Telomerase inhibition in malignant gliomas: a systematic review.

Glioblastoma (GBM) is the most frequent adult malignant brain tumour and despite different therapeutic efforts, the median overall survival still ranges from 14 to 18 months. Thus, new therapeutic strategies are urgently needed. However, the identification of cancer-specific targets is particularly challenging in GBM, due to the high heterogeneity of this tumour in terms of histopathological, molecular, genetic and epigenetic features. Telomerase reactivation is a hallmark of malignant glioma. An activating mutation of the hTERT gene, encoding for the active subunit of telomerase, is one of the molecular criteria to establish a diagnosis of GBM, IDH-wildtype, in the 2021 WHO classification of central nervous system tumours. Telomerase inhibition therefore represents, at least theoretically, a promising strategy for GBM therapy: pharmacological compounds, as well as direct gene expression modulation therapies, have been successfully employed in in vitro and in vivo settings. Unfortunately, the clinical applications of telomerase inhibition in GBM are currently scarce. The aim of the present systematic review is to provide an up-to-date report on the studies investigating telomerase inhibition as a therapeutic strategy for malignant glioma in order to foster the future translational and clinical research on this topic.

Post-operative segmental cerebral venous sinus thrombosis: risk factors, clinical implications, and therapeutic considerations.

Cerebral venous sinus thromboses (CVSTs) are rare complications of neurosurgical interventions and their management remains controversial as most of cases appear clinically silent. Here, we analyzed our institutional series of patients with CVSTs evaluating clinical and neuroradiological characteristics, risk factors, and outcome. From the analysis of our institutional PACS, we collected a total of 59 patients showing postoperative CVSTs after supratentorial or infratentorial craniotomies. For every patient, we collected demographics and relevant clinical and laboratory data. Details on thrombosis trend were retrieved and compared along the serial radiological assessment. A supratentorial craniotomy was performed in 57.6% of cases, an infratentorial in 37.3%, while the remaining were a single cases of trans-sphenoidal and neck surgery (1.7%, respectively). A sinus infiltration was present in almost a quarter of patients, and in 52.5% of cases the thrombosed sinus was exposed during the craniotomy. Radiological signs of CVST were evident in 32.2% of patients, but only 8.5% of them developed a hemorrhagic infarct. CVST-related symptoms were complained by 13 patients (22%), but these were minor symptoms in about 90%, and only 10% experienced hemiparesis or impaired consciousness. The majority of patients (78%) remained completely asymptomatic along the follow-up. Risk factors for symptoms occurrence were interruption of preoperative anticoagulants, infratentorial sinuses involvement and evidence of vasogenic edema and venous infarction. Overall, a good outcome defined mRS 0-2 was observed in about 88% of patients at follow-up. CVST is a complication of surgical approaches in proximity of dural venous sinuses. CVST usually does not show progression and courses uneventfully in the vast majority of cases. The systematic use of post-operative anticoagulants seems to not significantly influence its clinical and radiological outcome.

The anterolateral triangle as window on the foramen lacerum from transorbital corridor: anatomical study and technical nuances.

