1. Amukotuwa SA, Straka M, Smith H, et al. Automated Detection of Intracranial Large Vessel Occlusions on Computed Tomography Angiography. Stroke. 2019;50(10):2790-2798. doi:10.1161/STROKEAHA.119.026259

The authors assessed the accuracy and speed of a commercially available fully automated LVO-detection tool in a cohort of patients presenting to a regional hospital with suspected stroke. Consecutive patients who underwent multimodal computed tomography with thin-slice CTA between January 1, 2017 and December 31, 2018 for suspected acute ischemic stroke within 24 hours of onset were retrospectively identified. The multimodal CTs were assessed by 2 neuroradiologists in consensus for the presence of an intracranial anterior circulation LVO or M2-segment middle cerebral artery occlusion (the reference standard). The patients’ CTA’s were then processed using an automated LVO-detection algorithm (RAPID CTA). Receiver-operating characteristic analysis was used to determine sensitivity, specificity, and negative predictive value of the algorithm.

CTAs from 477 patients were analyzed (271 men and 206 women). Median processing time was 158 seconds. Seventy-eight patients had an anterior circulation LVO, and 28 had an isolated M2-segment middle cerebral artery occlusion. The sensitivity, negative predictive value, and specificity were 0.94, 0.98, and 0.76, respectively for detection of an intracranial LVO and 0.92, 0.97, and 0.81, respectively for detection of either an intracranial LVO or M2-segment middle cerebral artery occlusion.

There were 71 false positives. A cause of asymmetrical vascular density in the supraclinoid and Sylvian cisterns was identified in 64 of these patients. Ipsilateral decreased vascular density was caused by: chronic M1-MCA stenosis (n=5); high-grade supraclinoid ICA stenosis (n=1); cervical ICA occlusion with decreased density and caliber of the supraclinoid ICA (n=1); old ipsilateral MCA territory infarction with attenuation of the M1 or M2 segments (n=4); and early bifurcation of the MCA (n=12).

They conclude that the algorithm evaluated in this study had high sensitivity and NPV for LVO detection in a cohort of patients who underwent multimodal CT for a clinically suspected stroke. M2-MCA occlusions were also reliably detected, which is important since these patients can be considered for thrombectomy. While sensitivity is in the range previously reported for neuroradiologists, the specificity is much lower than that of experienced human readers. The algorithm should therefore be used as a screening tool to expedite diagnosis rather than a surrogate for an experienced human reader.

2. Haslett JJ, Genadry L, Zhang X, et al. Systematic Review of Malpractice Litigation in the Diagnosis and Treatment of Acute Stroke. Stroke. 2019;50(10):2858-2864. doi:10.1161/STROKEAHA.119.025352

The authors used three large legal databases were used to search for jury verdicts and settlements in cases related to the acute care of stroke patients in the United States. Search terms included “stroke” and “medical malpractice.” Cases were screened to include only cases in which the allegation involved negligence in the acute care of a patient suffering a stroke.

They found 246 medical malpractice cases related to the acute management of ischemic stroke and 26 related to intracranial hemorrhage. Seventy-one cases specifically alleged a failure to treat with tPA and 7 cases alleged a failure to treat, or to timely treat, with thrombectomy. Overall there were 151 cases (56%) which ended with no payout, 74 cases (27%) were settled out of court, and 47 cases (17%) went to court and resulted in a verdict for the plaintiff. The average payout in settlements was $1 802 693, and the average payout in plaintiff verdicts was $9 705 099.

Thirty-eight states were represented, with the highest number of cases coming from New York (37 cases), California (34 cases), and Florida (32 cases).

Doctors in a variety of specialties were involved in litigation:

Emergency department doctor 33%

Primary care/ Internist. 27%

Neurologist 17%

Neurosurgeon, interventional radiologist 9%

Radiologist. 4%

The average time to resolution of cases involving management of stroke was 4.9 years.

They conclude that a failure to administer tPA is a prevalent allegation in stroke medical malpractice. Allegations of a failure to timely transfer a patient and a failure to timely perform thrombectomy were also seen in this analysis, and it is anticipated that cases with these allegations will increase in frequency in the coming years.

