We read with great interest the study by Djebbari and colleagues
reporting on the factors predicting improvement in motor disability in
writer’s cramp treated with botulinum toxin injections [1].
The authors
found a significant improvement on the BFM scale in both severity and
disability scores after patients were treated with botulinum toxin
injections. The pronation/flexion pattern of dyst...
We read with great interest the study by Djebbari and colleagues
reporting on the factors predicting improvement in motor disability in
writer’s cramp treated with botulinum toxin injections [1].
The authors
found a significant improvement on the BFM scale in both severity and
disability scores after patients were treated with botulinum toxin
injections. The pronation/flexion pattern of dystonia was a predictor of
the best and the most sustained improvement. The study confirmed the
beneficial effect of botulinum toxin injections in the treatment of
writer’s cramp. Although this work is of great interest, we would like to
comment on a few points that caught our attention.
The authors chose to include 3 patients with primary writing tremor (PWT)
among their cohort. Although PWT is a writing dysfunction there is an
ongoing debate whether it represents a focal form of essential tremor (ET)
[2, 3], a dystonic tremor variant [4], both [5] or is an altogether
separate nosologic entity with a pathophysiology different from that of
both focal dystonia and ET [6]. Inclusion of these patients in this study
may have introduced significant bias leading to the skewing of the
reported results. Furthermore, there are no separate data presented for
this interesting subgroup of patients, since there have been no reports on
the treatment of PWT with botulinum toxin injections. There is only a
statement in the abstract that PWT was “little improved”. Improvement of
PWT may be also attributed to the beneficial action of botulinum toxin on
several types of tremors including ET, dystonic, parkinsonian and others
[7-11].
We believe there is confusion in the existing literature regarding the
clinical definition of PWT. Most authors choose to define PWT as tremor
that appears “only” or “exclusively” during writing, usually referencing
the seminal report by Rothwell et al. [12]. However, the patient described
in the latter report had short-lived bursts of tremor on any motor act
involving pronation of the forearm, as for example lifting a cup or using
a screwdriver and not only during writing. Therefore, we suggest that PWT
should be defined as an action-induced tremor triggered “primarily” by
writing, since it may involve other activities.
Although the results of this study may have been slightly influenced by
the decision of the authors to include PWT patients in their cohort
without considering them as a distinct group, we strongly agree with their
conclusion that their results may help clinicians to identify patients who
are likely to benefit most from BTX treatment, and to select the most
appropriate injection strategy in a subset of population with pure
writer’s cramp.
References
(1). Djebbari R, du Montcel ST, Sangla S, Vidal JS, Gallouedec G, Vidailhet
M. Factors predicting improvement in motor disability in writer's cramp
treated with botulinum toxin. J Neurol Neurosurg Psychiatry
2004;75(12):1688-91.
(2). Koller WC, Martyn B. Writing tremor: its relationship to essential
tremor. J Neurol Neurosurg Psychiatry 1986;49(2):220.
(6). Modugno N, Nakamura Y, Bestmann S, Curra A, Berardelli A, Rothwell J.
Neurophysiological investigations in patients with primary writing tremor.
Mov Disord 2002;17(6):1336-40.
(7). Brin MF, Lyons KE, Doucette J, Adler CH, Caviness JN, Comella CL, et
al. A randomized, double masked, controlled trial of botulinum toxin type
A in essential hand tremor. Neurology 2001;56(11):1523-8.
(8). Pacchetti C, Mancini F, Bulgheroni M, Zangaglia R, Cristina S, Sandrini
G, et al. Botulinum toxin treatment for functional disability induced by
essential tremor. Neurol Sci 2000;21(6):349-53.
(9). Jankovic J, Schwartz K, Clemence W, Aswad A, Mordaunt J. A randomized,
double-blind, placebo-controlled study to evaluate botulinum toxin type A
in essential hand tremor. Mov Disord 1996;11(3):250-6.
(10). Henderson JM, Ghika JA, Van Melle G, Haller E, Einstein R. Botulinum
toxin A in non-dystonic tremors. Eur Neurol 1996;36(1):29-35.
