Letters to the Editor
Stroke welcomes Letters to the Editor and will publish them, if suitable, as space permits. They should not exceed 750 words (including references)
and may be subject to editing or abridgment. Please submit letters in duplicate, typed double-spaced. Include a fax number for the corresponding author and
a completed copyright transfer agreement form (published in every issue).
Homocysteine, Vitamin B6, and Endothelial
Dysfunction in Circulatory Disorders
endothelial dysfunction in hyperhomocyst(e)inemia: effects of L-arginine
and B vitamins. Cardiovasc Res. 2003;57:244 –252.
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To the Editor:
We read with interest the recent article by Kelly and colleagues1
dealing with the relationship among serum vitamin B6 measured as
pyridoxal 5⬘-phosphate (PLP), serum total homocysteine (tHcy), and
C-reactive protein (CRP) in patients after ischemic stroke. The results of
their study with univariate and multivariable analyses demonstrated that
among stroke patients, CRP was a predictor of PLP. In addition, they
indicated that among control subjects, both CRP and tHcy were
independent predictors of PLP, although there was no association
between CRP and tHcy. The authors proposed that vitamin B6 but not
tHcy might be a marker of inflammatory status and vascular diseases.
There is evidence that homocysteines might disturb the bioavailability of nitric oxide (NO), which would, at least in part, contribute
to the pathophysiology of circulatory disorders. Stühlinger et al2
examined the relationship among homocysteine, NO, and endothelial function in patients with peripheral arterial disease, and demonstrated that experimentally-induced hyperhomocysteinemia increased plasma asymmetric dimethylarginine (ADMA), an
endogenous NO synthase inhibitor, an effect that was temporally
related to a decline in endothelial vasodilator function. This is an
important mechanism for the endothelial dysfunction that occurs in
hyperhomocysteinemia.3 In a study presented earlier, we demonstrated that estrogen-induced improvement of membrane fluidity (a
reciprocal value of microviscosity) of erythrocytes was counteracted
by ADMA, suggesting that ADMA might actively participate in the
regulation of rheologic behavior of cell membranes and microcirculation in postmenopausal women.4 In this context, we speculate
that the decreased bioavailability of NO due to ADMA might
partially explain the increased risk for endothelial dysfunction in
subjects with hyperhomocysteinemia. Because accumulation of
ADMA and increased oxidative stress might be involved in vascular
diseases,5 we would like to know whether vitamin B6 and CRP
might be linked to plasma NO metabolite and ADMA levels in the
present study of Kelly and colleagues. It would be important to
assess more precisely the relationships among vitamin B6, CRP, and
tHcy, and their contribution to the mechanisms underlying endothelial dysfunction and vascular complications in circulatory disorders.
Response:
We thank Drs Tsuda and Nishio for their interest in our paper. We
agree that both experimental and clinical evidence suggests that accumulation of asymmetric dimethylarginine (ADMA) may be an important mediator of homocysteine-related systemic and cerebral endothelial
dysfunction, likely via inhibition of endothelial nitric oxide synthase
(eNOS).1–4 These data add to previous studies suggesting that homocysteine may cause endothelial injury and dysfunction by other mechanisms, including free radical-induced membrane lipid peroxidation,
reduced nitric oxide production, and impaired expression and activity of
the antioxidant enzyme glutathione peroxidase.1
In population health terms, these mechanisms are likely to be
most relevant in individuals with plasma total homocyst(e)ine
(tHcy) in the mild-to-moderate range (15 to 100 ␮mol/L).
