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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

ObjectiveTo evaluate whether eculizumab helps patients with anti–acetylcholine receptor–positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension.MethodsPatients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study.ResultsA total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1–4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected.ConclusionEculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population.ClinicalTrials.gov IdentifierREGAIN, NCT01997229; REGAIN open-label extension, NCT02301624.Classification of EvidenceThis study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo.

In this multicenter cross-sectional study, we determined sensory profiles of patients with (NL-1) and without neuropathic pain (NL-0) after nerve lesion and assessed immune-related systemic gene expression. Patients and matched healthy controls filled in questionnaires and underwent neurological examination, neurophysiological studies, quantitative sensory testing, and blood withdrawal. Neuropathic pain was present in 67/95 (71%) patients (NL-1). Tactile hyperalgesia was the most prominent clinical sign in NL-1 patients (P < 0.05). Questionnaires showed an association between neuropathic pain and the presence of depression, anxiety, and catastrophizing (P < 0.05 to P < 0.01). Neuropathic pain was frequently accompanied by other chronic pain (P < 0.05). Quantitative sensory testing showed ipsilateral signs of small and large fiber impairment compared to the respective contralateral side, with elevated thermal and mechanical detection thresholds (P < 0.001 to P < 0.05) and lowered pressure pain threshold (P < 0.05). Also, more loss of function was found in patients with NL-1 compared to NL-0. Pain intensity was associated with mechanical hyperalgesia (P < 0.05 to P < 0.01). However, quantitative sensory testing did not detect or predict neuropathic pain. Gene expression of peptidylglycine α-amidating monooxygenase was higher in NL patients compared with healthy controls (NL-1, P < 0.01; NL-0, P < 0.001). Also, gene expression of tumor necrosis factor-α was higher in NL-1 patients compared with NL-0 (P < 0.05), and interleukin-1s was higher, but IL-10 was lower in NL-1 patients compared with healthy controls (P < 0.05 each). Our study reveals that nerve lesion presents with small and large nerve fiber dysfunction, which may contribute to the presence and intensity of neuropathic pain and which is associated with a systemic proinflammatory pattern.

Complex regional pain syndrome (CRPS) typically develops after fracture or trauma. Many of the studies so far have analyzed clinical and molecular markers of CRPS in comparison with healthy or pain controls. This approach, however, neglects mechanisms occurring during physiological trauma recovery. Therefore, we compared the clinical phenotype, sensory profiles, patient-reported outcomes, and exosomal immunobarrier microRNAs (miRs) regulating barrier function and immune response between CRPS and fracture controls (FCs) not fulfilling the CRPS diagnostic criteria. We included upper-extremity FCs, acute CRPS I patients within 1 year after trauma, a second disease control group (painful diabetic polyneuropathy), and healthy controls. Fracture controls were not symptoms-free, but reported some pain, disability, anxiety, and cold pain hyperalgesia in quantitative sensory testing. Patients with CRPS had higher scores for pain, disability, and all patient-reported outcomes. In quantitative sensory testing, ipsilateral and contralateral sides differed significantly. However, on the affected side, patients with CRPS were more sensitive in only 3 parameters (pinprick pain and blunt pressure) when compared to FCs. Two principal components were identified in the cohort: pain and psychological parameters distinguishing FC and CPRS. Furthermore, the immunobarrier-protective hsa-miR-223-5p was increased in plasma exosomes in FCs with normal healing, but not in CRPS and healthy controls. Low hsa-miR-223-5p was particularly observed in subjects with edema pointing towards barrier breakdown. In summary, normal trauma healing includes some CRPS signs and symptoms. It is the combination of different factors that distinguish CRPS and FC. Fracture control as a control group can assist to discover resolution factors after trauma.

Complex regional pain syndrome (CRPS) develops after fracture. The acute CRPS phenotype resembles exaggerated inflammation, which is explained by local and systemic activation of a proinflammatory network including peptides and cytokines. Epidemiologic data suggest that inactivation of the peptidase angiotensin-converting enzyme in patients treated for hypertension increases the odds to develop CRPS. This hint leads us to investigate the serum protease network activity in patients with CRPS vs respective controls. For this purpose, we developed a dabsyl-bradykinin (DBK)-based assay and used it to investigate patients with CRPS, as well as healthy and pain (painful diabetic neuropathy [dPNP]) controls. The major result is that the degradation of DBK to fragments 1-8 and 1-5 in healthy control and dPNP is shifted to higher values for DBK1-8 and lower values for DBK1-5 at 1 hour of incubation in patients with CRPS. Using this novel reporter peptide assay, we have been able to show that the resolving protease network for mediators such as BK might be different in patients with CRPS; having a look at the clinical signs, which resemble inflammation, this resolving protease network is probably less effective in CRPS.

Background: There is an unmet need for treatment options for generalised myasthenia gravis that are effective, targeted, well tolerated, and can be used in a broad population of patients. We aimed to assess the safety and efficacy of efgartigimod (ARGX-113), a human IgG1 antibody Fc fragment engineered to reduce pathogenic IgG autoantibody levels, in patients with generalised myasthenia gravis. Methods: ADAPT was a randomised, double-blind, placebo-controlled, phase 3 trial done at 56 neuromuscular academic and community centres in 15 countries in North America, Europe, and Japan. Patients aged at least 18 years with generalised myasthenia gravis were eligible to participate in the study, regardless of anti-acetylcholine receptor antibody status, if they had a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of at least 5 (>50% non-ocular), and were on a stable dose of at least one treatment for generalised myasthenia gravis. Patients were randomly assigned by interactive response technology (1:1) to efgartigimod (10 mg/kg) or matching placebo, administered as four infusions per cycle (one infusion per week), repeated as needed depending on clinical response no sooner than 8 weeks after initiation of the previous cycle. Patients, investigators, and clinical site staff were all masked to treatment allocation. The primary endpoint was proportion of acetylcholine receptor antibody-positive patients who were MG-ADL responders (≥2-point MG-ADL improvement sustained for ≥4 weeks) in the first treatment cycle. The primary analysis was done in the modified intention-to-treat population of all acetylcholine receptor antibody-positive patients who had a valid baseline MG-ADL assessment and at least one post-baseline MG-ADL assessment. The safety analysis included all randomly assigned patients who received at least one dose or part dose of efgartigimod or placebo. This trial is registered at ClinicalTrials.gov (NCT03669588); an open-label extension is ongoing (ADAPT+, NCT03770403). Findings: Between Sept 5, 2018, and Nov 26, 2019, 167 patients (84 in the efgartigimod group and 83 in the placebo group) were enrolled, randomly assigned, and treated. 129 (77%) were acetylcholine receptor antibody-positive. Of these patients, more of those in the efgartigimod group were MG-ADL responders (44 [68%] of 65) in cycle 1 than in the placebo group (19 [30%] of 64), with an odds ratio of 4·95 (95% CI 2·21–11·53, p

Natalizumab is an effective therapy in the treatment of relapsing-remitting multiple sclerosis; it induces lymphocytosis (NIL, natalizumab-induced lymphocytosis) and changes the peripheral lymphocyte pattern. This study aims to evaluate NIL, peripheral blood lymphocyte subsets, CD4/CD8 ratio, and their impacts on JCV index and clinical data—No Evidence of Disease Activity (NEDA-3) and annualized relapse rate (ARR) in patients treated with natalizumab. Forty-one patients (33 women) were included in the study. The mean duration of follow-up on natalizumab treatment was 6.7 ± 3.2 years. Significant increases in relative lymphocytosis after 1 month, with a median of 40.4% (− 34.1 to + 145.5%) (p

