Journal Scan – This Month in Other Journals, October 2020

1. Dea N, Versteeg AL, Sahgal A, et al. Metastatic spine disease: should patients with short life expectancy be denied surgical care? An international retrospective cohort study. Neurosurgery 2020;87(2):303–11

Recent advances in medical oncology, especially with targeted molecular treatment, have resulted in patients with metastatic spine disease and a seemingly dismal prognosis living longer and challenging traditional surgical decision-making. This coupled with breakthroughs in radiation and surgical technology, particularly separation surgery, has left the oncologist and surgeon alike with more treatment options to maintain or improve health-related quality of life (HRQOL), but with little guidance to apply them.

Historically, the essential prerequisite to any surgical indication for patients with metastatic disease to the spine was to have an expected survival of at least 3 mo. This surgical requirement comes from the premise that patients with short life expectancy should not be subjected to invasive surgical treatment as the likelihood of health-related quality of life improvement was low, adverse event (AE) profile high, and the economic balance unfavorable. These assumptions, however, are not evidenced-based, and appear to arise from inclusion criteria of landmark studies. Furthermore, oncologists and surgeons are often inaccurate when it comes to predicting life expectancy of a cancer patient.

Patients who underwent surgery for spinal metastases between August 2013 and May 2017 were retrospectively identified from an international cohort study. Health-related quality of life was evaluated using generic and disease-specific outcome tools at baseline and at 6 and 12 wk postsurgery. The primary outcome was the HRQOL at 6wk post-treatment measured by the Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ).

A total of 253 patients were included: 40 patients died within the first 3 mo after surgery and 213 patients survived more than 3 mo. Patients surviving <3 mo after surgery presented with lower baseline performance status. Adjusted analyses for baseline performance status did not reveal a significant difference in health-related quality of life between groups at 6wk post-treatment. No significant difference in patient satisfaction at 6wk with regard to their treatment could be detected between both groups.

In conclusion, patients with good baseline performance status may benefit from surgical treatment, even if they survive less than 3 mo. However, the surgical approach should be tailored to consider the patient’s medical status and expected survival. When adjusted for baseline performance status, HRQOL 6 wk post-treatment is independent of survival. The extent of surgical intervention, baseline performance status, and patient preferences should be at the forefront of the decision-making process.

1 figure, 4 tables, no imaging

2. Shabani S, Kaushal M, Budde MD, et al. Diffusion tensor imaging in cervical spondylotic myelopathy: a review. J Neurosurg Spine 2020;33(July):1–8

CSM, a degenerative disease that results in microstructural damage of the spinal cord, is one of the most common causes of disability in elderly patients. Although conventional MRI is the gold standard for radiographic evaluation, it has had limited capability as a biomarker to predict neurological recovery and as an aid to select patients for surgical intervention. In the past decade, DTI has shown the ability to predict disease severity and neurological recovery in CSM patients. The data on the utility of DTI parameters seem to support the case for fractional anisotropy as a potential biomarker for prognostication in CSM, yet more research is still needed to determine the optimal anatomical location for calculating DTI parameter(s) that show the strongest correlation with symptom severity. Further, the application of DTI is limited because of time constraints and unclear protocols for measuring DTI parameters among the different centers.

3 figures, 1 table summarizing the current imaging studies in CSM

3. Häni L, Fung C, Jesse CM, et al. Insights into the natural history of spontaneous intracranial hypotension from infusion testing. Neurology [Internet] 2020;95(3):e247–55. Available from: http://www.neurology.org/lookup/doi/10.1212/WNL.0000000000009812

Case control study on 137 patients for possible SIH. Study population had extrathecal contrast accumulation seen on magnetic resonance myelography, CT myelography, or fluoroscopy after intrathecal contrast application or direct intraoperative visualization of the dural breach proved that there was a CSF leak. The reference population consisted of patients who had no evidence of CSF leakage despite multimodal, noninvasive as well as invasive testing and cranial and spinal imaging.

