Treatment with thrombolytic therapy in ischemic stroke is effective and safe but data on its safety and efficacy in different stroke subtypes and etiologies is lacking. Different parameters can influence the effectiveness and risk of thrombolysis in stroke patients and knowledge of these factors can be useful to inform therapeutic decisions, often involving actions outside the general consensus or decisions based on risk/benefit. This information may also be useful as a prognostic element and help guide rehabilitation conduct. Among the numerous parameters that can be analyzed, laterality of the arterial territory affected represents a favorable element which is readily and quickly assessed. Cerebrovascular events often cause neuropsychological deficits that are related to the side of the stroke, for example, aphasia in the left cerebral hemisphere (LCH) and neglect in the right cerebral hemisphere (RCH).
RCH strokes are often underestimated by clinical rating scales11 .Audebert HJ, Singer OC, Gotzler B, Vatankhah B, Boy S, Fiehler J et al.
Postthrombolysis hemorrhage risk is affected by stroke assessment bias between
hemispheres. Neurology, 2011;76(7):629-36.
http://dx.doi.org/10.1212/WNL.0b013e31820ce505
https://doi.org/10.1212/WNL.0b013e31820c...
,22 .The National Institute of Neurological Disorders; Stroke rt-PA Stroke Study
Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med.
1995;333(24):1581-7. http://dx.doi.org/10.1056/NEJM199512143332401
https://doi.org/10.1056/NEJM199512143332...
because
deficits such as language disorders (typical of the LCH) are more easily recognized than
neglect or agnosias, typical of the RCH22 .The National Institute of Neurological Disorders; Stroke rt-PA Stroke Study
Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med.
1995;333(24):1581-7. http://dx.doi.org/10.1056/NEJM199512143332401
https://doi.org/10.1056/NEJM199512143332...
,33 .Fink JN. Underdiagnosis of right-brain stroke. Lancet.
2005;366(9483):349-51. http://dx.doi.org/10.1016/S0140-6736(05)67004-3
https://doi.org/10.1016/S0140-6736(05)67...
. Imaging
studies show that RCH stroke patients can be rated lower by the NIH scale, despite having a
large cerebral infarct area33 .Fink JN. Underdiagnosis of right-brain stroke. Lancet.
2005;366(9483):349-51. http://dx.doi.org/10.1016/S0140-6736(05)67004-3
https://doi.org/10.1016/S0140-6736(05)67...
,44 .Cheng B, Forkert ND, Zavaglia M, Hilgetag CC, Golsari A, Siemonsen S et al.
Influence of stroke infarct location on functional outcome measured by the modified rankin
scale. Stroke. 2014;45(6):1695-702.
http://dx.doi.org/10.1161/STROKEAHA.114.005152
https://doi.org/10.1161/STROKEAHA.114.00...
. Stroke severity, as measured by the NIH scale,
an internationally accepted instrument, is one of the criteria used for patient selection. The
scale could be adjusted by hemisphere affected for a more accurate assessment of patient
hemorrhage risk11 .Audebert HJ, Singer OC, Gotzler B, Vatankhah B, Boy S, Fiehler J et al.
Postthrombolysis hemorrhage risk is affected by stroke assessment bias between
hemispheres. Neurology, 2011;76(7):629-36.
http://dx.doi.org/10.1212/WNL.0b013e31820ce505
https://doi.org/10.1212/WNL.0b013e31820c...
, should the hypothesis of a
relationship between laterality and severity be proven. These factors may contribute to less
frequent thrombolysis of RCH stroke patients who consequently do not receive adequate
treatment. Difficulties detecting symptoms of RCH stroke are challenges which must be overcome
in order to optimize conduct, particularly during the acute phase of stroke.
The topographic relationship regarding the side of the middle cerebral artery affected (right
or left) can represent a further element contributing to risk assessment and quantification of
prognosis. The issue remains controversial in the literature11 .Audebert HJ, Singer OC, Gotzler B, Vatankhah B, Boy S, Fiehler J et al.
Postthrombolysis hemorrhage risk is affected by stroke assessment bias between
hemispheres. Neurology, 2011;76(7):629-36.
http://dx.doi.org/10.1212/WNL.0b013e31820ce505
https://doi.org/10.1212/WNL.0b013e31820c...
,55 .Sato S, Heeley E, Arima H, Delcourt C, Hirakawa Y, Pamidimukkala V et al.
