Impairment of neuromuscular transmission in transient global amnesia – Does it really exist?

BackgroundThe main hypotheses regarding mechanisms of transient global amnesia (TGA) are ischemia in hippocampal structures, epileptic genesis, and migraine. In accordance with the hypothesis of a shared, common pathophysiological mechanism in both TGA and migraine, neuromuscular transmission (NMT) abnormalities previously found in migraine were also suspected in TGA.ObjectiveThe aim of our study was to analyze NMT in TGA patients to reveal a subclinical impairment of neuromuscular transmission as a possible indicator of underlying channelopathy, which would point to a shared etiology with migraine.Materials and methodsThe study group consisted of 15 patients (6 males) with TGA (mean age 69.5 ± 7.4 yrs). The duration of amnesia ranged from 1 to 6 h (mean 4.4 h). Single fiber electromyography (SFEMG), the most sensitive tool for NMT assessment, of the voluntarily activated frontal muscle was performed 1–5 days after a TGA incident.ResultsAbnormal SFEMG was found in 1 patient (6.6%). In all other patients, SFEMG was in the normal range.ConclusionOur neurophysiological study does not confirm NMT defects in TGA. The role of channelopathy with NMT dysfunction in the pathogenesis of TGA is rather unlikely, whereas subclinical NMT abnormalities were certainly proven in migraine.     

Episodic memory in transient global amnesia: encoding,storage, or retrieval deficit?

OBJECTIVES: To assess episodic memory (especially anterograde amnesia) during the acute phase of transient global amnesia to differentiate an encoding, a storage, or a retrieval deficit. METHODS: In three patients, whose amnestic episode fulfilled all current criteria for transient global amnesia, a neuropsychological protocol was administered which included a word learning task derived from the Grober and Buschke's procedure. RESULTS: In one patient, the results suggested an encoding deficit, and in two others, a storage deficit. CONCLUSIONS: The encoding/storage impairment concerning anterograde amnesia documented in our patients stands in clear contrast with the impairment in retrieval which must underly the retrograde amnesia that also characterises transient global amnesia. This dissociation in turn favours the idea of a functional independence among the cognitive mechanisms that subserve episodic memory.     

Assessing attention in the zebrafish: Are we there yet?

Traditionally, rodent sustained attention models are used for studying the neurobiological underpinnings of attention, for assessing the disruptive and interactive effects of drugs and environmental toxins and for predicting the efficacy of pharmacotherapies for attention disorders. Virtually all-major psychiatric disorders are characterized by disturbances in attention or concentration. Additionally, many psychoactive drugs produce simultaneous effects on a variety of psychological processes. Behavioral measures in tasks designed to assess cognitive processes in rodents characterize and dissociate these multiple influences. While the zebrafish (Danio rerio) has been at the vanguard of neurobiological research and is increasing in popularity as a model organism for behavioral applications, their attentional capacity has not been fully assessed. Here we review some of the more popular animal models and discuss the utility of a choice discrimination zebrafish model.     

Can we solve the mysteries of the National Vietnam Veterans Readjustment Study?

The National Vietnam Veterans Readjustment Study (NVVRS) researchers reported that 30.9% of all men who served in that conflict developed posttraumatic stress disorder (PTSD) even though only about 15% had been assigned to combat units. Scholars, mainly historians, have questioned the accuracy of the PTSD prevalence rate. The purpose of this article is to evaluate the merits of several hypotheses adduced to explain the high apparent PTSD prevalence in the NVVRS. Empirical and conceptual analysis suggests that malingering is unlikely to account for many cases. Also, deployment to Vietnam in the absence of exposure to classic traumatic stressors is likewise unlikely to account for many cases. There are three plausible explanations for the high prevalence rate of PTSD in the NVVRS. First, DSM-III-R PTSD criteria, used in the NVVRS, did not require that symptoms produce impairment. Accordingly, some PTSD-positive cases may actually have been leading productive lives, despite occasional nightmares, or other stress responses. Second, some men assigned to non-combat duty (e.g., medics) may have been exposed to PTSD-inducing stressors. Third, some respondents may have invoked the Vietnam-PTSD narrative to make sense of postwar psychological difficulties having diverse causes unrelated to their military service. These three factors likely contribute to the high PTSD prevalence rate in the NVVRS.     

What is simulated in the action observation network when we observe actions?

In the last decade there has been a great amount of research investigating the role of simulation in our ability to infer the underlying intentions of any observed action. The majority of studies have focussed on the role of mirror neurons and the network of cortical areas active during action observation (AON) in inferring the goal of an observed action. However, it remains unclear what precisely is simulated when we observe an action and how such simulations can enable the observer to infer the underlying intention of that action. In particular it is not known how simulation in the AON enables the inference of the same goal when the kinematics observed to achieve that goal differ, such as when reaching to grasp an object with the left or right hands. Here we performed a behavioural study with healthy human subjects to address this question. We show that the subjects were able to detect very subtle changes in the kinematics of an observed action. In addition, we fitted the behavioural responses with a model based on the predictive coding account of mirror neurons. This is a Bayesian account of action observation that can be explained by the free-energy principle. Here we show that we can model all the effects observed when the action observation system is considered within a predictive coding framework.     

Intervening to reduce the risk of future disability from multiple sclerosis: are we there yet?

