Usman Omar Ghani
Chapter 3: Aims and objectives
(Luders H: 2000)
Aim:
To critically evaluate the detection, diagnosis and ...
Usman Omar Ghani
• Through informal methods, obtain information from relatives of Ohtahara
syndrome, concerning there pres...
Usman Omar Ghani
3.1 Research methodology
Memory valley park, Sanfransisco (Luders H: 2000)
Introduction
There were many u...
Usman Omar Ghani
A questionnaire was designated to evaluate the current understanding of Ohtahara
syndrome in the medical ...
Usman Omar Ghani
Dr. Geoff Woods (consultant paediatric neurologist at St. James hospital, Leeds).
Dr. Woods was selected ...
Usman Omar Ghani
Dr. Ian McShane (senior neurologist at John Radcliff hospital, in Oxford).
Dr. McShane had been involved ...
Usman Omar Ghani
3.2 Internet sites
Two sites were selected for there support to rare inherited disorders, the first was
w...
Usman Omar Ghani
Susan Titbits
It was through Tammie Horak that contact was made with Susan Titbits. From
previous posted ...
Usman Omar Ghani
The first three questions are set out to evaluate the understanding of what Ohtahara
syndrome is. If the ...
Usman Omar Ghani
3.4.1 General Practioneer doctors
General Practioneers were selected because of there close association w...
Usman Omar Ghani
The questionnaires were taken by hand and given to the medical secretary, was
informed the results will b...
Usman Omar Ghani
Both children’s wards at High Wycome and Luton Hospital were given questionnaires
for there paediatrics t...
Usman Omar Ghani
Chapter 4: Results
4.1 Statement of facts
Dr. Sawney
My first line of investigation was with Dr. Sawney, ...
Usman Omar Ghani
Recommendations
• Contact Dr. Geoff Woods.
Dr. Geoff Woods
Dr. Woods was a senior geneticist at St. James...
Usman Omar Ghani
Contact a family
Contact a family is a UK charity which helps families who care for children with rare
di...
Usman Omar Ghani
• The official internet site for families touched by Ohtahara syndrome,
moderated by Tammie Horak.
4.3 Fa...
Usman Omar Ghani
4.4 Letters of support (refer to appendix)
I began receiving letters of support from the families touched...
Usman Omar Ghani
continuous morphine and valium. I spent an hour and a half at the family’s house.
Little or no questions ...
Usman Omar Ghani
medication to be targeted at the root cause; a diagnostic kit would allow parents of
existing Ohtahara in...
Usman Omar Ghani
4.7 Contacting Dr. Ohtahara
Dr. Ohtahara was the person responsible for discovering and categorising the
...
Usman Omar Ghani
4.9 Discussion on results
4.9.1 Opinion formers
Medical professionals associated with Ohtahara syndrome w...
Usman Omar Ghani
believed to be genetic and therefore did not fit in his research aims. I used a counter
argument on my pe...
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Dr. McShane and I was informed that a study of this kind was needed as a prequel for
further technical st...
Usman Omar Ghani
Dr. Ohtahara’s letter to Dr. Woodman affirms that there are no reported cases of
inherited form of Ohtaha...
Usman Omar Ghani
The third message orchestrated from the families was the difficulty in managing and
controlling the syndr...
Usman Omar Ghani
financial worry for there infants, it is important to point out that the point of delivery
free medical s...
Usman Omar Ghani
• Internet provided a faster mode of communication with my contacts.
4.9.4 The questionnaire (refer to ap...
Usman Omar Ghani
• Results from the participants at both locations (High Wycome and
Luton/Dunstable hospital) compared.
Nu...
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Numbers of questionnaires sent and received
0
2
4
6
8
10
12
New surgery
(Chesham)
Green meadows
surgery
(...
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Table 11 Summarises the number of questions asked and answered correctly
from the New Surgery. The result...
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• The results reflected good knowledge of the syndrome by all the partners at
the surgery.
