Broad white matter impairment in multiple system atrophy.

Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by the widespread aberrant accumulation of α-synuclein (α-syn). MSA differs from other synucleinopathies such as Parkinson's disease (PD) in that α-syn accumulates primarily in oligodendrocytes, the only source of white matter myelination in the brain. Previous MSA imaging studies have uncovered focal differences in white matter. Here, we sought to build on this work by taking a global perspective on whole brain white matter. In order to do this, in vivo structural imaging and diffusion magnetic resonance imaging were acquired on 26 MSA patients, 26 healthy controls, and 23 PD patients. A refined whole brain approach encompassing the major fiber tracts and the superficial white matter located at the boundary of the cortical mantle was applied. The primary observation was that MSA but not PD patients had whole brain deep and superficial white matter diffusivity abnormalities (p < .001). In addition, in MSA patients, these abnormalities were associated with motor (Unified MSA Rating Scale, Part II) and cognitive functions (Mini-Mental State Examination). The pervasive whole brain abnormalities we observe suggest that there is widespread white matter damage in MSA patients which mirrors the widespread aggregation of α-syn in oligodendrocytes. Importantly, whole brain white matter abnormalities were associated with clinical symptoms, suggesting that white matter impairment may be more central to MSA than previously thought.

Recommendations for tilt table testing and other provocative cardiovascular autonomic tests in conditions that may cause transient loss of consciousness : Consensus statement of the European Federation of Autonomic Societies (EFAS) endorsed by the American Autonomic Society (AAS) and the European Academy of Neurology (EAN).

An expert committee was formed to reach consensus on the use of Tilt Table Testing (TTT) in the diagnosis of disorders that may cause transient loss of consciousness (TLOC) and to outline when other provocative cardiovascular autonomic tests are needed. While TTT adds to history taking, it cannot be a substitute for it. An abnormal TTT result is most meaningful if the provoked event is recognised by patients or eyewitnesses as similar to spontaneous ones. The minimum requirements to perform TTT are a tilt table, a continuous beat-to-beat blood pressure monitor, at least one ECG lead, protocols for the indications stated below and trained staff. This basic equipment lends itself to perform (1) additional provocation tests, such as the active standing test carotid sinus massage and autonomic function tests; (2) additional measurements, such as video, EEG, transcranial Doppler, NIRS, end-tidal CO2 or neuro-endocrine tests; (3) tailor-made provocation procedures in those with a specific and consistent trigger of TLOC. TTT and other provocative cardiovascular autonomic tests are indicated if the initial evaluation does not yield a definite or highly likely diagnosis, but raises a suspicion of (1) reflex syncope, (2) the three forms of orthostatic hypotension (OH), i.e. initial, classic and delayed OH, as well as delayed orthostatic blood pressure recovery, (3) postural orthostatic tachycardia syndrome or (4) psychogenic pseudosyncope. A therapeutic indication for TTT is to teach patients with reflex syncope and OH to recognise hypotensive symptoms and to perform physical counter manoeuvres.

Dry immersion as a model of deafferentation: A neurophysiology study using somatosensory evoked potentials.

INTRODUCTION: Dry immersion is a ground-based experiment simulating the effects of weightlessness, and it is a model of acute symmetrical bilateral deafferentation. This exploratory study aimed to investigate the effects of three days of dry immersion (DI) on sensory thresholds and the functioning of lemniscal pathways, assessed by somatosensory evoked potentials (SEPs). METHODS: Twelve healthy male volunteers (32+/-4.8 years) participated in the study. Sensory thresholds and SEPs of the tibial nerve of both limbs were recorded before (D-1) and on the third day of dry immersion (D3). RESULTS: Sensory thresholds significantly decreased on D3 (-20.75 +/-21.7%; z = -2.54; p = 0.0109 on the right side and -22.18+/-17.28%; z = -3.059; p = 0.002 on the left side). The amplitude of P40 responses did not differ between D-1 and D3. Latencies of all central responses until P30 were shortened on D3 (N21 right:-0.57+/-0.31; z = -3.06; p = 0.002; N21 left -0.83+/-0.53; z = -2.94; p = 0.003; P30 right: -1.26+/-1.42; z = -3.059; p = 0.002; P30 left: -1.11+/-1.55; z = -2.27; p = 0.02). CONCLUSION: Three days of dry immersion can induce hyperexcitability of lemniscal pathways. SIGNIFICANCE: This may be explained by a change in the expression of membrane channels and/or medullar plasticity and/or hypersensitization of peripheral sensory receptors induced by this acute deafferentation. Additional studies are needed to further elucidate the mechanisms.

Combined cardiovascular and sweating autonomic testing to differentiate multiple system atrophy from Parkinson's disease.

OBJECTIVES: It can be difficult to differentiate multiple system atrophy (MSA) with predominant parkinsonism (MSA-P), a very disabling but rare disease, from Parkinson's disease (PD). Autonomic dysfunction, particularly cardiovascular autonomic neuropathy (CAN), is classically more pronounced in MSA. We investigated whether testing for CAN combined with sweat function assessment was helpful to differentiate patients with MSA from those with PD. METHODS: In this retrospective study, 62 patients with MSA-P and 96 with PD, comparable in age, BMI and sex ratio with disease duration of 4.3±2.5 years for MSA vs. 11.5±6 years for PD (P<0.0001) were tested for CAN using heart rate changes with deep breathing (HR-DB), stand test (HR-ST) and Valsalva maneuver (HR-VM) and blood pressure changes during stand test (BPs-ST and BPd-ST), Valsalva maneuver (BPs-VM-II and IV), hand grip (BPd-HG) and the total "Ewing" score tests (EwS), and for sweating function using electrochemical skin conductance for hands and feet (HESC and FESC). RESULTS: In MSA-P abnormal EwS, HR-DB, BP-ST and ESC were more frequent compared to PD, despite longer disease duration for PD. Using a model adjusted for sex, BMI, age, disease duration and treatment, the Odds Ratio for having MSA-P vs. PD based on EwS was 2.71, on HR-DB 2.36, on BP-ST 2.87 and on ESC 4.94 while it was 11.68 (2.17-62.79) for the combination of the three last tests. CONCLUSION: Assessment of HR-DB, BP-ST and ESC, that is, rapid and non-invasive could be helpful in combination as a first simple screening to differentiate MSA-P from PD.

