Reply to: Psychological Interventions have a place in Management of Paediatric Headache
Michael J Morton, Honorary Clinical Senior Lecturer in Child & Adolescent Psychiatry, University of Glasgow
We are very grateful to Dr Morton for highlighting the importance of CBT and other psychological / talking therapies for children and young people with headaches, and for drawing our attention to the recent systematic review by Ng et al. Where resources exist and permit referral, this can be offered as an adjunct to acute / rescue treatment advice and as an alternative or adjunct to preventative drug therapies and acupuncture for migraine, and may be transformative for worrying tension-type headaches. Even for the trigeminal autonomic cephalalgias (including paroxysmal hemicranias) and idiopathic stabbing headache, CBT and psychological support for the child and young person and their family and carers can be really helpful. Where access to psychological interventions is difficult or inadequate, we should still request it and support the development of these crucial services. Thank you for this important contribution.
I am very impressed indeed with your sound advice for trainees.
Senior trainees should spend more time in clinic.
Access to Outpatient referral console for all tier 2 trainees.
Suggest that senior trainees should manage all general paediatric referrals as we already do it as part of CAU referral form.
Senior trainees should be able to suggest to GP’s any investigations that might make the first consultation a one stop shop.
Admin sessions should not be eaten into because of service provision responsibilities for trainees.
Telemedicine for more urgent referrals and to avoid falsification of referrals
Every GP trainee to conduct at least one new patient clinic to understand paediatric OP dynamics and procedure.
The management of headache should be imbued with a psychological understanding that is not sufficiently emphasised in the ADC review by Whitehouse & Agrawal. Like all pain disorders, headache has an important psychological component, which should be acknowledged as part of the assessment in order to open up a conversation that may lead to an effective non-pharmacological intervention. The recent review of treatments for paediatric migraine (Ng et al, 2017) confirms the power of one specific model of intervention in relation to one specific headache diagnosis. A creative use of mental health expertise in the Headache Clinic has the potential to change practice in relation to a range of presentations.
A Systematic Review and Meta-analysis of the Efficacy of Cognitive Behavioral Therapy for the Management of Pediatric Migraine
Qin Xiang Ng, MBBS; Nandini Venkatanarayanan, BMedSci, BMBS; Lakshmi Kumar, MBBS
Headache, 2017;57(3):349-362.
Dr Kraemer is correct in pointing out that the presence of a child
mental health team integrated into the paediatric team in the hospital is,
where resources allow, often the best way to manage children and young
people with medically unexplained symptoms, and indeed with a range of
other physical and psychological presentations. See also Cottrell, 2015,
http://adc.bmj.com/content/100/4/308
Dr Kraemer is correct in pointing out that the presence of a child
mental health team integrated into the paediatric team in the hospital is,
where resources allow, often the best way to manage children and young
people with medically unexplained symptoms, and indeed with a range of
other physical and psychological presentations. See also Cottrell, 2015,
http://adc.bmj.com/content/100/4/308
Professor Cottrell's guidance for paediatricians confronted with
patients whose symptoms cannot be explained minimises the real problem
that arises when a mental health opinion may be required. He says "the use
if words like 'psychological' is unhelpful and is associated with making
things up" which is indeed the case. A very useful study by Furness et al
(2009) interviewed hospital paediatricians and child health nurses...
Professor Cottrell's guidance for paediatricians confronted with
patients whose symptoms cannot be explained minimises the real problem
that arises when a mental health opinion may be required. He says "the use
if words like 'psychological' is unhelpful and is associated with making
things up" which is indeed the case. A very useful study by Furness et al
(2009) interviewed hospital paediatricians and child health nurses and
concluded "Making the transition from physical to psychological care was
perceived as one of the most difficult stages in the professional-carer
relationship because of parental resistance to giving up the notion of an
identifiable, treatable physical cause for the symptoms in favour of an
approach addressing psychological and social issues" (Furness et al.,
2009, p. 579).
Although he mentions in passing the usefulness of a joint
consultation with a mental health colleague, Prof Cottrell fails to
mention the need for paediatric departments to have their own in-house
mental health teams. It is then possible to manage the transition less
offensively. If the doctor says - rightly - that the problem is hers, she
can say truthfully to the child and family that she needs help and has a
colleague in the department who will join her at the next consultation.
