Safety and Tolerability of Active Immunotherapy Targeting α-Synuclein with PD03A in Patients with Early Parkinson's Disease: A Randomized, Placebo-Controlled, Phase 1 Study.

Background: Immunotherapies targeting α-synuclein aim to limit its extracellular spread in the brain and prevent progression of pathology in Parkinson's disease (PD). PD03A is a specific active immunotherapy (SAIT) involving immunization with a short peptide formulation.

Objective: This phase 1 study characterized the safety and tolerability of PD03A in patients with early PD.

A Phase 1 Randomized Trial of Specific Active α-Synuclein Immunotherapies PD01A and PD03A in Multiple System Atrophy.

Multiple system atrophy (MSA) is a rare and fatal neurodegenerative disease with limited symptomatic treatment options. Aggregation of α-synuclein in oligodendrocytes is believed to be a central mechanism of the neurodegenerative process. PD01A and PD03A are 2 novel therapeutic vaccine candidates containing short peptides as antigenic moieties that are designed to induce a sustained antibody response, specifically targeting pathogenic assemblies of α-synuclein.

Safety and immunogenicity of the α-synuclein active immunotherapeutic PD01A in patients with Parkinson's disease: a randomised, single-blinded, phase 1 trial.

Background: Robust evidence supports the role of α-synuclein pathology as a driver of neuronal dysfunction in Parkinson's disease. PD01A is a specific active immunotherapy with a short peptide formulation targeted against oligomeric α-synuclein. This phase 1 study assessed the safety and tolerability of the PD01A immunotherapeutic in patients with Parkinson's disease.

Altered interregional molecular associations of the serotonin transporter in attention deficit/hyperactivity disorder assessed with PET.

Altered serotonergic neurotransmission has been found to cause impulsive and aggressive behavior, as well as increased motor activity, all exemplifying key symptoms of ADHD. The main objectives of this positron emission tomography (PET) study were to investigate the serotonin transporter binding potential (SERT BP ) in patients with ADHD and to assess associations of SERT BP between the brain regions. 25 medication-free patients with ADHD (age ± SD; 32.

Compliance as a stable function in the treatment course of bipolar disorder in patients stabilized on olanzapine: results from a 24-month observational study.

Compliance is a key factor in the maintenance treatment of bipolar disorder. This noninterventional study was conducted to explore factors associated with higher levels of compliance in bipolar patients, all treated in routine clinical settings. Bipolar outpatients (Clinical Global Impression of Severity score ≤3) who had been stabilized with olanzapine mono- or combination therapy for ≥4 weeks were enrolled in the study.

The norepinephrine transporter in attention-deficit/hyperactivity disorder investigated with positron emission tomography.

Importance: Attention-deficit/hyperactivity disorder (ADHD) research has long focused on the dopaminergic system's contribution to pathogenesis, although the results have been inconclusive. However, a case has been made for the involvement of the noradrenergic system, which modulates cognitive processes, such as arousal, working memory, and response inhibition, all of which are typically affected in ADHD. Furthermore, the norepinephrine transporter (NET) is an important target for frequently prescribed medication in ADHD.

Multiple sclerosis deep grey matter: the relation between demyelination, neurodegeneration, inflammation and iron.

In multiple sclerosis (MS), diffuse degenerative processes in the deep grey matter have been associated with clinical disabilities. We performed a systematic study in MS deep grey matter with a focus on the incidence and topographical distribution of lesions in relation to white matter and cortex in a total sample of 75 MS autopsy patients and 12 controls. In addition, detailed analyses of inflammation, acute axonal injury, iron deposition and oxidative stress were performed.

Pathology of multiple sclerosis and related inflammatory demyelinating diseases.

This article provides a comprehensive overview of the pathology of multiple sclerosis (MS), including recent insights into its molecular neuropathology and immunology. It shows that all clinical manifestations of relapsing and progressive MS display the same basic features of pathology, such as chronic inflammation, demyelination in the white and gray matter, and diffuse neurodegeneration within the entire central nervous system. However, the individual components of the pathological spectrum vary quantitatively between early relapsing and late progressive MS.

Attention deficit hyperactivity disorder in the European adult population: prevalence, disease awareness, and treatment guidelines.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurobiological disorder with childhood onset and persistence into adolescence and adulthood.

Methods: Our literature review reports scientific publications and guidelines on the treatment of adult ADHD, with a particular focus on European countries, identified by literature searches in Medline and Embase. The final literature search was performed in July 2012, incorporating literature from 1974 to 2012.

Baseline characteristics of European and non-European adult patients with attention deficit hyperactivity disorder participating in a placebo-controlled, randomized treatment study with atomoxetine.

Background: Attention deficit/hyperactivity disorder (ADHD) often presents as an impairing lifelong condition in adults; yet it is currently underdiagnosed and undertreated in many European countries. This analysis examines the characteristics of adult patients with ADHD in a European (EUR) and non-European (NE) patient population.

