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Objectives: A deep knowledge of the surgical anatomy of the target area is mandatory for a successful operative procedure. For this purpose, over the years, many teaching and learning methods have been described, from the most ancient cadaveric dissection to the most recent virtual reality, each with their respective pros and cons. Photogrammetry, an emergent technique, allows for the creation of three-dimensional (3D) models and reconstructions. Thanks to the spreading of photogrammetry nowadays it is possible to generate these models using professional software or even smartphone apps. This study aims to compare the neuroanatomical photogrammetric models generated by the two most utilized smartphone applications in this domain, Metascan and 3D-Scanner, through quantitative analysis. Methods: Two human head specimens (four sides) were examined. Anatomical dissection was segmented into five stages to systematically expose well-defined structures. After each stage, a photogrammetric model was generated using two prominent smartphone applications. These models were then subjected to both quantitative and qualitative analysis, with a specific focus on comparing the mesh density as a measure of model resolution and accuracy. Appropriate consent was obtained for the publication of the cadaver's image. Results: The quantitative analysis revealed that the models generated by Metascan app consistently demonstrated superior mesh density compared to those from 3D-Scanner, indicating a higher level of detail and potential for precise anatomical representation. Conclusion: Enabling depth perception, capturing high-quality images, offering flexibility in viewpoints: photogrammetry provides researchers with unprecedented opportunities to explore and understand the intricate and magnificent structure of the brain. However, it is of paramount importance to develop and apply rigorous quality control systems to ensure data integrity and reliability of findings in neurological research. This study has demonstrated the superiority of Metascan in processing photogrammetric models for neuroanatomical studies. [ABSTRACT FROM AUTHOR]

Neurological conditions are the leading cause of disability and mortality combined, demanding innovative, scalable, and sustainable solutions. Brain health has become a global priority with adoption of the World Health Organization's Intersectoral Global Action Plan in 2022. Simultaneously, rapid advancements in artificial intelligence (AI) are revolutionizing neurological research and practice. This scoping review of 66 original articles explores the value of AI in neurology and brain health, systematizing the landscape for emergent clinical opportunities and future trends across the care trajectory: prevention, risk stratification, early detection, diagnosis, management, and rehabilitation. AI's potential to advance personalized precision neurology and global brain health directives hinges on resolving core challenges across four pillars—models, data, feasibility/equity, and regulation/innovation—through concerted pursuit of targeted recommendations. Paramount actions include swift, ethical, equity-focused integration of novel technologies into clinical workflows, mitigating data-related issues, counteracting digital inequity gaps, and establishing robust governance frameworks balancing safety and innovation. [ABSTRACT FROM AUTHOR]

Background: To assess the state of neurological scientific research in Italy in the time interval 2020–2023. Methods: Elsevier's modular integrated platform "SciVal" was used to analyze bibliometric research products starting from scientific production data uploaded onto Scopus. We considered the research area "Neurology" in the 01/01/2020–14/06/2023 time interval, and the following variables were extracted: number of published studies, number of citations, Field-Weighted Citation Impact, and percentage of international collaborations. The contribution of Italian scientists to the neurological research was compared to that of the other nations. Results: Research identified 90,633 scientific papers in the neurological area worldwide, with a total of 472,750 citations. The products assigned to Italian groups were 6670 (53,587 citations, Field-Weighted Citation Impact 1.68, 41% international collaborations). Conclusions: According to the present study, Italian neurological research 2020 to 2023 ranks fifth globally and third in Europe. [ABSTRACT FROM AUTHOR]

Background: Neurological disorders remain a worldwide concern due to their increasing prevalence and mortality, combined with the lack of available treatment, in most cases. Exploring protective and risk factors associated with the development of neurological disorders will allow for improving prevention strategies. However, ascertaining neurological outcomes in population-based studies can be both complex and costly. The application of eHealth tools in research may contribute to lowering the costs and increase accessibility. The aim of this systematic review is to map existing eHealth tools assessing neurological signs and/or symptoms for epidemiological research. Methods: Four search engines (PubMed, Web of Science, Scopus & EBSCOHost) were used to retrieve articles on the development, validation, or implementation of eHealth tools to assess neurological signs and/or symptoms. The clinical and technical properties of the software tools were summarised. Due to high numbers, only software tools are presented here. Findings: A total of 42 tools were retrieved. These captured signs and/or symptoms belonging to four neurological domains: cognitive function, motor function, cranial nerves, and gait and coordination. An additional fifth category of composite tools was added. Most of the tools were available in English and were developed for smartphone device, with the remaining tools being available as web-based platforms. Less than half of the captured tools were fully validated, and only approximately half were still active at the time of data collection. Interpretation: The identified tools often presented limitations either due to language barriers or lack of proper validation. Maintenance and durability of most tools were low. The present mapping exercise offers a detailed guide for epidemiologists to identify the most appropriate eHealth tool for their research. Funding: The current study was funded by a PhD position at the University of Groningen. No additional funding was acquired. [ABSTRACT FROM AUTHOR]

The author comments on a review of studies on neuroelectric correlates relating to human sexuality, which references a research paper by A. Ziogas et al., published in a 2020 issue of "Archives of Sexual Behavior." It discusses the insights offered by Ziogas' team regarding limitations and directions for future inquiry of the subject, the selection of sexual stimuli and comparison stimuli, and a comparison between responses to sexual stimuli and sexual processing.

The original article can be found online at https://doi.org/10.1007/s00415-023-12012-6.Correction to: Journal of Neurology (2024) 271:211–230https://doi.org/10.1007/s00415-023-12012-6In the original version of this article, in table 3 hyperlinks in the tool description are missing.The original article has been corrected.By Vasco Ribeiro Ferreira; Esther Metting; Joshua Schauble; Hamed Seddighi; Lise Beumeler and Valentina GalloReported by Author; Author; Author; Author; Author; Author [Extracted from the article]

Sarcopenia has an insidious start that can induce physical malfunction, raise the risk of falls, disability, and mortality in the old, severely impair the aged persons' quality of life and health. More and more studies have demonstrated that sarcopenia is linked to neurological diseases in recent years. This review examines the advancement of sarcopenia and neurological illnesses research. [ABSTRACT FROM AUTHOR]

Objective: Multiverse analysis provides an ideal tool for understanding how inherent, yet ultimately arbitrary methodological choices impact the conclusions of individual studies. With this investigation, we aimed to demonstrate the utility of multiverse analysis for evaluating generalisability and identifying potential sources of bias within studies employing neurological populations. Methods: Multiverse analysis was used to evaluate the robustness of the relationship between post-stroke visuospatial neglect and poor long-term recovery outcome within a sample of 1113 (age = 72.5, 45.1% female) stroke survivors. A total of 25,600 t-test comparisons were run across 400 different patient groups defined using various combinations of valid inclusion criteria based on lesion location, stroke type, assessment time, neglect impairment definition, and scoring criteria across 16 standardised outcome measures. Results: Overall, 33.9% of conducted comparisons yielded significant results. 99.9% of these significant results fell below the null specification curve, indicating a highly robust relationship between neglect and poor recovery outcome. However, the strength of this effect was not constant across all comparison groups. Comparisons which included < 100 participants, pre-selected patients based on lesion type, or failed to account for allocentric neglect impairment were found to yield average effect sizes which differed substantially. Similarly, average effect sizes differed across various outcome measures with the strongest average effect in comparisons involving an activities of daily living measure and the weakest in comparisons employing a depression subscale. Conclusions: This investigation demonstrates the utility of multiverse analysis techniques for evaluating effect robustness and identifying potential sources of bias within neurological research. [ABSTRACT FROM AUTHOR]