3. Matthews PM. Chronic inflammation in multiple sclerosis — seeing what was always there. Nat Rev Neurol. 2019;15(10):582-593. doi:10.1038/s41582-019-0240-y

Conventional clinical MRI has unquestionably revolutionized the diagnosis and monitoring of MS but is relatively insensitive to the chronic inflammation in grey and white matter that is so prominent on postmortem neuropathology. The past two decades have seen the introduction of new research imaging methods to address this challenge. Quantitative dynamic MRI with contrast agents is sensitive to the reduction of BBB integrity associated with inflammation and to trafficking of inflammatory myeloid cells into the brain parenchyma from the blood. MRI imaging sequences provide greater contrast for grey matter lesions. Quantitative lesion volume measures, T2* MRI and susceptibility imaging are sensitive to the activity of macrophages in the rims of white matter lesions. PET and magnetic resonance spectroscopy (MRS) methods can also be used to assess innate immune activation in the brain (or spinal cord). Together, these methods are beginning to make the major neuropathological features of chronic CNS inflammation observable.

Key points include:

Advanced MRI and PET methods enable visualization of features related to chronic inflammation in progressive and relapsing–remitting forms of MS.

Quantitative analysis of uptake of gadolinium contrast agent and ultra- small paramagnetic particles provide in vivo evidence of chronic, low- grade inflammation in people with progressive or relapsing–remitting MS (RRMS).

Lesions associated with activated macrophages/microglia (slowly expanding T2 hyperintense lesions and lesions with high susceptibility- weighted MRI signals at their rims) are more common in progressive MS than in RRMS.

Persistent focal leptomeningeal inflammation, detectable with gadolinium contrast enhanced T2 fluid attenuation inversion recovery MRI in many people with MS (particularly progressive MS), is associated with cortical lesions and accelerated cortical atrophy.

Translocator protein PET can detect increased innate immune activation in brains of people with MS; typically, activation is greater in secondary progressive MS than in RRMS.

Indirect evidence suggests that magnetic resonance spectroscopy measures of myo- inositol and some recently introduced PET measures can reflect contributions of astrocyte activation to brain innate immune responses.

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4. Zijlmans M, Zweiphenning W, van Klink N. Changing concepts in presurgical assessment for epilepsy surgery. Nat Rev Neurol. 2019;15(10):594-606. doi:10.1038/s41582-019-0224-y

In 1966, Talairach and Bancaud defined the epileptogenic focus as the anatomical area where seizures originate. Four decades later, on the basis of electrocorticography (ECoG), in which electrical activity is recorded from electrodes placed directly on the surface of the brain, Lüders et al. defined the epileptogenic zone as the cortical area that needs to be removed to obtain seizure freedom. This definition implies the existence of one or more circumscribed cortical areas containing epileptogenic tissue and has been challenged. Specifically, findings from stereo-EEG (SEEG), which simultaneously measures electrical activity from superficial and deeper structures of the brain, suggest the existence of epileptogenic brain networks involved in the initiation and propagation of epileptic activities, which might necessitate multitargeted treatments alongside focal resection.

Currently, patients being evaluated for epilepsy surgery undergo an extensive presurgical work- up, starting with MRI and EEG with synchronized video registration (video- EEG) and, if needed, PET or ictal SPECT. This noninvasive phase is followed either by invasive diagnostics with long- term stereo-EEG or ECoG to explore surgical possibilities, or directly by a resection, possibly guided by intraoperative ECoG. The various techniques visualize different aspects of the epileptogenic focus or network on the basis of structural, functional, electrographical and metabolic abnormalities. The planned resection requires delineation of the epileptogenic focus from functionally eloquent cortex, which can be partly achieved with noninvasive methods such as functional MRI (fMRI) and invasive methods such as electrocortical stimulation.

For presurgical planning, a key question is: what do the presurgical techniques need to disclose to optimize surgical decision- making? In addition to the structural lesion, which can be visualized by MRI, various zones have been conceptualized:

The high- frequency oscillation (HFO) zone generates HFOs, which can be detected by stereo- EEG (SEEG), electrocorticography (ECoG) or magnetoencephalography (MEG). The irritative zone generates interictal epileptiform discharges, which can be detected by ECoG, EEG, MEG or combined EEG and functional MRI. The seizure onset zone (SOZ) is the brain area from which seizures start, and can be recognized with SEEG, ECoG or ictal single- photon emission CT (SPECT). The ictal network consists of brain areas that are involved in seizures. The structural lesion is the area with visible abnormal brain tissue (for example, on MRI).

The authors suggest that centers should at least have access to a 3 T MRI scanner with a dedicated epilepsy protocol, as well as PET, video-EEG and invasive EEG. These resources should preferably be complemented by at least one electrical source localizing technique (ESI, MEG or EEG–fMRI), SPECT, and postprocessing of MRI, PET and SPECT scans.

