1. Rocha EA, Topcuoglu MA, Silva GS, Singhal AB. RCVS2 score and diagnostic approach for reversible cerebral vasoconstriction syndrome. Neurology. 2019;92(7):e639-e647. doi:10.1212/WNL.0000000000006917.
Over the last 2 decades, reversible cerebral vasoconstriction syndrome (RCVS) has become recognized as a group of conditions characterized by rapidly changing and reversible segmental cerebral artery narrowing and dilation, usually heralded by severe sudden-onset headaches. Although one third to half the patients can develop stroke, over 90% have benign clinical outcome. Primary angiitis of the CNS (PACNS) has been an important mimic due to the presence of headaches, strokes, and angiographic abnormalities.
The authors identified consecutive patients from their institutional databases admitted in 2013–2017 with newly diagnosed RCVS (n = 30) or non-RCVS arteriopathy (n = 80). Admission clinical and imaging features were compared. Multivariate logistic regression modeling was used to develop a discriminatory score. Score validity was tested in a separate cohort of patients with RCVS and its closest mimic, primary angiitis of the CNS (PACNS).
The RCVS group had significantly more women, vasoconstrictive triggers, thunderclap headaches, normal brain imaging results, and better outcomes. Beta coefficients from the multivariate regression model yielding the best c-statistic (0.989) were used to develop the RCVS2 score (range −2 to +10; recurrent/single thunderclap headache present = +5; carotid artery intracranial involvement = -2; vasoconstrictive trigger = +3; sex = female +1; subarachnoid hemorrhage present = +1). Score ≥5 had 99% specificity and 90% sensitivity for diagnosing RCVS, and score ≤2 had 100% specificity and 85% sensitivity for excluding RCVS. Scores 3–4 had 86% specificity and 10% sensitivity for diagnosing RCVS. The score showed similar performance to distinguish RCVS from PACNS in the validation cohort.
The RCVS group had significantly more normal results on parenchymal brain imaging, and when abnormal, showed significantly fewer brain infarcts but a 10-fold higher frequency of PRES-like lesions. The non-RCVS group accumulated significantly more lesions on serial imaging. SAH was more common in RCVS and convexity (nonaneurysmal) SAHs were exclusively seen in RCVS. Arteriopathy was almost always diagnosed with transfemoral or CT angiography in either group. The intracranial segment of the internal carotid artery was more often involved in non-RCVS, mostly due to moyamoya and intracranial atherosclerosis. The posterior circulation arteries were more often abnormal and the abnormalities more diffuse in RCVS.
The RCVS2 score and diagnostic approach can be used to promptly diagnose and distinguish RCVS from mimics using easily available admission variables.
5 Tables, 1 figure. No MRI. Table 4 lists the scoring criteria
2. Goriounova NA, Heyer DB, Wilbers R, et al. Large and fast human pyramidal neurons associate with intelligence. Elife. 2018;7:1-21. doi:10.7554/eLife.41714.
3. Miller EN, Sherwood CC. What single neurons can tell us. Elife. 2019;8:8-10. doi:10.7554/eLife.44560.
A fundamental question in neuroscience is what properties of neurons lie at the heart of human intelligence and underlie individual differences in mental ability. Thus far, experimental research on the neurobiological basis of intelligence has largely ignored the neuronal level and has not directly tested what role human neurons play in cognitive ability, mainly due to the inaccessibility of human neurons.
To investigate whether structural and functional properties of neurons of the human temporal cortex associate with general intelligence, the authors collected a unique multimodal data set from 46 human subjects containing single cell physiology (31 subjects, 129 neurons), neuronal morphology (25 subjects, 72 neurons), pre-surgical MRI scans and IQ test scores. Human cortical brain tissue was removed as a part of surgical treatment for epilepsy or tumor. The tissue almost exclusively originated from middle temporal gyrus, approximately 4 cm posterior to the temporal pole as a block of ~1–1.5 cm in diameter and was removed to gain access to the disease focus in deeper lying structures such as hippocampus or amygdala. In all patients, the resected neocortical tissue was not part of the epileptic focus or tumor and displayed no structural/functional abnormalities in preoperative MRI investigation, electrophysiological whole- cell recordings or microscopic investigation of histochemically stained tissue.
After resection the tissue was immediately placed in ice-cold artificial cerebrospinal fluid (aCSF) and within 15 min transported to the lab, sliced and maintained to enable single cell physiological recordings.
First, they confirmed that higher IQ scores correlate with a thicker temporal cortex, based on measurements of pre-operative MRI scans. Then, for each patient, two or three pyramidal neurons from the upper cortical layers were selected and measured. Differences in dendritic length and branching explained approximately 25% of the variance in IQ scores between individuals in a sample of 25 patients. Longer dendrites have extra surface area, which could help increase the number of synapses the neuron can form. With more of these connections, the pyramidal neurons can produce an output signal that integrates more inputs from neighboring neurons in a given time.
Further analyses show that pyramidal neurons with larger dendritic trees fire more quickly, which allows them to transmit information faster. Indeed, recording the activity of cells in brain slices obtained from 31 patients demonstrated that higher IQ scores were associated with neurons firing more quickly, especially during sustained neuronal activity.
