NHS Specialised Services Commissioning
Rare Neuromuscular Disorders Group
Congenital Myasthenic Syndromes:
Oxford University Hospitals NHS Trust
Annual Report September 2012
Service Overview
Page 2
Service Objectives, Performance Measures
Page 4
Patient Feedback
Page 5
Service Developments
Page 6
Future Development Plans
Page 7
Service Engagement & Communication
Page 8
Appendices
.Pages 9 -10
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The Congenital Myasthenic Syndrome (CMS) service at the Oxford Radcliffe
Hospital combines a specialist genetic analysis laboratory with a dedicated
inpatient (funded locally) and outpatient clinical service to offer a
multidisciplinary service for patients across the country.
The core CMS team comprises of:
Clinical team
Dr Jackie Palace
Dr Sandeep Jayawant
Dr Stephanie Robb
Dr Ravi Knight
Dr Sarah Finlayson
Vacancy
Christina Goldsworthy
Karen Glover
Julia Goodgame
Consultant Neurologist (Service Lead)
Consultant Paediatric Neurologist
Consultant Paediatric Neurologist (GOSH)
Consultant Neurophysiologist
CMS Clinical Fellow
Physiotherapist
Myasthenia Specialist Nurse
CMS Service Coordinator
Clinical Service Manager, CMS/NMO
Laboratory team
Weatherall Institute of Molecular Medicine
Prof David Beeson
Lead Molecular Geneticist
Dr Wei-Wei Liu
Molecular Geneticist
Oxford University Hospitals Team
Dr Anneke Seller
Director of Genetics Laboratories
Dr Tracy Lester
Principle Clinical Scientist
Dr Mike Oldridge
Clinical Scientist
Service Overview
The service sees around 160 patients each year, both as outpatients and
inpatients, and offers remote advice to doctors around the country regarding
the diagnosis and management of CMS patients. The clinical team review
patients primarily in an outpatient setting, often performing additional
investigations such as QMG scores (Quantitative Myasthenia Gravis Score)
and EMGs (Electromyogram). The outpatient clinics are also attended by a
Clinical Genetics Research Nurse, Julie Phipps, funded by the UKCLRN.
Monthly joint clinics with Dr Stephanie Robb and the Oxford clinical team are
now routinely established. Joint clinics alternate between GOSH and Oxford
and allow good practice to be shared between centres.
Both the clinical and laboratory teams offer an advice service to healthcare
professionals around the country. This involves e-mail, telephone and letter
correspondence regarding numerous patients, including those seen in clinic
who are under local follow up and patients who are unable to be seen at the
centre due to geographical access issues.
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The Diagnostic Genetics Laboratory at the Churchill Hospital, Oxford
provide specialised genetic screening for patients with suspected CMS or
related rare neuromuscular conditions. There are currently a number of genes
screened for that are associated with CMS: CHRNA1, CHRNB1, CHRND,
CHRNE, CHRNG, RAPSN, COLQ, CHAT and DOK7. Each of these code for
a gene involved in maintaining the function of the neuromuscular junction.
In addition to these screens, further screening for the MuSK, AGRN, GFPT1
and DPAGT1 genes is available on a research basis by Professor Beeson’s
group, based at the Weatherall Institute of Molecular Medicine
If a mutation in the genetic code is identified additional tests can also be
undertaken in Professor Beeson’s laboratory to determine the pathogenicity.
These include:
-
Electrophysiology to assess AChR channel kinetics for fast or slow
channel syndromes
AChR cell surface expression to test for AChR deficiency syndromes
AChR clustering assays to test pathogenicity of RAPSN and DOK7
variants
Exon trapping to test for intronic variants
Reporter assays to test for promoter variants
Expression assays to test CHAT mutations
Once the screening has been performed the patients are either reviewed in
outpatient clinic, or alternatively, the details of the case are reviewed by the
clinical team and remote advice offered to the referring clinician.
