Focal Pathology Research Articles

GAMER MRI: Gated-attention mechanism ranking of multi-contrast MRI in brain pathology

IntroductionDuring the last decade, a multitude of novel quantitative and semiquantitative MRI techniques have provided new information about the pathophysiology of neurological diseases. Yet, selection of the most relevant contrasts for a given pathology remains challenging. In this work, we developed and validated a method, Gated-Attention MEchanism Ranking of multi-contrast MRI in brain pathology (GAMER MRI), to rank the relative importance of MR measures in the classification of well understood ischemic stroke lesions. Subsequently, we applied this method to the classification of multiple sclerosis (MS) lesions, where the relative importance of MR measures is less understood. MethodsGAMER MRI was developed based on the gated attention mechanism, which computes attention weights (AWs) as proxies of importance of hidden features in the classification. In the first two experiments, we used Trace-weighted (Trace), apparent diffusion coefficient (ADC), Fluid-Attenuated Inversion Recovery (FLAIR), and T1-weighted (T1w) images acquired in 904 acute/subacute ischemic stroke patients and in 6,230 healthy controls and patients with other brain pathologies to assess if GAMER MRI could produce clinically meaningful importance orders in two different classification scenarios. In the first experiment, GAMER MRI with a pretrained convolutional neural network (CNN) was used in conjunction with Trace, ADC, and FLAIR to distinguish patients with ischemic stroke from those with other pathologies and healthy controls. In the second experiment, GAMER MRI with a patch-based CNN used Trace, ADC and T1w to differentiate acute ischemic stroke lesions from healthy tissue. The last experiment explored the performance of patch-based CNN with GAMER MRI in ranking the importance of quantitative MRI measures to distinguish two groups of lesions with different pathological characteristics and unknown quantitative MR features. Specifically, GAMER MRI was applied to assess the relative importance of the myelin water fraction (MWF), quantitative susceptibility mapping (QSM), T1 relaxometry map (qT1), and neurite density index (NDI) in distinguishing 750 juxtacortical lesions from 242 periventricular lesions in 47 MS patients. Pair-wise permutation t-tests were used to evaluate the differences between the AWs obtained for each quantitative measure. ResultsIn the first experiment, we achieved a mean test AUC of 0.881 and the obtained AWs of FLAIR and the sum of AWs of Trace and ADC were 0.11 and 0.89, respectively, as expected based on previous knowledge. In the second experiment, we achieved a mean test F1 score of 0.895 and a mean AW of Trace = 0.49, of ADC = 0.28, and of T1w = 0.23, thereby confirming the findings of the first experiment. In the third experiment, MS lesion classification achieved test balanced accuracy = 0.777, sensitivity = 0.739, and specificity = 0.814. The mean AWs of T1map, MWF, NDI, and QSM were 0.29, 0.26, 0.24, and 0.22 (p < 0.001), respectively. ConclusionsThis work demonstrates that the proposed GAMER MRI might be a useful method to assess the relative importance of MRI measures in neurological diseases with focal pathology. Moreover, the obtained AWs may in fact help to choose the best combination of MR contrasts for a specific classification problem.

Somatic TARDBP variants as a cause of semantic dementia.

The aetiology of late-onset neurodegenerative diseases is largely unknown. Here we investigated whether de novo somatic variants for semantic dementia can be detected, thereby arguing for a more general role of somatic variants in neurodegenerative disease. Semantic dementia is characterized by a non-familial occurrence, early onset (<65 years), focal temporal atrophy and TDP-43 pathology. To test whether somatic variants in neural progenitor cells during brain development might lead to semantic dementia, we compared deep exome sequencing data of DNA derived from brain and blood of 16 semantic dementia cases. Somatic variants observed in brain tissue and absent in blood were validated using amplicon sequencing and digital PCR. We identified two variants in exon one of the TARDBP gene (L41F and R42H) at low level (1-3%) in cortical regions and in dentate gyrus in two semantic dementia brains, respectively. The pathogenicity of both variants is supported by demonstrating impaired splicing regulation of TDP-43 and by altered subcellular localization of the mutant TDP-43 protein. These findings indicate that somatic variants may cause semantic dementia as a non-hereditary neurodegenerative disease, which might be exemplary for other late-onset neurodegenerative disorders.

Comparison between Different Diagnostic Strategies in Low-Risk Reproductive Age and Pre-Menopausal Women Presenting Abnormal Uterine Bleeding.

