Journal Scan

Journal Scan – This Month in Other Journals, January 2018

Wilkinson RJ, Rohlwink U, Misra UK, et al. Tuberculous meningitis. Nat Rev Neurol. 2017;13(10):581-598. doi:10.1038/nrneurol.2017.120.

Tuberculosis remains a global health problem, with an estimated 10.4 million cases and 1.8 million deaths resulting from the disease in 2015. The most lethal and disabling form of tuberculosis is tuberculous meningitis, for which more than 100,000 new cases are estimated to occur per year. In adults, the best-documented risk factor for tuberculous meningitis is HIV‑1 co‑infection. Among HIV-infected individuals who live in areas where tuberculosis is highly endemic, the proportion of HIV‑1‑associated meningitis cases attributable to Mycobacterium tuberculosis can exceed 50%. Individuals with tuberculous meningitis and a HIV‑1 co‑infection have a twofold to threefold increase in relative risk of death from any cause with overall mortality around 40%, even in those individuals prescribed antiretroviral therapy. Drug-resistant tuberculous meningitis in people co‑infected with HIV‑1 has a particularly poor prognosis, approaching 100% mortality.

Bacterial replication must occur in the CNS for tuberculous meningitis pathogenesis to proceed. However, the bacillary load in the CSF rarely exceeds 100–1000 bacterial colonies per milliliter, and viable bacilli are difficult to detect in the majority of individuals. Early studies in experimental animal models showed that the meningitis syndrome and even death of tuberculin-sensitized animals could be induced by meningeal inoculation with dead bacilli. Much of the tissue damage is therefore attributed to a dysregulated host inflammatory response. Once bacilli have traversed the blood–brain barrier, they are taken up by microglia and can also replicate in these cells, leading to the induction of microglial cytokine and chemokine production.

The importance of infarction to long-term outcomes has led to interest in cranial vessel imaging. CTA has been used to define lesions in the anterior and posterior cerebral circulation, and has demonstrated that the supraclinoid portion of the internal carotid artery …

Journal Scan – This Month in Other Journals, December 2017

Raza SM, Gidley PW, Meis JM, Grosshans DR, Bell D, DeMonte F. Multimodality Treatment of Skull Base Chondrosarcomas: The Role of Histology Specific Treatment Protocols. Neurosurgery. 2017;81(3):520-530. doi:10.1093/neuros/nyx042.

The authors studied the impact of histological subtype/grade on progression-free survival (PFS) and the indications for surgery, radiation, and chemotherapy based on histology in 37 patients with skull base chondrosarcomas. Of the conventional histologic subtype, 23% were grade 1, 63% were grade 2, and 14% were grade 3. In addition to surgery, mesenchymal / dedifferentiated CSAs (18% of the cohort) underwent neoadjuvant chemotherapy and 48.6% of the overall cohort received adjuvant radiotherapy. Histological grade/subtype and treatment factors were assessed for impact on median PFS. Conventional subtype vs mesenchymal / dedifferentiated was positively associated with median PFS (166 vs 24 months). Increasing conventional grade inversely correlated with median PFS. Gross total resection positively impacted PFS in conventional CSAs (111.8 vs 42.9months) and mesenchymal / dedifferentiated CSAs (58.2 vs 1.0 month). Adjuvant radiotherapy significantly impacted PFS in conventional grades 2 and 3. They conclude that there is a potential need for histological subtype/grade specific treatment protocols. For conventional CSAs, surgery alone provides optimal results grade 1 CSAs, while resection with adjuvant radiotherapy yields the best outcome for grade 2 and 3 CSAs.

6 Figures and 5 Tables

Harteveld AA, van der Kolk AG, van der Worp HB, et al. Detecting Intracranial Vessel Wall Lesions With 7T-Magnetic Resonance Imaging. Stroke. 2017;48(9):2601-2604. doi:10.1161/STROKEAHA.117.017868.

