We are grateful for the notificiation that restless legs syndrome
(RLS) has been found to be associated also with demyelinating neuropathies
other than CMT type 1. It would be interesting to further investigate the
putative association between RLS and sensory symptoms in the conditions Dr
Luigetti and Dr Della Marca mention in the response to our article. With
regard to the prevalence of RLS in patients with CMT1 we would...
We are grateful for the notificiation that restless legs syndrome
(RLS) has been found to be associated also with demyelinating neuropathies
other than CMT type 1. It would be interesting to further investigate the
putative association between RLS and sensory symptoms in the conditions Dr
Luigetti and Dr Della Marca mention in the response to our article. With
regard to the prevalence of RLS in patients with CMT1 we would like to
state that we found a prevalence of 40.9% in the study population (not
50%). In our study, diagnosis of RLS was only confirmed when all four
diagnostic criteria for RLS (proposed by Allen et al.)were met. Thus, over
-estimation of RLS frequency cannot be ascribed to diagnostic inaccuracy.
However, we already mentioned in our article that RLS prevalence was
unexpectedly high in our study which may be due to a selection of patients
with RLS during patient recruitment.
We read with great interest the paper by Boentert et al. [1]
regarding the prevalence of sleep disorders in Charcot-Marie-Tooth (CMT)
1A patients. The Authors found the presence of Restless Leg Syndrome (RLS)
in about 50% of patients with different forms of CMT, including CMT1A,
CMT1B and CMTX. Considering these results the Authors conclude that RLS is
highly prevalent not only in axonal subtypes of CMT but also in primari...
We read with great interest the paper by Boentert et al. [1]
regarding the prevalence of sleep disorders in Charcot-Marie-Tooth (CMT)
1A patients. The Authors found the presence of Restless Leg Syndrome (RLS)
in about 50% of patients with different forms of CMT, including CMT1A,
CMT1B and CMTX. Considering these results the Authors conclude that RLS is
highly prevalent not only in axonal subtypes of CMT but also in primarily
demyelinating subforms of CMT [2].
Our experience confirms a significant association of RLS with
demyelinating neuropathies including inflammatory neuropathies, as chronic
inflammatory demyelinating neuropathy (CIDP), or inherited neuropathy, as
CMT1A. We found the presence of RLS in 6/26 (23%) patients with CIDP and
4/14 (28%) patients with CMT1A (Luigetti et al., in press
http://www.aasmnet.org/jcsm/AcceptedPapers.aspx [3]). Interestingly, we
have not noted any significant association between RLS and hereditary
neuropathy with liability to pressure palsy (HNPP) that is another form of
demyelinating inherited neuropathy that shares a common genetic origin
with CMT1A, being caused by the deletion of the same region of chromosome
17 that is duplicated in CMT1A.
Probably in HNPP, where peripheral nerves are only more susceptible to
external noxious stimuli, the somato-sensory pathway is generally
preserved, thus explaining the absence of an increased prevalence of RLS
in this condition.
One major issue in evaluating the prevalence of RLS in neuropathies is the
tool used for the diagnosis. In their paper, Boentert et al. [1] applied
the criteria proposed by Allen et al. [4], even though the Authors do not
specify how many of the four requested criteria should be met to confirm
the diagnosis. In a previous paper, addressing the association between RLS
and neuropathies, different criteria were applied: i.e. Hattan et al. [5]
"considered any subject who responded positively to three of the four
questions to be screen-positive for RLS." The decision to assess RLS by
the presence of three rather than all four criteria can lead to over
esteem the prevalence of RLS in a cohort of neuropathic patients. Larger
multicenter studies, based on widely accepted diagnostic criteria, are
needed to evaluate the strength of the association between RLS and
neuropathies.
Marco Luigetti and Giacomo Della Marca.
Institute of Neurology, Catholic University of Sacred Heart, Rome-Italy
References
1) Boentert M, Knop K, Schuhmacher C, et al. Sleep disorders in
charcot-marie-tooth disease type 1. J Neurol Neurosurg Psychiatry 2013
2) Gemignani F, Marbini A, Di Giovanni G, et al. Charcot-marie-tooth
disease type 2 with restless legs syndrome. Neurology 1999;52:1064-6.
3) Luigetti M, Del Grande A, Testani E, et al. Restless leg syndrome
in different types of demyelinating neuropathies: A single-centre pilot
study. Journal of clinical sleep medicine : JCSM : official publication of
the American Academy of Sleep Medicine in press
4) Allen RP, Picchietti D, Hening WA, et al. Restless legs syndrome:
Diagnostic criteria, special considerations, and epidemiology. A report
from the restless legs syndrome diagnosis and epidemiology workshop at the
national institutes of health. Sleep Med 2003;4:101-19.
