Journal Scan

Journal Scan – This Month in Other Journals, September 2017

McKeith IG, Boeve BF, Dickson DW, et al. Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology. 2017;65(12):1863-1872. doi:10.1212/WNL.0000000000004058

The Dementia with Lewy Bodies (DLB) Consortium last reported on diagnosis and management in December 2005, and its recommendations have been widely cited for both clinical and research use. The revised DLB criteria which are presented incorporate new developments and result from a review process that combined the reports of 4 multidisciplinary, expert working groups with a meeting that included patient and care partner participation. Dementia, defined as a progressive cognitive decline of sufficient magnitude to interfere with normal social or occupational functions, or with usual daily activities, is an essential requirement for DLB diagnosis. Disproportionate attentional, executive function, and visual processing deficits relative to memory and naming are typical. DLB consciousness fluctuations are typically delirium-like, occurring as spontaneous alterations in cognition, attention, and arousal. They include waxing and waning episodes of behavioral inconsistency, incoherent speech, variable attention, or altered consciousness that involves staring or zoning out.

Recurrent, complex visual hallucinations occur in up to 80% of patients with DLB and are a frequent clinical signpost to diagnosis. They are typically well-formed, featuring people, children, or animals, sometimes accompanied by related phenomena including passage hallucinations (transient visual hallucinations consisting of people or animals that pass sideways out of the visual field), sense of presence, and visual illusions.

Spontaneous parkinsonian features, not due to antidopaminergic medications or stroke, are common in DLB, eventually occurring in over 85%. Parkinsonism in Parkinson disease (PD) is defined as bradykinesia in combination with rest tremor, rigidity, or both. Many DLB patients’ parkinsonism falls short of this, so documentation of only one of these cardinal features is required.

REM sleep behavior disorder is a parasomnia manifested by recurrent …

Journal Scan – This Month in Other Journals, August 2017

Charidimou A, Boulouis G, Xiong L, et al. Cortical superficial siderosis and first-ever cerebral hemorrhage in cerebral amyloid angiopathy. Neurology. 2017;88(17):1607-1614. doi:10.1212/WNL.0000000000003866.

Cortical superficial siderosis (cSS) on T2*-GRE or SWI is a strong hemorrhagic signature of cerebral amyloid angiopathy (CAA)—a common small vessel disease characterized by cerebrovascular amyloid deposition affecting superficial cortical microvascular networks, leading to spontaneous lobar intracerebral hemorrhage (ICH). Cortical superficial siderosis results from bleeding episodes within or adjacent to cortical sulci, presumably from amyloid-laden superficial cortical and leptomeningeal arterioles. Cortical superficial siderosis is a common manifestation of cerebral amyloid angiopathy, being found in 40%–60% of patients.

In this study, consecutive patients meeting modified Boston criteria for probable CAA in the absence of ICH from a single-center cohort were analyzed. Cortical superficial siderosis and other small vessel disease MRI markers were assessed according to recent consensus recommendations. Patients were followed prospectively for future incident symptomatic lobar ICH.

The cohort included 236 patients with probable CAA without lobar ICH at baseline. Cortical superficial siderosis prevalence was 34%. During a median follow-up of 3.26 years, 27 of 236 patients (11.4%) experienced a first-ever symptomatic lobar ICH. Cortical superficial siderosis was a predictor of time until first ICH. The risk of symptomatic ICH at 5 years of follow-up was 19% for patients with cortical superficial siderosis at baseline vs 6% for patients without cortical superficial siderosis. In multivariable Cox regression models, cortical superficial siderosis presence was the only independent predictor of increased symptomatic ICH risk during follow-up.

The authors found that cortical superficial siderosis on T2*-GRE/SWI MRI is associated with an increased risk of future first-ever symptomatic lobar ICH. The prognostic value of cSS in this setting was strong and independent of age and other neuroimaging markers of CAA severity, including lobar cerebral microbleed burden and WMH. Hence, cortical superficial …

Journal Scan – This Month in Other Journals, July 2017

Rabinstein AA. Treatment of Acute Ischemic Stroke. Continuum (Minneap Minn). 2017;23(1, Cerebrovascular Disease):62-81. doi:10.1212/CON.0000000000000420.

