1. Benarroch EE. Choroid plexus-CSF system: Recent developments and clinical correlations. Neurology. 2016;86(3):286–96. doi:10.1212/WNL.0000000000002298.

Excellent comprehensive review of the role and function of the choroid plexus in health and disease.  2 Tables and 1 graphic.

Fun facts you have learned, and then probably forgotten. I sure have.

-80% of CSF is secreted by the choroid plexus (20% from brain interstitial space)

-Choroid plexus secretes CSF at a rate of 0.4 mL/min/g of tissue

-500 cc per day

-Total volume of 150cc, so the CSF exchanges 3-4X per day

-Main determinants of CSF secretion are the active secretion of Na⁺ via the Na⁺-K⁺ ATPase and the production of bicarbonate by action of carbonic anhydrase in choroid epithelial cells

– Three parts of the glymphatic system: 1) para-arterial CSF influx; 2) paravenous interstitial fluid clearance route; 3) transparenchymal pathway depending on astroglial water transport via AQP4 channels

-Glymphatic system estimated to remove 40%–80% of solutes and proteins, including amyloid-beta peptide and tau, from the superficial cerebral cortex

2. Cui Z, Pan L, Song H, et al. Intraoperative MRI for optimizing electrode placement for deep brain stimulation of the subthalamic nucleus in Parkinson disease. J Neurosurg. 2016;124(1):62–69. doi:10.3171/2015.1.JNS141534.

The authors note that various methods have been used to localize the subthalamic nucleus (STN), including MRI, brain atlas–imaging fusion for preoperative planning, intraoperative microelectrode recording (MER), intraoperative MRI (iMRI), temporary efficacy during the operation, postoperative MRI, and sustained effect during the postoperative period.  In this study, 206 DBS electrodes were implanted in the STN in 110 patients with Parkinson disease. All patients underwent intraoperative MRI after implantation to define the accuracy of lead placement. Fifty-six DBS electrode positions in 35 patients deviated from the center of the STN, according to the result of the initial post-placement iMRI scans. After adjustment with iMRI, all electrodes were located in the center of the STN. Intraoperative MRI revealed 2 intraparenchymal hemorrhages in 2 patients, brain shift in all patients, and leads penetrating the lateral ventricle in 3 patients.  They conclude that use of iMRI allows surgeons to assess and adjust the position of DBS electrodes to better achieve placement in the center of the STN.

Seems like intraoperative microelectrode recording the the way to go in the U.S. I have never seen intraoperative MR positioning of these leads performed.

3. Davis KA, Nanga RPR, Das S, et al. Glutamate imaging (GluCEST) lateralizes epileptic foci in nonlesional temporal lobe epilepsy. Sci Transl Med. 2015;7(309):309ra161. doi:10.1126/scitranslmed.aaa7095.

Human and animal studies suggest that glutamate can serve as a marker of epileptic networks and supports the hypothesis that glutamate is elevated in epileptogenic foci. Magnetic resonance spectroscopy (MRS) studies in patients designed to measure glutamate have been performed with lower-field MRI magnets, and the results have been inconclusive. Unlike

the resonances of N-acetylaspartate (NAA) and creatine (Cr), which are singlets, glutamate’s resonances are triplets or higher order multiplets, resulting in smaller spectral peaks distributed

over a broader range of frequencies. Additionally, glutamate shows spectral overlap with glutamine.  The chemical exchange saturation transfer (CEST) technique measures proton exchange between the exchangeable protons of the solute with the much larger pool of bulk water protons. For glutamate (Glu), the amine proton resonates at 3 ppm down-field from water, making glutamate a good neurotransmitter for chemical exchange saturation transfer imaging with MRI scanners at 7 T and higher. Four non-lesional drug-resistant epilepsy patients and 11 healthy controls evaluated. In all four epilepsy patients, concentrations of glutamate (measured by GluCEST) were higher in the epileptogenic (ipsilateral) hippocampus than in the contralateral hippocampus, both qualitatively and quantitatively.  They conclude that they have demonstrated the feasibility of lateralizing seizure foci in TLE, and suggest that GluCEST could also potentially localize drug resistant neocortical epilepsy, where current epilepsy imaging techniques are even more limited.

Very small numbers, but a very interesting result.

4. Sekar A, Bialas AR, de Rivera H, et al. Schizophrenia risk from complex variation of complement component 4. Nature. 2016;530(7589):177–183. doi:10.1038/nature16549.

This is a very complex study but points to a potential underlying mechanism for schizophrenia. To start with, complement component 4 (C4) is a critical component of the classical complement cascade, an innate immune system pathway that rapidly recognizes and eliminates pathogens and cellular debris. In the brain, other genes in the classical complement cascade have been implicated in the elimination or ‘pruning’ of synapses. Schizophrenia’s strongest genetic association involves variation in the major histocompatibility complex (MHC) locus. The authors show that this association arises in part from many structurally diverse alleles of the C4 genes. They found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A. They did this by analyzing single nucleotide polymorphism (SNP) data from 28,799 schizophrenia cases and 35,986 controls, from 40 cohorts in 22 countries contributing to the Psychiatric Genomics Consortium.

5. Dhindsa RS, Goldstein DB. Schizophrenia: From genetics to physiology at last. Nature. 2016;530(7589):162–163. doi:10.1038/nature16874.

