Near infrared imaging system for preventing blood vision obstruction in endoscopy.

Spinal endoscopy procedure is commonly used in the diagnosis and treatment of various health problems and is effective. Bleeding is one of the most common complications of spinal endoscopy procedures. Blood vision obstruction (BVO), that is, obstruction of the endoscopic camera lens caused by the accumulation of blood in the surgical field, is a serious problem in endoscopic procedures. This study presents what we believe to be a new approach to addressing BVO with external multispectral imaging. The study was completed using a BVO simulation model, and the results reveal that this technology can be used to effectively overcome BVO and provide clear images of the anatomy, enabling more effective diagnosis and treatment. This technique may enable improvement of the outcomes of endoscopic procedures and could have far-reaching implications in the field of endoscopy.

Neuroplasticity of peripheral axonal properties after ischemic stroke.

OBJECTIVE: This study investigated how peripheral axonal excitability changes in ischemic stroke patients with hemiparesis or hemiplegia, reflecting the plasticity of motor axons due to corticospinal tract alterations along the poststroke stage. METHODS: Each subject received a clinical evaluation, nerve conduction study, and nerve excitability test. Nerve excitability tests were performed on motor median nerves in paretic and non-paretic limbs in the acute stage of stroke. Control nerve excitability test data were obtained from age-matched control subjects. Some patients underwent excitability examinations several times in subacute or chronic stages. RESULTS: A total of thirty patients with acute ischemic stroke were enrolled. Eight patients were excluded due to severe entrapment neuropathy in the median nerve. The threshold current for 50% compound muscle action potential (CMAP) was higher in paretic limbs than in control subjects. Furthermore, in the cohort with severe patients (muscle power ≤ 3/5 in affected hands), increased threshold current for 50% CMAP and reduced subexcitability were noted in affected limbs than in unaffected limbs. In addition, in the subsequent study of those severe patients, threshold electrotonus increased in the hyperpolarization direction: TEh (100-109 ms), and the minimum I/V slope decreased. The above findings suggest the less excitable and less accommodation in lower motor axons in the paretic limb caused by ischemic stroke. CONCLUSION: Upper motor neuron injury after stroke can alter nerve excitability in lower motor neurons, and the changes are more obvious in severely paretic limbs. The accommodative changes of axons progress from the subacute to the chronic stage after stroke. Further investigation is necessary to explore the downstream effects of an upper motor neuron insult in the peripheral nerve system.

Domain-Specific Cognitive Prosthesis for Face Memory and Recognition.

The present study proposes a cognitive prosthesis device for face memory impairment as a proof-of-concept for the domain-specific cognitive prosthesis. Healthy subjects (n = 6) and a patient with poor face memory were enrolled. An acquaintance face recognition test with and without the use of cognitive prosthesis for face memory impairment, face recognition tests, quality of life, neuropsychological assessments, and machine learning performance of the cognitive prosthesis were followed-up throughout four weeks of real-world device use by the patient. The healthy subjects had an accuracy of 92.38 ± 4.41% and reaction time of 1.27 ± 0.12 s in the initial attempt of the acquaintance face recognition test, which changed to 80.48 ± 6.23% (p = 0.06) and 2.11 ± 0.20 s (p < 0.01) with prosthesis use. The patient had an accuracy of 74.29% and a reaction time of 6.65 s, which improved to 94.29% and 3.28 s with prosthesis use. After four weeks, the patient's unassisted accuracy and reaction time improved to 100% and 1.23 s. Functional MRI study revealed activation of the left superior temporal lobe during face recognition task without prosthesis use and activation of the right precentral motor area with prosthesis use. The prosthesis could improve the patient's performance by bypassing the brain area inefficient for facial recognition and employing the area more efficiently for the cognitive task.

Current and Potential Pharmacologic Therapies for Traumatic Brain Injury.

