Structural connectivity changes in unilateral hearing loss.

Network connectivity, as mapped by the whole brain connectome, plays a crucial role in regulating auditory function. Auditory deprivation such as unilateral hearing loss might alter structural network connectivity; however, these potential alterations are poorly understood. Thirty-seven acoustic neuroma patients with unilateral hearing loss (19 left-sided and 18 right-sided) and 19 healthy controls underwent diffusion-weighted and T1-weighted imaging to assess edge strength, node strength, and global efficiency of the structural connectome. Edge strength was estimated by pair-wise normalized streamline density from tractography and connectomics. Node strength and global efficiency were calculated through graph theory analysis of the connectome. Pure-tone audiometry and word recognition scores were used to correlate the degree and duration of unilateral hearing loss with node strength and global efficiency. We demonstrate significantly stronger edge strength and node strength through the visual network, weaker edge strength and node strength in the somatomotor network, and stronger global efficiency in the unilateral hearing loss patients. No discernible correlations were observed between the degree and duration of unilateral hearing loss and the measures of node strength or global efficiency. These findings contribute to our understanding of the role of structural connectivity in hearing by facilitating visual network upregulation and somatomotor network downregulation after unilateral hearing loss.

Haploinsufficiency of POU4F1 causes an ataxia syndrome with hypotonia and intention tremor.

De novo, heterozygous, loss-of-function variants were identified in Pou domain, class 4, transcription factor 1 (POU4F1) via whole-exome sequencing in four independent probands presenting with ataxia, intention tremor, and hypotonia. POU4F1 is expressed in the developing nervous system, and mice homozygous for null alleles of Pou4f1 exhibit uncoordinated movements with newborns being unable to successfully right themselves to feed. Head magnetic resonance imaging of the four probands was reviewed and multiple abnormalities were noted, including significant cerebellar vermian atrophy and hypertrophic olivary degeneration in one proband. Transcriptional activation of the POU4F1 p.Gln306Arg protein was noted to be decreased when compared with wild type. These findings suggest that heterozygous, loss-of-function variants in POU4F1 are causative of a novel ataxia syndrome.

Trigeminal neuralgia associated with multiple sclerosis: A multimodal assessment of brainstem plaques and response to Gamma Knife radiosurgery.

BACKGROUND: Gamma Knife radiosurgery (GKRS) is a minimally invasive procedure for trigeminal neuralgia secondary to multiple sclerosis (MS-TN). Patients with MS-TN experience suboptimal response rates to treatment, and the relationship between trigeminal microstructure and treatment outcome is poorly understood. OBJECTIVE: To characterize imaging features of MS-TN pain and GKRS response. METHODS: 3 T diffusion-weighted imaging (DWI), T1-w, T2-w, and fluid-attenuated inversion recovery (FLAIR) sequences were acquired for 18 MS-TN patients undergoing GKRS. Brainstem plaques were standardized into a common space to determine plaque distribution. Ratio of T1-w/T2-w or "myelin maps (MM)" was generated. Multi-tensor tractography was used to delineate the radiosurgical target (RT), root entry zone (REZ), and proximal pontine segment (PPS) of the trigeminal nerves. RESULTS: Laterality of MS-TN is associated with increased axial diffusivity at the PPS, whereas decreased MM at the PPS correlated with poor GKRS response. Preoperatively, GKRS responders have higher fractional anisotropy at the RT, higher axial diffusivity at the REZ, and higher MM intensities at the PPS. CONCLUSION: This study demonstrates that diffusivities and MM intensities are important correlates of pain and treatment response, respectively. Overall, preoperative multimodal assessment of the central trigeminal pathway is a better indicator of GKRS response than postoperative assessment of the reduction in fractional anisotropy peripherally.

Relationship Between Visceral Infarction and Ischemic Stroke Subtype.

