Perspectives

Book
Clot-busting for stroke
It’s human nature to remember our that necessitated a formal statistical stroke physicians who happen to
“firsts”. I still remember the first time reanalysis of the NINDS trial dataset have a variety of backgrounds,
I gave intravenous alteplase for acute in 2004, and extension of the time including geriatrics, internal medicine,
ischaemic stroke to a young man with window for treatment from 3 h to neurology, and clinical pharmacology.
severe neurological impairment. His 4·5 h after the positive findings of the I noticed some other errors, one of
wife, heavily pregnant with their first European Cooperative Acute Stroke which is that tPA is the only treatment
child, faced the prospect of becoming Study (ECASS) III trial in 2008. for acute ischaemic stroke; aspirin,
the carer for both her child and husband hemicraniectomy, and stroke unit
in just a few weeks. But the young man “This lack of cooperation is care all have solid evidence behind
responded to alteplase and made a common in stroke research and them now. Another concern, repeated
remarkable, almost “Lazarus”, recovery. it is vital that we, as trialists several times, is that streptokinase,
He walked out of hospital 4 days later in and investigators, take part in another thrombolytic, is dangerous in
time to be with his wife when she gave stroke. Pharmacologically, if alteplase tPA for Stroke: The Story of a
each other’s trials.” Controversial Drug
birth. In addition to being my “first”, his is effective then streptokinase
Justin A Zivin, John Galbraith
case taught me another lesson that we The most interesting part of the should be as well, as shown for heart Simmons. Oxford University
need patient-specific outcomes, in his book in my view is when the authors attack. Unfortunately, the trials Press, 2011. Pp 224. £17·99.
ISBN 9780195393927
case golfing ability. Before the stroke, discuss why tPA was not taken up that studied streptokinase in stroke
he had a handicap of 6, at 4 months immediately by the wider US stroke were confounded by the presence
after the stroke it was 22, and then community after 1995. Zivin and of concomitant antithrombotics
down to 10 at 18 months, clearly an Simmons mention some of the and meta-analyses show that the
excellent result. potential reasons: the reticence of combination of thrombolytic plus
The introduction of thrombolysis neurologists to work out of hours; antiplatelet is dangerous causing
into routine clinical practice for aversion by some emergency care increased bleeding into the brain. Trials
hyperacute ischaemic stroke has been physicians to using tPA in stroke of tPA largely avoided co-treatment
long and tortuous, as described in tPA (although they were well versed with with antithrombotics. Should we
for Stroke: The Story of a Controversial its use in heart attack); and poor test streptokinase again? No, it’s not
Drug by Justin Zivin and John Galbraith remuneration for treating stroke worth the effort now; let’s just get on
Simmons. The main story began in out of hours. The authors also assert with using what is already available,
1995 with the reporting of the US that Genentech did not aggressively namely, tPA.
National Institute of Neurological develop a market for tPA in stroke. Perhaps the key message in
Disorders and Stroke (NINDS) trials of Unfortunately, Zivin and Simmons tPA for Stroke is that there is now
alteplase, a type of tissue plasminogen focus on the US players so that vital overwhelming evidence for the
activator (tPA), in people with aspects of the story that took place use of tPA within the treatment
ischaemic stroke when treated within elsewhere are poorly covered. paradigm tested in the NINDS and
3 h of onset. Alteplase reduced death The authors do, however, specifically ECASS-3 trials—ie, as early as possible
and dependency by a sizeable 12% and attack the slowness of introducing tPA and within 3 h to 4·5 h after stroke
did so without increasing death or in the UK. While true, this problem is onset. But to achieve this goal, stroke
severe dependency. hardly unique to the UK and the data services must be redesigned with
This book describes the discovery in the book do not reflect the current training and expansion of staff to
of tPA and its development, and state of UK stroke treatment. Although allow 24-h treatment and with open
then presents the tribulations still not good enough, more than 10% access to neuroimaging. Indeed, the
of implementing its widespread of UK hospitals are now thrombolysing tPA story has not yet ended. If tPA
use. Zivin and Simmons highlight more than 10% of their patients and works up to 4·5 h, will it work even
that, although there was no other in London and Nottingham (where I later to 6 h, as is being asked by the
treatment for acute ischaemic stroke work) it’s over 14% of eligible patients. large International Stroke Trial-3
back in 1995, the take-up of alteplase The book also wrongly suggests that in (IST-3)? Or, as studies in Australia,
was awful, and remains poor even the UK general practitioners look after Europe, and the US are currently
today. They relate the milestones urgent cases. As with an increasing investigating, might tPA work even
of this unusual therapeutic journey, number of countries, stroke in the later if patients are selected on the
including disbelief about the results UK is managed by trained specialist basis of neuroimaging criteria? Newer