Internationally, the reported prevalence of elevated tHcy varies
according to the nutritional status of the specific population. In
the United States, data from the Framingham cohort and other
sources indicate that the prevalence of elevated tHcy has fallen
by approximately 50% since the introduction of folic acid grain
fortification in 1998, with greatest benefit observed among
individuals with higher prefortification tHcy levels.5
In our postfortification sample, we found identical tHcy distributions among individuals with stroke and matched controls, perhaps
reflecting a disproportionate benefit of fortification among patients
with vascular disease and higher prefortification tHcy. In our study,
low B6 status was associated with stroke independent of established
risk factors, a relationship that was partly mediated via inflammation
as measured by C-reactive protein.6,7 We did not measure ADMA in
this sample, but we are investigating the relationships between
inflammation, nutritional status, and oxidant stress following acute
ischemic stroke in ongoing studies.
Peter J. Kelly, MB, MS, MRCPI
Karen L. Furie, MD, MPH
Department of Neurology
Stroke Service
Massachusetts General Hospital
Boston, Massachusetts
Kazushi Tsuda, MD, FAHA
Ichiro Nishio, MD
Division of Cardiology
Department of Medicine
Wakayama Medical University
Wakayama, Japan
1. Faraci FM, Lentz SR. Hyperhomocysteinemia, oxidative stress, and
cerebral vascular dysfunction. Stroke. 2004;35:345–347.
2. Faraci FM, Brian JE, Heistad DD. Responses of cerebral blood vessels to an
endogenous inhibitor of nitric oxide synthase. Am J Physiol 1995;269;
H1522–H1527.
3. Boger RH, Bode-Boger SM, Sydow K, Heistad DD, Lentz SR. Plasma
concentration of asymmetric dimethylarginine, an endogenous inhibitor of
nitric oxide synthase, is elevated in monkeys with hyperhomocyst(e)inemia or
hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2000;20:1557–1564.
4. Stühlinger MC, Oka RK, Graf EE, Schmolzer I, Upson BM, Kapoor O,
Szuba A, Malinow R, Wascher TC, Pachinger O, Cooke JP. Endothelial
dysfunction induced by hyperhomocyst(e)inemia. Role of aymmetric dimethylarginine. Circulation. 2003;108:933–938.
5. Jacques PF, Selhub J, Bostom AG, Wilson PWF, Rosenberg IH. The effect
of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med. 1999;340:1449 –1454.
6. Kelly PJ, Shih VE, Kistler JP, Barron M, Lee H, Mandell R, Furie KL. Low
vitamin B6, but not homocyst(e)ine, is associated with increased risk of
stroke/TIA in the era of folic acid grain fortification. Stroke. 2003;34:e51–e54.
7. Kelly P, Kistler J, Shih V, Mandell R, Atassi N, Barron M, Silveira S, Furie
KL. Inflammation, homocysteine, and vitamin B6 status following ischemic stroke. Stroke. 2004;35:12–15.
1. Kelly PJ, Kistler JP, Shih VE, Mandell R, Atassi N, Barron M, Lee H,
Silveira S, Furie KL. Inflammation, homocysteine, and vitamin B6 status
after ischemic stroke. Stroke. 2004;35:12–15.
2. Stühlinger MC, Oka RK, Graf EE, Schmolzer I, Upson BM, Kapoor O,
Szuba A, Malinow R, Wascher TC, Pachinger O, Cooke JP. Endothelial
dysfunction induced by hyperhomocyst(e)inemia. Role of aymmetric dimethylarginine. Circulation. 2003;108:933–938.
3. Tsuda K, Nishio I. Asymmetric dimethylarginine and circulatory disorders
in postmenopausal women. Circulation. 2004;109:e35.
4. Tsuda K, Kinoshita Y, Kimura K, Nishio I, Masuyama Y. Electron paramagnetic resonance investigation on modulatory effect of 17beta-estradiol
on membrane fluidity of erythrocytes in postmenopausal women. Arterioscler Thromb Vas Biol. 2001;21:1306 –1312.