BACKGROUND AND PURPOSE: Most cryptogenic strokes are thought to have an embolic source. We sought to determine whether cryptogenic strokes are associated with visceral infarcts, which are usually embolic. METHODS: Among patients prospectively enrolled in CAESAR (Cornell Acute Stroke Academic Registry), we selected those with a contrast-enhanced abdominal computed tomographic scan within 1 year of admission. Our exposure variable was adjudicated stroke subtype per the Trial of ORG 10172 in Acute Stroke Treatment classification. Our outcome was renal or splenic infarction as assessed by a single radiologist blinded to stroke subtype. We used Fisher exact test and multiple logistic regression to compare the prevalence of visceral infarcts among cardioembolic strokes, strokes of undetermined etiology, and noncardioembolic strokes (large- or small-vessel strokes). RESULTS: Among 227 patients with ischemic stroke and a contrast-enhanced abdominal computed tomographic scan, 59 had a visceral infarct (35 renal and 27 splenic). The prevalence of visceral infarction was significantly different among cardioembolic strokes (34.2%; 95% confidence interval [CI], 23.7%-44.6%), strokes of undetermined etiology (23.9%; 95% CI, 15.0%-32.8%), and strokes from large-artery atherosclerosis or small-vessel occlusion (12.5%; 95% CI, 1.8%-23.2%; P=0.03). In multiple logistic regression models adjusted for demographics and vascular comorbidities, we found significant associations with visceral infarction for both cardioembolic stroke (odds ratio, 3.5; 95% CI, 1.2-9.9) and stroke of undetermined source (odds ratio, 3.3; 95% CI, 1.1-10.5) as compared with noncardioembolic stroke. CONCLUSIONS: The prevalence of visceral infarction differed significantly across ischemic stroke subtypes. Cardioembolic and cryptogenic strokes were associated with a higher prevalence of visceral infarcts than noncardioembolic strokes.

Contribution of systemic inflammation to permanence of KATP-induced neonatal diabetes in mice.

Gain-of-function (GOF) mutations in the ATP-sensitive potassium (KATP) channels cause neonatal diabetes. Despite the well-established genetic root of the disease, pathways modulating disease severity and treatment effectiveness remain poorly understood. Patient phenotypes can vary from severe diabetes to remission, even in individuals with the same mutation and within the same family, suggesting that subtle modifiers can influence disease outcome. We have tested the underlying mechanism of transient vs. permanent neonatal diabetes in KATP-GOF mice treated for 14 days with glibenclamide. Some KATP-GOF mice show remission of diabetes and enhanced insulin sensitivity long after diabetes treatment has ended, while others maintain severe insulin-resistance. However, insulin sensitivity is not different between the two groups before or during diabetes induction, suggesting that improved sensitivity is a consequence, rather than the cause of, remission, implicating other factors modulating glucose early in diabetes progression. Leptin, glucagon, insulin, and glucagon-like peptide-1 are not different between remitters and nonremitters. However, liver glucose production is significantly reduced before transgene induction in remitter, relative to nonremitter and nontreated, mice. Surprisingly, while subsequent remitter animals exhibited normal serum cytokines, nonremitter mice showed increased cytokines, which paralleled the divergence in blood glucose. Together, these results suggest that systemic inflammation may play a role in the remitting versus non-remitting outcome. Supporting this conclusion, treatment with the anti-inflammatory meloxicam significantly increased the fraction of remitting animals. Beyond neonatal diabetes, the potential for inflammation and glucose production to exacerbate other forms of diabetes from a compensated state to a glucotoxic state should be considered.

Left Atrial Appendage Morphology and Embolic Stroke of Undetermined Source: A Cross-Sectional Multicenter Pilot Study.

BACKGROUND: The left atrial appendage (LAA) is the main source of thrombus in atrial fibrillation, and there is an association between non-chicken wing (NCW) LAA morphology and stroke. We hypothesized that the prevalence of NCW LAA morphology would be higher among patients with cardioembolic (CE) stroke and embolic stroke of undetermined source (ESUS) than among those with noncardioembolic stroke (NCS). METHODS: This multicenter retrospective pilot study included consecutive patients with ischemic stroke from 3 comprehensive stroke centers who previously underwent a qualifying chest computed tomography (CT) to assess LAA morphology. Patients underwent inpatient diagnostic evaluation for ischemic stroke, and stroke subtype was determined based on ESUS criteria. LAA morphology was determined using clinically performed contrast enhanced thin-slice chest CT by investigators blinded to stroke subtype. The primary predictor was NCW LAA morphology and the outcome was stroke subtype (CE, ESUS, NCS). RESULTS: We identified 172 patients with ischemic stroke who had a clinical chest CT performed. Mean age was 70.1 ± 14.3 years and 51.7% were male. Compared with patients with NCS, the prevalence of NCW LAA morphology was higher in patients with CE stroke (58.7% versus 46.3%, P = .1) and ESUS (58.8% versus 46.3%, P = .2), but this difference did not achieve statistical significance. CONCLUSION: The prevalence of NCW LAA morphology may be similar in patients with ESUS and CE, and may be higher than that in those with NCS. Larger studies are needed to confirm these associations.