Abnormal uterine bleeding (AUB) is a common symptom in the female population, with an estimated prevalence of 10 to 30% in fertile age and up to 90% in perimenopausal women. In most cases, AUB is due to a benign cause. However, it can also be a symptom of atypical endometrial hyperplasia or endometrial cancer, a more common disease during menopause which can also affect women in their reproductive age. Considering the high prevalence of this symptom an appropriate diagnostic algorithm is needed. Concerns about the risks, pain, and stress associated with an endometrial biopsy and its impact on the healthcare system make the choice of AUB diagnostic strategy extremely relevant. Even if the scientific community agrees on the definition of AUB, International Guidelines show some differences in the management of women of reproductive age with AUB, especially regarding the age cut-off as an independent indication for endometrial biopsy. This study compared different diagnostic strategies to identify a diagnostic pathway with high sensitivity and specificity but low impact on the health system’s resources. The analysis was based on three diagnostic algorithms defined as part of the guidelines of leading scientific societies. Women of reproductive age with AUB (n = 625) and without risk of endometrial cancer were included in the study. Results showed that the best criterion to investigate AUB in women at low risk of endometrial cancer is not age cut-off but the presence or absence of focal endometrial pathology at the ultrasound and the response to the progestin therapy. This approach makes it possible to perform fewer outpatient hysteroscopic biopsies without excluding positive cases from the examination.

Evaluation of transforaminal epidural steroid injections for discogenic axial lumbosacral back pain utilizing PROMIS as an outcome measure

Background contextDiscogenic lumbosacral back pain continues to present a challenging clinical entity with limited, controversial therapeutic options. No study to date has evaluated the efficacy of fluoroscopically guided transforaminal epidural steroid injections (TFESI) in a homogenous patient population with axial lumbosacral back pain from discogenic pathology utilizing strict, explicitly clinical and radiographic criteria. Additionally, there is a paucity of published data utilizing Patient Reported Outcome Measurement Information System (PROMIS) scores as an outcome measure for interventional spine procedures. PurposeEvaluate the therapeutic effect of TFESIs in a specific subset of patients with discogenic axial lumbosacral back pain. Investigate PROMIS as an outcome measure for interventional spine procedures targeting focal degenerative spinal pathology. Study design/settingRetrospective review of patients presenting to a multidisciplinary, tertiary academic spine center. Patient sampleThree thousand eight hundred eighty-one patients were screened for inclusion. A total of 26 patients with discogenic axial low back, based on strict clinical and radiographic criteria, underwent TFESIs. All patients had axial low back pain without radicular pain, ≥3 clinical features of discogenic pain, corroborative radiographic features of active discogenic pathology on lumbar spine magnetic resonance imaging without confounding spinal pathology. Outcome measuresPROMIS Pain Interference (PI) v1.1, PROMIS Physical Function (PF) v1.2/v2.0, and PROMIS Depression (D) v1.0 outcome scores were collected at baseline and postprocedure follow-up. MethodsQuery of an institutional, patient reported outcome database and subsequent retrospective review of electronic medical records was performed. Statistical analysis comparing baseline and postprocedural PROMIS outcome scores and correlation between these instruments was performed. Additionally, an exploratory investigation of minimal clinically important difference achievement rates was performed. ResultsAnalysis determined a statistically significant improvement in PROMIS PI (p=.017, 95% CI=−8.02 to −1.82) and PROMIS PF (p=.003, 95% CI=0.91–8.72) scores after treatment with TFESIs. At post treatment time points, TFESI had medium effect size on pain (d=0.55) and function (d=0.59). Change in PROMIS D scores (p=.488, 95% CI −1.74–3.54; d=.08) did not demonstrate statistical significance. Pearson correlation demonstrated a moderate negative correlation (r=−0.544, p=.004) between PROMIS PF with PROMIS PI. Correlation between PROMIS PF (r=−0.239, p=.24) and PROMIS PI (r=0.198, p=.33) with PROMIS D was not significant. Fourteen (53.8%) and 9 (34.6%) subjects achieved minimum clinically important difference (MCID) for PROMIS PI and PROMIS PF, respectively. Nine subjects (34.6%) achieved MCID for PROMIS D despite not otherwise reaching statistical significance otherwise. ConclusionsUtilizing PROMIS as an outcome measure, discogenic axial lumbosacral back pain patients appear to benefit from TFESI in terms of pain and physical function. This study contributes to the growing body of literature utilizing PROMIS scores in patients with clinical sequelae of degenerative spinal pathology; however, prospective studies are needed.