5. Sydow K, Schwedhelm E, Arakawa N, Bode-Boger SM, Tsikas D, Hornig
B, Frohlich JC, Boger RH. ADMA and oxidative stress are responsible for
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Letters to the Editor
Blood Pressure in Acute Stroke and Its
Prognostic Value
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To the Editor:
We read with interest the recent paper by Castillo and
colleagues evaluating the prognostic relevance of admission
blood pressure (BP) values and describing a U-shaped effect in
patients with acute ischemic stroke, as well as Boysen’s editorial
comment on this issue.1,2 The study’s conclusion was that both
high and low admission BP values are associated with poor
prognosis regarding early neurological deterioration, infarct volume, and mortality at 3 months. After adjustment for the use of
antihypertensive drugs and BP drop ⬎20mm Hg, the authors
found that the latter was the most important prognostic factor for
poor outcome.
Before accepting these important conclusions, we think that
some comments are needed. We have also evaluated the prognostic value of admission BP values in an unselected collective
of acute stroke patients. Our findings demonstrated that early and
late mortality in patients with ischemic stroke as well as in
patients with intracerebral hemorrhage followed a U-shaped
pattern in relation to systolic and diastolic BP at admission.3 Low
admission BP values were associated with heart failure and
coronary artery disease, whereas high BP values were associated
with history of hypertension and lacunar stroke. Death due to
cardiovascular disease was significantly more frequent among
patients with admission BP values beneath the U-point of
130 mm Hg, whereas death due to brain edema was significantly
more frequent above this U-point.3 We also demonstrated by
means of 24-hour BP monitoring that persisting elevated systolic
24-hour BP values during the acute phase of stroke are associated
with subsequent brain edema formation in patients not receiving
antihypertensive medication during the BP monitoring.4 Investigating the relationship of 24-hour BP to baseline characteristics
in stroke subtypes of different etiopathogenic mechanisms, we
found that high and low 24-hour BP values correlated with brain
edema and heart failure, respectively, in patients with cardioembolic stroke; whereas low BP values correlated with coronary
artery disease in lacunar patients.5
The study of Castillo and colleagues differs from our own
work in several aspects that deserve attention. Castillo et al
suggest that both low and high admission BP values are associated with a higher mortality. However, with the exception of
atrial fibrillation, no other data concerning concomitant diseases
are given. In addition, details about the exact causes of death in
deceased patients would be useful. Such data would be interesting and, if in accordance with ours,3,5 they would then support
Boysen’s thesis that the U-shape relationship may reflect cardiac
failure being more important in stroke patients with low systolic
BP.2 Another issue, which probably needs further discussion, is
whether not only ischemic but also edematous tissue was
included in the hypodense zone, which was used for infarct
volume calculation. Should that be the case, it would be in
accordance with our results.3,4 Moreover, the International
Stroke Trial (IST) described an independent association between
death resulting from presumed cerebral edema and high systolic
BP.6 We therefore support Boysen’s assumption that the U-shape
relationship may reflect an adverse effect on brain edema in
those with very high BP values.2 Additionally, the finding that a
BP drop ⬎20 mm Hg within the first day is the most important
prognostic factor of poor outcome should be faced with caution.
Christensen et al have reported that an early spontaneous BP
decline is associated with good outcome.7 Furthermore, elevated
weighted mean arterial blood pressure values were associated
with poor outcome in the GAIN Trial.8 Finally, according to our
data, the lower incidence of brain edema observed in hyperacute
stroke patients who sustained a spontaneous BP decline could be
attributed to an earlier normalization of poststroke hypertension.4
The fact that in Castillo’s study the physicians of the emergency
department treated 22% of all patients with antihypertensive
agents without following specific guidelines for BP management
raises the question whether that was really indicated in all these
cases. It is obvious that the described BP drop is not spontaneous
and at least in part drug-induced. It also remains unclear if some
or all of the patients who received antihypertensive medication in
the stroke unit were already premedicated in the emergency
department. This might have caused an excessive BP decline
leading to hypoperfusion and clinical deterioration, especially in
cases of lacunar stroke.
