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NASA NTRS2021

Chapter 4: Aerospace Neurology

In the practice of medicine, the neurologist is called upon to answer the following questions: (1) Does the patient have neurologic disease? (2) If so, what is the localization of the lesion or lesions? (3) What is the pathophysiology of the process? (4) What is the preliminary differential diagnosis? Utilizing the tools of the neurologic and medical history, the neurologic examination, ancillary studies, and one’s education, training, and experience, the neurologist arrives at a diagnosis. The aerospace medicine physician (evaluator) has the additional challenge of relating the neurologic condition to aviation safety and achieving an appropriate aeromedical disposition. Whether it is the aviation medical examiner (AME), flight surgeon, or Federal Aviation Administration (FAA) regulator, the aerospace medicine physician shoulders the responsibility of a determination that may decide one’s career in aviation or spaceflight. Considering the individual, and yet preserving aerospace safety, is a never-ending challenge for the aerospace medicine physician. The evaluator has the dual responsibility of applying the standards and also considering exceptions to the standards in allowing waivers from standards, while assuring aerospace safety.

Joseph I Sirven↗
NASA NTRS1974

Neurological applications of man-machine systems analysis

Quantitative descriptions of human control properties are formulated that take into account the dynamics of muscle actuation units, neuromuscular sensor units, and sensory feedback mechanics. Detailed dynamic measurements on neurologically disordered patients are correlated with clinical manifestations of various neurological syndromes to quantify operator behavior.

Mcruer, D. T.↗
NASA NTRS1978

Human Neurological Development: Past, Present and Future

Neurological development is considered as the major human potential. Vision, vestibular function, intelligence, and nutrition are discussed as well as the treatment of neurological disfunctions, coma, and convulsive seizures.

Pelligra, R.↗
NASA NTRS1993

Transcranial Doppler ultrasound and the etiology of neurologic decompression sickness during altitude decompression

The presence of gas bubbles in the arterial circulation can occur from iatrogenic mishaps, cardiopulmonary bypass devices, or following decompression, e.g., in deep-sea or SCUBA diving or in astronauts during extravehicular activities (EVA). We have examined the pathophysiology of neurological decompression sickness in human subjects who developed a large number of small gas bubbles in the right side of the heart as a result of hypobaric exposures. In one case, gas bubbles were detected in the middle cerebral artery (MCA) and the subject developed neurological symptoms; a 'resting' patent foramen ovalae (PFO) was found upon saline contrast echocardiography. A PFO was also detected in another individual who developed Spencer Grade 4 precordial Doppler ultrasound bubbles, but no evidence was seen of arterialization of bubbles upon insonation of either the MCA or common carotid artery. The reason for this difference in the behavior of intracardiac bubbles in these two individuals is not known. To date, we have not found evidence of right-to-left shunting of bubbles through pulmonary vasculature. The volume of gas bubbles present following decompression is examined and compared with the number arising from saline contrast injection. The estimates are comparable.

Norfleet, W. T.↗
NASA NTRS1996

Patent Foramen Ovale: Association between the Degree of Shunt by Contrast Transesophageal Echocardiography and the Risk of Future Ischemic Neurologic Events

This study investigated whether there is an association between the degree of interatrial shunting across a patent foramen ovale, as determined by saline contrast transesophageal echocardiography, and the risk of subsequent systemic embolic events, including stroke. Thirty-four patients found to have patent foramen ovale during transesophageal echocardiography were divided into two groups on the basis of the maximum number of microbubbles in the left heart in any single frame after intravenous saline contrast injection: group 1 (n = 16) with a "large" degree of shunt (220 microbubbles) and group 2 (n = 18) with a "small" degree of shunt (23 but <20 microbubbles). Patients were followed up over a mean period of 21 months for subsequent systemic embolic events, including transient ischemic attack and stroke. Five (31%) of the patients with large shunts had subsequent ischemic neurologic events, whereas none of the patients with small shunts had embolic events (p= 0.03). These events occurred in spite of antiplatelet or anticoagulant therapy. We conclude that patients with a large degree of shunt across a patent foramen ovale, as determined by contrast transesophageal echocardiography, are at a significantly higher risk for subsequent adverse neurologic events compared with patients with a small degree of shunt.