As our understanding of these conditions increases it has become apparent
that treatment choice is determined by the underlying pathogenic mechanism
of the CMS subtype the patient has. Some of the treatments used routinely in
some CMS subtypes cause deterioration in other subtypes. Accumulated
experience has allowed development of a treatment algorithm [Appendix 1]
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Service Objectives and Outcomes
The purposes and goals of the service
 Treat effectively [Appendix 1]
 Make a definitive diagnosis (including prenatal diagnosis where
requested) [Appendix 2]
 Provide information for patients, families and their schools and other
health care professions about CMS.
(See later - Page 8: Service Engagement and Communication)
Outcomes
We audit the
 Waiting times for clinics
Often a delay in patient waiting times is due to patient choice; over 90% of
patients that breached the 6 week waiting times target were initially offered an
appointment within the target.
and

Geographical data (PCT) and remote reviews - of patients for both
clinical and laboratory activities.
As a national centre for CMS, Oxford aims to offer equal access to patients
from across the whole of England and Scotland. Some patients cite transport
costs as a limiting factor. For patients living far from Oxford we try to offer
them the flexibility to schedule their appointments to fit in with leisure travel
plans. In cases where the patients are physically unable to attend outpatient
clinic remote advice is offered to their local clinician regarding their diagnosis
and management.
However, as well as offering a national service, the team also offer advice on
international patients. Around 9% of the remote DNA reviews were
international referrals, helping to establish the centre at Oxford as
international expert in CMS.
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Patient Feedback
Patient Satisfaction Questionnaire
Feedback from patients, relatives and carers offers important insight into the
quality of service provided. These views are collected in the form of a
questionnaire that is given to the patients and their carers when they attend
an outpatient clinic appointment. The team have recently developed a new
outpatient questionnaire, in order to capture more information about the
performance of the service measured against the quality indicators and to
identify any gaps in service provision.
This updated questionnaire has been in use from April 2011, therefore
analysis of the data is still in early stages. However early indicators are
encouraging:
- 82% said that they were completely satisfied with the response the
received from the team when they contacted the service for advice
- 84% of patients said that their questions or concerns were addressed
completely at their appointment
- 84% of respondents felt that they had enough time with the clinical
team to discuss their condition
The full analysis of this data will inform future service developments. Patients
who previously responded that they would have like more information
regarding the condition will soon be able to address this issue by obtaining a
CMS patient information DVD which is near to completion.
National Survey
NSCT commissioned a Picker Institute survey to enable baseline
measurement of the patient experience for users of nationally commissioned
services.
Patients of highly specialised services reported generally positive experiences
of care overall, but with room for improvement in some key areas:





Receiving advice on how to access financial help and benefits
Receiving advice on needs for social care, health services and
volunteer/support groups
Access to an NHS out of hours telephone advice line;
Opportunity for family and close friends to speak with a doctor about
concerns they had
An excerpt from the survey results for the CMS service is shown in Appendix
12 and plans to improve areas identified as problematic are discussed further
in Future Development Plans (Page 7).
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Service Developments
Charitable Funds Grant
In early 2012 the service was successful in a bid for a grant from the JR
Paediatric Charitable Fund. We were awarded two sums of money the first
(£300) for purchasing toys to be used for distraction in clinic. We plan to
spend a part of this on a portable DVD player to be used to distract children
during EMGs which many children find difficult. The remainder will be spent
on toys for a range of ages that can also be used to assess strength and
function as well as make attending clinic a more pleasant experience.
The second sum of money was to purchase a dynamometer that can be used
to measure muscle strength in children (approx. £1600). The application is
currently being dealt with by medical engineering. At present we only have an
adult dynamometer and a paediatric device should improve our assessment of
children.
Provision of 3,4 Diaminopyridine
Over the last two years there have been major problems with the availability of
the drug 3, 4-Diaminopyridine (3,4-DAP) which a significant proportion of our
patients rely on. Since last year the UKs main supplier has ceased production
and the drug is now sourced from an alternative and sole supplier. Since the
transition in April 2012 there have been no supply issues. We continue to
monitor this situation.
QIDIS 2011 Database Project
In 2011 a QIDIS grant was awarded to develop IT resources for the collection
of service activity, quality measures and clinical outcome data.