Green Meadow’s...
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• Less than 50% of the participants were correct in there assessment of the
syndrome.
Dr. How’s Surgery (...
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Flitwick health care centre (refer to table 14 and figure 23)
The results from the questionnaire illustra...
Usman Omar Ghani
Comparisons of results from all four surgeries (refer to table 15 and figure 24).
As figure 24 illustrate...
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• The New Surgery had a better understanding of Ohtahara syndrome, than the
other three surgeries.
Compar...
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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
Number of q...
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• Staff at SCBU in High Wycome hospital displayed greater knowledge and
understanding of Ohtahara syndrom...
Usman Omar Ghani
Paediatrics at High Wycome and Luton/Dunstable
hospital
0
0.5
1
1.5
2
2.5
3
3.5
1 2 3 4 5 6 7 8 9 10 11 1...
Usman Omar Ghani
Table 18 Summary tables showing the number of questions asked and answered
correctly from all the partici...
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It must also be pointed out that no prior knowledge was known on my part that if the
staff at Luton/Dunst...
Usman Omar Ghani
Paediatrics at
High Wycome
hospital
6 0 6 0 6 0
High Wycome
SCBU
3 0 3 0 3 0
Luton/Dunstable
SCBU.
4 0 2 ...
Usman Omar Ghani
As figure 28 illustrates there is an over whelming agreement and support for future
research on this synd...
Usman Omar Ghani
From the personal contact with families touched by Ohtahara syndrome, the under
lying message is the need...
Usman Omar Ghani
questions and personal life experience dictates in the reply given. My opinion is that
every life has a r...
Usman Omar Ghani
doubt in the presence of a genetic link. In comparison Dr Kamal Sawney is of
the view that this disorder ...
Usman Omar Ghani
References
1. Aicardi J, Goutieres F, encephalopathy myoclonic neonate, Rev EEG
neurophysiol 1978; 8:99-1...
Usman Omar Ghani
14. Dreifuss, Proposal for revised clinical and electroencephalographic
classification of epileptic seizu...
Usman Omar Ghani
31. Messing RO; Commission on classification and terminology of the
international league against epilepsy...
Usman Omar Ghani
45. Spreafico R, Angelini L, Binelli S, et al. burst suppression and impairment of
neocortical ontogenesi...
Usman Omar Ghani
Appendix 1 Supporting letter from Dr Ohtahara
MSc Medical Diagnostics Thesis August, 2002120
Usman Omar Ghani
Appendix 2 Supporting letter from Dr Kamal Sawney
Appendix 3 Supporting letter from Dr Alison Shaw (refer...
Usman Omar Ghani
MSc Medical Diagnostics Thesis August, 2002122
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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...
Usman Omar Ghani
Appendix 5 Notes on rare disorder meeting, from Dr Alison Shaw
Dear Usman,
Greetings: assalaam alaikum.
M...
Usman Omar Ghani
thalassaemia (middle east and Pakistan); Tay Sachs (Ashkenazi Jews)
Consanguineous families with rare con...
Usman Omar Ghani
Appendix 6 Supporting letter from Mrs Tamara Horak
June 11, 2002
Dr. Anthony Woodman (Research Project Di...
Usman Omar Ghani
That does not mean that I have communication with all of them. Some families have
told me about others in...
Usman Omar Ghani
Appendix 7 Supporting letter from Mrs Jennifer Ghiodia
July 20th
, 2002
Dr. Anthony Woodman (Research Pro...
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We have had the opportunity to visit three other families and gotten quite close with
many more families ...
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Appendix 8 Supporting letter from Mr and Mrs Walters
15 Parry Close
Oxford
OX3 OHY
01865 790 337
21 July ...
Usman Omar Ghani
Appendix 9 Supporting letter from Mr and Mrs Heelas
Dr Anthony Woodman,
Medical Diagnotics Director,
Cran...