Fifty subjects (25 patients and 25 matched healthy controls) underwent 7T-magnetic resonance imaging with an intracranial vessel wall sequence before and after contrast administration.  Consecutive patients (>18 years of age) presenting with ischemic stroke or transient ischemic attack in the posterior cerebral circulation, as well as age- and sex-matched volunteers without a history of cerebrovascular disease, were screened for inclusion. Healthy volunteers …

Journal Scan – This Month in Other Journals, November 2017

Linzey JR, Wilson TJ, Sullivan SE, Thompson BG, Pandey AS. Frontal Sinus Breach During Routine Frontal Craniotomy Significantly Increases Risk of Surgical Site Infection: 10-Year Retrospective Analysis. Neurosurgery. 2017;0(0):1-8. doi:10.1093/neuros/nyx046.

Frontotemporal craniotomies are at particular risk for breaching the frontal sinus, especially when the patient has a large frontal sinus or the surgeon is attempting to expose anterior communicating (ACOM) artery aneurysms. Frontal sinus breach (FSB) has the potential to cause postoperative complications due to the introduction of microflora from the frontal sinus into the sterile environment of the intracranial compartment. 

In this retrospective study, the authors are attempting to determine if FSB is a risk factor for developing cranial surgical site infections in patients undergoing craniotomies for clip ligation of anterior circulation aneurysms. They hypothesized that the surgical site infection (SSI) rate for craniotomies with an FSB would be significantly higher than for craniotomies without an FSB, given the contamination of the intracranial compartment during FSB. This study included 862 patients undergoing 910 craniotomies. Primary outcome of interest was occurrence of a cranial surgical site infection. Of the 910 craniotomies, 141 (15.5%) involved FSB. Of those involving FSB, 22 (15.6%) developed a cranial surgical site infection, compared to only 56 of the 769 without FSB (7.3%). Cranial surgical site infection requiring reoperation was much more likely in patients with FSB compared to those without a breach (7.8% vs 1.6%). Patients with FSBs had 2 times the odds of developing a cranial surgical site infection as those without FSB. The authors overall infection rate of 8.6% for craniotomies is comparable with other published data.  In addition, the length of surgical procedure was associated with increased risk of infection, which supports previously published data.  As expected, longer procedures were also more common in patients with FSB compared to those without, …

Journal Scan – This Month in Other Journals, October 2017

Horn A, Reich M, Vorwerk J, et al. Connectivity Predicts deep brain stimulation outcome in Parkinson disease. Ann Neurol. 2017;82(1):67-78. doi:10.1002/ana.24974.

The benefit of deep brain stimulation (DBS) for Parkinson disease (PD) may depend on connectivity between the stimulation site and other brain regions, but which regions and whether connectivity can predict outcome in patients remain unknown. The authors attempted to identify the structural and functional connectivity profile of effective DBS to the subthalamic nucleus (STN) and test its ability to predict outcome.

The authors utilized a training dataset of 51 PD patients with subthalamic nucleus DBS which was combined with publicly available human connectome data (diffusion tractography and resting state functional connectivity) to identify connections reliably associated with clinical improvement (motor score of the Unified Parkinson Disease Rating Scale [UPDRS]). This connectivity profile was then used to predict outcome in an independent cohort of 44 patients. Resting state functional connectivity data was obtained on 1,000 healthy subjects using a 3T Siemens (Erlangen, Germany) MRI, part of the Brain Genomics Superstruct Project (https://dataverse.harvard.edu/dataverse/GSP). MRI data from 90 patients were obtained from the Parkinson’s Progression Markers Initiative (PPMI) database.  Scanning parameters can be found on the project website (www.ppmi-info.orgz). In the training dataset, connectivity between the DBS electrode and a distributed network of brain regions correlated with clinical response including structural connectivity to supplementary motor area and functional anticorrelation to primary motor cortex. This same connectivity profile predicted response in an independent patient cohort.

The authors cite four main conclusions: 1) a specific pattern of structural and functional connectivity with subthalamic nucleus DBS electrodes correlates with clinical outcome across patients in PD. 2) structural and functional connectivity are independent predictors of DBS response. 3) connectivity profiles derived from one patient cohort can predict clinical outcome in …

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 dream …

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% …