An Initial miRNA Profile of Persons With Persisting Neurobehavioral Impairments and States of Disordered Consciousness After Severe Traumatic Brain Injury.

OBJECTIVE: To examine the merits of using microRNAs (miRNAs) as biomarkers of disorders of consciousness (DoC) due to traumatic brain injury (TBI). SETTINGS: Acute and subacute beds. PARTICIPANTS: Patients remaining in vegetative and minimally conscious states (VS, MCS), an average of 1.5 years after TBI, and enrolled in a randomized clinical trial ( n = 6). Persons without a diagnosed central nervous system disorder, neurotypical controls ( n = 5). DESIGN: Comparison of whole blood miRNA profiles between patients and age/gender-matched controls. For patients, correlational analyses between miRNA profiles and measures of neurobehavioral function. MAIN MEASURES: Baseline measures of whole blood miRNAs isolated from the cellular and fluid components of blood and measured using miRNA-seq and real-time polymerase chain reaction (RT-PCR). Baseline neurobehavioral measures derived from 7 tests. RESULTS: For patients, relative to controls, 48 miRNA were significantly ( P < .05)/differentially expressed. Cluster analysis showed that neurotypical controls were most similar to each other and with 2 patients (VS: n = 1; and MCS: n = 1). Three patients, all in MCS, clustered separately. The only female in the sample, also in MCS, formed an independent group. For the 48 miRNAs, the enriched pathways identified are implicated in secondary brain damage and 26 miRNAs were significantly ( P < .05) correlated with measures of neurobehavioral function. CONCLUSIONS: Patients remaining in states of DoC an average of 1.5 years after TBI showed a different and reproducible pattern of miRNA expression relative to age/gender-matched neurotypical controls. The phenotypes, defined by miRNA profiles relative to persisting neurobehavioral impairments, provide the basis for future research to determine the miRNA profiles differentiating states of DoC and the basis for future research using miRNA to detect treatment effects, predict treatment responsiveness, and developing targeted interventions. If future research confirms and advances reported findings, then miRNA profiles will provide the foundation for patient-centric DoC neurorehabilitation.

Testicular Pain and Mesenteric Adenitis as an Atypical Presentation of COVID-19.

A 21-year-old Caucasian male with no past medical history presented to the emergency department with right lower quadrant pain radiating to the right testicle for two days. He reported an occasional dry cough that day but denied any fever or other infectious symptoms. The patient was afebrile with a normal physical examination. CT of the abdomen and pelvis showed prominent right lower quadrant lymphadenopathy. Viral panel for common respiratory pathogens returned negative. A nasopharyngeal swab for SARS-CoV-2 by Xpert® Xpress SARS-CoV-2 reverse transcriptase-polymerase chain reaction (Cepheid Inc., Sunnyvale, CA) was positive. The patient remained in quarantine for 14 days. He was reevaluated seven weeks later with spontaneous resolution of his abdominal pain and the continued absence of upper respiratory symptoms. A repeat CT scan seven weeks later showed persistent mesenteric lymphadenopathy. Repeat COVID-19 testing was not performed at this time. While the frequency of atypical presentation of COVID-19 remains unknown, healthcare providers must continue to remain vigilant and consider COVID-19 as a differential diagnosis in any patient presenting to the emergency department despite the lack of respiratory and gastrointestinal symptoms. Further research is warranted to examine the possibility of asymptomatic spread in asymptomatic patients with persistent radiologic findings and to assess whether repeat COVID-19 testing is warranted in such patients.

Safety Considerations for the Use of Transcranial Magnetic Stimulation as Treatment for Coma Recovery in People With Severe Traumatic Brain Injury.

OBJECTIVE: For persons in states of disordered consciousness (DoC) after severe traumatic brain injury (sTBI), we report cumulative findings from safety examinations, including serious adverse events (AEs) of a repetitive transcranial magnetic stimulation (rTMS) parameter protocol in 2 different studies. PARTICIPANTS: Seven persons in states of DoC after sTBI with widespread neuropathology, but no large lesions in proximity to the site of rTMS. One participant had a ventriculoperitoneal shunt with programmable valve. METHODS: Two clinical trials each providing 30 rTMS sessions to the right or left dorsolateral prefrontal cortex, involving 300 to 600 pulses over 1 or 2 sessions daily. One study provided concomitant amantadine. Safety indicators monitored related to sleep, temperature, blood pressure, skin integrity, sweating, weight loss, infections, and seizure. RESULTS: Average changes for monitored indicators were of mild severity, with 75 nonserious AEs and 1 serious AE (seizure). The participant incurring a seizure resumed rTMS while taking antieplieptics without further seizure activity. CONCLUSIONS: Considering elevated risks for this patient population and conservative patient selection, findings indicate a relatively safe profile for the specified rTMS protocols; however, potential for seizure induction must be monitored. Future research for this population can be broadened to include patients previously excluded on the basis of profiles raising safety concerns.

