Asociaciones de hallazgos diagnósticos con actividad de la enfermedad en el síndrome de Sjogren primario: un análisis de conglomerados / Associations of diagnostic findings with disease activity in primary Sjogren's syndrome: a cluster analysis

Objective The diagnosis of primary Sjӧgren's syndrome still relies upon a constellation of clinical, laboratory, imaging, and pathological findings. We aimed to evaluate the relation of the disease activity with the results of diagnostic tests for primary Sjӧgren's syndrome. Methods A principal component with cluster analysis was performed to classify 69 patients with primary Sjӧgren's syndrome based on the results of diagnostic evaluations. Results Anti-SSA autoantibody was the most represented feature on the principal components. The anti-SSA and ultrasound score were positively correlated (p=0.001). We identified two distinct clusters of low or high disease activity (p<0.001). Except for disease duration and serum beta2-microglobulin, the clusters were significantly different in salivary flow (p= 0.004), ultrasound findings (p<0.001), IgG (p= 0.001), and salivary beta2-microglobulin (p= 0.048). Also, positive findings were significantly different between the clusters in rheumatoid factor, antinuclear antibody, anti-SSA, and anti-SSB (all p≤0.013). Conclusion Patients with higher syndrome activity were best recognized with serological and ultrasound assessments. However, patients with lower syndrome activity had a longer disease duration, higher stimulated salivary flow rate, and a positive biopsy of minor salivary glands (56%) (AU)

Objetivo El diagnóstico del síndrome de Sjӧgren primario todavía se basa en una constelación de hallazgos clínicos, de laboratorio, de imagen y patológicos. Nuestro objetivo fue evaluar la relación de la actividad de la enfermedad con los resultados de las pruebas diagnósticas para el síndrome de Sjӧgren primario. Métodos Se realizó un análisis de componentes principales mediante conglomerados para clasificar a 69 pacientes con síndrome de Sjӧgren primario en función de los resultados de las evaluaciones de diagnóstico. Resultados El autoanticuerpo anti-SSA fue la característica más representada en los componentes principales. El anti-SSA y la puntuación de ultrasonido se correlacionaron positivamente (p=0,001). Identificamos dos grupos distintos de baja o alta actividad de la enfermedad (p<0,001). Excepto por la duración de la enfermedad y la microglobulina beta2 sérica, los grupos fueron significativamente diferentes en el flujo salival (p=0,004), los hallazgos de ultrasonido (p<0,001), IgG (p=0,001) y microglobulina beta2 salival (p=0,048). Además, los hallazgos positivos fueron significativamente diferentes entre los grupos en factor reumatoide, anticuerpo antinuclear, anti-SSA y anti-SSB (todos p≤0,013). Conclusión Los pacientes con mayor actividad del síndrome se reconocieron mejor con evaluaciones serológicas y ecográficas. Sin embargo, los pacientes con menor actividad del síndrome tenían una mayor duración de la enfermedad, mayor tasa de flujo salival estimulado y una biopsia productiva de glándulas salivales menores (56%) (AU)

Associations of diagnostic findings with disease activity in primary SjÓ§gren's syndrome: a cluster analysis.

OBJECTIVE: The diagnosis of primary SjÓ§gren's syndrome still relies upon a constellation of clinical, laboratory, imaging, and pathological findings. We aimed to evaluate the relation of the disease activity with the results of diagnostic tests for primary SjÓ§gren's syndrome. METHODS: A principal component with cluster analysis was performed to classify 69 patients with primary SjÓ§gren's syndrome based on the results of diagnostic evaluations. RESULTS: Anti-SSA autoantibody was the most represented feature on the principal components. The anti-SSA and ultrasound score were positively correlated (p=0.001). We identified two distinct clusters of low or high disease activity (p<0.001). Except for disease duration and serum beta2-microglobulin, the clusters were significantly different in salivary flow (p= 0.004), ultrasound findings (p<0.001), IgG (p= 0.001), and salivary beta2-microglobulin (p= 0.048). Also, positive findings were significantly different between the clusters in rheumatoid factor, antinuclear antibody, anti-SSA, and anti-SSB (all p≤0.013). CONCLUSION: Patients with higher syndrome activity were best recognized with serological and ultrasound assessments. However, patients with lower syndrome activity had a longer disease duration, higher stimulated salivary flow rate, and a positive biopsy of minor salivary glands (56%).

Evaluating the effect of finely ground, dry-rolled, and crumbled corn grain on performance, feeding behavior, and starch digestion in Holstein dairy heifers.

