Weight reduction and the impact on apnea-hypopnea index: A systematic meta-analysis.

Obstructive sleep apnea (OSA) is strongly associated with obesity. While the relationship between weight reduction and apnea-hypopnea index improvement has been documented, to our knowledge, it has not been quantified adequately. Therefore, this study aimed to quantify the relationship between weight reduction and AHI change. METHODS: A systematic literature search was performed using meta-analyses (PRISMA) guidelines for studies reporting AHI and weight loss in people with obesity/overweight and OSA between 2000 and 2023. A linear and quadratic model (weighted by treatment arm sample size) predicted percent change from baseline AHI against mean percent change from baseline weight. The quadratic term was statistically significant (P < 0.05), so the quadratic model (with 95 % prediction interval) was used. RESULTS: The literature search identified 27 studies/32 treatment arms: 15 using bariatric surgery and lifestyle intervention each and 2 using pharmacological interventions. Included studies were ≥3 months with weight intervention and participants had AHI ≥15/h. Weight reduction in people with OSA and obesity was associated with improvements in the severity of OSA. BMI reduction of 20 % was associated with AHI reduction of 57 %, while further weight reduction beyond 20 % in BMI was associated with a smaller effect on AHI. As the prediction intervals are relatively wide, a precise relationship could not be conclusively established. CONCLUSION: The degree of AHI index improvement was associated with the magnitude of weight reduction. The model suggests that with progress in weight reduction beyond 20 %, the incremental decrease in BMI appeared to translate to a smaller additional effect on AHI.

Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity.

BACKGROUND: Obstructive sleep apnea is characterized by disordered breathing during sleep and is associated with major cardiovascular complications; excess adiposity is an etiologic risk factor. Tirzepatide may be a potential treatment. METHODS: We conducted two phase 3, double-blind, randomized, controlled trials involving adults with moderate-to-severe obstructive sleep apnea and obesity. Participants who were not receiving treatment with positive airway pressure (PAP) at baseline were enrolled in trial 1, and those who were receiving PAP therapy at baseline were enrolled in trial 2. The participants were assigned in a 1:1 ratio to receive either the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or placebo for 52 weeks. The primary end point was the change in the apnea-hypopnea index (AHI, the number of apneas and hypopneas during an hour of sleep) from baseline. Key multiplicity-controlled secondary end points included the percent change in AHI and body weight and changes in hypoxic burden, patient-reported sleep impairment and disturbance, high-sensitivity C-reactive protein (hsCRP) concentration, and systolic blood pressure. RESULTS: At baseline, the mean AHI was 51.5 events per hour in trial 1 and 49.5 events per hour in trial 2, and the mean body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) was 39.1 and 38.7, respectively. In trial 1, the mean change in AHI at week 52 was -25.3 events per hour (95% confidence interval [CI], -29.3 to -21.2) with tirzepatide and -5.3 events per hour (95% CI, -9.4 to -1.1) with placebo, for an estimated treatment difference of -20.0 events per hour (95% CI, -25.8 to -14.2) (P<0.001). In trial 2, the mean change in AHI at week 52 was -29.3 events per hour (95% CI, -33.2 to -25.4) with tirzepatide and -5.5 events per hour (95% CI, -9.9 to -1.2) with placebo, for an estimated treatment difference of -23.8 events per hour (95% CI, -29.6 to -17.9) (P<0.001). Significant improvements in the measurements for all prespecified key secondary end points were observed with tirzepatide as compared with placebo. The most frequently reported adverse events with tirzepatide were gastrointestinal in nature and mostly mild to moderate in severity. CONCLUSIONS: Among persons with moderate-to-severe obstructive sleep apnea and obesity, tirzepatide reduced the AHI, body weight, hypoxic burden, hsCRP concentration, and systolic blood pressure and improved sleep-related patient-reported outcomes. (Funded by Eli Lilly; SURMOUNT-OSA ClinicalTrials.gov number, NCT05412004.).

Evidence-based commentary on the diagnosis, management, and further research of degenerative cervical spinal cord compression in the absence of clinical symptoms of myelopathy.