OBJECTIVE: Neurosurgical indications for the superior eyelid transorbital endoscopic approach (SETOA) are rapidly expanding over the last years. Nevertheless, as any new technique, a detailed knowledge of the anatomy of the surgical target area, the operative corridor, and the specific surgical landmark from this different perspective is required for a safest and successful surgery. Therefore, the aim of this study is to provide, through anatomical dissections, a detailed investigation of the surgical anatomy revealed by SETOA via anterolateral triangle of the middle cranial fossa. We also sought to define the relevant surgical landmarks of this operative corridor. METHODS: Eight embalmed and injected adult cadaveric specimens (16 sides) underwent dissection and exposure of the cavernous sinus and middle cranial fossa via superior eyelid endoscopic transorbital approach. The anterolateral triangle was opened and its content exposed. An extended endoscopic endonasal trans-clival approach (EEEA) with exposure of the cavernous sinus content and skeletonization of the paraclival and parasellar segments of the internal carotid artery (ICA) was also performed, and the anterolateral triangle was exposed. Measurements of the surface area of this triangle from both surgical corridors were calculated in three head specimens using coordinates of its borders under image-guide navigation. RESULTS: The drilling of the anterolateral triangle via SETOA unfolds a space that can be divided by the course of the vidian nerve into two windows, a wider "supravidian" and a narrower "infravidian," which reveal different anatomical corridors: a "medial supravidian" and a "lateral supravidian," divided by the lacerum segment of the ICA, leading to the lower clivus, and to the medial aspect of the Meckel's cave and terminal part of the horizontal petrous ICA, respectively. The infravidian corridor leads medially into the sphenoid sinus. The arithmetic means of the accessible surface area of the anterolateral triangle were 45.48 ± 3.31 and 42.32 ± 2.17 mm2 through transorbital approach and endonasal approach, respectively. CONCLUSION: SETOA can be considered a minimally invasive route complementary to the extended endoscopic endonasal approach to the anteromedial aspect of the Meckel's cave and the foramen lacerum. The lateral loop of the trigeminal nerve represents a reliable surgical landmark to localize the lacerum segment of the ICA from this corridor. Nevertheless, as any new technique, a learning curve is needed, and the clinical feasibility should be proven.

Daily mocha coffee intake and psycho-cognitive status in non-demented non-smokers subjects with subcortical ischaemic vascular disease.

Coffee intake has been recently associated with better cognition and mood in mild vascular cognitive impairment (mVCI). As tobacco can reduce the caffeine half-life, we excluded smokers from the original sample. Hamilton Depression Rating Scale (HDRS), mini-mental state examination (MMSE), Stroop Colour-Word Interference Test (Stroop), activities of daily living (ADL0) and instrumental ADL were the outcome measures. Significant differences were observed in higher consumption groups (moderate intake for HDRS; high intake for MMSE and Stroop) compared to the other groups, as well as in age and education. With age, education and coffee used as independent predictors, and HDRS, Stroop and MMSE as dependent variables, a correlation was found between age and both MMSE and Stroop, as well as between education and MMSE and between HDRS and Stroop; coffee intake negatively correlated with HDRS and Stroop. Higher coffee consumption was associated with better psycho-cognitive status among non-smokers with mVCI.

Unusual case of long survival patient with leptomeningeal carcinomatosis from breast cancer.

Leptomeningeal carcinomatosis (LC) is defined as infiltration of the leptomeninges by metastatic carcinoma and often represents the end stage of cancer disease. In breast cancer, LC is associated with a median survival of approximately 6-8 weeks without specific treatment. It could increase by only few months with personalized treatment plans. Usually, the median time of onset of leptomeningeal spread is 18 months and it is diagnosed in up to 70% of patients with active and progressive systemic disease. We present an uncommon case of LC in a patient with history of breast cancer with a 10 year-disease-free condition and an overall survival after LC diagnosis of 10 months. Central Nervous System (CNS) Magnetic Resonance Imaging (MRI) showed contrast enhancement of medullary cone and cauda. Despite the negativity of cytological analysis of Cerebral-Spinal Fluid (CSF), the patient underwent meningeal and radicular biopsy in November 2019. The neuropathological examination confirmed the diagnosis of LC. The patient was started on the aromatase inhibitor anastrozole. A whole body contrast Computed Tomography (CT) scan at three months follow-up was negative for further disease dissemination. The patient is currently under oncological and radiological follow-up after more than 10 months from diagnosis. Although nowadays diagnosis of LC is prompted by cytological examination of CSF, its negativity should not halt the diagnostic process. In the presence of a high clinical suspicion of LC, we suggest the biopsy of lesion.

Fear and disgust: case report of two uncommon emotional disturbances evoked by visual disperceptions after a right temporal-insular stroke.

