Part2.doc

Usman Omar Ghani

Chapter 3: Aims and objectives

(Luders H: 2000)

Aim:

To critically evaluate the detection, diagnosis and management of Ohtahara

syndrome.

Objectives:

To review the current literature describing the neurophysiology, aetiology and

management of Ohtahara syndrome.

To identify and interview international experts and attain there opinions on

Ohtahra syndrome.

Through the usage of a questionnaire, sample the current level of knowledge on

Ohtahra syndrome in the health professionals in the United Kingdom.

MSc Medical Diagnostics Thesis August, 2002 71

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Through informal methods, obtain information from relatives of Ohtahara

syndrome, concerning there present experiences of detection, diagnosis and

management of Ohtahara syndrome.

To make preliminary recommendations as to the pathway for future research into

Ohtahara syndrome.


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3.1 Research methodology

Memory valley park, Sanfransisco (Luders H: 2000)

Introduction

There were many unanswered questions for Ohtahara syndrome and the only line of

contact was Dr. Kamal Sawney, who was our consultant paediatrician at High

Wycome hospital. The line of contact commenced with Dr. Sawney and subsequent

recommendations were given to approach Dr. Alison Shaw and Dr. Ian McShane at

John Radcliff hospital, in Oxford. Other opinion formers who were approached

include Dr. Geoff woods (St. James Hospital in Leeds), Dr. Howard (Great Ormond

street hospital in London), contact a family supporting group, and last but not least

Dr. Ohtahara the preliminary founder of Ohtahara syndrome. Except Dr. Ohtahara and

Dr. Howard, all the remaining opinion formers had been interviewed under informal

surroundings at there practising locations. Dr, Ohtahara and Dr. Howard were in

contact by forms of written and email exchanges.

Contact was made with families touched by Ohtahara syndrome, commencing with

Tammie Horak (moderator and owner of the official Ohtahara web site), moving onto

Susan Titbits (who resides in the United Kingdom), and the Adams, Newton and

Heelas families (with whom personal contact was made by either home visits or

telephone communication),


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A questionnaire was designated to evaluate the current understanding of Ohtahara

syndrome in the medical community, and delivered by hand or posted to general

practioneers, nurses and paediatrics at children’s wards.

3.1 Contact with opinion formers.

Dr. Kamal Sawney (consultant paediatrician at High Wycome hospital).

Dr. Sawney was selected because of his close association with our encounter with

Ohtahara syndrome. He is a consultant paediatrician at High Wycome hospital, who

managed our Ohtahara cases.

Dr. Sawney had built a strong bond with me, and that made him very approachable,

first contact was made via a phone conversation to arrange a meeting, which was set

for the 18th of April 20002, at High Wycome hospital.

It was an informal meeting, which lasted for over two hours. There were no set

questions, prior to the meeting, just suggestions.

Key notes were made during the meeting, specifically the names of further contacts

and there addresses.

Dr. Alison Shaw (senior social science lecturer at Brunel University).

Dr. Shaw was also heavily involved with our experience with Ohtahara syndrome. In

addition Dr. Sawney recommended that contact should be made with her.

Dr. Shaw was approached by phone call and subsequent communication was achieved

via emails and telephone conversations.

The communication with Dr. Shaw was informal and advice was attained on further

lines of contact. There were set questions in place, specifically the original aims. Her

views on these aims were asked.

Dr. Shaw’s views and recommendations were stored on email exchanges.


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Dr. Geoff Woods (consultant paediatric neurologist at St. James hospital, Leeds).

Dr. Woods was selected for contact, because of his interests in rare metabolic

disorders and on the recommendations from Dr. Alison Shaw.

A letter was written to Dr. Woods, explaining my research aims and objectives and

asking for an appointment to see him. A reply from Dr. Woods gave me an

opportunity to meet him at St. James hospital in Leeds, on the 15th of May 2002.

The method of interview was based on set questions on my aims and his research

interests. During the meeting written notes were taken on recommendations and

further contacts.

Howard (consultant paediatric neurologist at Great Ormand Street hospital).

Dr. Howard was selected because of recommendations from Dr. Woods, which

suggested that Dr. Howard was located in a specialist hospital for infants and the

neurological experience Dr. Howard had would be beneficial to my research.

An appointment for an interview was requested by written letter.

Contact a family

This support group was contacted because of recommendations by Dr. Woods, and in

that the group provided a support network for rare disorders. There was a hope of

making contact with families affected by Ohtahara syndrome.

Initial contact was by telephone conversation and an address was attained, and a letter

was written asking for details on Ohtahara cases, in there group.

The written letter, asked for any information they hold on Ohtahara syndrome and any

further contacts that can be suggested.

A photo copy of the letter was kept for reference.


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Dr. Ian McShane (senior neurologist at John Radcliff hospital, in Oxford).

Dr. McShane had been involved with our own experience with Ohtahara syndrome;

he is also one of the senior paediatric neurologists in the United Kingdom. Dr.

McShane has extensive experience backed up with over twenty five years experience

working with infants touched by rare neurological disorders.

A letter requesting an appointment was sent to Dr. McShane, which explained my

research aims and objectives. The interview with Dr. McShane was structured with

prior planned questions, which were sent to him in the original letter, in order that Dr.

Mcshane had awareness of the issues being raised. The meeting was attended by me

and Dr. Alison Shaw, the duration of the meeting lasted nearly two hours, and the

information was assimilated on note form by me and Dr. Shaw.

Dr. Ohtahara

It was extremely necessary to have the views and opinions of Dr. Ohtahara; after all

he was the founding father of this disorder.

A group member from the Ohtahara site, James Pearce informed me that he has been

trying for some time to contact Dr. Ohtahara, without success. I attained

Dr.Ohtahara’s email address from Mr. Pearce and wrote to him, explaining my

personal and academic association with Ohtahara syndrome. No reply came, I than

located Dr. Ohtahara’s mail address from Mr. Pearce and wrote him a letter, with my

mail and email address attached. A week later I received my first channel of

communication with Dr. Ohtahara, a brief email confirming receipt of my letter.

The main line of communication with Dr. Ohtahara was primarily written letter and

then subsequent email exchanges. The first few emails were self explanatory on my

own experience with Ohtahara syndrome, with latter emails placing suggestions to Dr.

Ohtahara and asking for his recommendations.

The replies from Dr. Ohtahara were printed from the computer and placed for

referencing.


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3.2 Internet sites

Two sites were selected for there support to rare inherited disorders, the first was

www.nord.org (national organization for rare disorders). This site was recommended

by Dr. Geoff Woods (St. James hospital, Leeds). It was selected because it gave a

support network to families of rare disorders.

The second site was located at http://groups.yahoo.com/group/ohtaharasyndrome; it

was selected because it was the official site for Ohtahara syndrome families.

Both sites had written opinions of family members and these opinions were in the

form of posted emails, which included archives dating back to 1994.

Relevant information from the posted emails was printed and used for references.

3.3 Relatives of Ohtahara syndrome.

Tammie Horak

Tammie Horak is the grandmother of an Ohtahara child Tyler. Initial contact with

Mrs. Horak was made through the official web site for Ohtahara families, which was

set up and moderated by Mrs. Horak.

Being the site owner Mrs. Horak had been involved with many families and had

immense knowledge on this disorder. I needed clarification of the official site

members and the contact details of other members who were not on site.

The information given by Mrs. Horak was in the form of emails and written letters,

and this information was printed and filed for reference purposes.


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Susan Titbits

It was through Tammie Horak that contact was made with Susan Titbits. From

previous posted emails on the Ohtahara web site, I was able to attain Mrs. Titbit’s

home telephone number; this formed the bases for initial contact via a telephone call.

I needed to attain information from Mrs. Titbits, on the number of Ohtahara families

that were in contact with her, and her own personal encounter with this syndrome.

Contact addresses and telephone numbers of other family members touched by

Ohtahara syndrome, were noted.

The Adams, Newton’s and Heelas families.

The families were from the United Kingdom. The initial contact was achieved via the

telephone and a meeting was arranged at there residence.

I needed to gain personal insight into there daily management of this disorder, which

effected there child. I needed to know at what age was there child diagnosed of having

Ohtahara syndrome? What medication was given? If any further investigations were

planned by there neurologist?

The information gained from the personal visits noted on written paper and further

contact details of the children’s neurologist were taken.

3.4 Ohtahara syndrome questionnaire (refer to appendix to see the questions)

A questionnaire was designed to evaluate current understanding of Ohtahara

syndrome in the medical community. The questionnaire is aimed at: general

practioneers, nurses at special care baby units and paediatrics working on baby wards.

The questionnaire was set out in a list form comprising of multiple choice questions.

The linguistical language used was plain and in short form; the questionnaire was

designed to be completed in the least amount of time needed, and bearing in mind

how busy the participants are.


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The first three questions are set out to evaluate the understanding of what Ohtahara

syndrome is. If the participant had not heard of Ohtahra syndrome and ticked “no” in

the questionnaire, than the rest of the questionnaire will be basically guess work rather

than a clear understanding.

Question 4 assesses the knowledge of the participant on the aetiology of this

syndrome, while question 5 assess on the disorders incidence in the general public.

Question 6 tries to categorize the age group which is affected for this disorder.

Question 7 asks for the symptoms for this disorder and question 8 defines the mode of

diagnoses for Ohtahara syndrome.

Question 9 is designed to assess the participant’s knowledge on the management of

this disorder, once it has been diagnosed.

Question 10 is based on the epidemiology of this disorder, and assesses weather the

participant knows of the epidemiology of this disorder.

From question 11, the questions are designed for the personal opinion of the

participant; the questions are general and broad. Can Ohtahara be prevented? It is a

yes or no question.

Question 13 asks the participant if they would require more knowledge on the subject,

which leads onto question 14, assessing there recommendations for a need for more

research into this disorder.

The questionnaire concludes with question 15, which summarizes the proposed

project post this thesis and asks if they would give there backing. How supporting is

the participant of any further research into Ohtahara syndrome.

A letter from me was enclosed with the questionnaire to all participants (see

appendix).

At the end of the questionnaire a brief description of Ohtahara syndrome is attached,

to enlighten participants of the disorder.


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3.4.1 General Practioneer doctors

General Practioneers were selected because of there close association with the general

population, as a first contact mode for health issues. During the period of gestation the

GP is the first line of contact, and expectant mothers are closely monitored and

assessed by the family doctor.

Four surgeries were sent the questionnaire; New surgery (Chesham,

Buckinghamshire); Green meadows surgery (Amersham); Flitwick Health Centre

(Flitwick in Bedfordshire); and Dr. Hows surgery (Chesham in Buckinghamshire).

New Surgery (Chesham)

Our family doctor is based at the New Surgery, which has 6 partners in practise. This

surgery was selected to assess information co-ordination between the partners and to

evaluate the level of understanding of this disorder in the other five patners, bearing in

mind three of its patients died from Ohtahara syndrome in the past five years.

The questionnaires were taken by hand and given to the medical secretary, to be

passed onto the doctors, and the results to be collected by hand in a fortnight.

Green meadows surgery

This surgery was selected because of its location in Buckinghamshire, it is located

between the New surgery and High Wycome hospital and is has a large number of

partners, comprising of 8 practising general practioneers.

The questionnaires were taken by hand and handed in at the surgery; the filled

questionnaires were to be collected in a fortnight.

