Astrogliosis marker 11C-SL25.1188 PET in traumatic brain injury with persistent symptoms.

Traumatic brain injury (TBI) is common but little is known why up to a third of patients have persisting symptoms. Astrogliosis, a pathophysiological response to brain injury, may be a potential therapeutic target, but demonstration of astrogliosis in the brain of humans with TBI and persistent symptoms is lacking. Astroglial marker monoamine oxidase B (MAO-B) total distribution volume (11C-SL25.1188 VT), an index of MAO-B density, was measured in 29 TBI and 29 similarly aged healthy control cases with 11C-SL25.1188 PET, prioritizing prefrontal cortex (PFC) and cortex proximal to cortical convexity. Correlations of PFC 11C-SL25.1188 VT with psychomotor and processing speed; and serum blood measures implicated in astrogliosis were determined. 11C-SL25.1188 VT was greater in TBI in PFC (P = 0.00064) and cortex (P = 0.00038). PFC 11C-SL25.1188 VT inversely correlated with Comprehensive Trail Making Test psychomotor and processing speed (r = -0.48, P = 0.01). In participants scanned within 2 years of last TBI, PFC 11C-SL25.1188 VT correlated with serum glial fibrillary acid protein (r = 0.51, P = 0.037) and total tau (r = 0.74, P = 0.001). Elevated 11C-SL25.1188 VT argues strongly for astrogliosis and therapeutics modifying astrogliosis towards curative phenotypes should be tested in TBI with persistent symptoms. Given substantive effect size, astrogliosis PET markers should be applied to stratify cases and/or assess target engagement for putative therapeutics targeting astrogliosis.

Neuroinflammation After COVID-19 With Persistent Depressive and Cognitive Symptoms.

Importance: Persistent depressive symptoms, often accompanied by cognitive symptoms, commonly occur after COVID-19 illness (hereinafter termed COVID-DC, DC for depressive and/or cognitive symptoms). In patients with COVID-DC, gliosis, an inflammatory change, was suspected, but measurements of gliosis had not been studied in the brain for this condition. Objective: To determine whether translocator protein total distribution volume (TSPO VT), a marker of gliosis that is quantifiable with positron emission tomography (PET), is elevated in the dorsal putamen, ventral striatum, prefrontal cortex, anterior cingulate cortex, and hippocampus of persons with COVID-DC. Design, Setting, and Participants: This case-control study conducted at a tertiary care psychiatric hospital in Canada from April 1, 2021, to June 30, 2022, compared TSPO VT of specific brain regions in 20 participants with COVID-DC with that in 20 healthy controls. The TSPO VT was measured with fluorine F 18-labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide ([18F]FEPPA) PET. Main Outcomes and Measures: The TSPO VT was measured in the dorsal putamen, ventral striatum, prefrontal cortex, anterior cingulate cortex, and hippocampus. Symptoms were measured with neuropsychological and psychological tests, prioritizing outcomes related to striatal function. Results: The study population included 40 participants (mean [SD] age, 32.9 [12.3] years). The TSPO VT across the regions of interest was greater in persons with COVID-DC (mean [SD] age, 32.7 [11.4] years; 12 [60%] women) compared with healthy control participants (mean [SD] age, 33.3 [13.9] years; 11 [55%] women): mean (SD) difference, 1.51 (4.47); 95% CI, 0.04-2.98; 1.51 divided by 9.20 (17%). The difference was most prominent in the ventral striatum (mean [SD] difference, 1.97 [4.88]; 95% CI, 0.36-3.58; 1.97 divided by 8.87 [22%]) and dorsal putamen (mean difference, 1.70 [4.25]; 95% CI, 0.34-3.06; 1.70 divided by 8.37 [20%]). Motor speed on the finger-tapping test negatively correlated with dorsal putamen TSPO VT (r, -0.53; 95% CI, -0.79 to -0.09), and the 10 persons with the slowest speed among those with COVID-DC had higher dorsal putamen TSPO VT than healthy persons by 2.3 (2.30 divided by 8.37 [27%]; SD, 2.46; 95% CI, 0.92-3.68). Conclusions and Relevance: In this case-control study, TSPO VT was higher in patients with COVID-DC. Greater TSPO VT is evidence for an inflammatory change of elevated gliosis in the brain of an individual with COVID-DC. Gliosis may be consequent to inflammation, injury, or both, particularly in the ventral striatum and dorsal putamen, which may explain some persistent depressive and cognitive symptoms, including slowed motor speed, low motivation or energy, and anhedonia, after initially mild to moderate COVID-19 illness.

Bleomycin for Head and Neck Venolymphatic Malformations: A Systematic Review.

BACKGROUND: Venolymphatic malformations are rare benign vascular lesions of the head and neck. Sclerotherapy has become the first-line therapy of these lesions with bleomycin being a sclerosing agent commonly used. PURPOSE: To perform a systematic review of the published literature to synthesize evidence on the safety and efficacy of bleomycin for the treatment of head and neck venolymphatic malformations. DATA SOURCES: A systematic review of the literature (January 1995-May 2019) was performed in PubMed, Embase, and Cochrane Library databases to identify studies on sclerotherapy of venolymphatic malformations of the head and neck. STUDY SELECTION: A total of 32 studies with participants met the inclusion criteria among which 1121 patients were included in the systematic review. DATA ANALYSIS: Two reviewers independently screened and extracted data and assessed the risk of bias. The primary outcome was the subjective or objective reduction of lesion size as well as minor and major complications. DATA SYNTHESIS: The bleomycin/pingyangmycin sclerotherapy achieved subjective or objective lesion size reduction in 96.3% (95% CI 94.1%-98.5%) of patients. Minor complications were observed in 16.2% and major complications in 1.1%. CONCLUSION: Bleomycin is a highly effective treatment of venolymphatic malformations of the head and neck with a low rate of major adverse events. This study represents an update on the "available" evidence, but only low-to-moderate quality studies were available. LIMITATIONS: This study reviewed 32 studies performed in different parts of the world, but there was heterogeneity of the study designs and interventions.