In conclusion, we agree that high and low BP correlates with
poor prognosis and that it is unlikely that there will be one
treatment for all stroke patients.1,2 Prospective randomized clinical trials with sufficient size and power to include representative
patient groups of different age, concomitant diseases, severity,
and etiology are required to clarify the issue of optimal BP
management in the acute stroke setting.
Georgios Tsivgoulis, MD
Konstantinos Spengos, MD
Department of Neurology
University of Athens, Eginition Hospital
Athens, Greece
Konstantinos N. Vemmos, MD
Acute Stroke Unit
Department of Clinical Therapeutics
University of Athens, Alexandra Hospital
Athens, Greece
1. Castillo J, Leira R, Garcia MM, Serena J, Blanco M, Dávalos A. Blood
pressure decrease during the acute phase of ischemic stroke is associated
with brain injury and poor stroke outcome. Stroke. 2004;35:520 –526.
2. Boysen G. Editorial comment–persisting dilemma: to treat or not to treat
blood pressure in acute ischemic stroke. Stroke. 2004;35:526 –527.
3. Vemmos KN, Tsivgoulis G, Spengos K, Zakopoulos N, Synetos A, Kotsis
V, Vassilopoulos D, Mavrikakis M. Association between 24-h blood
pressure monitoring variables and brain oedema in patients with
hyperacute stroke. J Hypertens. 2003;21:2167–2173.
4. Vemmos KN, Tsivgoulis G, Spengos K, Zakopoulos N, Synetos A, Manios
E, Konstantopoulou P, Mavrikakis M. U-shaped relationship between
mortality and admission blood pressure in patients with acute stroke.
J Intern Med. 2004;255:257–265.
5. Vemmos KN, Spengos K, Tsivgoulis G, Zakopoulos N, Manios E, Kotsis
V, Daffertshofer M, Vassilopoulos D. Factors influencing acute blood
pressure values in stroke subtypes. J Hum Hypertens. 2004;18:253–259.
6. Leonardi-Bee J, Bath PM, Phillips SJ, Sandercock PA; IST Collaborative
Group. Blood pressure and clinical outcomes in the International Stroke
Trial. Stroke. 2002;33:1315–1320.
7. Christensen H, Meden P, Overgaard K, Boysen G. The course of blood
pressure in acute stroke is related to the severity of the neurological
deficits. Acta Neurol Scand. 2002;106:142–147.
8. Aslanyan S, Fazekas F, Weir CJ, Horner S, Lees KR; GAIN International
Steering Committee and Investigators. Effect of blood pressure during the
acute period of ischemic stroke on stroke outcome. A tertiary analysis of
the GAIN international trial. Stroke. 2003;34:2420 –2425.
Response:
We appreciate the interest of Tsivgoulis et al in our article on
the association of high and low systolic and diastolic blood
pressure (BP), as well as a relevant drop in BP, with poor
prognosis in patients with ischemic stroke.1 We think that their
letter raises some interesting points that may help clarify the
issue of optimal BP management in the acute stroke setting.
Although we did an observational study without the aim of
investigating the etiopathogenic mechanisms linked to stroke
prognosis, a further exploratory analysis of our data allows us to
give some light to the several mechanisms that have been
proposed to explain the association between both high and low
BP and outcome.
Letters to the Editor
1787
Place of Antihypertensive Treatment Administration and BP Change
Place Where Hypotensive Treatment Was Administered
No Treatment
n⫽214
Emergency Unit
n⫽55
Stroke Unit
n⫽19
Emergency and Stroke Units
n⫽12
Decrease of systolic BP between admission and the first day (mm Hg)
⫺3 (⫺7,2)
⫺28 (⫺51,⫺14)
⫺11 (⫺16,⫺7)
⫺39 (⫺69,⫺29)
Decrease of diastolic BP between admission and the first day (mm Hg)
⫺3 (⫺9,⫺1)
⫺22 (⫺33,⫺11)
⫺11 (⫺22,⫺5)
⫺18 (⫺32,⫺18)
Mortality (%)
17.5
16.1
11,5
25.0
Early neurological deterioration (%)
20.5
43.3
22.6
41.7
By stroke subtype*
Cardioembolic/Undetermined
22/76 (28.9%)
17/32 (53.1%)
Atherothrombotic
21/91 (23.1%)
6/47 (12.8%)
Lacunar
3/8 (37.5%)
5/6 (83.3%)
6/17 (35.3%)
0/8 (0%)
1/5 (20%)
1/6 (17.7%)
0/3 (0%)
0/1 (0%)
*Total number of patients by stroke subtype/percentage with early neurological deterioration.
