Tibial nerve stimulation in the management of primary sexual dysfunction in patients with multiple sclerosis: a pilot randomized control trial.

INTRODUCTION: Sexual dysfunction (SD) is a common symptom that affects 40-90% of patients with multiple sclerosis (MS). Previous studies have highlighted the negative impact of sexual dysfunction in the mental health status and overall quality of life in patients with MS. METHODS: The aim of this study was to examine the effects of transcutaneous tibial nerve stimulation (TTNS) in the primary SD symptoms in patients with MS. A total of 40 participants were randomized (1:1 ratio) to either TTNS or Sham group and received three 20 min sessions over the course of two months. Pre and post intervention SD was evaluated using the Multiple Sclerosis Intimacy Questionnaire (MISQ-15). RESULTS: Statistically significant improvements in the aspects of primary sexual dysfunction were observed in the TTNS group pre-post intervention (specifically erectile function (for males)/vaginal lubrication (for females) (p < .001), orgasm quality and satisfaction for both male and female patients (p < .001), sexual desire (p < .05) and bladder related symptomatology (p < .005). In the sham group pre-post intervention, the only observed improvement was in the sexual desire aspect (p < .05). Post intervention the groups significantly differed erectile function/vaginal lubrication and orgasm quality and satisfaction (p < .05). CONCLUSIONS: Our findings underline the efficacy of TTNS in improving primary SD symptoms as well as bladder problems in both male and female patients with MS. TTNS demonstrated significant improvement in the following domains: erectile function, vaginal lubrication, orgasm quality, satisfaction, bladder-related symptoms, and sexual desire.

Sexual dysfunction therapeutic approaches in patients with multiple sclerosis: a systematic review.

OBJECTIVE: Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disease of the central nervous system (CNS). The most common clinical manifestations of MS are spasticity, pain, vesico-urethral disorders, cognitive impairments, chronic fatigue and sexual dysfunction. This review aims to explore the possible therapeutic options for managing sexual dysfunction in people with MS (PwMS). METHOD: A thorough search of the PubMed Medline database was performed. Records were limited to clinical studies published between 01/01/2010 up to 01/01/2022. The results were screened by the authors in pairs. RESULTS: The search identified 36 records. After screening, 9 records met the inclusion-exclusion criteria and were assessed. The pharmacological approaches investigated the effectiveness of sildenafil, tadalafil and onabotulinumtoxinA. Of the interventional studies the non-pharmacological investigated, the effectiveness of aquatic exercises, the application of pelvic floor exercises,the combination of pelvic floor exercises and mindfulness technique, the combination of pelvic floor exercises and electro muscular stimulation with electromyograph biofeedback, the application of yoga techniques and the efficacy of assistive devices like the clitoral vacuum suction device and the vibration device. CONCLUSION: The management of sexual dysfunction in PwMS needs to be further investigated. A team of healthcare professionals should be involved in the management of SD in order to address not only the primary (MS-related) SD symptoms but the secondary and tertiary as well. The main limitations that were identified in the existing literature were related to MS disease features, sample characteristics and evaluation tools and batteries.

Potential Role of Antibodies against Aquaporin-1 in Patients with Central Nervous System Demyelination.

Aquaporins (AQPs; AQP0-AQP12) are water channels expressed in many and diverse cell types, participating in various functions of cells, tissues, and systems, including the central nervous system (CNS). AQP dysfunction and autoimmunity to AQPs are implicated in several diseases. The best-known example of autoimmunity against AQPs concerns the antibodies to AQP4 which are involved in the pathogenesis of neuromyelitis optica spectrum disorder (NMOSD), an autoimmune astrocytopathy, causing also CNS demyelination. The present review focuses on the discovery and the potential role of antibodies against AQP1 in the CNS, and their potential involvement in the pathophysiology of NMOSD. We describe (a) the several techniques developed for the detection of the AQP1-antibodies, with emphasis on methods that specifically identify antibodies targeting the extracellular domain of AQP1, i.e., those of potential pathogenic role, and (b) the available evidence supporting the pathogenic relevance of AQP1-antibodies in the NMOSD phenotype.

Classical Cerebrospinal Fluid Biomarkers in Dementia with Lewy Bodies.

