I have read with interest the article written by Finsterer et al.
However, I do have several concerns and remarks in relation to it.
First, the authors describe a stenotic lesion at the L-ICA that I do not
actually see in the diagnostic angiogram. Moreover, this lesion was
treated wih a stent-graft.
Second, the image of the R-ICA corresponds to a classic carotid artery
dissection, probabl...
I have read with interest the article written by Finsterer et al.
However, I do have several concerns and remarks in relation to it.
First, the authors describe a stenotic lesion at the L-ICA that I do not
actually see in the diagnostic angiogram. Moreover, this lesion was
treated wih a stent-graft.
Second, the image of the R-ICA corresponds to a classic carotid artery
dissection, probably related to a minor trauma (abortion is referred in
the text, thus consider intubation, cervical hyperextention, coughing,
vomiting as etiological factors). The clinical presentation is classic of
a repetitive embolic phenomena.
Third, The pattern of fibromuscular dyaplasia is questionable.
Fourth, I do not agree with the implantation of stent graft for a disease
that can be easily managed with self expandable bare stents.
And last, the cervical surgical access to the carotid artery in order to
implant a stent in a young patient (straightforward arteries)seems
uneccessary when compared to the endovascular transfemoral route has been
the route of choice for years.
We thank Dr Celio Levyman for his supportive comments.[1]
We fully agree
with him that, in patients with baroreflex failure, it is necessary to
adopt approaches to combat orthostatic hypotension without increasing
supine hypertension. It is also important to follow up an open study with
a blinded study. We expect to complete, within the next month, a double-
blind placebo controlled study, funded by...
We thank Dr Celio Levyman for his supportive comments.[1]
We fully agree
with him that, in patients with baroreflex failure, it is necessary to
adopt approaches to combat orthostatic hypotension without increasing
supine hypertension. It is also important to follow up an open study with
a blinded study. We expect to complete, within the next month, a double-
blind placebo controlled study, funded by NIH, on this subject. The study
has 4 arms: pyridostigmine; pyridostigmine + subthreshold dose of
midodrine (2.5 mg); and pyridostigmine + low dose (5 mg) midodrine;
placebo, in the treatment of neurogenic orthostatic hypotension.
Reference
(1) Levyman C. A new light to orthostatyc hypotension [electronic response to Singer et al Acetylcholinesterase inhibition: a novel approach in the treatment of neurogenic orthostatic hypotension] jnnp.com 2003http://jnnp.bmjjournals.com/cgi/eletters/74/9/1294#68
The issue of orthostatic hypotension is a very common an important
diseable picture of many diseases, as Singer et al. points. Parkinson
disease and diabetic neuropathy are the most common clinical situation of
these cases, and even the very well controlled patient, with tilt-test
table measures to the choice of therapeutic strategies in most cases shows
frustanting results.
The issue of orthostatic hypotension is a very common an important
diseable picture of many diseases, as Singer et al. points. Parkinson
disease and diabetic neuropathy are the most common clinical situation of
these cases, and even the very well controlled patient, with tilt-test
table measures to the choice of therapeutic strategies in most cases shows
frustanting results.
This novel approach, with pyridostigmine, in this open study, is a
very important way to enlight the paths of this cases:I have used the
similar approach in a few patients, with all methods of observation and
control of side effects, and the results were similar of the paper
presented.
We need more research like those, with well-designed statistical and
evidence-based sources, to prescribe acetylcholinesterase inibition as the
prime indication.
Of course, this paper open a novel view of treatment of this kind of
hypotension, perhaps with other measures and/or drugs.
As it is well known, endorphin levels change in different circumstances, for example, in injury, illness, or as a result of circadian influences, among
others.[1-7] It would be helpful to know which was the primary stimulus for
endorphin level changes in MS patients. Perhaps a further experiment can
show that it is or is not circadian.
As it is well known, endorphin levels change in different circumstances, for example, in injury, illness, or as a result of circadian influences, among
others.[1-7] It would be helpful to know which was the primary stimulus for
endorphin level changes in MS patients. Perhaps a further experiment can
show that it is or is not circadian.