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According to the findings reported by Tsivgoulis et al2 and to the
Boysen’s editorial comment,3 our data support the notion that the
U-shape mortality pattern reflects cardiovascular diseases being
more frequent in stroke patients with low systolic BP. In the 9
patients with cardiac causes of death (acute myocardial infarction,
n⫽5; heart failure, n⫽4) median [range] admission systolic BP (126
[108 –162] versus 166 [130 –218] mm Hg, P⬍0.001) and diastolic
BP (67 [55– 81] versus 83 [70 –120] mm Hg, P⬍0.001) were lower
than in those with stroke- or infection-related death (n⫽16 and
n⫽11, respectively).
As Tsivgoulis et al mention, part of the hypodensity volume on
CT may reflect brain edema instead of definitive necrosis. Although
we did not evaluate the potential mass effect of the ultimate infarct
volume, systolic BP (217 [190 –234] versus 168 [144 –181] mm Hg,
P⬍0.001) and diastolic BP (117 [108 –132] versus 86 [75–
102] mm Hg, P⬍0.0001) were higher in the 98 patients with early
hypodensity on CT. Systolic BP was also significantly higher in the
12 patients who died because of brain edema compared with those
with other causes of mortality (226 [184 –240] versus 140 [122–
175] mm Hg, P⬍0.001). Therefore, high systolic BP above the
U-point of 180 mm Hg could have adverse effects on brain edema,
and consequently increase early neurological deterioration and
mortality.
A further point of interest is that high BP may also produce basal
lamina disturbances, promoting hemorrhagic transformation (HT)
of the cerebral infarct.4,5 In our study, HT was seen in 27% of
patients with systolic BP ⬎180 mm Hg, whereas it was present in
7% of patients with systolic BP below these values (P⬍0.001). HT
was associated with neurological worsening and poor outcome,
although the poor prognosis could be attributed to the HT itself in
only 8 patients with parenchymal hemorrhage.
As we recognize in our study, the wrong use of antihypertensive drugs in many instances could lead to hypoperfusion
and clinical deterioration. The administration of these agents
in the emergency unit was associated with a greater reduction
in BP in comparison with that observed when therapy was
given by neurologists in the stroke unit (Table). Accordingly,
early neurological deterioration was more frequent in patients
who received the treatment in the emergency unit than in those
treated in the stroke unit. This effect was of more particular
importance in patients with cardioembolic stroke than in those
with lacunar stroke. This finding is consistent with the idea
that a drop in BP might have a less detrimental effect in
lacunar infarctions or in large territorial ischemia where a
penumbral area is more likely, a hypothesis that has been
suggested to explain the different outcome in patients with
lacunar and territorial infarctions in the IMAGES Trial.6
José Castillo, MD, PhD
Department of Neurology
Hospital Clı́nico Universitario
Santiago de Compostela, Spain
Antoni Dávalos, MD, PhD
Department of Neurology
Hospital Universitari Doctor Josep Trueta
Girona, Spain
1. Castillo J, Leira R, Garcia MM, Serena J, Blanco M, Dávalos A. Blood
pressure decrease during the acute phase of ischemic stroke is associated
with brain injury and poor stroke outcome. Stroke. 2004;35:520 –526.
