1. Bourcier R, Goyal M, Liebeskind DS, et al. Association of Time From Stroke Onset to Groin Puncture With Quality of Reperfusion After Mechanical Thrombectomy. JAMA Neurol. 2019;76(4):405. doi:10.1001/jamaneurol.2018.4510.
Challenges in the field of acute ischemic stroke (AIS) related to large-vessel occlusion (LVO) focus on reducing time to reperfusion, optimizing imaging methods for patient selection, and evaluating the best technical approach. Reperfusion is significantly associated with clinical outcome in patients undergoing endovascular thrombectomy (EVT). Reperfusion is commonly scored with the modified TICI (mTICI) grading scale, with 0 indicating persistent complete occlusion and 3 indicating complete reperfusion. Because grade 2b was shown to be the best cutoff for predicting favorable outcome at 90 days, grades 2b and 3 are termed successful reperfusion. A pooled analysis of the first 5 randomized clinical stroke trials, which predominantly used stent retrievers as the primary approach, demonstrated that successful reperfusion was obtained in 71% of patients, whereas the rate of mTICI 0 to 2a varied from 12% to 41%. Successful reperfusion is influenced by device choice and strategy, use of intravenous (IV) alteplase, collateral status, and thrombus size, location, or composition.
The authors sought to analyze the rate of reperfusion after endovascular thrombectomy started at different intervals after symptom onset in patients with AIS. They conducted a meta-analysis of individual patient data from 7 randomized trials of the Highly Effective Reperfusion Using Multiple Endovascular Devices (HERMES) group. This is a multicenter cohort study of the intervention arm of randomized clinical trials included in the HERMES group. Patients with anterior circulation AIS who underwent endovascular thrombectomy for M1/M2 or intracranial carotid artery occlusion were included.
Among the 728 included patients decreases in rates of successful reperfusion defined as a TICI score of 2b/3 were observed with increasing time from admission or first imaging to groin puncture. The magnitude of effect was a 22% relative reduction per additional hour between admission and puncture and a 26% relative reduction per additional hour between imaging and puncture.
In conclusion, fast reperfusion is a major modifiable factor associated with better clinical outcome when successful reperfusion is achieved, and the intermediary outcome, the rate of successful reperfusion, is higher with faster in-hospital process times.
2. Hu Y-S, Lee C-C, Guo W-Y, et al. Trigeminal Nerve Atrophy Predicts Pain Recurrence After Gamma Knife Stereotactic Radiosurgery for Classical Trigeminal Neuralgia. Neurosurgery. 2019;84(4):927-934. doi:10.1093/neuros/nyy122.
The major categories of surgical treatments for trigeminal neuralgia are microvascular decompression (MVD) and ablative procedures, such as Gamma Knife surgery (GKS). MVD is more cost-effective and has a lower rate of pain recurrence than GKS. GKS is typically performed in patients with high anesthesia risks or a preference for less invasive management strategies.
The authors sought to determine whether nerve characteristics contribute to Gamma Knife surgery (GKS) outcomes in unilateral classic trigeminal neuralgia (CTN) without previous surgery. From 2006 to 2012, 67 patients with unilateral CTN without previous surgery received GKS with a maximal dose of 90 Gy delivered to the trigeminal nerve juxta brainstem. Two evaluators, blinded to the side of pain, analyzed the magnetic resonance images before GKS to obtain the parameters, including nerve cross-sectional area (CSA), vessel type of neurovascular compression (NVC), and site of NVC along the nerve. Patients with nerve atrophy (CSA of ≤ 4.4 mm2) had a lower 5-yr probability of maintaining pain relief after initial response than those without nerve atrophy (65% vs 86%). They conclude that trigeminal nerve atrophy may predict pain recurrence in patients with initial post-GKS relief of CTN. Arterial and proximal NVC are not predictive of GKS outcomes.
On the basis of the aforementioned findings, they propose a management strategy for patients with intractable CTN. For example, GKS may provide adequate long-term pain relief to patients without trigeminal nerve atrophy who prefer a less invasive treatment strategy. By contrast, patients with trigeminal nerve atrophy and NVC should undergo MVD if medically fit. Otherwise, a tailored radiosurgery, such as trigeminal nerve volume-based optimizing dosimetry or repeat GKS may be explored.