References
(1) Covelli V,
Massari F, Fallacara C, Munno I, Jirillo E, Savastano S,
Tommaselli AP, Lombardi G. Interleukin-1
beta and beta-endorphin circadian rhythms are inversely
related in normal and stress-altered sleep.
Int J Neurosci. 1992 Apr;63(3-4):299-305.
(2) Iranmanesh A,
Lizarralde G, Johnson ML, Veldhuis JD. Circadian,
ultradian, and episodic release of beta-endorphin in men,
and its temporal coupling with cortisol.J Clin
Endocrinol Metab. 1989 Jun;68(6):1019-26.
(3) Sekiya K, Nawata H, Kato K, Motomatsu T,
Ibayashi H. Diurnal rhythms of
proopiomelanocortin-derived N-terminal peptide,
beta-lipotropin, beta-endorphin and adrenocorticotropin in
normal subjects and in patients with Addison's disease and
Cushing's disease. Endocrinol Jpn. 1986 Oct;33(5):713-9.
(4) Melmed S. Series Introduction: The immuno-neuroendocrine interface. J Clin Invest, December 2001, Volume 108, Number 11, 1563-1566
(5) Barreca T, Siani C, Franceschini R, Francaviglia N, Messina
V, Perria C, Rolandi E. Diurnal beta-endorphin changes in human cerebrospinal fluid. Life Sci. 1986 Jun 16;38(24):2263-7.
(6) Shanks MF, Clement-Jones V, Linsell
CJ, Mullen PE, Rees LH, Besser GM. A study of 24-hour profiles of plasma
met-enkephalin in man. Brain Res. 1981 May 18;212(2):403-9.
(7) Gil-Ad I, Dickerman Z, Amdursky S, Laron Z.
Diurnal rhythm of plasma beta endorphin, cortisol and growth
hormone in schizophrenics as compared to control subjects.
Psychopharmacology (Berl). 1986;88(4):496-9.
We read with interest the letter by Dr Gupta on our paper entitled
“A diffusion tensor magnetic resonance imaging study of brain tissue from
patients with migraine”.[1] Nevertheless, we believe that he missed the main
result of this study as well as the scope for which it was designed and
conducted. The aim of this study was to investigate whether occult’ tissue
damage, which goes undetected when usin...
We read with interest the letter by Dr Gupta on our paper entitled
“A diffusion tensor magnetic resonance imaging study of brain tissue from
patients with migraine”.[1] Nevertheless, we believe that he missed the main
result of this study as well as the scope for which it was designed and
conducted. The aim of this study was to investigate whether occult’ tissue
damage, which goes undetected when using conventional MRI, could be
detected in patients with migraine, as it is the case in many other
neurological conditions.[2] The main result was that such changes do indeed
occur in the normal-appearing brain tissue (NABT) of these patients (and, to the best of our knowledge, this is the first time that such a finding
has been shown). Clearly, this sets up the stage for future research,
which might put these observations in a clinical perspective, but this was
not (and could not be) the aim of a preliminary study which has first to
show that these NABT abnormalities do exist in patients with migraine.
Against this background, we can now consider the specific points
raised by Dr Gupta. 1. NABT changes and laterality of headache. We understand the enthusiasm
of Dr. Gupta for his own work, but we have difficulties in understanding
how “more definitive clinico-pathological correlation” can be achieved by
considering “the lateralization of the observed white matter abnormalities
to the aura as well as to the headache”. We believe this approach might
strengthen clinical/MRI correlations, but we cannot see how it can provide
pathologically specific information about the nature of the NABT changes
we described. Dr. Gupta’s reference to the lateralization of aura is also
puzzling, considering his following comment.
2. Patients with aura vs. patients without aura. We are aware that these
two patients’ groups share "more similarities than differences". This was
one of the reasons why we run such an additional comparison, which,
anyway, constituted only a marginal point of this study (about one line in
the Results). Dr Gupta should welcome these results with enthusiasm,
since they represent additional scientific evidence to the point he made.
3. NABT changes and pathogenesis. Again, it is unclear how pharmacological
studies might help in understanding the nature of NABT changes. We do not
know whether such NABT changes do or do not have a "pathogenetic
implication" – this study was not designed to respond to this question and
further studies are warrented to clarify this issue. Dr Gupta’s statement
that "radiological changes in the brain [...] are, therefore, probably
secondary features that [...] do not have any pathogenetic implication” is
likely to be an example of an enthusiastic, but scientifically unproven,
speculation.