Some muscular dystrophies may have a negative impact on fertility. A decreased ovarian reserve is 1 of the factors assumed to be involved in fertility impairment. AMH (anti-Müllerian hormone) is currently considered the best measure of ovarian reserve. A total of 21 females with myotonic dystrophy type 1 (MD1), 25 females with myotonic dystrophy type 2 (MD2), 12 females with facioscapulohumeral muscular dystrophy (FSHD), 12 female carriers of Duchenne muscular dystrophy mutations (cDMD) and 86 age-matched healthy controls of reproductive age (range 18 – 44 years) were included in this case control study. An enzymatically amplified 2-site immunoassay was used to measure serum AMH level. The MD1 group shows a significant decrease of AMH values (median 0.7 ng/mL; range 0 – 4.9 ng/mL) compared with age-matched healthy controls (P

Background Complement is likely to have a role in refractory generalised myasthenia gravis, but no approved therapies specifically target this system. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis. We further assessed the efficacy and safety of eculizumab in this patient population in a phase 3 trial. Methods We did a phase 3, randomised, double-blind, placebo-controlled, multicentre study (REGAIN) in 76 hospitals and specialised clinics in 17 countries across North America, Latin America, Europe, and Asia. Eligible patients were aged at least 18 years, with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or more, Myasthenia Gravis Foundation of America (MGFA) class II-IV disease, vaccination against Neisseria meningitides, and previous treatment with at least two immunosuppressive therapies or one immunosuppressive therapy and chronic intravenous immunoglobulin or plasma exchange for 12 months without symptom control. Patients with a history of thymoma or thymic neoplasms, thymectomy within 12 months before screening, or use of intravenous immunoglobulin or plasma exchange within 4 weeks before randomisation, or rituximab within 6 months before screening, were excluded. We randomly assigned participants (1:1) to either intravenous eculizumab or intravenous matched placebo for 26 weeks. Dosing for eculizumab was 900 mg on day 1 and at weeks 1, 2, and 3; 1200 mg at week 4; and 1200 mg given every second week thereafter as maintenance dosing. Randomisation was done centrally with an interactive voice or web-response system with patients stratified to one of four groups based on MGFA disease classification. Where possible, patients were maintained on existing myasthenia gravis therapies and rescue medication was allowed at the study physician's discretion. Patients, investigators, staff, and outcome assessors were masked to treatment assignment. The primary efficacy endpoint was the change from baseline to week 26 in MG-ADL total score measured by worst-rank ANCOVA. The efficacy population set was defined as all patients randomly assigned to treatment groups who received at least one dose of study drug, had a valid baseline MG-ADL assessment, and at least one post-baseline MG-ADL assessment. The safety analyses included all randomly assigned patients who received eculizumab or placebo. This trial is registered with ClinicalTrials.gov, number NCT01997229. Findings Between April 30, 2014, and Feb 19, 2016, we randomly assigned and treated 125 patients, 62 with eculizumab and 63 with placebo. The primary analysis showed no significant difference between eculizumab and placebo (least-squares mean rank 56·6 [SEM 4·5] vs 68·3 [4·5]; rank-based treatment difference -11·7, 95% CI -24·3 to 0·96; p=0·0698). No deaths or cases of meningococcal infection occurred during the study. The most common adverse events in both groups were headache and upper respiratory tract infection (ten [16%] for both events in the eculizumab group and 12 [19%] for both in the placebo group). Myasthenia gravis exacerbations were reported by six (10%) patients in the eculizumab group and 15 (24%) in the placebo group. Six (10%) patients in the eculizumab group and 12 (19%) in the placebo group required rescue therapy. Interpretation The change in the MG-ADL score was not statistically significant between eculizumab and placebo, as measured by the worst-rank analysis. Eculizumab was well tolerated. The use of a worst-rank analytical approach proved to be an important limitation of this study since the secondary and sensitivity analyses results were inconsistent with the primary endpoint result; further research into the role of complement is needed. Funding Alexion Pharmaceuticals.

Background This retrospective cross-sectional study reports 1 month and 1 year intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) case fatality rates and their temporal trends in the Czech Republic between 1998 and 2015. Methods Utilizing the National Register of Hospitalized Patients, we randomly selected 600 patients hospitalized for ICH and 600 patients hospitalized for SAH for each year from 1998 to 2015, and identified those who died, regardless of cause, using the Czech National Mortality Registry. We calculated crude and age-adjusted 1 month and 1 year case fatality rates for ICH and SAH. Long-term trends of the crude rates were analyzed using a one-sided Cochran Armitage test. Results A total of 21,600 cases hospitalized for SAH and ICH (10,800 for each) between 1998 and 2015 were randomly selected for analysis. One month case fatality of SAH overall and in women has decreased by 0.2% (P = .006) and 0.3% per year (P = .04), respectively. Overall 1 year case fatality of SAH has decreased by 0.2% per year (P = .03). One month case fatality rate of ICH overall and in men has decreased by 0.2% (p=0.01) and 0.4% (P = .0007), respectively. One year case fatality of ICH in men has decreased by 0.2% per year (P = .047). Conclusions One month and 1 year case fatality rates for SAH and ICH have been decreasing in the Czech Republic between 1998 and 2015, and are similar or lower than those reported from other developed European countries.

Background It is not known if risk factors differ between ischemic stroke (IS) subtypes in Central and Eastern Europe. Aims We performed a community-based analysis of risk factors in patients admitted with IS over a 1 year period in Brno, the second largest city in the Czech Republic (CR). Methods Based on the National Register of Hospitalized Patients, all patients with IS admitted in Brno in 2011 were identified. Comprehensive discharge summaries from hospital admissions were collected and reviewed. IS subtype and relevant risk factors were ascertained for all patients. The age- and sex-adjusted association of risk factors with IS subtypes was determined. Results Overall, 682 patients with IS were admitted in 2011 to Brno hospitals. The distribution of IS subtypes was: 35% cardioembolism, 28% large-artery atherosclerosis, 23% small-artery occlusion, 7% stroke of undetermined etiology, 7% stroke of other determined etiology. Several of the risk factors showed high prevalence in the overall sample – e.g. hypertension (84%) and hyperlipidemia (61%). Cardioembolism as compared to other subtypes was positively associated with a history of myocardial infarction, cardiac failure, and atrial fibrillation. Small-artery occlusion was positively associated with history of dementia. No significant association was found between IS subtypes and history of IS, hypertension, diabetes, obesity, alcohol abuse or smoking. Conclusions We found high frequency of stroke risk factors in all IS subtypes. These findings have implications for stroke prevention strategies in the CR and across Central Europe.

Supplemental Digital Content is available in the text, The aim of this observational, cross-sectional study was to analyse lumbar magnetic resonance imaging (MRI) findings in patients with non-specific chronic low back pain (CLBP), and to evaluate any correlation with pain intensity and their capacity to predict neuropathic pain (NP) in these patients. Fifty-two patients with non-specific CLBP, between 21 and 62 years of age, 50% men, were investigated. Lumbar MRI was employed to assess disc degeneration, endplate changes, Modic changes, disc displacement, facet degeneration, foraminal stenosis and central lumbar spinal stenosis. The characteristics of pain were evaluated and patients were divided into 2 subgroups: with NP (24 patients) and without NP (28 patients), based on the results of a DN4-interview. Correlations between particular MRI changes and their relations to the intensity of pain were evaluated. Logistic regression was used to disclose predictors of NP. Lumbar spine degenerative features were frequent in patients with non-specific CLBP, with L4/5 the most affected level. A significant correlation emerged between the severity of degenerative changes in particular lumbar spine structures (correlation coefficient ranging between 0.325 and 0.573), while no correlation was found between severity of degenerative changes and pain. Multivariate logistic regression revealed only 2 independent predictors of NP – female sex (odds ratio [OR] = 11.9) and a mean pain intensity of ≥4.5 in the previous 4 weeks (OR = 13.1). Degenerative changes in the lumbar spine are frequent MRI findings, but do not correlate with the intensity of pain and do not predict NP. However, female sex and pain intensity do predict NP.

