Distinctive Under-Expression Profile of Inflammatory and Redox Genes in the Blood of Elderly Patients with Cardiovascular Disease.

PURPOSE: Chronic low-grade inflammation and oxidative stress are present in most of the pathologic mechanisms underlying non-communicable diseases. Inflammation and redox biomarkers might therefore have a value in disease prognosis and therapy response. In this context, we performed a case-control study for assessing in whole blood the expression profile of inflammation and redox-related genes in elderly subjects with various comorbidities. PATIENTS AND METHODS: In the blood of 130 elderly subjects with various pathologies (cardiovascular disease, hypertension, dyslipidemia including hypercholesterolemia, type 2 diabetes mellitus), kept under control by polyvalent disease-specific medication, we investigated by pathway-focused qRT-PCR a panel comprising 84 inflammation-related and 84 redox-related genes. RESULTS: The study highlights a distinctive expression profile of genes critically involved in NF-κB-mediated inflammation and redox signaling in the blood of patients with cardiovascular disease, characterized by significant down-regulation of the genes NFKB2, NFKBIA, RELA, RELB, AKT1, IRF1, STAT1, CD40, LTA, TRAF2, PTGS1, ALOX12, DUOX1, DUOX2, MPO, GSR, TXNRD2, HSPA1A, MSRA, and PDLIM1. This gene expression profile defines the transcriptional status of blood leukocytes in stable disease under medication control, without discriminating between disease- and therapy-related changes. CONCLUSION: The study brings preliminary proof on a minimally invasive strategy for monitoring disease in patients with cardiovascular pathology, from the point of view of inflammation or redox dysregulation in whole blood.

Characterizing Advanced Parkinson's Disease: Romanian Subanalysis from the OBSERVE-PD Study.

OBSERVE-PD was a cross-sectional, multicountry, observational study conducted in 128 Movement Disorders Centers (MDCs) in 18 countries. Overall, the study enrolled 2615 patients. The aim was to determine the proportion of patients with advanced Parkinson's disease (APD) versus non-APD from MDCs and to uncover the clinical burden of APD, as well as a correlation between overall assessment of APD and several indicators of APD. The advanced stage of the disease and severity were assessed by investigators using their clinical judgement. Data were collected during a single visit between February 2015 and January 2016. Agreement on physician judgement of APD diagnosis and fulfillment of at least one previously established APD indicator was calculated. Motor and nonmotor symptoms (NMSs), activities of daily living, treatment complications, quality of life (QoL), conventional treatments, and device-aided therapy (DAT) eligibility were assessed. Here, country-specific results of 161 Romanian patients with PD are presented. In total, 59.0% of patients were diagnosed with APD and 78.8% met at least one APD indicator. There was only moderate agreement between clinical judgement of APD and overall fulfillment of APD indicators. All scores related to motor symptoms, NMSs, and treatment complications, as well as to QoL, showed a higher disease burden for patients with APD versus non-APD. Physicians considered 73.7% of patients with APD eligible for DAT. The majority of patients eligible for DAT (54.3%) did not receive such treatment. Our results highlight the importance of earlier recognition of APD, by combining clinical judgement with more standardized clinical tools, such as generally recognized APD criteria. However, timely diagnosis of APD alone is not enough to improve patient outcomes. Other critical factors include patient acceptance and access to appropriate treatment.

Clinical Characteristics and Outcomes of Patients with Intracerebral Hemorrhage - A Feasibility Study on Romanian Patients.

Intracerebral hemorrhage is a significant public health problem, as it is a disease associated with overwhelming mortality and disability. We performed a retrospective feasibility study of patients admitted with acute intracerebral hemorrhage in our department for four months. Our aims were to identify peculiarities of the risk factors, demographic and clinical characteristics of intracerebral hemorrhage patients from our population, to estimate a feasible recruitment rate for a larger prospective study of patients with intracerebral hemorrhage and to analyze and correct potential drawbacks in the methodology of a more extensive prospective study of patients with intracerebral hemorrhage hospitalized in our department. During the study period, we admitted 53 patients with intracerebral hemorrhage in our department. The mean age of the patients was 69.1 years, and 53% were men. Arterial hypertension was the most common etiologic factor leading to intracerebral hemorrhage. 50.01% of patients died during hospitalization, 31.19% were discharged with significant disability, and 18.8% had a favorable short-term outcome. Higher hematoma volumes, male sex, deep location of the hemorrhage, and age between 51 and 60 years were factors associated with an unfavorable short-term outcome.

