Sir,
I read with much interest the review by Weerasinghe and Lueck on the
diagnosis of optic neuritis. The authors provide an extensive and detailed
analysis on the differential diagnoses and the management of the disease.
The importance of retinal electrophysiology is also acknowledged when
differentiating retinal disorders that can mimic optic neuritis.
Surprisingly, however, the diagnostic role of pattern-reversal Visua...
Sir,
I read with much interest the review by Weerasinghe and Lueck on the
diagnosis of optic neuritis. The authors provide an extensive and detailed
analysis on the differential diagnoses and the management of the disease.
The importance of retinal electrophysiology is also acknowledged when
differentiating retinal disorders that can mimic optic neuritis.
Surprisingly, however, the diagnostic role of pattern-reversal Visual
Evoked Potentials (VEPs) is not discussed, not even mentioned. VEPs can
assess visual pathway function at a millisecond time scale and no other
visual function measure shares this temporal sensitivity. More than 40
years ago Martin Halliday demonstrated a delay in the VEPs after an attack
of optic neuritis. Since then, a huge number of studies have provided
converging evidence about the importance of VEPs recording in optic
neuritis and Multiple Sclerosis (MS).
Doubtless, the clinical use of VEPs has changed over time and the advent
of magnetic resonance imaging (MRI) have reduced the use of VEPs in
clinical practice. However, even in the MRI era, an abnormal VEP in
unaffected eyes of patients with MS provides evidence for clinically
silent demyelinating lesions in the optic pathway. This, in turn, is
extremely useful in identifying dissemination in space and, therefore, in
establishing the diagnosis of MS.
In their review, the authors also fail to mention another important
electrophysiological test, i.e. the Pattern Electroretinogram (PERG). The
PERG is generated by the activity of the retinal ganglion cells. Taken
together, PERG and VEPs are useful to identify the site(s) of dysfunction
along the retinocortical pathway. In a typical case of optic neuritis PERG
and VEP recordings might not be necessary. However, these techniques can
still retain many roles: first, to show the magnitude of conduction block
of the optic nerve fibres in the acute stage of the disease. Secondly, to
demonstrate the optic nerve conduction delay due to demyelination. Third,
to follow remyelination, which is seldom correlated to an improvement in
visual acuity, through the shortening of VEP latency. Finally, to define
the eventual retrograde degeneration of ganglion cells, which is reflected
by an amplitude reduction of the PERG N95 peak. Moreover, when diagnosing
atypical optic neuritis, these neurophysiologic techniques should be
implemented as a part of a comprehensive assessment.
Of note, the visual pathway can now be more precisely evaluated in detail
by means of new neurophysiological tests (multifocal VEPs and ERG). These
techniques provides higher sensitivity and specificity in detecting
abnormalities in visual function in optic neuritis and MS
We welcome debate around this emerging condition. We all recognise a
situation when as clinicians we have had a strong feeling that a patient
has a functional complaint from early on in the consultation. However, the
differential diagnosis for Functional Cognitive Disorder is
neurodegenerative dementia which itself affects behaviour and personality
and could, therefore, influence many of the cues clinicians pick up on
wh...
We welcome debate around this emerging condition. We all recognise a
situation when as clinicians we have had a strong feeling that a patient
has a functional complaint from early on in the consultation. However, the
differential diagnosis for Functional Cognitive Disorder is
neurodegenerative dementia which itself affects behaviour and personality
and could, therefore, influence many of the cues clinicians pick up on
when "divining" a functional diagnosis.
Anecdotally, we have seen patients in our clinic diagnosed with a
functional disorder at other centres whom we have subsequently discovered
to have definite neurodegenerative disease. As an example, we were
referred a patient thought to have a psychiatric disorder and functional
left leg movements. After a detailed assessment including CSF biomarkers
and SPECT scanning, we suspected organic disease. His positive C9orf72
genetics have recently demonstrated he suffers from a genetic form of
Frontotemporal dementia and we believe that this altered his behaviour
such that he manifested a functional syndrome at the start.
Preceding medical events such as general anaesthesia or chemotherapy can
be triggers for health anxiety or FCD, but could also be a source of
cognitive symptoms. General anaesthesia (particularly if performed for
cardiac indications) is a risk factor for hypoxic or ischaemic brain
damage (which if focal can present with isolated cognitive deficits).
Chemotherapy agents can cause neurological complications (e.g.
methotrexate encephalopathy); their use also implies a history of
malignancy with consequent risk of tumour recurrence and direct or
indirect neurological complications.
