Psychiatric disorders in the families of schizotypal subjects.

In a study of the families of 21 schizotypal patients, we found an increased morbidity risk for schizophrenia compared with that in the families of 21 nonschizotypal patients and 42 controls. The Axis I diagnoses did not influence the distribution of the morbidity risk in the families of the schizotypal patients. If the schizotypal subjects also had other personality disorders, the morbidity risk for schizophrenia among their relatives was lower, although not significantly.     

''Gender gap'' in multiple sclerosis: magnetic resonance imaging evidence

The authors evaluated the gender difference in the magnetic resonance imaging characteristics of the lesions occurring in the brain of 413 multiple sclerosis (MS) patients. Men had fewer contrast-enhancing lesions (P = 0.01), but a higher proportion of lesions evolving into 'black holes' (P = 0.001), when compared with women. Thus, our data indicate that men with MS are prone to develop less inflammatory, but more destructive lesions than women. This study results provides support for a modulation of the MS pathological changes by gender.     

Two-year maintenance treatment with citalopram, 20 mg, in unipolar subjects with high recurrence rate

BACKGROUND: The efficacy of citalopram, 20 to 60 mg/day, in relapse prevention in major depression was demonstrated in 6-month placebo-controlled studies. The authors tested the efficacy of citalopram, 40 mg/day, in relapse prevention over a 4-month period and citalopram, 20 mg/day, in recurrence prevention over a 24-month period. METHOD: Fifty inpatients with recurrent major depressive disorder (DSM-IV criteria) who had had at least one depressive episode during the 18 months preceding the index episode were openly treated with citalopram, 40 mg/day. Thirty-six subjects had a stable response to citalopram and remained in the continuation treatment with citalopram, 40 mg/day, for 4 months as outpatients. At the time of recovery, 32 patients gave their written informed consent before entering the 24-month maintenance period with citalopram, 20 mg/day. They were evaluated monthly by trained psychiatrists on the basis of the 21-item Hamilton Rating Scale for Depression. Every 3 months, patients were given the Sheehan Disability Scale, a self-rating instrument, to assess their psychosocial adjustment. RESULTS: No relapse was observed in the 4-month continuation period. Sixteen (50%) of 32 patients who entered the 24-month maintenance period had a new recurrence. Patients with recurrence showed a persistent moderate disability on Sheehan Disability Scale score, while no further differences were highlighted in clinical and demographic characteristics between patients with and without recurrence. CONCLUSION: In agreement with previous findings, these data suggest that a full dose of antidepressant is strongly recommended in prophylactic therapy of patients with recurrent major depression. Moreover, it appears that psychosocial impairment may increase the risk of recurrence, thus conditioning a poor outcome.     

Real world experience with teriflunomide in multiple sclerosis: the TER-Italy study

Journal of Neurology - To identify baseline factors associated with disease activity in patients with relapsing–remitting multiple sclerosis (RRMS) under teriflunomide treatment. This was an...     

Clinical course of central nervous system demyelinating neurological adverse events associated with anti-TNF therapy

Journal of Neurology - Previous studies have reported an association between anti-tumor necrosis factor alpha (anti-TNFα) treatment and central nervous system (CNS) events. We described eight...     

Prior antiplatelet drug use and short-term mortality in older patients with acute ischemic stroke (AIS)

Some studies suggest that previous treatment with antiplatelet agents (AA) might reduce ischemic stroke severity and improve outcomes in terms of clinical deficits or mortality. We evaluated the effect of the prior chronic use of AA on short-term (30 days) mortality in a sample of consecutive patients with AIS. Four hundred thirty-nine older patients (>65 years) with “major” AIS (modified Rankin scale ≥ 3) consecutively admitted to the University ward of Internal Medicine or Geriatrics were enrolled. Stroke was classified according to Oxfordshire Community Stroke Project (OCSP). Data recorded included: (1) clinical features; (2) medical history including home therapies, and vascular risk factors; (3) routine clinical chemistry analyzes (verb)/analyses (noun). Short-term (30 days) mortality was 27.6%. One hundred fifteen subjects (26.2%) were taking AA before admission. Compared with subjects not treated, subjects taking AA were characterized by higher prevalence of recurrent stroke (35% vs. 22%). In this group, a trend toward a higher prevalence of congestive heart failure (CHF), smoking, and altered levels of consciousness (ALC) was noted. Stroke type and short-term mortality (33% vs. 26.2%; odds ratio = OR = 1.25; 95% confidence interval = CI = 0.75-2.10, age and gender adjusted) were not different between the two groups. Adjustment for glucose, CHF, previous stroke, smoking, and ALC did not change mortality risk (OR = 0.83; 95%CI = 0.40-1.72). We conclude that in older patients hospitalized for “major” AIS, prior use of AA was not associated with any benefit in terms of short-term mortality both in patients with first, as well as in those with recurrent ischemic stroke.     

