Enlarged Virchow Robin spaces associate with cognitive decline in multiple sclerosis.

The clinical significance of Virchow Robin spaces (VRS) in inflammatory brain disorders, especially in multiple sclerosis (MS), is still undefined. We analysed enlarged VRS (eVRS) by means of phase sensitive inversion recovery (PSIR) MRI sequence and investigated their association with inflammation or brain atrophy, and to clinical or physical disability. Forty-three MS patients (21 clinically isolated syndrome suggestive of MS [CIS], 15 RRMS, 7 progressive [PMS]) and 10 healthy controls (HC) were studied. 3DT1, 3DFLAIR and 2DPSIR images were obtained with a 3T MRI scanner. eVRS number and volume were calculated by manual segmentation (ITK-SNAP). Freesurfer was used to assess brain parenchymal fraction (BPF). All patients underwent clinical (EDSS) and cognitive (Rao's BRB and DKEFS) evaluation. eVRS number and volume resulted significantly higher on 2D-PSIR compared to both 3D-T1 (p<0.001) and 3D-FLAIR (p<0.001) and were significantly increased in CIS compared to HC (p<0.05), in PMS and RRMS compared to CIS (p<0.001) and in male versus female patients (p<0.05). eVRS volume increased significantly with disease duration (r = 0.6) but did not correlate with EDSS. eVRS significantly correlated with SPARTd (r = -0.47) and DKEFSfs (r = -0.46), especially when RRMS and PMS were merged in a single group (r = 0.89, p = 0.002 and r = 0.66, p = 0.009 respectively), while no correlation was found with BPF (r = 0.3), gadolinium-enhancing lesions (r = 0.2) and WMT2 lesion volume (r = 0.2). 2DPSIR allowed the detection of an impressive higher number of eVRS compared to 3DT1 and 3DFLAIR. eVRS associate with SPARTd and DKEFSfs failure in relapse-onset MS, suggesting they may contribute to cognitive decline in MS

A Retrospective Study on the Efficacy of Subcutaneous Immunoglobulin as Compared to Intravenous Formulation in Patients with Chronic Lymphocytic Leukemia and Secondary Antibody Deficiency

Secondary antibody deficiency (SAD) is a common complication in chronic lymphocytic leukemia (CLL) which favors the development of life-threatening infections. Subcutaneous immunoglobulins (IG) (SCIG) have been proven to be as effective as intravenous immunoglobulin (IVIG) in primary immunodeficiencies. Since only a few studies investigated SCIG in secondary antibody deficiency, the aim of this study was to assess the efficacy and safety of SCIG or IVIG in CLL patients with secondary antibody deficiency. One hundred and sixteen CLL patients were recruited, 63% were males, and the median age was 68 years; 44% had bronchiectasis and 76% never smoked. Forty-nine patients received IVIG and 88 SCIG, including 28 patients who shifted from IVIG to SCIG. Despite similar baseline IgG levels, patients receiving SCIG achieved higher IgG after at least +6 months (p = 0.0009). We observed that SCIG can decrease the cumulative incidence of first (HR 0.39 p p = 0.0411) infection more than IVIG. The effect was remarkable in that patients were able to reach at least 6 g/L of IgG after 6 months of treatments (p < 0.0001). Replacement therapies were well tolerated with less adverse events and a lower discontinuation rate in patients was managed with SCIG than IVIG. In this study we describe the clinical features of a large cohort of CLL with secondary antibody deficiency receiving IG. We demonstrated that SCIG are active and well tolerated drugs that allows to reach higher IgG levels and decrease the rate of infections better than IVIG, in particular when IgG levels reach 6 g/L

Enlarged Virchow Robin spaces associate with cognitive decline in multiple sclerosis - Fig 4

<p><b>The comparison of PSIR (a,c,e,g) and FLAIR (b,d,f,h) images allows a clear discrimination of eVRS from white matter and grey matter lesions.</b> In (a) and (b) several round-shaped (circle) and one stripe-like (rectangle) eVSR are clearly identified on PSIR, while on the FLAIR image they can hardly be recognised. A cluster of small inflammatory lesions that appear hypointense in PSIR and hyperintense in FLAIR are visible in (c) and (d). The comparison of PSIR and FLAIR images is necessary to discriminate small inflammatory lesions from eVRS. Several eVRS can be observed in the basal ganglia in (e) and (f): also in this case PSIR significantly improves the evaluation of their number and volume. In (g) and (f) some eVRS (rectangles) are observed in the convexity of a CIS patient (* indicates a mixed white/grey matter lesion).</p

The number and volume of eVRS are higher in RRMS patients compared to age-matched CIS patients.

<p>PSIR images showing the WM of the convexities of a normal control (NC) subject, a patients with a clinically isolated syndrome (CIS) suggestive of MS (the patients had dissemination in space of T2 lesions and the presence of oligoclonal IgG in the CSF) and a relapsing-remitting MS patients. The three subjects were matched for age. While eVRS are not observed in HC, their number and volume were significantly higher in RRMS compared to CIS.</p

Volumes and numbers of eVRS obtained on PSIR, T1 and FLAIR images.

<p>Volumes and numbers of eVRS obtained on PSIR, T1 and FLAIR images.</p

Demographic and clinical features of patients and healthy controls included in the study.

<p>Demographic and clinical features of patients and healthy controls included in the study.</p