Multiple sclerosis (MS) is an inflammatory demyelinating disease where T cells attack the brain and the spinal cord. It is known that often particular T-cell clones are expanded in the target tissue, but it is still unknown, whether identical T-cell clones are present at distinct anatomical sites, or whether the T-cell spectrum is locally diverse. Therefore we compared the T-cell receptor (TCR) repertoire in distinct lesions and normal-appearing white matter (NAWM) from post-mortem brains of four MS patients. We analysed 19 lesions (inactive demyelinated, 15; slowly expanding chronic, 3; active lesions, 1) and 5 NAWM regions. The TCR beta-chain repertoire was investigated by CDR3 spectratyping. For each anatomical site 325 semi-nested PCR reactions were performed. About 800 Vbeta-NDN-Jbeta combinations were sequenced. Each of the four patients had distinct T-cell clones that were present in more than two anatomically distinct regions. These clones were not restricted to lesions, but were also present in NAWM. Some clones were present in all investigated lesions, and additionally, in NAWM sites. A single T-cell clone was detected in nine different sites in one patient. None of the clones was shared among different patients. Thus, pervasive T-cell clones exist in distinct regions of MS brain, and these clones are 'private' (unique) to individual patients. Analysis of the hypervariable NDN region revealed 'silent' nucleotide exchanges, i.e. nucleotide exchanges that code for identical amino acids. Such silent nucleotide exchanges suggest that the corresponding T-cell clones were recruited and stimulated by particular antigens. To attribute some of the pervasive clones to particular T-cell subsets, we isolated individual CD8+ T cells from cryosections by laser microdissection and characterized their TCR by single-cell PCR. These experiments revealed that at least some of the pervasive T-cell clones belonged to the CD8+ compartment, supporting the pathogenic relevance of this T-cell subset.

BACKGROUND AND PURPOSE Meningiomas are the most common primary intracranial tumors, typically treated with surgery and adjuvant radiation in cases of subtotal resection and/or higher histopathologic grade. Contrast‐enhanced magnetic resonance imaging (MRI) is the gold standard for postoperative assessment and adjuvant treatment planning. However, MRI can have limited accuracy particularly in the presence of posttreatment change. [68Ga]‐DOTATATE is a Positron Emission Tomography (PET) radiotracer targeting somatostatin receptor 2A (SSTR2A). SSTR2A is a reliable biomarker of meningiomas. We report a consecutive case series of 20 patients evaluated with [68Ga]‐DOTATATE PET/MRI, propose a novel approach to quantitative analysis, and discuss clinical implications. METHODS We present a consecutive case series of 20 patients with clinically suspected or pathology‐proven meningioma evaluated between July 2018 and February 2019. [68Ga]‐DOTATATE PET/MRI was obtained in order to confirm the diagnosis or determine tumor recurrence/progression to help guide surgical and/or radiation therapy management in cases in which MRI findings were indeterminate or equivocal. RESULTS Seventeen (85%) patients had undergone prior surgery and 11 (55%) underwent adjuvant radiation therapy. In 17 patients [68Ga]‐DOTATATE confirmed the presence of recurrent meningioma. A total of 49 meningiomas were identified (median: 2 meningiomas/patient, range 0‐14). There was excellent differentiation between meningioma and posttreatment change based on our approach of target lesion/superior sagittal sinus maximum standardized uptake values ratio (16.6 vs. 1.6, P < .0001). CONCLUSIONS [68Ga]‐DOTATATE PET/MRI is a promising tool in the assessment of both treatment naïve and resected/irradiated meningiomas, allowing improved diagnosis and extent of disease evaluation. Future prospective studies are needed to determine utility of [68Ga]‐DOTATATE PET/MRI in treatment response assessment.

BACKGROUND AND PURPOSE In recent years, the role of CTA and CTP for vasospasm diagnosis in the setting of ASAH has been the subject of many research studies. The purpose of this study was to perform a meta-analysis of the diagnostic performance of CTA and CTP for vasospasm in patients with ASAH by using DSA as the criterion standard. MATERIALS AND METHODS The search strategy for research studies was based on the Cochrane Handbook for Systematic Reviews, including literature data bases (PubMed, Embase, Cochrane Database of Systematic Reviews, and the Web of Science) and reference lists of manuscripts published from January 1996 to February 2009. The inclusion criteria were the following: 1) published manuscripts, 2) original research studies with prospective or retrospective data, 3) patients with ASAH, 4) CTA or CTP as the index test, and 5) DSA as the reference standard. Three reviewers independently assessed the quality of these research studies by using the QUADAS tool. Pooled estimates of sensitivity, specificity, LR+, LR−, DOR, and the SROC curve were determined. RESULTS CTA and CTP searches yielded 505 and 214 manuscripts, respectively. Ten research studies met inclusion criteria for each CTA and CTP search. Six CTA and 3 CTP studies had sufficient data for statistical analysis. CTA pooled estimates had 79.6% sensitivity (95% CI, 74.9%–83.8%), 93.1% specificity (95% CI, 91.7%–94.3%), 18.1 LR+ (95% CI, 7.3–45.0), and 0.2 LR− (95% CI, 0.1–0.4); and CTP pooled estimates had 74.1% sensitivity (95% CI, 58.7%–86.2%), 93.0% specificity (95% CI, 79.6%–98.7%), 9.3 LR+ (95% CI, 3.4–25.9), and 0.2 LR− (95% CI, 0.04–1.2). Overall DORs were 124.5 (95% CI, 28.4–546.4) for CTA and 43.0 (95% CI, 6.5–287.1) for CTP. Area under the SROC curve was 98 ± 2.0% for CTA and 97 ± 3.0% for CTP. CONCLUSIONS The high diagnostic accuracy determined for both CTA and CTP in this meta-analysis suggests that they are potentially valuable techniques for vasospasm diagnosis in ASAH. Awareness of these results may impact patient care by providing supportive evidence for more effective use of CTA and CTP imaging in ASAH.

PurposeThis study explores whether meningioma expresses epidermal growth factor receptor (EGFR) and determines if there is a correlation between the WHO grade of this tumor and the degree of EGFR expression.MethodsFollowing institutional review board approval, 113 meningioma specimens from 89 patients were chosen. Of these, 85 were used for final analysis. After a blinded review, immunohistochemical stains for EGFR were performed. Staining intensity (SI) was scored on a scale 0-3 (from no staining to strong staining). Staining percentage of immunoreactive cells (SP) was scored 1-5 (from the least to the maximum percent of the specimen staining). Immunohistochemical score (IHS) was calculated as the product of SI and SP.ResultsEighty-five samples of meningioma were classified in accordance with World Health Organization (WHO) criteria: benign 57/85 (67%), atypical 23/85 (27%), and malignant 5/85 (6%). The majority of samples demonstrated a moderate SI for EGFR. IHS for EGFR demonstrated a significant association between SI and histopathologic subtype. Also, there was a correlation between the SP and histopathologic subtype (p = 0.029). A significant association was determined when the benign and the atypical samples were compared to the malignant with respect to the SP (p = 0.009). While there was a range of the IHS for the benign and the atypical histologic subtypes, malignant tumors exhibited the lowest score and were statistically different from the benign and the atypical specimens (p < 0.001).ConclusionsTo our knowledge, this represents the largest series of meningioma samples analyzed for EGFR expression reported in the literature. EGFR expression is greatest in benign meningiomas and may serve a potential target for therapeutic intervention with selective EGFR inhibitors.