This is an excellent and comprehensive review of current acute stroke treatment.  The three main principles of acute stroke care are: (1) achieve timely recanalization of the occluded artery and reperfusion of the ischemic tissue, (2) optimize collateral flow, and (3) avoid secondary brain injury. The author states there is incontrovertible evidence that IV thrombolysis with rtPA and endovascular thrombectomy with a retrievable stent improve neurologic outcomes in patients with acute ischemic stroke. Both treatments should be administered as quickly as possible after stroke onset, can be combined, and are safe in appropriately selected candidates. IV thrombolysis with rtPA is proven to be effective in improving functional outcomes after an ischemic stroke up to 4.5 hours after symptom onset. IV rtPA infused within 3 hours of symptom onset increases the chances of functional independence at 3 months by one-third. The benefit is time dependent and much stronger when the drug is administered within the first 90 minutes after symptom onset.

Regarding mechanical thrombectomy, the six positive trials shared the requirement of CT angiograms for patient screening (only patients with documented internal carotid artery or proximal middle cerebral artery occlusions could be entered into the studies), emphasized the importance of prompt intervention, and almost exclusively used retrievable stents to achieve reperfusion. All of the trials enrolled patients with severe neurologic deficits and good prestroke functional status who presented mostly within 6 hours of symptom onset. Major early ischemic changes on the baseline CT scan were a reason for exclusion. Patients treated with mechanical thrombectomy had high rates of reperfusion and much better functional outcomes at 90 days. Mechanical thrombectomy was also proven to be quite safe, with a pooled rate of symptomatic 

Journal Scan – This Month in Other Journals, June 2017

Elshafeey N, Hassan I, Zinn PO, Colen RR. From K-space to Nucleotide. Top Magn Reson Imaging. 2017;26(1):1. doi:10.1097/RMR.0000000000000114.

Radiogenomics is a relatively new field within radiology that links different imaging features with diverse genomic events. Genomics advances provided by the Cancer Genome Atlas and the Human Genome Project have enabled researchers to harness and integrate this information with noninvasive imaging phenotypes to create a better 3-dimensional understanding of tumor behavior and biology.  This review summarizes the radiogenomic literature regarding brain tumors, both glioblastoma and lower grades.

As you know, the typical gross appearance of glioblastoma on MR is characterized as an irregular, ring-enhancing tumor with a central necrotic core and surrounding area of FLAIR hyperintensity. Each of these 3 imaging components (aka. phenotypes) of the tumor reflect a distinct tumor biology such as neovascularization and active tumor [contrast-enhancing component], edema/invasion (peritumoral T2/FLAIR hyperintensity), or cell death (necrosis). As an example of the potential power of volumetric features of glioblastoma on prognosis, in a cohort of 78 patients glioblastoma tumor volumes were quantified and combined with patient age and Karnofsky performance score (KPS) to create an easy-to-use 3-step scoring system VAK (Volume-Age, KPS) that can predict patient outcome.

Additionally, specific genomic and epigenetic events have shown a predilection for specific locations within the brain. As background, MGMT, a gene that encodes for a DNA repair enzyme, is associated with a better survival in those patients with MGMT promoter methylation receiving alkylating agents such as temozolomide.  In treatment-naive glioblastoma patients, it has been found that patients with unmethylated O-6- methylguanine-DNA methyltransferase (MGMT) promoter predominated in the right temporal lobe. Glioblastoma with MGMT promoter methylation, EGFR amplification, and EGFRvIII mutations tended to occur in in the left temporal lobe.  Most IDH1-mutated and intact PTEN tumors were in the frontal lobe.

