Paul Camarata

Safety and efficacy of minimally invasive surgery plus alteplase in intracerebral haemorrhage evacuation (MISTIE): a randomised, controlled, open-label, phase 2 trial

BACKGROUND Craniotomy, according to the results from trials, does not improve functional outcome after intracerebral haemorrhage. Whether minimally invasive catheter evacuation followed by thrombolysis for clot removal is safe and can achieve a good functional outcome is not known. We investigated the safety and efficacy of alteplase, a recombinant tissue plasminogen activator, in combination with minimally invasive surgery (MIS) in patients with intracerebral haemorrhage. METHODS MISTIE was an open-label, phase 2 trial that was done in 26 hospitals in the USA, Canada, the UK, and Germany. We used a computer-generated allocation sequence with a block size of four to centrally randomise patients aged 18-80 years with a non-traumatic (spontaneous) intracerebral haemorrhage of 20 mL or higher to standard medical care or image-guided MIS plus alteplase (0·3 mg or 1·0 mg every 8 h for up to nine doses) to remove clots using surgical aspiration followed by alteplase clot irrigation. Primary outcomes were all safety outcomes: 30 day mortality, 7 day procedure-related mortality, 72 h symptomatic bleeding, and 30 day brain infections. This trial is registered with ClinicalTrials.gov, number NCT00224770. FINDINGS Between Feb 2, 2006, and April 8, 2013, 96 patients were randomly allocated and completed follow-up: 54 (56%) in the MIS plus alteplase group and 42 (44%) in the standard medical care group. The primary outcomes did not differ between the standard medical care and MIS plus alteplase groups: 30 day mortality (four [9·5%, 95% CI 2·7-22.6] vs eight [14·8%, 6·6-27·1], p=0·542), 7 day mortality (zero [0%, 0-8·4] vs one [1·9%, 0·1-9·9], p=0·562), symptomatic bleeding (one [2·4%, 0·1-12·6] vs five [9·3%, 3·1-20·3], p=0·226), and brain bacterial infections (one [2·4%, 0·1-12·6] vs zero [0%, 0-6·6], p=0·438). Asymptomatic haemorrhages were more common in the MIS plus alteplase group than in the standard medical care group (12 [22·2%; 95% CI 12·0-35·6] vs three [7·1%; 1·5-19·5]; p=0·051). INTERPRETATION MIS plus alteplase seems to be safe in patients with intracerebral haemorrhage, but increased asymptomatic bleeding is a major cautionary finding. These results, if replicable, could lead to the addition of surgical management as a therapeutic strategy for intracerebral haemorrhage. FUNDING National Institute of Neurological Disorders and Stroke, Genentech, and Codman.SUMMARY Background Craniotomy, when evaluated in trials, does not improve outcome after intracerebral haemorrhage (ICH). Whether minimally invasive catheter evacuation followed by thrombolysis is safe and can achieve a good functional outcome by removing clot is unknown. We investigated safety and efficacy of alteplase with minimally invasive surgery (MIS) in patients with intracerebral haemorrhage. Methods MISTIE was an international, randomized, open-label study and was done in 26 hospitals in the USA, Canada, the UK, and Germany. Patients (aged 18–80 years), with non-traumatic (spontaneous) ICH ≥20 mL were randomly allocated, centrally, to medical care or image-guided MIS plus rt-PA (0.3 mg or 1.0 mg every 8 hours for up to 9 doses) to remove clot using surgical aspiration followed with alteplase clot irrigation. The primary efficacy outcome was the adjusted dichotomized modified Rankin Scale (mRS) 0–3 vs 4–6 assessed at day 180 after symptom onset. Analysis was by intention to treat. (ClinicalTrials.gov number NCT00224770). Findings Between February 2, 2006 and April 8, 2013, 96 subjects were randomized and completed follow-up: 54 received treatment and 42 medical care. Primary safety outcomes: mortality, symptomatic bleeding, brain infections, as well as withdrawal of care, did not differ between groups. Asymptomatic hemorrhages were more common in the surgical group (3 (7%) vs. 12 (22%) p= 0.05) producing a difference of 15.1% (95% CI: 1.5% to 28.6%). The estimated absolute benefit, i.e., the unadjusted difference in observed proportions of all subjects with mRS 0–3 (33% vs 21%) at 180 days comparing MISPA vs. medical control, is 0.109 [95%CI: −0.088, 0.294; p=0.26], and is 0.162 [95%CI: 0.003, 0.323; p=0.05] after adjustment for potential imbalances in baseline severity between study arms (primary efficacy outcome). Interpretation MIS+rt-PA appears safe with an apparent advantage of better functional outcome at 180 days. Increased asymptomatic bleeding is a major cautionary finding. The MISTIE trial results, if replicable, could produce a meaningful functional benefit adding surgical management as a therapeutic strategy for ICH. Funding National Institute of Neurologic Disorders and Stroke, Genentech, and Codman.

