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Recent eLetters

Displaying 1-10 letters out of 85 published

  1. OPTIC NEURITIS AND VISUAL ELECTROPHYSIOLOGY

    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

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  2. Reply from Pennington et al.

    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).

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  3. Re: Pennington et al. Functional cognitive disorder: what is it and what to do about it?

    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

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  4. A case of functional cognitive disorder with acute onset?

    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.

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  5. Re:Comment on Death in pregnancy: a call for neurological action (JP Leach. Practical Neurology 2015)

    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.

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  6. Comment on Death in pregnancy: a call for neurological action (JP Leach. Practical Neurology 2015)

    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

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  7. Are the new ABN guidlines for MS of any use in clinical practice?

    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.

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  8. Re:Letter to Practical Neurology: comment on MG: ABN's management guidelines (Sussman et al. Practical Neurology 2015 )

    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.

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  9. Letter to Practical Neurology: comment on MG: ABN's management guidelines (Sussman et al. Practical Neurology 2015 )

    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

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  10. A need to increase understanding of brain injury in professionals carrying out DoLS assessments

    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.

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