Establishing the aetiology of cognitive complaints is the key challenge in
the memory or general neurology clinic. Large-scale research studies
suggest there is a continuum between Subjective Cognitive Impairment
(where individuals report cognitive symptoms but perform normally on
testing), MCI and dementia2. Given treatments may be effective only in the
earliest stages, identifying prodromal dementia will in the future be
increasingly important. Distinguishing incipient dementia at the Mild
Cognitive Impairment (MCI) phase from Functional Cognitive Disorder (FCD)
can be difficult, but is of vital importance to ensure patients receive
appropriate prognostic information including reassurance where necessary
and are entered into clinical trials where appropriate. This distinction
becomes particularly tricky in high-functioning individuals, and those
with co-morbid psychiatric conditions. The clinical history is very
useful, and conversational analysis has been successfully used to
differentiate dementia from FCD1. However we would counsel against solely
using the clinical history to distinguish FCD from incipient dementia at
the MCI phase. We know that anxiety, depression and abnormal behaviour may
occur in early dementia all of which might confound use of a clinical
history to differentiate incipient dementia from FCD.
Neuropsychology assessments are very useful in this context- they can
reveal patterns of deficits that are not consistent with organic
pathology, deficits out of keeping with FCD, or highlight significant
psychiatric symptoms warranting referral to psychiatry or psychology
services. Neurologists are often not trained in identifying psychiatric
disorders, therefore a structured neuropsychology assessment including
questionnaires looking for symptoms of depression or anxiety can often be
very helpful.
The authors would regard neuroimaging as an essential part of the
assessment, as recommended by NICE3. Even a patient with a 'classic' FCD
history may be harbouring structural brain pathology. To give a clinical
example, a 56 year old man presented to our general neurology clinic with
intermittent word finding difficulties during conversations and when
typing. He had a history of anxiety disorder, and his language appeared
normal during the consultation and on formal assessment. Neurological
examination was normal, and a functional cause was suspected. However on
MR imaging a large glioblastoma multiforme was found. Not performing
neuroimaging risks missing individuals with a strategic infarct,
malignancy or other structural pathology. Whilst such cases are not
common, missing such a diagnosis would have very serious consequences for
the patient.
The authors agree that investigations such as SPECT, CSF biomarkers and
autoantibodies should be used selectively, but these can be helpful in
difficult cases. We plan to explore further the additive clinical value of
each of these tests.
Discovering the aetiology of cognitive symptoms often requires us to
operate at the limits of current knowledge about how the brain guides
behaviour. We do not believe we are at the point where we can always offer
certainty to a patient. However, we find it possible to reassure patients
effectively even when we represent this uncertainty to them. If we suspect
functional cognitive disorder, we introduce the concept at the first
consultation and offer reassurance saying we will do further tests and
follow up to rule out rarities. We find this is actually quite effective
as a means of reassurance, perhaps more so than being entirely dogmatic
that there cannot be organic pathology as most patients will know it is
more or less impossible to prove a negative in neurology. Overall we feel
that whilst we might strongly suspect FCD clinically at the first
consultation, it is unwise in almost all cases to make a firm diagnosis of
FCD without appropriate investigations. Even after diagnosis and initial
management of FCD, a period of clinical follow up can be informative. It
is only such follow up that has allowed us to begin to understand critical
components of FCD and to summarise clinical features of the condition.
References
1. Elsey, C., Drew, P., Jones, D., Blackburn, D., Wakefield, S., Harkness,
K., Venneri, A. & Reuber, M. Towards diagnostic conversational
profiles of patients presenting with dementia or functional memory
disorders to memory clinics. Patient Educ. Couns. pii: S0738, (2015).
2. Garcia-ptacek, S., Cavallin, L., Kramberger, M. G., Winblad, B., Jelic,
V. & Eriksdotter, M. Subjective Cognitive Impairment Subjects in Our
Clinical Practice. 419-430 (2014). doi:10.1159/000366270
3. NICE. Dementia diagnosis and assessment. (2015).
Pennington and colleagues review of Functional Cognitive Disorder
(FCD) [1] is very welcome to guide practice in a complex condition that is
presenting increasingly to general and cognitive neurology clinics.
However, in our view Pennington's presumption towards specialist
assessment, investigation and surveillance is unnecessary and misses an
opportunity to provide patients with a prompt diagnosis, explanation and
reas...
Pennington and colleagues review of Functional Cognitive Disorder
(FCD) [1] is very welcome to guide practice in a complex condition that is
presenting increasingly to general and cognitive neurology clinics.
However, in our view Pennington's presumption towards specialist
assessment, investigation and surveillance is unnecessary and misses an
opportunity to provide patients with a prompt diagnosis, explanation and
reassurance and immediate treatment for the FCD and/or significant
relevant co-morbidities e.g. depression, chronic fatigue syndrome (CFS).
In particular, we cannot agree with Pennington's comment that "Functional
cognitive disorder should be diagnosed only after excluding other causes
of cognitive decline as far as possible". We believe that clinicians
should aim to make a positive "rule in" diagnosis of FCD, exactly as
proposed for other functional disorders [2] and that this can be done in
the context of the general neurology clinic.