Partial Resectoscopic Endometrial Ablation As a Viable Alternative to Global Ablation: A Case Series and Demonstration

Study Objective In the past decade, recognition of late onset endometrial ablation failures - generally resulting from intra-uterine scarring around residual or recovered endometrium - has increased interest in alternative treatments for heavy menstrual bleeding, such as partial ablation. This video presents the history of this uncommon procedure, a case series, and a demonstration of our preferred technique. Design This retrospective case series illustrates operative indications and limited outcomes with an average of 1.4 years of follow-up. The surgical video demonstrates principles for a safe and effective procedure. Setting Minimally invasive gynecologic sub-specialty group within a suburban community teaching hospital system. Patients or Participants From 2010-2019, 11 of 132 (8%) patients identified by billing procedure codes met inclusion criteria that a partial endometrial ablation was performed for heavy menstrual bleeding. Interventions A 9mm bipolar resectoscope was used to remove 50-65% of the endometrium and superficial myometrium (at least 4mm depth), including the anterior or posterior surface and the lateral walls. Any concomitant focal pathology was also removed. Measurements and Main Results Seven of 11 patients were 45 years old or younger. All patients declined or failed hormonal therapies and declined hysterectomy. Operative time averaged 45 minutes. There were no intraoperative or postoperative complications. Of 9 patients with at least 1 year of follow-up, 6 reported eumenorrhea. Ultimately 3 of 11 patients underwent or desired hysterectomy to date. Conclusion This video reviews the limited literature and one center's experience with partial resectoscopic endometrial ablation as an alternative to global ablation and includes a demonstration of proper technique. In the past decade, recognition of late onset endometrial ablation failures - generally resulting from intra-uterine scarring around residual or recovered endometrium - has increased interest in alternative treatments for heavy menstrual bleeding, such as partial ablation. This video presents the history of this uncommon procedure, a case series, and a demonstration of our preferred technique. This retrospective case series illustrates operative indications and limited outcomes with an average of 1.4 years of follow-up. The surgical video demonstrates principles for a safe and effective procedure. Minimally invasive gynecologic sub-specialty group within a suburban community teaching hospital system. From 2010-2019, 11 of 132 (8%) patients identified by billing procedure codes met inclusion criteria that a partial endometrial ablation was performed for heavy menstrual bleeding. A 9mm bipolar resectoscope was used to remove 50-65% of the endometrium and superficial myometrium (at least 4mm depth), including the anterior or posterior surface and the lateral walls. Any concomitant focal pathology was also removed. Seven of 11 patients were 45 years old or younger. All patients declined or failed hormonal therapies and declined hysterectomy. Operative time averaged 45 minutes. There were no intraoperative or postoperative complications. Of 9 patients with at least 1 year of follow-up, 6 reported eumenorrhea. Ultimately 3 of 11 patients underwent or desired hysterectomy to date. This video reviews the limited literature and one center's experience with partial resectoscopic endometrial ablation as an alternative to global ablation and includes a demonstration of proper technique.

Focal Pathology of Mammary Glands in Teenage Girls

Diseases of the mammary glands (usually benign) have the incidence of 5–12% in the structure of children diseases. Breast cancer is extremely rare (less than 1% of all breast diseases). This review contains actual data on the most common focal pathology of mammary glands in teenage girls such as: focal hyperplasia, cysts and breast fibroepithelial tumors. Clinical manifestations, morphological picture and diagnostics are described. Main approaches to treatment of patients with focal pathology of mammary glands are defined. The presented data is crucial for timely diagnosis of focal pathology of mammary glands, selection of examination tactics, management and necessary measures for oncological diseases prevention in children.

Is it safe to stop at C7 during multilevel posterior cervical decompression and fusion? – multicenter analysis