5) Hattan E, Chalk C, Postuma RB. Is there a higher risk of restless
legs syndrome in peripheral neuropathy? Neurology 2009;72:955-60.
We would like to thank Mr Rajendran his detailed and elaborate
comment regarding our trial on the initial monotherapy of epilepsy with
levetiracetam or lamotrigine (Rosenow et al JNNP 2012) . It is always a
good sign when a clinical study finds the interest not only of those
already actively contributing to a field of research but also of junior
colleagues which have not previously published in the area of clinical
epil...
We would like to thank Mr Rajendran his detailed and elaborate
comment regarding our trial on the initial monotherapy of epilepsy with
levetiracetam or lamotrigine (Rosenow et al JNNP 2012) . It is always a
good sign when a clinical study finds the interest not only of those
already actively contributing to a field of research but also of junior
colleagues which have not previously published in the area of clinical
epilepsy. It appears that Mr Rajendran misunderstood some of the data
presented by us especially regarding three major topics: 1) The number of
protocol violations and number of patients in the per protocol analysis
set, 2) the basics of hypothesis testing, and 3) the meaning of ITT and PP
analysis in clinical trial analysis. We would like to use the opportunity
to clarify these issues in a point by point fashion for him and the
interested readership of JNNP.
1) The number of protocol violations and number of patients in
the per protocol analysis set.
We frankly described in our article that the proportion of patients with
protocol violations was relatively high (about 40%). Unfortunately, Mr.
Rajendran mixed up the number of patients in our per protocol analysis
set: Levetiracetam, n=116 and Lamotrigine, n=129 with the number of
patients with protocol violations: Levetiracetam, n=90 (43.7%) and
Lamotrigine, n=74 (36.5%). Therefore, there were about 40% of protocol
violations and we did not reflect on the power.
2) The basics of hypothesis testing.
Hypothesis testing aims at refusing the nullhypothesis and as a result at
accepting the alternative hypothesis. We did not aim "to demonstrate that
the null hypothesis is indeed true" this would indeed by an unusual
approach. We summarised statistically correctly in our discussion that "we
found no significant differences between LEV and LTG".
3) The meaning of ITT and PP analysis in clinical trial
analysis.
We performed our primary analysis on the basis of the ITT-set and the PP-
set which is fully in accordance with ICH E9. Both analyses should be
performed, ?so that any differences between them can be the subject of
explicit discussion and interpretation" (ibid, S. 26). We did not find
differences between the results of the analyses and therefore, we drew the
conclusion that "it is unlikely, that the protocol violation rate did
influence the results of the primary endpoint". This interpretation is
much less assertive as Mr. Rajendran summarized our interpretation and
from our point of view it is fully justified by the results.
I would like to commend the authors on this informative review on the
utility of dopamine transporter SPECT in the diagnostic workup of
Parkinsonian syndromes. I acknowledge that this review is set in the
context of the labelled indications for DaTSCAN as outlined by the EMA and
FDA however from a pragmatic perspective I would like to highlight the
utility of dopamine transporter SPECT in differentiating drug-induced
Par...
I would like to commend the authors on this informative review on the
utility of dopamine transporter SPECT in the diagnostic workup of
Parkinsonian syndromes. I acknowledge that this review is set in the
context of the labelled indications for DaTSCAN as outlined by the EMA and
FDA however from a pragmatic perspective I would like to highlight the
utility of dopamine transporter SPECT in differentiating drug-induced
Parkinsonism from Idiopathic Parkinson's disease (or other
neurodegenerative Parkinsonian syndromes) where diagnostic uncertainty
exists. Phenomenology can be unrewarding when trying to differentiate
drug-induced Parkinsonism, a common cause of Parkinsonism in the elderly,
from Idiopathic Parkinson's disease. The presence of normal dopamine
transporter SPECT imaging can be reassuring for both the clinician and the
patient when confirming a drug-induced aetiology (1). An important caveat
however is that dopamine antagonists and related agents can unmask
incipient Parkinson's disease thus regular examination and followup remain
perhaps the most important tools in the investigation of Parkinsonism.
Reference:
1. Cummings JL, Henchcliffe C, Schaier S et al. The role of
dopaminergic imaging in patients with symptoms of dopaminergic system
neurodegeneration. Brain 2011: 134; 3146-3166.
OLD IS STILL GOOD IF NOT GOLD
The review article on use of aspirin for acute migraine headaches in
adults and an editorial on the same is worth appreciation and is an
excellent documentations, specially for poor patients of third world
countries. Of course the authors have revised and given the message
through an esteemed journal to the neurologists in particular...