Stone, David A.↗
NASA NTRS2001

Screening EEG in Aircrew Selection: Clinical Aerospace Neurology Perspective

As clinical aerospace neurologists we do not favor using screening EEG in pilot selection on unselected and otherwise asymptomatic individuals. The role of EEG in aviation screening should be as an adjunct to diagnosis, and the decision to disqualify a pilot should never be based solely on the EEG. Although a policy of using a screening EEG in an unselected population might detect an individual with a potentially increased relative risk, it would needlessly exclude many applicants who would probably never have a seizure. A diagnostic test performed on an asymptomatic individual without clinical indications, in a population with a low prevalence of disease (seizure) may be of limited or possibly detrimental value. We feel that rather than do EEGs on all candidates, a better approach would be to perform an EEG for a specific indication, such as family history of seizure, single convulsion (seizure) , history of unexplained loss of consciousness or head injury. Routine screening EEGs in unselected aviation applications are not done without clinical indication in the U.S. Air Force, Navy, or NASA. The USAF discontinued routine screening EEGs for selection in 1978, the U.S. Navy discontinued it in 1981 , and NASA discontinued it in 1995. EEG as an aeromedical screening tool in the US Navy dates back to 1939. The US Navy routinely used EEGs to screen all aeromedical personnel from 1961 to 1981. The incidence of epileptiform activity on EEG in asymptomatic flight candidates ranges from 0.11 to 2.5%. In 3 studies of asymptomatic flight candidates with epileptiform activity on EEG followed for 2 to 15 years, 1 of 31 (3.2%), 1 of 30 (3.3%), and 0 of 14 (0%) developed a seizure, for a cumulative risk of an individual with an epileptiform EEG developing a seizure of 2.67% (2 in 75). Of 28,658 student naval aviation personnel screened 31 had spikes and/or slow waves on EEG, and only 1 later developed a seizure. Of the 28,627 who had a normal EEG, 4 later developed seizures, or .0139% (4/28627). After review of the value of the EEG as a screening tool, the US Navy now uses EEG only for certain clinical indications (head injury, unexplained loss of consciousness, family history of epilepsy, and abnormal neurological exam). Currently the US Navy does not use EEG for screening for any flight applicant without a neurologic indication. In the US Navy, an electroencephalographic pattern is determined to be epileptiform by a neurologist.

Clark, Jonathan B.↗
NASA NTRS2019

Mice Exposed to Combined Chronic Low-Dose Irradiation and Modeled Microgravity Develop Long-Term Neurological Sequelae

Spaceflight poses many challenges for humans. Ground-based analogs typically focus on single parameters of spaceflight and their associated acute effects. This study assesses the long-term transcriptional effects following single and combination spaceflight analog conditions using the mouse model, simulated microgravity via hindlimb unloading (HLU) and/or low-dose irradiation (LDR) for 21-days, followed by 4 months of readaptation. Changes in gene expression and epigenetic modifications in whole brain samples during readaptation were analyzed by DESeq2 and reduced representation bisulfite sequencing (RRBS). The results showed minimal gene expression alterations at 4-months within single treatment conditions of HLU and LDR. Following combined HLU+LDR, gene ontology and methylation analyses showed multiple altered pathways involved in neurogenesis and neuroplasticity, regulation of neuropeptides and cellular signaling. In brief, neurological readaptation following combined chronic LDR and HLU is a dynamic process that impacts brain structure and function and may lead to late onset neurological sequelae

Overbey, Eliah G.↗
NASA NTRS1972

The use of a battery of tracking tests in the quantitative evaluation of neurological function

A tracking test battery has been applied in a drug trail designed to compare the efficacy of L-DOPA and amantadine to that of L-DOPA and placebo in the treatment of 28 patients with Parkinson's disease. The drug trial provided an ideal opportunity for objectively evaluating the usefulness of tracking tests in assessing changes in neurologic function. Evaluating changes in patient performance resulting from disease progression and controlled clinical trials is of great importance in establishing effective treatment programs.