Study Design.Cross-sectional population-based observational study.Objective.To estimate the prevalence of nonmyelopathic spondylotic cervical cord compression (NMSCCC) and cervical spondylotic myelopathy (CSM) in a population older than 40 years and to evaluate the magnetic resonance imaging (MRI) characteristics of these conditions.Summary of Background Data.The prevalence of neither NMSCCC nor CSM is known and there exists no commonly accepted quantitative MRI definition of cervical cord compression.Methods.A group of 183 randomly recruited volunteers, 93 women, median age 66 years, range 40-80 years, underwent MRI examination of the cervical spine and spinal cord on a 1.5 T device using conventional sequences from disc levels C2/C3 to C6/C7. The imaging criterion for cervical cord compression was defined as a change in spinal cord contour at the level of an intervertebral disc on axial or sagittal MRI scan.Results.MRI signs of cervical cord compression were found in 108 individuals (59.0%; 95% CI: 51.5%-66.2%); their numbers increased with age from 31.6% in the fifth decade to 66.8% in the eighth. Clinical signs of symptomatic CSM were found in two cases (1.1%), and 75 cases (41.0%) were without compression. An anteroposterior cervical canal diameter at the level of intervertebral disc (CDdisc) of less than 9.9 mm was associated with the highest probability of NMSCCCodds ratio (OR)=32.5, followed by a compression ratio of 0.5: OR=11.1.Conclusion.The prevalence of NMSCCC in a population older than 40 years is higher than previously reported and increases with age. CDdisc and compression ratio had the highest capacity to discriminate between subjects with and without asymptomatic compression, and their cut-off values could be used to objectify criteria for cervical cord compression.

Background and Purpose Administration of evidence-based pharmacotherapy improves stroke outcome while the use of non–evidence-based medications may not be of benefit and leads to unnecessary patient care costs. The aim of our study was to determine the frequency of guideline-approved and guideline-disapproved pharmacotherapy use in acute stroke management in the Czech Republic (CR). Methods Using the ICD-10 codes, 500 stroke and transient ischemic attack (TIA) patients were randomly selected (random selection of 10 hospitals and then 50 patients from each hospital) from the National Registry of Hospitalized Patients for strokes occurring in 2011. Discharge summaries were reviewed for medications prescribed during hospitalization and at discharge. Results Of the 500 requested discharge summaries, 484 were available for review (response rate 97%). Up to 479 (96%) summaries were sufficient for evaluation and of these, 393 were confirmed to have a stroke or TIA diagnosis. Brain imaging (computed tomography or magnetic resonance imaging) was performed in 97% of the 393 cases. Intravenous thrombolysis was administered to 7% of patients with ischemic stroke (rate was 0%-25% in different hospitals). Up to 97% of patients with ischemic events (TIA or ischemic stroke) were treated with antiplatelets or anticoagulants. At least 1 non–evidence-based medication was administered to 28% of the 393 patients (rate was 5%-89% in different hospitals). Conclusions Guideline-disapproved pharmacotherapy is common in stroke and TIA patients in the CR and processes should be put into place to lessen the frequency of their use. The use of guideline-approved medications is also high and should be further promoted.

Natalizumab-related progressive multifocal leukoencephalopathy (PML) is associated with the presence of anti-John Cunningham virus (JCV) antibodies. The aim of this investigation was to evaluate the long-term stability of anti-JCV antibody serum levels and their relation to various demographic, clinical and radiological characteristics in patients suffering from multiple sclerosis (MS).Seventy-eight relapsing-remitting MS patients treated with natalizumab and evaluated for the presence of serum anti-JCV antibodies over a time period of 1-6 years (3-11 samples) were included in the study. Anti-JCV antibody levels and their changes were correlated with various demographic, clinical and radiological findings.Median follow-up time was 43.5 months, with a median of 5.3 samples available per patient. At baseline, 46 (59%) of the patients were seropositive. During follow-up, anti-JCV antibody status changed from negative to positive or vice versa in 23% of patients. Baseline anti-JCV antibody index correlated positively with age (p = 0.03).with stable positive anti-JCV antibody index had more T2 hyperintensities (20.2 vs. 13.1; p 0.007) on cerebral magnetic resonance imaging (MRI) and were also older than the stable negative anti-JCV antibody index group of patients (45.2.vs. 40.3 years; p 0.01). No significant increase in T2 hyperintensities after seroconversion was revealed. Average duration from beginning of natalizumab therapy to seroconversion (n = 13) was 33 months. Annual seroconversion rate of anti-JCV antibody status was 6.5%. A baseline anti-JCV antibody index of0.90 (n = 33) predicted stable seropositivity (100%), while baseline anti-JCV antibody index0.20 did not predicted stable seronegativity (59%). PML was not diagnosed in any of the patients studied during the follow-up.A positive baseline anti-JCV antibody index of0.90 predicts stable positive JCV serostatus, in contrast with a baseline anti-JCV antibody index of0.20, which remained negative in 59% of cases. Stable positive anti-JCV index patients have more MRI T2 hyperintensities and are older compared with stable negative anti-JCV index patients.

Objectives: Assessment of neuropathic pain in chronic low back syndromes is important. However, there is currently no gold standard for its diagnosis. The aim of this observational cross-sectional study was to assess the neuropathic component of pain in various chronic low back pain syndromes using a range of diagnostic tests. Materials and Methods: Included in this study were 63 patients with chronic axial low back pain (ALBP), 48 patients with chronic radicular syndromes (CRS) comprising 23 with discogenic compression (CDRS) and 25 with lumbar spinal stenosis (LSS), and 74 controls. PainDETECT questionnaire (PDQ), quantitative sensory testing (QST), and skin biopsy with evaluation of intraepidermal nerve fiber density (IENFD) were used to assess the neuropathic pain component. Results: Positive PDQ (>= 19) was obtained more frequently in patients with CDRS and LSS (26.1% and 12.0%, respectively) compared with patients with ALBP (1.6%, P

Study design This was an observational cross-sectional study. Objective The purpose of this study was to evaluate whether the degree of stenosis on magnetic resonance imaging (MRI) relates to the severity of clinical symptoms, disability, or neurological deficit in patients with symptomatic central lumbar spinal stenosis (LSS). Summary of background data The relationship between radiologic findings and the clinical manifestations of LSS remains unclear. Materials and methods A total of 84 patients (42 men, median age 70 y) with neurogenic claudication and central degenerative LSS were included in the study. The MRI parameters describing severity (anteroposterior diameter of dural sac, cross-sectional area of the dural sac, stenosis ratio, and Schizas qualitative morphologic classification were evaluated at maximum stenotic level) and the extent of stenosis (the number of central stenotic levels) were correlated to symptoms (pain intensity, walking capacity), functional disability (measured in terms of the Oswestry Disability Index), and neurological signs of LSS (neurological status was evaluated and scored by Neurological Impairment Score in LSS). Results A statistically significant correlation emerged only between the Neurological Impairment Score in LSS and Schizas morphologic classification (P=0.006). Pain intensity, walking capacity, and functional disability displayed no correlation with the MRI parameters of LSS. Conclusions LSS is a clinicoradiologic syndrome with complex relationships between degree of radiologic stenosis disclosed by MRI and clinical manifestations. Neurological impairment in the lower extremities reflects the degree of morphologic LSS on MRI. This study did not identify any association between the degree of stenosis and functional disability, pain intensity, or walking capacity. Level of evidence Level II.