The present article reviewed the pharmacologic therapies of traumatic brain injury (TBI), including current and potential treatments. Pharmacologic therapies are an essential part of TBI care, and several agents have well-established effects in TBI care. In the acute phase, tranexamic acid, antiepileptics, hyperosmolar agents, and anesthetics are the mainstay of pharmacotherapy, which have proven efficacies. In the post-acute phase, SSRIs, SNRIs, antipsychotics, zolpidem and amantadine, as well as other drugs, have been used to manage neuropsychological problems, while muscle relaxants and botulinum toxin have been used to manage spasticity. In addition, increasing numbers of pre-clinical and clinical studies of pharmaceutical agents, including potential neuroprotective nutrients and natural therapies, are being carried out. In the present article, we classify the treatments into established and potential agents based on the level of clinical evidence and standard of practice. It is expected that many of the potential medicines under investigation will eventually be accepted as standard practice in the care of TBI patients.

Altered sensory nerve excitability in fibromyalgia.

BACKGROUND/PURPOSE: To investigate nerve excitability changes in patients with fibromyalgia and the correlation with clinical severity. METHODS: We enrolled 20 subjects with fibromyalgia and 22 sex and age-matched healthy subjects to receive nerve excitability test and nerve conduction study to evaluate the peripheral axonal function. RESULTS: In the fibromyalgia cohort, the sensory axonal excitability test revealed increased superexcitability (%) (P = 0.029) compared to healthy control. Correlational study showed a negative correlation between increased subexcitability (%) (r = -0.534, P = 0.022) with fibromyalgia impact questionnaire (FIQ) score. Computer modeling confirmed that the sensory axon excitability pattern we observed in fibromyalgia cohort was best explained by increased Barrett-Barrett conductance, which was thought to be attributed to paranodal fast K+ channel dysfunction. CONCLUSION: The present study revealed that paranodal sensory K+ conductance was altered in patients with fibromyalgia. The altered conductance indicated dysfunction of paranodal fast K+ channels, which is known to be associated with the generation of pain.

Immune-mediated axonal dysfunction in seropositive and seronegative primary Sjögren's syndrome.

OBJECTIVE: The present study investigates the peripheral neuropathy in Primary Sjögren's syndrome (pSS) using the nerve excitability test to further elucidate how peripheral nerves are affected by the autoantibodies. METHODS: Each patient received clinical evaluation, examination for anti-SSA/Ro and anti-SSB/La antibodies titer, paired motor and sensory nerve excitability test, thermal quantitative sensory test (QST), and nerve conduction study (NCS). RESULTS: A total of 40 pSS patients wasenrolled. Motor axonal study of the pSS with positive anti-SSA/Ro or anti-SSB/La antibodies (n = 28) was found to have increased stimulus for 50% compound muscle action potential (CMAP) (P < 0.05), increased rheobase (P < 0.01), increased minimum I/V slope (P < 0.01) and hyperpolarizing I/V slope (P < 0.05), increased relative refractory period (RRP, P < 0.001), decreased accommodation of threshold electrotonus toward depolarizing current (P < 0.05), and increased accommodation toward hyperpolarizing current (P < 0.05). Seronegative pSS (n = 10) showed much less prominent motor axonal changes, showing only increased minimum I/V slope (P < 0.05). Sensory axonal study in seropositive pSS patients is found to have increased stimulus for 50% sensory nerve action potential (SNAP) (P < 0.01), decreased latency (P < 0.01), increased RRP (P < 0.01), and increased subexcitability (P < 0.05). Seronegative pSS patients have shown no significant sensory axonal changes. Thermal QST showed more prominent abnormalities in seronegative pSS compared to seropositive pSS. INTERPRETATION: Anti-SSA/Ro and anti-SSB/La autoantibodies might cause dysfunction in nodal and internodal region of the axon and small nerve fibers; meanwhile, autoreactive antibodies in seronegative pSS mainly affect small nerve fibers. Thus, the underlying pathophysiology for the two types of pSS is different.

Novel Insights into the Pathogenesis of Spinal Sarcopenia and Related Therapeutic Approaches: A Narrative Review.

Spinal sarcopenia is a complex and multifactorial disorder associated with a loss of strength, increased frailty, and increased risks of fractures and falls. In addition, spinal sarcopenia has been associated with lumbar spine disorders and osteoporosis, which renders making decisions on treatment modalities difficult. Patients with spinal sarcopenia typically exhibit lower cumulative survival, a higher risk of in-hospital complications, prolonged hospital stays, higher postoperative costs, and higher rates of blood transfusion after thoracolumbar spine surgery. Several studies have focused on the relationships between spinal sarcopenia, appendicular muscle mass, and bone-related problems-such as osteoporotic fractures and low bone mineral density-and malnutrition and vitamin D deficiency. Although several techniques are available for measuring sarcopenia, each of them has its advantages and shortcomings. For treating spinal sarcopenia, nutrition, physical therapy, and medication have been proven to be effective; regenerative therapeutic options seem to be promising owing to their repair and regeneration potential. Therefore, in this narrative review, we summarize the characteristics, detection methodologies, and treatment options for spinal sarcopenia, as well as its role in spinal disorders.