The use and interpretation of diagnostic cerebrospinal fluid (CSF) biomarkers for neurodegenerative disorders, such as Dementia with Lewy bodies (DLB), represent a clinical challenge. According to the literature, the composition of CSF in DLB patients varies. Some patients present with reduced levels of amyloid, others with full Alzheimer Disease CSF profile (both reduced amyloid and increased phospho-tau) and some with a normal profile. Some patients may present with abnormal levels of a-synuclein. Continuous efforts will be required to establish useful CSF biomarkers for the early diagnosis of DLB. Given the heterogeneity of methods and results between studies, further validation is fundamental before conclusions can be drawn.

Prevalence, Characteristics, and Outcomes of Undetermined Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis.

Background and Purpose: There are scarce data regarding the prevalence, characteristics and outcomes of intracerebral hemorrhage (ICH) of undetermined (unknown or cryptogenic) etiology. We sought to determine the prevalence, radiological characteristics, and clinical outcomes of undetermined ICH. Methods: Systematic review and meta-analysis of studies involving patients with spontaneous ICH was conducted to primarily assess the prevalence and clinical-radiological characteristics of undetermined ICH. Additionally, we assessed the rates for ICH secondary to hypertensive arteriopathy and cerebral amyloid angiopathy. Subgroup analyses were performed based on the use of (1) etiology-oriented ICH classification, (2) detailed neuroimaging, and (3) Boston criteria among patients with cerebral amyloid angiopathy related ICH. We pooled the prevalence rates using random-effects models, and assessed the heterogeneity using Cochran Q and I2 statistics. Results: We identified 24 studies comprising 15 828 spontaneous ICH patients (mean age, 64.8 years; men, 60.8%). The pooled prevalences of hypertensive arteriopathy ICH, undetermined ICH, and cerebral amyloid angiopathy ICH were 50% (95% CI, 43%­58%), 18% (95% CI, 13%­23%), and 12% (95% CI, 7%­17% [P<0.001 between subgroups]). The volume of ICH was the largest in cerebral amyloid angiopathy ICH (24.7 [95% CI, 19.7­29.8] mL), followed by hypertensive arteriopathy ICH (16.2 [95% CI, 10.9­21.5] mL) and undetermined ICH (15.4 [95% CI, 6.2­24.5] mL). Among patients with undetermined ICH, the rates of short-term mortality (within 3 months) and concomitant intraventricular hemorrhage were 33% (95% CI, 25%­42%) and 38% (95% CI, 28%­48%), respectively. Subgroup analysis demonstrated a higher rate of undetermined ICH among studies that did not use an etiology-oriented classification (22% [95% CI, 15%­29%]). No difference was observed between studies based on the completion of detailed neuroimaging to assess the rates of undetermined ICH (P=0.62). Conclusions: The etiology of spontaneous ICH remains unknown or cryptogenic among 1 in 7 patients in studies using etiology-oriented classification and among 1 in 4 patients in studies that avoid using etiology-oriented classification. The short-term mortality in undetermined ICH is high despite the relatively small ICH volume.

Demyelination with autoimmune features: a distinct clinical entity? Results from a longitudinal cohort.

OBJECTIVE: CNS demyelinating syndromes occurring in the context of SLE may represent a manifestation of neuropsychiatric lupus, or an overlap of SLE and multiple sclerosis (MS). We evaluated prospectively patients presenting with demyelinating syndrome for clinical and serological evidence of SLE and characterized the evolution of their clinical syndrome to a defined disease. METHODS: Patients with CNS demyelinating syndromes not fulfilling the criteria for MS were evaluated in a rheumatology unit for features of SLE and followed longitudinally (enrolment period 2016-20). Clinical, laboratory and neuroimaging data were recorded at every visit, following multidisciplinary evaluation. At end of follow-up, patients were assessed for their final neurological and rheumatological diagnosis, and classified accordingly. RESULTS: A total of 79 patients were included in the study [91.1% female, mean (s.d.) age at first demyelinating episode 38.4 (10.3) years, median (interquartile range) observation period 39 (57) months]. At last follow-up, 38 patients (48.1%) had evolved into MS. Of the remaining patients, 7 (17.1%) had SLE, while 34 (82.9%) had features of systemic autoimmunity without fulfilling classification criteria for SLE. The most common rheumatological features of these patients were inflammatory arthritis (73.5%), acute cutaneous lupus (47.1%) and positive ANA (72.1%). Importantly, these patients were less likely to have elevated IgG index (odds ratio 0.11, 95% CI 0.04, 0.32) and positive oligoclonal bands (odds ratio 0.21, 95% CI 0.08, 0.55). CONCLUSION: A significant number of patients with demyelination do not fulfill criteria for either MS or SLE at follow-up. These patients exhibit lupus-like autoimmune features and may represent a distinct entity, 'demyelination with autoimmune features'.