3 figures, 1 table

5. Khalil JG, Smuck M, Koreckij T, et al. A prospective, randomized, multicenter study of intraosseous basivertebral nerve ablation for the treatment of chronic low back pain. Spine J. 2019;19(10):1620-1632. doi:10.1016/j.spinee.2019.05.598

Although the diagnosis of vertebrogenic pain is a relatively new clinical concept, there is a substantial body of basic science evidence supporting the vertebral endplates as a significant source of LBP. Immunohistochemical studies have demonstrated nociceptors at the endplates that trace back to the basivertebral nerve (BVN), a branch of the sinuvertebral nerve that was first described by Antonacci et al. in 1998. The endplates’ dual role of nutritional support for the disc and structural support for the spine are at odds, making them vulnerable to damage. Endplate damage can lead to cellular communication between the immunologically privileged disc nucleus and vertebral bone marrow, triggering chronic inflammation, a process that is visible as Modic changes on MR. This leads to endplate nerve proliferation that, in the presence of chemical sensitization and mechanical stimulation, can result in pain signals transmitted to the central nervous system by the BVN that are perceived as LBP. These findings led to interest in utilizing therapeutic radiofrequency (RF) ablation of the BVN in a specific subgroup of the chronic LBP population suspected of having vertebrogenic pain.

The purpose of this RCT was to compare the effectiveness of intraosseous RF ablation of the BVN to standard care for the treatment of chronic LBP in a specific subgroup of patients suspected to have vertebrogenic related symptomatology. A total of 140 patients with chronic LBP of at least 6 months duration, with Modic Type 1 or 2 vertebral endplate changes between L3 and S1, were randomized 1:1 to undergo either RF ablation of the BVN or continue standard care. Self reported patient outcomes were collected using validated questionnaires at each study visit. An interim analysis to assess for superiority was prespecified and overseen by an independent data management committee when a minimum of 60% of patients had completed their 3-month primary endpoint visit. The interim analysis showed clear statistical superiority (p<.001) for all primary and secondary patient-reported outcome measures in the RF ablation arm compared with the standard care arm. This resulted in a data management committee recommendation to halt enrollment in the study and offer early cross-over to the control arm. In the RF ablation arm, 74.5% of patients achieved a ≥10-point improvement in ODI, compared with 32.7% in the standard care arm (p<0.001).

The present study further defines the role of radiofrequency ablation of the BVN. The authors therefore report on a large randomized controlled trial of patients with chronic LBP and type 1 or 2 Modic changes. Patients treated with RF ablation of the BVN exhibited significant improvement in ODI, VAS, SF-36, and EQ-5D-5L at 3 months. In addition, patients in the treatment arm were found to have higher satisfaction than in the control arm.

6 figures, 3 tables

6. Aoun SG, Peinado Reyes V, El Ahmadieh TY, et al. Stem cell injections for axial back pain: a systematic review of associated risks and complications with a case illustration of diffuse hyperplastic gliosis resulting in cauda equina syndrome. J Neurosurg Spine. September 2019:1-8. doi:10.3171/2019.6.SPINE19594

Axial low-back pain is a disease of epidemic proportions that exerts a heavy global toll on the active workforce and results in more than half a trillion dollars in annual costs. Stem cell injections are being increasingly advertised as a restorative solution for various degenerative diseases and are becoming more affordable and attainable by the public. There have been multiple reports in the media of these injections being easily available abroad outside of clinical trials, but scientific evidence supporting them remains scarce. The authors present a case of a serious complication after a stem cell injection for back pain and provide a systematic review of the literature of the efficacy of this treatment as well as the associated risks and complications.

The authors found 12 studies, which detailed follow-up periods ranged from 6 months to 6 years, with 50% having a follow-up period of 1 year or less. Most studies reported favorable outcomes, although 36% used subjective measures. There was a tendency for pain relief to wane after 6 months to 2 years, with patients seeking a surgical solution. Only 1 study was a randomized controlled trial (RCT).

There are still insufficient data to support stem cell injections for back pain. Additional RCTs with long term follow-up are necessary.

Only 3 studies (25%) used allograft as a source of stem cells, which variously used mesenchymal stem cells (MSCs) from donors, allogeneic umbilical cord cells and a combination of allogeneic MSCs and fetal neuronal stem cells. Of the studies in which autograft was the source of the cells, 6 (67%) used MSCs from pelvic bone marrow aspirate with or without interval expansion of the cell lines or hypoxic treatment. Two studies used fat graft allograft cells, and one used nucleus pulposus autograft with interval culture and expansion prior to reinjection.

