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Background: Intraoperative neurophysiologic monitoring (IONM) is a technique that is helpful for assessing the nervous system during spine surgery. Methods: This is a review of the field describing the basic mechanisms behind the techniques of IONM. These include the most often utilized trancranial motor evoked potentials (Tc-MEPs), somatosensory evoked potentials (SSEPs), and stimulated and spontaneous EMG activity. It also describes some of the issues regarding practices and qualifications of practitioners. Results: Although the anatomic pathways responsible for the Tc-MEP and SSEP are well known and these clinical techniques have a high sensitivity and specificity, there is little published data showing that monitoring actually leads to improved patient outcomes. It is evident that IONM has high utility when the risk of injury is high, but may be only marginally helpful when the risk of injury is very low. The monitoring team must be well trained, be able to provide the surgeon feedback in real time, and coordinate activities with those of the surgical and anesthesia teams. Conclusions: Although IONM is a valuable technique that provides sensitive and specific indications of neurologic injury, it does have limitations that must be understood. Maintaining a high quality of practice with appropriately trained personnel is critical. [ABSTRACT FROM AUTHOR]

Abstract: Although in-vitro peripheral nerve preparations are useful tools in studying the physiology of axons, their function invariably declines gradually over time. This study investigates the effects of age and temperature on both the in-vitro stability of rat sciatic nerve and the response of the nerve to acute hypoxia. Comparison of the effects of age and temperature in these two models can clarify a possible connection between the hypoxic response and the stability of in-vitro preparations. In in-vitro preparations, the amplitude of the nerve action potential (NAP) declines more rapidly at high temperatures than low temperatures. At high temperatures, the decline in NAP amplitude is faster in nerves taken from younger animals while at low temperatures, the NAP amplitude is the same in both young and old animals. This dependence is similar to that of the time required for the NAP to reach 50% of its baseline value after recovery from hypoxia and the NAP amplitude after a 1.5-h period of hypoxia. It is different from the behavior of the time required for the NAP to drop to 50% of its initial value during hypoxia since the effects of temperature and age on this parameter are independent. This provides evidence of a relationship between the injury caused by hypoxia and the changes that occur after transection. However, since the effect of age on the changes in conduction velocity after transection and after hypoxia are different, the two processes must differ in the response of myelin to the metabolic changes in these conditions. [Copyright &y& Elsevier]

Background context: Electroencephalography (EEG) is one of the oldest and most commonly utilized modalities for intraoperative neuromonitoring. Historically, interest in the EEG patterns associated with anesthesia is as old as the discovery of the EEG itself. The evolution of its intraoperative use was also expanded to include monitoring for assessing cortical perfusion and oxygenation during a variety of vascular, cardiac, and neurosurgical procedures. Furthermore, a number of quantitative or computer-processed algorithms have also been developed to aid in its visual representation and interpretation. The primary clinical outcomes for which modern EEG technology has made significant intraoperative contributions include: (1) recognizing and/or preventing perioperative ischemic insults, and (2) monitoring of brain function for anesthetic drug administration in order to determine depth of anesthesia (and level of consciousness), including the tailoring of drug levels to achieve a predefined neural effect (e.g., burst suppression). While the accelerated development of microprocessor technologies has fostered an extraordinarily rapid growth in the use of intraoperative EEG, there is still no universal adoption of a monitoring technique(s) or of criteria for its neural end-point(s) by anesthesiologists, surgeons, neurologists, and neurophysiologists. One of the most important limitations to routine intraoperative use of EEG may be the lack of standardization of methods, alarm criteria, and recommendations related to its application. Lastly, refinements in technology and signal processing can be expected to advance the usefulness of the intraoperative EEG for both anesthetic and surgical management of patients. Objective: This paper is the position statement of the American Society of Neurophysiological Monitoring. It is the practice guidelines for the intraoperative use of raw (analog and digital) and quantitative EEG. Methods: The following recommendations are based on trends in the current scientific and clinical literature and meetings, guidelines published by other organizations, expert opinion, and public review by the members of the American Society of Neurophysiological Monitoring. This document may not include all possible methodologies and interpretative criteria, nor do the authors and their sponsor intentionally exclude any new alternatives. Results: The use of the techniques reviewed in these guidelines may reduce perioperative neurological morbidity and mortality. Conclusions: This position paper summarizes commonly used protocols for recording and interpreting the intraoperative use of EEG. Furthermore, the American Society of Neurophysiological Monitoring recognizes this as primarily an educational service. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Determine whether EEG findings could be used as an independent prognostic indicator of outcomes in a general patient population. Methods: A large electronic medical record was used to merge the results of EEG studies with the results of medical evaluations including: medications prescribed, medical diagnoses, blood test results, imaging results, and outcomes in 3193 patients. Univariable and multivariable analyses were undertaken to determine whether the EEG had a role in predicting outcomes independent of other factors in a clinic population. Results: Patients with abnormal EEG’s had significantly higher mortalities, greater cost of healthcare and more evaluation visits than patients with normal EEG’s in every age range independent of the presence other medical conditions. The costs associated with caring for a patient with an abnormal EEG were roughly three times that of a patient with a normal EEG. The risk of death in the multivariable analysis was 3.7 times higher in patients with an abnormal EEG than in patients with a normal EEG. Conclusions: In addition to its traditional diagnostic implications, the EEG may convey information about general level of illness and the cost of caring for patients. Significance: Certain EEG findings may identify high risk patients and thus may open the door to possible interventions. [Copyright &y& Elsevier]

