Mixed Effects of Deep Brain Stimulation on Depressive Symptomatology in Parkinson’s Disease: A Review of Randomized Clinical Trials

Although ~50% of patients with Parkinson’s disease (PD) experience depression, treatment for this important and debilitating comorbidity is relatively understudied. Deep brain stimulation (DBS) has been increasingly utilized for the management of tremors in progressive PD. Several preliminary studies have shown the potential benefit of DBS for non-motor PD symptoms such as depression. Here, we critically evaluate seven recent randomized clinical trials of the effectiveness of DBS in reducing depressive symptomatology among individuals with PD. Findings are mixed for the effectiveness of DBS as a treatment for depression in PD. Our review suggests that this is due, in large part, to the anatomical and methodological variation across the DBS studies. We provide a comprehensive discussion of these variations and highlight the need to conduct larger, more controlled studies aimed specifically at evaluating the treatment of depression in PD patients

Towards a Critique of Educative Violence: Walter Benjamin and ‘Second Education’

Although modern systems of mass education are typically defined in their opposition to violence, it has been argued that it is only through an insistent and critical focus upon violence that radical thought can be sustained. This article seeks to take up this challenge in relation to Walter Benjamin’s lesser-known writings on education. Benjamin retained throughout his life a deep suspicion about academic institutions and about the pedagogic, social and economic violence implicated in the idea of cultural transmission. He nonetheless remained committed to the possibility of another kind of revolutionary potential inherent to true education and, when he comes to speak of this in his Critique of Violence, it is remarkable that he describes it as manifesting an educative violence. This article argues that Benjamin’s philosophy works toward a critique of educative violence that results in a distinction between a ‘first’ and ‘second’ kind of education and asks whether destruction might have a positive role to play within pedagogical theories in contrast to current valorisations of creativity and productivity

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Midbrain–hindbrain involvement in lissencephalies

OBJECTIVES: To determine the involvement of the midbrain and hindbrain (MHB) in the groups of classic (cLIS), variant (vLIS), and cobblestone complex (CBSC) lissencephalies and to determine whether a correlation exists between the cerebral malformation and the MHB abnormalities. METHODS: MRI scans of 111 patients (aged 1 day to 32 years; mean 5 years 4 months) were retrospectively reviewed. After reviewing the brain involvement on MRI, the cases were reclassified according to known mutation (LIS1, DCX, ARX, VLDLR, RELN, MEB, WWS) or mutation phenotype (LIS1-P, DCX-P, RELN-P, ARX-P, VLDLR-P) determined on the basis of characteristic MRI features. Abnormalities in the MHB were then recorded. For each structure, a score was assigned, ranging from 0 (normal) to 3 (severely abnormal). The differences between defined groups and the correlation between the extent of brain agyria/pachygyria and MHB involvement were assessed using Kruskal-Wallis and χ McNemar tests. RESULTS: There was a significant difference in MHB appearance among the three major groups of cLIS, vLIS, and CBSC. The overall score showed a severity gradient of MHB involvement: cLIS (0 or 1), vLIS (7), and CBSC (11 or 12). The extent of cerebral lissencephaly was significantly correlated with the severity of MHB abnormalities (p = 0.0029). CONCLUSION: Our study focused on posterior fossa anomalies, which are an integral part of cobblestone complex lissencephalies but previously have not been well categorized for other lissencephalies. According to our results and the review of the literature, we propose a new classification of human lissencephalies. © 2009 by AAN Enterprises, Inc.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Dilated perivascular spaces: An informative radiologic finding in Sanfilippo syndrome type A

WOS: 000255340200011PubMed: 18410855Mucopolysaccharidosis type IIIA, or Sanfilippo syndrome type A, is a lysosomal storage disorder caused by deficiency of heparan N-sulfamidase, resulting in defective degradation and subsequent storage of heparan sulfate. It is characterized by progressive nervous system involvement. Cribriform changes in the corpus callosum, basal ganglia, and white matter, diffuse high-intensity signal in the white matter, and cerebral atrophy have been described in patients with this disorder. This case report describes a child with Sanfilippo syndrome type A who exhibited fairly mild clinical findings but-an unusual magnetic resonance imaging pattern that included multiple moderate-sized cysts (probably enlarged perivascular spaces) within the corpus callosum and an abnormal appearance of the clivus and cervical vertebrae. This case calls attention to the variety of appearances possible with magnetic resonance imaging in Sanfilippo syndrome type A. (C) 2008 by Elsevier Inc. All rights reserved