Paola Caruso

Vitamin D, Homocysteine, and Folate in Subcortical Vascular Dementia and Alzheimer Dementia

Dementia is a worldwide health problem which affects millions of patients; Alzheimers disease (AD) and subcortical vascular dementia (sVAD) are the two most frequent forms of its presentation. As no definite therapeutic options have been discovered, different risk factors for cognitive impairment have been searched for potential therapies. This report focuses on the possible evidence that vitamin D deficiency and hyper-homocysteinemia can be considered as two important factors for the development or the progression of neurodegenerative or vascular pathologies. To this end, we assessed: the difference in vascular risk factors and vitamin D-OH25 levels among groups of sVAD, AD, and healthy age-matched controls; the association of folate, B12, homocysteine, and vitamin D with sVAD/AD and whether a deficiency of vitamin D and an increment in homocysteine levels may be related to neurodegenerative or vessel damages. The commonly-considered vascular risk factors were collected in 543 patients and compared with those obtained from a healthy old volunteer population. ANOVA group comparison showed that vitamin D deficiency was present in demented cases, as well as low levels of folate and high levels of homocysteine, more pronounced in sVAD cases. The statistical models we employed, with regression models built, and adjustments for biochemical, demographic and neuropsychiatric scores, confirmed the association between the three measures (folate decrease, hyperhomocysteinemia and vitamin D decrease) and dementia, more pronounced in sVAD than in AD.

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.

Basal ganglia: Their role in complex cognitive procedures in experimental models and in clinical practice

Apart from the well known role of the basal ganglia (BG) in motor control, their important role in regulating the cognitive functions is emerging. This article traces the scientific work that explores this role of BG in reinforcement learning, perceptual decision making, and other nonmotor pathways (speech fluency, cognition, attention and behaviour). It also highlights the important role played by the BG networks in determining the development of a childs brain. It retraces the various pathways and connections of the BG with the cerebral cortex, cerebellum and other regions that may be utilized in the establishment of complex cognitive procedures. Various diseases that may be the direct result of disruption of these basal ganglionic networks and interconnections are also recounted.

Expression of the Endocannabinoid Receptor 1 in Human Stroke: An Autoptic Study

OBJECTIVE Stroke is one of the leading causes of disability and death in the world. The endocannabinoid (eCB) system is upregulated in several neurological diseases including stroke. A previous animal study demonstrated an increased expression of the endocannabinoid receptor 1 (CB1R) in the penumbra area surrounding the ischemic core, suggesting a crucial role in inflammation/reperfusion after stroke. Regarding the localization of CB1/CB2 receptors, animal studies showed that cortical neurons, activated microglia, and astroglia are involved. Our aim was to evaluate the cerebral expression of CB1R in the ischemic brain areas of 9 patients who died due to acute cerebral infarction in the middle cerebral artery territory. METHODS The cerebral autoptic tissue was collected within 48 hours since death. Ischemic and contralateral normal-appearing areas were identified. After tissue preprocessing, 4-µm-thick cerebral sections were incubated with the primary CB1R antibodies (Cayman Chemical Company, Ann Arbor, MI). Thereafter, all cerebral sections were hematoxylin treated. In each section, the total cell number and CB1R-positive cells were counted and the CB1R-positive cell count ratio was calculated. For statistical analysis, Students t-test was used. RESULTS In normal tissue, CB1R-positive neurons were the majority; a few non-neuronal cells expressed CB1R. In the ischemic areas, a few neurons were detectable. A significant increase in total CB1R staining was found in the ischemic regions compared to contralateral areas. CONCLUSIONS We found an increase in CB1R expression in the ischemic region (neuronal and non-neuronal cell staining), suggesting the inflammatory reaction to the ischemic insult. Whether such response might mediate neuroprotective actions or excitotoxicity-related detrimental effects is still unclear.

Management of restless legs syndrome in chronic liver disease: A challenge for the correct diagnosis and therapy

AIM To investigate the association between restless legs syndrome (RLS) and well-defined chronic liver disease, and the possible therapeutic options. METHODS Two hundred and eleven patients with chronic liver disease, complaining of sleep disturbances, painful leg sensation and daily sleepiness, were included. Patients with persistent alcohol intake, recent worsening of clinical conditions, or hepatitis C virus were excluded. Diagnosis of RLS was suggested by the Johns Hopkins questionnaire and verified by fulfilling the diagnostic criteria by Allen. All patients were tested, both at baseline and during follow-up, with the Hamilton rating scale for depression, sleep quality assessment (PSQI), Epworth sleepiness scale (ESS), International Restless Legs Syndrome Study Group evaluation, and international RLS severity (IRLS) scoring system. Iron-free level, ferritin, folate, vitamin B12 and D-OH25 were detected. Neurological examinations and blood test occurred at the beginning of the therapy, after 2 wk, and at the 28th, 75th, 105th, 135th, 165th and 205th day. Regarding therapy, pramipexole or gabapentin were used. RESULTS Patients were moderately depressed, with evident nocturnal sleep problems and concomitant daily sleepiness. Sleep problems and involuntary leg movements had been underestimated, and RLS syndrome had not been considered before the neurological visit. All (211/211) patients fulfilled the RLS diagnostic criteria. Twenty-two patients considered their symptoms as mild, according to IRSL, but 189 found them moderate to very severe. No correlation was found between ammonium level and ESS or PSQI. Augmentation was rather precocious in our patients (135th day), and more frequent (35%) than previous data (8.3%-9.1%). The dosage of dopamine agonists was found to be associated with augmentation and appears in range with the literature. Previous intake of alcohol and lower levels of vitamins have been related to the phenomenon in our study. CONCLUSION RLS is a common disorder, requiring rapid diagnosis and treatment. Further research is therefore fundamental.