Abstract: The information content of signals subject to constraints such as the total power at a set of frequencies is well understood. This paper illustrates a general approach to the computation of the entropy of a constrained signal. Although general solutions will be derived, exact solutions may be difficult and so three approximation techniques are discussed. One is based on the cumulant expansion. The lowest-order results from this expansion have a simple form. The use of an asymptotic expression to compute the signal entropy is explored when the constraints are such that the number of states available to the signal is small. The role of direct numerical calculations is discussed. Results are discussed in light of the problem of computing the entropy of a signal constrained by its moments. The lowest-order terms in the cumulant expansion of the entropy are used to find a generalized correlation filter to detect signals subject to different constraints. The critical role that entropy has in determining the sensitivity and specificity of such a detector is discussed. Another application is the computation of the entropy of a signal subject to polyspectral constraints. It is demonstrated that the entropy change is governed by the higher-order coherence. Applications of these findings to the detection of signals subject to polyspectral constraints is discussed as are the limitations of the second-order cumulant expansion. More general expressions for the entropy of such systems are derived. [Copyright &y& Elsevier]

Background: Although the neurologic status of patients undergoing cardiac operations has been well studied at other times, there are few studies of neurologic status in the immediate postoperative state. This study used standardized nursing neurologic evaluations to describe the sequence of neurologic changes during the first few hours after cardiac operations and the factors that influence them. Methods: In this prospective study, patients arriving in the intensive care unit after cardiac operations were serially assessed using the using the Neurologic Intensive Care Evaluation (NICE) for up to 24 hours postoperatively. The study evaluated the effects on outcome of various preoperative and intraoperative variables, as well as the NICE scores. Results: Recovery of brainstem reflexes occurred at 1.4 ± 1.4 hours, and the fully alert state occurred at a mean of 5.1 ± 3.8 hours after admission to the intensive care unit in patients without a new neurologic deficit. Patients with new neurologic deficits or patients discharged to supervised care settings took longer to reach each neurologic milestone. Older patients, patients with more complex surgical procedures, and patients with higher cardiovascular risk factors took longer to become fully alert. The time to reach the highest NICE score was a strong predictor of the duration of intubation but only weakly predicted other outcome variables in a multivariable analysis. Conclusions: Standardized, serial nursing neurologic assessments of postoperative cardiac patients provide insight into the immediate postoperative period and may be a useful tool for early identification of patients at risk for adverse outcomes. [Copyright &y& Elsevier]

Detecting acute nerve compression using neurophysiologic studies is an important part of the practice of clinical intra-operative neurophysiology. The goal of this paper was to study the changes in the compound muscle action potential (CMAP) during acute mechanical compression. This is the type of injury most likely to occur during surgery. Thus, understanding the changes in the CMAP during this type of injury will be useful in the detection and prevention using intra-operative neurophysiologic monitoring. The model involved compression of the hamster sciatic nerve over a region of 1.3 mm with pressures up to 2000 mmHg for times on the order of 3 minutes. In this model CMAP amplitude dropped to 50% of its baseline value when a pressure of roughly 1000 mmHg is applied while, at the same time, nerve conduction velocities decline by only 5%. The ability to detect statistically significant changes in the CMAP at low force levels using other descriptors of the CMAP including duration, latency variation, etc alone or in conjunction with amplitude and velocity measures was investigated. However, these other parameters did not allow for earlier detection of significant changes. This study focused on a model in which nerve injury on a short time scale is purely mechanical in origin. It demonstrated that a pure compression injury produced large changes in CMAP amplitude prior to large changes in conduction velocity. On the other hand, ischemic and stretch injuries are associated with larger changes in conduction velocity for a given value of CMAP amplitude reduction. [ABSTRACT FROM AUTHOR]

