Search Results (19)

Background: Neurosurgical interventions are often indicated for patients with subcortical, supratentorial intracerebral hemorrhage (ICH); however, the optimal treatment modality is controversial. Whether minimally invasive surgery (MIS) may be superior to conventional craniotomy (CC) or decompressive craniectomy (DC) in real-world clinical practice is unknown. Methods: This was a retrospective cohort study of hospitalization data from the 2016–22 Nationwide Readmissions Database. International Classification of Diseases—10th edition (ICD-10) codes were used to identify patients with primary supratentorial subcortical ICH who underwent neurosurgical treatment. Patients with ICH in other brain compartments (other than intraventricular hemorrhage) were excluded. Coprimary outcomes were routine discharge to home without rehabilitation needs (excellent outcome) and in-hospital mortality. Outcomes were compared between MIS versus CC and MIS versus DC, with multivariable adjustments for patient demographics and comorbidities. Results: A total of 3829 patients were identified; 418 underwent MIS (10.9%), 2167 (56.6%) underwent CC, and 1244 (32.5%) underwent DC. Compared to CC patients, MIS patients were less likely female (p = 0.004) but otherwise had similar patient characteristics; compared to DC patients, MIS patients were older, less likely female, more likely to have mental status abnormalities, more likely to have underlying dementia, less likely to undergo external ventricular drainage, more likely to have vascular risk factors (hypertension, hyperlipidemia, diabetes), and less likely to have underlying coagulopathy (all p < 0.05). After multivariable adjustments, MIS patients had higher odds of excellent outcomes compared to CC (OR 1.99 [95%CI 1.06–3.30], p = 0.039), and similar odds compared to DC (OR 1.10 [95%CI 0.66–1.86], p = 0.73). In terms of in-hospital mortality, MIS had lower odds compared to DC (OR 0.63 [95%CI 0.41–0.96], p = 0.032) and similar odds compared to CC (OR 0.81 [95%CI 0.56–1.18], p = 0.26). Conclusions: For patients with subcortical, supratentorial ICH requiring surgical evacuation, MIS was associated with higherhigher rates of excellent outcomes compared to CC and lower rates of in-hospital mortality compared to DC. However, since key variables such as hematoma size and symptom severity were not available, residual confounding could not be excluded, and results should be interpreted cautiously. Dedicated prospective or randomized studies are needed to confirm these findings. Full article

Background/Objectives: Low-grade inflammation in the form of microglial activation may be involved in neurodegenerative and vascular dementias. Subcortical small-vessel disease (SSVD) is the main form of vascular dementia, associated with brain barrier dysfunction and endothelial and monocyte activation. IL-6 and IL-17A are known proinflammatory cytokines that contribute to the disruption of blood–brain barrier integrity and microvascular dysfunction, features that are central to SSVD pathophysiological pathways. We herein compared cerebrospinal fluid (CSF) IL-6 and IL-17A concentrations in SSVD and AD patients as well as control subjects and examined the potential associations among IL-6 and IL-17A levels with cognitive and ΜRΙ changes. The albumin quotient (Qalb) was also calculated. Methods: CSF IL-6 and IL-17A (18 SSVD, 17 AD, and 12 healthy controls) were measured with solid-phase sandwich ELISAs, while albumin levels were measured by immunonephelometry. MMSE, FAB, and the CLOX tests were used for cognitive assessment and MRI was used for atrophy and white matter hyperintensities. Results: Significantly elevated CSF levels of Qalb and IL-6 were found in SSVD patients compared to both AD (p = 0.02) and controls (p = 0.002), respectively. Moreover, CSF IL-6 levels displayed a significant inverse correlation with CLOX2 scores (r = −0.641, p = 0.02), as well as a positive correlation with the total normalized CSF volume (r = 0.7, p = 0.01). CSF IL-17A levels were found to be reduced in SSVD patients, compared to controls and AD patients (p < 0.0001 and p = 0.002, respectively). The IL-6/IL-17A ratio with a cut-off value > 1.004 displayed a sensitivity of 83.33% (95%CI; 60.78% to 94.16%) and a specificity of 68.97% (95%CI; 50.77% to 82.72%) for the discrimination of SSVD from AD patients and controls. Conclusions: In the present pilot single-center study, we found increased CSF IL-6 and IL-6/IL-17A ratio levels in SSVD patients that correlated with reduced scores in the CLOX2 test and increased CSF volume. These preliminary findings deserve further evaluation in larger cohorts in order to elucidate their potential as surrogate biomarkers for the discrimination of SSVD from AD pathology. Full article

