Effect of OSAS on cerebral vasoreactivity and cIMT before and after CPAP treatment.

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) has been shown to be an important risk factor for ischaemic cerebral disease. Specific Doppler parameters may be used to measure cerebral vascular dynamics opening the door to new markers/predictors of risk. The objective of our study was to shed light on how the treatment of OSA with continuous positive airway pressure (CPAP) may have an impact on these parameters and, consequently, lower the risk of cerebral ischemic events in these patients. METHODS: A total of 40 untreated patients diagnosed with moderate to severe obstructive sleep apnoea were submitted to a comprehensive ultrasonographic transcranial Doppler evaluation. The parameters measured were: Breath holding index (BHI), mean blood flow velocity (MBFV) and pulsatility index in middle cerebral artery. Colour Doppler ultrasound was also used to measure carotid intima-media thickness (cIMT). These parameters were compared before and after CPAP treatment. RESULTS: After CPAP treatment, MBFV and BHI were shown to be increased (without statistical significance), while cIMT and polysomnographic parameters were significantly decreased. CONCLUSION: The improvement of cerebral vasoreactivity parameters and cIMT after long-term CPAP treatment suggest that treatment of OSA may influence the cerebral vascular regulation and consequently reduce the risk of stroke.

Genome-Wide Multiple Sclerosis Association Data and Coagulation.

The emerging concept of a crosstalk between hemostasis, inflammation, and immune system prompt recent works on coagulation cascade in multiple sclerosis (MS). Studies on MS pathology identified several coagulation factors since the beginning of the disease pathophysiology: fibrin deposition with breakdown of blood brain barrier, and coagulation factors within active plaques may exert pathogenic role, especially through the innate immune system. Studies on circulating coagulation factors showed complex imbalance involving several components of hemostasis cascade (thrombin, factor X, factor XII). To analyze the role of the coagulation process in connection with other pathogenic pathways, we implemented a systematic matching of genome-wide association studies (GWAS) data with an informative and unbiased network of coagulation pathways. Using MetaCore (version 6.35 build 69300, 2018) we analyzed the connectivity (i.e., direct and indirect interactions among two networks) between the network of the coagulation process and the network resulting from feeding into MetaCore the MS GWAS data. The two networks presented a remarkable over-connectivity: 958 connections vs. 561 expected by chance; z-score = 17.39; p-value < 0.00001. Moreover, genes coding for cluster of differentiation 40 (CD40) and plasminogen activator, urokinase (PLAU) shared both networks, pointed to an integral interplay between coagulation cascade and main pathogenic immune effectors. In fact, CD40 pathways is especially operative in B cells, that are currently a major therapeutic target in MS field. The potential interaction of PLAU with a signal of paramount importance for B cell pathogenicity, such as CD40, suggest new lines of research and pave the way to implement new therapeutic targets.

Propensity Score-Based Analysis of Percutaneous Closure Versus Medical Therapy in Patients With Cryptogenic Stroke and Patent Foramen Ovale: The IPSYS Registry (Italian Project on Stroke in Young Adults).

BACKGROUND: We sought to compare the benefit of percutaneous closure to that of medical therapy alone for the secondary prevention of embolism in patients with patent foramen ovale (PFO) and otherwise unexplained ischemic stroke, in a propensity scored study. METHODS AND RESULTS: Between 2000 and 2012, we selected consecutive first-ever ischemic stroke patients aged 18 to 45 years with PFO and no other cause of brain ischemia, as part of the IPSYS registry (Italian Project on Stroke in Young Adults), who underwent either percutaneous PFO closure or medical therapy for comparative analysis. Primary end point was a composite of ischemic stroke, transient ischemic attack, or peripheral embolism. Secondary end point was brain ischemia. Five hundred and twenty-one patients qualified for the analysis. The primary end point occurred in 15 patients treated with percutaneous PFO closure (7.3%) versus 33 patients medically treated (10.5%; hazard ratio, 0.72; 95% confidence interval, 0.39-1.32; P=0.285). The rates of the secondary end point brain ischemia were also similar in the 2 treatment groups (6.3% in the PFO closure group versus 10.2% in the medically treated group; hazard ratio, 0.64; 95% confidence interval, 0.33-1.21; P=0.168). Closure provided a benefit in patients aged 18 to 36 years (hazard ratio, 0.19; 95% confidence interval, 0.04-0.81; P=0.026) and in those with a substantial right-to-left shunt size (hazard ratio, 0.19; 95% confidence interval, 0.05-0.68; P=0.011). CONCLUSIONS: PFO closure seems as effective as medical therapy for secondary prevention of cryptogenic ischemic stroke. Whether device treatment might be more effective in selected cases, such as in patients younger than 37 years and in those with a substantial right-to-left shunt size, deserves further investigation.

Cerebral ischemia in young patients (under 45 years of age): clinical and neuroradiological follow-up.

Ischemic stroke in young patients is a relatively rare event. Few studies have examined the long-term prognosis. The aim of this study was to evaluate the long-term outcome to identify clinical, laboratory and radiologic patterns as possible predictors for mortality, recurrence and functional recovery. We prospectively evaluated 94 patients (42 males and 52 females, aged 14-45 years, mean age 35.5 years, SD 8.4) admitted to our Neurological Department, for first acute ischemic stroke. A 48-month follow-up was performed. The patients were classified according to TOAST and Baltimore classification and Bamford criteria. The severity of the neurological deficit on admission was assessed using the NIHSS. The follow-up included a clinical visit, the modified Ranking scale (mRs) score, Barthel index (BI), and magnetic resonance imaging and intra-extracranial vessel Angio MRI. A good functional outcome (mRS 0-1) was found in 74 patients and unfavourable outcome (mRS 2-6) in 20 patients. 16 patients had a recurrent cerebral ischemic event: 5 patients had stroke and 11 patients had TIA. The average incidence annual rate of recurrence was 4.5% and a mortality rate was of 1.06%. Our study does not demonstrate any predictive factor related to clinical outcome. The relevant data of neuroradiological follow-up is the presence of clinically silent lesions in nine patients, considered as a recurrent stroke. To attribute a prognostic role to these lesions, clinical and neuroradiological follow-up needs to be continued.

Asymmetric posterior reversible encephalopathy syndrome in patient with hyperplastic anterior choroidal artery.

We describe a case of asymmetric PRES due to the presence of hyperplastic anterior choroidal artery (AChA) in a man affected by sever hypertension. Posterior reversible encephalopathy syndrome (PRES) has become synonymous with a unique pattern of brain vasogenic edema and predominates in the parietal and occipital regions, accompanied by clinical neurological alterations. Sever hypertension is a risk factor that exceeds the limits of brain autoregulation, leading to breakthrough brain edema. In our knowledge this is the first case reported in literature, in which a similar vascular abnormality is linked to a PRES syndrome.