Usman Omar Ghani
Appendix 10 Supporting letter from Sir Reggie Shefield
Dear Usman,
Thank you for your telephone call the ...
Usman Omar Ghani
Appendix 11 Supporting letter from Mrs Vliet
Usman Omar Ghani
Care of dr. Antony Woodman (director of med...
Usman Omar Ghani
Appendix 12 Supporting letter from Mr and Mrs Pearce
20/7/02
USMAN OMAR GHANI/
CARE OF DR. ANTHONY WOODMA...
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  1. 1. 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, 200271
  2. 2. Usman Omar Ghani • 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. MSc Medical Diagnostics Thesis August, 200272
  3. 3. Usman Omar Ghani 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), MSc Medical Diagnostics Thesis August, 200273
  4. 4. Usman Omar Ghani 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. MSc Medical Diagnostics Thesis August, 200274
  5. 5. Usman Omar Ghani 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. MSc Medical Diagnostics Thesis August, 200275
  6. 6. Usman Omar Ghani 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. MSc Medical Diagnostics Thesis August, 200276
  7. 7. Usman Omar Ghani 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. MSc Medical Diagnostics Thesis August, 200277
  8. 8. Usman Omar Ghani 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. MSc Medical Diagnostics Thesis August, 200278
  9. 9. Usman Omar Ghani 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. MSc Medical Diagnostics Thesis August, 200279
  10. 10. Usman Omar Ghani 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. MSc Medical Diagnostics Thesis August, 200280
  11. 11. Usman Omar Ghani 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. MSc Medical Diagnostics Thesis August, 200281
  12. 12. Usman Omar Ghani 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. MSc Medical Diagnostics Thesis August, 200282
  13. 13. Usman Omar Ghani 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. MSc Medical Diagnostics Thesis August, 200283
  14. 14. Usman Omar Ghani 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. MSc Medical Diagnostics Thesis August, 200284
  15. 15. Usman Omar Ghani 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. MSc Medical Diagnostics Thesis August, 200285
  16. 16. Usman Omar Ghani • 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. MSc Medical Diagnostics Thesis August, 200286
  17. 17. Usman Omar Ghani 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 MSc Medical Diagnostics Thesis August, 200287
  18. 18. Usman Omar Ghani 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: 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. 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 MSc Medical Diagnostics Thesis August, 200288
  19. 19. Usman Omar Ghani 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. MSc Medical Diagnostics Thesis August, 200289
  20. 20. Usman Omar Ghani 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: 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. 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. MSc Medical Diagnostics Thesis August, 200290
  21. 21. Usman Omar Ghani 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 MSc Medical Diagnostics Thesis August, 200291
  22. 22. Usman Omar Ghani believed to be genetic and therefore did not fit in his research aims. I used a counter 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 MSc Medical Diagnostics Thesis August, 200292
  23. 23. Usman Omar Ghani Dr. McShane and I was informed that a study of this kind was needed as a prequel for 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). MSc Medical Diagnostics Thesis August, 200293
  24. 24. Usman Omar Ghani 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 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. MSc Medical Diagnostics Thesis August, 200294
  25. 25. Usman Omar Ghani 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 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 MSc Medical Diagnostics Thesis August, 200295