2. Vemmos KN, Tsivgoulis G, Spengos K, Zakopoulos N, Synetos A, Kotsis V,
Vasilopoulos D, Mavrikakis M. Association between 24-h blood pressure
monitoring variables and brain edema in patients with hyperacute stroke.
J Hypertens. 2003;21:2167–2173.
3. Boysen G. Editorial comment–persisting dilemma: to treat or not to treat blood
pressure in acute ischemic stroke. Stroke. 2004;35:526–527.
4. Bath FJ, Bath PMW. What is correct management of blood pressure in acute
stroke? The Blood Pressure in Acute Stroke Collaboration. Cerebrovasc Dis.
1997;7:205–213.
5. Dávalos A, Castillo J, Leira R, Serena J, Aneiros A, Castellanos M.
Metalloproteinase-9 (MMP-9), early CT signs of cerebral ischemia and
high blood pressure in acute stroke. Cerebrovasc Dis. 2001; 11(suppl
4):118.
6. Intravenous Magnesium Efficacy in Stroke (IMAGES) Study Investigators.
Magnesium for acute stroke (Intravenous Magnesium Efficacy in Stroke
Trial): randomised controlled trial. Lancet. 2004;363:439– 445.
Spasticity After Stroke: Why Bother?
To the Editor:
Perseveration of behavior is a significant clinical symptom
among intentional disorders of organic brain disease, attributed
by some authors especially to prefrontal brain impairment.
However, the perseverative preoccupation of professional neurologists and therapists with the purpose of overpowering the
spasticity ogre seems to be an endemic, intractably-taught
delusion that afflicts both academic scholars and clinicians.1,2
In 1951, Thomas Twitchell published a 37-page analysis of the
clinical course of recovery of 121 acute hemiplegic stroke
patients in the Boston City Hospital.3 Early on they were
examined daily, and 25 were carefully followed for weeks or
months until they reached a stable status of recovery or disability.
Twitchell described in great detail both the usual and exceptional
patterns of functional recovery, along with the associated patterns of reflex phenomena. Following transient flaccidity associated with acute paralysis, resistance to passive stretch evolved
during the first several days.
1788
Letters to the Editor
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Twitchell concluded, “The great disability which results when
recovery is halted in the phase of heightened proprioceptive
activity has prompted many earlier investigations. Walshe (1919)
clarified the previously confused views as to the nature of
spasticity, and showed its identity with the type of exaggeration
of postural reflexes seen in decerebrate rigidity. The analysis of
Sherrington and his collaborators subsequently identified the
stretch reflex as the fundamental reaction of such disorder. It has
often been assumed that if spasticity could be abolished, willed
movement could be more effectively performed. The present
study indicates that the first movements to appear following
hemiplegia are themselves facilitated stretch reflexes. The problem at that stage is not so much to abolish the spastic reaction, as
to harness its diffuse hyperactivity.” Burke’s extensive neurophysiological analysis points out that spasticity may be a functionally useful adaptation to pyramidal tract injury.4 The only
substantive clinical performance accomplishment of baclofen is
partial diminution of phasic flexor spasms.5 Tizanidine does no
better.6
Like the nociceptive extensor plantar reflex of Babinski and
tendon jerk proprioceptive hyperreflexia, spasticity is also a
release phenomenon. There are no data or rationale to suggest
that severing the extensor hallucis longus tendon may improve
recovery from stroke. Similarly, regarding spasticity, I have yet
to find any adequately controlled demonstration that the steadfast
fad of fixing this phantom facilitates functional recovery from
hemiplegia; there is much evidence to the contrary.4 –13 The
integrated forebrain and hindbrain organizations that accomplish
fine adaptive coordination, as in handwriting, piano playing,
walking down steps, or ballet dancing, are orders of magnitude
beyond the simplistic spinal reflex concept of competitive force
between agonist and antagonist about a single joint.