Repa, B. S.↗
NASA NTRS1973

The use of a tracking test battery in the quantitative evaluation of neurological function

A number of tracking tasks that have proven useful to control engineers and psychologists measuring skilled performance have been evaluated for clinical use. Normal subjects as well as patients with previous diagnoses of Parkinson's disease, multiple sclerosis, and cerebral palsy were used in the evaluation. The tests that were studied included step tracking, random tracking, and critical tracking. The results of the present experiments encourage the continued use of tracking tasks as assessment precedures in a clinical environment. They have proven to be reliable, valid, and sensitive measures of neurological function.

Repa, B. S.↗
NASA NTRS1974

HEW and the neurologically handicapped

Some of the neurological disorders and therapeutic devices are considered with which the Department of Health, Education, and Welfare (HEW) is most concerned. The organization of the Department, because it is a rather complex one with many different agencies involved, is also described.

Huber, W. V.↗
NASA NTRS1992

Neurology of microgravity and space travel

Exposure to microgravity and space travel produce several neurologic changes, including SAS, ataxia, postural disturbances, perceptual illusions, neuromuscular weakness, and fatigue. Inflight SAS, perceptual illusions, and ocular changes are of more importance. After landing, however, ataxia, perceptual illusions, neuromuscular weakness, and fatigue play greater roles in astronaut health and readaptation to a terrestrial environment. Cardiovascular adjustments to microgravity, bone demineralization, and possible decompression sickness and excessive radiation exposure contribute further to medical problems of astronauts in space. A better understanding of the mechanisms by which microgravity adversely affects the nervous system and more effective treatments will provide healthier, happier, and longer stays in space on the space station Freedom and during the mission to Mars.

Fujii, M. D.↗
NASA NTRS2011

Diagnosis and Treatment of Neurological Disorders by Millimeter-Wave Stimulation

Increasingly, millimeter waves are being employed for telecomm, radar, and imaging applications. To date in the U.S, however, very few investigations on the impact of this radiation on biological systems at the cellular level have been undertaken. In the beginning, to examine the impact of millimeter waves on cellular processes, researchers discovered that cell membrane depolarization may be triggered by low levels of integrated power at these high frequencies. Such a situation could be used to advantage in the direct stimulation of neuronal cells for applications in neuroprosthetics and diagnosing or treating neurological disorders. An experimental system was set up to directly monitor cell response on exposure to continuous-wave, fixed-frequency, millimeter-wave radiation at low and modest power levels (0.1 to 100 safe exposure standards) between 50 and 100 GHz. Two immortalized cell lines derived from lung and neuronal tissue were transfected with green fluorescent protein (GFP) that locates on the inside of the cell membrane lipid bi-layer. Oxonol dye was added to the cell medium. When membrane depolarization occurs, the oxonal bound to the outer wall of the lipid bi-layer can penetrate close to the inner wall where the GFP resides. Under fluorescent excitation (488 nm), the normally green GFP (520 nm) optical signal quenches and gives rise to a red output when the oxonol comes close enough to the GFP to excite a fluorescence resonance energy transfer (FRET) with an output at 620 nm. The presence of a strong FRET signature upon exposures of 30 seconds to 2 minutes at 5-10 milliwatts per square centimeter RF power at 50 GHz, followed by a return to the normal 520-nm GFP signal after a few minutes indicating repolarization of the membrane, indicates that low levels of RF energy may be able to trigger non-destructive membrane depolarization without direct cell contact. Such a mechanism could be used to stimulate neuronal cells in the cortex without the need for invasive electrodes as millimeter waves penetrate skin and bone on the order of 15 mm in depth. Although 50 GHz could not readily penetrate from the outer skull to the center of the cortex, implants on the outer skull or even on the scalp could reach the outer layer of the cerebral cortex where substantial benefit could be realized from such non-contact type excitation.