Dr. How’s Surgery

This surgery was selected because of its historical routes in Chesham; it has been in

residence since 1952, with a second generation doctor in practise. It is a small surgery

with two partners from the same family.


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The questionnaires were taken by hand and given to the medical secretary, was

informed the results will be sent by post.

Flitwick health centre

This health centre was selected because of its rural location, in comparison to the

above surgeries. The health centre is close to the university and is easily accessible. It

has 5 practising partners.

The questionnaires were taken by hand and given to the external medical secretary,

and arrangements were made to collect the results in a fortnight’s time.

3.4.2 Special care baby units at High Wycome and Luton Hospital.

Special care baby units form the first line of diagnostic investigations for unwell post

natal babies. Tests and investigations are carried out and the babies are continuously

monitored for treatment. It is here were any abnormal movements or symptoms are

analysed and investigated.

The special care baby unit at High wycome hospital was selected to participate in the

questionnaire because of there close involvement with our cases, and weather there

was an increased awareness at this site in comparison to the Luton Hospital site,

bearing in mind the special care baby unit at High wycome had dealt with three cases

of Ohtahara syndrome in the past five years. The questionnaire is aimed at the nurses

at both hospitals.

The questionnaires were personally handed to the clerk at reception, and arrangements

were made to collect the results in a fortnight.

3.4.3 Paediatrics

Paediatrics specialise in post natal infants and assess there symptoms on children’s

ward. They are responsible for the direction of investigation for an unwell infant, and

how quickly the symptoms are picked on, the aetiology is located that treatment may

than commence.


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Both children’s wards at High Wycome and Luton Hospital were given questionnaires

for there paediatrics to fill in.

The questionnaires were handed by hand to the receptionist and self addressed

envelopes were enclosed for replying.

3.4.4 Information required from the questionnaire

The questionnaire is designated to give an indication of the level of awareness of

Ohtahara syndrome in the medical community, and there recommendations for a

further in-depth study on this syndrome, specifically at grass root level by general

practioneers, nurses at special care baby units and paediatrics.

Inadition comparisons will be made of the different general practioneers surgeries, in

particular at the New Surgery (were they dealt with our cases) and special care baby

units at both hospitals (High Wycome and Luton).

The number of filled in questionnaires returned and by which profession will be

analysed, as will the level of awareness be compared within the medical profession.

The results from the questionnaire will be analysed by comparative graphs and

numerical tables. In all there were 49 questionnaires sent.


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Chapter 4: Results

4.1 Statement of facts

Dr. Sawney

My first line of investigation was with Dr. Sawney, it was the start of the thesis and I

had an informal interview with him. I was informed, it was a difficult and rare

disorder to analyse, because it was rare, there was little literature on it. Dr Sawney

informed me he would make arrangements for me to meet Dr. McShane, from John

Radcliff hospital, in Oxford, and I should also write to him requesting an

appointment. He also suggested I get in touch with a researcher from Brunel

University, Dr. Alison Shaw, whom we had met before at Dr. Hearly’s geneticist

clinic.

Recommendations

Contact Dr. Alison Shaw.

Contact Dr. Ian McShane.

Dr. Alison Shaw

Second line of contact was Dr. Alison Shaw; she was researching the effects of rare

disorders on ethnic minorities. I spoke to her on the telephone and explained my

research aims, which at that time were;

1. Attempting to find the aetiology of Ohtahara syndrome.

2. Devising a diagnostic kit for detecting the disorder prior to birth.

3. Investigating to the reason why anti epileptic medication had limited

effects on infants of Ohtahara syndrome.

Dr. Alison Shaw was encouraged by my research and promised to do all is needed to

assist me. It was suggested that I should contact Dr. Geoff Woods, of St. James

hospital in Leeds.


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Recommendations

Contact Dr. Geoff Woods.

Dr. Geoff Woods

Dr. Woods was a senior geneticist at St. James hospital, in Leeds. He had attained a

grant from the Welcome trust, to research genetically based disorders in Pakistani

families.

An appointment was arranged to meet Dr. Woods, in Leeds. I had a very constructive

experience at Dr. Wood’s laboratory. I had learnt a great deal on his research aims,

but there was little he could do to assist me.

Dr. Woods had little knowledge of Ohtahara syndrome, the fact it was not an inherited

disorder, he could offer me no additional information. How ever, at the conclusion of

the meeting, Dr. Woods suggested that I contact a senior neurologist Dr. Howard at

Great Ormond street hospital, gave me the addresses of contact a family service, and

an internet site that had support groups for rare metabolic disorders.

Recommendations

Contact Dr. Howard.

Address of an internet site for rare metabolic disorders; NORD.

Address of “contact a family”.

Dr. Howard

Dr. Howard is a senior consultant neurologist at Great Ormand Street London, I wrote

twice to Dr. Howard requesting a meeting and on both occasions failed to receive a

reply.


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Contact a family

Contact a family is a UK charity which helps families who care for children with rare

disorders, contact was made with them, and they had no families on file with

Ohtahara syndrome and sent me an information page on Ohtahara syndrome.

Recommendations

They had no members that had been touched by the Ohtahara syndrome.

4.2 Internet sites

All relevant literature on Ohtahara syndrome had been down loaded and printed for

the literature review. Yet I lacked direct communication with Ohtahara families. One

site suggested by Dr. Wood, was www.nord.org. It stands for National Organization

for Rare Disorders.

Entering the site gave me an opportunity to visualise many profiles of families with

rare disorders. I searched through the whole site, not one profile had families that had

been touched by Ohtahara syndrome.

I decided to make contact with as many families as possible, by emailing them and

asking for there assistance in locating Ohtahara families. The replies came back in

there dozens, all touched by my personal experience. Yet one reply made a true

difference, it was from a lady from the United States of America, in California, her 4

year old daughter had West Syndrome, which had evolved from Ohtahara syndrome.

Debbie Spencer gave me the email address of a lady from her state, Tammie Horak

whose 5 year old grandson Tyler had Ohtahara syndrome.

Recommendations

Email addresses of families touched by Ohtahara syndrome.


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The official internet site for families touched by Ohtahara syndrome,

moderated by Tammie Horak.

4.3 Families touched by Ohtahara

Tammie Horak

Through effective communication with Tammie, I was surprised to realize that,

Tammie had set up a support group for Ohtahara families, which was located at:

http://groups.yahoo.com/group/ohtaharasyndrome. The group had 32 members. I

began active participation with the group and began getting there involvement in my

research. From the list of members, there was a lady from Great Britain, who had a 13

year old child with Ohtahara syndrome, Susan Titbits.

Recommendations

The email address of Susan Titbits who was in the United Kingdom.

Susan Titbits

Susan Titbits had orchestrated similar support methods as Tammie in America.

Through Susan I was able to locate 14 living cases of Ohtahara syndrome and 2

families who had lost children to Ohtahara, in Britain, Northern Ireland and the

Republic of Ireland.

Recommendations

Located the names and addresses of 14 other cases in the United Kingdom.

Families touched by Ohtahara syndrome

Contact was made with all the families and the support network was connected with

the families around the world. In total I had located 34 cases in America, 4 in

Australia and New Zealand, 2 reported cases from the Indian sub-continent and 19

cases from the United Kingdom and Ireland (including three of my children), bringing

the total to 59 families who had been touched by Ohtahara syndrome, 11 of the infants

had died leaving 48 living infants with Ohtahara syndrome, around the world.


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4.4 Letters of support (refer to appendix)

I began receiving letters of support from the families touched by Ohtahara syndrome,

the underlying message was the same, and they needed to be heard and wanted

answers to the same questions: Why is the aetiology of Ohtahara syndrome not

known? Why does the current medication for Ohtahara syndrome have limited effect?

Why are there different forms of this disorder? Some infants die within the first year

of life and others (Susan Titbits child) are a live into there teens.

The more my involvement progressed with other families, the more I realised how

difficult this disorder was to understand, it was not rare to me, because it had affected

nearly 60 other families around the world, each with a similar story. At this stage my

quest for direction into research avenues was extensive, it seemed trying to find the

reason why medication had little effect was equally as important as locating an

aetiology, I therefore decided to leave all options open.

4.5 Personal visits

Apart from our three cases of Ohtahara syndrome, I knew little of other cases in the

United Kingdom, yet through my contacts I was able to make three home visits to

families in the United Kingdom. One family whom I had spoken to on the telephone

extensively was the Adams, they lived in Southampton, and they had a 7 month old

daughter Chloe with Ohtahara syndrome. I spent an afternoon with them and

questioned the family on Chloe’s current state of health. Like many other babies with

this syndrome, Chloe was diagnosed 6 weeks after birth, after many tests had been

fruitless; an EEG was performed, which verified the presence of Ohtahara syndrome.

The Adam’s family’s frustration was based on the helplessness of current medicine. I

was able to build a strong bond with the family and was encouraged by there strength

and determination to cope with the problem.

The second family I had direct contact with, lived in Northern England, in Derby. The

Newton’s had a son Jason, who was nearly a year old. Jason’s health was in a very

bad way, when I arrived at there residence, his condition had detiarated and he was on


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continuous morphine and valium. I spent an hour and a half at the family’s house.

Little or no questions were asked, it was there to see how Ohtahara syndrome had

affected Jason. The Newton’s had decided to keep Jason at home and allow him the

dignity to pass away at his home. Two days later I had a phone call from Jason’s

mother, two hours after I departed from there house hold, Jason had gone to a more

peaceful place, where there was no pain or suffering.

The third family whom I had intended to visit lived in the same Northern area as the

Newton’s family, were in Burton on Trent. They were Neil and Marion Heelas, before

I had a chance to see there beloved son, Joshua passed away. The Heelas family were

very supportive to research and offered all assistance.

Other planned trips included; Northern Ireland, there are 8 living cases of Ohtahara

syndrome in close proximidity to each other; I make regular contact with them.

I requested the medical notes of some of the infants mentioned above, to date I have

received 6 complete medical files of the children with Ohtahara syndrome.

4.6 Meeting with Dr. Ian McShan

The timing of the appointment with Dr. McShane could not have been better; I had a

great deal of literature and personal contact with families with Ohtahara, yet had no

real direction to take the research forth.

I was joined at the meeting by Dr. Alison Shaw, at John Radcliff hospital in Oxford.

The first part of the meeting evolved over my current research on Ohtahara and my

aims for the research:





I explained the reasons why these aims were important to the quest for some answers

to the Ohtahara syndrome: Locating the aetiology would allow more specific


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medication to be targeted at the root cause; a diagnostic kit would allow parents of

existing Ohtahara infants, to test for any future pregnancies to be effected by Ohtahara

and give a possible option for termination of the unborn foetus; finally, if the problem

of medication was solved and the drugs were able to cross the blood brain barrier, the

disorder could be better controlled and managed.

The response from Dr. McShane was less encouraging, he systematically located

flaws in all three research avenues: there are no current investigating tools to locate

the aetiology, each case of Ohtahara could have a different aetiology to the next, the

technology has not yet been set in place for such detailed investigations; a diagnostic

kit was impossible at this stage, because Ohtahara syndrome is diagnosed by EEG’s

and an EEG cannot be performed on unborn foetus; the medication problem was

beyond research because drug companies do not test medication on young infants,

only on animals and there were too many ethical questions involved.