Neurological and psychiatric (mental health) disorders have a large impact on health burden globally. Cognitive disorders (including dementia) and stroke are leading causes of disability. Mental health disorders, including depression, contribute up to one-third of total years lived with disability. The Neurological and mental health Global Epidemiology Network (NeuroGEN) is an international multi-database network that harnesses administrative and electronic medical records from Australia, Asia, Europe and North America. Using these databases NeuroGEN will investigate medication use and health outcomes in neurological and mental health disorders. A key objective of NeuroGEN is to facilitate high-quality observational studies to address evidence-practice gaps where randomized controlled trials do not provide sufficient information on medication benefits and risks that is specific to vulnerable population groups. International multi-database research facilitates comparisons across geographical areas and jurisdictions, increases statistical power to investigate small subpopulations or rare outcomes, permits early post-approval assessment of safety and effectiveness, and increases generalisability of results. Through bringing together international researchers in pharmacoepidemiology, NeuroGEN has the potential to be paradigm-changing for observational research to inform evidence-based prescribing. The first focus of NeuroGEN will be to address evidence-gaps in the treatment of chronic comorbidities in people with dementia. [ABSTRACT FROM AUTHOR]

Cassava (Manihot esculenta Crantz) is a tropical plant that is used as fresh food, processed food, or raw material for the preparation of flours with high nutritional value. However, cassava contains cyanogenic glycosides, such as linamarin and lotaustralin, that can trigger severe toxic effects and some neurological disorders, including motor impairment, cognitive deterioration, and symptoms that characterize tropical ataxic neuropathy and spastic epidemic paraparesis (Konzo). These alterations that are associated with the consumption of cassava or its derivatives have been reported in both humans and experimental animals. The present review discusses and integrates preclinical and clinical evidence that indicates the toxic and neurological effects of cassava and its derivatives by affecting metabolic processes and the central nervous system. An exhaustive review of the literature was performed using specialized databases that focused on the toxic and neurological effects of the consumption of cassava and its derivatives. We sought to provide structured information that will contribute to understanding the undesirable effects of some foods and preventing health problems in vulnerable populations who consume these vegetables. Cassava contains cyanogenic glycosides that contribute to the development of neurological disorders when they are ingested inappropriately or for prolonged periods of time. Such high consumption can affect neurochemical and neurophysiological processes in particular brain structures and affect peripheral metabolic processes that impact wellness. Although some vegetables have high nutritional value and ameliorate food deficits in vulnerable populations, they can also predispose individuals to the development of neurological diseases. [ABSTRACT FROM AUTHOR]

A new study provides evidence for an association between COVID-19 and long-term neurological syndromes. The findings highlight the need for further research into the long-term neurological consequences of SARS-CoV-2 infection and the development of strategies that lessen the effects of these consequences on patient quality of life and on healthcare systems. [ABSTRACT FROM AUTHOR]

The article discusses the history of the studies regarding mechanism of action of phenytoin drug as an anticonvulsant in neuropharmacology. Topics include the first period from 1937-1949 with the study on the mechanism of action by neurologists from Harvard Medical School, the second period from 1949-1972 with studies of physiologists on the effect in sodium ions and nerve cell excitation, and the third period from 1972–1980 on its sodium permeability inhibition through ion channels.

Clinical and sub clinical cases of Coenurosis due to Coenurus cerebralis in goats were documented based on clinical, post mortem examination, identification of parasitic stages, gross and histopathological lesions in brain of animals died due to abnormal neurological symptoms. The most prominent site of predilection of coenuri cysts in brain was cerebral hemispheres and multiple cysts were found in majority of the cases. Generalized congestion, thinning of brain parenchyma due to pressure atrophy, gliosis, neuronal degeneration, protoscolices in brain parenchyma and inflammatory cell reactions predominantly comprised of lymphocytes and macrophages were prominent neuropathological lesions observed in brain. This study had significant implications in understanding the neuropathological lesions to suggest suitable prevention and control measures in organized goat farms in India. [ABSTRACT FROM AUTHOR]

In this hospital-based surveillance and nested age-matched case-control study, authors performed laboratory investigations to assess potential infectious and non-infectious causes of acute neurological illness in children (age d'15 y) who were admitted with new-onset seizures or altered sensorium to two hospitals in Muzaffarpur, India. Age-matched controls were residents of same area who were admitted to the same hospitals for a non-neurologic illness within seven days of the date of admission of the case. Clinical specimens (blood, cerebrospinal fluid, and urine) and environmental specimens (litchi fruits) were tested for evidence of infectious pathogens, pesticides, toxic metals, and other non-infectious causes, including presence of hypoglycin A or methylenecyclopropylglycine (MCPG)-naturally occurring fruit-based toxins that cause hypoglycemia and metabolic derangement. Out of 390 patients meeting the case definition admitted to the two referral hospitals, 122 (31%) died. On admission, 204 (62%) of 327 had blood glucose concentration d'70 mg/dL. In comparison of 104 cases with 104 age-matched controls, litchi consumption (matched odds ratio [mOR] 9.6; 95% CI 3.6, 24) and absence of an evening meal (mOR 2.2; 95% CI 1.2, 4.3) in the 24 h preceding illness onset were associated with illness. The absence of an evening meal significantly modified the effect of eating litchis on illness (OR 7.8; 95% CI 3.3, 18.8 without evening meal; and OR 3.6; 95% CI 1.1, 11.1 with an evening meal). Metabolites of hypoglycin A, MCPG, or both were detected in 48 (66%) of 73 urine specimens from cases and none from 15 controls; 72 (90%) of 80 case-patient specimens had abnormal plasma acylcarnitine profiles, consistent with severe disruption of fatty acid metabolism. In 36 litchi arils tested, hypoglycin A concentrations ranged from 12.4 μg/g to 152.0 μg /g, and MCPG ranged from 44.9 μg/g to 220.0 μg/g. Authors concluded that outbreak of acute encephalopathy in Muzaffarpur was associated with both hypoglycin A and MCPG toxicity. [ABSTRACT FROM AUTHOR]

Facial (lip and jaw) tremors can be an early sign of Parkinson's disease (PD), essential tremor and other parkinsonisms. Its response to acute dopaminergic therapy and further predictive clinical diagnosis has not been previously addressed. The aim of this study was to evaluate facial tremors response to acute dopaminergic therapy and further predictive value for clinical diagnosis. A retrospective review of medical records from patients with recent onset of facial tremor, with or without parkinsonism, submitted to acute levodopa challenge for clinical prediction of sustained long-term dopaminergic response was conducted. Twenty-eight out of 559 patients (5 %) had facial tremors, which responded to levodopa in 46 % of patients. Facial tremors response to acute levodopa challenge showed 92 % sensitivity and 93 % specificity to predict a final PD diagnosis. In PD patients, facial tremor magnitude of response to levodopa was not different from that of hand rest tremor (p = 0.8). Facial tremors, although infrequent, can be an early sign of PD. Positive response to acute levodopa challenge predicts long-term PD diagnosis. [ABSTRACT FROM AUTHOR]