The response to transcranial electrical stimulation of the brain is an important means of assessing motor pathways in the anesthetized patient. The purposes of this study were to elucidate the pattern of axonal excitation produced by transcranial stimulation and to demonstrate how this pattern is affected by changes in the conductivity or geometry of the skull–CSF–brain complex. To this end, analytic solutions to the problem of electrodes placed on a three shell spherical model were obtained under constant current conditions. The potentials, currents and fields generated were computed and the “activating function” was computed for an idealized set of radially organized axons in order to estimate the degree of membrane depolarization produced by stimulation. The degree to which electromagnetic/radiation effects change these solutions was also estimated.The pattern of stimulation was only slightly dependent on the conductivity and the thickness of the CSF layer. Axons very close to the anode were stimulated with lowest threshold at the brain surface. Axons further away were stimulated with higher thresholds and the point of maximum stimulation moved nearer the center of the sphere. Near the cathode, stimulation was maximal about 5–7° away from the edge of the electrode but the peak magnitude of the activating function was generally 20 times lower than over the anode. [Copyright &y& Elsevier]

Background: Classifying the types of extracellular potentials recorded when neural structures are activated is an important component in understanding nerve pathophysiology. Varying definitions and approaches to understanding the factors that influence the potentials recorded during neural activity have made this issue complex. Methods: In this article, many of the factors which influence the distribution of electric potential produced by a traveling action potential are discussed from a theoretical standpoint with illustrative simulations. Results: For an axon of arbitrary shape, it is shown that a quadrupolar potential is generated by action potentials traveling along a straight axon. However, a dipole moment is generated at any point where an axon bends or its diameter changes. Next, it is shown how asymmetric disturbances in the conductivity of the medium surrounding an axon produce dipolar potentials, even during propagation along a straight axon. Next, by studying the electric fields generated by a dipole source in an insulating cylinder, it is shown that in finite volume conductors, the extracellular potentials can be very different from those in infinite volume conductors. Finally, the effects of impulses propagating along axons with inhomogeneous cable properties are analyzed. Conclusion: Because of the well-defined factors affecting extracellular potentials, the vague terms far-field and near-field potentials should be abandoned in favor of more accurate descriptions of the potentials. [ABSTRACT FROM AUTHOR]

Describes a method for the approximation of the information content of a signal with bispectral constraints. Solutions for the signal distribution function and signal entropy; Use of perturbation theory approach; Development of a non-linear signal detection algorithm.

Monitoring the vagus nerve and the recurrent laryngeal nerve during surgical procedures may reduce the probability of significant nerve injury. As such, a number of methods to monitor these nerves have been devised including placing electrodes directly into the vocal cords or recording from surface electrodes. In direct comparison, monitoring the identical muscles, bipolar hookwire electrodes displayed approximately one order of magnitude greater amplitude, of both spontaneously occurring and evoked electrical activity than double wire endotracheal tube electrodes. The enhanced sensitivity of the hookwire electrodes, despite the technical difficulties with placement, suggests their use when maximum sensitivity is required. [ABSTRACT FROM AUTHOR]

Some brain functions decline at a linear rate throughout adulthood. Others remain relatively stable until very late in the life cycle. This study characterized the effects of aging on the regional cerebral distribution of hexamethylpropylene amine oxime (HMPAO) in healthy human volunteers. The sample consisted of 26 men and 18 women with a mean age of 41.6±14.9 years (range: 19-73). Their past medical histories, physical examinations, and laboratory screening tests were normal. Single-photon emission tomography (SPET) scans of the brain were performed with a standardized acquisition and processing protocol on a triple-headed camera equipped with fan beam collimators. A 3-D restorative filter and a correction for uniform attenuation were applied before the images were reinterpolated in planes parallel to the line connecting the frontal and occipital poles. Mean counts per pixel were measured in multiple regions of interest (ROIs) within each hemisphere by custom fitting a set of templates to the images. The mean activity in each ROI was compared with the mean activity per pixel in the whole brain. Regression analyses were used to relate the activity ratios to age with both linear and nonlinear models. The relative concentration of radioactivity decreased significantly with age in most, but not all, gray matter structures. It increased in the white matter regions. The nonlinear model of aging fit the data significantly better than a straight line did. Most of the changes with age occurred during young adulthood. No further changes were detectable after the onset of middle age. The median breakpoint age at which the rate of change became negligible was 36.6 years. Aging significantly affects the relative uptake of HMPAO in healthy humans. It decreases in many gray matter regions and increases in most white matter regions. However, the changes do not appear to be linear. Most seem to occur during young adulthood before people reach their late thirties. The... [ABSTRACT FROM AUTHOR]