I do applaud the rediscovery by Sommerfeld et al that the
“focus on spasticity in stroke rehabilitation is out of step with its
clinical importance.” I hope, too, that the editorial reviewer, Dr
Kramer, may cease to search for “additional studies needed to
refine guidelines for treating spasticity after stroke.” George
Leigh Mallory’s personal rationale for climbing to the peak of
Everest was “because it is there.” Mallory failed. “Because it is
there” constitutes neither scientific nor ethical rationale for the
reflex temptation to treat this reflex.
William M. Landau, MD
Department of Neurology
School of Medicine
Washington University in Saint Louis
Saint Louis, Missouri
1. Sommerfeld DK, Eek EU, Svensson AK, Holmqvist LW, von Arbin MH.
Spasticity after stroke: its occurrence and association with motor
impairments and activity limitations. Stroke. 2004;35:134 –139.
2. Cramer SC. Editorial comment–spasticity after stroke: what’s the catch?
Stroke. 2004;35:139 –140.
3. Twitchell TE. The restoration of motor function following hemiplegia in
man. Brain. 1951;74:443– 480.
4. Burke D. Spasticity as an adaptation to pyramidal tract injury. Adv
Neurol. 1988;47:401– 423.
5. Landau WM. Spasticity: What is it? What is it not? In: Feldman RG,
Young RR, Koella WP, eds. Spasticity: Disordered Motor Control.
Chicago, Ill: Yearbook Medical Publishers; 1980;17–24.
6. Landau WM. Clinical Neuromythology XIV. There you go again: the
steadfast fad of fixing spasticity. Neurology. 1995;45:2295–2296.
7. Landau WM, Weaver RA, Hornbein TF. Fusimotor nerve function in
man: differential nerve block studies in normal subjects and in spasticity
and rigidity. Arch Neurol. 1960;3:10 –23.
8. Landau WM. Spasticity: the fable of a neurological demon and the
emperor’s new therapy. Arch Neurol. 1974;31:217–219.
9. Sahrmann SA, Norton BJ. The relationship of voluntary movement to
spasticity in the upper motor neuron syndrome. Ann Neurol. 1977;2:
460 – 465.
10. Landau WM. Clinical Neuromythology II. Parables of palsy pills and PT
pedagogy: a spastic dialectic. Neurology. 1988;38:1496 –1499.
11. Landau WM, Hunt CC. Dorsal rhizotomy, a treatment of unproven
efficacy. J Child Neurol. 1990;5:174 –178.
12. McLaughlin JF, Bjornson KF, Astley SJ, Graubert C, Hays RM, Roberts
TS, Price R, Temkin N. Selective dorsal rhizotomy: efficacy and safety in
an investigator masked randomized clinical trial. Dev Med Child Neurol.
1998;40:220 –232.
13. Landau WM. Muscle tone: hypertonus, spasticity, rigidity. In: Elsevier’s
Encyclopedia of Neuroscience, 3rd edition. 2001; 1–5.
Response:
We thank Professor Landau for his appreciated comment on
our article1 about spasticity after stroke. In the reported and
commented study1 we found spasticity in only a minority of the
hemiparetic patients assessed 3 months after acute stroke. The
results from our population-based study provide an original
clinical support of the theories proposed by Professor Landau in
his comment of our article. Additional data, including the
number of patients presenting with possible spasticity, ie, exaggerated reflexes as well as intrinsic changes of the muscles,
according to the modified Ashworth scale,2 18 months after
stroke, will soon be presented.
In the spiritual reflection on spasticity, Professor Landau
points out the lack of scientific proof supporting the common
interest in spasticity after stroke. Considering available scientific
proof, both theoretical3 and clinical,1,4 the former assumption
that hemiparesis depends on the lesion of the upper motor neuron
with accompanying spasticity can no longer remain the basis for
physiotherapy assessments or interventions in stroke rehabilitation. Physiotherapists “treating spasticity” most certainly do not
treat any exaggerated reflexes but possibly the intrinsic changes
of the muscles. As Professor Landau suggests: let us restrain the
reflex temptation to treat this reflex.