Effects of vestibular training on motion sickness, nystagmus, and subjective vertical.

Pitch head-and-trunk movements during constant velocity rotation are a provocative vestibular stimulus that produces vertigo and nausea. When exposed to this stimulus repeatedly, motion sickness symptoms diminish as the subjects habituate. Acetylleucine is a drug that is used to treat acute vestibular vertigo. In this study, we wanted to ascertain whether this drug (a) lessened motion sickness or delayed habituation; (b) accelerated the recovery following habituation; and (c) whether changes in the subjective vertical accompanied habituation. Twenty subjects were administered acetylleucine or placebo in a double-blind study during a five-day vestibular training. Horizontal vestibulo-ocular reflex, optokinetic nystagmus, smooth pursuit, and subjective visual vertical were evaluated before, during, and up to two months after the vestibular training. Based on Graybiel's diagnostic criteria, motion sickness decreased steadily in each vestibular training session, and there was no difference between the scores in the acetylleucine and placebo groups. Post-rotatory nystagmus peak velocity and time constant also declined in both groups at the same rate. Thus, acetylleucine neither reduced the nausea associated with this provocative stimulus, nor hastened the acquisition or retention of vestibular habituation of motion sickness and nystagmus. There was no difference in optokinetic nystagmus and smooth pursuit between the acetylleucine and placebo groups. However, subjects showed larger error in the subjective visual vertical after habituation, which indicates that spatial orientation is also affected by vestibular training.

Towards human exploration of space: the THESEUS review series on neurophysiology research priorities.

The THESEUS project (Towards Human Exploration of Space: a European Strategy), initiated within the seventh Framework Programme by the European Commission, aimed at providing a cross-cutting, life-science-based roadmap for Europe's strategy towards human exploration of long space missions, and its relevance to applications on Earth. This topic was investigated by experts in the field, in the framework of the THESEUS project whose aim was to develop an integrated life sciences research roadmap regarding human space exploration. In particular, decades of research have shown that altered gravity impairs neurological responses at large, such as perception, sleep, motor control, and cognitive factors. International experts established a list of key issues that should be addressed in that context and provided several recommendations such as a maximal exploitation of currently available resources on Earth and in space.

The Bellagio Report: Cardiovascular risks of spaceflight: implications for the future of space travel.

BACKGROUND: Long-duration space missions, as well as emerging civilian tourist space travel activities, prompted review and assessment of data available to date focusing on cardiovascular risk and available risk mitigation strategies. The goal was the creation of tools for risk priority assessments taking into account the probability of the occurrence of an adverse cardiovascular event and available and published literature from spaceflight data as well as available risk mitigation strategies. METHODS: An international group of scientists convened in Bellagio, Italy, in 2004 under the auspices of the Aerospace Medical Association to review available literature for cardiac risks identified in the Bioastronautics Critical Path Roadmap (versions 2000, 2004). This effort led to the creation of a priority assessment framework to allow for an objective assessment of the hazard, probability of its occurrence, mission impact, and available risk mitigation measures. RESULTS/CONCLUSIONS: Spaceflight data are presented regarding evidence/ no evidence of cardiac dysrhythmias, cardiovascular disease, and cardiac function as well as orthostatic intolerance, exercise capacity, and peripheral resistance in presyncopal astronauts compared to non-presyncopal astronauts. Assessment of the priority of different countermeasures was achieved with a tabular framework with focus on probability of occurrence, mission impact, compliance, practicality, and effectiveness of countermeasures. Special operational settings and circumstances related to sensitive portions of any mission and the impact of environmental influences on mission effectiveness are addressed. The need for development of diagnostic tools, techniques, and countermeasure devices, food preparation, preservation technologies and medication, as well as an infrastructure to support these operations are stressed. Selected countermeasure options, including artificial gravity and pharmacological countermeasures need to be systematically evaluated and validated in flight, especially after long-duration exposures. Data need to be collected regarding the emerging field of suborbital and orbital civilian space travel, to allow for sound risk assessment.

[Change of cerebral blood flow velocity during 4 d head-down tilt bed rest].

Objective. To investigate the change of cerebral blood flow velocity during 4 d head-down tilt (HDT) bed rest in humans. Method. Eight healthy male volunteers were exposed to -6 degrees HDT bed rest for 4 d. Orthostatic tolerance was assessed by means of standard tilt test. Cerebral blood flow velocity in the right middle cerebral artery was measured by transcranial Doppler sonography before HDT (supine), on days 1, 3 and 4 of HDT and on day 2 post HDT. Result. After 4 d HDT, the frequency of orthostatic intolerance was significantly higher than those before HDT (P<0.05). The systolic, diastolic and mean blood velocities in the middle cerebral artery tended to decrease on days 1 and 3 of HDT, and decreased significantly on day 4 of HDT, compared with pre-HDT, and returned to basal levels on day 2 post HDT. The mean arterial blood pressure and diastolic blood pressure increased significantly, while the body weight decreased significantly during HDT. Conclusion. It is suggested that 4 d HDT may decrease cerebral blood flow velocity and increase the frequency of orthostatic intolerance. This decrease of cerebral blood flow velocity may be partially responsible for the increased risk of orthostatic intolerance.