Despite a number of studies addressing the anatomical and biomechanical challenges of long segment, posterior cervical fusion surgery, recommendations for appropriate caudal "end level" vary widely. Compare revision rates, patient reported outcomes and radiographic outcomes in patients in whom 3+ level posterior fusions ended in the cervical spine versus those in whom the fusion was extended into the thoracic spine. Multicenter retrospective analysis. Visual analog scale (VAS), Oswestry disability index (ODI), cervical lordosis, C2-C7 sagittal plumbline, T1 slope, and revision rate. We assembled a radiographic and clinical database of patients that had undergone three or more level posterior cervical fusions for degenerative disease from January 2013 to May 2015 at one of four busy spine centers. Only those patients with at least 2 years of postoperative (postop) follow-up were included. Patients were divided into two groups: group I (fusion ending at C6 or C7) and group II (fusion extending into the thoracic spine). All radiographic measurements (cervical lordosis, T1 slope, and C2-C7 sagittal plumbline) were performed by an independent experienced clinical researcher. Two hundred and sixty-four patient cases were reviewed and sorted into the two outlined groups, Group I (n=168) and Group II (n=96). Demographically, mean age, percentage of females, non-smokers and anterior support were greater in Group II than in Groups I (p<.05). Mean estimated blood loss (EBL), operative time (OR) and length of hospital stay (LOS) were significantly higher in Group II (p<.05). Rate of revision was not clinically or statistically significantly different (p>.05) between Group I (11.1%) and Group II (9.4%). The majority of the revision surgeries occurred between 2 to 5 years postop. A greater number of subjacent degeneration/spondylolisthesis events were noted in Group I compared with Group II (3.6% vs. 1.2%). There were significant improvements in mean clinical outcomes (ie, VAS and ODI) at two years postop in both groups, but there were no statistically significant differences between the groups (p>.05). Mean cervical lordosis at 2 years postop improved in all groups (12.8° vs. 14.1°); however, there was no significant statistical difference in change for mean cervical lordosis (2 weeks vs. 2 year postop) between the two groups. Similary, there were no significant statistical differences in change for mean C2-C7 sagittal plumbline and T1 slope (2 weeks vs. 2 year postop) between the two groups(p>.05). Caudal end level did not significantly affect revision rates, patient reported outcomes or radiographic outcomes. Higher EBL, OR, and LOS in group II suggest that, absent focal C7-T1 pathology, extension of posterior cervical fusions into the thoracic spine may not be necessary. Extension of posterior cervical fusions into the thoracic spine may be recommended for higher risk patients with limitations to strong C7 bone anchorage. In others, it is safe to stop at C7.

Biotin-Responsive Basal Ganglia Disease: EEG Characteristics and Seizure Phenotypes

Objective: To discuss EEG findings and seizure phenotypes in “biotin-responsive basal ganglia disease” (BRBGD), a rare, autosomal recessive, life-threatening, but potentially reversible encephalopathy with characteristic MRI findings. Methods: We report on two patients with BRBGD in whom we correlated the EEG findings with MRI abnormalities. We also review the literature on EEG and seizure types in this syndrome. Results: Our patient 1 had a focal electrographic seizure corresponding to a homotopic focal MRI pathology. Patient 2 had a normal EEG. The literature review showed both partial and generalized convulsive seizures with occasional occurrence of infantile spasms. Conclusion: 1- The data suggest both electro-clinical and electro-anatomical dissociation in BRBGD. 2-Seizures in BRBGD are primarily caused by the underlying metabolic encephalopathy, although focal epileptiform discharges may signify a homotopic focal cerebral pathology caused by BRBGD.

Magnetic Resonance Imaging of Enthesitis in Spondyloarthritis, Including Psoriatic Arthritis-Status and Recent Advances.

Enthesitis, inflammation at the attachment sites of tendons, ligaments, fascia, and joint capsules to bones plays a critical role in the pathogenesis of spondyloarthritis (SpA), including psoriatic arthritis (PsA). Magnetic resonance imaging (MRI) has aided in a better understanding of pathophysiology, early diagnosis, prognostication, therapeutic outcomes, and follow up of enthesitis. The concept of enthesitis as a focal insertional pathology has transformed over the past decade, with the help of MRI, to a more widespread entity involving both bone and surrounding soft tissues. The utility of MRI in the differential diagnosis of suspected enthesitis has recently been explored. With the emergence of the treat-to-target concept, and a domain-based approach in the management of SpA, objective and sensitive monitoring of response to targeted therapy becomes prudent. Properties like high sensitivity, ability to image intra-osseous pathology along with surrounding structures exemplify the utility of MRI technology. Considering the lack of a comprehensive, validated MRI score the Outcome Measures in Rheumatology (OMERACT) MRI in Arthritis Working Group, informed by a systematic literature review, developed the first international, consensus-based MRI-scoring system, combined with MRI definitions of pathologies for enthesitis in patients with spondyloarthritis (SpA) and PsA. An atlas with representative images of each grade of the scoring system was subsequently developed by the group to aid readers interested in using the heel enthesitis MRI scoring system (HEMRIS). The HEMRIS can find utility in clinical trials targeting enthesitis as the primary outcome. MRI also finds value for global assessment of the total burden of enthesitis. The concept of whole-body MRI (WBMRI), enabling visualization of entheses throughout the body using a single image is relatively new. The MRI whole-body score for inflammation in peripheral joints and entheses (MRI-WIPE) is a promising scoring system, which is undergoing further testing in clinical trials and longitudinal cohorts evaluating global measures of inflammation at entheses. This review discusses the role of MRI in diagnosis and monitoring of enthesitis in SpA and PsA, along with recent advances in the field, based on published literature.