Very few neurological research is published regarding health effects of global economic crisis. Our aim was to assess the impact of economic recession on frequency and severity of headaches. We also tested if depression, anxiety and experiences associated with crisis, such as unemployment, were reflected in headaches. This is a retrospective observational study in the Emergency setting of tertiary Clinic from 1 January 2008 until 31 December 2009 and from 1 January 2010 until 31 December 2011. Demographic data were collected of 1094 consecutive adult patients with headache. Multinomial logistic regression performed to examine if hospital anxiety depression (HAD), HAD anxiety, experience of serious life events, year of survey had influence on type of headache. The total number of headache cases increased significantly from 2008 to 2011 (p < 0.001). Tension type and medication overuse headaches remained unchanged over time (p > 0.05), while migraines decreased. Secondary and not otherwise specified (NOS) increased significantly (p < 0.05). The most common, overtime, was Tension type headache, followed by migraines (in 2008, 2011) and NOS (2010). Chi square test showed significant correlation between type of headache and year, as well medication type and year (p < 0.05). Common analgesics, the most common medication, increased five times during survey period (77 % 2008 to 87.6 % 2011). Multivariate analysis revealed stronger association for experience serious events with NOS vs. tension type headache [odds ratio (OR) 0.13; 95 % confidence interval (CI) 0.03, 0.7]. This is the first study showing that the prolonged economic crisis affected headache frequency accompanied by a higher use of analgesics. [ABSTRACT FROM AUTHOR]

A wide range of viruses from different virus families in different geographical areas, may cause immediate or delayed neuropathological changes and neurological manifestations in humans and animals. Infection by neurotropic viruses as well as the resulting immune response can irreversibly disrupt the complex structural and functional architecture of the central nervous system, frequently leaving the patient or affected animal with a poor or fatal prognosis. Mechanisms that govern neuropathogenesis and immunopathogenesis of viral infections are highlighted, using examples of well-studied virus infections that are associated with these alterations in different populations throughout the world. A better understanding of the molecular, epidemiological and biological characteristics of these infections and in particular of mechanisms that underlie their clinical manifestations may be expected to provide tools for the development of more effective intervention strategies and treatment regimens. [ABSTRACT FROM AUTHOR]

General medical problems and complications have a major impact on the quality of life in all stages of Parkinson's disease. To introduce an effective treatment, a comprehensive analysis of the various clinical symptoms must be undertaken. One must distinguish between (1) diseases which arise independently of Parkinson's disease, and (2) diseases which are a direct or indirect consequence of Parkinson's disease. Medical comorbidity may induce additional limitations to physical strength and coping strategies, and may thus restrict the efficacy of the physical therapy which is essential for treating hypokinetic-rigid symptoms. In selecting the appropriate medication for the treatment of any additional medical symptoms, which may arise, its limitations, contraindications and interactions with dopaminergic substances have to be taken into consideration. General medical symptoms and organ manifestations may also arise as a direct consequence of the autonomic dysfunction associated with Parkinson's disease. As the disease progresses, additional non-parkinsonian symptoms can be of concern. Furthermore, the side effects of Parkinson medications may necessitate the involvement of other medical specialists. In this review, we will discuss the various general medical aspects of Parkinson's disease. [ABSTRACT FROM AUTHOR]

Background: Hardware-related complications frequently occur in deep brain stimulation. Microscopy and spectroscopy techniques are effective methods for characterizing the morphological and chemical basis of malfunctioning DBS electrodes. A previous report by our team revealed the morphological and chemical alterations on a malfunctioning explanted electrode when it was compared to a new device. The aim of this preliminary study was to verify whether these morphological and chemical alterations in the materials were a direct result of the hardware malfunctioning or if the failure was correlated to a degradation process over time. Methods: Two DBS electrodes were removed from two patients for reasons other than DBS system impairment and were analyzed by a scanning electron microscope and by an energy-dispersive X-ray spectroscopy. The results were compared to a malfunctioning device and to a new device, previously analyzed by our group. Results: The analysis revealed that the wear of the polyurethane external part of all the electrodes was directly correlated with the duration of implantation period. Moreover, these alterations were independent from the electrodes functioning and from parameters used during therapy. Conclusions: This is the first study done that demonstrates a time-related degradation in the external layer of DBS electrodes. The analyses of morphological and chemical properties of the implanted devices are relevant for predicting the possibility of hardware's impairment as well as to improve the bio-stability of DBS systems. [ABSTRACT FROM AUTHOR]

The article explores the contributions of German-American neuropathologist Karl Theodor Neubuerger to the field of neurology. Neubuerger is recognized for merging clinical insights from his patients with the latest neurological and psychiatric research. The influence of mentor and neuro-oncologist Walther Spielmeyer on the work of Neubuerger is discussed, as well as Neubuerger's relationships with the Rockefeller Foundation and the Kaiser Wilhelm Society.

Over the recent years, the application of neuroimaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) has considerably advanced the understanding of complex neurological disorders. PET is a powerful molecular imaging tool, which investigates the distribution and binding of radiochemicals attached to biologically relevant molecules; as such, this technique is able to give information on biochemistry and metabolism of the brain in health and disease. MRI uses high intensity magnetic fields and radiofrequency pulses to provide structural and functional information on tissues and organs in intact or diseased individuals, including the evaluation of white matter integrity, grey matter thickness and brain perfusion. The aim of this article is to review the most recent advances in neuroimaging research in common neurological disorders such as movement disorders, dementia, epilepsy, traumatic brain injury and multiple sclerosis, and to evaluate their contribution in the diagnosis and management of patients. [ABSTRACT FROM AUTHOR]

Headache is a common presenting complaint in the Emergency Department. The aim of this study was to delineate the demographic profile of patients presenting a chief complaint of headache and to assess the application of diagnostic algorithms for the management of these patients. We examined patients admitted to the Spedali Civili Hospital ED between January 2005 and December 2009 who complained of headache not related to trauma and all patients hospitalized for headache in Neurological Clinic, from ED, between January 2008 and December 2009. 7495 patients were examined at ED for headaches. 72 % of patients were discharged, 22 % were admitted. From 2005 to 2009, there was a definite decrease in the rate of hospitalization due to headache (15 vs 9.9 % in Department of Neurology and 26 vs 18.9 % in all Departments). Considering the decrease year by year, this reduction was significant from 2007 to 2008, when the algorithms were adopted. The most common diagnosis in the ED was 'Non-specific headache' (41 %), followed by 'Primary headaches and complications of primary headaches' (20.8 %), 'Secondary headaches not associated with risk of serious disease' (20.4 %) and 'Secondary headache associated with risk of serious disease' (5 %). Over 2-year period (2008-2009) we found an increase in the diagnosis of 'Primary headaches and complications of primary headaches' and 'Secondary headaches associated with risk of serious disease' compared with a decrease of 'nonspecific headache' and 'secondary headaches not associated with risk of serious disease'. The use of the diagnostic algorithms and collaborative network between the ED and the Headache Center can improve the management of patients with headache in ED. [ABSTRACT FROM AUTHOR]

