I read with interest the review by Tada et al. [1], which, based on
the current knowledge on the cerebellar systems, propose an interesting
framework to interpret cerebellar ataxias in clinical settings.
The Authors classify cerebellar ataxias into two main categories: those
with a loss of Purkinje cells, translating into a malformation of internal
models; and those with a disturbance of afferent systems, causing a mis-
s...
I read with interest the review by Tada et al. [1], which, based on
the current knowledge on the cerebellar systems, propose an interesting
framework to interpret cerebellar ataxias in clinical settings.
The Authors classify cerebellar ataxias into two main categories: those
with a loss of Purkinje cells, translating into a malformation of internal
models; and those with a disturbance of afferent systems, causing a mis-
selection of internal models. From a clinical point of view, the first
type of deficit, as observed in SCA31 and SCA6, results in decomposition
and dysmetria. In addition, the loss of Purkinje cells may initially
affect just the quality, and not the quantity, of internal models, and new
internal models could be reconstructed using the residual circuits. This
could explain why patients with pure cerebellar ataxia initially respond
well to rehabilitation. Concerning the second category, a further
classification differentiates the disturbances of the
corticopontocerebellar system, such as in MSA-C and SCA2, from those of
the spinocerebellar system, such as in SCA1, SCA3, FRDA and AOA1. In all
of them there is dysmetria and dysrhythmia but, while the pontocerebellar
disturbance affects the internal model selection for well-trained limb
movements, such as writing or playing an instrument; disturbances of the
spinocerebellar system affect actions requiring continuous feedback from
the periphery, such as stance and gait. Finally, a third type of ataxia,
such as the DRPLA, involves the efferent system (deep nuclei), resulting
in a deficit of the overall cerebellar function.
This classification has the great value of building a bridge between
basic research and clinical knowledge, and it's simple enough to be
implemented in everyday clinical practice, but it deserves some comments.
First, as already acknowledged by the Authors, the pathology of
degenerative ataxias is much more complex than the proposed
schematization, as there is usually a combined degeneration of various
systems and the very initial pathological alterations in many cases are
still controversial [2].
Second, the proposed classification is based on the classical view
that the cerebellar cortex has a uniform structure and that a unique
neural computation (the so called "cerebellar transform") is performed
throughout it [3]. This implies that the functional role of the different
cerebellar areas is dictated by its input and output connections and that,
once known these connections, the impact of a lesion can be predicted
relatively easily. Nowadays, it looks that this traditional concept
requires sophistication. In fact, as underlined in a recent review by
Cerminara et al. [4], cytoarchitectural and physiological variations have
been identified in the cerebellar cortex, supporting the non-orthodox
hypothesis that the cerebellar cortex, and therefore its information
processing, is not uniform. In this case, classifying ataxias just on the
basis of the anatomical regions affected could not be enough to predict
the functional deficit. Interestingly, it seems that, the configuration of
Purkinje cells death in neurodegeneration is not random, being probably
genetically determined [4]. Therefore, a deeper knowledge of these
patterns and at the same time of the cerebellar cortex computations could
lead to a more accurate phenotypic classification of ataxias.
Third, Tada et al. [1] focused their observations on motor symptoms.
As the cerebellum is nowadays known to have also non-motor roles, a
similar classification regarding cognitive functions in ataxias would be
of interest, even if, again, the complexity of neurodegeneration would
make this task quite arduous [5].
Finally, formally exploring the motor differences between these
categories, with an accurate registration of movement kinematics and a
motor learning task, would be of interest. This would require testing
subjects in an early stage of disease, to evaluate if motor performance
and motor learning vary across the different neurodegeneration patterns
and with disease progression. This approach could finally lead to
development of new rating scales but also to an improvement of actual
neurorehabilitation approaches.
References
1. Tada M, Nishiwaza M, Onodera O. Journal of Neurology Neurosurgery
and Psychiatry 2015; 0:1-7. doi: 10.1136/jnnp-2013-307225
2. Fratkin JD and Vig PJS. Handbook of Clinical Neurology 2012;
103:111-125.
