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.     

The impact of mood disorders in neurological diseases: should neurologists be concerned?

Depression is one of the most frequent comorbid psychiatric disorders identified in patients with neurological disorders. The prevalence rates range between 20 and 50% of patients with stroke, epilepsy, multiple sclerosis, and Parkinson's disease. Despite these relatively high prevalence rates, depression remains underrecognized and undertreated in these patients. And yet, depression accounts for poor quality-of-life ratings and has a negative impact on the recovery from neurological symptoms. In this article, we review the epidemiological and clinical characteristics of mood disorders in patients with multiple sclerosis, Parkinson's disease, stroke, and epilepsy, and focus on the impact mood disorders have on the quality of life of these patients and on their recovery from their neurological deficits.     

Axonal mRNA localization and local translation in neurodegenerative diseases

The regulation of mRNA localization and local translation play vital roles in the maintenance of cellular structure and function.Many human neurodegenerative diseases,such as fragile X syndrome,amyotrophic lateral sclerosis,Alzheimer’s disease,and spinal muscular atrophy,have been characterized by pathological changes in neuronal axons,including abnormal mRNA translation,the loss of protein expression,or abnormal axon transport.Moreover,the same protein and mRNA molecules have been associated with variable functions in different diseases due to differences in their interaction networks.In this review,we briefly examine fragile X syndrome,amyotrophic lateral sclerosis,Alzheimer’s disease,and spinal muscular atrophy,with a focus on disease pathogenesis with regard to local mRNA translation and axon transport,suggesting possible treatment directions.     

Epidemiology of neurological diseases in elderly people: what did we learn from the Rotterdam Study?

The Rotterdam Study is a prospective cohort study that has been ongoing since 1990 in the city of Rotterdam, the Netherlands, among 7983 people aged 55 years or older. One part of the study targets neurological diseases, others deal with cardiovascular, ophthalmological, and endocrine diseases. The findings of the Rotterdam Study have been presented in some . Here we give the reasons for the study and its design, and present a summary of what has been learned about the frequencies and causes of neurological diseases. Perhaps the most important message from the Rotterdam Study is the great potential for prevention or postponement of neurological diseases in elderly people. The time for preventive nihilism is over.     

Lost in myth,lost in translation: Philippe Pinel’s 1809 Medico-Philosophical Treatise on Mental Alienation

Philippe Pinel is widely regarded as one of the founders of modern evidence-based psychiatry. Yet, until recently, his most important contributions to psychiatric theory and practice were effectively lost in myth, or lost in translation. It is instructive to review the history of these developments in order to correct any errors or omissions that may stand in the way of an accurate recognition of Pinel’s contributions to psychiatry, while at the same time highlighting some of his achievements that have been hidden by his celebrated mythical status as a pioneering humanitarian reformer. The aim of this article is to motivate further historical study of Pinel’s work, especially his 1809 Medico-Philosophical Treatise on Mental Alienation, which has only recently become available in English translation.     

Neurological disease caused by Oropouche virus in northern Brazil: should it be included in the scope of clinical neurological diseases?

Journal of NeuroVirology - We describe two neurological cases of Oropouche virus infection in northern Brazil, where the virus is endemic but neglected as a pathogen. This study reiterates the...     

Absolute quantitation in neurological PET: do we need it?

This article addresses the question posed in the title by examining the effects of parameters traditionally associated with improved absolute quantitation, on the analysis of 12 acquired immune deficiency syndrome dementia complex (ADC) patients compared to a normal control group. Results are discussed within the framework of the subprofile scaling model (SSM) for analyzing patterns of regional covariation. It is demonstrated that the ability to extract measures of group discrimination and disease progression are unaffected by (1) limited improvements in image resolution, (2) the use of transmission scan smoothing, (3) the application of a scatter deconvolution correction, and (4) converting region-of-interest measurements of counts per voxel to measurements of regional CMRglc. This "robustness" of the SSM approach is partly due to the extraction of disease-related subject weights, independent of any subject's global scaling effects. It is argued that other analysis techniques that initially reduce intersubject variation (e.g., using regional ratios or normalizing by global metabolic rates before applying traditional multivariate procedures) lack analytic features that may be important to identify multidimensional, disease-related image patterns. Based on the ADC patient data, it is concluded that measures of group discrimination and disease progression will not necessarily benefit from the organization of parameters traditionally associated with improved absolute quantitation.     

