Stroke recovery and rehabilitation trials have
received much criticism for underdosing the tested intervention,1 which
remains an important consideration when interpreting past trials in the field.2
In this trial of aerobic exercise during
inpatient rehabilitation by Klassen et al.,3 the
intensity (heart rate reserve during training and walking steps) and amount
(minutes of training) of aerobic exercise were increased from usual care. The
control group (usual care) typically received 1 hour, 5 days/week, while the
Determining Optimal Post-Stroke Exercise 1 (DOSE1) group received 1 hour, 5
days/week (with a target of double the intensity of the control group), and the
DOSE2 group received 2 hours, 5 days/week (with a target of quadruple the
intensity of the control group), each for a 4-week duration (20 sessions).
In May of this year, amidst the sweeping
COVID-19 global pandemic, the New England Journal of Medicine published
a paper detailing how large vessel occlusive disease might be a presenting
feature in patients with strokes secondary to the infection.1 The
authors of this particular paper, cited above, build upon the NEJM
observation with imaging evidence to posit that strokes secondary to COVID-19
are also more severe in nature.
Patients were selected and included to be a
part of the comparative cohort if COVID-19 was diagnosed (via real-time PCR)
and had documented acute large vessel occlusion between the observation and
recruitment timeframe between March 15 and April 30, 2020. Two of the authors
of the study were blinded to the COVID-19 status of the patient and were asked
to quantify the infarct core volume for all patients with large vessel
occlusion during the time period. During the study, fifteen patients with large
vessel occlusion and confirmed COVID-19 infection were treated.
Smoking has been identified as the most
important lifestyle risk factor for subarachnoid hemorrhage (SAH) and accounts
for at least one third of all cases.
Familial risk is defined as the probability of
a healthy family member being affected by the same disease that has already
affected at least one other family member. Familial risk of SAH depends on a
number of factors, including genetic and environmental factors. It has been a
challenge to estimate the genetic risk of SAH in relatives given the relatively
low incidence of SAH. The accurate estimation of genetic risk could have
significant implications on prophylactic screening protocols of intracranial
aneurysms. Large twin cohorts provide a “shortcut” to carry out the estimation
of heritability. Twin studies usually provide the natural way to separate
familial resemblance from genetic influence. The Nordic Twin Study in 2010
indicated that most twin pairs were discordant for SAH, i.e., only one twin
died from SAH. However, the role of risk factors in explaining this discordance
was not studied.
In this article, Dr. Elkind and colleagues aimed to elucidate the putative relationship between infection and stroke, which has gained increased recognition in the era of coronavirus disease 2019 (COVID-19).1 Multiple studies in the past, such as the Cardiovascular Health Study and the Atherosclerosis Risk in Communities study, have provided evidence that systemic infection can trigger or precipitate acute ischemic stroke since bacteremia is a strong stimulus to inflammation and thrombosis. The proposed mechanisms by which infections can trigger stroke include infection-related platelet activation and aggregation, inflammation-related thrombosis, impaired endothelial function, infection-provoked cardiac arrhythmias, and dehydration-induced thrombosis (Figure). On further characterization, it is now known that a variety of infections are associated with an increased risk of ischemic stroke, with the strongest association found for urinary tract infection (UTI) (OR 5.32, 95% CI, 3.69-7.68) within 7 days.2
The authors focus particularly on
the role of viral infections as a trigger for stroke. Influenza has been
previously studied as a stroke trigger, especially in high-risk elderly
population. Data from California provide evidence that the odds of ischemic
stroke are higher in the first 15 days after influenza-like illness (OR 2.88,
95%CI 1.86-4.47).3 Many herpes viruses also have a neurotropic
tendency, with strong evidence linking Cytomegalovirus (CMV) to atherogenesis
and Varicella zoster virus (VZV) to cerebral arteriopathy. Infectious burden
(IB) is described as a cumulative effect of exposure to an increasing number of
pathogens and lately has gained popularity due to its role in carotid and
cerebral atherosclerosis. For example, higher mean IB index in Hispanics,
non-Hispanic Blacks, and women in the Northern Manhattan Study provides
indirect evidence to explain disparities in stroke risk. Recently, multiple
studies have reported an increased risk for stroke in patients who are infected
with COVID -19, with incidence ranging from 0.5 to 3%. The incidence is higher
in critically ill patients with COVID-19 approaching 6%. Moreover, unexplained
large vessel occlusions have been identified as a frequent presentation.
Brain atrophy refers to a
loss of brain cells or a loss in the networks between brain cells, and is a
common feature for many neurodegenerative diseases. Ischemic stroke is usually
viewed as an acute cerebrovascular injury, and not as a neurodegenerative
condition. Nevertheless, there is now emerging evidence demonstrating that
stroke can cause persistent regional brain atrophy for months and even years
after the initial event. Further, this regional brain atrophy after stroke has
been linked to several late phase functional disturbances, including cognitive
impairment. Notably, stroke increases the risk of developing vascular dementia.
The CANVAS study (Cognition
and Neocortical Volume After Stroke) is a longitudinal study in people recruited
from Melbourne hospitals, Australia, following ischemic stroke, comparing brain
volume and cognitive function over 3 years with a group of healthy age- and
sex-matched control participants.(1) In this article, Brodtmann and colleagues
examined the trajectories of total and regional brain volume changes in the first
year following stroke. Specifically, brain magnetic resonance imaging (MRI) was
performed on stroke and healthy control participants, with 86 stroke
participants completing testing at baseline, 125 at 3 months, and 113
participants at 12 months, as well as 40 healthy control participants. Five
brain measures — hippocampal volume, thalamic volume, total brain and
hemispheric brain volume, and cortical thickness — were examined to evaluate
whether brain atrophy rates differed between time points and groups.