Degenerative cervical myelopathy (DCM) represents the final consequence of a series of degenerative changes in the cervical spine, resulting in cervical spinal canal stenosis and mechanical stress on the cervical spinal cord. This process leads to subsequent pathophysiological processes in the spinal cord tissues. The primary mechanism of injury is degenerative compression of the cervical spinal cord, detectable by magnetic resonance imaging (MRI), serving as a hallmark for diagnosing DCM. However, the relative resilience of the cervical spinal cord to mechanical compression leads to clinical-radiological discordance, i.e., some individuals may exhibit MRI findings of DCC without the clinical signs and symptoms of myelopathy. This degenerative compression of the cervical spinal cord without clinical signs of myelopathy, potentially serving as a precursor to the development of DCM, remains a somewhat controversial topic. In this review article, we elaborate on and provide commentary on the terminology, epidemiology, natural course, diagnosis, predictive value, risks, and practical management of this condition-all of which are subjects of ongoing debate.

Tirzepatide for the treatment of obstructive sleep apnea: Rationale, design, and sample baseline characteristics of the SURMOUNT -OSA phase 3 trial.

BACKGROUND: Weight reduction is a standard recommendation for obstructive sleep apnea (OSA) treatment in people with obesity or overweight; however, weight loss can be challenging to achieve and maintain without bariatric surgery. Currently, no approved anti-obesity medication has demonstrated effectiveness in OSA management. This study is evaluating the efficacy and safety of tirzepatide for treatment of moderate to severe OSA in people with obesity. METHODS: SURMOUNT-OSA, a randomized, placebo -controlled, 52-week phase 3 trial, is investigating the efficacy and safety of tirzepatide for treatment of moderate to severe OSA (apnea hypopnea- index ≥15 events/h) in participants with obesity (body mass index ≥30 kg/m2) and an established OSA diagnosis. SURMOUNT-OSA is made of 2 intervention-specific appendices (ISAs): ISA-1 includes participants with no current OSA treatment, and ISA-2 includes participants using positive airway pressure therapy. Overall, 469 participants have been randomized 1:1 to receive tirzepatide or placebo across the master protocol (ISA-1, n = 234; ISA-2, n = 235). All participants are also receiving lifestyle intervention for weight reduction. RESULTS: The primary endpoint for the individual ISAs is the difference in apnea hypopnea- index response, as measured by polysomnography, between tirzepatide and placebo arms at week 52. Secondary endpoints include sleep apnea-specific hypoxic burden, functional outcomes, and cardiometabolic biomarkers. The trial employs digital wearables, including home sleep testing to capture time to improvement and accelerometry for daily physical activity assessment, to evaluate exploratory outcomes. CONCLUSION: SURMOUNT-OSA brings a novel design to investigate if tirzepatide provides clinically meaningful improvement in obesity-related OSA by targeting the underlying etiology. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05412004.

Screening and differential diagnosis of delirium in neurointensive stroke patients.

Diagnosing delirium in neurointensive care is difficult because symptoms of delirium, such as inappropriate speech, may be related to aphasia due to primary brain injury. Therefore, validated screening tools are needed. The aim of this study was to compare two Czech versions of already validated screening tools - the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) - in a cohort of acute stroke patients. We also aimed to assess the pitfalls of delirium detection in the context of non-convulsive status epilepticus (NCSE). We analysed 138 stroke patients admitted to the neurological intensive care unit (ICU) or stroke unit. According to expert judgement, which was used as the gold standard, 38 patients (27.54%) developed delirium. The sensitivity and specificity of the ICDSC were 91.60% and 95.33%, respectively, and the positive and negative predictive values were 76.76% and 98.54%, respectively. Similarly, the sensitivity and specificity of CAM-ICU were 75.63% and 96.74%, respectively, and the positive and negative predictive values were 79.65% and 95.93%, respectively. We did not detect an episode of NCSE mimicking delirium in any of our stroke patients who were judged to be delirious by expert assessment. Our results suggest that the ICDSC may be a more suitable tool for delirium screening than the CAM-ICU in patients with neurological deficit. NCSE as a mimic of delirium seems to be less common in the acute phase of stroke than previously reported.

Screening for dysphagia in patients with relapsing-remitting multiple sclerosis.

