Effects of long-duration space flights on characteristics of the vertical gaze fixation reaction.

The aim of the study was to examine effects of long-duration exposure to weightlessness on characteristics of the vertical gaze fixation reaction (GFR). The subjects were to perform the target acquisition task on visual stimuli that appeared at a distance of 16 deg. up- and down from the primary position in a random order. Experiments were performed before launch, during flight and after landing. Before flight time of gaze fixation reaction did not exceed 650 ms. During space flight (SF) it extended up to 900-1000 ms and more. The velocities of head movement in space decreased, but the velocities of eye counterrotation decreased to a lesser degree. This difference resulted in sharp increase of vertical vestibular ocular reflex (VOR) gain (up to 4.3 values in one of the cosmonauts) during the 1st month of flight; further it decreased reaching the values of 0.5-0.7 on the 5th month of SF. After landing vertical VOR gain increased greatly again. These results in the vertical axis are in agreement with the data of Kozlovskaya et al., which showed in experiments with monkeys that horizontal VOR gain increased together with redundant inadequate responses of vestibular nucleus on vestibular stimulation and that in the course of adaptation to these conditions central nervous system inhibited vestibular input from the motor control system.

The vegetative state--a syndrome in search of a name.

In 2002, Bryan Jennett chose the caption "A syndrome in search of a name" for the first chapter of his book "The vegetative state--medical facts, ethical and legal dilemmas", which, in summary, can be taken as his legacy. Jennett coined the term "VegetativeState" (VS), which became the preferential name for the syndrome of wakeful unresponsiveness in the English literature, with the intention to specify the concern and dilemmas in connection with the naming "vegetative", "persistent" and "permanent". In Europe, Apallic Syndrome (AS) is still in use. The prevalence of VS/AS in hospital settings in Europe is 0.5-2/100.000 population year; one-third traumatic brain damage, 70% following intracranial haemorrhages, tumours, cerebral hypoxemia after cardiac arrest, and end stage of certain progressive neurological diseases. VS/AS reflects brain pathology of (a) consciousness, self-awareness, (b) behaviour, and (c) certain brain structures, so that patients are awake but total unresponsive. The ambiguity of the naming "vegetative" (meant to refer to the preserved vegetative (autonomous nervous system) can suggest that the patient is no more a human but "vegetable" like. And "apallic" does not mean being definitively and completely anatomically disconnected from neocortical structures. In 2009, having joined the International Task Force on the Vegetative State, we proposed the new term "Unresponsive Wakefulness Syndrome" (UWS) to enable (neuro-)scientists, the medical community, and the public to assess and define all stages accurately in a human way. The Unresponsive Wakefulness Syndrome (UWS) could replace the VS/AS nomenclature in science and public with social competence.

Mild traumatic brain injury.

Traumatic Brain Injury (TBI) is among the most frequent neurological disorders. Of all TBIs 90% are considered mild with an annual incidence of 100­300/100.000. Intracranial complications of Mild Traumatic Brain Injury (MTBI) are infrequent (10%), requiring neurosurgical intervention in a minority of cases (1%), but potentially life-threatening (case fatality rate 0,1%). Hence, a true health management problem exists because of the need to exclude the small chance of a life threatening complication in large numbers of individual patients. The 2002 EFNS guidelines used a best evidence approach based on the literature until 2001 to guide initial management with respect to indications for CT, hospital admission, observation and follow up of MTBI patients. This updated EFNS guideline version for initial management inMTBI proposes a more selectively strategy for CT when major (dangerous mechanism, GCS<15, 2 points deterioration on the GCS, clinical signs of (basal) skull fracture, vomiting, anticoagulation therapy, post traumatic seizure) or minor (age, loss of consciousness, persistent anterograde amnesia, focal deficit, skull contusion, deterioration on the GCS) risk factors are present based on published decision rules with a high level of evidence. In addition clinical decision rules for CT now exist for children as well. Since 2001 recommendations, although with a lower level of evidence, have been published for clinical in hospital observation to prevent and treat other potential threads to the patient including behavioral disturbances (amnesia, confusion and agitation) and infection.