Background Vasospasm following ruptured intracranial aneurysms has always been a challenging condition to treat. Objective The aim of this study was to correlate between clinical and radiographic vasospasms after aneurysmal subarachnoid hemorrhage (SAH) and to point out the other important causes of neurological deterioration Methods This is a retrospective study conducted on 25 consecutive patients between June 2013 and February 2014 who presented with SAH. Altogether there were 18 male and seven female patients with ages ranging from 42 to 65 years. All patients underwent initial four-vessel or computed tomography (CT) angiography. All patients were treated by direct surgical clipping and all of them were operated upon 48-72 h from admission. All patients were assessed clinically and radiologically by CT scan and conventional angiography or CT angiography at day 10 of postbleeding. Results Out of 25 cases with aneurysmal SAH, 20 developed radiographic vasospasm, with only 11 cases developing clinical vasospasm. Conclusion The incidence of radiographic (angiographic) vasospasm was 80%, with only 55% of cases developing clinical vasospasm. Proper evaluation with laboratory tests and neuroimaging should be carried out in all cases to detect the actual cause of neurological deterioration and to start the proper treatment. [ABSTRACT FROM AUTHOR]

Background: As a lifelong disease, diabetes impairs the quality of life by limiting the eating and drinking habits and by bringing out the risk of kidney, eye, cardiovascular and diabetic neurological diseases in the long run. Loss of health might result in mourning, grief, rebellion, denial, anxiety, rage and sometimes these feelings might overcome the patient's coping skills leading to depression [Clinical Psychiatry 11 (Suppl 3) 3-18, 2008]. How individuals suffering from depression perceive and interpret the incidents around them is also important [Rel. Scie. Acad. J. III, 2: 129-152, 2003]. Accordingly, the determination of the correlation of the depression with the perceived social support level by the patients with diabetic foot was programmed and performed in order to take essential precautions, to generate proper solutions and treatment process and to make supportive plans for patients with developing diabetic foot and depression. Methods: The data was obtained from 128 patients who applied to hospital within the scope of research between July 1st 2011 and January 31st 2012 that were diagnosed with diabetes and had diabetic foot. Pearson chi-square, Fisher Exact and Likelihood ratio, chi-square, Student t test and one way analysis of variance, Levene's test, One way ANOVA, Welch and Games Howell tests were used in the analysis and evaluation. The data was collected by meeting face to face the individuals and by making use of the patient files and using the "Personal Information Form" which includes introductory information about individuals with diabetic foot, "Beck Depression Scale" which is applied to determine emotion status of individuals and "Multidimensional Scale of Perceived Social Support" which is applied to determine the level of social support individuals perceive. Results: In the performed statistical evaluation, mean scores of Beck Depression scale and MSPSS family support, friend support, special person support sub-dimension and scale total scores were found to be in negative statistical correlation (p < 0.01). Conclusions: In the treatment and care of the patients with diabetic foot; anxiety and depression status of the patients, as well as physical status, should also be evaluated routinely. The individuals provided to take professional care. [ABSTRACT FROM AUTHOR]

Advance information, such as object weight, size and texture, modifies predictive scaling of grip forces in a grip-lift task. Here, we examined the influence of probabilistic advance information about object weight. Fifteen healthy volunteers repeatedly grasped and lifted an object equipped with a force transducer between their thumb and index finger. Three clearly distinguishable object weights were used. Prior to each lift, the probabilities for the three object weights were given by a visual cue. We examined the effect of probabilistic pre-cues on grip and lift force dynamics. We expected predictive scaling of grip force parameters to follow predicted values calculated according to probabilistic contingencies of the cues. We observed that probabilistic cues systematically influenced peak grip and load force rates, as an index of predictive motor scaling. However, the effects of probabilistic cues on force rates were nonlinear, and anticipatory adaptations of the motor output generally seemed to overestimate high probabilities and underestimate low probabilities. These findings support the suggestion that anticipatory adaptations and force scaling of the motor system can integrate probabilistic information. However, probabilistic information seems to influence motor programs in a nonlinear fashion. [ABSTRACT FROM AUTHOR]

To examine the tradeoff between manual reaction times (RTs) and smooth pursuit accuracy, we manipulated manual RTs to a visual target presented during pursuit by using a deadline procedure that required different response speeds to a target (300, 400, or 500 ms). Participants attempted to pursue a moving row of circles as accurately as possible, while responding to a target within a preset time. Stimulus velocity and target position were manipulated. As the preset time became shorter, participants responded with faster manual RTs and larger pursuit velocity errors, irrespective of the stimulus velocity, indicating a tradeoff between manual RTs and pursuit accuracy. Pursuit velocity errors were also larger after target onset. These results not only suggest that attentional resources as well as spatial shifts of attention play an important role in maintaining accurate pursuit, but also support the notion that a manual RT task is useful for revealing the operation of attention during pursuit. [ABSTRACT FROM AUTHOR]

The involvement or noninvolvement of a clock-like neural process, an effector-independent representation of the time intervals to produce, is described as the essential difference between event-based and emergent timing. In a previous work (Bravi et al. in Exp Brain Res 232:1663-1675, . doi:), we studied repetitive isochronous wrist's flexion-extensions (IWFEs), performed while minimizing visual and tactile information, to clarify whether non-temporal and temporal characteristics of paced auditory stimuli affect the precision and accuracy of the rhythmic motor performance. Here, with the inclusion of new recordings, we expand the examination of the dataset described in our previous study to investigate whether simple and complex paced auditory stimuli (clicks and music) and their imaginations influence in a different way the timing mechanisms for repetitive IWFEs. Sets of IWFEs were analyzed by the windowed (lag one) autocorrelation-wγ(1), a statistical method recently introduced for the distinction between event-based and emergent timing. Our findings provide evidence that paced auditory information and its imagination favor the engagement of a clock-like neural process, and specifically that music, unlike clicks, lacks the power to elicit event-based timing, not counteracting the natural shift of wγ(1) toward positive values as frequency of movements increase. [ABSTRACT FROM AUTHOR]

The use of non-routine MRI sequences such as DIR has highlighted the role of gray matter (GM) pathology in multiple sclerosis (MS). The aim of this study was to assess the detection and relevance of cortical lesions (CLs) using MRI in early (<5 years) MS patients. 3D DIR and 3D FLAIR images at 3T from 122 patients [93 relapsing-remitting MS (RRMS), 29 clinically isolated syndrome (CIS)] were scored for CLs by two blinded readers. Patients were divided into two groups depending on the presence or absence of CLs. For FLAIR, 51 CLs were identified, of which 13 were purely intracortical and 38 mixed CLs; for DIR, this was 60 in total and 16 and 44, respectively. In both groups, there was no difference in GM fraction. Neuropsychological testing was performed for a subgroup of 66 patients. In 22.1 % of patients CLs were identified. The number of CLs revealed an association with lower working memory scores and semantical word fluency. Overall, CLs imaged with 3D FLAIR and 3D DIR sequences are found more frequently in RRMS patients than CIS and may also be a correlate for mild neuropsychological pathology. [ABSTRACT FROM AUTHOR]