www.thelancet.com Vol 377 May 14, 2011 1643

types of thrombolytic agents, such as patients older than 80 years, and reading this account of the story of
desmoteplase, are also in clinical test. those presenting up to 6 h after stroke tPA, as will those with an interest in
For a book dedicated to describing onset. As it is, we will have to wait for medical history. But for me the book’s
controversy, Zivin and Simmons the trial to report in 2012. This lack emphasis on the US aspects of the tPA
overlook what is a key issue for me— of cooperation is common in stroke controversy means this story remains
namely, the way that some stroke research and it is vital that we, as incomplete.
experts have not contributed to trialists and investigators, take part in
PB is a member of the IST-3 Data Monitoring
recruitment in the IST-3 trial. If more each other’s trials. Committee and uses tPA to treat stroke patients.
of the stroke fraternity had joined So who is this book for? Stroke
this study we would have known physicians, whether specialist or Philip Bath
some years ago whether to treat in training, will be curious about philip.bath@nottingham.ac.uk

In brief
DVD Life at the kerb Even the onset of his stroke suggest using the lift even more
Stroke is not usually a laughing has its tragi-comic hue: never bracing: if they can have bungee-
matter. Until, that is, New York has dysarthria been used to such jumping and other adventure sports,
stand-up comedian John Kawie comic effect, as he vainly tries to why can’t he have escalators?
resumes his career after a major defend himself from accusations The dark and wildly funny heart of
stroke. This DVD of his comeback of being drunk (an experience not the performance is the group therapy
session offers something special for uncommon in young-onset stroke). session, where Kawie is given a glove
John Kawie: Brain Freeze clinicians involved with stroke. From Humour also provides a cheeky puppet that gives him licence to
Written and performed by Kawie’s entrance—if bounding and assertion of dignity in the face of express his savage rage and bile at
John Kawie, directed by
Mark Maxey. Big Round Records hemiparetic can be contained in the the many indignities that come with oversimplifications, pat answers, and
LLC, 2010. same phrase—and his few prefatory personal care by others, particularly the expectations of conforming to
http://www.brainfreezedvd.com curses that he has to climb stairs up to the stellar miscasting of personal certain “positive” patterns of recovery.
the stage, we are shocked out of our care assistants at home. At a deeper level it is a cry of anguish
professional reserve, and challenged In a phenomenon recognised but and anger at what he has lost, and an
to rethink, and engage with, the poorly articulated in rehabilitation, uncomfortable prompt to clinicians
individuality of our patients. Kawie provides a new variation to as to whether our processes allow for
Stroke medicine is overfixated William Osler’s dictum on learning a therapeutic and individual venting
with the acute at the expense of the from patients: in this case, it is the of these losses.
chronic—a myopia neurovascularia other patients, rather than physicians, The chief casualties of Kawie’s
whereby an intense focus on the acute who are learning from each other. remarkable performance in Brain
hospital phase is followed by a loss of A friendship struck up with a brain- Freeze are pity and professional
interest afterwards in the challenges injured patient, initiated through a complacency. He challenges us to
patients face with the new ways of shared admiration for the shapely replace pity with an identification of
living that stroke demands. All great posterior of one of the therapists, our shared destiny, fragility, and spirit.
humour has the human condition provides the spark for his realisation In turn, clinicians need to identify
at its heart and this is no exception, that his future lies in his own hands. and struggle with what James Joyce
even if no aspect of human decency Kawie’s key props are his residual termed the “hemiplegia of the will”
or reserve is spared from Kawie’s deficits, from the difficulty of that sometimes prevents us from
relentless dissection. Unsparing of a buttoning his coat with a hemiparesis seeing the bigger picture. Maybe, after
fellow-sufferer who has fallen into a to memory problems: he jokes about recovering from our helpless laughter,
self-pitying mode, complaining that needing Post-Its to jog his memory, we too might rouse ourselves to get
he cannot hail a taxi from inside the and then opens his coat to show his out of our insitutionalised lobby
lobby, Kawie’s response, that “life lining completely covered with the and discover that at its best, stroke
is at the kerb”, becomes a leitmotif multicoloured reminder notes. His medicine, like life, is at the kerb.
for the engagement, recovery, and adventures with escalators in his
accommodation that underpin his beloved bookstore are excruciatingly Desmond O’Neill
return to public life. funny, but his rejoinder to those who doneill@tcd.ie

1644 www.thelancet.com Vol 377 May 14, 2011