06(9.6) 0.15(8.0)
EMGav vs GSRa 0.03(8.3) 1.0(4.8) 0.46(4.9)
GSRv 1.0(-1.0) 1.0(3.3) 1.0(-1.3)
GSRav 1.0(2.1) 1.0(2.5) 1.0(.82)
Control 0.12(7.9) 0.25(6.0) 0.78(5.5)
GSRa vs GSRv 0.007(-9.3) 1.0(-1.5) 0.31(-6.2)
GSRav 0.14(-6.1) 1.0(-2.2) 1.0(-4.1)
Control 1.0(-.36) 1.0(-1.1) 1.0(6.4)
GSRv vs GSRav 1.0(3.2) 1.0(-.73) 1.0(2.1)
Control 0.02(9.0) 1.0(2.7) 0.16(6.8)
GSRav vs Control 0.45(5.8) 1.0(3.4) 0.71(4.7)
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III] Analgesic consumption:
Kruskall Wallis H test found no significant differences between groups at baseline on analgesic consumption
[H(6,N=151)=5.36,p=0.49]. (Table 4)
Table 4: Consumption of analgesics. [n(percent)analgesic usage, Mean rank]
p value calculated by Kruskall Wallis test
Groups Baseline 1 month 3 months 6 months 1 year p value
EMGa(n=27) 23(100), 54.5 20(75), 44 15(60), 37.7 15(53.3), 34.9 11(45.4), 31.5 0.003
EMGv (n=28) 24(95.8), 56.6 20(70), 45.4 17(58.8), 40.5 14(42.8), 33.6 12(41.6), 33.1 0.002
EMGav(n=27) 24(87.5), 58.8 21(90.4), 60.3 23(60.8), 45.8 18(50), 40.5 12(33.3), 32.3 0.001
GSRa(n=26) 23(91.3), 53.5 20(85), 50.6 19(68.4), 47.9 15(40), 36.2 14(50), 34.7 0.01
GSRv(n=29) 20(100), 40.5 14(85.7), 35.8 12(66.6), 29.6 10(60), 27.5 9(44.4), 22.4 0.007
GSRav(n=28) 22(95.4), 50.3 18(100), 40.5 15(85.7), 37.8 14(71.4), 36.6 12(50), 33.7 0.08
Control (n=27) 17(82.3), 42.2 16(68.7), 38.1 14(57.1), 33.1 12(83.3), 24.6 10(60), 30.9 0.04
p value 0.49 0.71 0.99 0.04 0.98
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Repeated Measures Analysis of variance (RMANOVA):
Primary variables:
1. Average frequency of headache/week:
Intra group: All groups showed a significant reduction in average
frequency of headache/week at the end of one year except control group
[F(1,21)=2.98, p=0.06, ηp2=0.09] (Table 5, Figure 4). A post-hoc analysis
to find the point of significance, revealed significant differences after six
months of intervention in all EMG groups (Table 6), whereas GSRv and
GSRav found reductions in the first and third month itself, the reduction
then plateaued thereafter up to one year. GSRa showed a difference only at
one year (p=0.01) (Table 7).
Inter group: ANOVA findings on intergroup analysis showed a
significant difference between all groups at one month [F(1,11)=610,
p=0.001, ηp2=0.98], three months [F(1,8)=157,p=0.001, ηp
2=0.95],
six months [F(1,5)=57.6,p=0.001,ηp2=0.92] and one year
[F(1,2)=61.1,p=0.01, ηp2=0.96] (Table 5). A post-hoc showed the point of
significance between EMGav and GSRv (p=0.04, 95%CI:-1.2-6.8) at one
month (Table 9), between EMGa v/s control (p=0.02, 95%CI:-4.2-6.8),and
EMGavv/s GSRv (p=0.05, 95%CI:3.9-8.4) at three months (Table 10),
EMGv v/s EMGav (p=0.05, 95%CI:-5.8-0.4) and control (p=0.05,
95%CI:-4.2-1.4), EMGav v/s control (p=0.02, 95%CI:-2.2-4.5) and
GSRav v/s control (p=0.05, 95%CI:-5.3-1.2) in the sixth month (Table 11)
and between five pairs with EMGav showing most of the differences at
one year. (Table 12)
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Table 5: Intra and Inter group analysis of pain variables of all groups. Mean+SD(95%CI)