Siegel, Peter H.↗
NASA NTRS2018

Pilot Study on the Investigation of Tear Fluid Biomarkers as an Indicator of Ocular, Neurological, and Immunological Health in Astronauts

The purpose of this pilot study is to investigate the collection, preparation, and analysis of tear biomarkers as a means of assessing ocular, neurological, and immunological health. At present, no published data exists on the cytokine profiles of tears from astronauts exposed to long periods of microgravity and space irradiations. In addition, no published data exist on cytokine (biomarker) profiles of tears that have been collected from irradiated non-human biological systems (primates and other animal models). A goal for the proposed pilot study is to discover novel tear biomarkers which can help inform researchers, clinicians, epidemiologist and healthcare providers about the health status of a living biological system, as well as informing them when a disease state is triggered. This would be done via analysis of the onset of expression of pro-inflammatory cytokines, leading up to the full progression of a disease (i.e. cancer, loss of vision, radiation-induced oxidative stress, cardiovascular disorders, fibrosis in major organs, bone loss). Another goal of this pilot study is to investigate the state of disease against proposed medical countermeasures, in order to determine whether the countermeasures are efficacious in preventing or mitigating these injuries. An example of an up and coming tear biomarker technology, Ascendant Dx, a clinical stage diagnostic company, is developing a screening test to detect breast cancer using proteins from tears. The team utilized Liquid Chromatography -Mass Spectrometry with Mass analysis (LC MS/MS) as a discovery platform followed by validation with ELISA to come up with a panel of protein biomarkers that can differentiate breast cancer samples from control ("cancer free") samples with results far surpassing the results of imaging techniques in use today. Continued research into additional proteins is underway to increase the sensitivity and specificity of the test and development efforts are on the way to transfer the test onto a fast, accurate and inexpensive point of care platform. In conclusion, the expected results from this proposed pilot study are to: a) establish an SOP for retrieving/storing/transporting tear fluid samples from multicentre sites b) establish a normal range for relevant biomarkers in tears; and c) establish a database (biobank) of tears of space naïve versus veteran astronauts, to establish a personal baseline for long-term ocular health monitoring

Morton, Stephen↗
NASA NTRS2019

Mice Exposed to Combined Chronic Low-Dose Irradiation and Modeled Microgravity Develop Long-Term Neurological Sequelae

A combination of spaceflight-relevant factors (fluid-shift and radiation) created a different gene expression profile than either factor individually. Some gene pathways including reduced transcriptional machinery, increased neurogenesis and neuropeptide production, and dysregulated cell structure and cell signaling. Gene expression differences can persist for at least 4 months after a 21- day exposure to a combination of fluid-shift and radiation in the brain tissue of mice. Brain-related transcriptional changes are dynamic during readaptation phase from exposure to spaceflight-like conditions, which may lead to long-term neurological consequences.

Overbey, Eliah G.↗
NASA NTRS1971

Investigation of the neurological correlates of information reception

Animals trained to respond to a given pattern of electrical stimuli applied to pathways or centers of the auditory nervous system respond also to certain patterns of acoustic stimuli without additional training. Likewise, only certain electrical stimuli elicit responses after training to a given acoustic signal. In most instances, if a response has been learned to a given electrical stimulus applied to one center of the auditory nervous system, the same stimulus applied to another auditory center at either a higher or lower level will also elicit the response. This kind of transfer of response does not take place when a stimulus is applied through electrodes implanted in neural tissue outside of the auditory system.

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