References
(1) Rocca MA, Colombo B, Inglese M, Codella M, Comi G, Filippi M. A
diffusion tensor magnetic resonance imaging study of brain tissue from
patients with migraine. J Neurol Neurosurg Psychiatry 2003; 74: 501-503.
(2) Filippi M. In-vivo tissue characterization of multiple sclerosis and
other white matter diseases using magnetic resonance based techniques. J
Neurol 2001; 248: 1019-1029. Review.
Rocca and colleagues, using diffusion tensor magnetic resonance imaging (DT-MRI) found white matter abnormalities in normal appearing brain tissue occult to conventional MRI.[1] As these authors underscore, the
nature of such abnormalities remain obscure and are unlikely to ever be
resolved by histopathological studies. The biological significance of
these subtle white matter abnormalities, nevertheless, w...
Rocca and colleagues, using diffusion tensor magnetic resonance imaging (DT-MRI) found white matter abnormalities in normal appearing brain tissue occult to conventional MRI.[1] As these authors underscore, the
nature of such abnormalities remain obscure and are unlikely to ever be
resolved by histopathological studies. The biological significance of
these subtle white matter abnormalities, nevertheless, will be determined
by correlation to the clinical and pharmacological underpinnings of
migraine. Data regarding lateralization of the observed white matter
abnormalities to the aura as well as to the headache might have allowed
more definitive clinico-pathological correlation of these findings. Rocca
et al. offer no data regarding the relation of observed white matter
abnormalities and laterality of headache or neuroanatomical concordance
between aura and headache in their patients.[1] In the study of
pathophysiology of migraine, no bio-clinical correlate is more important
than lateralization of the headache.[2]
No difference was found between migraine patients with (MA+) and
without (MA-) aura.[1] The neurological aura of migraine dominates thinking
of neurologists.[3] A recent study underscored absence of headache in MA+
patients.[4] The results of this study [1] do not support any basic
pathophysiologic difference between MA+ and MA-. MA+ is more often than
not associated with headache that usually begins with the aura or
immediately thereafter and shows more similarities than differences from
headache of MA-.[5,6]
A pharmacological absolute helps to understand findings of this
study1 in the clinical perspective. Atenolol, nadolol, and verapamil are
effective prophylactic agents for both MA+ and MA- that modulate primary
physiological aberration(s) but do not readily cross the blood-brain
barrier.[7] Radiological changes in the brain1 as well as brain magnesium
depletion [8] are, therefore, probably secondary features that like regional
cerebral blood flow patterns [2] do not have any pathogenetic implication.
References
(1) Rocca MA, Colombo B, Inglese M, et al. A diffusion tensor magnetic
resonance imaging study of brain tissue from patients with migraine. J
Neurol Neurosurg Psychiatry 2003;74:501-3.
(2) Gupta VK. Regional cerebral blood flow patterns in migraine: what
is the contribution to insight into disease mechanisms? Eur J Neurol
1995;2:586-7.
(3) Goadsby PJ. Sporadic hemiplegic migraine. Stamp collecting or food
for thought. Neurology 2003;60:536-7.
(4) Thomsen LL, Ostergaard E, Olesen J, et al. Evidence for a separate
type of migraine with aura. Sporadic hemiplegic migraine. Neurology
2003;60:595-601.
(5) Rasmussen BK, Jensen R, Olesen J. A population-based analysis of
the diagnostic criteria of the International Headache Society. Cephalalgia
1991;11:129-34.
(6) Ranson R, Igarashi H, MacGregor EA et al. The similarities and
differences of migraine with aura and migraine without aura: a preliminary
study. Cephalalgia 1991;11:189-92.
(7) Gupta VK. Nitric oxide and migraine: another systemic influence
postulated to explain a lateralizing disorder. Eur J Neurol 1996;3:172-3.
(8) Gupta VK. Magnesium therapy for migraine: do we need more trials
or more reflection? Headache 2003;in press.