BACKGROUND: In multiple sclerosis (MS), dysphagia is an important and common clinical symptom. Although often overlooked and underdiagnosed, it can have a significant impact on a patient's life, including social integration, and it can lead to malnutrition, aspiration pneumonia, and suffocation, i.e., life-threatening complications. Early detection of dysphagia is essential to prevent these risks. However, the optimal screening method and the inter-relationship between different methods used for dysphagia screening are not clear. The aim of this study was to compare the diagnostic performance of a simple question about swallowing problems, the DYsphagia in MUltiple Sclerosis (DYMUS) swallowing questionnaire, and the Timed Water Swallowing Test (TWST) to detect dysphagia in people with relapsing-remitting MS (RRMS). METHODS: Patients with MS were asked about subjective swallowing difficulties and, regardless of their response, completed the DYMUS questionnaire and underwent the TWST at their routine follow-up visit. Patients with at least one positive screening method were offered an objective assessment of swallowing function using the Fiberoptic Endoscopic Evaluation of Swallowing (FEES). The results were statistically analyzed and correlated with demographic and MS-related parameters. RESULTS: Of the 304 people with RRMS enrolled in the study, 46 (15.1 %) reported having subjective difficulty swallowing when asked a simple question. The DYMUS questionnaire was positive in 59 (19.4 %) of the 304 patients; 51 (16.8 %) had an abnormality on the TWST. A clear correlation (r = 0.351, p < 0.01) was found between the DYMUS and TWST results, but a significant proportion of patients (about half) had an abnormality on only one of these tests. The positivity of at least one of the screening methods used (DYMUS or TWST) had a better chance of identifying a patient with dysphagia than a simple question (p < 0.001). Of the patients with a positive result for difficulty swallowing, 37 underwent FEES, which confirmed dysphagia in 94.6% of this subgroup. Patients with higher Expanded Disability Status Scale (EDSS) scores, female gender, and older age were at higher risk of developing dysphagia. CONCLUSION: The DYMUS questionnaire and TWST had a confirmed potential to identify more patients with dysphagia than a simple question about swallowing problems. However, our study found only a partial overlap between DYMUS and TWST; a combination of these two methods was more sensitive in identifying patients with MS at risk of dysphagia. Furthermore, the screening showed excellent specificity: almost 95 % of the positively screened patients had dysphagia confirmed by objective methods. Age, female gender, and a higher EDSS score appear to be potential risk factors for dysphagia in patients with MS.

Randomized Double-Blind Placebo-Controlled Trial of the Corticosteroid-Sparing Effects of Immunoglobulin in Myasthenia Gravis.

BACKGROUND AND OBJECTIVES: Myasthenia gravis (MG) is an autoimmune disease characterized by dysfunction at the neuromuscular junction. Treatment frequently includes corticosteroids (CSs) and IV immunoglobulin (IVIG). This study was conducted to determine whether immune globulin (human), 10% caprylate/chromatography purified (IGIV-C) could facilitate CS dose reduction in CS-dependent patients with MG. METHODS: In this randomized double-blind placebo-controlled trial, CS-dependent patients with MG (Myasthenia Gravis Foundation of America Class II-Iva; AChR+) received a loading dose of 2 g/kg IGIV-C over 2 days (maximum 80 g/d) or placebo at week 0 (baseline). Maintenance doses (1 g/kg IGIV-C or placebo) were administered every 3 weeks through week 36. Tapering of CS was initiated at week 9 and continued through week 36 unless the patient worsened (quantitative MG score ≥4 points from baseline). CS doses were increased (based on the current CS dose) in patients who worsened. Patients were withdrawn if worsening failed to improve within 6 weeks or if a second CS increase was required. The primary efficacy end point (at week 39) was a ≥50% reduction in CS dose. Secondary and safety end points were assessed throughout the study and follow-up (weeks 42 and 45). The study results and full protocol are available at clinicaltrials.gov/ct2/show/NCT02473965. RESULTS: The primary end point (≥50% reduction in CS dose) showed no significant difference between the IGIV-C treatment (60.0% of patients) and placebo (63.3%). There were no significant differences for secondary end points. Safety data indicated that IGIV-C was well tolerated. DISCUSSION: In this study, IGIV-C was not more effective than placebo in reducing daily CS dose. These results suggest that the effects of IGIV-C and CS are not synergistic and may be mechanistically different. TRIAL REGISTRATION INFORMATION: The trial was registered on clinicaltrialsregister.eu (EudraCT #: 2013-005099-17) and clinicaltrials.gov (identifier NCT02473965). CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that IVIG infusions in adult patients with MG do not increase the percentage of patients achieving a ≥50% reduction in corticosteroid dose compared with placebo.