The process of aging is accompanied by a dynamic restructuring of the immune response, a phenomenon known as immunosenescence. Further, damage to the endothelium can be both a cause and a consequence of many diseases, especially in elderly people. The purpose of this study was to carry out immunological and biochemical profiling of elderly people with acute ischemic stroke (AIS), chronic cerebral circulation insufficiency (CCCI), prediabetes or newly diagnosed type II diabetes mellitus (DM), and subcortical ischemic vascular dementia (SIVD). Socio-demographic, lifestyle, and cognitive data were obtained. Biochemical, hematological, and immunological analyses were carried out, and extracellular vesicles (EVs) with endothelial CD markers were assessed. The greatest number of significant deviations from conditionally healthy donors (HDs) of the same age were registered in the SIVD group, a total of 20, of which 12 were specific and six were non-specific but with maximal differences (as compared to the other three groups) from the HDs group. The non-specific deviations were for the MOCA (Montreal Cognitive Impairment Scale), the MMSE (Mini Mental State Examination) and life satisfaction self-assessment scores, a decrease of albumin levels, and ADAMTS13 (a Disintegrin and Metalloproteinase with a Thrombospondin Type 1 motif, member 13) activity, and an increase of the VWF (von Willebrand factor) level. Considering the significant changes in immunological parameters (mostly Th17-like cells) and endothelial CD markers (CD144 and CD34), vascular repair was impaired to the greatest extent in the DM group. The AIS patients showed 12 significant deviations from the HD controls, including three specific to this group. These were high NEFAs (non-esterified fatty acids) and CD31 and CD147 markers of EVs. The lowest number of deviations were registered in the CCCI group, nine in total. There were significant changes from the HD controls with no specifics to this group, and just one non-specific with a maximal difference from the control parameters, which was α1-AGP (alpha 1 acid glycoprotein, orosomucoid). Besides the DM patients, impairments of vascular repair were also registered in the CCCI and AIS patients, with a complete absence of such in patients with dementia (SIVD group). On the other hand, microvascular damage seemed to be maximal in the latter group, considering the biochemical indicators VWF and ADAMTS13. In the DM patients, a maximum immune response was registered, mainly with Th17-like cells. In the CCCI group, the reaction was not as pronounced compared to other groups of patients, which may indicate the initial stages and/or compensatory nature of organic changes (remodeling). At the same time, immunological and biochemical deviations in SIVD patients indicated a persistent remodeling in microvessels, chronic inflammation, and a significant decrease in the anabolic function of the liver and other tissues. The data obtained support two interrelated assumptions. Taking into account the primary biochemical factors that trigger the pathological processes associated with vascular pathology and related diseases, the first assumption is that purine degradation in skeletal muscle may be a major factor in the production of uric acid, followed by its production by non-muscle cells, the main of which are endothelial cells. Another assumption is that therapeutic factors that increase the levels of endothelial progenitor cells may have a therapeutic effect in reducing the risk of cerebrovascular disease and related neurodegenerative diseases. Full article

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited disease with unknown mechanisms and a broad phenotypic spectrum. It is caused by pathogenic variants in the NOTCH3 gene. The symptoms of the disease mainly include recurrent strokes with vascular risk factors, migraine with aura, dementia, and mood disturbances. Case presentation: Peripheral blood samples were collected from five patients from four unrelated families to extract genomic DNA. In four patients, analysis of exons 2, 3, 4, 5, 6 and adjacent intronic regions of the NOTCH3 gene was made via Sanger sequencing. Two previously undescribed nucleotide variants were identified in two patients: missense variant c.208G>T, (p.Gly70Cys) in exon 1 and splice-site variant c.341-1G>C in intron 3. Further DNA of two other patients were analyzed using a next-generation sequencing-based custom AmpliSeq™ panel for 59 genes associated with leukodystrophies. Two novel missense variants in the NOTCH3 gene were identified, c.1136G>A, (p.Cys379Tyr) in exon 7 and c.1547G>A, (p.Cys516Tyr) in exon 10. The pathogenic variant c.1547G>A, (p.Cys516Tyr) was confirmed in the fifth patient (family case) by Sanger sequencing. All patients had a history of headaches, transient ischemic attacks, memory impairment, and characteristics of MRI results. Three patients had strokes and two patients had psychiatric symptoms. Conclusion: We found four previously undescribed pathogenic variants in the NOTCH3 gene in five patients with CADASIL and described their clinical and genetic characteristics. These results expand the mutational spectrum of CADASIL. Full article