OLD IS STILL GOOD IF NOT GOLD
The review article on use of aspirin for acute migraine headaches in
adults and an editorial on the same is worth appreciation and is an
excellent documentations, specially for poor patients of third world
countries. Of course the authors have revised and given the message
through an esteemed journal to the neurologists in particulars and
physicians and general practitioners in general. The standard texts are
already full of such information i.e. aspirin and acetaminophen is
considered superior to simple analgesics1. Aspirin is useful in mild form
of head pain, alone or in combination with acetaminophen or caffeine, and
may prevent migraine if taken in effervescent or soluble form early in the
attack after a drug to promote gastric absorption, such as
metoclopramide2. There are combinations of paracetamol in Indian market
like domcet and grenil but there is also need of the combination of
aspirin along with domperidone and proton pump inhibitoer or ranitidine,
for prompt absorption and avoid gastric irritation respectively, which at
times can be lethal, and also to promote empty stomach ingestion if
required as patient may be in agony to avoid food intake. Regarding the
mechanism of aspirin it helps in prevention of neurogenic
extravasation2.Aspirin can be an effective agent in migraine, providing it
can be adequately absorbed, which can be done with metoclopramide.
Intravenous aspirin has been used in Japan and Europe for headaches and
facial pains3. Aspirin has also been used as prophylaxis, where it was
found to be 20% superior to placebo, which effect is of course modest but
significant4. Episodic tension headaches also often respond promptly to
aspirin or acetaminophen2. Since approximately half of migraine sufferers
are undiagnosed, it is reasonable to conclude that majority of migraine
attacks are treated solely with analgesics such as acetaminophen, aspirin
(dose being 650-1000mg) or non-steroidal anti-inflammatory drugs5. So
aspirin or acetaminophen have been used in migraine for over 50 years and
probably remain the drugs used most frequently in acute therapy5,6.
REFERENCES-
1. Stephen D. Silberstein, Fredrerich G., Freitag, Marcelo E. Bigal.
Migraine treatment in "Wolff's Headache and other Head Pains". Indian
Edition (Editors Stephen D Silberstein, Richard B Lipton, David W Dodick)
Oxford University Press 2008;203-204.
2. James W. Lange, Peter J. Goadsby. Mechanism and Management of Headache.
7th Edition. Publisher Butterworth- Heinemann. First Indian Reprint 2005
; page 31, 136, 100, 175.
3. Fukuda Y and Izumikawa. Intravenous aspirin for intractable headache
and facial pain. Headache, 1988; 28: 47-50.
4. Buring J. E. ,Peto R.,Hennekens and C. H. Low dose aspirin for migraine
prophylaxis JAMA 1996; 264: 1711-1713.
5.-Stephen J. Peroutka, Migraine in; Principles of drug therapy in
neurology. 2nd Edition(Indian edition); editors- Michael J. Johnston and
Robert A. Gross. Oxford university press 2008, Reprinted 2010; 161-164.
6. Limmroth Katsarava Z., Diener H.C. Acetyle salicylic acid in treatment
of headache. Cephalgia 1999; 19: 545-551.
Introduction-
We read the article written by Garcin et al. (4) about transcranial
magnetic stimulation (TMS) as an efficient treatment for psychogenic
movement disorders (PMD) with great interest. The authors report the
efficacy of TMS on 24 adult patients with chronic PMD. Twenty low
frequency stimuli were delivered over the motor cortex with a circular
coil. The authors observed an immediate significant improvement in...
Introduction-
We read the article written by Garcin et al. (4) about transcranial
magnetic stimulation (TMS) as an efficient treatment for psychogenic
movement disorders (PMD) with great interest. The authors report the
efficacy of TMS on 24 adult patients with chronic PMD. Twenty low
frequency stimuli were delivered over the motor cortex with a circular
coil. The authors observed an immediate significant improvement in 75% of
patients treated with complete resolution in a third of these patients. We
would like to relate our similar experience with TMS for patients with
PMD.
Patients and methods-
We retrospectively reviewed the medical records of 19 patients (14
females, 5 males) with PMD who received TMS in Rouen University Hospital's
Neurophysiology Department between January 2004 and September 2010.
Average age was 29.7 +- 15.3 years (mean +- SD, min-max: 8-61 years).
Symptoms were tremor (n=10), myoclonia (n=5), or dystonia (n=4). Movement
disorders affected either one upper limb (n=10), one lower limb (n=3),
both upper limbs (n=1), both lower limbs (n=2), the face (n=2), or
hemibody (n=1). Median symptom duration at the time of consultation was 21
days (min-max: 1-2000). Symptoms were acute (<30 days) in 12 patients,
subacute (between 30 days and 6 months) in 3 patients, or chronic (>6
months) in 4 patients.