Variability of BOLD response evoked by foot vibrotactile stimulation: influence of vibration amplitude and stimulus waveform.

The aim of the present was study to evaluate cortical and subcortical neural responses on vibrotactile stimulation of the food and to assess somatosensory evoked BOLD responses in dependence of vibration amplitude and stimulus waveform. Sixteen healthy male subjects received vibrotactile stimulation at the sole of the right foot. The vibration stimulus was delivered through a moving magnet actuator system (MMAS). In an event-related design, a series of vibration stimuli with a duration of 1 s and a variable interstimulus interval was presented. Four stimulation conditions were realized using a 2 (amplitudes 0.4 mm or 1.6 mm) x 2 (waveform sinusoidal or amplitude modulated) factorial design. Stimulating with 0.4 mm amplitude compared to 1.6 mm stimulus amplitude more strongly activated the pre- and postcentral gyrus bilaterally and the right inferior, medial and middle frontal gyrus. In the reverse comparison significant differences were observed within the left inferior parietal lobule, the left superior temporal gyrus, and the left temporal transverse gyrus. In the comparison of sinusoidal versus modulated waveform and vice versa no significant activation differences were obtained. The inter-subject variability was high but when all four stimulation conditions were jointly analyzed, a significant activation of S1 was obtained for every single subject. This study demonstrated that the BOLD response is modulated by the amplitude but not by the waveform of vibrotactile stimulation. Despite high inter-individual variability, the stimulation yielded reliable results for S1 on the single-subject level. Therefore, our results suggest that vibrotactile testing could evolve into a clinical tool in functional neuroimaging.

Alterations of characteristics of horizontal gaze fixation reaction in long-term space flights.

The study was performed to explore effects of long-duration SF on the characteristics of horizontal gaze fixation reaction (hGFR). Changes in GFR observed in long-duration space flight (SF) point out to serious disturbances of the VOR system due to, apparently, altered vestibular activity. Two strategies of reaction adaptation to the microgravity conditions were discovered in cosmonauts of civic occupations and pilots.

Stepping-like movements in humans with complete spinal cord injury induced by epidural stimulation of the lumbar cord: electromyographic study of compound muscle action potentials.

STUDY DESIGN: It has been previously demonstrated that sustained nonpatterned electric stimulation of the posterior lumbar spinal cord from the epidural space can induce stepping-like movements in subjects with chronic, complete spinal cord injury. In the present paper, we explore physiologically related components of electromyographic (EMG) recordings during the induced stepping-like activity. OBJECTIVES: To examine mechanisms underlying the stepping-like movements activated by electrical epidural stimulation of posterior lumbar cord structures. MATERIALS AND METHODS: The study is based on the assessment of epidural stimulation to control spasticity by simultaneous recordings of the electromyographic activity of quadriceps, hamstrings, tibialis anterior, and triceps surae. We examined induced muscle responses to stimulation frequencies of 2.2-50 Hz in 10 subjects classified as having a motor complete spinal cord injury (ASIA A and B). We evaluated stimulus-triggered time windows 50 ms in length from the original EMG traces. Stimulus-evoked compound muscle action potentials (CMAPs) were analyzed with reference to latency, amplitude, and shape. RESULTS: Epidural stimulation of the posterior lumbosacral cord recruited lower limb muscles in a segmental-selective way, which was characteristic for posterior root stimulation. A 2.2 Hz stimulation elicited stimulus-coupled CMAPs of short latency which were approximately half that of phasic stretch reflex latencies for the respective muscle groups. EMG amplitudes were stimulus-strength dependent. Stimulation at 5-15 and 25-50 Hz elicited sustained tonic and rhythmic activity, respectively, and initiated lower limb extension or stepping-like movements representing different levels of muscle synergies. All EMG responses, even during burst-style phases were composed of separate stimulus-triggered CMAPs with characteristic amplitude modulations. During burst-style phases, a significant increase of CMAP latencies by about 10 ms was observed. CONCLUSION: The muscle activity evoked by epidural lumbar cord stimulation as described in the present study was initiated within the posterior roots. These posterior roots muscle reflex responses (PRMRRs) to 2.2 Hz stimulation were routed through monosynaptic pathways. Sustained stimulation at 5-50 Hz engaged central spinal PRMRR components. We propose that repeated volleys delivered to the lumbar cord via the posterior roots can effectively modify the central state of spinal circuits by temporarily combining them into functional units generating integrated motor behavior of sustained extension and rhythmic flexion/extension movements. This study opens the possibility for developing neuroprostheses for activation of inherent spinal networks involved in generating functional synergistic movements using a single electrode implanted in a localized and stable region.