3. D'Angelo E, Casali S. Frontiers in Neural Circuits 2013; 10:116.
doi: 10.3389/fncir.2012.00116. eCollection 2012.
4. Cerminara NL, Lang EJ, Sillitoe RV, Apps R. Nature Reviews
Neuroscience 2015; 16:79-93.
We read the recently published UK guideline for treating myasthenia
gravis (MG) patients in pregnancy with great interest [1]. As stated by
the workgroup in their article, few studies are available concerning drug
safety in pregnancy in these patients. In our experience, most drugs
indeed carry a very small risk in the treatment of MG during pregnancy.
However, based on additional literature we would advise some caution...
We read the recently published UK guideline for treating myasthenia
gravis (MG) patients in pregnancy with great interest [1]. As stated by
the workgroup in their article, few studies are available concerning drug
safety in pregnancy in these patients. In our experience, most drugs
indeed carry a very small risk in the treatment of MG during pregnancy.
However, based on additional literature we would advise some caution
regarding use of azathioprine and cyclosporine during pregnancy.
Cleary and others described pregnancy outcomes in 476 women using AZT
during early pregnancy, mostly for inflammatory bowel disease [2]. A
significant increase in atrioventricular septum defects was found (OR
3.18), pre-term birth, low birth weight and small stature were also more
significant. A trend towards an increase in all birth defects was found
(OR 1.41, 95% CI 0.98-2.04) was found in women with IBD and azathioprine,
compared to IBD patients without azathioprine.
For cyclosporine, a meta-analysis of multiple studies shows a non-
significant increase of malformations (OR 3.83, 95% CI 0.75-19.6) and
borderline significant prematurity (OR 1.52, 95% CI 1.00-2.32) [3].
Although inconclusive, the limited data available suggests at least some
caution. Overall, prematurity and low birth weight are reported more
frequently in women exposed to cyclosporine, although it is unclear if
these are related to cyclosporine or maternal disease [4].
In our opinion, both azathioprine and cyclosporine cannot be
considered completely safe. Although both are unlikely to be major
teratogens, we consider both to be relatively contra-indicated. Our
recommendation would be
1) to discuss the small risks associated with use of azathioprine and
cyclosporine and
2) to discontinue both immunosuppressants from planned conception and
during the first trimester in patients with stable disease and no or mild
weakness.
References
1. Norwood F, Dhanjal M, Hill M, et al. Myasthenia in pregnancy: best
practice guidelines from a U.K. multispecialty working group. J Neurol
Neurosurg Psychiatry. 2014 May;85(5):538-43.
2. Cleary BJ, Kallen B. Early pregnancy azathioprine use and
pregnancy outcomes. Birth Defects Res A Clin Mol Teratol. 2009
Jul;85(7):647-54.
3. Bar Oz B, Hackman R, Einarson T, et al. Pregnancy outcome after
cyclosporine therapy during pregnancy: a meta-analysis. Transplantation.
2001 Apr 27;71(8):1051-5.
4. Paziana K, Del Monaco M, Cardonick E, et al. Ciclosporin use
during pregnancy. Drug Saf. 2013 May;36(5):279-94.
We thank Dr. Voci for his comments[1] on our article.[2] As described
in the paper, our data comprise Hospital Episode Statistics (HES) obtained
from the English national Health and Social Care Information Centre
(HSCIC) and mortality record abstracts obtained from the Office for
National Statistics. All data from both sources were anonymised to the
same standard by encryption of personal identifiers before being supplied...
We thank Dr. Voci for his comments[1] on our article.[2] As described
in the paper, our data comprise Hospital Episode Statistics (HES) obtained
from the English national Health and Social Care Information Centre
(HSCIC) and mortality record abstracts obtained from the Office for
National Statistics. All data from both sources were anonymised to the
same standard by encryption of personal identifiers before being supplied
to the Oxford study team for record linkage studies.