  26. 26. Usman Omar Ghani 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. • 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. MSc Medical Diagnostics Thesis August, 200296
  27. 27. Usman Omar Ghani • Internet provided a faster mode of communication with my contacts. 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. MSc Medical Diagnostics Thesis August, 200297
  28. 28. Usman Omar Ghani • Results from the participants at both locations (High Wycome and Luton/Dunstable hospital) compared. 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 MSc Medical Diagnostics Thesis August, 200298
  29. 29. Usman Omar Ghani Numbers of questionnaires sent and received 0 2 4 6 8 10 12 New surgery (Chesham) Green meadows surgery (Chesham) Dr. How’s Surgery (Chesham) Flitwick health centre (Flitwick) Special care baby unit (High Wycome) Special care baby unit (Luton and Dunstable hospital) Paediatrics at High Wycome Hospital. Paediatrics at Luton and Dunstable hospital 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). MSc Medical Diagnostics Thesis August, 200299
  30. 30. Usman Omar Ghani 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 Numberofcorrectanswers 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. MSc Medical Diagnostics Thesis August, 2002100
  31. 31. Usman Omar Ghani • 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 surgery Number 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 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 1 2 3 4 5 6 7 8 9 10 11 12 Number of questions Numberofcorrectanswers 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. MSc Medical Diagnostics Thesis August, 2002101
  32. 32. 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 12 Number 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 Numberofcorrectanswers 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. MSc Medical Diagnostics Thesis August, 2002102
  33. 33. Usman Omar Ghani 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 12 Number 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 numberofcorrectanswers Number of questions answered 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. MSc Medical Diagnostics Thesis August, 2002103
  34. 34. Usman Omar Ghani 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 12 New Surgery 5 5 3 3 2 5 5 5 4 2 3 5 Green meadows surgery 3 2 1 0 2 2 3 3 4 1 2 2 Dr. Hows surgery 1 1 1 0 1 2 1 0 1 0 0 0 Flitwick 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 Numberofcorrect answers New Surgery Green meadows surgery Dr. Hows surgery Flitwick health centre Fig. 24 Bar chart showing the number of questions asked and answered correctly from the four medical surgeries participating in the questionnaire. MSc Medical Diagnostics Thesis August, 2002104
  35. 35. 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 asked Number 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 MSc Medical Diagnostics Thesis August, 2002105
  36. 36. Usman Omar Ghani 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 Number of questions asked Numberofcorrect answers Number of correct answers, High Wycome SCBU Number of correct answers, 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). MSc Medical Diagnostics Thesis August, 2002106
  37. 37. 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 asked Paediatrics 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 MSc Medical Diagnostics Thesis August, 2002107
  38. 38. Usman Omar Ghani Paediatrics at High Wycome and Luton/Dunstable hospital 0 0.5 1 1.5 2 2.5 3 3.5 1 2 3 4 5 6 7 8 9 10 11 12 Number of questions asked Numberofcorrect answers Paediatrics at Luton & Dunstable hospital Paediatrics at High Wycome 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. MSc Medical Diagnostics Thesis August, 2002108