In the case reported associated with the article, the patient had received allogeneic MSCs that were reportedly injected into the disc space, but seemed to have resulted in their mis-differentiation into an overgrowth of gelatinous nervous support cells that coated the nerve roots and the inside of the dura and caused neural compression and malfunction. Given the location of the pathology, it is possible that one of the injections may have inadvertently been administered in the intrathecal space.

7. Schievink WI, Maya MM, Moser FG, et al. Lateral decubitus digital subtraction myelography to identify spinal CSF–venous fistulas in spontaneous intracranial hypotension. J Neurosurg Spine. September 2019:1-4. doi:10.3171/2019.6.SPINE19487

The authors compared findings of DSM with patients in the lateral decubitus position versus the prone position and now report a significantly increased yield of identifying spinal CSF–venous fistulas with this modification of their imaging protocol. The population consisted of 23 patients with SIH who underwent DSM in the lateral decubitus position and 26 patients with SIH who underwent DSM in the prone position. A CSF–venous fistula was demonstrated in 17 (74%) of the 23 patients who underwent DSM in the lateral decubitus position compared to 4 (15%) of the 26 patients who underwent DSM in the prone position. 

DSM is performed with the patient under general endotracheal anesthesia, with deep paralysis and suspended respiration for maximal detail and temporal resolution. Patients are positioned in the lateral decubitus position in a biplane angiography suite, with tilt table capability. Pillows or foam padding are placed to reduce positional scoliosis and optimize cervicothoracic alignment. A fluoroscopically guided lumbar puncture is performed at the L2–3 level with a 22-gauge needle. An opening pressure is obtained at this time. Then, accurate needle position is confirmed with an injection of 0.5 ml of Omnipaque. Patients are then further positioned based on the area of interest, tilting the table to achieve contrast flow to the cervicothoracic spine. Finally, contrast is injected manually at 1 ml per second, with suspended respiration for 40–80 seconds while acquiring biplane subtraction images at 2 frames per second. If this first DSM session fails to identify a CSF–venous fistula, then the study is repeated on another day in the same position but on the contralateral side. If the first DSM session does demonstrate a CSF–venous fistula, then the study is not repeated on the contralateral side.

They conclude that among SIH patients in whom conventional spinal imaging showed no evidence of a CSF leak, DSM in the lateral decubitus position demonstrated a CSF–venous fistula in about three-fourths of patients compared to only 15% of patients when the DSM was performed in the prone position, an approximately five-fold increase in the detection rate. Spinal CSF–venous fistulas are not rare among patients with SIH.

8. Berro DH, L’Allinec V, Pasco-Papon A, et al. Clip-first policy versus coil-first policy for the exclusion of middle cerebral artery aneurysms. J Neurosurg. September 2019:1-8. doi:10.3171/2019.5.JNS19373

Middle cerebral artery (MCA) aneurysms are a particular subset of intracranial aneurysms that can be excluded by clipping or coiling. A comparison of the results between these two methods is often limited by a selection bias in which wide-neck and large aneurysms are frequently treated with surgery. Here, the authors report the results of two centers using opposing policies in the management of MCA aneurysms: one center used a clip-first policy while the other used a coil-first policy, which limited the selection bias and ensured a good comparison of these two treatment modalities.

A total of 187 aneurysms were treated during the inclusion period; 88 aneurysms were treated by coiling and 99 aneurysms by clipping. The baseline patient and radiological characteristics were similar between the two groups, but the clinical presentation of the ruptured aneurysm cohort differed slightly. In the ruptured cohort (n = 90), although patients in the coiling group had a higher rate of additional surgery, the complication rate, functional outcome, and risk of death were similar between the two treatment groups. In the unruptured cohort (n = 97), the complication rate, functional outcome, and risk of death were also similar between the two treatment groups, although the risk of discomfort related to the temporal muscle atrophy was higher in the surgical group. Overall, the rate of complete occlusion was higher in the clipping group (84.2%) than in the coiling group (31%), which led to a higher risk in the coiling group of aneurysm retreatment within the first 2 years (p = 0.04).

They conclude that clipping and coiling for MCA aneurysm treatment provide the same clinical outcome for ruptured and unruptured aneurysms. However, clipping provides higher short- and long-term rates of complete exclusion, which in turn decreases the risk of aneurysm retreatment.

3 tables