All patients had adequate temporal window to perform TCD examination. Appearance of at least 1 contrast induced MB signal on the c-TCD trace was regarded pathognomonic for RLS. Patients were prepared with an 18-gauge needle inserted into the cubital vein and were examined in the supine position. Insonation of one MCA using TCD was performed.

The contrast agent was prepared using 9 ml isotonic saline solution and 1 ml air mixed with a three-way stopcock by exchange of saline/air mixture between the syringes and injected as a bolus. The MB were recorded with TCD at rest and in case of little or FG-4592 no detection of MB in the MCA under basal conditions the examination was repeated 5 s post injection following Valsalva maneuver (VM) with controlled duration (10 s) and pressure (forced expiration see more against a manometer to 40 mmHg). All examinations

were done by a single experienced operator (J.S.). Grading or RLS was performed by counting the number of embolic tracks on the power M-mode and Doppler spectrogram in real time and offline. A four-level categorization according to the MB count was applied: (1) 0 MB (negative result); (2) 1–10 MB (low-grade shunt); (3) >10 MB + no curtain (medium-grade); (4) curtain (large-grade). Patients with c-TCD diagnosed RLS underwent transoesophagal echocardiography (TEE) to detect cardiac causes of the shunt. The echocardiographers were blinded as to the status of the individual patients. In the case of negative TEE contrast-enhanced chest CT for the presence of pulmonary arteriovenous malformations (AVM) was performed. The protocol of the study has been accepted by the local Ethics Committee. Written informed consent was obtained from each patient. Fifty patients (mean age 38 years; females 76%), 25 with CHVS and 25 from CG were included to analysis. The groups did not differ with regard to mean age and sex. Table 1 represents demographic

data and baseline neurological characteristics Tobramycin of the analyzed population. Six patients with CHVS (24%) and none from CG had concomitant migraine. Sixteen (64%) patients with CHVD had documented RLS basing on c-TCD examination compared with 3 subjects from CG (12%, p < 0.05) ( Table 2). All patients with RLS from CG had low-grade shunt compared with CHVD group in which 50% of subjects with shunt had medium- or large-grade shunts. Ten of 16 patients with CHVS and RLS (63%) had spontaneous shunt with MB detected at rest compared with 1 of 3 from CG (33%), the rest subjects had provocative RLS detected only after VM. Transoesophagal echocardiography confirmed patent foramen ovale (PFO) in 10 patients with CHVS (40%) and 2 from CG (8%, p < 0.05). PFO was a major cause of RLS in CHVS and CG patients (63% vs 67%, respectively). Basing on chest CT examination, pulmonary AVM was found in 2 patients (10%) with CHVS (13% of patients with RLS and CHVS) and none from CG.