The main data item used in the algorithm for linkage between
successive HES records for the same person was "HES ID", an encrypted
unique personal identifier generated by HSCIC. HES ID was present for 100%
of the HIV HES records, 100% of the reference cohort, and 100% of the
multiple sclerosis HES records. For the linkage of HES records to death
records, probabilistic matching was used, based on encrypted NHS number,
encrypted postcode, encrypted date of birth, and sex.
To illustrate the quality of the matching, and further to Dr. Voci's
suggestion, we have followed up the HIV cohort for tuberculosis, a disease
known to be associated with HIV. The rates in the HIV cohort were very
substantially elevated compared with those in the reference cohort
comprising people without HIV: there were 539 observed and 33.8 expected
cases of tuberculosis in the HIV cohort; and 4763 observed and 5268.2
expected cases of tuberculosis in the reference cohort. The rate ratio,
standardised for age and other factors as described in our original
article,2 was 17.6 (95% CI 16.1 to 19.3). Restricting the outcomes to
death records only, the standardised rate ratio was also very high: there
were 34 observed and 1.4 expected cases of tuberculosis in the HIV cohort,
and 496 observed and 528.6 expected cases of tuberculosis in the reference
cohort. The standardised rate ratio was 25.5 (95% CI 17.5 to 36.17), i.e.
there was a 25-fold increased death rate from tuberculosis in the HIV
cohort. We have confidence in the dataset and the methods used to match
and link records in it.
References
1. Voci C. How accurate is the record linkage? J Neurol Neurosurg
Psychiatry
2. Gold J, Goldacre R, Maruszak H, et al. HIV and lower risk of
multiple sclerosis: beginning to unravel a mystery using a record-linked
database study. J Neurol Neurosurg Psychiatry 2014 Aug 4 [Epub ahead of
print] doi: 10.1136/jnnp-2014-307932
This is an interesting study. However, I am somewhat concerned
whether the record linkage could be appropriately performed. In most
healthcare information systems, HIV patients characteristics are
protected. Did the authors have enough information on the patients to
perform probabilistic matching?
It would be of interest if the authors could show that the matching is
adequate by showing that there is not a general reduce...
This is an interesting study. However, I am somewhat concerned
whether the record linkage could be appropriately performed. In most
healthcare information systems, HIV patients characteristics are
protected. Did the authors have enough information on the patients to
perform probabilistic matching?
It would be of interest if the authors could show that the matching is
adequate by showing that there is not a general reduced risk of developing
other autoimmune diseases and confirming known HIV associations, for
example with TB.
Professor Kawada expresses three concerns regarding the outcomes of
our study into how cognitive deficits progress in the years following a
stroke [1]. Firstly, he cites Rajan et al. [2] as finding that cognitive
decline was greater after stroke than before stroke, and suggests that our
study should have considered pre-stroke cognitive decline. How doing so
would have affected our outcomes or their interpretation is uncle...
Professor Kawada expresses three concerns regarding the outcomes of
our study into how cognitive deficits progress in the years following a
stroke [1]. Firstly, he cites Rajan et al. [2] as finding that cognitive
decline was greater after stroke than before stroke, and suggests that our
study should have considered pre-stroke cognitive decline. How doing so
would have affected our outcomes or their interpretation is unclear. We
found greater decline in MMSE scores for stroke patients than for a well-
matched healthy control group. This complements the findings of Rajan et
al., whose cognitive measure was a composite of four tests that included
the MMSE. We also found that 23% of our patients had a further stroke
during follow-up, and which was associated with accelerated cognitive
decline. This is also in keeping with the findings of Rajan et al., but
goes further to highlight a need to consider how overall outcomes are
affected by including patients with repeat strokes in analyses of post-
stroke cognitive decline.
The second concern of Professor Kawada involves a recommendation that we
conduct sensitivity analyses in light of a report of warfarin being
associated with higher rates of haemorrhagic stroke than dabigatran
etexilate, particularly in Asians as compared with non-Asians [3]. This
seems beyond the scope or aims of our study.
Professor Kawada's third concern involves our observation of increased
rates of dementia in stroke patients, and he seems to suggest that pre-
stroke cognitive functioning must be considered when making such claims.