BACKGROUND: Emotional processes and responses are underestimated in stroke patients because the massive clinical picture of large hemispheric strokes often hides these symptoms. We report on a patient with peculiar unpleasant emotional responses after temporal stroke. CASE PRESENTATION: We describe a 62-years old man with significant unpleasant emotional responses that occurred after an acute episode of confusional state, disorientation, agitation, vertigo, postural instability, vomiting, and photophobia. Since then, he complained that vision of pictures containing curved/multicolored lines or tangles was associated with an uncomfortable feeling of fear and disgust, lasting few minutes, so that he avoided looking at them. Notably, he also showed an abnormal facial expression of disgust and fear, together with neurovegetative reaction and horripilation, at the presentation of pictures of objects or animals containing curved, multicolored, or tangled lines. A post-acute infarction of the right temporal-insular region, together with mild periventricular white matter changes, were evident at the brain magnetic resonance imaging. CONCLUSIONS: The anterior insula is crucial in transforming unpleasant sensory input into visceromotor reactions and the accompanying feeling of disgust. It is also known that temporal pole modulates visceral emotional functions in response to emotionally evocative perceptual stimuli. In the present case, the ischemic lesion of anterior part of the insula and temporal pole may have caused a decoupling of emotional and visceral response to complex visual stimuli. Further reports will provide a significant contribution to the taxonomy of these complex and relatively uncommon non-motor post-stroke symptoms that negatively affect quality of life.

The growth of the neurocranium: literature review and implications in cranial repair.

BACKGROUND: Postnatal growth of neurocranium is prevalently completed in the first years of life, thus deeply affecting the clinical presentation and surgical management of pediatric neurosurgical conditions involving the skull. This paper aims to review the pertinent literature on the normal growth of neurocranium and critically discuss the surgical implications of this factor in cranial repair. METHODS: A search of the electronic database of Pubmed was performed, using the key word "neurocranium growth", thus obtaining 217 results. Forty-six papers dealing with this topic in humans, limited to the English language, were selected. After excluding a few papers dealing with viscerocranium growth or pathological conditions not related to normal neurocranium growth 18 papers were finally included into the present review. RESULTS AND CONCLUSIONS: The skull growth is very rapid in the first 2 years of life and approximates the adult volume by 7 years of age, with minimal further growth later on, which is warranted by the remodeling of the cranial bones. This factor affects the outcome of cranioplasty. Thus, it is essential to consider age in the planning phase of cranial repair, choice of the material, and critical comparison of results of different cranioplasty solutions.

Chiari type I and hydrocephalus.

PURPOSE: The association between Chiari type I malformation (CIM) and hydrocephalus raises a great interest because of the still unclear pathogenesis and the management implications. The goal of this paper is to review the theories on the cause-effect mechanisms of such a relationship and to analyze the results of the management of this condition. METHODS: A review of the literature has been performed, focusing on the articles specifically addressing the problem of CIM and hydrocephalus and on the series reporting about its treatment. Also, the personal authors' experience is briefly discussed. RESULTS: As far as the pathogenesis is concerned, it seems clear that raised intracranial pressure due to hydrocephalus can cause a transient and reversible tonsillar caudal ectopia ("pressure from above" hypothesis), which is something different from CIM. A "complex" hypothesis, on the other hand, can explain the occurrence of hydrocephalus and CIM because of the venous engorgement resulting from the hypoplasia of the posterior cranial fossa (PCF) and the occlusion of the jugular foramina, leading to cerebellar edema (CIM) and CSF hypo-resorption (hydrocephalus). Nevertheless, such a mechanism can be advocated only in a minority of cases (syndromic craniosynostosis). In non-syndromic CIM subjects, the presence of hydrocephalus could be explained by an occlusion of the basal CSF pathways, which would occur completely in a minority of cases (only 7-10% of CIM patients show hydrocephalus) while it would be partial in the remaining cases (no hydrocephalus). This hypothesis still needs to be demonstrated. As far as the management is concerned, the strategy to treat the hydrocephalus first is commonly accepted. Because of the "obstructive" origin of CIM-related hydrocephalus, the use of endoscopic third ventriculostomy (ETV) is straightforward. Actually, the analysis of the literature, concerning 63 cases reported so far, reveals very high success rates of ETV in treating hydrocephalus (90.5%), CIM (78.5%), and syringomyelia symptoms (76%) as well as in giving a radiological improvement of both CIM (74%) and syringomyelia (89%). The failures of ETV were not attributable to CIM or syringomyelia. Only 11% of cases required PCF decompression after ETV. CONCLUSIONS: The association between CIM and hydrocephalus probably results from different, multifactorial, and not yet completely understood mechanisms, which place the affected patients in a peculiar subgroup among those constituting the heterogeneous CIM population. ETV is confirmed as the best first approach for this subset of patients.