Continuum of sensory profiles in diabetes mellitus patients with and without neuropathy and pain.

BACKGROUND: Quantitative sensory testing (QST) assesses the functional integrity of small and large nerve fibre afferents and central somatosensory pathways; QST was assumed to provide insight into the mechanisms of neuropathy. We analysed QST profiles and phenotypes in patients with diabetes mellitus to study whether these could differentiate patients with and without pain and neuropathy. METHODS: A standardized QST protocol was performed and 'loss and gain of function' abnormalities were analysed in four groups of subjects: diabetic patients with painful (pDSPN; n = 220) and non-painful distal symmetric polyneuropathy (nDSPN; n = 219), diabetic patients without neuropathy (DM; n = 23) and healthy non-diabetic subjects (n = 37). Based on the QST findings, diabetic subjects were further stratified into four predefined prototypic phenotypes: sensory loss (SL), thermal hyperalgesia (TH), mechanical hyperalgesia (MH) and healthy individuals. RESULTS: Patients in the pDSPN group showed the greatest hyposensitivity ('loss of function'), and DM patients showed the lowest, with statistically significant increases in thermal, thermal pain, mechanical and mechanical pain sensory thresholds. Accordingly, the frequency of the SL phenotype was significantly higher in the pDSPN subgroup (41.8%), than expected (p < 0.0042). The proportion of 'gain of function' abnormalities was low in both pDSPN and nDSPN patients without significant differences. CONCLUSIONS: There is a continuum in the sensory profiles of diabetic patients, with a more pronounced sensory loss in pDSPN group probably reflecting somatosensory nerve fibre degeneration. An analysis of 'gain of function' abnormalities (allodynia, hyperalgesia) did not offer a key to understanding the pathophysiology of spontaneous diabetic peripheral neuropathic pain. SIGNIFICANCE: This article, using quantitative sensory testing profiles in large cohorts of diabetic patients with and without polyneuropathy and pain, presents a continuum in the sensory profiles of diabetic patients, with more pronounced 'loss of function' abnormalities in painful polyneuropathy patients. Painful diabetic polyneuropathy probably represents a 'more progressed' type of neuropathy with more pronounced somatosensory nerve fibre degeneration. The proportion of 'gain of function' sensory abnormalities was low, and these offer limited understanding of pathophysiological mechanisms of spontaneous neuropathic pain.

Relapsing MRI-negative myelitis associated with myelin-oligodendrocyte glycoprotein autoantibodies: a case report.

BACKGROUND: Serum antibodies to myelin-oligodendrocyte glycoprotein (MOG) are biomarkers of MOG-IgG-associated disorder (MOGAD), a demyelinating disease distinct from both multiple sclerosis and aquaporin-4-IgG neuromyelitis optica spectrum disorder. The phenotype of MOGAD is broad and includes optic neuritis, transverse myelitis, and acute demyelinating encephalomyelitis. Myelitis is common with MOGAD and typically results in acute and severe disability, although prospects for recovery are often favorable with prompt immunotherapy. CASE PRESENTATION: This contribution presents a unique case report of a young male patient exhibiting relapsing myelitis with normal spinal cord and brain magnetic resonance imaging. Comprehensive diagnostic assessment revealed myelin-oligodendrocyte glycoprotein-IgG-associated disorder. CONCLUSION: MOGAD is one of the conditions which should be considered in MRI-negative myelitis. The diagnosis, however, may prove difficult, especially if the patient is not exhibiting other neurological symptoms of MOGAD. Conus or epiconus involvement is common in MOGAD; the patient reported herein exhibited incomplete rostral epiconus symptoms which, together with somatosensory evoked potential abnormalities, led to the diagnosis.

Quantitative MR Markers in Non-Myelopathic Spinal Cord Compression: A Narrative Review.