Early sensory neurophysiological changes in prediabetes.

AIMS/INTRODUCTION: To elucidate whether axonal changes arise in the prediabetic state and to find a biomarker for early detection of neurophysiological changes. MATERIALS AND METHODS: We enrolled asymptomatic diabetes patients, as well as prediabetic and normoglycemic individuals to test sensory nerve excitability, and we analyzed those findings and their correlation with clinical profiles. RESULTS: In nerve excitability tests, superexcitability in the recovery cycle showed increasing changes in the normoglycemic, prediabetes and diabetes cohorts (-19.09 ± 4.56% in normoglycemia, -22.39 ± 3.16% in prediabetes and -23.71 ± 5.15% in diabetes, P = 0.002). Relatively prolonged distal sensory latency was observed in the median nerve (3.12 ± 0.29 ms in normoglycemia, 3.23 ± 0.38 ms in prediabetes and 3.45 ± 0.43 ms in diabetes, P = 0.019). Superexcitability was positively correlated with fasting plasma glucose (r = 0.291, P = 0.009) and glycated hemoglobin (r = 0.331, P = 0.003) in all participants. CONCLUSIONS: Sensory superexcitability and latencies are the most sensitive parameters for detecting preclinical physiological dysfunction in prediabetes. In addition, changes in favor of superexcitability were positively correlated with glycated hemoglobin for all participants. These results suggest that early axonal changes start in the prediabetic stage, and that the monitoring strategy for polyneuropathy should start as early as prediabetes.

Elucidating Unique Axonal Dysfunction Between Nitrous Oxide Abuse and Vitamin B12 Deficiency.

Introduction: Abuse of nitrous oxide (N2O) has an unusually high lifetime prevalence in developed countries and represents a serious concern worldwide. Myeloneuropathy following the inhalant abuse is commonly attributed to the disturbance of vitamin B12 metabolism, with severe motor deficits are often noted. The present study aims to elucidate its underlying pathophysiology. Methods: Eighteen patients with N2O abuse or vitamin B12 deficiency were recruited. Comprehensive central and peripheral neuro-diagnostic tests were performed, including whole spine MRI, and thermal quantitative sensory testing (QST). Specifically, paired motor and sensory nerve excitability tests were performed in order to obtain a complete picture of the sensorimotor axonal damage. Results: The mean duration of N2O exposure for the N2O abuse patients was 17.13 ± 7.23 months. MRI revealed T2 hyperintensity in 87.5% of the N2O abuse patients and 50% of the vitamin B12 deficiency patients. In N2O abuse patients, the motor nerve excitability test showed decreased in peak response (7.08 ± 0.87 mV, P = 0.05), increased latency (7.09 ± 0.28 ms, P < 0.01), increased superexcitability (-32.95 ± 1.74%, P < 0.05), and decreased accommodation to depolarizing current [TEd (40-60 ms) 56.53 ± 0.70%, P < 0.05]; the sensory test showed only decreased peak response (30.54 ± 5.98 µV, P < 0.05). Meanwhile, motor test in vitamin B12 deficiency patients showed only decreased accommodation to depolarizing current [TEd (40-60 ms) 55.72 ± 1.60%, P < 0.01]; the sensory test showed decreased peak response (25.86 ± 3.44 µV, P < 0.05) increased superexcitability (-28.58 ± 3.71%, P < 0.001), increased subexcitability (8.31 ± 1.64%, P < 0.05), and decreased accommodation to depolarizing current [TEd (peak) 67.31 ± 3.35%, P < 0.001]. Conclusion: Compared to vitamin B12 deficiency, N2O abuse patients showed prominent motor superexcitability changes and less prominent sensory superexcitability changes, hinting a unique pathological process different from that of vitamin B12 deficiency. N2O abuse might cause axonal dysfunction not only by blocking methionine metabolism but also by toxicity affecting the paranodal region.