This is despite his further reference to studies reporting an independent
effect of stroke on dementia, including one we also cite [4], and our
exclusion of patients with a diagnosis of dementia prior to their stroke.
The purpose of our study was to examine how cognitive deficits progress in
the years following a stroke, which we did by comparing stroke patients,
either with or without a further stroke, against a suitable control group.
We believe that extending our analyses to include pre-stroke cognitive
functioning and effects of incident stroke rates would be additional
purposes, and that not including these should not alter the interpretation
of our results.
References
1 Sachdev PS, Lipnicki DM, Crawford JD, et al. Progression of
cognitive impairment in stroke/TIA patients over 3 years. J Neurol
Neurosurg Psychiatry 2014 Mar 21 [Epub ahead of print].
2 Rajan KB, Aggarwal NT, Wilson RS, et al. Association of cognitive
functioning, incident stroke, and mortality in older adults. Stroke
2014;45:2563-7.
3 Hori M, Connolly SJ, Zhu J, et al. Dabigatran versus warfarin:
effects on ischemic and hemorrhagic strokes and bleeding in Asians and non
-Asians with atrial fibrillation. Stroke 2013;44:1891-6.
4 Savva GM, Stephan BC. Epidemiological studies of the effect of
stroke on incident dementia: a systematic review. Stroke 2010;41:e41-6.
Sachdev et al. conducted a 3-year follow-up study to know the
progress of cognitive deficits after stroke or transient ischemic attack
(TIA) (1). The authors gathered 183 stroke/TIA patients and 97 healthy
controls, and concluded that cognitive decline in post-stroke patients was
not greater than in controls, except for verbal memory, although rates of
incident dementia were 5.9% per year in patients and 0.4% in controls,...
Sachdev et al. conducted a 3-year follow-up study to know the
progress of cognitive deficits after stroke or transient ischemic attack
(TIA) (1). The authors gathered 183 stroke/TIA patients and 97 healthy
controls, and concluded that cognitive decline in post-stroke patients was
not greater than in controls, except for verbal memory, although rates of
incident dementia were 5.9% per year in patients and 0.4% in controls,
respectively. I have some queries on their study outcome.
First, Rajan et al. conducted a cohort study to check bidirectional
causality of the association between incident stroke and cognitive
function in 7217 older adults with 3-year intervals (2). They concluded
that baseline cognitive function was associated with incident stroke, and
the level of cognitive decline was 1.9-fold higher after stroke, compared
with periods before stroke. This study shows that the level of cognitive
decline should also be compared in stroke/TIA patients before and after
events.
As the second concern, there is a report that effects of different
types of anticoagulant medication for stroke subtype differ and they are
affected by races (3). I recommend the authors conducting sensitivity
analysis with use of stroke subtype such as ischemic and hemorrhagic
stroke, by considering medication, which would be possible by the enough
number of incident strokes.
As the third concern, Savva et al. reported a systematic review of
the effect of stroke on incident dementia (4). In their study, stroke
increased 2-folds risk of incident dementia in the older population, and
the increase could not be explained by demographic or cardiovascular risk
factors or by pre-stroke cognitive decline. Relating to their study,
Dregan et al. estimated the occurrence in post-stroke dementia as a
function of pre-stroke cognitive status and incident stroke, and concluded
that stroke and pre-stroke cognitive impairment were independently
associated with increased risk of post-stroke dementia (5). These reports
show that the level of cognitive function should be checked in stroke/TIA
patients before and after events. I understand that the study design by
Sachdev et al. can also evaluate the progress of cognitive impairment in
stroke/TIA patients with adjustment of confounders. My recommendation
would be achieved by a follow-up study in large number of subjects without
stroke or TIA as a baseline study.
References
1 Sachdev PS, Lipnicki DM, Crawford JD, et al. Progression of
cognitive impairment in stroke/TIA patients over 3 years. J Neurol
Neurosurg Psychiatry 2014 Mar 21. doi: 10.1136/jnnp-2013-306776
2 Rajan KB, Aggarwal NT, Wilson RS, et al. Association of cognitive
functioning, incident stroke, and mortality in older adults. Stroke
2014;45:2563-7.