Degenerative spinal cord compression is a frequent pathological condition with increasing prevalence throughout aging. Initial non-myelopathic cervical spinal cord compression (NMDC) might progress over time into potentially irreversible degenerative cervical myelopathy (DCM). While quantitative MRI (qMRI) techniques demonstrated the ability to depict intrinsic tissue properties, longitudinal in-vivo biomarkers to identify NMDC patients who will eventually develop DCM are still missing. Thus, we aim to review the ability of qMRI techniques (such as diffusion MRI, diffusion tensor imaging (DTI), magnetization transfer (MT) imaging, and magnetic resonance spectroscopy (1H-MRS)) to serve as prognostic markers in NMDC. While DTI in NMDC patients consistently detected lower fractional anisotropy and higher mean diffusivity at compressed levels, caused by demyelination and axonal injury, MT and 1H-MRS, along with advanced and tract-specific diffusion MRI, recently revealed microstructural alterations, also rostrally pointing to Wallerian degeneration. Recent studies also disclosed a significant relationship between microstructural damage and functional deficits, as assessed by qMRI and electrophysiology, respectively. Thus, tract-specific qMRI, in combination with electrophysiology, critically extends our understanding of the underlying pathophysiology of degenerative spinal cord compression and may provide predictive markers of DCM development for accurate patient management. However, the prognostic value must be validated in longitudinal studies.

Semi-automated detection of cervical spinal cord compression with the Spinal Cord Toolbox.

Background: Degenerative cervical spinal cord compression is becoming increasingly prevalent, yet the MRI criteria that define compression are vague, and vary between studies. This contribution addresses the detection of compression by means of the Spinal Cord Toolbox (SCT) and assesses the variability of the morphometric parameters extracted with it. Methods: Prospective cross-sectional study. Two types of MRI examination, 3 and 1.5 T, were performed on 66 healthy controls and 118 participants with cervical spinal cord compression. Morphometric parameters from 3T MRI obtained by Spinal Cord Toolbox (cross-sectional area, solidity, compressive ratio, torsion) were combined in multivariate logistic regression models with the outcome (binary dependent variable) being the presence of compression determined by two radiologists. Inter-trial (between 3 and 1.5 T) and inter-rater (three expert raters and SCT) variability of morphometric parameters were assessed in a subset of 35 controls and 30 participants with compression. Results: The logistic model combining compressive ratio, cross-sectional area, solidity, torsion and one binary indicator, whether or not the compression was set at level C6/7, demonstrated outstanding compression detection (area under curve =0.947). The single best cut-off for predicted probability calculated using a multiple regression equation was 0.451, with a sensitivity of 87.3% and a specificity of 90.2%. The inter-trial variability was better in Spinal Cord Toolbox (intraclass correlation coefficient was 0.858 for compressive ratio and 0.735 for cross-sectional area) compared to expert raters (mean coefficient for three expert raters was 0.722 for compressive ratio and 0.486 for cross-sectional area). The analysis of inter-rater variability demonstrated general agreement between SCT and three expert raters, as the correlations between SCT and raters were generally similar to those of the raters between one another. Conclusions: This study demonstrates successful semi-automated compression detection based on four parameters. The inter-trial variability of parameters established through two MRI examinations was conclusively better for Spinal Cord Toolbox compared with that of three experts' manual ratings.

Degenerative Cervical Myelopathy: Development and Natural History [AO Spine RECODE-DCM Research Priority Number 2].

STUDY DESIGN: Narrative review. OBJECTIVES: To discuss the current understanding of the natural history of degenerative cervical myelopathy (DCM). METHODS: Literature review summarizing current evidence pertaining to the natural history and risk factors of DCM. RESULTS: DCM is a common condition in which progressive arthritic disease of the cervical spine leads to spinal cord compression resulting in a constellation of neurological symptoms, in particular upper extremity dysfunction and gait impairment. Anatomical factors including cord-canal mismatch, congenitally fused vertebrae and genetic factors may increase individuals' risk for DCM development. Non-myelopathic spinal cord compression (NMSCC) is a common phenomenon with a prevalence of 24.2% in the healthy population, and 35.3% among individuals >60 years of age. Clinical radiculopathy and/or electrophysiological signs of cervical cord dysfunction appear to be risk factors for myelopathy development. Radiological progression of incidental Ossification of the Posterior Longitudinal Ligament (OPLL) is estimated at 18.3% over 81-months and development of myelopathy ranges between 0-61.5% (follow-up ranging from 40 to 124 months between studies) among studies. In patients with symptomatic DCM undergoing non-operative treatment, 20-62% will experience neurological deterioration within 3-6 years. CONCLUSION: Current estimates surrounding the natural history of DCM, particularly those individuals with mild or minimal impairment, lack precision. Clear predictors of clinical deterioration for those treated with non-operative care are yet to be identified. Future studies are needed on this topic to help improve treatment counseling and clinical prognostication.