(11). Trosch RM, Pullman SL. Botulinum toxin A injections for the treatment
of hand tremors. Mov Disord 1994;9(6):601-9.
In the midst of our search for palilalia (pathological perseveration
of words and phrases) in the context of Parkinsonism we encountered the
interesting case report by Owens and Okun regarding a mentally retarded
man with parkinsonism presumably due to 2-hydroxyglutaric aciduria, who
had palilalia among other neurological deficits.[1] The main message, namely
the consideration of urine organic acids t...
In the midst of our search for palilalia (pathological perseveration
of words and phrases) in the context of Parkinsonism we encountered the
interesting case report by Owens and Okun regarding a mentally retarded
man with parkinsonism presumably due to 2-hydroxyglutaric aciduria, who
had palilalia among other neurological deficits.[1] The main message, namely
the consideration of urine organic acids testing in adults with atypical
parkinsonian disorders, is somewhat undermined by the juvenile onset of
the case (with “cerebral palsy” in the 20s). Nevertheless, we want to draw
attention to an important clinical issue that this case raises.
We should begin by addressing the relevant clinical question, namely,
when do we test for organic acidurias in adults with Parkinsonism? It has
been advised we should have a low testing threshold for these and other
metabolic disorders when any signal abnormality is present in the basal
ganglia, especially in children;[2] in the case of most organic acidurias,
it implies hypointensity on T1W or hyperintensity on T2W and FLAIR
sequences within the pallidum or putamen. We would not have tested for
organic acidurias in an adult exclusively on the basis of white matter
hyperintensities and ex-vacuo ventricular dilatation, as reported here.
However, when reviewing the FLAIR images published, hyperintensities of
the external segment of the globus pallidus (GPe) are indeed found (figure 1, left) and, remarkably, no comment is made of this finding, significant
– one would have presumed – to the decision of proceeding to test for
hydroxyglutaric aciduria.
Pertinent to the scope of our initial search and unbeknown to Owens
and Okun, their report may now be used to support a localizing value for
palilalia. Kuoppamäki et el.[3] have recently studied an adult with
Parkinsonism and palilalia resulting from alcohol-induced respiratory
acidosis who, to our surprise, had isolated bilateral lesions of the GPe.
As we have just learned, the very short list of palilalia associated with
non-Parkinson’s disease parkinsonisms only includes the atypical variant
(late onset with slow progression) of pantothenate kinase-associated
neurodegeneration[4] and postencephalitic parkinsonism.[5] The GP suffers iron
deposition in the former (with the classical eye-of-the-tiger appearance)
and presumably viral-induced gliosis in the latter (in which the
substantia nigra is the primary target).[6] Careful pathologic studies of
the globus pallidus in postencephalitic parkinsonism indeed reflect
predominant cell loss in the “outer segment... with relative normality of
the inner segment of the pallidum” in all cases brought for postmortem
assessment.[6] When assessing our next patient with palilalia, we will
attend to its potential localizing value.
References
1. Owens WE, Okun MS. Dystonia, tremor, and parkinsonism in a 54
year old man with 2-hydroxyglutaric aciduria.
J.Neurol.Neurosurg.Psychiatry 2004;75:1362-3.
2. Gascon GG, Ozand PT, Brismar J. Movement disorders in childhood
organic acidurias. Clinical, neuroimaging, and biochemical correlations.
Brain Dev. 1994;16 Suppl:94-103.
3. Kuoppamaki M, Rothwell JC, Brown RG, Quinn N, Bhatia KP,
Jahanshahi M. Parkinsonism following bilateral lesions of the globus
pallidus: performance on a variety of motor tasks shows similarities with
Parkinson's disease. J.Neurol.Neurosurg.Psychiatry 2005;76:482-90.
4. Hayflick SJ, Westaway SK, Levinson B, Zhou B, Johnson MA, Ching
KH, Gitschier J. Genetic, clinical, and radiographic delineation of
Hallervorden-Spatz syndrome. N.Engl.J.Med. 2003;348:33-40.
