Resting state cortical electroencephalographic rhythms and white matter vascular lesions in subjects with Alzheimer's disease: an Italian multicenter study

Resting state electroencephalographic (EEG) rhythms do not deteriorate with the increase of white matter vascular lesion in amnesic mild cognitive impairment (MCI) subjects [1], although white matter is impaired along Alzheimer's disease (AD). Here we tested whether this is true even in AD subjects. Closed-eye resting state EEG data were recorded in 40 healthy elderly (Nold), 96 amnesic MCI, and 83 AD subjects. White matter vascular lesions were indexed by magnetic resonance imaging recorded in the MCI and AD subjects (about 42% of cases following ADNI standards). The MCI subjects were divided into two sub-groups based on the median of the white matter lesion, namely MCI+ (people with highest vascular load; n = 48) and MCI- (people with lowest vascular load; n = 48). The same was true for the AD subjects (AD+, n = 42; AD-, n = 41). EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz), beta1 (13-20 Hz), beta2 (20-30 Hz), and gamma (30-40 Hz). LORETA software estimated cortical EEG sources. When compared to Nold group, MCI and AD groups showed well known abnormalities of delta and alpha sources. Furthermore, amplitude of occipital, temporal, and limbic alpha 1 sources were higher in MCI+ than MCI- group. As a novelty, amplitude of occipital delta sources was lower in AD+ than AD- group. Furthermore, central, parietal, occipital, temporal, and limbic alpha sources were higher in amplitude in AD+ than AD- group. Amplitude of these sources was correlated to global cognitive status (i.e., Mini Mental State Evaluation score). These results suggest that in amnesic MCI and AD subjects, resting state posterior delta and alpha EEG rhythms do not deteriorate with the increase of white-matter vascular lesion. These rhythms might be more sensitive to AD neurodegenerative processes and cognitive status rather than to concomitant lesions to white matter.     

Oxidative stress treatment for clinical trials in neurodegenerative diseases

Oxidative stress is a metabolic condition arising from imbalance between the production of potentially reactive oxygen species and the scavenging activities. Mitochondria are the main providers but also the main scavengers of cell oxidative stress. The role of mitochondrial dysfunction and oxidative stress in the pathogenesis of neurodegenerative diseases is well documented. Therefore, therapeutic approaches targeting mitochondrial dysfunction and oxidative damage hold great promise in neurodegenerative diseases. Despite this evidence, human experience with antioxidant neuroprotectants has generally been negative with regards to the clinical progress of disease, with unclear results in biochemical assays. Here we review the antioxidant approaches performed so far in neurodegenerative diseases and the future challenges in modern medicine.     

Implication of a genetic variant at PICALM in Alzheimer’s disease patients and centenarians

A common polymorphism (rs3851179) in the PICALM (phosphatidylinositol-binding clathrin assembly protein) gene has been recently associated with reduced risk of developing late-onset Alzheimer’s disease (LOAD). We analyzed the genotype and allele distributions of the PICALM polymorphism in 813 Italian subjects, including LOAD patients and centenarians. The segregation of the PICALM rs3851179 showed no statistically significant difference between LOAD cases and controls. The implication of a genetic variant at PICALM is confirmed for the first time, in centenarians, thus suggesting a possible role in longevity.     

Migraine attacks,aura, and polycythemia: a vasculoneural pathogenesis?

Headache is a frequent symptom of polycythemia. A case study of a polycythemia vera patient affected by migraines, with and without aura, who developed headache attacks with aura in association with elevated haematocrit and haemoglobin levels is presented. A vasculoneural pathogenesis is supposed.     

Chronic pain therapy and hypothalamic-pituitary-adrenal axis impairment

Opiates and/or nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most effective therapies for chronic pain, but their prolonged time of use can affect health conditions through physical and psychological side effects. They include the very common gastrointestinal effects and changes that can induce osteoporosis, depression, impaired cognition and a generally poor quality of life, which per se can induce and maintain a chronic painful condition. For this reason it is becoming imperative to expand our knowledge of the interaction of these substances with body functions apparently not directly involved in nociception and pain, such as neuroendocrine functions. The purpose of this study was to determine, in male and female patients suffering from chronic pain, the effect of conventional pain therapy (opiates, NSAIDs) on hypothalamic-pituitary-adrenal (HPA) axis function. This was assessed by measuring the blood levels of adrenal-related hormones (adrenocorticotrophin hormone, ACTH; cortisol; dehydroepiandrosterone, DHEA and dehydroepiandrosterone sulfate, DHEAS). The second purpose of the study was to test the hypothesis that these hormones are associated with the psychological profile shown by the chronic pain patients. The results showed significant changes induced by pain therapy on the HPA axis: ACTH, cortisol, DHEA and DHEAS blood levels decreased in all subjects taking opiates or NSAIDs to treat pain. Moreover these changes showed significant correlations with psychological features of the subjects depending on age and sex.     