  39. 39. 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 12 New Surgery 5 5 3 3 2 5 5 5 4 2 3 5 Green meadows surgery 3 2 1 0 2 2 3 3 4 1 2 2 Dr. How’s surgery 1 1 1 0 1 2 1 0 1 0 0 0 Flitwick health centre 2 2 1 1 1 2 1 0 1 1 0 1 Paediatrics 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 Number 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 Number of questions asked Numberofcorrectanswers New Surgery Green meadows surgery Dr. Hows surgery Flitwick health centre Paediatrics at Luton & Dunstable hospital Paediatrics at High Wycome hospital Number of correct answers, High Wycome SCBU Number of correct answers, Luton & Dunstable SCBU Fig. 27 Comparison of results received from all the participants in the study. MSc Medical Diagnostics Thesis August, 2002109
  40. 40. 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 15 For the questions. yes no yes no yes no New Surgery 5 0 5 0 5 0 Green meadows surgery 6 0 6 0 6 0 Dr. Hows surgery 2 0 1 1 2 0 Flitwick health centre 5 0 5 1 5 0 Paediatrics at Luton & Dunstable hospital 4 0 4 0 4 0 MSc Medical Diagnostics Thesis August, 2002110
  41. 41. Usman Omar Ghani Paediatrics at High Wycome hospital 6 0 6 0 6 0 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 question 13 question 14 question 15 Yes or no numberofparticipants New Surgery Green meadows surgery Dr. Hows surgery Flitwick health centre Paediatrics at Luton & Dunstable hospital Paediatrics at High Wycome hospital High Wycome SCBU Luton/Dunstable SCBU. Fig. 28 Comparison of results received from all the participants in the study. MSc Medical Diagnostics Thesis August, 2002111
  42. 42. 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. MSc Medical Diagnostics Thesis August, 2002112
  43. 43. 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 MSc Medical Diagnostics Thesis August, 2002113
  44. 44. 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 MSc Medical Diagnostics Thesis August, 2002114
  45. 45. Usman Omar Ghani doubt in the presence of a genetic link. In comparison Dr Kamal Sawney is of 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. MSc Medical Diagnostics Thesis August, 2002115
  46. 46. Usman Omar Ghani References 1. Aicardi J, Goutieres F, encephalopathy myoclonic neonate, Rev EEG neurophysiol 1978; 8:99-101. 2. Aicardi J. Early myoclonic encephalopathy. In: Roger J, Dravet, Bureau M editors. Epileptic syndromes in infancy, childhood and adolescence, London: John Libby Eurotext, 1985, pp 124-128. 3. Andermann and Hart; epilepsia partialis continua; a clinical and historical review; 2001, 1:481-6. 4. Annegers JF: The History of Epilepsy. In Wyllie E (edition), Philadelphia, Lea and Febiger, 1993, pp 157-164. 5. Ben-Menachem E: Potential antileptic drugs; 4th edition. New York, Raven Press, 1995, pp 1063-1070. 6. Ben-Menachem E: Potential antileptic drugs; in levy RH, Mattson RH (editors): Antileptic drugs, 4th edition. New York, Raven Press, 1995, pp 1063- 1070. 7. Bradley W; et al; Neurology in clinical practice: The neurological disorders, vol 11, 2nd edition, Butterworth-Heinemmann, Boston, pp 1078, 1480, 1996. 8. Cavazzuti GB, Nalin A, Ferrari F, Grandori L, Beghini GE. Encefalopatia epilettica ad insorgenza neonatale. Clinical pediatrics: 1978; 60; 239-46. 9. Clark M, Gill J, Noronha M, Mckinlay I. Early infantile epileptic encephalopathy with suppression-burst; Ohtahara syndrome, 32 reported cases in the United States of America. Dev Med child neurology; 1987; 29:520-8. 10. Commission of classification and terminology of the international league against epilepsy. Proposal for revised classification of epilepsy and epileptic syndromes. Epilepsia 1989; 30:389-399. 11. Dalla Bernardina B, dulac O, Fejerman N, et al. early myoclonic epileptic encephalopathy (EMEE), eur paediatric: 1983;140;248-52. 12. Delgado-Escueta AV, Treiman DM, Walsh GO: The treatable epilepsy. N Engl J Med, 1983; pp 1508-1514. 13. Denslow GT, Aicardi syndrome; A report of four cases and review of literature journal of pediatric opthal and strabismus: 1979, pp10-15. MSc Medical Diagnostics Thesis August, 2002116