However, Dr. McShane emphasised that all three research avenues were plausible in

the future, when technology was in place and at this stage they were aspirations. I

explained that I needed one avenue of research to take this MSc project forward onto

a bigger PhD project. Than Dr. McShane suggested an option, which would

completely change the focus of the project.

Recommendations from Dr. McShane.

Dr. McShane explained that many rare disorders have the same problem, in that they

occur in frequently at different parts of the world and the epidemiology, incidence and

distribution in the population are not collectively noted. What is required for Ohtahara

syndrome is a study covering the demographic and epidemiological overview of

Ohtahara syndrome, its incidence, distribution in the population, and possible causes,

together with a discussion of its social aspects and the presentation of a database of

Ohtahara cases. Such an overview is necessary as a prerequisite for any future

research into Otahara syndrome, its management and antenatal diagnostic

possibilities. Currently, there is no such overview and no existing database on

affected children.


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4.7 Contacting Dr. Ohtahara

Dr. Ohtahara was the person responsible for discovering and categorising the

disorder, to approach Dr. Ohtahara and expect a response back was an aspiration. This

became reality when he replied back.

Subsequent weeks resulted in building a positive reportage with Dr. Ohtahara, it

appeared he had retired from the chair of Tokyo research council and the pace of life

had also slowed down. He was however, impressed by my determination to research

Ohtahara syndrome and gave a supporting letter to Dr. Woodman.

I informed Dr. Ohtahara of my research aims, which had included the previous three:





4. Study covering the demographic and epidemiological overview of

Ohtahara syndrome, its incidence, distribution in the population, and

possible causes, together with a discussion of its social aspects and the

presentation of a database of Ohtahara cases.

Recommendations from Dr. Ohtahara

I than asked for Dr. Ohtahara’s suggestions to the best line of research, aiming to

make sure Dr. Ohtahara’s thoughts tally with Dr. McShane’s. The reply from Dr.

Ohtahara confirmed Dr. Mcshane’s recommendations and option 4 became the bases

for the research.


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4.9 Discussion on results

4.9.1 Opinion formers

Medical professionals associated with Ohtahara syndrome were selected and

interviewed on there knowledge and understanding of this disorder. Dr. Sawney was

the first line of contact, his knowledge and understanding of Ohtahara syndrome was

from case histories of families touched by Ohtahara syndrome. Dr. Sawney had first

hand experience with our three encounters with this syndrome, therefore made him an

ideal opinion former. It was Dr. Sawney’s initial recommendations to pursue Dr.

Alison Shaw and Dr. Ian McShane (infants with neurological problems were referred

for consultation and further investigation to Dr. McShane, who is a senior neurologist)

for further knowledge on this disorder.

Communication with Dr. Alison Shaw centred on my search for a specific direction of

research; the three initial lines of research were presented to Dr. Shaw (refer to

appendix):

Attempting to find the aetiology of Ohtahara syndrome.

Devising a diagnostic kit for detecting the disorder prior to birth.

Investigating to the reason why anti epileptic medication had limited effects

on infants of Ohtahara syndrome.

Dr. Alison Shaw did not have the clinical and technical expertise to endorse the

feasibility of these options, her current understanding of this syndrome centred on the

level of involvement she had with our experience of this syndrome, her personal

research into rare disorders effecting ethnic minorities tallied with our encounter with

this disorder. Dr. Shaws recommendation was to contact a senior geneticist Dr. Geoff

Woods, of St. James hospital in Leeds.

Dr. Geoff Woods’s research centred on the ethnicity, geographical and regional

patterns to do with rare inherited genetical disorders in ethnic populations.

Unfortunately Ohtahara syndrome was not on the list of rare genetic disorders, that

Dr. Woods was researching. Dr. Woods reasoning was that Ohtahara syndrome is not

believed to be genetic and therefore did not fit in his research aims. I used a counter


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argument on my personal experience and suggested there could be no other medical

reason for Ohtahara syndrome repeating on three consecutive pregnancies, other than

the fact it was inherited. Dr. Woods accepted my personal opinion, but on a

professional capacity could not be accepted with out medical research proof. Dr.

Woods suggested if it can be proved that Ohtahara syndrome is inherited, than he

would be more than happy to include this disorder into his research. Dr. Wood’s

suggested that I contact Dr. Howard.

Dr. Howard is a senior neurologist at Great Ormond street hospital, in London. It is

unfortunate that I received no reply from Dr. Howard’s office, her expertise and

knowledge on neurological disorders effecting infants would have been beneficial for

my line of research.

Dr. Ian McShane is an experienced paediatric neurologist at John Radcliff hospital, in

Oxford. He had personal contact with our cases of Ohtahara syndrome and was highly

recommended by other opinion formers (Dr. Sawney and Dr. Alison Shaw), Dr.

McShane’s knowledge and understanding of Ohtahara syndrome far exceeded other

opinion formers I had contact with (with the exception of Dr. Ohtahara himself).

Dr. McShane had the clinical and technical knowledge to advice me that my three

original aims were feasible and compliable but in appropriate to implement, reason

being given was the lack of technology and clinical expertise in this specific field. Dr.

McShane argued that any specific study should have clear aims and objectives and

those aims should be viable in accordance with current technology, and if I was

serious on a study for this disorder, than I needed to construct a study covering the

demographic and epidemiological overview of Ohtahara syndrome, its incidence,

distribution in the population, and possible causes, together with a discussion of its

social aspects and the presentation of a database of Ohtahara cases.

Dr. McShane’s recommendations slightly disillusioned me, I wanted direct research

into the aetiology and prevention of Ohtahara syndrome and this was pointed out to

Dr. McShane and I was informed that a study of this kind was needed as a prequel for


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further technical studies to come forth from this research, and as to date there has

been research orchestrated around the world, on specific cases, no collective case data

is available and more research is required to understand this syndrome. From this

meeting I had gained a clear direction for the type of research needed for Ohtahara

syndrome.

It was in 1978 that the syndrome known as early infantile epileptic encephalopathy,

(the term ‘Epileptic Encephalopathy’ (EE) refers to a heterogenous group of

conditions in which even in absence of progressive metabolic and/or structural brain

abnormality-ties, the extremely abnormal brain electrical activity may not only be the

cause of seizures, but also interfere with cognitive functions, leading to an arrest or

regression in behaviour, the disorders sharing these characteristics, and thus included

in this group are, early myoclonic encephalopathy (EME), and early infantile epileptic

encephalo-pathy), was given the name of Ohtahara syndrome.

Dr. Ohtahara had successfully classified this syndrome as a form of epileptic

encephalopathy. It was an aspiration to have any form of contact with Dr. Ohtahara,

which became reality when Dr. Ohtahara responded to my letters. If any individual

had knowledge and understanding of this disorder, it was Dr. Ohtahara. It must have

been my personal encounters with this syndrome that gave me an edge over other

unsuccessful attempts by individuals to make contact with Dr. Ohtahara. I needed to

gain recommendations from Dr. Ohtahara on his thoughts on future research, before

Dr. Ohtahara could give me his recommendations needed to know my academic and

scientific potentials, which I gave to him in subsequent email exchanges (refer to

appendix).

Dr. Ohtahara was informed of my 4 research aims (three initial ones and the fourth

suggested by Dr. Ian McShane) and his recommendation was asked for the most

realistic option of research. Dr. Ohtahara confirmed Dr. McShanes suggested option

and sent a letter of support to Dr. Anthony Woodman (refer to appendix).

Dr. Ohtahara’s letter to Dr. Woodman affirms that there are no reported cases of

inherited form of Ohtahara syndrome. Yet the evidential formation of our three


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siblings having Ohtahara syndrome gives indication that genetical inheritance played

a part in our family. It is important to high light this point that any future research

needs clarification that this syndrome can be inherited.

4.9.2 Families touched by Ohtahara syndrome

Every family that had been touched by Ohtahara syndrome, had there own personal

knowledge and understanding of this syndrome. From the personal visits and email

communications with these families, it was evidential that the diagnosis of this

syndrome was in the majority of cases delayed till the 6th week of birth. A pattern

emerged from all the cases I had contact with that initial investigation were aimed at

blood, CSF and urine sample analysis, the results of each came back normal. The

usage of the EEG formed the latter part of investigations. In retrospect the EEG is less

painful and less intrusive than other investigatory methods (blood test) and should be

used at an earlier stage in investigations.

Specifically in our first encounter with Ohtahara syndrome, the time span for

conformational diagnoses of Ohtahara syndrome took 6 weeks. Our child had to

endure countless painful intrusive investigations, which proved fruitless. It is

important to point out the need for earlier diagnostic usage of the EEG, were

symptoms indicate a neurological problem.

Early diagnosis needed using the EEG.

The second message that was portrayed by these families was the lack of information

on this syndrome. After a diagnosis was made no clear relay of information was

available, this was indicated by the lack of knowledge by the medical community

(refer to questionnaire results discussion).

There is a lack of information available on Ohtahara syndrome.

The third message orchestrated from the families was the difficulty in managing and

controlling the syndrome. The infants are continuously tried on different anti

convulsion drugs, with little or no success. The quality of life for these infants is poor


Usman Omar Ghani

and manageability is made difficult with the poor control of seizures and the adverse

side effects of treatment. Many infants developed respiratory and gastrological

problems, and systematic all juggling of different anti convulsion drugs was

administered to have any impact on the seizures.

The difficulty in controlling and managing the syndrome.

Contact with other families had also contradicted an opinion that was given by Dr.

Sawney, that Ohtahara infant’s life expectancy is limited to one year. This proved to

be correct in our own encounters with the syndrome. Yet there are living Ohtahara

children who have reached the age of 15 years (Susan Titbit’s child) and many of the

families on the Ohtahara web site have infants who have bypassed the one year

expectancy. It is therefore important to point out that there is no specific age

expectancy for Ohtahara babies, it is evidential that many die at an early stage in life,

yet equally important there are living testimonial Ohtahara infants growing into there

teens. Unfortunately these infants are severely handicapped and require around the

clock nursing.

There is no set life expectancy for Ohtahara infants.

The families who had been touched by Ohtahara syndrome are residing all over the

globe. From email communication with families living in the United State’s of

America, I was able to have an insight into there level of medical assistance from the

countries health service. The families had to rely immensely on self finance and

health insurance to make medical payments. Often anti convulsion drugs were

purchased from different medical institutions. It was noticed (on the internet site) that

there was a high level of interactive communication between the families in America

on the best place to purchase certain medicine. In comparison the families touched by

Ohtahara syndrome, that lived in the United Kingdom had the need for medical

service paid for by the National Health Service. This meant the parents had less of a

financial worry for there infants, it is important to point out that the point of delivery

free medical service available in the United Kingdom allows parents to manage there

lives with out the worry of financial contributions to treatment.


Usman Omar Ghani

Financial contribution required by parents of ohtahara infants residing in

America, while there counter parts had complete free point of care health

service.

The families of Ohtahara infants had built up a frame work of moral support to each

other; the internet site developed by Tammie Horak had given the first platform for

collective gathering of families touched by this disorder. There were members of the

internet Ohtahara web site whom had lost infants to this disease and they remained on

site to give continuous support to others. I informed my family contacts of my desire

to do a more in-depth study of this disorder, and supporting letters came from many

families (refer to appendix).