Very useful editorial that summarizes the Sekar paper. As Dr. Dhindsa states: “Although pruning undoubtedly represents a challeng­ing therapeutic target, the authors’ beautiful and comprehensive study gives much-needed inspiration for all those researchers who are trying to leverage genetics to advance our understanding of the biology of neuropsychi­atric diseases.”

We should all strive for research papers that are described as “beautiful”!

6. Grade M, Hernandez Tamames JA, Pizzini FB, Achten E, Golay X, Smits M. A neuroradiologist’s guide to arterial spin labeling MRI in clinical practice. Neuroradiology. 2015;57(12):1181–202. doi:10.1007/s00234-015-1571-z.

Excellent review of ASL starting with basic principles, types of labeling (continuous ASL (CASL), pseudocontinuous ASL (pCASL), and pulsed ASL (PASL), but also covering acquisition parameters, and positioning.  Clinical applications covered included cerebrovascular disease (acute and chronic ischemia and cerebrovascular reserve), dementia, and neuro-oncology.  15 figures and 227 references.

7. Ronsin S, Deiana G, Geraldo AF, et al. Pseudotumoral presentation of cerebral amyloid angiopathy-related inflammation. Neurology. 2016;86(10):912–9. doi:10.1212/WNL.0000000000002444.

The authors reviewed the characteristics of 5 newly diagnosed and 23 previously reported patients in whom cerebral amyloid angiopathy–related inflammation findings were initially misinterpreted as neoplasms. Most cases (85%) occurred in patients  greater than 60 years old. MRI demonstrated infiltrative white matter lesions that exhibited a regional mass effect without parenchymal enhancement (93%).  These findings were often interpreted as low-grade glioma or lymphoma. The primary reason for the misinterpretation of the imaging findings was the absence of T2*-weighted gradient recalled echo sequences on initial imaging (89%). Perfusion MRI and MRS showed markedly reduced rCBF and a normal metabolic ratio. They conclude that T2*-GRE or SWI should be performed during the diagnostic workup of brain masses, especially in elderly patients presenting with subacute cognitive decline and no parenchymal postcontrast enhancement. 1 Figure, 2 Tables.

Not sure how lymphoma gets in the differential, since between 0-8% of these  CAA cases showed enhancement (as the authors note in the Discussion – lack of enhancement in lymphoma is rare).

8. Korja M, Kaprio J. Controversies in epidemiology of intracranial aneurysms and SAH. Nat Rev Neurol. 2015;12(1):50–55. doi:10.1038/nrneurol.2015.228.

The authors believe that the complex methodological challenges in conducting studies of epidemiology and risk factors for unruptured intracranial aneurysms (UIAs) and SAH might have led to conclusions being drawn on the basis of epidemiological data of variable quality.  Therefore misconceptions about unruptured intracranial aneurysms and SAH have arisen. In this Perspectives article, they discuss three possible misconceptions about the epidemiology of unruptured intracranial aneurysms and SAH:

Do small unruptured intracranial aneurysms rupture? (yes!)  Up to 85–90% of ruptured intracranial aneurysms are ≤10mm in, ~70‑80% are <7 mm in size and ~50% are ≤5 mm in size. Large population-based long-term studies from Finland and Norway have confirmed that the overall risk of SAH depends on smoking, sex and blood pressure.

Can we learn from SAH in Finland? (yes!) The reported incidence of SAH in Finland is exceptionally high. The population-based and nationwide incidence rates of SAH for very few countries are known. They argue that rejecting the external validity of Finnish studies on the basis of incidence rates without having reliable estimates of SAH incidence elsewhere in the world can affect the knowledge and understanding of the risk factors for SAH.

‘Familial’ does not equal ‘genetic’. The statement that 10% of SAH cases are associated with a family history of SAH is often (mis)interpreted to mean that 10% of SAHs are familial. The incidence of a familial SAH is low: 3% of patients with SAH have one first-degree relative with SAH, and only 0.2% of patients with SAH have two or more first-degree relatives with SAH.

9. Tetreault L, Ibrahim A, Cote P, Singh A, Fehlings MG. A systematic review of clinical and surgical predictors of complications following surgery for degenerative cervical myelopathy. J Neurosurg Spine. 2015;24(January):1–23. doi:10.3171/2015.3.spine14971.

The authors conducted a systematic review of the literature and determined that 60 studies met the inclusion criteria and were included in the review. These studies included 36 prognostic cohort studies and 28 comparative intervention studies. High level evidence suggests that older patients are at a greater risk of perioperative complications. Based on low evidence, other clinical factors such as body mass index, smoking status, duration of symptoms, and baseline severity score, are not predictive of complications. In regards to surgical factors, low to moderate evidence suggests that estimated blood loss, surgical approach, and number of levels do not affect rates of complications. A longer operative duration (moderate evidence), however, is predictive of perioperative complications and a 2-stage surgery is related to an increased risk of major complications (high evidence). They conclude that this knowledge will allow clinicians to identify high-risk patients and institute rigorous prevention strategies. Furthermore, surgeons can use this information to objectively discuss surgical risks with their patients.

Seems like a lot of work for some fairly straight forward conclusions.