Objective: Positron emission tomography permits precision identification of the cerebral regions involved in physiologic functions. As the cerebral localization for visceral sensation has not been identified, our aim was to examine the cerebral viscerotopic representation for rectal sensation. Methods: Cerebral-evoked potentials were measured in five healthy volunteers who underwent rectal balloon distension. Simultaneously, cerebral blood flow was measured using positron emission tomography with 15H2O. Results: A cerebral-evoked potential occurred with rectal balloon distension. An increase in cerebral blood flow was noted in the pre- and postcentral gyrus and (be thalamus. Conclusion: The techniques for measuring cerebral-evoked potentials and cortical blood flow are useful in the delineation of the cerebral regions subserving visceral sensation. [ABSTRACT FROM AUTHOR]

The article discusses the study on the causes of syncope in patients with and without cardiovascular disease. Evaluated are signs of various diseases including acute coronary syndrome, cardiac conduction diseases, valvular heart disease and congestive heart failure. Explored is the transient altered level of consciousness.

Alzheimer's disease (AD) is a progressive and incurable neurodegenerative disorder that primarily affects persons aged 65 years and above. It causes dementia with memory loss and deterioration in thinking and language skills. AD is characterized by specific pathology resulting from the accumulation in the brain of extracellular plaques of amyloid-β and intracellular tangles of phosphorylated tau. The importance of mitochondrial dysfunction in AD pathogenesis, while previously underrecognized, is now more and more appreciated. Mitochondria are an essential organelle involved in cellular bioenergetics and signaling pathways. Mitochondrial processes crucial for synaptic activity such as mitophagy, mitochondrial trafficking, mitochondrial fission, and mitochondrial fusion are dysregulated in the AD brain. Excess fission and fragmentation yield mitochondria with low energy production. Reduced glucose metabolism is also observed in the AD brain with a hypometabolic state, particularly in the temporo-parietal brain regions. This review addresses the multiple ways in which abnormal mitochondrial structure and function contribute to AD. Disruption of the electron transport chain and ATP production are particularly neurotoxic because brain cells have disproportionately high energy demands. In addition, oxidative stress, which is extremely damaging to nerve cells, rises dramatically with mitochondrial dyshomeostasis. Restoring mitochondrial health may be a viable approach to AD treatment. [ABSTRACT FROM AUTHOR]

SARS-CoV-2, a single-stranded RNA coronavirus, causes an illness known as coronavirus disease 2019 (COVID-19). Long-term complications are an increasing issue in patients who have been infected with COVID-19 and may be a result of viral-associated systemic and central nervous system inflammation or may arise from a virus-induced hypercoagulable state. COVID-19 may incite changes in brain function with a wide range of lingering symptoms. Patients often experience fatigue and may note brain fog, sensorimotor symptoms, and sleep disturbances. Prolonged neurological and neuropsychiatric symptoms are prevalent and can interfere substantially in everyday life, leading to a massive public health concern. The mechanistic pathways by which SARS-CoV-2 infection causes neurological sequelae are an important subject of ongoing research. Inflammation- induced blood-brain barrier permeability or viral neuro-invasion and direct nerve damage may be involved. Though the mechanisms are uncertain, the resulting symptoms have been documented from numerous patient reports and studies. This review examines the constellation and spectrum of nervous system symptoms seen in long COVID and incorporates information on the prevalence of these symptoms, contributing factors, and typical course. Although treatment options are generally lacking, potential therapeutic approaches for alleviating symptoms and improving quality of life are explored. [ABSTRACT FROM AUTHOR]

The Guidelines for Qualifications of Neurodiagnostic Personnel (QNP) document has been created through the collaboration of the American Clinical Neurophysiology Society (ACNS), the American Society of Neurophysiological Monitoring (ASNM), the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM), and ASET The Neurodiagnostic Society (ASET). The quality of patient care is optimized when neurophysiological procedures are performed and interpreted by appropriately trained and qualified practitioners at every level. These societies recognize that neurodiagnostics is a large field with practitioners who have entered the field through a variety of training paths. This document suggests job titles, associated job responsibilities, and the recommended levels of education, certification, experience, and ongoing education appropriate for each job. This is important because of the growth and development of standardized training programs, board certifications, and continuing education in recent years. This document matches training, education, and credentials to the various tasks required for performing and interpreting neurodiagnostic procedures. This document does not intend to restrict the practice of those already working in neurodiagnostics. It represents recommendations of these societies with the understanding that federal, state, and local regulations, as well as individual hospital bylaws, supersede these recommendations. Because neurodiagnostics is a growing and dynamic field, the authors fully intend this document to change over time. [ABSTRACT FROM AUTHOR]

The author discusses the significant aspects of morbidity and mortality (M&M) conferences as an educational tool. He also offers information on the five factors that play an important role in the success of M&M conferences. The factors are attendance, preparation, leadership, collegiality, and follow-up.

