DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY

EDITORIAL

Next generation child neurologists

One day when I was a trainee in paediatrics on a cardiology rotation, I admitted an infant presenting with cardiac
failure. I was somewhat shocked when the cardiologist,
after introducing himself, performed a cardiac echo first
and then listened to the history and clinical findings. I was
shocked because this approach seemed to breach what had
been drummed into us at medical school about the correct
clinical method of history followed by examination followed
by investigations to test the hypotheses generated by clinical assessment. In later years I came to recognize that the
cardiologist was being pragmatic, saving time and
resources, cutting to the chase to enable early treatment
and, importantly, by rapidly making a diagnosis being able
to have an informed discussion with the parents about
treatment and prognosis.
The introduction of new technologies often leads to a
change in paradigm. In neurology we have witnessed this
in the last few decades following the introduction of magnetic resonance imaging (MRI). In the early days performing an MRI on a child had to be strenuously justified and
often argued for. Now, in most cases, those arguments are
a thing of the past and for many neurological presentations
the MRI is a routine first step in the patient work-up.
Radiologists, usually and appropriately, require the patient
to have been examined and a history taken before the scan
is requested. However, there are many clinical situations
where an MRI will be required no matter what the fine
details of clinical examination reveal. Examples abound: a
new onset paralytic squint, unexplained encephalopathy,
infantile spasms, neurological regression, to name but a
few.
We are currently, and excitingly, witnessing the ground
shift in medicine with the rapid evolution and increasing
availability of next generation sequencing (NGS) techniques such as whole exome sequencing (WES) and whole
genome sequencing (WGS). This will have an impact on
all of medicine, but for specialties such as child neurology
where there is such a high proportion of genetic disorders,
the consequences will be truly revolutionary.
Of the many predicted benefits following from NGS
two examples can be considered. As in the example above,
early diagnosis is a high priority for parents. Irrespective of
whether there is a treatment or cure, patient and parent
surveys repeatedly highlight the distress and frustration
caused by protracted investigation and delay in final diagnosis.1 In disorders where there is a treatment, this is even
more pressing.
A rather different example of the potential benefits of
being able to make a molecular diagnosis, is the prospect
for unraveling disease mechanisms and the development of
4

new treatments. For many diseases this is an unknown, but

there are already examples of surprises that have followed
from the discovery of the molecular basis of diseases, e.g.
the use of TGFb blockers in Marfan syndrome2 or riboflavin in Vialetto-van Laere syndrome.3
For non-Mendelian disorders it is more complex and
WES/WGS will generate large amounts of data that will
need to be interpreted. Nonetheless treatments, especially
for cancers, are already being stratified by genome and we
are likely to see this aspect of medicine evolve rapidly in
the next decade.
Clinical neurology developed in an era when there was
no neuroimaging and limited possibility for investigation.
The neurological examination that evolved was detailed,
lengthy, and complex, and for non-neurologists, mysterious
and intimidating. The clinical method developed by the
brilliant early exponents of this art has become a meme in
clinical neurology. Evidence for this at least in the UK
is the model of the Gowers clinical meeting that continues
to have a pervasive influence within the UK. The clinical
method developed in adult neurology was never so easily
applied in child neurology. Not least because localization
is often not possible in a developing or abnormal brain,
but also because the child, understandably, would often
not permit a full neurological examination. Nonetheless
the primacy of the history and clinical examination in child
neurology has remained unchallenged.
Whether we like it or not, this may be changing. A
recent commentary on NGS4 observes that the costs of a
genotype-first approach are now less (and still falling) than
the traditional phenotype-first approach that we currently
employ. The authors do not make a judgement on whether
this is good or bad but consider the promiscuity of
genetic information that is coming our way and how this
might be utilized in the future.
Alongside this generic revolution other changes in the
landscape of child neurology have occurred with an
increasing subspecialization in knowledge reflecting
advances in many areas. Epilepsies, stroke, movement disorders, muscle disease, demyelinating diseases are but
some examples. Each of these fields have their own evolving investigative tools, technologies, and treatments, the
availability and efficacy of which impact on the relative
role of the traditional clinical method in patient management.
Clinical assessment will always be central to patient
management, indeed in the NGS era, clinical phenotyping
will become even more important in the face of the identification of large numbers of variants of possible or uncertain significance. However the relative primacy of the
2014 Mac Keith Press

clinical method is changing and we need to recognize this

as we embrace the new technologies.
The training of specialist doctors is constrained by time
and resources, and the curriculum must give not only
breadth and depth but must also prioritize areas that are
most relevant to modern clinical practice. The next generation of child neurologists will need to be completely familiar with standard MRI as well as the many evolving MRI
tools. They will also need to be aware of the increasing
numbers of therapies which are becoming available in
many subspecialty areas. Furthermore whether we like it or

not a genome-first approach is likely to happen and the

neurologist of tomorrow will need to be fully literate in
genomic medicine.

JOHN LIVINGSTON
President of BPNA
Department of Paediatric Neurology, Leeds Teaching Hospitals NHS Trust, Leeds,
UK.
doi: 10.1111/dmcn.12651

REFERENCES
Optimising

3. Foley AR, Menezes MP, Pandraud A, et al. Treatable

4. Lu JT, Campeau PM, Lee BH. Genotypephenotype cor-

Resources: A Vision for the UK Rare Disease Strategy.

childhood neuronopathy caused by mutations in the ribo-

relation: promiscuity in the era of next-generation

London: Rare Disease UK, 2011. www.raredisease.org.uk.

flavin transporter RFVT2. Brain 2014; 137: 4456.

sequencing. N Engl J Med 2014; 371: 5936.

1. Rare

Disease

UK.

Improving

Lives,

2. Travis T. Old drug, new hope for Marfan syndrome.

Science 2006; 312: 367.

Editorial