Carbon Ion Radiotherapy in the Management of the Tumors of the Peripheral Nervous System.

BACKGROUND/AIM: Malignant peripheral nerve sheaths tumors (MPNST) are rare, highly aggressive and radioresistant tumors of soft tissue. Carbon ion radiotherapy (CIRT) seems to be an attractive treatment option when surgery is not possible or refused by the patient. The aim of this study was to report our preliminary results (outcomes and toxicity) of CIRT in the treatment of MPNSTs. PATIENTS AND METHODS: Our study retrospectively analyzed 13 patients (median age=54 years; range=23-72 years) with MPNST treated with CIRT for a median total dose of 73.6 Gy (relative biological effectiveness) (range=70.4-76.8 Gy) between 2013 and 2016. RESULTS: Six local progressions were recorded, with a median local progression-free survival of 23.2 months (range=2.2-45.4 months). Acute toxicities were mild. Late toxicity of grade 2 or more was noted in two patients. CONCLUSION: CIRT yielded good local control with a low rate of acute and late toxicities.

Predicting Magnetostimulation Thresholds in the Peripheral Nervous System using Realistic Body Models.

Rapid switching of applied magnetic fields in the kilohertz frequency range in the human body induces electric fields powerful enough to cause Peripheral Nerve Stimulation (PNS). PNS has become one of the main constraints on the use of high gradient fields for fast imaging with the latest MRI gradient technology. In recent MRI gradients, the applied fields are powerful enough that PNS limits their application in fast imaging sequences like echo-planar imaging. Application of Magnetic Particle Imaging (MPI) to humans is similarly PNS constrained. Despite its role as a major constraint, PNS considerations are only indirectly incorporated in the coil design process, mainly through using the size of the linear region as a proxy for PNS thresholds or by conducting human experiments after constructing coil prototypes. We present for the first time, a framework to simulate PNS thresholds for realistic coil geometries to directly address PNS in the design process. Our PNS model consists of an accurate body model for electromagnetic field simulations, an atlas of peripheral nerves, and a neurodynamic model to predict the nerve responses to imposed electric fields. With this model, we were able to reproduce measured PNS thresholds of two leg/arm solenoid coils with good agreement.

Post Pelvic Radiotherapy Affectation of the Lower Urinary Tract Peripheral Innervation in Men.

INTRODUCTION: The periurethral electromyography (EMGs) alterations in men who underwent pelvic radiotherapy (RT), either isolated or combined with surgery, have not been frequently described in the literature. OBJECTIVE: The study aimed to compare the EMG's data in men undergoing RT versus the non-irradiated control group. MATERIAL AND METHODS: The study included 61 consecutive males, who had undergone RT (27 of them had been operated) and 99 control consecutive patients who underwent a retrospective assessment. The EMGs were performed using a concentric electrode needle perineally, localizing the sphincter by visual and auditory signal (electromyograph MMS Solar Active). RESULTS: 14.8% denervation, 62.9% reinnervation, 14.9% denervation + reinnervation and 7.4% EMG normal. The age (p < 0.001) and neurogenic bladder data (p < 0.001) are risk factors. The smaller the prostate size (obtained by rectal examination) post-RT, the more the chance for an abnormal EMG (p < 0.001). The fact of having had received RT (p < 0.001) is the only risk factor. CONCLUSION: RT produces lesions over the pudendal nerve, showing denervation even in late periods. The surgery did not behave as a risk factor.

Cancer treatment-related neuropathic pain syndromes--epidemiology and treatment: an update.

Cancer treatment-related chronic neuropathic pain (NP) is a pervasive and distressing problem that negatively influences function and quality of life for countless cancer survivors. It occurs because of cancer treatment-induced damage to peripheral and central nervous system structures. NP becomes chronic when pain signal transmission persists, eventually sensitizing neurons in the dorsal horn and other pain-processing regions in the central nervous system. Frequently overlooked, NP due to cancer treatment has been understudied. Consequently, only a few pharmacologic interventions have been shown to be effective based on the results of randomized controlled trials. Future research designed to explore pathophysiologic mechanisms and effective mechanism-targeted interventions is sorely needed.

