Lancet Neurology 2015

Treatment


1. Lancet. 2015 Sep 26;386(10000):1299-310. doi: 10.1016/S0140-6736(15)00277-9.

Diagnosis and treatment of acute extremity compartment syndrome.

von Keudell AG(1), Weaver MJ(2), Appelton PT(3), Bae DS(4), Dyer GS(5), Heng
M(6), Jupiter JB(6), Vrahas MS(5).

Author information: 
(1)Orthopedic Trauma Initiative at Harvard Medical School, Boston, MA, USA.
Electronic address: avonkeudell@mgh.harvard.edu. (2)Orthopedic Trauma Initiative
at Harvard Medical School, Boston, MA, USA; Department of Orthopedic Surgery,
Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
(3)Orthopedic Trauma Initiative at Harvard Medical School, Boston, MA, USA;
Department of Orthopedic Surgery, Beth Israel Deaconess Hospital, Harvard Medical
School, Boston, MA, USA. (4)Orthopedic Trauma Initiative at Harvard Medical
School, Boston, MA, USA; Department of Orthopedic Surgery, Boston Children's
Hospital, Harvard Medical School, Boston, MA, USA. (5)Orthopedic Trauma
Initiative at Harvard Medical School, Boston, MA, USA; Department of Orthopedic
Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA;
Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical
School, Boston, MA, USA. (6)Orthopedic Trauma Initiative at Harvard Medical
School, Boston, MA, USA; Department of Orthopedic Surgery, Massachusetts General
Hospital, Harvard Medical School, Boston, MA, USA.

Acute compartment syndrome of the extremities is well known, but diagnosis can be
challenging. Ineffective treatment can have devastating consequences, such as
permanent dysaesthesia, ischaemic contractures, muscle dysfunction, loss of limb,
and even loss of life. Despite many studies, there is no consensus about the way
in which acute extremity compartment syndromes should be diagnosed. Many surgeons
suggest continuous monitoring of intracompartmental pressure for all patients who
have high-risk extremity injuries, whereas others suggest aggressive surgical
intervention if acute compartment syndrome is even suspected. Although surgical
fasciotomy might reduce intracompartmental pressure, this procedure also carries
the risk of long-term complications. In this paper in The Lancet Series about
emergency surgery we summarise the available data on acute extremity compartment
syndrome of the upper and lower extremities in adults and children, discuss the
underlying pathophysiology, and propose a clinical guideline based on the
available data.

Copyright © 2015 Elsevier Ltd. All rights reserved.

PMID: 26460664  [PubMed - indexed for MEDLINE]


2. Lancet Neurol. 2015 Sep;14(9):914-25. doi: 10.1016/S1474-4422(15)00111-8. Epub
2015 Jul 13.

Posterior reversible encephalopathy syndrome: clinical and radiological
manifestations, pathophysiology, and outstanding questions.

Fugate JE(1), Rabinstein AA(2).

Author information: 
(1)Department of Neurology, Mayo Clinic, Rochester, MN, USA. Electronic address: 
fugate.jennifer@mayo.edu. (2)Department of Neurology, Mayo Clinic, Rochester, MN,
USA.

Erratum in
    Lancet Neurol. 2015 Sep;14(9):874.

Almost two decades have elapsed since posterior reversible encephalopathy
syndrome (PRES) was described in an influential case series. This usually
reversible clinical syndrome is becoming increasingly recognised, in large part
because of improved and more readily available brain imaging. Although the
pathophysiological changes underlying PRES are not fully understood, endothelial
dysfunction is a key factor. A diagnosis of PRES should be considered in the
setting of acute neurological symptoms in patients with renal failure, blood
pressure fluctuations, use of cytotoxic drugs, autoimmune disorders, or
eclampsia. Characteristic radiographic findings include bilateral regions of
subcortical vasogenic oedema that resolve within days or weeks. The presence of
haemorrhage, restricted diffusion, contrast enhancement, and vasoconstriction are
all compatible with a diagnosis. In most cases, PRES resolves spontaneously and
patients show both clinical and radiological improvements. The range of symptoms
that can comprise the syndrome might be broader than usually thought. In its mild
form, this disorder might cause only one clinical symptom (headache or seizure)
and radiographically might show few areas of vasogenic oedema or even normal
brain imaging in some rare cases. In severe forms, PRES might cause substantial
morbidity and even mortality, most often as a result of acute haemorrhage or
massive posterior fossa oedema causing obstructive hydrocephalus or brainstem
compression.