5. Sterling W. Palilalie et le symptome linguosalivaire dans le
Parkinsonisme encephalitique. Rev.Neurol.(Paris) 1924;1:205-20.
6. Martin JP. The globus pallidus in post-encephalitic parkinsonism.
J.Neurol.Sci. 1965;2:344-65.
We read the retrospective study by Adab et al [1] with interest; this
paper raises the issue of risk of developmental delay in children aged 6
years and over born to epileptic mothers treated with antiepileptic agents
during pregnancy. More specifically, foetal exposure to valproate could
involve significant risk of impairment of verbal IQ in such children,
despite no change in full scale IQ.
We read the retrospective study by Adab et al [1] with interest; this
paper raises the issue of risk of developmental delay in children aged 6
years and over born to epileptic mothers treated with antiepileptic agents
during pregnancy. More specifically, foetal exposure to valproate could
involve significant risk of impairment of verbal IQ in such children,
despite no change in full scale IQ.
These data are of considerable importance for clinicians whose task it is
to inform and treat women of childbearing age: we therefore wish to obtain
as much detailed information as possible in addition to the data published
in this article so as to better assess the type and degree of cognitive
risk involved.
The practical dilemma is perfectly set out by the authors: the risk of
death of pregnant mothers associated with epileptic seizures during
pregnancy is 10-fold higher than among the general population and
prophylactic treatment against seizures is consequently indicated. The
extent of foetal malformation can at present be accurately estimated
overall (global risk 2 to 3 times greater than among the general
population) with specific damage depending on individual drugs (neural
tube defects with valproate and, to a lesser extent, with carbamazepine),
which does not in itself rule out prescription of an antiepileptic
provided adequate foetal monitoring is performed. However, if the risk of
developmental delay were objectively demonstrated in children exposed to
certain antiepileptic drugs, this could lead to reassessment of the
benefit/risk ratio of the incriminated treatments during pregnancy, or
even to avoidance of such treatment.
The authors provide a particularly valuable discussion of the potential
bias associated with the retrospective nature of their study.
The efficacy of valproate in the treatment of both partial seizures and
generalised seizures is well established [2]. The published study data
support this efficacy: of the 63 women treated with valproate alone for
all syndromes, 47 presented no seizures (or experienced only non-
convulsive seizures), i.e. 75% success rate for satisfactory control of
epilepsy during pregnancy.
We feel it is essential that details of cognitive evaluation for
children born to mothers treated with valproate based be provided, centred
on the following questions:
1. The IQ results are expressed as a mean value and confidence
interval, making it awkward to assess the degree of inter-individual
variation. It would be useful to provide the range of values recorded for
each group
2. VIQ is a composite measurement of verbal intelligence based on five
subtests designed to investigate different areas: Information,
Comprehension, Similarities, Vocabulary and Arithmetic. It would therefore
be preferable to provide the individual scores in each of these subtests,
at least for the group of children exposed to valproate exhibiting the
greatest impairment. Specific impairment concerning one or more subtest
results would constitute a strong argument supporting a direct effect of
valproate. In contrast, a heterogeneous impairment profile would tend
rather to point to multifactorial origin. Demonstration of a specific
deficiency would be particularly revealing: a deficit in verbal reasoning
(Similarities) would tend to suggest a direct effect on verbal
intelligence of exposure to valproate, while such a conclusion would be
much less clear-cut in the event of deficits in subtests more sensitive to
socio-economic conditions (Information, Comprehension).
3. The results shown in figure 1 are puzzling: 42% of children exposed to
valproate had a VIQ of less than 70 (last two bars to the right of the
figure). It would be of value to provide details of the precise cognitive
profile of this subgroup together with the PIQ values. If the PIQ of these
children (or certain of these children), already impaired in terms of
verbal IQ, is also deficient, then we are dealing with mentally impaired
children. As things stand, it is impossible to evaluate this point
adequately, since the FSIQ and PIQ values are given indiscriminately for
all children exposed to valproate. Precise data concerning this subgroup
are required in order to determine the reality of Specific Language
Impairment (if the PIQ of these children is unchanged), or to illustrate
the heterogeneous nature of the different situations in the absence of
specificity of cognitive profiles.