Aims This paper aims to investigate whether intraepidermal nerve-fibre density (IENFD) may be used as a marker of the course of neuropathy in patients with Type2 diabetes mellitus. Methods Skin biopsies from the distal leg were serially evaluated in a group of 30 patients with Type2 diabetes mellitus (median age 60years, 17 men) with a short duration of diabetes (2years (median 33.8months). Eighteen patients with Type2 diabetes mellitus had symptoms or signs of distal symmetrical diabetic polyneuropathy, 12 had no neuropathy. Results At first skin biopsy, IENFD was normal in all controls and in patients without neuropathy (mean 9.5 and 7.9fibres/mm, respectively) compared with abnormal IENFD in 77.8% in patients with polyneuropathy (mean 3.4fibres/mm). The annual rate of intraepidermal nerve-fibre (IENF) loss expressed as a percentage of the first IENFD value in patients with diabetic polyneuropathy was significantly higher [mean (se), 11.95 (3.82)%] compared with controls [1.92 (1.81)%, P

Background Stroke is a common cause of mortality and morbidity in Eastern Europe. However, detailed epidemiological data are not available. The National Registry of Hospitalized Patients (NRHOSP) is a nationwide registry of prospectively collected data regarding each hospitalization in the Czech Republic since 1998. As a first step in the evaluation of stroke epidemiology in the Czech Republic, we validated stroke cases in NRHOSP. Methods Any hospital in the Czech Republic with a sufficient number of cases was included. We randomly selected 10 of all 72 hospitals and then 50 patients from each hospital in 2011 stratified according to stroke diagnosis (International Classification of Diseases Tenth Revision [ICD-10] cerebrovascular codes I60, I61, I63, I64, and G45). Discharge summaries from hospitalization were reviewed independently by 2 reviewers and compared with NRHOSP for accuracy of discharge diagnosis. Any disagreements were adjudicated by a third reviewer. Results Of 500 requested discharge summaries, 484 (97%) were available. Validators confirmed diagnosis in NRHOSP as follows: transient ischemic attack (TIA) or any stroke type in 82% (95% confidence interval [CI], 79-86), any stroke type in 85% (95% CI, 81-88), I63/cerebral infarction in 82% (95% CI, 74-89), I60/subarachnoid hemorrhage in 91% (95% CI, 85-97), I61/intracerebral hemorrhage in 91% (95% CI, 85-96), and G45/TIA in 49% (95% CI, 39-58). The most important reason for disagreement was use of I64/stroke, not specified for patients with I63. Conclusions The accuracy of coding of the stroke ICD-10 codes for subarachnoid hemorrhage (I60) and intracerebral hemorrhage (I61) included in a Czech Republic national registry was high. The accuracy of coding for I63/cerebral infarction was somewhat lower than for ICH and SAH.

The aim of this prospective cross-sectional observational comparative study was to determine the prevalence of spondylotic cervical cord compression (SCCC) and symptomatic cervical spondylotic myelopathy (CSM) in patients with symptomatic lumbar spinal stenosis (LSS) in comparison with a general population sample and to seek to identify predictors for the development of CSM. A group of 78 patients with LSS (48 men, median age 66 years) was compared with a randomly selected age- and sex-matched group of 78 volunteers (38 men, median age 66 years). We evaluated magnetic resonance imaging findings from the cervical spine and neurological examination. The presence of SCCC was demonstrated in 84.6 % of patients with LSS, but also in 57.7 % of a sample of volunteers randomly recruited from the general population. Clinically symptomatic CSM was found in 16.7 % of LSS patients in comparison with 1.3 % of volunteers (p = 0.001). Multivariable logistic regression proposed the Oswestry Disability Index of 43 % or more as the only independent predictor of symptomatic CSM in LSS patients (OR 9.41, p = 0.008). The presence of symptomatic LSS increases the risk of SCCC; the prevalence of SCCC is higher in patients with symptomatic LSS in comparison with the general population, with an evident predominance of more serious types of MRI-detected compression and a clinically symptomatic form (CSM). Symptomatic CSM is more likely in LSS patients with higher disability as assessed by the Oswestry Disability Index.

Introduction: Small fiber pathology can develop in the acute phase of critical illness and may explain chronic sensory impairment and pain in critical care survivors. Methods: Eleven adult ischemic stroke patients in a neurocritical care unit were enrolled in an observational cohort study. Intraepidermal never fiber density (IENFD) in the distal leg was assessed on admission to the intensive care unit and 10-14 days later, together with electrophysiological testing. Results: Of the 11 patients recruited, 9 (82%) had sepsis or multiple organ failure. Median IENFD on admission (5.05 fibers/mm) decreased significantly to 2.18 fibers/mm (P

Different sensory profiles in diabetic distal symmetrical sensory-motor polyneuropathy (DSPN) may be associated with pain and the responsiveness to analgesia. We aimed to characterize sensory phenotypes of patients with painful and painless diabetic neuropathy and to assess demographic, clinical, metabolic, and electrophysiological parameters related to the presence of neuropathic pain in a large cohort of well-defined DSPN subjects. This observational cross-sectional multi-center cohort study (performed as part of the ncRNAPain EU consortium) of 232 subjects with nonpainful (n = 74) and painful (n = 158) DSPN associated with diabetes mellitus of type 1 and 2 (median age 63 years, range 21-87 years; 92 women) comprised detailed history taking, laboratory tests, neurological examination, quantitative sensory testing, nerve conduction studies, and neuropathy severity scores. All parameters were analyzed with regard to the presence and severity of neuropathic pain. Neuropathic pain was positively correlated with the severity of neuropathy and thermal hyposensitivity (P < 0.001). A minority of patients with painful DSPN (14.6%) had a sensory profile, indicating thermal hypersensitivity that was associated with less severe neuropathy. Neuropathic pain was further linked to female sex and higher cognitive appraisal of pain as assessed by the pain catastrophizing scale (P < 0.001), while parameters related to diabetes showed no influence on neuropathic pain with the exception of laboratory signs of nephropathy. This study confirms the value of comprehensive DSPN phenotyping and underlines the importance of the severity of neuropathy for the presence of pain. Different sensory phenotypes might be useful for stratification of patients with painful DSPN for analgesic treatment and drug trials.

Purpose The aim of this prospective observational cohort study was to evaluate long-term outcomes in patients with mild-to-moderate lumbar spinal stenosis (LSS) and to analyse the predictors of clinical outcomes. Methods A group of 53 patients were re-examined after a median period of 139 months. Evaluations were made of subjective clinical outcome, objective clinical outcome and its predictors, any correlation between subjective and objective outcome, and the development of changes in radiological and electrophysiological parameters after 12 years. Results Satisfactory objective and subjective clinical outcomes were recorded in 54.7 and 43.4 % of patients, respectively. No statistically significant correlation between objective and subjective clinical outcome was found (Spearman coefficient = 0.225, p = 0.132). Patients with isolated unsatisfactory subjective outcome exhibited the highest Functional Comorbidity Index of all subgroups. Electrophysiological and radiological findings did not demonstrate statistically significant changes after 12-year follow-up. Multivariate logistic regression confirmed only the lowest transverse diameter of spinal canal ^13.6 mm as an independent predictor of unsatisfactory clinical outcome (OR = 5.51). Conclusions Satisfactory objective and subjective clinical outcomes were disclosed in about half of the patients with mild-to-moderate LSS in a 12-year follow-up. The number of comorbid diseases had an unfavourable effect on subjective evaluation of clinical outcome. The lowest transverse diameter of spinal canal proved to be the only independent predictor of deterioration of clinical status in LSS patients.