Copyright © 2015 Elsevier Ltd. All rights reserved.

PMID: 26184985  [PubMed - indexed for MEDLINE]


3. Lancet Neurol. 2015 Nov 25. pii: S1474-4422(15)00296-3. doi:
10.1016/S1474-4422(15)00296-3. [Epub ahead of print]

Prehospital treatment with levetiracetam plus clonazepam or placebo plus
clonazepam in status epilepticus (SAMUKeppra): a randomised, double-blind, phase
3 trial.

Navarro V(1), Dagron C(2), Elie C(3), Lamhaut L(2), Demeret S(4), Urien S(3), An
K(2), Bolgert F(4), Tréluyer JM(3), Baulac M(5), Carli P(2); SAMUKeppra
investigators.

Author information: 
(1)Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière Hospital,
Epilepsy Unit, and Brain and Spine Institute, Pitié-Salpêtrière Hospital and
Université Pierre et Marie Curie, Paris, France. Electronic address:
vincent.navarro@psl.aphp.fr. (2)AP-HP, Necker-Enfants Malades Hospital, SAMU 75, 
and Université Paris Descartes, Paris, France. (3)AP-HP, Paris Descartes Clinical
Research Unit/Clinical Investigation Centre and Université Paris Descartes,
France. (4)AP-HP, Pitié-Salpêtrière Hospital, Neurological Intensive Care Unit,
Paris, France. (5)Assistance Publique-Hôpitaux de Paris (AP-HP),
Pitié-Salpêtrière Hospital, Epilepsy Unit, and Brain and Spine Institute,
Pitié-Salpêtrière Hospital and Université Pierre et Marie Curie, Paris, France.

BACKGROUND: Generalised convulsive status epilepticus (GCSE) should be treated
quickly. Benzodiazepines are the only drug treatment available so far that is
effective before admission to hospital. We assessed whether addition of the
antiepileptic drug levetiracetam to the benzodiazepine clonazepam would improve
prehospital treatment of GCSE.
METHODS: We did a prehospital, randomised, double-blind, phase 3,
placebo-controlled, superiority trial to determine the efficacy of adding
intravenous levetiracetam (2·5 g) to clonazepam (1 mg) in treatment of GCSE in 13
emergency medical service centres and 26 hospital departments in France.
Randomisation was done at the Paris Descartes Clinical Research Unit with a list
of random numbers generated by computer. Adults with convulsions lasting longer
than 5 min were randomly assigned (1:1) by prehospital physicians to receive
levetiracetam or placebo in combination with clonazepam. All physicians and
paramedics were masked to group assignments. If the status epilepticus lasted
beyond 5 min after drug injection, a second dose of 1 mg clonazepam was given.
The primary outcome was cessation of convulsions within 15 min of drug injection.
We analysed the modified intention-to-treat population that had received at least
one injection of clonazepam and levetiracetam or placebo, excluding patients
without valid consent and those randomised more than once. The trial is
registered at EudraCT, number 2007-005782-35.
FINDINGS: Between July 20, 2009, and Dec 15, 2012, 107 patients were randomly
assigned to receive placebo and 96 were assigned to receive levetiracetam. The
trial was discontinued on Dec 15, 2012 when interim analysis showed no evidence
of a treatment difference, and 68 patients in each group were included in the
modified intention-to-treat analysis. Convulsions stopped at 15 min of drug
injection in 57 of 68 patients (84%) receiving clonazepam and placebo and in 50
of 68 patients (74%) receiving clonazepam and levetiracetam (percentage
difference -10·3%, 95% CI -24·0 to 3·4). Three deaths, 19 of 47 (40 %) serious
adverse events, and 90 of 197 (46%) non-serious events were reported in the
levetiracetam group, and four deaths, 28 of 47 (60%) serious events, and 107 of
197 (54%) non-serious events were reported in the placebo group.
INTERPRETATION: The addition of levetiracetam to clonazepam treatment presented
no advantage over clonazepam treatment alone in the control of GCSE before
admission to hospital. Future prehospital trials could assess the efficacy of
clonazepam alone as a first-line treatment in status epilepticus and the efficacy
of a second injection of clonazepam with another antiepileptic drug as
second-line treatment.
FUNDING: UCB Pharma.

Copyright © 2015 Elsevier Ltd. All rights reserved.

PMID: 26627366  [PubMed - as supplied by publisher]


4. Lancet Neurol. 2015 Aug;14(8):846-54. doi: 10.1016/S1474-4422(15)00140-4. Epub
2015 Jun 25.

Endovascular stent thrombectomy: the new standard of care for large vessel
ischaemic stroke.