Cingulate cortex function and multi-modal connectivity mapped using intracranial stimulation.

The cingulate cortex is part of the limbic system. Its function and connectivity are organized in a rostro-caudal and ventral-dorsal manner which was addressed by various other studies using rather coarse cortical parcellations. In this study, we aim at describing its function and connectivity using invasive recordings from patients explored for focal drug-resistant epilepsy. We included patients that underwent stereo-electroencephalographic recordings using intracranial electrodes in the University Emergency Hospital Bucharest between 2012 and 2019. We reviewed all high frequency stimulations (50 â€‹Hz) performed for functional mapping of the cingulate cortex. We used two methods to characterize brain connectivity. Effective connectivity was inferred based on the analysis of cortico-cortical potentials (CCEPs) evoked by single pulse electrical stimulation (SPES) (15 â€‹s inter-pulse interval). Functional connectivity was estimated using the non-linear regression method applied to 60 â€‹s spontaneous electrical brain signal intervals. The effective (stimulation-evoked) and functional (non-evoked) connectivity analyses highlight brain networks in a different way. While non-evoked connectivity evidences areas having related activity, often in close proximity to each other, evoked connectivity highlights spatially extended networks. To highlight in a comprehensive way the cingulate cortex's network, we have performed a bi-modal connectivity analysis that combines the resting-state broadband h2 non-linear correlation with cortico-cortical evoked potentials. We co-registered the patient's anatomy with the fsaverage FreeSurfer template to perform the automatic labeling based on HCP-MMP parcellation. At a group level, connectivity was estimated by averaging responses over stimulated/recorded or recorded sites in each pair of parcels. Finally, for multiple regions that evoked a clinical response during high frequency stimulation, we combined the connectivity of individual pairs using maximum intensity projection. Connectivity was assessed by applying SPES on 2094 contact pairs and recording CCEPs on 3580 contacts out of 8582 contacts of 660 electrodes implanted in 47 patients. Clinical responses elicited by high frequency stimulations in 107 sites (pairs of contacts) located in the cingulate cortex were divided in 10 groups: affective, motor behavior, motor elementary, versive, speech, vestibular, autonomic, somatosensory, visual and changes in body perception. Anterior cingulate cortex was shown to be connected to the mesial temporal, orbitofrontal and prefrontal cortex. In the middle cingulate cortex, we located affective, motor behavior in the anterior region, and elementary motor and somatosensory in the posterior part. This region is connected to the prefrontal, premotor and primary motor network. Finally, the posterior cingulate was shown to be connected with the visual areas, mesial and lateral parietal and temporal cortex.

The Role of Polysomnography in Identifying Sleep Disorders in Children with Migraine.

Migraine pathophysiology and sleep share common neural pathways, and there are clinical as well as paraclinical observations, which lead to the hypothesis of an association between migraine and sleep disorders. The objective of this study consisted of the evaluation of a possible correlation between migraine and sleep disorders in children, as reflected by sleep architecture and electroencephalographic patterns. Eighteen patients aged five to seventeen were recruited for the migraine group, and sixteen age-matched patients with no criteria for migraine or any underlying organic disorder, diagnosed with emotional disorders, were enrolled in the control group. All patients underwent inpatient full night polysomnographic recordings, the results of which were analyzed using appropriate statistical methods. Patients in the migraine group had decreased REM sleep (p = 0.049) and increased N1 sleep (p = 0.018) percentages, compared to the control group. Also, more arousals (p = 0.011) and lower sleep latency (p = 0.029) were noted in the migraine group. A statistically significant association was observed between migraine and sleep disorders when the latter was defined with respect to normal values of polysomnographic parameters published in studies conducted on healthy children. Polysomnography can be a useful tool for studying sleep in pediatric migraine patients. The results of this study can be regarded as a starting point for a better understanding of the complex role of sleep in the developing brain and of eventual intricacies with migraine pathophysiological mechanisms.

Sleep modulates effective connectivity: A study using intracranial stimulation and recording.