The underlying message was the same in each letter; the parents own personal

experience, the feeling of helplessness, there desire for answers and above all

there enthusiastic support for such a study.

4.9.3 Internet communication

My research relied heavily on the usage of the internet. I was able to attain the

majority of relevant literature on this disorder, from the web. Most of all it gave me an

opportunity to make contact with opinion formers and families touched by this

disorder. Continuous email exchange on a daily basis gave me an insight into many

families’ lives, which were battling with this disorder. Often specific questions were

answered quickly and this made information gathering easier and faster to manage.

There is no better way of understanding how a syndrome affects the families, without

direct contact with those families. The majority of families touched by this syndrome

resided abroad; emailing provided the fastest and most efficient way of making

contact with them.

Internet provided a faster mode of communication with my contacts.


Usman Omar Ghani

4.9.4 The questionnaire (refer to appendix)

There were (49) questionnaires sent to medical professionals and (35) questionnaires

were received back. All the received questionnaires were correctly formatted and the

results were noted by configuration of the correct ticked answers, to the multiple

questions, which were placed in results tables.

The results of the questionnaire were in co-operated into summary tables, showing the

number of questions and the number of correct answers given. (Please refer to the

appendix for reference to the type of questions in the questionnaire). The information

from the summary tables is transferred onto bar charts, which show correlated

comparison of correct and incorrect answers.

Comparative assessments were made on the different surgeries, and the nurses and

paediatrics at High Wycome and Luton/Dunstable hospitals.

The last three questions on the questionnaire (refer to appendix), in co-operated the

ideology of the participant in the need for future research in Ohtahara syndrome. The

results of which are displayed on bar charts.

The questionnaire was designed to evaluate current understanding of Ohtahara

syndrome in the medical community. Particular comparisons were made between two

locations High Wycome and Luton/Dunstable hospital staff. General Practioneers

practising in four surgeries (New surgery, Green Meadow surgery, Dr. How’s surgery

and the Flitwick health care centre) were asked to fill in the questionnaire and the

results compared. The results from Questions 1-12 are evaluated first, with the results

from question 13-15 analysed separately.

Results from the New Surgery compared with internal partners and with the

other three surgeries.

Results from the participants at both locations (High Wycome and

Luton/Dunstable hospital) compared.


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Number of questionnaires sent and received (refer to table 10 and figure 19).

There were in total 49 questionnaires sent and out of which 35 were received back,

fully completed. The most number of questionnaires sent were to Luton/Dunstable

special care baby unit (10) of which 6 were returned completed. The least number of

questionnaires sent were to Dr. How’s surgery (2), of which both were returned back

fully completed.

Table 10, showing the number of questionnaires sent and received, the summary information is displayed in figure 19.

Table 10, Number of questionnaires sent and received.

Sent Received

New surgery (Chesham) 6 5

Green meadows surgery (Chesham) 8 6

Dr. How’s Surgery (Chesham) 2 2

Flitwick health centre (Flitwick) 6 5

Special care baby unit (High Wycome) 7 4

Special care baby unit (Luton and Dunstable hospital) 10 6

Paediatrics at High Wycome Hospital. 4 3

Paediatrics at Luton and Dunstable hospital. 6 4

Total 49 35


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Numbers of questionnaires sent and received

0

2

4

6

8

10

12

New surgery(Chesham)

Green meadowssurgery

(Chesham)

Dr. How’sSurgery

(Chesham)

Flitwick healthcentre (Flitwick)

Special carebaby unit (High

Wycome)

Special carebaby unit (Lutonand Dunstable

hospital)

Paediatrics atHigh Wycome

Hospital.

Paediatrics atLuton andDunstablehospital

Questionnaires destination

Sent

Receivied

Fig. 19 Bar chart showing the number of questionnaires sent and received.

As figure 19 illustrates the only location were all the questionnaires were sent back

was Dr. How’s surgery, this could be explained by the fact the practise is small (2

partners) in size and more attention can be given to external issues. Other larger

locations (SCBU and paediatrics at children’s wards) returned just over half of the

questionnaires completed. This could be due to the work load of the participants and

the availability of time, as children’s wards are generally busy.

There were 49 questionnaires sent and 35 were received back completed.

Dr. How’s surgery was the only surgery to return all the questionnaires.

New Surgery Chesham (refer to table 11 and figure 20)

The New Surgery has had first hand experience with Ohtahara syndrome; they were

involved in our infant’s management of the syndrome. It was important to understand

how much knowledge they had of this syndrome and the degree of information

interaction between the partners (our family general practioneer comprised one of the

six partners at the surgery).


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Table 11 Summarises the number of questions asked and answered correctly from the New Surgery. The results are shown in a bar chart in figure 20.

New surgery

Number of questions asked 1 2 3 4 5 6 7 8 9 10 11 12 Number of correct answers 5 5 3 3 2 5 5 5 4 2 3 5

New surgery results of questionnaire

0

1

2

3

4

5

6

1 2 3 4 5 6 7 8 9 10 11 12

Number of questions

Nu

mb

er

of

co

rre

ct

an

sw

ers

Series1

Fig. 20 Bar chart showing the number of questions asked and answered correctly from the New Surgery.

As figure 20 illustrates the doctors were correct in identifying the syndrome, both the

first two questions were answered correctly. Questions 6, 7, 8 and 12 were also

answered correctly. Indicating that they were aware of the age group, the symptoms,

mode of diagnoses and the prognoses of the disorder. Questions 5 and 10 were the

least answered correctly, suggesting they were not aware of the incidence and the

epidemiology of the syndrome. Over all the results of the questionnaire illustrate that

the partners are all aware of the syndrome and there is a good degree of cross

communication between the partners.

The New Surgery displayed a good understanding of Ohtahara syndrome.


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The results reflected good knowledge of the syndrome by all the partners at

the surgery.

Green Meadow’s Surgery (refers to table 12 and figure 21).

Less than half the partners at the practice were correct in identifying the syndrome

(3), none of the participants had the correct answer for question 4 (what causes the

syndrome?) and there was a similar pattern for the remaining questions.

Table 12 Number of questions asked and answered correctly from Green Meadows surgery. Results are displayed in a bar chart in figure 21.

Green meadow’s surgeryNumber of questions 1 2 3 4 5 6 7 8 9 10 11 12

Number of correct answers 3 2 1 0 2 2 3 3 4 1 2 2

Green meadow surgery

00.5

11.5

22.5

33.5

44.5

1 2 3 4 5 6 7 8 9 10 11 12

Number of questions

Nu

mb

er o

f co

rrec

t an

swer

s

Series1

Fig. 21 Bar chart showing the number of questions asked and answered correctly from Green Meadows surgery.

As figure 21 indicates, question 9 (treatment of Ohtahara syndrome) was answered

most correctly by the participants. This result may have been expected due to the

general practioneer’s extensive knowledge on drug treatment for diseases.


Usman Omar Ghani

Less than 50% of the participants were correct in there assessment of the

syndrome.

Dr. How’s Surgery (refers to table 13 and figure 22).

The results from the questionnaire illustrated that one of the two partners had

knowledge of the syndrome.

Table 13 Number of questions asked and answered correctly from Dr. How’s surgery. Results are displayed in figure 22.

Dr. How’s surgery

Number of questions 1 2 3 4 5 6 7 8 9 10 11 12Number of correct answer 1 1 1 0 1 2 1 0 1 0 0 0

Dr. How's surgery

0

0.5

1

1.5

2

2.5

1 2 3 4 5 6 7 8 9 10 11 12

Number of questions

Nu

mb

er o

f co

rrec

t an

swer

s

Dr. How's surgery

Fig. 22 Bar chart showing the number of questions asked and answered correctly from Dr How’s Surgery.

As figure 22 indicates questions 4, 8, and 10-12 were answered incorrectly.

Illustrating the participants had no knowledge on the cause, diagnoses, epidemiology,

prevention and prognoses of this disorder.

Knowledge on Ohatahara syndrome was limited to one partner at the surgery.


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Flitwick health care centre (refer to table 14 and figure 23)

The results from the questionnaire illustrated a similar pattern to the other surgeries

(with the exception of the New surgery), in that less than half of the partners (2) had

ever heard of this syndrome and that number repeated itself through out the other

questions. Questions 8 and 11 were both answered incorrectly by all the participants,

indicating a lack of knowledge in the diagnoses and prevention of the syndrome.

Table 14 Number of questions asked and answered correctly from the Flitwick health care centre. Table summary is shown in figure 23.

Flitwick health care centre

Number of questions asked 1 2 3 4 5 6 7 8 9 10 11 12Number of questions answered 2 2 1 1 1 2 1 0 1 1 0 1

Flitwick health care centre

0

0.5

1

1.5

2

2.5

1 2 3 4 5 6 7 8 9 10 11 12

Number of questions asked

nu

mb

er o

f co

rrec

t an

swer

s

Number of questionsanswered

Fig. 23 Bar chart showing the number of questions asked and answered correctly from the Flitwick health care centre.

Results indicated a lack of understanding about Ohtahara syndrome, with less

than 50% of the participants ever hearing of the disorder.


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Comparisons of results from all four surgeries (refer to table 15 and figure 24).

As figure 24 illustrates the New Surgery had most knowledge and understanding of

Ohtahara syndrome. The participants of the surgery had the most correct answers, this

could be attributed to there contact with three cases of Ohtahara syndrome, in the past

five years. The remaining three surgeries had similar pattern of results, there

knowledge of the syndrome was limited, and this can be due to the lack of direct

contact with families affected by this syndrome. It should be clarified that the Green

Meadow’s surgery had the most questionnaires returned (6) and Dr. How’s surgery

the least (2), reflecting on the size of each respected surgery.

Table 15 Comparison of questionnaire results from the four surgeries participating in the questionnaire. Results are shown in bar chart form in figure 24.

Name of surgery Number of questions Correct answers: 1 2 3 4 5 6 7 8 9 10 11 12New Surgery 5 5 3 3 2 5 5 5 4 2 3 5Green meadows surgery 3 2 1 0 2 2 3 3 4 1 2 2Dr. Hows surgery 1 1 1 0 1 2 1 0 1 0 0 0Flitwick health centre 2 2 1 1 1 2 1 0 1 1 0 1

Comparison of questionnaire results from general practioneers

0

1

2

3

4

5

6

1 2 3 4 5 6 7 8 9 10 11 12

Number of questions

Nu

mb

er o

f co

rrec

t an

swer

s

New Surgery


Dr. Hows surgery


Fig. 24 Bar chart showing the number of questions asked and answered correctly from the four medical surgeries participating in the questionnaire.


Usman Omar Ghani

The New Surgery had a better understanding of Ohtahara syndrome, than the

other three surgeries.

Comparison of results from the special care baby units (SCBU) of High Wycome

and Luton/Dunstable hospitals (refers to table 16 and figure 25).

I had anticipated that there should have been more awareness at the SCBU at High

Wycome hospital, rather than its counter part in Luton/Dunstable hospital. Reason

being that the unit at High Wycome hospital had treated three cases of Ohtahara

syndrome in the past five years. As figure 25 illustrates there was more awareness of

this disorder at the High Wycome SCBU, the participants correctly answered more

questions than there counter parts in Luton/Dunstable.

Table 16 Number of questions asked and answered correctly from the nurses at special care baby units, at High Wycome and Luton/Dunstable hospitals. Refer to figure 25 for comparison of results in bar chart formation.