Campbell BC(1), Donnan GA(2), Lees KR(3), Hacke W(4), Khatri P(5), Hill MD(6),
Goyal M(7), Mitchell PJ(8), Saver JL(9), Diener HC(10), Davis SM(11).

Author information: 
(1)Department of Medicine and Neurology, Melbourne Brain Centre, Royal Melbourne
Hospital, University of Melbourne, Parkville, Australia. Electronic address:
bruce.campbell@mh.org.au. (2)The Florey Institute of Neuroscience and Mental
Health, University of Melbourne, Parkville, Australia. (3)Acute Stroke Unit and
Cerebrovascular Clinic, Institute of Cardiovascular and Medical Sciences,
Gardiner Institute, Western Infirmary and Faculty of Medicine, University of
Glasgow, Glasgow, UK. (4)Department of Neurology, Universitätsklinik Heidelberg, 
Ruprechts Karl Universität Heidelberg, Heidelberg, Germany. (5)Department of
Neurology and Rehabilitation Medicine, University of Cincinnati, Cincinnati, OH, 
USA. (6)Department of Clinical Neurosciences, Hotchkiss Brain Institute,
University of Calgary, Foothills Hospital, Calgary AB, Canada. (7)Department of
Radiology, University of Calgary, Foothills Hospital, Calgary, AB, Canada.
(8)Department of Radiology, Royal Melbourne Hospital, University of Melbourne,
Parkville, Australia. (9)Department of Neurology and Comprehensive Stroke Center,
David Geffen School of Medicine, University of California, Los Angeles, Los
Angeles, CA, USA. (10)Department of Neurology and Stroke Centre, University
Hospital Essen, Essen, Germany. (11)Department of Medicine and Neurology,
Melbourne Brain Centre, Royal Melbourne Hospital, University of Melbourne,
Parkville, Australia.

BACKGROUND: Results of initial randomised trials of endovascular treatment for
ischaemic stroke, published in 2013, were neutral but limited by the selection
criteria used, early-generation devices with modest efficacy, non-consecutive
enrollment, and treatment delays.
RECENT DEVELOPMENTS: In the past year, six positive trials of endovascular
thrombectomy for ischaemic stroke have provided level 1 evidence for improved
patient outcome compared with standard care. In most patients, thrombectomy was
performed in addition to thrombolysis with intravenous alteplase, but benefits
were also reported in patients ineligible for alteplase treatment. Despite
differences in the details of eligibility requirements, all these trials required
proof of major vessel occlusion on non-invasive imaging and most used some
imaging technique to exclude patients with a large area of irreversibly injured
brain tissue. The results indicate that modern thrombectomy devices achieve
faster and more complete reperfusion than do older devices, leading to improved
clinical outcomes compared with intravenous alteplase alone. The number needed to
treat to achieve one additional patient with independent functional outcome was
in the range of 3·2-7·1 and, in most patients, was in addition to the substantial
efficacy of intravenous alteplase. No major safety concerns were noted, with low
rates of procedural complications and no increase in symptomatic intracerebral
haemorrhage. WHERE NEXT?: Thrombectomy benefits patients across a range of ages
and levels of clinical severity. A planned meta-analysis of individual patient
data might clarify effects in under-represented subgroups, such as those with
mild initial stroke severity or elderly patients. Imaging-based selection, used
in some of the recent trials to exclude patients with large areas of irreversible
brain injury, probably contributed to the proportion of patients with favourable
outcomes. The challenge is how best to implement imaging in clinical practice to
maximise benefit for the entire population and to avoid exclusion of patients
with smaller yet clinically important potential to benefit. Although favourable
imaging identifies patients who might benefit despite long delays from symptom
onset to treatment, the proportion of patients with favourable imaging decreases
with time. Health systems therefore need to be reorganised to deliver treatment
as quickly as possible to maximise benefits. On the basis of available trial
data, intravenous alteplase remains the initial treatment for all eligible
patients within 4·5 h of stroke symptom onset. Those patients with major vessel
occlusion should, in parallel, proceed to endovascular thrombectomy immediately
rather than waiting for an assessment of response to alteplase, because
minimising time to reperfusion is the ultimate aim of treatment.

Copyright © 2015 Elsevier Ltd. All rights reserved.