Hippocampus diffusivity abnormalities in classical trigeminal neuralgia.

Introduction: Patients with chronic pain frequently report cognitive symptoms that affect memory and attention, which are functions attributed to the hippocampus. Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder characterized by paroxysmal attacks of unilateral orofacial pain. Given the stereotypical nature of TN pain and lack of negative symptoms including sensory loss, TN provides a unique model to investigate the hippocampal implications of chronic pain. Recent evidence demonstrated that TN is associated with macrostructural hippocampal abnormalities indicated by reduced subfield volumes; however, there is a paucity in our understanding of hippocampal microstructural abnormalities associated with TN. Objectives: To explore diffusivity metrics within the hippocampus, along with its functional and structural subfields, in patients with TN. Methods: To examine hippocampal microstructure, we utilized diffusion tensor imaging in 31 patients with TN and 21 controls. T1-weighted magnetic resonance images were segmented into hippocampal subfields and registered into diffusion-weighted imaging space. Fractional anisotropy (FA) and mean diffusivity were extracted for hippocampal subfields and longitudinal axis segmentations. Results: Patients with TN demonstrated reduced FA in bilateral whole hippocampi and hippocampal body and contralateral subregions CA2/3 and CA4, indicating microstructural hippocampal abnormalities. Notably, patients with TN showed significant correlation between age and hippocampal FA, while controls did not exhibit this correlation. These effects were driven chiefly by female patients with TN. Conclusion: This study demonstrates that TN is associated with microstructural hippocampal abnormalities, which may precede and potentially be temporally linked to volumetric hippocampal alterations demonstrated previously. These findings provide further evidence for the role of the hippocampus in chronic pain and suggest the potential for targeted interventions to mitigate cognitive symptoms in patients with chronic pain.

Electrostatic effects in filamentous protein aggregation.

Electrostatic forces play a key role in mediating interactions between proteins. However, gaining quantitative insights into the complex effects of electrostatics on protein behavior has proved challenging, due to the wide palette of scenarios through which both cations and anions can interact with polypeptide molecules in a specific manner or can result in screening in solution. In this article, we have used a variety of biophysical methods to probe the steady-state kinetics of fibrillar protein self-assembly in a highly quantitative manner to detect how it is modulated by changes in solution ionic strength. Due to the exponential modulation of the reaction rate by electrostatic forces, this reaction represents an exquisitely sensitive probe of these effects in protein-protein interactions. Our approach, which involves a combination of experimental kinetic measurements and theoretical analysis, reveals a hierarchy of electrostatic effects that control protein aggregation. Furthermore, our results provide a highly sensitive method for the estimation of the magnitude of binding of a variety of ions to protein molecules.

Brain imaging signatures of neuropathic facial pain derived by artificial intelligence.

Advances in neuroimaging have permitted the non-invasive examination of the human brain in pain. However, a persisting challenge is in the objective differentiation of neuropathic facial pain subtypes, as diagnosis is based on patients' symptom descriptions. We use artificial intelligence (AI) models with neuroimaging data to distinguish subtypes of neuropathic facial pain and differentiate them from healthy controls. We conducted a retrospective analysis of diffusion tensor and T1-weighted imaging data using random forest and logistic regression AI models on 371 adults with trigeminal pain (265 classical trigeminal neuralgia (CTN), 106 trigeminal neuropathic pain (TNP)) and 108 healthy controls (HC). These models distinguished CTN from HC with up to 95% accuracy, and TNP from HC with up to 91% accuracy. Both classifiers identified gray and white matter-based predictive metrics (gray matter thickness, surface area, and volume; white matter diffusivity metrics) that significantly differed across groups. Classification of TNP and CTN did not show significant accuracy (51%) but highlighted two structures that differed between pain groups-the insula and orbitofrontal cortex. Our work demonstrates that AI models with brain imaging data alone can differentiate neuropathic facial pain subtypes from healthy data and identify regional structural indicates of pain.

Differential expression of a brain aging biomarker across discrete chronic pain disorders.