Special care baby unit (H. Wycome)

1 2 3 4 5 6 7 8 9 10 11 12

Number of questions askedNumber of correct answers, High Wycome SCBU

3 2 3 3 2 3 4 3 2 4 3 3

Special care baby unit (Luton&Dunstable)

Number of correct answers, Luton & Dunstable SCBU

2 1 2 2 1 1 1 0 2 1 0 1


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Special care baby unit (SCBU) questionnaire results

0

1

2

3

4

5

1 2 3 4 5 6 7 8 9 10 11 12 13


Nu

mb

er o

f co

rrec

t an

swer

s

Number of correctanswers, High WycomeSCBU

Number of correctanswers, Luton &Dunstable SCBU

Fig. 25 Comparison of SCBU questionnaire results for High Wycome and Luton & Dunstable hospitals.

There was particularly high scoring in question 7 and 10, from the SCBU at High

Wycome hospital. Indicating they had a good level of awareness for the symptoms of

Ohtahara syndrome. This result is encouraging because the nursing staffs at SCBU is

the “eyes and ears” for assessing the sick infant, any abnormal signs of an illness can

be picked up and noted by the staff. This is very important for early symptomatic

detection and iniation of further investigations. A good knowledge of the

epidemiology (that it is not known for Ohtahara syndrome) is illustrated by the level

of correct answers for question 10.

As figure 25 illustrates staff at SCBU at Luton/Dunstable hospital, had a lower

understanding of Ohtahara syndrome than there counter parts, this could be due to the

lack of direct involvement with families touched by this disorder. Particularly there

was a lack of understanding for the diagnosis of this syndrome (question8) and a low

understanding of the incidence, age group, symptoms, epidemiology and prognosis of

this syndrome (questions 5-8 and 10-12).

It should be noted that the SCBU at Luton/Dunstable hospital had returned more

questionnaires (6) than there counter part in High Wycome (4).


Usman Omar Ghani

Staff at SCBU in High Wycome hospital displayed greater knowledge and

understanding of Ohtahara syndrome than there counter parts at

Luton/Dunstable hospital, especially in the symptomatic detection of the

syndrome.

Comparisons of results from the paediatrics at High Wycome and

Luton/Dunstable hospitals (refer to table 17 and figure 26).

Paediatrics work closely with new born babies at SCBU and children’s wards. It is

expected of them to display a good level of understanding for symptomatic detection

of unwell new born babies.

As figure 26 illustrates there is a good understanding of Ohtahara syndrome in

paediatrics working at High Wycome hospital. There was a strong understanding of

the fact they had heard of this syndrome, its other classification name, the cause,

incidence, symptoms and epidemiology of the syndrome (questions 1, 3, 4, 6, 7 and

10).

In comparison paediatrics at Luton/Dunstable hospital displayed a lower

understanding of this syndrome; particularly there were no correct answers for the

prevention of the syndrome (question 11).

Table 17 Number of questions asked and answered correctly from paediatrics at High Wycome and Luton/Dunstable hospitals. Refer to bar chart figure 26, showing comparison of results from both places.

Paediatrics at children’s ward

1 2 3 4 5 6 7 8 9 10 11 12

Number of questions askedPaediatrics at Luton & Dunstable hospital

2 2 1 2 1 2 1 1 1 2 0 1

Paediatrics at High Wycome hospital

3 2 3 3 2 3 3 2 2 3 2 2


Usman Omar Ghani

Paediatrics at High Wycome and Luton/Dunstable hospital

0

0.51

1.5

2

2.53

3.5

1 2 3 4 5 6 7 8 9 10 11 12


Nu

mb

er o

f co

rrec

t an

swer

s Paediatrics at Luton &Dunstable hospital

Paediatrics at HighWycome hospital

Fig. 26 Comparison of results from paediatrics at High Wycome and Luton/Dunstable hospitals.

It should be noted that there were more questionnaires received from paediatrics at

Luton/Dunstable hospital (4) than there counter parts at High Wycome hospital (3).

Paediatrics at high Wycome hospital displayed a better knowledge and

understanding of Ohtahara syndrome.

Comparisons of results from all sources (refer to table 18 and figure 27).

The over all results from the questionnaire (questions 1-12) have been summarised

(refer to table 18) and in cooperated onto a bar chart (refer to figure 27). The over all

picture shows that the new Surgery and staff at High Wycome hospital had a better

understanding of Ohtahara syndrome than there counter parts. It can be argued that

the participants from these locations had direct involvement with three known cases

of Ohtahara syndrome (our family cases); this gave them additional advantage over

the other participants.


Usman Omar Ghani

Table 18 Summary tables showing the number of questions asked and answered correctly from all the participants in the research study. Refer to figure 27 for comparison of results.

Number of questions Correct answers: 1 2 3 4 5 6 7 8 9 10 11 12New Surgery 5 5 3 3 2 5 5 5 4 2 3 5Green meadows surgery 3 2 1 0 2 2 3 3 4 1 2 2Dr. How’s surgery 1 1 1 0 1 2 1 0 1 0 0 0Flitwick health centre 2 2 1 1 1 2 1 0 1 1 0 1Paediatrics at Luton & Dunstable hospital 2 2 1 2 1 2 1 1 1 2 0 1Paediatrics at High Wycome hospital 3 2 3 3 2 3 3 2 2 3 2 2Number of correct answers, High Wycome SCBU

3 2 3 3 2 3 4 3 2 4 3 3

Number of correct answers, Luton & Dunstable SCBU

2 1 2 2 1 1 1 0 2 1 0 1

Results

0

1

2

3

4

5

6

1 2 3 4 5 6 7 8 9 10 11 12


Nu

mb

er o

f co

rrec

t an

swer

s

New Surgery


Dr. Hows surgery


Paediatrics at Luton & Dunstablehospital

Paediatrics at High Wycomehospital

Number of correct answers, HighWycome SCBU

Number of correct answers, Luton& Dunstable SCBU

Fig. 27 Comparison of results received from all the participants in the study.


Usman Omar Ghani

It must also be pointed out that no prior knowledge was known on my part that if the

staff at Luton/Dunstable hospital and the other surgeries had any form of contact with

familes touched by Ohtahara syndrome.

Staff at High Wycome hospital and the New Surgery displayed better

knowledge of Ohtahara syndrome than there counter parts.

Results for questionnaire numbers (13-15) from all the participants in the study.

(Refer table 19 and figure 28 for comparative results on a bar chart).

These three questions (13-15 refer to appendix) were designed to evaluate if the

participant requires more information on the syndrome, there recommendations for

more research and out lines the aim of a broad overview of the syndrome and asks if

they would support such a study.

Table 19 showing the results for questionnaire numbers (13-15) from all the participants in the study. Refer to figure 28 for comparative results on a bar chart.

Refer to appendix question 13 question 14 question 15For the questions.

yes no yes no yes no

New Surgery 5 0 5 0 5 0


6 0 6 0 6 0

Dr. Hows surgery

2 0 1 1 2 0


5 0 5 1 5 0

Paediatrics at Luton & Dunstable hospital

4 0 4 0 4 0

Paediatrics at 6 0 6 0 6 0


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High Wycome hospital

High Wycome SCBU

3 0 3 0 3 0

Luton/Dunstable SCBU.

4 0 2 2 4 0

participants

0

1

2

3

4

5

6

7

yes no yes no yes no

question13

question14

question15

Yes or no

nu

mb

er o

f p

arti

cip

ants

New Surgery

Green meadowssurgery

Dr. Hows surgery

Flitwick healthcentre

Paediatrics atLuton & Dunstablehospital

Paediatrics at HighWycome hospital

High WycomeSCBU

Luton/DunstableSCBU.

Fig. 28 Comparison of results received from all the participants in the study.


Usman Omar Ghani

As figure 28 illustrates there is an over whelming agreement and support for future

research on this syndrome. There were only two declines for question 14 (the need for

more research), they were from the Flitwick health centre and Dr. How surgery. At

the end of the questionnaire the participants from both sites gave reason to why they

felt more research was not needed, the message from both was that it is a very rare

syndrome and it would be very difficult to find participants to take part in any study.

It can be argued that the research on this thesis has demonstrated that Ohtahara

syndrome may be rare and little is know about it, but there is a community of over 40

families in the world who are trying to manage there lives around this syndrome and

who are more than happy to participate in any research study.

Other rare disorders, for example cystic fibrosis (Cystic fibrosis (CF) is an inherited

disorder that affects several "outwardly secreting" (exocrine) glands, including

respiratory, pancreatic, salivary, and sweat glands. CF predominately affects

Caucasians from northern Europe and is considered very rare in other populations)

had similar problems as Ohtahara syndrome in that, there were late diagnosis and

management problems of the disease (refer to appendix 5 page 124). Initial research

concentrated on accumulating information on the incidence, epidemiology and setting

up a data base of known cases. Subsequent research used the frame work of

information on the data base and technical coherent studies materialized. Resulting in

more research into the aetiology and treatment of CF.

4.9.5 Summary

The questionnaire has illustrated the divide in knowledge of Ohtahara syndrome,

between different locations. As pointed out earlier this may have been due to there

direct contact with families touched by Ohtahara syndrome.

It is important to out line that staff at postnatal/ SCBU and paediatrics should have an

inclination to observe and detect specific symptoms which could indicate a more

serious syndrome. The early diagnoses and detection of any serious syndrome is

helpful in the management and treatment of the disorder.


Usman Omar Ghani

From the personal contact with families touched by Ohtahara syndrome, the under

lying message is the need for faster diagnoses, too much time is by passed by causing

the new born unnecessary intrusive tests, there is only one clear indicator for

neurological abnormalities; that is the EEG, it is relatively painless and is the only

diagnostic tool for Ohtahara syndrome. It is therefore recommended that it should be

used at an early stage in neurological investigations by medical professionals.

Too often anti convulsion therapy is limited to widely know drugs for epilepsy

(phenol barbiton and clobazam) and many families reported the lack of desire from

there clinicians to try other anti convulsion drugs. It is recommended that the

neurologist should aim to try other medication (vigabatrin) and aim to improve the

quality of life as much as possible.

4.9.6 Conclusion

Before commencing on this project my knowledge of Ohtahara syndrome tallied with

any informal person reading this thesis; that it is a rare syndrome and little is known

about it. Yet my aims and objectives have taken me to meet opinion formers and

families touched by this disorder, I gained an ocean of knowledge from these people.

It is a syndrome that effects human beings who cannot talk, cannot express there level

of pain, are to the mercy of others, these beings are new born babies who enter this

world, bringing with them a syndrome that has no cure and no form of treatment.

From day one of there lives they experience nothing more than pain, distress and

discomfort. For many victims of Ohtahara syndrome leave this world with little

memory of joy, just pain and distress.

What does current conventional medicine do for the Ohtahara babies? There seizures

are difficult to control and there quality of life is poor. By attempting to control the

seizure holds back the syndrome, but it is not taken away, the underlying problem

remains. The question should be asked; does modern day medicine increase the length

of life and therefore prolong the suffering of the victim with the fatal condition?

Would Ohtahara babies live as long as they do if it were not for modern medicine?

What would happen if things were left to Mother Nature? These are all very difficult


Usman Omar Ghani

questions and personal life experience dictates in the reply given. My opinion is that

every life has a right to existence and every opportunity should be taken to make the

life as comfortable as possible. Therefore the following recommendations should be

considered.