The article celebrates the life and work of electroencephalography (EEG) technologist Theda Sannit.

Objective: To investigate whether paresthesia of the lower extremities following exposure to the World Trade Center (WTC) disaster was associated with signs of neuropathy, metabolic abnormalities, or neurotoxin exposures. Methods: Case-control study comparing WTC-exposed paresthesia cases with "clinic controls" (WTC-exposed subjects without paresthesias), and "community controls" (WTC-unexposed persons). Results: Neurological histories and examination findings were significantly worse in cases than controls. Intraepidermal nerve fiber densities were below normal in 47% of cases and sural to radial sensory nerve amplitude ratios were less than 0.4 in 29.4%. Neurologic abnormalities were uncommon among WTC-unexposed community controls. Metabolic conditions and neurotoxin exposures did not differ among groups. Conclusions: Paresthesias among WTC-exposed individuals were associated with signs of neuropathy, small and large fiber disease. The data support WTC-related exposures as risk factors for neuropathy, and do not support non-WTC etiologies. [ABSTRACT FROM AUTHOR]

OBJECTIVE To determine the prevalence of electrographic seizure (ES) and electrographic status epilepticus (ESE) in dogs and cats that underwent electroencephalography (EEG) because of suspected seizure activity and to characterize the clinical characteristics, risk factors, and in-hospital mortality rates for dogs and cats with ES or ESE. DESIGN Retrospective case series. ANIMALS 89 dogs and 15 cats. PROCEDURES Medical records of dogs and cats that underwent EEG at a veterinary neurology service between May 2009 and April 2015 were reviewed. Electrographic seizure was defined as ictal discharges that evolved in frequency, duration, or morphology and lasted at least 10 seconds, and ESE was defined as ES that lasted > 10 minutes. Patient signalment and history, physical and neurologic examination findings, diagnostic test results, and outcome were compared between patients with and without ES or ESE. RESULTS Among the 104 patients, ES and ESE were diagnosed in 21 (20%) and 12 (12%), respectively. Seventeen (81%) patients with ES had no or only subtle signs of seizure activity. The in-hospital mortality rate was 48% and 50% for patients with ES and ESE, respectively, compared with 19% for patients without ES or ESE. Risk factors for ES and ESE included young age, overt seizure activity within 8 hours before EEG, and history of cluster seizures. CONCLUSIONS AND CLINICAL REVELANCE Results indicated that ES and ESE were fairly common in dogs and cats with suspected seizure activity and affected patients often had only subtle clinical signs. Therefore, EEG is necessary to detect patients with ES and ESE. [ABSTRACT FROM AUTHOR]

Objective: Paresthesias can result from metabolic disorders, nerve entrapment following repetitive motions, hyperventilation pursuant to anxiety, or exposure to neurotoxins. We analyzed data from community members exposed to the World Trade Center (WTC) disaster of September 11, 2001, to evaluate whether exposure to the disaster was associated with paresthesias. Methods: Analysis of data from 3141 patients of the WTC Environmental Health Center. Results: Fifty-six percent of patients reported paresthesias at enrollment 7 to 15 years following the WTC disaster. After controlling for potential confounders, paresthesias were associated with severity of exposure to the WTC dust cloud and working in a job requiring cleaning of WTC dust. Conclusions: This study suggests that paresthesias were commonly associated with WTC-related exposures or post-WTC cleaning work. Further studies should objectively characterize these paresthesias and seek to identify relevant neurotoxins or paresthesia-inducing activities. [ABSTRACT FROM AUTHOR]

Objective: The objective of this research is to determine whether responders and survivors of the World Trade Center (WTC) disaster experience symptoms of neuropathy at a rate higher than those not exposed. Methods: A survey of neuropathic symptoms in patients who were and were not exposed at the WTC based upon the Michigan Neuropathy Screening Instrument (MNSI). Results: Even after correction for medical comorbidities, age, and depression, neuropathic symptoms are much more common in those exposed to WTC dust and increase with increasing exposure. Conclusions: This study provides evidence that exposure to WTC dust is associated with neuropathic symptoms. [ABSTRACT FROM AUTHOR]

