Thalidomide causes sinus bradycardia in ALS.

OBJECTIVE: Neuroinflammation contributes to motor neuron degeneration in ALS. Thalidomide (THL) shows potent anti-inflammatory properties and increased the lifespan in ALS transgenic mice. Thalidomide was therefore suggested as atherapeutic intervention for the treatment of ALS.We conducted a pilot, randomized clinical trial of THL in patients with ALS to assess safety, feasibility, and preliminary estimates of treatment efficacy. METHODS: Patients were randomized to THL in combination with riluzole (n = 18) or riluzole alone (n = 19). THL was initiated at 100 mg per day for 6 weeks. Thereafter, the dose was increased every week by 50 mg until reaching the dose of 400 mg per day and planned to continue for another 12 weeks. RESULTS: Within 12 weeks of THL treatment, nine THL patients (50%) developed bradycardia defined as a heart rate below 60 beats per minute (bpm) and ranged from 46 to 59 bpm. Mean heart rate dropped by 17 bpm with THL treatment. Severe symptomatic bradycardia of 30 bpm occurred in one patient. A further patient died from sudden unexpected death. The study was terminated prematurely for safety concerns. The secondary outcome variables showed similar results for both groups. CONCLUSION: Bradycardia was the most common adverse event of THL treatment in ALS. THL-related bradycardia does not appear to be ALS-specific. It is conceivable, however, that the unexpected frequency and severity of THL-induced bradycardia may be related to subclinical involvement of the autonomic nervous system in ALS. The cardiac toxicity discourages further clinical trials and compassionate use of THL in ALS. ClinicalTrials.gov Identifier: NCT00231140.

Point-of-care testing for interleukin-6 in cerebro spinal fluid (CSF) after subarachnoid haemorrhage.

BACKGROUND: Intrathecal interleukin (IL)-6 is considered to be a proinflammatory biomarker for cerebral inflammatory response. This is of clinical importance for the prediction of vasospasm after subarachnoid haemorrhage (SAH). We evaluated a bedside technique for the quantitative measurement of IL-6 in the cerebrospinal fluid (CSF). MATERIAL/METHODS: 32 samples of CSF and serum were taken from 11 patients suffering from SAH on day 3, 4 and 5 after bleeding. A lateral flow immunoassay chip-test (POC-Test) was used for bedside testing and the results were compared to the standard chemiluminescence-based ELISA (Immulite) performed in a specialized laboratory. RESULTS: For CSF analysis Immulite and POC-Test show linear correlation (r2=0.81). The high IL-6 values found in SAH are depicted more easily by the POC-Test, because it has a working range of up to 10.000 pg/ml instead of up to 1000 pg/ml for Immulite. Serum IL-6 values were clearly lower, suggesting CNS inflammation in SAH. CONCLUSIONS: The new chip-test provides a handy tool for the neurosurgical intensive care unit, analysing CSF IL-6 concentrations within 20 minutes. This is the first time a point-of care test for IL-6 in CSF was evaluated. The test results match the values achieved by the standard Immulite technique. Therefore a tool for clinical routine interleukin-6 investigation is provided which could find use in a broad variety of neurosurgical and neurological diseases.

A new qualitative interleukin-6 bedside test can predict pneumonia in patients with severe head injury--comparison to the standard Immulite test and a semiquantitative bedside test.

Severe head injury (SHI) leads to systemic immunosuppression, which is processed by central mechanisms and is associated with a high risk of pneumonia. The timely identification of an immunodepressed condition in SHI patients might help prevent infections by changing the intensive care strategy. The aim of this prospective study is to evaluate a new method for identifying immunodepression and predicting pneumonia. We correlated interleukin (IL)-6 levels determined by the standard test (Immulite) and performed by specialized laboratories with those obtained using the new bedside test (PicoScan) with the occurrence of pneumonia in patients with SHI. Thirty-two patients with isolated SHI were investigated. Analyses were performed on serum samples taken 2 to 24 hours after trauma. Pearson correlation coefficient was 0.924 (P<0.001) for IL-6 values determined by PicoScan versus Immulite and Spearman rho was 0.572 for visual interpretation versus Immulite (P=0.01). Immulite and PicoScan have a positive predictive value of 91% and 100%, respectively, and a negative predictive value of 76% and 86%. The present study investigated for the first time the determination of IL-6 concentrations by PicoScan in patients. Our findings show a good correlation with the results of the standard Immulite test and suggest that the PicoScan may be used as a handy tool to predict pneumonia in SHI patients.