A further update on the role of excitotoxicity in the pathogenesis of Parkinson's disease.

Increased levels of extracellular glutamate and hyperactivation of glutamatergic receptors in the basal ganglia trigger a critical cascade of events involving both intracellular pathways and cell-to-cell interactions that affect cell viability and promote neuronal death. The ensemble of these glutamate-triggered events is responsible for excitotoxicity, a phenomenon involved in several pathological conditions affecting the central nervous system, including a neurodegenerative disease such as Parkinson's disease (PD). PD is an age-related disorder caused by the degeneration of dopaminergic neurons within the substantia nigra pars compacta, with a miscellaneous pathogenic background.

Dopamine receptor agonists for Parkinson's disease.

Introduction: Prolonged administration of l-3,4-dihydroxyphenylalanine (l-DOPA) for Parkinson's disease (PD) is hampered by motor complications related to the progressive incapacity of residual nigrostriatal neurons to properly utilize the drug. Direct stimulation of dopaminergic (DAergic) receptors with specific compounds (DA agonists) has, therefore, become an additional therapeutic tool for PD.

Areas Covered: DA agonists have considerable anti-parkinsonian symptomatic efficacy, although they are less potent than l-DOPA.

Diagnostic value of IgG4 Indices in IgG4-related hypertrophic pachymeningitis.

Diagnosis of IgG4-Related Hypertrophic Pachymeningitis (IgG4-HP) relies on meningeal biopsies, because cerebrospinal fluid (CSF) diagnostic biomarkers are lacking. Here, we determined whether IgG4 intrathecal production could distinguish IgG4-HP from other disorders presenting with HP (OHP). In patients with IgG4-HP, the median CSF IgG4 concentration, IgG4 Index and IgG4Loc were significantly higher than in both controls and OHP.

Amyotrophic lateral sclerosis and skeletal muscle: an update.

Amyotrophic lateral sclerosis (ALS) is the most frequent adult-onset motor neuron disease characterized by degeneration of upper and lower motor neurons (MNs), generalized weakness and muscle atrophy. The "neurocentric" view of ALS assumes that the disease primarily affects motor neurons, while muscle alterations only represent a consequence, in the periphery, of motor neuron loss. However, this outlook was recently challenged by evidence suggesting that non-neural cells such as microglia, astrocytes, peripheral blood mononuclear cells (PBMCs) and skeletal muscle fibres participate in triggering motor neuron degeneration, and this stressed the concept that alterations in different cell types may act together to exacerbate the disease.

The world can look better: enhancing beauty experience with brain stimulation.

Aesthetic appreciation is part of our everyday life: it is a subjective judgment we make when looking at a painting, a landscape, or--in fact--at another person. Neuroimaging and electrophysiological evidence suggests that the left dorsolateral prefrontal cortex (DLPFC) plays a critical role in aesthetic judgments. Here, we show that the experience of beauty can be artificially enhanced with brain stimulation.

Functional neuroanatomy of disorders of consciousness.

Our understanding of the mechanisms of loss and recovery of consciousness, following severe brain injury or during anesthesia, is changing rapidly. Recent neuroimaging studies have shown that patients with chronic disorders of consciousness and subjects undergoing general anesthesia present a complex dysfunctionality in the architecture of brain connectivity. At present, the global hallmark of impaired consciousness appears to be a multifaceted dysfunctional connectivity pattern with both within-network loss of connectivity in a widespread frontoparietal network and between-network hyperconnectivity involving other regions such as the insula and ventral tegmental area.

Limbic hyperconnectivity in the vegetative state.

Objective: To investigate functional connectivity between the default mode network (DMN) and other networks in disorders of consciousness.

Methods: We analyzed MRI data from 11 patients in a vegetative state and 7 patients in a minimally conscious state along with age- and sex-matched healthy control subjects. MRI data analysis included nonlinear spatial normalization to compensate for disease-related anatomical distortions.

SOD1 and DJ-1 converge at Nrf2 pathway: a clue for antioxidant therapeutic potential in neurodegeneration.

Neurodegenerative diseases share diverse pathological features and among these oxidative stress (OS) plays a leading role. Impaired activity and reduced expression of antioxidant proteins have been reported as common events in several aging-associated disorders. In this review paper, we first provide an overview of the involvement of reactive oxygen species- (ROS-) induced oxidative damage in Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS).