Implantable Cardiac Monitoring in the Secondary Prevention of Cryptogenic Stroke.

OBJECTIVE: In this study, we sought to evaluate the impact of implantable cardiac monitoring (ICM) in the prevention of stroke recurrence after a cryptogenic ischemic stroke or transient ischemic attack (TIA). METHODS: We evaluated consecutive patients with cryptogenic ischemic stroke or TIA admitted in a comprehensive stroke center during an 8-year period. We compared the baseline characteristics and outcomes between patients receiving conventional cardiac monitoring with repeated 24-hour Holter-monitoring during the first 5 years in the outpatient setting and those receiving continuous cardiac monitoring with ICM during the last 3 years. Associations on the outcomes of interest were further assessed in multivariable regression models adjusting for potential confounders. RESULTS: We identified a total of 373 patients receiving conventional cardiac monitoring and 123 patients receiving ICM. Paroxysmal atrial fibrillation (PAF) detection was higher in the ICM cohort compared to the conventional cardiac monitoring cohort (21.1% vs 7.5%, p < 0.001). ICM was independently associated with an increased likelihood of PAF detection during follow-up (hazard ratio [HR] = 1.94, 95% confidence interval [CI] = 1.16-3.24) in multivariable analyses. Patients receiving ICM were also found to have significantly higher rates of anticoagulation initiation (18.7% vs 6.4%, p < 0.001) and lower risk of stroke recurrence (4.1% vs 11.8%, p = 0.013). ICM was independently associated with a lower risk of stroke recurrence during follow-up (HR = 0.32, 95% CI = 0.11-0.90) in multivariable analyses. INTERPRETATION: ICM appears to be independently associated with a higher likelihood of PAF detection and anticoagulation initiation after a cryptogenic ischemic stroke or TIA. ICM was also independently related to lower risk of stroke recurrence in our cryptogenic stroke / TIA cohort. ANN NEUROL 2020;88:946-955.

A Novel SNCA A30G Mutation Causes Familial Parkinson's Disease.

BACKGROUND: The SNCA gene encoding α-synuclein (αSyn) is the first gene identified to cause autosomal-dominant Parkinson's disease (PD). OBJECTIVE: We report the identification of a novel heterozygous A30G mutation of the SNCA gene in familial PD and describe clinical features of affected patients, genetic findings, and functional consequences. METHODS: Whole exome sequencing was performed in the discovery family proband. Restriction digestion with Bbvl was used to screen SNCA A30G in two validation cohorts. The Greek cohort included 177 familial PD probands, 109 sporadic PD cases, and 377 neurologically healthy controls. The German cohort included 136 familial PD probands, 380 sporadic PD cases, and 116 neurologically healthy controls. We also conducted haplotype analysis using 13 common single nucleotide variants around A30G to determine the possibility of a founder effect for A30G. We then used biophysical methods to characterize A30G αSyn. RESULTS: We identified a novel SNCA A30G (GRCh37, Chr4:90756730, c.89 C>G) mutation that co-segregated with the disease in five affected individuals of three Greek families and was absent from controls. A founder effect was strongly suggested by haplotype analysis. The A30G mutation had a local effect on the intrinsically disordered structure of αSyn, slightly perturbed membrane binding, and promoted fibril formation. CONCLUSION: Based on the identification of A30G co-segregating with the disease in three families, the absence of the mutation in controls and population databases, and the observed functional effects, we propose SNCA A30G as a novel causative mutation for familial PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Delayed recurrent enhancing white matter lesions complicating coiling of intracranial aneurysm.