Uncovering sensory axonal dysfunction in asymptomatic type 2 diabetic neuropathy.

This study investigated sensory and motor nerve excitability properties to elucidate the development of diabetic neuropathy. A total of 109 type 2 diabetes patients were recruited, and 106 were analyzed. According to neuropathy severity, patients were categorized into G0, G1, and G2+3 groups using the total neuropathy score-reduced (TNSr). Patients in the G0 group were asymptomatic and had a TNSr score of 0. Sensory and motor nerve excitability data from diabetic patients were compared with data from 33 healthy controls. Clinical assessment, nerve conduction studies, and sensory and motor nerve excitability testing data were analyzed to determine axonal dysfunction in diabetic neuropathy. In the G0 group, sensory excitability testing revealed increased stimulus for the 50% sensory nerve action potential (P<0.05), shortened strength-duration time constant (P<0.01), increased superexcitability (P<0.01), decreased subexcitability (P<0.05), decreased accommodation to depolarizing current (P<0.01), and a trend of decreased accommodation to hyperpolarizing current in threshold electrotonus. All the changes progressed into G1 (TNSr 1-8) and G2+3 (TNSr 9-24) groups. In contrast, motor excitability only had significantly increased stimulus for the 50% compound motor nerve action potential (P<0.01) in the G0 group. This study revealed that the development of axonal dysfunction in sensory axons occurred prior to and in a different fashion from motor axons. Additionally, sensory nerve excitability tests can detect axonal dysfunction even in asymptomatic patients. These insights further our understanding of diabetic neuropathy and enable the early detection of sensory axonal abnormalities, which may provide a basis for neuroprotective therapeutic approaches.

Sensory axonal dysfunction in cervical radiculopathy.

OBJECTIVE: The aim of this study was to evaluate changes in sensory axonal excitability in the distal nerve in patients with cervical radiculopathy. METHODS: The patients were classified by the findings of cervical MRI into two subgroups: 22 patients with C6/7 root compression and 25 patients with cervical cord and root compression above/at C6/7. Patients were investigated using conventional nerve conduction studies (NCS) and nerve excitability testing. Sensory nerve excitability testing was undertaken with stimulation at the wrist and recording from digit II (dermatome C6/7). The results were compared with healthy controls. Both preoperative and postoperative tests were performed if the patient underwent surgery. RESULTS: Sensory axonal excitability was significantly different in both cohorts compared with healthy controls, including prolonged strength-duration time constant, reduced S2 accommodation, increased threshold electrotonus hyperpolarisation (TEh (90-100 ms)), and increased superexcitability. The changes in these excitability indices are compatible with axonal membrane hyperpolarisation. In five patients who underwent surgery, the postoperative sensory excitability was tested after 1 week, and showed significant changes in TE (TEh (90-100 ms) and TEh slope, p<0.05) between presurgery and postsurgery. CONCLUSIONS: The present study demonstrated distal nerve axonal hyperpolarisation in patients with cervical radiculopathy. These findings suggest that the hyperpolarised pattern might be due to Na(+)-K(+) ATPase overactivation induced by proximal ischaemia, or could reflect the remyelinating process. Distal sensory axons were hyperpolarised even though there were no changes in NCS, suggesting that nerve excitability testing may be more sensitive to clinical symptoms than NCS in patients with cervical radiculopathy.

Early identification of 'acute-onset' chronic inflammatory demyelinating polyneuropathy.