Thirty stimuli were delivered over the motor cortex (contralaterally to
symptoms or bilaterally in case of bilateral movement disorders), with a
circular coil at low frequency (0.2 Hz) with a maximum intensity of 2.5
Tesla. If symptoms persisted 2 days after the first treatment (n=3), a
second stimulation session was carried out between the 2nd and 7th days
using the same parameters. The diagnosis of PMD which presents as a
neurologic disease but without any organic damage to the nervous system
was explained to each patient. TMS efficacy was classified in two groups
according to subjective evaluations realized by both the patient and the
neurologist: Patients were classified in the "effective" group if recovery
was complete or if the patient presented a dramatic improvement and in the
"ineffective" group if mild or no improvement was observed. The local
ethics committee approved this retrospective study.
Results-
TMS was effective in 95% of the 19 patients with PMD. A complete recovery
was observed in 15 patients (79%). Ten patients recovered immediately
after TMS, 2 patients recovered almost immediately after TMS (within a few
minutes or hours, but less than 24 hours), and 3 patients recovered after
the second TMS session. TMS was ineffective in 1 patient, a 49-year-old
woman with a right-hand tremor that had appeared after an armed robbery
three years earlier.
No side effects were noted. The initial symptoms recurred in 4 patients:
One patient experienced a single recurrence of her PMD one month after
treatment. Three patients had multiple recurrences between one month and
one year after treatment. TMS was once again used to treat these
recurrences and was immediatly and entirely effective for all recurrences.
At least one precipitating event was identified in 12 patients. Nine
patients described precipitating events that were psychosocial in nature
(work-related stress, personal conflict, the death of family member). A
physically traumatic event in the affected limb occured in 4 patients,
and, in 2 of these patients, the injury was considered particularly minor.
No precipitating event was found in 7 patients. Seven patients had
psychiatric comorbidities such as anxiety and depressive disorders.
Discussion-
We find TMS to be effective in treating PMD, confirming the results of
Garcin et al. (4). We observed a much higher response rate among our
patients, but this was to be expected as very few chronic patients were
included (4 patients) in our study. In the study of Garcin et al., the
population was composed solely of chronic patients who are thought to be
more difficult to treat. Treatment is less effective the later it is
implemented, suggesting that PMD should be diagnosed and treated as
quickly as possible (5). Dafotakis et al. found that tremor decreased in
11 patients with psychogenic tremor after one TMS session with similar
parameters, but Dafotakis et al. used a figure-eight coil for their
protocol (3). The two techniques differ in terms of the stimulated
cortical volume. (A circular coil stimulates a larger cortical volume than
a figure-eight coil.)
The TMS procedure used in our protocol (the same as that of Garcin et
al.(4)) has proven to be safe in other psychogenic disorders (1,2).
Our TMS procedure is widely available since even modest neurophysiology
departments have a circular coil on hand that is used for motor evoked
potentials.
The efficacy mechanisms of TMS stimulation are unknown. One possible
explanation is that TMS stimulation modifies cortical excitability or
connectivity. A small number of stimuli applied with a figure-eight coil
are known to not modify cortical excitability, but the studies that
illustrate this lake of modification were not done with a circular coil.
In addition, a placebo effect cannot be ruled out. A multicentric
randomized controlled trial versus placebo is ongoing (NCT01352910) to
measure the importance of the placebo effect.
Conclusion-
A majority of patients with PMD recover following transcranial magnetic
stimulation suggesting that TMS should be used in PMD.
The Authors are to be applauded for highlighting the benefits of
aspirin in the treatment of migraine. It would be a major step forward for
migraine sufferers were they to be treated with aspirin or triptans in the
emergency department, rather than paracetamol, codeine or other opiates as
is frequently the case. The use of such drugs, all relatively useless in
migraine, delays the effective management of pai...
The Authors are to be applauded for highlighting the benefits of
aspirin in the treatment of migraine. It would be a major step forward for
migraine sufferers were they to be treated with aspirin or triptans in the
emergency department, rather than paracetamol, codeine or other opiates as
is frequently the case. The use of such drugs, all relatively useless in
migraine, delays the effective management of pain and delays discharge.
However, most neurologists offer slightly different advice to that of
the authors: we prefer domperidone rather than the centrally-acting
antiemetic metoclopramide.
Introduction-
We read the article written by Garcin et al. (4) about transcranial
magnetic stimulation (TMS) as an efficient treatment for psychogenic
movement disorders (PMD) with great interest. The authors report the
efficacy of TMS on 24 adult patients with chronic PMD. Twenty low
frequency stimuli were delivered over the motor cortex with a circular
coil. The authors observed an immediate significant improvement in...
