Riccardo Altavilla

Diffusion-weighted lesions after carotid artery stenting are associated with cognitive impairment.

The effect of carotid artery stenting (CAS) on cognitive function is still debated. Cerebral microembolism, detectable by post-procedural diffusion-weighted imaging (DWI) lesions, has been suggested to predispose to cognitive decline. Our study aimed at evaluating the effect of CAS on cognitive profile focusing on the potential role of cerebral microembolic lesions, taking into consideration the impact of factors potentially influencing cognitive status (demographic features, vascular risk profile, neuropsychological evaluation at baseline and magnetic resonance (MR) markers of brain structural damage). Thirty-seven patients with severe carotid artery stenosis were enrolled. Neurological assessment, neuropsychological evaluation and brain MR were performed the day before CAS (E0). Brain MR with DWI was repeated the day after CAS (E1), while neuropsychological evaluation was done after a 14-month median period (E2). Volumes of both white matter hyperintensities and whole brain were estimated at E0 on axial MR FLAIR and T1w-SE sequences, respectively. Unadjusted ANOVA analysis showed a significant CAS*DWI interaction for MMSE (F=7.154(32), p=.012). After adjusting for factors potentially influencing cognitive status CAS*DWI interaction was confirmed for MMSE (F=7.092(13), p=.020). Patients with DWI lesions showed a mean E2-E0 MMSE reduction of -3.1, while group without DWI lesions showed a mean E2-E0 MMSE of +1.1. Our study showed that peri-procedural brain microembolic load impacts negatively on cognitive functions, independently from the influence of patients-related variables.

The Ineffective Role of Cathodal tDCS in Enhancing the Functional Motor Outcomes in Early Phase of Stroke Rehabilitation: An Experimental Trial

Transcranial direct current stimulation (tDCS) is a noninvasive technique that could improve the rehabilitation outcomes in stroke, eliciting neuroplastic mechanisms. At the same time conflicting results have been reported in subacute phase of stroke, when neuroplasticity is crucial. The aim of this double-blind, randomized, and sham-controlled study was to determine whether a treatment with cathodal tDCS before the rehabilitative training might augment the final outcomes (upper limb function, hand dexterity and manual force, locomotion, and activities of daily living) in respect of a traditional rehabilitation for a sample of patients affected by ischemic stroke in the subacute phase. An experimental group (cathodal tDCS plus rehabilitation) and a control group (sham tDCS plus rehabilitation) were assessed at the beginning of the protocol, after 10 days of stimulation, after 30 days from ending of stimulation, and at the end of inpatient rehabilitation. Both groups showed significant improvements for all the assessed domains during the rehabilitation, except for the manual force, while no significant differences were demonstrated between groups. These results seem to indicate that the cathodal tDCS, provided in an early phase of stroke, does not lead to a functional improvement. To depict a more comprehensive scenario, further studies are needed.

1-Hz Repetitive Transcranial Magnetic Stimulation Increases Cerebral Vasomotor Reactivity: A Possible Autonomic Nervous System Modulation

BACKGROUND Neuromodulation techniques, i.e. repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), can modify cerebral hemodynamics. High frequency rTMS appeared to decrease cerebral vasomotor reactivity (VMR), while there is still poor evidence about the effect of low frequency (LF) rTMS on cerebral blood flow (CBF) and VMR. HYPOTHESIS The present study aimed to test if LF rTMS decreases CBF and increases cerebral VMR. Monolateral or bilateral hemispheric involvement and duration of the effect were considered. A possible role of autonomic nervous system in CBF and VMR modulation was also investigated. METHODS Twenty-four right-handed healthy subjects underwent randomly real (12) or sham (12) 20-min 1-Hz rTMS on left primary motor cortex. Mean flow velocity and VMR of middle cerebral arteries were evaluated by means of transcranial Doppler before (T0), after 10 min (T1) and after 2 (T2), 5 (T3) and 24 h (T4) from rTMS. Heart rate variability (HRV) was studied within the same timing interval, assessing low frequency/high frequency (LF/HF) ratio as index of autonomic balance. RESULTS After real rTMS compared with sham stimulation, MFV decreased bilaterally at T1 (F = 3.240, P = .030) while VMR increased bilaterally (F = 5.116, P = .002) for at least 5 h (T3). LF/HF ratio decreased early after real rTMS (F = 2.881, P = .040). CONCLUSION 1-Hz rTMS may induce a bilateral long-lasting increase of VMR, while its effect on MFV is short-lasting. Moreover, HRV changes induced by rTMS suggest a possible autonomic nervous system modulation.