PMID: 26119323  [PubMed - indexed for MEDLINE]


5. Lancet Neurol. 2015 Apr;14(4):361-7. doi: 10.1016/S1474-4422(15)70018-9. Epub
2015 Feb 12.

Antiplatelet treatment compared with anticoagulation treatment for cervical
artery dissection (CADISS): a randomised trial.

CADISS trial investigators, Markus HS, Hayter E, Levi C, Feldman A, Venables G,
Norris J.

Collaborators: Peycke J, Willson M, Hicks C, Hayter E, Madigan J, Clifton A,
Menon R, Kennedy F, Khan U, Feldman A, Hollocks M, Markus HS, King A, Madigan J, 
Markus HS, Norris J, Venables GS, Kerry S, Hassan A, Levi C, Ford GA, Bath PM,
Weir C, Kalra L, Briley D, Bhalla A, Reid J, Kumar R, Mawer S, Smith M, Ali K,
Sharma P, Dutta D, Nor AM, Boswell R, Baldwin N, Rudd A, Stanley D, Burger I,
Kalra L, Hassan A, Price C, Dixit A, MacWalter R, Cohen D, Davey R, Cassidy T,
Gunathilagan G, Jenkinson D, Harrington F, James M, Venables G, Smyth N, Emsley
H, Shaw L, Lovett J, Guyler P, Macleod M, Colam B, Salman RA, Markus HS, Gompertz
P, Kelly D, Salih I, Davies B, Shetty H, Mistri A, Hargroves D, Rashed K, Clarke
B, Collas D, Gerraty R, Sturm J, Levi C, Kleinig T, Wong A, Hand P, Delcourt C.

Erratum in
    Lancet Neurol. 2015 Jun;14(6):566.

Comment in
    Lancet Neurol. 2015 Apr;14(4):342-3.

BACKGROUND: Extracranial carotid and vertebral artery dissection is an important
cause of stroke, especially in young people. In some observational studies it has
been associated with a high risk of recurrent stroke. Both antiplatelet drugs and
anticoagulant drugs are used to reduce risk of stroke but whether one treatment
strategy is more effective than the other is unknown. We compared their efficacy
in the Cervical Artery Dissection in Stroke Study (CADISS), with the additional
aim of establishing the true risk of recurrent stroke.
METHODS: We did this randomised trial at hospitals with specialised stroke or
neurology services (39 in the UK and seven in Australia). We included patients
with extracranial carotid and vertebral dissection with onset of symptoms within
the past 7 days. Patients were randomly assigned (1:1) by an automated telephone
randomisation service to receive antiplatelet drugs or anticoagulant drugs
(specific treatment decided by the local clinician) for 3 months. Patients and
clinicians were not masked to allocation, but investigators assessing endpoints
were. The primary endpoint was ipsilateral stroke or death in the
intention-to-treat population. The trial was registered with EUDract
(2006-002827-18) and ISRN (CTN44555237).
FINDINGS: We enrolled 250 participants (118 carotid, 132 vertebral). Mean time to
randomisation was 3·65 days (SD 1·91). The major presenting symptoms were stroke
or transient ischaemic attack (n=224) and local symptoms (headache, neck pain, or
Horner's syndrome; n=26). 126 participants were assigned to antiplatelet
treatment versus 124 to anticoagulant treatment. Overall, four (2%) of 250
patients had stroke recurrence (all ipsilateral). Stroke or death occurred in
three (2%) of 126 patients versus one (1%) of 124 (odds ratio [OR] 0·335, 95% CI
0·006-4·233; p=0·63). There were no deaths, but one major bleeding (subarachnoid
haemorrhage) in the anticoagulant group. Central review of imaging failed to
confirm dissection in 52 patients. Preplanned per-protocol analysis excluding
these patients showed stroke or death in three (3%) of 101 patients in the
antiplatelet group versus one (1%) of 96 patients in the anticoagulant group (OR
0·346, 95% CI 0·006-4·390; p=0·66).
INTERPRETATION: We found no difference in efficacy of antiplatelet and
anticoagulant drugs at preventing stroke and death in patients with symptomatic
carotid and vertebral artery dissection but stroke was rare in both groups, and
much rarer than reported in some observational studies. Diagnosis of dissection
was not confirmed after review in many cases, suggesting that radiographic
criteria are not always correctly applied in routine clinical practice.
FUNDING: Stroke Association.

Copyright © 2015 Markus et al. Open Access article distributed under the terms of
CC BY. Published by Elsevier Ltd.. All rights reserved.

PMID: 25684164  [PubMed - indexed for MEDLINE]

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