Motor and Perceptual Recovery in Adult Patients with Mild Intellectual Disability.

Introduction: The relationship between intellectual disability (ID) and hand motor coordination and speed-accuracy, as well as the effect of aging on fine motor performance in patients with ID, has been previously investigated. However, only a few data are available on the impact of the nonpharmacological interventions in adult patients with long-term hand motor deficit. Methods: Fifty adults with mild ID were enrolled. A group of thirty patients underwent a two-month intensive ergotherapic treatment that included hand motor rehabilitation and visual-perceptual treatment (group A); twenty patients performing conventional motor rehabilitation alone (group B) served as a control group. Data on attention, perceptual abilities, hand dexterity, and functional independence were collected by a blind operator, both at entry and at the end of the study. Results: After the interventions, group A showed significantly better performance than group B in all measures related to hand movement from both sides and to independence in activities of daily living. Discussion: Multimodal integrated interventions targeting visual-perceptual abilities and motor skills are an effective neurorehabilitative approach in adult patients with mild ID. Motor learning and memory-mediated mechanisms of neural plasticity might underlie the observed recovery, suggesting the presence of plastic adaptive changes even in the adult brain with ID.

Cognitive Impairment and Celiac Disease: Is Transcranial Magnetic Stimulation a Trait d'Union between Gut and Brain?

Celiac disease is a systemic disorder with multifactorial pathogenesis and multifaceted symptomatology. In response to gluten exposure, a significant part of the general population produces antibodies that have been hypothesized to be deleterious to the brain. Among the well-known neurological manifestations, adult celiac patients often complain cognitive symptoms, ranging from the so-called "brain fog" till an overt dementia. Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique that can contribute to the assessment and monitoring of celiac patients, even in those without a clear neurological involvement. The studies here reviewed seem to converge on an impaired central motor conductivity and a "hyperexcitable celiac brain" to TMS, which partially reverts back after a long-term gluten restriction. Notably, a clear hyperexcitability is a stably reported feature of both degenerative and vascular dementia. Therefore, given its potential neuroprotective effect, the gluten-free diet should be introduced as early as possible, although the overall response of neurological symptoms (and cognition in particular) is still controversial. Identifying new and possibly modifiable risk factors may be of crucial importance for patients, clinicians, and researchers.

Correlation between Motor Cortex Excitability Changes and Cognitive Impairment in Vascular Depression: Pathophysiological Insights from a Longitudinal TMS Study.

Background. Transcranial magnetic stimulation (TMS) highlighted functional changes in dementia, whereas there are few data in patients with vascular cognitive impairment-no dementia (VCI-ND). Similarly, little is known about the neurophysiological impact of vascular depression (VD) on deterioration of cognitive functions. We test whether depression might affect not only cognition but also specific cortical circuits in subcortical vascular disease. Methods. Sixteen VCI-ND and 11 VD patients, age-matched with 15 controls, underwent a clinical-cognitive, neuroimaging, and TMS assessment. After approximately two years, all participants were prospectively reevaluated. Results. At baseline, a significant more pronounced intracortical facilitation (ICF) was found in VCI-ND patients. Reevaluation revealed an increase of the global excitability in both VCI-ND and VD subjects. At follow-up, the ICF of VCI-ND becomes similar to the other groups. Only VD patients showed cognitive deterioration. Conclusions. Unlike VD, the hyperfacilitation found at baseline in VCI-ND patients suggests enhanced glutamatergic neurotransmission that might contribute to the preservation of cognitive functioning. The hyperexcitability observed at follow-up in both groups of patients also indicates functional changes in glutamatergic neurotransmission. The mechanisms enhancing the risk of dementia in VD might be related either to subcortical vascular lesions or to the lack of compensatory functional cortical changes.

Repetitive transcranial magnetic stimulation in patients with drug-resistant major depression: A six-month clinical follow-up study.