3 Hori M, Connolly SJ, Zhu J, et al. Dabigatran versus warfarin:
effects on ischemic and hemorrhagic strokes and bleeding in Asians and non
-Asians with atrial fibrillation. Stroke 2013;44:1891-6.
4 Savva GM, Stephan BC; Alzheimer's Society Vascular Dementia
Systematic Review Group. Epidemiological studies of the effect of stroke
on incident dementia: a systematic review. Stroke 2010;41:e41-6.
5 Dregan A, Wolfe CD, Gulliford MC. Does the influence of stroke on
dementia vary by different levels of prestroke cognitive functioning?: a
cohort study. Stroke 2013;44:3445-51.
I endorse the authors' use of multiple information sources to
identify prevalent delirium in medical and surgical inpatients 1-2: family
and other informants, junior and senior physicians, medical case notes and
nurses. Although the authors did not use the model I developed, I suggest
that their paper is about distinguishing rapid cognitive decline (RCD, one
form being delirium) from slow cognitive decline (SCD) in dementia...
I endorse the authors' use of multiple information sources to
identify prevalent delirium in medical and surgical inpatients 1-2: family
and other informants, junior and senior physicians, medical case notes and
nurses. Although the authors did not use the model I developed, I suggest
that their paper is about distinguishing rapid cognitive decline (RCD, one
form being delirium) from slow cognitive decline (SCD) in dementia and
mild cognitive impairment (Diagnostic and Statistical Manual of Mental
Disorders or DSM-V major minor neurocognitive disorder). Until each
cognitive domain is measured in RCD patients by a 6-minute battery of non-
copyrighted paper and pencil neuropsychological tests, I prefer the
umbrella term rapid cognitive decline (RCD) over RCD subtypes such as
delirium. My prospective randomised controlled trial, Central Coast
Australia Delirium Intervention Study (CADIS), examined a new RCD
phenotype. CADIS enrolled 130 Confusion Assessment Method (CAM) positive
elderly who had at least 25% relative decline in attention or executive
function and stringent measures to exclude behavioral and psychological
symptoms of dementia (BPSD) 3-5. RCD is classified by cognitive domain
into five main subtypes: 1) Delirium: RCD involving mainly attention,
executive function, word-list memory; 2) Transient global amnesia: RCD
involving memory and orientation with sparing of other domains; 3)
Dysphasia: RCD involving mainly language, often from acute ischemic stroke
(AIS); 4) Executive dysfunction RCD due to AIS; 5) Visuospatial impairment
RCD from AIS. RCD in CADIS was associated with rapid cognitive recovery
(RCR).
I wish to focus on seven issues in the author's methods, results and
conclusions which lead to false positive delirium diagnosis in severe
hearing impairment, dementia and behavioral and psychological symptoms of
dementia (BPSD). 1) While spatial span forward (SSF) is an excellent test
for inattention, months of the year backwards (MOTYB) reflects both
attention and executive function. If MOTYB resolved from say 2 / 12
months accurate on admission to 12 / 12 months at discharge this rapid
recovery this would prove that abnormal MOTYB was due to delirium rather
than dementia. If MOTYB did not change then an abnormal score on admission
should not be used as evidence of delirium; 2) Digit span forward (DSF) in
CADIS proved highly robust and sensitive to change: 6-DSF fell by 54%
prior to admission and improved by 54% from admission to recovery. DSF is
quicker and easier to measure than SSF and MOTYB. 3) Investigators did not
exclude severely deaf subjects or use amplifiers with headphones (cost
US$120) for the deaf to ameliorate hearing deficits, leading to false
positive attribution to delirium. 4) The opening sentence of the
discussion section decries underdetection of delirium, which I agree is a
major problem. The greater problem of overdiagnosis, however, receives
almost no attention in the medical literature - false positive diagnosis
of delirium in dementia with or without BPSD. Behavioral decline is