Bleomycin for orbital and peri-orbital veno-lymphatic malformations - A systematic review.

BACKGROUND: Orbital and peri-orbital venolymphatic malformations (VLM) are low flow vascular malformations. Intralesional bleomycin is now commonly being used to treat such malformations. OBJECTIVE: The purpose of this systematic review is to synthesize evidence on the safety and efficacy of bleomycin/pingyangmycin sclerotherapy for the treatment of orbital and peri-orbital VLM. METHODS: We searched Medline, Embase, Scopus and Cochrane database for studies reporting outcomes of bleomycin/pingyangmycin sclerotherapy for orbital and peri-orbital VLM between 1974 to April 5th, 2019. Nine retrospective cohort studies enrolling 132 patients were included. Two reviewers independently screened and extracted data and assessed the risk of bias. Predefined outcome measures were subjective and objective reduction of the lesion and associated complications. RESULTS: Subjective reduction of the lesions was seen in 96.2% of the studies. Objective reduction of the lesion and symptomatic improvement were reported in 91.6 and 95% of the studies respectively. Non responders were 9.0%. Minor adverse events were reported in 18.1% of the studies. Major complications like pulmonary toxicity or pulmonary fibrosis was not encountered in any of the included studies. Quality of evidence was generally low. CONCLUSION: Bleomycin/pingyangmycin sclerotherapy is very effective and relatively safe for the treatment of orbital and periorbital VLM and is not associated with any major side effects including pulmonary fibrosis.Limitations: The systematic review is limited mainly due to low quality of the included studies with retrospective design.

Diagnostic Yield of MRI for Sensorineural Hearing Loss - An Audit.

PURPOSE: Contrast-enhanced magnetic resonance imaging (CEMRI) of the head is frequently employed in investigations of sensorineural hearing loss (SNHL). The yield of these studies is perceptibly low and seemingly at odds with the aims of wise resource allocation and risk reduction within the Canadian healthcare system. The purpose of our study was to audit the use and diagnostic yield of CEMRI for the clinical indication of SNHL in our institution and to identify characteristics that may be leveraged to improve yield and optimize resource utilization. MATERIALS AND METHODS: The charts of 500 consecutive patients who underwent CEMRI of internal auditory canal for SNHL were categorized as cases with relevant positive findings on CEMRI and those without relevant findings. Demographics, presenting symptoms, interventions and responses, ordering physicians, and investigations performed prior to CEMRI testing were recorded. Chi-squared test and t-test were used to compare proportions and means, respectively. RESULTS: CEMRI studies revealed relevant findings in 20 (6.2%) of 324 subjects meeting the inclusion criteria. Pre-CEMRI testing beyond audiometry was conducted in 35% of those with relevant positive findings compared to 7.3% of those without (p < 0.001). Auditory brainstem response/vestibular-evoked myogenic potentials were abnormal in 35% of those with relevant CEMRI findings compared to 6.3% of those without (p < 0.001). CONCLUSION: CEMRI is a valuable tool for assessing potential causes of SNHL, but small diagnostic yield at present needs justification for contrast injection for this indication. Our findings suggest preferred referral from otolaryngologists exclusively, and implementation of a non-contrast MRI for SNHL may be a better diagnostic tool.

Imaging of the Spontaneous Low Cerebrospinal Fluid Pressure Headache: A Review.

Spontaneous intracranial hypotension (SIH) is a significant cause of chronic, postural headaches. Spontaneous intracranial hypotension is generally believed to be associated with cerebrospinal fluid (CSF) leaks, and these leaks can be posttraumatic, iatrogenic, or idiopathic in origin. An integral part of the management of patients with this condition consists of localizing and stopping the leaks. Radiologists play a central role in the workup of this condition detecting leaks using computed tomography, magnetic resonance imaging, or nuclear imaging. In this article, we briefly review SIH and the various imaging modalities, which can be used to identify and localize a spontaneous CSF leak.

T2 Hypointensity Aids in the Diagnosis of Intracranial Metastatic Adenocarcinoma.

BACKGROUND: The T2 hypointensity has been suggested to be associated with intracranial metastatic adenocarcinomas (IMA). The purpose of our study was to determine the association of T2 hypointensity with IMA. METHODS: All patients with pathologically confirmed metastatic brain tumors who had a magnetic resonance imaging (MRI) at our institution in the last 10 years were retrospectively assessed. Qualitative assessment of the lesions on MRI was done by two separate readers who were blinded to the pathological diagnosis. For qualitative assessment, the T2 hypointensity in the lesion was compared with the contralateral normal appearing white matter. Odds ratio, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. RESULTS: Of 107 patients with intracranial metastasis, only 73 (40 females; 33 males; mean age 61 years) had MRI available for review. Of these, only 46 (25 females; 21 males; mean age 61 years) had pathologically proven IMA. T2 hypointensity was seen in 20% of IMA. The odds ratio of T2 hypointensity in IMA was 3 compared to nonadenocarcinomas but was not statistically significant (p = 0.16). Intralesional hemorrhage was seen in 20. When controlled for hemorrhage, the odds ratio for T2 hypointensity in IMA was 4.7. The specificity, sensitivity, PPV, and NPV for T2 hypointensity to diagnose IMA were 92%, 19%, 81%, and 40%, respectively. CONCLUSION: T2 hypointensity was seen only in 20% of IMA with an odds ratio of 4.7. T2 hypointensity showed a high specificity and PPV for diagnosis of IMA.