Kelkar and Parry [1] regard perivascular inflammatory infiltrates as
indicative of an immune microvasculitis that contributes to nerve damage
in diabetes mellitus (DM), in particular mononeuritis multiplex. These
authors believe that the variable therapeutic responses to corticosteroids
alone or in combination with chlorambucil that they observed support the
concept of immunopathogenesis of neural damage...
Kelkar and Parry [1] regard perivascular inflammatory infiltrates as
indicative of an immune microvasculitis that contributes to nerve damage
in diabetes mellitus (DM), in particular mononeuritis multiplex. These
authors believe that the variable therapeutic responses to corticosteroids
alone or in combination with chlorambucil that they observed support the
concept of immunopathogenesis of neural damage in DM.
In sharp contrast to the relatively very short duration of DM in this
cohort,1 diabetic neuropathies tend to occur in the setting of long-
standing hyperglycaemia over decades, whether insulin-dependent or not.[2]
Secondly, diabetic mononeuropathy is characterized by a high degree of
spontaneous reversibility, usually over a several week period. In this
clinical situation, it is difficult to conclude with conviction regarding
the clinical utility of therapy with corticosteroids that, in turn, can
aggravate the diabetic metabolic state. Thirdly, significant weight loss
as seen in three of the four patients with type 2 DM1 is anomalous. Most
patients with uncomplicated type 2 DM are overweight or obese; weight gain
is the usual outcome of therapy with oral hypoglycaemic agents or insulin.
Fourthly, significantly raised erythrocyte sedimentation rate (ESR) (above
50 mm I hour) is not a feature of DM itself. Finally, the metabolic
disturbance in these patients appears to have been well controlled as seen
by near-normal HbA1C levels,[1] which feature generally does not predispose
to neuropathy. In short, the severe but early-onset neuropathy seen in
these diabetic patients1 does not appear to be linked to uncontrolled
hyperglycaemia.
Weight loss, high ESR, and a good response to corticosteroids are
characteristic features of sarcoidosis.[3] At least 25% of patients of DM
(with retinopathy) have serum elevations of angiotensin converting
enzyme.[4] Overall frequency of peripheral neuropathy in neurosarcoidosis is
18%.[5] Mononeuritis multiplex with scattered and asymmetrical sensory and
motor deficits, as described in this cohort,[1] is the most frequently seen
peripheral nerve lesion in neurosarcoidosis.6 Granulomatous T lymphocyte
infiltration in affected tissues, including peripheral nerves, is
diagnostic of sarcoidosis, but tissue evidence of disease cannot always be
obtained.[7]
The mechanism of weight loss [1] in diabetic mononeuropathy as well as
amyotrophy (an uncertain nosologic term)[2] is unknown. In the absence of
markers of vasculitis such as antinuclear antibody and rheumatoid factor,[1]
occult sarcoidosis may underlie weight loss and rapidly evolving steroid-
responsive neuropathy in DM. Corticosteroid refractory neuropathy that
resolves later spontaneously [1] is not likely to be of sarcoid origin and
indicates a miscellaneous vasculitis.
References
(1) Kelkar P, Parry GJ. Mononeuritis multiplex in diabetes mellitus:
evidence for underlying immune pathogenesis. J Neurol Neurosurg Psychiatry 2003;74:803-6.
(2) Asbury AK. Diseases of the peripheral nervous system. In
Harrison’s principles of internal medicine. 12th ed. Wilson JD Braunwald E, Isselbacher KJ, Petersdorf RG, Martin JB, Fauci AS, Root RK, Eds. New York: McGraw–Hill, Inc; 1991:2096-2107.
(3) Mayock RL, Bertrand P, Morrison CE et al. Manifestations of
sarcoidosis. Analysis of 145 patients, with a review of nine series
selected from the literature. Am J Med 1963;35:67-89.
(4) Lieberman J. Angiotensin-converting enzyme in nonpulmonary sarcoidosis.
Semin Res Med 199213:399-401.
(5) James DG, Sharma OP. Neurosarcoidosis. Proc R Soc Med 1967;60:1169-70.
(6) Oksanen V. Neurosarcoidosis. Semin Resp Med 1992;13:459-67.
(7) Gupta VK. Steroid-responsive hypercalcaemic nephropathy in diabetes
mellitus probably due to occult sarcoidosis. Nephron 1996;74:214-5.
