Joost de Vries

Time to Reperfusion and Treatment Effect for Acute Ischemic Stroke: A Randomized Clinical Trial

IMPORTANCE Intra-arterial treatment (IAT) for acute ischemic stroke caused by intracranial arterial occlusion leads to improved functional outcome in patients treated within 6 hours after onset. The influence of treatment delay on treatment effect is not yet known. OBJECTIVE To evaluate the influence of time from stroke onset to the start of treatment and from stroke onset to reperfusion on the effect of IAT. DESIGN, SETTING, AND PARTICIPANTS The Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) was a multicenter, randomized clinical open-label trial of IAT vs no IAT in 500 patients. The time to the start of treatment was defined as the time from onset of symptoms to groin puncture (TOG). The time from onset of treatment to reperfusion (TOR) was defined as the time to reopening the vessel occlusion or the end of the procedure in cases for which reperfusion was not achieved. Data were collected from December 3, 2010, to June 3, 2014, and analyzed (intention to treat) from July 1, 2014, to September 19, 2015. MAIN OUTCOMES AND MEASURES Main outcome was the modified Rankin Scale (mRS) score for functional outcome (range, 0 [no symptoms] to 6 [death]). Multiple ordinal logistic regression analysis estimated the effect of treatment and tested for the interaction of time to randomization, TOG, and TOR with treatment. The effect of treatment as a risk difference on reaching independence (mRS score, 0-2) was computed as a function of TOG and TOR. Calculations were adjusted for age, National Institutes of Health Stroke Scale score, previous stroke, atrial fibrillation, diabetes mellitus, and intracranial arterial terminus occlusion. RESULTS Among 500 patients (58% male; median age, 67 years), the median TOG was 260 (interquartile range [IQR], 210-311) minutes; median TOR, 340 (IQR, 274-395) minutes. An interaction between TOR and treatment (P = .04) existed, but not between TOG and treatment (P = .26). The adjusted risk difference (95% CI) was 25.9% (8.3%-44.4%) when reperfusion was reached at 3 hours, 18.8% (6.6%-32.6%) at 4 hours, and 6.7% (0.4%-14.5%) at 6 hours. CONCLUSION AND RELEVANCE For every hour of reperfusion delay, the initially large benefit of IAT decreases; the absolute risk difference for a good outcome is reduced by 6% per hour of delay. Patients with acute ischemic stroke require immediate diagnostic workup and IAT in case of intracranial arterial vessel occlusion. TRIAL REGISTRATION trialregister.nl Identifier: NTR1804.

New Generation of Flow Diverter (Surpass) for Unruptured Intracranial Aneurysms: A Prospective Single-Center Study in 37 Patients

Background and Purpose— In patients harboring intracranial aneurysms, the major goal in treatment is to prevent bleeding. A new generation of an endoluminal device (Surpass Flow Diverter [Surpass]) was developed to reconstruct parent artery and occlude the aneurysm. We present our clinical and angiographic single-center experience. Methods— Patients with a wide range of complex unruptured aneurysms were treated with the Surpass placed in the parent artery and bridging the aneurysm. Clinical and angiographic follow-up were performed at 6 months. Data were prospectively collected. Results— Thirty seven patients (mean age, 56 years; range, 32–79), harboring 49 unruptured aneurysms were treated at our center. All except 1 patient were treated with a single device. Successful delivery of the device was achieved in all patients. All 35 nonbifurcation aneurysm necks were covered completely, whereas 14 bifurcation aneurysms were only partially covered. There was no major periprocedural morbidity or mortality. During follow-up, 4 patients (10.4%) experienced transient neurological deficit. One patient (3%) developed a minor stroke at 4-month follow-up with persistent neurological deficit. Twelve patients had neurological symptoms related to their aneurysm and 7 showed improvement of these symptoms during follow-up. At 6-month follow-up, 29 of 31 aneurysms studied that had complete neck coverage showed a complete occlusion (94%) including 1 case with a 95% to 100% occlusion, whereas 5 of the 10 bifurcation aneurysms were occluded. Conclusions— Our study shows high safety and efficacy profile of a new generation endoluminal device in treatment of complex intracranial aneurysms. Long-term studies of treated bifurcation aneurysms are needed.

