Josef Bednarik

Risk factors for critical illness polyneuromyopathy

AbstractAlthough numerous clinical, laboratory, and pharmacological variables have been reported as significant risk factors for critical illness polyneuromyopathy (CIPM), there is still no consensus on the aetiology of this condition.Objectives of the study were to assess the clinical and electrophysiological incidence and risk factors for CIPM.A cohort of critically ill patients was observed prospectively for a one–month period and the association between neuromuscular involvement and various potential risk factors was evaluated. Sixty one critically ill patients completed the follow–up (30 women, 31 men, median age 59 years).CIPM development was detected clinically in 17 patients (27.9 %) and electrophysiologically in 35 patients (57.4 %). CIPM was significantly associated with the presence and duration of systemic inflammatory response syndrome and the severity of multiple, respiratory, central nervous, and cardiovascular organ failures. The median duration of mechanical ventilation was significantly longer in patients with CIPM than in those without (16 vs 3 days, p < 0.001). Independent predictors of CIPM obtainable within the 1st week of critical illness were the admission sequential organ failure assessment score (odds ratio [OR], 1.15; 95% confidence interval [CI], 1.02–1.36), the 1st week total sequential organ failure assessment scores (OR, 1.14; 95 % CI, 1.06–1.46) and the 1st week duration of systemic inflammatory response syndrome (OR, 1.05; 95% CI, 1.01–1.15). They were able to correctly predict the development of CIPM at the end of the 1st week in about 80% of critically ill cases.In conclusion, the presence and duration of systemic inflammatory response syndrome and the severity of multiple and several organ failures are associated with increased risk of the development of CIPM.

Presymptomatic spondylotic cervical cord compression

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.

Small-fibre involvement in diabetic patients with neuropathic foot pain.

Aims  To assess small‐fibre involvement in diabetic patients with neuropathic pain.

Poststroke delirium incidence and outcomes: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU).

Objective: 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. Design: A prospective observational cohort study. Setting: The stroke unit of a university hospital. Patients: 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. Interventions: None. Measurements and Main Results: 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 (&kgr; = 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). Conclusions: 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.

Magnetic resonance diffusion tensor imaging in patients with cervical spondylotic spinal cord compression: correlations between clinical and electrophysiological findings.

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.

Etiology of small-fiber neuropathy

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.

Numerical defects in CD8+CD28- T-suppressor lymphocyte population in patients with type 1 diabetes mellitus and multiple sclerosis.

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.

microRNAs in nociceptive circuits as predictors of future clinical applications

Neuro-immune alterations in the peripheral and central nervous system play a role in the pathophysiology of chronic pain, and non-coding RNAs – and microRNAs (miRNAs) in particular – regulate both immune and neuronal processes. Specifically, miRNAs control macromolecular complexes in neurons, glia and immune cells and regulate signals used for neuro-immune communication in the pain pathway. Therefore, miRNAs may be hypothesized as critically important master switches modulating chronic pain. In particular, understanding the concerted function of miRNA in the regulation of nociception and endogenous analgesia and defining the importance of miRNAs in the circuitries and cognitive, emotional and behavioral components involved in pain is expected to shed new light on the enigmatic pathophysiology of neuropathic pain, migraine and complex regional pain syndrome. Specific miRNAs may evolve as new druggable molecular targets for pain prevention and relief. Furthermore, predisposing miRNA expression patterns and inter-individual variations and polymorphisms in miRNAs and/or their binding sites may serve as biomarkers for pain and help to predict individual risks for certain types of pain and responsiveness to analgesic drugs. miRNA-based diagnostics are expected to develop into hands-on tools that allow better patient stratification, improved mechanism-based treatment, and targeted prevention strategies for high risk individuals.

Cross-sectional transverse area and hyperintensities on magnetic resonance imaging in relation to the clinical picture in cervical spondylotic myelopathy.

Study Design. Prospective observational cohort study. Objective. To ascertain the threshold of critical spondylotic cervical cord compression and its relation to MRI-increased signal intensities. Summary of Background Data. The critical degree of spinal cord compression required to induce significant clinical signs remains unknown. 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 MRI hyperintensities were recorded and related to clinical status and quantified by modified JOA score (mJOA). Results. A statistically significant difference in mJOA 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. This difference was highly significant (P = 0.001) in a subgroup with MRI hyperintensities (187 patients, P = 0.001), whereas within the group of patients without hyperintensities this difference was not observed (P = 0.63). Conclusion. The critical degree of spinal cord compression needed to induce clinically significant signs was found between 50 and 60 mm2 of cross-sectional transverse area at the level of maximal compression in association with MRI hyperintensities.

A mutation in the X-linked Emery–Dreifuss muscular dystrophy gene in a patient affected with conduction cardiomyopathy

A screening for mutation in the X-linked Emery-Dreifuss muscular dystrophy (X-EMD) gene was performed among patients affected with severe heart rhythm defects and/or dilated cardiomyopathy. Patients were selected from the database of the Department of Cardiology of the University Hospital Brno. One patient presented a mutation in the X-EMD gene and no emerin in his skeletal muscle. The patient had a severe cardiac disease but a very mild muscle disorder that had not been diagnosed until the mutations was found. This case shows that mutations in X-EMD gene, as it was shown for autosomal-dominant EMD, can cause a predominant cardiac phenotype.