Corn processing methods including finely ground (FGC), dry rolled (DRC), and crumbled corn (CRC) were evaluated to determine their effects on average daily gain (ADG), structural growth, starch digestibility, feeding behavior, and blood metabolites of young dairy heifers. In this study, 36 Holstein heifers [91 ± 4 d of age, 105 ± 6.5 kg of body weight (BW); mean ± standard deviation] housed in 9 pens (4 heifers per pen) were fed diets (dry matter basis) containing 20% forage (wheat straw) and 80% corn-based concentrate for 60 d. Pens were randomly assigned to 1 of 3 dietary treatments based on the type of corn grain used for the diets: (1) ground corn (FGC; fine: 1.11 ± 0.52 mm); (2) dry-rolled corn (DRC; 2.30 ± 0.68 mm); and (3) crumbled corn (CRC; 2.54 ± 0.70 mm). Heifers had ad libitum access to diets and water throughout the experiment and the feed intake was measured daily. Animals were weighed at the beginning (91 d of age) and end (151 d of age) of the study. The ADG (kg of BW/d) was calculated at the end of experiment at an individual level. Feeding behavior was recorded based on direct observation by monitoring each heifer every 5 min during a 22-h period at 150 d of age. The CRC and DRC tended to increase feed intake compared with FGC, whereas heifers fed CRC tended to have a greater withers height compared with other treatments. Feed efficiency was not affected; however, ADG and final BW increased in heifers fed the CRC diet compared with other diets. Feeding CRC increased total-tract starch digestibility compared with FGC and DRC diets (97.8 vs. 93.1 and 89.5%, respectively). Compared with FGC diet, feeding DRC and CRC tended to increase rumination time. The molar proportion of propionate was greater, and the molar proportion of acetate and acetate-to-propionate ratio were lower in heifers fed CRC than in those fed DRC. The blood glucose and insulin-like growth factor concentrations increased in heifers fed CRC compared with feeding DRC; however, blood urea concentrations decreased by CRC feeding. In conclusion, thermal processing (CRC diet) improved total-tract starch digestibility, ADG, feed intake, and skeletal growth, but had no effect on feed efficiency during the experimental period. Our results indicated that the thermal processing of corn grain improved growth performance of weaned heifers; however, the performance of heifers over a 60-d period did not differ between mechanical processing methods (grinding and dry rolling).

The impact of early musical training on striatal functional connectivity.

Evidence from language, visual and sensorimotor learning suggests that training early in life is more effective. The present work explores the hypothesis that learning during sensitive periods involves distinct brain networks in addition to those involved when learning later in life. Expert pianists were tested who started their musical training early (<7 years of age; n = 21) or late (n = 15), but were matched for total lifetime practice. Motor timing expertise was assessed using a musical scale playing task. Brain activity at rest was measured using fMRI and compared with a control group of nonmusicians (n = 17). Functional connectivity from seeds in the striatum revealed a striatal-cortical-sensorimotor network that was observed only in the early-onset group. In this network, higher connectivity correlated with greater motor timing expertise, which resulted from early/late group differences in motor timing expertise. By contrast, networks that differentiated musicians and nonmusicians, namely a striatal-occipital-frontal-cerebellar network in which connectivity was higher in musicians, tended to not show differences between early and late musicians and not be correlated with motor timing expertise. These results parcel musical sensorimotor neuroplasticity into a set of musicianship-related networks and a distinct set of predominantly early-onset networks. The findings lend support to the possibility that we can learn skills more easily early in development because during sensitive periods we recruit distinct brain networks that are no longer implicated in learning later in life.

Molecular epidemiology of Mycobacterium tuberculosis isolates in Iran using spoligotyping.

Spoligotyping can help assess the transmission of Mycobacterium tuberculosis strains. We aimed to study the genotyping of M. tuberculosis isolated from patients with tuberculosis from the west of Iran by spoligotyping. Forty-seven M. tuberculosis isolates were collected from the west of Iran. All samples were cultured on Löwenstein-Jensen medium incubated at 37°C for 8 weeks. Bacterial isolates were identified as M. tuberculosis using standard biochemical tests. Drug resistance patterns of M. tuberculosis to rifampicin and isoniazid were determined, and multidrug-resistant (MDR) strains were isolated. After DNA extraction, spoligotyping was performed. We found new spoligotypes 4162 and 4163, which correlated with atypical lineage. Atypical and unknown lineages also had correlations with the MDR tuberculosis rate (4%). The most prevalent spoligointernational types were orphan (34%), 2669 (23.4%) and 127 (14.8%) types. The most prevalent clades were Ural-2 (NEW-1) (25.53%) and atypical (23.40%) lineages. The predominant clade was Ural-2 (NEW-1) and an atypical lineage restricted to Iran. The rate of MDR was low. Knowledge of the circulating isolates in the west of Iran will help implement control programmes, so knowledge of the dynamic transmission of local isolates is crucial.