Higher mortality in patients with right hemispheric intracerebral haemorrhage: INTERACT1
and 2. J Neurol Neurosurg Psychiatry. 2015;pii: jnnp-2014-309870.
http://dx.doi.org/10.1136/jnnp-2014-309870
https://doi.org/10.1136/jnnp-2014-309870...
,66 .Fink JN, Frampton CM, Lyden P, Lees KR. Does hemispheric lateralization
influence functional and cardiovascular outcomes after stroke?: an analysis of
placebo-treated patients from prospective acute stroke trials. Stroke.
2008;39(12):3335-40. http://dx.doi.org/10.1161/STROKEAHA.108.523365
https://doi.org/10.1161/STROKEAHA.108.52...
,77 .Golsari A, Cheng B, Sobesky J, Schellinger PD, Fiehler J, Gerloff C et al.
Stroke lesion volumes and outcome are not different in hemispheric stroke side treated
with intravenous thrombolysis based on magnetic resonance imaging criteria. Stroke
2015;46(4):1004-8. http://dx.doi.org/10.1161/STROKEAHA.114.007292
https://doi.org/10.1161/STROKEAHA.114.00...
and
warrants further analyses.
Brain hemorrhage after thrombolysis is the most feared complication of the procedure22 .The National Institute of Neurological Disorders; Stroke rt-PA Stroke Study
Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med.
1995;333(24):1581-7. http://dx.doi.org/10.1056/NEJM199512143332401
https://doi.org/10.1056/NEJM199512143332...
,88 .Sociedade Brasileira de Doenças Cerebrovasculares. Primeiro consenso
brasileiro para trombólise no acidente vascular cerebral isquêmico agudo. Arq
Neuropsiquiatr. 2002;60(3A):675-80.
http://dx.doi.org/10.1590/S0004-282X2002000400032
https://doi.org/10.1590/S0004-282X200200...
and studies analyzing possible predictors of risk are of great
clinical interest.
Sato et al.55 .Sato S, Heeley E, Arima H, Delcourt C, Hirakawa Y, Pamidimukkala V et al.
Higher mortality in patients with right hemispheric intracerebral haemorrhage: INTERACT1
and 2. J Neurol Neurosurg Psychiatry. 2015;pii: jnnp-2014-309870.
http://dx.doi.org/10.1136/jnnp-2014-309870
https://doi.org/10.1136/jnnp-2014-309870...
, in a study analyzing a large
casuistic (2708 patients with supratentorial hemorrhage) found a higher death rate in
right-sided stroke but no effect of laterality on severity of sequelae among survivors.
Audebert et al.11 .Audebert HJ, Singer OC, Gotzler B, Vatankhah B, Boy S, Fiehler J et al.
Postthrombolysis hemorrhage risk is affected by stroke assessment bias between
hemispheres. Neurology, 2011;76(7):629-36.
http://dx.doi.org/10.1212/WNL.0b013e31820ce505
https://doi.org/10.1212/WNL.0b013e31820c...
stated that the higher
hemorrhage rates in RCH stroke reported were due to bias introduced by the scales
employed.
Brott et al.99 .Brott T, Tomsick T, Feinberg W, Johnson C, Biller J, Broderick J et al.
Baseline silent cerebral infarction in the Asymptomatic Carotid Atherosclerosis Study.
Stroke. 1994;25(6):1122-9. http://dx.doi.org/10.1161/01.STR.25.6.1122
https://doi.org/10.1161/01.STR.25.6.1122...
found a 15% higher incidence
of silent infarction in RCH compared to LCH; patients with previous silent stroke may have
poorer prognosis after thrombolysis, a finding which, if confirmed, can be used as an
auxiliary criteria to guide patient conduct.
The study of Ducci et al.1010 .Dal-Prá Ducci R, Lange MC, Moro CH, Harger R, Longo AL, Cabral NL, et al.
Does the side of middle cerebral artery compromise matters in the mortality after
thrombolysis in ischemic stroke? Arq Neuropsiquiatr. 2015;73(8):644-47.
http://dx.doi.org/10.1590/0004-282X20150079
https://doi.org/10.1590/0004-282X2015007...