Interaction of MRI field gradients with the human body.

In this review, the effects of low-frequency electromagnetic fields encountered specifically during magnetic resonance imaging (MRI) are examined. The primary biological effect at frequencies of between 100 and 5000 Hz (typical of MRI magnetic field gradient switching) is peripheral nerve stimulation, the result of which can be a mild tingling and muscle twitching to a sensation of pain. The models for nerve stimulation and how they are related to the rate of change of magnetic field are examined. The experimental measurements, and analytic and computational modelling work in this area are reviewed. The review concludes with a discussion of current regulation in this area and current practice as both are applied to MRI.

Influence of frequency and temperature on the mechanisms of nerve conduction block induced by high-frequency biphasic electrical current.

The influences of stimulation frequency and temperature on mechanisms of nerve conduction block induced by high-frequency biphasic electrical current were investigated using a lumped circuit model of the myelinated axon based on Schwarz and Eikhof (SE) equations. The simulation analysis showed that a temperature-frequency relationship was determined by the axonal membrane dynamics (i.e. how fast the ion channels can open or close.). At a certain temperature, the axonal conduction block always occurred when the period of biphasic stimulation was smaller than the action potential duration (APD). When the temperature decreased from 37 to 15 degrees C, the membrane dynamics slowed down resulting in an APD increase from 0.4 to 2.4 ms accompanied by a decrease in the minimal blocking frequency from 4 to 0.5 kHz. The simulation results also indicated that as the stimulation frequency increased the mechanism of conduction block changed from a cathodal/anodal block to a block dependent upon continuous activation of potassium channels. Understanding the interaction between the minimal blocking frequency and temperature could promote a better understanding of the mechanisms of high frequency induced axonal conduction block and the clinical application of this method for blocking nerve conduction.

A charge-balanced pulse generator for nerve stimulation applications.

Nerve stimulation typically employs charge-balanced current injection with a delay between the cathodal and anodal phases. Typically these waveforms are produced using a microprocessor. However, once appropriate stimulus parameters are chosen, they tend to remain fixed within an application, making computational power unnecessary. In such cases, it would be advantageous to replace the microprocessor with integrated circuitry and hardware controls for maintaining fixed pulse parameters. We describe here an architecture that generates controllable charge-balanced pulses but requires no computer processing components. The circuitry has been engineered such that minimum size and power consumption can be achieved when fabricated into an IC chip, making it ideal for many long term, portable nerve stimulation devices and applications.

A neurobiological basis for ELF guidelines.

It is well understood that electric currents applied directly to the body can stimulate peripheral nerve and muscle tissue; such effects can be fatal if breathing is inhibited or ventricular fibrillation is induced. Exposure to extremely low frequency electric and magnetic fields will also induce electric fields and currents within the body, but these are almost always much lower than those that can stimulate peripheral nerve tissue. Guidance on exposure to such fields is based on the avoidance of acute effects in the central nervous system. This paper reviews the physiological processes involved in nerve cell excitability in the peripheral and central nervous system, and the experimental evidence for physiologically weak electric field effects. It is concluded that the integrative properties of the synapses and neural networks of the central nervous system render cognitive function sensitive to the effects of physiologically weak electric fields, below the threshold for peripheral nerve stimulation. However, the only direct evidence of these weak field interactions within the central nervous system is the induction of phosphenes in humans--the perception of faint flickering light in the periphery of the visual field, by magnetic field exposure. Other tissues are potentially sensitive to induced electric fields through effects on voltage-gated ion channels, but the sensitivity of these ion channels is likely to be lower than those of nerve and muscle cells specialized for rapid electrical signaling. In addition, such tissues lack the integrative properties of synapses and neuronal networks that render the central nervous system potentially more vulnerable.

Interventional therapies in the management of complex regional pain syndrome.