4.9.7 Recommendations

Early detection of the syndrome is advisable, the sooner treatment can

commence the easier it is to manage the syndrome.

Staff working with new born babies should be more vigilant in there

monitoring of the babies, in relation to symptomatic detection.

More information should be given to parents of Ohtahara syndrome,

specifically clinicians should advocate using the internet and search some

family support groups, as this will give the parents a chance to have direct

contact with other families touched by this syndrome.

Once the syndrome has been diagnosed, all efforts should be advocated at

making the quality of life as good as possible.

Ohtahara syndrome is rare, yet this study has demonstrated that there are over

6o families touched by this disorder, to date there has been no collective data

base and many cases go unreported. It is equally important to point out in the

third world; many infants go undiagnosed, untreated and pass away with out

any form of documentation. It is therefore recommended that research from

paediatric hospitals in these countries be commenced and a data base set up to

give a more accurate number of Ohtahara infants in the world.

In the opinion of Dr Ohtahara there is no proven link in genetic inheritance

with this disorder (refer to appendix 1), I would argue that due to the repetition

of this syndrome in three consecutive siblings, in our family, there leaves little

doubt in the presence of a genetic link. In comparison Dr Kamal Sawney is of


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the view that this disorder maybe autosomal recessive in some cases (refer to

appendix 2), this view contradicts of that held by Dr Ohtahara. There is also

mounting evidence that a family with one affected child and consanguinity can

give gene mapping information. A family with 3 affected children and also

consanguineous can give an extensive amount of information, enough to map

the gene. Consanguineous families are invaluable in the search for genes, can

help find the gene, and help the family. I therefore recommend that future

research is aimed at locating the effected gene in Ohtahara syndrome.

Conclusive recommendation

The results from the questionnaire and the recommendations of the opinion formers

(refer to letters in appendix) illustrate the need for an in-depth research project set up

to provide a demographic and epidemiological overview of Ohtahara syndrome,

together with a discussion of its social aspects and the presentation of Ohtahara data

base cases. This recommendation is backed up by Dr. Ohtahara himself (refer to

appendix), Dr. Ian McShane, Dr. Kamal Sawney, Dr. Geoff Woods, Dr. Alison Shaw

and supporting letters from families touched by Ohtahara syndrome.


Usman Omar Ghani

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45. Spreafico R, Angelini L, Binelli S, et al. burst suppression and impairment of

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Febiger, 1993, pp 145-156.

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Medline site, 2002.


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Appendix 1 Supporting letter from Dr Ohtahara


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Appendix 2 Supporting letter from Dr Kamal Sawney

Appendix 3 Supporting letter from Dr Alison Shaw (refer to page 122).


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Appendix 4 Notes of meeting with Dr. Ian McShane, from Dr Shaw

Dear Usman,

Yes, I;m back (I was lecturing, so it wasn't really a break!). I have

printed out a copy of the notes I made at our meeting with DR. Mcshane and

will put them in the post to you - I hope they are of some help.

As I understood it, he thought that your medical diagnostic research

ideas were not realistic. This is not because the research is unnecessary

- it clearly is - but because any chance of success in finding an answer

to a diagnostic question requires skills that you don't have and involves

use of technolgies that have not been invented yet - in other words, your

questions may be currently unanswerable given the current state of

technical research expertise - and he thought that a project of this sort

would not get funded for these reasons.

However, while you may think this is not very encouraging - though it is

probably a realistic assessment - he did think it might be worth reviewing

the extent of the problem in terms of incidence and demography and the

current research activity. The purpose of such an overview would be to

provide background information that would be useful in subsequent

research. The overview would include details of incidence worldwide, and

a review of what research is currently going on. A research proposal

aiming to do this, indicating your methods and your timescale, is

something you could get together by September.

By the way, are you thinking of seeing Jane Hurst again? I hope to speak

to you soon. I am putting my notes in the post to you now, and I expect by

now you have had Dr. McShane's letter as well which will presumably

summarise these points.

I hope all is well. Best wishes to Farzana, and to Alisha, and speak to

you soon,

Alison


Usman Omar Ghani

Appendix 5 Notes on rare disorder meeting, from Dr Alison Shaw

Dear Usman,

Greetings: assalaam alaikum.My email address is: [email protected] am sending you some notes that I made on Helen Middleton'Price's talk atthe RSM meeting on 4th February.Let me know if this message reaches you successfully, and I will sendyou some further references.Please give my greetings to Farzana, and to Alisha,Best wishes,Alison

I made the following notes on Helen Middleton-Price's talk which wascalled 'DNA testing: how far can we go', and given at a meeting called'consanguineous marriage in the UK: a multidisciplinary strategy' MacKeith Meetings- 4 FEbruary 2002. Helen Middleton-Price is atthe Institute of Child Health, London. I don't think this is confidentialinformation. Much of this information is generally available in books andon websites. But if you want to use any of this in what you write, youwill need to reference your sources. You will probably find much the sameinformation at the website address gives.Anyway, here are my notes.

There is DNA testing for the more common severe conditions: CysticFibrosis, incidence 1/2500; Duchenne Muscular Dystrophy 1/3000; Fragile X1/1500

There are specialist services for rare conditions, selected in relation toresearch interests. Great Ormond Street hospital provides a service forrare metabolic disorders, X-linked conditions and cranio-spatialdisorders.

There has been a dramatic increase in demand for DNA testing. 5000 geneticconditions have been identified, and the genes for 1000 of them havealready been found. Most new discoveries are for rare conditions, and DNAservices are currently offered only for more or less 200 rare conditionsin the UK.

The Department of Health is currently formalising a genetic testingnetwork, a collaborative network, involving transfer of samples for raredisease testing. 'Reference laboratories' are being set up by D.O.H inSalisbury and Manchester to provide new high through-put services for rareor 'orphan' conditions.

There are significant risks in certain ethnic groups:CF (in northern European populations); Sickle-cell (AfroCAribbean) ;


http://sea1fd.sea1.hotmail.msn.com/cgi-bin/compose?curmbox=F122681863&a=ef2ef3373cfbfeba5bdeaaa49ad84edc&mailto=1&[email protected]&msg=MSG1015702633.1&start=702645&len=3999&src=&type=x

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thalassaemia (middle east and Pakistan); Tay Sachs (Ashkenazi Jews)

Consanguineous families with rare conditions are a precious researchresource, enabling the identification of genes for rare conditions, andthey have been instrumental in the identification of heterogeneous genesfor common conditions.

A family with one affected child and consanguinity gives you mappinginformation.A family with 3 affected children and also consanguineous gives a massiveamount of information, enough to map the gene.So consanguineous families are invaluable in the search for genes, canhelp find the gene, and help the family.A research project the NAMR (National Autozygosity Maping Resource)involves Leeds, Leicester, and Birmingham.See the website: www.namr.org.uk

Two consanguineous families were crucial in the identification of Usher ICgene (Usher syndrome) a gene for deafness (Usher IC). Now FISH(fluorescent in=situ hybridization) can be used to confirm the diagnosis,rather than invasive tests.Reference for this is : Bitner-Glindzicz et al 2000 Nature Genetics, 16,56-60.

_____________________________________________________________________________Dr.Alison ShawDepartment of Human SciencesBrunel University


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Appendix 6 Supporting letter from Mrs Tamara Horak

June 11, 2002

Dr. Anthony Woodman (Research Project Director)C/O Usman Omar GhaniCranfield UniversitySilsoe CampusSilsoeBedfordshireMK45 4DTEngland

Dear Sir,

Seven years ago my family entered a world we never expected to see. Our grandson, Tyler, was born full term, at 7 lbs. 15 oz., but our world was shattered. My daughter asked me at 7 months if you could feel seizures in the womb (she was feeling his tonic seizures). I had no idea. Tyler was born seizing two months later. He spent his first six weeks of life in the NICU hooked up to every machine and monitor in sight. He seized continually, and thus began his journey into the world of seizure meds. His first EEG was done when he was about 18 hours old and it showed the burst suppression pattern. The neuro called the brain pattern, “scrambled eggs”. It was that of a four-month fetus. He had his first MRI at 24 hours old. It showed a healthy, normal brain. The tests to find a dx went on for months; 2 CAT SCANS, 2 PET SCANS, 2 MRI’S, special blood work, metabolic tests, mitochondrial tests, urine tests, long chain fatty acid test, 3 spinal taps more EEG’S. At 7 months of age, his second MRI showed atrophy of the frontal and temporal lobes. In the meantime, we had a stream of unanswered questions, no one to talk to, and no one to give us answers, no hope, and a terrifying sense of total and complete isolation. It was mind numbing and very destructive. My husband and I went from grandparents to full time caregivers very early on and my daughter’s brief marriage, quickly ended in divorce. Tyler continued to seize. We witnessed 50-100 prolonged, tonic seizures every day and gradually several more seizure types began appearing: atonic seizures, gelastic seizures, myoclonic jerks, petite mals, temporal seizures, silent seizures, gran mals.

The dx of Ohtahara Syndrome gave us a name, but little else. I began searching for any research on this illness and found very little. After nearly four years, I went on the Internet and began searching for other families in the hopes of making a connection. Slowly, and after putting Tyler’s story on every seizure or epilepsy website that had a message board, I began to find the families. I now know of, have communicated with, or spoken to, 80 families around the world with 83 children. That does not mean that I have communication with all of them. Some families have told me about others in their countries that they have heard of, but have not been able to communicate with. We now have a website for families with OS and some of the families that I have found (or the new ones that are finding us) communicate there.


Usman Omar Ghani

Our web address is: [email protected]. I send the new families what little in the way of research papers I have along with a picture of Tyler, and try to make their journey a little easier and give them some hope. We have lost 25 of the little ones (the oldest was 4 years old). They have died from pneumonia’s, sudden death (can you imagine waking up in the morning to find YOUR little one dead in his bed?), infections, suffocation (he rolled over in his sleep for the first time in three years and couldn’t lift his head to breath), being born without the ability to breath is its own, or in the arms of their mothers. Some have died by inches as the severe, continuous seizures, slowly shut down one organ after the other. No family should ever have to face this kind of pain.

Tyler is one of oldest boys in the world with OS that I know of. He is cortically blind, quadriplegic, severely developmentally delayed, no speech, and has severe, intractable seizures, but has a smile that could cure the ills of the world and a giggle that could light up all the dark corners. We have been through all of the AED’s on the market with little success. The only drug, which gave us, a measure of control for the tonic seizures, quit working after four years. We tried the Keto Diet, cranial sacral treatments, natural remedies (herbs, oils etc.), and did all the testing in the hopes of surgery. We were told a few weeks ago that there is nothing else the medical community can do for us and Tyler now has hundreds of seizures every day. I know that there is not a miracle cure out there for our children, but someone needs to do something to stop this disorder, better treat this disorder, or at the very least, find what connects our families together, because something surely does.

Every few weeks a new family with a precious, suffering baby, pops up on either the OS site, or my personal email address. They are all looking for answers and at least now, they have a place to start and a place to speak with other families. WE NEED HELP, from the medical community. Because of the rarity of this disorder, very little is being done to research it. Not enough money, not enough time, not enough interest, not enough children…don’t try telling that to our families. WE live with this 24/7 and watch our little ones struggle daily just to survive against tremendous odds!!