Introduction: The response of the peripheral nerve to anoxia is modulated by many factors including glucose and temperature. The purposes of this article are to demonstrate the effects of these factors on the pathological changes induced by anoxia and to compare the electrophysiologic changes and pathological changes in the same nerves. Methods: Sciatic nerves were harvested from rats and placed in a perfusion apparatus where neurophysiologic responses could be recorded continuously during a 16 h experiment. After the experiment, light microscopy and electron microscopy were performed. Results: Light microscopic images showed mild changes from anoxia at normoglycemia. Hypoglycemic anoxia produced massive axonal swelling while hyperglycemic anoxia produced apparent changes in the myelin. Anoxic changes were not uniform in all axons. Electron microscopy showed only minor disruptions of the cytoskeleton with anoxia during normoglycemia. At the extremes of glucose concentration especially with hyperglycemia, there was a more severe disruption of intermediate filaments and loss of axonal structure with anoxia. Hypothermia protected axons from the effect of anoxia and produced peak axonal swelling in the 17-30°C range. Conclusions: The combination of hyperglycemia or hypoglycemia and anoxia produces extremely severe axonal disruption. Changes in axonal diameter are complex and are influenced by many factors. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most prevalent form of dementia worldwide and is characterized by progressive memory loss and cognitive impairment. Our understanding of AD pathogenesis is limited and no effective disease-modifying treatment is available. Mitochondria are cytoplasmic organelles critical to the homeostatic regulation of glucose and energy in the cell. Mitochondrial abnormalities are found early in the course of AD and dysfunctional mitochondria are involved in AD progression. The resulting respiratory chain impairment, neuronal apoptosis, and generation of reactive oxygen species are highly damaging to neurons. Restoration of mitochondrial function may provide a novel therapeutic strategy for AD. This review discusses the specifics of mitochondrial fragmentation, imbalances in fission and fusion, and DNA damage seen in AD and the contribution of compromised mitochondrial activity to AD etiopathogenesis. It explores how an understanding of the processes underlying mitochondrial failure may lead to urgently needed treatment innovations. It considers individual mitochondrial proteins that have emerged as promising drug targets and evaluates neuroprotective agents that could improve the functional state of mitochondria in the setting of AD. There is great promise in exploring original approaches to preserving mitochondrial viability as a means to achieve breakthroughs in treating AD. • AD is an incurable, progressive chronic neurodegenerative disorder and the leading cause of dementia worldwide. • The causes of AD are not known and there is no disease-modifying therapy for AD. • Disruption of mitochondrial bioenergetics and dynamics occur early in the course of AD and are characteristic of AD. • Defining and correcting expression of dysregulated mitochondrial genes could be a treatment approach in AD. • The transfer of healthy mitochondria into AD neurons may be feasible in the future. [ABSTRACT FROM AUTHOR]

The functions of different G-proteinαβγ subunit combinations are traditionally ascribed to their variousα components. However, the discovery of similarly diverse γ subtypes raises the possibility that they may also contribute to specificity. To test this possibility, we used a gene targeting approach to determine whether the closely related γ3 and γ7 subunits can perform functionally interchangeable roles in mice. In contrast to single knock-out mice that show normal survival, Gng3-/-Gng7-/- double knock-out mice display a progressive seizure disorder that dramatically reduces their median life span to only 75 days. Biochemical analyses reveal that the severe phenotype is not due to redundant roles for the two γ subunits in the same signaling pathway but rather is attributed to their unique actions in different signaling pathways. The results suggest that the γ3 subunit is a component of a Gi/o protein that is required for γ-aminobutyric acid, type B, receptor-regulated neuronal excitability, whereas the γ7 subunit is a component of a Golf protein that is responsible for A2A adenosine or D1 dopamine receptor-induced neuro-protective response. The development of this mouse model offers a novel experimental framework for exploring how signaling pathways integrate to produce normal brain function and how their combined dysfunction leads to spontaneous seizures and premature death. The results underscore the critical role of the γ subunit in this process. [ABSTRACT FROM AUTHOR]

Abstract: The extracellular matrix of peripheral nerve is formed from a diverse set of macromolecules, including glycoproteins, collagens and proteoglycans. Recent studies using knockout animal models have demonstrated that individual components of the extracellular matrix play a vital role in peripheral nerve development and regeneration. In this study we identified fibrillin-1 and fibrillin-2, large modular structural glycoproteins, as components of the extracellular matrix of peripheral nerve. Previously it was found that fibrillin-2 null mice display joint contractures, suggesting a possible defect of the peripheral nervous system in these animals. Close examination of the peripheral nerves of fibrillin-2 deficient animals described here revealed some structural abnormalities in the perineurium, while general structure of the nerve and molecular composition of nerve extracellular matrix remained unchanged. We also found that in spite of the obvious motor function impairment, fibrillin-2 null mice failed to display changes of nerve conduction properties or nerve regeneration capacity. Based on the data obtained we can conclude that peripheral neuropathy should be excluded as the cause of the impairment of locomotory function and joint contractures observed in fibrillin-2 deficient animals. [Copyright &y& Elsevier]

