Curcumin Prevents Cerebellar Hypoplasia and Restores the Behavior in Hyperbilirubinemic Gunn Rat by a Pleiotropic Effect on the Molecular Effectors of Brain Damage.

Bilirubin toxicity to the central nervous system (CNS) is responsible for severe and permanent neurologic damage, resulting in hearing loss, cognitive, and movement impairment. Timely and effective management of severe neonatal hyperbilirubinemia by phototherapy or exchange transfusion is crucial for avoiding permanent neurological consequences, but these therapies are not always possible, particularly in low-income countries. To explore alternative options, we investigated a pharmaceutical approach focused on protecting the CNS from pigment toxicity, independently from serum bilirubin level. To this goal, we tested the ability of curcumin, a nutraceutical already used with relevant results in animal models as well as in clinics in other diseases, in the Gunn rat, the spontaneous model of neonatal hyperbilirubinemia. Curcumin treatment fully abolished the landmark cerebellar hypoplasia of Gunn rat, restoring the histological features, and reverting the behavioral abnormalities present in the hyperbilirubinemic rat. The protection was mediated by a multi-target action on the main bilirubin-induced pathological mechanism ongoing CNS damage (inflammation, redox imbalance, and glutamate neurotoxicity). If confirmed by independent studies, the result suggests the potential of curcumin as an alternative/complementary approach to bilirubin-induced brain damage in the clinical scenario.

B Vitamins and Fatty Acids: What Do They Share with Small Vessel Disease-Related Dementia?

Many studies have been written on vitamin supplementation, fatty acid, and dementia, but results are still under debate, and no definite conclusion has yet been drawn. Nevertheless, a significant amount of lab evidence confirms that vitamins of the B group are tightly related to gene control for endothelium protection, act as antioxidants, play a co-enzymatic role in the most critical biochemical reactions inside the brain, and cooperate with many other elements, such as choline, for the synthesis of polyunsaturated phosphatidylcholine, through S-adenosyl-methionine (SAM) methyl donation. B-vitamins have anti-inflammatory properties and act in protective roles against neurodegenerative mechanisms, for example, through modulation of the glutamate currents and a reduction of the calcium currents. In addition, they also have extraordinary antioxidant properties. However, laboratory data are far from clinical practice. Many studies have tried to apply these results in everyday clinical activity, but results have been discouraging and far from a possible resolution of the associated mysteries, like those represented by Alzheimer's disease (AD) or small vessel disease dementia. Above all, two significant problems emerge from the research: No consensus exists on general diagnostic criteria-MCI or AD? Which diagnostic criteria should be applied for small vessel disease-related dementia? In addition, no general schema exists for determining a possible correct time of implementation to have effective results. Here we present an up-to-date review of the literature on such topics, shedding some light on the possible interaction of vitamins and phosphatidylcholine, and their role in brain metabolism and catabolism. Further studies should take into account all of these questions, with well-designed and world-homogeneous trials.

Thalamus and Language: What do we know from vascular and degenerative pathologies.

Language is a complex cognitive task that is essential in our daily life. For decades, researchers have tried to understand the different role of cortical and subcortical areas in cerebral language representations and language processing. Language-related cortical zones are richly interconnected with other cortical regions (particularly via myelinated fibre tracts), but they also participate in subcortical feedback loops within the basal ganglia (caudate nucleus and putamen) and thalamus. The most relevant thalamic functions are the control and adaptation of cortico-cortical connectivity and bandwidth for information exchange. Despite having the knowledge of thalamic and basal ganglionic involvement in linguistic operations, the specific functions of these subcortical structures remain rather controversial. The aim of this study is to better understand the role of thalamus in language network, exploring the functional configuration of basal network components. The language specificity of subcortical supporting activity and the associated clinical features in thalamic involvement are also highlighted.

Complex neurological symptoms in bilateral thalamic stroke due to Percheron artery occlusion.

The artery of Percheron is a rare anatomical variant where a single thalamic perforating artery arises from the proximal posterior cerebral artery (P1 segment) between the basilar artery and the posterior communicating artery and supplies the rostral mesencephalon and both paramedian territories of the thalami. Almost one-third of human brains present this variant. Occlusion of the artery of Percheron mostly results in a bilateral medial thalamic infarction, which usually manifests with altered consciousness (including coma), vertical gaze paresis, and cognitive disturbance. The presentation is similar to the "top of the basilar syndrome", and early recognition should be prompted. We describe the case of a young female with this vessel variant who experienced a bilateral thalamic stroke. Magnetic resonance angiography demonstrated bilateral thalamic infarcts and a truncated artery of Percheron. Occlusion of the vessel was presumably due to embolism from a patent foramen ovale. Thrombolysis was performed, with incomplete symptom remission, cognitive impairment, and persistence of speech disorders. Early recognition and treatment of posterior circulation strokes is mandatory, and further investigation for underlying stroke etiologies is needed.

