Cannabinoid drugs for neurological diseases: what is behind?

In recent years progress has been made in the development of pharmaceuticals based on the plant Cannabis sativa or on synthetic molecules with a similar action. Some of these pharmaceuticals, such as the mouth spray Sativex, have recently been approved for the treatment of spasticity in multiple sclerosis, but they are not the first and others, such as Marinol or Cesamet for the treatment of vomiting and nausea, and anorexia-cachexia syndrome, had already been approved. This incipient clinical use of cannabinoid drugs confirms something that was already known from fairly ancient times up to practically the last century, which is the potential use of this plant for medicinal applications - something which was brought to a standstill by the abusive use of preparations of the plant for recreational purposes. In any case, this incipient clinical use of cannabinoid drugs is not backed just by the anecdote of the medicinal use of cannabis since ancient times, but instead the boost it has been given by scientific research, which has made it possible to identify the target molecules that are activated or inhibited by these substances. These targets are part of a new system of intercellular communication that is especially active in the central nervous system, which is called the 'endogenous cannabinoid system' and, like many other systems, can be manipulated pharmacologically. The aim of this review is to probe further into the scientific knowledge about this system generated in the last few years, as a necessary step to justify the development of pharmaceuticals based on its activation or inhibition and which can be useful in different neurological diseases.     

Brief psychiatric rating scale expanded version: How do new items affect factor structure?

Our goal was to suggest a factor structure for the Brief Psychiatric Rating Scale Expanded Version (BPRS-E) based upon a large and diverse sample and to determine which of the new items improved the factors derived from the 18-item version of the scale that have been used in clinical research for decades. We investigated the consistency of our proposed model over time and across demographic groups. As part of the Texas Medication Algorithm Project, the BPRS-E was administered to a total of 1440 psychiatric outpatients in three different diagnostic groups on multiple occasions. The sample was randomly split so that exploratory factor analysis could be done with the first half, and the model could be confirmed on the second half. A four-factor structure including factors assessing depression/anxiety, psychosis, negative symptoms, and activation was found. For each factor, we specify items in the expanded version that added to the breadth of the commonly used clinical factors while improving or maintaining goodness of fit and reliability. The final model proposed was consistent over time and across diagnosis, phase of illness, age, gender, ethnicity, and level of education. The BPRS-E has a stable four-factor structure, making it useful as a clinical outcome measure.     

Different diagnostic criteria for Parkinson disease: what are the pitfalls?

As there are no definite diagnostic tests or reliable biomarkers for Parkinson disease (PD), its diagnosis still relies on the presence of a combination of cardinal motor features, along with the exclusion of other causes of Parkinsonism and the presence of some of supportive features. To date, several diagnostic criteria have been developed for different purposes through expert opinions or comprehensive review of the literature. However, none of them are without limitations. In this article, we review different diagnostic criteria for PD which have been published in the English medical literature, highlighting specific limitations and pitfalls. With considerable progress in the understanding of PD, particularly in a view of diverse clinical symptomatology and its evolution, it will be difficult to establish a single criterion that is capable of capturing all cases at different disease stages. Rather, we should aim to develop a set of criteria which include a consensus on clinical gold standard or reliable biomarkers at different levels of diagnostic certainty for different purposes. Despite a more refined set of criteria that may aid in the recognition of PD, the accuracy of its diagnosis still largely depends on the observational skills and clinical sensitivity of the treating physician.     

Unmet need: what justifies the search for a new antidepressant?

The burden of major depressive disorder is huge, as is clearly documented by World Health Organization data. A major component of this burden is the episodic nature of depression. Depressive episodes may be precipitated by stress and if left untreated can become episodic, recurrent, and chronic. Hippocampal atrophy may be a consequence of chronic depression, but antidepressants and mood stabilizers have been suggested to prevent or reverse this damage. Adequate treatment is essential for preventing depression from becoming chronic. Unfortunately, current antidepressant treatments fall short of being adequate for many patients. Shortcomings such as low remission/high treatment-resistance rates, slow onset of action, side effects, and drug-drug interactions influence patient adherence, which may be as low as 56% after the first 3 months of treatment. Since many patients may need long-term antidepressant treatment, new antidepressants need to be developed that are effective, tolerable, and safe and that improve maintenance of wellness.     