  47. 47. Usman Omar Ghani 14. Dreifuss, Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia, 22:249-260, 1981. 15. DU Plessis AJ, Kaufmann WE, Kupsky WJ. Intra-uterine onset myoclonic encephalopathy associated with cerebral cortical dysgenesis. J Child neurol, 1993; 8: 164-70. 16. Dulac O; Infantile spasms and west syndrome, 1993, pp 464-491. 17. Engel J Jr (edition): Surgical treatment of the epilepsies, 2nd edition, New York, Raven press, 1993. 18. Gastaunt H and Broughton R (editors), Epileptic Seizures. Springfield, IL: Charles C Thomas, 1972. 19. Goldstien R F, GABA correlation with Gabapentin, institude of laboratory animals, Manhatten School of medicine, 1995). 20. Grandgeorge D, Favier A, Bost M, et al. A proposed neonatal myoclonic observation; 1980; pp 577-84. 21. Hallet M: Myoclonus, relation to epilepsy. Epilepsia 1985; 26 (edition 1); pp.67-74. 22. Hauser WA; commission on classification and terminology of the international league against epilepsy: Proposed for revised classification of epilepsy and epileptic syndromes, 1991, pp.389-399. 23. Hauser WA; The natural history of temporal lobe epilepsy, raven press, 1991, pp 133-144. 24. Laura D Errante, gabapentin and vigabatrin increase GABA levels in the human neocortical slice, department of neurosurgery, CT 06620-8018: 2002. 25. Luders H; Generalized disturbances of brain function: encephalopathies, coma and brain death, 3rd edition, Reshnal press, 2000, pp. 154-163. 26. Macmillan, types and orientation of neurons within the six layer neocortex, review of neuroscience, New York, 1980. 27. Markowitz J, experimental surgery, rodent animals, Baltimore, Maryland, 2nd edition, pp 124-125, 1986. 28. Martin HJ, Angelini L, Binelli s, et al. encephalopathy epileptic neonate’s disorder, neurophysiology clinical 1981; pp 397-403. 29. McLean MJ: Gabapentin. Epilesia 1995; 36 (suppl 2): S87-S94. 30. Messenheimer JA. Lamotrigine, epilepsia 1995. MSc Medical Diagnostics Thesis August, 2002117
  48. 48. Usman Omar Ghani 31. Messing RO; Commission on classification and terminology of the international league against epilepsy: A proposed international classification of epileptic seizures. Eplisia 1981; vol 22, pp 489-501. 32. Miller SP, Dilenge ME, Meagher-Villemure K. infantile epileptic encephalopathy and migrational disorder. Pediatric neurol 1998; 19(1): 50-4. 33. Murakami N, Ohtsuka Y, Ohtahara S. Early infantile epileptic syndromes with suppression-burst: early myoclonic encephalopathy vs. Ohtahara syndrome. Japan J Psychiatry neurol 1993; 47: 197-200. 34. Ogihara M, Kinoue K, Takamiya H, etal. A case of early infantile epileptic encephalopathy (EIEE) with anatomical cerebral asymmetry and myoclonus. Brain dev 1993; 15: 133-9. 35. Ohtahara S. Clinic-electrical delineation of epileptic encephalopathies in childhood. Asian Med J 1978; 21:499-509. 36. Ohtahara S. seizure disorders in infancy and childhood. Brain development, 1984; 6: 509-519. 37. Oliver Wong, surgical out come for neocrtical focal epilepsy. 2nd edition. New York, Raven press, cd rom 897564/99; 1998. 38. Otahara S, Ohtsuka Y, Yamatogi Y, Oka E, Inoue H. early-infantile epileptic encephalopathy with suppression-bursts. In: Roger J, Wolf P, editors. Epileptic syndromes in infancy, in childhood and adolescence. London: John Libbey and company ltd; 1992: 25-34. 39. Panayiotopoulos et al, epilepsia in term by Temkin, 2nd edition: 1989. 40. Plouin P: Benign idiopathic neonatal convulsions; epileptic syndromes in neonates, 2nd edition, 1992, pp 3-12. 41. Renier WO. The malignant epilepsy of childhood and adolescence. In: Aldenkamp AP, Dreifuss FE, Reiner WO, Suumeijer PBM, editors. Epilepsy in children and adolescence. Boca raton: CRC Press, 1995; pp 162-165. 42. Robain and Dulac, epileptic syndrome association with olivary dentate nuclei dysplasia, Rev Itrol; 1992; 143-7. 43. Serratosa JM, Delgado-Escueeta AV: Juvenile myoclonic epilepsy. In Wyllie edition, 1993, pp 552-570. 44. Snead OC: Basic mechanisms of generalized absence seizures. ANN Neurol 1995; 37:146-157. MSc Medical Diagnostics Thesis August, 2002118