3 tables,

Journal Scan – This Month in Other Journals, May 2017

Wilson JR, Tetreault LA, Kim J, et al. State of the Art in Degenerative Cervical Myelopathy: An Update on Current Clinical Evidence. Neurosurgery. 2017;80(3S):S33-S45. doi:10.1093/neuros/nyw083.

Degenerative cervical myelopathy (DCM) is used to describe myelopathy resulting from degenerative pathology in the cervical spine including spondylosis, degenerative disc disease, ossification of the posterior longitudinal ligament (OPLL), and ossification of the ligamentum flavum. The authors provide a wide-ranging overview of the state of the art in degenerative cervical myelopathy, with a focus on updating the spine surgeon on the current evidence surrounding pathophysiology, natural history, imaging, outcome measures, and outcome prediction tools. They also provide an overview of the evidence for surgical vs. nonoperative management, and a summary of the literature regarding the most commonly used approaches to the cervical spine.

The pathophysiology of DCM includes both static and dynamic factors. Static factors result from congenital stenosis or acquired stenosis secondary to spondylosis and disc degeneration.Dynamic factors relate to exacerbation of spinal cord compression seen with physiological and, in the setting of degenerative subluxation, pathological motion of the cervical spine. In addition to physical compression, there is a reduction in blood supply leading to ischemia within the cord.  Pathological features of DCM include gray and white matter degeneration, anterior horn cell loss, cystic cavitation, and Wallerian degeneration of the posterior columns adjacent to the site of compression.

There is also likely a secondary cascade of neuroinflammation consisting of microglia activation and macrophage recruitment which occurs at the site of mechanical compression within the spinal cord. In the noncompressed nonmyelopathic spinal cord, the blood-spinal cord-barrier is isolated from the peripheral immune system; however, chronic compression renders the cord susceptible to cell infiltration that may be involved in neural

Journal Scan – This Month in Other Journals, April 2017

Zurawski J, Lassmann H, Bakshi R. Use of Magnetic Resonance Imaging to Visualize Leptomeningeal Inflammation in Patients With Multiple Sclerosis. JAMA Neurol. 2017;74(1):100. doi:10.1001/jamaneurol.2016.4237.

You are well aware that MS is a chronic demyelinating disease traditionally characterized by an initial relapsing-remitting clinical course and focal inflammatory lesions that have a predilection for the periventricular white matter.  However, histopathologic and imaging studies have illustrated a more complex pathologic substrate involving cortical demyelination, gray matter atrophy, and meningeal inflammation.  The authors evaluate the status and prospects regarding the emerging role of MR to visualize leptomeningeal enhancement (LME) in patients with MS and place these findings in the proper pathobiologic and clinical context.

Absinta et al (Absinta M, Vuolo L, Rao A, et al. Gadolinium-based MRI characterization of leptomeningeal inflammation in multiple sclerosis. Neurology. 2015;85(1):18-28.) found that LME was significantly more common than had been initially reported, and its presence was associated with patient age, disease severity, and clinical type of MS. The authors used high-resolution 3T 3-dimensional T2 FLAIR MRI with a voxel size of 1.0 × 1.0 × 1.0mm and postcontrast images obtained 10 minutes after gadolinium injection. They demonstrated LME in 74 of 299 patients with MS (24.7%) compared with only 1 of 37 (2.7%) age-matched controls with out MS. Perhaps of particular importance, LME was twice as frequent (33%) in patients with progressive forms of MS (present in 44 patients with secondary progressive MS) (SPMS) and 74 patients with primary progressive MS (PPMS) compared with those with relapsing-remitting (RR) disease (19%). Disease duration, and Expanded Disability Status Scale scores were associated with LME. Whole-brain and cortical atrophy were also associated with LME. There was no association between LME and WM lesion enhancement or WM lesion volume. Leptomeningeal enhancement topography abutted the pial surface on the cerebral convexity (19% …

Journal Scan – This Month in Other Journals, March 2017

Daou B, Chalouhi N, Starke RM, et al. Clipping of previously coiled cerebral aneurysms: efficacy, safety, and predictors in a cohort of 111 patients. J Neurosurg. 2016;125(December):1-7. doi:10.3171/2015.10.JNS151544.