External fixation in pelvic fractures

Pelvic fractures account for 4–5% of all fracturated patients, and they occur in 4–5% of politraumatized patients. In the most of the cases, they are consequent to high-energy trauma with a high percentage of lesions of other organs (cerebral, thoracic, and abdominal lesions. The most of the patients (80%) who die are dying within the first hours after trauma for a massive hemorrhagic shock. When the pelvic fracture and the patient’s hemodynamic conditions are both unstable, osteosynthesis of the fracture is mandatory. Fracture stabilization should be performed within the first hour after trauma (as soon as possible), and it should be considered as part of the resuscitation procedure. We usually make an urgent stabilization of pelvic fracture with an anterior external fixator technique. We have revised all unstable pelvic fractures treated in our department (Orthopaedic Clinic Pisa University) from 2000 up to the 2005 to determine a correct treatment protocol for these lesions. Pelvic stabilization, reducing the pelvic volume and bleeding from the stumps of fracture, determines the arrest of the hemorrhage, as evidenced by the sharp decline in the number of transfusions in postoperative period. In these cases, there is an absolute indication for an urgent pelvic stabilization. Pelvic stabilization, whether temporary or permanent, allows to control the bleeding because it (1) leads to a reduction in the volume pelvis with a containment on the retro-peritoneal hematoma (2) reduces bleeding from the fracture fragments (3) reduces motility fracture promoting the blood clotting. The stabilization of the pelvis also makes it easier to manage the patient and his mobilization for the implementation of subsequent investigations. In our experience, external fixator accounts for its characteristics the gold standard approach for the urgent stabilization of these lesions, and, for most of them, it can be used as the definitive treatment. External fixation is a quick and easy procedure for pelvic fractures stabilization for surgeons with experience with this technique.     

Four‐week trunk‐specific rehabilitation treatment improves lateral trunk flexion in Parkinson's disease

People with Parkinson's disease (PD) often have a posture characterized by lateral trunk flexion poorly responsive to antiparkinsonian drugs. To examine the effects of a rehabilitation programme (daily individual 90‐minute‐sessions, 5‐days‐a‐week for 4‐consecutive weeks) on lateral trunk flexion and mobility, 22 PD patients with mild to severe lateral trunk flexion, and 22 PD patients without trunk flexion were studied. Patients were evaluated using the Unified Parkinson's Disease Rating Scale motor subscale (UPDRS‐III) score, and the kinematic behavior of the trunk was recorded by means of an optoelectronic system to determine: a) trunk flexion, inclination and rotation values in the erect standing posture; b) ranges of trunk flexion and inclination during trunk movements. After the treatment, significant decreases in trunk flexion [24°(4) vs. 14°(3), P < 0.001] and inclination in the static condition [23°(5) vs. 12°(4), P < 0.001)] were observed, both of which were maintained at the 6‐month follow up. During the trunk flexion task, a significantly increased range of trunk flexion [64°(15) vs. 83°(15), P < 0.001] was observed; similarly, during the lateral bending task, the range of trunk inclination was found to be significantly increased, both toward the side of the trunk deviation [29°(8) vs. 42°(13), P < 0.01] and toward the contralateral side [14°(6) vs 29°(11), P < 0.01]. No further significant changes were observed at the 6‐month follow‐up. Trunk flexion and inclination values in the upright standing posture correlated slightly with the UPDRS‐III score. Our findings show that significant improvements in axial posture and trunk mobility can be obtained through the 4‐week rehabilitation programme described, with a parallel improvement in clinical status. © 2010 Movement Disorder Society     

Lack of association between the APEX1 Asp148Glu polymorphism and sporadic amyotrophic lateral sclerosis

Impairments in DNA repair enzymes have been observed in amyotrophic lateral sclerosis (ALS) tissues, particularly in the activity of the apurinic/apyrimidinic endonuclease 1 (APEX1). Moreover, it was suggested that the common APEX1 Asp148Glu polymorphism might be associated with ALS risk. To further address this question we performed the present study aimed at evaluating the contribution of the APEX1 Asp148Glu polymorphism in sporadic ALS (sALS) risk and clinical presentation, including age and site of onset and disease progression. We screened 134 sALS Italian patients and 129 matched controls for the presence of the APEX1 Asp148Glu polymorphism. No difference in APEX1 Asp148Glu allele and genotype frequencies was found between the groups, nor was the polymorphism associated with age and site of onset or disease progression. Present results do not support a role for the APEX1 Asp148Glu polymorphism in sALS pathogenesis in the Italian population.     

Clinical Features and Complications of the HLA-B27-associated Acute Anterior Uveitis: A Metanalysis

In this article, we report a literature-based metanalysis we have conducted to outline the clinical features of the HLA-B27 Acute Anterior Uveitis (AAU). The examined material was based on observational studies in which participants were affected by Acute Anterior Uveitis and divided into HLA B27+ and HLA B27–. We performed a search on articles with the words “HLA B27 uveitis” dated before May 2014. Among these, 29 articles were selected for a second review. After a further evaluation, 22 articles were analyzed. The clinical characteristics studied in the metanalysis were: (1) systemic disease; (2) sex distribution; (3) laterality; (4) visual acuity; (5) hypopion; (6) anterior chamber’s fibrin; (7) elevated intraocular pressure (IOP) during inflammation; (8) glaucoma; (9) posterior synechiae; (10) cataract; (11) cystoid macular edema; (12) papillitis. We have calculated a relative risk (RR) for each outcome measured. The results obtained remark some of the peculiar features linked to the HLA B27 Acute Anterior Uveitis, such as strong association with ankylosing spondylitis (RR = 6.80) and systemic diseases (RR = 9.9), male prevalence (RR = 1.2), unilateral (RR = 1.1) or alternating bilateral (RR = 2.2) involvement, hypopion (RR = 5.5), fibrinous reaction and even papillitis (R = 7.7). Simultaneous bilateral (RR = 0.3) AAU is more frequent in HLA-B27 negative form. We report higher risk of elevated IOP and glaucoma (RR = 0.6) in B27– Acute Anterior Uveitis. No significant difference between HLA B 27 positive and negative AAU was observed according to final visual acuity and complications such as posterior synechiae, cataract, and maculare edema. We trust that this will inform on the clinical evaluation and therapeutic decision in addressing a still ill-defined ophthalmologic condition.