Background Contemporary stroke incidence data are not available in some countries and regions, including in Eastern Europe. Based on previous validation of the accuracy of the National Registry of Hospitalized Patients (NRHOSP), we report the incidence of hospitalized stroke in the Czech Republic (CR) using the NRHOSP. Methods The results of the prior validation study assessing the accuracy of coding of stroke diagnoses in the NRHOSP were applied, and we calculated (1) the overall incidence of hospitalized stroke and (2) the incidence rates of hospitalized stroke for the three main stroke types: cerebral infarction (International Classification of Diseases Tenth Revision, CI I63), subarachnoid hemorrhage (SAH I60), and intracerebral hemorrhage (ICH I61). We calculated the average annual age- and sex-standardized incidence. Results The overall incidence of hospitalized stroke was 241 out of 100,000 individuals. The incidence of hospitalized stroke for the main stroke types was 8.2 cases in SAH, 29.5 in ICH, and 211 in CI per 100,000 individuals. The standardized annual stroke incidence adjusted to the 2000 World Health Organization population for overall stroke incidence of hospitalized stroke was 131 per 100,000 individuals. Standardized stroke incidence for stroke subtypes was 5.7 cases in SAH, 16.7 in ICH, and 113 in CI per 100,000 individuals. Conclusions These studies provide an initial assessment of the burden of stroke in this part of the world. The estimates of hospitalized stroke in the CR and Eastern Europe suggest that ICH is about three times more common than SAH, and hemorrhagic stroke makes up about 18% of strokes.

The growth-associated protein 43 (GAP-43) is known as a marker of regenerating nerve fibers and their continuous remodeling in the adult human skin. The purpose of this pilot study was to investigate a possible role for GAP-43 in the detection of the early stages of small-fiber neuropathy in patients with type 2 diabetes mellitus (DM2) as compared with a well- established and validated parameter – intra-epidermal nerve fiber density (IENFD) of protein gene product 9.5 (PGP 9.5) immunoreactive intra-epidermal C fibers. In a group of 21 patients with DM2 within three years of diagnosis (13 men, 8 women; mean age 53.9 +- 12.8; range 30 – 74) and a group of 17 healthy volunteers (8 men, 9 women; mean age 55.8 +- 8.5; range 45 – 70 years), skin punch biopsies were taken from a distal calf and double immunostained with both PGP 9.5 and GAP-43. In healthy controls, 96.8% of 629 PGP 9.5 immunoreactive fibers were immunostained with GAP-43; the proportion of PGP 9.5 intra-epidermal nerve fibers immunoreactive for GAP-43 in control subjects ranged from 86.5 to 100%. In DM2 patients, IENFD was significantly lower compared to controls (median, 1.5 vs. 11.2/mm; p

To describe the epidemiology and time spectrum of delirium using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and to validate a tool for delirium assessment in patients in the acute poststroke period.A prospective observational cohort study.The stroke unit of a university hospital.A consecutive series of 129 patients with stroke (with infarction or intracerebral hemorrhage, 57 women and 72 men; mean age, 72.5 yrs; age range, 35-93 yrs) admitted to the stroke unit of a university hospital were evaluated for delirium incidence.None.Criterion validity and overall accuracy of the Czech version of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) were determined using serial daily delirium assessments with CAM-ICU by a junior physician compared with delirium diagnosis by delirium experts using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria that began the first day after stroke onset and continued for at least 7 days. Cox regression models using time-dependent covariate analysis adjusting for age, gender, prestroke dementia, National Institutes of Stroke Health Care at admission, first-day Sequential Organ Failure Assessment, and asphasia were used to understand the relationships between delirium and clinical outcomes. An episode of delirium based on reference Diagnostic and Statistical Manual assessment was detected in 55 patients with stroke (42.6%). In 37 of these (67.3%), delirium began within the first day and in all of them within 5 days of stroke onset. A total of 1003 paired CAM-ICU/Diagnostic and Statistical Manual of Mental Disorders daily assessments were completed. Compared with the reference standard for diagnosing delirium, the CAM-ICU demonstrated a sensitivity of 76% (95% confidence interval [CI] 55% to 91%), a specificity of 98% (95% CI 93% to 100%), an overall accuracy of 94% (95% CI 88% to 97%), and high interrater reliability (κ = 0.94; 95% CI 0.83-1.0). The likelihood ratio of the CAM-ICU in the diagnosis of delirium was 47 (95% CI 27-83). Delirium was an independent predictor of increased length of hospital stay (hazard ratio 1.63; 95% CI 1.11-2.38; p = .013).Poststroke delirium may frequently be detected provided that the testing algorithm is appropriate to the time profile of poststroke delirium. Early (first day after stroke onset) and serial screening for delirium is recommended. CAM-ICU is a valid instrument for the diagnosis of delirium and should be considered an aid in delirium screening and assessment in future epidemiologic and interventional studies in patients with stroke.

Study design A prospective study evaluating a cohort of patients with spondylotic cervical spine compression. Objective To analyze the potential of diffusion tensor imaging (DTI) of the cervical spinal cord in the detection of changes associated with spondylotic myelopathy, with particular reference to clinical and electrophysiological findings. Summary of background data Conventional magnetic resonance imaging (MRI) may provide confusing findings because of a frequent disproportion between the degree of the spinal cord compression and clinical symptoms. The DTI is known to be more sensitive to subtle pathological changes of the spinal cord compared with conventional MRI. Methods The DTI of the cervical spinal cord was performed within a group of 52 patients with spondylotic spinal cord compression and 13 healthy volunteers on a 1.5-T MRI scanner. All patients underwent clinical examination that differentiated between asymptomatic and symptomatic myelopathy subgroups, and 45 patients underwent electrophysiological examination. We measured the apparent diffusion coefficient and fractional anisotropy of the spinal cord at C2/C3 level without compression and at the maximal compression level (MCL). Sagittal spinal canal diameter, cross-sectional spinal cord area, and presence of T2 hyperintensity at the MCL were also recorded. Nonparametric statistical testing was used for comparison of controls with subgroups of patients. Results Significant differences in both the DTI parameters measured at the MCL, between patients with compression and control group, were found, while no difference was observed at the noncompression level. Moreover, fractional anisotropy values were lower and apparent diffusion coefficient values were higher at the MCL in the symptomatic patients than in the asymptomatic patients. The DTI showed higher potential to discriminate between clinical subgroups in comparison with standard MRI parameters and electrophysiological findings. Conclusion The DTI appears to be a promising imaging modality in patients with spondylotic spinal cord compression. It reflects the presence of symptomatic myelopathy and shows considerable potential for discriminating between symptomatic and asymptomatic patients.

Multiple sclerosis (MS) is characterized by autoimmune attack leading to demyelination of the white matter in the central nervous system with devastating clinical consequences. Several immune-mediated destruction mechanisms were previously proposed including different T-cell subsets but complex view on immune system function in patients with MS is missing. In the present study, T-lymphocyte populations and pro-inflammatory as well as suppressive cytokine profiles were evaluated in detail in previously untreated patients with relapsing-remitting MS (RRMS). CD4(+) and CD8(+) naïve, central memory (Tcm), effector memory (Tem), terminal effector memory (Ttem), CD4(+) regulatory T-cells (Treg) and CD8(+) T-suppressor cells (Ts) were analysed using flow cytometry, and levels of ten plasma cytokines were determined using fluorescent bead-based immunoassay. We evaluated two groups of RRMS with minor (n=33) and major (n=25) clinical impairment and compared them with healthy controls (n=40) in order to detect any correlation between severity of MS clinical symptoms and immune disturbances. Significant differences were noted in CD4(+)CD45RA(+)CCR7(+) naïve T-cells, CD4(+)CD45RO(+)CCR7(-) and CD8(+)CD45RO(+)CCR7(-) Tem cells, while no differences were recognized in Tcm, Ttem, Treg and Ts cells in RRMS patients. Nine out of ten studied cytokines were disturbed in plasma samples of patients with RRMS. In conclusion, we demonstrate complex immune dysbalances in untreated MS patients.