That way the patient does not feel rejected with an abrupt "there's
nothing wrong with you" but is instead invited to attend a joint clinical
consultation and at the same time to witness a conversation between
medicine and mental health that can more usefully lead to an understanding
of the problem, wherever it is located. I describe this process in
narrative and historical detail in 'The view from the bridge: bringing a
third position to child health' (Kraemer, 2016).
Furness, P., Glazebrook, C., Tay, J., Abbas, K. and Slaveska-Hollis,
K. (2009). Medically Unexplained Physical Symptoms in Children: Exploring
Hospital Staff Perceptions. Clinical Child Psychology and Psychiatry,
14(4), 575-87.
Kraemer, S. (2016) The view from the bridge: bringing a third
position to child health, In (eds.) S. Campbell, R. Catchpole & D.
Morley, Child & Adolescent Mental Health: new insights to practice.
Palgrave Macmillan. http://bit.ly/1Ry2QHy
Intensive Care and Department of Surgery, Erasmus MC-Sophia
Children's Hospital, Rotterdam, The Netherlands and Department of
Development and Regeneration, KU Leuven, Leuven, Belgium
Karel.allegaert@uzleuven.be
We have read with great interest the review article on the
pharmacology, prescribing and controversies of codeine in paediatrics and
we agree to a very large extent to the position t...
Intensive Care and Department of Surgery, Erasmus MC-Sophia
Children's Hospital, Rotterdam, The Netherlands and Department of
Development and Regeneration, KU Leuven, Leuven, Belgium
Karel.allegaert@uzleuven.be
We have read with great interest the review article on the
pharmacology, prescribing and controversies of codeine in paediatrics and
we agree to a very large extent to the position taken by the authors: the
use of codeine is becoming more and more obsolete. Replacing codeine by
its metabolite, i.c. morphine is a rational decision since this results in
better predictability of the between individual exposure and subsequent
(side)effects [Andrzejowski et al, Arch Dis Child Ed Practice 2016]. In
adults, this variability in exposure is mainly driven by pharmacogenetics
(PG, i.c. cytochrome P450 (CYP)2D6). In infants and children, this is
driven by both maturation and PG of CYP2D6. On this point, we disagree
with the author's suggestion that CYP2D6 maturation is slow. Although one
can debate on how to classify the rate of maturation, the review suggests
that CYP2D6 maturation is slow. To the very best of our knowledge, its
maturation is quite fast, and this matters for both codeine as well as for
other compounds, like e.g. tramadol.
The pattern of CYP2D6 maturation has been described based on in vivo
observations for tramadol [Allegaert et al, Clin Pharmacokinet 2015] as
well as for dextromethorphan [Blake et al, Clin Pharm Ther 2007] and have
been linked with in vitro observations [Tjollyn et al, AAPS J 2015]. All
observations documented extensive variability in part explained by
pharmacogenetics (CYP2D6, but more recently also OCT1) and fast maturation
[Matic et al, Ther Drug Monit 2016], with already relevant activity in
early infancy.
This goes beyond academic relevance, since this means that the CYP26
driven metabolism of codeine as well as tramadol, already in part depends
on PG polymorphisms and that clinicians should be aware of this when
prescribing or evaluating the dose/effect response in every individual
child, including neonates or young infants. Although tramadol has also non
-opioid related analgesic mechanisms, the major 'opioid' metabolite (M1, O
-desmethyl tramadol) is generated through CYP2D6 metabolism. Consequently,
the PG polymorphisms very likely already affect the PK/PD response of
tramadol and its variability in early infancy. Even more, the subsequent
renal elimination capacity makes M1 accumulation more likely.
In conclusion, we agree to a very large extent to the position taken by
the authors that the use of codeine is becoming more and more obsolete,
and replacing codeine by its metabolite, i.c. morphine is a rational
decision. However, because CYP2D6 maturation is fast, these conclusions
also already apply to neonates and young infants.
Dear Editor, we would like to congratulate Dr Bate et al for so
eloquently highlighting the importance of public and patient involvement
specifically in paediatric research [1]. We would like to further the
discussion by highlighting the involvement of adolescents and young adults
who by virtue of age may be in either paediatric and/or adult-focussed
research. Mattila et al reported that young people in this age group who...