OBJECTIVE: Sleep is an active process with an important role in memory. Epilepsy patients often display a disturbed sleep architecture, with consequences on cognition. We aimed to investigate the effect of sleep on cortical networks' organization. METHODS: We analyzed cortico-cortical evoked responses elicited by single pulse electrical stimulation (SPES) using intracranial depth electrodes in 25 patients with drug-resistant focal epilepsy explored using stereo-EEG. We applied the SPES protocol during wakefulness and NREM - N2 sleep. We analyzed 31,710 significant responses elicited by 799 stimulations covering most brain structures, epileptogenic or non-epileptogenic. We analyzed effective connectivity between structures using a graph-theory approach. RESULTS: Sleep increases excitability in the brain, regardless of epileptogenicity. Local and distant connections are differently modulated by sleep, depending on the tissue epileptogenicity. In non-epileptogenic areas, frontal lobe connectivity is enhanced during sleep. There is increased connectivity between the hippocampus and temporal neocortex, while perisylvian structures are disconnected from the temporal lobe. In epileptogenic areas, we found a clear interhemispheric difference, with decreased connectivity in the right hemisphere during sleep. CONCLUSIONS: Sleep modulates brain excitability and reconfigures functional brain networks, depending on tissue epileptogenicity. SIGNIFICANCE: We found specific patterns of information flow during sleep in physiologic and pathologic structures, with possible implications for cognition.

Nociceptive pain unmasking a serious pathology - paraneoplastic hypertrophic osteoarthropathy: A case report.

RATIONALE: Hypertrophic osteoarthropathy, also named Pierre Marie-Bamberger syndrome, represents a rare medical condition that may be considered either a primary or a secondary disease, and lung malignancies are responsible for more than two-thirds of the cases with secondary forms of the disease. PATIENT CONCERNS: We present the case of a 41-year-old man referred to our Neurology Department for pain that was considered secondary to cervical disc protrusions. The neurologic examination was normal. However, the general examination showed digital clubbing, right lateral cervical adenopathy, and pachydermia. The radiographic examinations of the upper and lower limbs depicted osseous abnormalities typical for periostosis, and the computed tomography of the thorax showed the presence of a mass lesion in the right upper pulmonary lobe. High values of vascular endothelial growth factor were also found. The patient was admitted to the Pneumology Clinic, where biopsy was performed from the lateral cervical adenopathy. DIAGNOSES: The anatomopathological examination revealed multiple neoplastic infiltrates suggestive of adenocarcinoma metastasis. Based on the clinical examination and radiological and histologic findings, the diagnosis of pulmonary adenocarcinoma with lymph nodes metastases and paraneoplastic hypertrophic osteoarthropathy was established. INTERVENTIONS: The patient received treatment with nonsteroidal antiinflammatory drugs and opiate analgesics that relieved the pain. OUTCOMES: The patient was referred to the Oncology Department for further treatment of the primary pathology. He received different types of chemotherapeutics, immunotherapy, and radiotherapy. However, despite all therapeutic measures, the disease rapidly progressed and the patient died 9 months later. LESSONS: This is an interesting case of a patient with an overlooked pathology, which was refereed to our clinic for further investigations of a pain that was considered neuropathic, secondary to small cervical protrusions. Conversely, the pain proved to be nociceptive and Pierre Marie-Bamberger syndrome was the positive diagnosis in our patient, as it can be associated with numerous diseases, especially of neoplastic origin.

Illusory own body perceptions mapped in the cingulate cortex-An intracranial stimulation study.

Body awareness is the result of sensory integration in the posterior parietal cortex; however, other brain structures are part of this process. Our goal is to determine how the cingulate cortex is involved in the representation of our body. We retrospectively selected patients with drug-resistant epilepsy, explored by stereo-electroencephalography, that had the cingulate cortex sampled outside the epileptogenic zone. The clinical effects of high-frequency electrical stimulation were reviewed and only those sites that elicited changes related to body perception were included. Connectivity of the cingulate cortex and other cortical structures was assessed using the h2 coefficient, following a nonlinear regression analysis of the broadband EEG signal. Poststimulation changes in connectivity were compared between two sets of stimulations eliciting or not eliciting symptoms related to body awareness (interest and control groups). We included 17 stimulations from 12 patients that reported different types of body perception changes such as sensation of being pushed toward right/left/up, one limb becoming heavier/lighter, illusory sensation of movement, sensation of pressure, sensation of floating or detachment of one hemi-body. High-frequency stimulation in the cingulate cortex (1 anterior, 15 middle, 1 posterior part) elicits body perception changes, associated with a decreased connectivity of the dominant posterior insula and increased coupling between other structures, located particularly in the nondominant hemisphere.