Delayed cerebral ischemia
(DCI) is one of the complications of aneurysmal subarachnoid hemorrhage (SAH)
that can lead to increased morbidity and mortality. The risk of DCI is
associated with the initial volume of hemorrhage and the extent of the neurologic
injury. Anetsberger et al. conducted a randomized controlled trial to compare
goal-directed hemodynamic therapy (GDHT) to standard clinical care in reducing
the frequency of DCI in patients with aneurysmal SAH.
Treatment for both groups
included enteral nimodipine, normothermia, euglycemia, electrolyte stability,
and appropriate ventilation with similar systolic blood pressure (BP) and mean
arterial pressure (MAP) goals before and after identified vasospasm. A
transpulmonary thermodilution monitor was used in all patients to monitor
hemodynamic variables such as cardiac output, ejection fraction, and
extravascular lung water.
Regardless of the presence of vasospasm, the GDHT group received volume therapy according to a standardized algorithm (Supplemental Figure I). The study did not explicitly define standard clinical care, but it was noted that avoidance of hypovolemia and hyponatremia are recommended and that there is an absence of consensus guidance for achieving those goals.
The current guidelines of the American Heart Association/American
Stroke Association (AHA/ASA) recommend high-intensity statin therapy initiation
or continuation with the aim of achieving a 50% or greater reduction in low-density
lipoprotein cholesterol (LDL-C) levels in patients with stroke who are 75 years
of age or younger. In patients who are unable to tolerate high-intensity
therapy, moderate intensity statins should be started with the goal of
achieving a 30% to 49% reduction in LDL-C levels.
The first evidence that stroke patients
could benefit from statins came out from the Heart Protection Study that was a
double-blind, randomized, placebo-controlled study in which patients received
either placebo or simvastatin 40 mg daily. This study showed that in patients
with high risk for cardiovascular disease, cholesterol lowering with
simvastatin was associated with reduction in all-cause mortality and major
vascular event risk.
As a consequence of the COVID-19 pandemic, the Malaysia Stroke Council, in collaboration with Angels Initiative, organized the first-ever Malaysia Stroke Virtual Conference 2020. This virtual conference had an excellent scientific program which covered hyperacute stroke, stroke emergency, stroke rehab, basic/translational stroke research, and many more topics (https://msconference2020.com/programme.php). The program included live plenary lectures, symposia, e-posters, a virtual expo, and a Game of Stroke tournament. In addition to talks by leading Malaysian clinicians and researchers, this virtual conference also featured experts around the world, including Professor Sheila Martins (Brazilian Stroke Network), Professor Valery Feigin (University of Auckland), and Dr Ramesh Sahathevan (Ballarat Health Service).
The Deputy Director General of Health Malaysia Datuk Dr Hj. Rohaizat Hj. Yon officiated the opening ceremony of the conference. He also presented the World Stroke Organisation Angels Awards to five Malaysian hospitals: Hospital Tuanku Jaafar in Seremban (Gold), Hospital Seberang Jaya (Gold), Sarawak General Hospital (Gold and Diamond), Regency Specialist Hospital (Gold), and Pantai Hospital Penang (Diamond), as recognition for outstanding stroke care.
The first live plenary session was by Dr.
Law Wan Chung (Sarawak General Hospital), who spoke about “Data Monitoring: Why
I Need This For My Stroke Centre?”. Dr. Law presented some exciting data
related to thrombolysis outcome and stroke outcome from the Sarawak General
Hospital. He highlighted that 1442 ischemic stroke patients were admitted to
the hospital between June 2013 and August 2018, and the mean age was 60. The
incidence of stroke in individuals under age 60 has risen at an alarming rate; in
this case, approximately 13% were under 45 years.
Regaining the ability to walk is the primary therapy goal for the
majority of stroke survivors. However, gait rehabilitation does not end when a
patient is able to walk up and down the corridor for six meters. People living
with stroke need to be able to walk independently, with or without aids, on
stable and unstable surfaces, in crowded environments full of distractions,
under time pressure of moving traffic, while performing dual tasks, and all
this in an energy-efficient manner. To optimize the walking pattern of stroke
survivors, we need to fully understand the underlying impairments and recovery
process. The aim of this study was to investigate the longitudinal progression
in functional mobility during the first year after stroke and determine the rate
of change between different levels of stroke severity.
In total, 140 participants who are over 18 years of age, diagnosed
with stroke according to the World Health Organization (WHO) criteria, living
near the rehabilitation center (Sahlgrenska University Hospital, Sweden), The National
Institutes of Health Stroke Scale (NIHSS) ≤16, Barthel Index (BI) ≥50,
life expectance ≥1 year, were included in this study. The Timed
up-and-Go test (TUG) was used to assess functional mobility after 5 days of
onset, within 24 hours of discharge, 1 after discharge, 3 months and 1-year
post-stroke. In addition, clinical and activity limitations were assessed with
the NIHSS, Fugl-Meyer Assessment, Montreal Cognitive Assessment, modified
Rankin Scale (mRS) and BI.