JOURNAL WATCH
Journal Watch
By Aimee Aysenne, MD and Chitra Venkatasubramanian, MBBS, MD, MSc
This spring has brought us several novel
approaches to the treatment of intracerebral
hemorrhage. Here are three of the most
anticipated studies.
Intraventricular tPA – “CLEAR”ing the
intraventricular hemorrhage. Hanley DF et
al. for the CLEAR III investigators. Lancet 2017;
389: 603-611
CLEAR III (Clot Lysis: Evaluating Accelerated
Resolution of Intraventricular Hemorrhage)
is a phase 3 randomized double blind
prospective multicenter trial investigating
intraventricular low dose alteplase (tPA)
versus saline for intraventricular hemorrhage
(IVH) administered via external ventricular
drainage (EVD). Patients with obstructive
hydrocephalus due from spontaneous IVH
+/- intracerebral hemorrhage (ICH) ≤ 30 cc
and baseline mRS 0-1 were eligible. An EVD
was placed as part of routine care and head
CT was repeated 6 hours after placement.
Randomized groups received saline or 1 mg
of tPA every 8 hours via the EVD. Dosing was
completed when 12 doses were administered
or improvement in IVH on head CT to pre specified endpoints.
Concurrent medical management was standard according to AHA
guidelines. The primary outcome was mRS scores 0-3 vs 4-6 at 180
days. Planned secondary analyses included survival, volume of
clot removed and intensity of ICU management. Post hoc analyses
included the number of patients with mRS 5 (bed bound) at 180
days and the improvement achieved for patients with IVH > 20 ml.
Pre-specified safety thresholds were utilized.
Five hundred patients were randomized. Baseline features were
similar between groups. A third had dual EVDs. Proportion of
mRS 0-3 was no different between groups, even with multivariate
analysis. Mortality was reduced in the tPA group, but this was
associated with an increase of patients with mRS 5 in the tPA
group. None of the other functional outcome measures were
different. All safety parameters favored tPA with a reduction in
reported serious adverse events. Symptomatic bleeding was not
different. Planned secondary analyses showed significant relation
between amount of clot removal, good outcome and mortality.
Conclusion: The CLEAR III trial did not demonstrate improved
functional outcomes in patients with IVH using a combination
of low dose alteplase + EVD. Functional outcomes in this trial
were better than historically in both groups. Higher clot volume
removal (> 80 percent of IVH) was associated with better
outcomes, but only 30 percent of tPA patients achieved this goal
as continued therapy to this endpoint was mandated in the study.
The investigators are planning a future trial to answer remaining
questions.
Lumbar Drain After Intraventricular tPA May Decrease
Permanent Shunt Dependence
Staykov, D.S. et al. Annals of Neurology, 2017; 81:93-103
This is a single center open randomized control trial evaluating
lumbar drainage (LD) following intraventricular tPA for IVH. The
primary endpoint is the need for permanent ventriculoperitoneal
shunt (VPS) placement at 90 days. Secondary endpoints include
mortality, functional and safety outcomes. The IVF procedure,
timing, and dosage of rt-PA were conducted in accordance to the
CLEAR-III protocol. When clearance of blood was demonstrated
on CT, patients were randomized LD or EVD management.
After placement of the drain, the EVD was then clamped and
was removed if ICP was normal for 24 hours. CSF drainage
was continued via EVD in the control group and via LD in the
intervention group for 48 hours then clamped for 24 hours. If
there was no increased size of the ventricles on head CT, catheters
were removed. If there was ventricular enlargement, second
and third weaning attempts were made prior to VPS. The study
was stopped early as the primary end point reached statistical
significance; 16 patients were in the control group and 14 were
in the treatment group. No patients in the LD group required
VPS, and 7/16 of the control group of required VPS placement.
Secondary endpoints were similar in both groups including
bleeding and infections. No patients herniated. Functional
outcomes and mortality were the same in both groups.
Conclusion: The use of lumbar drainage after the administration
of intraventricular tPA for IVH was safe, feasible and effectively
reduced the need for VPS. The small sample size is the major
limitation. Further studies are needed to better assess the effect of
lumbar drainage after intraventricular fibrinolysis.
MISPACE: A Promising New Approach to Minimally Invasive
Surgical Evacuation of ICH
Labib MA, et al. Neurosurgery 2016; 80(4): 515-524
Prior trials for hematoma evacuation after ICH have not been
shown to improve outcomes. MISPACE is a retrospective review
of the feasibility and safety of a minimally invasive subcortical
parafascicular access for clot evacuation in patients with ICH.
Patients with supratentorial ICH with minimal or no IVH were
enrolled from 11 institutions. Twelve participating surgeons
underwent a two-day training. Imaging of white matter tracts
using DTI was done when possible to avoid white matter tracts
during the surgery. A small craniotomy was performed with
minimal disruption of the pia and mobilization of any surface
veins to avoid venous damage. An obturator was then inserted
to gently dilate the opening and minimize damage. Bimanual
clot removal (from the deepest part first) was performed using
manual and automated microsurgical instrumentation with
meticulous hemostasis.
Thirty-nine patients were enrolled in the study; 46 percent of ICH
involved thalamus and basal ganglia. The median ICH volume was
36 cc with a median depth of 1.4 cm from cortical surface; median
ICH score was 2. Median time from symptom onset to surgery was
24.5 hours. Median GCS at presentation was 10 and postoperative
GCS was 14 and was statistically significant. Ninety-five percent
of patients had a clot reductions > 75. Half of the patients have
a mRs < 2 at follow-up; 38 percent had mRS 4 or 5. There were
minimal bleeding and infectious complications.
Conclusion: MISPACE approach demonstrated an improvement
in GCS post-operatively with few complications and no deaths
in selected patients. Mortality seen in this study (0 percent) was
lower than the predicted based on ICH score. Further investigation
is necessary to determine how this technique can be generalized to
improve outcomes in a larger population.
Aimee Aysenne,
MD
Chitra
Venkatasubramanian,
MBBS, MD, MSc
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