BACKGROUND AND PURPOSE: In recent years, the use of coiling has gained increased popularity for the treatment of intracranial aneurysms, and stroke physicians are confronted with rare pathologies associated with this relatively new and evolving treatment method, such as embolization of pieces of the polymeric filaments from the coils and a subsequent inflammatory response. In particular, white matter enhancing lesions are a rare complication after aneurysm endovascular therapy (EVT), suggesting a foreign body reaction to shedding of hydrophilic coating from the endovascular devices into the blood stream. The description of such a case aims to raise the clinicians' awareness of the symptomatic delayed and recurring inflammatory changes that may occur after endovascular aneurysmal treatment with the use of coiling devices. CASE DESCRIPTION: A 64-year-old woman underwent coiling of a ruptured right posterior communicating artery aneurysm. She was asymptomatic after EVT. One year later, she presented with headache, acoustic hallucinations, paresthesias and left arm weakness. Brain magnetic resonance imaging (MRI) revealed multiple enhancing white matter lesions in the right hemisphere. She was treated with pulse intravenous methylprednisolone, followed by oral prednisolone; all clinical symptoms resolved and imaging findings improved substantially. Two years after tapering the steroids, follow-up symptoms recurred and repeat brain MRI revealed new enhancing white matter lesions. DISCUSSION AND CONCLUSIONS: There is an increasing number of similar reports of enhancing white matter lesions after coiling of intracranial aneurysms, with the incidence estimated to be between 0.5% and 2.3% in different cohort studies. Close monitoring for the appearance of new neurologic symptoms that could suggest delayed brain reactivity should be recommended.

Evolving Causes of Rapidly Progressive Dementia: A 5-Year Comparative Study.

BACKGROUND: Rapidly progressive dementia (RPD) is a clinical syndrome developing in <1 to 2 years. Recent progress in RPD evaluation is significant, so RPD's prevalence may change over time. The aim of our new case series was to estimate the relative frequency of RPDs' causative entities, considering the recent advances in RPDs' diagnosis, and compare the results with those of our previous report. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 47 patients who were referred to Attikon University Hospital during a 5-year period for a suspected RPD. RESULTS: Neurodegenerative diseases were the most frequent causes (38%), followed by prion disease (19%) and autoimmune encephalopathy (AE, 17%). AE cases were by far more common than in our previous report, while other than AE secondary causes were significantly decreased. Mean time to dementia was 9 months in neurodegenerative diseases and 5 months in non-neurodegenerative. Main clinical findings across all patients were memory impairment (66%) and behavioral-emotional disturbances (48%). CONCLUSIONS: Neurodegenerative diseases are common causes of RPD and have a slower evolution than non-neurodegenerative. Diagnostic novelties enabled the recognition of AE, whereas more common secondary causes are probably now diagnosed in primary settings since the recognition of RPD as distinct clinical entity is continually increasing.

Statin Pretreatment and Microembolic Signals in Large Artery Atherosclerosis.

OBJECTIVE: Although statin pretreatment (SP) is associated with better outcomes in patients with acute cerebral ischemia after an ischemic stroke/transient ischemic attack, data on the underlying mechanism of this beneficial effect are limited. APPROACH AND RESULTS: We sought to evaluate the potential association between SP and microembolic signal (MES) burden in acute cerebral ischemia because of large artery atherosclerosis (LAA). We prospectively evaluated consecutive patients with first-ever acute cerebral ischemia because of LAA in 3 tertiary stroke centers over a 2-year period. All patients underwent continuous 1-hour transcranial Doppler monitoring of the relevant vessel at baseline (≤24 hours). SP was recorded and dichotomized as high dose or low-to-moderate dose. SP was documented in 43 (41%) of 106 LAA patients (mean age, 65.4±10.3 years; 72% men; low-to-moderate dose, 32%; high dose, 8%). There was a significant (P=0.022) dose-dependent effect between SP and MES prevalence: no SP (37%), SP with low-to-moderate dose (18%), and SP with high dose (0%). Similarly, a significant (P=0.045) dose-dependent effect was documented between SP and MES burden: no SP (1.1±1.8), SP with low-to-moderate dose (0.7±1.6), and SP with high dose (0±0). In multivariable logistic regression analysis adjusting for demographics, vascular risk factors, location of LAA, stroke severity, and other prevention therapies, SP was associated with lower likelihood of MES presence (odds ratio, 0.29; 95% confidence interval, 0.09-0.92; P=0.036). In addition, SP was found also to be independently related to higher odds of functional improvement (common odds ratio, 3.33; 95% confidence interval, 1.07-10.0; P=0.037). CONCLUSIONS: We found that SP in patients with acute LAA is related with reduced MES presence and lower MES burden with an apparently dose-dependent association.