Abstract: Sarcoglycans are originally identified in muscle for their involvement in limb-girdle muscular dystrophies. They form a multi-meric complex (α-, β-, γ-, δ-sarcoglycan) that associates with dystrophin, dystroglycan and other proteins to constitute the larger dystrophin–glycoprotein complex at the muscle membrane. Three sarcoglycan subunits (ε-, β-, δ-sarcoglycan) were previously identified in Schwann cells and shown to associate with dystroglycan and a Schwann cell-specific dystrophin isoform (Dp116) at the outermost Schwann cell membrane. Currently, little is known about the exact composition and function of the sarcoglycan complex in the peripheral nervous system. In this study, we showed that the Schwann cell sarcoglycan complex consists of ε-, β-, δ-sarcoglycan and the newly identified ζ-sarcoglycan subunit. The expression of sarcoglycans precedes the onset of myelination and is induced by neurons. In sarcoglycan-deficient BIO14.6 hamsters, loss of the Schwann cell sarcoglycan complex reduces the steady state levels of α-dystroglycan and Dp116. Ultrastructural analysis of sciatic nerves from the mutant animals revealed altered myelin sheaths and disorganized Schmidt–Lanterman incisures indicative of myelin instability. The disruption in myelin structure increased in severity with age. Nerve conduction studies also showed subtle electrophysiological abnormalities in the BIO14.6 hamsters consistent with reduced myelin stability. Together, these findings suggest an important role of sarcoglycans in the stability of peripheral nerve myelin. [Copyright &y& Elsevier]

Cigarette smoke enhances placental inflammation and interferes with steroidogenesis. However, the chemicals in the smoke responsible for these biological activities are unclear. 2,6 xylidine (also called 2,6 Dimethylaniline, DMA) is a component of cigarette smoke that has carcinogenic properties but its effects on the placenta are unknown. Therefore, we hypothesized that DMA may interfere with placental steroidogenesis or enhance placental inflammation. Placental explant cultures were treated with 0–50,000 nM DMA and concentrations of progesterone (P 4), estradiol (E 2), testosterone (T), IL-1β, TNF-α, IL-6, sgp130, HO-1, IL-10, 8-Isoprostane (8-IsoP), and BDNF in the conditioned medium were quantified. Since many environmental toxins enhance the proinflammatory host response to infection, we also performed experiments on placental cultures co-stimulated with 107 heat-killed E. coli. DMA alone significantly reduced P 4 and T secretion but enhanced E 2 secretion. The toxin also reduced placental secretion of IL-6, sgp130, and BDNF. For bacteria-stimulated cultures, DMA increased secretion of P 4 and T, and proinflammatory cytokines (IL-1β, TNF-α) but had mixed effects on anti-inflammatory markers, increasing some (sgp130, IL-10) and reducing others (HO-1). However, DMA enhanced 8-IsoP levels by bacteria-stimulated placental cultures, suggesting that it increases oxidative stress by the tissues. These studies suggest that DMA affects secretion of biomarkers by the placenta and may promote inflammation. Further studies are needed to determine if these observed changes occur in vivo and the extent to which DMA exposure increases the risk of adverse pregnancy outcomes associated with smoking in pregnancy. [ABSTRACT FROM AUTHOR]

Although there are many biochemical methods to measure amyloid-β (Aβ)42 concentration, one of the critical issues in the study of the effects of Aβ42 on the nervous system is a simple physiological measurement. The in vitro rat sciatic nerve model is employed and the nerve action potential (NAP) is quantified with different stimuli while exposed to different concentrations of Aβ42. Aβ42 predominantly reduces the NAP amplitude with minimal effects on other parameters except at low stimulus currents and short inter-stimulus intervals. The effects of Aβ42 are significantly concentration-dependent, with a maximum reduction in NAP amplitude at a concentration of 70 nM and smaller effects on the NAP amplitude at higher and lower concentrations. However, even physiologic concentrations in the range of 70 pM did reduce the NAP amplitude. The effects of Aβ42 became maximal 5-8 h after exposure and did not reverse during a 30 min washout period. The in vitro rat sciatic nerve model is sensitive to the effects of physiologic concentrations of Aβ42. These experiments suggest that the effect of Aβ42 is a very complex function of concentration that may be the result of amyloid-related changes in membrane properties or sodium channels.