Patients underwent a lumbar puncture in the lateral recumbent position with a 20-gauge (0.9 mm outer diameter) needle. The needle was connected via a 3-way stopcock to a pressure transducer and the infusion pump. They monitored CSF pressure constantly through the same needle and recorded the data. Following a baseline recording of lumbar CSF pressure for 5 minutes, infusion was started at a constant rate of 2 mL/min using Ringer’s lactate and continued until a total of 50 mL had been infused (i.e., for 25 minutes). After cessation of the infusion, they continued the pressure recordings until a significant drop in intrathecal pressure close to the baseline pressure was evident. If the patient developed a headache or nausea during the infusion test or if the recorded pressure rose above 60mmHg, they terminated the test early. (BTW… 60mm Hg = 80 cm water!)

Data on the natural history of SIH are sparse. They state the results clearly demonstrate a distinct pattern of CSF fluid dynamics depending on the duration of symptoms. The clinical picture seems to be associated with CSF dynamics. Whereas patients with acute symptoms display a clear pathologic profile on lumbar infusion testing, all measures of CSF fluid dynamics change with increasing symptom duration. The results suggest that these changes ensue after a disease duration of 2–3 months. Patients with long-standing complaints frequently present with atypical symptoms and show a nonpathological pattern of CSF fluid dynamics with a normal opening pressure (up to 90% in the current series). This finding needs to be considered when evaluating patients with intractable headache or other symptoms for possible SIH.

4 figures, 1 table, no imaging

4. Hendricks BK, Yoon JS, Yaeger K, et al. Wide-neck aneurysms: systematic review of the neurosurgical literature with a focus on definition and clinical implications. J Neurosurg 2019;133(July):1–7

Wide-necked aneurysms (WNAs) are a variably defined subset of cerebral aneurysms that require more advanced endovascular and microsurgical techniques than those required for narrow-necked aneurysms. The neurosurgical literature includes many definitions of WNAs, and a systematic review has not been performed to identify the most commonly used or optimal definition. The purpose of this systematic review was to highlight the most commonly used definition of WNAs.

The search of the neurosurgical literature identified 809 records, of which 686 were excluded (626 with < 30 patients; 60 for lack of a WNA definition), leaving 123 articles for analysis. Twenty-seven unique definitions were identified and condensed into 14 definitions. The most common definition was neck size ≥ 4 mm or dome-to-neck ratio < 2, which was used in 49 articles (39.8%). The second most commonly used definition was neck size ≥ 4 mm, which was used in 26 articles (21.1%). The rest of the definitions included similar parameters with variable thresholds.

The incidence of WNA is highly dependent on subtle changes in the definition, as exemplified by Pierot et al., (Radiology 258:546–553, 2011) who studied 768 patients with ruptured aneurysms, of which 114 (14.8%) were classified as WNAs based on neck size alone. When the dome-to-neck ratio alone is used to define a WNA, the incidence ranges from 33.7% to 84.4%, depending on the dome-to-neck ratio (1.5 vs 2) and on the imaging modality used for analysis. However, a post hoc analysis of data from the Barrow Ruptured Aneurysm Trial indicates that WNAs, as defined by a neck size ≥ 4 mm and a dome-to-neck ratio < 2, results in a 54.1% incidence of WNAs. The implications of this finding highlight the need for a universal definition.

2 figures, 2 tables

5. Bunevicius A, McDannold NJ, Golby AJ. Focused ultrasound strategies for brain tumor therapy. Oper Neurosurg 2020;19(1):9–18

Low-intensity MRgFUS is an emerging technology, which allows a temporally and spatially predictable, controllable, and safe disruption of the BBB. Substantially lower intensity ultrasound energy used for BBB disruption does not cause irreversible tissue damage. Instead, low-intensity ultrasound bursts are combined with circulating microbubbles, which concentrate the ultrasound effects on the vasculature, resulting in a temporary and local disruption (permeabilization) of the BBB. Exogenous microbubbles are lipid spheres encapsulating a perfluorocarbon gas, which are commonly used as ultrasound contrast agents. Microbubbles can also be composed of proteins and polymers with other gases, resulting in different physiochemical properties. The introduction of the microbubbles reduces the exposure level needed by orders of magnitude compared to those used for thermal ablation, removing the skull-related limitations of high-intensity FUS.