Usman has suffered much and like the rest of us wants answers. Please help him to find them. Please help us to stop OS from ever destroying the life of another precious child. We are willing to do whatever is needed to find answers, but we need your help.

Thank you.

Sincerely,

Mrs. Tamara Horak


Usman Omar Ghani

Appendix 7 Supporting letter from Mrs Jennifer Ghiodia

July 20th, 2002

Dr. Anthony Woodman (Research Project Director)C/O Usman Omar GhaniCranfield UniversitySilsoeBedfordshireMK45 4DTEngland

Dear Sir,

Five years ago our son was born and our lives changed forever. Our son, Sebastian was born full term, at 8lbs 7 oz with Apgars of 9 at one minute and 9 at five minutes. We took Sebastian home from hospital at a day and a half old and were sure he was having seizures, but everyone we showed him too said babies don’t have seizures. While pregnant I told doctors of the strange movements I had felt and they said babies have hiccups. We now know he was having seizures. At two weeks old Sebastian was admitted to ICU at BC Children’s hospital and we spent the next many months in hospital. He had endless tests including: EEG’s, CAT Scans, MRI’s, Barium swallows, EKG’s, Woods Lamp, Muscle Biopsy, Skin Biopsy’s, Genetic Gene testing, Blood, Urine, Stool testing galore, Lumbar Puncture’s (spinal tap), Apnea Studies, Bio-medical testing, Endoscopy, Metabolic testing, Mitochondrial Tests, the eye exam to see how well the brain is developing compared to the back of eyes, tube in the nose to see his voice box, four feeding studies and numerous more. His Diagnosis was actually found after his first EEG. We were told Sebastian had Ohtahara Syndrome and he would not live till his first birthday. He went through a very rough first few months of life and after nearly losing him several times we were finally able to come home and watch his many types seizures and wait.

We started researching this Ohtahara Syndrome, but there was very little out there, so we started going online and searching for other families. Slowly families began contacting us and we started learning more.

Sebastian is one of the strongest children with OS that we know of. He is a very amazing little boy; he is very developmentally delayed and cannot do anything for himself. He wears glasses and is always looking around; his seizures are always there but have been fairly well controlled in the past. Sebastian is learning to use his Tech-Talk to try to learn to communicate, he is good with using eye cues when given two choices, but unable to tell us what he wants, need, or how he feels. We have been told he has tried all drugs out their and their are not many more options for him.

We have had the opportunity to visit three other families and gotten quite close with many more families also facing this disorder. I believe there are similarities in these children and with research and interest in the medical community answers can be found. Since our family began living with Ohtahara Syndrome we have not seen any


Usman Omar Ghani

new research or interest in this disorder. We watch our son constantly struggle against such terrible odds and finally someone wants to find answers and help families, don’t take that away from us.

Usman has offered something no one else has, please allow him to help us all find answers we are all looking for. Please help us to stop Ohathara Syndrome from destroying the life of another precious child.Please feel free to contact us, we will help in any way we can. Phone # 604-937-5040; email address [email protected]

Thank you.

Sincerely,

Mrs. Jennifer Ghioda


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Appendix 8 Supporting letter from Mr and Mrs Walters

15 Parry CloseOxford

OX3 OHY

01865 790 337

21 July 2002

DR. ANTHONY WOODMAN (DIRECTOR OF MEDICAL DIAGNOSTICS)UNIVERSITY OF CRANFIELDSILSOE CAMPUSSILSOEBEDFORDSHIREMK45 4DT

Dear Sir

I am writing in support of Usman Omar Ghani’s proposal for research fund in to Ohtahara’s syndrome.

I am the mother of a 9 week old girl – Katia who has been diagnosed with this syndrome. It has had a major effect on all our lives and the lack of information about the condition has made a distressing situation more acute.

Until this diagnosis was made nobody I know had heard of the condition including our GP. For all of us any research into the causes, treatment and prognosis of Ohtara’s would be wonderful. At present all the information is very clinical and in itself distressing to read.

I believe Usman would give the families who are effected by this condition a valuable service in studying this syndrome and we would be prepared to offer any information to support him in this.

Yours sincerely

Helen and Ben Walters


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Appendix 9 Supporting letter from Mr and Mrs Heelas

Dr Anthony Woodman,

Medical Diagnotics Director,

Cranfield university.

Dear Sir,

I am writing to give all my support for the research of Ohtahara Syndrome. My son Joshua first started to fit when he was 20 days old, he had an E.E.G which was described as grossly abnormal, (Burst Suppression) but his M.R.I. scan was fine. The doctor precribed two anti-convulants and continued to observe before sending him home with a decrease in seizures, but this didn't last long, less than two weeks later Josh was re-admitted with 100 fits per day. The doctors continued to investigate for metabolic defaults but nothing was found and they also tried to control Joshua's seizures with a change of medication. Joshua was diagnosed with Ohtahara Syndrome at the begining of the year he spent the majority of his short life in hospitals for management of his seizures which before he passed away were lasting 90 minutes, ten times a day. In April, The consultant could no longer control Joshua's seizures, even with emergancy medication, he was then put under pallative care, which consisted of 4 anti convulsants, 1 sedaditive med and morphine in his last week of life. Josh was still seizing through even this until he past away with respiratory problems at acorns childrens hospice in Walsall.

I cannot explain in words how devastating this syndrome is, and the more information and research that can be collected on this condition the better and hopefully children like joshua will never have to go through what he endured.

Yours sincerely

Mr & Mrs Heelas.


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Appendix 10 Supporting letter from Sir Reggie Shefield

Dear Usman, Thank you for your telephone call the day before yesterday. I am writing to say that I am happy to give you any support in your attempt to get a research programme initiated by Dr Anthony Woodman at Cranfield University. You may be able to get funding from the Wellcome Foundation but Dr. Woodman should handle that himself. If I can be of any assistance do not hesitate to either Email or ring me. Yours sincerely,Reginald Sheffield Sir Reginald Sheffield,estate office,normanby,scunthorpe,n.lincs,01724720618.


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Appendix 11 Supporting letter from Mrs Vliet

Usman Omar GhaniCare of dr. Antony Woodman (director of medical diagnostics)University of CranfieldSilsoe campusSilsoeBedfordshireMK 45 4 DT

Hello,

My name is Esmeralda and my boyfriends name is Jeroen. We live in TheNetherlands. Our son Derek was born on 2 may 2002 en is diognosedwith OS after 4 weeks of age. His EEG shows ´burst suppression´. Hehas had lot of tests: blood, urine, brainfluid, MRI but the resultswere all negative.

Five days after he was born we took him to the hospital because herolled his eyes and streched his back in a strange way.They gave him Phenobarbital, Fenytoine (not used anymore), Sabril(not used anymore), Rivotril, Vitamin B6 and Topamax in variousdoses. Derek was in the hospital for 9 weeks, but still has 1 or 2seizures every 30 minutes.He is home for 2 weeks now and we do not see any improvement. We arepositive that he is not looking at us and is not following thingswhit his eyes.

There is not much information on the net (or anywhere else) about OS.The only information we got from our neurologist is the article aboutthe study of 16 cases described by Dr. Otahara.It would be fantastic when there is more research done so we, asparents, will know more about the prospect of our children.

Kind regards,

Esmeralda van VlietSterrenlaan 142665 BT BleiswijkThe Netherlands


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Appendix 12 Supporting letter from Mr and Mrs Pearce

20/7/02

USMAN OMAR GHANI/CARE OF DR. ANTHONY WOODMAN (DIRECTOR OF MEDICAL DIAGNOSTICS)UNIVERSITY OF CRANFIELDSILSOE CAMPUSSILSOEBEDFORDSHIREMK45 4DT

Dear Usman/DrWoodman,

We have a 5-month-old daughter, Amanda Catherine who at 3 months of age was Diagnosed with Ohtahara Syndrome. Amanda is the youngest of our 3 girls. EmilieMoira is currently 4 1/2, turning 5 in January, and Jennifer Amy will be 3 in mid August, neither of them have OS.

We have been in the UK for just over a year, and are flying home to Auckland, New Zealand on Tuesday 2nd September. I had a normal pregnancy and Amanda was born on due date by emergency c-section. She went into fatal distress. Her APGAR scores were 9 and 10. All was fine at her 6-week check. Although she hadn't smiled yet, everyone said it was still early days and it would come.

As time went on things about her development started to "niggle" me. Having the other 2 I could compare. At 3 months of age to the day, she fitted at home after having just been fed. This fit lasted 1-2 mins and involved all over shaking. We took her to the emergency doctors, who advised us to take her to Wexham Park Hospital then and there.

At this stage she hadn't smiled, had no head control and wasn't fixing and following. We were there for 5 days. On day 3 we went up to Oxford for an EEG. The following day Dr Ian McShane told us she had something called Ohtahara Syndrome, what it was and what the outcome could be. We were and still are devastated with the news. Since then we have had her on Vigabatrin, (which we just found out isn't having any effect), Biotin, Pyridoxal and the latest one Prednisolonetablets. We go back to Oxford next week for another EEG to find out if thesteroids are having any effect. We felt so isolated. I wouldn't wish thison anyone and hope like hell that Usman gets the funding he needs so we canall benefit from the answers. We fully support the research Usman is doingas so little is know about this syndrome. We don't know how Amanda gotthis, and what the outcome will be. We do know we love her and her sisters and want the best for her we can get. We do need to know more about OS, to help the families currently with it and for the ones who unfortunately mayfollow. We urge you to support this research project and approve funding.Regards Michelle PearceMSc Medical Diagnostics Thesis August, 2002 134

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Appendix 13 supporting letter from Janice Groenewold

Dr. Anthony Woodman,C/- Usman Omar Ghani,Cranfield University,Silsoe Campus,Silsoe,BedfordshireMK45 4DT,England. Dear Sir,Thankyou for the opportunity of writing this letter.We could celebrate the birth of our 6th child on the 1st of May 1993.She was full term and I had a wonderful pregnancy. I gave birth to her by normal delivery and everything was very good.She had a good strong cry and her reflexes were also good. There were no complications and she breast fed very well.We went home from hospital on the 3rd day.Everything was fine with her at home the next day. That evening she was a little fussy but nothing to be worried about.She was fine till about 9.30 in the morning when I notice her making jerking motions with her eyes. This went on for about 5 minutes and them she stopped. She later did it again and again. I took her to the doctors and he sent us to the Hospital.

Once we were at the hospital she eye jerked some more but also she started cyling with her arms and legs. She would get very red in the face and cry. This went on for hours whilst they did tests for menagitis and blood tests for who knows what.She was hospitalized. They then told us that she was having siezures. We spent the next 6 weeks in Neo-nates (newborn icu)All the while she was having constant siezures like clockwork. The was given phenobarbitone and Phenetoin and also doses of Clonazepam. All test done with urine and blood work came back normal.She had a cranial CT Scan which showed: '<compression of the left lateral ventricle pariculaly at the fontal horn. There was also slight swelling the left frontoparietal region and hypodensity of the deep white matter, particulartly in the left frontal and bilateral temporal areas. It was reported as features consistent with an area of oedema or infarction. Head unltrasound showed similar compression of the left lateral ventricle. An early EEG showed burst suppression pattern bu5 no overt siezure activity. A repeat EEG however showed burst suppression over the right hemisphere paradoxically and also evedince of frequent seizure activity.>'2 weeks later while still in hosptal she had a video EEG with:<confirmed Infantile spasms lasting approx 30 minutes and associaterd with Hypsarrythmia maximal on the right.