Although the sensitive detection of putaminal iron deposition by T2*-weighted imaging (T2*-WI) is of diagnostic value for multiple system atrophy (MSA), the diagnostic significance of the pontine hot-cross bun (HCB) sign with increased ferritin-bound iron in the background remains unknown. We retrospectively evaluated the cases of 33 patients with cerebellar-form MSA (MSA-C) and 21 with MSA of the parkinsonian form (MSA-P) who underwent an MRI study with a 1.5-T system. Visualization of the HCB sign, posterior putaminal hypointensity and putaminal hyperintense rim on T2*-WI was assessed by two neurologists independently using an established visual grade, and were compared with those on T2-weighted imaging (T2-WI). The visual grade of pontine and putaminal signal changes was separately assessed for probable MSA (advanced stage) and possible MSA (early stage). T2*-WI demonstrated significantly higher grades of HCB sign than T2-WI (probable MSA-C, n = 27, p < 0.001; possible MSA-C, n = 6, p < 0.05; probable MSA-P, n = 13, p < 0.01). The visual grade of the HCB sign on T2*-WI in the possible MSA-C patients was comparable to that in the probable MSA-C patients. Although the HCB sign in MSA-P was of lower visual grade than in MSA-C even on T2*-WI, some patients showed evolution of the HCB sign preceding the appearance of the putaminal changes. These findings suggest that T2*-WI is of extreme value for detecting the HCB sign, which is often cited as a hallmark of MSA. The appearance of the HCB sign on T2*-WI might not only support but also improve the diagnosis of MSA. [ABSTRACT FROM AUTHOR]

The objective of the study was to develop and validate a practical prognostic index for patients with amyotrophic lateral scleroses (ALS) using information available at the first clinical consultation. We interrogated datasets generated from two population-based projects (based in the Republic of Ireland and Italy). The Irish patient cohort was divided into Training and Test sub-cohorts. Kaplan-Meier methods and Cox proportional hazards regression were used to identify significant predictors of prognoses in the Training set. Using a weighted grading system, a prognostic index was derived that separated three risk groups. The validity of index was tested in the Irish Test sub-cohort and externally confirmed in the Italian replication cohort. In the Training sub-cohort ( n = 117), significant predictors of prognoses were site of disease onset (HR = 1.7, p = 0.012); ALSFRS-R slope prior to first evaluation (HR = 2.8, p < 0.0001), and executive dysfunction (HR = 2.11, p = 0.001). The risk group system generated using these results predicted median survival time in the Training set, the Test set ( n = 87) and the Italian cohort ( n = 122) with no overlap of the 95 % CI ( p < 0.0001). In the validation cohorts, a high-risk classification was associated with a positive predictive value for poor prognosis of 73.3-85.7 % and a negative predictive value (NPV) for good prognosis of 93.3-100 %. Classification into the low-risk group was associated with an NPV for bad prognosis of 100 %. A simple algorithm using variables that can be gathered at first patient encounter, validated in an independent patient series, reliably predicts prognoses in ALS patients. [ABSTRACT FROM AUTHOR]

The progressive course of amyotrophic lateral sclerosis (ALS) results in an ever-changing spectrum of the care needs of patients with ALS. Knowledge of prognostic factors for the functional course of ALS may enhance clinical prediction and improve the timing of appropriate interventions. Our objective was to systematically review the evidence regarding prognostic factors for the rate of functional decline of patients with ALS, assessed with versions of the ALS Functional Rating Scale (ALSFRS). Two reviewers independently assessed the methodological quality of the thirteen included studies using the Quality in Prognosis Studies (QUIPS) tool. The overall quality of evidence for each prognostic factor was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, considering risk of bias, imprecision, inconsistency, indirectness, and publication bias. The quality of evidence for the prognostic value of age at onset, site of onset, time from symptom onset to diagnosis, and ALSFRS-Revised baseline score was low, mainly due to the limited data and inconsistency of results in the small number of studies included. The prognostic value of initial rate of disease progression, age at diagnosis, forced vital capacity, frontotemporal dementia, body mass index, and comorbidity remains unclear. We conclude that the current evidence on prognostic factors for functional decline in ALS is insufficient to allow the development of a prediction tool that can support clinical decisions. Given the limited data, future prognostic studies may need to focus on factors that have a predictive value for a decline in ALSFRS(-R) domain scores, preferably based on internationally collected and shared data. [ABSTRACT FROM AUTHOR]

Gait disorders represent a common and diverse challenge in Neurological practice. The literature on this field is expanding and is seeking to address mainstream clinical issues as well as a greater understanding of pathophysiological mechanisms. This update will introduce a range of these concepts. [ABSTRACT FROM AUTHOR]

It has been suggested that corticomotoneuronal drive to ankle dorsiflexors is greater than to ankle plantar flexor muscles, despite the finding that plantar flexors are no less active than TA during walking and standing. The present study was undertaken to determine whether there was differential involvement of distal lower limb muscles in amyotrophic lateral sclerosis (ALS), to elucidate pathophysiological mechanisms of selective muscle involvement. Prospective studies were undertaken in 52 ALS patients, including clinical assessment, disease staging (revised ALS functional rating scale), Medical Research Council sum score, and a scale of upper motor neurone (UMN) dysfunction. Motor unit number estimates (MUNE) and compound muscle action potentials (CMAP) from ankle dorsiflexors and plantar flexors were used to provide objective measures. A novel 'split leg index' was calculated as follows: SLI = CMAPDF ÷ CMAPPF. In ALS, there was significantly greater reduction of MUNE and CMAP amplitude recorded from plantar flexors when compared to dorsiflexors, suggesting preferential involvement of plantar flexor muscles, underpinning a 'split leg' appearance. The SLI correlated with clinical plantar flexor strength ( R= −0.56, p < 0.001). In no patient did the SLI suggest preferential dorsiflexor involvement. In subgroup analyses, mean SLI was greatest in lower limb-onset ALS. In conclusion, the present study has established dissociated involvement of muscles acting around the ankle in ALS. We suggest this reflects underlying differences in cortical, descending or local spinal modulation of these muscles. [ABSTRACT FROM AUTHOR]

Impulse control disorders (ICDs) are reported in Parkinson's disease (PD) in association with dopaminergic treatment. Approximately 25 % of patients with ICDs have multiple co-occurring ICDs (i.e. more than one diagnosed ICD). The extent to which dopaminergic neurotransmission in PD patients with multiple ICDs differs from those with only one diagnosed ICD is unknown. The aims of this study are: (1) to investigate dopamine neurotransmission in PD patients diagnosed with multiple ICDs, single ICDs and non-ICD controls in response to reward-related visual cues using positron emission tomography with C-raclopride. (2) to compare clinical features of the above three groups. PD individuals with mulitple ICDs ( n = 10), single ICD ( n = 7) and no ICDs ( n = 9) were recruited and underwent two positron emission tomography (PET) scans with C-raclopride: one where they viewed neutral visual cues and the other where they viewed a range of visual cues related to different rewards. Individuals with both multiple ICDs and single ICDs showed significantly greater ventral striatal dopamine release compared to non-ICD PD individuals in response to reward cues, but the two ICD groups did not differ from each other in the extent of dopamine release. Subjects with multiple ICDs were, however, significantly more depressed, and had higher levels of impulsive sensation-seeking compared to subjects with single ICDs and without ICDs. This is the first study to compare dopamine neurotransmission using PET neuroimaging in PD subjects with multiple vs. single ICDs. Our results suggest that striatal dopamine neurotransmission is not directly related to the co-occurrence of ICDs in PD, potentially implicating non-dopaminergic mechanisms linked to depression; and suggest that physicians should be vigilant in managing depression in PD patients with ICDs. [ABSTRACT FROM AUTHOR]