This retrospective cohort study evaluated the efficacy and safety of microsurgical clipping in the treatment of recurrent, previously coiled cerebral aneurysms and to identify risk factors that can affect the outcomes of this procedure. The mean patient age was 50.5 years, the mean aneurysm size was 7 mm, and 97.3% of aneurysms were in the anterior circulation. Complete aneurysm occlusion, as assessed by intraoperative angiography, was achieved in 97.3% of aneurysms (108 of 111 patients). Among patients, 1.8% had a recurrence after clipping. Retreatment was required in 4.5% of patients after clipping. Major complications were observed in 8% of patients and mortality in 2.7%. Ninety percent of patients had a good clinical outcome. Aneurysm size and location in the posterior circulation were significantly associated with higher complications. All 3 patients who had coil extraction experienced a postoperative stroke.

They conclude that surgical clipping is an appropriate treatment strategy for the management of recurrent cerebral aneurysms after endovascular coiling. Direct clipping of the aneurysm neck is feasible in most cases of recurrent, previously coiled cerebral aneurysms. Coil extraction should not regularly be attempted because it is associated with high morbidity. In other words, when direct clipping is not possible because of coil loops extending into the aneurysm neck, or with transmural calcification and scarring, other techniques such as wrapping should be considered.

Serrone JC, Tackla RD, Gozal YM, et al. Aneurysm growth and de novo aneurysms during aneurysm surveillance. J Neurosurg. 2016;125(6):1374-1382. doi:10.3171/2015.12.JNS151552.

Over an 11.5-year period, the authors recommended surveillance imaging to 192 patients with 234 unruptured intracranial aneurysms. The incidence of unruptured intracranial aneurysm growth and de novo aneurysm formation …

Journal Scan – This Month in Other Journals, February 2017

Domino JS, Baek J, Meurer WJ, et al. Emerging temporal trends in tissue plasminogen activator use. Neurology. 2016;87(21):2184-2191. doi:10.1212/WNL.0000000000003349.

Mexican Americans (MA) have an increased stroke burden when compared to their non-Hispanic white (NHW) counterparts, including increased stroke incidence and poorer neurologic, functional, and cognitive outcomes.

The authors explored the temporal trends in tissue plasminogen activator (tPA) administration for acute ischemic stroke (AIS) in a biethnic community without an academic medical center. Cases of AIS were identified from 7 hospitals in the Brain Attack Surveillance in Corpus Christi (BASIC) project, a population-based surveillance study from 2000-2012. There were 5,277 AIS cases identified from 4,589 individuals. tPA use was steady at 2% and began increasing in 2006, reaching 11% in subsequent years. Although ethnicity did not modify the temporal trend, Mexican Americans were less likely to receive tPA than non- Hispanic whites due to emerging ethnic differences in later years. The results suggest that increases in tPA use were greater in higher severity patients compared to lower severity patients, and a gap between MAs and NHWs in tPA administration may be emerging.  The authors conclude that as physician experience with tPA and its use in community settings increases, follow-up studies should continue to explore temporal trends in tPA as well as identify possible strategies to improve tPA use in MAs.

2 Figures (graphs), 2 Tables

Goldstein LB. IV tPA for acute ischemic stroke. Neurology. 2016;87(21):2178-2179. doi:10.1212/WNL.0000000000003366.

In this editorial on the Domino et al. paper, Dr. Goldstein notes that there were considerable barriers that slowed IV tPA adoption after it was approved by the FDA in 1996.  Eight years after FDA approval, IV tPA was being given to only 1%–2% of stroke patients. Transformation of the structure and organization of stroke care delivery were needed, and in part led to …

Journal Scan – This Month in Other Journals, January 2017

Akoudad S, Wolters FJ, Viswanathan A, et al. Association of Cerebral Microbleeds With Cognitive Decline and Dementia. JAMA Neurol. 2016;73(8):934. doi:10.1001/jamaneurol.2016.1017.