Non Invasive Blood Flow Features Estimation in Cerebral Arteries from Uncertain Medical Data.

A methodology for non-invasive estimation of the pressure in internal carotid arteries is proposed. It uses data assimilation and Ensemble Kalman filters in order to identify unknown parameters in a mathematical description of the cerebral network. The approach uses patient specific blood flow rates extracted from Magnetic Resonance Angiography and Magnetic Resonance Imaging. This construction is necessary as the simulation of blood flows in complex arterial networks, such as the circle of Willis, is not straightforward because hemodynamic parameters are unknown as well as the boundary conditions necessary to close this complex system with many outlets. For instance, in clinical cases, the values of Windkessel model parameters or the Young's modulus and the thickness of the arteries are not available on per-patient cases. To make the approach computational efficient, a reduced order zero-dimensional compartment model is used for blood flow dynamics. Using this simplified model, the proof-of-concept study demonstrates how to use the EnKF as an optimization tool to find parameters and how to make the inverse hemodynamic problem tractable. The predicted blood flow rates in the internal carotid arteries and the predicted systolic and diastolic brachial blood pressures are found to be in good agreement with the clinical measurements.

Polymorphism of the IL-18 and CD40 genes and Liver Transplant Outcome in Iranian Patients.

BACKGROUND: Cytokines and co-stimulatory molecules are important factors determining the outcome of transplantation. OBJECTIVE: To investigate the effect of IL-18 and CD40 gene polymorphisms on the outcome of liver transplantation. METHODS: 150 liver transplant recipients were included in this study. Alleles and genotypes frequencies for IL-18 (rs1946519) and CD40 (rs1883832) were determined in 28 acutely rejected (AR group) and 122 non-acutely rejected (non-AR group) liver transplant recipients. IL-18 and CD40 gene polymorphisms were evaluated by PCR-RFLP methods. RESULTS: There were no significant associations between IL-18 and CD40 polymorphism with acute rejection in liver transplant patients. IL-18TT and TG genotypes had a significant association with rejection in women compared to men. After grouping the liver recipients according to living vs cadaver donors, a significant association was found between CC genotype of CD40 and rejection in male living donor recipients. IL-18 TG genotype had a significant association with rejection in female cadaver donor recipients. CONCLUSION: There is no correlation between all genotype and alleles of IL-80 and CD40 polymorphism and the outcome of liver transplantation. However, gender and type of donor affect the correlation between all genotype and alleles of IL-18 and CD40, and the outcome of liver transplantation.

Maladaptive connectivity of Broca's area in schizophrenia during audiovisual speech perception: an fMRI study.

Speech comprehension relies on auditory as well as visual information, and is enhanced in healthy subjects, when audiovisual (AV) information is present. Patients with schizophrenia have been reported to have problems regarding this AV integration process, but little is known about which underlying neural processes are altered. Functional magnetic resonance imaging was performed in 15 schizophrenia patients (SP) and 15 healthy controls (HC) to study functional connectivity of Broca's area by means of a beta series correlation method during perception of audiovisually presented bisyllabic German nouns, in which audio and video either matched or did not match. Broca's area of SP showed stronger connectivity with supplementary motor cortex for incongruent trials whereas HC connectivity was stronger for congruent trials. The right posterior superior temporal sulcus (RpSTS) area showed differences in connectivity for congruent and incongruent trials in HC in contrast to SP where the connectivity was similar for both conditions. These smaller differences in connectivity in SP suggest a less adaptive processing of audiovisually congruent and incongruent speech. The findings imply that AV integration problems in schizophrenia are associated with maladaptive connectivity of Broca's and RpSTS area in particular when confronted with incongruent stimuli. Results are discussed in light of recent AV speech perception models.

Tracking post-error adaptation in the motor system by transcranial magnetic stimulation.