The importance of training strategy adaptation: a learner-oriented approach for improving older adults' memory and transfer.

We investigated the benefits of strategy-adaptation training for promoting transfer effects. This learner-oriented approach--which directly encourages the learner to generalize strategic behavior to new tasks--helps older adults appraise new tasks and adapt trained strategies to them. In Experiment 1, older adults in a strategy-adaptation training group used 2 strategies (imagery and sentence generation) while practicing 2 tasks (list and associative learning); they were then instructed on how to do a simple task analysis to help them adapt the trained strategies for 2 different unpracticed tasks (place learning and text learning) that were discussed during training.

Dysregulation of the immune system in Aicardi-Goutières syndrome: another example in a TREX1-mutated patient.

Aicardi-Goutières syndrome (AGS) is a rare genetic encephalopathy characterized by neurological and extraneurological involvement. A clinical overlap between AGS and systemic lupus erythematosus (SLE) has been reported. We describe an AGS patient who developed autoimmune manifestations: thyroiditis, cANCA positivity, antiphospholipid antibodies and cerebral ischemia.

Neural and immune mechanisms in the pathogenesis of Parkinson's disease.

Although almost 50 years have passed since impaired dopaminergic transmission was identified as the main neurochemical defect in Parkinson's disease (PD), the cause of the disease remains unknown. A restricted number of biological mechanisms are likely to contribute to the process of cell death in the nigrostriatal pathway. These mechanisms include mitochondrial defects and enhanced formation of reactive oxygen species--leading to oxidative damage--and abnormal protein aggregation.

A precocious cerebellar ataxia and frequent Fever episodes in a 16-month-old infant revealing ataxia-telangiectasia syndrome.

Ataxia-telangiectasia (AT) is the most frequent progressive cerebellar ataxia in infancy and childhood. Immunodeficiency which includes both cellular and humoral arms has variable severity. Since the clinical presentation is extremely variable, a high clinical suspicion will allow an early diagnosis.

Brain-derived neurotrophic factor gene variants and Alzheimer disease: an association study in an Alzheimer disease Italian population.

Brain-derived neurotrophic factor (BDNF) promotes neuronal survival during development and protects neurons from insults of various kinds. Changes in production of BDNF have been reported in differing neurodegenerative pathologies and, in particular, in Alzheimer disease (AD). We studied 200 AD patients and 408 healthy controls for BDNF Val66Met(G196A) polymorphism, 200AD and 384 healthy controls for BDNF 270 C/T polymorphism, and 200AD and 393 healthy controls for BDNF 11757 G/C polymorphism by restriction fragment length polymorphism (RFLP) and real-time PCR.

Regulation of FMO and PON detoxication systems in ALS human tissues.

Amyotrophic lateral sclerosis (ALS) is an adult-onset, progressive, and fatal neurodegenerative disease with unknown etiology. Recent evidence suggests an association between the exposure to toxic environmental factors and sporadic ALS. The flavin-containing monooxygenases (FMOs) and paraoxonase (PONs) genes encode enzymes involved in xenobiotic detoxication and are associated with ALS.

Epileptic Encephalopathies with Status Epilepticus during Sleep: New Techniques for Understanding Pathophysiology and Therapeutic Options.

Encephalopathy with status epilepticus during sleep (ESES) is an epileptic encephalopathy, as defined by the International League Against Epilepsy (ILAE) Task Force on Classification and Terminology, that is, a condition in which the epileptic processes themselves are believed to contribute to the disturbance in cerebral function. Clinical manifestations of ESES are heterogeneous: apart from different seizure types, they consist in combinations of cognitive, motor, and behavioural disturbances associated with a peculiar electroencephalographic pattern of paroxysmal activity significantly activated during slow sleep, which culminates in a picture of continuous spikes and waves during sleep (CSWS). The pathophysiological mechanisms underlying this condition are still incompletely understood.

Transdermal hormonal therapy in perimenstrual migraine: why, when and how?

Experimental and clinical evidence is strongly in favor of a role for estrogens in migraine. It is clear that estrogen fluctuations represent trigger factors for the attacks, while the resolution of these fluctuations (menopause) may be associated to the remission or, conversely, to the worsening of the disease. However, the exact mechanisms and mediators underlying the effects of estrogens in migraine are largely unknown.