Seasonal adherence to, and effectiveness of, subcutaneous interferon ß-1a administered by RebiSmart® in patients with relapsing multiple sclerosis: results of the 1-year, observational GEPAT-SMART study.

BACKGROUND: Little is known about whether tolerability and adherence to treatment can be influenced by weather and temperature conditions. The objective of this study was to assess monthly and seasonal adherence to and safety of sc IFN-ß1a (Rebif®, Merck) in relapsing-remitting multiple sclerosis (RRMS) patients using the RebiSmart® electronic autoinjector. METHODS: A multicentre, prospective observational study in Greece in adult RRMS patients with EDSS < 6, under Rebif®/RebiSmart® treatment for ≤6 weeks before enrollment. The primary endpoint was monthly, seasonal and annual adherence over 12 months (defined in text). Secondary endpoints included number of relapses, disability, adverse events. RESULTS: Sixty four patients enrolled and 47 completed all study visits (Per Protocol Set - PPS). Mean annual adherence was 97.93% ± 5.704 with no significant monthly or seasonal variations. Mean relapses in the pre- and post- treatment 12-months were 1.1 ± 0.47 and 0.2 ± 0.54 (p < 0.0001, PPS). 10 patients (22%) showed 3-month disability progression, 19 (40%) stabilization and 18 (38%) improvement. EDSS was not correlated to pre- (r = 0.024, p = 0.87) or post-treatment relapses (r = 0.022, p = 0.88). CONCLUSION: High adherence with no significant seasonal or weather variation was observed over 12 months. While the efficacy on relapses was consistent with published studies, we could not identify a relationship between relapses and disability. TRIAL REGISTRATION: Greek registry of non-interventional clinical trials ID: 200136 , date of registration: February 18th, 2013.

Hemicraniectomy for Malignant Middle Cerebral Artery Syndrome: A Review of Functional Outcomes in Two High-Volume Stroke Centers.

BACKGROUND AND PURPOSE: Despite recent landmark randomized controlled trials showing significant benefits for hemicraniectomy (HCT) compared with medical therapy (MT) in patients with malignant middle cerebral artery infarction (MMCAI), HCT rates have not substantially increased in the United States. We sought to evaluate early outcomes in patients with MMCAI who were treated with HCT (cases) in comparison to patients treated with MT due to the perception of procedural futility by families (controls). METHODS: We retrospectively evaluated consecutive patients with acute MMCAI treated in 2 tertiary care centers during a 7-year period. Pretreatment National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) at 3 months were documented. Functional independence (FI) and survival without severe disability (SWSD) were defined as mRS of 0-2 and 0-4, respectively. RESULTS: A total of 66 patients (37 cases and 29 controls) fulfilled the study inclusion criteria (mean age 59 ± 15 years, 52% men, median admission NIHSS score: 19 points [interquartile range {IQR}: 16-22]). Cases were younger (51 ± 11 versus 68 ± 13 years; P < .001) and tended to have lower median admission NIHSS than controls (18 [IQR:16-20] versus 20 [IQR:18-23]; P = .072). The rates of FI and SWSD at 3 months were higher in cases than controls (16% versus 0% [P = .031] and 62% versus 0% [P < .001]), while 3-month mortality was lower (24% versus 77%; P < .001). Multivariable Cox regression analyses adjusting for potential confounders identified HCT as the most important predictor of lower risk of 3-month mortality (hazard ratio: .02, 95% confidence interval: .01-0.10; P < .001). CONCLUSIONS: HCT is a critical and effective therapy for patients with MMCAI but cannot provide a guarantee of functional recovery.