Neurotrophins and neurodegenerative diseases: receptors stuck in traffic?

Neurotrophins are well known for their physiological role as key modulators of neuronal survival, neurite out-growth, and synaptic connectivity during development and into adulthood. Moreover, neurotrophins are potent agents, ameliorating neuronal degeneration in many model systems for neurological diseases. However, a causal role for mutations in neurotrophins or neurotrophin receptors in human neurodegenerative diseases has been largely lacking. As neurotrophin receptors are located at synapses and as their signaling involves the neuronal nucleus, they need to bridge tantalizing distances in order to retrogradely communicate their survival signals. On the other hand, anterogradely transported neurotrophins are released at the synapse and act on postsynaptic cells. Antero- and retrograde signaling and trafficking is an emerging focus of interest in neurotrophin research. Some neurodegenerative diseases are known to affect transport of organelles. Thus, it appears likely that neurodegeneration could be caused by "indirect" effects on neurotrophin trafficking and, hence, signaling. In this review we summarize recent work on neurotrophins in neurodegenerative diseases with special focus on possible implications of disturbed trafficking of organelles and retrograde axonal signaling.     

ADAM proteases: protective role in Alzheimer's and prion diseases?

Alzheimer's disease, as well as most of other neurodegenerative disorders, is characterized by the deposition of insoluble proteinaceous aggregates. Hence, any intervention aimed at reducing this process could be envisioned as a therapeutic way to slow down the disease. In the case of Alzheimer's disease, the culprit protein is the 40-43 amino acid-long amyloid beta peptide (Abeta). This fragment is generated from the beta-amyloid precursor protein (betaAPP) by two distinct enzymes, namely the beta- and the gamma-secretases. In the past years, a tremendous effort has been made to develop potent and specific inhibitors of these proteolytic activities. Beside these Abeta-forming proteases, a third cleavage performed by the so-called alpha-secretase takes place in the middle of the Abeta sequence and not only precludes its formation but also generates the secreted product sAPPalpha that possesses neurotrophic and neuroprotective properties. This beneficial cleavage has been shown to be strongly upregulated by protein kinase C (PKC) agonists and to be, at least partially, triggered by ADAM proteases (A Disintegrin And Metalloprotease). Recently, a proteolytic attack with similar characteristics has been shown to occur in the middle of the "toxic" 106-126 domain of the prion protein (PrPc), which PrPsc isoform is the causative agent of transmissible spongiform encephalopathies. As both Abeta and PrP(106-126) trigger neurotoxicity and cell death, this ADAM-dependent proteolytic attack could represent a valuable therapeutic target in order to deplete cells from these endogenous "toxins"and prevent the associated aggregates usually detected in affected brains.     

Cytokines and chemokines in neuro-Behçet's disease compared to multiple sclerosis and other neurological diseases

Cytokines and chemokines in cerebrospinal fluid (CSF) can have implications on the pathogenesis of neuro-Beh?et's disease (NB). CSF and serum samples from 33 patients with NB, 25 with multiple sclerosis (MS), 20 patients with infectious and/or inflammatory neurological diseases (IN) and 14 with other noninflammatory neurological diseases (NIN) were investigated by ELISA. In the CSF, CXCL10 levels were significantly higher in NB and IN than NIN and MS, whereas CXCL8 was increased in NB compared to NIN. CCL2 levels in MS CSF and sera were lower, whereas CXCL8 in MS sera was higher than the other groups. IL-12 was elevated in CSF of IN compared to NB and NIN and also in the CSF of MS compared to NIN. No difference was detected for IL-10 and IL-17. These results reflect that NB has a mediator pattern in resemblance with non-specific inflammations such as neuro-infections compared to autoimmune disorders such as multiple sclerosis, suggesting that a currently unknown infection might be the trigger of a vasculitic process in the central nervous system (CNS).