Opsoclonus-Myoclonus Syndrome Associated With West-Nile Virus Infection: Case Report and Review of the Literature.

Opsoclonus-myoclonus syndrome (OMS) is a very rare condition with different autoimmune, infectious and paraneoplastic aetiologies or in most cases idiopathic. We report the case of a 75-year-old woman who was admitted in our department in early fall for altered mental status, opsoclonus, multifocal myoclonus, truncal titubation and generalized tremor, preceded by a 5 day prodrome consisting of malaise, nausea, fever and vomiting. Brain computed tomography and MRI scans showed no significant abnormalities and cerebrospinal fluid changes consisted of mildly increased protein content and number of white cells. Work-up for paraneoplastic and autoimmune causes of OMS was negative but serologic tests identified positive IgM and IgG antibodies against West Nile virus (WNV). The patient was treated with Dexamethasone and Clonazepam with progressive improvement of mental status, myoclonus, opsoclonus and associated neurologic signs. Six months after the acute illness she had complete recovery. To our knowledge this is the 14th case of WNV associated OMS reported in the literature so far. We briefly describe the clinical course of the other reported cases together with the different treatment strategies that have been employed.

Etiologic classification of ischemic stroke: Where do we stand?

Despite major technological advances in ischemic stroke diagnostic techniques, our current understanding of stroke mechanisms and etiology continues to remain unclear in a significant percent of patients. As a result, several etiological ischemic stroke classifications have emerged during the last two decades but their reliability and validity is far from perfect and further world-wide research is needed in order to achieve the so much needed "standard reference language". An ideal ischemic stroke classification should both comprise all underlying pathologies that could potentially concur to an index event and emphasize the most likely etiological and pathophysiological mechanism. Currently available approaches to ischemic stroke classification are either phenotypic or causative in nature, a multitude of criteria being published by different authors. Phenotypic classifications are targeted towards describing the concurring underlying pathologies, without highlighting the most probable ischemic stroke etiology, while causative classifications focus on establishing the most likely cause, neglecting other associated diseases. A judicious use of this two different concepts might improve clinical research as well as daily clinical practice.

Transient Global Amnesia After Cerebral Angiography With Iomeprol: A Case Report.

Transient global amnesia is now considered a very rare complication of cerebral angiography. Various etiological mechanisms have been suggested to account for this complication, but no consensus has been reached yet. This case report documents one of the few reported cases of cerebral angiography-related transient global amnesia associated with magnetic resonance imaging (MRI) evidence of unilateral hippocampal ischemia, most probably as a consequence of a transient reduction in regional hippocampal blood flow. However, the possibility of a direct neurotoxic effect of the nonionic contrast media Iomeprol on the Cornu ammonis - field 1 neurons cannot be firmly ruled out.We describe the case of a 54-year-old woman admitted to our department for left upper limb weakness with acute onset 8 days before. The brain computed tomography (CT) scan performed at admission revealed subacute ischemic lesions in the right watershed superficial territories and a right thalamic lacunar infarct. Diagnostic digital subtraction cerebral angiography was performed 4 days after admission with the nonionic contrast media Iomeprol. A few minutes after completion of the procedure, the patient developed symptoms suggestive for transient global amnesia. The brain MRI performed 22 hours after the onset of symptoms demonstrated increased signal within the lateral part of the right hippocampus on the diffusion-weighted imaging (DWI) sequences, associated with a corresponding reduction in the apparent diffusion coefficient (ADC) and increased signal on the fluid-attenuated inversion recovery (FLAIR) sequences, consistent with acute hippocampal ischemia and several T2/FLAIR hyperintensities in the right watershed superficial territories and in the right thalamus, corresponding to the lesions already identified on the CT scan performed at admission. A follow-up MRI, performed 2 months later, demonstrated the disappearance of the increased signal within the right hippocampus on the DWI, T2/FLAIR, and ADC sequences.The precise mechanism of transient global amnesia related to cerebral angiography is still unclear, and further studies aimed to determine the definite pathophysiology of this syndrome and consequently to establish specific preventive measures are needed. Although the condition itself is considered to be self-limited, the long-term prognosis and the risk of recurrence in the cases where subsequent angiographic procedures are performed are not established yet.