Pennington et al rightly point out features in the history that suggest
FCD but in our view they underestimate their significant diagnostic value.
Additional positive features for FCD in our experience are a high number
of presenting symptoms, the patient's emotional response to the symptoms
being more distressing than the actual consequences of any cognitive
lapses, co-morbid mood disorders, chronic pain or fatigue and recent
relevant life events including physical illnesses such as mild traumatic
brain injury, anesthesia or chemotherapy exposure.
Brief cognitive instruments (such as MoCA, ACE) are of limited value in
this context and have an opportunity cost in a 30 minute general neurology
consultation. Instead we suggest listening for particular features in the
patient's spontaneous speech that point towards FCD. A richly detailed
history in which multiple examples of cognitive lapses are described, and
in which events are precisely located in time, the patient's ability to
reference an earlier part of the consultation [4], and normal expressive
language (e.g. the absence of word finding pauses) are all evidence of
normal cognitive function. These can be fed back to the patient to help
explain the diagnosis, in the same way that a positive Hoover's sign can
be explained to a patient with functional lower limb weakness.
We argue that most patients with suspected FCD do not need investigations
such as brain imaging or neuropsychology. These are much more likely to
produce false positives with attendant iatrogenic harm than to shed any
light on the diagnosis, particularly in younger patients where the pre-
test probability of dementia is extremely low. The authors write that
"Cerebral atrophy that is out of keeping for the patient's age ... should
prompt further investigations". We would regard lower than expected brain
volume as a non-specific finding in a patient with typical FCD symptoms.
The temptation to perform further tests to clarify non-specific findings
from a previous test demonstrates the perils of embarking on low yield
investigations in the first place. Tests for anti-VGKC and NMDA receptor
antibodies should be reserved for patients presenting with the clinical
syndromes associated with these antibodies, which are readily
differentiated from FCD on the basis of the clinical history.
We believe that routine neuropsychological assessment for the diagnosis of
FCD is clinically unnecessary, not cost-effective and potentially
misleading. For example, a neuropsychology report stating that "early
neurodegeneration cannot be ruled out" in a case where the clinician
strongly suspects FCD may reduce patients' confidence in the diagnosis.
We would virtually never consider amyloid positron emission tomography or
cerebrospinal fluid biomarkers appropriate for patients with suspected FCD
(although they may have a role in rare cases in which a diagnosis of
Alzheimer's disease needs to be changed to FCD and this is not initially
accepted by patients, family and other healthcare professionals[5]).
These tests are abnormal only in Alzheimer's disease so cannot "rule out"
dementia in any case.
We welcome Pennington's comments about the need to develop treatments for
FCD. One of us (JAC) often recommends two books to patients that
beautifully illustrate the idiosyncrasies of normal memory; Forgetting by
Daaisma and Moonwalking with Einstein by Joshua Foer. For patients with
mild FCD, normalising their symptoms e.g. by explaining how we (the
neurologist) make many of the same mistakes can be helpful. An emerging
nosology can help practitioners select an individualised explanatory model
and prioritise treatment i.e. (1) FCD in isolation, with or without
dementia-related health anxiety, (2) FCD in the context of a psychiatric
co-morbidity (most typically depression) and (3) FCD as a feature of
another functional disorder e.g. CFS, fibromyalgia (adapted from [6]).
The stability of functional neurological diagnoses is well demonstrated
and the same likely applies to FCD, as Pennington and colleagues point
out. We therefore disagree with the suggestion that it is necessary to
follow patients up to ensure that their cognitive function remains stable.
Follow-up might of course be offered for other reasons e.g. where the
clinician needs more time to explain the diagnosis.
In summary, while welcoming Pennington and colleagues important
contribution to this emerging area of neurological practice, we urge
general neurologists to have confidence in making a positive diagnosis of
FCD, particularly in younger patients. We believe that unnecessary
specialist referral, investigation and surveillance of patients with FCD
risks delaying treatment and potentially incorrect diagnoses of pre-
dementia (e.g. MCI) or dementia itself.
References
1. Pennington C, Newson M, Hayre A, et al. Functional cognitive disorder:
what is it and what to do about it? Pract Neurol 2015;15:436-444
2. Stone J. Functional neurological disorders: the neurological assessment
as treatment. Neurophysiol Clin 2014;44:363-373
3. Stone J, Reuber M, Carson A. Functional symptoms in neurology: mimics
and chameleons. Pract Neurol 2013;13:104-113
4. Jones D, Drew P, Elsey C, et al. Conversational assessment in memory
clinic encounters: interactional profiling for differentiating dementia
from functional memory disorders. Aging Ment Health 2015;
DOI:10.1080/13607863.2015.1021753
5. Coebergh JA, Wren DR, Mumford CJ. 'Undiagnosing' neurological disease:
how to do it, and when not to. Pract Neurol 2014;14:436-439
6. Stone J, Pal S, Blackburn D. Functional (Psychogenic) Cognitive
Disorders: A Perspective from the Neurology Clinic. J Alzheimers Dis
2015;48 Suppl 1:S5-S17
While reading Pennington et al's (2015) article on Functional
Cognitive Disorder, I was struck by the similarity between their
descriptions and a patient seen in clinic (patient X), with the exception
that X's symptoms appeared over the course of a few days with no
identifiable precipitating event. Extensive physical tests and brain
imaging investigations were carried out and no organic disease was found
yet symptoms we...