A Pilot Trial Examining the Merits of Combining Amantadine and Repetitive Transcranial Magnetic Stimulation as an Intervention for Persons With Disordered Consciousness After TBI.

OBJECTIVE: Report pilot findings of neurobehavioral gains and network changes observed in persons with disordered consciousness (DoC) who received repetitive transcranial magnetic stimulation (rTMS) or amantadine (AMA), and then rTMS+AMA. PARTICIPANTS: Four persons with DoC 1 to 15 years after traumatic brain injury (TBI). DESIGN: Alternate treatment-order, within-subject, baseline-controlled trial. MAIN MEASURES: For group and individual neurobehavioral analyses, predetermined thresholds, based on mixed linear-effects models and conditional minimally detectable change, were used to define meaningful neurobehavioral change for the Disorders of Consciousness Scale-25 (DOCS) total and Auditory-Language measures. Resting-state functional connectivity (rsFC) of the default mode and 6 other networks was examined. RESULTS: Meaningful gains in DOCS total measures were observed for 75% of treatment segments and auditory-language gains were observed after rTMS, which doubled when rTMS preceded rTMS+AMA. Neurobehavioral changes were reflected in rsFC for language, salience, and sensorimotor networks. Between networks interactions were modulated, globally, after all treatments. CONCLUSIONS: For persons with DoC 1 to 15 years after TBI, meaningful neurobehavioral gains were observed after provision of rTMS, AMA, and rTMS+AMA. Sequencing and combining of treatments to modulate broad-scale neural activity, via differing mechanisms, merits investigation in a future study powered to determine efficacy of this approach to enabling neurobehavioral recovery.

Placebo-Controlled Trial of Familiar Auditory Sensory Training for Acute Severe Traumatic Brain Injury: A Preliminary Report.

BACKGROUND: Sensory stimulation is often provided to persons incurring severe traumatic brain injury (TBI), but therapeutic effects are unclear. OBJECTIVE: This preliminary study investigated neurobehavioral and neurophysiological effects related to sensory stimulation on global neurobehavioral functioning, arousal, and awareness. METHODS: A double-blind randomized placebo-controlled trial where 15 participants in states of disordered consciousness (DOC), an average of 70 days after TBI, were provided either the Familiar Auditory Sensory Training (FAST) or Placebo of silence. Global neurobehavioral functioning was measured with the Disorders of Consciousness Scale (DOCS). Arousal and awareness were measured with the Coma-Near-Coma (CNC) scale. Neurophysiological effect was measured using functional magnetic resonance imaging (fMRI). RESULTS: FAST (n = 8) and Placebo (n = 7) groups each showed neurobehavioral improvement. Mean DOCS change (FAST = 13.5, SD = 8.2; Placebo = 18.9, SD = 15.6) was not different, but FAST patients had significantly (P = .049; 95% confidence interval [CI] = -1.51, -.005) more CNC gains (FAST = 1.01, SD = 0.60; Placebo = 0.25, SD = 0.70). Mixed-effects models confirm CNC findings (P = .002). Treatment effect, based on CNC, is large (d = 1.88, 95% CI = 0.77, 3.00). Number needed to treat is 2. FAST patients had more fMRI activation in language regions and whole brain (P values <.05) resembling healthy controls' activation. CONCLUSIONS: For persons with DOC 29 to 170 days after TBI, FAST resulted in CNC gains and increased neural responsivity to vocal stimuli in language regions. Clinicians should consider providing the FAST to support patient engagement in neurorehabilitation.

Accurate detection of metabolically active "brown" and "white" adipose tissues with computed tomography.

BACKGROUND: Adipose tissues (AT) are highly metabolically active complex endocrine organs and are classified into white (WAT) and brown AT (BAT) with proinflammatory and anti-inflammatory characteristics. The current study investigated the accuracy of computed tomography (CT) to quantitatively detect BAT and WAT based on Hounsfield unit (HU) threshold compared to standardized uptake values (SUVs) of corresponding AT with the use of positron emission tomography (PET). METHODS: One hundred twenty-four patients who underwent whole-body (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT were studied. The SUVs and HUs of regions of BAT and WAT were measured and compared in these scans. The receiver operator characteristic (ROC) analysis was used to detect the HU threshold values for the detection of BAT and WAT. RESULTS: The CT HU of BAT, with high (18)F-FDG uptake, was significantly higher compared to WAT (-67.1 ± 8.2 [-10 to -87] versus -93.5 ± 10.1 [-88 to -190], P = .0006). Generalized linear-regression models revealed that mean CT HU of BAT was 26.4 HU higher than that of WAT (P = .001). A strong agreement between CT HU and PET SUV in measuring metabolically active AT (r(2) = 0.81, P = .0001) was observed. The ROC curve showed that the optimal cutoff value of CT HU to detect BAT was HU ≥-87 with sensitivity of 83.3% and specificity of 100%, and the negative CT HU below -87 is highly specific for WAT. CONCLUSION: In our study, CT can accurately and quantitatively detect BAT and WAT based on CT HU threshold, which is -10 to -87 for BAT and -88 to -190 for WAT.