Such marked impairment of verbal intelligence in a child aged over 6 years
in effect generally has a negative impact on learning at school.
Under
these conditions, it is normally possible to establish a precise
diagnosis. However, the precise diagnoses available for certain children
exposed to valproate such as Asperger syndrome or dyspraxia are surprising
since they normally correspond rather to impairment of non-verbal
functions and the link with impairment of VIQ is far from clear.
4. Certain results require further explanation:
a) Why do children exposed to phenytoin have a higher VIQ than children in
the other comparative groups? Is the difference significant?
b) Why is it that in contrast with those exposed to valproate in
monotherapy, the VIQ of children exposed to valproate in polytherapy does
not differ significantly from that of unexposed children (Table 4). Does
combined administration of certain antiepileptic drugs play a protective
role? Are plasma concentrations of valproate lower in polytherapy than in
monotherapy?
5. As regards genetic factors, it is essential to take account not only of
the intelligence level of mothers but also of familial history of learning
disorders both in the group of children considered as normal (VIQ>80)
and in children with impairments (VIQ<80) for each group exposed to
valproate. The distribution of environmental factors (socio-cultural level
of mothers and fathers, alcoholism among mothers) should be defined for
each study group in view of their extremely harmful effects on cognition
among children subject to such factors.
6. The incidence of tonic-clonic seizures during pregnancy should also be
specified for the specific subgroup of severely impaired children.
Irrespective of the methodological problems posed by this study, it
nevertheless highlights the importance of systematic
monitoring of drugs following their initial market launch.
Doubts concerning foetal exposure to medicines centre on risk of
malformations, which may be detected rapidly at birth. However, systematic
and centralised recording is necessary to demonstrate any increase over
time in initially low risks. For instance, 15 years elapsed before any
description and evaluation was offered concerning the incidence of neural
tube defects associated with valproate [3], and there was a corresponding
period of 27 years for carbamazepine following its market launch [4].
Obviously, systematic study of any psychomotor and/or behavioural
consequences of exposure of the foetal brain during its development to
medicines displaying cerebral tropism is more difficult, since the
observation period required is much longer (3 to 7 years). It was thus
several decades after the initial market launch before evidence could be
obtained regarding any retrospective suspicions surrounding older
antiepileptic drugs (phenytoin, phenobarbital, valproate).
This period of
uncertainty could have been shortened by the introduction of systematic
prospective monitoring of psychomotor and behavioural effects in children
exposed in utero immediately after commercialisation in order to quantify
the associated risks and compare them for different antiepileptic drugs.
The absence of systematic prospective monitoring creates an unacceptable
time lapse in risk evaluation. The data provided by Adab et al, although
retrospective, cannot be concealed from existing mothers or future mothers
treated with valproate. In all likelihood, the drug information centres
(French regional pharmacovigilance centres) will now add to the risk of
malformation for valproate, first reported, that of impairment of verbal
intelligence quotient, even in the absence of change in FSIQ.
In this
context, none of the drugs proposed as an alternative to valproate, such
as lamotrigine for instance, can be considered as presenting lower risk of
retarded development in principle since there are no available studies.
However, the absence of studies cannot be equated with absence of risk.
While the wish expressed by the authors ("It is essential that adequately
controlled prospective studies are established now to identify the level
of risk for cognitive impairment in children of women taking both new and
established AEDs during pregnancy") may well be utopian, the health
authorities should nevertheless insist that all foetal exposure is
accompanied by prospective monitoring of exposed children (psychomotor and
behavioural testing between the ages of 5 and 7 years) immediately
following the commercial launch of a medicine in order to evaluate the
associated risks of developmental delay. Today, this risk is unknown for
all new antiepileptic drugs.