While reading Pennington et al's (2015) article on Functional
Cognitive Disorder, I was struck by the similarity between their
descriptions and a patient seen in clinic (patient X), with the exception
that X's symptoms appeared over the course of a few days with no
identifiable precipitating event. Extensive physical tests and brain
imaging investigations were carried out and no organic disease was found
yet symptoms were reportedly severe and having a major impact on X's
functioning. Here I discuss X's case (with identifiable information
changed in order to respect patient confidentiality) and propose that
there may be a sub-type of functional cognitive disorder with an acute
onset.
Patient X is a 48 year old house-wife and local preacher. She
presented to clinic with her husband after being referred by her GP due to
the development of severe confusion and cognitive impairment developing
from a previously high level of functioning just a few days earlier.
Symptoms began to appear on the Sunday evening and peaked on the Tuesday,
with no change between then and the clinic assessment (Thursday). X
reported completely 'losing track of time' and reported severe memory loss
which her husband had first noticed. During the assessment, she claimed
inability to answer any of our questions herself and repeatedly looked to
her husband for answers. When asked why she could not answer the
questions, she said that she 'could not remember' and described problems
with attention, concentration and executive function. This appeared
inconsistent with her performance in daily life as she had managed to
maintain her previous social roles, although we had no objective baseline
for comparison.
X had no previous psychiatric history and no significant medical
history. She was not taking any regular medications except for the oral
contraceptive pill. She reported a normal upbringing. The only
identifiable recent stressor was that X had recently started a new
university course, part of which involved looking at different personality
types, which she said had 'confused' and 'worried' her.
It was first thought that she may have organic disease as her
symptoms came on suddenly, however she returned to psychiatry clinic
following extensive tests as no physical cause could be found. Could this
be a case of functional cognitive disorder with acute onset? Further
assessment and follow-up of patient X and others like her could unravel a
subgroup of patients who fall into this category.
The outlined model of cooperative and integrative services for
pregnant women with neurological conditions is warmly welcomed (and not a
little envied!). While such services are provided the English centres
mentioned, it is sad that such high quality provision remains patchy and
incomplete. This nettle-grasping should no longer be quiet, but should be
loudly heralded and made the norm. The recently updated SIGN guideline...
The outlined model of cooperative and integrative services for
pregnant women with neurological conditions is warmly welcomed (and not a
little envied!). While such services are provided the English centres
mentioned, it is sad that such high quality provision remains patchy and
incomplete. This nettle-grasping should no longer be quiet, but should be
loudly heralded and made the norm. The recently updated SIGN guidelines
recommend a joint approach from all corners, and disparate organisations
such as the ILAE, the ABN, the Medical Royal Colleges, and the RCOG need
to come together to make such synergy routine. Only then can we ensure
that complications of epilepsy during pregnancy and the first post-partum
year follow other obstetric complications in decreasing incidence.
Dear Sirs,
We welcome Dr Leach's comments and a call for action from Neurologists,
regarding service provision for women of childbearing age with
neurological disorders1. We would also like to highlight that quietly, a
number of us are grasping the nettle.
Risk is inherent in clinical practice. Managing risk effectively and pro-
actively in preference to reactively minimises the likelihood of a poor
outcome. This can be...
Dear Sirs,
We welcome Dr Leach's comments and a call for action from Neurologists,
regarding service provision for women of childbearing age with
neurological disorders1. We would also like to highlight that quietly, a
number of us are grasping the nettle.
Risk is inherent in clinical practice. Managing risk effectively and pro-
actively in preference to reactively minimises the likelihood of a poor
outcome. This can be achieved by identifying those at risk and adapting
practices to avoid that risk. This has not often been more concisely put
than by Cicero who is quoted as stating that "To make a mistake is only
human; to persist in a mistake is idiotic". We agree that at the very
least, missing an opportunity to avoid a maternal death is idiotic, and
certainly tragic.
A joint approach is needed and at St George's University Hospitals NHS
Foundation Trust, Consultants in Obstetrics, Obstetric anaesthetics,
Neurology, Neurosurgery and Neuroradiology have together with excellent
support from Maternal Medicine Midwifery and Neurology Clinical Nurse
Specialists, been working collaboratively for some time.