Distinguishing patients with acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy prior to relapse is often challenging at the onset of their clinical presentation. In the present study, nerve excitability tests were used in conjunction with the clinical phenotype and disease staging, to differentiate between patients with acute-onset chronic inflammatory demyelinating polyneuropathy and patients with acute inflammatory demyelinating polyneuropathy at an early stage, with the aim to better guide treatment. Clinical assessment, staging and nerve excitability tests were undertaken on patients initially fulfilling the diagnostic criteria of acute inflammatory demyelinating polyneuropathy soon after symptom onset and their initial presentation. Patients were subsequently followed up for minimum of 12 months to determine if their clinical presentations were more consistent with acute-onset chronic inflammatory demyelinating polyneuropathy. Clinical severity as evaluated by Medical Research Council sum score and Hughes functional grading scale were not significantly different between the two cohorts. There was no difference between the time of onset of initial symptoms and nerve excitability test assessment between the two cohorts nor were there significant differences in conventional nerve conduction study parameters. However, nerve excitability test profiles obtained from patients with acute inflammatory demyelinating polyneuropathy demonstrated abnormalities in the recovery cycle of excitability, including significantly reduced superexcitability (P < 0.001) and prolonged relative refractory period (P < 0.01), without changes in threshold electrotonus. In contrast, in patients with acute-onset chronic inflammatory demyelinating polyneuropathy, a different pattern occurred with the recovery cycle shifted downward (increased superexcitability, P < 0.05; decreased subexcitability, P < 0.05) and increased threshold change in threshold electrotonus in both hyperpolarizing and depolarizing directions [depolarizing threshold electrotonus (90-100 ms) P < 0.005, hyperpolarizing threshold electrotonus (10-20 ms), P < 0.01, hyperpolarizing threshold electrotonus (90-100 ms), P < 0.05], perhaps suggesting early hyperpolarization. In addition, using excitability parameters superexcitability, subexcitability and hyperpolarizing threshold electrotonus (10-20 ms), the patients with acute inflammatory demyelinating polyneuropathy and acute-onset chronic inflammatory demyelinating polyneuropathy could be clearly separated into two non-overlapping groups. Studies of nerve excitability may be able to differentiate acute from acute-onset chronic inflammatory demyelinating polyneuropathy at an early stage. Characteristic nerve excitability parameter changes occur in early acute-onset chronic inflammatory demyelinating polyneuropathy, to match the clinical phenotype. Importantly, this pattern of change was strikingly different to that shown by patients with acute inflammatory demyelinating polyneuropathy, suggesting that nerve excitability techniques may be useful in distinguishing acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy at the initial stage.

Updates on current advances in gene therapy.

Gene therapy is the attempt to treat diseases by means of genetic manipulation. Numerous challenges remain to be overcome before it becomes available as a safe and effective treatment option. Retroviruses and adenoviruses are among the most commonly used viral vectors in trials. The retrovirus introduces the gene it carries into the target cell genome while the adenovirus introduces the gene into the target cell nucleus without incorporating it into the target cell genome. Other viral vectors such as adeno-associated viruses, pseudotyped viruses and herpes simplex viruses, are also gaining popularity. Proposed non-viral methods for gene transfer include physical methods and the employment of chemical vectors (lipoplexes, polyplexes and inorganic nanoparticles). Recent studies have investigated potential applications of gene therapy in correcting genetic diseases, treating malignant disorders and for treatment of other diseases. Trials on gene therapy for SCID and Leber's congenital amaurosis have achieved considerable success, but the widely publicized adverse reaction in X-linked SCID patient receiving gene therapy raised concerns for safety profile of gene therapy. For that, several methods of improving safety and efficacy of gene therapy have been proposed. At present, the three main gene therapy strategies for treatment of cancer are application to oncolytic viruses, suicide-gene therapy and gene-based immunotherapy. Gendicine, the first approved anticancer drugs based on the use of gene therapy principle, is based on the use of oncolytic viruses. More evidence for wider clinical applications of gene therapy are expected as more gene therapy studies progress from the preclinical phase to clinical trial.

Updates on current advances in gene therapy / Actualizaciones acerca de los adelantos presentes en terapia genética

Gene therapy is the attempt to treat diseases by means of genetic manipulation. Numerous challenges remain to be overcome before it becomes available as a safe and effective treatment option. Retroviruses and adenoviruses are among the most commonly used viral vectors in trials. The retrovirus introduces the gene it carries into the target cell genome while the adenovirus introduces the gene into the target cell nucleus without incorporating it into the target cell genome. Other viral vectors such as adenoassociated viruses, pseudotyped viruses and herpes simplex viruses, are also gaining popularity. Proposed nonviral methods for gene transfer include physical methods and the employment of chemical vectors (lipoplexes, polyplexes and inorganic nanoparticles). Recent studies have investigated potential applications of gene therapy in correcting genetic diseases, treating malignant disorders and for treatment of other diseases. Trials on gene therapy for SCID and Leber's congenital amaurosis have achieved considerable success, but the widely publicized adverse reaction in Xlinked SCID patient receiving gene therapy raised concerns for safety profile of gene therapy. For that, several methods of improving safety and efficacy of gene therapy have been proposed. At present, the three main gene therapy strategies for treatment of cancer are application to oncolytic viruses, suicidegene therapy and genebased immunotherapy. Gendicine, the first approved anticancer drugs based on the use of gene therapy principle, is based on the use of oncolytic viruses. More evidence for wider clinical applications of gene therapy are expected as more gene therapy studies progress from the preclinical phase to clinical trial.