Disa K. Sommerfeld, PT, PhD
Department of Geriatric Medicine
Danderyd Hospital
Danderyd, Sweden
and Neurotec Department
Division of Physiotherapy
Karolinska Institute
Huddinge, Sweden
Elsy Eek, PT, MSc
Department of Geriatric Medicine
Danderyd Hospital
Danderyd, Sweden
Anna-Karin Svensson, PT, MSc
Lotta Widén Holmqvist, PT, PhD
Neurotec Department
Division of Physiotherapy
Karolinska Institutet
Huddinge, Sweden
Magnus H. von Arbin, MD, PhD
Stroke Unit, Division of Internal Medicine
Karolinska Institutet
Stockholm, Sweden
1. Sommerfeld DK, Eek EU, Svensson AK, Holmqvist LW, von Arbin MH.
Spasticity after stroke: its occurrence and association with motor
impairments and activity limitations. Stroke. 2004;35:134 –139.
2. Bohannon RW, Smith MB. Interrater reliability of a modified Ashworth
scale of muscle spasticity. Phys Ther. 1987;67:206 –207.
3. Sheean G. The pathophysiology of spasticity. Eur J Neurol. 2002;9:3–9.
4. O’Dwyer NJ, Ada L, Neilson PD. Spasticity and muscle contracture
following stroke. Brain. 1996;119:1737–1749.
Letters to the Editor
Neurobiology of Poststroke Depression
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To the Editor:
Eriksson et al1 find that the substantial proportion of stroke
patients reporting depressive mood but not using treatment with
antidepressants suggests that patient selection for treatment
should be more precise. This may be accomplished by monitoring speech hesitation pauses (SHPs), which are behavioral
correlates of mood. Neurobiological features are demonstrated
by (1) the correlation of rate and variability in duration of SHPs
4.79⫾2.48 per minute, 1.50⫾0.33 seconds (mean ⫾SD) with the
left and right hemisphere, respectively; and (2) the association of
the reduction of blood pressure with longer, less recurrent SHPs
of about 2 seconds.
These responses are linked to the feeling of rhythmical and
prefrontal cortex modulation of dopamine lateralized to the right
hemisphere during the delayed alternation task. This hypothesis
is supported by (1) optimum response organization and working
memory at intermediate dopamine tone in a mediofrontalstriatal
activation system, a study demonstrating that auditory training
induces asymmetrical changes in cortical neural activity; (2) a
report that pauses convey meaning beyond words; (3) the role of
silence in expressing the inexpressible (Aldous Huxley); and (4)
the much-quoted “Heard melodies are sweet, but those unheard
are sweeter” (John Keats).2– 4
1789
Therefore, the analysis of SHPs on a time-base may be
included in the development of a comprehensive measure of
poststroke depression, optimal poststroke assessment intervals, and determination of a representative population
reference.5
Ernest H. Friedman, MD
Department of Medicine and Psychiatry
Case University
Cleveland, Ohio
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2. Friedman EH. Re: Interhemispheric asymmetries of motor cortex excitability in the postacute stroke stage (letter). Stroke. 2004;35:e73.
3. Friedman EH. Music and neuroscience (letter). Update, New York
Academy of Sciences Magazine. April/May 2004:1.
4. Shriberg E, Bates R, Stolcke A, Taylor P, Jurafsky D, Ries K, Coccaro N,
Martin R, Meteer M, van Ess-Dykema C. Can prosody aid the automatic
classification of dialog acts in conversational speech? Lang Speech. 1998;
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5. Bhogal SK, Teasell R, Foley N, Speechley M. Lesion location and poststroke depression. Systematic review of the methodological limitations in
the literature. Stroke. 2004;35:794 – 802.
Spasticity After Stroke: Why Bother?
William M. Landau
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Stroke. 2004;35:1787-1788; originally published online July 1, 2004;
doi: 10.1161/01.STR.0000136388.80433.eb
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