OBJECTIVE: In this study we aimed to assess the long-term efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) on depressive symptoms and cognitive performance in patients with drug-resistant major depressive disorder (MDD). METHODS: Fifteen drug-resistant depressed outpatients completed an acute trial with augmentative high-frequency rTMS over the left dorsolateral prefrontal cortex (DLPFC) and were compared with 15 drug-resistant MDD patients who underwent sham procedure. Depressive symptoms were evaluated with the Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale. The Frontal Assessment Battery and the Stroop Color-Word Test Interference (Stroop T) were used to probe executive functions. Outcome measures were obtained at baseline, 4 weeks after the rTMS, as well as 3 months and 6 months after the end of the stimulation protocol. RESULTS: After the active rTMS, patients showed a significant decrease in the scores at the depression rating scales that lasted for 6 months. A transient improvement was also observed at the Stroop T, although it did not persist in time. CONCLUSIONS: High-frequency rTMS over the left DLPFC may have long-term antidepressant effect in drug-resistant MDD. TMS is a valuable tool for the add-on treatment of mood disorders and for the design of customized stimulation protocols.

Epileptic seizure as a precipitating factor of vascular progressive supranuclear palsy: a case report.

BACKGROUND: Vascular progressive supranuclear palsy (vPSP) is an uncommon akinetic-rigid syndrome characterized by asymmetric lower body involvement, predominant corticospinal and pseudobulbar signs, urinary incontinence, cognitive impairment, and increased frequency of stroke risk factors, together with neuroimaging evidence of vascular disease. CASE REPORT: We report a case of a patient with a PSP-like phenotype and marked cognitive impairment who significantly worsened after a generalized epileptic seizure that occurred a few months after its clinical onset. RESULTS: Signs of widespread ischemic subcortical vascular disease, together with atrophy of the midbrain tectum, corpus callosum, and cerebral cortex, were evident on brain magnetic resonance imaging. CONCLUSIONS: vPSP is a condition that should be considered when a patient presents with a gradually progressive clinical picture suggestive of idiopathic PSP associated with neuroimaging evidence of cerebrovascular disease. The occurrence of epileptic seizures has not been reported before in vPSP but they might trigger the onset or precipitate the course of the PSP-like disorders.

The prognostic value of emergency microsurgical clipping of ruptured anterior circulation aneurysms.

BACKGROUND: The treatment of aneurysmal subarachnoid hemorrhage poses a formidable challenge, given the high mortality rate and associated mortality. Current recommendations are for treatment to be initiated within 24 hours of diagnosis. METHODS: In our study, we compared a cohort of 66 patients who received prompt microsurgical treatment within 6 hours of diagnosis with a cohort of 51 patients who received prompt microsurgical treatment within 12 hours of diagnosis. RESULTS: The modified Rankin Scale was utilized to evaluate the follow-up of patients at 30 days, 12 months, and 18 months following surgery. We performed a parametric comparison of the distributions of the means of groups, and our results indicate that treatment within 6 hours of diagnosis results in a lower incidence of obstructive hydrocephalus and a more favorable outcome. CONCLUSIONS: A favorable outcome was observed in patients who were treated within 6 hours. The availability of a specialized vascular team ensures the highest levels of care.

H3K27-Altered Diffuse Glioma of the Spinal Cord in Adult Patients: A Qualitative Systematic Review and Peculiarity of Radiological Findings.

Background: Primary spinal cord diffuse gliomas (SpDG) are rare tumors that may harbor, like diffuse intrinsic pontine gliomas (DIPG), H3K27M mutations. According to the WHO (2021), SpDGs are included in diffuse midline H3K27-altered gliomas, which occur more frequently in adults and show unusual clinical presentation, neuroradiological features, and clinical behavior, which differ from H3 G34-mutant diffuse hemispheric glioma. Currently, homogeneous adult-only case series of SpDG, with complete data and adequate follow-up, are still lacking. Methods: We conducted a qualitative systematic review, focusing exclusively on adult and young adult patients, encompassing all studies reporting cases of primitive, non-metastatic SpDG with H3K27 mutation. We analyzed the type of treatment administered, survival, follow-up duration, and outcomes. Results: We identified 30 eligible articles published between 1990 and 2023, which collectively reported on 62 adult and young adult patients with primitive SpDG. Postoperative outcomes were assessed based on the duration of follow-up, with outcomes categorized as either survival or mortality. Patients who underwent surgery were followed up for a mean duration of 17.37 months, while those who underwent biopsy had a mean follow-up period of 14.65 months. Among patients who were still alive, the mean follow-up duration was 18.77 months. The radiological presentation of SpDG varies widely, indicating its lack of uniformity. Conclusion: Therefore, we presented a descriptive scenario where SpDG was initially suspected to be a meningioma, but was later revealed to be a malignant SpDG with H3K27M mutation.