Numerous studies in small and large animal glioma models have evaluated the safety and efficacy of BBB opening with FUS. In animal studies, BBB opening is immediate, repeatable, resolves within 6 to 8 h, and does not cause axonal or neuronal injury. In addition to this, an enhanced delivery of various drugs has been shown in small to large animal models. These drugs include trastuzumab, doxorubicin, TMZ, methotrexate, and carboplatin. In addition, this approach has been used to deliver viruses and cells.

Despite abundant preclinical evidence in glioma animal models indicating efficacy of BBB disruption using low-intensity FUS for enhanced delivery of various chemotherapeutic agents and viral vectors to the CNS, evidence regarding safety and efficacy of this treatment method in patients with brain tumors remains limited. One published study to date evaluated safety and efficacy of transcranial MRgFUS for drug delivery in glioma patients. A small phase I, single arm, open label study of 5 patients with high-grade glioma investigated transcranial low-intensity MRgFUS with the ExAblate Neuro system with microbubble injection for BBB opening in conjunction with systemic administration of subtherapeutic dose of chemotherapy (liposomal doxorubicin n = 1 or temozolomide n = 4) that was administered one hour prior MRgFUS. Surgical tumor resection was performed the next day. The procedure was well-tolerated, with successful opening of the BBB based on increased gadolinium enhancement.

3 figures, 2 tables

6. Casetta I, Fainardi E, Saia V, et al. Endovascular thrombectomy for acute ischemic stroke beyond 6 hours from onset. Stroke [Internet] 2020;51(7):2051–57. Available from: https://www.ahajournals.org/doi/10.1161/STROKEAHA.119.027974

From the Italian Registry of Endovascular Thrombectomy, the authors extracted clinical and outcome data of patients treated for stroke of known onset beyond 6 hours. Additional inclusion criteria were prestroke modified Rankin Scale score ≤2 and ASPECTS score ≥6. Patients were selected on individual basis by a combination of CT perfusion mismatch (difference between total hypoperfusion and infarct core sizes) and CT collateral score. The primary outcome measure was the score on modified Rankin Scale at 90 days.

Out of 3057 patients, 327 were treated beyond 6 hours. Their mean age was 66.8 years, the median baseline National Institutes of Health Stroke Scale 16, and the median onset to groin puncture time 430 minutes. The most frequent site of occlusion was middle cerebral artery (45.1%). Functional independence (90-day modified Rankin Scale score, 0–2) was achieved by 41.3% of cases. Symptomatic intracranial hemorrhage occurred in 6.7% of patients, and 3-month case fatality rate was 17.1%. The probability of surviving with modified Rankin Scale score, 0–2 was significantly lower in patients treated beyond 6 hours as compared with patients treated earlier.  No differences were found regarding recanalization rates and safety outcomes between patients treated within and beyond 6 hours.

Taken together, the data obtained in the present study suggest the possibility to extend the time window for EVT beyond 6 hours after onset in the real world using a combined approach based on the concomitant visual assessment of CTA collateral extent and CTP mismatch even in those centers not equipped with automated software programs able to calculate the different parameters of target mismatch. Nevertheless, the lack of a control group of untreated patients limits the strength of these findings since it precludes an actual assessment of treatment effect.