counted falsely as disorganized thinking. In many countries with national
health services if a GP wishes to admit a dementia patient with behavioral
problems she or he will insist on acute onset and new confusion knowing
that if the patient were labelled as BPSD the hospital physicians would
recommend management in the community. Furthermore there is a certain
prestige in diagnosing delirium which is absent with BPSD. 5) The
questions used by geriatricians to identify disorganised thinking such as
"Would a stone float on water?" or interpreting a proverb are impaired in
moderate to severe dementia and not specific for delirium. 6) The authors
state in the last paragraph of the introduction that their aim was to
determine if SSF and MOTYB would predict delirium by DSM-IV. While their
findings confirmed this, the data they present is silent on reversibility
and magnitude / rate of cognitive decline and cognitive recovery. 7) CAM
item 4 in table 1, altered level of consciousness during the interview
could have arisen from factors other than delirium such as sedative or
antipsychotics for BPSD, sleep deprivation from acute symptoms or tests
after midnight or temporary lack of CPAP in obstructive sleep apnoea (CPAP
often not taken in ambulance to emergency department). In conclusion I
believe that the speed of cognitive decline (25% per 24 hours) and the
speed of cognitive recovery are the gold standards for delirium and other
forms of RCD. This parallels the time course of many disease pairs: acute
kidney injury compared to chronic kidney disease or asthma compared to
chronic obstructive pulmonary disease. The suggestion that certainty in
diagnosis wait 2-3 days after hospital admission to measure recovery is no
different than the waiting period to confirm blood stream infection or to
wait for tests not available in medium or small hospitals after midnight
such as MRI imaging to show a new cerebral infarct on T2 or FLAIR when
initial CT scan shows no acute changes. It is time for logic-based
medicine to correct evidence-based medicine (EBM) when EBM started on an
imperfect delirium phenotype from DSM which was perpetuated in 1990 with
CAM.
References
1. O'Regan NA, Ryan DJ, Boland E et al Meagher D. Attention! A good
bedside test for delirium? J Neurol Neurosurg Psychiatry 2014;85:1122-1131
2. Ryan DJ, O'Regan NA, Caoimh RO et al, Paula T Trzepacz, David Meagher.
Delirium in an adult acute hospital population: predictors, prevalence and
detection. BMJ Open 2013;3:e001772
3. Regal P. Delirium Reversibility and Instrumental Activities of Daily
Living. Geriatrics and Gerontology International October 2014;14:in press
4. Regal, P. Serial Montreal Cognitive Assessments demonstrate reversible
cognitive impairment in patients with acute transient ischemic attack and
minor stroke. Stroke 2014;45:e193
5. Regal P. Need for new methods to study delirium. Internal Medicine
Journal 2013;43:1053-4
The JNNP recently published an interesting study which used magnetic
stimulation to the spine of people with Parkinson's disease, and showed a
promising improvement in camptocormia compared to a group receiving 'sham'
stimulation [1]. In an Editorial Comment, Caslake [2] argued that the
participants in this particular study may not have been sufficiently
blinded as to the group to which they had been assigned. Although th...
The JNNP recently published an interesting study which used magnetic
stimulation to the spine of people with Parkinson's disease, and showed a
promising improvement in camptocormia compared to a group receiving 'sham'
stimulation [1]. In an Editorial Comment, Caslake [2] argued that the
participants in this particular study may not have been sufficiently
blinded as to the group to which they had been assigned. Although the
stimulation used by Arii and colleagues was delivered to the spine and not
to the head (trans-spinal magnetic stimulation, TSMS, rather than
transcranial magnetic stimulation, TMS), we believe there are general
principles of experimental design that are of relevance to studies using
these technologies.