A New Framework for Investigating the Biological Basis of Degenerative Cervical Myelopathy [AO Spine RECODE-DCM Research Priority Number 5]: Mechanical Stress, Vulnerability and Time.

STUDY DESIGN: Literature Review (Narrative). OBJECTIVE: To propose a new framework, to support the investigation and understanding of the pathobiology of DCM, AO Spine RECODE-DCM research priority number 5. METHODS: Degenerative cervical myelopathy is a common and disabling spinal cord disorder. In this perspective, we review key knowledge gaps between the clinical phenotype and our biological models. We then propose a reappraisal of the key driving forces behind DCM and an individual's susceptibility, including the proposal of a new framework. RESULTS: Present pathobiological and mechanistic knowledge does not adequately explain the disease phenotype; why only a subset of patients with visualized cord compression show clinical myelopathy, and the amount of cord compression only weakly correlates with disability. We propose that DCM is better represented as a function of several interacting mechanical forces, such as shear, tension and compression, alongside an individual's vulnerability to spinal cord injury, influenced by factors such as age, genetics, their cardiovascular, gastrointestinal and nervous system status, and time. CONCLUSION: Understanding the disease pathobiology is a fundamental research priority. We believe a framework of mechanical stress, vulnerability, and time may better represent the disease as a whole. Whilst this remains theoretical, we hope that at the very least it will inspire new avenues of research that better encapsulate the full spectrum of disease.

Intensive Circuit Class Therapy in Patients with Relapsing-Remitting Multiple Sclerosis.

OBJECTIVE: Long-term physiotherapy is of considerable benefit to patients with multiple sclerosis (MS) who have motor dysfunction or gait impairment. The aim of this study was to determine the effectiveness of a 12-week intensive circuit class therapy for patients with MS, with a wider focus on fatigue and gait ability. METHODS: A total of 46 patients with relapsing-remitting MS were divided randomly into 2 groups: 23 patients (mean Expanded Disability Status Scale (EDSS) 2.33 ± 0.74) participated in an intensive 12-week course of intensive circuit class therapy, and 23 patients (mean EDSS 2.04 ± 0.63) served as a control group. The EDSS, Timed Up and Go (TUG) test and Four-Stage Balance Test (FSBT) made up the physical testing part, supplemented by questionnaires such as the Modified Fatigue Impact Scale (MFIS), 12-Item Multiple Sclerosis Walking Scale (MSWS-12), Beck Depression Inventory (BDI) and 36-Item Short Form Survey (SF-36). RESULTS: Significant improvements were found among intensive circuit class therapy-exercising patients in FSBT (p < 0.05), TUG test (p < 0.01), MFIS (p < 0.01), BDI (p < 0.05), MSWS-12 (p < 0.05) and the 3 subscales of SF-36 after 12 weeks of intensive circuit class therapy, while there were no significant changes in the control group. CONCLUSION: Intensive circuit class therapy is an effective therapeutic approach for improving gait and balance problems in patients with MS. It has also proved to alleviate fatigue and symptoms of depression.

Evaluating Magnetic Resonance Diffusion Properties Together with Brain Volumetry May Predict Progression to Multiple Sclerosis.

RATIONALE AND OBJECTIVES: Although the gold standard in predicting future progression from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) consists in the McDonald criteria, efforts are being made to employ various advanced MRI techniques for predicting clinical progression. This study's main aim was to evaluate the predictive power of diffusion tensor imaging (DTI) of the brain and brain volumetry to distinguish between patients having CIS with future progression to CDMS from those without progression during the following 2 years and to compare those parameters with conventional MRI evaluation. MATERIALS AND METHODS: All participants underwent an MRI scan of the brain. DTI and volumetric data were processed and various parameters were compared between the study groups. RESULTS: We found significant differences between the subgroups of patients differing by future progression to CDMS in most of those DTI and volumetric parameters measured. Fractional anisotropy of water diffusion proved to be the strongest predictor of clinical conversion among all parameters evaluated, demonstrating also higher specificity compared to evaluation of conventional MRI images according to McDonald criteria. CONCLUSION: Conclusion: Our results provide evidence that the evaluation of DTI parameters together with brain volumetry in patients with early-stage CIS may be useful in predicting conversion to CDMS within the following 2 years of the disease course.