The commission of an error triggers cognitive control processes dedicated to error correction and prevention. Post-error adjustments leading to response slowing following an error ("post-error slowing"; PES) might be driven by changes in excitability of the motor regions and the corticospinal tract (CST). The time-course of such excitability modulations of the CST leading to PES is largely unknown. To track these presumed excitability changes after an error, single pulse transcranial magnetic stimulation (TMS) was applied to the motor cortex ipsilateral to the responding hand, while participants were performing an Eriksen flanker task. A robotic arm with a movement compensation system was used to maintain the TMS coil in the correct position during the experiment. Magnetic pulses were delivered over the primary motor cortex ipsilateral to the active hand at different intervals (150, 300, 450 ms) after correct and erroneous responses, and the motor-evoked potentials (MEP) of the first dorsal interosseous muscle (FDI) contralateral to the stimulated hemisphere were recorded. MEP amplitude was increased 450 ms after the error. Two additional experiments showed that this increase was neither associated to the correction of the erroneous responses nor to the characteristics of the motor command. To the extent to which the excitability of the motor cortex ipsi- and contralateral to the response hand are inversely related, these results suggest a decrease in the excitability of the active motor cortex after an erroneous response. This modulation of the activity of the CST serves to prevent further premature and erroneous responses. At a more general level, the study shows the power of the TMS technique for the exploration of the temporal evolution of post-error adjustments within the motor system.

The molecular prevalence of viral infections in transplant candidates with bone marrow suppression, shiraz, southern iran, 2010.

BACKGROUND: Transient bone marrow suppression, characterized by acute inability of the bone marrow to produce circulating blood cells, may strongly relate to the pathogenesis of some viral infections. OBJECTIVE: To study the prevalence of some DNA and RNA viruses in patients with transient bone marrow suppression. METHODS: EDTA-treated blood samples were collected from 27 patients with clinically- and laboratory-confirmed transient bone marrow suppression. The genomic DNA of hepatitis B virus, adenovirus, polyomavirus BK, and parvovirus B19, and genomic RNA of hepatitis C and G viruses were extracted and amplified by sensitive and specific in-house simple and nested PCR and RT-PCR protocols, respectively. The risk factors that might be related to the studied viral infections were analyzed. RESULTS: Hepatitis B virus infection was diagnosed in 9 (33%) of 27 patients; adenovirus infection in 2 (7%); and parvovirus B19 infection in 7 (26%) of 27 patients. The genomic DNA of polyomovirus BK was not detected in any patients. Both hepatitis C and G viruses were found in 3 (11%) of 27 patients. CONCLUSION: Diagnosis of the high prevalence of hepatitis B virus, and parvovirus B19 in patients with transient bone marrow suppression, reflects the importance of these viral infections in introducing bone marrow suppression. This hypothesis should be confirmed in further studies.

Rapid and sensitive high performance liquid chromatographic determination of zonisamide in human serum application to a pharmacokinetic study.

An accurate and very rapid method for determination of zonisamide an antiepileptic drug, in human serum is described. The analytical procedure involves liquid-liquid extraction of the analyte and an internal standard (vanillin) from human serum by ethyl acetate as extracting solvent. Chromatographic separation was achieved using a monolithic C18 analytical column and a mixture of 0.05 M phosphate buffer containing triethylamine (1 ml/l; pH 2.7) and methanol (83:17 v/v) was used as the mobile phase. The detection wavelength was set at 240 nm. The calibration curve was linear over a concentration range of 0.015-6.4 µg/ml of zonisamide in human serum. The total run time of analysis was 3.5 min and the lower limits of detection and quantification were 0.005 and 0.015 µg/ml, respectively. The method validation was carried out in terms of specificity, sensitivity, linearity, precision, accuracy and stability. The validated method was applied in a randomised crossover bioequivalence study of two different zonisamide preparations in 24 healthy volunteers, and the assay was sensitive enough to measure drug levels up to 8 days following a single dose administration of zonisamide.

A role for coding functional variants in HNF4A in type 2 diabetes susceptibility.