The objective of this study is to investigate the hyperintense lesions on diffusion-weighted magnetic resonance imaging (DWI) and its clinical correlation in sporadic Creutzfeldt-Jakob disease (sCJD). Patients who suffered from sCJD and followed up at the Department of Neurology at the General Hospital of the People's Liberation Army during the period of June 1, 2007 to July 1, 2014 were reviewed. The location of the hyperintense lesions on DWI, apparent diffusion coefficient (ADC) values of the hyperintense lesions were correlated with symptoms and clinical course. A total of 58 sCJD patients and ten healthy controls were included. Hyperintense lesions on DWI were observed in all the patients. The patients with basal ganglia (BG) hyperintense lesions on DWI had shorter disease duration and higher incidence of myoclonus (92 versus 44 %) than those without BG hyperintense lesions. The patients with occipital cortex hyperintense lesions on DWI had shorter disease duration between symptom onset and akinetic mutism than those without these lesions. The lower of the BG ADC value the faster presence of akinetic mutism and the shorter disease duration the patients will have. The presence of BG and occipital cortex hyperintense lesions on DWI and BG ADC values is correlated with the clinical course and clinical symptoms. [ABSTRACT FROM AUTHOR]

The purpose of this study was to identify the clinical, [F]-fluorodeoxyglucose positron emission tomography (FDG-PET) and amyloid-PET findings in a large cohort of posterior cortical atrophy (PCA) patients, to examine the neural correlates of the classic features of PCA, and to better understand the features associated with early PCA. We prospectively recruited 25 patients who presented to the Mayo Clinic between March 2013 and August 2014 and met diagnostic criteria for PCA. All patients underwent a standardized set of tests and amyloid imaging with [C] Pittsburg compound B (PiB). Seventeen (68 %) underwent FDG-PET scanning. We divided the cohort at the median disease duration of 4 years in order to assess clinical and FDG-PET correlates of early PCA ( n = 13). The most common clinical features were simultanagnosia (92 %), dysgraphia (68 %), poly-mini-myoclonus (64 %) and oculomotor apraxia (56.5 %). On FDG-PET, hypometabolism was observed bilaterally in the lateral and medial parietal and occipital lobes. Simultanagnosia was associated with hypometabolism in the right occipital lobe and posterior cingulum, optic ataxia with hypometabolism in left occipital lobe, and oculomotor apraxia with hypometabolism in the left parietal lobe and posterior cingulate gyrus. All 25 PCA patients were amyloid positive. Simultanagnosia was the only feature present in 85 % of early PCA patients. The syndrome of PCA is associated with posterior hemisphere hypometabolism and with amyloid deposition. Many of the classic features of PCA show associated focal, but not widespread, areas of involvement of these posterior hemispheric regions. Simultanagnosia appears to be the most common and hence sensitive feature of early PCA. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction is implicated in amyotrophic lateral sclerosis, where the progressive degeneration of motor neurons results in muscle atrophy, paralysis and death. Abnormalities in both central nervous system and muscle mitochondria have previously been demonstrated in patient samples, indicating systemic disease. In this case-control study, venous blood samples were acquired from 24 amyotrophic lateral sclerosis patients and 21 age-matched controls. Platelets and peripheral blood mononuclear cells were isolated and mitochondrial oxygen consumption measured in intact and permeabilized cells with additions of mitochondrial substrates, inhibitors and titration of an uncoupler. Respiratory values were normalized to cell count and for two markers of cellular mitochondrial content, citrate synthase activity and mitochondrial DNA, respectively. Mitochondrial function was correlated with clinical staging of disease severity. Complex IV (cytochrome c-oxidase)-activity normalized to mitochondrial content was decreased in platelets from amyotrophic lateral sclerosis patients both when normalized to citrate synthase activity and mitochondrial DNA copy number. In mononuclear cells, complex IV-activity was decreased when normalized to citrate synthase activity. Mitochondrial content was increased in amyotrophic lateral sclerosis patient platelets. In mononuclear cells, complex I activity declined and mitochondrial content increased progressively with advancing disease stage. The findings are, however, based on small subsets of patients and need to be confirmed. We conclude that when normalized to mitochondria-specific content, complex IV-activity is reduced in blood cells from amyotrophic lateral sclerosis patients and that there is an apparent compensatory increase in cellular mitochondrial content. This supports systemic involvement in amyotrophic lateral sclerosis and suggests further study of mitochondrial function in blood cells as a future biomarker for the disease. [ABSTRACT FROM AUTHOR]

The logopenic variant of primary progressive aphasia (lvPPA) has been associated with Alzheimer disease, although this relationship is still subject to debate. The purpose of this study is to determine the frequency of amyloid biomarkers in patients with lvPPA, and record any potential clinical or topographic differences between patients with and without amyloid deposits. We conducted cognitive examination and positron-emission tomography studies with fluorodeoxyglucose (F) and florbetapir (F) in a cohort of 16 patients diagnosed with lvPPA. We evaluated the prevalence of amyloid deposits as well as any clinical and metabolic differences between the groups with and without significant presence of amyloid deposits. Eleven patients (69 %) were considered amyloid-positive. The amyloid-positive group displayed less metabolic activity in the left temporoparietal region than the control group, while the amyloid-negative group showed lower metabolism in the left temporoparietal region extending to the anterior temporal and basal frontal regions. The percentage of change in patients with clinical and FDG-PET follow-up did not differ between the amyloid-positive and amyloid-negative subgroups. The frequency of amyloid-positive cases confirms that lvPPA is frequently associated with Alzheimer disease. Amyloid-negative patients show a different cerebral metabolic pattern. These findings show the relevance of using amyloid PET to study lvPPA, and also suggest that the logopenic variant may not be specific to Alzheimer disease in certain cases. [ABSTRACT FROM AUTHOR]

Gait and balance disorders are the major source of motor disabilities in advanced forms of Parkinson's disease (PD). Low-frequency stimulation of the pedunculopontine nucleus area (PPNa-DBS) has been recently proposed to treat these symptoms with variable clinical results. To further understand the effects of PPNa-DBS on resistant gait and balance disorders, we performed a randomised double-blind cross-over study in six PD patients. Evaluation included clinical assessment of parkinsonian disability, quality of life and neurophysiological recordings of gait. Evaluations were done 1 month before, 4 and 6 months after surgery with four double-blinded conditions assessed: with and without PPNa-DBS, with and without levodopa treatment. Four patients completed the study and two patients were excluded from the final analysis because of peri-operative adverse events (haematoma, infection). Clinically, the combination of PPNa-DBS and levodopa treatment produced a significant decrease of the freezing episodes. The frequency of falls also decreased in three out of four patients. From a neurophysiological point of view, PPNa-DBS significantly improved the anticipatory postural adjustments and double-stance duration, but not the length and speed of the first step. Interestingly, step length and speed improved after surgery without PPNa-DBS, suggesting that the lesioning effect of PPNa-DBS surgery alleviates parkinsonian akinesia. Quality of life was also significantly improved with PPNa-DBS. These results suggest that PPNa-DBS could improve gait and balance disorders in well-selected PD patients. However, this treatment may be riskier than others DBS surgeries in these patients with an advanced form of PD. [ABSTRACT FROM AUTHOR]