Collateral Status on Baseline Computed Tomographic Angiography and Intra-Arterial Treatment Effect in Patients with Proximal Anterior Circulation Stroke

Background and Purpose— Recent randomized trials have proven the benefit of intra-arterial treatment (IAT) with retrievable stents in acute ischemic stroke. Patients with poor or absent collaterals (preexistent anastomoses to maintain blood flow in case of a primary vessel occlusion) may gain less clinical benefit from IAT. In this post hoc analysis, we aimed to assess whether the effect of IAT was modified by collateral status on baseline computed tomographic angiography in the Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN). Methods— MR CLEAN was a multicenter, randomized trial of IAT versus no IAT. Primary outcome was the modified Rankin Scale at 90 days. The primary effect parameter was the adjusted common odds ratio for a shift in direction of a better outcome on the modified Rankin Scale. Collaterals were graded from 0 (absent) to 3 (good). We used multivariable ordinal logistic regression analysis with interaction terms to estimate treatment effect modification by collateral status. Results— We found a significant modification of treatment effect by collaterals (P=0.038). The strongest benefit (adjusted common odds ratio 3.2 [95% confidence intervals 1.7–6.2]) was found in patients with good collaterals (grade 3). The adjusted common odds ratio was 1.6 [95% confidence intervals 1.0–2.7] for moderate collaterals (grade 2), 1.2 [95% confidence intervals 0.7–2.3] for poor collaterals (grade 1), and 1.0 [95% confidence intervals 0.1–8.7] for patients with absent collaterals (grade 0). Conclusions— In MR CLEAN, baseline computed tomographic angiography collateral status modified the treatment effect. The benefit of IAT was greatest in patients with good collaterals on baseline computed tomographic angiography. Treatment benefit appeared less and may be absent in patients with absent or poor collaterals. Clinical Trial Registration— URL: http://www.trialregister.nl and http://www.controlled-trials.com. Unique identifier: (NTR)1804 and ISRCTN10888758, respectively.

Histological effects of fibrin glue on nervous tissue: a safety study in rats.

BACKGROUND Little is known of the histologic effects of fibrin glue on normal nervous tissue. To verify the safety of intracranial application of fibrin glue, we investigated the histologic effects of fibrin glue on brain tissue and intracranial nerves of rats. METHODS In Group I (n = 12), bifrontal craniotomy with opening of the dura and arachnoid was performed, and on one side one droplet of fibrin glue was applied into the subarachnoid space. In Group II (n = 12), a unilateral temporal craniotomy was performed, the cavernous sinus was opened, and one drop of fibrin glue was applied to the trigeminal nerve. The controls for Group II (n = 8) were operated in the same way but without application of the fibrin glue. Rats were sacrificed at 1, 3, 7, and 28 days after surgery. The brains and nerves were processed for histologic examination and were semi-quantitatively scored for neuronal damage, gliosis, edema, fibroplasia, inflammatory reaction, axonal damage, and myelin damage. RESULTS No differences were found in the occurrence of neuronal damage, gliosis, edema, fibroplasia, axonal damage, or myelin damage between rats with and without fibrin glue application. In Group I the inflammatory reaction seen at Day 7 was more severe on the fibrin glue side when compared to the control side. At Day 28, however, this difference had resolved. CONCLUSIONS In this morphological safety study, intracranial application of fibrin glue in a rat model does not induce extra brain damage, intracranial nerve damage, or scar tissue formation.

The use of Gore-Tex membrane for adhesion prevention in tethered spinal cord surgery: technical case reports.

OBJECTIVE The incidence of retethering caused by postoperative adhesions at the repair site after initial tethered spinal cord surgery is not uncommon. To assess the effectiveness of a Gore-Tex membrane in preventing these adhesions, only clinical radiological and experimental animal evaluation has been reported. In this report, we describe two cases in which Gore-Tex membrane was implanted at the initial untethering surgery and in which we were able to confirm the real effectiveness of the Gore-Tex membrane during a second operation. METHODS In the first patient, Gore-Tex membrane was used for dural repair in the untethering surgery of the split spinal cord malformation. Because of the suspicion of a thickened filum terminale, repeated surgery was indicated 10 months after the initial procedure. In the second patient, Gore-Tex membrane was implanted during the initial untethering surgery for a lipomyeloschisis and a dermal sinus. Because of a persistent fistula of the dermal sinus, a second operation was necessary 1 year after the first operation. RESULTS During the repeated surgery, a thorough inspection of the implanted Gore-Tex membrane revealed no adhesions between the Gore-Tex membrane and the intradural content in both cases. CONCLUSION We support the use of Gore-Tex membrane in the prevention of postoperative dural adhesions in the repair of spinal dysraphism.

Hemi-cauda equina syndrome from herniated lumbar disc: a neurosurgical emergency?