Focal lung pathology detection in radiology: Is there an effect of experience on visual search behavior?

In radiology, 60% to 80% of diagnostic errors are perceptual. The use of more efficient visual search behaviors is expected to reduce these errors. We collected eye-tracking data from participants with different levels of experience when interpreting chest X-rays during the completion of a pathology-detection task. Eye-tracking measures were assessed in the context of three existing visual search theories from the literature to understand the association between visual search behavior and underlying processes: the long-term working memory theory, the information-reduction hypothesis, and the holistic model of image perception. The most experienced participants (radiology residents) showed the highest level of performance, albeit their visual search behaviors did not differ from the intermediate group. This suggests that radiology residents better processed the represented information on the X-ray, using a visual search strategy similar to the intermediate group. Since similar visual search resulted in more information extraction in the radiology residents compared with the intermediates, we suggest that this result might support the long-term working memory theory. Furthermore, compared with novices, intermediates and radiology residents fixated longer on areas that were more important to avoid missing any pathology, which possibly confirmsthe information-reduction hypothesis. Finally, the larger distances between fixations observed in more experienced participants could support theholistic model of image perception. In addition, measures of generic skills were related to a lower time cost for switching between global and local information processing. Our findings suggest that the three theories may be complementary in chest X-ray interpretation. Therefore, a unified theory explaining perceptual-cognitive superiority in radiology is considered.

Indications for abdominal imaging: When and what to choose?

Imaging has a very important role in evaluating abdominal pathology. A good knowledge of indications is of crucial importance in the management of the patient with abdominal pathology. Ultrasound, which on its own can lead to an accurate diagnosis, plays a pivotal role in the management of abdominal pathology. The use of ultrasound contrast agents has significantly improved ultrasound diagnostic capacities in both hepatic and non-hepatic pathology. The use of computed tomography should be limited due to the potential harmful side effects of ionizing radiation, but it has established roles in evaluating severe abdominal traumatic and non-traumatic emergencies as well as in staging oncologic patients. Magnetic resonance imaging has very limited utility in abdominal emergencies due to difficulty of accessing the scanner and the long duration of the examination compared to computed tomography or ultrasound. However, magnetic resonance imaging has well-established clinical roles particularly for evaluating diffuse or focal hepatic pathology, benign and malignant bile duct pathology, pancreatic tumors, inflammatory bowel disease and rectal tumors. The aims of the following paper are to familiarize the clinician with the indications for imaging in abdominal pathology, to guide the clinician and radiologist in choosing the correct technique for a particular clinical situation, to prevent the overuse of imaging techniques and to prevent misdiagnosis of disease and incorrect therapy resulting from inappropriate imaging.

Decompressive craniectomy in pediatric non-traumatic intracranial hypertension: a single center experience

Purpose: To study the clinical profile and predictors of outcome in children undergoing decompressive craniectomy (DC) for non-traumatic intracranial hypertension (ICH).Materials and methods: Mixed observational study of children, aged 1 month-12 years, who underwent DC for non-traumatic ICH in a tertiary care pediatric intensive care unit from 2012 to 2017. Data on clinical profile and outcome were retrieved retrospectively and survivors were assessed prospectively. The primary outcome was neurological outcome using Glasgow Outcome Scale-Extended (GOS-E) at minimum 6 months’ post-discharge. GOS-E of 1–4 were classified as a poor and 5–8 as a good outcome.Results: Thirty children, median (IQR) age of 6.5 (2, 50) months, underwent DC; of which 26 (86.7%) were boys. Altered sensorium (n = 26, 86.7%), seizures (n = 25, 83.3%), pallor (n = 19, 63.3%) and anisocoria (n = 14, 46.7%) were common signs and symptoms. Median (IQR) Glasgow Coma Scale at admission was 9 (6,11). Commonest etiology was intracranial bleed (n = 24; 80%). Median (IQR) time to DC was 24 (24,72) h. Eight (26.7%) children died; 2 during PICU stay and 6 during follow-up. Neurological sequelae at discharge (n = 28) were seizures (n = 25; 89.2%) and hemiparesis (n = 16; 57.1%). Twenty-one children were followed-up at median (IQR) duration of 12 (6,54) months. Good neurological outcome was seen in 14/29 (48.2%) and hemiparesis in 10/21 (47.6%) patients. On regression analysis, anisocoria at admission was an independent predictor of poor outcome [OR 7.33; 95%CI: 1.38–38.87; p = 0.019].Conclusions: DC is beneficial in children with non-traumatic ICH due to a focal pathology and midline shift. Evidence on indications and timing of DC in NTC is still evolving.