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common heritable form of vascular dementia in adults. It is well-established that CADASIL results in neurocognitive dysfunction and mood disturbance. There is also cumulative evidence that CADASIL patients are more susceptible to ischemic heart disease. The aim of this study is to review the current literature regarding the incidence of coronary artery disease in CADASIL patients with a focus on the various management options and the clinical challenges associated with each of these treatment strategies. We conducted a literature search using Cochrane, MEDLINE, and EMBASE for papers that reported the occurrence of coronary artery disease in patients with CADASIL. We supplemented the search with a manual search in Google Scholar. Only case reports, case series, and original articles were included. The search resulted in six reports indicating the association between coronary artery disease and CADASIL and its management. Evidence suggests that extracranial manifestations of CADASIL may include coronary artery disease, presenting as a more extensive burden of disease in younger patients. Surgical and percutaneous revascularization strategies are feasible, but the incidence of peri-procedural stroke remains significant and should be weighed against the potential benefit derived from either of these strategies. A multidisciplinary approach to therapy, with perspectives from neurologists, cardiologists, and cardiac surgeons, is needed to provide the appropriate treatment to the CADASIL patient with severe coronary artery disease. Future studies should be directed toward the development of targeted therapies that may help with the early detection and prevention of disease progress in these patients. Full article

Alzheimer’s disease (AD) is characterized by the presence of β-amyloid (Aβ) and tau, and subcortical vascular cognitive impairment (SVCI) is characterized by cerebral small vessel disease (CSVD). They are the most common causes of cognitive impairment in the elderly population. Concurrent CSVD burden is more commonly observed in AD-type dementia than in other neurodegenerative diseases. Recent developments in Aβ and tau positron emission tomography (PET) have enabled the investigation of the relationship between AD biomarkers and CSVD in vivo. In this review, we focus on the interaction between AD and CSVD markers and the clinical effects of these two markers based on molecular imaging studies. First, we cover the frequency of AD imaging markers, including Aβ and tau, in patients with SVCI. Second, we discuss the relationship between AD and CSVD markers and the potential distinct pathobiology of AD markers in SVCI compared to AD-type dementia. Next, we discuss the clinical effects of AD and CSVD markers in SVCI, and hemorrhagic markers in cerebral amyloid angiopathy. Finally, this review provides both the current challenges and future perspectives for SVCI. Full article

NAFLD is the most common cause of abnormality in liver function tests. NAFLD is considered a potential cardiovascular risk factor and is linked to cardiovascular risk factors such as obesity, hypertension, type 2 diabetes, and dyslipidemia. Few previous studies have investigated whether NAFLD could be independently associated with cognitive impairment. The current study aims to find a possible role of NAFLD in the development of subcortical vascular dementia (sVaD). We considered NAFLD as a possible independent vascular risk factor or, considering its metabolic role, associated with other commonly accepted sVaD risk factors, i.e., lack of folate, vitamin B12, and vitamin D-OH25, and increased levels of homocysteine. We studied 319 patients diagnosed with sVaD. All patients underwent an abdominal ultrasound examination to classify steatosis into four levels (1—none up to 4—severe). sVaD patients were divided into two groups according to the presence or absence of NAFLD. Our results demonstrated a strong correlation between NAFLD and sVaD. Patients with the two comorbidities had worse neuropsychological outcomes and a worse metabolic profile. We also found a robust relationship between NAFLD and severe vitamin B12, folate, vitamin D hypovitaminosis, and higher hyperhomocysteinemia levels. This way, it is evident that NAFLD contributes to a more severe metabolic pathway. However, the strong relationship with the three parameters (B12, folate and vitamin D, and homocysteinemia) suggests that NAFLD can contribute to a proinflammatory condition. Full article

Small-vessel disease (SVD), also known as microvascular endothelial dysfunction, is a disorder with negative consequences for various organs such as the heart and brain. Impaired dilatation and constriction of small vessels in the heart lead to reduced blood flow and ischemia independently of coronary artery disease (CAD) and are associated with major cardiac events. SVD is usually a silent form of subcortical vascular burden in the brain with various clinical manifestations, such as silent-lacunar-ischemic events and confluent white-matter hyperintensities. Imaging techniques are the main help for clinicians to diagnose cardiac and brain SVD correctly. Markers of inflammation, such as C-reactive protein, tumor-necrosis-factor α, and interleukin 6, provide insight into the disease and markers that negatively influence nitric-oxide bioavailability and promote oxidative stress. Unfortunately, the therapeutic approach against SVD is still not well-defined. In the last decades, various antioxidants, oxidative stress inhibitors, and superoxide scavengers have been the target of extensive investigations due to their potential therapeutic effect, but with unsatisfactory results. In clinical practice, traditional anti-ischemic and risk-reduction therapies for CAD are currently in use for SVD treatment. Full article