Quickly and efficiently extracting evoked potential information from noise is critical to the clinical practice of intraoperative neurophysiologic monitoring (IONM). Currently this is primarily done using trained professionals to interpret averaged waveforms. The purpose of this paper is to evaluate and compare multiple means of electronically extracting simple to understand evoked potential characteristics with minimum averaging. A number of evoked potential models are studied and their performance evaluated as a function of the signal to noise level in simulations., Methods: which extract the least number of parameters from the data are least sensitive to the effects of noise and are easiest to interpret. The simplest model uses the baseline evoked potential and the correlation receiver to provide an amplitude measure. Amplitude measures extracted using the correlation receiver show superior performance to those based on peak to peak amplitude measures. In addition, measures of change in latency or shape of the evoked potential can be extracted using the derivative of the baseline evoked response or other methods. This methodology allows real-time access to amplitude measures that can be understood by the entire OR staff as they are small, dimensionless numbers of order unity which are simple to interpret. The IONM team can then adjust averaging and other parameters to allow for visual interpretation of waveforms as appropriate., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:M.S. is president of the Fresno Institute of NeuroscienceJ.S. is a consultant with Inomed and is on the board of directors of NervioJ.W. has nothing to declare., (© 2023 The Authors.)

As the search for modalities to cure Alzheimer's disease (AD) has made slow progress, research has now turned to innovative pathways involving neural and peripheral inflammation and neuro-regeneration. Widely used AD treatments provide only symptomatic relief without changing the disease course. The recently FDA-approved anti-amyloid drugs, aducanumab and lecanemab, have demonstrated unclear real-world efficacy with a substantial side effect profile. Interest is growing in targeting the early stages of AD before irreversible pathologic changes so that cognitive function and neuronal viability can be preserved. Neuroinflammation is a fundamental feature of AD that involves complex relationships among cerebral immune cells and pro-inflammatory cytokines, which could be altered pharmacologically by AD therapy. Here, we provide an overview of the manipulations attempted in pre-clinical experiments. These include inhibition of microglial receptors, attenuation of inflammation and enhancement of toxin-clearing autophagy. In addition, modulation of the microbiome-brain-gut axis, dietary changes, and increased mental and physical exercise are under evaluation as ways to optimize brain health. As the scientific and medical communities work together, new solutions may be on the horizon to slow or halt AD progression.

Summary: The Guidelines for Qualifications of Neurodiagnostic Personnel (QNP) document has been created through the collaboration of the American Clinical Neurophysiology Society (ACNS), the American Society of Neurophysiological Monitoring (ASNM), the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM), and ASET-The Neurodiagnostic Society (ASET). The quality of patient care is optimized when neurophysiological procedures are performed and interpreted by appropriately trained and qualified practitioners at every level. These societies recognize that neurodiagnostics is a large field with practitioners who have entered the field through a variety of training paths. This document suggests job titles, associated job responsibilities, and the recommended levels of education, certification, experience, and ongoing education appropriate for each job. This is important because of the growth and development of standardized training programs, board certifications, and continuing education in recent years. This document matches training, education, and credentials to the various tasks required for performing and interpreting neurodiagnostic procedures. This document does not intend to restrict the practice of those already working in neurodiagnostics. It represents recommendations of these societies with the understanding that federal, state, and local regulations, as well as individual hospital bylaws, supersede these recommendations. Because neurodiagnostics is a growing and dynamic field, the authors fully intend this document to change over time., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Clinical Neurophysiology Society.)

Although dementia is a common and devastating disease that has been studied intensely for more than 100 years, no effective disease modifying treatment has been found. At this impasse, new approaches are important. The purpose of this paper is to provide, in the context of current research, one clinician's perspective regarding important challenges in the field in the form of specific challenges. These challenges not only illustrate the scope of the problems inherent in finding treatments for dementia, but can also be specific targets to foster discussion, criticism and new research. One common theme is the need to transform research activities from small projects in individual laboratories/clinics to larger multinational projects, in which each clinician and researcher works as an integral part. This transformation will require collaboration between researchers, large corporations, regulatory/governmental authorities and the general population, as well as significant financial investments. However, the costs of transforming the approach are small in comparison with the cost of dementia., Competing Interests: The authors declare no conflict of interest.

Despite intensive research, effective treatments for many common and devastating diseases are lacking. For example, huge efforts and billions of dollars have been invested in Alzheimer's disease (AD), which affects over 50 million people worldwide. However, there is still no effective drug that can slow or cure AD. This relates, in part, to the absence of an animal model or cellular system that incorporates all the relevant features of the disease. Therefore, large scale studies on human populations and tissues will be key to better understanding dementia and developing methods to prevent or treat it. This is especially difficult because the dementia phenotype can result from many different processes and is likely to be affected by multiple personal and environmental variables. We hypothesize that analyzing massive volumes of demographic data that are currently available and combining this with genomic, proteomic, and metabolomic profiles of AD patients and their families, new insights into pathophysiology and treatment of AD may arise. While this requires much coordination and cooperation among large institutions, the potential for advancement would be life-changing for millions of people. In many ways this represents the next step in the information revolution started by the Human Genome Project., Competing Interests: Conflict of interest: All authors declare no conflicts of interest in this paper., (© 2022 the Author(s), licensee AIMS Press.)