We thank Dr Kumar for his interest[1] in our article.[2] I agree, that our data
are not sufficient to evaluate the true risk of recurrence of cerebral
venous and sinus thrombosis (CVST) in women with inherited thrombophilic
disorders. However, we stated in our article that the risk of recurrence
is probably higher if a thrombophilia is present and that all women with
either prior cerebral or extrace...
We thank Dr Kumar for his interest[1] in our article.[2] I agree, that our data
are not sufficient to evaluate the true risk of recurrence of cerebral
venous and sinus thrombosis (CVST) in women with inherited thrombophilic
disorders. However, we stated in our article that the risk of recurrence
is probably higher if a thrombophilia is present and that all women with
either prior cerebral or extracerebral venous thromboembolism who are
pregnant or planning to conceive should be tested for thrombophilia. Our
conclusion was very cautious: "Our data do not justify a negative advice
on pregnancy in women with a history of CVST". We wanted to communicate
that further sucessful pregnancies in women with a history of CVST are
possible. Excluding the one women whose pregnancy was terminated due to a
possible teratogenic risk (because pregnancy occurred during oral
anticoagulation), there were 2 spontaneous abortions. We agree that these
complications might have been due to a thrombophilic state such as an
antiphospholipid antibody syndrome emphasizing the need for thrombophilic
testing. However, all other medical complications (seizures, gestosis)
were controllable and resulted in the birth of healthy children.
In conclusion, we agree that further prospective studies are needed to
determine the true risk of recurrence and that testing for thrombophilic
states is definately necessary. Women with a previous CVST need close
neurological and gynecologic surveillance but a history of CVST does not
exclude the possibility of further sucessful pregnancies.
References
(1) Kumar S, Alexander M, Gnanamuthu C. Risk of recurrent cerebral venous and sinus thrombosis during subsequent pregnancy and puerperium [electronic response to S Mehraein et al. Risk of recurrence of cerebral venous and sinus thrombosis during subsequent pregnancy and puerperium] jnnp.com 2003 http://jnnp.bmjjournals.com/cgi/eletters/74/6/814#53
(2) S Mehraein, H Ortwein, M Busch, M Weih, K Einhäupl, and F Masuhr. Risk of recurrence of cerebral venous and sinus thrombosis during subsequent pregnancy and puerperium. J Neurol Neurosurg Psychiatry 2003; 74:814-816.
Have test, will screen. Screening people with hereditary haemorrhagic
telangiectasia (HHT) for brain arteriovenous malformations (AVMs) could be
relatively easy – and therefore attractive – but where lies the balance
between risk (both physical and psychological) and benefit?
The ideal screening test should aim to detect a disease that
significantly impacts upon public health, before the disease...
Have test, will screen. Screening people with hereditary haemorrhagic
telangiectasia (HHT) for brain arteriovenous malformations (AVMs) could be
relatively easy – and therefore attractive – but where lies the balance
between risk (both physical and psychological) and benefit?
The ideal screening test should aim to detect a disease that
significantly impacts upon public health, before the disease reaches a
critical point (i.e. brain haemorrhage), and detection before this point
should confer a beneficial outcome with intervention (i.e. one or more of
surgical excision, radiotherapy, or endovascular embolisation). The test
itself (MRI and/or catheter angiography) should be sensitive enough to
detect the disease, specific enough to minimise false positives, and it
should be well tolerated with few side effects. Lastly, the population to
be screened should have a high prevalence of the disease, and should be
willing to undergo treatment. If overall there is a fine balance between
benefit and cost (mortality, morbidity, and/or financial), then a
randomised controlled trial (RCT) comparing screening strategies against
each other is called for.