ABSTRACT: Chronic pain has widespread, detrimental effects on the human nervous system and its prevalence and burden increase with age. Machine learning techniques have been applied on brain images to produce statistical models of brain aging. Specifically, the Gaussian process regression is particularly effective at predicting chronological age from neuroimaging data which permits the calculation of a brain age gap estimate (brain-AGE). Pathological biological processes such as chronic pain can influence brain-AGE. Because chronic pain disorders can differ in etiology, severity, pain frequency, and sex-linked prevalence, we hypothesize that the expression of brain-AGE may be pain specific and differ between discrete chronic pain disorders. We built a machine learning model using T1-weighted anatomical MRI from 812 healthy controls to extract brain-AGE for 45 trigeminal neuralgia (TN), 52 osteoarthritis (OA), and 50 chronic low back pain (BP) subjects. False discovery rate corrected Welch t tests were conducted to detect significant differences in brain-AGE between each discrete pain cohort and age-matched and sex-matched controls. Trigeminal neuralgia and OA, but not BP subjects, have significantly larger brain-AGE. Across all 3 pain groups, we observed female-driven elevation in brain-AGE. Furthermore, in TN, a significantly larger brain-AGE is associated with response to Gamma Knife radiosurgery for TN pain and is inversely correlated with the age at diagnosis. As brain-AGE expression differs across distinct pain disorders with a pronounced sex effect for female subjects. Younger women with TN may therefore represent a vulnerable subpopulation requiring expedited chronic pain intervention. To this end, brain-AGE holds promise as an effective biomarker of pain treatment response.

Pain Relief Reverses Hippocampal Abnormalities in Trigeminal Neuralgia.

Chronic pain patients frequently report memory and concentration difficulties. Objective testing in this population points to poor performance on memory and cognitive tests, and increased comorbid anxiety and depression. Recent evidence has suggested convergence between chronic pain and memory deficits onto the hippocampus. The hippocampus consists of heterogenous subfields involved in memory consolidation, behavior regulation, and stress modulation. Despite significant studies outlining hippocampal changes in human and chronic pain animal models, the effect of pain relief on hippocampal abnormalities remains unknown. Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder which is highly amenable to surgical interventions, providing a unique opportunity to investigate the effect of pain relief. This study investigates the effect of pain relief on hippocampal subfields in TN. Anatomical MR images of 61 TN patients were examined before and 6 months after surgery. Treatment responders (n = 47) reported 95% pain relief, whereas non-responders (n = 14) reported 40% change in pain on average. At baseline, patients had smaller hippocampal volumes, compared to controls. After surgery, responders' hippocampal volumes normalized, largely driven by CA2/3, CA4, and dentate gyrus, which are involved in memory consolidation and neurogenesis. We propose that hippocampal atrophy in TN is pain-driven and successful treatment normalizes such abnormalities. PERSPECTIVE: Chronic pain patients have structural abnormalities in the hippocampus and its subfields. Pain relief normalizes these structural abnormalities and impacts patients in a sex-dependent manner.

Sex differences in patient journeys to diagnosis, referral, and surgical treatment of trigeminal neuralgia: implications for equitable care.

OBJECTIVE: Trigeminal neuralgia (TN) is an orofacial pain disorder that is more prevalent in females than males. Although an increasing number of studies point to sex differences in chronic pain, how sex impacts TN patients' journeys to care has not been previously addressed. This study sought to investigate sex differences in patients' journeys to diagnosis, referral, and treatment of TN within a large national context. METHODS: Patients with classic TN (n = 100; 50 females and 50 males) were randomly selected through chart reviews at the largest surgical treatment center for TN in Canada for a cross-sectional study. Statistical tests, including Welch's t-test, the chi-square test, Pearson's correlations, and analyses of covariance, were conducted with Python. RESULTS: Key discrepancies between sexes in access to care were identified. Females had a significantly longer referral time interval (average 53.2 months vs 20.4 months, median 27.5 months vs 11.0 months, p = 0.018) and total time interval (average 121.1 months vs 67.8 months, median 78.0 months vs 45.2 months, p = 0.018) than males, despite reporting higher pain intensity at referral. Although medically intolerant patients had a significantly shorter referral time interval than medically tolerant patients (average 13.0 months vs 41.0 months, median 6.0 months vs 17.0 months, p < 0.001), medically tolerant females had a significantly longer referral time interval than medically tolerant males (average 59.9 months vs 21.7 months, median 30.0 months vs 12.0 months, p = 0.017). No statistically significant differences were detected between the sexes for diagnostic time interval (average 63.3 months vs 43.0 months, median 24.0 months vs 24.0 months, p = 0.263) or treatment time interval (average 4.6 months vs 4.7 months, median 4.0 months vs 3.0 months, p = 0.986). CONCLUSIONS: Critical sex differences in patients' journeys to TN surgical treatment were identified, with females enduring considerably longer referral timelines and expressing significantly greater pain intensity than males at referral. Taken together, our findings suggest the presence of unconscious bias and discrimination against females and highlight the need for expediting TN treatment referral for female TN patients.