BACKGROUND We report experience with patients presenting with a specific combination of symptoms: unilateral sciatica, unilateral sensibility loss in the dermatomes S1 to S5 (hemi-saddle) and subjective micturation problems secondary to ruptured lumbar disc. Because of its similarities with a cauda equina syndrome, this combination of symptoms was thought to be a unilateral cauda equina syndrome and it was called hemi-cauda equina syndrome. Consequently, it was treated as an emergency. METHODS Ten patients were evaluated. They compromised 2.3% of all patients undergoing lumbar discectomy. RESULTS Outcome is good with only 10% persisting minor neurologic deficit (sensibility loss in dermatomes S3 to S5). With the exception of urinary retention or incontinence, duration of symptoms and signs does not seem to influence outcome. Comparing signs, symptoms and radiographic findings with those of a cauda equina syndrome which were recently and thoroughly studied, they were found to be more severe in cases of cauda equina syndrome. Especially, the good outcome, (apparently unrelated to the duration of symptoms in cases of hemi-cauda equina syndrome) contrasted with the treatment results of cauda equina syndrome. CONCLUSIONS We defined the hemi-cauda equina syndrome from ruptured disc as a combination of unilateral leg pain, unilateral sensibility loss in dermatomes S1 to S5 and sphincter paralysis (proven urinary retention or incontinence). Motor deficit is not necessarily present. Emergency surgery is warranted. Patients presenting with micturation complaints other than urinary retention or incontinence do not suffer from a hemi-cauda equina syndrome.

Primary hypertension and neurovascular compression: a meta-analysis of magnetic resonance imaging studies

OBJECT Several studies have suggested that neurovascular compression (NVC) of the brainstem might be a cause of hypertension. Because this compression syndrome might be demonstrated by MR imaging studies, several authors have tried to assess its prevalence in small series of patients with hypertension. This article presents a meta-analysis of these studies. METHODS The studies reviewed by the authors were based on MR imaging and included the presence of left-sided NVC of the left rostral ventrolateral medulla oblongata (RVLM) and/or the cranial nerves IX and X root entry zone in patients with apparent primary hypertension compared with normotensive patients. Several studies also included patients with secondary hypertension as an additional control group, which is analyzed separately. RESULTS Meta-analysis included data from 14 studies (597 patients with primary hypertension and 609 controls). The effect size was OR 2.68 (95% CI 1.51-4.75, p = 0.001) (random effect), which is consistent with the hypothesis that NVC of the left RVLM is more frequent in patients with apparent primary hypertension compared with normotensive individuals. Stratification for the study design revealed an effect size for prospective studies of OR 1.97 (95% CI 0.74-5.30, p = 0.178) and for retrospective studies of OR 3.36 (95% CI 1.66-6.79, p = 0.001). CONCLUSIONS This meta-analysis indicates a statistically significant effect size for left-sided NVC in apparent primary hypertension. However, this effect is absent if subanalysis is confined to prospective studies.

Flow diverter implantation in a rat model of sidewall aneurysm: a feasibility study

Background More challenging animal models are needed to elucidate the efficacy of flow diverter (FD) designs and the mechanisms behind observed complications. The purpose of this study is to demonstrate the feasibility of implanting a FD in a sidewall aneurysm rat model. Methods An end-to-side anastomosis was created in the abdominal aorta of 36 rats using a decellularized donor pouch. A FD was subsequently implanted. Results After up to 3 months of follow-up, we observed that rats displayed normal growth and behavior. Mortality within the groups was low (2 rats, 5.6%). All aneurysms thrombosed after FD implantation and showed progressive soft tissue replacement of the thrombus during follow-up. The abdominal aortas remained patent. Conclusions This model can be used to test the effects of FDs in future studies.

A training paradigm to enhance performance and safe use of an innovative neuroendovascular device

Training has been important to facilitate the safe use of new devices designed to repair vascular structures. This paper outlines the generic elements of a training program for vascular devices and uses as an example the actual training requirements for a novel device developed for the treatment of bifurcation intracranial aneurysms. Critical elements of the program include awareness of the clinical problem, technical features of device, case selection, and use of a simulator. Formal proctoring, evaluation of the training, and recording the clinical outcomes complement these elements. Interventional physicians should embrace the merits of a training module to improve the user experience, and vendors, physicians, and patients alike should be aligned in the goal of device training to improve its success rate and minimize complications of the procedure.

Endovascular Neurosurgery in the Netherlands: Historical Developments and Achievements

The historical developments of endovascular neurosurgery in the Netherlands are described.