Linac‐based stereotactic radiosurgery (SRS) in the treatment of refractory trigeminal neuralgia: Detailed description of SRS procedure and reported clinical outcomes

Purpose/Objectives To present our linac‐based SRS procedural technique for medically and/or surgically refractory trigeminal neuralgia (TN) treatment and simultaneously report our clinical outcomes. Materials and Methods Twenty‐seven refractory TN patients who were treated with a single fraction of 80 Gy to TN. Treatment delivery was performed with a 4 mm cone size using 7‐arc arrangement with differential‐weighting for Novalis‐TX with six MV‐SRS (1000 MU/min) beam and minimized dose to the brainstem. Before each treatment, Winston‐Lutz quality assurance (QA) with submillimeter accuracy was performed. Clinical treatment response was evaluated using Barrow Neurological Institute (BNI) pain intensity score, rated from I to V. Results Out of 27 patients, 22 (81%) and 5 (19%) suffered from typical and atypical TN, respectively, and had median follow‐up interval of 12.5 months (ranged: 1–53 months). For 80 Gy prescriptions, delivered total average MU was 19440 ± 611. Average beam‐on‐time was 19.4 ± 0.6 min. Maximum dose and dose to 0.5 cc of brainstem were 13.4 ± 2.1 Gy (ranged: 8.4–15.9 Gy) and 3.6 ± 0.4 Gy (ranged: 3.0–4.9 Gy), respectively. With a median follow‐up of 12.5 months (ranged: 1–45 months) in typical TN patients, the proportion of patients achieving overall pain relief was 82%, of which half achieved a complete pain relief with BNI score of I‐II and half demonstrated partial pain reduction with BNI score of IIIA‐IIIB. Four typical TN patients (18%) had no response to radiosurgery treatment. Of the patients who responded to treatment, actuarial pain recurrence free survival rates were approximately 100%, 75%, and 50% at 12 months, 15 months, and 24 months, respectively. Five atypical TN patients were included, who did not respond to treatment (BNI score: IV‐V). However, no radiation‐induced cranial‐toxicity was observed in all patients treated. Conclusion Linac‐based SRS for medically and/or surgically refractory TN is a fast, effective, and safe treatment option for patients with typical TN who had excellent response rates. Patients, who achieve response to treatment, often have durable response rates with moderate actuarial pain recurrence free survival. Longer follow‐up interval is anticipated to confirm our clinical observations.