References
(1) Adab, N, Kini U, Vinten J et al. J Neurol Neurosurg Psychiatry
2004;75:1575-1583
(2) The Scottish Intercollegiate Guidelines Network (SIGN). Guideline 70,
http:/www.sign.ac.uk/guidelines/published/index.html (accessed 9 August
2004).
(3) Robert E, Guilbaud P. Maternal valproic acid and congenital neural tube
defects. Lancet 1982;2(8304):937
(4) Rosa FW. Spina bifida in infants of women treated with carbamazepine
during pregnancy. N Engl J Med 1991;324(10):674-7
I suggest the findings of Evans, et al., may be explained by low
testosterone. Low testosterone has been connected with some symptoms of
Parkinson's such as apathy (J Neurol Neurosurg Psychiatry. 2004
Sep;75(9):1323-6). The low level of "sensation seeking traits" may be
evidence of low levels of testosterone in Parkinson's as testosterone may
be connected with the described behaviors.
I suggest the findings of Evans, et al., may be explained by low
testosterone. Low testosterone has been connected with some symptoms of
Parkinson's such as apathy (J Neurol Neurosurg Psychiatry. 2004
Sep;75(9):1323-6). The low level of "sensation seeking traits" may be
evidence of low levels of testosterone in Parkinson's as testosterone may
be connected with the described behaviors.
It is my hypothesis that Parkinson's results from low testosterone
and low dehydroepiandrosterone (DHEA). DHEA begins to naturally decline
around age 20, reaching very low levels in old age. I suggest this loss
of DHEA exposes gene-activation defects which appear in older individuals
in a number of neurodegenerative diseases, including Parkinson's. DHEA
has been demonstrated to stimulate tyrosine hydroxylase which is reduced
in Parkinson's.
The authors are to be congratulated on a good article. Do you they have any experience with this method in the treatment of epilepsy? Thank you and please continue the good work.
The paper provides an interesting perspective about schizophrenia. Even
though Kraeplin described the illness as 'dementia praecox', it's
intriguing to find paucity of literature mentioning dementia like features
in schizophrenia.
It appears from the paper that a significant minority of
patients with schizophrenia may have such presentation. However,in such
cases it's very difficult to label...
The paper provides an interesting perspective about schizophrenia. Even
though Kraeplin described the illness as 'dementia praecox', it's
intriguing to find paucity of literature mentioning dementia like features
in schizophrenia.
It appears from the paper that a significant minority of
patients with schizophrenia may have such presentation. However,in such
cases it's very difficult to label the socio-occupational dysfunction
solely due to the symptoms of dementia as contribution of schizophrenic
symptoms would have been there.
In the paper, in some patients disorientation and urinary incontinence are
strikingly clear, while memory impairement is more apparent on neuro-
psychological testing. This provides the need to rule out the presence of
superimposed chronic hypoactive delirium on schizophrenia as delirium has
been described in such patients.
Furthermore, if these patients are a subgroup of schizophrenia leading to
dementia,what kind of treatment modality is required, need to be looked
into.
I speculate that clozapine would be a better choice as patients
appear to be 'treatment resistant'with features of urinary incontinence
(high anticholinergic effect of clozapine)and dementia (some reports of
efficacy of low-dose clozapine).
Gainotti et al [1] find that the recovery over time of non-treated
depressed patients with stroke was less than the non-depressed and the
depressed but treated patients with stroke and was particularly manifested
on the Rivermead mobility index. Neurobiological features are suggested by
the correlation of the rate of speech hesitation pauses of 1 s (SHP),
4.79+/-2.48/min, 1.50+/-0.33 s (mean+/-SD), behavioral correlates of...