Apolipoprotein E Genotype and Cerebrovascular Alterations Can Influence Conversion to Dementia in Patients with Mild Cognitive Impairment

The presence of apolipoprotein E (APOE) ε4 allele is the only recognized genetic risk factor for the sporadic form of Alzheimers disease. The aim of this study was to investigate the relationship between APOE genotype and the functional and anatomic status of cerebral vessels in patients with mild cognitive impairment (MCI). Moreover, we explored whether the possible correlation between APOE genotype and cerebrovascular parameters influences the risk of conversion from MCI to dementia. 75 MCI patients underwent a complete neuropsychological battery at baseline and after 24 months to evaluate the possible conversion to dementia. Ultrasound assessment of neck and intracranial vessels was performed to assess common carotid artery intima-media thickness (IMT), plaque index, and cerebrovascular reactivity (breath-holding index, BHI). APOE genotype was determined to classify patients as carriers (APOE ε4+) and non-carriers (APOE ε4-). Pathologic values of BHI and IMT were significantly more common in ε4 carriers than in non-carriers [OR 6.603 (95% CI: 1.678-25.997), p < 0.05 and OR 5.195 (95% CI 1.319-20.464), p < 0.05; logistic regression adjusted model]. The risk of conversion to dementia was significantly higher in APOE ε4+ patients than in APOE ε4- ones (OR: 6.818; 95% CI:1.894-24.545, p = 0.003). A path-analysis model showed that APOE genotype influences the progression to dementia directly and indirectly by increasing the risk of pathologic values of IMT or BHI. Our data, besides confirming an increased susceptibility of MCI patients with APOE ε4 to develop dementia, show an association between functional and anatomic impairment of the cerebral vessels and APOE ε4+ genotype.

Cerebral Hemodynamics and Systemic Endothelial Function Are Already Impaired in Well-Controlled Type 2 Diabetic Patients, with Short-Term Disease

Objective Impaired cerebral vasomotor reactivity (VMR) and flow-mediated dilation (FMD) were found in selected subgroups of type 2 diabetes mellitus (T2DM) patients with long-term disease. Our study aimed to evaluate cerebral hemodynamics, systemic endothelial function and sympatho-vagal balance in a selected population of well-controlled T2DM patients with short-term disease and without cardiac autonomic neuropathy (CAN). Research Design and Methods Twenty-six T2DM patients with short-term (4.40±4.80 years) and well-controlled (HbA1C = 6.71±1.29%) disease, without any complications, treated with diet and/or metformin, were consecutively recruited. Eighteen controls, comparable by sex and age, were enrolled also. Results FMD and shear rate FMD were found to be reduced in T2DM subjects with short-term disease (8.5% SD 3.5 and 2.5 SD 1.3, respectively) compared to controls (15.4% SD 4.1 and 3.5 SD 1.4; p<.001 and p<.05). T2DM patients also displayed reduced VMR values than controls (39.4% SD 12.4 vs 51.7%, SD 15.5; p<.05). Sympatho-vagal balance was not different in T2DM patients compared to healthy subjects. FMD and shear rate FMD did not correlate with VMR in T2DM patients or in controls (p>.05). Conclusions In well-controlled T2DM patients with short-term disease cerebral hemodynamics and systemic endothelial function are altered while autonomic balance appeared to be preserved.

Acute hyperglycemia reduces cerebrovascular reactivity: The role of glycemic variability

CONTEXT Cerebral vasomotor reactivity (CVR) is reduced in patients with diabetes mellitus (DM), and glucose variability (GV) might be responsible for cerebrovascular damage. OBJECTIVE Studying patients with insulin resistance without DM, we explored the role of GV in impairing CVR. PATIENTS We studied 18 metabolic syndrome (MS) patients without DM, 9 controls (C), and 26 patients with DM. MAIN OUTCOME MEASURES Groups were compared in terms of CVR, GV, and 24-hour blood pressure. To evaluate the impact of acute hyperglycemia on CVR, a hyperglycemic clamp was performed in MS patients and controls. RESULTS Baseline CVR was reduced in DM vs C and MS (C vs DM = 20.2, 95% CI = 3.5-36.9, P = .014; and MS vs DM = 22.2, 95% CI = 8.6-35.8, P = .001), but similar between MS and C (MS vs C = 2.0, 95% CI = -14.7 to 18.7, P = .643). During acute hyperglycemia, CVR fell in MS and C to values comparable to DM. GV progressively increased from C to MS to DM. In MS, CVR at 120 minutes and GV displayed a negative correlation (r = -0.48, P = .043), which did not change after controlling for mean 24-hour systolic and diastolic blood pressure. In MS, the CVR reduction was significantly correlated to GV (r = 0.55, P = .02). CONCLUSIONS GV is increased in patients with MS but without DM and is the major predictor of CVR reduction induced by acute hyperglycemia, possibly representing the earliest cause of cerebrovascular damage in DM.