Intracerebral laser interstitial thermal therapy followed by tumor resection to minimize cerebral edema

OBJECTIVE Laser interstitial thermal therapy (LITT) is used in numerous neurosurgical applications including lesions that are difficult to resect. Its rising popularity can be attributed to its minimally invasive approach, improved accuracy with real-time MRI guidance and thermography, and enhanced control of the laser. One of its drawbacks is the possible development of significant edema, which contributes to extended hospital stays and often necessitates hyperosmolar or steroid therapy. Here, the authors discuss the use of minimally invasive craniotomy to resect tissue ablated with LITT in attempt to minimize cerebral edema. METHODS Five patients with glioblastoma multiforme prospectively underwent LITT followed by resection. The LITT was performed with the aid of an MR-compatible skull-mounted frame in the MRI suite. Ablated tumor was then resected via small craniotomy by using the NICO Myriad system or cavitron ultrasonic surgical aspirator. Postoperative management involved dexamethasone administration slowly tapered over several weeks. RESULTS The use of resection following LITT, as compared with open resection or LITT alone, did not extend the hospital stay except in 1 patient who required 3-day inpatient management of edema with a trapped ventricle. No new neurological deficits were encountered, although 1 patient developed seizures postoperatively. No increase in infection rates was identified. CONCLUSIONS Resection of ablated tumor is a viable option to reduce the incidence of neurological deficits due to edema following LITT. This approach appears to mitigate cerebral edema by increasing available volume for mass effect and reducing the tissue burden that may promote an inflammatory response.

Individualized Surgical Approach Planning for Petroclival Tumors Using a 3D Printer.

Objectives To determine the utility of three-dimensional (3D) printed models in individualized petroclival tumor resection planning by measuring the fidelity of printed anatomical structures and comparing tumor exposure afforded by different approaches. Design Case series and review of the literature. Setting Tertiary care center. Participants Three patients with petroclival lesions. Main Outcome Measures Subjective opinion of access by neuro-otologists and neurosurgeons as well as surface area of tumor exposure. Results Surgeons found the 3D models of each patients skull and tumor useful for preoperative planning. Limitations of individual surgical approaches not identified through preoperative imaging were apparent after 3D models were evaluated. Significant variability in exposure was noted between models for similar or identical approaches. A notable drawback is that our printing process did not replicate mastoid air cells. Conclusions We found that 3D modeling is useful for individualized preoperative planning for approaching petroclival tumors. Our printing techniques did produce authentic replicas of the tumors in relation to bony structures.

Collateral damage: heat transfer as a possible mechanism of optic nerve injury during neurosurgical intervention.

Purpose: To determine factors associated with increased heat transfer during neurosurgical drilling as a mechanism for optic nerve injury. Methods: On a nonembalmed cadaver, the optic canal was exposed through a standard craniotomy and optic nerve sparing exenteration. The temperature was measured with a thermocoupler during each 30-second continuous drill session using 2 types of neurosurgical drills. The location of the probe, drill site, drill power, and irrigation rate were varied. Results: A <1°C change was measured in the optic canal at all test distances with the Cavitron Ultrasonic Surgical Aspirator and diamond drill. The use of manual irrigation decreased the mean change in temperature (&Dgr;T) in the sphenoid bone from 4.7°C without irrigation to 1.3°C with irrigation. Increasing Cavitron Ultrasonic Surgical Aspirator power from 50% to 80% at an irrigation rate of 4 ml/minute more than doubled &Dgr;T in sphenoid bone from 3.2°C at 50% to 8.1°C at 80%. Increasing irrigation from 2 to 4 ml/minute decreased mean &Dgr;T by −1.1°C (3.2°C at 2 ml/minute versus 2.1°C at 4 ml/minute) at Cavitron Ultrasonic Surgical Aspirator power of 50%, but at Cavitron Ultrasonic Surgical Aspirator power of 80%, increasing irrigation increased mean &Dgr;T by 3.0°C (3.7°C at 2 ml/minute versus 6.8°C at 4 ml/minute). Conclusions: Care must be taken during neurosurgical procedures to decrease heat transfer during drilling to nearby structures. With increase in drill power, there is a noticeable increase in temperature change from baseline. These temperature changes can be mediated by irrigation, although the effect of increasing irrigation rate to suppress the raise in temperature decreases with increasing drill power.