Gainotti et al [1] find that the recovery over time of non-treated
depressed patients with stroke was less than the non-depressed and the
depressed but treated patients with stroke and was particularly manifested
on the Rivermead mobility index. Neurobiological features are suggested by
the correlation of the rate of speech hesitation pauses of 1 s (SHP),
4.79+/-2.48/min, 1.50+/-0.33 s (mean+/-SD), behavioral correlates of mood,
with immobility in the face of stress, the state of the circulation
(angina/hypertension) and sixfold incidence of clinical coronary heart
disease (CHD) in two groups of men with normal coronary structure followed
prospectively for 10 years, P<_0.05 _2.="_2." depression="depression" independently="independently" and="and" negatively="negatively" influences="influences" autonomic="autonomic" control="control" of="of" heart="heart" rate="rate" in="in" patients="patients" with="with" acute="acute" myocardial="myocardial" infarction="infarction" _3.="_3." p="p"/> These findings are supported by: the correlation of rate and
variability in duration of SHP with the left and right hemisphere,
respectively; and an exaggerated cerebral cortical response and
exaggerated asymmetry to mental stress in patients with CHD; profound
effects on angina through consciously focusing attention on breathing and
intervening pauses; the association of the reduction of blood pressure
with longer, less recurrent SHP (about 2 s); and reports that the
microvascular response to the onset of neural activity is delayed
consistently about 3 s and is linked to increased coherence of
electroencephalograph gamma-band activity (30-50 Hz or broader, centered
on 40 Hz) associated with the execution of more complex tasks.
These findings give precise, objective methods with which to evaluate
the effect of mental stress on the microvasculature and suggest
interventions reduce the risk of vascular events, optimize mood, and
enhance performance. Therefore, cognitive-behavioral and/or
pharmacotherapeutic intervention to balance asymmetric brain functions and
alleviate depression can be evaluated by the analysis of pauses on a time-
base. This method is supported by reports that exaggerated heart rate
oscillations during slow deep breathing in meditation is a dynamic state
that increases effective connectivity between distinct cortical systems by
the entrainment of gamma-frequency oscillations [1], counterbalancing the
distributed anatomical and functional organization of brain activity,
enabling the emergence of coherent behavior and cognition [4].
References
(1) Gainotti G, Antonucci G, Marra C, Paolucci S. Relation between depression after stroke, antidepressant therapy, and functional recovery. J Neurol Neurosurg Psychiatry 2001;71:258-261.
(2) Friedman EH. Socioeconomic inequalities in cardiovascular disease (letter). Eur Heart J 2001;22:715.
(3) Pitzalis MD, Iacoviello M, Fioretti A, Guida P, Massari
F, Mastropasqua F, Dello Russo G, Rizzon S. Depression
but not anxiety influences the autonomic control of heart
rate after myocardial infarction. American Heart Journal
2001;141:765-771.
(4) Varela F, Lachaux JP, Rodriguez E, Martinerie J. The
brainweb: phase synchronization and large-scale
integration. Nature Reviews Neuroscience 2001;2:229-239.
Thijs and Dijk present a case of pure autonomic failure with
emotional-stress induced pre-syncope.[1] These investigators believe that
this case is remarkable as stress increases sympathetic outflow and
commonly raises blood pressure in healthy subjects.[1][2]
The role of the two limbs of the autonomic nervous system (ANS) is
not completely understood. The general impression that the sympat...
Thijs and Dijk present a case of pure autonomic failure with
emotional-stress induced pre-syncope.[1] These investigators believe that
this case is remarkable as stress increases sympathetic outflow and
commonly raises blood pressure in healthy subjects.[1][2]
The role of the two limbs of the autonomic nervous system (ANS) is
not completely understood. The general impression that the sympathetic and
the parasympathetic components of the ANS are mutually antagonistic is
simplistic.[3] In fact, these two limbs of the ANS coordinate and
facilitate each other in order to maintain organ function and homeostasis.
The best example of this facilitation is seen at the level of the pupil. A
heightened ANS – combined sympathetic and parasympathetic – tone possibly
underlies the miosis seen in migraine patients during and in between
attacks.[3] It is only in the functional regulation of hollow, tubular
organs that an unambiguous mutually antagonistic “filling” or “emptying”
function for the sympathetic or the parasympathetic nervous system,
respectively, can be supported.