Invasive procedures have long held a place in the therapeutic armamentarium for the management of complex regional pain syndrome (CRPS). However, this has evolved considerably, particularly as research into the mechanisms of CRPS has called into question long-held presumptions about the key role of sympathetic dysfunction in the syndrome. This review summarizes some of the key information currently available about interventional treatments, including nerve blocks, spinal cord and peripheral nerve stimulation, chemical and surgical sympathectomies, and deep brain stimulation. The potential roles for these procedures in facilitating functional rehabilitation goals that are primary to the treatment of CRPS are emphasized.

Nerve conduction abnormalities in patients with MELAS and the A3243G mutation.

BACKGROUND: Mitochondrial DNA point mutations are especially deleterious to tissues with high energy demand, including the peripheral nervous system. Neuropathy has been associated with several mitochondrial diseases, including MELAS (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes). OBJECTIVE: To evaluate nerve conduction in a genotypically and phenotypically homogeneous group of patients with MELAS and the A3243G mutation. DESIGN: We studied 30 patients with MELAS and the A3243G mutation using neurophysiological techniques, medical history questionnaires, laboratory tests, and a standardized neurological examination. RESULTS: Twenty-three subjects (77%) had abnormal nerve conduction measures. Symptoms suggestive of neuropathy were present in only half of the patients, but almost all had decreased reflexes or distal sensory findings on examination. Nerve conduction abnormalities were predominantly axonal and sensory and mainly present in the legs. Patients with nerve conduction abnormalities tended to be older and were more likely male. CONCLUSIONS: Peripheral nerve impairment is common in those with MELAS and the A3243G mutation, and may be subclinical. Male sex and older age may add to the genetic disposition to develop neuropathy.

Decreasing pain in electrical nerve stimulation.

OBJECTIVE: Do large stimulation electrodes reduce pain in nerve conduction testing? METHODS: Fourteen healthy subjects (6 men, 22-42 years) blinded for study design underwent 8 H-reflex studies, using a large (36 x 36 mm) or a small (6 x 6 mm) electrode, placed on either the patella or the popliteal fossa; either site could be used for the cathode or the anode. Stimulation intensity was adjusted to obtain M- and H-waves. Intensity and other characteristics of pain were noted, as were M- and H-wave parameters. RESULTS: Pain was felt strongest near the smaller electrode when two sizes were used. Large electrodes reduced pain without compromising H- or M-waves. CONCLUSIONS: Large stimulation electrodes reduce pain. SIGNIFICANCE: The results apply for tests relying on amplitude measurements.

Late effects of radiotherapy for pediatric extremity sarcomas.