Worth noting the imaging side of this:

Cerebral blood flow, cerebral blood volume, and mean-transit-time CTP maps were generated for each patient. CTP was evaluated according to the classical CTP mismatch model: (1) mean-transit-time lesion indicating total hypoperfusion; (2) cerebral blood volume lesion referring to infarct core. CTP mismatch was defined as the difference between total hypoperfusion and infarct core size and was evaluated by visual inspection. For each modality, patients were judged to be candidates for EVT based on the following criteria: (1) non-contrast CT ASPECTS ≥6; (2) good collateral circulation (single-phase CTA or multi-phase CTA); (3) CTP mismatch with an infarct core size ≤50% of total hypoperfusion extent or involving less than one-third of the MCA territory extent.

5 tables

7. Bullard AJ, Hutchison BC, Lee J, et al. Estimating risk for future intracranial, fully implanted, modular neuroprosthetic systems: a systematic review of hardware complications in clinical deep brain stimulation and experimental human intracortical arrays. Neuromodulation 2020;23(4):411–26

The safety surrounding neuromodulation technology is a critical question for both established and emerging systems. Hardware related complications can result in potential injury to the patient, repeated surgical procedures, and reduced clinical efficacy. In this comprehensive, systematic review, they found that DBS had an incidence rate of 19.04% for total hardware-related complications. The most common adverse events were infection, followed by lead migration, lead fracture or failure, hemorrhage, skin erosion, IPG malfunction, and malfunction of the extension cable.

76 articles after screening where humans had been implanted with the Utah array. The Utah array, a 96-channel microelectrode array (Blackrock Microsystems), has been implanted intracortically in a total of 48 subjects as of September 2018. This consists of patients implanted for epilepsy and other intraoperative opportunities where tissue would have been ablated, and patients with paralysis. The demographic of Utah array implants is dominated by acute cases, usually to study epilepsy, anesthesia, or cognition, memory, or language. A smaller subset of the cases is chronic implants, used to study brain machine interfaces for motor control of prosthesis and stimulation for sensory mapping. Of the 48 people implanted with the Utah array, 30 were implanted for less than 30 days and 18 people were implanted chronically for more than 30 days.

This review focused primarily on the Utah array, using the existing intracranial DBS system as a benchmark for safety data of future implantable neuroprostheses systems that will employ the Utah array for brain-machine interface (BMI) applications.

4 figures, 6 tables

8. Kaufmann TJ, Smits M, Boxerman J, et al. Consensus recommendations for a standardized brain tumor imaging protocol for clinical trials in brain metastases. Neuro Oncol 2020;22(6):757–72

A meeting was held on March 22, 2019, among the FDA, clinical scientists, pharmaceutical and biotech companies, clinical trials cooperative groups, and patient advocacy groups to discuss challenges and potential solutions for increasing development of therapeutics for central nervous system metastases. A key issue identified at this meeting was the need for consistent tumor measurement for reliable tumor response assessment, including the first step of standardized image acquisition with an MRI protocol that could be implemented in multicenter studies aimed at testing new therapeutics. This document builds upon previous consensus recommendations for a standardized brain tumor imaging protocol (BTIP) in high-grade gliomas and defines a protocol for brain metastases (BTIP-BM) that addresses unique challenges associated with assessment of CNS metastases. The “minimum standard” recommended pulse sequences include: (i) parameter matched pre- and post-contrast inversion recovery (IR)–prepared, isotropic 3D T1-weighted gradient echo (IR-GRE); (ii) axial 2D T2-weighted turbo spin echo acquired after injection of gadolinium-based contrast agent and before post-contrast 3D T1-weighted images; (iii) axial 2D or 3D T2-weighted fluid attenuated inversion recovery; (iv) axial 2D, 3-directional diffusion weighted images; and (v) post-contrast 2D T1-weighted spin echo images for increased lesion conspicuity. Recommended sequence parameters are provided for both 1.5T and 3T MR systems. An “ideal” protocol is also provided, which replaces IR-GRE with 3D TSE T1-weighted imaging pre- and post-gadolinium, and is best performed at 3T, for which dynamic susceptibility contrast perfusion is included. Recommended perfusion parameters are given.

2 figures, 3 tables (parameters)

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