The aim of this study was to evaluate the etiology in a group of 84 patients with painful sensory neuropathy with predominant small-fiber dysfunction (54 men and 30 women, median: 58; range: 25-83 years) recruited from a population of the South Moravian region of the Czech Republic. Involvement of small nerve fibers was verified by abnormal thermal thresholds and/or reduced intraepidermal nerve fiber densities. Motor signs or symptoms or significant clinical signs of sensory large-fiber involvement were exclusionary; 33 patients, however, had sensory nerve conduction abnormalities. For comparison, the prevalence of risk factors was assessed in a group of 47 asymptomatic age- and sex-matched controls (30 men and 17 women, median: 59; range: 29-85 years). The multivariate regression model disclosed that diabetes mellitus (odds ratio [OR] = 4.08), chronic alcoholism (OR = 5.31), and serum cholesterol levels (OR = 4.51) were the only parameters independently associated with small-fiber involvement. No possible etiology was detected in 19 patients (22.6%). In conclusion, the spectrum of risk factors and proportion of idiopathic cases in geographically defined small-fiber polyneuropathy sample is similar to that referred in large-fiber polyneuropathy.

In this prospective study, intraepidermal nerve fiber densities (IENFD) and subepidermal nerve plexus densities (SENPD) were quantified by immunostaining in skin punch biopsies from the distal calf in 99 patients with clinical symptoms of painful sensory neuropathy and from 37 age-matched healthy volunteers. The clinical diagnosis was based on history and abnormal thermal thresholds on quantitative sensory testing (QST). In patients with neuropathy, IENFD and SENPD were reduced to about 50% of controls. Elevated warm detection thresholds on QST correlated with IENFD but not with SENPD. Using receiver-operating characteristic (ROC) curve analysis of IENFD values, the diagnostic sensitivity for detecting neuropathy was 0.80 and the specificity 0.82. For SENPD, sensitivity was 0.81 and specificity 0.88. With ROC analysis of both IENFD and SENPD together, the diagnostic sensitivity was further improved to 0.92. The combined examination of IENFD and SENPD is a highly sensitive and specific diagnostic tool in patients suspected to suffer from painful sensory neuropathies but with normal values on clinical neurophysiological studies.

Summary Background Neuromuscular weakness in paediatric patients with sepsis and multiple organ dysfunction is increasingly reported. However, many aspects of neuromuscular involvement in critically ill children are not completely understood. As more patients survive the critical illness, an understanding of the long-term outcomes of this condition is needed. Aims To describe clinical and electrophysiological features and evaluate the long-term outcomes in critically ill paediatric patients with neuromuscular complications. Methods A case series of five critically ill children was observed prospectively for a 1-month period. Selected clinical and laboratory parameters were evaluated. Electrophysiological studies were performed during the first week and then 1 month later in order to detect signs of critical illness polyneuromyopathy (CIPM). Patients with neuromuscular involvement completed a 1-year follow-up. Results Electrophysiological abnormalities were detected in two patients. Flaccid quadriplegia was a clinical presentation. Both children had electromyographic evidence of chronic partial denervation at follow-up, findings indicative of a preceding axonal neuropathy. Marked but incomplete recovery within 1 year after the onset of the disease occured in both patients. With a mild residual functional handicap the health-related quality of life was not significantly impaired (Barthel Index>80). Conclusions In both our patients with CIPM, the long-term clinical outcome is markedly better than we expected when electromyography in the 1-year follow-up demonstrated a persistent severe chronic partial denervation. These findings can have important implications for the management and rehabilitation of paediatric intensive care survivors.

Objectives To update a previously established list of predictors for neurological cervical cord dysfunction in nonmyelopathic degenerative cervical cord compression (NMDCCC). Material and Methods A prospective observational follow‐up study was performed in a cohort of 112 consecutive NMDCCC subjects (55 women and 57 men; median age 59 years, range 40–79 years), either asymptomatic (40 subjects) or presenting with cervical radiculopathy or cervical pain (72 subjects), who had completed a follow‐up of at least 2 years (median duration 3 years). Development of clinical signs of degenerative cervical myelopathy (DCM) as the main outcome was monitored and correlated with a large number of demographic, clinical, electrophysiological, and MRI parameters including diffusion tensor imaging characteristics (DTI) established at entry. Results Clinical evidence of the first signs and symptoms of DCM were found in 15 patients (13.4%). Development of DCM was associated with several parameters, including the clinical (radiculopathy, prolonged gait and run‐time), electrophysiological (SEP, MEP and EMG signs of cervical cord dysfunction), and MRI (anteroposterior diameter of the cervical cord and cervical canal, cross‐sectional area, compression ratio, type of compression, T2 hyperintensity). DTI parameters showed no significant predictive power. Multivariate analysis showed that radiculopathy, cross‐sectional area (CSA) ≤ 70.1 mm2, and compression ratio (CR) ≤ 0.4 were the only independent significant predictors for progression into symptomatic myelopathy. Conclusions In addition to previously described independent predictors of DCM development (radiculopathy and electrophysiological dysfunction of cervical cord), MRI parameters, namely CSA and CR, should also be considered as significant predictors for development of DCM.

Introduction A-waves, which are observed following the M-wave during motor nerve conduction studies (NCS), are late responses that are frequently found in many types of neurogenic disorders. However, A-waves are also common in healthy individuals, where their significance remains unclear. The aim of this study was to examine whether the occurrence of A-waves does in fact represent an increased risk for the future development of changes upon NCS or needle electromyography (EMG) in the corresponding nerve. Methods Nerve conduction studies/needle electromyography findings at control examination were evaluated in relation to the occurrence of initial A-waves in 327 individuals who had undergone repeated NCS/EMG examination and exhibited normal initial findings, with or without the occurrence of A-waves as the only acceptable abnormality. Results The odds ratio, which reflects the predictive power of the occurrence of A-waves at the initial testing for the development of an abnormality (neuropathy or radiculopathy) at the follow-up examination, ranged from 2.7 (p = .041) in the tibial nerve and 3.9 (p = .034) in peroneal one, to 30.0 (p = .002) in the ulnar nerve. Conclusions A-waves constitute an initial abnormality in all nerves, and they may be predictive for the future development of broader NCS/EMG abnormalities in the corresponding nerve.

The aim of this study was to investigate the characteristics of prediabetes (preDM) and early (

The Oswestry Disability Index (ODI) is an interview-based instrument generally accepted as a measure of disability in patients with lumbar spinal stenosis (LSS). There is, however, no generally accepted measure for neurological impairment in LSS. We therefore developed a scoring system [neurological impairment score in lumbar spinal stenosis (NIS-LSS)] for the assessment of neurological impairment in the lower limbs of patients with LSS, then performed a validation study to facilitate its implementation in the routine clinical evaluation of patients with LSS.The NIS-LSS is based on the combined evaluation of tendon reflexes, tactile and vibratory sensation, pareses, and the ability to walk and run; the total score ranges from 0 (inability to walk) to 33 points (no impairment). A group of 117 patients with LSS and a control group of 63 age- and sex-matched healthy volunteers were assessed with the NIS-LSS to evaluate capacity to discriminate between LSS patients and controls. A correlation with the ODI was performed for assessment of construct validity.The median NIS-LSS was 27 points in LSS patients compared with 33 points in controls. The NIS-LSS discriminated LSS patients from healthy controls to a high degree of significance: the optimum NIS-LSS cut-off value was 32 points with a sensitivity of 85.5% and a specificity of 81.3% (p0.001). Overall NIS-LSS correlated significantly with the ODI score (p0.001). Vibratory sensation (p = 0.04), presence of paresis (p = 0.01) and especially the ability to walk and run (p0.001) were the NIS-LSS elements that correlated most closely with the degree of disability assessed by the ODI.The NIS-LSS is a simple and valid measure of neurological impairment in the lower limbs of patients with LSS (without comorbidity), discriminating them from healthy controls to a high degree of sensitivity and specificity and correlating closely with the degree of disability. It extends our ability to quantify neurological status and to follow changes arising out of the natural course of the disease or the effects of treatment.