Goriounova et al. have shown that distinct changes in the microanatomy of pyramidal neurons influence the working properties of these cells. Relatedly, a thicker cortex may arise from pyramidal cells with more elaborate dendritic networks. In turn, this would lead to more rapid information processing, and ultimately, increased intellectual performance.
4. Janssen PM, Venema E, Dippel DWJ. Effect of Workflow Improvements in Endovascular Stroke Treatment. Stroke. 2019;50(3):665-674. doi:10.1161/STROKEAHA.118.021633.
Providing an optimal diagnostic process and rapid endovascular stroke treatment requires close collaboration of the emergency medical service, emergency department team, stroke team, neurointerventional team, and anesthesia team. Diagnostic imaging and endovascular treatment facilities should be available with little time delay. Several strategies to reduce the time to endovascular stroke treatment have been proposed. However, the effect of individual and combined strategies on reducing time to treatment is unclear. The authors performed a systematic review and meta-analysis on the effectiveness of specific workflow improvement interventions for rapid delivery of endovascular stroke treatment.
Fifty-one studies (3 randomized controlled trials, 13 prepost intervention studies, and 35 observational studies) with in total 8467 patients were included. Most frequently reported workflow intervention types concerned anesthetic management (n=26), in-hospital patient transfer management (n=14), and prehospital management (n=11). Patients in the intervention group had shorter time to treatment intervals (weighted mean difference, 26 minutes) compared with controls. Subgroup meta-analysis of intervention types also showed a shorter time to treatment in the intervention group: a mean difference of 12 minutes for anesthetic management, 37 minutes for prehospital management, 41 minutes for in-hospital patient transfer management, 47 minutes for teamwork, and 64 minutes for feedback. The mean difference in time to treatment of studies with multiple interventions implemented simultaneously was 50 minutes in favor of the intervention group. Patients in the intervention group had increased likelihood of favorable outcome.
Interventions in the workflow of endovascular stroke treatment lead to a significant reduction in time to treatment and results in an increased likelihood of favorable outcome. Acute stroke care should be reorganized by making use of the examples of workflow interventions described in this review to ensure the best medical care for stroke patients.
3 Figures, 3 Tables
5. de Havenon A, Mlynash M, Kim-Tenser MA, et al. Results From DEFUSE 3. Stroke. 2019;50(3):632-638. doi:10.1161/STROKEAHA.118.023407.
The effect of leptomeningeal collaterals for acute ischemic stroke patients with large vessel occlusion in the late window (>6 hours from last known normal) remains unknown. The authors sought to determine if collateral status on baseline computed tomography angiography impacted neurological outcome, ischemic core growth, and moderated the effect of endovascular thrombectomy in the late window.
Of the 130 patients in the cohort, 33 (25%) had poor collaterals and 97 (75%) had good collaterals. There was no difference in the rate of functional independence with good versus poor collaterals in unadjusted analysis or after adjustment for treatment arm. Good collaterals were associated with significantly smaller ischemic core volume and less ischemic core growth. The difference in the treatment effect of endovascular thrombectomy was not significant. Collateral status also did not affect the rate of stroke related death.
In conclusion, in DEFUSE 3, good collaterals on single phase CTA were associated with smaller ischemic core volume at baseline and reduced ischemic core growth but not with improved neurological outcome, success of endovascular therapy, hemorrhagic complications, or death. They also did not find an association between collaterals and many of the traditional demographic predictors of baseline collateral status.
They note that these unexpected findings require further study to confirm their validity and to better understand the role of collaterals for anterior circulation large vessel occlusion stroke patients in the late therapeutic window.
3 Tables, 2 Figures, no imaging
6. Patel AP, Fisher JL, Nichols E, et al. Global, regional, and national burden of brain and other CNS cancer, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18(4):376-393. doi:10.1016/S1474-4422(18)30468-X.
Typical GBDS with one table that is 9 pages in length.
In 2016, there were 330,000 incident cases of CNS cancer and 227,000 deaths globally, and age-standardized incidence rates of CNS cancer increased globally by 17·3% between 1990 and 2016. The highest age-standardized incidence rate was in the highest quintile of Socio-demographic Index (SDI). Age-standardized incidence rates increased with each SDI quintile. East Asia was the region with the most incident cases of CNS cancer for both sexes in 2016, followed by western Europe and south Asia. The top three countries with the highest number of incident cases were China, the USA, and India. CNS cancer was responsible for 7·7 million disability-adjusted life-years (DALYs) globally, a non-significant change in age-standardized DALY rate.
7. Kahraman-Koytak P, Bruce BB, Peragallo JH, Newman NJ, Biousse V. Diagnostic Errors in Initial Misdiagnosis of Optic Nerve Sheath Meningiomas. JAMA Neurol. 2019;76(3):326. doi:10.1001/jamaneurol.2018.3989.