PURPOSE: To determine the long-term effects of radiotherapy (RT) in children treated for extremity sarcoma. PATIENTS AND METHODS: Between 1964 and 1997, 15 of 33 children treated with RT for extremity sarcomas at the University of Iowa have survived with a median follow-up was 20 years (range, 6-36 years). There were 10 boys and 5 girls with a median age of 13 years (range, 3.5-20 years) at the time of irradiation. The diagnosis was Ewing's sarcoma in 8 (53%), synovial sarcoma in 4 (27%), alveolar rhabdomyosarcoma in 2, and fibrosarcoma in 1. Location of primary tumor was lower extremity in 10 (67%) and upper extremity in 5 (33%). RT was given as the definitive therapy for 9 children (median dose, 55.8 Gy; range, 45-66 Gy) and as an adjuvant postoperative treatment in 6 (median, 63 Gy; range, 41.4-66.4 Gy). (60)Co was used in 6 (40%), 4 mV in 4, 6 mV in 2, and 250 kV photons in 2 patients; 1 child was treated with a combination of 12 and 15 MeV electrons for a Ewing's sarcoma of the distal femur. Another child had a 25 Gy intraoperative RT boost after 41.4 Gy conventional RT. Late effects to the muscle, soft tissue, and growing bone were assessed using the objective portion of the LENT-SOMA scale proposed by the Late Effects Consensus Conference. RESULTS: Late effects were seen in all patients and included atrophy in 12 (80%), fibrosis in 12 (80%), bone growth abnormalities in 10 (67%), impairment of mobility and extremity function in 6 (40%), edema in 3 (20%), and peripheral nerve injury in 2 (13%). Ten of 15 (67%) children had Grade 1 or 2 growing bone, muscle, soft tissue, or peripheral nerve complications. Two patients (13%) had a Grade 3 mobility and extremity function score and had moderate to severe limitation of movement. Two children (13%) required epiphysiodesis because of a shorter treated leg. The patient who received an intraoperative RT boost of 25 Gy developed sensory dysfunction of the ulnar nerve 11 years after RT. Another developed radial nerve palsy 3 years after marginal resection and postoperative RT and required tendon transfer repair. One patient had radiation-induced vasculitis with popliteal artery thrombosis 23 years after RT. Five (33%) developed a fracture of the irradiated bone at a median time of 8 years after RT (range: 9 months to 22.2 years); all had Ewing's sarcoma, and 3 of these patients were subsequently found to have a secondary bone cancer (osteosarcoma 2, malignant fibrous histiocytoma 1) in the RT field. One of these patients also developed breast cancer 26 years after lung RT for metastatic Ewing's sarcoma. Overall, 11 surgical procedures in 8 children were performed to correct a limb preservation treatment toxicity. CONCLUSIONS: Although most children treated with RT for a pediatric extremity sarcoma have minimal late toxicity by LENT-SOMA scale, approximately half required a surgical procedure to correct a late effect. A fracture in the irradiated bone may be the presenting sign or may precede a radiation-induced bone malignancy, as seen in 3 of the patients in this study.

Microwave effects on the nervous system.

Studies have evaluated the electroencephalography (EEG) of humans and laboratory animals during and after Radiofrequency (RF) exposures. Effects of RF exposure on the blood-brain barrier (BBB) have been generally accepted for exposures that are thermalizing. Low level exposures that report alterations of the BBB remain controversial. Exposure to high levels of RF energy can damage the structure and function of the nervous system. Much research has focused on the neurochemistry of the brain and the reported effects of RF exposure. Research with isolated brain tissue has provided new results that do not seem to rely on thermal mechanisms. Studies of individuals who are reported to be sensitive to electric and magnetic fields are discussed. In this review of the literature, it is difficult to draw conclusions concerning hazards to human health. The many exposure parameters such as frequency, orientation, modulation, power density, and duration of exposure make direct comparison of many experiments difficult. At high exposure power densities, thermal effects are prevalent and can lead to adverse consequences. At lower levels of exposure biological effects may still occur but thermal mechanisms are not ruled out. It is concluded that the diverse methods and experimental designs as well as lack of replication of many seemingly important studies prevents formation of definite conclusions concerning hazardous nervous system health effects from RF exposure. The only firm conclusion that may be drawn is the potential for hazardous thermal consequences of high power RF exposure.

Effect of light/dark regimen on N-nitrosoethylurea-induced transplacental carcinogenesis in rats.

Pregnant females were randomly subdivided into three groups (24 rats per group) and kept at the 12:12 h light/dark regimen (group 1), at the constant light illumination (24 h a day, group 2) or at the continuous darkness (group 3). N-nitrosoethylurea (NEU) has been injected into the tail vein of all rats (80 mg/kg) on the 18-19th day of the pregnancy. After the delivery the lacting dams and their progeny during the lactation period (1 month after delivery) were kept also at the three different light/dark regimens. Then all offspring from each group was kept at the 12:12 h light/dark regimen, males and females separately, and were observed until natural death. The exposure to constant light significantly promoted the transplacental carcinogenesis whereas the exposure to constant darkness inhibited it. The incidence of total tumors, tumors of both a peripheral nervous system and kidney was 2.6; 2.5 and 8.5 times higher, and survival significantly shorter, correspondingly, in rats from the group 2 exposed to the constant light regimen as compared to the group 1 (12:12 h light/dark regimen) (P<0.05). On the other hand, the exposure to the continuous darkness during the pregnancy and the lactation period significantly inhibited the transplacental carcinogenesis in the offspring of rats treated with NEU. The incidence of total tumors, tumors of a peripheral nervous system was by 2.4 and 2.7 times less, and survival longer, respectively, in exposed to the darkness rats from the group 3 as compared to the group 1 (12:12 h light/dark regimen) (P<0.05). Thus, our data firstly have shown the modifying effect of light-dark regimen on the realization of the transplacental carcinogenesis induced by NEU in rats.