Introduction-
We read the article written by Garcin et al. (4) about transcranial
magnetic stimulation (TMS) as an efficient treatment for psychogenic
movement disorders (PMD) with great interest. The authors report the
efficacy of TMS on 24 adult patients with chronic PMD. Twenty low
frequency stimuli were delivered over the motor cortex with a circular
coil. The authors observed an immediate significant improvement in 75% of
patients treated with complete resolution in a third of these patients. We
would like to relate our similar experience with TMS for patients with
PMD.
Patients and methods-
We retrospectively reviewed the medical records of 19 patients (14
females, 5 males) with PMD who received TMS in Rouen University Hospital's
Neurophysiology Department between January 2004 and September 2010.
Average age was 29.7 +- 15.3 years (mean +- SD, min-max: 8-61 years).
Symptoms were tremor (n=10), myoclonia (n=5), or dystonia (n=4). Movement
disorders affected either one upper limb (n=10), one lower limb (n=3),
both upper limbs (n=1), both lower limbs (n=2), the face (n=2), or
hemibody (n=1). Median symptom duration at the time of consultation was 21
days (min-max: 1-2000). Symptoms were acute (<30 days) in 12 patients,
subacute (between 30 days and 6 months) in 3 patients, or chronic (>6
months) in 4 patients.
Thirty stimuli were delivered over the motor cortex (contralaterally to
symptoms or bilaterally in case of bilateral movement disorders), with a
circular coil at low frequency (0.2 Hz) with a maximum intensity of 2.5
Tesla. If symptoms persisted 2 days after the first treatment (n=3), a
second stimulation session was carried out between the 2nd and 7th days
using the same parameters. The diagnosis of PMD which presents as a
neurologic disease but without any organic damage to the nervous system
was explained to each patient. TMS efficacy was classified in two groups
according to subjective evaluations realized by both the patient and the
neurologist: Patients were classified in the "effective" group if recovery
was complete or if the patient presented a dramatic improvement and in the
"ineffective" group if mild or no improvement was observed. The local
ethics committee approved this retrospective study.
Results-
TMS was effective in 95% of the 19 patients with PMD. A complete recovery
was observed in 15 patients (79%). Ten patients recovered immediately
after TMS, 2 patients recovered almost immediately after TMS (within a few
minutes or hours, but less than 24 hours), and 3 patients recovered after
the second TMS session. TMS was ineffective in 1 patient, a 49-year-old
woman with a right-hand tremor that had appeared after an armed robbery
three years earlier.
No side effects were noted. The initial symptoms recurred in 4 patients:
One patient experienced a single recurrence of her PMD one month after
treatment. Three patients had multiple recurrences between one month and
one year after treatment. TMS was once again used to treat these
recurrences and was immediatly and entirely effective for all recurrences.
At least one precipitating event was identified in 12 patients. Nine
patients described precipitating events that were psychosocial in nature
(work-related stress, personal conflict, the death of family member). A
physically traumatic event in the affected limb occured in 4 patients,
and, in 2 of these patients, the injury was considered particularly minor.
No precipitating event was found in 7 patients. Seven patients had
psychiatric comorbidities such as anxiety and depressive disorders.
Discussion-
We find TMS to be effective in treating PMD, confirming the results of
Garcin et al. (4). We observed a much higher response rate among our
patients, but this was to be expected as very few chronic patients were
included (4 patients) in our study. In the study of Garcin et al., the
population was composed solely of chronic patients who are thought to be
more difficult to treat. Treatment is less effective the later it is
implemented, suggesting that PMD should be diagnosed and treated as
quickly as possible (5). Dafotakis et al. found that tremor decreased in
11 patients with psychogenic tremor after one TMS session with similar
parameters, but Dafotakis et al. used a figure-eight coil for their
protocol (3). The two techniques differ in terms of the stimulated
cortical volume. (A circular coil stimulates a larger cortical volume than
a figure-eight coil.)
The TMS procedure used in our protocol (the same as that of Garcin et
al.(4)) has proven to be safe in other psychogenic disorders (1,2).
Our TMS procedure is widely available since even modest neurophysiology
departments have a circular coil on hand that is used for motor evoked
potentials.
The efficacy mechanisms of TMS stimulation are unknown. One possible
explanation is that TMS stimulation modifies cortical excitability or
connectivity. A small number of stimuli applied with a figure-eight coil
are known to not modify cortical excitability, but the studies that
illustrate this lake of modification were not done with a circular coil.
In addition, a placebo effect cannot be ruled out. A multicentric
randomized controlled trial versus placebo is ongoing (NCT01352910) to
measure the importance of the placebo effect.
Conclusion-
A majority of patients with PMD recover following transcranial magnetic
stimulation suggesting that TMS should be used in PMD.