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.

Wake-up stroke and CT perfusion: effectiveness and safety of reperfusion therapy

ObjectiveIschemic stroke is a neuroemergency condition highly treatable with thrombolysis and thrombectomy. Recently, observational studies have brought insights into clinical and imaging characteristics of wake-up stroke, which interested up to 25% of ischemic stroke patients. In clinical practice, wake-up strokes are usually not considered for reperfusion therapy. The aim of this study was to investigate the use CT perfusion imaging in patients with wake-up stroke and to assess the effect of neuroimaging information provided by CT perfusion maps on the efficacy and safety of thrombolysis and thrombectomy.Patients and methodWe studied 22 wake-up stroke (WUS) patients (13F/9M mean age) who underwent reperfusion therapy after the eligibility assessed by the CT perfusion imaging (< 50% core-to-penumbra ratio and negative CT perfusion).ResultsMean National Institutes of Health Stroke Scale (NIHSS) was 8.1 ± 4.9 at admission while 3.3 ± 5.1 at discharge, significantly different from admission (p < 0.001). As many as ten patients had mRS lower than 3 at discharge. Intracranial hemorrhage occurred in five patients and caused symptoms worsening only in two patients (decrease of NIHSS score of 4 points) of which one patient died.ConclusionThe main finding of this study is that wake-up stroke with adequate selection by CT perfusion may benefit reperfusion treatment.

Early Recovery of Aphasia through Thrombolysis: The Significance of Spontaneous Speech

BACKGROUND Aphasia is one of the most devastating stroke-related consequences for social interaction and daily activities. Aphasia recovery in acute stroke depends on the degree of reperfusion after thrombolysis or thrombectomy. As aphasia assessment tests are often time-consuming for patients with acute stroke, physicians have been developing rapid and simple tests. The aim of our study is to evaluate the improvement of language functions in the earliest stage in patients treated with thrombolysis and in nontreated patients using our rapid screening test. MATERIALS AND METHODS Our study is a single-center prospective observational study conducted at the Stroke Unit of the University Medical Hospital of Trieste (January-December 2016). Patients treated with thrombolysis and nontreated patients underwent 3 aphasia assessments through our rapid screening test (at baseline, 24 hours, and 72 hours). The screening test assesses spontaneous speech, oral comprehension of words, reading aloud and comprehension of written words, oral comprehension of sentences, naming, repetition of words and a sentence, and writing words. RESULTS The study included 40 patients: 18 patients treated with thrombolysis and 22 nontreated patients. Both groups improved over time. Among all language parameters, spontaneous speech was statistically significant between 24 and 72 hours (P value = .012), and between baseline and 72 hours (P value = .017). CONCLUSIONS Our study demonstrates that patients treated with thrombolysis experience greater improvement in language than the nontreated patients. The difference between the 2 groups is increasingly evident over time. Moreover, spontaneous speech is the parameter marked by the greatest improvement.

Vitamin D in Neurological Diseases: A Rationale for a Pathogenic Impact

It is widely known that vitamin D receptors have been found in neurons and glial cells, and their highest expression is in the hippocampus, hypothalamus, thalamus and subcortical grey nuclei, and substantia nigra. Vitamin D helps the regulation of neurotrophin, neural differentiation, and maturation, through the control operation of growing factors synthesis (i.e., neural growth factor [NGF] and glial cell line-derived growth factor (GDNF), the trafficking of the septohippocampal pathway, and the control of the synthesis process of different neuromodulators (such as acetylcholine [Ach], dopamine [DA], and gamma-aminobutyric [GABA]). Based on these assumptions, we have written this review to summarize the potential role of vitamin D in neurological pathologies. This work could be titanic and the results might have been very fuzzy and even incoherent had we not conjectured to taper our first intentions and devoted our interests towards three mainstreams, demyelinating pathologies, vascular syndromes, and neurodegeneration. As a result of the lack of useful therapeutic options, apart from the disease-modifying strategies, the role of different risk factors should be investigated in neurology, as their correction may lead to the improvement of the cerebral conditions. We have explored the relationships between the gene-environmental influence and long-term vitamin D deficiency, as a risk factor for the development of different types of neurological disorders, along with the role and the rationale of therapeutic trials with vitamin D implementation.

THIAMINE AND ALCOHOL FOR BRAIN PATHOLOGY: Super-imposing or different causative factors for brain damage?

BACKGROUND Drinking more than the recommended limits is a worldwide emerging problem, difficult to circumscribe, and alcohol-related brain damages are an under-recognized health problem. Alcohol-cognitive disruption can be considered as transient and recoverable if the alcohol consumption is limited and occasional; if not, it can progress to the so-called Alcohol-Related Dementia (ARD), or to the Wernicke encephalopathy, or it can even induce the Korsakoff syndrome, an irreversible and long-lasting medical condition. ARD still remains poorly diagnosed and addressed, despite having increased research interest being a frustrating condition, a relatively non-progressive, or even partially reversible condition in abstinent ex-drinkers. On the contrary, Wernicke encephalopathy, with its neurological symptoms (ocular coordination imbalance and gait ataxia), is a dramatic medical condition, potentially lethal which can lead towards Korsakoff dementia. The alcohol consumption is a strong reinforcing condition of the thiamine deficit, the main biochemical determinant factor that starts the cascade of the brain irreversible damaging events. CONCLUSION Our review focuses on the possible common neural pathways of this three condition, on the biochemical basis of the damages, and tries to underline the strong need of better understanding the pathogenesis of the brain lesions, including epigenetics and the nutritional aspects of the problem.