Dear Editor, we would like to congratulate Dr Bate et al for so
eloquently highlighting the importance of public and patient involvement
specifically in paediatric research [1]. We would like to further the
discussion by highlighting the involvement of adolescents and young adults
who by virtue of age may be in either paediatric and/or adult-focussed
research. Mattila et al reported that young people in this age group who
were not involved in research were at risk of poor health outcomes
compared to those who had been [2]. It is also widely reported that young
people are at risk of lapses in care at this time of transition from child
to adult centred services [3] and therefore also at risk of being lost to
research follow-up. The involvement of people of all ages (including young
people) in research is now widely advocated but research priorities are
still largely driven by professional agendas. Evidence from adult
literature has reported a mismatch between researcher and patient
generated lists of research topics. To date, there have been no studies
exploring the priorities of young people with long term conditions
including rheumatic disease other than a few in which a minority of young
people were involved in a larger group of carers and professionals [4,5].
Therefore, there is a need to determine the priorities of young people
across the wide adolescent and young adult age range to inform future
research programmes and funding in this area. In rheumatology, the YOURR
project (Young People's Opinions Underpinning Rheumatology Research) was
therefore established as an early initiative of the Barbara Ansell
National Network for Adolescent Rheumatology (BANNAR) funded by Arthritis
Research UK. Interim guidance regarding involvement of young people in
rheumatology research was developed at the outset supported by a mapping
document of models of good practice in the UK [6, 7]. This was necessary
ground work to inform a study, data collection for which has almost
completed, and the protocol paper just published [8], which explores young
people's beliefs about research priorities in the adolescent rheumatology
field, to inform BANNAR. BANNAR aims to provide a platform to ensure that
young people in the UK have the best chance to benefit from developments
in the field of adolescent rheumatology. Integral to BANNAR is equitable
representation from young people with rheumatic conditions. This project
will help ensure full representation from young people with rheumatic
diseases in the development of a research strategy for BANNAR and will
ultimately inform a young person's led involvement strategy, ensuring
meaningful involvement in future research programmes.
[1]. Bate J, Ranasinghe N, Ling R, Preston J, Nightingale R, Denegri
S. Public and patient involvement in paediatric research. Arch Dis Child
Educ Pract Ed. 2016 Jun;101(3):158-61
[2]. Mattila VM, Parkkari J, Rimpela A. Adolescent survey non-response and
later risk of death. A prospective cohort study of 78609 persons with 11
year follow-up. BMC Public Health 2007;7:87.
[3]. Clinton-McHarg T, Paul C, Sanson-Fisher R, D'Este C, Williamson A.
Determining research priorities for young people with haematological
cancer: a value-weighting approach. Eur J Cancer. 2010 Dec;46 (18):3263-70
[4]. Morris C, Simkiss D, Busk M, Morris M, Allard A, Denness J, Janssens
A, Stimson A, Coghill J, Robinson K, Fenton M, Cowan K. Setting research
priorities to improve the health of children and young people with
neurodisability: a British Academy of Childhood Disability-James Lind
Alliance Research Priority Setting Partnership.BMJ Open. 2015 Jan
28;5(1):e006233.
[5]. Hazel E, Zhang X, Duffy CM, Campillo S. High rates of unsuccessful
transfer to adult care among young adults with juvenile idiopathic
arthritis. Pediatric Rheumatology 2010;8:2
[6]. Dack K, Williams H, Parsons S, Thomson W, McDonagh JE on behalf of
the Barbara Ansell National Network for Adolescent Rheumatology. Summary
of good practice when involving young people in health-related research.
2015 http://bannar.org.uk
[7]. McDonagh JE, Parsons S. BANNAR Guidance for Involvement of Young
People in Rheumatology Research. Interim Statement. 2015
http://bannar.org.uk
[8]. Parsons S, Dack K, Starling B, Thomson W, McDonagh JE. Study
Protocol: Determining what young people with rheumatic disease consider
important to research (the Young People's Opinions Underpinning
Rheumatology Research YOURR project) Research Involvement and Engagement
2016, 11 June [Epub ahead of print]
The author makes an interesting point about the current legislation and automatic inclusion of data in trials where prior informed consent is not possible.
EU legislation focuses on when research without prior consent (RWPC) can occur and the need to obtain consent for continued participation, but does not cover the options for use of data collected prior to consent. The exception to this is where consent is not pr...