Plasma Glial Fibrillary Acidic Protein in the Differential Diagnosis of Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Plasma GFAP (glial fibrillary acidic protein) has recently emerged as a potential biomarker for the differentiation of acute intracerebral hemorrhage (ICH) from acute ischemic stroke (AIS). We prospectively assessed the diagnostic accuracy of GFAP in the differential diagnosis of ICH. METHODS: Consecutive patients presenting to the emergency department within 6 hours from symptom onset were evaluated. All patients underwent extensive diagnostic work-up and were classified according to discharge diagnosis in AIS, ICH, subarachnoid hemorrhage, and stroke mimics. GFAP was also measured in healthy volunteers (controls). Baseline stroke severity was evaluated using National Institutes of Health Stroke Scale. Receiver operating characteristic curve analysis was used to identify the optimal cutoff point for the differentiation between subgroups. Correlation analyses of GFAP plasma concentrations with baseline National Institutes of Health Stroke Scale and onset to sampling time were performed with the nonparametric Spearman rank test and fractional polynomial regression, respectively. RESULTS: Our study population consisted of 270 individuals (AIS: 121, ICH: 34, stroke mimics: 31, subarachnoid hemorrhage: 5, controls: 79). No differences on baseline stroke severity and onset to sampling time were detected between AIS and ICH. Higher median plasma GFAP values were documented in ICH compared with AIS, stroke mimics, and controls (P<0.001). Receiver operating characteristic analysis highlighted a cutoff value of 0.43 ng/mL as the optimal threshold for the differentiation between ICH and AIS (sensitivity: 91%, specificity: 97%). No association was detected between plasma GFAP concentrations and baseline stroke severity for both AIS (P=0.515) and ICH (P=0.387). In the fractional polynomial analysis, the association between GFAP concentration and onset to sampling time was best described by a J-shaped curve for AIS and an inverted U-shaped curve for ICH, with a peak at 2 hours. CONCLUSIONS: Plasma GFAP seems to be a sensitive and specific biomarker for the differentiation of ICH from both AIS and other acute neurological disorders, with the optimal diagnostic yield being present in the second hour from symptom onset.

Transcranial Doppler versus transthoracic echocardiography for the detection of patent foramen ovale in patients with cryptogenic cerebral ischemia: A systematic review and diagnostic test accuracy meta-analysis.

OBJECTIVE: Patent foramen ovale (PFO) can be detected in up to 43% of patients with cryptogenic cerebral ischemia undergoing investigation with transesophageal echocardiography (TEE). The diagnostic value of transthoracic echocardiography (TTE) in the detection of PFO in patients with cryptogenic ischemic stroke or transient ischemic attack has not been compared with that of transcranial Doppler (TCD) using a comprehensive meta-analytical approach. METHODS: We performed a systematic literature review to identify all prospective observational studies of patients with cryptogenic cerebral ischemia that provided both sensitivity and specificity measures of TTE, TCD, or both compared to the gold standard of TEE. RESULTS: Our literature search identified 35 eligible studies including 3,067 patients. The pooled sensitivity and specificity for TCD was 96.1% (95% confidence interval [CI] = 93.0-97.8%) and 92.4% (95% CI = 85.5-96.1%), whereas the respective measures for TTE were 45.1% (95% CI = 30.8-60.3%) and 99.6% (95% CI = 96.5-99.9%). TTE was superior in terms of higher positive likelihood ratio values (LR+ = 106.61, 95% CI = 15.09-753.30 for TTE vs LR+ = 12.62, 95% CI = 6.52-24.43 for TCD; p = 0.043), whereas TCD demonstrated lower negative likelihood values (LR- = 0.04, 95% CI = 0.02-0.08) compared to TTE (LR- = 0.55, 95% CI = 0.42-0.72; p < 0.001). Finally, the area under the summary receiver operating curve (AUC) was significantly greater (p < 0.001) in TCD (AUC = 0.98, 95% CI = 0.97-0.99) compared to TTE studies (AUC = 0.86, 95% CI = 0.82-0.89). INTERPRETATION: TCD is more sensitive but less specific compared to TTE for the detection of PFO in patients with cryptogenic cerebral ischemia. The overall diagnostic yield of TCD appears to outweigh that of TTE.