Radiologic appearance of chronic parapharyngeal Teflon granuloma.

Although Teflon has been used for almost 5 decades to provide tissue augmentation in various surgical indications, including head and neck surgery, its use has significantly declined in the last 2 decades, primarily because of its implication in granuloma formation. Teflon granulomas have been shown to cause false positives on positron emission tomography imaging and have been reported to have a characteristic magnetic resonance imaging (MRI) appearance. We report a patient with a large chronic Teflon granuloma of the parapharyngeal space that caused significant bony erosion of the atlas vertebra. The lesion's MRI signal characteristics were indistinguishable from those of surrounding tissues, while it showed characteristic hyperdensity on computed tomography due to the presence of fluorine atoms within Teflon. As MRI may supersede or replace computed tomography for a number of indications, and as Teflon has been used in large numbers of patients whose records may not always be available, knowledge of these findings has clinical relevance.

Glossopharyngeal schwannoma of the suprahyoid carotid space: case report and discussion of the relationship to the carotid artery.

BACKGROUND: The distinction between lesions of the deep parotid space and those of the carotid space has been greatly facilitated by cross-sectional imaging, particularly magnetic resonance imaging (MRI), due to 1) good assessment of parapharyngeal fat displacement, and 2) reliable and consistent identification of the carotid artery. While masticator space masses consistently displace the carotid artery posteriorly, it is generally assumed that carotid space masses, particularly schwannomas, displace the carotid artery anteriorly. We report on a patient with a rare glossopharyngeal schwannoma of the carotid space that caused posterior displacement of the carotid artery. METHODS: A 38-year-old female presented with headaches and a pharyngeal sensation of a foreign body without dysgeusia and dysphagia. Computed tomography (CT) and MRI showed a left carotid space mass, suggestive of a schwannoma, although the internal carotid artery was displaced posteriorly. The mass was hypovascular at angiography. The patient underwent surgical excision of her lesion via a left cervical-parotid approach. RESULTS: In our patient with a carotid space mass, all imaging features suggested a schwannoma, except for posterior displacement of the carotid artery. A glossopharyngeal nerve schwannoma was found at surgery. Schwannomas of the glossopharyngeal nerve are uncommon, and those originating from the extracranial course of the nerve are extremely rare. CONCLUSIONS: Schwannomas of the suprahyoid carotid space most commonly arise from the vagus nerve and have a typical pattern, which includes anterior displacement of the carotid artery. A rare exception to this has been reported in schwannomas of the sympathetic nerve, which may displace the carotid artery posteromedially. Our patient had a schwannoma of the extracranial glossopharyngeal nerve, which caused posterolateral carotid displacement.

Magnetic resonance imaging of the orbit.

Magnetic resonance imaging (MRI) employs the nuclear resonance phenomenon to produce images of living tissues. Unlike computed tomography (CT), which relies solely on differences in the propensity of tissues to absorb X-rays to produce various contrasts, MRI offers a wide variety of pulse sequences, each of which exploits differences in the magnetic properties of protons in living tissue to produce contrast resolution. When optimal protocols are used, MRI contrast resolution in the orbital soft tissues is superior to that provided by any other imaging modality. Other advantages of MRI over CT include the ability to select the plane of imaging, and improved safety due to the lack of ionizing radiation.

Culture-Negative intracerebral abscesses in children and adolescents from Streptococcus anginosus group infection: a case series.

We report the use of 16S ribosomal RNA gene amplification and sequencing to diagnose culture-negative intracerebral abscesses in younger patients. These 3 cases demonstrate the optimal application of gene sequencing from direct specimens for patients with negative culture results compromised by antibacterial therapy but histories highly suggestive of acute bacterial infection.

Interventional neuroradiology for the ophthalmologist.

The past two decades have witnessed major advances in diagnosing vascular conditions that affect blood supply and hemorrhagic risk to the brain and the eye. Technological improvements have resulted in the ability to better radiologically image the cerebrovascular system and to deliver pharmacological and embolic agents that have high specificity. Neuroradiological interventional therapy has become the preferred option in managing many conditions that were previously treated by standard neurosurgical procedures. Some of these conditions were considered either inoperable or treatable only with unacceptable neurosurgical risks. This article reviews the current state of the neuroradiological interventional management in conditions that may be encountered in ophthalmological practice.

Radiologic case study. Cervical spine trauma: unstable fractures, C2-C7 injuries, and imaging guidelines.

Enhance your diagnostic skills with this "test yourself" monthly column, which features a radiograph and challenges you to make a diagnosis.

Orbital rhabdomyosarcoma and simulating lesions.

The appropriate diagnosis and treatment of orbital rhabdomyosarcoma requires close cooperation and communication between the radiologist, the ophthalmologist, and the medical and radiation oncologists. The clinical presentation, imaging characteristics, and staging of orbital rhabdomyosarcoma are discussed. A discussion of several important simulating lesions and their distinguishing characteristics follows.