The author makes an interesting point about the current legislation and automatic inclusion of data in trials where prior informed consent is not possible.
EU legislation focuses on when research without prior consent (RWPC) can occur and the need to obtain consent for continued participation, but does not cover the options for use of data collected prior to consent. The exception to this is where consent is not provided: ???he or she should be informed of their right to object to the use of data obtained from the clinical trial???. Therefore, this situation is open to interpretation.
We acknowledge the concerns of the letter author regarding not automatically including data. If data are not automatically included there is the potential for bias in the study results if the decision to provide consent for use the data is associated with patient outcome. This could potentially lead to erroneous conclusions with far reaching implications. However, the research community needs to consider the timeframes around stabilisation of the patient with respect to the potential need for continued delivery of the intervention, additional tests and timing of data to be collected after this point. It would be difficult to argue against the current legislation that consent should not be requested here.
CONNECT and studies conducted in neonatal intensive care indicate that children and parents not only want to be informed, but also want to make the decision about the inclusion of their information in research. One question to reflect on is who ???owns??? the data? If it???s the patient, then they (and their parents) surely have the right to be asked for it to be used.
We believe that the automatic inclusion of data with an ???opt out??? approach should be limited to circumstances where a face to face discussion with the family has not been possible before they leave hospital, or is not deemed appropriate at that point in time (e.g. when a child had died) and there has been no response to attempts to contact the family. This approach is currently used in a NIHR HTA funded EcLiPSE Study: Emergency treatment with Levetiracetam or Phenytoin in Status Epilepticus: http://www.nets.nihr.ac.uk/projects/hta/12127134
In developing the CONNECT guidance we had to work within UK and EU legislation ??? otherwise our guidance would have been of no practical use. Article 35 of the 2014 EU legislation stipulates that research in emergency situations should only pose ???a minimal risk to, and impose a minimal burden on the subject in comparison with the standard treatment of the subject???s condition???. Our interpretation is that if a trial intervention posed more than a minimal risk, then a REC should not approve the trial. The CONNECT study findings were in keeping with this, showing that parents supported doing RWPC in trials of interventions already used in clinical care, although they were concerned about doing RWPC in trials involving new interventions, or significant changes in clinical practice.
Dyer et al. wrote an instructive review on how to interpret malaria
tests (1). However there are two important caveats in the interpretation
of these tests which they did not mention. First, a positive test does not
necessarily confirm a diagnosis of malaria. Second, a positive test does
not necessarily mean that malaria is the only diagnosis.
Strictly speaking, the tests described by Dyer et al. are parasite
de...
Dyer et al. wrote an instructive review on how to interpret malaria
tests (1). However there are two important caveats in the interpretation
of these tests which they did not mention. First, a positive test does not
necessarily confirm a diagnosis of malaria. Second, a positive test does
not necessarily mean that malaria is the only diagnosis.
Strictly speaking, the tests described by Dyer et al. are parasite
detection tests rather than malaria tests, since the diagnosis of malaria
requires that there is symptomatic infection with a Plasmodium species.
This is not just a semantic point. Children who live in a malaria endemic
country may develop naturally acquired immunity with repeated infections
(2, 3). This immunity decreases the likelihood of developing symptoms
during infection and permits the asymptomatic carriage of blood stage
parasites. Children from high transmission countries who are visiting or
migrating to the UK and develop a febrile illness may be found to have a
positive parasitological test, but their illness may have a totally
different cause. In these cases it is always sensible to treat for
malaria, but a high index of suspicion of another cause should be
maintained, particularly if the child is seriously ill.
Related to this, there is a well-recognised association between
malaria and risk of invasive bacterial infection (4). Children with
malaria are more likely to develop Gram-negative bacteraemia, particularly
infection with non-Typhoidal Salmonella. For this reason, it should not be
assumed that a positive parasite detection test in an unwell febrile child
makes a diagnosis of malaria and excludes another infection. Recent
guidelines recommend the prudent approach that any child with features of
severe malaria should be treated with broad spectrum antibiotics until it
is clear that there is no co-infection (5).
1. Dyer E, Waterfield T, Eisenhut M. How to interpret malaria tests.
Arch Dis Child Educ Pract Ed 2016;101(2):96-101.
2. Crompton PD, Moebius J, Portugal S, et al. Malaria immunity in man and
mosquito: insights into unsolved mysteries of a deadly infectious disease.