Methods: Baseline data from the open-label treatment period of a randomized trial of atomoxetine in adult patients with ADHD (N=2017; EUR, n=1217; NE, n=800) were examined.

Improvement of the noradrenergic symptom cluster following treatment with milnacipran.

Depression has a major impact on social functioning. Decreased concentration, mental and physical slowing, loss of energy, lassitude, tiredness, and reduced self-care are all symptoms related to reduced noradrenergic activity. Depressed mood; loss of interest or pleasure; sleep disturbances; and feelings of worthlessness, pessimism, and anxiety are related to reduced activity of both serotonergic and noradrenergic neurotransmission.

Memantine for patients with Parkinson's disease dementia or dementia with Lewy bodies: a randomised, double-blind, placebo-controlled trial.

Background: Previous studies have suggested that patients with Lewy-body-related dementias might benefit from treatment with the N-methyl D-aspartate receptor antagonist memantine, but further data are needed. Therefore, the efficacy and safety of memantine were investigated in patients with mild to moderate Parkinson's disease dementia (PDD) or dementia with Lewy bodies (DLB).

Methods: Patients (≥50 years of age) with mild to moderate PDD or DLB were recruited from 30 specialist centres in Austria, France, Germany, the UK, Greece, Italy, Spain, and Turkey.

Multiple sclerosis and Alzheimer's disease.

Objective: Chronic inflammation with microglia activation is thought to play a major role in the formation or clearance of Alzheimer's disease (AD) lesions, as well as in the induction of demyelination in multiple sclerosis (MS). In MS, the cortex is severely affected by chronic, long-lasting inflammation, microglia activation, and demyelination. To what extent chronic inflammation in the cortex of MS patients influences the development of AD lesions is so far unresolved.

Widespread demyelination in the cerebellar cortex in multiple sclerosis.

Neocortical demyelination in the forebrain has recently been identified as an important pathological feature of multiple sclerosis (MS). Here we describe that the cerebellar cortex is a major predilection site for demyelination, in particular in patients with primary and secondary progressive MS. In these patients, on average, 38.

Dysferlin is a new marker for leaky brain blood vessels in multiple sclerosis.

Dysferlin is a muscle protein involved in cell membrane repair and its deficiency is associated with muscular dystrophy. We describe that dysferlin is also expressed in leaky endothelial cells. In the normal central nervous system (CNS), dysferlin is only present in endothelial cells of circumventricular organs.

Remyelination is extensive in a subset of multiple sclerosis patients.

Although spontaneous remyelination does occur in multiple sclerosis lesions, its extent within the global population with this disease is presently unknown. We have systematically analysed the incidence and distribution of completely remyelinated lesions (so-called shadow plaques) or partially remyelinated lesions (shadow plaque areas) in 51 autopsies of patients with different clinical courses and disease durations. The extent of remyelination was variable between cases.

Cortical demyelination in multiple sclerosis: a substrate for cognitive deficits?

Recent studies highlight cortical demyelinated lesions as a feature of multiple sclerosis (MS) pathology, which has received little attention so far. Here, we describe that cortical plaques are frequent and widespread, in particular in patients with primary or secondary progressive MS. Furthermore, we describe that certain cortical areas, such as the cingulated gyrus, the insular cortex and the temporobasal cortex, are more affected than others.

Cortical demyelination and diffuse white matter injury in multiple sclerosis.

Focal demyelinated plaques in white matter, which are the hallmark of multiple sclerosis pathology, only partially explain the patient's clinical deficits. We thus analysed global brain pathology in multiple sclerosis, focusing on the normal-appearing white matter (NAWM) and the cortex. Autopsy tissue from 52 multiple sclerosis patients (acute, relapsing-remitting, primary and secondary progressive multiple sclerosis) and from 30 controls was analysed using quantitative morphological techniques.

Cortical lesions and brain atrophy in MS.

Multiple sclerosis is generally considered a disease of the white matter. However, this is only one pathological aspect of the disease as demyelination is prominent in the grey matter of deep cerebral nuclei and the cerebral cortex. In this review, we discuss the possibility that disease involvement of grey matter structures may significantly contribute to clinical disability in multiple sclerosis patients.

Ascorbic acid supplement during luteal phase in IVF.

Purpose: To evaluate the impact of ascorbic acid of different doses as additional support during luteal phase in infertility treatment by means of a prospective, randomized, placebo-controlled, group comparative, double-blind study.

Methods: Voluntary daily oral intake of either ascorbic acid (1, 5, or 10 g/day) or Placebo for 14 days after follicle aspiration for IVF-ET procedure. Data was obtained on 620 cases of women, age <40 years, undergoing first IVF-embryo transfer cycles in two private outpatient infertility clinics.