Brain magnetic resonance imaging is a predictor of bimanual performance and executive function in children with unilateral cerebral palsy.

To examine the association between brain magnetic resonance imaging (MRI) characteristics and executive function and bimanual performance in children with unilateral cerebral palsy (CP). Clinical MRI brain scans were classified as: (1) predominant pathological pattern (normal, white matter injury [WMI]; grey matter injury; focal vascular insults [FVI]; malformations; or miscellaneous); and (2) focal lesions (frontal, basal ganglia, and/or thalamus). Assessments included: (1) bimanual performance; (2) unimanual dexterity; and (3) executive function tasks (information processing, attention control, cognitive flexibility, and goal setting) and behavioural ratings (parent). From 131 recruited children, 60 were ineligible for analysis, leaving 71 children (47 males, 24 females) in the final sample (mean age 9y [SD 2y], 6y-12y 8mo). Brain MRIs were WMI (69%) and FVI (31%); and frontal (59%), thalamic (45%), basal ganglia (37%), and basal ganglia plus thalamic (21%). Bimanual performance was lower in FVI versus WMI (p<0.003), and with frontal (p=0.36), basal ganglia (p=0.032), and thalamic/basal ganglia lesions (p=0.013). Other than information processing, executive function tasks were not associated with predominant pattern. Frontal lesions predicted attention control (p=0.049) and cognitive flexibility (p=0.009) but not goal setting, information processing, or behavioural ratings. Clinical brain MRI predicts cognitive and motor outcomes when focal lesions and predominate lesion patterns are considered. What this paper adds Early brain magnetic resonance imaging (MRI) predicts bimanual performance and cognitive outcomes. Brain MRI may identify children requiring targeted interventions. Basal ganglia with/without thalamic lesions predicted bimanual performance. Frontal lesions were associated with attention control and cognitive flexibility. Brain MRI predominant patterns predicted motor, not cognitive outcomes, other than information processing.

Negative outcome predictors of West syndrome

West syndrome is infantile epileptic encephalopathy characterized by the triad of symptoms: infantile spasms, changes in the electroencephalogram (EEG) in the form of hypsarrhythmia and psychomotor retardation. Revealing of the predictors of clinical outcome can contribute to the selection of the optimal therapy and determine the terms of dynamic monitoring and improve treatment outcome.&#x0D; Aim: to identify predictors of West syndrome outcome.&#x0D; Materials and methods. The study included 132 patients who underwent treatment from 2000 to 2018. At the onset of the observation the age of children was from 5 months to 17 years 11 months. The age of the onset of spasms ranged from 1 day to 3 years 2 months. Depending on the etiological factor patients were divided into 3 groups: group 1 patients with a structural form (60 patients; 45.5%), group 2 patients with a genetic form (39 children; 29.5%), group 3 patients with the disease of unknown etiology (33 children; 25.0%). Evaluating the treatment, special attention was paid to the effectiveness of the first three lines of AEDs and hormones, as well as the further selection of AEDs.&#x0D; Results. Epileptic spasms were controlled in 76 children (57.6%), all seizures were controlled in 48 (36.4%) children. Patients of the 3rd group demonstrated a higher frequency of spasms arresting (87.9% in comparison to 48.7 and 46.7%) and complete remission (72.7% in comparison to 26.7 and 27.6% respectively). Normal neuropsychic development before the onset of spasms, the absence of epi-activity or the presence of regional epi-activity on the EEG in dynamics, the presence of diffuse changes in MRI had positive prognostic value for spasms control. Neonatal seizures, the presence of epi-activity on the EEG and focal deficiency before spasms, the presence of other seizures, pathology of vision and hearing, and necessity to use 2 drugs had negative prognostic value. The best compensation of motor and psychoverbal development was noted in patients who had remission.&#x0D; Conclusions. Predictors of negative outcome of West syndrome include structural and genetic forms of the disease, neonatal seizures, epi-activity on EEG, impaired neuropsychic development and the focal pathology before spasms, the presence of other seizures, the persistence of epi-activity in dynamics and the absence of the first-line therapy effect.