3. Duyckaerts C, Clavaguera F, Potier M-C. The prion-like propagation hypothesis in Alzheimerʼs and Parkinsonʼs disease. Curr Opin Neurol. 2019;32(2):266-271. doi:10.1097/WCO.0000000000000672.
The proteins that accumulate in Alzheimer’s and Parkinson’s diseases may alter the folding of the corresponding normal protein by corruptive templating. The seeding and propagation properties of the aggregated proteins qualify them as ‘propagons’ that may act at different levels: molecular, within tissues, between tissues, and between individuals (To avoid the term ‘prion’ in diseases other than Creutzfeldt–Jakob and related disorders, the term ‘propagon’ has been proposed to describe a misfolded protein acting as a corruptive template and propagating the abnormal folding in vitro, in vivo within tissue (when the propagation is limited to one organ such as the brain), at a systemic level (when the propagation involves different organs such as an entry by the digestive system and a development in the brain), and finally from individual to individual).
Proteins accumulated in Alzheimer’s disease and in Parkinson’s disease all behave as propagons. There is good evidence of human to human iatrogenic transmission of Ab lesion. Human transmission of tau pathology seems independent, and the evidence is weak. There is no hint of transmission of the alpha synuclein lesion, although experimental data prove that it is one of the most efficient propagons. The long incubation periods make epidemiological research on the topic particularly difficult, but the sporadic nature of the two disorders should stimulate the research of transmissible pathogenic agents.
The possibility of iatrogenic CAA must now be considered as a cause of symptomatic cerebral amyloid angiopathy, especially in young people, and should prompt the clinician to enquire about a history of neurosurgical treatments or of treatments related to cadaver derived preparations. Four young cases of CAA without risk factors but with a history of neurosurgical procedure during childhood or teenage years have been identified retrospectively and could be related to iatrogenic transmission . They recommend that these case reports should also lead to the exclusion of donors with Alzheimer’s disease in all graft procedures as a precaution.
4. Lapucci C, Saitta L, Bommarito G, et al. How much do periventricular lesions assist in distinguishing migraine with aura from CIS? Neurology. March 2019:10.1212/WNL.0000000000007266. doi:10.1212/WNL.0000000000007266.
The authors sought to evaluate in clinically isolated syndrome (CIS) and migraine with aura (MA) how the number of periventricular lesions (PVLs) detected at MRI influences diagnostic performance when the Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) or the 2017 revised criteria are applied.
White matter hyperintensities (WMH) of 84 patients with MA and 79 patients with CIS were assessed using manual segmentation technique. Lesion probability maps (LPMs) and voxel-wise analysis of lesion distribution by diagnosis were obtained.
Compared to patients with migraine with aura, patients with CIS showed a significant overall higher T2WMH mean number and volume (17.9 vs 6.2 and 3.1 vs 0.3) and a significantly higher T2 WMH mean number in infratentorial, periventricular, and juxtacortical areas. Lesion probability maps identified the periventricular regions as the sites with the highest probability of detecting T2 WMH in patients with CIS. Voxel-wise analysis of lesion distribution by diagnosis revealed a statistically significant association exclusively between the diagnosis of CIS and the periventricular lesions.
They conclude that periventricular lesions play a key role in the differential diagnosis between MA and CIS, particularly when there are more than 3.
Logistic regression analysis confirmed that PVLs represent the best factor separating CIS from MA, playing a key role in the differential diagnosis particularly when there are more than 3, with an 85% decrease in the probability to be migraineur for each additional PVL over the first one. MAGNIMS criteria demonstrated the highest specificity in differentiating CIS from MA (100% vs 87%) against a predictable lower sensitivity (63% vs 72%).
Check out figure 1, and show it to your fellows and residents…. It shows the distribution we all recognize, but it is somehow comforting to see the data.
5. Mutsaerts HJMM, Mirza SS, Petr J, et al. Cerebral perfusion changes in presymptomatic genetic frontotemporal dementia: a GENFI study. Brain. 2019;142(4):1108-1120. doi:10.1093/brain/awz039.