Correlation of radiation tolerance dose of normal human organs with organ weight, blood, and water content.

The concerted effort to minimize the radiation exposure to normal human tissues while delivering a high radiation dose to the tumor often results in complications. This limits the efficacy of radiation treatment. Analysis of radiation tolerance dose with organ weight in 15 human organs yields a correlation coefficient of 0.62, whereas the correlation of radiation tolerance dose with blood and water content yields correlation coefficients of 0.82 and 0.60, respectively. Results indicate that as the organ weight and/or blood and water content increases, radiation tolerance dose decreases.

[Effects of low-intensity EHF-radiation on peripheral sections of the nervous system]. / Vplyv nyz'kointensyvnoho NVCh-vyprominiuvannia na peryferychni viddily nervovoï systemy.

A study was made on effects of EHF-radiation on man. The study was conducted in 40 volunteers who ranged from 20 to 30 years old using the EHF-apparatus "Yav-I" (wavelength 7.1 mm, wattage 5 mW/cm2). As a result of 50 min exposure to EHF-radiation of the area of the GI(II)4 acupuncture point in EEG study a rearrangement has been recorded of cortical rhythm patterns characteristic of a healthy man, that suggested the development of an unspecific reaction of activation such as increase in the tone of the brain cortex. In the investigation designed to study indication of EHF EMF, it has been shown that a field with the above parameters is recognized by 78 percent of examinees.

Possible complications of magnetic coil stimulation in living tissue: assessment of changes in epiphyseal cartilage.

To assess the influence of repeated magnetic coil stimulation (MCS) of the peripheral nervous system on epiphyseal cartilage, we evaluated histological and structural changes after repeated MCS applied to the knee joints of young rabbits. There was a slight but significant histological change when repeated MCS at 100% intensity (100% of the maximal output) exceeded 600 times per day. However, we found no gross structural effects on the bone. We conclude that, if these results can be extrapolated to humans, MCS should be safe for stimulating peripheral nervous system for clinical electrophysiologic examinations in children.

In vitro frog sciatic nerve as a peripheral nerve model for studies of the mechanism of action of low energy lasers: Part one.

BACKGROUND AND OBJECTIVE: There have been numerous reports of modulation of peripheral nerve action potential characteristics through application of low energy laser irradiation (LELI), although no mechanism has yet been advanced to explain these observations. In order to investigate the mechanism of LELI effects in peripheral nerve tissue, a well-characterized, reliable, and robust peripheral nerve preparation is required. The objective of this study was to evaluate the in vitro frog sciatic nerve as a candidate model for future LELI mechanism studies. MATERIALS AND METHODS: Following 60-minute baseline recordings of compound action potential (CAP) amplitude, latency, depolarization rate, and repolarization rate, helium-neon (HeNe) laser irradiation (632 nm, 15 min, 1-7 J, 44-320 J/cm2) was delivered to one of two sites on the nerve. Laser-induced changes in CAP parameters were analyzed during irradiation and for 60 minutes post-irradiation using a repeated measures linear regression model. RESULTS: In the treatment group that received 7 J of HeNe energy over the recording electrode, CAP latency increased relative to nonirradiated controls during the postirradiation period. No other treatment group demonstrated laser-induced changes in CAP characteristics at any time during the experiment. CONCLUSION: HeNe irradiation demonstrated limited ability to alter the CAP under these conditions. As such, the in vitro frog sciatic nerve is an inappropriate model for mechanism of action studies.