AIMS/HYPOTHESIS: Rare mutations in the gene HNF4A, encoding the transcription factor hepatocyte nuclear factor 4α (HNF-4A), account for ~5% of cases of MODY and more frequent variants in this gene may be involved in multifactorial forms of diabetes. Two low-frequency, non-synonymous variants in HNF4A (V255M, minor allele frequency [MAF] ~0.1%; T130I, MAF ~3.0%)-known to influence downstream HNF-4A target gene expression-are of interest, but previous type 2 diabetes association reports were inconclusive. We aimed to evaluate the contribution of these variants to type 2 diabetes susceptibility through large-scale association analysis. METHODS: We genotyped both variants in at least 5,745 cases and 14,756 population controls from the UK and Denmark. We also undertook an expanded association analysis that included previously reported and novel genotype data obtained in Danish, Finnish, Canadian and Swedish samples. A meta-analysis incorporating all published association studies of the T130I variant was subsequently carried out in a maximum sample size of 14,279 cases and 26,835 controls. RESULTS: We found no association between V255M and type 2 diabetes in either the initial (p = 0.28) or the expanded analysis (p = 0.44). However, T130I demonstrated a modest association with type 2 diabetes in the UK and Danish samples (additive per allele OR 1.17 [95% CI 1.08-1.28]; p = 1.5 × 10⁻4), which was strengthened in the meta-analysis (OR 1.20 [95% CI 1.10-1.30]; p = 2.1 × 10⁻5). CONCLUSIONS/INTERPRETATION: Our data are consistent with T130I as a low-frequency variant influencing type 2 diabetes risk, but are not conclusive when judged against stringent standards for genome-wide significance. This study exemplifies the difficulties encountered in association testing of low-frequency variants.

Genetic association analysis of LARS2 with type 2 diabetes.

AIMS/HYPOTHESIS: LARS2 has been previously identified as a potential type 2 diabetes susceptibility gene through the low-frequency H324Q (rs71645922) variant (minor allele frequency [MAF] 3.0%). However, this association did not achieve genome-wide levels of significance. The aim of this study was to establish the true contribution of this variant and common variants in LARS2 (MAF > 5%) to type 2 diabetes risk. METHODS: We combined genome-wide association data (n = 10,128) from the DIAGRAM consortium with independent data derived from a tagging single nucleotide polymorphism (SNP) approach in Dutch individuals (n = 999) and took forward two SNPs of interest to replication in up to 11,163 Dutch participants (rs17637703 and rs952621). In addition, because inspection of genome-wide association study data identified a cluster of low-frequency variants with evidence of type 2 diabetes association, we attempted replication of rs9825041 (a proxy for this group) and the previously identified H324Q variant in up to 35,715 participants of European descent. RESULTS: No association between the common SNPs in LARS2 and type 2 diabetes was found. Our replication studies for the two low-frequency variants, rs9825041 and H324Q, failed to confirm an association with type 2 diabetes in Dutch, Scandinavian and UK samples (OR 1.03 [95% CI 0.95-1.12], p = 0.45, n = 31,962 and OR 0.99 [0.90-1.08], p = 0.78, n = 35,715 respectively). CONCLUSIONS/INTERPRETATION: In this study, the largest study examining the role of sequence variants in LARS2 in type 2 diabetes susceptibility, we found no evidence to support previous data indicating a role in type 2 diabetes susceptibility.

Long-term treatment of spasticity with botulinum toxin type A: an analysis of 1221 treatments in 137 patients.

OBJECTIVES: Spasticity is a complex disorder that causes significant disability in affected patients. We here present long-term results of botulinum toxin type A (BoNT-A) treatment in spasticity of various etiologies in the upper and lower limbs. PATIENTS AND METHODS: We evaluated long-term results of BoNT-A treatment with Dysport and Botox for up to 12 years in 137 patients with spasticity of various etiologies. The focus was laid on efficacy, dosage, safety and side effects over time in a retrospective analysis of the database of our movement disorder clinic. RESULTS: The mean clinical benefit, latency and duration of response were comparable for both products. Side effects were generally mild and comparable for the two products. We found a significant negative correlation between time from onset of spasticity to start of BoNT-A treatment and degree of improvement after treatment. CONCLUSION: Our data confirm the safety and efficacy of BoNT-A treatment of spasticity of different etiologies over a long period of time. Furthermore, the data imply that BoNT-A treatment should be started early after appearance of spasticity to obtain better treatment response.

Audiovisual integration of speech is disturbed in schizophrenia: an fMRI study.

Speech perception is an essential part of social interaction. Visual information (lip movements, facial expression) may supplement auditory information in particular under inadvertent listening situations. Schizophrenia patients have been shown to have a deficit in integrating articulatory motions with the auditory speech input. The goal of this study was to investigate the neural basis of this deficit in audiovisual speech processing in schizophrenia patients by using fMRI. Disyllabic nouns were presented in congruent (audio matches visual information) and incongruent conditions in a slow event related fMRI design. Schizophrenia patients (n=15) were compared to age and gender matched control participants. The statistical examination was conducted by analysis of variance with main factors: audiovisual congruency and group membership. The patients' brain activity differed from the control group as evidenced by congruency by group interaction effects. The pertinent brain sites were located predominantly in the right hemisphere and comprised the pars opercularis, middle frontal sulcus, and superior temporal gyrus. In addition, we observed interactions bilaterally in the fusiform gyrus and the nucleus accumbens. We suggest that schizophrenia patients' deficits in audiovisual integration during speech perception are due to a dysfunction of the speech motor system in the right hemisphere. Furthermore the results can be also seen as a reflection of reduced lateralization of language functions to the left hemisphere in schizophrenia.

