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 Lateral Mass Fractures of the Cervical Spine. Spine (Phila Pa 1976). 2016;41(18):1421-1427. doi:10.1097/BRS.0000000000001536.

An uncommon and poorly described subset of cervical spine fracture dislocations is the ‘‘floating’’ lateral mass fracture with fractures of the adjacent pedicle and lamina. The purpose of this study was to characterize the so called floating lateral mass (FLM) fracture with the mechanism of injury, anatomical injury pattern, associated vascular injuries, neurological deficits, and key radiographic features from a prospectively collected trauma registry from 2007-2012. Sixty consecutive cases were identified from the trauma registry. The mean follow-up was 9 months. The most common level was C6. The most common mechanism of injury was a high speed motor vehicle accident (45%). Radiographic rotational displacement manifested as an anterolisthesis. CT showed facet joint widening at the level above and below in 63%. Vertebral artery injuries occurred in 22%. Neurological deficits occurred as radiculopathy in 38% and spinal cord injury in 18%. The radiographic hallmark is the ‘‘horizontalization’’ of the lateral mass best seen on the parasagittal view of the CT with the subluxation and opening of the facet joint above and below the level of injury as occurred in 63% of patients. Subluxation and rotational listhesis was present in about 73% of cases. MR demonstrates a significant disc injury in 81% of patients, with the lower level involved about three-quarters of cases.

5 Figures, 4 Tables

Pollom EL, Song J, Durkee BY, et al. Prognostic value of midtreatment FDG-PET in oropharyngeal cancer. Head Neck. 2016;38(10):1472-1478. doi:10.1002/hed.24454.

The authors retrospectively examined pretreatment and midtreatment FDG-PET parameters in patients with locally advanced oropharyngeal cancer who were treated with definitive chemoradiation. They hypothesized that midtreatment FDG-PET parameters can help identify those who are responders or nonresponders during treatment, which will correlate with disease control and survival. They conducted a retrospective review of 74 patients with stage III to IVB oropharyngeal squamous cell carcinoma who received definitive chemoradiation. Patients were included only if they underwent both pretreatment and midtreatment FDGPET planning scans.

Midtreatment metabolic tumor volume (MTV) using a threshold of SUV 2.0 was associated with progression free survival and overall survival. Nodal total lesion glycolysis (TLG) velocity >5% decrease/week was associated with improved progression free survival. The conclude that the study suggests that midtreatment PET parameters, as characterized by metabolic tumor volume and total lesion glycolysis, can be prognostic for disease progression and death in patients with oropharyngeal cancer.

3 Figures, 3 Tables

Rawal RB, Farzal Z, Federspiel JJ, Sreenath SB, Thorp BD, Zanation AM. Endoscopic Resection of Sinonasal Malignancy: A Systematic Review and Meta-analysis. Otolaryngol — Head Neck Surg. 2016;155(3):376-386. doi:10.1177/0194599816646968.

The expanded endonasal approach has allowed for extirpation of benign sinonasal tumors via minimally invasive techniques since its introduction in 1996. While endonasal approach indications continue to broaden for benign disease processes, open craniofacial resection continues to be the gold standard for extirpation of malignant sinonasal tumors. The preference of open technique is often driven by the desire for an en bloc resection of tumor with negative margins rather than a progressive resection with negative margins. However, after 2 decades since the introduction of endoscopic technology, and with continued advancement in hemostatic techniques, reconstruction, and safety precautions, its use in malignant disease resection continues increase. Thirty-five case series were included in this analysis, consisting of 952 patients. A wide variety of tumor types are included in these papers including adenoid cystic carcinoma, melanoma, squamous cell carcinoma, sinonasal adenocarcinoma, and sinonasal undifferentiated carcinoma. Two- and 5-year survival rates for patients in aggregate modeling were 87.5% and 72.3%, respectively. They conclude that overall 2- and 5-year survival rates are comparable and sometimes greater than those from open craniofacial resection. Survival rates significantly differed by cancer grade but not by cancer stage.

4 Tables, 8 Figures (Kaplan-Meier curves)

Samuel A, Anandasivam N, Diaz-Collado P, Lukasiewicz A, Webb M, Grauer J. Management of Acute Traumatic Central Cord Syndrome. Contemp Spine Surg. 2016;17(10).