In the case of HHT, it is rare but can cause significant mortality
and morbidity. The exact prevalence of brain AVMs in HHT is uncertain but ³5%. [1] For brain AVMs in general, high quality information about
prognosis and satisfactory evidence for interventional treatment are
lacking: prospective, population-based studies of prognosis are in their
infancy,[2,3] and there are no randomised controlled trials comparing
different interventions either against each other or conservative
management.[4] Catheter angiography is more sensitive than MRI for brain
AVM detection in HHT,[1] and it carries <_0.1 risk="risk" of="of" permanent="permanent" neurological="neurological" complications.5="complications.5" p="p"/>Easey et al. recently addressed the important dilemma of whether or
not to screen for brain AVMs in HHT by assessing the prevalence of stroke
in the families of individuals with HHT.[6] Their sizeable HHT cohort and
collective experience with the condition are invaluable, but their
conclusion that individuals with HHT should be screened for asymptomatic
brain AVMs is not justified by their data. The design of their study does
not address the question they pose and their findings are not
generaliseable.
Easey et al’s study was retrospective and diagnosed HHT on the basis
of clinical diagnostic criteria rather than strictly by mutation analysis
of ALK1 and endoglin genes. This is unfortunate because there is an
increasing body of evidence to suggest that HHT caused by mutations in the
endoglin gene (HHT1) has a distinct and possibly more severe phenotype
than HHT caused by mutations in the ALK1 gene (HHT2).[7]
Of the 98 families studied comprising probands and their relatives in
their generation (n=674), a staggering 200 (30%) were unaffected or
unlikely to have HHT. Strangely, the authors argue against simply studying
the screening group of interest (people with definite HHT) and include
data on strokes in 30% of their cohort who did not, or were unlikely to
have, HHT. Furthermore, all strokes were considered whatever their
aetiology; pulmonary – rather than brain – AVMs may have contributed to
many of these. The total number of people affected by the screening
condition of interest (brain AVMs) is not mentioned, but a brain AVM was
detected on catheter angiography in only 7 of the 35 probable/definite
haemorrhages in the cohort of 674 individuals (table 3). Recurrent events
were not studied. Time-dependent outcome analysis was not used.
The authors then conclude with their finding of a higher relative
risk for stroke by indirect comparison of their heterogeneous cohort with
the Oxford Community Stroke Project. Crucially, they have not directly
established the contribution of the screening condition of interest (brain
AVMs) to this excess risk, nor the effects of treating symptomatic and
incidental brain AVMs.
Our reservations about Easey et al's study are more than pedantic
methodological criticisms; the argument for screening is simply not
persuasive. Their data and the rest of the literature thus far simply do
not justify screening people with HHT for brain AVMs. Screening in this
context does occur in some HHT clinics, but it should not be a practice
standard on the existing evidence.
We are not advocating doing nothing. It may be that screening is
appropriate, but only in certain age groups, or people with particular
mutations. Surely the best solution would be for geneticists, respiratory
physicians, radiologists, radiotherapists, neurosurgeons and neurologists
looking after people with HHT to unite and conduct a properly designed RCT
of screening (and treatment) for brain AVMs?
References
(1) Fulbright RK, Chaloupka JC, Putman CM, Sze GK, Merriam MM, Lee GK,
Fayad PB, Awad IA, White RI, Jr. MR of hereditary hemorrhagic
telangiectasia: prevalence and spectrum of cerebrovascular malformations.
AJNR 1998;19:477-84.
(2) Al-Shahi R, Warlow C. A systematic review of the frequency and prognosis
of arteriovenous malformations of the brain in adults. Brain 2001;124:1900-26.
(3) Al Shahi R, Bhattacharya JJ, Currie DG, Papanastassiou V, Ritchie V,
Roberts RC, Sellar RJ, Warlow CP. Scottish Intracranial Vascular
Malformation Study (SIVMS): Evaluation of Methods, ICD-10 Coding, and
Potential Sources of Bias in a Prospective, Population-Based Cohort.
Stroke 2003;34:1156-62.
(4) Al-Shahi R, Warlow CP. Interventions for treating arteriovenous
malformations of the brain in adults (Protocol for a Cochrane Review). In:
The Cochrane Library, Issue 2, 2003. Oxford: Update Software 2002.
(5) Cloft HJ, Joseph GJ, Dion JE. Risk of cerebral angiography in patients
with subarachnoid hemorrhage, cerebral aneurysm, and arteriovenous
malformation: a meta-analysis. Stroke 1999;30:317-20.
(6) Easey AJ, Wallace GM, Hughes JM, Jackson JE, Taylor WJ, Shovlin CL.