Early use of high-efficacy disease‑modifying therapies makes the difference in people with multiple sclerosis: an expert opinion

Multiple sclerosis (MS) is a chronic and progressive neurological disease that is characterized by neuroinflammation, demyelination and neurodegeneration occurring from the earliest phases of the disease and that may be underestimated. MS patients accumulate disability through relapse-associated worsening or progression independent of relapse activity. Early intervention with high-efficacy disease-modifying therapies (HE-DMTs) may represent the best window of opportunity to delay irreversible central nervous system damage and MS-related disability progression by hindering underlying heterogeneous pathophysiological processes contributing to disability progression. In line with this, growing evidence suggests that early use of HE-DMTs is associated with a significant greater reduction not only of inflammatory activity (clinical relapses and new lesion formation at magnetic resonance imaging) but also of disease progression, in terms of accumulation of irreversible clinical disability and neurodegeneration compared to delayed HE-DMT use or escalation strategy. These beneficial effects seem to be associated with acceptable long-term safety risks, thus configuring this treatment approach as that with the most positive benefit/risk profile. Accordingly, it should be mandatory to treat people with MS early with HE-DMTs in case of prognostic factors suggestive of aggressive disease, and it may be advisable to offer an HE-DMT to MS patients early after diagnosis, taking into account drug safety profile, disease severity, clinical and/or radiological activity, and patient-related factors, including possible comorbidities, family planning, and patients’ preference in agreement with the EAN/ECTRIMS and AAN guidelines. Barriers for an early use of HE-DMTs include concerns for long-term safety, challenges in the management of treatment initiation and monitoring, negative MS patients’ preferences, restricted access to HE-DMTs according to guidelines and regulatory rules, and sustainability. However, these barriers do not apply to each HE-DMT and none of these appear insuperable.

     

The N‐terminal fragment of the β‐amyloid precursor protein of Alzheimer's disease (N‐APP) binds to phosphoinositide‐rich domains on the surface of hippocampal neurons

The function of the β‐amyloid precursor protein (APP) of Alzheimer's disease is poorly understood. The secreted ectodomain fragment of APP (sAPPα) can be readily cleaved to produce a small N‐terminal fragment (N‐APP) that contains heparin‐binding and metal‐binding domains and that has been found to have biological activity. In the present study, we examined whether N‐APP can bind to lipids. We found that N‐APP binds selectively to phosphoinositides (PIPs) but poorly to most other lipids. Phosphatidylinositol 4,5‐bisphosphate (PI(4,5)P₂)‐rich microdomains were identified on the extracellular surface of neurons and glia in primary hippocampal cultures. N‐APP bound to neurons and colocalized with PIPs on the cell surface. Furthermore, the binding of N‐APP to neurons increased the level of cell‐surface PI(4,5)P₂ and phosphatidylinositol 3,4,5‐trisphosphate. However, PIPs were not the principal cell‐surface binding site for N‐APP, because N‐APP binding to neurons was not inhibited by a short‐acyl‐chain PIP analogue, and N‐APP did not bind to glial cells which also possessed PI(4,5)P₂ on the cell surface. The data are explained by a model in which N‐APP binds to two distinct components on neurons, one of which is an unidentified receptor and the second of which is a PIP lipid, which binds more weakly to a distinct site within N‐APP. Our data provide further support for the idea that N‐APP may be an important mediator of APP's biological activity. © 2014 Wiley Periodicals, Inc.