Very nice succinct review of the clinical presentation and pathophysiology of acute traumatic central cord syndrome and operative management. First described in 1954, acute traumatic central cord syndrome (ATCCS) is the most common form of incomplete cervical spinal cord injury. ATCCS accounts for 70% of incomplete cervical spinal cord injuries and occurs in approximately 11,000 patients annually. ATCCS is distinguished from other spinal cord pathologies as the deficit is primarily related to the central regions of the cord and classically affects upper extremities more than lower extremities. ATCCS has a bimodal age distribution, with younger patients suffering higher-energy injury in the setting of congenital cervical spinal stenosis and older patients suffering lower-energy injury in the setting of degenerative cervical stenosis. Of the different SCI syndromes, ATCCS has demonstrated the greatest potential for improvement of neurologic symptoms, even with conservative therapy. While early reports focused on nonoperative treatment, more recent studies with advancements in imaging and techniques, have demonstrated that operative treatment of patients with ATCCS is both safe and efficacious for speeding up and optimizing potential neurologic recovery. Timing of surgery remains controversial. In one survey of more than 900 spine surgeons, only 13.5% agreed that operating within 2 to 4 hours is indicated after ATCCS in an older patient with preexisting cervical stenosis, whereas 16.0% agreed with operating after 6 weeks. This contrasts with 96% of surgeons who agreed that surgery within 24 hours is indicated after a traumatic incomplete SCI in a younger patient.

2 Figures

Saver JL, Goyal M, van der Lugt A, et al. Time to Treatment With Endovascular Thrombectomy and Outcomes From Ischemic Stroke: A Meta-analysis. JAMA. 2016;316(12):1279. doi:10.1001/jama.2016.13647.

The authors undertook a meta-analysis of the relation between time to treatment and outcome from endovascular mechanical thrombectomy for acute ischemic stroke. There were 1287 adults in 5 randomized trials. Compared with medical therapy alone, thrombectomy up to 7.3 hours after symptom onset was associated with improved outcomes. Rates of functional independence after thrombectomy were 64%with reperfusion at 3 hours vs 46% with reperfusion at 8 hours.

The magnitude of the association between time to treatment and outcome was clinically meaningful. Based on the current study, and assuming the findings are generalizable to the population of patients with acute ischemic stroke due to large vessel occlusion, among every 1000 patients achieving substantial endovascular reperfusion, for every 15-minute faster emergency department door–to-reperfusion time, an estimated 39 patients would have a less-disabled outcome at 3 months, including 25 more who would achieve functional independence (mRS 0-2).

Keep in mind that the use of imaging to exclude patients with a large core of permanently infarcted brain tissue in the trials in this pooled analysis may have influenced the strength of the association between symptom onset-to-randomization and symptom onset–to-reperfusion times and outcomes. Four of the 5 trials formally excluded patients with large ischemic cores evident on initial brain imaging from study participation.

2 Tables, 3 Figures (graphs)

Schwedt TJ. Thunderclap Headache. Continuum (Minneap Minn). 2015;21(4 Headache):1058-1071. doi:10.1212/CON.0000000000000201.

This is an excellent review of the various causes of thunderclap headache. By definition, thunderclap headache is a severe headache with an abrupt onset, reaching maximum intensity in less than 1 minute. Thunderclap headache is a medical emergency that requires urgent evaluation. The primary differential possibilities include aneurysmal subarachnoid hemorrhage and reversible cerebral vasoconstriction syndrome (RCVS). Other causes include infection, cerebral venous sinus thrombosis, cervical artery dissection, complicated sinusitis, hypertensive crisis, intracerebral hemorrhage, ischemic stroke and spontaneous intracranial hypotension. Approximately 70% of patients with subarachnoid hemorrhage present with headache as a main symptom; 50% of patients will present with thunderclap headache. Patients who have thunderclap headache with nondiagnostic brain CT and lumbar puncture should be further evaluated with contrast-enhanced brain MRI and noninvasive vascular imaging of the head and neck.

Worth remembering are the diagnostic criteria for reversible cerebral vasoconstriction syndrome:
1. Thunderclap headache with or without focal neurologic deficits or
seizures
2. Monophasic course without new symptoms more than 1 month after initial
onset of symptoms
3. Multifocal, multivessel, segmental vasoconstriction of cerebral arteries
4. Absence of aneurysmal subarachnoid hemorrhage
5. Normal or near-normal CSF
6. Complete or substantial normalization of cerebral arteries within 12 weeks
of symptom onset

3 Tables and 3 figures

Turner R. Uses, misuses, new uses and fundamental limitations of magnetic resonance imaging in cognitive science. Philos Trans R Soc B Biol Sci. 2016;371(1705):20150349. doi:10.1098/rstb.2015.0349.