Our Epilepsy Group run a regular clinic together with Maternal Medicine
Midwives for all women with Epilepsy delivering at St George's, and there
is a monthly joint Neurology and Obstetric clinic in maternal medicine
where women with complex (and sometimes more simple) neurological
disorders can be advised regarding pregnancy, delivery and breastfeeding.
Careful individualized plans for Neurological (including surgical and
vascular), Obstetric, Anaesthetic and midwifery led care are made for
these women.
We know from prospective data collection (risk also comes from not knowing
what you are doing) that unplanned episodes and adverse outcomes have been
avoided.
We are also aware that similar clinical services are available at other
Hospitals including University College London Hospitals, at Queen
Charlotte's and Chelsea Hospital, part of Imperial College Healthcare NHS
Trust, and has long been available at Birmingham Women's NHS foundation
Trust.
A call from the NHS England Strategic Clinical Networks was recently made
for a Neurologist advisor to join the London Maternity morbidity and
mortality expert panel. This is an opportunity to act and work together
that the clinicians at St George's will not be missing.
Yours sincerely,
Dr Dominic Paviour, Consultant Neurologist
Dr Ingrid Watt Coote, Consultant in Obstetrics and Maternal Medicine
Dr Hannah Cock, Consultant Neurologist and Epileptologist,
Ms Amanda Reeve, Clinical Nurse Specialist, Atkinson Morley Epilepsy Group
Trudy Williams, Specialist Midwife in Maternal Medicine
St George's University Hospital NHS Foundation Trust, London
References:
1. Death in pregnancy: a call for neurological action
John Paul Leach, Pract Neurol 2015;15:244-245 doi:10.1136/practneurol-2015
-001097
As a jobbing MS neurologist in Southampton I am really not sure how
these guidelines are going to assist in my clinical practice.
Perhaps first and foremost, if I was to follow these guidelines I
would find myself frequently in breach of NHS commissioning criteria with
perhaps severe implications for both myself and my hospital trust given
the cost of these therapies. As such I feel the authors should have give...
As a jobbing MS neurologist in Southampton I am really not sure how
these guidelines are going to assist in my clinical practice.
Perhaps first and foremost, if I was to follow these guidelines I
would find myself frequently in breach of NHS commissioning criteria with
perhaps severe implications for both myself and my hospital trust given
the cost of these therapies. As such I feel the authors should have given
a little more attention to this issue, highlighting where guidance is
against what we are actually allowed to do.
My experience of multiple sclerosis patients is that they do not
simply fall into two broad categories of active vs more active and
therefore I find the division of the drugs into two broad categories
equally unhelpful and unnecessary. Perhaps the most obvious example is
that fingolimod has considerably more potency than some of the other
category one drugs and by these guidelines own definitions fingolimod
could easily be classed as a category two treatment and therefore be a
good option for more active patients, as it is already under the NHS
commissioning criteria.
The guidelines recommend using alemtuzumab or natalizumab in patients
with more active disease as defined by one relapse in the previous year on
interferon with MRI criteria. In clinical practice treatment decisions in
such patients are heavily influenced by factors such as disease duration,
treatment duration, relapse severity, prior relapse frequency on and off
treatment, and gadolinium enhancement on MRI (with number of T2 lesions
not being particularly useful). These guidelines could and should have
been more progressive in discussing a correct approach for different
patient types. Among other considerations that should have been discussed
include treating young women with highly active multiple sclerosis for
whom alemtuzuamb now provides the possibility of potent treatment and
pregnancy at the same time, and JC virus negative patients for whom
natalizumab offers a virtually risk free high potency therapy assuming
that JCV status is regularly monitored whilst on treatment.
Finally in non-relapsing established progressive disease there is
absolutely no evidence to support immunomodulation and given the costs of
therapy I really think this guidance could have taken a bolder approach in
making firm recommendations about cessation of treatment to support
clinicians in their discussions with such patients.
Overall I feel these guidelines offer a fairly simplistic and non-
commital approach, that as UK neurologists we are often unable to follow
due to commissioning restrictions, and with the wide range of therapies
now available a more progressive, customised approach that addresses a
wide range of patient characteristics is what is required.
I am grateful to Drs Wong and Plant for their invaluable comments,
based on their enormous experience of patients presenting with suspected
ocular myasthenia.
The Guidelines are intended to offer non-specialists an approach to
management that will work, safely, in the majority of patients. Within
them, we stressed repeatedly the need to seek specialist opinion when in
any doubt, and their letter emphasises the benefit of...
I am grateful to Drs Wong and Plant for their invaluable comments,
based on their enormous experience of patients presenting with suspected
ocular myasthenia.
The Guidelines are intended to offer non-specialists an approach to
management that will work, safely, in the majority of patients. Within
them, we stressed repeatedly the need to seek specialist opinion when in
any doubt, and their letter emphasises the benefit of seeking such help.