The influence of microgravity on memorized arm movements.

To investigate sensory and motor functions in microgravity, goal-oriented arm movements were performed by 9 cosmonauts in weightlessness. The ability to reproduce predefined motor patterns was examined pre-, in-, and post-flight under two different paradigms: In a first test, the cosmonaut had to reproduce passively learned movements with eyes closed, while in the second test, the cosmonaut learned the pattern with eyes open. The different learning paradigms effected the metric parameters of the memorized stimulus pattern while the influence of the different gravity levels resulted in significant offsets and torsions of the reproduced figures. In comparing the inflight condition with preflight, intact proprioceptive afference seemed to play an important role for reproducing movements from motor short-time memory correctly.

Initiating extension of the lower limbs in subjects with complete spinal cord injury by epidural lumbar cord stimulation.

We provide evidence that the human spinal cord is able to respond to external afferent input and to generate a sustained extension of the lower extremities when isolated from brain control. The present study demonstrates that sustained, nonpatterned electrical stimulation of the lumbosacral cord--applied at a frequency in the range of 5-15 Hz and a strength above the thresholds for twitches in the thigh and leg muscles--can initiate and retain lower-limb extension in paraplegic subjects with a long history of complete spinal cord injury. We hypothesize that the induced extension is due to tonic input applied by the epidural stimulation to primary sensory afferents. The induced volleys elicit muscle twitches (posterior root muscle-reflex responses) at short and constant latency times and coactivate the configuration of the lumbosacral interneuronal network, presumably via collaterals of the primary sensory neurons and their connectivity with this network. We speculate that the volleys induced externally to the lumbosacral network at a frequency of 5-15 Hz initiate and retain an "extension pattern generator" organization. Once established, this organization would recruit a larger population of motor units in the hip and ankle extensor muscles as compared to the flexors, resulting in an extension movement of the lower limbs. In the electromyograms of the lower-limb muscle groups, such activity is reflected as a characteristic spatiotemporal pattern of compound motor-unit potentials.

Slowing of human arm movements during weightlessness: the role of vision.

The human motor system responds to weightlessness by the slowing of movement. It has been suggested that deficits in visuo-motor co-ordination cause this effect. We studied the mechanisms of the slowing of movement in three long-term missions to the Russian space station Mir. In particular, the role of vision in the control of movement in microgravity has been studied in these experiments on seven cosmonauts, pre-, in-, and post-flight. The cosmonauts made arm movements to visual targets under the following conditions of visual control: no visual control, interrupted visual control, and undisturbed visual control. The results showed that the slowing of movement during weightlessness was manifested by decreases of peak velocity and peak acceleration, was not associated with a prolongation of the movement phase of deceleration, and was not affected by manipulation of the conditions of visual control. The slowing of movement tended to subside after the months of the flight and completely disappeared within days after the landing. Accuracy of the movements strictly depended on the constraints imposed on the vision and remained unaffected in-flight. The data presented demonstrate that the slowing of movement in microgravity is not directly related to deficits in sensori-motor co-ordination and is not associated with a reduction of the accuracy of movement. The strategy for motor control in microgravity seems to be directed towards the generation of smooth movements and the maintenance of their accuracy.