La terapia genética es el intento de tratar enfermedades por medio de la manipulación genética. Quedan aún numerosos retos que superar antes de que esté tipo de tratamiento se encuentre disponible como una opción segura y eficaz. Los retrovirus y los adenovirus se hallan entre los vectores virales más comúnmente utilizados en ensayos: el retrovirus introduce el gen - del cual es portador - en el genoma de la célula de destino, mientras el adenovirus introduce el gen en el núcleo de la célula de destino sin incorporarlo al genoma de la célula de destino. Otros vectores virales tales como los virus adenoasociados, los virus pseudotipados, y los virus del herpe simple, también están ganando popularidad. Los métodos no virales propuestos para la transferencia de genes incluyen tanto métodos físicos como el empleo de vectores químicos (lipoplexes, polisomas y nanopartículas inorgánicas). Estudios recientes han investigado las aplicaciones potenciales de la terapia genética en la corrección de las enfermedades genéticas, el tratamiento de los trastornos malignos y para el tratamiento de otras enfermedades. Los ensayos de terapia genética para SCID y la amaurosis congénita de Leber han logrado un éxito considerable, pero la reacción adversa ampliamente divulgada en el caso de los pacientes con SCID ligada al cromosoma, que recibían terapia génica, causó preocupación en cuanto al perfil de seguridad de la terapia génica. Por esa razón, se han propuesto varios métodos para mejorar la seguridad y la eficacia de la terapia génica. En la actualidad, las tres estrategias principales de terapia de genes para el tratamiento del cáncer son la aplicación de virus oncolíticos, la terapia con gen suicida, y la inmunoterapia genética. La gendicina, el primer medicamento anticancerígeno aprobado, basado en el uso del principio de la terapia génica, se basa en el uso de virus oncolíticos. Se esperan más evidencias a favor de aplicaciones clínicas más amplias de la terapia génica, a medida que más estudios de terapia génica progresan de la fase preclínica a la fase de ensayo clínico.

Recent progressions in stem cell research: breakthroughs achieved and challenges faced.

Stem cell studies have been conducted to study characteristics of stem cells, to develop better techniques for patient-specific stem cell lines generation, and to explore the therapeutic potential of stem cells. Techniques that enable efficient generation of new stem cell lines would facilitate research and allow generation of patient-specific stem cell lines for transplantation therapy. Somatic-Cell Nuclear Transfer (SCNT), which involves injection of donor cell nucleus into enucleated ovum, is the standard technique for new embryonic stem (ES) cell lines generation; presently its efficiency is low. A newer technique, pluripotent stem cell induction, reprograms somatic cells into induced pluripotent stem (iPS) cells by introducing certain factors into somatic cells. While certain adult stem cell treatments have been investigated on human participants, most ES cell or iPS cell treatments were still experimented on animal models. Recently, therapeutic potential of stem cell for several disorders was demonstrated. Researchers demonstrated stem cell's potential for treating hematologic disorders by correcting sickle cell anemia in rat model with iPS cells. Its potential role in treating cardiovascular disorder was demonstrated as injection of damaged rat heart with human ES cells derived cardiomyocyte plus "prosurvival" cocktail improved heart function. It might also treat nervous system disorders; injected into brain, ES cells derived neurons replace some loss cells in stroke rats and iPS cells derived neurons improved Parkinsonian syndrome in rats. Progress was also seen in other aspects of regenerative medicine. To overcome controversies caused by embryo destruction for obtaining ES cells, single blastomer stem cell derivation, Cdx2-inactivation, and parthenogenesis were proposed. All ES cell, iPS cell, and adult stem cell research should be continued with support from all sides.