To assess predisposing and precipitating risk factors and create a predictive model for post-stroke delirium.A prospective observational study in a cohort of consecutive patients with ischemic stroke or intracerebral haematoma admitted within 24 hours of stroke onset.Patients were assessed daily for delirium during the first week by means of DSM-IV criteria and risk factors were recorded.One hundred patients completed a 7-day evaluation (47 women and 53 men, median age 77 years). An episode of delirium was detected in 43 patients (43%). Using multivariate logistic regression, a predictive statistical model was developed that utilized independent risk factors: age (OR = 1.08; 95% CI = 1.02-1.15); intracerebral haemorrhage (OR = 6.11; 95% CI = 1.62-22.98), lesion volume40 ccm (OR = 3.99; 95% CI = 1.29-12.39) and either elevated gamma-glytamyl transferase (OR = 4.88; 95% CI = 1.45-16.35) and elevated serum bilirubin (OR = 3.70; 95% CI = 1.32-10.38) or maximum sequential organ failure assessment score2 (OR = 3.33; 95% CI = 1.06-10.45) with acceptable sensitivity and specificity (69.0% and 80.7%). In ischemic strokes, total anterior circulation infarctions were more frequently associated with delirium (73.3% developed delirium) compared with the remainder of the groups combined (p = 0.004; OR = 6.66; 95% CI = 1.85-24.01).Higher age, metabolic disturbances, intracerebral haemorrhage and larger ischemic hemispheric strokes increase the risk of post-stroke delirium.

Multiple sclerosis (MS) is a chronic disease characterized by demyelination and chronic inflammation of the central nervous system (CNS). Many of the immune cells including T and B cells seem to be involved in disease pathogenesis by inducing or controlling the immune responses in the nervous system of MS patients. The objective of this study was to evaluate the differences in subpopulations of T cells between MS patients and healthy controls and the effects of interferon beta (INF-beta) and glatiramer acetate (GA) treatment on T cell subpopulations.We have investigated the frequency of subpopulations of T cells using flow cytometry in 84 relapsing-remitting MS patients; forty-five patients started treatment with INF-beta and eighteen patients with GA, twenty-one patients were not treated. We collected blood samples at the beginning and after 6 and 12 months.We observed a significant decrease in CD4(+)CD25(+) Treg cells (p=0.03) and a significant increase in T helper cells (p=0.002) and central memory T cells (p=0.03) in MS patients compared to healthy controls. After INF-beta therapy, we demonstrated a significant increase in naive T cells (p=0.008), a decline in central memory T cells (p=0.01). After GA therapy, we observed a significant increase in naive T cells (p=0.04), a decrease in central memory T cells (p=0.03) and an increase in T-suppressor cells (p=0.008).In conclusion, we demonstrated the imbalance of T-cell subpopulations in MS patients and the potential benefit of DMD (disease modifying drugs) treatment on its restoration.

Type 1 diabetes mellitus (T1D) and multiple sclerosis (MS) are organ-specific autoimmune diseases leading to an attack of auto-aggressive lymphocytes against the pancreatic beta-cells and central nervous system, respectively. Using four-colour flow cytometry, T-lymphocyte populations having an important function in autoimmune processes were analyzed. T-regulatory cells (Treg) CD4(+)CD25(+)CD127(low), T-suppressor cells (Ts) CD8(+)CD28(-), activated helper CD4(+)CD25(+)CD127(+) and cytotoxic CD8(+)CD25(+) T-cells and also naive CD4(+)CD45RA(+) and memory T-cells CD4(+)CD45RO(+) were compared in the group of patients with T1D (n=30), MS (n=31) and in the group of healthy controls (n=29). Significant differences in Ts cells, activated helper and cytotoxic cells and also memory T-cells were recognized in the group of T1D patients compared to healthy controls. Ts population was significantly lowered in MS patients as well. However, no significant differences were noticed in Treg population. The observed data demonstrate significant differences among patients with T1D and MS in comparison to healthy individuals.

Spondylotic cervical cord compression detected by imaging methods is a prerequisite for the clinical diagnosis of spondylotic cervical myelopathy (SCM). Little is known about the spontaneous course and prognosis of clinically "silent" presymptomatic spondylotic cervical cord compression (P-SCCC). The aim of the present study was to update a previously published model predictive for the development of clinically symptomatic SCM, and to assess the early and late risks of this event in a larger cohort of P-SCCC subjects. A group of 199 patients (94 women, 105 men, median age 51 years) with magnetic resonance signs of spondylotic cervical cord compression, but without clear clinical signs of myelopathy, was followed prospectively for at least 2 years (range 2-12 years). Various demographic, clinical, imaging, and electrophysiological parameters were correlated with the time for the development of symptomatic SCM. Clinical evidence of the first signs and symptoms of SCM within the follow-up period was found in 45 patients (22.6%). The 25th percentile time to clinically manifested myelopathy was 48.4 months, and symptomatic SCM developed within 12 months in 16 patients (35.5%). The presence of symptomatic cervical radiculopathy and electrophysiological abnormalities of cervical cord dysfunction detected by somatosensory or motor-evoked potentials were associated with time-to-SCM development and early development (or =12 months) of SCM, while MRI hyperintensity predicted later (12 months) progression to symptomatic SCM. The multivariate predictive model based on these variables correctly predicted early progression into SCM in 81.4% of the cases. In conclusion, electrophysiological abnormalities of cervical cord dysfunction together with clinical signs of cervical radiculopathy and MRI hyperintensity are useful predictors of early progression into symptomatic SCM in patients with P-SCCC. Electrophysiological evaluation of cervical cord dysfunction in patients with cervical radiculopathy or back pain is valuable. Meticulous follow-up is justified in high-risk P-SCCC cases.

Introduction: The critical degree of spinal cord compression required to induce pathological changes in clinical practice remains unknown. The aim of this study is to ascertain the threshold of critical compression and its relation to MR-increased signal intensities in the spinal cord. Study group and methods: The study group consisted of 243 patients, mean age 53.9 +-9.8 years, with spondylotic cervical spine compression. The transverse cross-sectional area of the spinal cord at the level of maximum compression was measured, while MR hyperintensities were recorded and related to clinical status as quantified by mJOA score. Results: A statistically significant difference was shown between patients with a spinal cord sectional area of under 50 mm2 and a group of patients with a spinal cord sectional area of over 60 mm2 . A statistically significant difference in mJOA score was found between patients with smaller (under 50 mm2) or larger (over 70 mm2) transverse spinal cord areas within the group with hyperintensities (p = 0.001), whereas within the group of patients without hyperintensities, this difference was not observed (p = 0.63). Conclusions: The critical degree of spinal cord compression needed to induce clinically pathological changes is between 50 and 60 mm2.

A prospective 3-year randomized study comparing conservative and surgical treatment of spondylotic cervical myelopathy to establish predictive factors for outcome after conservative treatment and surgery. The clinical, electrophysiological and imaging parameters were examined to reveal how they characterized the clinical outcome. The patients with a good outcome in the conservatively treated group were of older age before treatment, had normal central motor conduction time (CMCT), and possessed a larger transverse area of the spinal cord. The patients with a good outcome in the surgically treated group had a more serious clinical picture (expressed in mJOA score and slower walk). Patients should rather be treated conservatively if they have a spinal transverse area larger than 70 mm2, are of older age and have normal CMCT. Surgery is more suitable for patients with clinically worse status and a lesser transverse area of spinal cord.