Standardizing T1-w/T2-w ratio images in trigeminal neuralgia to estimate the degree of demyelination in vivo.

BACKGROUND: Novel magnetic resonance (MR) imaging techniques have led to the development of T1-w/T2-w ratio images or "myelin-sensitive maps (MMs)" to estimate and compare myelin content in vivo. Currently, raw image intensities in conventional MR images are unstandardized, preventing meaningful quantitative comparisons. We propose an improved workflow to standardize the MMs, which was applied to patients with classic trigeminal neuralgia (CTN) and trigeminal neuralgia secondary to multiple sclerosis (MSTN), to assess the validity and feasibility of this clinical tool. METHODS: T1-w and T2-w images were obtained for 17 CTN patients and 17 MSTN patients using a 3 T scanner. Template images were obtained from ICBM152. Multiple sclerosis (MS) plaques in the pons were labelled in MSTN patients. For each patient image, a Gaussian curve was fitted to the histogram of its intensity distribution, and transformed to match the Gaussian curve of its template image. RESULTS: After standardization, the structural contrast of the patient image and its histogram more closely resembled the ICBM152 template. Moreover, there was reduced variability in the histogram peaks of the gray and white matter between patients after standardization (p < 0.001). MM intensities were decreased within MS plaques, compared to normal-appearing white matter (NAWM) in MSTN patients (p < 0.001) and its corresponding regions in CTN patients (p < 0.001). CONCLUSIONS: Images intensities are calibrated according to a mathematic relationship between the intensities of the patient image and its template. Reduced variability among histogram peaks allows for interpretation of tissue-specific intensity and facilitates quantitative analysis. The resultant MMs facilitate comparisons of myelin content between different regions of the brain and between different patients in vivo. MM analysis revealed reduced myelin content in MS plaques compared to its corresponding regions in CTN patients and its surrounding NAWM in MSTN patients. Thus, the standardized MM serves as a non-invasive, easily-automated tool that can be feasibly applied to clinical populations for quantitative analyses of myelin content.

Regional brain morphology predicts pain relief in trigeminal neuralgia.

BACKGROUND: Trigeminal neuralgia, a severe chronic neuropathic pain disorder, is widely believed to be amenable to surgical treatments. Nearly 20% of patients, however, do not have adequate pain relief after surgery. Objective tools for personalized pre-treatment prognostication of pain relief following surgical interventions can minimize unnecessary surgeries and thus are of substantial benefit for patients and clinicians. PURPOSE: To determine if pre-treatment regional brain morphology-based machine learning models can prognosticate 1 year response to Gamma Knife radiosurgery for trigeminal neuralgia. METHODS: We used a data-driven approach that combined retrospective structural neuroimaging data and support vector machine-based machine learning to produce robust multivariate prediction models of pain relief following Gamma Knife radiosurgery for trigeminal neuralgia. Surgical response was defined as ≥ 75% pain relief 1 year post-treatment. We created two prediction models using pre-treatment regional brain gray matter morphology (cortical thickness or surface area) to distinguish responders from non-responders to radiosurgery. Feature selection was performed through sequential backwards selection algorithm. Model out-of-sample generalizability was estimated via stratified 10-fold cross-validation procedure and permutation testing. RESULTS: In 51 trigeminal neuralgia patients (35 responders, 16 non-responders), machine learning models based on pre-treatment regional brain gray matter morphology (14 regional surface areas or 13 regional cortical thicknesses) provided robust a priori prediction of surgical response. Cross-validation revealed the regional surface area model was 96.7% accurate, 100.0% sensitive, and 89.1% specific while the regional cortical thickness model was 90.5% accurate, 93.5% sensitive, and 83.7% specific. Permutation testing revealed that both models performed beyond pure chance (p < 0.001). The best predictor for regional surface area model and regional cortical thickness model was contralateral superior frontal gyrus and contralateral isthmus cingulate gyrus, respectively. CONCLUSIONS: Our findings support the use of machine learning techniques in subsequent investigations of chronic neuropathic pain. Furthermore, our multivariate framework provides foundation for future development of generalizable, artificial intelligence-driven tools for chronic neuropathic pain treatments.