Predictors of Short- and Long-Term Mortality in Ischemic Stroke: A Community-Based Study in Brno, Czech Republic.

BACKGROUND AND OBJECTIVE: Short- and long-term mortality following ischemic stroke (IS) and their predictors have not been defined in the Czech population, and studies on long-term mortality are largely missing for the populations of Central Europe. METHODS: Using the National Register of Hospitalized Patients and the Czech National Mortality Registry, we analyzed data on 1-month, 1-year, and 3-year all-cause mortality for patients admitted with IS to any of the 4 hospitals with a certified stroke unit in Brno, Czech Republic, in 2011. We reviewed discharge summaries and recorded potential factors impacting mortality after the index stroke event. Using univariate and multivariable analyses, we identified predictors of mortality at all 3 time points. RESULTS: In our multivariable model, statin use (odds ratio [OR] 0.095, p < 0.0001), age at stroke (OR 1.03, p = 0.0445), and admission National Institutes of Health Stroke Scale (NIHSS) score (OR 1.16, p < 0.0001) predicted 1-month mortality, while statin use (OR 0.43, p = 0.0004), history of cardiac failure (OR 2.17, p = 0.0137), age at stroke (OR 1.07, p < 0.0001), and admission NIHSS score (OR 1.14, p < 0.0001) predicted 1-year mortality. Statin use (OR 0.54, p = 0.0051), history of cardiac failure (OR 2.13, p = 0.0206), age at stroke (OR 1.07, p < 0.0001), and admission NIHSS score (OR 1.11, p < 0.0001) also predicted 3-year mortality. CONCLUSIONS: Our study is the first to report data on short- and long-term mortality rates and their predictors in patients hospitalized with IS in the Czech population. Our results indicate that mortality rates and predictors of mortality are consistent with those reported in studies from other populations throughout the world.

Risk factors for depression and anxiety in painful and painless diabetic polyneuropathy: A multicentre observational cross-sectional study.

BACKGROUND: Despite the high prevalence of depression and anxiety in chronic pain conditions, current knowledge concerning emotional distress among painful diabetic polyneuropathy (pDSPN) and other diabetes mellitus (DM) sufferers is limited. METHODS: This observational multicentre cohort study employed the Hospital Anxiety and Depression Scale, the Beck Depression Inventory II and the State-Trait Anxiety Inventory to assess symptoms of depression and anxiety in several groups with diabetes, as well as in a control group. The study cohort included 347 pDSPN patients aged 63.4 years (median), 55.9% males; 311 pain-free diabetic polyneuropathy (nDSPN) patients aged 63.7 years, 57.9% males; 50 diabetes mellitus (DM) patients without polyneuropathy aged 61.5 years, 44.0% males; and 71 healthy controls (HC) aged 63.0 years, 42.3% males. The roles played in emotional distress were explored in terms of the biological, the clinical (diabetes-, neuropathy- and pain-related), the socio-economic and the cognitive factors (catastrophizing). RESULTS: The study disclosed a significantly higher prevalence of the symptoms of depression and anxiety not only in pDSPN (46.7% and 60.7%, respectively), but also in patients with nDSPN (24.4% and 44.4%) and DM without polyneuropathy (22.0% and 30.0%) compared with HCs (7.0% and 14.1%, p < 0.001). Multiple regression analysis demonstrated the severity of pain and neuropathy, catastrophic thinking, type 2 DM, lower age and female sex as independent contributors to depression and anxiety. CONCLUSIONS: In addition to the severity of neuropathic pain and its cognitive processing, the severity of diabetic polyneuropathy and demographic factors are key independent contributors to emotional distress in diabetic individuals. SIGNIFICANCE: In large cohorts of well-defined painless and painful diabetic polyneuropathy patients and diabetic subjects without polyneuropathy, we found a high prevalence of the symptoms of depression and anxiety, mainly in painful individuals. We have confirmed neuropathic pain, its severity and cognitive processing (pain catastrophizing) as dominant risk factors for depression and anxiety. Furthermore, some demographic factors (lower age, female sex), type 2 diabetes mellitus and severity of diabetic polyneuropathy were newly identified as important contributors to emotional distress independent of pain.

In vivo Molecular Signatures of Cervical Spinal Cord Pathology in Degenerative Compression.