Cardiovascular autonomic function is far more complex, with
integration of local receptor distribution and catecholamine availability
to a higher level of control exerted by the central nervous system. Vaso-
vagal syncope is a commonly encountered cause of hypotensive syncope in
the unselected general population that is almost always associated with
stress. The pronounced bradycardia that characterizes vaso-vagal syncope
can be explained only by a simultaneous and over-riding neuro-cardiac
parasympathetic activation in the face of concomitant sympathetic nervous
system activation; such bradycardiogenic vagal stimulation is particularly
remarkable in patients with otherwise normal sympathoadrenal systems.
Normal heart rate variability during rest and deep breathing [1] indicates
a normal vagotonic influence in this patient. Sinus bradycardia and
prolonged PR interval is a marker of increased parasympathetic cardiac
tone [3] which features were not seen in this patient.[1] In general, it
cannot be maintained that emotional stimuli consistently raise blood
pressure in all patients.
The key issue in this patient seems to be hyperventilation-induced
hypotension in the supine position.[1] Stress does not generally induce
hyperventilation, as is evident from the clinical phenotype of anxiety
neurosis or panic attacks (DSMIIIR). Hyperventilation is certain form of
stress-related respiratory disorder that does not cause symptomatic
hypotension; the hyperventilating subject almost never complains of pre-
syncope or syncope. The authors suggest hyperventilation-related
hypocapnia as the mechanism of hypotension through direct peripheral
vasodilatation [1] but hypercapnia rather than hypocapnia is associated
with peripheral vasodilatation. Also, increase of heart rate during
hyperventilation in this patient [1] appears unrelated to attenuation of a
normal cardiac vagal innervation.
Lowering of peripheral vascular resistance during hyperventilation in
patients with autonomic failure or in healthy subjects during ganglionic
blockade [1] is probably linked to neuro-hormonal aberrations other than
those involving catecholamines. Vasopressin is believed to play a
prominent role in the regulation of the peripheral vascular resistance;
vasopressin may serve both as a vasoconstrictor and as a vasodilator.[4]
As a fundamentally adaptive stress-related neuropeptide subserving peptide
-catechol servomechanisms,[4] hyperventilation-related vasopressin (or
other vasodilator substance) release might be relevant to hypotension in
autonomic failure. A comprehensive analysis of hypotension in autonomic
failure requires to address all neuro-hormonal influences with potential
to affect the blood pressure.
References
1. Thijs RD, Dijk JG. Stress-induced hypotension in pure autonomic
failure. J Neurol Neurosurg Psychiatry published online 14 Dec 2005;
doi:10.1136/jnnp.2005.074369
2. Ziegler MG. Psychological stress and the autonomic nervous system.
In: Robertson D, Biaggioni I, Burnstock G, Low PA, eds. Primer on the
autonomic nervous system.
Amsterdam: Elsevier Academic Press 2004: 189-190.
3. Gupta VK. Parasympathetic hyperfunction during migraine attacks.
Headache 2004;44:730-731.
4. Gupta VK. A clinical review of the adaptive potential of
vasopressin in migraine. Cephalalgia 1997;17: 561-569.
Young and Mathias studied the cardiovascular effects of rapid water
ingestion in multiple system atrophy (MSA) and pure autonomic failure
(PAF) and discuss the possible mechanisms responsible for the hypertensive
response. [1] Involvement of increased sympathetic nerve activity or
denervation supersensitivity appears unlikely. Besides the response being
as great in PAF as in MSA (with a more rapid ons...
Young and Mathias studied the cardiovascular effects of rapid water
ingestion in multiple system atrophy (MSA) and pure autonomic failure
(PAF) and discuss the possible mechanisms responsible for the hypertensive
response. [1] Involvement of increased sympathetic nerve activity or
denervation supersensitivity appears unlikely. Besides the response being
as great in PAF as in MSA (with a more rapid onset in PAF) and the greater
probability of an increase in baseline blood pressure, [1] absence of
tachycardia following water ingestion does not support the occurrence of
sympathetic hyperfunction, either reactive or following denervation
supersensitivity.