Sex differences in brain modular organization in chronic pain.

ABSTRACT: Men and women can exhibit different pain sensitivities, and many chronic pain conditions are more prevalent in one sex. Although there is evidence of sex differences in the brain, it is not known whether there are sex differences in the organization of large-scale functional brain networks in chronic pain. Here, we used graph theory with modular analysis and machine-learning of resting-state-functional magnetic resonance imaging data from 220 participants: 155 healthy controls and 65 individuals with chronic low back pain due to ankylosing spondylitis, a form of arthritis. We found an extensive overlap in the graph partitions with the major brain intrinsic systems (ie, default mode, central, visual, and sensorimotor modules), but also sex-specific network topological characteristics in healthy people and those with chronic pain. People with chronic pain exhibited higher cross-network connectivity, and sex-specific nodal graph properties changes (ie, hub disruption), some of which were associated with the severity of the chronic pain condition. Females exhibited atypically higher functional segregation in the mid cingulate cortex and subgenual anterior cingulate cortex and lower connectivity in the network with the default mode and frontoparietal modules, whereas males exhibited stronger connectivity with the sensorimotor module. Classification models on nodal graph metrics could classify an individual's sex and whether they have chronic pain with high accuracies (77%-92%). These findings highlight the organizational abnormalities of resting-state-brain networks in people with chronic pain and provide a framework to consider sex-specific pain therapeutics.

Trigeminal neuralgia associated with a solitary pontine lesion: clinical and neuroimaging definition of a new syndrome.

Conventional magnetic resonance imaging of patients with trigeminal neuralgia (TN) does not typically reveal associated brain lesions. Here, we identify a unique group of TN patients who present with a single brainstem lesion, who do not fulfill diagnostic criteria for multiple sclerosis (MS). We aim to define this new clinical syndrome, which we term TN associated with solitary pontine lesion (SPL-TN), using a clinical and neuroimaging approach. We identified 24 cases of SPL-TN, 18 of which had clinical follow-up for assessment of treatment response. Lesion mapping was performed to determine the exact location of the lesions and site of maximum overlap across patients. Diffusion tensor imaging was used to assess the white-matter microstructural properties of the lesions. Diffusivity metrics were extracted from the (1) SPL-TN lesions, (2) contralateral, unaffected side, (3) MS brainstem plaques from 17 patients with TN secondary to MS, (4) and healthy controls. We found that 17/18 patients were nonresponders to surgical treatment. The lesions were uniformly located along the affected trigeminal pontine pathway, where the site of maximum overlap across patients was in the area of the trigeminal nucleus. The lesions demonstrated abnormal white-matter microstructure, characterized by lower fractional anisotropy, and higher mean, radial, and axial diffusivities compared with the unaffected side. The brainstem trigeminal fiber microstructure within a lesion highlighted the difference between SPL-TN lesions and MS plaques. In conclusion, SPL-TN patients have identical clinical features to TN but have a single pontine lesion not in keeping with MS and are refractory to surgical management.

Modeling knowledge resource selection in expert librarian search.

Providing knowledge at the point of care offers the possibility for reducing error and improving patient outcomes. However, the vast majority of the physician's information needs are not met in a timely fashion. The research presented in this paper characterizes an expert librarian's search strategies as it pertains to the selection and use of various electronic information resources. The 10 searches conducted by the librarian to address the physician's information needs varied in terms of complexity and question type. The librarian employed a total of 10 resources and used as many as 7 in a single search. The longer term objective is to model the sequential process in sufficient detail as to be able to contribute to the development of intelligent automated search agents.

Temporal disconnection between pain relief and trigeminal nerve microstructural changes after Gamma Knife radiosurgery for trigeminal neuralgia.