Variables EMGa EMGv EMGav GSRa GSRv GSRav Control p value
Frequency Baseline 7.1± 2.6(5.9-8.2) 7.6±1.6(6.8-8.4) 7.5±3.2(6.1-9) 5.4±2.8(4.1-6.7) 4.6±2.3(3.5-5.7) 5.9±2.4(4.8-6.9) 6.2±2.1(5.2-7.1) 0.01
1 month 6± 2.4 (4.9-7) 6.2±2.9(4.8-7.5) 6.5±2.8(5.2-7.7) 5.1±2.5(3.9-6.2) 3.1±1.6(2.3-3.9) 4.4±2(3.5-5.3) 5.4±1.6(4.7-6.2) 0.001
3months 5.3± 3.1 (3.9-6.7) 6.2±3.8(4.3-8) 5.8±2.7(4.6-7) 3.8±1.3(3.2-4.4) 3.7±0.9(2.2-3.1) 3.8±1.9(2.9-4.7) 5±2.6(3.8-6.2) 0.001
6months 3.7±1.7 (2.9-4.4) 4.6±2.1(3.6-5.6) 4.5±2.8(3.2-5.7) 4.1±2.2(3.1-5.2) 3.7±2.2(2.6-4.7) 3.9±2.4(2.8-4.9) 5.3±2.4(4.2-6.4) 0.001
1 year 3±2.2 (2.1-4) 3.5±1.5(2.8-4.2) 2.9±1.7(0.5-2) 2.7±1.5(2-3.4) 2.9±1.9(2-3.8) 2.6±1.5(0.9-2.3) 4.6±2.4(3.5-5.7) 0.01
p value 0.005 0.04 0.003 0.006 0.004 0.02 0.06
Duration Baseline 15.1±5.4(12.8-7.5) 11.4±7.1(8-14.7) 13.2±6.4(10.4-16.1) 12.3±6.7(9.3-15.4) 14.2±6.3(11.2-17.1) 11±6.6(8.1-14) 10.2±4.7(8.1-12.3) 0.03
1 month 11.6±6(9-14.2) 8±4.5(5.8-10.1) 9.2±4.8(7-11.3) 8.6±5.5(6.1-11.1) 9.9±2.8(5.5-8.2) 7.5±5.2(5.1-9.8) 7.4±3.4(5.8-8.9) 0.001
3months 8.1±4.7(6-10.2) 6.7±3.2(5.1-8.2) 7.5±3.8(5.8-9.2) 5.6±3.7(3.9-7.3) 5.1±3(3.6-6.5) 5±3.1(3.6-6.4) 5.3±2.8(4.1-6.6) 0.001
6months 5.3±3.1(3.9-6.6) 5.2±2.5(4-6.4) 5.5±2.7(4.3-6.6) 5±3.5(3.4-6.6) 6.9±5.3(4.4-9.4) 4.9±3(3.5-6.2) 6.5±3.4(4.9-8) 0.001
1 year 3.6±2.4(2.5-4.6) 4.4±2.2(3.3-5.4) 4.2±1.6(0.5-1.9) 3.3±1.7(2.5-4) 5±2(2.1-3.9) 3±1.8(1.2-2.9) 5.2±3.3(3.7-6.7) 0.01
p value 0.005 0.004 0.002 0.006 0.005 0.003 0.002
Intensity Baseline 6.9±1.6(6.2-7.6) 7.5±1.3(6.8-8.1) 6.7±1.4(6.1-7.3) 5.9±2(5-6.8) 6.4±2.1(5.4-7.4) 5.5±2.3(4.5-6.6) 5.8±1.9(5-6.7) 0.02
1 month 5.7±1.1(5.2-6.2) 5±1.2(4.4-5.6) 4.7±2(3.7-5.6) 4.4±1.8(3.6-5.3) 3.2±1(2.7-3.6) 4±1.8(3.2-4.8) 4.2±1.6(3.5-5) 0.001
3months 3.6±1.8(2.8-4.3) 3.3±0.9(2.8-3.7) 3.7±1.7(2.9-4.5) 3.9±1.2(3.3-4.4) 2.6±1(2-3.1) 3.3±1.9(2.4-4.1) 3.3±1.4(2.6-3.9) 0.001
6months 3.1±1.4(2.5-3.8) 3.3±1(2.8-3.7) 2.7±1.6(2-3.5) 2.7±1.2(2.1-3.2) 2.6±1.9(1.7-3.5) 2.4±1.7(1.6-3.2) 3.4±1.4(2.7-4) 0.001
1 year 1.9±1.3(1.3-2.5) 2.5±1.4(1.8-3.1) 1.9±1.1(0.3-1.3) 2.2±1.3(1.6-2.8) 1.9±1.2(1.3-2.4) 2.2±1.2(0.8-1.9) 3.1±1.4(2.5-3.7) 0.001
p value 0.006 0.01 0.01 0.01 0.03 0.002 0.05
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Figure 4: Trend of average frequency of headache through the time measures.
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Table 6: Intra group comparison of pain variables in EMG groups
p value (Mean difference)
Pain variables
Average
frequency of
headache
Average
duration of
headache
Average
intensity of
headache
EMGa baseline v/s 1 month .16(1.1) .001 (3.1) .04(1.2)
3 months .20(1.7) .00 (7.0) .00(3.3)
6 months .00(3.3) .00(9.8) .00(3.7)
1 year .00(4.0) .00(11.9) .00(5.0)
EMGa1 month v/s 3 months 1.0(.65) .01(3.5) .00(2.1)
6 months .001(2.2) .00(6.3) .00(2.5)
1 year .001(2.9) .00(8.0) .00(3.8)
EMGa 3 months v/s 6 months .006(1.6) .00(2.8) 1.0(.43)
1 year .006(2.2) .001(4.5) .007(1.6)
EMGa 6 months v/s 1 year 1.0(.65) .14(1.6) .02(1.2)
EMGv baseline v/s 1 month .20(1.4) .10(3.4) .00