A review on endovascular techniques for treatment of direct post-traumatic carotid-cavernous fistula supported by case presentations.

Direct carotid-cavernous fistula is an abnormal arteriovenous communication between the carotid artery and the cavernous sinus occurring spontaneously or following head trauma. The aim of this paper is to report our experience and a review of the literature regarding the curative effect of endovascular treatment for patients with post-traumatic direct CCF. We present five patients with direct post-traumatic CCF in whom endovascular treatment was applied and the outcomes of the endovascular treatment. Direct post-traumatic CCF may be completely occluded without technique-related complications using detachable balloons, coils as embolic material or by using covered stents placed in the parent vessel to exclude the fistula from circulation. Postembolization angiographies revealed that the fistula was successfully obliterated. Few days after the procedure the ophthalmic symptoms were much reduced, and completely resolved soon after.In conclusion endovascular treatment represents an effective method for complete occlusion the direct CCF no matter of the technique chosen.

Duodopa infusion treatment: a point of view from the gastroenterologist.

In patients with advanced Parkinson's disease, the continuous delivery to the small intestine via a jejunal tube of levodopa/carbidopa, formulated as a gel suspension (Duodopa) represents a new treatment method. The continuous release results in less variability in levodopa concentrations and fewer motor fluctuations and dyskinesias than with oral administration. The method which requires a very good collaboration between the neurologist and the gastroenterologist is used with increasing frequency in selected centres especially in severe patients. First, a classic PEG gastrostomy kit is placed under propofol sedation. This allows the passage of a pig tail catheter which is deployed in the jejunum and it is attached to a portable pump via a special tubing system. We present our experience of seven cases (5 males, mean age 60 years) with a follow up of one year. One patient died due to respiratory failure and aspiration pneumonia probably related to the endoscopic procedure. At one year, all patients agreed that the neurological benefit offsets the procedure related problems and the technical issues related to the enteral infusion system.

Cutting the Gordian knot: the blockage of the jejunal tube, a rare complication of Duodopa infusion treatment.

We present the case of a 21-year-old man with advanced refractory Parkinson's disease treated with Duodopa continuous infusion. With this therapy, the patient had a spectacular recovery but after six months, he experienced an aggravation of his symptoms. A failure of his pumping system was suspected but we discovered that the jejunal tube was blocked due to a knot around a bezoar. This is the first complication of this kind described with the Duodopa infusion technique.

Occludin is overexpressed in Alzheimer's disease and vascular dementia.

The tight junctions (TJs) are key players in the control of blood-brain barrier (BBB) properties, the most complex TJs in the vascular system being found in the endothelial cells of brain capillaries. One of the main TJs proteins is occludin, which anchors plasma membranes of neighbour cells and is present in large amounts in the brain endothelia. Previous studies demonstrated that disruption of BBB in various pathological situations associates with changes in occludin expression, and this change could be responsible for malfunction of BBB. Therefore in this study, applying an immunohistochemical approach, we decided to explore the occludin expression in frontal cortex (FC) and basal ganglia in ageing control, Alzheimer's disease (AD), and vascular dementia (VD) brains, as far as all these pathologies associate microangiopathy and disruption of BBB. Strikingly, we found selected neurons, astrocytes and oligodendrocytes expressing occludin, in all cases studied. To estimate the number of occludin-expressing neurons, we applied a stereological approach with random systematic sampling and the unbiased optical fractionator method. We report here a significant increase in ratio of occludin-expressing neurons in FC and basal ganglia regions in both AD and VD as compared to ageing controls. Within the cerebral cortex, occludin was selectively expressed by pyramidal neurons, which are the ones responsible for cognitive processes and affected by AD pathology. Our findings could be important in unravelling new pathogenic pathways in dementia disorders and new functions of occludin and TJs.