She had absence of knee and bicep jerks and had a weak asymmetric moro relflex.>She was now also diagnosed with Ohtahara Syndrome which meant absolutely nothing to us.


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By this time she was 2 month old and very floppy. She could not hold her head up or move her arms or legs.She continued to have lots of siezures and was hospitalized many time in the first 2 years of her life.It was with constant physio that at 9 months old I felt for the first time that she was pushing her leg against me.This gave us much hope that we could work with strengthening her muscles. The siezures and the drugs robbed her of her strength. We have battled on over the years with much labour of Love. Over the years she has improved greatly tothe extent that she can sit un-aided, could crawl for some time but now bum shuffles, and also she will walk if you hold her arms.She does not talk, but we know that in many things she understands what is being said.We have tried to do sign with her but it is very difficult for her. She will not feed herself although we are working on it most of the time. She goes to school 5 days a week and is generally a very healthy girl. She is rarely sick although she does get quite a number of urine infections. This will be addressed very soon.Kym has been on almost all of the siezure medications that there are. It seems that they work for some time and then the just fade away. Also some medications that she has had gave her terrible side effects.

She is now on Phenobarbitone, Primidone, and Frisium. We also use Rivotril drops when she has a cluster of siezures. This always seems to help for her.It is frustrating to know that these siezures will never be controled completely by medication. It is heartbreaking to see her have these siezures every day and night. It would be like a prayer answered to find a cure for our children with Ohtahara Syndrome. Please support Usman in the work that he needs to do to find some answers and if at all possible a cure to this syndrome. Thankyou for reading a little history on Kym. Kind regards, Janice Groenewold,31 Orleans Drive,Port Kennedy. W.A. 6172Western Australia.


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Appendix 14 Supporting letter from Susan Titbits

Dr. Anthony Woodman (director of medical diagnostics)Cranfield universitySlisoeMK45 4DT

Dear Dr Anthony Woodman,

I have asked Usman Ghani to pass this email onto you, as a support for the project,as confirmation of our support for your research into Ohtahara syndrome.

We would be happy to assist you in anyway we can, and would certainly be happy for you to speak with us, meet with Sarah or indeed to speak with our local hospita;l paediatrician Dr Frances Howard.

Dr Howards address is as follows:Dr Frances HowardConsultant paediatricianFrimley park HospitalFrimleyCamberleySurrey

In addition I would be happy for you to speak with Sarah's Great ormond Street consultants-Dr Stuart Boyd, Dr Carlos de Sousa Dr Gwilym Hosking

We have recently had a series of reports and assessments on sarah for the purposes of securing for her a new school placement. These reports comprise medical, Occupational therapy, Physiotherapy, Speech/Communication and educational psychology assessments. We are happy to share these with you and Dr Woodman if they would prove helpful. We also have a summary of Sarah's life to date and are in the process of making a video for the schools issue I mentioned above and again you are welcome to copies of both.

Sarah at present is fit and well, her seizures are well controlled in comparison to the past!

She tends not to have Grand Mals anymore, but does have many absences, and partial and complex partial fits regularlyHer current medication includes Tegretol Retard and Epilim Chrono.

I have recently been in touch with Dr Yamatogi a colleague of Dr Ohtahara after reading a report I was directed to by the Yahoo Ohtahara website.

He is also awaire of your proposed study, I believe Mr. Ghani has been in direct communication with Dr. Ohtahara, this is a big achievement on his part, I, like many other families, have been trying to contact Dr. Ohtahara for nearly 15 years, without


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success, it is apperent Dr Ohtahara must have been impressed with his eargerness to do research in this disorder.

He has confirmed that to the best of his knowledge and experience, although Sarah is not the oldest surviving Ohtahara childat age 15, she is ceratinly the most capable in terms of physical abilities, and genberal intelligence-despite the fact she is clearly mentally handicapped.

Please feel free to contact me or any of Sarah's doctors mentioned if such contact would be helpful to you Dr Woodman.

I wish you luck with this very worthwhile project-it may not help our children, but if it can help future Ohtahara children then it will have been a worthwile effort, i do not know if you have children Dr Woodman, but any parent wuld understand the pain and heart ache of watching your children suffer in pain,we are not in a position to do anything, you can help us, if you were to set up this project, the whole medical research communiuty, as well as parents of effected children, would aplaud you, sir.

Sincerly

Susan Titbets


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Appendix 15 Supporting letter from Susan Donna Fay

Donna Fay 78 Redmersh Leam Lane Gateshead NE10 8PS Date 30/07/2002

Dr. Anthony WoodmanDirector of medical diagnosticsCranfield UniversitySilsoe CampusSilsoeMK45 4DT

Dear Mr Woodman

I have recently heard that you maybe setting up a PhD study in Ohtahara syndrome, with Mr. Usman Omar Ghani, he like many other families is a victim of Ohtahara disorder, he has worked very hard to bring people together, and bring people together to a family Ohtahara site, at present there are 35 members, I only joined last week.

We have a five year old son who has this syndrome, and would be extremely interested in any research relating to this condition as there is little or none known. There is no collective study to over view this condition, such a study would have massive impact on the collective knowledge of this disorder.

Connor was born on the 18-01-97 he is my second son. He weighed 9lb at birth and seemed extremely healthy.He was diagnosed with this syndrome at 5wks.

Dr Ramesh at the General Hospital Newcastle Upon Tyne is Connor'sneurologist,and I have spoken to him about your study, he gives his full support, and would be only to pleased to help if you were to contacthim.You can look at all of Connors medical records and EEG's. If there is any other information you require regarding this matter please do not hesitate to contact me. I strongly support this study and would ask you to set it up, for the sake of all families effected by Ohtahara syndrome.

Yours truly,

Donna FayMSc Medical Diagnostics Thesis August, 2002 139

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Appendix 16 Supporting letter from Joyce Edidin

July 24, 2002

Dr. Anthony Woodman (Research Project Director)c/o Usman Omar GhaniCranfield UniversitySilsoe CampusSilsoeBedfordshireMK45 4DT

Dear Sir,

I have a 22-month-old daughter diagnosed with Ohtahara Syndrome. I am writing this letter in support of Usman’s Research Project Proposal.

My daughter, Kaela, started seizing before she was born. At two days old she was admitted to Children’s Hospital in Seattle, Washington, USA. At 20 days old, after numerous tests and procedures, she had a tracheotomy and gastrotomy because she was apneic and could not swallow on her own. The doctors had no idea what was wrong with her. At 25 days old she had an EEG that indicated Ohtahara Syndrome. We were given a grave prognosis for her. Our life has not been the same ever since.

She is very bright and she understands a lot of what we say. We've taught her to respond to yes/no questions by blinking once for "yes." She'll take a big breath when we ask her to. Her tracheostomy has enabled us to keep her very healthy. She has a hard time moving her body unless she can get enough air in. She is trying to use her hands, arms, and legs now and tries to balance her head when held upright. All of these things she can now do after we have worked long hours with her.

We do not give Kaela anti-convulsants since we noticed that they didn’t really work on the other OS kids. Since the seizures are intractable there is no hope for her with standard seizure therapies. Instead, we follow the programs started by Glenn Doman, et al at the Institutes for the Achievement of Human Potential. We work many hours a day on her therapy, which has helped her develop, although very slowly.

This syndrome requires research, but until now no one has stepped forward to study this unpopular disorder. Most parents are told “sorry, there is nothing that we can do to help” and then sent home very distraught and confused, waiting for their severely brain-injured child to die. The callousness that our families have experienced is an atrocity. Please help take a step toward better understanding of this rare, little known syndrome by providing funding for Usman’s proposed research.Thank you for your time and thoughtful consideration for Kaela’s future and the future of all OS children.Most sincerely,


Usman Omar Ghani

Joyce EdidinAppendix 17 Ohtahara questionnaire

Usman Omar Ghani University of Cranfield. Silsoe campus Silsoe Bedfordshire MK45 4DT

To whom it may concern

Ref: Ohtahara Syndrome questionnaire.

Dear sir/madam,

I am researching a rare syndrome, for my MSc thesis at Cranfield University. Could you please take a few minutes and fill in the attached questionnaire. The aim of the questionnaire is to evaluate the current awareness of the rare disorder Ohtahara syndrome, in the medical community.

Your cooperation and time is appreciated, please be free to make any additional comments.

Yours truly,

Usman Omar Ghani


Usman Omar Ghani

Ohtahara syndrome questionnaire

Please tick the appropriate line.

1. Have you heard of Ohtahara syndrome?

…. Yes…. No

2. Ohtahara syndrome:

…. Is an epileptic syndrome.…. Is a neuro muscular syndrome.…. Is it a psychological syndrome.

3. Ohtahara syndrome is also known as:

….. Early myoclonic encephalopathy.…. Early infantile epileptic encephalopathy.…. Juvenile myoclonic epilepsy.

4. What causes Ohtahara syndrome?

…. Poisoning.…. Infection.…. Head injury.…. Genetic factors.…. Prenatal injury.…. Aetiology is yet unknown.

5. Ohtahara syndrome effects:

…. One in a million live cases.…. One in one hundred thousand live cases.…. One in forty thousand live cases.…. One in ten thousand live cases.…. Not known.

6. Ohtahara syndrome effects:

…. Mainly adults.…. The elderly.…. Infants from birth.…. Adolescence.MSc Medical Diagnostics Thesis August, 2002 142

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7. What are the symptoms of Ohtahara syndrome?

…. Tremor.…. Weight loss.…. Muscle deteriation.…. Tonic seizures, which maybe either generalized and symmetrical.

8. How is Ohtahara syndrome diagnosed?

…. Through an ECG.…. Through an EEG.…. Blood tests.

9. How can Ohtahara syndrome be controlled?

…. Drug medication.…. Physiotherapy.…. Diet control.…. Surgery.

10. Is the epidemiology of Ohtahara syndrome known?

…. Yes.…. No.…. Don’t know.

11. Can Ohtahara syndrome be prevented?


12. The prognosis of Ohtahara syndrome is:

…. Good.…. Poor.…. Don’t know.

13. Would you like to know more about Ohtahara syndrome?

…. Yes.…. No.

14. Is there a need for more medical research in Ohtahara syndrome?


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15. If there was a research project set up to provide a demographic and epidemiological overview of Ohtahara syndrome, together with a discussion of its social aspects and the presentation of Ohtahara data base cases, would you give your backing?


Additional information

What is Ohtahara Syndrome ?

Ohtahara syndrome is a neurological disorder characterized by seizures. The disorder affects newborns, usually within the first three months of life. Individuals with Ohtahara syndrome often have mental retardation or other developmental impairments. The cause of the disorder is unknown.

Is there any treatment?

There is no cure for Ohtahara syndrome. Treatment is symptomatic and supportive. Most drug therapy has limited effect.

What is the prognosis?

Ohtahara syndrome often is fatal. Survivors suffer from severe mental and physical impairment.

What research is being done?There has been research orchestrated around the world, on specific cases, to date no collective case data is available and more research is required to understand this syndrome.

Additional comments

Please feel free to write any additional comments:


Usman Omar Ghani


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