References-
1. Chastan N, Parain D: Psychogenic paralysis and recovery after
motor cortex transcranial magnetic stimulation. Mov Disord 25:1501-1504,
2010
2. Chastan N, Parain D, Verin E, et al: Psychogenic aphonia: spectacular
recovery after motor cortex transcranial magnetic stimulation. J Neurol
Neurosurg Psychiatry 80:94, 2009
3. Dafotakis M, Ameli M, Vitinius F, et al: [Transcranial magnetic
stimulation for psychogenic tremor - a pilot study]. Fortschr Neurol
Psychiatr 79:226-233, 2011
4. Garcin B, Roze E, Mesrati F, et al: Transcranial magnetic stimulation
as an efficient treatment for psychogenic movement disorders. J Neurol
Neurosurg Psychiatry
5. Gupta A, Lang AE: Psychogenic movement disorders. Curr Opin Neurol
22:430-436, 2009
We would like to share several observations that we made on Ammirati
et al.[1] recently published meta-analysis. The authors reviewed the
available English-language literature from 1990 to the present, comparing
microsurgery versus endoscopy for treatment of pituitary adenomas, and
conducted a systematic review and meta-analysis of the data obtained. The
authors concluded that the two treatment methods produced similar...
We would like to share several observations that we made on Ammirati
et al.[1] recently published meta-analysis. The authors reviewed the
available English-language literature from 1990 to the present, comparing
microsurgery versus endoscopy for treatment of pituitary adenomas, and
conducted a systematic review and meta-analysis of the data obtained. The
authors concluded that the two treatment methods produced similar
outcomesfor all of the variables analyzed, except for a statistically
significant higher rate of vascular complications with endoscopy. We want
to point out that endoscopy-assisted studies were included in the
microsurgery cohort, including most notably a study by Mortini et al.[2]
involving 1140 patients,which represented 32.4% of all of the microsurgery
cases and thus was weighted heavily in the analysis. The use of
intraoperative endoscopy after microscopic resection provides the
advantages of endoscopic procedures, such as better visualization of
structures and of lateral and suprasellar limits, as well as
differentiation between normal and diseased tissue. Inclusion of these
patients introduces significant bias, strongly favoring microsurgery by
giving it the advantages of endoscopy, and complicating a comparison
between the two methods. Additionally, the variety of complications that
were grouped together as vascular complications was highly heterogeneous,
encompassing carotid lesions, lesions in less important vessels like the
sphenopalatine artery, intracranial or sellar hemorrhages, ischemic
infarcts, and cavernous sinusbleeding. While all of these complications
are of a vascular nature, theircharacteristics and the resulting
morbidity/mortality can be quite different. The limitations of
microsurgery for treatment of significant invasions into the cavernous
sinus are well known. Thus, when approaching an invasive cavernous sinus
adenoma endoscopically for treatment, as in the study by Zhang et al.[3],
consideration of vascular complications from cavernous sinus bleeding is
not comparable to microsurgical approach caseswhere there was no initial
intention to treat invasive cavernous sinus tumors. Moreover, based on
available data, we can only be certain that 57,6% (2027/3518) of the
microscopic patients were macroadenomas, whereas 77% (1453/1887) of the
cases were macroadenomas in the endoscopic cohort. This heterogeneous
distribution of patients for something as fundamental as differentiation
between micro and macroadenomas could have influenced the meta-analysis
results, especially the observed rates of complete resection, vascular
complications and csf leak. It is also worth noting that of the 22
microsurgery studies included, only 12 had data on vascular complications,
whereas 17/24 endoscopic studies had such data. Meta-analysis variable
data are collected more frequently, in general, in endoscopic studies than
in microsurgery studies.As for the meta-analysis methodology, depending on
the heterogeneity between studies, fixed effect models or randomized
models were applied. Randomized models provide more conservative estimates
than fixed effect models, and therefore are more apt to miss existing
differences. These methods were used to compare ratesof diabetes
insipidus, hypopituitarism, and complete resection. All trended toward
favoring the endoscopy group, but without statistical significance. Death
rates for the microsurgery and endoscopy cohorts were 0.23% and 0.49%, csf
leak 6.34 vs 7%, meningitis 2,08 vs 1.11%, vascular complication 0.5 vs
1.58%, visual loss 0.60 vs 0.72%, diabetes insipidus temporary 10.23 vs
9.10% and permanent 4.25 vs 2.31%, hypopituitarism 11,64 vs 8.51%, nerve
injury 0.53 vs 0.28% and complete resection 64.44 vs 68.77% respectively.