We have previously argued that it is almost impossible to create a
convincing placebo control for experiments using stimulation such as TMS
or transcranial current stimulation (tCS) [3]. TMS by its nature is a
multisensory experience: driving a current through the hand-held coil
creates the intended magnetic pulse, but as a side-effect creates a
clicking sound and, depending on the stimulation target, a muscular
twitch or an illusory flash of light in the participant's vision. One
option for creating a sham condition is to use a "sham coil" which
reproduces the clicking sound but does not reproduce the side-effects. If
an individual, na?ve participant does not participate in both active and
control arms of the study, it can usually be argued that the presence or
absence of side-effects does not give the participant enough information
to know which treatment they had received. However in the study by Arii et
al. [1], and in many other reported in the literature, the participants
crossed over so that each person experienced both conditions. This means
that each participant was able to compare their second treatment to their
first, so reducing the blinding. In the case of the study by Arii et al.,
we note first that their Table 2 suggests a tell-tale additional
improvement in the group that received real stimulation after sham, and
second that the authors do not report subjective comments from the
participants except that two participants experienced discomfort.
The poverty of the control arm in stimulation therefore introduces a
challenge when designing experiments and trials to use these techniques.
One solution, as we mentioned, might be to divide participants into groups
who separately receive either real or sham stimulation. Another solution
could be to introduce an alternative stimulation target which is
hypothesised not to be involved in the behaviour of interest, although we
note that this is a difficult and somewhat subjective alternative [3]. At
a more philosophical level it could also be argued that so-called 'non-
invasive' [4] techniques such as TMS and tCS are inherently imperfect for
creating control and blinding conditions in awake and aware participants,
and therefore to qualify any reported results by adding participants'
comments and other observations so the degree of unblinding can be
assessed.
In conclusion, we agree with the comments of Caslake [2] that proper
experimental science requires a proper experimental control, however it is
important to acknowledge that proper blinding is very difficult to achieve
in many situations. Our use of non-invasive stimulation requires an
ethical balance between the need to preserve the scientific integrity of
an experiment or trial, and the desire to advance treatments for
debilitating conditions. We therefore advocate a culture of open reporting
of all relevant circumstances in an experiment.
Dr Nick Davis, Swansea University, UK
Dr Martyn Bracewell, Bangor University, UK.
References
1. Arii Y, Sawada Y, Kawamura K, et al. Immediate effect of spinal
magnetic stimulation on camptocormia in Parkinson's disease. Journal of
Neurology Neurosurgery and Psychiatry 2014;85:1221-26 doi: 10.1136/jnnp-
2014-307651
.
2. Caslake R. Dif?culties with control arms in repetitive magnetic
stimulation studies. Journal of Neurology Neurosurgery and Psychiatry
2014;85:1182 doi: 10.1136/jnnp-2014-307906.
3. Davis N, Gold E, Pascual-Leone A, et al. Challenges of proper
placebo control for noninvasive brain stimulation in clinical and
experimental applications. European Journal of Neuroscience
2013;38(7):2973-77
4. Davis N, van Koningsbruggen M. 'Non-invasive' brain stimulation is
not non-invasive. Frontiers in Systems Neuroscience 2013;7:76 doi:
10.3389/fnsys.2013.00076.
We are pleased that Dr. Cyron agrees with our statement. Although our
meta-analysis revealed that depression was more frequent in STN DBS
relative to GPi DBS, additional randomized trials which investigate long-
term outcome including UPDRS, quality of life and adverse events are
required to determine which target is more appropriate for patients with
PD. We hope our findings and suggestions would be useful for future
stu...
We are pleased that Dr. Cyron agrees with our statement. Although our
meta-analysis revealed that depression was more frequent in STN DBS
relative to GPi DBS, additional randomized trials which investigate long-
term outcome including UPDRS, quality of life and adverse events are
required to determine which target is more appropriate for patients with
PD. We hope our findings and suggestions would be useful for future
studies which provide valuable evidence as meta-analyses helped to
establish various treatment options historically.
This is a timely contribution to an issue overdue. STN-stimulation
has been the undisputed mainstay of DBS for Pakinson's disease more than a
decade. Reports on deleterious side effects mainly in the field of
cognition and emotion however accumulate. While the rather subtle effects
on cognitive abilities have been the subject of a plethora of
publications, changes in personality and behavior remain underreported.
Yet it...