Degenerative cervical myelopathy (DCM) is a severe consequence of degenerative cervical spinal cord (CSC) compression. The non-myelopathic stage of compression (NMDC) is highly prevalent and often progresses to disabling DCM. This study aims to disclose markers of progressive neurochemical alterations in NMDC and DCM by utilizing an approach based on state-of-the-art proton magnetic resonance spectroscopy (1H-MRS). Proton-MRS data were prospectively acquired from 73 participants with CSC compression and 47 healthy controls (HCs). The MRS voxel was centered at the C2 level. Compression-affected participants were clinically categorized as NMDC and DCM, radiologically as mild (MC) or severe (SC) compression. CSC volumes and neurochemical concentrations were compared between cohorts (HC vs. NMDC vs. DCM and HC vs. MC vs. SC) with general linear models adjusted for age and height (pFWE < 0.05) and correlated to stenosis severity, electrophysiology, and myelopathy symptoms (p < 0.05). Whereas the ratio of total creatine (tCr) to total N-acetylaspartate (tNAA) increased in NMDC (+11%) and in DCM (+26%) and SC (+21%), myo-inositol/tNAA, glutamate + glutamine/tNAA, and volumes changed only in DCM (+20%, +73%, and -14%) and SC (+12%, +46%, and -8%, respectively) relative to HCs. Both tCr/tNAA and myo-inositol/tNAA correlated with compression severity and volume (-0.376 < r < -0.259). Myo-inositol/tNAA correlated with myelopathy symptoms (r = -0.670), whereas CSC volume did not. Short-echo 1H-MRS provided neurochemical signatures of CSC impairment that reflected compression severity and clinical significance. Whereas volumetry only reflected clinically manifest myelopathy (DCM), MRS detected neurochemical changes already before the onset of myelopathy symptoms.

Progressive Tumefactive Demyelination as the Only Result of Extensive Diagnostic Work-Up: A Case Report.

Tumefactive demyelinating lesions belong to the rare variants of multiple sclerosis, posing a diagnostic challenge since it is difficult to distinguish them from a neoplasm or other brain lesions and they require a careful differential diagnosis. This contribution presents the case report of a young female with progressive tumefactive demyelinating brain and spinal cord lesions. An extensive diagnostic process including two brain biopsies and an autopsy did not reveal any explanatory diagnosis other than multiple sclerosis. The patient was treated by various disease-modifying treatments without significant effect and died from ascendent infection via ventriculoperitoneal shunt resulting in Staphylococcus aureus meningitis.

Diffusion magnetic resonance imaging reveals tract-specific microstructural correlates of electrophysiological impairments in non-myelopathic and myelopathic spinal cord compression.

BACKGROUND AND PURPOSE: Non-myelopathic degenerative cervical spinal cord compression (NMDC) frequently occurs throughout aging and may progress to potentially irreversible degenerative cervical myelopathy (DCM). Whereas standard clinical magnetic resonance imaging (MRI) and electrophysiological measures assess compression severity and neurological dysfunction, respectively, underlying microstructural deficits still have to be established in NMDC and DCM patients. The study aims to establish tract-specific diffusion MRI markers of electrophysiological deficits to predict the progression of asymptomatic NMDC to symptomatic DCM. METHODS: High-resolution 3 T diffusion MRI was acquired for 103 NMDC and 21 DCM patients compared to 60 healthy controls to reveal diffusion alterations and relationships between tract-specific diffusion metrics and corresponding electrophysiological measures and compression severity. Relationship between the degree of DCM disability, assessed by the modified Japanese Orthopaedic Association scale, and tract-specific microstructural changes in DCM patients was also explored. RESULTS: The study identified diffusion-derived abnormalities in the gray matter, dorsal and lateral tracts congruent with trans-synaptic degeneration and demyelination in chronic degenerative spinal cord compression with more profound alterations in DCM than NMDC. Diffusion metrics were affected in the C3-6 area as well as above the compression level at C3 with more profound rostral deficits in DCM than NMDC. Alterations in lateral motor and dorsal sensory tracts correlated with motor and sensory evoked potentials, respectively, whereas electromyography outcomes corresponded with gray matter microstructure. DCM disability corresponded with microstructure alteration in lateral columns. CONCLUSIONS: Outcomes imply the necessity of high-resolution tract-specific diffusion MRI for monitoring degenerative spinal pathology in longitudinal studies.