Parkinson disease (PD) patients may experience nonmotor symptoms (NMS) before Parkinsonism onset. Patients with idiopathic REM sleep behavior disorder (IRBD) eventually develop PD and may represent premotor PD. We aimed to evaluate the prevalence and perceived timeline of NMS in IRBD through validated scales and questionnaires used in PD research. In 44 IRBD patients and 40 matched controls, overall NMS evaluation was assessed by NMS questionnaire for Parkinson disease, olfaction by University of Pennsylvania Smell Identification Test, dysautonomia by scales for outcomes in Parkinson's disease-autonomic, constipation by Rome III criteria, depression by Hospital Anxiety and Depression Scale, cognitive impairment by Montreal cognitive assessment (MoCA) and hypersomnia by Epworth Sleepiness Scale. Patients were asked to report the perceived time of onset of hyposmia, constipation, and depression. Hyposmia (52.3 vs. 20.0 %, p = 0.002) and constipation (56.8 vs. 20.0 %, p = 0.001) were more frequent in patients than in controls. Patients reported more memory problems and showed a trend toward lower score in MoCA. Depression and hypersomnia were not more frequent in patients. The first symptom perceived was RBD in 38.6 % patients, hyposmia in 15.9 %, constipation in 11.4 %, and depression in 6.8 %. The temporal course of the NMS studied was heterogeneous. The three most common presentations were RBD followed by hyposmia; hyposmia followed by RBD; and hyposmia followed by RBD and constipation occurring at the same time span. IRBD patients frequently exhibit NMS that occur in premotor PD, particularly hyposmia and constipation. In IRBD, the perceived timeline of NMS is highly variable. This variability may suggest that pathological changes occurring in IRBD subjects are also heterogeneous and not restricted to the structures that regulate REM sleep. [ABSTRACT FROM AUTHOR]

The objective of the study was to investigate whether cognitive and behavioural impairment in Amyotrophic Lateral Sclerosis (ALS) contributes to caregiver burden, and whether carer burden affects patient outcome. Thirty-three dyads of incident patients with ALS and their primary caregivers ( n = 33) completed a series of measures to determine cognitive and behavioural profiles, (patients) and carer burden (carers) to investigate the psychological impact of ALS, and the impact of behavioural change since the onset of ALS. Caregivers were divided into high- and low-burden groups using previously established norms. High burden in carers was associated with significantly higher apathy ( p = 0.009), disinhibition ( p = 0.005), and executive dysfunction ( p = 0.015) in patients. Regression analyses for burden confirmed significant predictors such as change in apathy ( r = 0.390, F = 5.19, p = 0.03), disinhibition ( r = 0.530, F = 11.32, p = 0.002), and executive dysfunction ( r = 0.372, F = 4.66, p = 0.039), with total behaviour change contributing to 31 % of caregiver burden ( r = 0.563, F = 4.17, p = 0.015). Total distress as measured by the Hospital Anxiety and Depression Scale was also a significant predictor of caregiver burden, contributing to 38.5 % of variance ( r = 0.621, F = 18.79, p < 0.000). Caregiver burden did not affect survival ( p = 0.496). Caregiver burden in ALS is modulated by patient's cognitive and behavioural status, but does not significantly impact patient survival. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for motor impairments in Parkinson's disease (PD) but its effect on the motivational regulation of action control is still not fully understood. We investigated whether DBS of the STN influences the ability of PD patients to act for anticipated reward or loss, or whether DBS improves action execution independent of motivational valence. 16 PD patients (12 male, mean age = 58.5 ± 10.17 years) treated with bilateral STN-DBS and an age- and gender-matched group of healthy controls (HC) performed a go/no-go task whose contingencies explicitly decouple valence and action. Patients were tested with (ON) and without (OFF) active STN stimulation. For HC, there was a benefit in performing rewarded actions when compared to actions that avoided punishment. PD patients showed such a benefit reliably only when STN stimulation was ON. In fact, the relative behavioral benefit for go for reward over go to avoid losing was stronger in the PD patients under DBS ON than in HC. In PD patients, rather than generally improving motor functions independent of motivational valence, modulation of the STN by DBS improves action execution specifically when rewards are anticipated. Thus, STN-DBS establishes a reliable congruency between action and reward ('Pavlovian congruency') and remarkably enhances it over the level observed in HC. [ABSTRACT FROM AUTHOR]

The causes of weight loss in Huntington's disease (HD) are not entirely clear. The aim was to identify risk factors that are associated with a loss of metabolically active tissues, i.e. fat-free mass. A consecutive cohort of non-diabetic HD participants (manifest HD, n = 43; CAG: mean 43.6.0 ± 3.6; preHD, n = 10; CAG: mean 41.4 ± 1.4) and 36 healthy controls was recruited. Twenty-five HD participants were early-stage HD (UHDRS Total Functional Capacity [TFC] stages I and II), 12 mid-stage HD (TFC stage III), and 6 participants were in late-stage HD (TFC stages IV and V). Food intake, basic metabolic rate and glucose homeostasis were assessed. In addition, fat-free mass was determined using bioelectric impedance analysis, and leptin, insulin and ghrelin as key metabolic regulators. Sex ratio and age were similar in HD participants (71 % women; age 50.6 ± 10.9) and controls (66 % women; age 46.4 ± 14.5). Body mass index (BMI) was lower in HD participants than controls (median 24.1 vs. 25.9, p = 0.04). However, fat-free mass and basic metabolic rate were not statistically different between groups and showed no association with disease burden. In controls and HD participants, leptin was the most important predictor of fat-free mass. While BMI was lower in HD participants, fat-free mass was similar to controls with leptin as its most important predictor. Leptin levels and fat-free mass measurements using bioelectric impedance analysis may be good screening tools to identify HD patients at risk for weight loss. [ABSTRACT FROM AUTHOR]

Laryngeal dystonia (LD) is a task-specific focal dystonia of unknown pathophysiology affecting speech production. We examined the demographics of anecdotally reported alcohol use and its effects on LD symptoms using an online survey based on Research Electronic Data Capture (REDCap™) and National Spasmodic Dysphonia Association's patient registry. From 641 participants, 531 were selected for data analysis, and 110 were excluded because of unconfirmed diagnosis. A total of 406 patients (76.5 %) had LD and 125 (23.5 %) had LD and voice tremor (LD/VT). The consumption of alcohol was reported by 374 LD (92.1 %) and 109 LD/VT (87.2 %) patients. Improvement of voice symptoms after alcohol ingestion was noted by 227 LD (55.9 % of all patients) and 73 LD/VT (58.4 %), which paralleled the improvement observed by patient's family and/or friends in 214 LD (57.2 %) and 69 LD/VT (63.3 %) patients. The benefits lasted 1-3 h in both groups with the maximum effect after 2 drinks in LD patients ( p = 0.002), whereas LD/VT symptoms improved independent of the consumed amount ( p = 0.48). Our data suggest that isolated dystonic symptoms, such as in LD, are responsive to alcohol intake and this responsiveness is not attributed to the presence of VT, which is known to have significant benefits from alcohol ingestion. Alcohol may modulate the pathophysiological mechanisms underlying abnormal neurotransmission of γ-aminobutyric acid (GABA) in dystonia and as such provide new avenues for novel therapeutic options in these patients. [ABSTRACT FROM AUTHOR]

The purpose of this study is to investigate whether the topological organization of whole-brain functional network is disrupted in patients with Parkinson's disease (PD). We employed resting-state functional MRI (R-fMRI) and graph theory to investigate the topological organization of the functional connectome in 47 early-stage drug-naïve PD patients and 47 healthy control subjects. Correlations between network properties and clinical variables were tested. Both the PD and control groups showed small-world architecture in brain functional networks. However, the PD patients had lower clustering coefficient and local efficiency relative to control subjects, indicating disrupted topologic organization and a shift toward randomization in their functional brain network. At node and connection level, reduced node centralities and connectivity strength were found mainly in temporal-occipital regions and also in sensorimotor regions of PD patients. In PD patients, altered global network properties correlated with cognitive function, while motor impairment was correlated with local connection changes. This study demonstrates a disruption of whole-brain topological organization of the functional brain networks in early-stage drug-naïve PD patients and this disruption might contribute to preclinical changes in cognitive process in these patients. [ABSTRACT FROM AUTHOR]