A prospective 3-year randomized study comparing conservative and surgical treatment of spondylotic cervical myelopathy to establish predictive factors for outcome after conservative treatment and surgery. The clinical, electrophysiological and imaging parameters were examined to reveal how they characterized the clinical outcome. Statistically, pair-wise and multiple comparisons of different were used with the independent t-test and on one-way anova models followed by Tukey multiple-range tests. The patients with a good outcome in the conservatively treated group were of older age before treatment, had normal central motor conduction time (CMCT), and possessed a larger transverse area of the spinal cord. The patients with a good outcome in the surgically treated group had a more serious clinical picture (expressed in mJOA score and slower walk). Patients should rather be treated conservatively if they a spinal transverse area larger than 70 mm2, are of older age, and have normal CMCT. Surgery is more suitable for patients with clinically worse status and a lesser transverse area of spinal cord.

Study design We conducted a cohort study of clinically asymptomatic spondylotic cervical cord compression cases with the primary end point of the development of clinical signs of cervical myelopathy. Objectives To investigate whether various demographic, clinical, radiologic, and electrophysiological parameters could predict progression from clinically asymptomatic (preclinical) spondylotic cervical cord compression to symptomatic myelopathy. Summary of background data The data available on the prediction of the outcome in surgical and conservative treatment of spondylotic cervical myelopathy are controversial. Little is known about the clinical natural history of asymptomatic magnetic resonance image-detected spondylotic cervical cord compression and/or changes of signal intensity. Methods A group of 66 patients (32 women, 34 men, median age 50 years) with magnetic resonance signs of spondylotic cervical cord compression but without clear clinical signs of myelopathy was followed prospectively for at least 2 years (range, 2-8 years; median, 4 years). Various demographic, clinical, imaging, and electrophysiological parameters were correlated with clinical outcome. Results Clinical signs of myelopathy during the follow-up period were detected in 13 patients (19.7%). The only variables significantly associated with the development of clinically symptomatic spondylotic cervical myelopathy (SCM) were the presence of symptomatic cervical radiculopathy, electromyographic signs of anterior horn lesion, and abnormal somatosensory-evoked potentials. A multivariate logistic regression model based on these variables correctly classified 90% of cases into 2 subgroups: a group with development of symptomatic SCM and that without clinical manifestation of subclinical cervical cord compression. Conclusions Electrophysiological abnormalities together with clinical signs of cervical radiculopathy could predict clinical manifestation of preclinical spondylotic cervical cord compression.

Our research aimed at finding out values of carbohydrate-deficient transferin (CDT), gamma-glutamyltransferase (GGT) and mean corpuscular volume (MCV) for the purposes of future etiological diagnostics of alcohol neuropathy in thin fibres.We examined the serum of 80 control subjects (50 women and 30 men), and the serum of 33 alcoholics (20 men and 13 women) with the daily consumption of more than 60 g alcohol in the course of the last four weeks. CDT was determined with the use of microcolumn separation after iron saturation followed by turbidimetric immunoassay (ChronoAlcoI. D., Sangui Biotech, Inc.) on Cobas-Mira analyser. CDT is expressed as a percentage of the total transferin. Senzitivity, specificity, positive likelihood ration (+LR), ROC and the area under the ROC curve were determined using statistical program MedCalc.The senzitivity, specificity and positive likelihood ratio (+LR) for CDT-%, respectively, were 82.6, 96.7 and 24.8 for men (cut off 2.2%), and 60.0, 88.0 and 5.0 for women (cut off 2.5%). The respective values for GMT were 95.7, 90.0 and 9.6 for men (cut off 0.64 mu kat/l), and 90.0, 80.0 and 4.5 for women (cut off 0.38 mu kat/l); for MCV 82.6, 96.7 and 24.8 for men (cut off 95.0 fL), and 80.0, 100.0 and 20.0 for women (cut off 97.2 fL). The area under the ROC curve for CDT-%, GMT and MCV, respectively, were 0.940, 0.964 and 0.896 for men, and 0.829, 0.917 and 0.906 for women.In men, CDT-% and MCV showed the same values of the statistical parameters studied. GGT was more sensitive and less specific. In women, all the parameters studied presented a lesser diagnostic value, except for MCV with 100% specificity and +LR 20.0.

To evaluate the spectrum and time profile of electrophysiological parameters in the detection of neuromuscular involvement in critically ill patients and establish their correlation with biopsy findings. Prospective clinical and neurophysiological study. One general and one neurological intensive care unit in a university hospital. Forty-six critically ill patients with failure of at least two organ systems were enrolled and completed the 1-month follow up. Detailed clinical and electrophysiological evaluation including direct muscle stimulation was performed in all cases on entry and at the end of the follow-up. Muscle biopsy was performed in 11, and sural nerve biopsy in 5, cases. Electrophysiological signs of new or progressing neuromuscular involvement at the end of the first month were detected in 26 patients (56%) and could be classified into three groups: "pure motor syndrome" (12 cases), combined motor syndrome and sensory polyneuropathy (13 cases) and isolated sensory polyneuropathy (1 case). Direct muscle stimulation showed decreased muscle membrane excitability in 11 of these abnormal cases. Muscle biopsy disclosed various myopathic abnormalities in all 11 cases examined with motor syndrome, in 7 of them in association with denervation/re-innervation changes. Electrophysiological and histological examinations showed significant overlapping of several pathogenic components of neuromuscular involvement in critically ill patients, namely decreased muscle excitability, myopathy, axonal motor neuropathy and sensory neuropathy. The characterisation of the electrophysiological components of a complex polyneuromyopathy is preferred to the strict categorisation of abnormalities into critical illness myopathy and polyneuropathy.

Study design. A two-year follow-up prospective randomised electrophysiological and clinical study was performed in patients with spondylotic cervical myelopathy. Objective. To assess the value of somatosensory (SEP) and motor evoked potentials (MEP) in the evaluation and prediction of the effect of therapy. Summary of background data. Previous studies have yielded conflicting data concerning the correlation between the changes in evoked potential parameters and the clinical post-surgical outcome in spondylotic cervical myelopathy (SCM). Methods. Sixty-one patients with magnetic resonance imaging (MRI) signs of spondylotic cervical cord compression and clinical signs of cervical myelopathy were divided into two groups according to the degree of clinical cervical cord involvement. Forty-nine patients with mild and moderate SCM were randomised into groups that underwent either surgical or conservative therapy. Patients were evaluated clinically and by the means of SEP and MEP. Results. 1. The clinical and evoked potential (EP) changes showed good correlation as a group, but poor correlation intra-individually. 2. There were no significant EP and clinical group changes after 6 months and 2 years in mild myelopathy group treated either surgically and conservatively, while patients with severe myelopathy displayed significant improvement in both clinical and EP parameters after surgery. 3. In a subgroup of patients the isolated segmental medullar N 13 abnormality predicted favourable post-surgical clinical outcome. Conclusions. Longitudinal EPs showed limited utility in the evaluation of the results of therapy in an individual patient. They could be useful in the group assessment of the results of therapy and in labelling a subgroup of patients with potentially favourable post-surgical outcome.

The authors examined evoked motor potentials (MEP) of the upper extremities in a group of 43 patients with multiple sclerosis using transcranial cortical and spinal stimulation. As abnormal they rated a prolongation of the motor conduction time by more than 3 sigma above the mean value recorded in the control group or when the response could not be evoked. The central motor conduction time between the cortex and cervical spine was abnormal in 76.7% of patients. The authors did not find a correlation between the severity of the paresis and the degree of electrophysiological abnormality. In frust and mild pareses the sensitivity was 80%. The frequency of abnormalities correlated with the degree of the diagnostic certainty. In patients with a probable diagnosis (according to Poser) abnormalities were present in 41.6%, when the diagnosis was certain, in 90.3%. In prolongation of the time of central motor conduction among all abnormalities 65.1% were due to prolonged motor conduction and in 27.9% the response could not be evoked. MEP examination is a sensitive technique for the detection of clinical and subclinical lesions and as to its sensitivity it is better than visual EP.