Prolonged seizures: what are the mechanisms that predispose or cease to be protective? A review of animal data

There is no doubt that seizures change processes in neuronal networks which themselves impact on seizure susceptibility, and reports on such changes probably account for the majority of studies in experimental epileptology. As much as there is no doubt about this general fact, there is, to date, quite some disagreement on whether such changes are pro‐epileptic, anti‐epileptic, or both, and which are crucial and which are less so. While it is not possible to provide a general answer to this, this review attempts to categorise and highlight some of these findings, and relate them to specific ontogenetic or pathophysiological conditions. Data from studies of animal models (nearly exclusively) is presented, with a focus on two main aspects: ontogenetic particularities and pathophysiological conditions, supporting evidence of susceptibility and seizure termination mechanisms in adult animal models.     

Exploring rating scale responsiveness: does the total score reflect the sum of its parts?

Evaluating rehabilitation requires rating scales that detect change. The authors examined Barthel Index (BI) data from 1,495 patients at a neurorehabilitation unit to determine whether total scale responsiveness accurately reflects item responsiveness. Total score effect sizes were moderate to large (0.47 to 1.09). Item-level effect sizes (0.13 to 1.16) reveal floor (3.5 to 82.3%) and ceiling (9.7 to 95.4%) effects. Results suggest BI total score effect sizes may hide item-level weaknesses and may underestimate the impact of rehabilitation.     

The orphans of Eritrea: what are the choices?

The authors examined the emotional well-being, adaptability, and emotional distress of 10-13 year-old Eritrean war orphans cared for in 3 different social environments and 1 group of home-reared children using 2 scales of the Behavioral Assessment System for Children and informal interviews with the children. Orphans reunified with extended families had greater adaptive skills than institutional orphans but as many signs and symptoms of emotional distress as orphanage children. Group-home orphans had fewer signs and symptoms of emotional distress and greater adaptive skills than either reunified or institutional orphans, and they had fewer symptoms of emotional distress than home-reared children. However, placing orphans in small group homes was far more expensive than reunifying them with extended families. The public policy implications of the findings for the protection of unaccompanied children in impoverished developing countries are discussed.     

The neurogenic reserve hypothesis: what is adult hippocampal neurogenesis good for?

Several theories have proposed possible functions of adult neurogenesis in learning processes on a systems level, such as the avoidance of catastrophic interference and the encoding of temporal and contextual information, and in emotional behavior. Under the assumption of such functionality of new neurons, the question arises: what are the consequences of adult hippocampal neurogenesis beyond the temporally immediate computational benefit? What might provide the evolutionary advantage of maintaining neurogenesis in the dentate gyrus but almost nowhere else? I propose that over the course of life, activity-dependently regulated adult neurogenesis reveals its true significance in the retained ability for lasting and cumulative network adaptations. The hippocampal precursor cells that generate new neurons with their particular acute function represent a 'neurogenic reserve': the potential to remain flexible and plastic in hippocampal learning when the individual is exposed to novelty and complexity.     

Editorial: what is new in the treatment of gliomas?

PURPOSE OF REVIEW: In this editorial, we seek to critically analyse currently available options for the treatment of gliomas in order to provide guidance for evidence-based therapeutic decisions. RECENT FINDINGS: Several recently reported trials in gliomas have investigated ways of optimizing traditional treatments (i.e. radiotherapy and cytotoxic chemotherapy), as well as novel approaches such as molecularly targeted therapy. SUMMARY: Chemotherapy with temozolomide concomitant with radiotherapy remains a standard of care for glioblastoma, but current efforts are concentrated on confirming phase II results of protracted temozolomide schedules. The role of chemotherapy for grade III and II gliomas lacks phase III evidence but several trials are ongoing. Such trials are stratified by (or designed separately according to) chromosomes 1p/19q codeletion status, and such genetic analysis will thus be essential for therapeutic decisions in the future. The single positive results with targeted therapy remain to date the high response rates with bevacizumab and irinotecan in a phase II trial for recurrent malignant gliomas. Several questions regarding survival benefits and toxicity remain, however. Results of randomized trials of bevacizumab-based combinations are eagerly awaited, and if positive, they will point to antiangiogenesis strategies as the most promising current investigation venue in gliomas.