This is a timely contribution to an issue overdue. STN-stimulation
has been the undisputed mainstay of DBS for Pakinson's disease more than a
decade. Reports on deleterious side effects mainly in the field of
cognition and emotion however accumulate. While the rather subtle effects
on cognitive abilities have been the subject of a plethora of
publications, changes in personality and behavior remain underreported.
Yet it is these changes that can have catastrophic impacts on the
wellbeing of patients and their relatives. In my experience with GPI
stimulation behavior and mood are by far less affected or even improved.
In the light of these complications the advantage of greater reductions in
medication with STN stimulation appears less relevant. Depleting patients
of badly needed dopamin may even worsen axial symptoms, emotional state
and incentive.
I therefore strongly agree with the author's statement, that it is now
time to clarify this issue involving an appropriate number of patients.
I read with interest the review by Tada et al. [1], which, based on the current knowledge on the cerebellar systems, propose an interesting framework to interpret cerebellar ataxias in clinical settings. The Authors classify cerebellar ataxias into two main categories: those with a loss of Purkinje cells, translating into a malformation of internal models; and those with a disturbance of afferent systems, causing a mis- s...
We read the recently published UK guideline for treating myasthenia gravis (MG) patients in pregnancy with great interest [1]. As stated by the workgroup in their article, few studies are available concerning drug safety in pregnancy in these patients. In our experience, most drugs indeed carry a very small risk in the treatment of MG during pregnancy. However, based on additional literature we would advise some caution...
We thank Dr. Voci for his comments[1] on our article.[2] As described in the paper, our data comprise Hospital Episode Statistics (HES) obtained from the English national Health and Social Care Information Centre (HSCIC) and mortality record abstracts obtained from the Office for National Statistics. All data from both sources were anonymised to the same standard by encryption of personal identifiers before being supplied...
This is an interesting study. However, I am somewhat concerned whether the record linkage could be appropriately performed. In most healthcare information systems, HIV patients characteristics are protected. Did the authors have enough information on the patients to perform probabilistic matching? It would be of interest if the authors could show that the matching is adequate by showing that there is not a general reduce...
Professor Kawada expresses three concerns regarding the outcomes of our study into how cognitive deficits progress in the years following a stroke [1]. Firstly, he cites Rajan et al. [2] as finding that cognitive decline was greater after stroke than before stroke, and suggests that our study should have considered pre-stroke cognitive decline. How doing so would have affected our outcomes or their interpretation is uncle...
Sachdev et al. conducted a 3-year follow-up study to know the progress of cognitive deficits after stroke or transient ischemic attack (TIA) (1). The authors gathered 183 stroke/TIA patients and 97 healthy controls, and concluded that cognitive decline in post-stroke patients was not greater than in controls, except for verbal memory, although rates of incident dementia were 5.9% per year in patients and 0.4% in controls,...
I endorse the authors' use of multiple information sources to identify prevalent delirium in medical and surgical inpatients 1-2: family and other informants, junior and senior physicians, medical case notes and nurses. Although the authors did not use the model I developed, I suggest that their paper is about distinguishing rapid cognitive decline (RCD, one form being delirium) from slow cognitive decline (SCD) in dementia...
The JNNP recently published an interesting study which used magnetic stimulation to the spine of people with Parkinson's disease, and showed a promising improvement in camptocormia compared to a group receiving 'sham' stimulation [1]. In an Editorial Comment, Caslake [2] argued that the participants in this particular study may not have been sufficiently blinded as to the group to which they had been assigned. Although th...
We are pleased that Dr. Cyron agrees with our statement. Although our meta-analysis revealed that depression was more frequent in STN DBS relative to GPi DBS, additional randomized trials which investigate long- term outcome including UPDRS, quality of life and adverse events are required to determine which target is more appropriate for patients with PD. We hope our findings and suggestions would be useful for future stu...
This is a timely contribution to an issue overdue. STN-stimulation has been the undisputed mainstay of DBS for Pakinson's disease more than a decade. Reports on deleterious side effects mainly in the field of cognition and emotion however accumulate. While the rather subtle effects on cognitive abilities have been the subject of a plethora of publications, changes in personality and behavior remain underreported. Yet it...
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