Their views, by and large, don't contradict our basic approach, except
with respect to the timing of the introduction of azathioprine. With
respect to the specific issues that they raise:
Thyroid function should be assessed in all patients. We agree that if the
diagnosis of myasthenia is not secure, then it is appropriate to look for
evidence of thyroid ophthalmopathy, which would include antibody testing
and imaging studies.
Some patients seronegative for acetylcholine receptor antibodies may be
seropositive using other techniques, as they describe. However, if the
clinical diagnosis is of purely ocular myasthenia then the result will not
affect the immediate management as proposed in the Guidelines
We are not enthusiasts for the Tensilon? test and don't mourn its non-
availability! We have seen numerous patients incorrectly diagnosed as
having myasthenia on the basis of a test performed by somebody without
appropriate experience. We agree that other forms of anti-cholinesterase
testing may occasionally be helpful, and are grateful for their detailed
proposals. However, we have doubts about these being undertaken by non-
specialists.
We agree that physical treatments (e.g. eye patches and prisms) have their
place both acutely and in some patients with persisting diplopia despite
optimal drug treatment, but of course they become unnecessary inn the
majority of patients who respond extremely well to drug therapy.
We also agree that the evidence base for using alternate-days steroids, in
terms of reducing long-term side-effects, is minimal. At very high doses,
as may be needed in generalised myasthenia, steroid-induced myopathy may
be difficult to differentiate from myasthenic weakness. We have never seen
steroid-induced myopathy on an alternate day regime. In patients with
marked symptomatic fluctuation between steroid and non-steroid days, and
those with diabetes, we would often have a preference for a daily steroid
regime.
In the past, thymectomy has not been used widely for non-thymomatous
ocular myasthenia, perhaps largely because sternotomy represents major
surgery, with unacceptable cosmetic consequences, particularly for the
dominant young-female population. However, if the less invasive technique
of video-assisted thymectomy reduced the risk of generalisation, and for
some negated the need for immunosuppressant drug therapy, then it would
potentially be very valuable. Unfortunately, the International Thymectomy
Trial will not address these issues, and a further trial, at least in the
foreseeable future, seems unlikely. We think it is an option that is
appropriate to discuss with the patient.
Although azathioprine is often considered a relatively safe drug, and its
steroid-sparing effect potentially valuable to the patient, our experience
suggests that many patients have their myasthenia controlled on a modest
dose of prednisolone and that azathioprine is unnecessary. We are
concerned by long-term side-effects, particularly cutaneous malignancies,
increased risk of infection (including shingles) and the occasional case
of late-myelosuppression.
The points raised by Drs Wong and Plant emphasise the lack of data
concerning the treatment of MG and should encourage us to design studies
to help answer the really important questions in MG, such as whether it is
possible to determine initial optimal treatment requirements from clinical
or immunological features.
Dear Sirs,
Myasthenia gravis: Association of British Neurologists' management
guidelines We read with interest the ABN's management guidelines on
Myasthenia
Gravis[1] and commend the authors for putting toget
her guidelines for this condition where the evidence base is limited. The
comments here reflect our experience of managing a large number of
patients with ocular myasthenia gravis (OMG). Moor
fields Eye Hospital is th...
Dear Sirs,
Myasthenia gravis: Association of British Neurologists' management
guidelines We read with interest the ABN's management guidelines on
Myasthenia
Gravis[1] and commend the authors for putting toget
her guidelines for this condition where the evidence base is limited. The
comments here reflect our experience of managing a large number of
patients with ocular myasthenia gravis (OMG). Moor
fields Eye Hospital is thelargest and only 24-hour eye casualty in London
and as such patients with OMG
often present early to us.
Diagnostic tests
In addition to thyroid function, we also routinely
test for thyroid antibodies, as thyroid eye disease (TED) may coexist with
OMG. Thyroid function may benormal in such circumstances, and the presence
of TED may affect the response to treatment. There are two reasons for
this. Firstly the presence of thyroidantibodies is circumstantial evidence
for an autoimmune phenotype. Secondly patients with thyroid antibodies may
be euthyroid and still have dysthyroid eyedisease. The coexistence of TED
and OMG is important to recognize as the two
conditions are managed differently.
Approximately 50% of OMG patients are seronegative to anti-AChR
antibodies[2]. In addition to anti-MuSK antibodies
(MuSK+ MG can present as OMG only[3]), newer tests using the cell-based
assays can be helpful, and willlikely become more widely available, which
include:clustered anti-AChRantibodies (positive in up to 50% of
seronegative OMG[2]) and LRP4 antibodies(which is part of the MuSK
complex) [3].
At the time of writing, edrophonium (Tensilon) test
is no longer available.