Prevalence of Fabry disease and GLA variants in young patients with acute stroke: The challenge to widen the screening. The Fabry-Stroke Italian Registry.

BACKGROUND: Fabry disease (FD) is a treatable X-linked lysosomal storage disorder caused by GLA gene variants leading to alpha-galactosidase A deficiency. FD is a rare cause of stroke, and it is still controversial whether in stroke patients FD should be searched from the beginning or at the end of the diagnostic workup (in cryptogenic strokes). METHODS: Fabry-Stroke Italian Registry is a prospective, multicentric screening involving 33 stroke units. FD was sought by measuring α-galactosidase A activity (males) and by genetic tests (males with reduced enzyme activity and females) in patients aged 18-60 years hospitalized for TIA, ischemic stroke, or intracerebral hemorrhage. We diagnosed FD in patients with 1) already known pathogenic GLA variants; 2) novel GLA variants if additional clinical, laboratory, or family-derived criteria were present. RESULTS: Out of 1906 patients, we found a GLA variant in 15 (0.79%; 95%CI 0.44-1.29) with a certain FD diagnosis in 3 (0.16%; 95%CI 0.03-0.46) patients, none of whom had hemorrhage. We identified 1 novel pathogenic GLA variant. Ischemic stroke etiologies in carriers of GLA variants were: cardioaortic embolism (33%), small artery occlusion (27%), other causes (20%), and undetermined (20%). Mild severity, recurrence, previous TIA, acroparesthesias, hearing loss, and small artery occlusion were predictors of GLA variant. CONCLUSION: In this large multicenter cohort the frequency of FD and GLA variants was consistent with previous reports. Limiting the screening for GLA variants to patients with cryptogenic stroke may miss up to 80% of diagnoses. Some easily recognizable clinical features could help select patients for FD screening.

Sleep disorders in Parkinson's disease: a narrative review of the literature.

Parkinson's disease (PD) is classically considered to be a motor system affliction; however, also non-motor alterations, including sleep disorders, are important features of the disease. The aim of this review is to provide data on sleep disturbances in PD in the following grouping: difficulty initiating sleep, frequent night-time awakening and sleep fragmentation, nocturia, restless legs syndrome/periodic limb movements, sleep breathing disorders, drug induced symptoms, parasomnias associated with rapid eye movements (REM) sleep, sleep attacks, reduced sleep efficiency and excessive daytime sleepiness. Research has characterized some of these disturbances as typical examples of dissociated states of wakefulness and sleep that are admixtures or incomplete declarations of wakefulness, REM sleep, and non-REM (NREM) sleep. Moreover, sleep disorders may precede the typical motor system impairment of PD and their ability to predict disease has important implications for development of neuroprotective treatment; in particular, REM sleep behavior disorder may herald any other clinical manifestation of PD by more than 10 years.

Different patterns of cortical excitability in major depression and vascular depression: a transcranial magnetic stimulation study.