Disease-modifying therapies (DMTs) delay or may prevent the progression of patients with high-risk clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (MS), and from relapsing–remitting MS to secondary progressive MS. Current evidence on the effects of DMT on disability in MS is supported by the use of the Expanded Disability Status Scale (EDSS), which is dominated by ambulation, and usually used as a secondary outcome measure. Less is known about the long-term effects of DMTs on other aspects of functional status, particularly cognition, which is a key determinant of ability to work. The time scale for measurements of disability is at most a few years, with scant data from more than 10 years of observation. Longer prospective follow-up of large numbers of patients with CIS is needed to determine whether early intervention with a DMT influences long-term disease progression. Finally, the emergence of the radiologically isolated syndrome (RIS) as a clinical entity has shifted the debate about when to intervene to an even earlier time frame. Balancing the significant side-effects associated with DMT in general and the expected outcome of pharmacologic intervention is increasingly problematic for managing patients with uncertain prognosis, as many patients may have low-risk CIS, benign MS or patients with RIS only. Preventing long-term disability in MS should be recognised more clearly as an important outcome in its own right, with disability measured more consistently with more sensitive instruments beyond the use of the EDSS.     

Treatment of obesity in the primary care setting: are we there yet?

Obesity is a significant public health issue in the US constituting an independent risk factor for morbidity and mortality as well as complicating the management of other medical conditions. Yet, traditionally most physicians receive little training in evidence-based obesity interventions. Previous literature suggests many physicians believe they do not have effective tools to address obesity and/or that obesity management is not within their scope of practice. Given the new emphasis from NIH and AAFP urging physicians to conceptualize and treat obesity as a chronic medical condition, we examined obesity-related knowledge and practices among military and civilian primary care physicians. Results were similar across these two physician groups in suggesting many physicians still may be ill-prepared to manage obesity in the primary care setting. Implications for patient care and future research are discussed.     

Can we overcome the ‘clinico-radiological paradox’ in multiple sclerosis?

The association between common neuroradiological markers of multiple sclerosis (MS) and clinical disability is weak, a phenomenon known as the clinico-radiological paradox. Here, we investigated to which degree it is possible to predict individual disease profiles from conventional magnetic resonance imaging (MRI) using multivariate analysis algorithms. Specifically, we conducted cross-validated canonical correlation analyses to investigate the predictive information contained in conventional MRI data of 40 MS patients for the following clinical parameters: disease duration, motor disability (9-Hole Peg Test, Timed 25-Foot Walk Test), cognitive dysfunction (Paced Auditory Serial Addition Test), and the expanded disability status scale (EDSS). It turned out that the information in the spatial patterning of MRI data predicted the clinical scores with correlations of up to 0.80 (p?相似文献   

Can we protect the brain via preconditioning?Role of microRNAs in neuroprotection

正Preconditioning stimulus:Preconditioning is an adaptive response,whereby a small dose of a harmful substance protects the brain from a subsequent damaging insult(Dirnagl et al.,2009).The concept of preconditioning was first described in an ischemic heart model,it was observed that brief ischemic episodes protect against a subsequent ischemic insult(Murry et     

Basal ganglia volumetric studies in affective disorder: what did we learn in the last 15 years?

Until today, morphometric neuroimaging studies on affective disorders concentrate on the limbic system, especially the hippocampus, amygdala, and anterior cingulate. In most of the studies and reviews available today, the basal ganglia are of secondary interest. It seems that the basal ganglia are interest of neurologist, whereas the limbic system is reserved for psychiatric neuroimaging studies. We follow a different approach in this review, studying all available papers on MRI research of the basal ganglia in unipolar depression and bipolar disorder. We found a possibly larger neostriatum in bipolar and possibly smaller one in unipolar patients. None of the unipolar studies found any larger basal ganglion, and only one out of 12 bipolar studies found smaller basal ganglia. Both findings seemed to depend on age (tendency toward smaller volumes in unipolar and bipolar with older age), sex (men tending to pathology in both disorders) and bipolar patients show a possible influence of medication, which is not assessed so far in unipolar depression. We conclude that several methodological shortcomings in volumetric MRI research on the basal ganglia in affective disorders make it necessary to imply more research in this area. We suggest (a) better MRI methods (we do not have a single volumetric 3 Tesla study in this patient group); (b) studies of medication-na?ve patients (thus ruling out the medication effect); (c) Studies that directly compare unipolar depressed and bipolar patients are needed to determine whether these apparent differences in morphometric abnormalities, as observed through the mediating comparison with healthy subjects, are real.     

Can we pass from the experimental to the clinical phase in MS stem cell research?

A crucial point in development of new treatments is the step from the experimental level to the first clinical trials. For stem cell treatments in general, but for stem cell treatment in Multiple Sclerosis specifically, this is the question for the moment. To answer this question a rational analysis of the hypotheses and the suppositions behind the application of stem cells is necessary, as well as a review of the present knowledge, the risks and the gains to be expected. This is a personal analysis of 32 oral presentation and discussions of the European Charcot Foundation Symposium, Taormina 2006. It is the application of the Kenter and Cohen [Kenter MJH, Cohen AF. Establishing risk of human experimentation with drugs: lessons from TGN 1412. Lancet 2006; 368:1387-91] approach, adapted for stem cell treatment in MS. About half of the pertinent issues plead for the start of clinical experiments now. However, the absence of knowledge on deleterious effects and their predictability heavily weights against it. Organisational and funding aspects were discussed to prevent uncritical, uncontrolled clinical approaches.