Annual review of immunology 2014;32:157-87.
3. White NJ, Pukrittayakamee S, Hien TT, et al. Malaria. Lancet
2014;383(9918):723-35.
4. Takem EN, Roca A, Cunnington A. The association between malaria and non
-typhoid Salmonella bacteraemia in children in sub-Saharan Africa: a
literature review. Malar J 2014;13:400.
5. Lalloo DG, Shingadia D, Bell DJ, et al. UK malaria treatment guidelines
2016. J Infect 2016.
The recognition of endocrine-related hypernatraemia would be enhanced
if account were taken, not only of biochemically overt hypernatraemia(1),
but also of the possibility that this biochemical derangement might be
masked by co-existing inability to excrete salt-free water. The clinical
counterpart of this phenomenon is encapsulated in the statement "the
symptoms of cranial diabetes insipidus may be ma...
The recognition of endocrine-related hypernatraemia would be enhanced
if account were taken, not only of biochemically overt hypernatraemia(1),
but also of the possibility that this biochemical derangement might be
masked by co-existing inability to excrete salt-free water. The clinical
counterpart of this phenomenon is encapsulated in the statement "the
symptoms of cranial diabetes insipidus may be masked by concomitant ACTH
deficiency...(since) glucocorticoids are necessary for the kidneys to
excrete salt-free water"(2). This scenario has no adverse iatrogenic
sequelae if the recognition and treatment of cranial diabetes insipidus
antedates replacement therapy for co-existing ACTH deficiency. The danger
arises where glucocorticoid replacement therapy is instituted in the face
of unsuspected cranial diabetes insipidus because this might be
accompanied by a rapid rise in plasma sodium which, in one instance, was a
rise from pre-treatment hyponatraemia to post treatment hypernatraemia,
with consequent myelinosis(3). Even the use of ACTH for dynamic testing of
the hypothalamo/pituitary/adrenal axis may have an unmasking effect, this
time by precipitating profound polyuria as was the case in a patient with
suspected anterior pituitary failure in whom co-existing cranial diabetes
insipidus had not been identified(4). Where the investigators deliberately
set out to identify both anterior and posterior pituitary failure in 12
patients with suspected panhypopituitarism. 4 patients in whom unequivocal
carnial diabetes insipidus(charcterised by a negligible increase in plasma
vasopressin following hypertonic saline infusion) co-existed with ACTH
deficiency nevertheless had normal plasma sodium levels(range 140-143
mmol/l)(5). Patients in whom this constellation of parameters is
associated with blunted diuresis are the ones most likely to be missed if,
as in one study, the co-existence of hypernatraemia and polyuria is relied
upon as one of the screening tests for cranial diabetes insipidus(6).
References:
(1) Haycock GB
Hypernatraemia:diagnosis and treatment
Arch Dis Child 2006:91:ep8-ep13
(2) Bayliss PH and Cheetham T
Diabetes insipidus
Arch Dis Child 1998:79:84-89
(3)Lasheen I., Doi SAR., Al-Shoumer KAS
Glucocorticoid replacement in panyhpopituitarism complicated by myelinosis
Medical principles and Practice 2005:14:115-117
(4) Schwartz AR and Leddy AL
Recognition of diabetes insipidus in postpartum hypopituitarism
Obstetrics and Gynecology 1982:59:394-8
(5) Iwasaki Y., Oiso Y., Yamauchi K., et al
Neurohypophyseal function in postpartum hypopituitarism: impaired plasma
vasopressin respnse to osmotic stimuli
Journal of Clinical Endocrinology and Metabolism 1989:68:560-5
(6) Agha A., Rogers B., Mylotte D., et al
Neuroendocrine dysfunction in the acute phase of traumatic brain injury
Clinical Endocrinology 2004:60:584-91
Reply to: Psychological Interventions have a place in Management of Paediatric Headache
Michael J Morton, Honorary Clinical Senior Lecturer in Child & Adolescent Psychiatry, University of Glasgow
We are very grateful to Dr Morton for highlighting the importance of CBT and other psychological / talking therapies for children and young people with headaches, and for drawing our attention to the recent systematic review by Ng et al. Where resources exist and permit referral, this can be offered as an adjunct to acute / rescue treatment advice and as an alternative or adjunct to preventative drug therapies and acupuncture for migraine, and may be transformative for worrying tension-type headaches. Even for the trigeminal autonomic cephalalgias (including paroxysmal hemicranias) and idiopathic stabbing headache, CBT and psychological support for the child and young person and their family and carers can be really helpful. Where access to psychological interventions is difficult or inadequate, we should still request it and support the development of these crucial services. Thank you for this important contribution.