EFNS guideline on mild traumatic brain injury: report of an EFNS task force.

In 1999, a Task Force on Mild Traumatic Brain Injury (MTBI) was set up under the auspices of the European Federation of Neurological Societies. Its aim was to propose an acceptable uniform nomenclature for MTBI and definition of MTBI, and to develop a set of rules to guide initial management with respect to ancillary investigations, hospital admission, observation and follow-up.

Epidural electrical stimulation of posterior structures of the human lumbosacral cord: 3. Control Of spasticity.

OBJECTIVES: The purpose of this study was to evaluate the effect of spinal cord stimulation (SCS) on severe spasticity of the lower limbs in patients with traumatic spinal cord injury (SCI) under close scrutiny of the site and parameters of stimulation. MATERIALS AND METHODS: Eight SCI patients (four women, four men) were included in the study. Levels of spasticity before and during stimulation were compared according to a clinical rating scale and by surface electrode polyelectromyography (pEMG) during passive flexion and extension of the knee, supplemented by a pendulum test with the stimulating device switched either on or off over an appropriate period. RESULTS: Both the clinical and the experimental parameters clearly demonstrated that SCS, when correctly handled, is a highly effective approach to controlling spasticity in spinal cord injury subjects. The success of this type of treatment hinges on four factors: (1) the epidural electrode must be located over the upper lumbar cord segment (L1, L2, L3); (2) the train frequency of stimulation must be in the range of 50 - 100 Hz, the amplitude within 2 - 7 V and the stimulus width of 210 micross; (3) the stimulus parameters must be optimized by clinically assessing the effect of arbitrary combinations of the four contacts of the quadripolar electrode; and (4) amplitudes of stimulation must be adjusted to different body positions. CONCLUSIONS: Severe muscle hypertonia affecting the lower extremities of patients with chronic spinal cord injuries can be effectively suppressed via stimulation of the upper lumbar cord segment.

Adolf Hitler's Parkinson's disease and an attempt to analyse his personality structure.

It has been proved that Adolf Hitler suffered from idiopathic Parkinson's disease. No indication for postencephalitic parkinsonism was found in the clinical symptoms or the case history. Professor Max de Crinis established his diagnosis of Parkinson's disease in Hitler early in 1945 and informed the SS leadership, who decided to initiate treatment with a specially prepared 'antiparkinsonian mixture' to be administered by a physician. However, Hitler never received the mixture, this implies that the SS intended to remove the severely diseased 'Leader'. Two different character traits can be analysed in Hitler's personality: on the one hand the typical premorbid personality of parkinsonian patients with uncorrectable mental rigidity, extreme inflexibility and insupportable pedantry. On the other an antisocial personality disorder with lack of ethical and social values, a deeply rooted tendency to betray others and to deceive himself and uncontrollable emotional reactions. This special combination in Hitler's personality resulted in the uncritical conviction of his mission and an enormous driving for recognition. The neuropsychiatric analysis of Hitler's personality could lead to a better explanation of the pathological traits of one of the most conspicuous historical personalities.

The effect of head-to-trunk position on the direction of arm movements before, during, and after space flight.