Alternative methods of performing an anti-cholinest
erase test may includeneostigmine or pyridostigmine: Neostigmine adminis
tered intramuscularly has a long duration of action that allows pre- and
post
-test comparison and careful
documentation of ocular motility; a trial of oral pyridostigmine can also
be useful
as a diagnostic test. We tend to perform the pyrid
ostigmine challenge in the
following manner: For in-patients, we start with a
single oral dose of 30mg pyridostigmine and examine the patient one hour
later. A sequential increase by30mg is administered every 4 hours, i.e. up
to a single dose of 120mg. With the
four hour interval between each dose, the test may
therefore take two days to
complete. This method also allows observation of any dose-related adverse
effects e.g. diarrhoea. For the out-patient setting, pyridostigmine
challenge is performed over 8-12 weeks, with 2-3 cycles of two-weeks on,
two-weeks off pyridostgmine. The patient keeps a careful diary comparing
their symptoms during the two weeks on pyridostigmine, and the two weeks
off pyridostigmine. We prescribe a dose of 30mg three times daily, which
is increased over days to 120mg three times daily, and continue the
pyridosti
gmine challenge on 120mg three times daily if tolerated by the patient.
Treatment of ocular myasthenia gravis
In addition to symptomatic treatment with pyridostigmine, other
symptomatic treatments potentially useful include monocular occlusion (use
of an eye patch, or frosting of one lens on the spectacles) and prisms
(usually more useful if the
deficits become more fixed after long term OMG).
We prefer a daily dose of corticosteroid compared to alternate day dosing,
as is the preference or recommendations by other MG experts[4]. The
evidence for a better risk profile for alternate day dosing is limited.
The literature on this
seems to come predominantly from renal transplant in children, with
regards to
growth, although the evidence for this is mixed[5,6
]. In our experience, dailydosing can help with medication compliance At
present, we do not routinely refer our patients
with OMG for thymectomy, unless imaging suggests that a thymoma may be
present. This is an area that has unresolved questions. Some recent
retrospective studies suggest that early
thymectomy in non-thymomatous OMG could potentially improve outcome, but
this question remains to be addressed in a randomised controlled trial
[3]. The
MGTX trial studied the effect of thymectomy in MG,
is due to be reported in January 2016, but excluded patients with OMG[7].
It is also our practice to start azathioprine early
(i.e. approximately 1-2 months)
in patients who have response to corticosteroids.
In our experience, patients often relapse below 15-20mg prednisolone, and
there
fore find the relatively early introduction of azathioprine may help
weaning off prednisolone earlier. One argument against starting
azathioprine early is that some patients will be able to come off
prednisolone and remain in remission. In our experience this is an unusual
eventuality. After our patients have been in remission, we then start
to consider weaning off the corticosteroid-sparing
agent such as azathioprine if they have been on this alone for
approximately two years. The ABN guidelines by Sussman et al are a useful
resource for practicing neurologists, and we hope that our experience in
the management of large
numbers of patients with OMG described above could also be of value.
References
1 Sussman J, Farrugia ME, Maddison P,
et al.Myasthenia gravis: Association of
British Neurologists' management guidelines.
Practical Neurology2015;15
:199-206. doi:10.1136/practneurol-2015-001126
2 Jacob S, Viegas S, Leite MI,
et al.Presence and pathogenic relevance of
antibodies to clustered acetylcholine receptor in o
cular and generalized
myasthenia gravis.
Arch Neurol
2012;69:994-1001.doi:10.1001/archneurol.2012.437
3 Wong SH, Huda S, Vincent A,
et al. Ocular myasthenia gravis: controversies
and updates.Curr Neurol Neurosci Rep
2014;14:421. doi:10.1007/s11910-013-0421-9
4 Kumar V, Kaminski HJ. Treatment of myasthenia gravis.Curr Neurol
Neurosci Rep
2011;11:89-96. doi:10.1007/s11910-010-0151-1
5 Feldhoff C, Goldman AI, Najarian JS,
et al. A comparison of alternate day and daily ster
oid therapy in children following renal transplantation. Int J Pediatr
Nephrol
1984;5:11-4.
6 Diethelm AG, Sterling WA, Hartley MW,
et al. Alternate-day prednisone therapy in recipients of renalallografts.
Risk and benefits.
Arch Surg 1976;111:867-70.
7 Aban IB, Wolfe GI, Cutter GR,
et al.The MGTX experience: challenges in planning and executing an
international, multicenter clinical trial. J Neuroimmunol 2008;201-202:80-
4. doi:10.1016/j.jneuroim.2008.05.031
I read the article "Brain Injury and deprivation of liberty on
neurosciences wards" with interest - it is well-timed and provides a
helpful introduction to the the recent changes to deprivation of liberty
safeguarding criteria. Working in a residential neurorehabilitation centre
I am very familiar with the DoLS process as the majority of our client
group are admitted under this safeguard. As mentioned in the article, the...