The classic clinical presentation of ONSM is the triad of progressive visual loss, optic atrophy, and the presence of retinal choroidal collaterals. However, the simultaneous occurrence of all 3 findings is rare. Patients usually present with painless progressive monocular visual loss, which may lead to blindness if left untreated. Therefore, although ONSMs are histologically benign and relatively rare tumors, timely diagnosis and appropriate management are crucial to ensure a favorable visual outcome.
The authors retrospectively reviewed 35 of 39 patients with unilateral ONSM (89.7%) who were seen in the tertiary neuro-ophthalmology practice at Emory University School of Medicine between January 2002 and March 2017. The Diagnosis Error Evaluation and Research taxonomy tool was applied to cases with missed/delayed diagnoses.
Of 35 patients with unilateral ONSM (30 women [85.7%]; mean age, 45.26 years), 25 (71%) had a diagnosis delayed for a mean of 62.60 months. The most common diagnostic error (19 of 25 [76%]) was clinician assessment failure (errors in hypothesis generation and weighing), followed by errors in diagnostic testing (15 of 25 [60%]). The most common initial misdiagnosis was optic neuritis (12 of 25 [48%]), followed by the failure to recognize optic neuropathy in patients with ocular disorders. Five patients who received a misdiagnosis (20%) underwent unnecessary lumbar puncture, 12 patients (48%) unnecessary laboratory tests, and 6 patients (24%) unnecessary steroid treatment. Among the 16 patients who initially received a misdiagnosis that was later correctly diagnosed at our institution, 11 (68.8%) had prior magnetic resonance imaging (MRI) results that were read as healthy; 5 (45.5%) showed ONSM but were misread by a non-neuroradiologist and 6 (54.5%) were performed incorrectly (no orbital sequence or contrast). Sixteen of the 25 patients (64%) had a poor visual outcome.
They conclude that biased preestablished diagnoses, inaccurate funduscopic examinations, a failure to order the correct test (MRI brain/orbits with contrast), and a failure to correctly interpret MRI results were the most common sources of diagnostic errors and delayed diagnosis with worse visual outcomes and increased cost (more visits and tests).
3 Tables, 2 Figures, with one MRI
8. Dubey D, Pittock SJ, Krecke KN, et al. Clinical, Radiologic, and Prognostic Features of Myelitis Associated With Myelin Oligodendrocyte Glycoprotein Autoantibody. JAMA Neurol. 2019;76(3):301. doi:10.1001/jamaneurol.2018.4053.
Transverse myelitis (TM) is a potentially disabling neurologic syndrome with a variety of causes; single or recurrent episodes may result in permanent wheelchair dependence. In 1 study,70% of patients referred to a tertiary referral center with a diagnosis of idiopathic transverse myelitis were found to have a specific etiology for their myelopathy, highlighting that the causes of transverse myelitis are poorly recognized among the neurology community. The discovery of the serum diagnostic biomarkers, aquaporin-4 autoantibody (AQP4-IgG) targeting astrocytes, and myelin oligodendrocyte glycoprotein autoantibody (MOG-IgG) targeting oligodendrocytes has aided in the ability to classify patients with idiopathic TM into a specific disease category.
The authors evaluated the clinical, radiologic, and prognostic features of MOG-IgG myelitis and compare with myelitis with aquaporin-4–IgG (AQP4-IgG) and multiple sclerosis (MS). They retrospectively identified 199 MOG-IgG–positive Mayo Clinic patients from January 1, 2000, through December 31, 2017, through the neuroimmunology laboratory. Fifty-four patients met inclusion criteria of (1) clinical myelitis; (2) MOG-IgG positivity; and (3) medical records available. They excluded 145 patients without documented myelitis. Myelitis of AQP4-IgG (n = 46) and MS (n = 26) were used for comparison.
Of 54 included patients with MOG-IgG myelitis, the median age was 25 years and 24 were women (44%). Isolated transverse myelitis was the initial manifestation in 29 patients (54%), and 10 (19%) were initially diagnosed as having viral/postviral acute flaccid myelitis. Cerebrospinal fluid–elevated oligoclonal bands occurred in 1 of 38 (3%). At final follow-up 32 patients (59%) had developed 1 or more relapses of optic neuritis (n = 31); transverse myelitis (n = 7); or acute disseminated encephalomyelitis (n = 1). Clinical features favoring MOG-IgG myelitis vs AQP4-IgG or MS myelitis included prodromal symptoms and concurrent acute disseminated encephalomyelitis.
MRI features favoring MOG-IgG over AQP4-IgG or MS myelitis were T2-signal abnormality confined to gray matter (sagittal line and axial H sign) and lack of enhancement. Longitudinally extensive T2 lesions were of similar frequency in MOG-IgG and AQP4-IgG myelitis (37 of 47 [79%] vs 28 of 34 [82%]) but not found in MS. Multiple spinal cord lesions and conus involvement were more frequent with MOG-IgG than AQP4-IgG but not different from MS. Wheelchair dependence at myelitis nadir occurred in one-third of patients with MOG-IgG and AQP4-IgG but never with MS, although patients with MOG-IgG myelitis recovered better than those with AQP4-IgG.
3 Tables, 2 figures including MRI. (note particularly figure 2 which contrasts anti MOG, AQ4 and MS)