, “Does
the side of middle cerebral artery compromise matters in the mortality after thrombolysis in
ischemic stroke?”, published in this edition, addresses this interesting yet little
studied aspect. The authors compared groups that were similar for risk factors and ischemic
stroke types in a Brazilian cohort. Specific racial and ethnic groups are known to have
predominance for injury in different locations (cervical arteries in Caucasians and
intracerebral arteries in Asians1111 .Lee PH, Oh SH, Bang OY, Joo SY, Joo IS, Hunk K. Infarct patterns in
atherosclerotic middle cerebral artery versus internal carotid artery disease. Neurology.
2004;62(8):1291-6. http://dx.doi.org/10.1212/01.WNL.0000120761.57793.28
https://doi.org/10.1212/01.WNL.000012076...
). Thus,
although not homogeneous for race and ethnicity, this report on a Brazilian population is
valuable. A detailed investigation into the characteristics of the artery involved in the
stroke would also be elucidating, since atherothrombosis with unstable and/or complex plaques
carries a higher risk of hemorrhage compared to embolisms. A study of the arteries using the
multidetector computed tomography angiography method, which has proven useful for this
purpose1212 .Pacheco FT, Littig IA, Gagliardi RJ, Rocha AJ. Multidector computed
tomography angiography in clinically suspected hyperacute ischemic stroke in the anterior
circulation: an etiological workup in a cohort of Brazilian patients. Arq Neuropsiquiatr.
2015;73(5):408-14. http://dx.doi.org/10.1590/0004-282X201500
https://doi.org/10.1590/0004-282X201500...
may, in future investigations,
contribute to better etiological and physiopathological definition. Akin to all retrospective
studies, the investigation by Ducci et al.1010 .Dal-Prá Ducci R, Lange MC, Moro CH, Harger R, Longo AL, Cabral NL, et al.
Does the side of middle cerebral artery compromise matters in the mortality after
thrombolysis in ischemic stroke? Arq Neuropsiquiatr. 2015;73(8):644-47.
http://dx.doi.org/10.1590/0004-282X20150079
https://doi.org/10.1590/0004-282X2015007...
has some inherent bias, such as the fact that some patients may not have been included due to
missing data. Golsari et al.77 .Golsari A, Cheng B, Sobesky J, Schellinger PD, Fiehler J, Gerloff C et al.
Stroke lesion volumes and outcome are not different in hemispheric stroke side treated
with intravenous thrombolysis based on magnetic resonance imaging criteria. Stroke
2015;46(4):1004-8. http://dx.doi.org/10.1161/STROKEAHA.114.007292
https://doi.org/10.1161/STROKEAHA.114.00...
, in a recent
study involving patients thrombolysed due to stroke, quantified stroke and infarct volume
using diffusion magnetic resonance imaging. The authors analyzed evolution over three months
(using the modified Rankin scale), comparing groups with RCH and LCH strokes. No difference in
severity for stroke side was found but a difference in volume of tissue affected was
identified. This result may explain the findings of Ducci et al.1010 .Dal-Prá Ducci R, Lange MC, Moro CH, Harger R, Longo AL, Cabral NL, et al.
Does the side of middle cerebral artery compromise matters in the mortality after
thrombolysis in ischemic stroke? Arq Neuropsiquiatr. 2015;73(8):644-47.
http://dx.doi.org/10.1590/0004-282X20150079
https://doi.org/10.1590/0004-282X2015007...
The fact that the Ducci et al.1010 .Dal-Prá Ducci R, Lange MC, Moro CH, Harger R, Longo AL, Cabral NL, et al.
Does the side of middle cerebral artery compromise matters in the mortality after
thrombolysis in ischemic stroke? Arq Neuropsiquiatr. 2015;73(8):644-47.
http://dx.doi.org/10.1590/0004-282X20150079
https://doi.org/10.1590/0004-282X2015007...
study analyzed only thrombolysed patients allows its conclusions to
be used as criteria for indicating thrombolysis. This can contribute to the selection of
candidates for thrombolysis, inferring that the side of stroke should not be prioritized as an
inclusion and/or exclusion criteria and that clinical care and rehabilitation should be
established and followed independently of side affected, thereby preventing underdiagnosis of
patients with RCH strokes.