In epilepsy trials a substantial proportion of patients receiving placebo has some improvement or experience adverse events (AEs) which match those related to active drug. The characterization of factors influencing these responses is crucial for a better comprehension of study results and to improve design of new trials. Seventy-one placebo-controlled, double-blind trials in drug-resistant focal epilepsies has been selected. The effect of multiple factors on some outcome measures were explored using a meta-regression model. For subjective and objective AEs, risk difference (RD) was calculated and entered in an inverse variance-weighted linear meta-regression model as independent variable to evaluate the relationship with data reported in placebo-treated patients. The number of study arms influence the percentage of patients withdrawing because of AEs and the highest dose of the experimental drug used in each RCT correlates with withdrawal because of AEs and with subjective AEs. Higher titration speed is associated with lower percentages of responders and higher reporting of both objective and subjective AEs. The correlation between proportions of placebo-treated patients with subjective and objective neurological AEs and relative RD, was significant ( P = 0.002 r = 0.364 and P < 0.001 r = 0.650, respectively). Efficacy and tolerability outcomes of the placebo groups are intrinsically tied to the trial methodology and to the outcomes observed in patients treated with the active drug. The correlation for objective and subjective AEs between RD and the placebo-treated patients suggest that investigators are influenced by factors which operate within each specific trial. [ABSTRACT FROM AUTHOR]

Drug-associated cues elicit conditioned responses in human drug users, and are thought to facilitate a drug-seeking behavior. Yet, little is known about how these associations are acquired, or about the specificity of the conditioned response modalities. In this study, healthy, nondependent volunteers (N=90) completed a conditioning paradigm in which they received a moderate dose of methamphetamine paired with one stimulus and placebo with another stimulus, each on two separate occasions. Their responses to these cues were measured with a behavioral preference, self-reported 'liking', emotional reactivity, and attentional bias measures, both before and after the conditioning. Following the conditioning procedure, subjects exhibited a behavioral preference, positive emotional reactivity, and attentional bias toward the methamphetamine-associated cue, compared with the placebo stimulus. In addition, subjects who reported greater positive subjective drug effects during the conditioning displayed a more robust conditioning. This work demonstrates that healthy nondependent volunteers readily acquire conditioned responses to neutral stimuli paired with a drug. The procedure has significant value to study individual variation in acquisition of conditioned responses as a possible risk factor for drug taking, and to study the neural basis of conditioned drug responses. [ABSTRACT FROM AUTHOR]

Dysfunction of the orbitofrontal cortex (OFC) impairs the ability of individuals to flexibly adapt behavior to changing stimulus-reward (S-R) contingencies. Impaired flexibility also results from interventions that alter serotonin (5-HT) and dopamine (DA) transmission in the OFC and dorsomedial striatum (DMS). However, it is unclear whether similar mechanisms underpin naturally occurring variations in behavioral flexibility. In the present study, we used a spatial-discrimination serial reversal procedure to investigate interindividual variability in behavioral flexibility in rats. We show that flexibility on this task is improved following systemic administration of the 5-HT reuptake inhibitor citalopram and by low doses of the DA reuptake inhibitor GBR12909. Rats in the upper quintile of the distribution of perseverative responses during repeated S-R reversals showed significantly reduced levels of the 5-HT metabolite, 5-hydroxy-indoleacetic acid, in the OFC. Additionally, 5-HT2A receptor binding in the OFC of mid- and high-quintile rats was significantly reduced compared with rats in the low-quintile group. These perturbations were accompanied by an increase in the expression of monoamine oxidase-A (MAO-A) and MAO-B in the lateral OFC and by a decrease in the expression of MAO-A, MAO-B, and tryptophan hydroxylase in the dorsal raphé nucleus of highly perseverative rats. We found no evidence of significant differences in markers of DA and 5-HT function in the DMS or MAO expression in the ventral tegmental area of low- vs high-perseverative rats. These findings indicate that diminished serotonergic tone in the OFC may be an endophenotype that predisposes to behavioral inflexibility and other forms of compulsive behavior. [ABSTRACT FROM AUTHOR]

The differentiation of combined mesial and lateral temporal onset of seizures (mesio-lateral TLE, MLTLE) from lateral TLE (LTLE) is critical to achieve good surgical outcomes. However, the functional neuroimaging features in LTLE patients based on the ictal onset zone utilizing intracranial EEG (iEEG) in a large series have not been investigated. We enrolled patients diagnosed with MLTLE ( n = 35) and LTLE ( n = 53) based on the site of ictal onset zone from iEEG monitoring. MLTLE is defined when ictal discharges originate from the mesial and lateral temporal cortices independently, whereas seizures of LTLE arise exclusively from the lateral temporal cortex. Compared to patients with LTLE, patients with MLTLE were more likely to have 18F- fluorodeoxyglucose positron emission tomography (FDG-PET) hypometabolism and hyperperfusion on ictal single-photon emission computed tomography (SPECT) restricted to the temporal areas. MLTLE patients had more frequent aura or secondarily generalized seizures than LTLE patients. No significant differences were found in scalp EEG, MRI, and Wada asymmetry between groups. The overall seizure-free rate was good (73.8 %, mean follow-up = 9.7 years), which was not different (Engel class I, 74.3 % in MLTLE vs. 73.6 % in LTLE). Postsurgical memory function was spared in LTLE patients, while visual memory was impaired in MLTLE patients when their mesial temporal structures were sufficiently resected. It suggests that functional neuroimaging (interictal PET and ictal and interictal SPECT) may play a crucial role to differentiate between MLTLE and LTLE. [ABSTRACT FROM AUTHOR]

Our ability to control and inhibit behaviours that are inappropriate, unsafe, or no longer required is crucial for functioning successfully in complex environments. Here, we investigated whether a series of ocular motor (OM) inhibition tasks could dissociate deficits in patients with multiple sclerosis (MS), including patients with only a probable diagnosis (clinically isolated syndrome: CIS), from healthy individuals as well as a function of increasing disease duration. 25 patients with CIS, 25 early clinically definite MS patients (CDMS: ≤7 years of diagnosis), 24 late CDMS patients (>7 years from diagnosis), and 25 healthy controls participated. All participants completed a series of classic OM inhibition tasks [antisaccade (AS) task, memory-guided (MG) task, endogenous cue task], and a neuropsychological inhibition task [paced auditory serial addition test (PASAT)]. Clinical disability was characterised in CDMS patients using the Expanded Disability Severity Scale (EDSS). OM (latency and error) and PASAT performance were compared between patient groups and controls, as well as a function of disease duration. For CDMS patients only, results were correlated with EDSS score. All patient groups made more errors than controls on all OM tasks; error rate did not increase with increasing disease duration. In contrast, saccade latency (MG and endogenous cue tasks) was found to worsen with increasing disease duration. PASAT performance did not discriminate patient groups or disease duration. The EDSS did not correlate with any measure. These OM measures appear to dissociate deficit between patients at different disease durations. This suggests their utility as a measure of progression from the earliest inception of the disease. [ABSTRACT FROM AUTHOR]