Different responses to rivastigmine in subcortical vascular dementia and multi-infarct dementia.

Vascular dementia (VaD) is associated with a large amount of heterogeneity, as it groups together a broad category of patients in whom various manifestations of cognitive decline are attributed to cerebrovascular or cardiovascular disease. Thus, a study was designed to determine the effects of rivastigmine on cognitive function, global daily living performance, and behavioral disorders in VaD patients versus an active control (nimodipine), stratifying patients according to the type of VaD, subcortical vascular dementia (sVAD), and multi-infarct dementia (MID). The trial was a prospective study. This study shows that long-term treatment with rivastigmine, at dosages approved for therapeutic use in Alzheimer's disease, produces significant improvement in all behavioral symptoms in 2 forms of VaD, MID and sVaD, except delusions. It also suggests that rivastigmine may enable a reduction in concomitant neuroleptics and benzodiazepines in VaD, especially in MID. The results are discussed with an overview of the literature.

Vitamin B12 and folate depletion in cognition: a review.

In cross-sectional studies, low levels of folate and B12 have been shown to be associated with cognitive decline and dementia Evidence for the putative role of folate, vitamin B12 in neurocognitive and other neurological functions comes from reported cases of severe vitamin deficiencies, particularly pernicious anemia, and homozygous defects in genes that encode for enzymes of one-carbon metabolism. The neurological alterations seen in these cases allow for a biological role of vitamins in neurophysiology. Results are quite controversial and there is an open debate in literature, considering that the potential and differential role of folate and B12 vitamin in memory acquisition and cognitive development is not completely understood or accepted. What is not clear is the fact that vitamin B12 and folate deficiency deteriorate a pre-existing not overt pathological situation or can be dangerous even in normal subjects. Even more intriguing is the interaction between B12 and folate, and their role in developing hyperhomocysteinemia. The approach to the rehabilitation of the deficiency with adequate vitamin supplementation is very confusing. Some authors suggest it, even in chronic situations, others deny any possible role. Starting from these quite confusing perspectives, the aim of this review is to report and categorize the data obtained from the literature. Despite the plausible biochemical mechanism, further studies, based on clinical, neuropsychological, laboratory and (lastly) pathological features will be necessary to better understand this fascinating biochemical riddle.

Neuropsychological changes after subthalamic nucleus stimulation: a 12 month follow-up in nine patients with Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus has been recognized as one of the most promising techniques to decrease 'off' motor symptoms and motor fluctuations, allowing a reduction of drug therapy and limiting side effects of drug therapy. However, there is still open debate on the possible consequences of chronic subthalamic stimulation on general cognitive performance. A general amelioration of cognitive performance, in particular of executive functions has been reported but results are not homogeneous. We studied nine patients with Parkinson's Disease for 12 months following surgery for deep stimulation, studying their cognitive performances, paying particular attention to linguistic tests and selective alternating words production. Our results may be consistent with a slowing of cognitive activity, with a reduction of quantitative production, but with an increase in control of linguistic production, which is more precise and definite. We discuss the possible significance of these results, fully aware that only nine patients were involved, and that the potential for generalization is seriously limited, with a particular overview on the frontal-subthalamic pathway, which in our opinion is responsible for the results we observed.

Rivastigmine in subcortical vascular dementia: a randomized, controlled, open 12-month study in 208 patients.

Subcortical vascular dementia (VaD) is characterized by executive dysfunction and behavioral problems, reflecting deterioration of the frontal lobe. This study aimed to determine whether rivastigmine, a dual inhibitor of acetylcholinesterase (AChE) and butyryl-cholinesterase (BuChE), has any effects on the typical symptoms of subcortical VaD. Patients receiving rivastigmine showed a slight improvement in executive functions and in behavior. Side effects in both groups were tolerable and there were no study withdrawals. Moreover, there are no drug interactions with other therapies previously and concomitantly assumed. Improvements in domains that characterize subcortical VaD were observed, indicating that rivastigmine may have provided targeted treatment in areas of the brain that are particularly affected in this patient population.

Cognitive changes following subthalamic nucleus stimulation in two patients with Parkinson disease.

The limits of a drug therapy in severe forms of Parkinson disease have led to refining neurosurgery on the basal ganglia. Deep brain stimulation of the subthalamic nucleus has been recognized as one of the most promising techniques to decrease "off" motor symptoms and motor fluctuations, allowing a reduction of drug therapy and limiting side effects of the drugs. There is still open debate on the possible consequences of chronic subthalamic stimulation in other ways, apart from motor symptoms, of general cognitive performance. We examined and followed two patients with Parkinson disease for 9 mo. after surgery for deep stimulation, studying their cognitive performances. There is a general amelioration of cognitive performances, in particular as far as linguistic capabilities is concerned. We discuss the possible significance of these results, reminding strenuously that only two patients were involved, so the potential for generalization is seriously limited.