Cortical ischemic lesion burden measured by DIR is related to carotid artery disease severity.

Background: Over time, exposure to cerebrovascular risk factors and carotid artery disease may cause multiple asymptomatic brain cortical and subcortical microinfarcts, which are commonly found at brain autopsy. So far, lack of convenient neuroimaging tools limited the investigation of grey matter ischemic damage in vivo. We applied the Double Inversion Recovery (DIR) sequence to explore the impact of carotid artery disease on intracortical ischemic lesion load in vivo, taking into account the impact of demographic characteristics and vascular risk factors. Methods: DIR was acquired in 62 patients with common cerebrovascular risk factors stratified in three groups according to carotid artery disease severity. Intracortical lesions scored on DIR (DIRlns) were classified by vascular territory, lobe and hemisphere. White matter hyperintensities (WMHs) volume was also quantified on Fluid Attenuated Inversion Recovery sequence (FLAIR). Results: Among demographic characteristics and cerebrovascular risk variables explored, General Linear Model indicated that age and carotid artery disease were significantly associated to DIRlns. After correcting for age, DIRlns load was found to be significantly dependent on carotid artery stenosis severity (F(2, 58) = 5.56, p = 0.006). A linear positive correlation between DIRlns and WMHs was found after correcting for age (p = 0.003). Conclusions: Carotid disease severity is associated with DIRlns accrual. Microembolism and impaired cerebral hemodynamics may act as physiopathological mechanisms underlying cortical ischemic damage. The role of other factors, such as small vessel disease and the possible interaction with carotid disease, remains to be further explored.

Relationship among Diffusion Tensor Imaging, EEG Activity, and Cognitive Status in Mild Cognitive Impairment and Alzheimer's Disease Patients

Magnetic resonance (MR) diffusion tensor imaging (DTI) can detect microstructural alterations by means of fractional anisotropy (FA) in patients with dementia, also in relation to cognitive status. The present study aimed at investigating the possible relation among white matter damage in DTI, quantitative electroencephalography (EEG) spectral power, and cognitive status in Alzheimers disease (AD) and mild cognitive impairment (MCI) patients. Forty-seven subjects (8 moderate AD, 18 mild AD, 12 MCI, and 9 healthy controls) underwent brain MR, neuropsychological evaluation, and resting EEG recording. A progressive increase of EEG delta and theta spectral power was observed from controls to patients, mainly in more anterior areas, with a parallel widespread decrease of beta power. Moreover, a progressive decrease of FA from controls to patients in frontal areas and in the corpus callosum (genu) was observed. Correlation analyses indicated convergence among EEG rhythms changes, DTI values, and cognitive status mainly over anterior areas. The decrease of FA values and EEG spectral power changes might represent markers of neurodegenerative dysfunction, possibly preceding macrostructural atrophy.

Dorsolateral medullary ischemic infarction causing autonomic dysfunction and headache: a case report

Stroke can present, among other signs, with headache. Here, we describe the case of a man suffering from severe orbitary pain and autonomic dysfunction secondary to dorsolateral medullary ischemia. The anatomical relationship between lesion and symptomatology could be an indirect sign of hypothalamospinal tract involvement in the genesis of autonomic dysfunction and headache resembling a trigeminal autonomic cephalalgia.

Emerging Risk Factors for Dementia: The Role of Blood Pressure Variability

In the recent years, classical vascular risk factors have been suggested to play a role also in the development of degenerative dementia. Arterial hypertension has been implicated in the pathogenesis of dementia but no conclusive results have been produced yet; more recently, blood pressure variability (BPV) has been suggested as a more important risk factor for both silent brain vascular lesions and the development of dementia. Blood pressure variability is defined as the variation in blood pressure over time, measured on different time spans and in different ways. We reviewed current scientific literature about the role of BPV in the pathogenesis of dementia, and about the association of abnormal BPV patterns and different forms of dementia. We also suggested some hypothetical pathogenic mechanisms.