Should asymptomatic patients with hereditary haemorrhagic telangiectasia
(HHT) be screened for cerebral vascular malformations? Data from 22 061
years of HHT patient life. J Neurol Neurosurg Psychiatry 2003;74:743-8.
(7) Berg J, Porteous M, Reinhardt D, Gallione C, Holloway S, Thisanagayam U,
Lux A, McKinnon W, Marchuk D, Guttmacher A. Hereditary haemorrhagic
telangiectasia – a questionnaire base4d study to delineate the different
phenotypes caused by endoglin and ALK1 mutations. J Med Genet 2003; in press.
Afridi and Goadsby present a case of new onset migraine in a patient who developed a pontine bleeding episode from a cavernous angioma.[1] These
authors believe that the pontine bleed triggered the migraine attacks in
this patient and seek a parallel with the headaches observed following
implantation of stimulating electrodes [2] into the periaqueductal gray
matter (PAG).
Afridi and Goadsby present a case of new onset migraine in a patient who developed a pontine bleeding episode from a cavernous angioma.[1] These
authors believe that the pontine bleed triggered the migraine attacks in
this patient and seek a parallel with the headaches observed following
implantation of stimulating electrodes [2] into the periaqueductal gray
matter (PAG).
Structural changes following pontine bleed are unlikely to predispose
to an intermittent disorder such as migraine and are more likely to lead
to a persistent dysfunction, negative or positive. In 15 out of 175
patients undergoing brain electrode transplantation, significant headache
was observed.[2] Of these 15 patients, 13 had PAG electrodes implanted (with
four of these also receiving thalamic electrodes) while two patients had
thalamic electrodes only. Unlike the present case,1 headache was
continuous at onset in 14 of 15 patients.[2] Reserpine produced dramatic
initial resolution of headache,[2] whereas it causes a typical headache in
most migraine patients.[3,4] No migraine prophylactic agent offered any
benefit.[2] There is, thus, little pathophysiological similarity between
this case1 and the headaches following implantation of electrodes in the
PAG.[2]
Lateralization of migraine headache is one of its most characteristic
features. Simply because the physico-chemical substrate / idiosyncracy
responsible for unilateral headache has not yet been detected, it does not
mean that it is unimportant; what is immeasurable might be more important
than what is measurable.[5] If peripheral frontotemporal application of
nitroglycerine can precipitate ipsilateral headache [6] without any primary
involvement of the PAG in the afferent limb of headache, the relevance of
brain stem neuronal interconnections to lateralization of migraine
headache is limited. Secondly, generalisation is essential to the process
of theorizing.[7] Explaining laterality of headache of migraine (in patients
with bilateral headache) by neuronal interconnections at the pontine
level [1] will create significant conceptual pathophysiological limitations
for strictly unilateral headache in migraine patients as well for other
primary headaches that are strictly unilateral, such as cluster headache
(CH) and chronic paroxysmal hemicrania (CPH). In other words, if crossover
of experimental inhibitory PAG input [8] is indeed clinically relevant, why
does persistently unilateral headache occur at all in migraine or CH or
CPH? Furthermore, while stimulation of the ventrolateral PAG produces
inhibition of nociceptive signals experimentally,[8] PAG stimulation did not
affect headaches in patients.[2] On the contrary, in one patient the
headache was intensified ipsilaterally.[2] Finally, atenolol and nadolol are
effective migraine prophylactic agents that modulate primary
pathophysiological aberrations but do not readily cross the blood-brain
barrier, and, therefore, cannot affect brain function either at the level
of the cortex or the brain stem, including nociceptive mechanisms.[9]
Migraine has not been linked previously to pontine bleeding. Stress
is a common precipitant of migraine.[7] As expected following a neurological
episode with fear of loss of function,[10] this patient1 noted that stress
precipitated her headaches. It is important to consider, in the first
instance, as with other theories of migraine,[11] why antinociception should
be spontaneously altered during remissions and exacerbations of migraine.