When we evaluated surgeons with more than 500 microsurgeries from the
study by Ciric et al.[4], the death rate was 0.2%, csf leak 1.5%,
meningitis 0.5%, vascular complication (carotid artery injury +
hemorrhage residual tumor) 1.2%, visual loss 0.5%, diabetes insipidus
7.6%, hypopituitarism 7.2%. Thus, with respect to vascular complications,
death, diabetes insipidus, and hypopituitarism, the microsurgery group
turned out to be a select group of patients with results superior to those
obtained by highly experienced microsurgery specialists. This result could
be due to many reasons, such as those suggested above, including: a series
of patients with a high incidence of microadenomas; inclusion of endoscopy
-assisted cases in the microsurgery group; the long tradition and
evolution of microsurgery since the 1950s versus the recent history of
purely endoscopic techniques (first series reported in 1997); and the
significant experience of microscopic surgeons whose numerous studies
populated the meta-analysis. There were two microsurgery studies, which
described sets of 1140 and 638 patients; meanwhile,eight microsurgery
studies described the treatment of only functional tumors, and six of the
reviewed studies included more than 50 acromegalies or Cushing's syndrome
cases, implying that the surgeons in question treated a significant number
of adenomas. On the other hand, only one endoscopic study had more than
200 patients. If we compare the group of surgeons with less than 200
microscopic surgeries from the study by Ciric et al.[4] (results: death
rate 1.2%, csf leak 4.2%, meningitis 1.9%, vascular complication 4.2%,
visual loss 2.4%, diabetes insipidus 19%, hypopituitarism 20,6%), with
the metaanalisis endoscopic group, results strongly favor endoscopy.
Nevertheless, the rates of complete resection, hypopituitarism, diabetes
insipidus, meningitis, and nerve damage were all better for patients
treated purely endoscopically, although without statistical significance.
The authors of the review study criticize prior meta-analyses for being
biased toward endoscopy based solely on the argument of fewer included
patients; but they did not take into account their own inclusion criteria,
which were more restrictive, considering only studies comparing both
techniques, but not those using endoscopy-assisted microsurgery or those
without complete outcomes that would enablebetter data interpretation and
more solid and reliable results. In short, reading this study in isolation
can lead to erroneous conclusions given the aforementioned biases and
limitations.
Reference
1. Ammirati M, Wei L, Ciric I. Short-term outcome of endoscopic versus
microscopic pituitary adenoma surgery: a systematic review and meta-
analysis. J Neurol Neurosurg Psychiatry. Published Online First: 15
December 2012 doi:10.1136/jnnp-2012-303194.
2. Mortini P, Losa M, Barzaghi R, et al. Results of transsphenoidal
surgery in a large series of patients with pituitary adenoma. Neurosurgery
2005;56:1222-33.
3. Zhang X, Fei Z, Zhang W, et al. Endoscopic endonasal transsphenoidal
surgery for invasive pituitary adenoma. J Clin Neurosci 2008;15:241-5.
4. Ciric I, Ragin A, Baumgartner C, et al. Complications of
transsphenoidal surgery: results of a national survey, review of the
literature, and personal experience. Neurosurgery 1997;40:225-37.
We thank Dr. Juan A Simal-Julian and collaborators (1) for their
interest in our paper (2). We also appreciate the commentaries of Drs.
Oldfield and Jane jr (3), Laws (4) and Warnke (5).
We will first address the letter of Dr. Simal-Julian and then will
offer a few words on the commentaries of Drs. Oldfield and Jane jr, Laws
and Warnke.
Mortini et al (6) use the microscope to remove the adenoma via a s...
We thank Dr. Juan A Simal-Julian and collaborators (1) for their
interest in our paper (2). We also appreciate the commentaries of Drs.
Oldfield and Jane jr (3), Laws (4) and Warnke (5).
We will first address the letter of Dr. Simal-Julian and then will
offer a few words on the commentaries of Drs. Oldfield and Jane jr, Laws
and Warnke.
Mortini et al (6) use the microscope to remove the adenoma via a sub
labial trans-septal avenue. This is the classic microscopic approach for
the removal of pituitary adenoma.
The word endoscope does not appear in the key words and, in a 12 page long
paper containing more than 6,000 words, is mentioned only once in the
following paragraph "After the removal of large macro adenomas and
completion of hemostasis, the inspection of the intrasellar space is
carried out using rigid endoscop 4-mm in diameter with 0- and 30- degree
lenses (Karl Storz, Tuttlingen, Germany)" (6). We really do not think
that the Mortini's paper may be accurately characterized as endoscopic
assisted. The readers may make their own judgment.