A long-term follow-up of botulinum toxin A in cervical dystonia.

OBJECTIVE: Cervical dystonia (CD) is the most common form of adult-onset focal dystonia, and botulinum toxin A (BoNT-A) has become the first-line treatment for this condition. METHODS: In this work, we present data of 207 CD patients treated with BoNT-A for 6.7 +/- 3.5 years. One hundred and sixty-three patients were treated with Dysport (mean dose, 389 +/- 144 U) and 44 with Botox (mean dose, 145 +/- 44 U). RESULTS: The mean clinical benefit, based on a 0-3 scale (0=no effect, 1=slight, 2=moderate and 3=marked improvement) was similar for Dysport (2.5 +/- 0.3) and Botox (2.2 +/- 0.4). Adverse events were mild and similar for both products. Fewer than 2% of the patients developed neutralizing antibodies. DISCUSSION: These data confirm the efficacy and safety of BoNT-A treatment in CD over an extended period of up to 14 years.

Combined phacoemulsification and Ahmed valve glaucoma drainage implant: a retrospective case series.

PURPOSE: To report on the efficacy and safety of combined phacoemulsification and an Ahmed valve glaucoma drainage implant with respect to visual acuity improvement, intraocular pressure (IOP) control, and requirement for antiglaucoma medication. METHODS: A retrospective chart review was conducted of 41 eyes (31 patients) with coexisting visually significant cataracts and uncontrolled glaucoma who had combined phacoemulsification and Ahmed valve implantation. The outcome measures were: visual acuity, IOP, antiglaucoma medication requirements, and intra- and post-operative complications. Success was categorized as absolute (IOP<21 mmHg without the need for antiglaucoma medication) and relative (IOP<21 mmHg with one or more antiglaucoma medications). Failure was considered to be an IOP<6 mmHg or IOP>21 mmHg on maximally tolerated medications or any devastating complication. RESULTS: The mean patient age was 67.3+/-5.9 years old. The mean visual acuity improved from 0.73+/-0.5 to 0.16+/-0.16 (p=0.000). The mean IOP decreased from 28.2+/-3.1 to 16.8+/-2.1 (p=0.000, 40.4%), while the number of antiglaucoma medication decreased from 2.6+/-0.66 to 1.2+/-1.4 (p=0.000). The absolute and relative success rates were 56.1% and 31.7%, respectively; 5 eyes (12.2%) were considered failures. There were no intraoperative complications; postoperative complications occurred in 8 eyes (19.5%). A hypertensive phase was detected in 12 (29.3%) eyes. CONCLUSIONS: Combined phacoemulsification and Ahmed valve glaucoma drainage implantation is a safe and effective alternative to phacotrabeculectomy in patients with coexisting cataract and refractory glaucoma.

Role of endotoxin in the pathogenesis of critical illness polyneuropathy.

Critical illness polyneuropathy (CIP) occurs in association with sepsis and multiple organ failure; however, little is known about the pathomechanisms of CIP and its therapy. In order to determine the parameters which interfere with development of CIP, electrophysiological investigations of peripheral nerves and biochemical measures were correlated to each other. The present study includes 20 consecutive patients in an intensive care unit developing severe sepsis or septic shock. Nerve conduction studies and electromyography were performed with occurring sepsis (day 1, 7, 14) and neurophysiological parameters were correlated with biochemical measures, especially indicators of infection and inflammation. It was found that all patients developed neurophysiological signs of axonal motor polyneuropathy. There was a significant correlation between serum concentrations of endotoxin and interleukin-2 receptors (IL2-R) and reduction of the amplitude of the compound motor action potentials. Other clinical and biochemical parameters showed no significant correlations with neurophysiological data. This finding apparently indicates that endotoxin damages nerve axons directly or indirectly, e.g. by activation of inflammatory cascades (IL2-R). Endotoxin appears to be an essential factor in the pathogenesis of CIP in sepsis, and therapeutic options neutralizing endotoxin may prevent development of CIP.