This very interesting review tackles the following questions:
A. What can be learned about cognition from structural and functional BOLD MRI that other techniques cannot provide?
In cognitive studies, some researchers have strongly objected to the practice of statistical mapping of heavily smoothed and thresholded functional brain imaging data, labelling fMRI findings as ‘neo-phrenology’ and committing the mereological fallacy. That fallacy is ascribing to parts of a system attributes that can only be coherently ascribed to the entire system (thinking, learning, calculation can’t be simplified to belonging to a brain part).

B. What are the major flaws in current uses of fMRI?
Standard practice in the 1990’s and extending even to today’s research includes spatial smoothing of functional images by 8 mm, and group averaging. Among several reasons for this procedure, smoothing allowed for the residual mismatch of actual cortical areas after structural brain images had been spatially normalized into a standard template brain registered within MNI space, so that positive results could be anticipated from group averaging across normalized brains. Spatial location of activity was usually identified on a maximum probability atlas of Brodmann areas derived from the cytoarchitecture of 10 cadaver brains.

C. Are there other ways of analyzing MRI/fMRI data that provide deeper insight?
Machine learning techniques can be used to discriminate spatial patterns of brain activity specific to a particular stimulus or task from other related stimuli which do not require spatial smoothing- termed multivoxel pattern analysis (MVPA).

Encoding models begin with providing the experimental subject with a very large number of related stimuli or tasks, often naturalistic. These are analyzed into a large set of features. The goal is to determine the functional repertoire of each grey matter voxel, as encompassed by a model that characterizes the ‘feature space’ of the stimuli.

D. Are there developments in MRI and fMRI methodology that minimize the assumptions needed?
New generation of whole-body scanners at 7T and above have shown that submillimeter spatial resolution is achievable for structural, functional and connectivity imaging. For functional BOLD and structural imaging, submillimeter resolution has even been achieved with the latest generation of 3 T scanners. Such a resolution, consistent with the size of cortical columns, might constitute a threshold regarding realistic mechanistic explanations of brain function.

E. What are the likely fundamental limitations of all MRI methods?
In functional studies, the magnetic fields associated with coherent neural activity is easily observed using magnetoencephalography techniques, are too small to be localized using MRI methods. The only currently practical way that MRI can contribute to studies of brain function is via its sensitivity for the vascular response to neural activity. The MR signal associated with this vascular response can depend on the blood’s velocity, volume fraction and oxygenation. MRI sequences can be designed to be sensitive to one or more of these parameters, but there are fundamental limitations.

F. What are the poorly explored questions relevant to fMRI?
Direction of causation – Network models of brain function can only make testable predictions if they include a measurable variable describing the direction of causation between separate cortical or subcortical areas. This is accessible neuroanatomically only in cadaver brain, using anterograde and retrograde tracer methods. Columnar organization and sparse encoding versus population encoding are additional areas which need more study.

G. What are the most synergetic other techniques?
The authors view is that the most exciting noninvasive technique for quantitative studies of cognition in human brain is the measurement of CBV, using MRI blood nulling techniques. With the adequate SNR available at high magnetic field, this offers the hope of layer-specific identification of induced neural activity.

Ugurbil K. What is feasible with imaging human brain function and connectivity using functional magnetic resonance imaging. Philos Trans R Soc B Biol Sci. 2016;371(1705):1-14. doi:10.1098/rstb.2015.0361.

This article is part of the themed issue ‘Interpreting BOLD: a dialogue between cognitive and cellular neuroscience’. This article reviews some of the author’s work towards understanding the underlying mechanisms of the methodology, defining its limitations, and developing solutions to advance it. The review covers multiple topics, but I will just briefly mention one, that I sort-of understand.

Improving the spatial accuracy of fMRI with vascular filters is one topic the author has tackled. Between neuronal activity and receiving the fMRI signal is neurovascular/metabolic coupling. In addition, there is the equally important coupling between the cerebral consequences of vascular and metabolic events accompany neuronal activity and the MR detected signals that allow us to generate the ‘functional maps’. The first is a question of physiology. The latter involves, MR physics.

The primary question here is does blood flow changes initiated by neurovascular coupling ‘flood’ a large patch of cortex, larger than the territory of neuronal activity changes that cause it? To use a simple analogy, does the brain ‘water the entire garden for the sake of a thirsty flower’? There CBF experiments have shown instead of drenching the whole region with flow, the brain ‘waters the thirsty flower while it also sprinkles a large territory around it’.

There are several other major topics is this review that are worthwhile perusing, so I invite you to tackle this paper in your leisure.