BACKGROUND: Clinical and functional studies consider major depression (MD) and vascular depression (VD) as different neurobiological processes. Hypoexcitability of the left frontal cortex to transcranial magnetic stimulation (TMS) is frequently reported in MD, whereas little is known about the effects of TMS in VD. Thus, we aimed to assess and compare motor cortex excitability in patients with VD and MD. METHODS: Eleven VD patients, 11 recurrent drug-resistant MD patients, and 11 healthy controls underwent clinical, neuropsychological and neuroimaging evaluations in addition to bilateral resting motor threshold, cortical silent period, and paired-pulse TMS curves of intracortical excitability. All patients continued on psychotropic drugs, which were unchanged throughout the study. RESULTS: Scores on one of the tests evaluating frontal lobe abilities (Stroop Color-Word interference test) were worse in patients compared with controls. The resting motor threshold in patients with MD was significantly higher in the left hemisphere compared with the right (p < 0.05), and compared with the VD patients and controls. The cortical silent period was bilaterally prolonged in MD patients compared with VD patients and controls, with a statistically significant difference in the left hemisphere (p < 0.01). No differences were observed in the paired-pulse curves between patients and controls. CONCLUSIONS: This study showed distinctive patterns of motor cortex excitability between late-onset depression with subcortical vascular disease and early-onset recurrent drug resistant MD. The data provide a TMS model of the different processes underlying VD and MD. Additionally, our results support the "Vascular depression hypothesis" at the neurophysiological level, and confirm the inter-hemispheric asymmetry to TMS in patients with MD. We were unable to support previous findings of impaired intracortical inhibitory mechanisms to TMS in patients with MD, although a drug-induced effect on our results cannot be excluded. This study may aid the understanding of the pathogenetic differences underlying the clinical spectrum of depressive disorders.

Cellular stress response, sirtuins and UCP proteins in Alzheimer disease: role of vitagenes.

Alzheimer's Disease (AD) is a neurodegenerative disorder affecting up to one third of individuals reaching the age of 80. Different integrated responses exist in the brain to detect oxidative stress which is controlled by several genes termed Vitagenes. Vitagenes encode for cytoprotective heat shock proteins (Hsp), as well as thioredoxin, sirtuins and uncouple proteins (UCPs). In the present study we evaluate stress response mechanisms in plasma and lymphocytes of AD patients, as compared to controls, in order to provide evidence of an imbalance of oxidant/antioxidant mechanisms and oxidative damage in AD patients and the possible protective role of vitagenes.We found that the levels of Sirt-1 and Sirt-2 in AD lymphocytes were significantly higher than in control subjects. Interestingly, analysis of plasma showed in AD patients increased expression of Trx, a finding associated with reduced expression of UCP1, as compared to control group.This finding can open up new neuroprotective strategies, as molecules inducing this defense mechanisms can represent a therapeutic target to minimize the deleterious consequences associated to oxidative stress, such as in brain aging and neurodegenerative disorders.

Full-endoscopic lumbar discectomy. Tips & tricks for new users based on a retrospective observational study of the first 100 patients.

AIM: Full-endoscopic lumbar discectomy (FELD) is a successful surgical treatment for lumbar disc herniation. We reported our institutional experience with FELD and analyzed the pertinent literature. MATERIAL AND METHODS: We retrospectively enrolled 100 patients who had undergone full-endoscopic discectomy for lumbar disc herniation using either an interlaminar (IL) or transforaminal (TF) approach. All patients underwent pre-operative imaging. Before and after surgery, patients\' pain and disability levels were measured using visual analog scale (VAS) and Oswestry disability index (ODI) respectively. Clinical outcomes were assessed using the modified MacNab criteria. Patients were divided into two groups, Group 1 (cases 1-50) and Group 2 (cases 51-100), and their learning curve factors were compared using a Student\'s t-test. RESULTS: 69 cases were operated via an IL approach and the remaining 31 cases using a TF approach. There were 4 early conversions in microdiscectomy. The mean operative time of the 96 procedures was 57 min. In Group 1, the mean operative time was 61.7 minutes (range: 35-110); in Group 2, it was 52.3 minutes (range: 25-75). The difference between the two groups was statistically significant (p=0.009). No significant differences were found in conversions, early operations, and recurrences between Groups 1 and 2. Both groups experienced a significant reduction in postoperative VAS and ODI compared to preoperative scores. CONCLUSION: Our findings support previously reported information on the safety and effectiveness of the FELD. Herein, we share some practical tips and tricks based on our initial experience and on the review of the available literature, which could facilitate new users. In experienced hands endoscopic techniques make treatment of herniated discs feasible independently of patient age, anatomy, and/or targeted pathology features. Conversely, thoughtful patient selection and careful preoperative planning are highly recommended for new users.