The relationship of pro-inflammatory markers to vascular endothelial function after acute stroke.

Purpose/Aim: Data from chronic stroke studies have reported reduced blood flow and vascular endothelial function in the stroke-affected limb. It is unclear whether these differences are present early after stroke. First, we investigated whether vascular endothelial function in the stroke-affected limb would be different from healthy adults. Second, we examined whether between-limb differences in vascular endothelial function existed in the stroke-affected arm compared to the non-affected arm. Last, we tested whether reduced vascular endothelial function was related to pro-inflammatory markers that are present early after stroke. Materials and Methods: Vascular endothelial function was assessed by flow-mediated dilation (FMD) in the brachial artery within 72 h post-stroke. All participants withheld medications from midnight until after the procedure. Ultrasound scans and blood draws for pro-inflammatory markers occurred on the same day between 7:30 am and 9:00 am. Results: People with acute stroke had significantly lower FMD (4.2% ± 4.6%) than control participants (8.5% ± 5.2%, p = 0.037). Stroke participants had between-limb differences in FMD (4.2% ± 4.6% stroke-affected vs. 5.3% ± 4.4% non-affected, p = 0.02), whereas, the control participants did not. Of the pro-inflammatory markers, only vascular cell adhesion molecule-1(VCAM-1) had a significant relationship to FMD (stroke-affected limb, r = −0.62, p = 0.03; non-affected limb, r = −0.75, p = 0.005), but not tumor necrosis factor alpha nor interleukin-6. Conclusions: Vascular endothelial function is reduced starting in the early stage of stroke recovery. People with higher levels of VCAM-1 had a lower FMD response.

Permanent CSF shunting after intraventricular hemorrhage in the CLEAR III trial

Objective: To study factors associated with permanent CSF diversion and the relationship between shunting and functional outcomes in spontaneous intraventricular hemorrhage (IVH). Methods: Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage (CLEAR III), a randomized, multicenter, double-blind, placebo-controlled trial, was conducted to determine if pragmatically employed external ventricular drainage (EVD) plus intraventricular alteplase improved outcome, in comparison to EVD plus saline. Outcome measures were predictors of shunting and blinded assessment of mortality and modified Rankin Scale at 180 days. Results: Among the 500 patients with IVH, CSF shunting was performed in 90 (18%) patients at a median of 18 (interquartile range [IQR] 13–30) days. Patient demographics and IVH characteristics were similar among patients with and without shunts. In the multivariate analysis, black race (odds ratio [OR] 1.98; 95% confidence interval [CI] 1.18–3.34), duration of EVD (OR 1.10; CI 1.05–1.15), placement of more than one EVD (OR 1.93; CI 1.13–3.31), daily drainage CSF per 10 mL (OR 1.07; CI 1.04–1.10), and intracranial pressure >30 mm Hg (OR 1.70; CI 1.09–2.88) were associated with higher odds of permanent CSF shunting. Patients who had CSF shunts had similar odds of 180-day mortality, while survivors with shunts had increased odds of poor functional outcome, compared to survivors without shunts. Conclusions: Among patients with spontaneous IVH requiring emergency CSF diversion, those with early elevated intracranial pressure, high CSF output, and placement of more than one EVD are at increased odds of permanent ventricular shunting. Administration of intraventricular alteplase, early radiographic findings, and CSF measures were not useful predictors of permanent CSF diversion.

Magnetic Resonance Imaging in a Neurofibromatosis Type 2 Patient with a Novel MRI-Compatible Auditory Brainstem Implant

Auditory brainstem implantation has become a key technique for the rehabilitation of hearing in patients with neurofibromatosis type 2. The nature of this devastating genetic disease requires ongoing MRI for the patients lifespan. Today, most auditory brainstem implants require removal of the magnet that connects the internal device to the external speech processor to undergo imaging as their disease progresses. Patients have the option of having a short procedure to have the magnet taken out and replaced each time, or alternately using a headband to secure the processor over the receiver coil of the internal device. Novel magnet technology has led to the development of a freely rotating magnet that can be used inside the magnetic field of an MRI scanner without losing magnet strength and without being displaced from the body of the device. We report one of the first patients implanted with a Med-El Synchrony ABI in the United States who subsequently underwent successful imaging with MRI 1.5 tesla to follow for other existing schwannomas.