Furthermore, measurement of muscle sympathetic nerve
activity has provided direct evidence that water drinking in normal human
subjects increases sympathetic nerve traffic, leading to peripheral
vasoconstriction that is unaccompanied by significant changes in arterial
blood pressure. [2] Even in normal subjects, therefore, the relationship
between water ingestion-related sympathetic activation and blood pressure
is not straightforward. Finally, water drinking elicits a pressor response
even if the direct connection between brain stem cardiovascular centers
and spinal sympathetic neurons is interrupted. [3]
While there is no known link between endothelin and water ingestion,
the second suggested mechanism [1], vasopressin is suppressed following
water ingestion. Vasopressin release cannot be targeted as a possible
mechanism for the hypertensive response of water ingestion in MSA or PAF.
To consider a state-related significant disruption of vasopressin
secretion in the absence of a polyuric syndrome also challenges scientific
logic; five minutes after water ingestion, when the pressor effect of
water was first recorded [1], under normal circumstances hardly any water
would have been absorbed to affect fluid or electrolyte balance. To
suggest that rate of gastric water absorption might be different in MSA or
PAF, an underlying gastric mechanistic link to the known pathophysiology
of these conditions must be explicated to sustain the proposal. Finally,
cholinergic neurons that regulate vasopressin release are damaged in MSA;
metoclopramide that increases vasopressin in control subjects, does not
increase vasopressin secretion in MSA patients. [4]
Adaptation is a highly complex phenomenon. The body perceives the
remote as well as the near, the future as well as the present. [5]
Anticipatory reflexes possibly play an important homeostatic function in
human physiology; vomiting is one example of such a mechanism. [6] The
sympathetic nervous system regulates the renin-angiotensin system in the
upright posture. The body might anticipate a water load as a threat to its
integrity, particularly in the face of sympathetic nervous system
impairment.
Transiently improved renal perfusion following water ingestion
might assist in handling the water load. Also, the renin-angiotensin
system can raise the peripheral vascular resistance without causing
tachycardia, as has been recorded in this study. This hypothesis can be
investigated by studying release of renin following water ingestion in
patients with chronic autonomic failure.
As a management option for orthostatic symptoms, water drinking [1]
is a rather inconvenient strategy that appears to have a temporally-
limited hypertensive effect. Repeated water drinking during awake periods
can be a demanding therapeutic manœuvre. Long-acting analogues of
vasopressin or angiotensin II might manage symptomatic orthostatic
hypotension much better. The antidiuretic, V2-receptor specific,
vasopressin analogue desmopressin increases the intravascular volume and
has been proposed for the management of syncope. [7] Unlike rapid water
drinking, with controlled administration of desmopressin the body is
unlikely to perceive gradual fluid retention as a threat.
References
(1). Young TM, Mathias CJ. The effects of water ingestion on
orthostatic hypotension in two groups of chronic autonomic failure:
multiple system atrophy and pure autonomic failure. J Neurol Neurosurg
Psychiatry 2004;75:1737-1741.
(2). Scott EM, Greenwood JP, Gilbey SG, Stoker JB, Mary DA. Water
ingestion increases sympathetic vasoconstrictor discharge in normal human
subjects. Clin Sci (Lond) 2001;100:335-342.
(3). Tank J, Schroeder C, Stoffels M, Diedrich A, Sharma AM, Luft FC,
Jordan J. Pressor effect of water drinking in tetraplegic patients may be
a spinal reflex. Hypertension 2003;41:1234-1239.
(4). Norbiato G, Bevilacqua M, Righini V, Chebat E, Vago T, Bertora P,
Castelli L, Mangoni A. Altered vasopressin response to metoclopramide in
multiple system atrophy: evidence of a cholinergic defect in the
hypothalamus. Acta Neurol Scand 1992;85:299-303.
(5). Carell A. Man, the unknown. Hamish Hamilton Ltd., London. 1959,
p.149.
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