The authors wanted to determine whether microbleed count and location were associated with an increased risk for cognitive impairment and dementia. They evaluated a prospective population-based study set in the general community, and assessed the presence, number, and location of microbleeds at baseline (August 2005 to December 2011) on brain MRI in 4841 participants 45 years or older. Trained research physicians, blinded to clinical data, reviewed the MRs. Cerebral microbleeds were defined as small, round to ovoid areas of focal signal loss on T2- weighted images. Participants underwent neuropsychological testing at 2 time points approximately 6 years apart, and were also followed up for incident dementia. 3257 participants underwent baseline and follow-up cognitive testing. Microbleed prevalence was 15.3%. The presence of more than 4 microbleeds was associated with cognitive decline. The presence of microbleeds was associated with an increased risk for dementia after adjustment for age, sex, and educational level, including Alzheimer dementia.

The strengths of this study, according to the authors, is the longitudinal population based design with a large sample size, the use of an extensive neuropsychological test battery, and the virtually complete screening for incident dementia. Limitations include multiple statistical tests, increasing the chance of type I errors. Second, selection bias may have influenced the results, because healthier people without subjective memory complaints were more likely to receive follow-up cognitive testing. Most importantly perhaps, the microbleed number may not reflect the true biological number because microbleed detection strongly depends on technical imaging methods used. T2W images were used, and as we know, SWI is far superior for the detection of these lesions.

4 Tables

Manoso MW, Moore TA, Agel J, Bellabarba C, Bransford RJ. Floating

Journal Scan – This Month in Other Journals, December 2016

Austein F, Riedel C, Kerby T, et al. Comparison of Perfusion CT Software to Predict the Final Infarct Volume After Thrombectomy. Stroke. 2016 doi:10.1161/STROKEAHA.116.013147.

The purpose of the study was to determine the accuracy of different commercial perfusion CT software packages to predict the final infarct volume (FIV) after mechanical thrombectomy. Packages evaluated included 1) Philips Brain CT Perfusion Package, Philips Healthcare, The Netherlands, 2) Siemens (Syngo Volume Perfusion CT Neuro, Siemens Healthcare, Erlangen, Germany, and 3) RAPID (iSchemaView Inc, Menlo Park, CA). CTP data from 147 mechanically recanalized acute ischemic stroke patients were postprocessed. Ischemic core and final infarct volume were compared about thrombolysis in cerebral infarction (TICI) score and time interval to reperfusion. Final infarct volume was measured at follow-up imaging between days 1 and 8 after stroke. Significant differences were found between the packages about over- and underestimation of the ischemic core, with RAPID best-predicting hypoperfusion volume in nonsuccessfully recanalized patients. They conclude that this software package overestimated the final infarct volume to a significantly lower degree and estimated a malignant mismatch profile less often than other software.

Tan BYQ, Wan-Yee K, Paliwal P, et al. Good Intracranial Collaterals Trump Poor Alberta Stroke Program Early CT Score for Intravenous Thrombolysis in Anterior Circulation Acute Ischemic Stroke. Stroke. 2016 doi:10.1161/STROKEAHA.116.013879.

As a nice background and reference to describe the various collateral scoring systems, see: Yeo et al, Assessment of Intracranial Collaterals on CT Angiography in Anterior Circulation Acute Ischemic Stroke, AJNR 2015.

The authors evaluated the prognostic effect of the collateral circulation in patients with thrombolysed acute ischemic stroke who have large early infarct sizes as indicated by low ASPECTS score. They stratified patients using ASPECTS into 2 groups: large volume infarcts (ASPECTS≤ 7 points) and small volume infarcts (ASPECTS 8–10). They also evaluated a third group …