Factors associated with the presence of postoperative headache in elective surgery patients: a prospective single center cohort study.

PURPOSE: Headache is an important cause of minor postoperative morbidity. In this study we evaluated the association of anesthesia and surgery with the occurrence of postoperative headache in elective surgery patients. METHODS: After obtaining ethical approval, 446 patients were enrolled in this prospective, single-centre cohort study. Participants were interviewed preoperatively, and for five days postoperatively, regarding the appearance of headache, while demographics, lifestyle, type of anesthesia and surgery, the anesthetic drugs administered and intraoperative adverse effects were recorded. Multiple logistic regression analysis was conducted in order to identify independent factors associated with postoperative headache, both in the total sample and in patients without previous history of headache. RESULTS: The observed overall frequency of postoperative headache was 28.3% (N = 126) in the total sample. In patients with previous history of headache, the frequency of postoperative headache was 41% (N = 89), while in those with no history the frequency of postoperative headache was 16.2% (N = 37). Female gender [p = 0.024; odds ratio (OR) = 2.1], sevoflurane administration (p < 0.001; OR = 3.66), intraoperative hypotension (p = 0.008; OR = 2.12) and smoking (p = 0.006; OR = 1.74) were independently associated with postoperative headache. In patients without previous history, female gender (p = 0.005; OR = 4.77), sevoflurane administration (p = 0.001; OR = 6.9), intraoperative hypotension (p = 0.006; OR = 6.7) and caffeine consumption (p = 0.041; OR = 5.28) presented greater likelihood for postoperative headache, while smoking revealed no association. CONCLUSION: Female gender, sevoflurane, smoking and intraoperative hypotension were documented as independent risk factors for postoperative headache. In patients with no previous history of headache, caffeine consumption was an additional independent factor for postoperative headache, while smoking revealed no association.

Acute effects of coffee consumption on self-reported gastrointestinal symptoms, blood pressure and stress indices in healthy individuals.

BACKGROUND: It has been suggested that coffee may affect the gut-brain axis with conflicting outcomes. Moreover, there is insufficient evidence to determine whether the type or temperature of coffee consumed will have a different impact on the gut-brain axis. The purpose of this study was to investigate the effects of acute coffee consumption on the following: 1. self-reported GI symptoms and salivary gastrin, 2. stress indices [salivary cortisol and alpha-amylase (sAA)] and psychometric measures, and 3. blood pressure (BP), in healthy, daily coffee consuming individuals in non-stressful conditions. METHODS: This was a randomized, double blind, crossover clinical trial, in which 40 healthy individuals (20 men, 20 women), 20-55 years of age, randomly consumed four 200 ml coffee beverages containing 160 mg caffeine (hot and cold instant coffee, cold espresso, hot filtered coffee), 1 week apart. Salivary samples and psychometric questionnaires were collected at baseline and post-coffee consumption at 15,30, and 60 min for salivary gastrin and sAA measurements and at 60,120, and 180 min for cortisol measurements. BP was measured at beginning and end of each intervention. ClinicalTrials.gov ID: NCT02253628 RESULTS: Coffee consumption significantly increased sAA activity (P = 0.041), with significant differences only between cold instant and filter coffee at 15 and 30 min post-consumption (P < 0.05). Coffee temporarily increased salivary gastrin, without differences between coffee types. Coffee did not affect salivary cortisol or self-reported anxiety levels. Coffee consumption significantly increased BP, within the healthy physiological levels, in a gender specific manner at the end of the experimental periods, without differences between coffee types. CONCLUSION: Acute coffee consumption in non-stressful conditions activated sAA and BP but not salivary cortisol, indicating activation of the sympathetic nervous system. Post-coffee sAA increase without a concomitant cortisol increase may also indicate that coffee may have some anti-stress properties.

Neuropsychological and psychiatric aspects of multiple sclerosis: preliminary investigation of discrete profiles across neurological subtypes.