THE NEAREST AND LONG-TERM RESULTS OF SURGICAL TREATMENT OF FOCAL PATHOLOGY OF THE THYROID GLAND

Currently, thyroid gland diseases (TG) are in second place among other diseases of the endocrine system and the need for surgical interventions is increasing. Therefore the purpose of article is the analysis of the immediate and long-term results of surgical treatment of focal pathology of a thyroid gland. To a basis of work it is provided 10 - summer experience of BIH UR «Republican Clinical Diagnostic Center of Public Health Ministry of the Udmurt Republic». For characteristic of clinical material and studying of structure of nodal thyroid diseases stories of diseases and data of histologic researches of drugs TG of 623 patients were analysed. At various formations of a thyroid gland operations were carried out on the immediate and long-term results are analysed. In good-quality and malignancies of a thyroid gland specific indicators of local pulse and not pulse optical density are found. They define effective surgical tactics, indications to different types of an operative measure, promote prevention of a recurrence and complications in the next and remote postoperative the periods. The immediate and long-term results of treatment depend on the choice of an operative measure, timely diagnostics and also on recovery treatment after operation. When using in the presurgical period of the local optosonografichesky monitoring of focal pathology of a thyroid gland of bleedings, a necrosis of fabrics, iatrogenic complications and intraoperative damages of vessels, a recurrence offered and developed by us, lethality was not.

Thyroid and Pseudothyroid Dysfunction as a Cause That is Promoting the Relapse of Benign Focal Thyroid Pathology.

Several studies deal with learning causes stipulating nodular formations in the thyroid tissue, including those occurring against the ground of metabolic disorders of thyroid hormones. Our study’s objective was to determine the peculiarities of thyroid homeostasis disorders in patients suffering from benign nodular thyroid pathology with relapses of the disease and its relapse-free course. For this purpose, 96 female patients suffering from nodular thyroid pathology and 20 without thyroid pathology were examined. In the course of the study, the following were found in patients with benign focal thyroid pathology: disorders of the peripheral conversion of the thyroid hormones, compensatory activation of the hypothalamic-pituitary system evident in increased levels of the thyroid-stimulating hormone, ТSH/fT3 and ТSH/fT4 ratios, increasing titers of the anti-thyroid antibodies which can be hazardous for the risk of development of nodules or reflects the process of thyroid tissue damage; high level of thyroglobulin caused by an increased probability of relapse and rate of nodule growth, an increase of the thyroid gland volume associated with activation of the hypothalamic-pituitary system, increased antibodies titer and thyroid gland damage. Thus, changes of the examined indices in the blood can be used as prognostic markers concerning the relapse of nodule formation in the thyroid tissue.

Multifocal electroretinography in the study of focal and diffuse damage to the rabbit retina

To evaluate the possibility of using the system "Neuro-ERG" (with a module for multifocal ERG) in the study of focal and diffuse pathology in laboratory animals (rabbits). Focal retinal damage was modelled in 5 eyes of 5 rabbits by singular laser pulses (532 nm, 100 ms, power 30, 60, 100, 150 and 200 mW) and diffuse retinal damage was modelled in 5 eyes of 5 rabbits by exposure to polychromatic light for 14 days (9500 lm, 6400 K, 230 mW/cm2, 8 h/day). The pair of eyes and areas of intact retina in the eyes with focal retinal damage were used for control. Multifocal electroretinography (mfERG) was recorded using the «Neuro-ERG» system (Neurosoft, Russia) before exposure, after 1 hour (in focal damage model), and 1, 7 and 14 days after exposure. In addition, three-time recording of mfERG was made before and after the experiments. Analysis included the amplitude and time characteristics of mfERG components, as well as the level of reproducibility of mfERG at each recording. In the modeling of focal damage of the rabbit retina, significant changes in mfERG (pattern stimulus consisted of 61 hexagons) were detected when the retinal damage area was more than 170 µm in diameter or more than 35% of the hexagon area in the pattern-stimulus. A significant moderate inverse correlation (0.52<r<0.71, p<0.01) was found between the damage area and the amplitude P1 and density of the bioelectric response of the P1 component. When modeling diffuse damage, significant changes in mfERG (an increase of implict-time of P1 and a decrease in the amplitude and density of the bioelectric response of the P1 component) were detected on the 7th day after the beginning of exposure. Variability of mfERG recording on each registration averaged 5%. Multifocal ERG registration systems, including «Neuro-ERG» (Neurosoft, Russia), can be used in experimental studies of vitreoretinal pathology with rabbits as biological objects.