William Whitehouse and Shakti Agrawal
Dear Rachael,
I am very impressed indeed with your sound advice for trainees.
Senior trainees should spend more time in clinic.
Access to Outpatient referral console for all tier 2 trainees.
Suggest that senior trainees should manage all general paediatric referrals as we already do it as part of CAU referral form.
Senior trainees should be able to suggest to GP’s any investigations that might make the first consultation a one stop shop.
Admin sessions should not be eaten into because of service provision responsibilities for trainees.
Telemedicine for more urgent referrals and to avoid falsification of referrals
Every GP trainee to conduct at least one new patient clinic to understand paediatric OP dynamics and procedure.
Kindest regards,
Dr Sripriya Eachempati
ST6 Paediatrics, NNUH
The management of headache should be imbued with a psychological understanding that is not sufficiently emphasised in the ADC review by Whitehouse & Agrawal. Like all pain disorders, headache has an important psychological component, which should be acknowledged as part of the assessment in order to open up a conversation that may lead to an effective non-pharmacological intervention. The recent review of treatments for paediatric migraine (Ng et al, 2017) confirms the power of one specific model of intervention in relation to one specific headache diagnosis. A creative use of mental health expertise in the Headache Clinic has the potential to change practice in relation to a range of presentations.
A Systematic Review and Meta-analysis of the Efficacy of Cognitive Behavioral Therapy for the Management of Pediatric Migraine
Qin Xiang Ng, MBBS; Nandini Venkatanarayanan, BMedSci, BMBS; Lakshmi Kumar, MBBS
Headache, 2017;57(3):349-362.
Dr Kraemer is correct in pointing out that the presence of a child mental health team integrated into the paediatric team in the hospital is, where resources allow, often the best way to manage children and young people with medically unexplained symptoms, and indeed with a range of other physical and psychological presentations. See also Cottrell, 2015, http://adc.bmj.com/content/100/4/308
Conflict of Interest:...
Professor Cottrell's guidance for paediatricians confronted with patients whose symptoms cannot be explained minimises the real problem that arises when a mental health opinion may be required. He says "the use if words like 'psychological' is unhelpful and is associated with making things up" which is indeed the case. A very useful study by Furness et al (2009) interviewed hospital paediatricians and child health nurses...
K Allegaert
Intensive Care and Department of Surgery, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands and Department of Development and Regeneration, KU Leuven, Leuven, Belgium Karel.allegaert@uzleuven.be
We have read with great interest the review article on the pharmacology, prescribing and controversies of codeine in paediatrics and we agree to a very large extent to the position t...
Dear Editor, we would like to congratulate Dr Bate et al for so eloquently highlighting the importance of public and patient involvement specifically in paediatric research [1]. We would like to further the discussion by highlighting the involvement of adolescents and young adults who by virtue of age may be in either paediatric and/or adult-focussed research. Mattila et al reported that young people in this age group who...
The author makes an interesting point about the current legislation and automatic inclusion of data in trials where prior informed consent is not possible.
EU legislation focuses on when research without prior consent (RWPC) can occur and the need to obtain consent for continued participation, but does not cover the options for use of data collected prior to consent. The exception to this is where consent is not pr...
Dyer et al. wrote an instructive review on how to interpret malaria tests (1). However there are two important caveats in the interpretation of these tests which they did not mention. First, a positive test does not necessarily confirm a diagnosis of malaria. Second, a positive test does not necessarily mean that malaria is the only diagnosis.
Strictly speaking, the tests described by Dyer et al. are parasite de...
Dear Editor,
The recognition of endocrine-related hypernatraemia would be enhanced if account were taken, not only of biochemically overt hypernatraemia(1), but also of the possibility that this biochemical derangement might be masked by co-existing inability to excrete salt-free water. The clinical counterpart of this phenomenon is encapsulated in the statement "the symptoms of cranial diabetes insipidus may be ma...
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