This contribution deals with the examination of the consequences of different head-to-trunk positions on arm movements under normal gravity and during prolonged space flight. One of the objectives of this study was to investigate the influence of weightlessness on the condition of the spatial analysis system. Aimed arm movements in the horizontal plane (pointings towards two visual targets) were recorded, first with eyes open, head straight (learning part), then with eyes closed, head straight and during yaw or roll position of the head (performance part). Measurements related to these different head-to-trunk-positions were taken in one short-term and nine long-term cosmonauts preflight, inflight, and postflight. Terrestrial control experiments were carried out with an extended experimental design in 14 healthy volunteers. The analysis of these experiments revealed that, with eyes closed and the head in yaw position, cosmonauts before flight and control subjects exhibit significant slants of the movement plane of the arm. Contrary to terrestrial measurements, in space experiments roll tilt of the head to the right is correlated with considerable counterclockwise slant of the movement plane. This slant of the movement plane of the arm was interpreted as tilt of the internal representation of the horizontal coordinate. The effect is larger with greater distortion induced by the changed head position and with larger muscular involvement to keep this position. This effect is also increased by the reduction of information (for example, in microgravity). The amount and the direction of the horizontal offset of the arm movements are shown to be dependent on the head-to-trunk position, too. Additionally, we have found changes in the amplitude and in the duration of the arm movement, in the vertical offset, and in the curvature of the movement paths, depending on the experimental conditions.

Presence of Klùver-Bucy syndrome as a positive prognostic feature for the remission of traumatic prolonged disturbances of consciousness.

After severe brain injury a prolonged disturbance of consciousness may occur, sometimes with transient apallic syndrome (awakening without awareness of self and surroundings). Klùver-Bucy is described in the literature as a typical post-traumatic remission phase, in which the patients show an increase of oral automatisms and/or of sexual drive. The study describes Klùver-Bucy syndrome as a sign associated with favourable prognosis in the outcome of traumatic disturbances of consciousness in survivors of head trauma. Seventy-seven patients who had suffered severe brain injury due to traffic accidents entered into the study. All had experienced a relatively benign clinical course since they recovered full awareness, that is were able to communicate with their relatives. The occurrence of prolonged coma, of apallic syndrome and of Klùver-Bucy syndrome are related to outcome date in regards to the patient's work and family function at a mean of 32 months later. In particular, the duration of the apallic syndrome (duration of unconsciousness) was significantly correlated with the global outcome of the patients (p < 0.001).

Sleep spindles in the initial stages of the vegetative state.

The aim of this study was to look for the presence of spindling in the different stages of remission of the vegetative state to underline all possible correlations with lesional sites, severity of coma and final outcome. The nocturnal polygraphic recordings from 30 patients were examined: 20 (15M, 5F, mean age 31.7 years, range 16-41) had originally suffered a traumatic brain injury, 10 (4M, 6F, mean age 40.5 years, range 24-48) had hypoxic brain lesions. Evidence of spindling, always reduced in density and duration, was found in 44% of these patients, prevalently in the traumatic patients (53.3% versus 30% of hypoxic patients). No subjects in the full stage 0, 0-1 of the vegetative state (apallic syndrome) presented spindling. No significant correlation was found between spindling and the following parameters: gender, the time between the onset of coma and the polygraphic recording, or the site of the lesion.

Body iron stores and presence of carotid atherosclerosis. Results from the Bruneck Study.

We hypothesized that the formation of foam cells and fatty streaks requires a postsecretory oxidative modification of lipoproteins that targets them for rapid uptake by macrophages. Lipid peroxidation may in part depend on the concentration of tissue iron, one of the major oxidants in vivo. We analyzed the relation between sonographically assessed carotid atherosclerosis and body iron stores in a population sample of 847 men and women aged 40 to 79 years. In a logistic regression analysis adjusting for age, sex, and all major vascular risk markers, ferritin emerged as one of the strongest indicators of carotid artery disease in both sexes (40 to 59 years; odds ratio, 1.54 per 100 micrograms/L; P < .001). The predictive significance of ferritin was found to be synergistic with that of hypercholesterolemia. Variations in body iron stores between sexes may partly explain evident sex differences in the expression of carotid atherosclerosis. In the elderly (> or = 60 years) the predictive significance of ferritin was found to decrease parallel to that of apolipoprotein B. The current study suggests a possible role of body iron in early atherogenesis.