  49. 49. Usman Omar Ghani 45. Spreafico R, Angelini L, Binelli S, et al. burst suppression and impairment of neocortical ontogenesis: electro-clinical and neuropathologic findings in two infants with early myoclonic encephalopathy. Epilepsia 1993; 34: 800-8. 46. Spreafico R, Bosman C. Neonatal burst suppression and impairment of neocortical ontogenesis: electroclinical and neuropathologic findings in two infants with early myoclonic encephalopathy. Epilepsia 1993; 34 (5): pp 800- 8. 47. Temkin O: The Falling Sickness, 2nd edition, Baltimore, John Hopkins University Press, 1999. 48. Tominaga I, Kaihou M, Kimura T, et al. early infantile epileptic encephalopathy (Ohtahara syndrome) with poly-microgyria. French Rev Neurol (Paris) 1993; 149 (10): 532-5. 49. Treiman LJ, Treiman DM: Genetic aspects of epilepsy. In Wyllie (Ed): Leae Febiger, 1993, pp 145-156. 50. Van Ness PC, frontal and parietal lobe epilepsy, //htp.neuronal signals.org.ak...98. 51. Woodbury DM, Vagal stimulation induces epilepsy; usage of electro implant metals in rats; 1991; 14:94-107. 52. Wyllie E : Corpus Epilepsy, outcome with respect to seizures, 1991. 53. Yoshiki Miura, college of medical laboratory, Kyoto University, Kyoto, Medline site, 2002. MSc Medical Diagnostics Thesis August, 2002119
  50. 50. Usman Omar Ghani Appendix 1 Supporting letter from Dr Ohtahara MSc Medical Diagnostics Thesis August, 2002120
  51. 51. Usman Omar Ghani Appendix 2 Supporting letter from Dr Kamal Sawney Appendix 3 Supporting letter from Dr Alison Shaw (refer to page 122). MSc Medical Diagnostics Thesis August, 2002121
  52. 52. Usman Omar Ghani MSc Medical Diagnostics Thesis August, 2002122
  53. 53. Usman Omar Ghani 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 MSc Medical Diagnostics Thesis August, 2002123
  54. 54. Usman Omar Ghani Appendix 5 Notes on rare disorder meeting, from Dr Alison Shaw Dear Usman, Greetings: assalaam alaikum. My email address is: Alison.Shaw@brunel.ac.uk. I am sending you some notes that I made on Helen Middleton'Price's talk at the RSM meeting on 4th February. Let me know if this message reaches you successfully, and I will send you 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 was called 'DNA testing: how far can we go', and given at a meeting called 'consanguineous marriage in the UK: a multidisciplinary strategy' Mac Keith Meetings- 4 FEbruary 2002. Helen Middleton-Price is at the Institute of Child Health, London. I don't think this is confidential information. Much of this information is generally available in books and on websites. But if you want to use any of this in what you write, you will need to reference your sources. You will probably find much the same information at the website address gives. Anyway, here are my notes. There is DNA testing for the more common severe conditions: Cystic Fibrosis, incidence 1/2500; Duchenne Muscular Dystrophy 1/3000; Fragile X 1/1500 There are specialist services for rare conditions, selected in relation to research interests. Great Ormond Street hospital provides a service for rare metabolic disorders, X-linked conditions and cranio-spatial disorders. There has been a dramatic increase in demand for DNA testing. 5000 genetic conditions have been identified, and the genes for 1000 of them have already been found. Most new discoveries are for rare conditions, and DNA services are currently offered only for more or less 200 rare conditions in the UK. The Department of Health is currently formalising a genetic testing network, a collaborative network, involving transfer of samples for rare disease testing. 'Reference laboratories' are being set up by D.O.H in Salisbury and Manchester to provide new high through-put services for rare or 'orphan' conditions. There are significant risks in certain ethnic groups: CF (in northern European populations); Sickle-cell (AfroCAribbean) ; MSc Medical Diagnostics Thesis August, 2002124
  55. 55. Usman Omar Ghani thalassaemia (middle east and Pakistan); Tay Sachs (Ashkenazi Jews) Consanguineous families with rare conditions are a precious research resource, enabling the identification of genes for rare conditions, and they have been instrumental in the identification of heterogeneous genes for common conditions. A family with one affected child and consanguinity gives you mapping information. A family with 3 affected children and also consanguineous gives a massive amount of information, enough to map the gene. So consanguineous families are invaluable in the search for genes, can help 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 IC gene (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 Shaw Department of Human Sciences Brunel University MSc Medical Diagnostics Thesis August, 2002125