Databases were developed, are now in use. The improved collation of clinical,
laboratory and follow up data on patients has aided the preparation of activity
figures for the NCG. We expect that natural history studies of these rare
conditions will be facilitated by the databases, allowing evidence based
guidelines to be made regarding standards of care. The service has been
awarded a further QIDIS grant to populate the database.
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Future Development Plans
QIDIS Projects
2012 QIDIS funding will be used for the following:
1) Local Projects
a) Packaging the patient information DVD
b) Organise a patient information day
2) National Projects
a) Populate, and modify where necessary, the existing database
b) Develop a pre-attendance clinic information pack
c) Development of a clinical dashboard to include clinical outcomes,
patient safety and patient experience.
Paediatric physiotherapy outcomes
Physiotherapy outcome measures can be useful in monitoring change in
weakness and assessing response to treatment. However, at present, there is
only a standardised testing method developed for adult autoimmune
myasthenia which is not adequate for assessing children with CMS. This ongoing project aims to identify suitable assessment measures tailored to
paediatric CMS and is in collaboration with specialists at GOSH and
Newcastle. The data collected from assessments is held on one of the
databases developed with QIDIS funding.
Muscle MRI Project
The Myasthenia Gravis Association have funded an imaging study to
determine whether MRI of muscle can help to differentiate between different
subtypes of CMS. Some subtypes have a secondary myopathy and these
respond to different types of treatment. If muscle MRI can tell the difference
between subtypes then it may help to guide treatment where there is no
genetic diagnosis. This study is now up and running and we anticipate initial
results of pilot data within the next year.
New gene testing (GFPT1)
The gene GFPT1 has recently been identified by collaborative research
between the UK and Europe as crucial in causing a variation of congenital
myasthenic syndrome. Screening for this gene is currently only being carried
out in special cases when indicated by Prof Beeson’s laboratory team.
However, formal registration for GFPT1 by the UKGTN has recently been
approved and the aim is to include this screen in the routine diagnostic battery
of tests performed on DNA samples received by the service over the coming
year. This will improve the identification of patients affected by this mutation
and allow development of new methods of treatment targeted to this condition.
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Newly identified CMS-associated genes
In the last year new CMS-associated genes have been identified using next
generation sequencing techniques. The first of these, DPAGT1 has been
published, and further genes will be published in over the next year. At
present screening of these genes is undertaken in the research laboratory, but
proposals for formal registration for at least some of these genes (depending
on the prevalence) will be put forward over the coming year.
Bid for Funding for Staff to improve service provision of emotional
support and help with social care needs.
We wish to apply to NCG to for an additional member of staff in the CMS
service.
Feedback from the recent NHS Specialised Services Picker survey (see also
Page 6) identified areas in which the service underperformed and provision of
emotional and social support were most problematic.
We bid for funding to pay for a nurse (Band 7) for 16 hours a week (approx.
costs £19.5K). We would anticipate that they would operate as a point of
contact for patients to access support and that their role would involve running
a phone help-line for patients social issues.
Service Engagement and Communication
Website
A webpage for the service is hosted on the OUH website and includes:
referral information and pre-referral form as well as points of contact for
clinicians.
Patient Information DVD
The DVD filming and editing is essentially complete and the production has
been viewed and approved by both the Myasthenia Gravis Association (MGA)
and their sister charity MyasthenicKids. Copyright issues are currently being
addressed.
A QIDIS grant has been awarded to fund design and manufacture of the DVD
packaging (page 7, Future Developments, QIDIS).
Patient Information Booklet
(copies available)
Patient Day
See Page 7: Future Developments, QIDIS. At present there are no other
national CMS patient days having previously been organised by the
Myasthenia Gravis Association (MGA).
The aim of the day is to educate patients affected by the condition and offer
them a support network. It will also engage the adult CMS patient group
whose needs are not the main focus of Myasthenic Kids or the MGA.
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Appendix 1
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Appendix 2
Number of patients with confirmed diagnosis 2011- 2012
Undefined
6.34%
Not CMS
22.54%
Undefined
Defined Diagnosis
CMS no gene 2.11%
CMS Gene Positive
CMS no gene
Gene positive 68.31%
Not CMS
Out of 160 patients seen ~ 94% have a defined diagnosis, and ~ 68% of all
patients are genetically confirmed CMS.
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