Regarding vascular complications we included "...carotid or other vessels
injury, intracerebral hematoma, or any symptomatic intratumoral or
intrasellar hemorrhage. Venous bleeding from the cavernous sinus was
tabulated as a vascular complication (only) when it prevented the
completion of the surgical procedure. Epistaxis was not included among the
vascular complications" (2). We feel that this is a reasonable list of
vascular complications. Spheno-palatine artery injury, contrary to what
our colleagues state, was not tabulated as vascular complication even when
it required treatment be it cauterization or packing, because we
recognized that this is often, but not always, a minor complication. Again
the readers may make their own judgment.
We looked at the relationship between the tumor size in the endoscopic or
microscopic group and the vascular injury rate and we commented on that
"Furthermore the macro tumors or the extent of complete tumor resection, 2
variables that could have affected the vascular complication rate, were
found to be not statistically significant in the endoscopic or microscopic
series reporting vascular complications (p=0.24 and 0.10 for macro tumor
size and complete resection respectively)"(2)
The methodology we used was the same used by Tabaee et al (7)in a widely
quoted paper on endoscopic pituitary surgery "Tabaee et al have used
this methodological approach in 2009 when reviewing endoscopic pituitary
surgery." (2)
We agree with Drs. Oldfield and Jane (3) that there might be
indications where one or the other technique has superior results,
everything else being equal; we also agree with their statement that we
should identify these indications.
As we said in our paper ,quoting a source8 that has nothing to do with
endoscopic/microscopic pituitary surgery, the majority of surgical
innovations are incremental and are " ...prone to overoptimistic
assessments by their developers and ,therefore, need controlled
randomized studies, when possible" (2).
We disagree with Dr. Laws (4) that we denigrate endoscopic pituitary
surgery; on the contrary by trying to define what is that new
technologies/new processes bring to the fore we make them , in the long
term, more sustainable. Indeed we use endoscopy to deal with extradural
cranial base lesions and often inspect the resection cavity with
endoscopes after microsurgical removal of pituitary adenomas. It is
conceivable that in the medium term we, doctors and health care
organizations, will be reimbursed for the use of new technology/processes
only when the advantages associated with them are clearly evident and
measurable. So we agree with Dr. Warnke (5) that " ...if we want to
establish new techniques and get funding for its use: sound randomized
controlled trials with appropriate primary and secondary outcome measures"
(5) are sorely needed.
In summary, our paper is not pro or against anything but serves, we hope,
to remind us that we need to get better at how we introduce new
technology/processes, especially when any improvement might be at the
margins. We wish more attention would have been paid to the perspective
section of our contribution. The general concept of how we introduce
surgical innovations is, in our opinion, a progressive concept , not a
regressive or a naysayer posture and it is extremely relevant to the
whole field of surgery/neurosurgery.
References
1. Simal-Julian JA, Miranda-Lloret P, Perez-Borreda P et al: Microscopy
versus endoscopy in pituitary surgery. J Neurol Neurosurg Psychiatry.
Published Online First:January 18-2013
2. Ammirati M, Wei L, Ciric I. Short-term outcome of endoscopic versus
microscopic pituitary adenoma surgery: a systematic review and
metaanalysis.?J Neurol Neurosurg Psychiatry. Published Online First: 15
December 2012 doi:10.1136/jnnp-2012-303194
3. Oldfield EH, Jane JA Jr: Endoscopic versus microscopic pituitary
surgery. J Neurol Neurosurg Psychiatry. Published Online First: 23 January
2013 doi:10.1136/ jnnp-2012-304583
4. Laws ER. Complications of transsphenoidal surgery: the shortcomings of
meta-analysis. J Neurol Neurosurg Psychiatry. Published Online First: 16
February 2013 doi:10.1136/jnnp-2012-304541
5. Warnke P: Case series analysis, meta-analysis or no analysis in the
evaluation of neurosurgical techniques: get better or get out J Neurol
Neurosurg Psychiatry. Published Online First: March 5, 2013 doi:10.1136/
jnnp-2013-305130
6. Mortini P, Losa M, Barzaghi R et al. Results of transsphenoidal surgery
in a large series of patients with pituitary adenoma. Neurosurgery 2005;
56:1222-33
7. Tabaee A, Anand VK, Barron Y, et al. Endoscopic pituitary surgery: a
systematic review and meta-analysis. J Neurosurg 2009;111:545-54
8. McCulloch P, Altman DG, Campbell WB et al No surgical innovation
without evaluation: the IDEAL recommendations. Lancet 2009;374:1105-12
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We thank Dr. Juan A Simal-Julian and collaborators (1) for their interest in our paper (2). We also appreciate the commentaries of Drs. Oldfield and Jane jr (3), Laws (4) and Warnke (5).
We will first address the letter of Dr. Simal-Julian and then will offer a few words on the commentaries of Drs. Oldfield and Jane jr, Laws and Warnke.
Mortini et al (6) use the microscope to remove the adenoma via a s...
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