I read the article "Brain Injury and deprivation of liberty on
neurosciences wards" with interest - it is well-timed and provides a
helpful introduction to the the recent changes to deprivation of liberty
safeguarding criteria. Working in a residential neurorehabilitation centre
I am very familiar with the DoLS process as the majority of our client
group are admitted under this safeguard. As mentioned in the article, the
recent changes have led to an increase in the number of requests for DoLS
assessment, as many of our clients lack the capacity to consent to their
admission and meet the "acid test", but are not actively seeking to leave.
The local authority has been overwhelmed by requests and as such it can
take considerable time for the assessment to be completed, as the article
mentions.
A particular concern for the service is the lack of brain-injury
specific knowledge in DoLS assessors. In my experience the professionals
sent out to complete assessments are frequently from either a mental
health or learning disability background. They can require considerable
support in understanding the complexity of acquired brain injury,
particularly with relation to individuals who have impairments that are
not immediately apparent at a first meeting. It is frustrating that DoLs
assessors are required to give a "diagnosis" of a mental disorder
(frequently "organic personality disorder" is the only available label) as
part of the DoLS process when commonly the reason for referral is a
cognitive impairment (i.e. impaired insight, attention or memory) rather
than a psychiatric condition. Understandably these teams have a colossal
workload but I would suggest that it is to their advantage to make contact
with local brain injury services and seek consultation and training. This
can enable DoLs professionals to feel confident to meet the needs of a
population from whom they are likely to now receive ever increasing
referrals.
Sir, I read with much interest the review by Weerasinghe and Lueck on the diagnosis of optic neuritis. The authors provide an extensive and detailed analysis on the differential diagnoses and the management of the disease. The importance of retinal electrophysiology is also acknowledged when differentiating retinal disorders that can mimic optic neuritis. Surprisingly, however, the diagnostic role of pattern-reversal Visua...
We welcome debate around this emerging condition. We all recognise a situation when as clinicians we have had a strong feeling that a patient has a functional complaint from early on in the consultation. However, the differential diagnosis for Functional Cognitive Disorder is neurodegenerative dementia which itself affects behaviour and personality and could, therefore, influence many of the cues clinicians pick up on wh...
Pennington and colleagues review of Functional Cognitive Disorder (FCD) [1] is very welcome to guide practice in a complex condition that is presenting increasingly to general and cognitive neurology clinics. However, in our view Pennington's presumption towards specialist assessment, investigation and surveillance is unnecessary and misses an opportunity to provide patients with a prompt diagnosis, explanation and reas...
While reading Pennington et al's (2015) article on Functional Cognitive Disorder, I was struck by the similarity between their descriptions and a patient seen in clinic (patient X), with the exception that X's symptoms appeared over the course of a few days with no identifiable precipitating event. Extensive physical tests and brain imaging investigations were carried out and no organic disease was found yet symptoms we...
The outlined model of cooperative and integrative services for pregnant women with neurological conditions is warmly welcomed (and not a little envied!). While such services are provided the English centres mentioned, it is sad that such high quality provision remains patchy and incomplete. This nettle-grasping should no longer be quiet, but should be loudly heralded and made the norm. The recently updated SIGN guideline...
Dear Sirs, We welcome Dr Leach's comments and a call for action from Neurologists, regarding service provision for women of childbearing age with neurological disorders1. We would also like to highlight that quietly, a number of us are grasping the nettle. Risk is inherent in clinical practice. Managing risk effectively and pro- actively in preference to reactively minimises the likelihood of a poor outcome. This can be...
As a jobbing MS neurologist in Southampton I am really not sure how these guidelines are going to assist in my clinical practice.
Perhaps first and foremost, if I was to follow these guidelines I would find myself frequently in breach of NHS commissioning criteria with perhaps severe implications for both myself and my hospital trust given the cost of these therapies. As such I feel the authors should have give...
I am grateful to Drs Wong and Plant for their invaluable comments, based on their enormous experience of patients presenting with suspected ocular myasthenia. The Guidelines are intended to offer non-specialists an approach to management that will work, safely, in the majority of patients. Within them, we stressed repeatedly the need to seek specialist opinion when in any doubt, and their letter emphasises the benefit of...
Dear Sirs, Myasthenia gravis: Association of British Neurologists' management guidelines We read with interest the ABN's management guidelines on Myasthenia Gravis[1] and commend the authors for putting toget her guidelines for this condition where the evidence base is limited. The comments here reflect our experience of managing a large number of patients with ocular myasthenia gravis (OMG). Moor fields Eye Hospital is th...
I read the article "Brain Injury and deprivation of liberty on neurosciences wards" with interest - it is well-timed and provides a helpful introduction to the the recent changes to deprivation of liberty safeguarding criteria. Working in a residential neurorehabilitation centre I am very familiar with the DoLS process as the majority of our client group are admitted under this safeguard. As mentioned in the article, the...
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