Effect of sex and estrogens on neuronal activation in an animal model of migraine.

Objective: In this study, we evaluated the influence of sex and estrogen treatment on nitroglycerin (NTG)-induced neuronal activation in the rat brain.

Background: Systemic NTG activates cerebral nuclei of rat involved in nociceptive transmission, as well as in neuroendocrine and autonomic functions. These changes are considered relevant for migraine, since NTG consistently induces spontaneous-like attacks in migraineurs.

From Transcriptome to Noncoding RNAs: Implications in ALS Mechanism.

In the last years, numerous studies have focused on understanding the metabolism of RNA and its implication in disease processes but abnormal RNA metabolism is still unknown. RNA plays a central role in translating genetic information into proteins and in many other catalytic and regulatory tasks. Recent advances in the study of RNA metabolism revealed complex pathways for the generation and maintenance of functional RNA in amyotrophic lateral sclerosis (ALS).

Immunomodulatory therapies delay disease progression in multiple sclerosis.

Background: Few studies have analysed long-term effects of immunomodulatory disease modifying drugs (DMDs).

Objective: Assessment of the efficacy of DMDs on long-term evolution of multiple sclerosis, using a Bayesian approach to overcome methodological problems related to open-label studies.

Methods: MS patients from three different Italian multiple sclerosis centres were divided into subgroups according to the presence of treatment in their disease history before the endpoint, which was represented by secondary progression.

Modulation of RAGE isoforms expression in the brain and plasma of rats exposed to transient focal cerebral ischemia.

Activation of RAGE (receptor for advanced glycation endproducts) and of its subtypes may play a role in neuronal damage and neuroinflammation associated with brain ischemia, though the underlying mechanisms remain unclear. In this study, we have examined by Western blotting the expression of RAGE isoforms in the cerebral cortex and striatum of Wistar rats subjected to transient (1 or 2 h) middle cerebral artery occlusion (tMCAo). The findings show that the full-length RAGE (~50 kDa) and its isoforms in the 26-43 kDa range are significantly decreased in the ischemic cortex, but not in the striatum, after 1 and 2 h tMCAo when compared to the sham group.

[Accidents and headache].

Work accidents are a major cause of morbidity and mortality by creating a loss not only for the individual affected but also for society given the high number of absences from work that follows. Many have been efforts since the early 60 'to minimize the number of accidents but, although it is known a steady downward trend in recent years, in Italy in 2010 there were still 775,000 cases of accidents and 980 deaths. The study examined a population of 192 persons injured of which 41 have proven to be headache and data collected showed that the frequency of headache among the workers who suffer an injury is equal to 26.

Dissociated local arousal states underlying essential clinical features of non-rapid eye movement arousal parasomnia: an intracerebral stereo-electroencephalographic study.

Sleep has been shown to be a global phenomenon in which the presence of local processes of both activation and deactivation are finely orchestrated. Dysfunctional and independent action of the systems involved in non-rapid eye movement (NREM) sleep and wakefulness is deemed to be at the basis of arousal parasomnias. We show, in a patient with confusional arousals, persistence of sleep in the hippocampal and frontal associative cortices in contrast to the presence of awakening in the motor, cingulate, insular, amygdalar and temporopolar cortices.

Animal models of Parkinson's disease.

Animal models of Parkinson's disease (PD) have been widely used in the past four decades to investigate the pathogenesis and pathophysiology of this neurodegenerative disorder. These models have been classically based on the systemic or local (intracerebral) administration of neutoxins that are able to replicate most of the pathological and phenotypic features of PD in mammals (i.e.

New pharmacological avenues for the treatment of L-DOPA-induced dyskinesias in Parkinson's disease: targeting glutamate and adenosine receptors.

Introduction: Parkinson's disease (PD) therapy is still centered on the use of L-3,4-dihydroxyphenylalanine (L-DOPA), which is hampered by numerous side effects, including abnormal involuntary movements known as L-DOPA-induced dyskinesias (LIDs). LIDs are the result of pre- and postsynaptic changes at the corticostriatal level, induced by chronic and pulsatile stimulation of striatal dopaminergic receptors. These changes impact on synaptic plasticity and involve also selected, nondopaminergic receptors expressed by striatal projection neurons.