Cysteine oxidation states of extracellular proteins participate in functional regulation and in disease pathophysiology. In the most common inherited dementia, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), mutations in NOTCH3 that alter extracellular cysteine number have implicated NOTCH3 cysteine states as potential triggers of cerebral vascular smooth muscle cytopathology. In this report, we describe a novel property of the second EGF-like domain of NOTCH3: its capacity to alter the cysteine redox state of the NOTCH3 ectodomain. Synthetic peptides corresponding to this sequence (NOTCH3 N-terminal fragment 2, NTF2) readily reduce NOTCH3 N-terminal ectodomain polypeptides in a dose- and time-dependent fashion. Furthermore, NTF2 preferentially reduces regional domains of NOTCH3 with the highest intensity against EGF-like domains 12–15. This process requires cysteine residues of NTF2 and is also capable of targeting selected extracellular proteins that include TSP2 and CTSH. CADASIL mutations in NOTCH3 increase susceptibility to NTF2-facilitated reduction and to trans-reduction by NOTCH3 produced in cells. Moreover, NTF2 forms complexes with the NOTCH3 ectodomain, and cleaved NOTCH3 co-localizes with the NOTCH3 ectodomain in cerebral arteries of CADASIL patients. The potential for NTF2 to reduce vascular proteins and the enhanced preference for it to trans-reduce mutant NOTCH3 implicate a role for protein trans-reduction in cerebrovascular pathological states such as CADASIL. Full article

Correct in vivo diagnosis of Alzheimer’s disease (AD) helps to avoid administration of disease-modifying treatments in non-AD patients, and allows the possible use of such treatments in clinically atypical AD patients. Cerebrospinal fluid (CSF) biomarkers offer a tool for AD diagnosis. A reduction in CSF β-amyloid (marker of amyloid plaque burden), although compatible with Alzheimer’s pathological change, may also be observed in other dementing disorders, including vascular cognitive disorders due to subcortical small-vessel disease, dementia with Lewy bodies and normal-pressure hydrocephalus. Thus, for the diagnosis of AD, an abnormal result of CSF β-amyloid may not be sufficient, and an increase in phospho-tau (marker of tangle pathology) is also required in order to confirm AD diagnosis in patients with a typical amnestic presentation and reveal underlying AD in patients with atypical or mixed and diagnostically confusing clinical presentations. Full article

SARS-COV-2 is a severe medical condition. Old patients are very vulnerable, but they have been studied only as institutionalized patients. During the lock-down, little attention is dedicated to old, demented patients who lived at home. This study wants to examine their behavioral reactions by video-phone follow-up. We conducted a longitudinal study in subcortical vascular dementia (sVAD) patients. We enrolled 221 sVAD, not institutionalized patients. We divided sVAD patients into low-medium grade sVAD (A) and severe sVAD (B), based on neuroimaging severity degree and executive alterations. At baseline, at the end of lock-down, and two months later, global behavioral symptoms were recorded for each patient. We found significantly higher scores of general behavioral deterioration, anxiety, delusions, hallucinations and apathy after controlling for sVAD severity. The direct consequence was a drastic increment of psychotropic drugs prescribed and employed during the lock-down. Moreover, caregivers’ stress has been evaluated, together with their anxiety and depression levels. During the lock-down, their scores increased and reflected a severe worsening of their behavior. Our data demonstrate that social isolation induces a severe perception of loneliness and abandonment; these fears can exacerbate behavior disturbances in old-aged frail persons. Thus, these can be considered as indirect victims of SARS-COV-2. Full article