OBJECTIVE: Gamma Knife radiosurgery (GKRS) is a noninvasive surgical treatment option for patients with medically refractive classic trigeminal neuralgia (TN). The long-term microstructural consequences of radiosurgery and their association with pain relief remain unclear. To better understand this topic, the authors used diffusion tensor imaging (DTI) to characterize the effects of GKRS on trigeminal nerve microstructure over multiple posttreatment time points. METHODS: Ninety-two sets of 3-T anatomical and diffusion-weighted MR images from 55 patients with TN treated by GKRS were divided within 6-, 12-, and 24-month posttreatment time points into responder and nonresponder subgroups (≥ 75% and < 75% reduction in posttreatment pain intensity, respectively). Within each subgroup, posttreatment pain intensity was then assessed against pretreatment levels and followed by DTI metric analyses, contrasting treated and contralateral control nerves to identify specific biomarkers of successful pain relief. RESULTS: GKRS resulted in successful pain relief that was accompanied by asynchronous reductions in fractional anisotropy (FA), which maximized 24 months after treatment. While GKRS responders demonstrated significantly reduced FA within the radiosurgery target 12 and 24 months posttreatment (p < 0.05 and p < 0.01, respectively), nonresponders had statistically indistinguishable DTI metrics between nerve types at each time point. CONCLUSIONS: Ultimately, this study serves as the first step toward an improved understanding of the long-term microstructural effect of radiosurgery on TN. Given that FA reductions remained specific to responders and were absent in nonresponders up to 24 months posttreatment, FA changes have the potential of serving as temporally consistent biomarkers of optimal pain relief following radiosurgical treatment for classic TN.

Selective hippocampal subfield volume reductions in classic trigeminal neuralgia.

Trigeminal Neuralgia (TN) is a chronic neuropathic pain syndrome characterized by paroxysmal unilateral shock-like pains in the trigeminal territory most frequently attributed to neurovascular compression of the trigeminal nerve at its root entry zone. Recent advances in the study of TN suggest a possible central nervous system (CNS) role in modulation and maintenance of pain. TN and other chronic pain patients commonly experience alterations in cognition and affect, as well as abnormalities in CNS volume and microstructure in regions associated with pain perception, emotional modulation, and memory consolidation. However, the microstructural changes in the hippocampus, an important structure within the limbic system, have not been previously studied in TN patients. Here, we use grey matter analysis to assess whether TN pain is associated with altered hippocampal subfield volume in patients with classic TN. Anatomical magnetic resonance (MR) images of twenty-two right-sided TN patients and matched healthy controls underwent automated segmentation of hippocampal subfields using FreeSurfer v6.0. Right-sided TN patients had significant volumetric reductions in ipsilateral cornu ammois 1 (CA1), CA4, dentate gyrus, molecular layer, and hippocampus-amygdala transition area - resulting in decreased whole ipsilateral hippocampal volume, compared to healthy controls. Overall, we demonstrate selective hippocampal subfield volume reduction in patients with classic TN. These changes occur in subfields implicated as neural circuits for chronic pain processing. Selective subfield volume reduction suggests aberrant processes and circuitry reorganization, which may contribute to development and/or maintenance of TN symptoms.

Effect of Clinical History on Interpretation of Computed Tomography for Acute Stroke.

OBJECTIVE: We assessed whether providing detailed clinical information alongside computed tomography (CT) images improves their interpretation for acute stroke. METHODS: Using the prospective Cornell AcutE Stroke Academic Registry, we randomly selected 100 patients who underwent noncontrast head CT within 6 hours of transient ischemic attack or minor acute ischemic stroke and underwent magnetic resonance imaging (MRI) within 6 hours of the CT. Three radiologist investigators evaluated each of the 100 CT studies twice, once with and once without accompanying information on medical history, signs, and symptoms. In random sequence, each study was interpreted in one condition (ie, with or without detailed accompanying information) and then after a 4-week washout period, in the opposite condition. Using MRI diffusion-weighted imaging (DWI) as the reference standard, we classified CT interpretations as correct (true positives or negatives) or incorrect (false positives or negatives). We used logistic regression with sandwich estimators to compare the proportion of correct interpretations. RESULTS: In patients with DWI-defined infarcts, acute ischemia was called on 20% of CTs with detailed history and 18% without history. In patients without infarcts, the absence of ischemia was called on 77% of CTs with history and 77% without history. The proportion of correct interpretations of CTs accompanied by detailed clinical history (49%) did not differ significantly from those without history (47%; odds ratio: 1.1; 95% confidence interval: 0.8-1.4). CONCLUSIONS: Reported findings on head CT for evaluation of suspected acute ischemic stroke were similar regardless of whether detailed clinical history was provided.