References
-
1Audebert HJ, Singer OC, Gotzler B, Vatankhah B, Boy S, Fiehler J et al. Postthrombolysis hemorrhage risk is affected by stroke assessment bias between hemispheres. Neurology, 2011;76(7):629-36. http://dx.doi.org/10.1212/WNL.0b013e31820ce505
» https://doi.org/10.1212/WNL.0b013e31820ce505 -
2The National Institute of Neurological Disorders; Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333(24):1581-7. http://dx.doi.org/10.1056/NEJM199512143332401
» https://doi.org/10.1056/NEJM199512143332401 -
3Fink JN. Underdiagnosis of right-brain stroke. Lancet. 2005;366(9483):349-51. http://dx.doi.org/10.1016/S0140-6736(05)67004-3
» https://doi.org/10.1016/S0140-6736(05)67004-3 -
4Cheng B, Forkert ND, Zavaglia M, Hilgetag CC, Golsari A, Siemonsen S et al. Influence of stroke infarct location on functional outcome measured by the modified rankin scale. Stroke. 2014;45(6):1695-702. http://dx.doi.org/10.1161/STROKEAHA.114.005152
» https://doi.org/10.1161/STROKEAHA.114.005152 -
5Sato S, Heeley E, Arima H, Delcourt C, Hirakawa Y, Pamidimukkala V et al. Higher mortality in patients with right hemispheric intracerebral haemorrhage: INTERACT1 and 2. J Neurol Neurosurg Psychiatry. 2015;pii: jnnp-2014-309870. http://dx.doi.org/10.1136/jnnp-2014-309870
» https://doi.org/10.1136/jnnp-2014-309870 -
6Fink JN, Frampton CM, Lyden P, Lees KR. Does hemispheric lateralization influence functional and cardiovascular outcomes after stroke?: an analysis of placebo-treated patients from prospective acute stroke trials. Stroke. 2008;39(12):3335-40. http://dx.doi.org/10.1161/STROKEAHA.108.523365
» https://doi.org/10.1161/STROKEAHA.108.523365 -
7Golsari A, Cheng B, Sobesky J, Schellinger PD, Fiehler J, Gerloff C et al. Stroke lesion volumes and outcome are not different in hemispheric stroke side treated with intravenous thrombolysis based on magnetic resonance imaging criteria. Stroke 2015;46(4):1004-8. http://dx.doi.org/10.1161/STROKEAHA.114.007292
» https://doi.org/10.1161/STROKEAHA.114.007292 -
8Sociedade Brasileira de Doenças Cerebrovasculares. Primeiro consenso brasileiro para trombólise no acidente vascular cerebral isquêmico agudo. Arq Neuropsiquiatr. 2002;60(3A):675-80. http://dx.doi.org/10.1590/S0004-282X2002000400032
» https://doi.org/10.1590/S0004-282X2002000400032 -
9Brott T, Tomsick T, Feinberg W, Johnson C, Biller J, Broderick J et al. Baseline silent cerebral infarction in the Asymptomatic Carotid Atherosclerosis Study. Stroke. 1994;25(6):1122-9. http://dx.doi.org/10.1161/01.STR.25.6.1122
» https://doi.org/10.1161/01.STR.25.6.1122 -
10Dal-Prá Ducci R, Lange MC, Moro CH, Harger R, Longo AL, Cabral NL, et al. Does the side of middle cerebral artery compromise matters in the mortality after thrombolysis in ischemic stroke? Arq Neuropsiquiatr. 2015;73(8):644-47. http://dx.doi.org/10.1590/0004-282X20150079
» https://doi.org/10.1590/0004-282X20150079 -
11Lee PH, Oh SH, Bang OY, Joo SY, Joo IS, Hunk K. Infarct patterns in atherosclerotic middle cerebral artery versus internal carotid artery disease. Neurology. 2004;62(8):1291-6. http://dx.doi.org/10.1212/01.WNL.0000120761.57793.28
» https://doi.org/10.1212/01.WNL.0000120761.57793.28 -
12Pacheco FT, Littig IA, Gagliardi RJ, Rocha AJ. Multidector computed tomography angiography in clinically suspected hyperacute ischemic stroke in the anterior circulation: an etiological workup in a cohort of Brazilian patients. Arq Neuropsiquiatr. 2015;73(5):408-14. http://dx.doi.org/10.1590/0004-282X201500
» https://doi.org/10.1590/0004-282X201500
Publication Dates
-
Publication in this collection
Aug 2015
History
-
Received
02 June 2015 -
Received
09 June 2015