Three-Dimensional Printed Model Used to Teach Skull Base Anatomy Through a Transsphenoidal Approach for Neurosurgery Residents

BACKGROUND: Skull base anatomy through a transsphenoidal approach is challenging for the neurosurgical resident to conquer. OBJECTIVE: To demonstrate that stereolithography, or 3-dimensional (3-D) printing, is a useful educational tool for neurosurgery residents to learn skull base anatomy. METHODS: Before any formal teaching, residents were brought into the operating room where they were asked to identify key structures seen through an endoscopic transsphenoidal approach. Scoring was based on correctly naming the anatomical structures. After the initial testing, all residents participated in a didactic lecture reviewing this anatomy by using 2-dimensional pictures. Residents were then divided into 2 groups: A and B. Group B residents were additionally taught through neurosurgical simulation using a 3-D printed model and an endoscope. Following all formal teaching, residents were retested in the operating room. RESULTS: A maximum score of 8 points was possible if all structures were identified correctly. Group A had mean scores of 2.75 on initial testing compared with 5 after the lecture (P = .041 using 2-tailed t test). Group B had mean scores of 2.75 on initial testing compared with 7.5 after the lecture and 3-D model simulation (P = .002). When comparing mean scores after formal teaching in groups A and B, 5 vs 7.5 were obtained for lecture only vs lecture and 3-D model simulation, respectively (P = .031). CONCLUSION: Three-dimensional models used in neurosurgical simulation to teach skull base anatomy through a transsphenoidal approach showed objective and subjective improvement in testing scores in neurosurgery residents. This study confirms that 3-D models are a useful educational tool.

Classification and Microvascular Flap Selection for Anterior Cranial Fossa Reconstruction

Background Microvascular reconstruction of the anterior cranial fossa (ACF) creates difficult challenges. Reconstructive goals and flap selection vary based on the defect location within the ACF. This study evaluates the feasibility and reliability of free tissue transfer for salvage reconstruction of low, middle, and high ACF defects. Methods A retrospective review was performed. Reconstructions were anatomically classified as low (anterior skull base), middle (frontal bar/sinus), and high (frontal bone/soft tissue). Subjects were evaluated based on pathologic indication and goal, type of flap used, and complications observed. Results Eleven flaps in 10 subjects were identified and anatomic sites included: low (n = 5), middle (n = 3), and high (n = 3). Eight of 11 reconstructions utilized osteocutaneous flaps including the osteocutaneous radial forearm free flap (OCRFFF) (n = 7) and fibula (n = 1). Other reconstructions included a split calvarial graft wrapped within a temporoparietal fascia free flap (n = 1), latissimus myocutaneous flap (n = 1), and rectus abdominis myofascial flap (n = 1). All 11 flaps were successful without microvascular compromise. No complications were observed in the high and middle ACF defect groups. Two of five flaps in the low defect group using OCRFFF flaps failed to achieve surgical goals despite demonstrating healthy flaps upon re‐exploration. Complications included persistent cerebrospinal fluid leak (n = 1) and pneumocephalus (n = 1), requiring flap repositioning in one subject and a second microvascular flap in the second subject to achieve surgical goals. Conclusion In our experience, osteocutaneous flaps (especially the OCRFFF) are preferred for complete autologous reconstruction of high and middle ACF defects. Low skull base defects are more difficult to reconstruct, and consideration of free muscle flaps (no bone) should be weighed as an option in this anatomic area.