Frontotemporal dementia encompasses a pathologically heterogeneous group of neurodegenerative diseases, characterized clinically by prominent behavioral and/or language disruption. Frontotemporal dementia significantly impacts patients and their families during the prime of their lives when individuals have responsibilities to their careers, raising children and social interactions. It is highly heritable, with an autosomal dominant family history documented in about one-third of people with the disease.
Genetic forms of frontotemporal dementia are most commonly due to mutations in three genes, C9orf72 (Chromosome 9 Open Reading Frame 72), GRN (frontotemporal dementia with TDP43 inclusions, GRN gene related which encodes progranulin) or MAPT (microtubule-associated protein tau), with presymptomatic carriers from families representing those at risk. While cerebral blood flow shows differences between frontotemporal dementia and other forms of dementia, there is limited evidence of its utility in presymptomatic stages of frontotemporal dementia.
This study aimed to delineate the cerebral blood flow signature of presymptomatic, genetic frontotemporal dementia using a voxel-based approach. In the multicenter GENetic Frontotemporal dementia Initiative (GENFI) study, the authors investigated cross-sectional differences in arterial spin labelling MRI-based cerebral blood flow between presymptomatic C9orf72, GRN or MAPT mutation carriers (n = 107) and non-carriers (n = 113), using general linear mixed-effects models and voxel-based analyses. Cerebral blood flow within regions of interest derived from this model was then explored to identify differences between individual gene carrier groups and to estimate a timeframe for the expression of these differences. The voxel-based analysis revealed a significant inverse association between cerebral blood flow and the expected age of symptom onset in carriers, but not non-carriers. Regions included the bilateral insulae/orbitofrontal cortices, anterior cingulate/paracingulate gyri, and inferior parietal cortices, as well as the left middle temporal gyrus. For all bilateral regions, associations were greater on the right side. After correction for partial volume effects in a region of interest analysis, the results were found to be largely driven by the C9orf72 genetic subgroup.
These cerebral blood flow differences first appeared approximately 12.5 years before the expected symptom onset determined on an individual basis. Cerebral blood flow was lower in presymptomatic mutation carriers closer to and beyond their expected age of symptom onset in key frontotemporal dementia signature regions. These results suggest that arterial spin labelling MRI may be a promising non-invasive imaging biomarker for the presymptomatic stages of genetic frontotemporal dementia.
3 Tables 2 Figures
6. Gallay MN, Moser D, Jeanmonod D. Safety and accuracy of incisionless transcranial MR-guided focused ultrasound functional neurosurgery: single-center experience with 253 targets in 180 treatments. J Neurosurg. 2018;130(April):1-10. doi:10.3171/2017.12.JNS172054.
A total of 180 treatments with MRgFUS for chronic therapy-resistant idiopathic Parkinson’s disease, essential tremor (ET), cerebellar tremor (CT), and neuropathic pain (NP) were prospectively assessed for side-effects and targeting accuracy. Monitoring for later side-effects was continued for at least 3 months after the procedure in all but 1 case (0.6%); in that single case, the patient was lost to follow-up after an uneventful early postoperative course. The surgical targets were the pallidothalamic tract (pallidothalamic tractotomy, n =105), the cerebellothalamic tract (cerebellothalamic tractotomy, n = 50), the central lateral nucleus (central lateral thalamotomy, n = 84), the centrum medianum (centrum medianum thalamotomy, n = 12), and the globus pallidus (pallidotomy, n = 2). Cognitive testing was performed before, 1–2 days after, and 1 year after the procedure. The Mini–Mental State Examination (MMSE) was used for the first 29 cases and was then replaced by the Montreal Cognitive Assessment (MoCA). Lesion reconstruction and measurement of targeting accuracy were done on 2-day posttreatment MR images for each performed target.
The incisionless transcranial MRgFUS technology demonstrates a higher targeting accuracy and a lower side-effect profile than techniques requiring cerebral penetration. In the absence of penetration brain shift, this technique avoids the placement of a thermolesion away from the chosen target, thus suppressing the need for reversible therapeutic energy application. With the use of proper physiopathology-based targets, definitive therapeutic effects can be coupled with sparing of sensory, motor, and paralimbic/multimodal thalamocortical functions. Clinical efficacy, not analyzed in this investigation, will ultimately rest in proper target selection and optimized thermolesional coverage of the target.