  56. 56. Usman Omar Ghani Appendix 6 Supporting letter from Mrs Tamara Horak June 11, 2002 Dr. Anthony Woodman (Research Project Director) C/O Usman Omar Ghani Cranfield University Silsoe Campus Silsoe Bedfordshire MK45 4DT England 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. MSc Medical Diagnostics Thesis August, 2002126
  57. 57. Usman Omar Ghani 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. Our web address is: www.ohtaharasyndrome@yahoogroups.com. 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 MSc Medical Diagnostics Thesis August, 2002127
  58. 58. Usman Omar Ghani Appendix 7 Supporting letter from Mrs Jennifer Ghiodia July 20th , 2002 Dr. Anthony Woodman (Research Project Director) C/O Usman Omar Ghani Cranfield University Silsoe Bedfordshire MK45 4DT England 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. MSc Medical Diagnostics Thesis August, 2002128
  59. 59. Usman Omar Ghani 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 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 jenstelseb@telus.net Thank you. Sincerely, Mrs. Jennifer Ghioda MSc Medical Diagnostics Thesis August, 2002129
  60. 60. Usman Omar Ghani Appendix 8 Supporting letter from Mr and Mrs Walters 15 Parry Close Oxford OX3 OHY 01865 790 337 21 July 2002 DR. ANTHONY WOODMAN (DIRECTOR OF MEDICAL DIAGNOSTICS) UNIVERSITY OF CRANFIELD SILSOE CAMPUS SILSOE BEDFORDSHIRE MK45 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 MSc Medical Diagnostics Thesis August, 2002130
  61. 61. Usman Omar Ghani 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. MSc Medical Diagnostics Thesis August, 2002131
  62. 62. Usman Omar Ghani 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. MSc Medical Diagnostics Thesis August, 2002132
  63. 63. Usman Omar Ghani Appendix 11 Supporting letter from Mrs Vliet Usman Omar Ghani Care of dr. Antony Woodman (director of medical diagnostics) University of Cranfield Silsoe campus Silsoe Bedfordshire MK 45 4 DT Hello, My name is Esmeralda and my boyfriends name is Jeroen. We live in The Netherlands. Our son Derek was born on 2 may 2002 en is diognosed with OS after 4 weeks of age. His EEG shows ´burst suppression´. He has had lot of tests: blood, urine, brainfluid, MRI but the results were all negative. Five days after he was born we took him to the hospital because he rolled 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 various doses. Derek was in the hospital for 9 weeks, but still has 1 or 2 seizures every 30 minutes. He is home for 2 weeks now and we do not see any improvement. We are positive that he is not looking at us and is not following things whit 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 about the study of 16 cases described by Dr. Otahara. It would be fantastic when there is more research done so we, as parents, will know more about the prospect of our children. Kind regards, Esmeralda van Vliet Sterrenlaan 14 2665 BT Bleiswijk The Netherlands MSc Medical Diagnostics Thesis August, 2002133
  64. 64. Usman Omar Ghani 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 CRANFIELD SILSOE CAMPUS SILSOE BEDFORDSHIRE MK45 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. Emilie Moira 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 Prednisolone tablets. We go back to Oxford next week for another EEG to find out if the steroids are having any effect. We felt so isolated. I wouldn't wish this on anyone and hope like hell that Usman gets the funding he needs so we can all benefit from the answers. We fully support the research Usman is doing MSc Medical Diagnostics Thesis August, 2002134

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