Theophylline as an Add-On to Thrombolytic Therapy in Acute Ischemic Stroke: A Randomized Placebo-Controlled Trial.

BACKGROUND AND PURPOSE: Delayed recanalization increases the risk of infarct growth and poor clinical outcome in acute ischemic stroke. The vasoactive agent theophylline has shown neuroprotective effects in animal stroke models but inconclusive results in case series and randomized clinical trials. The primary objective of this study was to evaluate whether theophylline, as an add-on to thrombolytic therapy, is safe and effective in acute ischemic stroke patients. METHODS: The TEA-Stroke trial (The Theophylline in Acute Ischemic Stroke) was an investigator-initiated 2-center, proof-of-concept, phase II clinical study with a randomized, double-blinded, placebo-controlled design. The main inclusion criteria were magnetic resonance imaging-verified acute ischemic stroke, moderate to severe neurological deficit (National Institutes of Health Stroke Scale score of ≥4), and treatment with thrombolysis within 4.5 hours of onset. Participants were randomly assigned in the ratio 1:1 to either 220 mg of intravenous theophylline or placebo. The co-primary outcomes were early clinical improvement on the National Institutes of Health Stroke Scale score and infarct growth on magnetic resonance imaging at 24-hour follow-up. RESULTS: Theophylline as an add-on to thrombolytic therapy improved the National Institutes of Health Stroke Scale score at 24 hours by mean 4.7 points (SD, 5.6) compared with an improvement of 1.3 points (SD, 7.5) in the control group (P=0.044). Mean infarct growth was 141.6% (SD, 126.5) and 104.1% (SD, 62.5) in the theophylline and control groups, respectively (P=0.146). Functional independence at 90 days was 61% in the theophylline group and 58% in the control group (P=0.802). CONCLUSIONS: This proof-of-concept trial investigated theophylline administration as an add-on to thrombolytic therapy in acute ischemic stroke. The co-primary end points early clinical improvement and infarct growth at 24-hour follow-up were not significantly different after post hoc correction for multiplicity (Bonferroni technique). The small study size precludes a conclusion as to whether theophylline has a neuroprotective effect but provides a promising clinical signal that may support a future clinical trial. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: EudraCT number 2013-001989-42.

Pain profiling of patients with temporomandibular joint arthralgia and osteoarthritis diagnosed with different imaging techniques.

BACKGROUND: Clinical differentiation between pain mechanisms of temporomandibular joint (TMJ) arthralgia and osteoarthritis (OA) is challenging. The aims were to compare somatosensory function at the TMJs and conditioned pain modulation (CPM) effects between TMJ arthralgia and OA patients diagnosed clinically and based on different imaging techniques and age- and gender-matched healthy controls (n = 41). METHODS: Patients (n = 58) underwent standard clinical examination and three different TMJ imaging modalities. After each examination, they were classified into arthralgia or OA based on the findings. TMJ region somatosensory testing was performed in all participants. Z-scores were calculated for patients based on healthy reference data. CPM was tested by comparing pressure pain thresholds (PPTs) at TMJ and thenar (control) before, during and after the application of painful and nonpainful cold stimuli. Data were analyzed using analyses of variance. RESULTS: Somatosensory abnormalities were commonly detected in both patient groups. Assessment of somatosensory function at the TMJ revealed that arthralgia patients were less sensitive to warmth, cold and tactile stimuli than OA patients (P < 0.048). OA patients showed pressure hyperalgesia compared with arthralgia patients (P = 0.025). There was a significant CPM effect at both test sites during painful cold application in all groups (P < 0.001). There was no significant difference in the relative CPM effect between groups except for clinically diagnosed arthralgia patients showing reduced CPM effect compared with controls (P = 0.047). CONCLUSIONS: Pain profiles including somatosensory function differed between TMJ arthralgia and OA patients although CPM effects were similar in patients and controls. Thus, different TMJ pain conditions may share common pain mechanisms but the present study for the first time also indicated that differential pain mechanisms could be involved.

[Progressive multifocal leukoencephalopathy in a patient with multiple myeloma].

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease in the central nervous system. It is caused by reactivation of John Cunningham-virus and has a grave prognosis. PML occurs most frequently in HIV-patients, but can also be seen in patients with iatrogenic immunodeficiency. Here, we present a patient with multiple myeloma and cardiac amyloidosis who developed PML after receiving treatment with several chemotherapeutics. This case report underlines the importance of bearing PML in mind when immunocompromised patients develop diffuse neurological symptoms.