4 figures, 1 table….(2 MR figures)
7. Kamath AA, Friedman DD, Akbari SHA, et al. Glioblastoma Treated With Magnetic Resonance Imaging-Guided Laser Interstitial Thermal Therapy: Safety, Efficacy, and Outcomes. Neurosurgery. 2019;84(4):836-843. doi:10.1093/neuros/nyy375.
The authors performed a retrospective descriptive study of patients with histologically proven GBM who underwent laser interstitial thermal therapy (LITT). Data collected included demographics, tumor location and volume, tumor genetic markers, treatment volume, perioperative complications, and long-term follow-up data.
They performed 58 LITT treatments for GBM in 54 patients over 5.5 yr. Forty-one were recurrent tumors while 17 were frontline treatments. Forty GBMs were lobar in location, while 18 were in deep structures (thalamus, insula, corpus callosum). Average tumor volume was 12.5cm. Average percentage of tumor treated with the yellow thermal damage threshold (TDT) line (dose equivalent of 43◦C for 2 min) was 93.3%, and with the blue TDT line (dose equivalent of 43◦C for 10 min) was 88.0%. There were 7 perioperative complications (12%) and 2 mortalities (3.4%). Median overall survival after LITT for the total cohort was 11.5mo, and median progression free survival 6.6 mo.
The authors found LITT to be a safe and efficacious procedure based on the authors experience of 58 cases. Of the two mortalities (3.4%), one was a 78-yr old with a large parietooccipital GBM which hemorrhaged after treatment; the patient’s family elected for comfort measures only. The second patient developed fulminant Enterobacter meningitis, and analysis of the event traced this problem to a sterile-processing related contamination.
5 figures, 3 tables, mainly survival plots
8. Daou B, Atallah E, Chalouhi N, et al. Aneurysms with persistent filling after failed treatment with the Pipeline embolization device. J Neurosurg. 2018;130(April):1-7. doi:10.3171/2017.12.JNS163090.
Of 316 cases treated at a single institution, 281 patients had a long-term follow-up. A total of 52 (16.4%) aneurysms with residual filling were identified and constituted the study population. The mean patient age in this population was 58.8 years. The mean aneurysm size was 10.1 mm. Twelve aneurysms were fusiform (23%). Of the aneurysms with residual filling, there were 20 carotid ophthalmic (CO) aneurysms (20% of all CO aneurysms treated), 10 other paraclinoid aneurysms (16.4% of all paraclinoid aneurysms), 7 posterior communicating artery (PCoA) aneurysms (21.9% of all PCoA aneurysms), 7 cavernous internal carotid artery (ICA) aneurysms (14.9% of all cavernous ICA aneurysms), 4 vertebrobasilar (VB) junction aneurysms (14.8% of all VB junction aneurysms), and 3 middle cerebral artery (MCA) aneurysms (25% of all MCA aneurysms). Eleven patients underwent placement of more than one PED (21.2%), with a mean number of devices of 1.28 per case. Eight of 12 aneurysms were previously treated with a stent (15.4%). Nineteen patients underwent re-treatment (36.5%); the 33 patients who did not undergo re-treatment (63.5%) were monitored by angiography or noninvasive imaging. In multivariate analysis, age older than 65 years, prior stent placement across the target aneurysm, aneurysm location in the distal anterior circulation, and longer follow-up duration were associated with incomplete aneurysm occlusion.
Aneurysms with persistent filling represented 18.5% of all treated cases in this series with follow-up imaging. This highlights the efficacy of the PED that resulted in a rate of aneurysm occlusion of 81.5% after a 5-year experience with the device. This rate is consistent with those reported in other studies in the literature that have shown a high complete aneurysm occlusion rate, with most studies reporting occlusion rates > 80%, which compares favorably to that of endovascular coil embolization, where the reported complete occlusion rate is 66% (ISAT; International Subarachnoid Aneurysm Trial).
3 Tables, no images
