Patient-reported outcome measures in patients with familial cerebral cavernous malformations: results from the Treat_CCM trial.

Background: The Phase 1/2 Treat_CCM randomized controlled trial for people with familial cerebral cavernous malformations (FCCMs) confirmed the safety of propranolol and suggested beneficial effects on intracerebral hemorrhage or new focal neurological deficits, but the effects on patient-reported outcome measures have not been reported. Methods: Participants completed self-reported questionnaires at baseline, 1 and 2 years. Depression was assessed with the Beck Depression Inventory-II (BDI-2); Anxiety with the State-Trait Anxiety Inventory X1 and X2 (STAI X-1 and STAI X-2); and Quality of Life with the Short Form 36 (SF-36), split into the physical and mental component scales (PCS and MCS). Differences between treatment groups and the general population were assessed. Change over time by treatment was assessed by means of mixed models. Results: In total, 71 participants (48 propranolol and 23 standard care) were enrolled, of whom 61 (73%) completed questionnaires at baseline and 2-year FU. At baseline, no differences between treatment groups for any of the questionnaires were present. Twenty (31.7%) patients were considered depressed at baseline, while this proportion was lower in the propranolol group after 2 years (28.6% vs. 55.5%, p = 0.047). The STAI X-1 and X-2 scores were stable over time. PCS was lower in FCCM patients as compared with the general Italian population, while the MCS was similar to the general population. No effect of propranolol was found for both PCS and MCS. Conclusion: Depression is common among patients with FCCM. Patients randomized to propranolol had a lower proportion of participants with depression after 2 years.Clinical trial registration: https://clinicaltrials.gov/, identifier (NCT03589014).

Microembolic air load during contrast-transcranial Doppler: a trigger for migraine with aura?

BACKGROUND: There is a well-known association between migraine with aura (MA) and right-to-left shunt (RILES) because of patent foramen ovale (PFO). The occurrence of MA attacks after microbubble (MB) injection during contrast-enhanced transcranial Doppler (ce-TCD) has been recently described. OBJECTIVES: The aim of this study was to analyze the prevalence of RILES in a consecutive cohort of MA patients and to characterize the occurrence of MA attacks after diagnostic ce-TCD. METHODS: A total of 159 consecutive MA patients underwent ce-TCD with air-mixed saline to disclose RILES. RILES was characterized in terms of MB amount (small-moderate or large) and occurrence at rest and/or during Valsalva maneuver (permanent or latent). RESULTS: RILES was revealed in 79/159 patients (∼ 50%). Permanent RILES were detected in 56/79 (71%) and latent RILES in 23/79 (29%) MA patients. The occurrence of a typical MA attack was overall observed in 12/159 patients (7.5%; 95% CI: 4-12.8%), but arose only in RILES-positive ones, immediately after ce-TCD (12/79; 15.2%; P< .001). All 12 patients had permanent RILES (12/56; 21.4%; P= .015) and MA attack was mostly observed in large RILES-positive patients, even without statistical significance (P= .118). CONCLUSIONS: Microembolic air load could act as a trigger of MA attack. According to recent studies and to the clinical characteristics observed in our patients, microembolization because of MB injection might provoke a decrease in cerebral oxygen saturation, thus triggering cortical spreading depression and, thereafter, MA attack. Larger and prospective studies will be necessary to confirm our data and observe a wider correlation.

Aspirin resistance determined with PFA-100 does not predict new thrombotic events in patients with stable ischemic cerebrovascular disease.

OBJECTIVE: Evidence is growing that some patients are not responsive to the antithrombotic action of aspirin. We prospectively evaluated the ability of aspirin resistance status, determined by PFA-100, to predict new thrombotic events in patients with stable ischemic cerebrovascular disease. METHODS: We studied 129 consecutive patients with stroke, transient ischemic attack (TIA) or vascular cognitive impairment. We assessed relationships between aspirin resistance, risk factors for ischemic cerebrovascular disease, and occurrence of new thrombotic events (composite of stroke, TIA, myocardial infarction, and cardiovascular death). RESULTS: Aspirin resistance, found in 26 (20.1%) cases, was unrelated to any of the examined vascular risk factors. During mean follow-up of 56 months, new thrombotic events occurred in 19 patients (14.7%), four with aspirin resistance (15.4%) and 15 (14.6%) without aspirin resistance (p=1.00). CONCLUSION: Aspirin resistance determined by PFA-100 does not predict new thrombotic events in patients with stable ischemic cerebrovascular disease.

Postural dependency of right to left shunt: role of contrast-enhanced transcranial Doppler and its potential clinical implications.

BACKGROUND AND PURPOSE: Right to left shunt is involved in conditions in which postural changes may be pathogenically relevant. The aim of this work was to assess the frequency of posturally dependent right to left shunt. METHODS: In 109 consecutive right to left shunt-positive subjects (male/female=40/69, age 43+/-12 years), we assessed with contrast-enhanced transcranial Doppler the bubble load during normal breathing and after the Valsalva maneuver in both standing and recumbent position randomizing the order of testing. RESULTS: During normal breathing, the average bubble count was 11+/-20 in the recumbent and 26+/-60 in the standing position. After the Valsalva maneuver, it was 40+/-38 and 42+/-37, respectively. The increase of bubble load in standing position occurred in 42% of patients and was independent of the order of testing. CONCLUSIONS: The amount of permanent right to left shunt is posture-dependent in 40% of patients. Testing in the sitting position may thus be warranted in doubtful or inconclusive results obtained with the subject in the horizontal position.