Cognitive deficits affecting memory, attention, speed of information processing and executive functions are common in multiple sclerosis (MS). In this study we examine the possibility of discrete pattern of neuropsychological deficits of MS subtypes. 28 patients (13 RRMS, 6 CIS, and 9 SPMS) were assessed with a comprehensive neuropsycholgical battery. Results indicate that only the SPMS group demonstrates memory and executive impairment. This finding indicates possible differentiation of the three subtypes in terms of neuropsychological profiles. Psychiatric aspects of MS are also briefly discussed.

Decreased levels of alpha-synuclein in cerebrospinal fluid of patients with clinically isolated syndrome and multiple sclerosis.

Cerebrospinal fluid (CSF) α-synuclein (ASYN) levels are emerging as a possible biomarker in a number of neurodegenerative conditions; however, there has been little study of such levels in demyelinating conditions with neurodegeneration such as multiple sclerosis (MS). In this study, we aimed to assess CSF ASYN levels in MS spectrum [clinically isolated syndrome (CIS) and MS] patients and compare them to those obtained in control subjects with benign neurological conditions (BNC). We used a recently developed, ultra-sensitive sandwich enzyme-linked immunosorbent assay to measure and compare CSF ASYN levels in three categories of subjects: BNC (n = 38), CIS (n = 36) and MS [Relapsing Remitting (RRMS, n = 22) and Primary Progressive (PPMS, n = 15)]. We also performed secondary analyses, including relationship of CSF ASYN levels to aging, gender, presence of CSF oligoclonal bands (OB) and gadolinium (Gd)-enhancing demyelinating lesions on T1-weighted MRIs. CSF ASYN levels were found to be significantly lower in the CIS (78.2 ± 7.5 pg/mL), RRMS (76.8 ± 5.1 pg/mL), and PPMS (76.3 ± 6.7 pg/mL) groups compared to the BNC (125.7 ± 13.6 pg/mL) group. Secondary analyses did not reveal additional correlations. Our results suggest that in a cohort of CIS and MS patients, CSF ASYN levels are decreased, thus providing another possible link between MS and neurodegeneration. Future studies will need to be performed to confirm and extend these findings, to lead to a fuller understanding of the possible biological link between ASYN and MS. Alpha-synuclein levels in the Cerebrosinal Fluid (CSF) may reflect neurodegenerative processes. Here we measure CSF alpha-synuclein in demyelinating conditions ranging from Clinically Isolated Syndrome to Primary Progressive Multiple Sclerosis (MS). We find a similar magnitude of decreased alpha-synuclein compared to a control group in all such MS spectrum conditions; such a decrease may reflect an underlying early neurodegenerative disease process.

Complex atheromatous plaques in the descending aorta and the risk of stroke: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Proximal aortic plaques, especially in the aortic arch, have already been established as an important cause of stroke and peripheral embolism. However, aortic plaques situated in the descending thoracic aorta have recently been postulated as a potential embolic source in patients with cryptogenic cerebral infarction through retrograde aortic flow. The aim of the present study was to evaluate the potential association of descending aorta atheromatosis with cerebral ischemia. METHODS: We conducted a systematic review and meta-analysis of all available prospective observational studies reporting the prevalence of complex atheromatous plaques in the descending aorta in patients with stroke and in unselected populations undergoing examination with transesophageal echocardiography. RESULTS: We identified 11 eligible studies including a total of 4000 patients (667 patients with stroke and 3333 unselected individuals; mean age, 65 years; 55% men). On baseline transesophageal echocardiograpic examination, the prevalence of complex atheromatous plaques in the descending aorta was higher (P=0.001) in patients with stroke (25.4%; 95% confidence interval, 14.6-40.4%) compared with unselected individuals (6.1%; 95% confidence interval, 3.4-10%). However, no significant difference (P=0.059) in the prevalence of complex atheromatous plaques in the descending aorta was found between patients with cryptogenic (21.8%; 95% confidence interval, 17.5-26.9%) and unclassified (28.3%; 95% confidence interval, 23.9-33.1%) cerebral infarction. CONCLUSIONS: Our findings indicate that the presence of complex plaques in the descending aorta is presumably a marker of generalized atherosclerosis and high vascular risk. The present analyses do not provide any further evidence for a direct causal relationship between descending aorta atherosclerosis and cerebral embolism.