Using Two- and Three-Dimensional Human iPSC Culture Systems to Model Psychiatric Disorders.

Psychiatric disorders are among the most challenging human diseases to understand at a mechanistic level due to the heterogeneity of symptoms within established diagnostic categories, the general absence of focal pathology, and the genetic complexity inherent in these mostly polygenic disorders. Each of these features presents unique challenges to disease modeling for biological discovery, drug development, or improved diagnostics. In addition, live human neural tissue has been largely inaccessible to experimentation, leaving gaps in our knowledge derived from animal models that cannot fully recapitulate the features of the disease, indirect measures of brain function in human patients, and from analyses of postmortem tissue that can be confounded by comorbid conditions and medication history.

Morphological MRI phenotypes of multiple sclerosis differ in resting-state brain function

We aimed to assess differences in resting-state functional connectivity (FC) between distinct morphological MRI-phenotypes in multiple sclerosis (MS). Out of 180 MS patients, we identified those with high T2-hyperintense lesion load (T2-LL) and high normalized brain volume (NBV; a predominately white matter damage group, WMD; N = 37) and patients with low T2-LL and low NBV (N = 37; a predominately grey matter damage group; GMD). Independent component analysis of resting-state fMRI was used to test for differences in the sensorimotor network (SMN) between MS MRI-phenotypes and compared to 37 age-matched healthy controls (HC). The two MS groups did not differ regarding EDSS scores, disease duration and distribution of clinical phenotypes. WMD compared to GMD patients showed increased FC in all sub-units of the SMN (sex- and age-corrected). WMD patients had increased FC compared to HC and GMD patients in the central SMN (leg area). Only in the WMD group, higher EDSS scores and T2-LL correlated with decreased connectivity in SMN sub-units. MS patients with distinct morphological MRI-phenotypes also differ in brain function. The amount of focal white matter pathology but not global brain atrophy affects connectivity in the central SMN (leg area) of the SMN, consistent with the notion of a disconnection syndrome.

Regional hippocampal diffusion abnormalities associated with subfield-specific pathology in temporal lobe epilepsy.

ObjectiveHippocampal sclerosis (HS) is the most common pathology and best predictor of surgical outcome for medically refractory patients with temporal lobe epilepsy (TLE). Current clinical MRI methods can detect HS, but subfield pathology is poorly characterized, limiting accurate prediction of seizure‐free outcomes after surgery. Diffusion tensor imaging (DTI) can probe regional microstructural changes associated with focal hippocampal pathology, but is typically limited by low‐resolution whole‐brain acquisitions.MethodsHigh‐resolution (1 × 1 × 1 mm3) DTI, T1, and quantitative T2 of the hippocampus was acquired in 18 preoperative TLE patients and 19 healthy controls. Diffusion images were qualitatively assessed for loss of internal architecture, and whole‐hippocampus diffusion, volume, and quantitative T2 were compared across groups. Regional hippocampal diffusion abnormalities were examined in all subjects and compared to histology in four subjects who underwent anterior temporal lobectomy.ResultsHigh‐resolution mean diffusion‐weighted images enabled visualization of internal hippocampal architecture, used to visually identify HS with 86% specificity and 93% sensitivity. Mean diffusivity (MD) elevations were regionally heterogenous within the hippocampus and varied across TLE patients. The spatial location of diffusion abnormalities corresponded with the location of focal subfield neuron loss, gliosis, and reduced myelin staining abnormalities identified with postsurgical histology in four subjects who underwent anterior temporal lobectomy. Whole‐hippocampus MD and T2 relaxation times were higher, and fractional anisotropy (FA) and volumes were lower in TLE patients relative to controls. Left hippocampus MD correlated with verbal memory in the TLE group.SignificanceVisualization of internal architecture and focal diffusion abnormalities on high‐resolution diffusion imaging suggests potential clinical utility of diffusion imaging in TLE and may have significant implications for surgical planning and prediction of seizure‐free outcomes in individual patients.