Early detection of motor intentional disorders associated with dysfunction in the action–intention system of the brain is clinically important to provide timely intervention. This study developed a force tracking system that can record forces exerted by the index finger while tracking 5 N, 10 N, 15 N, and 20 N of target forces varying over time. The force tracking system quantified force control measures (initiation time IT; development time, DT, maintenance error, ME; termination time, TT; tracking error, TE) for the individual and overall force control phases. This study evaluated the effectiveness of the force tracking system for a normal control group (n = 12) and two patient groups diagnosed with subcortical vascular mild cognitive impairment (svMCI, n = 11) and subcortical vascular dementia (SVaD, n = 13). Patients with SVaD showed significantly worse force control capabilities in IT (0.84 s) and ME (1.71 N) than those with svMCI (0.64 s in IT, and 1.38 N in ME). Patients with svMCI had significantly worse capabilities in IT, ME, and TE (3.80 N) than the control group (0.49 s in IT, 0.78 N in ME, and 3.07 N in TE). The prevalence rates of force control capabilities lower than the 99% confidence interval of the control group ranged from 17% to 62% for the two patient groups. The force tracking system can sensitively quantify the severity of the force control deficiencies caused by dysfunction in the action–intention system of the brain. Full article

Dopamine (DA) is a key neurotransmitter involved in multiple physiological functions including motor control, modulation of affective and emotional states, reward mechanisms, reinforcement of behavior, and selected higher cognitive functions. Dysfunction in dopaminergic transmission is recognized as a core alteration in several devastating neurological and psychiatric disorders, including Parkinson’s disease (PD), schizophrenia, bipolar disorder, attention deficit hyperactivity disorder (ADHD) and addiction. Here we will discuss the current insights on the role of DA in motor control and reward learning mechanisms and its involvement in the modulation of synaptic dynamics through different pathways. In particular, we will consider the role of DA as neuromodulator of two forms of synaptic plasticity, known as long-term potentiation (LTP) and long-term depression (LTD) in several cortical and subcortical areas. Finally, we will delineate how the effect of DA on dendritic spines places this molecule at the interface between the motor and the cognitive systems. Specifically, we will be focusing on PD, vascular dementia, and schizophrenia. Full article

To date, interest in the role of coffee intake in the occurrence and course of age-related neurological and neuropsychiatric disorders has provided an inconclusive effect. Moreover, no study has evaluated mocha coffee consumption in subjects with mild vascular cognitive impairment and late-onset depression. We assessed the association between different quantities of mocha coffee intake over the last year and cognitive and mood performance in a homogeneous sample of 300 non-demented elderly Italian subjects with subcortical ischemic vascular disease. Mini Mental State Examination (MMSE), Stroop Colour-Word Interference Test (Stroop T), 17-items Hamilton Depression Rating Scalfe (HDRS), Activities of Daily Living (ADL), and Instrumental ADL were the outcome measures. MMSE, HDRS, and Stroop T were independently and significantly associated with coffee consumption, i.e., better scores with increasing intake. At the post-hoc analyses, it was found that the group with a moderate intake (two cups/day) had similar values compared to the heavy drinkers (≥three cups/day), with the exception of MMSE. Daily mocha coffee intake was associated with higher cognitive and mood status, with a significant dose-response association even with moderate consumption. This might have translational implications for the identification of modifiable factors for vascular dementia and geriatric depression. Full article

We studied 114 primitive cerebral neoplasia, that were surgically treated, and underwent radiotherapy (RT), and compared their results to those obtained by 190 patients diagnosed with subcortical vascular dementia (sVAD). Patients with any form of primitive cerebral neoplasia underwent whole-brain radiotherapy. All the tumor patients had regional field partial brain RT, which encompassed each tumor, with an average margin of 2.6 cm from the initial target tumor volume. We observed in our patients who have been exposed to a higher dose of RT (30–65 Gy) a cognitive and behavior decline similar to that observed in sVAD, with the frontal dysexecutive syndrome, apathy, and gait alterations, but with a more rapid onset and with an overwhelming effect. Multiple mechanisms are likely to be involved in radiation-induced cognitive impairment. The active site of RT brain damage is the white matter areas, particularly the internal capsule, basal ganglia, caudate, hippocampus, and subventricular zone. In all cases, radiation damage inside the brain mainly focuses on the cortical–subcortical frontal loops, which integrate and process the flow of information from the cortical areas, where executive functions are “elaborated” and prepared, towards the thalamus, subthalamus, and cerebellum, where they are continuously refined and executed. The active mechanisms that RT drives are similar to those observed in cerebral small vessel disease (SVD), leading to sVAD. The RT’s primary targets, outside the tumor mass, are the blood–brain barrier (BBB), the small vessels, and putative mechanisms that can be taken into account are oxidative stress and neuro-inflammation, strongly associated with the alteration of NMDA receptor subunit composition. Full article