Equally important, there is no clinical evidence of impaired nociception
in migraine. The acute phase of migraine attacks (with or without aura) is
associated with substantial increases in plasma methionine-enkephalin
(analgesia mediating opiate peptide) which return to baseline only slowly
in the pain-free period.[12] Also, peripheral pain threshold to low-
intensity stimulation was greater or unchanged during headache than during
the headache-free interval, and pressure-pain threshold was not correlated
to the tenderness scores obtained by manual palpation, thereby eliminating
the possibility of both a general ictal increase in sensitivity to pain as
well as focal dysfunction in the antinociceptive system.[13,14] Activation
of vasopressin related adaptive systems also enhances antinociception
during migraine attacks, the process beginning in the pre-prodromal and
prodromal phases.[15] The onset of migraine in this patient following
haemorrhage in brain stem cavernous angioma1 is a rare coincidence that
offers no support to theories of migraine pathogenesis involving brain
stem nociceptive dysfunction.
References
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Dear Editor
I have read with interest the article written by Finsterer et al. However, I do have several concerns and remarks in relation to it.
First, the authors describe a stenotic lesion at the L-ICA that I do not actually see in the diagnostic angiogram. Moreover, this lesion was treated wih a stent-graft. Second, the image of the R-ICA corresponds to a classic carotid artery dissection, probabl...
Dear Editor
We thank Dr Celio Levyman for his supportive comments.[1]
We fully agree with him that, in patients with baroreflex failure, it is necessary to adopt approaches to combat orthostatic hypotension without increasing supine hypertension. It is also important to follow up an open study with a blinded study. We expect to complete, within the next month, a double- blind placebo controlled study, funded by...
Dear Editor
The issue of orthostatic hypotension is a very common an important diseable picture of many diseases, as Singer et al. points. Parkinson disease and diabetic neuropathy are the most common clinical situation of these cases, and even the very well controlled patient, with tilt-test table measures to the choice of therapeutic strategies in most cases shows frustanting results.
This novel...
Dear Editor
As it is well known, endorphin levels change in different circumstances, for example, in injury, illness, or as a result of circadian influences, among others.[1-7] It would be helpful to know which was the primary stimulus for endorphin level changes in MS patients. Perhaps a further experiment can show that it is or is not circadian.
References
(1) Covelli V, Massari F, Falla...
Dear Editor
We read with interest the letter by Dr Gupta on our paper entitled “A diffusion tensor magnetic resonance imaging study of brain tissue from patients with migraine”.[1] Nevertheless, we believe that he missed the main result of this study as well as the scope for which it was designed and conducted. The aim of this study was to investigate whether occult’ tissue damage, which goes undetected when usin...
Dear Editor
Rocca and colleagues, using diffusion tensor magnetic resonance imaging (DT-MRI) found white matter abnormalities in normal appearing brain tissue occult to conventional MRI.[1] As these authors underscore, the nature of such abnormalities remain obscure and are unlikely to ever be resolved by histopathological studies. The biological significance of these subtle white matter abnormalities, nevertheless, w...
Dear Editor
Kelkar and Parry [1] regard perivascular inflammatory infiltrates as indicative of an immune microvasculitis that contributes to nerve damage in diabetes mellitus (DM), in particular mononeuritis multiplex. These authors believe that the variable therapeutic responses to corticosteroids alone or in combination with chlorambucil that they observed support the concept of immunopathogenesis of neural damage...
Dear Editor
We thank Dr Kumar for his interest[1] in our article.[2] I agree, that our data are not sufficient to evaluate the true risk of recurrence of cerebral venous and sinus thrombosis (CVST) in women with inherited thrombophilic disorders. However, we stated in our article that the risk of recurrence is probably higher if a thrombophilia is present and that all women with either prior cerebral or extrace...
Dear Editor
Have test, will screen. Screening people with hereditary haemorrhagic telangiectasia (HHT) for brain arteriovenous malformations (AVMs) could be relatively easy – and therefore attractive – but where lies the balance between risk (both physical and psychological) and benefit?
The ideal screening test should aim to detect a disease that significantly impacts upon public health, before the disease...
Dear Editor
Afridi and Goadsby present a case of new onset migraine in a patient who developed a pontine bleeding episode from a cavernous angioma.[1] These authors believe that the pontine bleed triggered the migraine attacks in this patient and seek a parallel with the headaches observed following implantation of stimulating electrodes [2] into the periaqueductal gray matter (PAG).
Structural changes fol...
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